Biphasic effect of GABAA receptor agonists on prolactin secretion: evidence for two types of GABAA receptor complex on lactotrophes

The effects of GABA receptor agonists on prolactin secretion in vitro was examined using a rapid superfusion system. GABA and muscimol caused a biphasic effect on prolactin secretion, both components of which were antagonised by bicuculline methiodide, while baclofen had no effect on basal or stimulated secretion, demonstrating the GABAA receptor specificity of both components. Homocarnosine caused only inhibition of secretion, and a range of partly rigid GABA analogues were relatively poor at causing stimulation of secretion. Both effects of muscimol were antagonised by low-chloride medium and the anion channel blocker DIDS, but strychnine and picrotoxinin were both potent and selective antagonists of the stimulatory effect. These results demonstrate a novel biphasic effect of GABAA agonists or prolactin secretion, the two components of which appear to be independent and mediated by different types or states of GABAA receptor/chloride channel complex.     

Elevated adenosine deaminase activity and hereditary hemolytic anemia. Evidence for abnormal translational control of protein synthesis.

We have investigated the molecular basis of the marked elevation in erythrocyte adenosine deaminase (ADA) activity in a kindred with hereditary hemolytic anemia. Red cell ADA-specific activity was verified to be 70- to 100-fold normal levels. Western blots demonstrated a corresponding increase in erythrocyte ADA-specific immunoreactive protein. Analysis of genomic DNA revealed no evidence for amplification or major structural changes in the ADA gene. ADA-specific messenger RNA (mRNA) from proband reticulocytes was comparable in size and amount to mRNA from control reticulocytes. Translation of proband poly A+ reticulocyte mRNA in a rabbit reticulocyte lysate system and immunoprecipitation of 35S-labeled protein products with anti-ADA antibody yielded a band of approximately 42,000 apparent mol wt that was absent in translation products from control reticulocyte mRNAs. These data suggest that the increased ADA activity in red cells in this disorder results from the increased translation of an aberrant ADA mRNA.     

Recommendations from a multi-study evaluation of proposed criteria for staging reproductive aging.

In 2001, the Stages of Reproductive Aging Workshop (STRAW) proposed bleeding and endocrine criteria for defining the early and late menopausal transition stages. Based on expert consensus, STRAW recommended a shorter interval of amenorrhea than the commonly used 90-day amenorrhea criteria for late transition and a >7-day change in cycle length for early transition. The ReSTAGE collaboration used prospective menstrual calendar data from four cohorts (TREMIN, Melbourne Women's Midlife Health Project, Seattle Midlife Women's Health Study, and Study of Women's Health Across the Nation) to quantitatively evaluate STRAW's recommendations. This empirical assessment supported the STRAW recommendations that (1) > or =60 days of amenorrhea be used to define the late menopausal transition and (2) that early transition is consistent with a persistent 7 or more day difference in length of consecutive cycles. Serum follicle stimulating hormone (FSH) values > or =40 IU/l was an independent marker of the transition and, when occurring together with a bleeding marker, increased prediction of final menstrual period. Such a FSH criterion could be incorporated into the STRAW paradigm to facilitate prediction of proximity of the final menstrual period.     

A comparison of pregnancy outcome in overweight and normal weight women

From a population of singleton pregnancies, 152 overweight women (greater than 110% of standard) were matched with normal weight women (95-110%) for age, height, parity, race, and smoking habits. Comparisons were made of initial weight (weight at the first prenatal visit) and gestational weight gain and pregnancy outcome. Mean birth weights and gestational ages of infants of normal and overweight women were not significantly different. For normal weight women birth weight increased significantly as height, initial weight, and body mas index increased (p less than 0.01), but no such relationship existed for overweight women. The lack of effect of initial weight on birth weight in overweight women is attributable, in part, to the significantly less gestational weight gains of these mothers (6.3 kg vs 8.2 kg). When normal and overweight gravida had gestational weight gains of less than 7 kg, offspring of overweight mothers were significantly heavier. Gestational weight gain was positively correlated with birth weight for both normal (p less than 0.0001) and overweight women (p less than 0.001). Within the overweight and normal weight groups, smokers had lower initial weights and gestational weight gains than nonsmokers. Offspring of normal weight smokers had a mean birth weight 232 g less than that of nonsmokers (p less than 0.01). The difference in birth weight between overweight smokers and nonsmokers (135 g) was not statistically significant. While there is substantial data to support a weight gain of 10-12 kg in normal weight gravida, it would appear that a gain of approximately 7 kg in overweight middle class women does not impair fetal growth as measured by birth weight.(ABSTRACT TRUNCATED AT 250 WORDS)     

In situ saphenous vein bypass grafts: angiographic evaluation and interventional repair of complications

In situ saphenous vein grafts are being used with increasing frequency for bypass procedures involving the femoral and popliteal arteries. Complications of these procedures include anastomotic stenoses and persistent arteriovenous fistulae that may result in failure of the graft. Balloon angioplasty and embolotherapy with detachable balloons were employed successfully in three or four recent cases of patients with complications from in situ grafts. Tailored angiography is essential for evaluating in situ grafts, and interventional techniques are extremely useful for managing complications.     

Endocrine and amine responses to D,L-fenfluramine in normal subjects.

To investigate indirectly the central neurotransmitter mechanisms of D,L-fenfluramine-induced hormone release, prolactin, adrenocorticotropic hormone, cortisol, growth hormone, 3-methoxy-4-hydroxyphenylglycol (MHPG), homovanillic acid (HVA), and 5-hydroxyindoleacetic acid (5HIAA) responses to D,L-fenfluramine (60 mg, oral) were examined in a single-blind, placebo-controlled trial in 14 normal subjects. As compared with placebo, D,L-fenfluramine significantly increased both prolactin and cortisol. There was a significant correlation between the cortisol and prolactin responses. HVA levels were also significantly increased, but there were no changes in MHPG or 5HIAA. The elevation in HVA significantly correlated with increases in both prolactin and cortisol. These findings are consistent with recent animal studies suggesting that D,L-fenfluramine-induced prolactin and cortisol release may be mediated, at least in part, by catecholaminergic systems.     

Effects of improved contrast on lung-nodule detection. A clinical ROC study

We evaluated the effects of unsharp masking and highly efficient scatter rejection on film-screen chest radiographs of cancer patients. Unsharp masking significantly improved the detectability of lung nodules and visibility of anatomic structures in poorly penetrated areas of the chest. Highly efficient scatter rejection by an improved antiscatter grid provided only modest additional benefits. The study supports the conclusion that nodule detection in poorly penetrated areas on conventional chest radiographs is limited primarily by display contrast, whereas in the well-penetrated lung fields it is limited primarily by confusing background structures, rather than inadequate contrast. A method for analyzing clinical nodule detection data by transforming the FROC data to ROC coordinates also is demonstrated.     

An Improved Method of Removing Polyurethane Foam-Covered Gel Prostheses

One of the advantages of polyurethane foam-covered prostheses has been that in the first 5 to 10 years after their use, the amount of capsular contraction was found much less than when similar ``slick' prostheses were used. Another advance was their fixation to the surrounding tissue thus giving a more natural appearance and movement with the muscles when the arms were moved in any direction. The formation of a thick capsule also acted as a protection against gel granuloma due to rupture of the prosthesis and has been thought to be a factor in the lower capsule contraction rate. The greatest disadvantage has been that its removal was extremely difficult and this has continued up until the technique described in this paper has been introduced.