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Biomedical subjects

M G Hammond

Publications and source records attributed to M G Hammond.

At least 55 records · Page 3Linked to original sources

Male transmission of the gene for isolated gonadotropin-releasing hormone deficiency.

Three black women, daughters of the same father but three unrelated mothers, presented with isolated gonadotropin deficiency (IGD). Clinically, the patients had no midline defects and intact smell and taste senses. Biochemically, the essential feature was very low unstimulated and stimulated follicle-stimulating hormone and luteinizing hormone levels, even after priming with gonadotropin-releasing hormone over a 5-day period. Growth hormone response to insulin-induced hypoglycemia was somewhat blunted, but prolactin, cortisol, and thyroid-stimulating hormone responses were quite normal. All three patients had the 46,XX karyotype; clinical or biochemical aberrations could not be demonstrated in any of the remaining family members. The disorder was, apparently, transmitted by the deceased father, who manifestly did not have an IGD deficiency nor any of the midline stigmata associated with IGD. The mode of inheritance seems most likely to be autosomal dominant with variable penetrance.

Adolescent↗

Associations between HLA antigens and nephrotic syndrome in African and Indian children in South Africa.

The nephrotic syndrome (NS) reported from Southern Africa is distinguished by unusual characteristics in African children and typical features among Indian children. A genetic basis for these differences is explored in 44 African and 33 Indian children with NS in this paper. HLA associations were detected in the 20 Indian children with minimal change NS (MCNS) and 12 African children with membranous NS. Previous studies of HLA antigens, which have all been performed on Caucasian children with MCNS or steroid-responsive NS (SRNS), have detected associations with HLAB and DR locus genes. In this report HLA Bw44, which is part of HLA B12, was found to be significantly more frequent in Indian children with MCNS or SRNS than in controls (45 and 12%, respectively, p less than 0.04; relative risk 5.8). In contrast, African children with membranous nephropathy had a significantly increased frequency of HLA Bw21 (15% in patients and 1% in controls, p less than 0.04; relative risk 22.1). HBsAg was positive in 9 of 11 patients tested in the latter group. We conclude that the interaction between heredity and environmental factors is central to the pathogenesis of membranous nephropathy and similar considerations may be important in the development of MCNS.

Adult↗

Peritoneal macrophages modulate human granulosa-luteal cell progesterone production.

Macrophages have been identified in the developing corpus luteum in several species, including man, and also constitute approximately 90% of cells in the peritoneal cavity. We studied the effect of peritoneal macrophages or blood monocytes on progesterone (P) synthesis by human granulosa cells from preovulatory follicles obtained at laparoscopy of 14 women undergoing in vitro fertilization. Pooled granulosa cells from follicles with mature ova were isolated by Ficoll-Hypaque gradient centrifugation. Washed granulosa cells (0.75 X 10(5)/ml) were incubated in Dulbecco's Minimum Essential Medium containing 20% calf serum with varying concentrations of pelvic macrophages (0.8-29 X 10(5)/ml) or fresh and mature blood monocytes (0.25-2.5 X 10(5)/ml). P production was determined by RIA of medium at 24-h intervals for 24-48 h. In situ concentrations of pelvic macrophages from 8 patients with tubal infertility increased cumulative P production to 140 +/- 17.8% (mean +/- SEM) of the control values. A similar increase (182 +/- 62.7%) was found with macrophages from 6 patients with endometriosis or unexplained infertility. Both fresh and mature monocytes stimulated P production to 225% and 261% of control values, respectively. Indomethacin (10(-4) M) or monoclonal antibody to somatomedin-C did not prevent stimulation of P production. These results suggest that peritoneal macrophages may exert luteotropic effects on cumulus cells while the ovulated oocyte resides in the tube, and incoming monocytes may be important in stimulating luteal cells in the developing corpus luteum.

Adult↗

Relationship of age and pubertal development to ovulation in adolescent girls.

A random sample of adolescent girls, 13 to 16 years of age, were surveyed with multiple serum progesterone determinations. The presence of ovulation was correlated with various indexes of pubertal development, including a pubertal developmental index that was devised using a summation of developmental factors. There was a significant correlation of ovulation with breast development, pubic hair development, and with the developmental index.

Adolescent↗

HLA A, B, C and DR antigens in young South African Indians with insulin-dependent diabetes mellitus.

The HLA status of South African Indian insulin-dependent diabetic patients in whom the age of onset of diabetes was under 35 years was compared with that of a group of healthy Indian controls. HLA A, B and C antigens were determined in 68 patients and 760 controls, while DR specificities were determined in 35 patients and 235 controls. The diabetic patients showed a significant increase in the frequencies of HLA B8 (19,1% v. 6,8%; relative risk 3,2; corrected P less than 0,04) and Aw24 (42,6% v. 26,8%; relative risk 2,2; corrected P less than 0,04) antigens compared with controls. HLA DR3 was found to be much more common in patients than in controls (31,4% v. 12,8%; relative risk 3,1; corrected P less than 0,035), but DR3/DR4 heterozygosity was associated with a much greater relative risk (7,25). Among patients of North Indian origin a strong association with DR4 was seen (45,5% v. 9,1% (controls); relative risk 8,3).

Diabetes Mellitus, Type 1↗

HLA-A, B, C and DR antigens in young South African blacks with Type 1 (insulin-dependent) diabetes mellitus.

The HLA status of South African black Type 1 (insulin-dependent) diabetic patients with age of onset under 35 years was compared with that of healthy black control subjects. HLA-A, B and C antigens were determined in 94 patients and 995 control subjects, while DR typing was carried out on 56 patients and 195 control subjects. There was a significant increase in the frequency of DR4 in patients as compared with control subjects (p less than 0.01; relative risk 3.4). DR3/DR4 heterozygosity was associated with a greater relative risk for developing Type 1 diabetes mellitus (3.7) than the presence of DR3 alone (relative risk 1.6). A significant negative association was observed between the presence of BW42 and Type 1 diabetes in this population sample (p less than 0.04; relative risk 0.3). A similar trend was observed with regard to DR2, the corrected p value just attaining statistical significance (p less than 0.05; relative risk 0.1).

Black People↗

Monitoring techniques for improved pregnancy rates during clomiphene ovulation induction.

Despite the introduction of new ovulation-inducing agents, CC remains the drug of choice for most anovulatory patients. Before initiating therapy, patients should be evaluated to determine the cause of anovulation. Patients with ovarian failure, hyperprolactinemia, hypothyroidism, or forms of CAH should be treated with the appropriate replacement therapy. Evaluation of male factor and tubal patency should be obtained. Once CC therapy is initiated, careful monitoring should be continued. Confirmation of ovulation by endometrial biopsy or serum P levels is essential. CC doses should be increased monthly until normal luteal function is demonstrated. If the patient does not conceive in three ovulatory cycles, her treatment should be further evaluated by postcoital testing, repeat serum P measurement, and review of her endocrine findings. Patients with poor cervical mucus may benefit from midcycle estrogen. Patients with elevated T may benefit from prednisone suppressive therapy. Patients with abnormal HSGs should have laparoscopy and surgical correction if feasible. After six ovulatory cycles without conception, all patients should undergo laparoscopy. If laparoscopy is normal, therapy can be continued for a total of 10 to 12 cycles. Patients with reduced fecundability (male factor, minimal endometriosis, or minimal tubal adhesions) may require a longer time to conceive.

Adrenal Hyperplasia, Congenital↗

Endocrine and immunologic studies in a patient with resistant ovary syndrome.

A patient with the resistant ovary syndrome is reported. To evaluate the hypothesis that the hypogonadism might be the result of circulating antibodies to gonadotropin receptors or to an abnormal gonadotropin molecule, a series of clinical and laboratory studies was carried out. Administration of human menopausal gonadotropin had no effect on the serum estradiol level. The patient's serum did not affect follicle-stimulating hormone binding to a membrane preparation of monkey testes, suggesting the absence of antibodies to follicle-stimulating hormone receptors, nor did the patient's serum affect in vitro responsiveness of human granulosa cells to human menopausal gonadotropin. Unresponsiveness to exogenous gonadotropins, combined with anatomically normal follicular apparatus and the absence of serum antibodies to gonadotropin receptors, supports the concept of a gonadotropin receptor or a postreceptor defect.

Adult↗

A double blind study to evaluate the effect of methyldopa on menopausal vasomotor flushes.

Vasomotor flush (VMF) is the most consistent symptom associated with the menopause. Nonsteroidal agents such as clonidine have been demonstrated to decrease VMF. Anecdotal reports suggested that VMF were reduced in hypertensive women receiving methyldopa, which is also an alpha2-adrenergic agonist. This study describes a double-blind cross-over placebo-controlled study to evaluate the effect of methyldopa on VMF. Diary reports were made and serum LH and digital skin temperature were measured in 10 menopausal women with 30 or more VMF/week and serum FSH levels of 40 mIU/ml or greater. The frequency of VMF, LH pulse, and temperature elevation during a 5-h observation period and VMF per week based on diary reports were compared for the baseline and fourth week of therapy with methyldopa (250 mg, three times daily) and placebo therapy. The patients reported some amelioration of VMF (P less than or equal to 0.02) during drug therapy. Objectively, only the frequency of LH peaks was decreased with methyldopa therapy (P less than or equal to 0.05). Because of significant side effects and minimal symptomatic improvement, methyldopa is not likely to be an acceptable therapy for VMF.

Adult↗

Retrograde menstruation in healthy women and in patients with endometriosis.

Blood was found in the peritoneal fluid in 90% of women with patent tubes at laparoscopy during perimenstrual time. If the fallopian tubes were occluded, then only 15% of patients had evidence of blood in the pelvis. Also, 90% of patients with endometriosis and eight of nine women on oral contraceptives had bloody fluid during the menstrual period. The present observations indicate that retrograde menstruation through the fallopian tubes into the peritoneal cavity is a very common physiologic event in all menstruating women with patent tubes.

Ascitic Fluid↗

Increased activation of pelvic macrophages in infertile women with mild endometriosis.

Pelvic fluid was collected from 66 women undergoing laparoscopic sterilization or diagnostic laparoscopy for evaluation of infertility. Cells consisting mainly of macrophages were separated, counted, and subjected to histochemical staining for acid phosphatase and myeloperoxidase as markers of cell irritation. Pelvic fluid was analyzed for acid phosphatase, neutral protease, and extractable prostaglandin E2 and F2 alpha. A higher proportion (46% versus 15%) of the macrophages in the group with mild endometriosis exhibited positive staining for acid phosphatase as compared with the fertile group. Pelvic fluid from patients with mild endometriosis had higher acid phosphatase and neutral protease activity than that from fertile patients (p less than 0.05, p less than 0.01). The content of either prostaglandin was not significantly higher in the endometriosis group as compared with the fertile group. The results suggest that mild endometriosis is associated with activation of macrophages and release of active substances into peritoneal fluid that may be responsible for the associated infertility.

Acid Phosphatase↗

Infertility in women exposed to diethylstilbestrol in utero.

To evaluate the reproductive consequences of prenatal diethylstilbestrol (DES) exposure, 33 infertile couples were studied in whom the female had been exposed to DES in utero. Infertility was attributed to uterotubal junction obstruction in 3 couples, anovulation in 7, endometriosis in 11, cervical obstruction in 2, adnexal adhesions in 2, oligospermia in 1 and luteal insufficiency in 3; in 4 couples no cause of infertility could be identified. No unique intraabdominal abnormalities attributable to DES exposure were observed. Four tubal pregnancies occurred in women with grossly normal oviducts. Nine of 11 women who had previously undergone surgical manipulation of the cervix (cryosurgery, cautery or conization) developed cervical stenosis, and 8 of them were found to have endometriosis. Despite our not having an appropriate referral infertility population for comparison, these findings are consistent with the following hypotheses regarding women prenatally exposed to DES: (1) surgical manipulation of the cervix more frequently leads to cervical stenosis and ultimately pelvic endometriosis, (2) tubal pregnancies may occur by a mechanism unrelated to salpingitis, and (3) the spectrum of problems causing infertility is similar to that in the non-DES-exposed population.

Adult↗

Factors affecting the pregnancy rate in clomiphene citrate induction of ovulation.

During the five years ending on December 31, 1981, 159 anovulatory and oligomenorrheic patients were treated with clomiphene citrate for induction of ovulation. Overall, 86% of these patients ovulated, and 49% of the patients who ovulated conceived. Life table analysis was employed to investigate factors contributing to reduced conception rates, including abnormal semen analysis, pelvic or tubal abnormalities, and poor cervical mucus. Elevated serum testosterone levels did not affect conception rates. The most significant factor contributing to reduced overall pregnancy rates was patient discontinuation of therapy. Cumulative pregnancy rates corrected for discontinuation approach 100% after ten cycles of therapy. During this period, the monthly probability of pregnancy (monthly fecundability) remained constant. Optimal pregnancy rates are attained if other infertility factors are corrected and treatment is continued for ten to 12 ovulatory cycles.

Cervix Mucus↗

Pelvic macrophages in normal and infertile women: the role of patent tubes.

The volume of peritoneal fluid and its macrophage content were examined in 80 women undergoing laparoscopy. The amount of pelvic fluid was not dependent on the patency of the fallopian tubes, and no statistical difference in the fluid volume was observed between the infertile groups, including those with endometriosis, as compared to the fertile group. The number of pelvic macrophages in fertile women was extremely high during the menstrual period, and during the rest of the cycle, it remained at a basal level. The number of pelvic macrophages in women with occluded tubes was low. Four of 21 infertile patients with mild endometriosis had very high numbers of pelvic macrophages, even in the luteal phase. These results suggest that the passage of endometrial irritants through the tubes elicits a macrophage response in the peritoneal cavities of both normal women and patients with endometriosis. Although most patients with endometriosis had normal numbers of peritoneal macrophages, it is possible that these macrophages differ qualitatively from normal, and this could explain the associated infertility.

Ascitic Fluid↗

Application of interspecies in vitro fertilization in the initial assessment of the infertile couple.

Methods to evaluate male reproductive potential are limited. Conventional semen analysis does not necessarily reflect sperm functionality. In this study we investigated the correlation of the interspecies penetration test with clinical evaluation of 106 infertile couples. In vitro penetration results in 92 of 106 men correlated well with clinical diagnosis. In 28 couples with a male infertility factor, the mean penetration rate was 18%, whereas in 78 infertile couples with no known male factor, the rate was 50%. The mean for all patients tested was 40%. This was well below a mean of 73% for a donor population. The major discrepancy between the interspecies penetration test and clinical findings occurred in a group of nine patients with 0% penetration who had been judged normal by history and semen analysis. In general, the interspecies penetration test correlates well with male clinical evaluation but does the complementary information in certain cases. At present, its greatest utility seems to be in evaluation of unexplained infertility, in unexplained failure of female therapy, or in selection of patients for donor insemination.

Animals↗

HLA antigens in black South African children with rheumatic heart disease.

The high incidence of rheumatic heart disease (RHD) in black South African children has been attributed mainly to poor socio-economic status and over-crowding. In order to elucidate whether other factors, in particular genetic, were responsible, the HLA-status of 61 black children with rheumatic heart disease was compared with that of 1165 normal controls. Overall, no differences were found, except a higher incidence of HLA-B25 and BW51 in the group with rheumatic heart disease, when the difference was not of statistical significance. Moreover, when the patients were considered in two groups, viz. (a) a "surgical" group which required cardiac surgery and (b) a "non-surgical" group in which cardiac failure was absent or could be easily controlled by medical therapy, the difference between the two groups was also not of statistical significance, though there was a higher incidence of HLA-A10 (which includes HLA-A25 and A26) in the "non-surgical" group. These data appear to agree with the results of other studies which found no significant association between HLA-status and RHD.

Black People↗

Clomiphene citrate therapy of infertile women with low luteal phase progesterone levels.

Sixty-nine infertile women with a midluteal serum progesterone level of 4 to 14 ng/ml were treated with a graduated dosage schedule of clomiphene citrate until the progesterone level on day 21 was greater than 20 ng/ml. Thirty-one pregnancies occurred, 58% during the first adequate treatment cycle and 19% during the second cycle. The abortion rate was 23%. After 6 adequate treatment cycles, laparoscopic evaluation was performed on 28 of 39 patients who did not conceive. Pathology was noted in 57%. Seven of 17 patients with intraperitoneal causes of infertility conceived after alternative therapy. The corrected pregnancy rate was 60%. Results of this study suggest that low luteal phase progesterone levels may compromise fertility and that clomiphene citrate enhances pregnancy rates.

Adult↗