Although melatonin (MEL) controls seasonal reproductive cyclicity in some mammalian species, its role in women is controversial. In this study data are presented related to the influence of MEL or ...MEL-progestin combinations on the pituitary-ovarian axis and ovulation in 32 women. MEL was administered in a dosage of 300 mg to 12 women for 4 months to 8 women daily (days 1-30) and to 4 women on days 5-17 of the cycle. MEL was also combined with the synthetic progestin norethisterone (NET) in an attempt to evaluate MEL's effect on a partially suppressed pituitary-ovarian axis. In 16 women, 4 combinations were tested on 4 women each on days 1-21: dosages of 300 mg MEL/0.75 mg NET, 75 mg MEL/0.75 mg NET, 7.5 mg MEL/0.75 mg NET, and 75 mg MEL/0.30 mg NET. In addition, 2 women were medicated with 300 mg MEL alone, and 2 were medicated with 300 mg MEL/0.15 mg NET on days 1-21 for 2 months. During the study, LH, FSH, estradiol (E2), and progesterone (P4) blood levels were determined at regular intervals. After a period of 4 months, daily administration of 300 mg MEL (days 1-30) caused significantly decreased mean LH levels compared to those in 8 nonmedicated controls (P less than 0.001). Also compared to nonmedicated control data, a significant inhibition of P4 in the first and fourth medication months (P less than 0.001) was observed. LH and E2 inhibition reached significance in the fourth medication month (P less than 0.005). Also, the treatments of 300 mg MEL (days 5-17) and 75 mg MEL combined with 0.3 mg NET caused a significant decrease in LH, E2, and P4 levels compared to those in the nonmedicated control group in the first and fourth medication months (P less than 0.05). The data further suggest an additive or synergistic effect between MEL and NET. The medications did not alter sleep-wake rhythms and were not complicated by any side-effects. The presented data suggest that MEL and MEL/NET combinations inhibit ovarian function in women, and that MEL/NET combinations can emerge as effective oral contraceptives.
To describe the efficacy and safety of laser lithotripsy during peroral cholangioscopy for the treatment of complex biliary stones.
Prospective, descriptive study.
Data were prospectively collected ...on all patients referred over a period of two years for peroral cholangioscopic laser lithotripsy following failure of endoscopic retrograde cholangiopancreatography (ERCP). The efficacy and safety of the treatment were studied.
Eleven patients were treated. ERCP with stone removal and mechanical lithotripsy had been undertaken previously in these patients, but was unsuccessful. In one patient, lithotripsy was not performed because the endoscope could not be positioned satisfactorily. This patient was operated. Ten patients were treated with laser lithotripsy. In 9 of the 10 patients lithotripsy led to complete removal of all stone. In one patient the stone extraction partially failed. One complication occurred, a rupture of the common bile duct which could be managed conservatively by a stent.
Peroral cholangioscopy guided laser lithotripsy of biliary stones appears to be a safe and effective treatment in patients in whom initial ERCP and mechanical lithotripsy is unsuccessful.
Abstract Purpose To develop a new schematic scheme for efficiently recording the key parameters of gas permeable contact lens (GP) fits based on current consensus. Methods Over 100 established GP ...fitters and educators met to discuss the parameters proposed in educational material for evaluating GP fit and concluded on the key parameters that should be recorded. The accuracy and variability of evaluating the fluorescein pattern of GP fit was determined by having 35 experienced contact lens practitioners from across the world, grading 5 images of a range of fits and the topographer simulation of the same fits, in random, order using the proposed scheme. The accuracy of the grading was compared to objective image analysis of the fluorescein intensity of the same images. Results The key information to record to adequately describe the fit of an GP was agreed as: the manufacturer, brand and lens parameters; settling time; comfort on a 5 point scale; centration; movement on blink on a ±2 scale; and the Primary Fluorescein Pattern in the central, mid-peripheral and edge regions of the lens averaged along the horizontal and vertical lens axes, on a ±2 scale. On average 50–60% of practitioners selected the median grade when subjectively rating fluorescein intensity and this was correlated to objective quantification ( r = 0.602, p < 0.001). Objective grading suggesting horizontal median fluorescein intensity was generally symmetrical, as was the vertical meridian, but this was not the case for subjective grading. Simulated fluorescein patterns were subjectively and objectively graded as being less intense than real photographs ( p < 0.01). Conclusion GP fit recording can be standardised and simplified to enhance GP practice.
Glucose clearance (glucose utilization divided by plasma glucose) is commonly used to assess glucose utilization under conditions in which plasma glucose concentrations vary. The validity of this ...practice requires that glucose clearance itself be independent of plasma glucose concentration. The present studies were, therefore, undertaken to determine the relationship between glucose clearance and plasma glucose concentration in man. Using the glucose clamp technique, rates of glucose utilization (measured isotopically with 3-3H-glucose) and glucose clearance were determined in 5 normal volunteers at steady-state plasma glucose concentrations of approximately 60, 95, 130, and 165 mg/dl, while plasma insulin concentrations were maintained constant (approximately 18 microU/ml) by infusion of insulin and somatostatin. Despite virtually identical 0.4 mg X kg-1 X min-1 increments in glucose utilization for each 35-mg/dl increment in plasma glucose, glucose clearance decreased as a function of plasma glucose concentration (r = -0.85, P less than 0.001). These results indicate that glucose clearance is not independent of changes in plasma glucose concentration and, thus, use of glucose clearance to evaluate glucose utilization of differing plasma glucose concentration is not valid. Whether this conclusion also applies to similar use of clearance for other substrates remains to be determined.
Infusion of glucagon causes only a transient increase in glucose production in normal and diabetic man. To assess the effect of intermittent endogenous hyperglucagonemia that might more closely ...reflect physiologic conditions, arginine (10 g over 30 min) was infused four times to 8 normal subjects and 13 insulin-dependent diabetic subjects (4 of whom were infused concomitantly with somatostatin to examine effects of arginine during prevention of hyperglucagonemia). Each arginine infusion was separated by 60 min. Diabetic subjects were infused throughout the experiments with insulin at rates (0.07-0.48 mU/kg per min) that had normalized base-line plasma glucose and rates of glucose appearance (Ra) and disappearance (Rd). Basal plasma glucagon and arginine-induced hyperglucagonemia were similar in both groups; basal serum insulin in the diabetics (16+/-1 muU/ml, P < 0.05) exceeded those of the normal subjects (10+/-1 muU/ml, P < 0.05) but did not increase with arginine. Serum insulin in normal subjects increased 15-20 muU/ml with each arginine infusion. In both groups each arginine infusion increased plasma glucose and Ra. Increments of Ra in the diabetics exceeded those of normal subjects, (P < 0.02); Rd was similar in both groups. In normal subjects, plasma glucose returned to basal levels after each arginine infusion, whereas in the diabetics hyperglycemia persisted reaching 151+/-15 mg/dl after the last arginine infusion. When glucagon responses were prevented by somatostatin, arginine infusions did not alter plasma glucose or Ra.
Infusion of arginine acutely increases plasma glucose and glucose production in man solely by stimulating glucagon secretion; physiologic increments in plasma glucagon (100-150 pg/ml) can result in sustained hyperglycemia when pancreatic beta cell function is limited.
To determine the mechanism by which hyperinsulinemia causes hypoglycemia in insulinoma patients, rates of glucose production and utilization, and circulating levels of insulin, glucagon, alanine, ...lactate, and glycerol were measured in 6 insulinoma patients during development of fasting hypoglycemia and in 8 normal volunteers studied over an identical interval. Initially, insulinoma patients had a greater plasma insulin (42 +/- 9 versus 15 +/- 1 microunits/ml) and glucagon levels (214 +/- 31 versus 158 +/- 21 pg/ml) than normal subjects, P less than 0.05, but their plasma glucose levels (81 +/- 4 mg/dl) and rates of glucose production and utilization (1.71 +/- 0.08 and 1.74 +/- 0.08 mg/kg . min, respectively) were not significantly different from those of normal subjects (93 +/- 2 mg/dl, 1.93 +/- 0.11, and 1.92 +/- 0.13 mg/kg . min, respectively). During a subsequent 8-h fast, glucose production and glucose utilization decreased in both groups, but more markedly in insulinoma patients. Since glucose utilization exceeded glucose production to a greater extent in insulinoma patients than in normal subjects, plasma glucose decreased to 44 +/- 3 mg/dl in insulinoma patients, but only to 84 +/- 1 mg/dl in normal subjects (P less than 0.001). Glucose utilization in insulinoma patients never exceeded that of normal subjects. These results demonstrate that fasting hypoglycemia in the insulinoma patients is usually due to suppression of glucose production rather than to acceleration of glucose utilization, as is widely thought. A direct effect of insulin on the liver is probably responsible, since circulating levels of gluconeogenic precursors are normal and since plasma glucagon increases during development of hypoglycemia in insulinoma patients.
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