Pharmacological distribution diagrams: a tool for de novo drug design

BACKGROUND: There is no empirical data available on attitudes concerning AIDS and habits towards HIV infected patients of physicians in general or private practice. In this study results of a self-evaluation are presented. METHODS: 178 physicians working with out-patients in different medical fields were randomly selected for a cross sectional study and interviewed using a standardised questionnaire. RESULTS: 89% think that they are sufficiently informed about AIDS (in the USA 20%). They regarded the risk of infection to be lower than the Anglo-American physicians. They believed there is a lack of interchange of information between colleagues regarding the degree of infectiousness of referred patients. A third of the physicians fear that other patients will go elsewhere if they find out that their physician is treating AIDS patients. 54% would hold special clinic sessions for HIV-patients outside the normal schedule for practice times. 89% believed that HIV patients were partly to blame for their illness. CONCLUSIONS: Although the physicians recognise the problem of HIV-infection, they partly deny the real necessities and facts. A reason for this could be the emotions underlying the general attitude to everything pertaining to HIV-disease. Attitudes to HIV-disease and the dealing with it in daily practice must be considered on the basis of individual emotional motives.     

Experimental fetal tracheal ligation reverses the structural and physiological effects of pulmonary hypoplasia in congenital diaphragmatic hernia

Infants with congenital diaphragmatic hernia (DH) and profound pulmonary hypoplasia are currently unsalvageable. The authors previously demonstrated that tracheal ligation (TL) accelerates fetal lung growth and reverses the pulmonary hypoplasia of fetal nephrectomy. The purpose of this study was to determine if the pulmonary hypoplasia of experimental DH could be similarly reversed and, if so, whether the resulting lungs would show better function than those of their DH counterparts. Eighteen fetal lambs were divided into three experimental groups of six animals each. In group 1, DH was created at 90 days' gestation. In group 2, DH was created at 90 days' gestation and TL performed during the same operation. Group 3 consisted of sham-operated controls. These animals were delivered near full-term, and their lungs analyzed by standard morphometric techniques. Ten additional fetal lambs were divided into two experimental groups of five animals each. In group 4, DH was created at 90 days' gestation. In group 5, DH was created at 90 days' gestation and TL performed 20 days later, at 110 days' gestation. These animals were pressure-ventilated via tracheostomy over a 2-hour period in which PaO2, PaCO2, and compliance were measured. Intratracheal pressure (ITP) was measured at the time of delivery in all groups. Upon retrieval, DH animals had abdominal viscera in the chest and small lungs; in contrast, DH/TL animals had the herniated viscera reduced from the chest by enlarged lungs. DH/TL lungs showed markedly increased growth, with significant increases in lung volume:body weight ratio (LV:BW; P = .0001), alveolar surface area (ALV.SA; P = .0001), and alveolar number (ALV#) (P = .0001) when compared with those of the DH or control group. This growth was associated with a normal maturation pattern based on histological appearance, normal airspace fraction, and normal alveolar numerical density. ITP in the DH/TL group was increased when compared with that of DH and control animals (P = .0001). Total lung DNA and protein were both elevated in the DH/TL animals (P = .0001). However, the DNA:protein ratio remained normal, suggesting lung growth had occurred through cell proliferation, not by hypertrophy. When ventilated over a range of settings, DH/TL lungs were more compliant (P = .0001) and achieved higher PaO2s (P < .003) and lower PaCO2s (P = .0001) than their DH counterparts. From these data, the authors conclude: (1) Experimental fetal DH produces hypoplastic lungs that are not capable of adequate gas exchange with conventional ventilation.(ABSTRACT TRUNCATED AT 400 WORDS)     

False aneurysm of the left ventricle and coronary aneurysms in Beh?et disease

A false left ventricular aneurysm and coronary artery aneurysm were discovered in a 29 year old patient with Beh?et's syndrome. The operation under cardiopulmonary bypass consisted of closing the neck of the false aneurysm by an endo-aneurysmal approach with a Gore-Tex patch. The coronary artery aneurysms were respected. There were no postoperative complications. Cardiac involvement is rare in Beh?et's syndrome (6%). The originality of this case is the association of two aneurysmal pathologies: the coronary and ventricular aneurysms due to the angiitis and the myocardial fragility induced by ischaemia.     

A major isoform of the maize plasma membrane H(+)-ATPase: characterization and induction by auxin in coleoptiles

The plasma membrane (PM) H(+)-ATPase has been proposed to play important transport and regulatory roles in plant physiology, including its participation in auxin-induced acidification in coleoptile segments. This enzyme is encoded by a family of genes differing in tissue distribution, regulation, and expression level. A major expressed isoform of the maize PM H(+)-ATPase (MHA2) has been characterized. RNA gel blot analysis indicated that MHA2 is expressed in all maize organs, with highest levels being in the roots. In situ hybridization of sections from maize seedlings indicated enriched expression of MHA2 in stomatal guard cells, phloem cells, and root epidermal cells. MHA2 mRNA was induced threefold when nonvascular parts of the coleoptile segments were treated with auxin. This induction correlates with auxin-triggered proton extrusion by the same part of the segments. The PM H(+)-ATPase in the vascular bundies does not contribute significantly to auxin-induced acidification, is not regulated by auxin, and masks the auxin effect in extracts of whole coleoptile segments. We conclude that auxin-induced acidification in coleoptile segments most often occurs in the nonvascular tissue and is mediated, at least in part, by increased levels of MHA2.     

Head scatter modelling for irregular field shaping and beam intensity modulation

Scattered radiation from within the treatment head can contribute significant dose to all parts of a radiotherapy treatment field. A multileaf collimator may be used to create an arbitrarily shaped field, and may also be used, under dynamic control, to modulate the beam intensity over the field. This method of intensity modulation is effectively a superposition of a large number of fields which have the same beam direction, but different shapes, and some of these shapes may have unusually small dimensions, particularly in the direction of the leaf movement. Two models for predicting the head scatter under these conditions have been investigated. These are a first-order Compton scatter approximation from the flattening filter, and an empirical fit to measured data using an exponential function. The first model only considers scatter from the flattening filter and has been applied to field sizes between 2 cm by 2 cm and 10 cm by 10 cm, where agreements are all within 1%. However it is not satisfactory at larger field sizes where small scatter contributions, from scattering sources other than the flattening filter, are integrated over large areas. The second model uses measured data between 4 cm by 4 cm and 30 cm by 30 cm to optimize the exponential function and is used to calculate the head scatter contribution for all field sizes. In this case good agreement is achieved over the full field size range, and hence this is a more generally applicable model. Results are presented for static irregularly shaped fields and intensity modulated beams created using a Philips multileaf collimator.     

Fulminant Guillain-Barré syndrome with universal inexcitability of peripheral nerves: a clinicopathological study

The pathological basis of nerve inexcitability in Guillain-Barré syndrome has not been established with certainty. We report the clinicopathological findings in a 67-year-old patient with fulminant Guillain-Barré syndrome who died 18 days after onset. Three serial electrophysiological studies revealed nerve inexcitability. Antibodies to Campylobacter jejuni were present but there was no antiganglioside reactivity. Spinal root sections revealed extensive and almost pure macrophage-associated demyelination with occasional presence of T lymphocytes and neutrophil leukocytes. Conversely, in femoral, median, and sural nerves the outstanding lesion was axonal degeneration, with some denuded axons remaining. Unmyelinated fibers, posterior root ganglia, and dorsal columns were preserved. Endoneurial postcapillary venules showed plump endothelial cells with loss of their tight junctions. We conclude that both primary demyelination and axonal degeneration secondary to inflammation account for nerve inexcitability. Our findings lend support to the hypothesis of increased endoneurial pressure as the cause of wallerian degeneration in nerve trunks.     

Chances of cure are not compromised with sphincter-saving procedures for cancer of the lower third of the rectum

BACKGROUND: The goal of this study was to compare patterns of recurrence and long-term outcome after sphincter-saving procedures (SSPs) and abdominoperineal resection (APR) in patients with tumors located in the lower third of the rectum. METHODS: We reviewed the charts of 1001 patients operated on for primary rectal adenocarcinoma between 1980 and 1991. All patients with tumors located between 5 and 7 cm from the anal verge and treated with curative intent were included. RESULTS: Of the 261 patients who met our criteria, 162 had undergone SSP and 99 had undergone APR. The local recurrence rates for SSP and APR were 8% and 11%, respectively (p = 0.41), and the distant metastases rates were 23% and 28%, respectively (p = 0.35). Recurrence and distant metastases rates for SSP and APR, respectively, did not differ by TNM classification: state I, 10% versus 9% (p = 0.9); stage II, 25% versus 43% (p = 0.13); and stage III, 56% versus 57% (p = 0.92). Five-year disease-free survival rates for SSP and APR patients were 70.5% and 62.3%, respectively (p = 0.2). CONCLUSIONS: Tumors in the lower third of the rectum can be treated with sphincter-saving procedures without compromising the chance of cure.     

Long-term results after allogeneic bone marrow transplantation for chronic myelogenous leukemia in chronic phase: a report from the Chronic Leukemia Working Party of the European Group for Blood and Marrow Transplantation

The purpose of this study was to determine the long-term results of allogeneic bone marrow transplantation for chronic myeloid leukemia. A retrospective analysis was carried out of the outcome of 373 consecutive transplants performed at 38 European institutions between 1980 and 1988 and reported to the registry of the European Group for Blood and Marrow Transplantation. All transplants were carried out for first chronic phase of chronic myelogenous leukemia using unmanipulated marow cells from HLA-identical sibling donors. The probability of survival and leukemia-free survival at 8 years were 54% (95% CI: 49-59) and 47% (95% CI: 41-52) respectively. The probabilities of developing acute GVHD (II-IV) at 100 days and chronic GVHD at 4 years after transplant were 47% (95% CI: 41-53) and 52% (95% CI: 46-58) respectively. The probabilities of transplant-related mortality and leukemic relapse 8 years after BMT were 41% (95% CI: 36-48) and 19% (95% CI: 14-25), respectively. Transplant within 12 months of diagnosis was associated with reduced transplant-related mortality (34 vs 45%, P = 0.013) and resulted in improved leukemia-free survival (52 vs 44%, P = 0.03). The probability of relapse was significantly reduced in patients who developed chronic GVHD (RR = 0.33, P = 0.004). The probability of relapse occurring more than 2 years after transplant was increased more than five-fold in patients transplanted from a male donor (RR = 5.5, P = 0.006). Sixty-seven patients in hematologic remission were studied for residual disease by two-step RT/PCR for BCR-ABL mRNA and 61 (91%) tested negative. We conclude that bone marrow transplantation can induce long-term survival in approximately one-half of CML patients; the majority of survivors have no evidence of residual leukemia cells when studied by molecular techniques. The probability of late relapse is increased with use of a male donor.     

Increase of striatal dopamine release by cadmium in nursing rats and its prevention by dexamethasone-induced metallothionein

Repeated daily intraperitoneal (i.p.) administrations of cadmium (CdCl2, 1 mg/kg per day for 5 days) increased striatal dopamine (DA) release (180% of controls) and turnover (150% of controls) in 13-day-old rats. Cd treatment also increased striatal metallothionein (MT) content (161%), Cd (127%) and lipid peroxidation (LPO, 190%). In addition, Cd treatment decreased striatal tyrosine hydroxylase (TH) activity (-28%), and such an effect may result from D-2 receptor blockade as a consequence of excessive dopamine release, since sulpiride (a specific D-2 receptor antagonist) administration to Cd-treated rats abolished the effect of Cd on TH. No effect was observed on striatal monoamine oxidase (MAO) activity. Dexamethasone (Dx) treatment increased striatal MT content and caused no effect on either DA release or turnover. However, Dx administration prevented the effects caused by Cd, including the increased DA release and enhanced striatal lipid peroxidation. These results indicate that toxic effects on the brain are to be expected as a result of Cd exposure and that Dx administration can attenuate them.