In most poorly controlled glyburide-treated type 2 diabetic patients drug withdrawal causes further increase in glycemia not accompanied by changes in insulin secretion.

To find out whether the secondary failure of glyburide in type 2 diabetes is complete or partial, we studied 38 patients, age (M +/- SD) 69 +/- 9 years, suffering from diabetes from 13.5 +/- 8.4 years and treated with glyburide for 5-13 years, with poor glycemic control (glycohemoglobin 10.6 +/- 2.6%). Serum glucose, insulin and C-peptide were assayed before and 1 h and 2 h after a simulated meal load (355 Cal), after which the drug was replaced with placebo for 4 weeks, and the test repeated. After glyburide withdrawal, fasting glycemia increased from 10.3 +/- 3.3 to 15.1 +/- 4.4 mmol/L (p < 0.001), but in 3/38 patients, it even decreased and in five others the changes were less than +/- 2 mmol/L. These changes negatively but only weakly correlated with initial glycemia: r = 0.4123, p < 0.010. The mean post-meal glycemia at 1 h and 2 h increased respectively by 3.3 and 5.9 mmol/L (both p < 0.001). Neither the levels of glycemia nor its changes after the glyburide withdrawal correlated with the levels of, or changes in, insulin or C-peptide. We conclude that in most but not all type-2 diabetic patients, poorly controlled with glyburide, the drug still retains some limited therapeutic effectiveness, and therefore its withdrawal causes further deterioration of control with the almost equal increases in fasting and post-meal levels of glycemia. These changes are not accompanied by decrease in insulin secretion.

Plasma neurotransmitter profile during different phases of the ovulatory cycle.

The influence of the different phases of the menstrual cycle on platelet-poor plasma norepinephrine (NE) and serotonin (5HT) was examined in 17 normal volunteers. The examinations were performed consecutively during 3 phases of the ovulatory cycle: 1) follicular phase, 2) ovulation, and 3) luteal phase. This investigation was initiated after a preliminary study in 51 volunteers showed wide and consistent variations of plasma NE and 5HT during the different phases of the cycle. Since in this first group the determinations had not been performed consecutively in the same subjects, and the changes observed in the different phases of the cycle could reflect interpersonal variations, the determinations were performed consecutively in a second group, concomitantly with serum estradiol (E2) and LH measurements. The results showed a decrease in plasma 5HT from the follicular phase [144.3 +/- 69.3 nmol/L (+/- SD)] to ovulation (55.7 +/- 41.4; P less than 0.001) and a subsequent increase in the luteal phase (141.3 +/- 96.4; P less than 0.01). The nadir in plasma 5HT showed an inverse correlation with serum LH (r = -0.07). Plasma NE increased from the follicular phase (1226.5 +/- 475.1 pmol/L) to ovulation (1694.0 +/- 564.4; P = 0.027) and reached a maximum in the luteal phase (2335.0 +/- 728.2; P = 0.0034). This rise correlated positively with serum E2. In conclusion, plasma 5HT and NE vary with the different phases of the menstrual cycle. Plasma NE rises during ovulation and seems to to correlate positively with serum E2 levels. Plasma 5HT reaches a nadir during ovulation and correlates inversely with serum LH.

Veralipride: alternative antidopaminergic treatment for menopausal symptoms.

The vasomotor hot flushes and increased perspiration symptomatic of the menopausal period reflect the adaptation of the body to the lowering of its preset basal temperature resulting from the interference of various central neurotransmitters of suprahypothalamohypophyseal origin. The present double-blind study was conducted to test the efficacy of veralipride, a synthetic antidopaminergic molecule, in eliminating the symptoms of menopause in 50 patients. Results indicated a total elimination of both hot flushes and excessive perspiration in 63% to 80% of the patients treated. The beneficial effects persisted up to 3 months of follow-up. Veralipride significantly increased dehydroepiandrosterone sulfate and estradiol levels. High values of prolactin were found, and some patients showed slight breast discharge; these changes disappeared 48 hours after the drug was stopped.

Improved treatment for anovulation in polycystic ovarian disease utilizing the effect of progesterone on the inappropriate gonadotrophin release and clomiphene response.

The treatment of anovulatory, clomiphene-resistant patients with polycystic ovarian disease (PCOD) is difficult. Ten such women were given progesterone, 50 mg/day i.m. for 5 days to achieve luteal phase concentrations. Immediately following progesterone treatment, plasma concentrations of FSH were reduced in all patients (P = 0.001) and seven of the 10 had reduced plasma LH concentrations. Following the withdrawal bleeding these seven all became responsive to clomiphene as shown by ovulation, and three conceived after a single progesterone/clomiphene cycle. LH pulsatility, studied in five women over 4 h, before and immediately following progesterone treatment, showed a slowing of the pulse frequency (62 +/- 26 min to 105 +/- 51 min, P less than 0.05) and an increase in pulse amplitude (6 +/- 1.9 IU/l to 16.7 +/- 20 IU/l). The LH and FSH response to GnRH was blunted by progesterone. It would thus appear that progesterone modulates LH pulsatility and reduces pituitary sensitivity to GnRH, reducing LH levels and possibly inducing more FSH synthesis and storage, similar to its action in the normal ovulatory cycle. These changes provide a more favourable environment for ovulation induction by clomiphene and we suggest that short-term progesterone treatment may be utilized to improve the efficiency and results of clomiphene treatment in PCOD.

HLA antigens A, B, C and DR in hay-fever families of similar environmental conditions.

Investigation of 98 members (healthy and affected) belonging to 17 hay-fever families, for clinical picture, total and specific IgE and HLA A, B, C and DR is presented. There was no significant correlation between hay-fever, total or specific IgE and a certain HLA antigen or haplotype. There was, however, an association between hay-fever and same haplotype within 4 of the 17 families.

Immunoglobulin E and A levels in atopic and anaphylactic children.

Seventy-six children between 18 months and 12 years of age were included in this study. Sixty-one were atopic and 15 had anaphylaxis due to bee stings or drugs. Immunoglobulins: A, G. M and E were determined and evaluated with respect to age and diagnosis. IgA levels were lower in atopic children between six and ten years than in normals. IgE levels were high in both atopic and anaphylactic patients but higher in the atopic than in the anaphylactic group. The results are discussed, focusing on the question of basic immunologic impairment in allergy.