Search PubMed⌕ Search

Biomedical subjects

E M Wallace

Publications and source records attributed to E M Wallace.

86 records · Page 5Linked to original sources

Evaluation of maternal serum immunoreactive inhibin as a first trimester marker of Down's syndrome.

BACKGROUND AND OBJECTIVE: Maternal serum immunoreactive inhibin has been shown to be significantly elevated in Down's affected pregnancies in the second trimester, suggesting that it may be useful in prenatal diagnosis. We have investigated whether it is similarly elevated in the first trimester. DESIGN: Stored maternal sera from women with Down's affected pregnancies and chromosomally normal control pregnancies were retrieved for analysis. These sera had been collected prospectively at either 11 or 12 weeks gestation as a routine antenatal booking procedure. SUBJECTS: From records, 11 women were identified as having had a Down's pregnancy. For each of these, 4 controls matched for gestation and duration-of-storage were also identified. MEASUREMENTS: Two different inhibin immunoassays were evaluated, one using an antibody raised against 31 kDa bovine inhibin and the other, a commercial two-site assay, using two antibodies directed against two distinct alpha-subunit epitopes. RESULTS: Neither assay detected a significant effect of gestation on serum inhibin levels. After combining the data from both gestations, no significant difference between the Down's samples and controls for either assay was detected. However, analysis of the data for each gestation separately revealed that one assay detected a significant difference in inhibin levels between Down's affected and unaffected pregnancies at 11 weeks gestation (mean +/- SEM 3186 +/- 195 vs 2020 +/- 172 ng/l, P < 0.01) but not at 12 weeks. The other, commercial, assay did not detect a significant difference at either gestation. In addition, there was poor association between the results of the two assays. CONCLUSIONS: These data suggest that immunoreactive inhibin, as detected by these assays, will not be useful as a late first trimester marker for Down's syndrome and also that these two assays detect different inhibin species in pregnancy serum.

Adult↗

Prostate-specific antigen and prostate gland size in men receiving exogenous testosterone for male contraception.

Steroid regimens containing androgens are being evaluated currently as hormonal contraceptives for men. The possible non-reproductive effects of such treatment were assessed during an efficacy trial using a prototype regime of 200 mg testosterone enanthate i.m. weekly. Prostatic function and size were monitored by regular rectal examination, blood levels of prostate-specific androgen (PSA) were measured in 30 men and prostatic size was measured by trans-rectal ultrasound imaging in a representative subgroup of five subjects for 12 months and for a further 6 months after discontinuation. Despite the sustained rise in serum levels of testosterone, oestradiol and dihydrotestosterone during treatment, there was no detectable increase in prostatic size on rectal examination or any significant change in blood concentrations of PSA. A small but significant increase (14.3 +/- 2.0%) in maximal prostate transverse area was observed in four men while the remaining one showed no change. Our preliminary data demonstrate the feasibility and importance of monitoring prostatic function in the development of androgen-containing male hormonal contraceptives.

Adult↗

Comparison between testosterone enanthate-induced azoospermia and oligozoospermia in a male contraceptive study. I: Plasma luteinizing hormone, follicle stimulating hormone, testosterone, estradiol, and inhibin concentrations.

Sex-steroid based male contraceptive regimes induce azoospermia in only 40-70% of Caucasian men. The reason(s) why the remainder maintains a low level of spermatogenesis (oligozoospermia) despite gonadotrophin suppression is unclear. In order to improve our understanding of this phenomenon, we examined the changes in sperm density and plasma LH, FSH, testosterone (T), oestradiol (E2), and inhibin (IN) in 28 normal men who received 200 mg testosterone enanthate (TE) im weekly during a male contraceptive efficacy trial. Gonadotrophins were measured by an ultrasensitive time-resolved immunofluorometric assay (DELFIA) with a sensitivity of 0.04 U/L, to determine the adequacy of suppression. Seventeen of the 28 men achieved azoospermia; the other 11 remained oligozoospermic (sperm density 3.3-4.7 x 10(6)/mL) after 6 months of TE exposure. Azoospermic subjects displayed a more rapid decline in sperm density, a significant difference being apparent by 5 weeks after starting TE. During TE treatment, both LH and FSH were consistently suppressed to below the limits of detection, whereas there was a 2.5-fold rise in T and E2 with a similar decrease in IN. There were no consistent differences in any of these hormone concentrations between the azoospermic and oligozoospermic groups. Recovery of sperm density to baseline levels or above 20 x 10(6)/mL was significantly slower in the azoospermic group. During the recovery phase, the azoospermic men exhibited significantly higher LH and FSH levels compared to baseline and to the oligozoospermic subjects even though no differences in circulating T, E2, or IN were observed. We conclude that incomplete gonadotrophin suppression or differences in sex steroid or inhibin levels are unlikely to be responsible for the maintenance of minor degrees of spermatogenesis in some men during TE administration. The rebound rise in gonadotrophins in azoospermic but not oligozoospermic responders during recovery may reflect a more profound degree of spermatogenic suppression in the former group.

Adult↗

Residual sperm function in oligozoospermia induced by testosterone enanthate administered as a potential steroid male contraceptive.

To investigate the fertility of men who remain oligozoospermic despite sex steroid suppression, the in-vitro fertilizing capacity of residual spermatozoa was assessed in 30 men receiving intramuscular testosterone enanthate (TE). Spermatozoa were prepared by either Percoll or repetitive centrifugation/washing. Although the mean (+/- SEM) pretreatment zona-free hamster oocyte penetration (HOP) rates were similar (59.4 +/- 10.1 and 63.8 +/- 10.8%), following the induction of oligozoospermia the Percoll-prepared spermatozoa exhibited a penetration rate (26.9 +/- 10.2%) which was markedly greater than that obtained for sperm prepared by repetitive washing (0 +/- 0%). In addition, the partners of two men exhibiting a HOP test with Percoll-prepared spermatozoa, conceived despite a sperm concentration of 3 x 10(6) ml-1 and a negative HOP test with spermatozoa prepared by repetitive washing. These results suggest that Percoll preparation optimizes the assessment of in-vitro sperm function and that the fertility of men with TE-induced severe oligozoospermia is suppressed but not abolished.

Adult↗

Routine programmed electrical stimulation in survivors of acute myocardial infarction for prediction of spontaneous ventricular tachyarrhythmias during follow-up: results, optimal stimulation protocol and cost-effective screening.

Of 3,286 consecutive patients treated for acute myocardial infarction, electrophysiologic testing was performed in 1,209 survivors (37%) free of significant complications at the time of hospital discharge to determine their risk of spontaneous ventricular tachyarrhythmias during follow-up. Sustained monomorphic ventricular tachycardia was inducible by programmed electrical stimulation in 75 (6.2%). Antiarrhythmic therapy was not routinely prescribed regardless of the test results. During the 1st year of follow-up, 14 infarct survivors (19%) with inducible ventricular tachycardia experienced spontaneous ventricular tachycardia or fibrillation in the absence of new ischemia compared with 34 (2.9%) of those without inducible ventricular tachycardia (p less than 0.0005). During the extended follow-up period (median 28 months) of those with inducible ventricular tachycardia, 19 (25%) had a spontaneous electrical event; 37% of these first events were fatal. These results suggest that the most cost-effective strategy for predicting arrhythmia will be obtained by restricting electrophysiologic testing to infarct survivors whose left ventricular ejection fraction is less than 40% and using a stimulation protocol containing four extrastimuli. Electrophysiologic testing is the single best predictor of spontaneous ventricular tachyarrhythmias during follow-up in infarct survivors. The majority (94%) with a negative test benefit from the more reliable reassurance that all is well, whereas the 25% risk of electrical events in those with inducible ventricular tachycardia justifies a prospective trial of effective prophylactic antiarrhythmic interventions.

Anti-Arrhythmia Agents↗

Immunosuppression by seminal plasma from fertile and infertile men: inhibition of natural killer cell function correlates with seminal PG concentration.

Human seminal plasma has uniquely high concentrations of PGE and 19-hydroxy PGE but the function of these PGs has not been elucidated. PGs of the E series have been shown to be paracrine and autocrine regulators of the function of immune cells and high levels of PGE have been shown consistently to suppress function in such cells. Human seminal plasma has a potent immunosuppressive effect and evidence is accumulating that this is largely due to PG components. In this study the effects of human seminal plasma on the killing activity of natural killer (NK) cells as judged by 51Cr release from K562 cells have been studied in groups of fertile and infertile men. Although there was no significant difference in the PGE, 19-hydroxy PGE or the NK cell inhibitory activity in the two groups, the inhibition of NK cell activity was closely correlated with the PGE and the 19-OH PGE content of the seminal plasma in the fertile group. This finding is further evidence that the major contribution to the immunosuppressive properties of human semen is provide by the high concentration of PGs of the E series in this fluid.

Alprostadil↗

Effects of decreasing exogenous GnRH pulse frequency on FSH and inhibin secretion in men with idiopathic hypogonadotropic hypogonadism.

The potential importance of GnRH pulse frequency modulation and steroid or inhibin negative feedback in the selective control of pituitary FSH secretion was investigated in 5 adult men with idiopathic hypogonadotropic hypogonadism in whom plasma testosterone has been previously normalized by pulsatile GnRH therapy. The effects of decreasing frequency of pulsatile iv GnRH administration from 2- to 4-hourly for 7 days were examined at constant GnRH bolus dose or constant daily dose and also with interrupted gonadal steroid feedback using a combination of an anti-androgen (flutamide 250 mg t.i.d.) and an aromatase inhibitor (aminogluthetimide 125 mg b.d.) orally for a further 7 days. Slowing GnRH pulse frequency from 2- to 4-hourly did not alter mean plasma FSH at constant bolus dose or constant total daily doses of GnRH. In two subjects with subnormal but not in another two with normal testicular volumes, FSH rise was observed when the 4-hourly GnRH pulse frequency was combined with the interruption of steroid feedback. These results are not compatible with a major role for GnRH pulse frequency modulation in the regulation of pituitary FSH secretion in the presence of normal gonadal steroid feedback. Irrespective of FSH concentrations, plasma inhibin immunoactivity did not change significantly with the alteration in GnRH pulse frequency. The role of inhibin in the control of FSH therefore remains undefined in men.

Adult↗

Effect of depot medroxyprogesterone acetate and testosterone oenanthate on serum lipoproteins in man.

Ten normal men were given three monthly intramuscular injections of 200mg of depot medroxyprogesterone acetate (DMPA) and 250mg of testosterone oenanthate (TE) as part of a male contraceptive trial. During the three months of treatment, serum high density lipoprotein cholesterol (HDL-C) and the HDL-C:LDL-C (low density lipoprotein cholesterol) ratio were significantly depressed compared to baseline. Although the long-term effect of this alteration in lipoprotein cholesterol metabolism in normolipidaemic men is currently uncertain, these results suggest that the potential cardiovascular risks of progestagen-containing regimens for male contraception will have to be seriously considered.

Adult↗

Using death certificates to estimate the completeness of AIDS case reporting in Ontario in 1985-87.

The completeness of AIDS (acquired immune deficiency syndrome) case reporting in Ontario was assessed by reviewing all AIDS death certificates compiled by the Registrar General between Jan. 1, 1985, and Dec. 31, 1987. Several demographic variables were used to match death certificates with cases reported to the provincial AIDS registry. The completeness of case reporting was then estimated by examining the ratio of reported deaths of patients with AIDS to the total number of deaths reviewed. The estimated completeness of case reporting was 81.1% in 1985, 71.5% in 1986 and 75.4% in 1987; the overall rate for 1985-87 was 75.2%. The difference in the completeness of case reporting from year to year was not statistically significant. There was a significant increase from 1985 to 1986 in the proportion of unreported cases in people who had never been married (p less than 0.02). Reporting was not associated with the patient's age, sex, occupation or place of residence. The deficiency in AIDS case reporting could adversely affect the long-term planning of health care resources and the development of programs to prevent and control the spread of AIDS.

Acquired Immunodeficiency Syndrome↗

Unexplained deaths in a children's hospital. An epidemiologic assessment.

During a nine-month period, July 1980 through March 1981, the mortality rate for patients on the cardiology ward of a children's hospital was 43.1 deaths per 10,000 patient-days, as compared with 11.0 deaths per 10,000 patient-days during the preceding 54 months. Twenty-five (76 per cent) of 33 infant deaths during this nine-month period occurred between midnight and 6:00 a.m., as compared with 1 of 10 infant deaths during a separate 27-month period (P less than 0.001). Although nearly all deaths occurred in patients with serious congenital heart disease, epidemic-period deaths were more likely to have an unexpected timing and a clinical pattern consistent with digoxin toxicity. In four patients, forensic and clinical digoxin measurements suggested that an intravenous overdose of digoxin had been administered shortly before death. Although a review of nursing schedules revealed a strong association (relative risk, 64.6) between infant deaths and the duty times of a particular nurse, the cause of the epidemic remains unclear. The study led to suggestions that the hospital strengthen central control over procedures for dispensing medicines and implement a system for monitoring the occurrence of deaths by time and place within the hospital.

Digoxin↗

Maternal and foetal activin A levels: associations with normal and abnormal labour.

In pregnancy the feto-placental unit is the major source of activin A. However, the role(s) of activin A in late pregnancy remain uncertain and controversial. In particular, whether activin A levels alter in association with labour is unclear. In a cross-sectional cohort study, maternal serum samples were collected from women at term prior to elective Caesarean section (n=11), during labour prior to a spontaneous vaginal delivery (n=31), an instrumental vaginal delivery (n=16) or an emergent Caesarean section (n=7). Umbilical artery blood samples were collected from 75 pregnancies, after an elective Caesarean section (n=9), a normal vaginal delivery (n=37), an instrumental vaginal delivery (n=15) or an emergent Caesarean section (n=14). Levels of activin A were measured and compared according to modes of delivery.Maternal, but not foetal, serum activin A was increased significantly in women who were delivered by an intrapartum Caesarean section compared to other modes of delivery. Foetal, but not maternal, serum activin A was significantly correlated with umbilical artery pH. Maternal serum activin A is increased in women undergoing an intrapartum Caesarean section compared to either a vaginal delivery or an elective Caesarean section. The mechanism(s) underlying this observation are not clear.

Activins↗