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Biosystems Engineering and Control Group 20

8043424

Characterization and analysis of skin wealing by computerized non-linear regression.

Weal formation in human skin may be induced by histamine, histamine releasers and other inflammatory mediators. Weals occur spontaneously in chronic urticaria, and in response to frictional pressure in dermographic urticaria. We present an improved method for the analysis of wealing in human skin by the use of non-linear regression. The method has the advantage of speed, and by the use of non-linear regression permits the full characterization of the response curves. The time course of histamine-induced wealing is a double exponential function corresponding to the separate components of weal appearance and disappearance. Dermographic wealing corresponds to an increasing exponential function with increasing pressure. The method of computerized non-linear regression is a considerable advance on previous methods for the analysis of urticarial wealing, the effect of vasoactive agents, and their therapeutic action.

8043423

Point mutations in the N-ras oncogene in malignant melanoma and congenital naevi.

DNA from formalin-fixed and paraffin-processed samples from 100 melanocytic lesions (39 malignant melanomas, 18 cases of dysplastic naevi, and 43 congenital naevi) was extracted, and the sequences around codons 12/13 and 61 of the N-ras oncogene were amplified using the polymerase chain reaction. The amplified product was then analysed both by dot-blotting and by direct sequencing for point mutations. By the dot-blotting technique, mutations were seen in 18 of 100 lesions. These were in one of five distant metastases (20%), in one of three nodal metastases (33%), in four of 31 (13%) primary melanomas, in none of 18 dysplastic naevi, and in 12 of 43 (28%) congenital naevi, all at codon 61. On direct sequencing, nine of 18 mutations were confirmed, in two of 31 (6%) primary tumours, one distant metastasis, and six of 43 (14%) congenital naevi. Of the 23 superficial spreading melanomas examined, eight were on sun-exposed skin. A superficial spreading melanoma, in which the N-ras mutation at codon 61 was confirmed, was on non-exposed skin, and an unconfirmed mutation was from an exposed site. One of three nodular melanomas with a confirmed mutation was on a light-exposed site, and the other two nodular melanomas were from non-exposed areas. All four lentigo maligna melanomas were from exposed sites, and one of these had an unconfirmed mutation. The only acral lentiginous melanoma, which had no mutation, was from a sun-exposed area.(ABSTRACT TRUNCATED AT 250 WORDS)

8043422

Skin fibroblast activity in pretibial myxoedema and the effect of octreotide (Sandostatin) in vitro.

The accumulation of glycosaminoglycans in the skin in pretibial myxoedema appears to be a response by local fibroblasts to a stimulating factor in the patient's serum, but the identity of the factor, its ability to stimulate skin fibroblasts as opposed to cultured thyroid cells, and the specificity of its effect to pretibial skin fibroblasts, are all controversial. We have studied fibroblasts cultured from the lesional skin of two women with pretibial myxoedema, and compared their proliferation and secretion of glycosaminoglycans with those of fibroblasts from the patients' forearms and from the forearm skin of two normal subjects. We found that in the presence of the patients' sera all six lines of fibroblasts secreted more glycosaminoglycans [205 +/- 21% (SD)] than with normal human sera (147 +/- 19%), or fetal calf serum (100%). Fibroblast proliferation showed the same pattern of differences: patients' sera 142 +/- 22%; normal human sera 116 +/- 9%, and fetal calf serum 100%. These experiments confirm the presence of a serum factor in pretibial myxoedema which is capable of stimulating the activity of skin fibroblasts in vitro, and show that its effects are not restricted to fibroblasts from pretibial skin or to those grown from the skin of the patients. Proliferation of normal fibroblasts cultured in medium supplemented with fetal calf serum was reduced by Sandostatin (octreotide), but it failed to inhibit their secretion of glycosaminoglycans. In contrast, secretion of glycosaminoglycans by a patient's pretibial skin fibroblasts was almost completely inhibited by 1 mM minoxidil. In the presence of patients' sera Sandostatin (0.1-10 micrograms/ml) reduced secretion of glycosaminoglycans by about 50%.(ABSTRACT TRUNCATED AT 250 WORDS)

8043421

Anticardiolipin antibodies in rheumatoid arthritis: their relation to rheumatoid nodules and cutaneous vascular manifestations.

One hundred and seventy-three consecutive patients with rheumatoid arthritis were examined for the presence of anticardiolipin antibodies (ACA), and for the clinical relevance and the relation of these antibodies to skin manifestations. Abnormally elevated IgG- and/or IgM-ACA levels were detected by an enzyme-linked immunosorbent assay in the sera of 55 (32%) patients. There was no statistical evidence of an association between ACA and a history of thrombosis in these patients. However, ACA were statistically significantly linked to the presence of rheumatoid nodules, which were found in 36 (21%) patients. In three patients, ACA were associated with vascular manifestations, including livedo reticularis, thrombophlebitis, and leucocytoclastic vasculitis. Our findings suggest that, although a subset of ACA may be linked to cutaneous vascular conditions, the major fraction of ACA in rheumatoid arthritis may have a different specificity than in other diseases, in which ACA are often linked to thrombotic events.

8043420

A population genetic study of psoriasis.

We present epidemiological data for 5197 families with psoriasis. Errors in reporting have been analysed. Analysis of the data provides indications of random mating with respect to whether the partner has the skin disease or not. Data on psoriasis among parents, siblings and children are provided, and particular attention has been paid to the age at onset of psoriasis. Psoriasis was present in the parents of about 36% of the probands. In families in which one or both parents have psoriasis, the occurrence of the disease among the siblings does not provide any information which differentiates between a dominant and recessive mode of inheritance, but is compatible with both. In families in which neither parent had psoriasis, provided there was a proband with psoriasis, the probability of the siblings suffering from psoriasis was close to 0.25, indicating a recessive mode of inheritance. The distribution of psoriasis among the parents of all probands, and among the children of probands, was also compatible with this mode of inheritance. The prevalence of psoriasis in the elderly was estimated to be about 5%, and the gene frequency in the whole population 25%. These findings show that, with regard to first-degree relatives, the inheritance of psoriasis can fit an autosomal recessive model. The concept of a recessive mode of inheritance may be used as a basis for genetic counselling.

8043419

bcl-2 expression reliably distinguishes trichoepitheliomas from basal cell carcinomas.

Trichoepitheliomas (TE) are benign follicular neoplasms which are frequently confused with basal cell carcinomas (BCC). It is important to distinguish these entities precisely, as the treatments and prognoses are different. To this end, we stained a series of formalin-fixed, paraffin-embedded specimens of unequivocal TE and BCC with antibodies directed against bcl-2, an oncogene associated with programmed cell death, and known to be overexpressed in some malignant tumours. The TE showed staining of tumour cells limited to the outermost layer of the proliferation. The BCC tumour cells demonstrated diffuse staining throughout the tumour nodules. This difference in staining pattern was then applied to more equivocal cases, and seemed clearly to separate the entities. The observed findings may prove to be of diagnostic help in distinguishing borderline cases, and also offer some possible explanations for the biological differences between these neoplasms.

8043418

Quantification of stratum corneum ceramides and lipid envelope ceramides in the hereditary ichthyoses.

Ceramides (sphingolipids) are the main polar lipids of the stratum corneum and play an important role in skin barrier function, cell adhesion and epidermal differentiation. In view of the function of ceramides in normal skin, this study aimed to assess their levels in patients with various types of hereditary ichthyosis, in which epidermal homeostasis is markedly abnormal. Stratum corneum samples were collected from 80 patients and 23 normal controls, and the intercellular and lipid envelope ceramides were analysed by high-performance thin-layer chromatography. The covalently bound ceramides (ceramides A and B) of the lipid envelope were present in all patients studied, and showed no significant differences from control samples. Total ceramides (ceramides 1-6) were decreased in bullous ichthyosiform erythroderma, which is presumably a secondary phenomenon similar to that seen in patients with atopic dermatitis. Patients with non-erythrodermic lamellar ichthyosis showed a marked decrease in levels of the important acylceramide, ceramide 1, whereas those with other types of autosomal recessive ichthyosis (limited lamellar ichthyosis and non-bullous ichthyosiform erythroderma) had mean levels similar to the controls. Ceramide 1 deficiency may therefore define a subgroup within the autosomal recessive ichthyoses. Sjögren-Larsson syndrome (SLS) shows a deficiency of both acyl-ceramides (ceramides 1 and 6), which would seem likely to disrupt the normal skin barrier function. Furthermore, glucosylceramides (cerebrosides) are known to be deficient in the neural tissue of patients with SLS. The relationship of these ceramide abnormalities to the underlying fatty alcohol oxidoreductase defect remains uncertain, but they may provide an interesting link between the nerve damage and cutaneous abnormalities seen in this rare neurodermatosis.

8043405

Pigmented follicular cyst.

A pigmented follicular cyst is an infrequent variant of an epithelial cyst which has rarely been reported since it was first described about 10 years ago. The condition consists of a single pigmented lesion which occurs predominantly in adult men, and is usually located on the head and neck region. We report an example of a pigmented follicular cyst, which was located in the axilla.

8043404

Photoallergic contact dermatitis to oxybenzone.

A 21-year-old woman developed an erythematous papulovesicular eruption of photo-exposed sites, following the use of an oxybenzone-containing sunscreen. Patch testing, photopatch testing, phototesting, and histology produced findings strongly suggestive of oxybenzone photoallergy. Photopatch testing with a monochromator source showed abnormal UVA responses, with evidence of immediate urticaria, and delayed-onset dermatitis. Sun-barrier use is associated with a risk of the development of contact or photocontact allergic reactions. The benzophenones are frequently used in high-protection factor sun-barrier preparations, and appear to have a particular ability to induce such responses.

8043403

Mucosal lichen sclerosus/lichen planus overlap syndromes.

Lichen sclerosus and lichen planus affecting cutaneous sites are easily distinguishable clinical. Clinical signs on mucosal sites, however, may not allow differentiation between these diseases, and reliance is frequently placed on histopathological findings. We report a series of seven patients with clinical evidence of coexisting vulval lichen sclerosus and lichenoid oral lesions. All patients had vulval biopsies, and four had oral biopsies. Histology of all the vulval biopsy specimens showed features consistent with lichen sclerosus. Two of these patients developed vulval intraepithelial neoplasia during the course of their disease, and one progressed to a well-differentiated squamous carcinoma. Histology of the oral lesions showed features that were predominantly those of lichen planus. There are, however, few reports of histologically proven oral lichen sclerosus. Variations in histopathological descriptions of lichen sclerosus, depending on duration of disease, have been reported, particularly with regard to the position of the inflammatory infiltrate in relation to the dermo-epidermal junction. We believe that these patients may have oral lichen sclerosus, or at the very least make up a distinctive group who need to be identified and followed up, as their risk of oral dysplasia is unknown.

8043401

Severe case of pemphigoid gestationis with unusual target antigen.

We report a severe case of pemphigoid gestationis (PG) with an unusual target antigen. The patient developed a severe itchy macular rash on the abdomen during her fifth pregnancy, at 38 weeks' gestation. The disease persisted for 8 months post-partum, and could only be controlled with high doses of systemic corticosteroids and dapsone. The diagnosis of PG was confirmed by direct and indirect immunofluorescence. A linear band of IgG and C3 was detected at the epidermal aspect of salt-split skin. Immunoblotting studies revealed circulating IgG antibodies binding to a single 200-kDa protein in epidermal extracts. Immunofluorescence studies using trypsinized human keratinocytes demonstrated uniform staining around the cell peripheries, suggesting that the target antigen was not associated with hemidesmosomes. These findings differ from the usual immunological features seen in PG, and suggest further heterogeneity of the antigens involved in PG.

8043402

Simultaneous occurrence of two rare cutaneous markers of poor prognosis in myelodysplastic syndrome: erythema elevatum diutinum and specific lesions.

We report the concomitant occurrence of erythema elevatum diutinum and specific skin lesions in a patient with a myelodysplastic syndrome (MDS). This patient's course, and review of other reported cases, support the opinion that neutrophilic dermatoses are associated with a poor prognosis of MDS. The simultaneous appearance of these manifestations could be the consequence of a particular chemotactism of myeloid cells, expressed after acute transformation.

8043400

Erythema gyratum repens. A case studied with immunofluorescence, immunoelectron microscopy and immunohistochemistry.

We report a patient with erythema gyratum repens (EGR), in whom a bronchial carcinoma was found. Direct immunofluorescence revealed granular deposits of immunoglobulins at the basement membrane zone (BMZ) in the skin, and in the lung tumour. Direct immunoelectron microscopy showed that the immune deposits were localized just beneath the lamina densa. Indirect immunofluorescence revealed circulating anti-BMZ antibodies. Immunohistochemical staining, using anti-transforming growth factor-beta, anti-epidermal growth factor receptor, anti-vimentin and anti-alpha-actin, was found to be more intense in the lesional skin and the lung tumour than in normal tissues. Possible mechanisms in the pathogenesis of EGR are discussed.

8043399

The hereditary palmoplantar keratoses: an updated review and classification.

The palmoplantar keratoses (PPKs) comprise a heterogeneous group of disorders of keratinization, which can be subdivided into hereditary and acquired forms. Many authors have attempted to classify the hereditary forms, and most classifications have been based on the morphology, distribution, associated symptoms and mode of inheritance. Subsequently, many new forms have been recognized, and what were previously considered to be distinct types have been shown to be variants of a single type, both of which limit the usefulness of previous classifications. Hence, we propose a new, updated classification, which enables accurate diagnosis of these disorders.

8043388

Effect of ultraviolet-inducible cytokines on melanoma growth in vivo: stimulation of melanoma growth by interleukin-1 and -6.

Ultraviolet light of wavelengths 280-320 nm (UVB) can induce transcription of cytokine mRNAs and increase expression of the corresponding proteins in the epidermis. In particular, UVB can stimulate keratinocyte synthesis of interleukin-1 (IL-1), IL-6, IL-8, tumor necrosis factor-alpha (TNF-alpha) and transforming growth factor-beta (TGF-beta). Several of these cytokines can influence the growth of tumour cells as well as the host response to these tumours. In this study we examined the effect of IL-1, IL-6, IL-8, TNF-alpha and TGF-beta on the growth of melanoma in vivo and in vitro, using the murine B16 melanoma and its syngeneic host, the C57BL/6 mouse. Mice were injected with 0.1-1.5 micrograms of recombinant cytokine subcutaneously every other day following a subcutaneous injection of 1 x 10(5) B16 cells (F-10 clone). In this model, tumours appeared within 12-14 days, and IL-1 and IL-6 stimulated tumour growth in vivo. TNF-alpha, TGF-beta, IL-2 and IL-8 had no significant effect. In contrast to the in vivo effects, TNF-alpha inhibited B16 cell growth in vitro and IL-6 stimulated B16 cell growth. The in vivo IL-1 effect on tumour growth in mice was examined in greater detail. IL-1-treated animals showed tumours approximately 5-fold greater in size than those of the control animals. The IL-1-treated animals also showed highly vascularized tumours that invaded underlying muscle tissue more rapidly than controls. These tumors also showed a strong positive reaction with antibody to intercellular adhesion molecule-1.(ABSTRACT TRUNCATED AT 250 WORDS)

8043387

Pattern analysis of photopatch test reactions.

In a multicenter study, photopatch test results from more than 1500 patients were evaluated between 1985 and 1990 and from 614 patients between 1990 and 1992. Photopatch testing was conducted according to a standardized procedure. Nearly half of the photoreactions were unclassifiable according to the classic definitions of photoallergic or phototoxic reactions. To facilitate the interpretation of these remaining photopatch test reactions, we developed a computerized substance specific reaction pattern analysis. By sequential readings from immediately after irradiation up to 72 h later and by morphological qualification of the reactions, the time course and morphological changes of each individual reaction were monitored. The summation of each individual photoreaction resulted in an overall reaction pattern of a specific substance. Four main categories could be distinguished. The first category was characterized by a peak immediately after irradiation followed by a descrescendo reaction. The second category comprized reactions combining an immediate with a delayed reaction. The third category exhibited a plateau-like delayed reaction. The fourth category showed delayed reactions in a crescendo pattern. Whereas category 1 represents classic phototoxic and category 4 classic photoallergic reaction patterns, the underlying mechanisms of categories 2 and 3 remain to be investigated. Typical substances of category 1 were many of the tested systemic drugs, such as furosemide, most of which are well-known phototoxic agents. Disinfectants, nonsteroidal anti-inflammatory agents and phenothiazines showed the reaction patterns of categories 2 and 3. A delayed type reaction (category 4) could be demonstrated for well-known photoallergens such as fenticlor, musk ambrette, and ultraviolet adsorbents in sunscreens.(ABSTRACT TRUNCATED AT 250 WORDS)

8043386

Detection of photoreactivity demonstrated in a modified local lymph node assay in mice.

Photoallergic and phototoxic reactions are an increasing problem in dermatologic practice. Currently available test models are heterogeneous and do not allow differentiation between photoallergic and phototoxic reactions. We have modified the local lymph node assay to screen for photoreactive compounds. We found an ultraviolet A (UVA) irradiation-dependent increase in the weights and cell counts of the auricular lymph nodes after application of 8-methoxypsoralen, tribromosalicylanilide, trichlorosalicylanilide, chlorpromazine and promethazine. In contrast to these photoreactive compounds, contact sensitizers did not produce any reaction to UVA irradiation in the local lymph node assay. This assay system has the advantage of being less expensive and less time-consuming and might even be able to differentiate between phototoxic, photoallergic and contact allergic reactions.

8043385

A quantitative study of the melanogenic effect of multiple suberythemal doses of different ultraviolet radiation sources.

The melanogenic potential of multiple suberythemogenic doses of 6 different ultraviolet (UV) sources was investigated. The UV sources emitted different amounts of UVA and UVB. The backs of 12 volunteers were exposed to the 6 UV sources 10 times during 4 weeks. Every volunteer was exposed to the same suberythemogenic dose (0.75 basic minimal erythema dose) of each of the UV sources. The changes in pigmentation and minimal erythema dose of the UV exposed test sites were registered during the 10 sessions. Three UVA sources with a low emission in the UVB area (0.2-3.1%) had a high melanogenic potential. Two UVB sources (UVB emission 74.3% and 94.5%) were unable to induce a significant increase in skin pigmentation. The 3 UVA sources with a low UVB output increased skin pigmentation significantly better than a UVA source with a UVB output of 6.9%. All 6 lamps were able to increase photoprotection significantly. The increase in photoprotection was not significantly different between any of the 6 UV sources. This study shows that, if humans are exposed to equally suberythemogenic doses of different types of UV radiation, then radiation obtained from UVA sources greatly enhances melanogenesis, whereas UVB radiation sources are unable to induce pigmentation.

8043384

Aging of the skin connective tissue: how to measure the biochemical and mechanical properties of aging dermis.

The connective tissue of the skin is composed mostly of collagen and elastin. Collagen makes up 70-80% of the dry weight of the skin and gives the dermis its mechanical and structural integrity. Elastin is a minor component of the dermis, but it has an important function in providing the elasticity of the skin. During aging, the synthesis of collagen gradually declines, and the skin thus becomes thinner in protected skin, especially after the seventh decade. Several factors contribute to the aging of the skin. In several hereditary disorders collagen or elastin are deficient, leading to accelerated aging. In cutis laxa, for example, elastin fibers are deficient or completely lacking, leading to sagging of the skin. Solar irradiation causes skin to look prematurely aged. Especially ultraviolet radiation induces an accumulation of abnormal elastotic material. These changes are usually observed after 60 years of age, but excessive exposure to the sun may cause severe photoaging as early as the second decade of life. The different biochemical and mechanical parameters of the dermis can be studied by modern techniques. The applications of these techniques to study the aging of dermal connective tissue are described in detail.

8043375

Preparing nurses for preceptorship.

The introduction of Project 2000 diploma-level courses in Scotland raised many questions about how a smooth preparation and transition could be effected. One of the main difficulties related to how the new students' supernumerary status would affect their learning experiences in clinical areas, and how practitioners could be helped to make the students' experiences valuable in educational terms. This article describes how one Scottish college decided to employ preceptorship as the framework for clinical supervision, and how it prepared practitioners for their new responsibilities.

8043374

Infection control. Communicating about infection control.

Our ten-part infection control series concludes with a look at a skill fundamental to nurses everywhere--communication. Just how well do nurses communicate with patients, professionals and other nurses about infection control issues?

8043373

Teaching cards for respiratory nurses.

The provision of information to patients with chronic respiratory problems is arguably one of the most important aspects of care. Mindful of the paucity of relevant information on this for respiratory nurses, the authors set out to compile teaching cards which would act as guidelines for nursing interventions with respiratory patients. The cards, the authors claim, are useful for nurses working in hospitals or patients' homes.

8043365

Carotid endarterectomy without arteriography.

Arteriography has been considered the "gold standard" for evaluation of the cerebrovascular circulation prior to carotid endarterectomy. However, arteriography is associated with a neurologic complication rate of up to 12% in certain high-risk groups. Previous studies have shown that the duplex scanner has greater sensitivity than arteriography when both are correlated to the surgical specimen. From January 1986 to December 1991 a total of 174 carotid endarterectomies were performed in 152 patients, of which 61% were symptomatic. A total of 110 carotid endarterectomies in 92 patients were performed without the use of arteriography. Of the 64 patients in whom arteriograms were obtained, 33 were made at consultation and the others for various indications. Operative findings confirmed the duplex scan findings in all cases. A total of 91% of patients had intraoperative completion arteriograms. Of the 55 patients who also had intracranial views taken, two had a 50% siphon stenosis and one patient had a small intracranial aneurysm. None of these findings would have changed our management. The overall neurologic complication rate was one (0.66%) death due to stroke and four (2.6%) patients with transient ischemic attacks. Carotid endarterectomy can be safely performed without preoperative arteriography based on a detailed history and physical examination that includes bilateral upper extremity blood pressures and a duplex scan performed by a validated laboratory.

8043364

A rare complication in elective repair of an abdominal aortic aneurysm: multiple transmural colonic infarcts secondary to atheroemboli.

Numerous complications may occur during elective and emergency repair of abdominal aortic aneurysms. The following report will document a rare complication in a patient with chronic renal failure. Multiple atheroemboli were found to produce transmural infarction of the left colon after elective repair of an abdominal aortic aneurysm. The pathologic process and the proposed mechanism of injury are also discussed.

8043363

Innovations in vascular imaging: arteriography, three-dimensional CT scans, and two- and three-dimensional intravascular ultrasound evaluation of an abdominal aortic aneurysm.

This report compares the information obtained from arteriography, CT scans, and intravascular ultrasound evaluation of an abdominal aortic aneurysm. The two- and three-dimensional imaging techniques described in this report add information that is redefining the pre- and intraoperative analysis of arterial lesions. The new data may have an influence on the evolution of diagnostic methods and future interventional therapy for vascular disease. This case highlights the developing potential of the methods.

8043362

Aneurysm of the gastroduodenal artery associated with stenosis of the superior mesenteric artery.

A 68-year-old patient was hospitalized after the incidental discovery of an aneurysm of the gastroduodenal artery associated with stenosis of the superior mesenteric artery. This patient had severe heart failure, which led to acute pulmonary edema and inoperable triple-vessel coronary disease. In the first of two procedures the superior mesenteric artery was dilated; 48 hours later the gastroduodenal artery aneurysm was embolized with minicoils and acryl glue. Immediate and follow-up arteriograms at 10 months showed that results were satisfactory. Transluminal treatment of both lesions is an alternative to surgical treatment, especially in high-risk patients.

8043361

Analysis and comparison of pressure gradients and ratios for predicting iliac stenosis.

Over the past 35 years five different pressure variables and their numeric criteria have been recommended to determine the hemodynamic significance of iliac artery stenosis. To analyze and compare the five variables, systolic and mean radial and femoral artery pressures were measured intraoperatively in 144 legs at rest and in 119 (83%) of these during hyperemic flow augmentation with papaverine. Iliac artery diameter stenosis measured from preoperative two-view arteriograms was 48 +/- 37% (mean +/- 1 SD). Resting systolic and resting mean pressure gradients (radial minus femoral artery pressure), hyperemic mean pressure gradients, hyperemic systolic pressure ratios (femoral/radial), and the percentage change from rest to hyperemia of the systolic pressure ratios were measured. For completeness a sixth variable, the hyperemic systolic pressure gradient, was also measured. High-grade (75%) stenosis is predicted with 95% confidence by resting pressure gradients > or = 52 mm Hg systolic and > or = 16 mm Hg mean and resting systolic pressure ratios < or = 0.61. Hyperemia is unnecessary and not useful for predicting > 50% stenosis. The rest-to-hyperemia percentage changes in systolic pressure ratios give poor results. Moderate (50%) stenosis is predicted with 95% confidence by resting pressure gradients > or = 34 mm Hg systolic and > or = 7 mm Hg mean, hyperemic mean pressure gradients > or = 30 mm Hg, and systolic pressure ratios < or = 0.73. Most published criteria have low accuracy, low predictive value, and a low optimal percentage of stenosis range. Simple pressure gradients give optimal results.

8043360

Peripheral vascular involvement in heart transplant patients.

Between 1984 and 1991 a total of 200 patients underwent heart transplantation in our unit. The records of 121 patients who were followed up for more than 1 year were reviewed for peripheral vascular abnormalities, which were found in 12 (9.9%). Most of these patients underwent transplantation for ischemic heart disease, and peripheral vascular disease preceded the heart transplantation in 80%. Although surgical risks are low in this setting, particular caution should be exercised to prevent septic complications in the femoral triangle. Among the risk factors studied, only elevated blood cholesterol was frequently found in the vascular patients before or after transplantation. Peripheral vascular involvement in heart transplant patients corresponds to the natural course of atheroma rather than to an accelerated process of atherosclerosis.

8043359

An institutional experience with arterial atheroembolism.

Seemingly minor blue-toe lesions resulting from atheroemboli are associated with unstable atherosclerotic plaques, which are at risk for causing recurrent emboli, tissue loss, and potentially death. At Washington University Medical Center, 62 patients (31 males and 31 females), ranging in age from 38 to 89 years (mean 62.8 +/- 11.7 years), were treated for cutaneous manifestations of atheroembolic disease. Most patients (62%) had spontaneous bouts of atheroembolism, but 13 (21%) had recently undergone an inciting invasive radiologic study, 10 (16%) were on anticoagulation therapy, and one (2%) experienced abdominal trauma. In addition to the cutaneous manifestations, 18 patients (29%) also developed coincidental deterioration in renal function and four (6%) had intestinal infarction from atheroemboli. Arteriography in nearly all patients (97%) implicated the aorta and iliac arteries most commonly (80%), with the femoral (13%), popliteal (3%), and subclavian (3%) arteries less frequently incriminated. Forty-two patients underwent bypass grafting procedures (36 anatomic and six extra-anatomic) after exclusion of the native diseased artery, 20 patients had endarterectomies (six with additional bypass grafts), and five patients had no corrective vascular procedures. The 30-day operative mortality rate was 5% in this series. Nineteen patients (31%) required minor amputations, whereas two required major leg amputations. Thus limb salvage was possible in 86 of 88 (98%) limbs. No further episodes of atheroembolism occurred in the involved limbs during follow-up (1 to 53 months, mean 20.2 months). We advocate urgent arteriography and surgical correction or bypass with exclusion of the offending lesion.(ABSTRACT TRUNCATED AT 250 WORDS)

8043358

Plantar or dorsalis pedis artery bypass in Buerger's disease.

The peripheral type of Buerger's disease is unresponsive to conservative therapy when accompanied by multisegmental occlusion at the level of the ankle. Between November 1983 and April 1993, we performed 15 bypasses below the ankle for this type of thromboangiitis obliterans in 13 patients (mean age 45.7 years), including four females. Ten patients had intractable toe ulcers with severe pain, and five had foot-threatening ischemia or disabling foot claudication. Eleven patients were heavy smokers, two were passive smokers, and six had a history of sympathectomy. All patients had occlusion of the three main crural arteries or both of the tibial arteries at the ankle. Of the 15 bypasses, 10 were to the medial or lateral plantar arteries, two were to the common plantar artery, and three were to the dorsalis pedis artery. There were three early and three late graft failures. The causes of early graft failure were thrombosis at the site of cross-clamping, anastomosis to a diseased segment, and arterial spasm. The three late failures (> 3 months) were due to disease progression in patients who continued to smoke, whereas all grafts remained patent and functioned well in patients who stopped smoking. Because patients with thromboangiitis obliterans are relatively young and active, early healing of ulcers and restoration of normal limb function are important objectives in their treatment. Bypass to the foot arteries can provide an excellent outcome, although special techniques and postoperative cessation of smoking are essential for success.

8043357

In vitro antistaphylococcal activity of collagen-sealed Dacron vascular prostheses bonded with rifampin, vancomycin, or amikacin.

The goals of this study were to evaluate the in vitro antistaphylococcal activity of vascular Dacron prostheses to which a type I collagen and an antibiotic had been bonded. Collagen was fixed to the prosthesis either by an original grafting procedure or by impregnation. The antibiotics used included rifampin, vancomycin, and amikacin. They were bonded to the prosthesis either at the same time as the collagen or by soaking the prosthesis in an antibiotic solution at the beginning of the experiment. Each prosthesis was sliced into 6 mm diameter circles and preserved in a solution of saline and albumin, which was changed every day. Three disks were retrieved from each prosthesis at the beginning of the experiment and then every 24 hours; these were placed in gelose smeared with Staphylococcus aureus. The diameter of the inhibition area of each disk was measured at 24 hours. The initial inhibition area (So), the time at which the inhibition area was equal to 50% of So, and the time at which the activity was nil were used to characterize the activity of the prostheses and to calculate a beta coefficient of decreasing activity. The prostheses bonded with vancomycin or amikacin did not show adequate activity. Those bonded with rifampin were effective for at least 4 days. When rifampin was grafted to the prosthesis, the So was 278.6 mm2, 50% of So was reached within 10.4 days, the duration of effective activity was 25.7 days, and the beta coefficient was 0.067. The two prostheses soaked in rifampin had a significantly more rapid decrease (beta = 0.19 and 0.56) and a shorter duration of effective activity (12.4 and 4.5 days). Both collagen-coated prostheses, whether impregnated or soaked with rifampin, have a sufficient duration of activity to be tested in an animal model.

8043356

Dilation of woven and knitted aortic prosthetic grafts: CT scan evaluation.

Because there are few reports in the literature concerning short- and medium-term outcome of woven and knitted aortic prosthetic grafts, we conducted CT evaluations in 58 asymptomatic patients (53 males and five females with a mean age of 63.5 years) undergoing infrarenal aortic reconstruction between June 1988 and June 1991. Joined CT slices after contrast enhancement, centered on the proximal anastomoses, prosthetic bodies, and prosthetic limbs, were obtained in the early (mean 19 days) and late (mean 19 months, range 6 to 40 months) postoperative periods. In end-to-side aortoprosthetic anastomoses (n = 28), early and late CT examinations revealed that the anteroposterior diameter increased 1.9% (p = NS) and 8.8% (p < 0.0001) for woven and knitted grafts, respectively. In end-to-end aortoprosthetic anastomoses, the diameter of the prosthetic body on early CT scans increased 12.6% (p < 0.0001) and 28% (p < 0.0001) for woven and knitted prosthetic grafts, respectively, as compared with diameter values provided by the manufacturer. Dilation continued to progress 2.2% (p < 0.04) for woven and 6.2% (p < 0.0002) for knitted prosthetic grafts on late CT scans. The mean diameter of the prosthetic graft limbs (n = 96) increased 22.3% (p < 0.0001) and 34.6% (p < 0.0001) for woven and knitted prosthetic grafts, respectively, on early CT scans as compared with manufacturers' values. Secondary increases were 3.2% (p < 0.002) and 7.7% (p < 0.007) for woven and knitted prosthetic grafts, respectively. These data show that dilation of aortic prostheses occurs early in most cases, most likely soon after declamping of the graft, as shown by recent intraoperative measurements.(ABSTRACT TRUNCATED AT 250 WORDS)

8043355

Late complications after aortic surgery.

The incidence of false aneurysms, anastomotic stenoses, and ureteric obstruction is reported to be low in patients who have undergone aortic surgery. The use of intravenous peripheral digital subtraction angiography (IVDSA) with completion excretory urography (CEU) may provide a more sensitive means of long-term detection of these complications. The aim of this study was to (1) establish the incidence of anastomotic aneurysms, anastomotic stenoses, and ureteric obstruction after aortic surgery; (2) identify local and systemic factors that predispose to these complications; and (3) evaluate IVDSA as a single radiologic investigation to diagnose these complications. Forty-four patients who had undergone aortic surgery 1 to 12.3 years previously agreed to undergo IVDSA and CEU. False aneurysms were found at 10 distal anastomoses (none at the aorta), for an anastomotic incidence of 11.2% and a patient incidence of 15.9%. Endarterectomy and the femoral artery as a site of distal anastomosis were important factors in the development of anastomotic aneurysms, as were detected radiologically at eight aortic anastomosis (18%). There were no distal anastomotic stenoses. Hypercholesterolemia was more common in this group (62.5%) than in the overall group (21.2%). Three asymptomatic ureteric obstructions were diagnosed in two patients, both of whom had emergency surgery for ruptured aortic aneurysms. The higher incidence of anastomotic aneurysms, anastomotic stenoses, and asymptomatic ureteric obstruction sound merits careful follow-up. IVDSA with CEU may be a simple and effective method of detection.

8043354

Carotid endarterectomy without arteriography: the preeminent role of the vascular laboratory.

The classic workup of patients considered for carotid endarterectomy (CE) has included contrast arteriography to delineate the nature and extent of the arterial pathology. Noninvasive testing (NIT) consisting of duplex scanning plus sound spectrum analysis is an alternative method for accurately evaluating the carotid bifurcation. The accuracy of our laboratory in comparing NIT to contrast arteriography has been established by use of the guidelines suggested by the Intersocietal Commission for the Accreditation of Vascular Laboratories. Forty-two patients underwent CE based on NIT alone. Seventeen had hemispheric transient ischemic attacks or minor strokes, six had amaurosis fugax, three had nonspecific symptoms, and 16 were asymptomatic. NIT identified a severe stenosis that was limited to the carotid bifurcation; the internal carotid artery distal to the bulb was normal. The predicted stenotic atherosclerotic lesion was confirmed at operation in all patients. One patient had a high bifurcation that required an extension of the original incision. Of three undiagnosed kinked distal internal carotid arteries found at operation, only one required surgical correction. No transient ischemic attacks, strokes, or deaths occurred postoperatively. CE can be performed in selected patients based on NIT alone, obviating the mortality, morbidity, and cost of arteriography. This algorithm demands that the NIT is unequivocal and the accuracy of the testing laboratory is established and maintained according to published standards.

8043353

Resistance of Listeria monocytogenes to the bacteriocin nisin.

Listeria monocytogenes NCTC 5105 and F6861 were evaluated for sensitivity to nisin. The results confirmed those previously published indicating marked differences in the sensitivity of the two strains. Mutants with increased resistance to nisin could be isolated from the less sensitive F6861 strain at a frequency of 10(-6) to 10(-7). Using a nisin specific enzyme-linked immunosorbent assay, the adsorption of nisin to the different strains and the resistant mutant were studied. At a range of nisin concentrations the amount adsorbed was found to reflect the sensitivity of the strain to nisin, with the more sensitive cells showing greater adsorption. In resistant cells, K+ efflux increased at a slower rate with increasing nisin concentration and had a lower maximum rate indicating that the mechanism of resistance involves a reduction in the accessibility or presence of suitable adsorption sites.

8043352

Fermentation and sensory characteristics of kimchi containing potassium chloride as a partial replacement for sodium chloride.

A study was designed to determine the effects of substituting up to 50% of the NaCl in kimchi, a fermented Chinese cabbage (Brassica pekinensis) product containing scallions, garlic, ginger and hot red pepper powder, with KCl. Brine water (15% salt) used to soak cabbage contained NaCl:KCl ratios of 1:0 (control), 5:1, 2:1 and 1:1 (wt:wt). Total acidity and pH of kimchi reached acceptable ranges of 0.4-0.6% (as lactic acid) and 4.4-4.7, respectively, after 13 days of incubation at 13 +/- 1 degree C. Kimchi made using brine water containing 5:1 and 2:1 (NaCl:KCl) salt ratios was characterized by faster growth of lactic acid bacteria and total aerobic microorganisms compared to the control formulation. Sensory qualities (saltiness, bitterness, sourness, hotness and texture) of kimchi prepared from cabbage soaked in brine containing NaCl and KCl at all test ratios were judged to be acceptable.

8043351

The occurrence and seasonal changes in the isolation of Listeria spp. in shop bought food stuffs, human faeces, sewage and soil from urban sources.

Eight hundred and twenty-two shop-bought food specimens, 136 soil and 692 faecal specimens were cultured for Listeria spp. in a regular, year round survey. 19.7% (162/822) of the foods, 93.9% (108/115) of the sewage, 14.7% (20/136) soils and 1% (7/692) of faeces yielded Listeria spp. with 10.5% foods, 60.0% sewage, 0.7% soils and 0.6% faeces containing L. monocytogenes. No seasonal variation was noted in isolates from either sewage or foods, with L. monocytogenes and L. innocua being the commonest species in both L. ivanovii when isolated from foods was strongly associated with mutton. Poultry was most likely to contain L. monocytogenes (65.6%, 21/32) and in the greatest numbers. A high percentage of beef (34.6%, 9/26), lamb (40%, 8/20), pork (28.1%, 9/32) and sausages (34.7%, 8/23) also contained L. monocytogenes. L. monocytogenes was rarely isolated from paté (1/40) or soft cheeses (1/251), both of which have been involved with foodborne listeriosis outbreak in the UK. Listeria spp. were commonest in faeces and soils in July to September but the predominant species isolated were different with L. monocytogenes and L. innocua the commonest from faeces and L. ivanovii and L. seeligeri the most common from soil.

8043350

Population dynamics of natural Saccharomyces strains during wine fermentation.

Using mitochondrial DNA restriction endonuclease analysis, the dynamics of the natural Saccharomyces cerevisiae strains present in spontaneous wine fermentations have been studied. We observed a sequential substitution of Sacch. cerevisiae strains along fermentation agreeing with different fermentation phases. When the restriction pattern's similarity (measured as the fraction of shared restriction fragments) was high, a clear sequential substitution of the strains was seen. However, when the similarity was low, although a sequential substitution could be also observed between secondary strains, a clearly predominant strain was present along the whole fermentation process.

8043349

Response of spheroplasts and chelator-permeabilized cells of gram-negative bacteria to the action of the bacteriocins pediocin SJ-1 and nisin.

We have attempted to bypass the outer membrane (OM) barrier of Escherichia coli and Salmonella typhimurium with pediocin SJ-1 (as compared with nisin) using chelating agents as OM permeabilizers. EDTA, and to less extent EGTA, enabled nisin, but not pediocin SJ-1, to permeate the cell OM of E. coli, to have access to the cytoplasmic membrane and to cause subsequent permeability changes, indicated by an increase in ANS fluorescence intensity and a shift of its emission maximum. Such spectral changes did not occur when, prior to addition, EDTA was saturated with Ca2+ and Mg2+. ANS fluorescence data indicated that, in spite of the fact that pediocin SJ-1 did traverse the EDTA-permeabilized OM of E. coli, it did not cause perturbation of its cytoplasmic membrane and was, therefore, unable to cause cell death. Spheroplasts prepared from E. coli were lysed when treated with nisin but not with pediocin SJ-1. We suggest that the resistance of Gram-negative bacteria to pediocin SJ-1 is due not only to this material's inability to permeate the OM but also (in contrast to nisin) to its inability to interact with the cytoplasmic membrane.

8043348

Changes in fatty acid composition of various lipid components of Zygosaccharomyces rouxii as influenced by solutes, potassium sorbate and incubation temperature.

The effects of water activity (aw), solutes, potassium sorbate and incubation temperature on the fatty acid methyl ester composition of the total extracted lipid, triacylglycerol, phospholipid, free fatty acid and steryl ester components of Zygosaccharomyces rouxii were determined. Oleic (C18:1) and linoleic (C18:2) acids were the major components of the total fatty acid fraction, regardless of culturing conditions. Cells grown at 35 degrees C contained a significantly higher percentage of C18:1 and a lower percentage of C18:2 than did cells grown at 21 degrees C. At both temperatures, cells cultured in low-aw (0.93) media contained a significantly higher percentage of C18:1, with a corresponding decrease in C18:2 content than did cells grown at aw 0.99, regardless of the addition of glucose, sucrose, or NaCl to suppress the aw. At 21 degrees C, cells cultured in high-aw (0.99) media supplemented with 300 micrograms sorbate per ml contained higher percentages of C18:1 than did cells cultured in media not supplemented with sorbate. Cells grown at 35 degrees C in low-aw media supplemented with sorbate contained substantially more C18:1 than did cells cultured without sorbate.

8043347

Seasonal occurrence of psychrotrophic Bacillus species in raw milk, and studies on the interactions with mesophilic Bacillus sp.

Mesophilic and psychrotrophic isolates of Bacillus species displayed seasonal incidences in raw and pasteurised milk. The incidence of mesophilic isolates was highest in the winter and lowest in the summer/autumn while pschrotroph incidence was conversely lowest in the winter and highest in the late summer/autumn. Spores of Bacillus sp. were isolated from raw milk taken from farm milk machines and bulk tanks, milk tankers, diary silos and pasteurised milk. A consistent seasonal fluctuation in incidence throughout these samples suggested that spores of Bacillus sp. derived from the farm environment survived as important contaminants right through the milk chain to the pasteurised product. Up to seven mesophilic Bacillus sp. were isolated from a single sample with three species commonly occurring in most samples. The predominant mesophilic species isolated were B. pumilus, B. licheniformis and B. subtilis. The dominant psychrotrophic isolate was B. cereus. Selected mesophilic isolates were examined for possible antagonistic effects on the growth of psychrotropic B. cereus and B. pumilus isolates. Bacillus subtilis and B. licheniformis were found to produce antagonistic factors. It was considered that these factors may influence the incidence and growth of psychrotrophic isolates in the farm environment or in milk but the factors are not yet fully characterised or identified.

8043345

Incidence and prognosis of obstruction of the left ventricular outflow tract in Liverpool (1960-91): a study of 313 patients.

To determine the incidence of the various types of obstruction of the left ventricular outflow tract in patients born in the five health districts of Liverpool and to compare their prognosis into early adult life. Notes of all patients with obstruction of the left ventricular outflow tract born in the study area between 1960 and 1991 were reviewed. Patients with hypoplastic left ventricle, mitral valve atresia, and those with discordant atrioventricular or ventriculoarterial connections were excluded. Survivors were traced and assessed clinically; eight were lost to follow up. Obstruction of the left ventricular outflow tract occurred in 313 patients (67% male), giving an incidence of 6.1/10,000 live births. The median (range) age at presentation was 13.9 months (0-20 yr). Aortic valve stenosis occurred in 71.2%: subvalve in 13.7%, supravalve in 7.7%, and multilevel in 7.4%. The median (range) duration of follow up was 10.0 (1-29) yr. Aortic regurgitation at presentation occurred more often (p < 0.001) in patients with subvalve stenosis than in those with other types of obstruction, but there was an increased incidence (p < 0.001) at follow up in patients with valve stenosis. Ninety eight patients (31.3%) underwent operation. The reoperation rate was 27% for valve stenosis and 9% for subvalve obstruction. No patients with supravalve stenosis underwent reoperation. The median duration from first operation to aortic valve replacement (17 patients) was 12.3 years. Hazard analysis confirmed that the risk of death was higher in patients presenting at a younger age, with more severe stenosis, and those with subaortic, multilevel obstruction or a syndrome. Hazard analysis also showed that the risk of a clinical event (surgery, balloon dilatation, or endocarditis) was greater in patients who presented at a younger age, with more severe stenosis or aortic regurgitation, and in those with subvalve or multilevel obstruction. Aortic valve stenosis was the most common type of obstruction. Hazard analysis indicates that the age and severity of obstruction at presentation have a significant effect on survival and freedom from a clinical event. The risk of premature death in patients presenting with moderately severe valve stenosis is reasonably small, but increases considerably in those with subvalve, supravalve, and multilevel obstruction. Patients who present with mild valve stenosis have a good prognosis. The risk of sudden death is less than previous predictions. Patients with subvalve and multilevel obstruction, even when mild at presentation, are more likely to undergo intervention or develop endocarditis than those with valve or supravalve stenosis. Follow up into adult life is essential.

8043346

Increase in plasma beta endorphins precedes vasodepressor syncope.

Endogenous opioids have a tonic inhibitory effect on sympathetic tone and have been implicated in the pathophysiology of vasodepressor syncope. Plasma beta endorphin concentrations increase after vasodepressor syncope induced by exercise or by fasting. To take frequent samples for plasma beta endorphin estimation during tilt testing, and to determine whether plasma beta endorphin increased before the start of syncope. 24 patients undergoing tilt testing for investigation of unexplained syncope. Tertiary referral centre. Blood samples were obtained during 70 degrees head up tilt testing. Plasma beta endorphin concentrations were estimated by radioimmunoassay (mean(SD) pmol/l). Patients with a positive test showed a rise in beta endorphin concentrations before syncope (baseline 4.4(1.5) v start of syncope 8.5(3.1), p < 0.002). In contrast, patients with a negative test showed no change in beta endorphin concentrations (baseline 3.4(1.0) v end of test 4.5(2.3), NS). After syncope all patients showed a large secondary increase in beta endorphins (32.3(18.6)). An increase in plasma beta endorphins precedes vasodepressor syncope. This finding supports a pathophysiological role for endogenous opioids.

8043344

Evidence of inadequate investigation and treatment of patients with heart failure.

To determine the referral rates to hospital and level of investigation of patients with heart failure, and to assess whether they are receiving optimum management. A retrospective survey. Nottingham Health District. 505 patients receiving loop diuretic treatment prescribed by their general practitioner. Referral to hospital as an inpatient or outpatient for assessment of assumed cardiac failure; investigations--electrocardiography, chest radiography, and echocardiography; treatment with angiotensin converting enzyme inhibitors. Only 56% of patients prescribed loop diuretics fulfilled the diagnostic criteria for heart failure. Of these, 74% had been referred to hospital, of whom 80% had had an electrocardiograph, 75% a chest radiograph, but only 31% an echocardiogram. Only 17% of patients with heart failure were being treated with angiotensin converting enzyme inhibitors in conjunction with loop diuretics. Patients with heart failure in the Nottingham Health District are not being adequately investigated or receiving the optimum treatment.

8043343

Complete atrioventricular septal defect with tetralogy of Fallot: diagnosis and management.

To report recent experience of patients with complete atrioventricular septal defect and tetralogy of Fallot, with emphasis on anatomical features, diagnosis, and management. Case notes were reviewed and patients were assessed at follow up by clinical examination and cross sectional and Doppler echocardiography. Tertiary cardiothoracic referral centre. Between 1987 and 1992 13 patients with atrioventricular septal defect and tetralogy of Fallot (12 with concordant and one with double outlet ventriculoarterial connections) underwent surgery; 10 underwent complete intracardiac repair. 11 patients had Down's syndrome. The complete diagnosis was established preoperatively by cross sectional echocardiography in all but one patient. A tri-leaflet left atrioventricular valve as seen in parasternal short axis views was the diagnostic feature of atrioventricular septal defect, with tetralogy of Fallot diagnosed from the presence of anterocephalad deviation of the outlet septum producing subvalvar pulmonary stenosis as seen in subcostal right anterior oblique views. Total correction consisted of closure of the atrioventricular septal defect by a combined right atrial and ventricular approach, reconstruction of the atrioventricular valves, and relief of the obstruction within the right ventricular outflow tract. Separate patches were used to close the atrial and ventricular septal defects. Modified Blalock-Taussig shunts were performed in three patients, who await intracardiac repair. Surgical correction was carried out at mean (range) age of 5 (2 to 15) years. Diagnostic methods, surgical results, and functional state after complete correction. The presence of an atrioventricular septal defect was missed preoperatively in one patient with tetralogy of Fallot. The characteristic goose neck deformity on the left ventriculogram was not present and the tri-leaflet nature of the left atrioventricular valve was not sought on echocardiography. Of the 10 patients who underwent complete repair, nine are alive and one died 34 days after operation with adult respiratory distress syndrome. Examination at necropsy showed an excellent surgical correction. Mean (range) follow up was 23 (8 to 48) months. All nine patients are alive and well (New York Heart Association Class 1). Accurate diagnosis and staged management with improved surgical techniques have lowered mortality of this complex combination of cardiac defects. The current policy of this group is to recommend a systemic to pulmonary arterial shunt procedure for symptomatic children younger than 2 years and total correction in older children.

8043342

Intravascular ultrasound imaging of angiographically normal coronary arteries: a prospective study in vivo.

Intravascular ultrasound imaging (IVUS) was performed to elucidate the discrepancy between clinical history and angiographic findings and to measure the diameter and area of the lumen of the normal left coronary artery in 55 patients who presented with chest pain but had normal coronary angiograms. The left coronary artery (LCA) was scanned with a 4.8F, 20 MHz mechanically rotated ultrasound catheter at 413 sites. Atherosclerotic lesions were identified at 72 (17%) sites in 25 patients. The mean (SD) (range) plaque area was 5.55 (3.56) mm2 (2-26 mm2) and it occupied 28.8 (9.6)% (13-70%) of the coronary cross sectional area. Calcification was detected at 24 (33%) atherosclerotic sites in nine patients. The correlation coefficients for the lumen dimensions measured at normal sites by IVUS and by angiography were r = 0.93 (SEE = 0.43) mm for lumen diameter and r = 0.89 (SEE = 4.27) mm2 for lumen area (both p < 0.001). 16 of the 30 patients in whom no atherosclerotic plaques were detected in the LCA lumen by IVUS had no risk factors of coronary artery disease. The cross sectional area of 90 consecutive images of left main coronary artery (LMCA), proximal left anterior descending coronary artery (proximal LAD), and mid LAD was measured in these 16 subjects. The mean (SEM) areas at end diastole were LMCA 17.33 (7.98) mm2; proximal LAD 13.56 (5.85) mm2; mid LAD 9.75 (4.67) mm2. During the cardiac cycle the cross sectional area changed by 10.2 (4.0)% in the LMCA, by 8.3 (4.7)% in the proximal LAD, and by 9.8 (4.0)% in the mid LAD. In 11 patients with plagues the change in cross sectional area in plague segments (5.8(3.1)%) was significantly lower than in the segments from patients without plagues (p < 0.001). Lumen area reached a maximum in early diastole rather than in late diastole. IVUS can imagine atherosclerotic lesions that are angiographically silent; it also provides detailed information about plague characteristics. The variation in coronary cross sectional area during the cardiac cycle should not be ignored during quantitative analysis. Maximum dimensions in normal segments are reached in early diastole. Further studies are needed to clarify the clinical significance of atherosclerosis detected by IVUS in patients presenting with chest pain but normal coronary angiography.

8043341

Haemodynamic deterioration after treatment with adenosine.

A 26 year old woman presented with a narrow complex tachycardia with a rate of 210 beats/min. Adenosine converted this to atrial fibrillation with a rate of 280 beats/min with associated haemodynamic deterioration that needed electrical cardioversion.

8043340

False aneurysm of the right ventricular outflow tract after total correction of tetralogy of Fallot: diagnosis by echocardiography and successful repair by neck cannulation for cardiopulmonary bypass.

A case of false aneurysm related to the left side of the heart with a connection to the right ventricular outflow tract was found by echocardiography after complete repair of tetralogy of Fallot. Cardiopulmonary bypass was established by cannulating the right internal jugular vein and the ipsilateral common carotid artery. The aneurysm was then excised and the right ventricular outflow tract reconstructed by direct sutures.

8043339

Noonan's cardiomyopathy: a non-hypertrophic variant.

To describe the association of the Noonan's phenotype and a primary, familial non-hypertrophic cardiomyopathy with restrictive pathophysiology. Observational study. Tertiary cardiac referral centre. Affected family members. Two generations of a single family were examined and a description of the clinical characteristics and electrocardiographic, echocardiographic, and haemodynamic data of those affected is given. Three family members have classic Noonan's phenotype and all have a non-dilated, non-hypertrophic cardiomyopathy. Inheritance is autosomal dominant but with variable penetrance. The electrocardiograms show increased left ventricular voltages in two patients. On echocardiography left ventricular wall and internal end diastolic dimensions are normal, and there is considerable bilateral atrial enlargement. Systolic function is moderately impaired in one patient and mildly impaired in another. Doppler echocardiography showed restrictive pathophysiology as an early end of left ventricular filling and considerable reversal of flow in the superior vena cava during atrial systole. Hypertrophic cardiomyopathy is well described in Noonan's syndrome. This is the first report of a non-hypertrophic cardiomyopathy with echocardiographic and haemodynamic features of restrictive pathophysiology.

8043337

Exercise induced vasodepressor syncope.

Five cases of exercise induced pure vasodepressor syncope in patients without significant structural heart disease are reported. Hypotension and symptoms of syncope or pre-syncope were induced by treadmill exercise testing and in each case limited exercise performance. Evidence of inappropriate peripheral vasodilation, probably as a consequence of ventricular mechanoreceptor stimulation, was shown in all five patients. Head up tilt testing resulted in hypotension in four patients and isoprenaline infusion in the supine position resulted in hypotension in the fifth. These patients had a new condition of exercise induced neurally mediated (vasodepressor) syncope without appreciable structural cardiac abnormalities.

8043338

Balloon dilatation of the aortic valve after previous surgical valvotomy: immediate and follow up results.

To evaluate the immediate and long-term results of transcatheter balloon dilatation of the aortic valve for restenosis after previous surgical valvotomy. Prospective follow up by clinical examination and cross sectional Doppler echocardiography of all patients fulfilling the above criteria. Tertiary paediatric cardiology referral centre. 22 patients (18 male, 4 female)--median (range) age 157.5 (12-254) months--underwent 25 balloon dilatation procedures at a median of 72 (8-155) months after surgery. The median age at surgical valvotomy was 82.5 (0.5-230) months and the systolic gradient across the aortic valve immediately after surgery was 31 (0-49) mm Hg. The indication for dilatation was a Doppler derived peak instantaneous gradient of > 60 mm Hg with grade 2 or less aortic regurgitation. A single balloon was used, and the median balloon to annulus ratio was 1 (0.9-1). After dilatation the catheter pullback gradient decreased acutely from 55 (35-75) to 30 (0-75) mm Hg (p < 0.01) and the Doppler gradient from 74 (52-92) to 40.5 (30-96) mm Hg (p < 0.01). In three patients who underwent a second dilatation of the aortic valve eight months after the first procedure, the pullback gradient decreased from 50 (50-60) to 15 (15-16) mm Hg. Aortic regurgitation grade increased from 1 (0-2) to 2 (1-3); only one patient had grade 3 regurgitation. Over a median follow up of 33 (2-67) months seven patients had aortic valve replacement for recurrent stenosis (six patients) or severe regurgitation (one patient with grade 3 regurgitation after dilatation, who had partial detachment of one of the valve leaflets). There was no significant difference for the pullback gradient (median of 19 v 32.5 mm Hg), Doppler gradient 24 hours after dilatation (33.5 v 50.5 mm Hg; p = 0.03), or the duration of follow up (27.5 v 18 months) between the 12 patients who did not require further dilatation or surgery and the 10 patients who did. Balloon dilatation of the aortic valve is a safe and feasible option for palliation of restenosis after surgical valvotomy for congenital aortic valve stenosis. In many patients, however, stenosis progressed and a further intervention was required.

8043336

Relative effects of left ventricular mass and conduction disturbance on activation in patients with pathological left ventricular hypertrophy.

To investigate the relative effects of left ventricular mass and conduction disturbance on the duration and axis of the QRS complex in patients with left ventricular hypertrophy and a normal cavity size. Retrospective and prospective study of 42 patients with pathological left ventricular hypertrophy and 17 normal controls by electrocardiography, echocardiography, and pulsed Doppler recordings. Tertiary cardiac referral centre. 42 patients (mean (SD) age 58(16)) with left ventricular hypertrophy and normal cavity size. 17 had stenotic or replaced aortic valves, 14 had hypertension, 9 had hypertrophic cardiomyopathy and 2 had left ventricular hypertrophy without obvious cause. 17 normal people (mean (SD) age 47(20)) were used as controls. The values of QRS duration segregated into two normally distributed populations, with a cut off point at 135 ms. When patients with QRS duration of < 135 ms (n = 30) were compared with those with QRS duration of > or = 135 ms (n = 12), there were no significant differences in age, heart rate, left ventricular size, shortening fraction, left ventricular mass and total QRS amplitude. Both the PR and QT intervals were, however, longer in patients with a QRS duration of > or = 135 ms, and the extent of incoordinate left ventricular wall motion during the preejection period was greater. When it was < 135 ms the QRS duration was strikingly correlated with left ventricular mass (r = 0.81, p < 0.01). The onsets of transverse septal motion and of posterior wall thickening were normal, as were the onsets of the longitudinal motion of left, septal, and right atrioventricular junctions. When the QRS duration was > or = 135 ms the onset of transverse septal motion and of the longitudinal right atrioventricular junction were both normal, but that of the posterior wall thickening (p < 0.01) and the longitudinal motion of the septum (p < 0.05) and lateral left ventricular wall (p < 0.01) were significantly delayed. Peak rates of left ventricular dimension decrease (p < 0.01) and increase (p < 0.01) were both reduced, as were the peak rates of the long axis shortening of the septum (p < 0.01) and left atrioventricular junction (p < 0.05), whereas the peak rates of posterior wall thickening and thinning did not differ between the two groups. Mean isovolumic relaxation time was longer (p < 0.05) in patients with QRS duration of > or = 135 ms and the peak velocity of the A wave and thus the A to E ratio was greater than in patients with a QRS duration of < 135 ms and that of the E wave was similar in the two groups. In patients with left ventricular hypertrophy the values of QRS duration are bimodally distributed, with a cut off point at 135 ms. When QRS duration is < 135 ms, left ventricular mass seems to be closely related to QRS duration, making it the dominant factor determining the activation time. Once QRS duration reaches > or = 135 ms the correlation with mass no longer exists. The statistical distribution, electrocardiographic characteristics, and incoordination pattern of left ventricular wall motion all suggest the development of a proximal left bundle branch block.

8043335

Relations between resting ventricular long axis function, the electrocardiogram, and myocardial perfusion imaging in syndrome X.

To investigate interrelations between ventricular long axis function, resting electrocardiogram, and myocardial perfusion imaging in a group of patients with syndrome X in order to define possible underlying mechanisms. Prospective echocardiographic, electrocardiographic, and myocardial perfusion imaging. A tertiary referral centre for cardiac diseases with invasive and non-invasive facilities. 50 consecutive patients with syndrome X selected on the basis of a history of angina, ST segment depression on exercise, and normal coronary arteriograms and 21 controls of similar age. Long axis motion of one or both ventricles assessed by echocardiography was abnormal in 37 patients. The onset of systolic shortening was delayed by > 130 ms (upper limit of normal 95% confidence interval) in eight patients, and was associated with prolonged shortening during the isovolumic relaxation period in seven (p < 0.01) (systolic abnormalities). The onset of diastolic lengthening was delayed by > 80 ms in 20. Early diastolic peak lengthening rate was < 4.5 cm.s-1 in 13 patients, and the relative amplitude of lengthening during atrial systole was > 45% in 18. On the resting electrocardiogram septal q waves were absent in 12 patients. This was associated with long axis systolic disturbances in seven patients (p < 0.05). T waves were abnormal in 10 and associated with delayed onset of early diastolic lengthening in all (p < 0.001). Late diastolic long axis disturbances were not associated with any consistent electrocardiographic abnormality. Myocardial perfusion imaging was abnormal in six of 33 patients, four of whom had systolic abnormalities (p < 0.03). Imaging was normal in the rest, but in 13 of them long axis function was abnormal in the left side and in four it was abnormal on the right ventricle. Both electrocardiography and imaging were normal in 10 patients. No patient with an abnormal electrocardiogram or myocardial perfusion had normal long axis motion on echocardiography. The function of the left and right ventricular long axes was abnormal in about 70% of a sample of patients with syndrome X. Systolic disturbances were consistently associated with absent septal q wave and abnormal myocardial perfusion imaging, while early diastolic disturbances correlated with T wave abnormalities. These associations suggest that the three different investigations detect related objective abnormalities in one or more subgroups of patients with syndrome X.

8043333

Short-term effects of right atrial, right ventricular apical, and atrioventricular sequential pacing on myocardial oxygen consumption and cardiac efficiency in patients with coronary artery disease.

To investigate the short-term effects of atrial, atrioventricular, and ventricular pacing on myocardial oxygen consumption, myocardial blood flow, and cardiac efficiency in patients with coronary artery disease. Prospective study that started at the end of diagnostic coronary angiography in 13 patients and was performed during atrial, atrioventricular, and ventricular pacing for 5 min, in random order, at 20 beats/min more than the heart rate of the patient's positive exercise test. A Baim thermodilution catheter in the coronary sinus was used to measure myocardial blood flow and oxygen consumption and a pacing electrode at the right ventricular apex and a catheter in the pulmonary artery were used to estimate cardiac output. Referral cardiology centre. 13 patients with coronary artery disease (mean (SD) age 53(5) years). All the patients had a positive exercise test and most of them (77%) had left anterior descending coronary artery disease. Mean (SD) cardiac output increased by 0.5(1.6) l/min during atrial pacing, increased by 0.1(1) l/min during atrioventricular pacing, and decreased by 0.8(1.2) l/min during ventricular pacing (P = 0.01 v atrial pacing, P = 0.03 v atrioventricular pacing). Diastolic pulmonary pressure increased by 6(4) mm Hg during atrial pacing, by 8.6(4) mm Hg during ventricular pacing (P = 0.02 v atrial pacing), and by 7.5(4.7) mm Hg during atrioventricular pacing. Changes in myocardial oxygen consumption and cardiac efficiency during the different pacing modes were similar. Atrial, atrioventricular, and ventricular pacing had similar short-term effects on myocardial oxygen consumption, myocardial blood flow, and cardiac efficiency in patients with coronary artery disease. Ventricular pacing, however, did not increase cardiac output.

8043332

Direct access exercise electrocardiography: a new service that improves the management of suspected ischaemic heart disease in the community.

To assess the safety and value of an exercise electrocardiography service for the diagnosis of suspected ischaemic heart disease to which general practitioners have direct access. Direct access to a hospital exercise electrocardiography service was offered on a trial basis to 122 general practitioners in a defined urban area. Maximal exercise tests were performed according to the modified Bruce protocol and the results were dispatched promptly to the referring doctors who were responsible for the subsequent management of their patients. All general practices in north and west Belfast (combined list size about 180,000) and the regional medical cardiology centre. 212 request forms were received in a two year period and 192 eligible patients attended for exercise testing. All patients were suspected to have pain due to myocardial ischaemia, were aged < or = 65, and had no contraindications to exercise testing. Proportion of general practitioners who used the service. Proportion of exercise tests that were positive. Referring doctors' assessment of the service. 43% of general practitioners referred patients and 34 tests (18%) were positive. No complications occurred. The pretest likelihood of ischaemic heart disease, assessed by the referring doctor, was high in 48 (25%), moderate in 82 (43%), and low in 62 (32%). A high pretest likelihood of ischaemic heart disease predicted a positive test result with a sensitivity of 50% and specificity of 80%. General practitioners decided to refer 19 (10%) patients to a hospital cardiology department for further assessment, including 16 of the 34 who had a positive exercise test. In most cases the service was found to be helpful and 97% of patients would have been referred directly to a hospital cardiology clinic if it had not been available. Direct access exercise electrocardiography for patients with suspected ischaemic heart disease is safe, feasible, and helpful to general practitioners. This service seems to reduce the number of patients referred to cardiology outpatient clinics and to facilitate the management of these patients in the community.

8043331

Usefulness of arterial blood gas estimations during exercise in patients with chronic heart failure.

Coexisting cardiorespiratory disease may contribute in individual cases to the increased ventilatory response to exercise in patients with chronic heart failure. To characterise further the arterial blood gas response to exercise and to explore the possible uses of blood gas sampling in clinical practice in patients with chronic heart failure. 37 patients with a primary diagnosis of chronic heart failure (age (range) 59 (45-80); left ventricular ejection fraction 24.5% (4%-44%)) underwent exercise testing with arterial blood gas analysis during exercise. In 34 patients there was a small fall in arterial carbon dioxide tension from a mean (SEM) of 4.9 (0.1) kPa at rest to 4.6 (0.1) kPa at peak exercise (p < 0.001). There was no significant change in arterial oxygen tension. During the recovery period arterial oxygen tension rose from 13.3 (0.3) kPa at peak exercise to 14.8 (0.3) kPa three minutes into recovery (p < 0.001). Arterial carbon dioxide tension was unchanged. In the remaining three patients there was considerable arterial hypoxaemia on exercise, from 10.4 kPa at rest to 7.7 kPa at peak exercise. All of these patients had an alternative diagnosis (patent foramen ovale with right to left shunt during exercise, pulmonary embolic disease, and clinically unsuspected obstructive airways disease). Patients with a presumptive diagnosis of chronic heart failure should undergo exercise testing with arterial blood gas analysis. Arterial hypoxaemia on exercise is rare in stable chronic heart failure. If hypoxia on exercise is detected, an alternative diagnosis should be sought.

8043330

Temporal influences on the prediction of postinfarction mortality by heart rate variability: a comparison with the left ventricular ejection fraction.

To examine the influence of the duration of follow up on the values of heart rate variability (HRV) and the left ventricular ejection fraction (LVEF) for predicting mortality after infarction. HRV is an index of autonomic balance that identifies patients at a high risk of arrhythmic events. The index is most depressed during the first few weeks after myocardial infarction whereas left ventricular function tends to deteriorate with time. The value of depressed HRV measured before discharge from hospital for predicting mortality after infarction should decline with time. The HRV and the LVEF were assessed in 433 survivors of a first acute myocardial infarction: HRV < 20 units and LVEF < 40% were taken as cut off points. Kaplan-Meier survival functions for total cardiac mortality and sudden cardiac death were calculated for the whole five year follow up period and for different intervening periods. During follow up of four weeks to five years there were 46 (10.6%) deaths and 15 (3.5%) patients died suddenly. Within the whole follow up period, HRV < 20 units and LVEF < 40% were both strongly associated with total cardiac mortality (p < 0.0001), but HRV was an independent predictor of total cardiac mortality only during the first six months of follow up. There were no deaths predicted by HRV < 20 units after the first year of follow up whereas LVEF < 40% had a sensitivity of 43% and a positive predictive accuracy of 9% for predicting death during this period. HRV < 20 units was better than LVEF < 40% in predicting sudden deaths during the first year of follow up but was an independent predictor only of those sudden deaths occurring within six months of infarction. The duration of follow up affects the prediction of sudden death and total cardiac mortality from HRV. Reduced HRV as measured before discharge from hospital does not seem to retain independent prognostic value after six months of follow up. These findings have potential implications for the serial evaluation of HRV and for the prevention of sudden death after myocardial infarction.

8043329

QT interval dispersion: a non-invasive marker of susceptibility to arrhythmia in patients with sustained ventricular arrhythmias?

To assess QT interval dispersion on the surface electrocardiogram in patients with sustained ventricular arrhythmias. A retrospective and prospective blinded controlled study of patients referred for investigation of ventricular arrhythmias at a tertiary cardiac centre. 89 consecutive patients with sustained ventricular arrhythmias due to chronic ischaemic heart disease, cardiomyopathy, or ventricular tachycardia (VT) in a normal heart. 32 patients did not meet the inclusion criteria; therefore 57 patients were compared with a control group of 40 patients with myocardial disease but no history of arrhythmias and 12 normal controls with no myocardial disease. Standard 12 lead electrocardiograms were enlarged, the QT intervals for each lead measured, and QT dispersion calculated. There was a significantly greater mean QT dispersion (77 ms) in patients with sustained ventricular arrhythmias compared with the control group (38 ms, p < 0.01). This held for all groups; after myocardial infarction VT (82 (22) ms v control 38 (10) ms; p < 0.01), dilated cardiomyopathy VT (76 (18) ms v control 40 (11) ms, p < 0.01), and normal heart VT (65 (7) ms v control 32 (8), p < 0.05). There was also a greater QT dispersion in patients with impaired left ventricular function and VT, with a correlation between left ventricular function and QT dispersion in patients with VT (r = 0.56, p < 0.01). QT interval dispersion may be a further non-invasive marker of susceptibility to ventricular arrhythmias.

8043323

Validation of increased intracranial pressure and high risk for increased intracranial pressure.

The authors designed this validation study to determine the defining characteristics of increased intracranial pressure and the risk factors for high risk for increased intracranial pressure. Using Fehring's Diagnostic Content Validity Model, a purposive sample of 219 nurses validated 17 major and 16 minor defining characteristics of increased intracranial pressure and nine major and six minor risk factors for high risk for increased intracranial pressure. Ratings were similar among nurses with diverse educational preparation but varied among nurses in different specialty areas, suggesting that practice setting is important in nursing diagnosis validation studies.

8043322

The alcoholic family: a nursing diagnosis validation study.

This study was designed to develop and validate a new nursing diagnosis, altered family processes: alcoholism. The Delphi technique was used to obtain nurse experts' (N = 201) ratings of terms for the definition, related factors, and defining characteristics. Degree of consensus was determined by analyzing the mean, frequencies, and Fehring's (1987) Diagnostic Content Validity Index for items. Findings supported a proposed definition and related factors including family history of alcoholism and lack of problem-solving skills. Defining characteristics were grouped into three categories: feelings (e.g. mistrust, insecurity, powerlessness, unhappiness), roles, and relationships (e.g. disturbed family dynamics, inconsistent parenting, marital problems), and behaviors (e.g. impaired communication, dependency, denial). Future research includes the proposal and testing of nursing interventions for alcoholic families.

8043321

Using metacognitive skills: the quality audit tool.

The authors describe a strategy used to teach clinical reasoning skills to novice diagnosticians. The strategy proposed is the Quality Audit Tool, an instrument designed to help novices use metacognitive skills to critique diagnostic statements and care plans. The Quality Audit Tool has eight frames (Diagnostic Statement, Diagnostic Cues, Functional Relationship, Outcome, Etiology, Nursing Orders, Evaluation, and Clinical Judgment); each frame has a content and process focus. Conducting a Quality Audit enables the novice diagnostician to understand relationships among the parts of a nursing diagnosis, recognize the metacognitive skills used in clinical reasoning, and evaluate knowledge and clinical reasoning against a set of standards.

8043318

Toxicity of a novel HMG-CoA reductase inhibitor in the common marmoset (Callithrix jacchus).

1. GR95030X, a potent inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, was administered daily to marmosets by gavage. In a Maximum Repeatable Dose (MRD) study, doses of up to 30 mg kg-1 day-1 were administered for 49 days. In a chronic study, animals received dosages equivalent to 0, 1, 2.5, 7.5 and 20 mg kg-1 day-1 for 204 or 205 days. Some animals were maintained without treatment for a recovery period of 29 or 30 days. 2. Clinical signs included poor coat condition, weakness with impaired coordination, lethargy and other behavioural changes. There was also alimentary disturbance, and some deaths occurred at doses of 20 mg kg-1 day-1 and above. 3. Adverse effects upon body weight were seen although some recovery was apparent after the cessation of treatment. 4. Serum cholesterol concentrations were reduced. Very large increases in serum ALT, AST and CK activities were recorded with CK-MM isoenzymes accounting for 80% or more of the total CK enzyme activity. 5. Treatment was associated with muscle fibre atrophy and a sarcolemmal response with little evidence of regeneration. Histological examination revealed vascular changes, glial proliferation and cell death in the brain, with no consistent distribution. Alveolar capillary congestion and alveolar proteinosis indicated that there may have been a reduction in cardiac function. 6. HMG-CoA reductase inhibitors have evident potential to cause myopathy in marmosets. This is believed to be the first report of such an effect.

8043317

Effects on operant learning and brain acetylcholine esterase activity in rats following chronic inorganic arsenic intake.

1. Very young and adult Wistar rats were given As5+, 5 mg arsenic kg-1 body weight day-1 (sodium arsenate). 2. Operant learning was tested in a Skinner box at the end of exposure and, in the case of developing animals, also after a recovery period. 3. Acetylcholine esterase (AChE) activity was estimated in discrete brain regions of these animals. 4. The animals exposed to arsenic took longer to acquire the learned behaviour and to extinguish the operant. AChE activity was inhibited in some regions of the brain.

8043316

Interaction of nitrobenzoates with haemoglobin in red blood cells and a haemolysate.

Haemoglobin, either in the intact red blood cells or in their haemolysate, readily reacts with mono- and di-nitrobenzoates. For all the nitroaromatics considered, the rate of the process is faster in the haemolysate than in the whole red blood cell. At low (< 8 mM) concentrations, almost quantitative production of methaemoglobin is observed and the process follows second order kinetics. At higher concentrations, the kinetics become complex and other haemoglobin derivatives are produced. The bimolecular rate constants obtained at low substrate concentrations show little relationship to the nitroaromatic reduction potential. The data indicate that mono-nitrobenzoate derivatives are very active in oxidizing haemoglobin in in vitro erythrocyte suspensions, the activities being similar to that of 3,5-dinitrobenzoate. The measured reactivity follows the order m-nitrobenzoate > 3,5-dinitrobenzoate > p-nitrobenzoate > o-nitrobenzoate and the reactivity of all the compounds is considerably larger than that of nitrobenzene. The present results constitute the first kinetic data bearing on the reactivity of nitroaromatics with haemoglobin, both free and incorporated in the intact red cell. Furthermore, they indicate that the interaction of the nitroaromatics with haemoglobin, leading to total oxidation and transformation, in spite of the total disruption of the membrane, does not produce significant lipid-peroxidation, as measured by chemiluminescence emission, production of TBA reactive material and oxygen consumption.

8043315

Immunotoxicological investigation of SCMF, a new pyrethroid pesticide in mice.

The toxicity of a new pyrethroid pesticide Supercypermethrin Forte (SCMF) was studied in male CFLP mice using classic toxicological (body weight, organ weights) and haematological (white blood cell count, haematocrit, nucleated cell content of femoral bone marrow) methods and immune function tests (PFC assay, DTH reaction). Four weeks of oral treatment in a 5 days per week system at doses of 1/10, 1/20, or 1/40 x LD50 did not cause evaluable changes in the measured parameters. When single calculated LD20, LD10, or LD5 doses of SCMF were administered on different days before termination to different groups of mice the two higher doses caused a time- and dose-dependent decrease in the splenic PCF number. Apart from some temporary toxic signs and an increase of haematocrit at the top dose the other examined parameters did not show evaluable changes. Under these experimental conditions toxic changes appeared only at the high dose range and, of those applied, the PFC assay proved to be the most sensitive method for detecting the toxicity of SCMF.

8043314

Clinical toxicology of ethylene glycol monoalkyl ethers.

The glycol ethers constitute a family of organic solvents commonly found in industrial and household products. Because of their widespread availability and potential for serious toxicity, physicians should be aware of the clinical toxicology of these compounds. Until recently, knowledge of the toxic effects of glycol ethers has been derived from animal studies and a limited number of case reports and small case series. A growing body of data from epidemiological studies, controlled human studies, and studies using human tissue now allows for advancement in the understanding of the acute and chronic toxicity of these compounds. This review summarizes and evaluates human and pertinent animal literature on the clinical toxicology of glycol ethers, with a focus on the commonly encountered monoalkyl ethers of ethylene glycol. Management options for acute poisoning, as well as measures for the control of workplace exposures, are discussed.

8043313

Intravenous pyridoxine in acute ethanol intoxication.

Intravenous pyridoxine was evaluated as an agent for the reversal of ethanol-induced central nervous depression in a randomised double blind controlled study of 108 patients presenting with a clinical diagnosis of acute ethanol intoxication to two accident and emergency departments. Level of consciousness, measured by a modified Glasgow coma scale, showed no significant change after a single 1 g dose of intravenous pyridoxine when compared to controls given saline. The mean fall in blood alcohol concentration after one hour was 33 mg dl-1 (7.2 mmol l-1) in both groups suggesting that pyridoxine has no antidotal action and no short term effect on the rate of metabolism of ethanol.

8043312

Study of lithium absorption by users of spas treated with lithium ion.

This study examines the possible dermal absorption of lithium ion into the blood serum of spa/hot tub bathers. Fifty-three participants (28 males and 25 females) spent 20 minutes per day, 4 days per week for 2 consecutive weeks in one of two assigned spas. The participants were randomly assigned to one of the two spas after matching based on sex, age, and use of oral contraceptives. The test spa contained 40 +/- 5 ppm lithium ion, while the control spa contained no additional lithium ion above the background levels of approximately 0.02 ppm. The exposure in the spa treated with lithium ion (from lithium chloride) simulated the maximum exposure that would be expected in a spa sanitized with lithium hypochlorite. The two spas were maintained at 101 +/- 2 degrees F. Serum lithium ion levels before and after spa use were determined using graphite-furnace atomic absorption spectroscopy with a minimum detectable level of lithium ion in serum of 2 micrograms l-1 (ppb). There was no statistically significant difference in serum lithium levels between the control and treatment group at any stage. We conclude that dermal exposure to lithium ion (as would be present after treatment of a spa with lithium hypochlorite) did not result in a detectable increase in the serum lithium ion level.

8043311

Acute dystonic drug reaction or tetanus? An unusual consequence of a 'Whizz' overdose.

The case history presented illustrates that, following an overdose of 'Whizz' and alcohol, a protracted dystonic syndrome can develop, clinically indistinguishable from tetanus. A prolonged period of ventilation may be necessary, but, in this case, complete recovery eventually occurred.

8043309

Clinical and pathological findings in fatal 1,3-dichloropropene intoxication.

1. A 27-year-old, previously healthy, worker accidentally drank a solution containing 1,3-dichloropropene. 2. He developed gastrointestinal distress, adult respiratory distress syndrome, haematological and hepatorenal functional impairment and died after 40 h. 3. Damage to the pancreas was also thought to have been caused by the chemical as part of a multiorgan disorder.

8043310

Effects of chronic manganese toxicity on tissue levels and urinary excretion of nicotinamide nucleotides in rats.

Male rats were exposed to manganese sulphate i.p. daily for a period of four weeks to see its effects on tissue levels and urinary excretion of total nicotinamide nucleotides (TNN). Increased levels of TNN were observed in blood and brain while the levels were found to be decreased in liver. There was a progressive increase in the excretion of TNN during the experimental period. TNN levels in blood and urine might serve as useful biological indicators of Mn toxicity.

8043308

Organochlorine pesticide residues in human milk in Kayseri.

In this study: dichlorodiphenyltrichloroethane (DDT) and its metabolites [DDT + dichlorodiphenyl-dichloroethylene (DDE)], BHC (HCH) and their main isomers such as alpha, beta, gamma BHC, aldrin and its metabolite dieldrin, heptachloride, heptachloride epoxide, were investigated in 51 samples of breast milk of 51 lactating women during 1988. The ages of the mothers, who were working in agriculture, ranged from 17 to 33 y (mean 24.2 y). The concentrations of hexachlorobenzene (HCB), alpha BHC, beta BHC, gamma BHC, heptachloride, aldrin, heptachloride epoxide, pp'DDE, dieldrin, op'DDT, pp'DDT were found as 84 +/- 23, 96 +/- 20, 522 +/- 120, 156 +/- 20, 198 +/- 130, 47 +/- 9, 11 +/- 4, 2389 +/- 280, 6.7 +/- 3, 70 +/- 12, 410 +/- 60 micrograms kg-1 milk, fat, respectively, measured by gas chromatography (GC) method. The concentrations of chlorinated pesticides in human milk samples from Kayseri were compared with similar data obtained from other countries. The amounts of total BHC and aldrin derivatives were below the acceptable daily intake (ADI), whereas the amount of total DDT derivates was above, of the World Health Organization (WHO).

8043307

Preimplantation embryo sexing by polymerase chain reaction amplification of the sry gene on single mouse blastomeres.

Accurate and rapid sex determination of preimplantation embryos has great potential both in animal breeding and in human pathology. In the past, sex determination has been accomplished by cytogenetic or immunologic means and by polymerase chain reaction amplification of Y-chromosome-specific repetitive sequences. More recently, amplification of the Y-specific single-copy ZFY gene has been used in humans for sex determination of preimplantation embryos. The experiments reported here indicate that another Y-chromosome-specific single-copy gene, the sex-determining region gene (sry) can be successfully amplified from single mouse blastomeres. Blastocysts positive for sry amplification were reimplanted to foster mothers, and six of six newborns were male. We conclude that sry gene amplification can represent a good marker for embryo sex determination.

8043306

Amplification of specific gene products from human serum.

The polymerase chain reaction (PCR) is an in vitro method for the primer-directed enzymatic amplification of specific DNA sequences. Ordinarily, sources with obvious DNA content such as cells, viruses, and plasmids serve as the origin of templates for the PCR. Here we report a simple and efficient method to obtain cellular DNA from serum suitable for use in PCR reactions or gene analysis. This procedure should facilitate the detection of disease and provide a basis for the examination of mutations in genes before the onset as well as during the progression of various diseases.

8043305

Screening yeast artificial chromosome libraries with robot-aided automation.

Screening of collections of yeast artificial chromosomes utilizing the polymerase chain reaction (PCR) requires large numbers of reactions in parallel. Four steps were implemented to reduce the labor involved: (a) The number of initial samples for DNA extractions was decreased by compressing libraries up to 12-fold. (b) DNA extraction from yeast clones was robot assisted. (c) A BIOMEK 1000 station was adapted to pipette samples for PCR assays. (d) Sample preparation was integrated with a temperature cycler constructed to carry out up to 576 reactions in six 8 x 12-well trays. The implementation of these steps increases the number of reactions per person per day by an order of magnitude. In tests with X-chromosome-specific probes, the robot-aided screening recovered all of the clones detected by slower manual methods.

8043304

Rescue of a single yeast artificial chromosome from a cotransformation event utilizing segregation at meiosis.

During the construction of yeast artificial chromosome (YAC) libraries to facilitate mapping of the human genome, two YACs may be cotransformed into the same yeast cell, making further analysis very difficult. We present a simple method to rescue the required YAC that utilizes the segregation of chromosomes at meiosis. In brief, we crossed the cotransformed yeast cell with a non-YAC-containing strain and induced the resulting diploid to sporulate and undergo meiosis. The new haploid generation included some yeast cells that contained only the desired YAC. These YACs were analyzed by conventional methods. To exclude the possibility that major rearrangement occurred during the procedure, we analyzed the YACs with restriction enzymes that cut only rarely. We conclude that this is a useful technique to rescue cotransformed YACs.

8043303

Increased calcium absorption in nephrolithiasis explained by uptake studies in ileal brush border membrane vesicles.

We previously showed that recurrent calcium renal stone formers have enhanced urinary excretions of calcium and oxalate resulting from malabsorption of citrate. In the present investigation, the mechanism of the citrate-induced increased calcium uptake was studied using guinea pig ileal brush border membrane vesicles. In this model, calcium is absorbed in a concentration dependent, single mechanism uptake with a Km of 275 +/- 30 umol/liter (SD) and a Vmax of 4.0 +/- 0.5 nmol/min.mg protein. Under conditions of maximal calcium uptake, both citrate and phosphate inhibited calcium absorption into brush border membrane vesicles (BBMVs). In contrast, when phosphate and citrate were added together, calcium absorption normalized. Citrate inhibition of calcium absorption appeared to be due to free citrate ions, and phosphate ions overcame this inhibition. Phosphate inhibition was mostly due to decreased concentrations of ionized calcium and partly to precipitation of insoluble calcium phosphate. These studies confirm that the effects of citrate in humans in enhancing calcium absorption occur in the lumen of the gut and are not related to further biochemical conversions of citrate by the gut cells, to effects of citrate on calcium-related hormones, or to the renal handling of calcium. Also, the effects of citrate on increasing calcium absorption should be increased or attenuated in patients who malabsorb citrate, and this explains the increased urinary calcium and oxalate excretions reported for recurrent calcium stone formers.

8043301

Choline deficiency in cultured adrenal medullary cells: effect on phosphatidylcholine biosynthesis.

The effect of choline deficiency on the composition and biosynthesis of the major membrane phospholipids was examined in adrenal medullary cells maintained in suspension cultures. The amount and proportions of phosphatidylcholine (PC) and phosphatidylethanolamine (PE) in these cells were not affected by the removal of choline from the culture media. However, the rate of biosynthesis of choline at the phosphatide level by the stepwise methylation of PE increased twofold within 24 h after choline was removed from the culture media, while ethanolamine incorporation into PE was increased by 50%. In contrast, the rate of incorporation of labeled choline into PC, presumably via CDP-choline, was virtually identical in cells that had been preincubated in the presence or absence of 1 mM choline. These results demonstrate that cultured cells of neural origin are capable of compensating for lack of exogenous choline by forming choline at the phosphatide level through the sequential methylation of PE. The hypolipidemic drug, DH-990, when added to the culture media, inhibited conversion of phosphatidylmonomethylethanolamine (PME) to PC, but had no effect on the N-methylation of PE. This differential effect indicates that the initial N-methylation of PE is catalyzed by an enzyme that is distinguishable from the enzyme(s) catalyzing the conversion of PME to PC.

8043300

Eicosapentaenoic acid enhances intracellular free calcium in cultured human endothelial cells.

Eicosapentaenoic acid (EPA) caused elevations of intracellular free Ca2+ concentration ([Ca2+]i) measured by fura-2 fluorescence in cultured human endothelial cells. The EPA-induced increase in [Ca2+]i could still be observed when either cyclooxygenase or lipoxygenase inhibitors were added. These results suggest that EPA itself rather than its metabolites has direct effects on intracellular Ca2+ mobilization, causing the elevation of [Ca2+]i.

8043299

Rat mammary arginase: isolation and characterization.

The extrahepatic arginase, AII, from rat mammary gland was isolated and its properties investigated and compared with those of the hepatic arginase, AI. Mammary arginase activity increased 300% at mid-lactation, an increase unaccompanied by an increase in liver arginase activity. Mammary gland contained two isozymes, separable by ion exchange chromatography. The major form, AII, was purified 103-fold and antisera were raised against it. A 1300-fold purification was achieved temporarily but the enzyme was unstable. Arginase AII was kinetically similar to AI: both had pH optima of 10 and Kms for L-arginine of 12-14 mM. Arginase AII differed from AI in having a near-neutral pI and a slightly larger subunit size (39,800 Da compared to 38,900 Da by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE)). Solution immunoprecipitation studies revealed that virtually all of the arginase present in liver was type AI, whereas kidney and mammary gland contained both isozymes. Western immunoblotting showed that the amount of immunoreactive mammary arginase AII protein increased at mid-lactation in parallel with the increase in activity. This suggests that the elevated arginase activity is due to de novo protein synthesis and/or reduced protein degradation, rather than activation of arginase.

8043298

Modulation of cyclic guanosine monophosphate production during Escherichia coli septic shock.

Endotoxin and other bacterial products induce the release of mediators which alter the circulation and cellular metabolism. Recent evidence suggests nitric oxide (NO) is one such mediator. The proposed mechanism by which NO produces hypotension is the activation of guanylate cyclase with subsequent biosynthesis of 3':5' cyclic guanosine monophosphate (cGMP). We studied the production of cGMP during Escherichia coli-induced septic shock in two experiments; the first with sepsis alone and the second using NG-monomethyl-L-arginine (L-NMMA), a competitive inhibitor of nitric oxide synthase. Animals in both experiments experienced significant bacteremia (P < 0.05), endotoxemia (P < 0.05), and lactic acidosis (P < 0.03). Mean arterial blood pressure decreased (P < 0.03) and heart rate increased (P < 0.05) within both groups but did not differ between groups. A significant increase in the production of circulating whole blood cGMP occurred at 3-5 h (P < 0.03). There was significantly less cGMP produced by the L-NMMA-treated animals (P < 0.01). These results demonstrate an elevation in cGMP during septic shock which is attenuated by the addition of L-NMMA. This suggests that NO may be present during gram-negative septic shock and its effects mediated through cGMP.

8043297

Structure and expression of mammalian peroxisome assembly factor-1 (PMP35) genes.

Mammalian genes encoding a 35-kDa peroxisomal membrane protein (PMP35, peroxisome assembly factor-1) are compared using the polymerase chain reaction and DNA sequencing. DNA sequencing of the 915 bp of the PMP35 coding regions was in complete agreement with previously published rat data and showed 36 and 133 nucleotide substitutions, respectively, in mouse and man. The 12 and 35 respective amino acid changes encoded by these nucleotide substitutions are clustered and compatible with putative membrane-spanning regions. Rat/human and rat/mouse comparisons yield silent mutation rates of 0.33 and 0.21% per site per million years and replacement mutation rates of 0.082 and 0.076%; transitions account for 67% (human/mouse) and 83% (rat/mouse) of nucleotide replacements among PMP35 genes. PMP35 gene expression in mouse tissues as measured by reverse transcriptase-PCR was responsive to clofibrate and disproportionately high in neural tissue.

8043295

Dual electron microscopic localization of mitochondrial creatine kinase in brain mitochondria.

Mitochondrial creatine kinase in brain mitochondria appears to be located at two different intramitochondrial sites. By using immunogold-labeling techniques, a peripheral immunoreactivity was localized between the two boundary membranes, while an additional, central immunoreactivity was found at the crista surface. The peripheral enzyme was accessible to the antibodies after treatment of the brain mitochondria with 100-300 micrograms digitonin/mg mitochondrial protein, which left 75% of the activity bound to the membranes. Electron microscopic analyses revealed that 43% of the labeled, peripheral creatine kinase was bound at those places where outer membrane vesicles remained attached to the inner envelope membrane, suggesting that the enzyme is involved in contact formation between outer and inner mitochondrial membranes. Postembedding staining of mitochondria on thin sections of brain tissue or in the isolated state led to the observation of a second location of creatine kinase inside the mitochondria, along the cristae, which was not accessible to the antibodies in isolated, digitonin-treated mitochondria.

8043296

Differential effects of phorbol 12-myristate 13-acetate and diacylglycerols on thromboxane A2-independent phospholipase A2 activation in collage-stimulated human platelets.

We investigated the priming effects of protein kinase C (PKC) activators such as phorbol 12-myristate 13-acetate (PMA), 1,2-DiC8 and OAG, and 1,3-DiC8 (a poor activator of PKC) on thromboxane A2 (TxA2)-independent phospholipase A2 (PLA2) activation in human platelets using collagen and A23187 as agonists. We measured PLA2 activation in collagen-stimulated platelets in the presence of BW755C, which abolished TxA2 synthesis, rise in cytosolic Ca2+, and aggregation. In the presence of PMA (50 nM), the amount of arachidonic acid (AA) released in platelets stimulated with collagen and A23187 represented 300% (13.85 nmol versus 4.5 nmol) and 400% (28 nmol versus 7 nmol) of controls (without PMA), respectively, while 1,2-DiC8, OAG, and 1,3-DiC8 increased TxA2-independent AA release by 50% in A23187-stimulated platelets and had no effect on the release of AA in collagen-stimulated platelets. Interestingly, 1,3-DiC8, which is a poor activator of PKC, was as effective as the other two DAGs (OAG and 1,2-DiC8) in priming TxA2-independent PLA2 activation, but was less effective than PMA in platelets stimulated with A23187. These results suggest that the TXA2-dependent IP3-mediated rise in cytosolic Ca2+ may not be obligatory for priming PLA2 activation in the presence of PMA in collagen-stimulated platelets. In contrast, 1,2-DiC8, OAG, and 1,3-DiC8 likely enhanced PLA2 activation via intracellular Ca2+ as they selectively affect this enzyme only in A23187-stimulated platelets. We also observed a significant increase in both saturated (palmitic and stearic acids) and unsaturated fatty acids (oleic and linoleic acids) in platelets stimulated by collagen or A23187 in the presence of PMA (50 nM), but not in the presence of DAGs. These findings imply that PMA may also affect the activation of DAG/MAG lipases, PLA1, or nonspecific PLA2. Since both 1,2-DiC8 and OAG exert no significant effect on the release of these fatty acids, the effects observed with PMA on DAG lipase/PLA1 may not involve a PKC-dependent mechanism. We, therefore, conclude that the mechanisms by which PMA and DAGs prime PLA2 activation are different and that the priming mechanism by DAGs may not involve PKC, but may require a rise in intracellular Ca2+.

8043293

Spontaneous rupture of a congenital diaphragmatic eventration.

A 51-year-old man presented as an emergency with acute intestinal obstruction following herniation of abdominal contents into the left hemithorax through a spontaneous rupture of his eventrated left hemidiaphragm. He underwent a left thoracotomy with reduction of the herniated abdominal contents, repair of the diaphragmatic rupture and plication of the diaphragm. He made an uneventful recovery and remains asymptomatic. This is the first reported case of spontaneous rupture of an eventration of the diaphragm.

8043294

Complete myocardial revascularization with arterial grafts without using the mammary artery.

We report on the case of a 60-year-old male patient who developed a crescendo angina 9 years after a coronary artery bypass procedure. Coronary angiography revealed triple vessel disease. None of the internal mammary arteries were available and the saphenous veins had previously been stripped. A complete myocardial revascularization by means of arterial grafts was still achieved by using both the epigastric arteries, and an in situ right gastroepiploic artery.

8043292

The Carpentier-Edwards pericardial aortic valve: intermediate results in 420 patients.

From July 1984 to December 1991, 420 patients underwent isolated aortic valve replacement with a Carpentier-Edwards pericardial bioprosthesis in our Institution. Of the patients 71.5% were male, the mean age was 66.9 +/- 11.9 years and 48% were in NYHA clinical stage III or IV. The operative mortality rate was 2.9% (12/420). All patients but six were followed up for an average of 3.9 years after their operation and total follow-up was 1444 patient-years. At this time of the study, over 80% of the patients are in NYHA class I or II, 6% are in atrial fibrillation and 7% receive anticoagulation treatment. There were 41 late deaths. After 8 years the actuarial survival rate is 80% +/- 6%. Nine patients died of valve-related causes (three endocarditis, three thromboembolic complication, one structural failure, and two sudden deaths). The actuarial rate of freedom from valve-related death was 97% +/- 3% at 8 years. Valve-related complications included 12 thromboembolic episodes (0.8% patient-year), 7 endocarditis (0.5% patient-year), 4 anticoagulant-related complications (0.2% patient-year), 6 reoperations (0.4% patient-year) and 2 structural valve failures (0.1% patient-year). After 8 years, freedom from thromboembolic complication was 96% +/- 3%, from endocarditis 97% +/- 2%, from reoperation 98% +/- 2% and from valve failure 99% +/- 1%. There were only two structural deteriorations (calcification and stenosis) and one explanation. No leaflet tear was observed. We conclude that these intermediate results are better than those obtained with previous pericardial bioprostheses.

8043291

Preconditioning the human heart during aorto-coronary bypass surgery.

Ischaemic preconditioning, with brief periods of ischaemia separated by reperfusion, increases myocardial resistance to infarction. In addition, preconditioning leads to preservation of myocardial adenosine triphosphate (ATP) during ischaemia. We propose that ischaemic preconditioning may share fundamental similarities with intermittent aortic cross-clamping utilised during aorto-coronary bypass surgery. The aim of this study was to test the hypothesis that controlled aortic cross-clamping is a form of preconditioning using conservation of ATP as the end point. Patients randomised to the preconditioned group (preconditioned, n = 10 patients), received a preconditioning stimulus of two 3-min periods of cross-clamping separated by 2 min of reperfusion prior to an ischaemic insult of 10 min ischaemia and ventricular fibrillation. In the control group (control, n = 10 patients) hearts received 10 min cross-clamping with fibrillation without prior preconditioning. Myocardial ATP, creatine phosphate (CP), and lactate were determined from biopsy specimens taken at the onset of cardiopulmonary bypass (A), at the end of preconditioning (B), and at the end of 10 min of ischaemic insult (C). expressed as mean +/- SE (mumol/g dry weight). Preconditioning resulted in a significant depletion of the myocardial ATP content (preconditioned, B: 11.7 +/- 0.9 vs A: 19.8 +/- 1.4; P < 0.01). Furthermore 10 min of ischaemia resulted in a significant depletion of ATP in the control patients (control, C: 7.2 +/- 0.3 vs B: 19.5 +/- 1.2; P < 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)

8043290

A prospective randomised study of continuous warm versus intermittent cold blood cardioplegia for coronary artery surgery: preliminary report.

Between October 1991 and March 1993, 281 consecutive patients underwent non-emergency isolated coronary artery surgery under the care of one surgeon (A.R.). They were prospectively randomised to receive either intermittent cold (Group I-144 patients) or continuous warm (Group II-137 patients) blood cardioplegia for myocardial protection. There were no significant differences in clinical outcome between the two groups, as judged by operative mortality, rates of peri-operative myocardial infarction, blood loss, need for circulatory support, post-operative neurological deficit, or duration of intensive care or hospital stay. However, sinus rhythm returned spontaneously with greater frequency (91.2% vs 45.8%, P < 0.001) in Group II patients. There was greater transmyocardial oxidative stress in Group I patients, as evidenced by a significant rise in oxidised glutathione in coronary sinus blood on myocardial reperfusion. Also, the serum CKMb isoenzyme level 2 h post-operatively was significantly raised in Group I patients, although this difference had disappeared by the day after surgery. In conclusion this preliminary report suggests that continuous warm blood cardioplegia provides comparable myocardial protection to that achieved with standard hypothermic techniques in patients undergoing coronary artery surgery.

8043289

Neurological complications during myocardial revascularization using warm-body, cold-heart surgery.

Does the use of warm-body perfusion in elderly patients with severe cerebrovascular disease lead to a higher incidence of stroke, due to hypotension secondary to low systemic vascular resistance? Two thousand, three hundred eighty-three (2,383) consecutive myocardial revascularizations were performed (1987-1992) using warm-body (perfusion 37 degrees C), cold-heart surgery (cold cardioplegic arrest). The perfusion pressure was maintained between 50-70 torr; hematocrit was kept around 20%. Prospective data during hospitalization revealed 23 operative deaths (1%), and 24 patients (1%) who developed new neurological signs after surgery. The latter formed three groups: Group I consisted of six patients with severe neurological deficits, who never regained consciousness and died after support systems withdrawal. Group II included 14 patients with postoperative clinical evidence of focal cerebral infarction (9 had hemiplegia, 2 had visual disturbance, and 3 showed alteration of memory), all of whom had residual defects at discharge; Group III was composed of four patients with minor neurological deficits after surgery (hemiparesis, gait disturbance, mental changes) which had cleared up by discharge. These data were compared retrospectively with 1605 patients (1980-1986) undergoing myocardial revascularization with moderate (25-30 degrees C) hypothermia and the same surgical team and operative techniques. Both groups had similar preoperative demographics except the warm group included more elderly patients, higher numbers with unstable angina and poor ejection fraction, and more frequent use of a mammary artery conduit. Neurological complications were 1% and 1.3% for the normothermic and hypothermic perfusion groups respectively. Incremental risk factors of stroke remain: age over 70 years, diffuse atherosclerosis of the aorta, carotid occlusive disease, and severe hypotension during perfusion.(ABSTRACT TRUNCATED AT 250 WORDS)

8043288

Major pulmonary resection by video assisted mini-thoracotomy. Initial experience in 35 patients.

Video-assisted thoracic surgery is emerging as a viable approach to increasingly complex intrathoracic therapeutic procedures. From February to July 1993, 35 patients (25 male, 10 female; mean age = 60 years, range: 17-74) underwent a major pulmonary resection using a video-assisted technique: lobectomy (n = 30) or pneumonectomy (n = 5). Pathology disclosed bronchogenic carcinomas (n = 26), metastases (n = 3), and miscellaneous disorders (n = 6). All procedures required one 10.5 mm port for the video-camera, one 3.5 to 5 cm utility thoracotomy through which surgical instrumentation was inserted and the operative specimen removed, and one occasional supplementary 12 mm port. Lung resections were performed with separated dissection and division of each component of the pedicle. The mean operative time was 145 min (SD: +/- 17). There were two postoperative deaths (5.7%) that were not directly related to the technique. Seven patients (20%) experienced non-fatal complications. After lobectomy, the mean duration of chest tube placement was 7.3 days (SD: +/- 1.6). The mean hospital stay was 11 days (SD: +/- 3). All the patients experienced minor postoperative chest pain. We conclude that video-assisted lung resections are technically feasible without an increased risk.

8043287

Thymectomy and malignancy.

Three hundred ninety patients who underwent thymectomy for myasthenia gravis (MG) were followed up to investigate the development of associated malignancies. There were 102 patients with thymoma and 288 without thymoma. Malignant neoplasms were detected in ten patients, four of whom already had the tumor at the time MG was diagnosed. Thus, malignancy developed after thymectomy in six patients. Malignant fibrous histiocytoma (MFH) developed in three patients, as well as gastric cancer, gastric leiomyosarcoma, rectal cancer, liver cancer, lung cancer, breast cancer, and thymic carcinoid in one patient each. Nine of the ten malignancies developed in the thymoma group, and only one in the non-thymoma group. The predicted number of patients with malignancy was 2.63 in the thymoma group and 2.65 in the non-thymoma group. Our findings suggest that the presence of thymoma facilitates the occurrence of extrathymic malignancy, and that thymectomy never enhances the occurrence of malignancy but possibly inhibits it.

8043286

Pneumonectomy for bronchogenic carcinoma in the elderly.

We have reviewed 70 consecutive elderly patients (70 years or older) who underwent pneumonectomy for bronchogenic carcinoma, in order to evaluate morbidity, mortality, and long-term survival. The majority of the patients had stage II (n = 32) or III (n = 25) disease. Fifteen deaths occurred in the peri-operative period (21%). Pre-operative factors associated with peri-operative death included a history of ischaemic heart disease (P = 0.001) and right-sided tumour (peri-operative mortality for right pneumonectomy = 37%, left pneumonectomy = 6%, P = 0.001). Poor lung function (as assessed by pre-operative spirometry), peripheral vascular disease, cerebrovascular disease, diabetes mellitus, and hypertension were not significant risk factors for peri-operative death. Post-operatively, the requirement for ventilation, or the development of post-operative myocardial infarction, adult respiratory distress syndrome and respiratory failure were significantly associated with peri-operative death. Over 60% of the patients developed one or more complications. The absolute survival rates for operative survivors were 51% and 27% at 1 and 5 years, respectively (stage I, 60% and 40%; stage II, 63% and 33%; stage III 33% and 14%). The absolute overall survival rates were 40% and 21% at 1 and 5 years, respectively. We conclude that pneumonectomy is justified in elderly patients but right-sided lesions and ischaemic heart disease should be considered as relative contra-indications.

8043285

In vivo comparison of free coronary grafts using the inferior epigastric (IEA), the gastroepiploic (GEA) and the internal thoracic artery (ITA).

The validity of alternative arterial conduits for myocardial revascularization in comparison to internal thoracic artery (ITA) has not been sufficiently defined. Evaluation of the functional in vivo vascular properties of the different conduits may be appropriate to give a perspective on long-term graft qualities. The intraoperative function of single free grafts to the left anterior descending artery (LAD) was compared in inferior epigastric (IEA, n = 13), internal thoracic (ITA, n = 12) and gastroepiploic artery (GEA, n = 12) conduits. Graft flows were measured at four points of time, 1) in situ free flow after distal dissection (IEA: 42.2 ml/min, ITA: 68.8 ml/min, GEA: 61.1 ml/min), 2) free flow following proximal grafting to the aorta (IEA: 48.1 ml/min, ITA: 63.7 ml/min, GEA: 84.2 ml/min), 3) selective graft flow after distal attachment to the LAD (IEA: 52.6 ml/min, ITA: 77.5 ml/min, GEA: 102.8 ml/min), and 4) selective LAD graft flow following paraverine (Pap) stimulation (IEA: 98.4 ml/min, ITA: 128.0 ml/min, GEA: 142.9 ml/min). Endothelium-dependent and -independent relaxation was evaluated by examination of the intraluminal graft pressures at mechanically controlled constant flow rates. Following stimulation with substance P (SP), the change of intraluminal pressure (dp) was similar in IEA (dp: -20.0 mmHg) and GEA grafts (dp: -21.1 mmHg). Only ITA conduits were less reactive to SP (-9.7 mmHg). The response to acetylcholine (ACh) could only be assessed in ITA (dp: -16.0 mmHg) and IEA (dp: -10.7 mmHg) grafts. Gastroepiploic arteries did not react on ACh stimulation (dp: +0.4 mmHg).(ABSTRACT TRUNCATED AT 250 WORDS)

8043284

The morphology of the inferior epigastric artery has implications on its use as a conduit for myocardial revascularization.

The inferior epigastric artery (IEA) is a new arterial graft for myocardial revascularization. We examined the inferior epigastric artery, the internal thoracic artery (ITA) and representative sections of the coronary arteries in 45 postmortem examinations, for microscopic signs of atherosclerosis. In addition, a morphometric evaluation of the intima and media of both conduits was performed. The intima of the ITA is significantly thicker, but atherosclerosis is absent. There are fewer fenestrations/mm in the internal elastic lamina (IEL) (4.00 +/- 1.60 versus 4.62 +/- 1.46) of the IEA and the combined thickness of media and intima is lower (0.20 +/- 0.04 mm versus 0.30 +/- 0.06 mm). However, 24% of IEAs showed medial calcification of variable degrees. We conclude that the IEA should not be used routinely for myocardial revascularization until the long-term patency of this graft has been explored.

8043283

The freedom from atherosclerosis of intramyocardial coronary arteries: reduction of mural stress--a key factor.

The phenomenon that coronary arteries which course entirely intramyocardially remain immune to atherosclerosis was investigated in 250 patients undergoing coronary bypass surgery. In 26 the circumflex artery gave off major branches whose distal portions ran entirely intramyocardially, which required coronary bypass grafting because of proximal disease. Of these, 24 had no atherosclerosis in the intramyocardial segment, one had a calcified plaque, and one had a recanalized thrombus. The cause of this phenomenon was studied further in 14 canine hearts by measuring intramyocardial pressure. The intramyocardial pressure in the subepicardial region was as high as 63% of the left ventricular cavity pressure and in the subendocardial region it was even greater than the left ventricular cavity pressure, which indicates that the pressure gradient across the artery wall is significantly reduced, and sometimes even eliminated. It is therefore concluded that the freedom from atherosclerosis of the intramyocardial coronary arteries is due to the lack of mural stress, i.e. the lower or absent transmural pressure gradient.

8043282

Musashi, a neural RNA-binding protein required for Drosophila adult external sensory organ development.

A family of neural RNA-binding proteins has recently been described in both vertebrates and invertebrates. We have identified a new member of this family, the Drosophila musashi (msi) locus, which is required for development of adult external sensory organs (sensilla). In contrast with wild-type sensilla, which contain two outer support cells, the msi mutation typically results in the appearance of extra outer support cells. The msi putative RNA-binding protein is localized to the nucleus and appears to be expressed in all cells in each sensillum and predominantly in neurons during embryogenesis. We propose that the msi protein regulates sensillum development by controlling the expression of target genes at the posttranscriptional level.

8043281

Immunohistochemical localization of metabotropic glutamate receptors, mGluR2 and mGluR3, in rat cerebellar cortex.

The distribution of the metabotropic glutamate receptors mGluR2 and mGluR3 was immunohistochemically examined in the rat cerebellar cortex at both light and electron microscope levels. An antibody was raised against a fusion protein containing a C-terminal portion of mGluR2. On immunoblot, the antibody reacted with both mGluR2 and mGluR3 in rat brain. mGluR2/3 immunoreactivity was expressed in cell bodies, dendrites, and axon terminals of Golgi cells, as well as in presumed glial processes. Golgi axon terminals with mGluR2/3 immunoreactivity were often encountered in the vicinity of glutamatergic mossy fiber terminals. The results suggest that transmitter glutamate may exert control influences upon Golgi cells not only through dendritic mGluR2/3, but also through axonal mGluR2/3.

8043280

Visualization of A beta 42(43) and A beta 40 in senile plaques with end-specific A beta monoclonals: evidence that an initially deposited species is A beta 42(43).

To learn about the carboxy-terminal extent of amyloid beta-protein (A beta) composition of senile plaques (SPs) in the brain affected with Alzheimer's disease (AD), we employed two end-specific monoclonal antibodies as immunocytochemical probes: one is specific for A beta 40, the carboxyl terminus of A beta 1-40, while the other is specific for A beta 42(43). In the AD cortex, all SPs that were labeled with an authentic antibody were A beta 42(43) positive, while only one-third of which, on the average, were A beta 40 positive. There was a strong correlation between A beta 40 positivity and mature plaques. Two familial AD cortices with the mutation of beta-amyloid protein precursor 717 (beta APP717) (Val to Ile) showed a remarkable predominance of A beta 42(43)-positive, A beta 40-negative plaques. Diffuse plaques, representing the earliest stage of A beta deposition, were exclusively positive for A beta 42(43), but completely negative for A beta 40.

8043279

A sequence in the main cytoplasmic loop of the alpha subunit is required for assembly of mouse muscle nicotinic acetylcholine receptor.

We have investigated the role of intracellular cytoplasmic sequences in the assembly of the mouse muscle nicotinic acetylcholine receptor (AChR) transiently expressed in COS cells. A chimeric protein in which the region from M1 to M4 of the alpha subunit was replaced by the corresponding region in the beta subunit was unable to support AChR assembly when substituted for the alpha subunit; a chimeric alpha subunit containing only the long cytoplasmic loop from the beta subunit was likewise inactive. Systematic mutation of short segments of the loop identified a sequence of 17 amino acids near the C-terminal end of the loop for which the beta sequence could not be substituted. Each of the inactive chimeric and mutated alpha subunits bound alpha-bungarotoxin when expressed alone and formed a heterodimer when expressed with the delta subunit. An alpha subunit truncated after M1 formed both an alpha delta heterodimer and an alpha delta beta heterotrimer, demonstrating that the cytoplasmic loop is dispensable for the early steps of assembly. A sequence in the long cytoplasmic loop of the alpha subunit thus appears to play a role in a late step of AChR assembly.