Biomedical subjects
S S Howards
Publications and source records attributed to S S Howards.
Injury to the pre-pubertal vas deferens. I. Histological analysis of pre-pubertal human vas.
There is very little information in the literature on the development of the human vas deferens. Therefore, the age at which the pre- or para-pubertal vas deferens becomes large enough for a vasovasostomy to be technically feasible is unknown. To determine the age or degree of sexual maturity at which a microscopic vasovasostomy is technically feasible, we collected surgical or autopsy vasa from 34 young males over a three year period, and correlated vasal size to age and Tanner stage (degree of sexual maturity ranging from 1-childhood to 5-adult). The specimens were embedded and sectioned transversely in glycol methacrylate. Using image analysis, the total transverse area and diameter, and luminal area and diameter was determined for each specimen. Surprisingly, there was no change in vasal size from birth up through 11 years. From age 15 years and on, the vas was adult in size. The vas develops to adult size between Tanner stages 2 and 3. The average external and luminal diameters of pre-midpuberty specimens (Tanner stages 1 and 2) were 1.0 and 0.19 (mm.) and the diameters of post-midpuberty specimens were 2.1 and 0.43 (mm.), respectively. These results suggest that, in the event of a recognized iatrogenic injury to the vas deferens after midpuberty, a repair by a traditional microsurgical vasovasostomy is possible. If the vas is injured before midpuberty it may be technically difficult to repair by traditional microsurgical methods.
Injury to the pre-pubertal vas deferens. II. Experimental repair.
We have previously shown that the human vas deferens does not change in cross-sectional size between birth and the middle of puberty. This suggests that if the human vas is injured prior to mid-puberty, repair by a traditional microsurgical vasovasostomy may be technically difficult. We propose that a chromic stent can be used to assist in the repair of vas injured before mid-puberty. This hypothesis was tested in Sprague-Dawley rats. At three weeks of age, male offspring were divided into three groups (eight to nine rats/group): 1) Sham group--a sham operation at three weeks, 2) VV group--bilateral transection of vasa at three weeks followed by a delayed repair at eight weeks by microsurgical vasovasostomy without a stent, 3) Stent group--bilateral transection of vasa at three weeks followed by immediate repair by aligning the lumens with a 6-0 chromic intravasal stent (suture) and holding the transected ends together with several seromuscular sutures. At four months all rats were fertility tested and a score was given to each rat (mean number of concepti among three females for each male rat). Analysis of anastomotic patency by flow rates and histology was performed. There was no statistical difference in the mean fertility score of 6.85 in the Stent group compared to 7.83 in the Sham group. However, a fertility score of 0.71 in the VV group was significantly decreased compared to the Stent and Sham group (p = .0003), despite no statistical difference between the groups in patency. This suggests that a recognized injury to the pre-pubertal human vas should be immediately repaired and the repair can be done using 6-0 chromic suture as an intravasal stent to help align the lumina of the smaller pre-pubertal vas.
American Urological Association response to two articles on the relationship of vasectomy and prostate cancer.
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Factors that influence fertility after vasovasostomy in rats.
OBJECTIVE: To determine if fertility after vasovasostomy of immunologically responsive Lewis rats differs from that of the less responsive Sprague-Dawley strain and to relate fertility to antisperm antibodies, fluid flow in the vas deferens, and testicular structure. DESIGN: Male rats received: (1) bilateral vasectomies; (2) vasectomies followed 3 months later by vasovasostomy; or (3) sham operations. SETTING: Research laboratory. MAIN OUTCOME MEASURES: Fertility was assessed by caging males with three females for 2 weeks and subsequently counting implantation sites. Antisperm antibodies were measured with an enzyme-linked immunosorbent assay, fluid flow through vas deferens segments was tested in vitro, and testicular structure was studied microscopically. RESULTS: Nearly all vasovasostomized Lewis rats were infertile (33 of 34), whereas 62% (18 of 29) Sprague-Dawley rats were fertile after vasovasostomy (P less than 0.001). In fertile Sprague-Dawley males, significant correlations existed between: (1) implantation sites or females impregnated; and (2) antisperm antibodies early after vasectomy, vas flow, and testicular morphology. CONCLUSIONS: Genetic differences affect fertility after vasovasostomy. Fertility after vasovasostomy is also influenced in a multifactorial manner by the immune response, mechanical elements, and structural changes in the reproductive tract.
Early testicular changes after vasectomy and vasovasostomy in Lewis rats.
The testes of Lewis rats were studied at intervals from 2 weeks to 3 months after bilateral vasectomy, vasectomy followed 1 month later by vasovasostomy, or sham operations. Aims were to determine the nature of early alterations after vasectomy, and to determine whether vasovasostomy after 1 month would result in reversal of vasectomy-induced changes. Approximately one-fourth of the testes in the vasectomy and vasovasostomy groups displayed histological changes, which consisted mainly of depletion of germ cells. The extent of the depletion varied greatly in different seminiferous tubules. In testes altered in this way, no abnormal infiltrations of lymphocytes, macrophages, or other cells were observed in the seminiferous epithelium or in the interstitium. The rete testis and straight tubules were normal in testes with altered seminiferous epithelium. A few testes in the vasectomy and vasovasostomy groups had necrotic centers. The results suggest that depletion of germ cells occurred as a result of shedding from the seminiferous epithelium into the lumen of the tubules. A cellular immune response, such as occurs in experimental allergic orchitis in other species, did not appear to be responsible for the observed loss of germ cells. This suggests a possible role for humoral antibody in this model, since there is an association between testicular changes and serum antisperm antibodies at longer intervals after vasectomy. Testicular alterations were not reversed by performance of a vasovasostomy 1 month after vasectomy.
Multicystic dysplastic kidney: natural history of prenatally detected cases.
To delineate the natural history of fetal multicystic dysplastic kidneys (MDKs), all cases that were prenatally detected in the Prenatal Diagnosis Center of the University of Virginia from September 1985 to 31 August 1988 were reviewed. All patients were followed through the Center with serial ultrasound evaluations at approximately 4-week intervals, and each liveborn infant was evaluated and followed by one of the authors (S.S.H.). Of the 14 cases detected, ten were detected in the second trimester, the earliest at 16.5 weeks' gestation. Of the nine fetuses with non-lethal disease, there were two cases in which the lesion remained unchanged during observation. Both had an initial diagnosis in the third trimester. In those cases diagnosed in the second trimester (7), all showed an initial increase in the size and number of cysts, followed by involutional changes either in utero (2) or in the neonatal period (3). Two infants had immediate surgical removal of the MDK, one because of respiratory compromise, and the other because of an uncertain diagnosis on renal scan. Abnormalities of the contralateral kidney were found in 7 of 14 fetuses. Five were lethal conditions. Associated non-renal abnormalities were common in bilateral MDK (80 per cent), but rare in unilateral MDK (11 per cent).
Acute torsion of a renal transplant: cause of organ loss.
Acute torsion of a renal allograft has not been previously described as a cause of organ loss. We present a case of acute torsion of a transplanted kidney in a patient with prune-belly syndrome which led to renal necrosis, necessitating organ removal.
On the maintenance of male fertility in the absence of native testosterone secretion: site-directed hormonal therapy in the rat.
A method of direct percutaneous injection of testosterone (T)-laden microspheres directly into the testis was used in an attempt to achieve the maintenance of normal intratesticular T concentrations, spermatogenesis, and fertility. Rats were divided into three groups: (1) sham operated/injection controls; (2) animals receiving 250 micrograms/d gonadotropin-releasing hormone (GnRH)-antagonist; and (3) animals receiving GnRH-antagonist as in group 1 plus 20 mg T-laden microspheres/testis. Treatment periods were 45 and 90 days. Serum T, testicular interstitial fluid T, testis weights, epididymal weights, daily sperm production (sperm x 10(6)/g/d), cauda sperm motility, and fertility were assessed in all animals. Gonadotropin-releasing hormone antagonist treatment reduced serum and testicular interstitial fluid to below detectable levels at day 45 and to similar levels at day 90. Supplementation with T-laden microspheres maintained testicular interstitial fluid T at concentrations not different from controls without elevation of serum T concentrations. All other values, including fertility were suppressed by GnRH-antagonist treatment and maintained by supplementation with T-laden microspheres.
Inflammatory changes in the epididymis after vasectomy in the Lewis rat.
The epididymides of Lewis rats were studied at intervals up to 7 months after vasectomy, vasectomy followed 3 months later by vasovasostomy, or sham operations. Epididymal histology was related to testicular alterations and to serum antisperm antibodies as determined with an enzyme-linked immunosorbent assay. In vasectomy and vasovasostomy groups. 13 of 33 rats had testicular alterations, which consisted mainly of pronounced depletion of germ cells. Over half of the rats with testicular alterations also had severe epididymal lesions that included interstitial changes characteristic of an inflammatory response. These consisted of aggregates of mononuclear cells, including lymphocytes, plasma cells, and macrophages. The lumina of epididymides with interstitial changes contained polymorphonuclear leukocytes and/or macrophages. All animals with altered testes had greatly decreased numbers of epididymal sperm. In many instances, the lumen of the proximal cauda epididymidis was collapsed, and columnar cells of the epididymal epithelium contained many very large lysosomes. The distal cauda epididymidis was distended with sperm and debris. None of the rats that lacked testicular alterations showed epididymal changes. Mean serum antisperm antibody levels were significantly higher for rats with epididymal interstitial changes than for animals without such epididymal alterations. Infiltrations of inflammatory cells into the epididymal interstitium and lumen are part of the constellation of changes that occurs after immunization with testicular homogenates to produce experimental allergic orchitis. The observations reported here support the hypothesis that reproductive tract alterations after vasectomy in this model have an immune basis.
Histologic analysis of orchiopexy in a cryptorchid rabbit model.
Although there is a consensus that very early orchiopexy is advantageous, there is little experimental data to support this view. Therefore, we studied early pre-pubertal versus later pre-pubertal orchiopexy in a cryptorchid rabbit model. Male offspring were divided into four groups with six to nine rabbits in each group: 1) controls (CON); 2) shams undergoing sham operations at both three weeks and two months of life (SHAM); 3) cryptorchid on day 3 with orchiopexy at three weeks and sham operation at two months (O3W); 4) cryptorchid on day 3 with sham operation at three weeks and orchiopexy at two months (02M). All animals were sacrificed post-puberty at six months of age; the tests were fixed in situ by perfusion fixation, embedded in glycol methacrylate, and underwent morphometric analysis in a blinded fashion. The average seminiferous tubular diameter (STD) of the CON, SHAM, O3W, and O2M groups was 234, 160, 116, and 123 microns, respectively. The average testicular biopsy score count (TBSC) of the CON, SHAM, O3W and O2M groups was 9.0, 5.2, 3.5 and 3.5, respectively. There is no significant difference in STD or TBSC between the O3W and O2M cryptorchid groups, and values for both of these groups were significantly different from those of the SHAM group. In addition, a significant effect of sham operation was demonstrated. These results demonstrate no advantage of very early orchiopexy in this model, and are consistent with the clinical literature which, in general, shows reduced reproductive potential of a cryptorchid testis after orchiopexy.
The influence of vasovasostomy on antisperm antibodies in rats.
Serum antisperm antibodies were studied in Sprague-Dawley rats after vasectomy and vasovasostomy. Animals received a bilateral vasectomy, a vasectomy followed 3 mo later by vasovasostomy, or sham operations. Blood samples were obtained at 1, 3, 4, and 7 mo, and antisperm antibodies were assayed by an enzyme-linked immunosorbent assay. After vasectomy reversal was performed at 3 mo, antisperm antibodies were significantly higher in rats in the vasovasostomy group at 4 mo than in animals that had a persisting vasectomy or sham operations. At 7 mo, the antisperm antibody level for the vasovasostomy group was approximately double that for the vasectomized rats. Spermatic granulomas occurred in 76% of rats after vasovasostomy. Antisperm antibody levels were higher in vasovasostomized animals with granulomas than in those lacking granulomas. The results suggest that vasovasostomy may stimulate an antibody response to sperm rather than lead to a reduced response, as was anticipated upon removal of the obstruction. Spermatic granulomas may serve as sires for continued antigenic challenge. The observed increase in antisperm antibodies after vasovasostomy in Sprague-Dawley rats may be related to their relatively low immunologic responsiveness to vasectomy, with vasovasostomy serving as a second major immunologic challenge, aided by the formation of an additional granuloma. In the more responsive Lewis strain, we previously observed a rise in antisperm antibodies after the initial vasectomy, with no further increase after vasovasostomy.
Transdermal testosterone treatment of hypogonadal men.
Hypogonadism, either primary or secondary, results in diminished libido and/or impotence. Conventional treatment consists of periodic intramuscular injections (usually bimonthly) of a depot testosterone preparation or daily oral ingestion of methyl testosterone. These conventional treatments may be associated with side effects, such as gynecomastia, liver function abnormalities and edema. A new method of administering testosterone is by daily application of a transdermal therapeutic system. We studied the efficacy and safety of the transdermal therapeutic system in 4 hypogonadal men. Three patients were treated for 12 weeks and 1 for 7 weeks, and they were evaluated weekly. Of 4 patients 3 had improvement in erectile and/or sexual function. Mean plasma testosterone levels increased significantly compared to pre-treatment values during 7 of 12 treatment weeks. There were no adverse effects of the transdermal therapeutic system as indicated by serial physical examinations, daily reports, blood chemistry studies, liver function tests, urinalysis and hematological profiles. This preliminary report of transdermal testosterone delivery indicates that it may provide an effective alternative method of gonadal steroid replacement.
Testicular alterations are linked to the presence of elevated antisperm antibodies in Sprague-Dawley rats after vasectomy and vasovasostomy.
The relationship between alterations in testicular histology and antisperm antibodies was studied after vasectomy and vasovasostomy in Sprague-Dawley rats, which are immunologically relatively non-responsive to vasectomy. Testes were prepared for histologic study at intervals up to seven months after vasectomy, vasectomy followed three months later by vasovasostomy, or sham operations. Antisperm antibodies were assessed with an ELISA. Testicular alterations, which were observed in a minority of animals after vasovasostomy, consisted mainly of depletion of germ cells. Mean serum antisperm antibody levels were greater for animals with altered testes than for rats with normal testicular histology. In addition, the proportion of rats that showed a positive antisperm antibody response was greater among animals with testicular changes than among those with unaltered testes. When the present results on Sprague-Dawley rats were compared with previous findings on the highly responsive Lewis strain, it was evident that the incidence of testicular changes and the proportion of positive antibody responders were greater in the Lewis strain. However, elevated antisperm antibodies and testicular alterations appeared to be more tightly linked in the less responsive Sprague-Dawley rats.
Multicystic dysplastic kidneys and diagnostic confusion on renal scan.
The combination of ultrasound and renal scan usually provides a reliable means of differentiating congenital ureteropelvic junction obstruction with hydronephrosis from multicystic dysplasia in the newborn with an abdominal mass. Rarely, a multicystic kidney will show definite function on a renal scan. We describe 2 newborns who were thought to have hydronephrosis based on a renal scan but who had typical multicystic dysplastic kidneys at operation.
Effects of granuloma formation at site of vasovasostomy.
Spermatic granulomas forming after vasectomy reversal have been thought to mechanically compromise the anastomosis. We have studied the physiologic effects of vasectomy and vasovasostomy in rats. Following delayed microsurgical vasovasostomy, fluid flow through the anastomosis and cauda epididymidal hydrostatic pressure are not significantly different in tracts that form, or do not form, sperm granulomas at the anastomosis. Given a properly performed microsurgical vasectomy reversal, a sperm granuloma arising from a small leak does not appear to mechanically compromise the anastomosis in the rat. Fertility after vasovasostomy is not significantly reduced in rats with granulomas.
The influence of vasovasostomy on testicular alterations after vasectomy in Lewis rats.
The occurrence of alterations in testicular weight and morphology after vasectomy and vasectomy reversal by vasovasostomy was studied in Lewis rats. Animals were studied 3, 4, and 7 months after bilateral vasectomy or a vasectomy followed 3 months later by vasovasostomy. Other rats served as sham-operated controls. The weights of the testes in vasectomy and vasovasostomy animals fell into two groups-small testes weighing less than 0.88 g and normal-sized testes of 1.2 g or more. When the extent of testicular alterations was estimated in sections for light microscopy by use of a semiquantitative testicular biopsy score count (TBSC), the morphology of the testes corresponded closely to the testis weight (r = .94), small testes having correspondingly low TBSC scores. In severely altered small testes, the seminiferous tubules were narrower than in sham-operated rats, and numbers of germ cells were greatly depleted. Many tubules contained only Sertoli cells and spermatogonia, although spermatocytes were present in a minority of tubules. A few seminiferous tubules contained multinucleate spermatids. Electron microscopy of severely altered tubules revealed closely apposed processes of Sertoli cells, which contained filaments, microtubules, and endoplasmic reticulum. In contrast, testes with normal weight in vasectomy and vasovasostomy groups resembled those of the sham-operated animals. Comparison of distributions of testicular biopsy score counts demonstrated differences between vasectomy and vasovasostomy groups as time after operation increased. At the 3-4-month intervals, approximately one-third of the testes were severely altered in both vasectomy and vasovasostomy groups.(ABSTRACT TRUNCATED AT 250 WORDS)
Initial experience with extracorporeal shock wave lithotripsy in children.
The clinical experience is presented of 4 United States centers at which extracorporeal shock wave lithotripsy was used for the treatment of renal calculi in 38 children 12 months to 16 years old. Patient characteristics, treatment specifics and followup data are detailed. Complete fragmentation of calculi was obtained in 97 per cent of those treated, with a 5 per cent complication rate. This experience demonstrates that with proper safeguards, extracorporeal shock wave lithotripsy can be performed safely and effectively in the pediatric population.