R 75251, a new inhibitor of steroid biosynthesis

R 75251, a new imidazole derivative, inhibited the conversion of androgens to estrogens, of progestins to androstenedione and testosterone, and of 11-deoxycorticosterone to corticosterone in human placenta microsomes, subcellular fraction of rat testis, bovine adrenocortical mitochondria, in cultured rat granulosa, testicular and adrenal cells, respectively. In vitro, no effect on cholesterol synthesis and cholesterol side-chain cleavage was found at concentrations up to 10 microM. In rat granulosa cells, no effect on progesterone production was detected. In vitro, no effect on steroid radioligand binding was observed. In male volunteers, a single dose of 300 mg of R 75251 significantly lowered plasma testosterone and estradiol for 24 hours and increased plasma concentration of 17 alpha-hydroxyprogesterone and progesterone. As compared with ketoconazole high dose (600 mg b.i.d), R 75251 (300 mg b.i.d) was at least as efficacious as inhibitor of testosterone synthesis when studied during ACTH stimulation. In contrast to ketoconazole, R 75251 did not significantly affect circulating adrenal androgen levels in male volunteers. Precursors of gluco- and mineralocorticoids such as 11-deoxycortisol and 11-deoxycorticosterone accumulated more than after ketoconazole administration. The data show that the cytochrome P450-dependent aromatase, 17-hydroxylase/17,20-lyase, and 11-hydroxylase are the target enzymes for R 75251.     

Penile flow- and blood pressure index and the effective dose of intracavernous papaverine

A simple test to predict the outcome of intracavernous papaverine treatment would be helpful in the management of erectile dysfunction. Doppler studies of the flaccid penis were compared with the results of intracavernous injection of papaverine. There was no correlation between these two. Therefore Doppler studies of the flaccid penis are not appropriate to predict the effect of intracavernous injection.     

Development of progressive glomerulosclerosis in experimental chronic serum sickness

A rat model of chronic serum sickness was used to study the pathogenesis of progressive glomerulosclerosis complicating experimental immune-complex glomerulonephritis. Chronic serum sickness was induced by immunising rats with bovine serum albumin followed by intraperitoneal administration of the antigen. Early lesions consisted of mesangial deposits of rat immunoglobulins, followed later by transient subendothelial and persistent subepithelial immune aggregates. On the basis of the peak level of proteinuria around day 80, three groups of rats were distinguished: I physiological proteinuria; II 50-500 mg/24 h; and III greater than 500 mg/24 h. The animals were killed at day 220 and the presence of mesangial proliferation, epithelial proliferation, and synechiae, as well as focal glomerulosclerosis was scored. It appeared that all and only proteinuric animals developed progressive glomerulosclerosis, although all three groups of animals passed through a phase with mesangial and subendothelial immune deposits. A strong correlation was found between the degree of proteinuria and the proportion of glomeruli affected. We conclude that the combination of mesangial and subendothelial deposits on the one hand and subepithelial deposits associated with increased protein loss on the other constitute a conditio sine qua non for the development of progressive glomerulosclerosis in this model. The use of specific antibodies to investigate the composition of the sclerotic lesions showed the presence of laminin and type IV collagen, but not of types I and III collagen in sclerotic areas of glomeruli. This indicates that the development of progressive glomerulosclerosis in this model is due to an increased production of glomerular basement membrane components by presumably solely glomerular cells after the occurrence of immunological glomerular injury.     

Predictive factors of mortality and morbidity in colectomy patients over 75 years of age. Report of 69 cases

Sixty nine patients over 75 years old who had a colectomy were retrospectively studied. The carcinoma of the colon represented the main indication for 42 cases (60.9%) and 22 patients (31.9%) were immediately operated. The influence of parameters such as age, sex, visceral defects, emergency, performance of a colostomy or associated intervention, type of colic pathology, was statistically studied. The age (p less than 0.05), emergency (p less than 0.03) and the number of defects greater than or equal to 3 (p less than 0.04) contribute to mortality. The number of defects greater than or equal to 3 (p less than 0.006) contributes to general morbidity. Only complications connected with the operation by itself significantly prolong the duration of hospitalization (p less than 0.02). The authors draw the conclusion that the age by itself is not a contra-indication for operation except in case of associated polyvisceral failure. In addition, it is required to carry out an early detection of colic lesions in elderly subjects in order to contemplate surgery before complications whose prognosis is fearsome (54.5% of death in emergency operation).     

Peak velocities of visually and nonvisually guided saccades in smooth-pursuit and saccadic tasks

 Smooth pursuit typically includes corrective catch-up saccades, but may also include such intrusive saccades away from the target as anticipatory or large overshooting saccades. We sought to differentiate catch-up from anticipatory and overshooting saccades by their peak velocities, to see whether the higher velocities of visually rather than nonvisually guided saccades in saccadic tasks may be found also in saccades in pursuit. In experiment 1, 12 subjects showed catch-up, anticipatory, and overshooting saccades to comprise 70.4% of all saccades in pursuit of periodic, 30°/s constant-velocity targets. Catch-up saccades were faster than the others. Saccadic tasks were run as well, on 19 subjects, including the 12 whose pursuit data were analyzed, with target-onset, target-remaining (saccade to the remaining target when the other three extinguish), and antisaccade tasks. For 17 of the 19 subjects, antisaccade velocities were lower than for either target-onset or target-remaining tasks. Velocities for the target-remaining task were near those for target onset, indicating that target presence, not its onset, defines visually guided saccades. Error and reaction-time data suggest greater cognitive difficulty for target remaining than for target onset, so that the cognitive difficulty of typical nonvisually guided saccade tasks is not sufficient to produce their lowered velocity. To produce reliably, in each subject, catch-up and anticipatory saccades with comparable amplitude distributions, nine new subjects were asked in experiment 2 to make intentional catch-up and anticipatory saccades in pursuit, and were presented with embedded target jumps to elicit catch-up saccades, all with periodic target trajectories of 15°/s and 30°/s. Velocities of intentional anticipatory saccades were lower than velocities of intentional catch-up saccades, while velocities of intentional and embedded catch-up saccades were similar. Target-onset and remembered-target saccadic tasks were run, showing the expected higher velocity for the target-onset task in each subject. Both experiments demonstrate higher peak velocities for catch-up saccades than for anticipatory saccades, suggesting that cortical structures preferentially involved in nonvisually guided saccades may initiate the anticipatory and overshooting saccades in pursuit. Received: 1 December 1995 / Accepted: 25 February 1997     

Species-, serogroup-, and serovar-specific epitopes are juxtaposed in variable sequence region 4 of the major outer membrane proteins of some Chlamydia trachomatis serovars.

Synthetic peptides and murine monoclonal antibodies were used to map cross-reactive chlamydial epitopes. A species-specific epitope in the central region of variable sequence region 4 abuts the amino-terminal end of a B-serogroup-specific or F/G-serogroup-specific epitope, which in turn abuts known serovar-specific epitopes. The carboxyl-terminal portion of variable sequence region 4 (residues 297 to 314) comprises a region of end-to-end B-cell epitopes in some serovars of the B and F/G serogroups.     

Amelioration of hypertrophic cardiomyopathy using nonsurgical septal ablation in a cirrhotic patient prior to liver transplantation.

A 53-year-old male with hepatitis C cirrhosis, who had been refused liver transplantation because of hypertrophic cardiomyopathy (HC), underwent nonsurgical septal ablation using alcohol with resolution of his ventricular outflow obstruction. This patient was able to subsequently undergo a successful deceased donor liver transplantation. This is the first reported case of alcohol induced septal ablation being performed in a cirrhotic patient with HC. Such nonsurgical procedures may be attractive in cirrhotic patients who are refused access to liver transplantation because of high surgical risk.