Biomedical subjects
Publications and source records attributed to H W Baker.
The progress of 80 couples who failed to conceive by donor insemination was followed through in vitro fertilization cycles using donor sperm. The outcome was better than that for couples undergoing IVF for tubal disease and significantly better than their chance with further cycles of donor insemination.
The number of sperm bound to the zona pellucida (ZP) were counted on 660 oocytes that failed to fertilize in vitro from 162 patients. Oocytes from clutches in which some fertilized had significantly more sperm bound to the ZP than did those from clutches in which all oocytes failed to fertilize. Oocytes from patients in whom all were not fertilized and no sperm bound to the ZP were able to bind normal fertile donor sperm after storage in ammonium sulphate solution. The number of sperm bound to the ZP was significantly related to the proportion of sperm with normal morphology and normal intact acrosomes in semen, sperm concentration inseminated, sperm motility and viability. The number of sperm bound to the ZP, sperm normal morphology, diagnosis of male infertility and sperm concentration in semen were significantly related to the fertilization rate by logistic regression analysis. Thus the number of sperm bound to the ZP is an indicator for IVF success and low binding appears to be more frequently associated with sperm defects than oocyte defects.
Sixty-three patients with advanced cancer underwent greater than or equal to 5,000 cGy combined with Concentric Coil magnetic-induction localized hyperthermia. Tumor regression (CR + PR) was compared to thermal dose received, incorporating the premise that hyperthermia response is a function of time as well as temperature. A computer program was developed (after Sapareto and Dewey [2]) which stored minimum tumor temperatures recorded spatially and temporally during treatment and correlated response with T43 (equivalent minutes at 43 degrees C during the first treatment) and CT43 (cumulative T43, computed by multiplying T43 by the actual number of identical subsequent treatments received during the course of therapy). Those who responded--N = 46 (73%)--had significantly higher median thermal doses than those who did not respond. Comparison of T43 and CT43 thermal dose values between responders and nonresponders was significantly different at p values of 0.05 and 0.04, respectively. The data indicate that magnetic-induction hyperthermia and high-dose XRT was an effective treatment combination in advanced disease and that tumor response improved as thermal dose increased.
The defect that remains after an extended hemilaryngectomy continues to be a challenge to the reconstructing surgeon. The reconstruction ideally must provide airway protection against aspiration, allow for phonation, and provide a durable mucosal surface. It also must be accomplished in one stage. Nine Labrador dogs underwent successful reconstruction of the hemilarynx using an axial island cheek flap based on the facial artery and vein. Adequate laryngeal function was demonstrated by maintenance of body weight, normal barium swallows, return of strong bark, and no evidence of aspiration pneumonia. Pathologic review confirmed a viable mucosal surface and incorporation of the Marlex and stainless steel wire mesh in a fibrous reaction. We have concluded that this method of reconstruction provides a result superior to currently used techniques.
Results of 106 in vitro fertilization procedures were used to evaluate the usefulness of tests of human sperm function for predicting fertilization rates. Sperm tests included concentration, motility, morphology, vitality (eosin Y exclusion), nuclear immaturity (aniline blue stain), and hypo-osmotic swelling. Only the number of sperm in the insemination medium, percentage normal morphology, and vitality were statistically significant in logistic regression models of fertilization rates. The other tests, such as the hypo-osmotic swelling test, did not give additional information about fertilization rates in this study. It is concluded that logistic regression analysis of factors affecting results of fertilization in vitro provides a powerful tool for evaluating some clinical tests of sperm function.
Two high-density media, Percoll (Pharmacia, Uppsala, Sweden) and Nycodenz (Nyegaard & Co., Oslo, Norway), were assessed for efficacy of selection of motile spermatozoa from oligozoospermic and asthenozoospermic semen samples. The results indicated initially that the media were equivalent for motile sperm selection. However, only the spermatozoa selected from discontinuous Nycodenz gradients retained their motility for at least 21 hours (60% motility compared with 5% motility). A significantly higher number of motile spermatozoa were harvested from discontinuous Nycodenz gradients than from matched control samples using the swim-up procedure (12.0 +/- 3.0 standard error of the mean [SEM] X 10(6)/ml versus 1.9 +/- 0.7 SEM X 10(6)/ml; 27 experiments, P less than 0.001). Discontinuous Nycodenz gradients may be useful for selection of motile spermatozoa from poor-quality semen for in vitro fertilization.
Four patients with persistent oligospermia and necrospermia were found to have severely degenerated sperm in the ejaculate. However, in those examined, testicular sperm were ultrastructurally normal, indicating that sperm degeneration and death was occurring during epididymal passage or storage or both or upon mixing with the seminal plasma at ejaculation. Seminal plasma was found to be nontoxic to normal donor sperm. In three patients, frequent ejaculation (two ejaculates per day for 4 or 5 days) was used to deplete epididymal sperm reserves and reduce the period spent in the epididymis. This resulted in a threefold to sevenfold increase in percentage of motile sperm in the ejaculate and a similar increase in sperm motility index. The authors propose the term "epididymal necrospermia" to describe this previously undefined type of male infertility.
Sperm acrosomes were examined with fluorescein-labeled pisum sativum agglutinin in 137 in vitro fertilization treatments. The percentage of sperm with normal intact acrosomes in semen was correlated with sperm concentration, morphology, viability, and motility. The proportion of sperm with normal intact acrosomes was significantly increased by the "swim up" selection from semen. Fertilization rates in the whole group studied were significantly related to percentage normal morphology, concentration of sperm inseminated and cause of infertility. However, with normal morphology less than 30%, the proportion of sperm with normal intact acrosomes in the insemination medium was the only significant factor related to fertilization rate in the logistic regression analysis. Thus, assessment of acrosomes may be of clinical value for predicting the fertility of men with poor sperm morphology.
A test for human sperm binding to the zona pellucida (ZP) was developed using oocytes which failed to fertilize in vitro. Heterospermic insemination with equal numbers of test and fertile donor sperm differentially labeled with fluorescein isothiocyanate or tetra-methylrhodamine B isothiocyanate controlled for variability in ZP-sperm binding capacity. The number of sperm bound to the ZP was independent of previous sperm binding in in vitro fertilization (IVF), preservation of the ZP in salt solution, and fluorochrome labeling but increased linearly with time and sperm concentration. Sperm from men who had one or more failed attempts at IVF with no or few oocytes fertilized usually displayed very low ZP binding ratios of test to normal sperm. This test may predict the ability of sperm to fertilize human oocytes in vitro and should be useful in studies of human gamete interaction.
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Several investigators have indicated that changes in tumor size may not occur after hyperthermia therapy even with substantial tumor cell kill, because of early edema and subsequent fibrosis of background stroma, suggesting that "tumor stabilization" might be an important benefit of thermal therapy. Recently, 9 institutions completed a national cooperative study of localized hyperthermia for patients with advanced, recurrent, or metastatic solid cancer that evaluated the potential significance of this response variable in a standardized clinical trial. Of 960 evaluable patients who completed at least one course of hyperthermia, thermoradiotherapy, or thermochemotherapy, 85 (9%) had complete responses for 1-34 months, 173 (18%) had partial responses for 1-39 months, 95 (10%) had minimal responses for 1-15 months, and 313 (33%) had disease stabilization for 1-32 months. Of 313 patients who had no change (i.e., +/- 25%) in the size of their tumors after hyperthermia, the response lasted only 1-3 months in 170 (54%) patients, a finding of questionable clinical significance. However, disease stabilization was observed for more than 3 months in 143 (46%), for more than 6 months in 67 (21%), more than 9 months in 33 (10%), and more than 12 months in 16 (5%). Disease stabilization was also associated with improved activity for 1-22 months in 79 (25%) of these patients, and improved pain for 1-22 months in 100 (32%). Disease stabilization appeared to be independent of tumor histology, location, or depth within the body, size, or minimum treatment temperature, but was somewhat more frequent after hyperthermia combination therapy. There is sufficient accumulative data to suggest that tumor stabilization after hyperthermia should not be dismissed as a placebo effect. This response variable well may be a unique and potentially important criterion of response to localized hyperthermia therapy.
To determine whether the absence of one ovary would influence adversely the outcome of in vitro fertilization, the results of 60 laparoscopic oocyte retrieval procedures in 34 single-ovary patients were compared with the outcome for all laparoscopic retrieval cycles during the same period (January 1984-August 1986) in patients with tubal infertility and two accessible ovaries (559 cycles in 335 patients). The median age was younger in the one-ovary group (31 vs 32) (P less than 0.05). The group with two accessible ovaries had significantly more follicles aspirated (median, 7 vs 5; P less than 0.001) and more oocytes obtained (median, 5 vs 4; P less than 0.001) per retrieval compared with the single-ovary group. However, the single-ovary group had a higher percentage fertilization (69 vs 62%; P less than 0.05) so that the number of embryos transferred per transfer patient (median, 3 vs 3) and pregnancy rate per cycle (9.7 vs 15.6%) did not differ significantly between groups. We conclude that patients with a single ovary have a compensatory increase in the ability to produce oocytes which may have greater potential for fertilization and subsequent development.
Repair of limited cervical esophageal defects can now be accomplished safely with mucosa-lined flaps. Free jejunal grafts have demonstrated excellent durability and function for circumferential defects. The axial cheek flap and laryngeal flap have also shown excellent functional results for noncircumferential defects. In addition, all three of these procedures offer the advantage of immediate reconstruction. The size of the esophageal defect, the physical condition of the patient, and the rehabilitative goals are critical in patient selection.
Proteins were analysed by sodium dodecylsulphate polyacrylamide gel electrophoresis in fluid taken from six epididymal regions in 10 men undergoing microsurgery to bypass epididymal obstructions resulting from various disorders. Some major proteins common to most samples were identified with apparent molecular weights of 95, 67, 56, and 44 kilodaltons. A degree of regional specificity in the synthesis and secretion of epididymal proteins was indicated. There appeared to be no correlation between protein pattern or the abundance of individual proteins and the cause of obstruction, although methodological constraints may have partially obscured any such relationship.
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Combined management of infertile couples is optimal. The most common problems in men are low sperm concentration and motility of unknown cause. Although there are no specific effective treatments, factors correlated with subsequent fertility are emerging that should be useful for advising couples of their chances. In the woman, disorders of ovulation can usually be treated successfully, but results of tubal surgery for past inflammatory damage remain poor. In vitro fertilization may be useful for idiopathic infertility and semen disorders of mild to moderate severity, as well as for tubal obstruction.