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Biomedical subjects

A J Conway

Publications and source records attributed to A J Conway.

34 records · Page 2Linked to original sources
PubMed1993

Activity of a nitrofurazone matrix urinary catheter against catheter-associated uropathogens.

Nitrofurazone-coated urinary catheter segments inhibited 51 (75%) of 70 urinary bacterial isolates from patients with indwelling catheters. Inhibition zones correlated significantly with the nitrofurazone MIC (r2 = 0.79, P = 0.0001). All strains except the Pseudomonas spp. were inhibited by < or = 64 micrograms of nitrofurazone per ml. MICs of nitrofurazone and nitrofurantoin correlated significantly (r2 = 0.93, P = 0.0001).

Bacteria↗
PubMed1992

Suppression of human spermatogenesis by testosterone implants.

Hormonally induced azoospermia is an effective, reversible form of male contraception; however, some men treated with weekly im testosterone enanthate (TE) injections fail to become azoospermic. As weekly injections cause widely fluctuating and supraphysiological testosterone levels, we tested the hypothesis that more stable, physiological testosterone levels would consistently produce azoospermia. Using a depot testosterone formulation which provides stable, physiological range testosterone levels for up to 6 months, we studied nine men before and after insertion of six 200 mg testosterone implants under the abdominal wall skin and compared the results with 38 men treated in a previous study with weekly im injections of 200 mg TE. Testosterone implants suppressed sperm output to near-azoospermia between the second to fourth postimplant months returning to normal by the sixth postimplant month. The fall in sperm output at the first month was greater after testosterone implants than TE injections (58% vs. 17%, P = 0.011) but similar proportions of men became azoospermic (5/9 vs. 25/38) or severely oligozoospermic (< 1 million/ml; 9/9 vs. 37/38). Plasma testosterone and estradiol levels remained mostly within the eugonadal range after implants but were markedly supraphysiological during TE injections. Both treatments suppressed immunoreactive LH and FSH to undetectable levels by ultrasensitive fluoroimmunoassay. Sex hormone-binding globulin levels were decreased and PRL levels increased by TE injections but neither was changed by testosterone implants. Prostate-specific antigen demonstrated a small rise of marginal significance (P = 0.065) after testosterone implants. Fewer men experienced acne after implants (0/9 vs. 25/38, p = 0.0004). Therefore a depot testosterone preparation with quasi-zero-order release demonstrates higher dose efficiency with similar (but not uniform) efficacy at inducing azoospermia but may cause fewer androgenic side-effects than weekly TE injections.

Adult↗
PubMed1990

Pharmacokinetics and pharmacodynamics of testosterone pellets in man.

We studied the pharmacokinetics and pharmacodynamics of sc implanted pellets of fused crystalline testosterone. Three different regimens (6 x 100 mg, 6 x 200 mg; and 3 x 200 mg) were compared in a prospective, cross-over clinical trial in which androgen deficient men were administered the three-dose combinations in a randomized starting order at intervals of at least 6 months. Plasma free and total testosterone, sex hormone-binding globulin, LH, and FSH were measured before and at monthly intervals for at least 6 months after 111 pellet implantation in 43 men with hypergonadotropic (n = 22) or hypogonadotropic (n = 21) hypogonadism. Total and free testosterone levels peaked at the first month and were maintained at physiological levels for 4 to 5 (600 mg doses) or 6 (1200 mg dose) months after a single implantation. Absorption of testosterone from 100 mg and 200 mg pellets closely approximated zero-order throughout the effective life of the pellets and exhibited a half-duration of 2.5 months. The estimated rate of release of testosterone was 1.5 (95% confidence limits 1.3-1.6) mg/day.200 mg pellet as determined from direct measurement of residue in pellets recovered after extrusion and confirmed independently from percent absorbed-time plots. The bioavailability of testosterone was virtually complete and the time course was predictable from the total implant dose and, to a lesser extent, total initial surface areas of pellets. Despite wide fluctuations in testosterone, SHBG levels were not changed during 6 months. In men with hypergonadotropic hypogonadism, both LH and FSH levels were uniformly and markedly suppressed by increased testosterone after pellet implants. LH and FSH were highly correlated with each other (r = 0.87) and inversely with total (r = 0.47 and 0.45, respectively) and free (r = 0.46 and 0.47) testosterone levels. Nadir LH levels occurred at 1-3 months (600 mg) and 1-4 months (1200 mg) reaching levels comparable with eugonadal controls. In contrast nadir FSH levels occurred at similar times but remained elevated compared with eugonadal controls. We conclude that fused pellets of crystalline testosterone provides very satisfactory depot androgen replacement exhibiting many desirable features for androgen replacement.

Adult↗
PubMed1988

Randomized clinical trial of testosterone replacement therapy in hypogonadal men.

We have compared the pharmacokinetics and pharmacodynamics of the three commonly used testosterone formulations in a prospective, randomized cross-over clinical trial. Plasma free and total testosterone and their ratio (proportion of unbound testosterone), sex hormone-binding globulin (SHBG), oestradiol, LH and FSH were measured in 15 hypogonadal men (nine hyper- and six hypogonadotrophic) who underwent, in a randomized sequence, three treatment periods each separated by an intervening washout period. The treatments were: (i) intramuscular injection of 250 mg mixed testosterone esters at 2-weekly intervals, (ii) oral testosterone undecanoate 120 mg bd, and (iii) subcutaneous testosterone pellets (6 x 100 mg). Pellet implantation gave the most prolonged effect with free and total testosterone levels being elevated for up to 4 months. This was accompanied by prompt and sustained suppression of plasma LH and FSH, an increase in plasma levels of oestradiol but no change in SHBG levels. In contrast, intramuscular injections induced marked but reproducible week-to-week fluctuations in free and total testosterone, which resulted in a small decrease in plasma SHBG levels, less marked suppression of LH and FSH and a smaller increase in plasma levels of oestradiol. Oral testosterone undecanoate produced the most variable plasma levels of free and total testosterone with a peak in the first treatment week and a fall thereafter and, despite maintenance of testosterone levels within the physiological range, there was no significant suppression of plasma levels of LH and FSH, and oestradiol levels were unchanged but levels of SHBG and total cholesterol were decreased. Free testosterone levels were increased disproportionately during testosterone treatment as the proportion of unbound testosterone was increased by all three treatments. All three testosterone preparations lowered plasma levels of urea and all were without biochemical or haematological toxicity. Reported sexual function was better maintained and side-effects were fewer with parenteral compared with oral treatments. The marked decrease in SHBG and cholesterol levels during oral testosterone undecanoate, when compared with parenteral treatments, occurred despite lesser androgenic effects (suppression of gonadotrophin levels and reported sexual function), which suggests that the liver is exposed to excessive androgenic load via the portal vein during oral treatment with testosterone esters. It is concluded that testosterone pellets give the closest approximation to zero-order (steady-state) delivery conditions for up to 4 months after a single insertion.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1985

Psychological and attitudinal profiles in donors for artificial insemination.

Few objective data are available concerning the psychological profiles and attitudes of sperm donors in artificial insemination programs. We studied 30 consecutive new volunteers and 45 established sperm donors using the Cattell 16PF personality profile and an attitudinal survey concerning motives for donation, attitudes toward uses of sperm, desire for knowledge of outcomes, and attitudes toward disclosures of identifying and nonidentifying information between the parties to artificial insemination. Donors differed from the population norms in 7 of 16 first-order and 1 of 4 second-order personality factors, and this difference appeared to reflect their self-selection as donors. The predominant motive for donation was altruism, but secondary motives were also common. Financial motivation was very low in this population with few students. Donors approved of all current and most hypothetical uses of sperm but were not in favor of disclosures of information to other participants in the program. Restriction of disclosures to nonidentifying details was more acceptable. Unmarried donors were more often motivated for nonaltruistic reasons and were more in favor of disclosures. Attitudes of sperm donors were mostly stable over at least 3 years, but an increasing minority with time envisaged circumstances that might lead to their withdrawal from the program.

Attitude↗
PubMed1984

Young's syndrome. Obstructive azoospermia and chronic sinopulmonary infections.

We studied 29 men with Young's syndrome, a combination of obstructive azoospermia and chronic sinopulmonary infections. Men with this syndrome have only mildly impaired respiratory function and normal spermatogenesis; the azoospermia is due to obstruction of the epididymis by inspissated secretions. The diagnosis is based on the occurrence of chronic sinopulmonary infections, persistent azoospermia, normal spermatogenesis, and characteristic epididymal findings, as well as exclusion of cystic fibrosis and the immotile-cilia syndrome. The sperm themselves appear to be normal in Young's syndrome. Pregnancies had occurred in five couples; in three paternity was documented by genotyping. Thus, improved microsurgical and medical therapy might restore fertility. We suggest that Young's syndrome has a prevalence comparable to that of Klinefelter's syndrome and is a common cause of both chronic sinopulmonary infection and azoospermia.

Adult↗
PubMed1984

Testicular function in potential sperm donors: normal ranges and the effects of smoking and varicocele.

Testicular exocrine (semen analysis) and endocrine (plasma LH, FSH, prolactin and testosterone) function was assessed in 119 consecutive healthy men presenting for screening as potential sperm donors. Since these volunteers were unbiased with respect to their fertility status, this sample of the general male population was suitable to determine normal ranges and the influence of a variety of physical (height, weight, standardized body weight, varicocele) and demographic (age, marital and fertility status, tobacco and alcohol consumption) factors on normal human testicular endocrine and exocrine function, without the confounding effects of bias in selection of subjects. The statistical distribution of all seminal parameters was non-gaussian, but cube-root transformation of the data normalized the distribution, allowing for parametric statistical analysis. The median (and 95% confidence limits) for the various semen parameters was 73.0 (10.6-235.3) million sperm per ml; 189.0 (12.6-868) million sperm per ejaculate; 50.4 (5.9-181.9) million motile sperm per ml; 133.0 (6.9-661.7) million motile sperm per ejaculate; 54.0 (7.0-172.9) million morphologically normal sperm per ml and 138.5 (7.5-672) million morphologically normal sperm per ejaculate. Testicular volume was correlated positively with measures of physique such as standardized body weight (r = 0.25, P less than 0.01) and body surface area (r = 0.30, P less than 0.002), and negatively with plasma levels of FSH (r = -0.31), P less than 0.002) but not LH. Sperm output was positively correlated with testicular volume (r = 0.28, P less than 0.005) and negatively correlated with plasma FSH (r = -0.31, P less than 0.002) and plasma LH (r = -0.31, P less than 0.002). Smoking was associated with a highly significant reduction in sperm output and motility. Men with varicocele (25%) were significantly taller, had slightly lower haemoglobin levels and moderate left (but not right) testicular atrophy, but neither seminal nor hormonal parameters were different from men without varicocele. There was no difference in any markers of human testicular function between men according to marital or fertility status, grades of moderate alcohol consumption or the presence of low titres of sperm antibodies.

Adult↗
PubMed1983

Prevalence, testicular function and seminal parameters in men with sperm antibodies.

A prospective survey of 289 unselected men, attending a male infertility clinic (200 subjects) or as donors presenting for an artificial insemination programme (89 subjects) was performed. High titres of sperm agglutinating antibodies (greater than 1/32) were present only in a group of (6.5%) of infertile men but not in volunteer donors. Low titres occurred with similar frequencies (12%) in both groups. The sperm immobilizing antibody test was less sensitive and more specific but of no additional diagnostic benefit. Patients with high titres of sperm antibodies had evidence of testicular damage with decreased testicular volumes, elevated serum FSH and LH levels and reduced sperm density and motility whereas low titres were not associated with any testicular or seminal pathology. These data suggest a sub-group of infertile men have evidence of spermatogenic damage and impaired sperm function associated with high titres of sperm antibodies. Immunologic infertility in these men may reflect either an underlying autoimmune orchitis or a secondary immune reaction following testicular damage of various causes.

Adult↗
PubMed1983

Heterozygote detection in congenital adrenal hyperplasia.

Detection of heterozygote carriers for congenital adrenal hyperplasia by use of a modified tetracosactide (a synthetic corticotropin) stimulation test with prior overnight dexamethasone suppression proved to have a diagnostic accuracy of 95%. Discrimination of heterozygotes from normals was best when we used a criterion based on the ratios of 17 alpha-hydroxyprogesterone to cortisol at baseline and at 30 min after intravenous administration of 250 micrograms of tetracosactide.

17-alpha-Hydroxyprogesterone↗
PubMed1980

Detection of varicocele by radionuclide blood-pool scanning.

Varicocele is a common and treatable cause of male subfertility. The authors describe a new technique for varicocele detection using radionuclide blood-pool imaging of the scrotum. Of 83 patients studied, 29 had a clinically palpable varicocele of various sizes, and 26 of them were demonstrated by this technique. Two of the false negatives were bilateral varicoceles. In the 41 patients with no clinically detectable varicocele, there were 10 positive and 10 marginally asymmetric studies. The results indicate that this technique detects unilateral varicoceles with high sensitivity, including some which are subclinical. There may be significant implications for treatment of infertility.

Adult↗
PubMedDate not supplied

Testicular function and glycemic control in diabetic men. A controlled study.

We have investigated testicular function in 28 insulin-dependent diabetic men under the age of 50 years and 119 age-matched controls. Diabetics had reduced testicular volume, semen volume, total and total motile sperm output while plasma LH and FSH levels were elevated. Reduction in semen volume and impotence were more common in long-standing complicated diabetes. Glycosylated hemoglobin (GHb) levels were positively correlated with plasma LH levels (r = 0.46, p less than 0.02) but there was no direct correlation of glycemic control and spermatogenesis. The differences in testicular function were due to decreased spermatogenesis and could not be explained by other forms of testicular pathology or the presence of diabetic neurovascular complications. We conclude that the function of the hypothalamic pituitary testicular axis is impaired in diabetic men, that this impairment is at least partly related to the degree of preceding glycemic control and that multiple levels of the axis may be dysfunctional.

Adult↗
PubMedDate not supplied

Testicular function and fertility in men with homozygous alpha-1 antitrypsin deficiency.

Fertility and testicular function were studied in eight men with severe homozygous (Pi ZZ variant genotype) alpha-1 antitrypsin (AAT) deficiency. Age- and marital duration standardized fertility, clinical androgenic features, mean testicular volume, plasma luteinizing hormone (LH) and follicle-stimulating hormone (FSH) and semen analysis were all normal apart from a reduction in semen volume. Mean plasma total and free testosterone were elevated and the percentage free testosterone reduced compared with age-matched, healthy fertile controls indicative of increased sex-hormone binding globulin (SHBG) levels representing an early marker for subclinical hepatic dysfunction associated with AAT-deficiency. In view of the preservation of normal fertility and testicular function despite chronic respiratory disease and premature death with deleterious AAT gene variants, it is proposed that the high prevalence of genetic polymorphism in the AAT protein may be maintained by the chronological asynchrony of the periods of maximal male reproductive activity (40 years) and the late onset (greater than 40 years) of symptoms in severe AAT deficiency rather than by any balance between reduced reproductive fitness of homozygotes and heterozygote advantage.

Fertility↗
PubMedDate not supplied

Hypothalamic-pituitary adrenal function in end-stage non-alcoholic liver disease.

Patients with end-stage liver disease have significant mortality often associated with intercurrent episodes of bleeding or sepsis. Intact adrenal function is essential in such situations. In order to test the hypothesis that adrenal insufficiency might be present in severe liver disease, hypothalamic-pituitary adrenal function was evaluated in patients with end-stage liver disease awaiting transplantation. The study had a prospective, open comparative design with patients restricted to those having non-alcoholic liver disease in order to avoid the confounding direct effects of alcohol on adrenocortical function. Fifty-one consecutive patients with end-stage, non-alcoholic liver disease undergoing evaluation for liver transplantation and 40 healthy controls were studied. Patients who had used corticosteroids (n = 8) or who were unable to complete the investigations (n = 5) were excluded leaving 38 patients eligible for analysis. Adrenal function was evaluated under basal conditions by single morning measurements of plasma total and free cortisol, corticosteroid-binding globulin, dehydroepiandrosterone sulfate and by adrenal stimulation indirectly using insulin-induced (0.1 U/kg, i.v.) hypoglycaemia and/or directly by adrenocorticotrophic hormone (ACTH); 250 micrograms tetracosactrin, i.v.) stimulation. Compared with healthy controls, patients with liver disease had a 64% reduction in maximal increments of plasma cortisol to indirect adrenal stimulation via insulin-induced hypoglycaemia and a 39% reduction to direct adrenal stimulation by ACTH (all P < 0.001). There was a significant negative correlation between the severity of underlying liver disease as assessed by Child-Pugh scores and peak control responses to ACTH (r = -0.647, P < 0.0001) and insulin-induced hypoglycaemia (r = -0.597, P < 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗