Gerald S. Bernstein

Gestational diabetes mellitus : the prevalence of glucose intolerance and diabetes mellitus in the first two months post partum

To determine the prevalence of abnormal carbohydrate metabolism in the early postpartum period in women with gestational diabetes mellitus, we performed 2-hour oral glucose tolerance tests between 5 and 8 weeks post partum in 246 women with recent gestational diabetes mellitus. Patients were stratified into three study groups based on their fasting serum glucose level during pregnancy: (1) group A1: all fasting serum glucose levels during pregnancy less than 105 mg/dl without insulin therapy; (2) group A2: any fasting serum glucose levels greater than 105 and less than 140 mg/dl before insulin therapy; (3) group B1: any pregnancy with fasting serum glucose levels greater than 140 mg/dl. Overall, 48 (19%) of the patients had an abnormal oral glucose tolerance test in the early postpartum period; 25 (10%) had impaired glucose tolerance and 23 (9%) had diabetes mellitus. The prevalence of postpartum diabetes mellitus (2% in group A1, 9% in group A2 and 44% in group B1) increased in parallel with the degree of maternal metabolic decompensation during pregnancy (p less than 0.05 for A1 versus A2; p less than 0.001 for A2 versus B1). The prevalence of impaired glucose tolerance was likewise greater in the B1 group (26%) than in either the A1 or the A2 group (p less than 0.05). Gestational age less than 24 weeks at diagnosis of gestational diabetes mellitus was an additional risk factor for postpartum glucose intolerance. Our findings support the use of an oral glucose tolerance test in the early puerperium, especially for patients with elevated fasting serum glucose levels during pregnancy.

Increased thyroxine turnover and thyroidal function after stimulation of hepatocellular binding of thyroxine by phenobarbital

Administration of phenobarbital to rats in a dosage schedule previously demonstrated to increase hepatocellular binding of thyroxine results in increased hormonal turnover, due both to increased deiodination and to fecal disposition of thyroxine iodine. The rate of biliary excretion of thyroxine iodine is roughly proportional to the hepatic content of exchangeable thyroxine. The enhanced peripheral disposition of thyroxine appears to lead to increased thyroidal function, as measured by isotopic iodine studies, and the maintenance of a normal nonradioactive serum PBI. On the other hand, thyroidectomized animals maintained on a constant replacement dose of L-thyroxine and treated with phenobarbital exhibit a marked fall in serum PBI. These findings suggest that increased thyroxine flux in phenobarbital-treated animals is secondary to primary stimulation of hepatocellular binding. Exchangeable intracellular thyroxine may thus be an important determinant of hormone turnover and, possibly, of hormonal action.

Randomised controlled trial of prophylactic antibiotics before insertion of intrauterine devices

Summary Background The value of antibiotic prophylaxis before insertion of an intrauterine device (IUD) remains uncertain. We undertook a triple-masked, randomised, placebo-controlled trial to find out whether such prophylaxis reduces the rate of IUD removal within 90 days. Methods 11 clinic sites in southern California enrolled women who requested IUD insertion and were at low risk of sexually transmitted infection according to self-reported medical history. We randomly assigned 1985 participants either 500 mg azithromycin or placebo capsules of identical appearance taken about 1 h before insertion of a Copper T 380A IUD. 118 women did not have an IUD inserted. We followed up 1833 of the remaining 1867 (98%) participants for at least 90 days after insertion. Findings The rate of IUD removal for any reason other than partial expulsion was 3·8% (35/918) in the antibiotic group and 3·4% (31/915) in the placebo group (relative risk 1·1 [95% Cl 0·7–1·8]). The two treatment groups sought medical attention with equal frequency (mean 38 visits per 100 women). During the 90 days after IUD insertion, only one woman from each assignment group had salpingitis, as defined by established criteria. Interpretation Prophylaxis with azithromycin did not affect the likelihood that a woman would retain her IUD at 90 days or the frequency of postinsertion medical attention. In appropriately screened women, the risk of upper-genitaltract infection is negligible after IUD insertion, with or without the administration of prophylactic antibiotics.

Pregnancies associated with sperm concentrations below 10 million/ml in clinical studies of a potential male contraceptive method, monthly depot medroxyprogesterone acetate and testosterone esters

A potential male contraceptive approach was evaluated in clinical trials involving monthly injections of depot medroxyprogesterone acetate and either subdermal implants of testosterone propionate or monthly injections of testosterone enanthate. Pregnancies occurred in partners of 9 men with recent sperm counts of 10 million/ml or below. In 5 of the 9 instances, the sperm counts were less than 1 million/ml. It appears that male contraceptive methods involving spermatogenic suppression may require attainment and maintenance of azoospermia. The pregnancy rate cannot be calculated, because the extent of other contraceptive use is uncertain. There were no spontaneous abortions. 6 pregnancies were carried to term, and all progeny were normal, based on physical examination at birth or 3 months after birth.

Estimation of Rapidly Exchangeable Cellular Thyroxine from the Plasma Disappearance Curves of Simultaneously Administered Thyroxine-131I and Albumin-125I

A mathematical analysis of the plasma disappearance curves of simultaneously injected thyroxine-(131)I and albumin-(125)I allows the development of simple formulas for estimating the pool size and transfer kinetics of rapidly exchangeable intracellular thyroxine in man. Evidence is presented that the early distribution kinetics of albumin-(125)I can be used to represent the expansion of the thyroxine-(131)I-plasma protein complex into the extracellular compartment. Calculations indicate that approximately 37% of total body extrathyroidal thyroxine is within such exchangeable tissue stores. The average cellular clearance of thyroxine is 42.7 ml per minute, a value far in excess of the metabolic clearance of this hormone. Results of external measurements over the hepatic area and studies involving hepatic biopsies indicate that the liver is an important but probably not the exclusive component of the intracellular compartment. The partition of thyroxine between cellular and extracellular compartments is determined by the balance of tissue and plasma protein binding factors. The fractional transfer constants are inversely related to the strength of binding of each compartment and directly proportional to the permeability characteristic of the hypothetical membrane separating compartments. Appropriate numerical values for these factors are assigned. An increased fractional entrance of thyroxine-(131)I into the cellular compartment was noted in a patient with congenital decrease in the maximal binding capacity of thyroxine-binding globulin and in three patients after the infusion of 5,5-diphenylhydantoin. Decreased intracellular space and impaired permeability characteristics were observed in five patients with hepatic disease. Studies of the rate of entrance of thyroxine-(131)I and albumin-(125)I into the pleural effusion of a patient with congestive heart failure suggested that transcapillary passage of thyroxine independent of its binding protein is not a predominant factor in the total distribution kinetics of thyroxine-(131)I. The thesis is advanced that the distribution of thyroxine, both within the extracellular compartment and between the extracellular and intracellular compartments, is accomplished largely by the carrier protein and the direct transfer of thyroxine from one binding site to another. The concept of free thyroxine is reassessed in terms of this formulation.

Differences in primary cellular factors influencing the metabolism and distribution of 3,5,3'-L-triiodothyronine and L-thyroxine.

Administration of phenobarbital, which acts exclusively on cellular sites, results in an augmentation of the liver/plasma concentration ratio of L-thyroxine (T4) in rats but no change in the liver/plasma concentration ratio of L-triiodothyronine (T3). Whereas phenobarbital stimulates the fecal clearance rate both of T3 and T4, it increases the deiodinative clearance rate of T4 only. These findings suggest basic differences in the cellular metabolism of T3 and T4. Further evidence pointing to cellular differences was obtained from a comparison of the distribution and metabolism of these hormones with appropriate corrections for the effect of differential plasma binding. The percentage of total exchangeable cellular T4 within the liver (28.5) is significantly greater than the corresponding percentage of exchangeable cellular T3 within this organ (12.3). Extrahepatic tissues bind T3 twice as firmly as T4. The cellular metabolic clearance rate (= free hormone clearance rate) of T3 exceeds that of T4 by a factor 1.8 in the rat. The corresponding ratio in man, 2.4, was determined by noncompartmental analysis of turnover studies in four individuals after the simultaneous injection of T4-(125)I and T3-(131)I. The greater cellular metabolic clearance rate of T3 both in rat and man may be related to the higher specific hormonal potency of this iodothyronine.

Study of medroxyprogesterone acetate and testosterone enanthate as a male contraceptive

The effect of im injections of medroxyprogesterone acetate (100 or 150 mg) and testosterone enanthate (200 mg) over a 4-month period on spermatogenesis and serum testosterone levels was studied in 14 healthy, normal men. Treatment reduced sperm counts and suppressed gonadotropin levels in all subjects. 10 subjects showed sperm counts of less than 5 million/ml, though only 2 became azoospermic. A return to pretreatment sperm concentrations was not observed until 16-41 weeks after the last injection. Testosterone enanthate did not maintain serum testosterone levels at pretreatment values, though none of the subjects reported a decrease in libido. 1 subject developed unilateral gynecostamia during treatment. It is concluded that the doses used in this study are probably insufficient to provide effective contraception in males.

The influence of copper on the motility of human spermatozoa

Abstract The effect of metallic copper and copper salts on the motility of human spermatozoa was studied as part of an investigation of the mechanism of action of the copper-containing intrauterine device (IUD). Copper released from an IUD inhibited sperm motility in vitro and in vivo within three to four hours. Comparable concentrations of copper sulfate were less effective. Preliminary experiments in which sperm were incubated up to four hours within a Millipore chamber in the uterine cavity of a patient using a copper device indicate that copper has little effect on sperm motility in utero . The three to four hours-long latent period required for the inhibition of sperm motility by copper suggests that immediate immobilization of sperm is not a major mechanism of action of the copper IUD in the human.

Effect of low-dose oral contraceptives on carbohydrate and lipid metabolism in women with recent gestational diabetes: Results of a controlled, randomized, prospective study

Women with recent gestational diabetes mellitus were randomly assigned to one of two low-dose oral contraceptives to evaluate the effect of low-dose oral contraceptives on carbohydrate and lipid metabolism. A cohort of similar women requesting a non-oral-contraceptive method served as controls. The two oral contraceptives studied were ethinyl estradiol (0.035 mg)-norethindrone (0.40 mg) and ethinyl estradiol (0.030 to 0.040 mg)-levonorgestrel (0.050 to 0.125 mg). A 75 gm, 2-hour oral glucose tolerance test and a fasting lipid profile (total cholesterol, triglyceride, high- and low-density lipoprotein cholesterols) were performed at entry, after 3 months, and after 6 to 13 months of treatment. The prevalence of diabetes at 6 to 13 months (27/156 patients) was not significantly different between groups (non-oral-contraceptive group, 17%; ethinyl estradiol-norethindrone, 15%; ethinyl estradiol-levonorgestrel, 20%). When examined by prior gestational diabetes mellitus class, diabetes mellitus was present in 7% of prior class A1 and 29% of women with prior class A2 disease (p less than 0.001). Mean cholesterol and low-density lipoprotein cholesterol levels were significantly improved in all three groups at 3 months and at 6 to 13 months, whereas triglycerides remained unchanged. There were no differences in cholesterol, low-density lipoprotein cholesterol, or triglycerides levels between the groups. After 6 to 13 months, there was a significant increase in high-density lipoprotein cholesterol in the ethinyl estradiol-norethindrone group compared with the ethinyl estradiol-levonorgestrel and non-oral-contraceptive groups.

Human Papillomavirus Type 16 DNA in Ocular and Cervical Swabs of Women With Genital Tract Condylomata

Human papillomavirus type 16 is associated with dysplasias and carcinomas of the conjunctiva and of the uterine cervix. To explore the relationship between cervical and ocular human papillomavirus infection, we examined DNA from bilateral limbal swabs and cervical swabs from 17 women (age range, 17 to 46 years; median, 31.7 years) with biopsy-proven human papillomavirus-related cervical dysplasia who had a normal ocular surface. Using polymerase chain reaction, we identified human papillomavirus 16 DNA in one or both eyes of 13 (76.5%) patients, six (46.2%) of whom had demonstrable human papillomavirus 16 DNA in cervical swabs as well. It thus appears that human papillomavirus 16 is present in the conjunctivae of some patients with human papillomavirus-related genital warts who have no ocular manifestations of infection. Although autoinoculation of conjunctiva may be the source of some ocular human papillomavirus, data suggest that other modes of transmission to the eye also exist. Additional study of the epidemiologic characteristics of ocular human papillomavirus, a widely prevalent virus known to be associated with dysplasias/atypias and cancer, is warranted.