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Objectives. We aimed to examine the strength of association between traditional cardiovascular risk factors and carotid plaque development in systemic lupus erythematosus (SLE) patients and controls. We also aimed to determine which lupus-related factors are associated with carotid plaque and whether SLE sensitizes patients to the effects of traditional factors. Methods. We studied 200 women with SLE and 100 controls. Demographic and risk factor data were collected and SLE features, including autoantibody profiles and therapy were noted. All subjects had B- mode ultrasound of their carotid arteries examined for the presence and distribution of plaque. Results. SLE patients

Human diabetic peripheral neuropathy is believed to have, at least in part, a microvascular basis. This study was designed to examine the effects of restoration of arterial blood supply on peripheral nerve function in six non-insulin-dependent diabetic patients with peripheral occlusive vascular disease. In the revascularised legs, transcutaneous oxygen increased from a median 37.5 (28.5-45.7 interquartile range) mmHg to 55.5 (53.5-62.5) mmHg, p = 0.036, mean increase 20.2 (14.8-25.6, 95% confidence intervals(CI) mmHg. This was accompanied by a significant improvement in peroneal motor nerve conduction velocity from 31.7 (26.5-36.3) m/s to 33.5 (32.9-39.4) m/s, p = 0.04, mean increase 4.7 (1.7-7.7, 95% CI) m/s. There was no significant change in transcutaneous oxygen or peroneal nerve motor conduction velocity in the contralateral control limbs. This improvement in conduction velocity with improved tissue oxygenation suggests that studies of agents which might indirectly bring about improvements in microvascular blood flow should be urgently considered.

Background Tissue engineering techniques have been employed successfully in the management of wounds, burns and cartilage repair. Current prosthetic alternatives to autologous vascular bypass grafts remain poor in terms of patency and infection risk. Growing biological blood vessels has been proposed as an alternative. Methods This review is based on a literature search using Medline, PubMed, ISIS and CAS of original articles and reviews, and unpublished material and abstracts. Results and conclusions Complete incorporation into host tissues and the maintenance of a viable and self-renewing endothelial layer are the fundamental goals to be achieved when developing a tissue-engineered blood vessel. Sourcing of cells and modulating their interaction with extracellular matrix and supporting scaffold have been the focus of intense research. Although the use of tissue-engineered blood vessels in humans is so far limited, advances in our knowledge of stem cell precursors and the development of new biomaterials should enable this technology to reach routine clinical practice within a decade.

We wish to identify genes associated with disease. To do so, we look for novel genes whose expression patterns mimic those of known disease-associated genes, a method we call Guilt-by-Association (GBA). GBA uses a combinatoric measure of association that provides superior results to those from correlation measures used in previous expression analyses. Using GBA, we have examined the expression of 40,000 human genes in 522 cDNA libraries, and have identified several hundred genes associated with known cancer, inflammation, steroid-synthesis, insulin-synthesis, neurotransmitter processing, matrix remodeling and other disease genes. The majority of the genes thus discovered show no significant sequence similarity to known genes, and thus could not have been identified by homology searches. We present here an example of the discovery of five genes associated with schizophrenia and Parkinson's disease. Of the 40,000 most-abundant human genes, these five genes are the most closely linked to the known disease genes, and thus are prime targets for pharmaceutical intervention.

Throughout the developed world, the population is aging at an alarming rate. This has become an issue of great concern. The growing number of elderly people within the community has several health and economic implications. The prevalence of atherosclerosis increases with age and directly impacts on the workload of both cardiac and vascular surgeons. The decision to operate should not be based on age alone but reflect an assessment of the risk benefit ratio of individual cases. Increased life expectancy, safer anaesthesia and less invasive surgical techniques have led to more patients being considered for surgical intervention. However, this will inevitably result in an overwhelming burden on national health resources, a factor that may force some practitioners to deny treatment on the grounds of chronological and not biological age.

Neural networks offer the potential of providing more accurate predictions of survival time than do traditional methods. Their use in medical applications has, however, been limited, especially when some data is censored or the frequency of events is low. To reduce the effect of these problems, we have developed a hierarchical architecture of neural networks that predicts survival in a stepwise manner. Predictions are made for the first time interval, then for the second, and so on. The system produces a survival estimate for patients at each interval, given relevant covariates, and is able to handle continuous and discrete variables, as well as censored data. We compared the hierarchical system of neural networks with a nonhierarchical system for a data set of 428 AIDS patients. The hierarchical model predicted survival more accurately than did the nonhierarchical (although both had low sensitivity). The hierarchical model could also learn the same patterns in less than half the time required by the nonhierarchical model. These results suggest that the use of hierarchical systems is advantageous when censored data is present, the number of events is small, and time-dependent variables are necessary.

This study was undertaken to determine the true incidence of renal impairment after aortic surgery and its association with intraoperative fluctuations in renal artery blood flow and cardiac output.Direct measurements of renal artery blood flow were undertaken with electromagnetic flowmetry in 19 patients undergoing elective infrarenal aortic surgery. Renal function was assessed before and after operation by measurement of creatinine clearance.Twelve patients (63%) had renal impairment as defined by a 40% or greater reduction in creatinine clearance after operation. This group of patients had significantly lower renal artery blood flow during the period of aortic cross-clamping than had those who preserved their renal function (p0.001).Renal impairment is common after infrarenal aortic surgery and may be a result of intraoperative ischemia secondary to reduced renal artery blood flow.

In an investigation of the effects of isovolemic hemodilution, 39 consecutive patients undergoing elective infrarenal aortic operation had detailed measurements of renal function, renal artery blood flow, and cardiac hemodynamics.The patients were randomly allocated to receive acute preoperative isovolemic hemodilution to a hematocrit of 28%, with 20 patients receiving hemodilution and 19 being control subjects.Twelve (63%) of the control group had renal impairment, compared with only four (20% in the group receiving hemodilution (p0.01). Hemodilution also prevented the fall in cardiac output induced by cross-clamping (p0.01) and significantly reduced the need for transfusion of donor blood (p0.01).Acute isovolemic hemodilution is clearly a useful adjunct in the management of patients undergoing elective aortic operation.

Transcutaneous oxygen, laser Doppler flowmetry, peroneal nerve motor conduction velocity and skin temperature were assessed in both legs of 34 diabetic patients, who had a mean age of 41 (range 29–77) years, and diabetes duration of 21 (3–34) years. Transcutaneous oxygen significantly correlated with peroneal nerve motor conduction velocity (r=0.59 p

Endothelial cells labeled with indium 111-oxine were seeded in supraconfluent densities onto fibronectin-coated expanded polytetrafluoroethylene (ePTFE) and gelatin-impregnated Dacron graft segments. These grafts with rapidly formed endothelial-cell monolayers were then exposed to varying shear stresses at flow rates of 200 and 300 ml/min, using tissue culture medium in an artificial flow circuit. As the loss of radioactivity represented endothelial-cell loss, cell retention was calculated by the ratio of counts recorded at different time points during 2 hours of flow to initial counts. Although initial cell adherence to gelatin-impregnated Dacron graft segments was poor compared to ePTFE, once cells were attached they resisted shear stress of flow better at 200 ml/min and equally well at 300 ml/min. The cell retention on fibronectin-coated ePTFE was 55.4 +/- 12.9% at 200 ml/min and 56.5 +/- 15.2% at 300 ml/min; cell retention for gelatin-impregnated Dacron graft segments was 69.0 +/- 6.0% and 66.5 +/- 5.5%, respectively. Qualitatively scanning electron microscopy of both ePTFE and gelatin-impregnated Dacron graft segments showed patchy coverage of grafts with cells. There was preferential attachment of endothelial cells to the nodes on ePTFE, although on gelatin-impregnated Dacron graft segments, cells conformed to the Dacron fibers at different levels and directions with evidence of bridging in the gaps between individual fibers. This study shows conclusively that rapidly formed endothelial-cell monolayers on ePTFE and gelatin-impregnated Dacron graft segments resisted a shear stress of flow equal to that seen in a femoropopliteal vein graft with significant cell retention at 2 hours.

Suppose that we wish to know the probability that an object belongs to a class. For example, we may wish to estimate the probability that a patient has a particular disease, given a set of symptoms, or we may wish to know the probability that a novel peptide binds to a receptor, given the peptide's amino-acid composition. The conventional approach is to first use a classification algorithm to find partitions in feature space and to assign each partition to a class, and then to estimate the conditional probabilities as the proportion of patients or peptides that are correctly and incorrectly classified in each partition. Unfortunately, this estimation method often gives probability estimates that are in error by 20% or more, and thus can cause incorrect decisions. We have implemented and compared alternative methods. In Monte Carlo simulations the alternative methods are substantially more accurate than is the current method.

Thirty-seven patients with stage 2 peripheral vascular disease were randomised to receive a six month course of Gingkco Biloba Extract (Tanakan) or matching placebo. Assessment, by claudication distance, A/B ratio, Doppler ankle pressure response to exercise together with recovery time, and a 10 cm analogue scale (LAS) estimation of maximal pain severity, was performed before treatment, and at 6, 12 and 24 weeks. LAS scores were significantly improved after 24 weeks in patients receiving EgB, but not placebo. Claudication distance was significantly increased by Egb. Although claudication distance also increased in the placebo group, this was not significant. A/B ratio and Doppler ankle responses to exercise did not show any significant change in either group at any time interval, nor did the post exercise recovery time. Gingkco Biloba Extract is a safe and effective method of improving walking distance and reducing pain severity in patients with intermittent claudication, although Doppler studies have failed to suggest any gross improvement in the perfusion of the ischaemic leg.

Isolated pairs of rabbit auricles have been observed in media containing 6, 24 or 75 mM-potassium, with corresponding reductions in sodium concentration. In 24 mM-potassium, adrenaline restored beating and excitability, as did calcium chloride, but ouabain had no effect. In 75 mM-potassium, adrenaline had no effect; calcium chloride caused a contracture; ouabain had no direct effect, but auricles which had been beating in the presence of ouabain contracted promptly on transfer to 75 mM-potassium. Left auricles, which do not beat spontaneously, were less sensitive to calcium and to ouabain. The results showed a membrane stabilizing action of calcium and an action on muscular contraction, and suggested that cardiac glycosides acted by causing accumulation of calcium at the activator site in the tissue.

Methods of comparing germination curves are described and these are discussed in relation to the problem under consideration. In a study of chemical factors which modify seed germination (here all inhibitory), the changes in the rate of germination appeared to be associated with the inhibitory factors. These curves could be adequately described by orthogonal polynomial regressions. It is noted that some coefficients devised to represent the course of germination were not adequate for these purposes. The reasons are discussed.

Myocardial infarction accounts for over 50 per cent of mortality following elective abdominal aortic surgery. Previous history of ischaemic heart disease and abnormal ECGs, common in vascular patients, are unreliable parameters for predicting myocardial response to stress. Exercise ECGs are often valueless, as claudication may mask myocardial insufficiency. Myocardial performance was studied preoperatively in 29 consecutive patients undergoing elective aortic bifurcation grafting, using a Swann-Ganz catheter to measure the rise in pulmonary artery wedge pressure (PAWP) produced by rapid intravenous infusion of plasma (200–400 ml). A Frank-Starling Curve was obtained by plotting LVSWI against PAWP. Two important values were obtained: (a) ‘Upslope’ or gradient of the ascending portion of the curve. Low values identify patients most at risk from cardiac complications. Six patients who suffered from postoperative cardiac complications had a mean ‘upslope’ value of 1·568 ± 0·681 (1 s.e.m.), whereas the 23 who did not, had a mean value of 7·094 ± 0·745 (1 s.e.m.), a significant difference (P < 0·001); (b) ‘PAWPmax’, the ventricular filling pressure above which work output dropped. Infusion beyond this may precipitate pulmonary oedema. PAWP was observed at levels greater than PAWPmax in all 6 patients who developed either pulmonary oedema or myocardial infarction. The myocardial performance curve can reliably identify high risk patients and permit control of intravenous therapy within individual safety limits, thereby preventing pulmonary oedema.

In 1974, between 2 and 8% of the 50,000 adult patients undergoing cardiac surgery in this country succumbed in the early post-operative period from left ventricular failure, despite various methods of pharmacologic and/or mechanical support. Our laboratories have concentrated on the development, modification, evaluation, and validation of an abdominally positioned left ventricular assist device which has the potential of reducing these mortalities. Continuous testing in animals, for periods exceeding 2 mos, satisfied reliability, durability and longevity requirements. The cumulative results of these investigations were reviewed at the National Heart and Lung Institute on August 21, 1975. Authorization for clinical trials of the device according to specific criteria and protocols46 was approved on November 1, 1975. The ALVAD is now in the early stages of clinical testing. The results of the current experiments demonstrate that ventricular outflow impedance and prosthetic inflow impedance are the major determinants of left ventricular assist device hemodynamic effectiveness. By markedly reducing outflow impedance, the ALVAD profoundly lowers ventricular pressure-work and oxygen demands while simultaneously increasing ventricular performance and maintaining or augmenting systemic perfusion. Moreover, our studies indicate that improved device designs (intended for intermediate and long-term implantation) and maximal performance can be achieved by focusing on these central determinants.

One hundred patients with phlebographically proved acute deep vein thrombosis of the legs were prospectively randomised into two treatment groups to compare the safety and efficacy of subcutaneous calcium heparin versus intravenous sodium heparin administered by constant infusion pump. The dose of heparin was determined by daily measurement of the kaolin cephalin clotting time. Treatment was maintained for up to 14 days, after which phlebography was repeated. Of 49 patients who received subcutaneous calcium heparin, two showed an increase in thrombus size, while eight showed complete lysis. In the 47 patients who received intravenous sodium heparin thrombus increased in size in 13 while only one showed evidence of complete lysis. These differences were significant. There were no significant differences between the two groups in the incidence of serious complications, although almost half of those receiving intravenous heparin had some minor problem with the constant infusion pump and just over half of those receiving subcutaneous heparin had some bruising at the injection site. This study showed that subcutaneous calcium heparin was more effective in helping lyse existing thrombus and preventing its propagation than intravenous sodium heparin.

Weisse Mause wurden 3 Wochen auf einem endlosen Band trainiert. Ihre Skelettmuskeln zeigten in vitro erhohte isometrische Spannung und geringere Ermudung bei tetanischer Reizung. Die Zunahme an Faserquerschnittsflache dieser Muskeln war relativ geringer als die Zunahme der Kraftentwicklung. Es wird angenommen, dass diese Disproportionalitat als Resultat einer Verdickung der Myofibrillen zu deuten ist.

Mit Hilfe eines Gradientenkalorimeters wurde die Warmeproduktion der weissen Laboratoriumsmaus wahrend des Wachstums verfolgt und 3 Stadien unterschieden: 1. anfanglich niedrige Warmeproduktion, 2. nach 5 Tagen starker Anstieg, 3. bei Sexualreife Absinken auf ein Plateau. Warmeabgabe durch Strahlung, Verdunsten, Leitung und Konvektion wurde separat registriert.