Tacrolimus versus cyclosporine induction therapy in pulmonary transplantation in miniature swine.

OBJECTIVE: Tacrolimus has been shown to provide superior immunosuppression in various solid organ transplant settings. The purpose of our study was to compare the survival of porcine lung allografts after induction with either cyclosporine A (CsA) or tacrolimus. METHODS: Single lung transplantation from MHC mismatched donors was performed in 10 minipigs. Immunosuppression included 1.5 mg/kg per day methylprednisolone and 1.0 mg/kg per day azathioprine. CsA (n=5) was adjusted to trough levels of 300-500 ng/ml, tacrolimus (n=5) was adjusted to 16-26 ng/ml. All immunosuppressive drugs were discontinued on postoperative day (POD) 28. Allograft survival was monitored by sequential chest radiographs, bronchoscopy and transbronchial biopsy histology. Peripheral blood leukocytes were scanned for donor chimerism and CD3, CD4, CD8 and CD25 expression. RESULTS: The animals survived a 4-week course of immunosuppression without radiological or histological signs of rejection on POD 28. Median allograft survival in CsA-treated animals was 55+/-15 days and all animals rejected their grafts within 42 days after withdrawal of immunosuppression. In tacrolimus-treated animals, median survival was 152+/-65 days with the longest survivor being electively sacrificed on POD 390 (P=0.0064). The degree of donor leukocyte chimerism and the frequency of CD4+CD25+ T-cells were higher in the tacrolimus group, however, these differences were not statistically significant. CONCLUSION: The results of our study show that primary immunosuppression with tacrolimus is superior to cyclosporine after pulmonary allotransplantation in a large animal model.     

A genetic study in hypertrophic cardiomyopathies (Czech population).

In order to verify the type of heredity and to identify other genealogical characteristics in the Czech population, the authors examined 105 families with incidence of hypertrophic cardiomyopathy (HCM). The probands' siblings presented a 24-percent empiric risk of the disease; in male probands the risk for brothers was four times that for sisters, in female probands it was three times higher for sisters than brothers. Sex ratio of affected siblings was 20:4 in male and 3:14 in female probands. Disease risk for children was substantially higher in younger probands (under 30 yrs. of age: 40%, above 51 yrs.: 6.7%). Reproduction fitness was decreased in the whole group more so in women. Gene penetration was estimated using the "safe carriers" method, as 50 p.c. Anticipation and more severe course were recorded in all families with HCM incidence in more than two generations. The HCM heredity does not resemble that of the autosomal dominant type. The heterogeneity, phenocopy and sexual modulation could not be excluded. Genetic counselling and, possibly, DNA diagnostics would be necessary to elucidate the hereditary nature of hypertrophic cardiomyopathy.     

Effect of accuracy constraint on joint coordination during pointing movements

Given the number of muscles and joints of the arm, more ways are available to produce an identical hand movement when pointing to a target than are strictly necessary. How the nervous system manages these abundant degrees of freedom was the focus of this study of pointing to targets of low and high indices of difficulty (ID). Two essential features of movement synergies were examined. The first reflects the preferred relations among the outputs of each movement element and was studied through principal component analysis. The second feature of synergy reflects the flexibility of those relationships evidenced by the use of multiple, goal-equivalent solutions to joint coordination. This second feature, which is the main focus of this report, was studied using the uncontrolled manifold approach. Motor abundance was defined operationally as the component of variance of joint combinations that left unchanged the value of important performance variables (goal-equivalent variability, GEV). This variance component was contrasted with the component of variance leading to a change in the value of these variables (non-goal-equivalent variability, NGEV). The difference between GEV and NGEV was evaluated with respect to the performance variables movement extent, movement direction, and path of the arm's center of mass. More than 90% of the variance of joint motions across the pointing trial were accounted for by one principal component, indicating a consistent temporal coupling among most joint motions in a single functional synergy. The flexible nature of this synergy was revealed by the variability analysis. All subjects had significantly higher GEV than NGEV for most of the movement path. Thus, variable patterns of joint coordination did not represent noise but the use of equivalent coordinative solutions related to stabilizing important performance variables. Higher GEV than NGEV was present regardless of the task's ID. One exception was at the time of peak velocity, leading to poorer control of movement extent than movement direction. Increasing the task's ID led to an overall reduction of joint configuraion variance, particularly GEV. These results support earlier work indicating that the use of goal-equivalent solutions to joint coordination is a common feature of the control of this and many other motor tasks. Functionally important performance variables appear to be controlled through flexible but task-specific coordination among the motor elements Electronic Publication     

Prefrontal enlargement of CSF spaces in agoraphobia: a qualitative CT-scan study.

1. This CT study was designed to assess brain morphology in 21 patients with agoraphobia and 21 normal control subjects matched for age and sex. 2. Internal and external CSF spaces were evaluated by qualitative assessment on a 3-point scale (normal, questionable, abnormal). 3. Patients showed bilateral enlargement of prefrontal CSF spaces (p < .05). The rating abnormal" was given in the left hemisphere to 6 (28.6%) of the patients, to 4 (19%) of the patients in the right hemisphere, but to none (0%) of the normal controls. 4. These findings suggest that alterations in brain morphology are involved in the etiology of agoraphobia.     

Potential preventive strategies and therapies in urinary tract infection

There are perhaps five strategies either presently advocated or under investigation for prevention of recurrent urinary tract infection (UTI): antibiotics, including natural peptides; functional foods; vaccines; probiotics; and miscellaneous, including avoidance of spermicides and maintenance of good hygiene. It is not possible to state the proportion of patients using antibiotics versus foods such as cranberry or using alternative approaches such as avoidance of spermicides. The majority of women who are referred to specialists will be prescribed long-term, low-dose antibiotics. However, given the magnitude of the problem, it is safe to state that large numbers of women are at least experimenting with alternative remedies such as drinking of cranberry juice or ingestion of herbal remedies with a view to enhancing their immune response. Vaccine development remains a long way from human use and has yet to be developed for organisms other than Escherichia coli. The use of probiotics to restore the normal vaginal flora and provide a competitive bacterial barrier to pathogens is close to becoming available as an alternative preventive approach. The next decade should see the introduction of new methods for reduction of the high incidence of UTI and better management of recurring urogenital infections.     

Inhibition of uropathogenic biofilm growth on silicone rubber in human urine by lactobacilli – a teleologic approach

The ability of three Lactobacillus strains to inhibit the adhesion and growth of naturally occurring uropathogens on silicone rubber was investigated in human urine. The importance of biosurfactant production by Lactobacillus in discouraging uropathogen growth was determined in relation to the binding affinities of the lactobacilli for silicone rubber. L. fermentum B54 markedly inhibited uropathogen growth on the silicone rubber disks after 8 days for all five men included in the study, albeit to various extents ranging from 77% to 100%. In urine from women, however, this inhibition was less clear, as it was absent for two of the four women participating in this study. L. casei rhamnosus 36 completely discouraged uropathogen growth on the disks after 8 days for three of the four women, whereas its effect in urine from men was less pronounced (inhibition ranged from 48% to 100% and was absent for one man). L. casei rhamnosus ATCC 7469^T was the least inhibitory Lactobacillus strain tested and inhibition was absent for a number of both male and female participants, possibly as a result of the low binding affinity of this strain for silicone rubber and of its inability to release biosurfactants. We conclude that the inhibition of uropathogen growth is dependent on the Lactobacillus strain involved, and for L. fermentum B54 it was demonstrated to be sex-related. Hence, inhibition must be considered a multifactorial process.