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Biomedical subjects

S S Howards

Publications and source records attributed to S S Howards.

At least 19 recordsLinked to original sources
PubMed2001

Gamete retrieval in terminal conditions.

There has been a growing interest and requests by patients facing intensive chemotherapy or surgically ablative procedures for gamete retrieval and preservation for future procreative efforts. There are technical difficulties in this area but little ethical discomfort. More troubling are the issues that arise with a terminally ill, incapable patient-one who is in a persistent vegetative state or who is declared brain dead or who is neurologically devastated with no hope for recovery, but not yet in either of the above states-or with a person who has suddenly died. In these cases, the surviving spouse, partner, or family members may request gamete retrieval for future reproductive efforts. Discussion of this topic within the Ethics Consultation Service at the University of Virginia demonstrated a need for development of insight derived from facts and ethical deliberation to help formulate a policy that would apply to such cases. A group was assembled with the expertise to explore the issue and to help formulate a policy that could be suggested for adoption by the hospital administration. The group consisted of a urologist with experience in sperm retrieval from terminally ill patients; the director of the laboratory supporting the assisted reproductive facility in the Department of Obstetrics and Gynecology; the chairperson of the Ethics Consultation Service (who is also a neonatologist); and 2 members of the Ethics Consultation Service, one a genetic counselor and the other an obstetrician-gynecologist with a master's degree in biomedical ethics. Current literature was reviewed, the expertise of the urological member and the reproductive laboratory director was explored, and the insight of the members of the Ethics Consultation Service was added. We explored the technical aspects of both male and female gamete retrieval and preservation and the reproductive potential of these stored gametes. We present a review of the current literature on both the technical and ethical aspects of the topic. Finally, we present a policy that we deem acceptable for adoption and that should be of value to other practitioners and facilities as they contemplate facing requests for gamete retrieval.

Advance Directives↗
PubMed2001

A novel technique for ventriculovesical shunting of congenital hydrocephalus.

PURPOSE: Hydrocephalus is typically treated with a ventriculoperitoneal or ventriculoatrial shunt. However, shunt malfunction, recurrent infection or other co-morbidities occasionally make these shunts inappropriate. As early as 1925 a ureterodural anastomosis was used to divert cerebrospinal fluid into the urinary system. Since then techniques for cerebrospinal fluid urinary diversion have improved. We designed a new technique to drain cerebrospinal fluid into the urinary system surgically while averting some of the problems encountered with previous methods. MATERIALS AND METHODS: We describe a new technique to perform a ventriculovesicular shunt, which we performed on a 17-year-old woman with congenital hydrocephalus. To put this unique operation into perspective we briefly review the history of cerebrospinal fluid urinary shunting. RESULTS: Our results were promising, with no evidence of distal shunt malfunction or infection postoperatively. CONCLUSIONS: Our novel technique of a ventriculovesical shunt with a polyester cuff that provides stabilization and infection control holds promise for patients with hydrocephalus who are not candidates for a ventriculoperitoneal or ventriculoatrial shunt.

Adolescent↗
PubMed2000

Antisperm autoantibody response is reduced by early repair of a severed vas deferens in the juvenile rat.

OBJECTIVE: To determine whether antisperm autoantibody production after prepubertal vas injury is influenced by immediate repair of the vas compared to delay of the reanastomosis until sexual maturity. DESIGN: Animal study comparing early repair, late repair, and sham-operated groups. SETTING: Research laboratory in a medical school. PATIENT(S): Lewis rats. INTERVENTION(S): After division of the vas deferens in juvenile rats, animals in an early repair group had the vasa repaired immediately by using an absorbable intraluminal stent. Animals in a late repair group had vasa obstructed by ligation until after puberty, when they underwent microsurgical vasovasostomy (age 60 days). MAIN OUTCOME MEASURE(S): Antisperm antibodies were assayed by ELISA. The weights of reproductive organs were determined, and samples of testis were studied by light microscopy. RESULT(S): The antisperm antibody response was less when the vas was repaired immediately than if the repair was delayed until after puberty. There was a low incidence of testicular alteration in the repair groups and none in sham-operated animals. CONCLUSION(S): If the vas deferens is injured or obstructed prepubertally, there may be a benefit to considering immediate repair to reduce the likelihood of developing antisperm autoantibodies, which have been associated with reduced fertility.

Analysis of Variance↗
PubMed1999

Degeneration of the seminiferous epithelium following epididymal obstruction in prepubertal rats.

The development of the testes was studied in rats following prepubertal obstruction of the epididymis. Male rats received bilateral ligation of the corpus epididymidis or a sham operation at 10 days of age, and temporal changes in testicular morphology and weights of reproductive organs were determined at intervals spanning sexual maturation. Development of the testes was normal through 35 days of age. The initial histological changes in the testes of ligated animals, observed at 56 days, included an increased diameter of the seminiferous tubule lumen, depletion of spermatids, and the presence of multinucleate spermatids. Subsequently, germ cells were greatly depleted in the testes of 91- and 128-day-old rats with ligated epididymides. After puberty, testicular weight and volume declined relative to corresponding sham-operated animals. On the other hand, the weights of the epididymides in ligated animals prior to puberty significantly exceeded those of sham-operated rats but weighed significantly less than those of rats in the sham group after sexual maturation. Testicular alterations occurred after increases in the weights of the epididymides. Testicular changes may have contributed to rather than resulted from an autoimmune response to spermatozoa because testicular alterations preceded increases in antisperm autoantibodies.

Animals↗
PubMed1999

Post-obstruction rat sperm autoantigens identified by two-dimensional gel electrophoresis and western blotting.

Although antisperm autoantibody responses to obstruction of the male reproductive system have been documented, information on the nature of the cognate sperm autoantigens has been limited. In the present study, the patterns of sperm autoantigens recognized by sera from rats after obstruction of the vas deferens or epididymis were studied by high resolution two-dimensional (2-D) gel electrophoresis and western blotting. Comparisons of patterns of autoantigens stained on 2-D western blots of sera from prepubertal vasectomy, prepubertal epididymal ligation and adult vasectomy groups revealed both similarities and differences. Sera from sham-operated animals showed no detectable reaction or much lighter staining of a small number of spots. Visualization of sperm autoantigens on 2-D western blots supported the hypothesis that there is a relatively small set of sperm proteins that can be regarded as dominant post-obstruction sperm autoantigens because they are recognized by multiple post-obstruction sera. The 2-D analysis revealed previously undetected distinctions in the autoantigens recognized after adult and prepubertal vasectomy, as well as variations with the site of obstruction. These differences in the response may be due in part to changes in antigens of spermatozoa in different parts of the tract and at different ages, as well as variations in exposure of sperm cell proteins to the immune system resulting from the sites of spermatic granulomas. Preparative 2-D gels and western blotting with post-obstruction sera are now being used to identify specific sperm autoantigens by microsequencing of selected proteins.

Animals↗
PubMed1999

Sperm mitochondria-associated cysteine-rich protein (SMCP) is an autoantigen in Lewis rats.

A common repertoire of rat sperm antigens have previously been identified by Western blotting of sperm proteins with sera obtained after vasectomy or isoimmunization with sperm. Aside from a determination of their apparent masses, however, the biochemical characteristics of these antigens have remained unknown. In this study, a rat testis cDNA expression library was screened with polyclonal antibodies obtained from rats immunized with isologous spermatozoa to identify and sequence a full-length clone encoding rat sperm mitochondria-associated cysteine-rich protein (SMCP). The open reading frame of SMCP was expressed in the pET22b vector, and recombinant SMCP (rec-SMCP) was purified. Sera from rats that had been vasectomized or hyperimmunized with isologous sperm specifically recognized rec-SMCP whereas preimmune sera from these experimental groups did not react. Rabbit antiserum produced to rec-SMCP recognized rec-SMCP on Western blots and precisely immunolocalized SMCP to the mid-piece of rat sperm. On Western blots against sperm extracts, the rabbit antibody recognized a major protein band of approximately 22-25 kDa that co-migrated with bands of identical mass that were recognized by sera from hyperimmune or vasectomized rats. These findings demonstrate that SMCP is a sperm autoantigen, recognized following vasectomy, and an isoantigen, recognized by antibodies generated through isologous immunization with sperm.

Amino Acid Sequence↗
PubMed1999

Chronic treatment with finasteride daily does not affect spermatogenesis or semen production in young men.

PURPOSE: Finasteride, an oral type 2, 5alpha-reductase inhibitor, is used in 1 mg. daily doses for the treatment of male pattern hair loss. A dose of 5 mg. finasteride daily reduces ejaculate volume by approximately 25%, and reduces prostate volume by approximately 20% and serum prostate specific antigen (PSA) by approximately 50% in men with benign prostatic hyperplasia. To our knowledge no data exist on the effect of 1 mg. finasteride daily on ejaculate volume or other semen parameters, or on the prostate in young men. Therefore, we studied the potential effect and reversibility of effect of 1 mg. finasteride daily on spermatogenesis, semen production, the prostate and serum PSA in young men. MATERIALS AND METHODS: In this double-blind, placebo controlled multicenter study 181 men 19 to 41 years old were randomized to receive 1 mg. finasteride or placebo for 48 weeks followed by a 60-week off-drug period. Of the 181 men 79 were included in a subset for the collection and analysis of sequential semen samples. RESULTS: There were no significant effects of 1 mg. finasteride on sperm concentration, total sperm per ejaculate, sperm motility or morphology. Ejaculate volume in subjects on finasteride decreased 0.3 ml. (-11%) compared to a decrease of 0.2 ml. (-8%) for placebo, with a median between treatment group difference of -0.03 ml. (1%, 90% confidence interval -10.4 to 13.1, p = 0.915). There were significant but small decreases in prostate volume (-2.6%) and serum PSA (-0.2 ng./ml.) in the finasteride group, which reversed on discontinuation of the drug. CONCLUSIONS: Treatment with 1 mg. finasteride daily for 48 weeks did not affect spermatogenesis or semen production in young men. The effects of 1 mg. finasteride daily on prostate volume and serum PSA in young men without benign prostatic hyperplasia were small and reversible on discontinuation of the drug.

Adult↗
PubMed1998

Male infertility. Evaluation and nonsurgical therapy.

Male infertility is a complicated and often poorly understood pathologic process. The cause of a man's infertility frequently remains unknown even after a thorough evaluation. Many of the currently available medical therapeutic options are empirical and lack documentation of efficacy. New diagnostic tests are emerging that may help define some previously obscure causes of infertility. Only when these abnormalities have been clearly identified will more specific and cost-effective treatment regimens be instituted.

Humans↗
PubMed1997

Distribution of leukocytes in the epithelium and interstitium of four regions of the Lewis rat epididymis.

BACKGROUND: Leukocytes expressing different surface markers were studied in four regions of the epididymis of Lewis rats. Cells resembling lymphocytes or monocytes had been described in the epididymis, but previous studies differed as to their nature and immunologic significance. METHODS: Frozen sections were immunocytochemically stained with monoclonal antibodies W3/25, OX-8, OX-42, and RLN-9D3, which are directed toward markers on CD4+ cells, CD8+ cells, macrophages, and B lymphocytes, respectively. The concentration of stained cells in the epithelium and interstitial tissue of the initial segment, caput, proximal cauda, and distal cauda regions was determined by a procedure based on the optical disector method. RESULTS: CD4+ leukocytes were present in greater concentration than CD8+ cells or macrophages in both the epithelium and interstitial tissue of all four regions. In the epithelium, the concentration of CD8+ leukocytes was greater than that of macrophages in the initial segment, caput, and distal cauda. In the interstitium, however, the concentration of macrophages exceeded that of CD8+ cells in both parts of the cauda. Macrophages and T lymphocytes were generally present in greater concentrations in the interstitium than in the epithelium, especially in the more proximal parts of the epididymis. In contrast to T cells, B lymphocytes were not detected in the interstitium or epithelium of any of part of the epididymis, despite prominent staining of B cells in other locations. CONCLUSIONS: The epididymal epithelium of the Lewis rat contains many T lymphocytes, which may correspond to 'halo' cells. CD4+ leukocytes predominate in all regions of the epididymis. The interstitium may function as a reservoir of leukocytes for the epithelial compartment. The epididymis is not normally a site for local immunoglobulin synthesis.

Animals↗
PubMed1997

Appearance of 'natural' antisperm autoantibodies after sexual maturation of normal Lewis rats.

Serum antisperm antibodies were assessed quantitatively with an ELISA in normal male Lewis rats at intervals between ages 10 and 128 days, spanning the onset of puberty. Antisperm antibodies rose between 56 and 91 days, and were significantly higher in 91- and 128-day old rats than at earlier intervals. The animals underwent normal pubertal development as indicated by increases in weights of the seminal vesicles and ventral prostate. The rise in antisperm antibodies correlated temporally with events in the postnatal development of the male reproductive system, with the increase in antisperm antibodies most closely following the time when spermatozoa reach the epididymis and proximal vas deferens at approximately 56 days. The observation that serum antisperm antibodies increased only after sexual maturation suggests that some differentiation antigens of sperm are processed and presented to the immune system under normal circumstances in this strain. Western blot analysis showed that the sera from normal postpubertal Lewis rats bound several proteins, including bands of > 100, 82-75, 78, 68, 65, 63, 54-55, 42, 37, 35, 26, and 20-22 kDa. The majority of these autoantibodies were sperm-specific as shown by the absence of comigrating bands in western blots of somatic tissue extracts, although antibodies in postpubertal sera recognized certain other proteins in somatic tissues. Several protein autoantigens, defined by sera from postpubertal animals, matched dominant autoantigens recognized by antibodies produced in response to vasectomy, prepubertal vas obstruction, or immunization with spermatozoa. This finding indicates that the antisperm antibody responses following sperm immunization, vasectomy or prepubertal vasal obstruction represent accentuation of an autoantibody response to sperm that develops normally following puberty.

Age Factors↗
PubMed1995

Effects of vasectomy on the epididymis.

Common principles can be discerned in the response of the epididymis to vasectomy, despite species differences. Increases in the size and number of lysosomes are the most frequent changes in the epididymal epithelium. The presence or absence of additional alterations such as changes in the height of the epithelium may be related to variations in distensibility of the vas deferens and epididymis. Direct measurements by micropuncture of epididymal and seminiferous tubule hydrostatic pressure indicate that, contrary to dogma, increased pressure in the distal epididymis after vasectomy is not generally transmitted to the seminiferous tubules. The epididymal interstitium shows microscopic changes indicative of chronic inflammation, with infiltration of macrophages, lymphocytes, and plasma cells, and rats with these lesions have higher antisperm antibody levels than animals lacking epididymal changes. Macrophages and neutrophils may enter the duct through the epididymal epithelium, at sites of rupture of the duct, and in the efferent ductules. Cyst-like spermatic granulomas occur in virtually all species where the epididymis or vas deferens ruptures with escape of spermatozoa. The sites and timing of granuloma formation may depend on the mechanical properties of the tract in different species, and they are probably important in the immune response to vasectomy. Postvasectomy sera in Lewis rats recognize a consensus repertoire of dominant autoantigens that closely resembles the antigens bound by sera from rats immunized with isologous spermatozoa. There are multiple routes for disposal of the sperm that continue to be produced after vasectomy.

Animals↗
PubMed1995

Antisperm autoantibody responses to vasectomy and vasovasostomy in Fischer and Lewis rats.

Antisperm autoantibodies were studied in Fischer and Lewis strains of rats after either vasectomy, vasectomy followed one month later by vasovasostomy, or sham operations. The time course of antibody response to sperm protein autoantigens was assayed by Western blot analysis of sera obtained at intervals up to 3 months. Rats of both strains responded to immunization with isologous spermatozoa with production of high titer hyperimmune sera. Sera from vasectomized Fischer rats showed antisperm antibodies on Western blots, but bands were stained with less intensity and frequency than for Lewis rats. In both Fischer and Lewis strains, major protein autoantigens were observed at 75-83, 68-71, 63, 57, 51, 41, and 21-23 kDa, lending support to the hypothesis that there is a set of dominant sperm autoantigens recognized by a consensus of postvasectomy rat sera. The lesser response of Fischer rats to vasectomy was not due to absence of dominant postvasectomy sperm autoantigens in Fischer sperm extracts, nor was it attributable to inability of Fischer rats to mount an immune response to these antigens, since immunization with isologous sperm was successful in raising antibodies to the dominant autoantigens. Vasovasostomy did not result in a general decrease in antisperm antibodies, and reactions to some antigens actually increased.

Animals↗
PubMed1995

Resident training survey in infertility.

PURPOSE: We characterize infertility training in urology residency programs. MATERIALS AND METHODS: A pilot survey was sent to randomly selected urological training programs. The modified final survey was sent to 126 approved urological residencies in North America. RESULTS: Of the 126 surveys 110 (87%) were returned. Among the programs 38% expressed interest in recruiting a faculty member with expertise in infertility, 32% indicated an inadequate number of patients available to train residents and 56% indicated that their residents were least competent in the treatment of infertile patients compared to the other urological subspecialty disciplines. CONCLUSIONS: This survey confirms the underemphasis of infertility in urological training programs and the need to enhance this training.

Data Collection↗
PubMed1995

Testicular development and the formation of spermatic granulomas of the epididymis after obstruction of the vas deferens in immature rats.

PURPOSE: Aims were to determine the effects of obstruction of the vas deferens prior to sexual maturation on testicular growth and the formation of spermatic granulomas. MATERIALS AND METHODS: The vas deferens was ligated and divided bilaterally in 10-day-old Lewis rats. RESULTS: Testis weight and volume did not differ significantly between obstructed rats and sham controls at the majority of the intervals studied, including the end of the experiment at 128 days, although some temporary changes were observed. Testes of obstructed animals showed normal histological differentiation. Nearly all obstructed animals developed spermatic granulomas of the epididymis once they matured. CONCLUSIONS: When obstructed prior to sexual maturation, the testes are affected only transiently, but significant epididymal alterations occur. Spermatic granulomas are located predominantly in the epididymis rather than the vas deferens.

Animals↗
PubMed1994

Temporal recognition of sperm autoantigens by IgM and IgG autoantibodies after vasectomy and vasovasostomy.

Temporal patterns of IgM and IgG autoantibodies to sperm proteins were studied by western blot analysis at intervals after bilateral vasectomy, vasectomy followed one month later by vasovasostomy, or sham operations. Responses were detected to eight major autoantigens at 21-23, 36, 41, 51, 57, 63, 68-71 and 75-83 kDa, by study of staining patterns of sequential serum samples from individual animals and by analysis of the incidence of reaction to each protein. The four lower molecular weight antigens (21-23, 36, 41 and 51 kDa) provoked mainly IgG responses. The strongly stained set of higher molecular weight antigens (57, 63, 68-71 and 75-83 kDa) tended to show more clearly defined temporal patterns of IgM followed by IgG response, including a high incidence of IgM antibody at the 2-week interval. Three of the larger peptides (57, 63 and 68-71 kDa) appeared highly immunogenic, since some reactions were detected even in sham-operated rats. The classical patterns of IgM and IgG antibody responses to the majority of the dominant sperm autoantigens are in accord with the hypothesis that vasectomy mimics immunization with spermatozoa. The high incidence of IgM antibodies in the earliest sample, taken 2 weeks after vasectomy, suggests that the initial immunizing event takes place within about a week after the operation. Vasovasostomy did not bring about a decrease in antisperm antibodies. Instead, some animals demonstrated an increased reaction to certain antigens after reversal of vasectomy, even though the vasovasostomies were anatomically successful.

Animals↗