Corticosteroids for the Enhancement of Fetal Lung Maturity: Impact on the Gravida with Preeclampsia and the HELLP Syndrome

Summary: This study was undertaken to determine maternal impact of corticosteroids administered for the promotion of fetal lung maturity in mothers with the HELLP syndrome. Twenty-seven of 427 women with the HELLP syndrome treated between 1980–1991 received a full course of steroids prior to preterm delivery. This group was compared to 27 matched control patients with the HELLP syndrome who received no corticosteroids. Subjects were matched for maternal age, race, sex of the fetus, and severity of the HELLP syndrome. The antepartum platelet count stabilized or increased in 25 of 27 steroid-treated women in contrast to 0 of 15 control women (p <0.00001). In comparison to control patients, LDH serum concentrations in steroid-treated patients stabilized or decreased and the SGOT/AST and SGPT/ALT stabilized or decreased during therapy (p < 0.005). The interval from delivery to platelet nadir in patients with Class III HELLP syndrome was shorter in the steroid-treated group (p<0.008) than in untreated patients.     

Proteolytic Processing Mechanisms in the Biosynthesis of Neuroendocrine Peptides: The Subtilisin-like Proprotein Convertases

The recent discovery of a novel family of precursor processing endoproteases has greatly accelerated progress in understanding the complex mechanisms underlying the maturation of prohormones, neuropeptides, and many other precursor-derived proteins. At least six members of this family have been found thus far in mammalian species, several having alternatively spliced isoforms, and related enzymes have been identified in many invertebrates, including molluscs, insects, nematodes, and coelenterates. The proprotein convertases are all dependent on calcium for activity and all possess highly conserved subtilisin-like domains with the characteristic catalytic triad of this serine protease (ordered Asp, His, and Ser along the polypeptide chain). Two members of this family, PC2(SPC2) and PC1/PC3(SPC3), appear to play a preeminent role in neuroendocrine precursor processing. Both convertases are expressed only in the brain and in the extended neuroendocrine system, while another important family member—furin/PACE (SPC1)—is expressed more ubiquitously, in almost all tissues, and at high levels in liver. SPC2 and SPC3 exhibit acidic pH optima and other properties which enhance their activity in the acidic, calcium-enriched environment of the dense-core secretory granules of the regulated pathway in neuroendocrine cells, while furin has a neutral pH optimum and is localized predominantly to the trans Golgi network where it is retained by a C-terminal transmembrane domain. Furin processes a wide variety of precursors in the constitutive pathway, such as those of growth factors, receptors, coagulation factors, and viral glycoproteins. Recent findings on the processing of proopiomelanocortin, proinsulin, proglucagon, and several other neuroendocrine precursors by SPC2 and SPC3 are discussed, along with information on the structure, properties, evolution, developmental expression, and regulation or the convertases. An inherited defect in the fat/fat mouse which affects the processing of proinsulin, and probably also many other prohormones, due to a point mutation in carboxypeptidase E has recently been identified and has begun to provide new insights into the functional integration of the individual processing steps.     

The role of surgery in the management of gestational trophoblastic disease

Between November 1967 and December 1994, 242 patients with gestational trophoblastic disease (GTD) were treated with chemotherapy by the Gynecology Service of Memorial Hospital. Eighty-seven of the patients (35.9%) underwent at least one major operation during the course of their illness. Twenty-six patients underwent two major operations, and in five patients, three major operations were performed, for a total of 118 procedures. The most frequent procedures were: hysterectomy, 56 (47.4%); hysterotomy, 15 (12.7%); thoracotomy, 13 (11%); and craniotomy, 5 (4.2%). Twenty-nine additional procedures ranging in complexity from oophorectomy to segmental liver resection were also performed. Twenty-nine operations (24.5%) were considered to be beyond the scope of most gynecologic surgeons. The overall complete remission rate for 242 patients was 90.4%. The rate for patients who underwent a major surgical procedure was 79.3% compared to 96.7% for patients whose treatment was with chemotherapy alone.
The data demonstrate that the integration of surgery in the management of GTD patients often requires a multidisciplinary approach that in many cases can best be achieved at specialized treatment centers.     

Benign trichogenic tumours: a report of two cases supporting a simplified nomenclature

We report two cases of a rare benign tumour of hair germ. Clinically, both were solitary, well-circumscribed, subcutaneous nodules located in the extremities. Histologically, the tumours were characterized by nests and thin cords of basaloid epithelial cells intimately associated with a cellular stroma. The basaloid cells exhibited peripheral palisading, keratinization in the form of keratotic cysts and squamoid transformation, and pilar differentiation. An unusual, but distinctive, cribriform pattern of growth was observed. There was no communication with the overlying epidermis. Abundant primitive hair germinal buds and rare more advanced abortive hair follicles were identified. These histological appearances encompass features of both trichoblastic fibroma and trichogenic trichoblastoma, thus distinguishing these neoplasms from other skin tumours and reinforcing the hypothesis that these tumours are closely related from a histogenetic point of view. The presence of overlapping histological features can be problematic for practising histopathologists who rarely encounter these conditions. With this in mind, the term benign trichogenic tumour may be more appropriate to encompass these two tumours and related neoplasms that appear to lie within the spectrum of hair follicle development.     

Superior mesenteric artery is more important than inferior mesenteric artery in maintaining colonic mucosal perfusion and integrity in rats

Mucosal hemodynamics (by reflectance spectrophotometry) and mucosal damage (by histologic examination) following acute colonic ischemia were evaluated in different anatomic locations in the colon of anesthetized rats. The reflectance spectrophotometer provides an index of mucosal hemoglobin concentration (IHB) and an index of oxygen saturation of hemoglobin (ISO₂). The patterns of ischemia without congestion (IHB, ISO₂) during superior mesenteric artery occlusion, and ischemia with congestion (IHB, ISO₂) during portal vein occlusion, previously demonstrated in the stomach and duodenum, are also applicable to the colon. The significant linear correlations between changes (as percent of baseline) in IHB, ISO₂, and hydrogen gas clearance suggest that changes in these indices are adequate indicators of changes in colonic mucosal perfusion. Superior mesenteric artery ligation produced significant reductions in both indices, and an increase in damage in the mucosa of the cecum, transverse colon, splenic flexure, and left colon, but not the rectum. Inferior mesenteric artery ligation produced only slight reduction in these indices and minimal damage only in the mucosa of the splenic flexure. These results support the hypothesis that the superior mesenteric artery is more important than the inferior mesenteric artery in maintaining colonic perfusion and colonic mucosal integrity in the rat.Supported by the American Society for Gastrointestinal Endoscopy Career Development Award (H850208, H870212), Veterans Administration Medical Research Funds; and in part by research grants (0162-01, 0162-02; 0291-01) from the Smokeless Tobacco Research Council, Inc.; and by funds provided by the Cigarette and Tobacco Surtax Fund of the State of California through the Tobacco Related Disease Research Program of the University of California.     

Quality care at risk in CMHCs: The need for Guidelines for Psychiatric Practice

The author discusses what he considers the inadequate attention paid to quality of care in many CMHCs. He suggests that the deterioration of quality is related to the exodus of competent psychiatrists. The Guidelines for Psychiatric Practice in Community Mental Health Centers should help to assure that quality care is delivered in a cost-effective manner. These guidelines should ultimately be incorporated into an accreditation process for CMHCs, and funding should be tied to such accreditation.This paper was presented at the Annual Meeting of the American College of Mental Health Administration, Woodstock, VT, March, 1988.     

Chlorinated hydrocarbon levels in human serum: Effects of fasting and feeding

Twenty healthy adult humans had serum samples drawn on four occasions within a 24-hr period: after a 12 hr overnight fast, 4–5 hr after a high fat breakfast, at midafternoon, and the next morning after another 12 hr fast. Nonfasting samples had 22% to 29% higher mean concentrations (p < 0.05) than did fasting samples for polychlorinated biphenyls (PCBs, 4.81 vs 3.74 ng/g serum wt), hexachlorobenzene (HCB, 0.163 vs 0.134 ng/g serum wt), andp,p-dichlorodiphenyldichloroethylene (p,p-DDE, 6.74 vs 5.37 ng/g serum wt) measured by electron capture gas liquid chromatography. Total serum lipids were estimated from measurements of total cholesterol, free cholesterol, triglycerides, and phospholipids and were 20% higher in nonfasting samples than in fasting samples (7.05 g/L vs 5.86 g/L). When PCBs, HCB, andp,p-DDE concentrations were corrected by total serum lipids, results from fasting and nonfasting samples were not statistically different. Because of the differences in these chlorinated hydrocarbon concentrations observed with different sample collection regimens, meaningful comparison of analytical results requires standardizing collection procedures or correcting by total serum lipid levels.     

Low birthweight in African Americans: does intergenerational well-being improve outcome?

The primary antecedent of infant mortality is low birthweight. Vital statistics data have shown that women of low socioeconomic status, regardless of race, are at greater risk for delivering low birthweight infants; however, prevailing data show that black women of the same socioeconomic status as white women have a twofold higher risk of giving birth to an infant weighing < 2500 g and a threefold risk of delivering a very low birthweight infant weighing < 1500 g. There is also evidence that intergenerational effects on birth outcome exist. However, virtually all studies of the effect of socioeconomic status on perinatal outcome have been cross-sectional; the effect of sustained intergenerational well-being has not been measured. To address this gap, this study was designed to demonstrate that in an African-American population with sustained high socioeconomic status and equal risk factors, the birthweight distribution and other reproductive outcomes are the same as those for comparable US white populations. Preliminary findings are reported here.