Unexpected clinical remission of cholestasis after rifampicin therapy in patients with normal or slightly increased levels of gamma-glutamyl transpeptidase

OBJECTIVE: Rifampicin is an effective drug against pruritus in intrahepatic cholestasis. However, there is no specific hepatic disease in which its use could cause undoubtedly biochemical improvement. The aim of this study was to describe patients with complete remission of cholestatic symptoms after rifampicin therapy. METHODS: We reported three female patients with intrahepatic cholestasis with no evidence of viral, metabolic, or autoimmune liver diseases. Total bilirubin levels ranged from 13.2 to 27.2 mg/dl (before the first treatment with rifampicin), and in all of them gamma-glutamyl transpeptidase values were within the normal range or slightly increased. Rifampicin therapy was administered orally, without any concomitant drug, with an effective dosage of 5-17 mg/kg/day. RESULTS: In all patients, pruritus ceased completely and bilirubin returned to normal values. The symptoms recurred after rifampicin withdrawal on, at least, three occasions in each patient, and these symptoms were always eliminated after its reintroduction. The patients had a total of 16 cholestatic episodes during a follow-up of 8 yr, with a complete clinical recovery in all of them. Undergoing therapy with a suitable dosage of rifampicin, none of the patients had a cholestatic crisis even during a period for as long as 12 months. The diagnosis of two patients was consistent with benign recurrent intrahepatic cholestasis, and it was not well defined in the remaining. CONCLUSION: Rifampicin may induce clinical remission, and perhaps prevent clinical relapses of intrahepatic cholestasis with normal or slightly increased levels of gamma-glutamyl transpeptidase.     

Prostate specific origin of dipeptidylpeptidase IV (CD-26) in human seminal plasma

PURPOSE: A number of peptidases which can metabolize certain bioactive peptides and growth factors have been identified in seminal plasma. Our goal in this study was to determine molecular properties and the tissue source(s) for one of these peptidases, dipeptidylpeptidase IV (DPP IV), in human seminal plasma. MATERIALS AND METHODS: We measured the activities of DPP IV with the dipeptide glycylprolyl-p-nitroanalide and its molecular forms using immunoblotting of seminal plasmas of men who were vasectomized or with different sperm concentrations, and in prostatic and seminal vesicle secretions of men undergoing prostatic surgery. RESULTS: DPP IV in seminal plasma of vasectomized men was a membrane associated dimer comprised of subunits of approximately 110 kDa. Its activity did not differ in seminal plasmas of vasectomized, azoospermic, oligozoospermic and normozoospermic men indicating no correlation with the concentration of sperm originally present in the semen. The DPP IV antigen (CD -26) and enzymic activity were present in prostatic secretion, but absent from that of the seminal vesicles. These data indicate that the prostate gland is the primary source of DPP IV activity in seminal plasma. There was little variation in its activities in repeat seminal plasma samples from the same individual, and there was no change in its activity with age to 50 years. CONCLUSIONS: DPP IV in seminal plasma was derived from the prostate gland and it may be useful as a bioindicator of prostate function and/or disease with age in men.     

Isolation of antigens recognized by coeliac disease autoantibodies and their use in enzyme immunoassay of endomysium and reticulin antibody-positive human sera

BACKGROUND & AIMS: Smooth muscle cells resident in the intestinal wall play a significant role in the healing of the injured intestine and in the fibrosis that complicates Crohn's disease. The cytokine interleukin 1 beta (IL-1 beta) is involved in inflammatory bowel disease. The aim of this study was to determine the action of IL-1 beta on proliferation and collagen metabolism in human intestinal smooth muscle cells. RESULTS: IL-beta caused a three-fold increase in [3H]thymidine uptake at 100 pmol/L. This mitogenic effect was equipotent with that of platelet-derived growth factor when cells were exposed to IL-beta for 48 vs. 24 hours. IL-beta inhibited the secretion of procollagen into culture medium by 70% and the accumulation of newly synthesized procollagen in cells by 55%. In addition, IL-beta caused a concentration-dependent inhibition of steady-state levels of procollagen I and III messenger RNA (85% inhibition at 100 pmol/L) and a 3-5-fold augmentation of collagenase messenger RNA levels. CONCLUSIONS: IL-beta is mitogenic for human intestinal smooth muscle cells, but this action is associated with a concomitant down-regulation of collagen synthesis and secretion and an augmention of collagenase expression.     

Intestinal obstruction in southeastern Nigerian children

In a 10-year (1981-1990) retrospective study of acute intestinal obstruction in the University of Calabar Teaching Hospital, Calabar, Nigeria, of the 295 paediatric cases reviewed, the major causes were ascaris worms (25%) and intussusception (22%). Other important lesions include imperforate anus (11%), volvulus (10%), external hernias (9%) and adhesions (7%) each. Ascaris-induced and hernial obstruction were most rampant in children aged above 5 years while intussusception had its peak frequency at the ages one to 12 months. Intussusception was largely (95%) ileo-caecal; volvulus involved mainly the ileum and ileo-caecum in 50% of cases each. The obstructed hernias were more common in the umbilicus (59%) than the groin (41%). The mortality (13%) was chiefly due to associated infection but lack of expertise in management of cases cannot be ignored. Generally, the pattern of intestinal obstruction among children in this region appears markedly different from that seen in Europe and North America. There is a need to create a specialist paediatric surgical unit as a means of reducing morbidity and mortality from this condition.     

Development of systemic lupus erythematosus in a male patient after 14 years on hemodialysis

Graves' disease (GD), myasthenia gravis (MG), and polymyositis (PM) are organ-specific autoimmune diseases. The association between GD and MG is well known, and an association between MG and PM has been reported. However, only one patient with all three diseases has been reported. We describe a patient with GD and PM developing 6 and 29 years, respectively after the onset of MG. This case suggests that the expression of autoimmunity occurred over a prolonged period of time and these organ-specific autoimmune diseases may be induced by a similar mechanism.     

Coupled B-snake grids and constrained thin-plate splines for analysis of 2-D tissue deformations from tagged MRI

Magnetic resonance imaging (MRI) is unique in its ability to noninvasively and selectively alter tissue magnetization and create tagged patterns within a deforming body such as the heart muscle. The resulting patterns define a time-varying curvilinear coordinate system on the tissue, which we track with coupled B-snake grids. B-spline bases provide local control of shape, compact representation, and parametric continuity. Efficient spline warps are proposed which warp an area in the plane such that two embedded snake grids obtained from two tagged frames are brought into registration, interpolating a dense displacement vector field. The reconstructed vector field adheres to the known displacement information at the intersections, forces corresponding snakes to be warped into one another, and for all other points in the plane, where no information is available, a C1 continuous vector field is interpolated. The implementation proposed in this paper improves on our previous variational-based implementation and generalizes warp methods to include biologically relevant contiguous open curves, in addition to standard landmark points. The methods are validated with a cardiac motion simulator, in addition to in-vivo tagging data sets.     

Neuropsychological dose effects of a freon, trifluoromethane (FC-23), compared to N2O

Animal studies show FC-23 to be a promising magnetic resonance imaging indicator of regional cerebral blood flow. In a Phase 1, dose ranging (investigative new drug) study, neuropsychological (NP) tests, subjective ratings, and intensive physiological monitoring were used to determine the maximum tolerated concentration of FC-23 for human application. Five normal healthy male volunteers were exposed to concentrations of FC-23 between 10% and 60% [randomly interleaved with exposures to both room air and 40% nitrous oxide (N2O)] in a within-subjects, double-blind design. Analyses of individual cases and ranked group data showed that individuals tolerated the 30% concentration of FC-23 according to established criteria. Planned comparisons indicated that inhalation of FC-23 produced smaller NP changes and fewer negative symptoms than 40% N2O but poorer NP performance and more negative symptoms than room air. This study indicated that FC-23 is not inert and that humans do not tolerate concentrations suitable for current MRI technology. NP and subjective data assisted in characterizing the sedative effect of FC-23.