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Biomedical subjects

H W Baker

Publications and source records attributed to H W Baker.

At least 145 records · Page 8Linked to original sources

Seminal transferrin, an index of Sertoli cell function: is it of clinical value?

To determine the clinical value of seminal transferrin measurements, transferrin concentrations in seminal plasma were determined by single radial immunodiffusion. Men with various disorders of spermatogenesis had significantly lower mean values than those with normal semen (170 micrograms/ejaculate, s.e.m. = 18.4), oligospermia (40.5 micrograms, s.e.m. = 7.2) or azoospermia due to primary seminiferous tubule failure (65.9 micrograms, s.e.m. = 29.1). In these subjects with patent genital tracts, seminal transferrin was directly correlated with sperm concentration and indirectly correlated with serum FSH levels. Seminal transferrin increased following gonadotrophin treatment of men with gonadotrophin deficiency from 19.6 micrograms (s.e.m. = 5.5) to 108.6 micrograms (s.e.m. = 31.7). Patients with genital tract obstructions also had low levels; vasal agenesis (21.8 micrograms, s.e.m. = 5.6), vasectomy (48.5 micrograms, s.e.m. = 21.0), epididymal obstruction (46.6 micrograms, s.e.m. = 7.1). These results confirm that most seminal transferrin comes from the testes and reflects Sertoli cell function. However, there is a very wide range of transferrin levels in normal semen and a number of normospermic samples have low values similar to those seen with abnormal Sertoli cell function or obstruction. Thus, measurement of seminal transferrin is of limited diagnostic value.

Genital Diseases, Male↗

Protein carboxyl methylase in asthenospermia.

Protein carboxyl methylase (PCM) activity was measured in human spermatozoa of 16 normal fertile men and 26 men with various forms of asthenospermia. PCM activities were in the range 14-635 pmol/min per 10(9) sperm. Six men with idiopathic asthenospermia had low PCM activity but the defect of sperm motility was not severe (sperm motility 25-50%). One man with zero sperm motility and sparse mitochondria in the midpiece spiral had high PCM activity. Two men, one with idiopathic asthenospermia and the other with asthenospermia following vasoepididymostomy, also had high PCM activities. PCM activity did not correlate with motility or motility index but there was a correlation between PCM activity and the proportion of immature forms in semen. Thus, the relationship between PCM activity and low motility of sperm is not simple and other cells also contribute to overall seminal PCM activity.

Epididymitis↗

Association between occupational group and sperm concentration in infertile men.

The association between infertility and occupational group was examined using information collected from 1695 male patients. Although lack of detail in the nine occupational classifications may have diluted effects, mean sperm concentrations were significantly different, being highest in administrative and professional groups and lowest in farming and transport groups. Reported exposures to heat and chemicals were also significantly different between occupations. Greater occupational exposure to toxins may contribute to lower sperm concentrations in some groups such as farmers. More detailed research is needed to elucidate the association between occupation and infertility in men.

Adult↗

Testicular vein ligation and fertility in men with varicoceles.

Pregnancy rates in 651 subfertile couples in which the man had a varicocele were analysed by life table methods and were not found to be significantly different before and after testicular vein ligation performed in 283 patients. Estimated proportions of couples conceiving were roughly 30% by one year and 45% by two years in both groups. The operation was also not associated with improvement in results of semen analysis. These findings suggest that testicular vein ligation for varicoceles does not improve fertility.

Female↗

Magnetic-induction hyperthermia. Results of a 5-year multi-institutional national cooperative trial in advanced cancer patients.

Nine US institutions performed 14,807 Phase I-II treatments of magnetic-induction (Magnetrode [Henry Medical Electronics, Inc., Los Angeles, CA]) hyperthermia in 1170 adults. All had advanced tumors: 20% had untreated inoperable cancer or disease progression despite surgery (10%), radiation therapy (XRT) (3%), chemotherapy (27%), or combinations (40%); 67% had pain; and 79% had reduced activity. Eighteen percent were advanced primaries, 26% were recurrent, and 56% metastatic tumors in the head and neck (7%), body wall (7%), extremity (4%), abdominal cavity (17%), pelvis (17%), lung (15%), or liver (30%); 36% were less than 5 cm and 64% greater than or equal to 5 cm. Treatments were to safe tolerance for 30 to 60 minutes for five or more treatments. Results in 960 evaluable patients were complete response 9% (1-34 months; median, 7 months), partial response 18% (1-39 months; median, 4 months), minimal response 10% (1-15 months; median, 3 months), and no change 33% (1-32 months; median, 3 months), with decreased pain in 30% and improved activity in 21%, independent of histologic type or site. Regression was dependent on treatment type and minimum temperature: heat only, 23%; heat + XRT, 60%; heat + less-than-standard XRT because of prior XRT failure, 39%, heat + intravenous (IV) chemotherapy, 28%; heat + same previously failed IV chemotherapy, 20%; heat + intraarterial (IA) chemotherapy, 28%; heat + same previously failed IA chemotherapy, 15%; heat + standard XRT + chemotherapy, 58%; heat + less-than-standard XRT + chemotherapy, 47%; less than 40 degrees C, 31%; 40 to 40.9 degrees C, 45%; 41 to 41.9 degrees C, 54%; 42 to 42.9 degrees C, 47%; 43 to 43.9 degrees C, 40%; 44 to 44.9 degrees C, 33%; 45 to 45.9 degrees C, 55%; 46 to 46.9 degrees C, 63%; greater than 47 degrees C, 100%. There were 49 (0.33%) skin burns and 2 systemic injuries (stomach ulcer at 1 month; lung fibrosis at 9 months). This trial indicates that localized hyperthermia has a significant role in palliation of human advanced solid cancer.

Body Temperature↗

Increased frequency of autoantibodies in men with sperm antibodies.

Autoantibodies to thyroid microsomes were more frequent in 102 infertile men with complement-dependent sperm-immobilizing activity (sperm immobilization test [SIT] ) in serum (11.8%) than in a control group of 277 men of comparable ages and semen quality without sperm antibodies (4.3%, P less than 0.05). Frequencies of organ-specific antibodies (antigastric parietal cell, antithyroglobulin, and antithyroid microsome) in 57 men with genital tract obstructions and positive SIT were similar to those for control subjects, and there were no significant differences in the frequencies of non-organ-specific autoantibodies (antinuclear antibody, rheumatoid factor, antimitochondrial, and anti-smooth muscle) in the three groups. Because in men without genital tract obstruction antithyroid microsomal autoantibodies were more common with sperm antibodies than without, the possibility of a genetic factor in the causation of sperm autoimmunity should be considered.

Adult↗

Interaction between human cervical mucus and sperm surface antibodies.

The immunobead test was used to study the immunoglobulin class of antibodies on sperm before and after penetration through a microcolumn of cervical mucus. Sixteen men with positive sperm antibodies (positive sperm immobilization test) and sperm that penetrated cervical mucus in prior tests were selected for study. However, at the time of study, sperm from seven subjects could not be recovered from the microcolumn. The nine subjects from whom motile sperm were obtained after passage through the column had better sperm mucus penetration tests, lower proportions of sperm binding to anti-IgA immunobeads, and higher proportions of sperm with tail-tip-only binding. Sperm recovered after penetration through the mucus microcolumn displayed a greatly reduced binding to anti-IgA immunobeads in all nine subjects, whereas similar reductions in anti-IgG binding occurred only in four subjects. These results confirm that IgA and sperm-head-directed antibodies are more important than IgG and sperm tail-tip-directed antibodies in impairing sperm penetration of cervical mucus.

Antibodies↗

Variability in the apparent molecular weight of inhibin.

An in vitro bioassay based on suppression of GnRH-stimulated FSH secretion by pituitary cells in culture was used to monitor inhibin activity after dialysis, gel filtration or polyacrylamide gel electrophoresis of protein preparations from a variety of gonadal secretions and extracts under native and dissociating conditions. The suggestion that inhibin is a peptide of molecular weight less than 5000 was not confirmed. Although some fractions of low molecular weight suppressed FSH secretion, the amount of activity was low and the dose response curves were not parallel with a standard preparation of inhibin. Under most conditions, inhibin eluted with an apparent molecular weight of about 90 000. However, gel filtration of rete testis fluid protein in 1 M acetic acid resulted in elution of inhibin activity with a lower apparent molecular weight and with polyacrylamide gel electrophoresis in 0.1% (w/v) sodium dodecylsulfate, the apparent molecular weight was 30 000. It is concluded that inhibin is a protein which tends to aggregate and coelute with larger molecules.

Animals↗

Spontaneous improvement in semen quality: regression towards the mean.

Regression towards the mean was demonstrated in semen analyses from 216 donors for artificial insemination by selecting those with low sperm concentration (less than 40 X 10(6)/ml), low motility (less than 50%) or low motility index (less than 120) in the first test. For each characteristic, the result was significantly higher in the second test, the means for first and second tests being, for sperm concentration 28 and 56 million per ml (n = 14, P less than 0.01), for motility 42 and 55% (n = 14, P less than 0.01) and for the motility index 95 and 131 (n = 24, P less than 0.001). Regression towards the mean occurs whenever extremes of the range of a variable and selected for re-measurement. Many of the current treatments for oligospermia and asthenospermia have been promoted because semen quality improved during uncontrolled studies in which this phenomenon may have been operative. Using means of multiple samples before and following therapeutic intervention will not prevent regression towards the mean, only reduce its magnitude. Thus, placebos are essential in the evaluation of treatments for male infertility.

Humans↗

Are conventional sperm morphology and motility assessments of predictive value in subfertile men?

Sperm morphology and motility are believed to be important prognostic factors for fertility. Results of a group of 67 men investigated for primary infertility who had mean sperm concentrations greater than 5 million per ml and who later produced pregnancies, were compared with those of 67 matched controls who remained infertile. All female partners were potentially fertile. The groups were matched for other known prognostic factors for fertility, namely, wife's age, the duration of infertility, sperm concentration and varicocele size. There were no significant differences between the two groups overall in the (mean +/- SEM)% of sperm with normal morphology (58.3 +/- 2.1; 58.5 +/- 2.2), or motility (40.6 +/- 1.8; 37.0 +/- 2.0). However, among oligospermic men from the two groups, sperm motility was significantly higher (P less than 0.05) in the subsequently fertile group (43.1 +/- 2.6%) than in the persistently infertile group (33.3 +/- 3.7). These results indicate that sperm morphology as currently assessed may not be important in predicting fertility in subfertile men with a mean sperm concentration over 5 million/ml and the % sperm motility may only be a relevant predictor in oligospermic men.

Humans↗

Effect of sperm antibodies in males on human in vitro fertilization (IVF).

The effect of sperm antibodies on the human fertilization process was evaluated by analyzing the Royal Women's Hospital in vitro fertilization (IVF) data. The results suggest that sperm autoantibodies, particularly those of IgA immunoglobulin class (determined by immunobead test (IBT] can interfere with IVF. Thus, in a group (n = 8) of couples where the male partner had 80% or more of his motile spermatozoa coated with IgG and IgA class sperm antibodies, an overall fertilization rate of only 27% (18/66 ova) was obtained. In contrast, in a group (n = 9) with positive IBT results, but with less than 80% of motile spermatozoa coated with IgA class antibodies, a normal fertilization rate of 72% (47/65 ova) was obtained. Three of these patients had 90% or more of their motile spermatozoa coated with IgG and less than 70% coated with IgA class antibodies. In this subgroup a good fertilization rate of 16/21 (76%) was obtained. Another observation derived from this investigation is that the oocytes that do fertilize in the presence of sperm antibodies can subsequently proceed with normal cleavage, implantation, and pregnancy. This provides a rationale for attempting to treat these patients by reducing the proportion of antibody-coated sperm in vitro for future IVF cycles.

Autoantibodies↗

Immunoglobulins on human sperm: validation of a screening test for sperm autoimmunity.

The immunobead test (IBT) is a new method of detecting antisperm antibodies with the advantages of enabling determination of the presence of antisperm antibodies during routine semen analysis, immunoglobulin isotypes and antibody specificity for binding to sperm structures such as head or tail. The IBT is compared with the conventional methods of detecting antisperm antibodies in serum; the tray agglutination test (TAT) and the sperm immobilization test (SIT). Positive IBT (50% or more of washed motile sperm binding to anti-IgG and/or anti-IgA immunobeads) were found in 6.8% of 689 men being investigated for infertility. Both IgG and IgA were found to be present in all cases. The IBT correlated closely with the serum antisperm antibody tests; of the 202 men tested by all three methods, 200 (99%) were either positive for circulating antibodies and IBT or negative for both. No men with serum antisperm antibodies lacked local antisperm antibodies as detected by IBT, and only two men (1%) were IBT positive in the absence of either one or both types of circulating antibodies. Individually, the TAT and the SIT correlated equally well with the IBT; 97% and 98% of men tested by TAT and IBT, and SIT and IBT respectively, were either positive by both or negative by both. It is concluded that the IBT is an excellent procedure for the detection of sperm antibodies.

Autoimmune Diseases↗

The island cheek flap: repair of cervical esophageal stricture and new extended indications.

Seven patients had reconstruction with an island cheek flap based on the facial vein and artery. The flap carries a swatch of buccal mucosa that can be rotated inferiorly as far as the superior mediastinum and superiorly to the oral cavity. Five patients had repair of cervical esophageal strictures and fistulas. In four, results were very successful. One patient had diminished but persistent dysphagia which was shown to be secondary to a carcinomatous polyneuropathy; however, he had complete resolution of aspiration after correction of his mechanical obstruction and tracheoesophageal fistula. Morbidity was minimal. Parotiditis developed in one patient who had Stensen's duct ligated. Minor numbness of the lip and a single case of Frey's syndrome were also observed. In another patient, reconstruction of the floor of the mouth preserved normal speech and swallowing. Finally, a permanent speech fistula was also created but was substantially taken down because of functional dissatisfaction. Other potential applications need to be explored.

Aged↗

A controlled trial of the use of erythromycin for men with asthenospermia.

A double-blind crossover controlled trial of Erythromycin was conducted in 78 men with asthenospermia (mean pretreatment sperm concentration greater than or equal to 20 X 10(6)/ml and motility less than 60%). Sperm motility increased above the pretreatment mean after the first one month course of treatment for both Erythromycin (7.9 +/- 2.6% P less than 0.01; mean +/- SEM) and the placebo group (7.5 +/- 2.2% P less than 0.01) and also after the second one month course of treatment, given one month after the first, for both Erythromycin (11.8 +/- 2.7% P less than 0.001) and placebo (11.4 +/- 2.8% P less than 0.001). There was no significant difference between the changes in sperm motility with Erythromycin and placebo. Twelve pregnancies occurred during the four month trial time--eight with Erythromycin and four with placebo (chi 2 = 2.51 P = NS). It is concluded that in infertile men, sperm motility tends to increase spontaneously with time. Erythromycin treatment has no significant effect on semen quality and a larger trial will be required to determine if Erythromycin increases fertility.

Clinical Trials as Topic↗

Is there a male menopause?

Inadequate sexual performance is a common complaint of middle aged men. Many studies have shown that testicular function changes with age (mainly falling testosterone and sperm production associated with rising gonadotrophin levels); the effects are most notable after 70 years and are less obvious in subjects who have good health.

Adult↗

Changes in the pituitary-testicular axis with age.

A large number of endocrinological studies of testicular function in men of different ages suggest that primary testicular failure becomes common and more severe with aging. There is an increasing frequency of impotence, reduced secondary sex hair and testicular atrophy. Serum LH and FSH levels rise, androgen production rates and levels fall and oestrogen levels rise. The clearance of oestradiol falls but the production rate is maintained, in part, through increased peripheral conversion of testosterone to oestradiol. The levels of SHBG rise and free testosterone levels are reduced. Leydig cell responsiveness to hCG is probably reduced but gonadotrope responsiveness to GnRH reasonably maintained in the elderly. There are histological changes in the seminiferous epithelium of old men but these are non-specific. Senescent testicular failure is mainly a primary gonadal disorder but its cause and significance are only poorly understood.

Adult↗