Atypical antiglomerular basement membrane disease associated with thin membrane nephropathy

Antiglomerular basement membrane (anti-GBM) disease is characteristically described with linear deposition of IgG along the GBM. We report two unusual cases of IgA and IgM anti-GBM disease associated with diffuse thinning of the GMB, and review the literature on atypical immunoglobulin species in this disorder. Both patients were male, aged 55 and 49 years, and presented with isolated microscopic haematuria, neither having shown evidence of impaired renal or pulmonary function on follow-up for 4 and 6 years respectively. Renal histology revealed minor focal mesangial changes only, but immunoperoxidase preparations demonstrated intense linear staining of the GBM with IgA in one case, and IgM with C3 in the other. On electron-microscopy there was diffuse thinning of the GBM in both cases, mean thickness 220 and 295 nm respectively (normal range 350-450 nm). Antinuclear antibodies were not detected and their glucose tolerance tests were normal. Assays for circulating IgG anti-GBM antibodies using indirect immunofluorescence (IF) and radioimmunoassay (RIA) were negative in both patients, although IgA anti-GBM antibodies with specificity confirmed by inhibition studies were identified in the first case. Thin GBMs in these patients may expose the Goodpasture antigen to toxic or infectious insults, thus altering its antigenic profile and promoting this unusual immune response.     

Portal venous velocity in biliary atresia

From December 1986 to April 1989, 38 patients with biliary atresia (eight newly diagnosed) were evaluated with doppler ultrasound of the portal venous system. Peak and mean velocities were computer derived from the spectral waveform. Good velocity was greater than 15 cm/s, intermediate velocity was 8 to 14 cm/s, abnormal velocity was less than 7 cm/s or hepatofugal. Patients were grouped according to clinical status: group 1 (n = 14), normal liver function; group 2 (n = 15), recurrent cholangitis; group 3 (n = 2), established bile drainage but complicated cirrhosis; group 4 (n = 7), failed portoenterostomy. All patients with normal liver function (group 1) had good or intermediate velocities. Thirteen of 15 patients with recurrent cholangitis (group 2) had good or intermediate velocities. Both patients in this group with abnormal velocities required transplantation. In group 3 the patient with abnormal velocity is on the transplant waiting list. In group 4, abnormal velocities preceded or coincided with deterioration of liver function in five of seven patients. Doppler ultrasound provides useful anatomic information, determines direction of flow, quantitates velocity of flow, and, when performed serially, provides adjunctive information on liver status in children with biliary atresia. These preliminary results suggest that patients with abnormal or significantly decreasing velocity are destined for transplantation. Patients with good portal venous velocity warrant ongoing, aggressive surgical management.     

Follistatin and activin A production by the male reproductive tract

Follistatin is a binding protein for the activin and inhibin family of hormones, regulating their biological activity. In the male reproductive tract, the interaction of these factors is likely to be involved in the regulation of the proliferation of several cell types. We have investigated the presence of follistatin and activin A in seminal plasma using specific immunoassays and have localized follistatin and activin/inhibin subunits in the adult human testis, prostate and seminal vesicle to establish their likely sources. High concentrations of immunoreactive follistatin were present in seminal plasma in normal men (mean 97.9 ng/ml; 1.43 ng/ml in peripheral plasma) and were similar in men with oligo/azoospermia and following vasectomy. Follistatin immunoreactivity was localized to both Leydig and Sertoli cells of the testis, and to epithelial cells of the prostate gland and seminal vesicle, which are likely to be the predominant sources of the hormone in seminal plasma. Activin A was also present in seminal plasma in normal men but was undetectable following vasectomy, thus deriving from the testis. Consistent with this finding, the betaA-subunit was immunolocalized in Sertoli and Leydig cells but was not present in seminal vesicle or prostate gland. The functional significance of the high concentrations of follistatin secreted into seminal plasma by the prostate gland and/or seminal vesicle is uncertain, but they may regulate the biological activity of testis-derived activin A and inhibin B.      

A lethal skeletal dysplasia with features of chondrodysplasia punctata and osteogenesis imperfecta: an example of Astley-Kendall dysplasia. Further delineation of a rare genetic disorder.

An unusual osteochondrodysplasia presenting with lethal neonatal short limbed dwarfism, defective ossification, and punctate calcification within cartilage is presented. The features resemble four cases previously described with Astley-Kendall dysplasia.     

Ibuprofen overdose in adults.

A prospective study of 63 ibuprofen overdose cases in adults (14 years or older) reported to the Rocky Mountain Poison and Drug Center between March 1987 and February 1988 was done to determine the incidence of renal injury and utility of timed plasma levels. No serious toxicity was noted. No CNS or other significant toxicity was seen with ingestion of less than 3 g. Two patients with normal serum creatinines had minor elevations of the blood urea nitrogen after ingesting 4 and 4.8 g. Timed plasma levels (125 total) from patients without coingestants from this study (48) and previously published reports (77) were compared with a previously described nomogram. The resulting nomogram revision may be useful in determining which initially asymptomatic patients are likely to remain so. Renal function tests are not routinely required for patients ingesting less than 6 g. Four h of observation is sufficient for asymptomatic patients not requiring psychiatric admission. Plasma ibuprofen levels are not required for proper patient management.     

Best medical practice in practice: measuring efficiency in mammography screening.

Breast cancer, screening and mammography have caused considerable debate in several countries. This article explores the concept of best medical practice in the context of mammographic screening for breast cancer. Maximizing the use of technology, ignores the risks intrinsic to technological intervention. To do no harm in modern medical practice means largely doing nothing. Best medical practice, therefore, requires a balancing of benefits and risks so that best practice is that which does more good than harm. At the same time, not all interventions that do more good than harm can be funded out of the current health care budget. Thus, best medical practice is economically efficient practice. From the conceptual notion of what is best medical practice, this article turns to the problem of what that means in practical terms. Can we recognize best medical practice when it occurs? The identification, measurement and valuation of costs and benefits are discussed as a specific case study, in the context of breast cancer screening. Many of the difficulties involved here, particularly on the benefit side, are highlighted, especially in the context of QALYs. Yet, whatever the difficulties involved they have to be seen in the context of otherwise settling for something less i.e. inefficient medical practice.