Biomedical subjects

D A Husmann

Publications and source records attributed to D A Husmann.

At least 55 records · Page 3Linked to original sources

PubMed1995

Current concepts in the pathophysiology of testicular undescent.

At present, we believe that descent of the testes within the human is a complex event mediated by both hormonal and mechanical factors. We hypothesize that descent of the testes occurs as a result of the secretion of an androgen-independent factor from a normal testis (descendin). This paracrine factor is responsible for the rapid proliferation (outgrowth) of the ipsilateral gubernaculum. The development of the gubernaculum results in creating a dilated inguinal canal, the width of which matches the testicular width. Descent of the testes through the inguinal canal is an interplay between abdominal pressure, a patent processus vaginalis, and androgen-induced gubernacular regression. We hypothesize that androgens (under control of an intact hypothalamic pituitary axis) alter the viscoelastic properties of the gubernaculum, reducing the turgidity of the gubernaculum and allowing intra-abdominal pressure to push the testis into the scrotum. Cryptorchidism can therefore result when any one or more of the involved factors malfunction.

Androgens↗

PubMed1995

Flutamide-induced cryptorchidism in the rat is associated with altered gubernacular morphology.

OBJECTIVES: One of the major controversies regarding descent of the testes is whether androgenic regulation of the gubernaculum testes exists. To determine if antiandrogens can alter the development of the gubernaculum within the fetus, the following experiment was performed. METHODS: Timed pregnant Sprague-Dawley rats were treated with either flutamide, dihydrotestosterone (DHT), or vehicle alone (controls) from gestational day (GD) 15 to 17. Fetal specimens were removed via cesarean section on GD 18 and 20. Serial coronal sections were obtained, and digital microscopy with computer-assisted reconstruction was used to ascertain the morphology of the three components of the gubernaculum, that is, the gubernacular cord and the mesenchymal and muscular components of the gubernacular bulb. RESULTS: Flutamide significantly prevented and DHT significantly enhanced gubernacular cord regression compared with controls (P < 0.01). Flutamide also resulted in a significant inhibition of the gubernacular bulb outgrowth, with diminution of both the mesenchymal and muscular components of the gubernacular bulb. CONCLUSIONS: These data suggest that androgens play an active role in gubernacular cord regression and gubernacular outgrowth within the fetal rodent.

Androgen Antagonists↗

PubMed1995

Antiandrogen induced cryptorchidism in the pig is associated with failed gubernacular regression and epididymal malformations.

PURPOSE: Can antiandrogens cause cryptorchidism in an animal model with a strip-like gubernaculum? If so, what anatomical abnormalities are associated with cryptorchidism? MATERIALS AND METHODS: Timed pregnant sows received the antiandrogen flutamide during defined gestational intervals. Fetal pigs were evaluated for the presence of testicular undescent and for morphological paratesticular abnormalities at 110 days of gestation (birth). RESULTS: Of 180 testes 84 (47%) were undescended and 9 (5%) were in the abdominal cavity. No undescended testis (0 of 200 testes) were found in control animals (p < 0.001). Epididymal anomalies were found in all intra-abdominal testes, which was significant when compared to the epididymal abnormalities found with inguinal undescended testes (0%) or descended testes (1%) (p < 0.001). Alterations in gubernacular morphology, in particular failure of gubernacular regression, were also directly associated with cryptochidism (p < 0.001). CONCLUSIONS: Androgens partially control transabdominal and transinguinal descent of the porcine testis. In addition, antiandrogen induced cryptorchidism is associated with epididymal malformation and failure of gubernacular regression. It remains to be determined if these latter findings are only associated with or the cause of testicular undescent.

Abnormalities, Drug-Induced↗

PubMed1995

Ureterocele associated with ureteral duplication and a nonfunctioning upper pole segment: management by partial nephroureterectomy alone.

We reviewed the records of 87 patients with a ureterocele associated with duplication and a nonfunctioning upper pole segment. All patients involved in this study were treated by partial nephroureterectomy and observation. Additional surgery to correct vesicoureteral reflux became necessary in 54 cases (62%). A careful retrospective chart and radiographic review identified that the need for additional surgery was directly related to the number of renal moieties that had a ureterocele or vesicoureteral reflux present. In particular, when a ureterocele alone was present 21 of 21 patients (100%) did not require additional surgery. When low grade (less than 3/5) reflux was present into 1 ureter 8 of 15 patients (60%) did not require surgery. The presence of high grade reflux into 1 moiety or vesicoureteral reflux into more than 1 moiety, regardless of the grade of reflux, almost inevitably resulted in the need for further surgery with only 2 of 50 patients (4%) with these abnormalities cured by partial nephroureterectomy alone. Our data suggest that this latter group of patients may be treated more efficaciously by complete genitourinary reconstruction rather than partial nephroureterectomy alone.

Adolescent↗

PubMed1995

Continuous epidural anesthesia after ureteroneocystostomy in children.

We retrospectively reviewed the records of 101 pediatric patients who underwent uncomplicated ureteral reimplantation and were treated with postoperative epidural catheters for pain management. A total of 50 pediatric patients treated without epidural anesthesia was used as the control group. Length of hospital stay, time to first bowel activity, doses of narcotics, incidence of postoperative fever and evidence of epidural catheter related morbidities were documented. The costs of postoperative epidural anesthesia versus standard analgesics were compared. There was no significant difference in length of hospital stay or return of bowel function between treatment groups. Total doses of narcotics given during the hospital stay were significantly less for the epidural group (p < 0.05). The children given epidural anesthesia also had a significant increase in the incidence of postoperative fever (p < 0.05) and 25% had catheter related problems that often resulted in early removal of the epidural catheter. The cost of pain management using an epidural catheter was significantly greater than that of the standard narcotic regimen ($708 versus $14, p < 0.001). Continuous epidural infusion provides satisfactory pain control after ureteroneocystostomy in children without delaying hospital discharge. This technique of pain management is associated with a significant increase in the incidence of postoperative fever and overall cost compared to standard methods of postoperative pain management.

Adolescent↗

PubMed1995

Urinary pH and urea concentration correlate to the bacterial colonization rate in gastric, colonic, ileal and myoperitoneal bladder augmentation.

We investigated how various types of augmentation cystoplasty alter the native bacteriostatic properties of urine, particularly urinary urea and pH, in the Sprague-Dawley rat. The augmentation cystoplasties studied included 1 cm.2 and 2 cm.2 patches of colon, ileum and stomach as well as myoperitoneal bladder flaps. Augmentations in order of decreasing incidence of bacteriuria and urinary pH are 2 cm.2 ileal greater than 1 cm.2 ileal greater than 2 cm.2 colonic greater than 1 cm.2 colonic greater than myoperitoneal greater than cystotomy alone greater than 1 cm.2 gastric greater than 2 cm.2 gastric. Urinary urea concentrations were similar between cystotomy alone, and myoperitoneal and gastric augments. In contrast, all colonic and ileal augments had significantly lower urea concentrations compared to the aforementioned groups. Our findings suggest that the type and size of augmentation directly affect urinary pH and urea nitrogen concentration, and the incidence of bacteriuria.

Animals↗

PubMed1995

Primary nocturnal enuresis: a comparison among observation, imipramine, desmopressin acetate and bed-wetting alarm systems.

Patients with primary nocturnal enuresis were entered into 4 treatment groups: observation, imipramine, desmopressin acetate or alarm therapy. Patients were weaned from therapy 6 months after inclusion in the study and were evaluated for continence at 3, 6, 9 and 12 months after beginning the study protocol. Of the 50 patients under observation 6% were continent at 6 months and 16% were continent within 12 months. Of 44 patients treated with imipramine 36% were continent at 6 months on medication; however, only 16% were continent at 12 months, off medication. Similarly, of the 88 patients treated with desmopressin acetate 68% were continent at 6 months but only 10% were continent at 12 months. Of the 79 patients treated with alarm therapy 63% were continent at 6 months and 56% were dry at 12 months. Although each form of therapy improved continence over observation alone (p < 0.01), only the bed-wetting alarm system demonstrated persistent effectiveness (p < 0.001).

Adolescent↗

PubMed1995

Micropenis: does early treatment with testosterone do more harm than good?

Micropenis secondary to hypogonadotropic hypogonadism was induced in the Sprague-Dawley rat using long acting microspheres of the gonadotropic agonist leuprolide acetate. Following the induction of micropenis treatment was initiated with testosterone at day 7, 28, 56 or 84 of life. All treatment protocols resulted in improved phallic growth compared to the untreated animals with micropenis (p < 0.01). Treatment of animals with testosterone beginning on day 7 of life resulted in premature growth of the penis and the redevelopment of micropenis in adulthood. In contrast, delaying testosterone therapy until day 56 (pubertal) or 84 (early postpubertal) resulted in complete penile development. These findings suggest that early exposure of the penis to androgens in childhood may eventually result in a significant reduction of phallic size in adulthood.

Animals↗

PubMed1995

Ureteropelvic junction obstruction with a simultaneous renal calculus: long-term followup.

We reviewed 111 patients who presented with simultaneous renal calculi and a ureteropelvic junction obstruction. Of 34 patients with ureteropelvic junction obstruction and a coexisting struvite stone 62% had recurrent calculi. The use of antibiotics significantly affected the incidence of recurrent struvite calculi. In particular, if prolonged prophylactic antibiotics (greater than 3 months) were used 15% of the patients had recurrent stones, compared to 90% if only perioperative antibiotics (less than 15 days) were used (p < 0.001). Patients with ureteropelvic junction obstruction and coexisting nonstruvite calculi were treated by either observation alone (53) or metabolic evaluation with appropriate intervention (24). Metabolic evaluation of patients with nonstruvite calculi revealed that 76% had an identifiable metabolic abnormality, treatment of which significantly decreased the incidence of recurrent renal calculi: 17% of the patients on interventional therapy had recurrent stones compared to 55% treated by observation alone (p < 0.001).

Anti-Bacterial Agents↗

PubMed1995

Retrograde filling of the renal vein on computerized tomography for blunt renal trauma: an indicator of renal artery injury.

Assessment of the traumatically injured pediatric patient with computerized tomography has become standard medical practice. We report the unique finding of retrograde flow of intravenous contrast material into the renal vein as a diagnostic indicator of traumatic renal artery injury. With the increasing use of high-speed computerized tomography as the initial study to evaluate and stage blunt abdominal trauma, this finding may assist the physician in the early diagnosis of severe renovascular injury.

Contrast Media↗

PubMed1994

Alterations in maternal epidermal growth factor (EGF) effect testicular descent and epididymal development.

OBJECTIVE: (1) To determine the ability of epidermal growth factor (EGF) to reverse antiandrogen-induced cryptorchidism and epididymal abnormalities; (2) to evaluate whether alterations in maternal EGF would result in abnormal testicular descent or mal development of the epididymis. METHODS: Experiment 1: Timed pregnant ICR mice were treated with either flutamide, flutamide plus EGF, or vehicle alone on gestational days 11 through birth. Experiment 2: Maternal EGF was abolished by removing the submandibular glands. Following timed mating, dams were treated with either flutamide, anti-EGF, DHT, or vehicle alone on gestational days 11 through birth. RESULTS: Experiment 1: Treatment with flutamide resulted in a 36 percent (26/72) incidence of undescended testes (UDT), and a 43 percent (31/72) incidence of abnormal epididymides. Rats treated simultaneously with flutamide plus EGF had a reduced incidence of UDT (14%, 6/42) and epididymal anomalies (19%, 8/42); p < 0.01. Experiment 2: The absence of maternal EGF resulted in a significant incidence of cryptorchidism in 11/50 (22%) testes, and epididymal anomalies in 19/50 (38%); p < 0.01. CONCLUSIONS: Our findings suggest that EGF stabilizes the wolffian duct system and partially mediates testicular descent.

Abnormalities, Drug-Induced↗

PubMed1994

Infundibulopelvic stenosis: a long-term followup.

We followed 21 patients with congenital infundibulopelvic stenosis, a rare obstructive disorder of the intrarenal collecting system, for a median of 11 years (range 2 to 28 years). Of these patients 19 (90%) had evidence of bilateral renal disease. In particular, 10 patients had bilateral infundibular pelvic stenosis, 6 a contralateral cystic dysplastic kidney and 3 a congenitally absent kidney. Extended observations of the patients with this disorder revealed that end stage renal disease or renal insufficiency developed in 8 patients (37%), all with bilateral renal anomalies. Renal biopsies in patients with end stage renal failure revealed widespread areas of renal dysplasia proximal to the stenotic infundibulum with focal or global glomerulosclerosis of the glomeruli, which was not involved in the dysplastic process. These pathological findings are consistent with the presence of a renal hyperfiltration injury. Our data suggest that the prognosis of infundibulopelvic stenosis is dependent upon the extent of total renal mass involved with the disease process and the duration of followup.

Adolescent↗

PubMed1994

Microphallus: eventual phallic size is dependent on the timing of androgen administration.

Micropenis secondary to hypogonadotropic hypogonadism in the Sprague-Dawley rat was induced by either injection of supraphysiological doses of dihydrotestosterone to the timed pregnant dam on gestational days 16 and 17 or by long acting microspheres of the gonadotropic agonist, leuprolide acetate. Following the induction of micropenis the animals were treated with dihydrotestosterone beginning at either day 7, 28, 56 or 84 of life. Within the study populations all animals treated with dihydrotestosterone had phallic enlargement greater than untreated controls (p < 0.01). However, animals beginning treatment on day 7 or 28 had persistent microphallus (p < 0.01). In contrast, if hormonal therapy was initiated on day 56 or 84 the phallus became normal in length. Immunohistological studies for androgen receptor expression revealed that early androgen exposure accelerated the loss of androgen receptor protein from the penis during growth. These data suggest that prepubertal exposure of the penis to androgens may significantly reduce the eventual penile size of the hypogonadotropic hypogonadal micropenis.

Animals↗

PubMed1994

Expression of androgen receptor protein within the lumbar spinal cord during ontologic development and following antiandrogen induced cryptorchidism.

One of the leading hypotheses regarding androgenic regulation of testicular descent is that the lumbar genitofemoral nucleus is morphologically altered by testosterone during a specific prenatal period. This hypothesis is based on the unproved assumption that androgen receptor is present in the fetal spinal cord. Using immunohistochemistry we identified androgen receptor in the rat lumbar spinal cord on gestational day 15, a day before the onset of maximal androgenic action for testicular descent. Experiments were performed to determine whether alterations in the morphology of the genitofemoral nucleus are associated with flutamide induced cryptorchidism. Studies revealed a reduction of motoneuron number in rats with flutamide induced cryptorchidism (124.2 +/- 18.9) compared to rats exposed to flutamide without cryptorchidism (269.3 +/- 20.2) and/or male controls (291.0 +/- 14.5, p < 0.01). These findings support the hypothesis that androgens can directly regulate development and morphology of the genitofemoral nucleus.

Animals↗

PubMed1994

Epidermal growth factor reverses antiandrogen induced cryptorchidism and epididymal development.

Epidermal growth factor, an androgen responsive paracrine factor, administered to pregnant mice has been reported to result in persistent wolffian ducts in female offspring. This fact led us to investigate whether epidermal growth factor can reverse the undescended testes and epididymal abnormalities associated with time specific flutamide administration. Timed pregnant Sprague-Dawley rats were treated with flutamide (undescended testes 74% and epididymal anomalies 53%) or flutamide plus epidermal growth factor (undescended testes 24% and epididymal anomalies 9%). The decrease in undescended testes and epididymal abnormalities following epidermal growth factor treatment was significant at p < 0.01. We performed immunohistological studies to evaluate whether flutamide alters epidermal growth factor expression in the paratesticular tissues during the time of maximal androgenic activity. These investigations revealed that antiandrogens did not alter epidermal growth factor expression in the fetal testes or epididymides. This finding suggests that epidermal growth factor does not reverse epididymal abnormalities or undescended testes by direct stimulation of the wolffian ducts or fetal testis.

Abnormalities, Drug-Induced↗

PubMed1994

Flutamide-induced testicular undescent in the rat is associated with alterations in genitofemoral nerve morphology.

Androgen regulation of testicular descent is an established fact. However, the mechanisms by which androgens assert their influence is unknown. One of the leading hypotheses regarding androgenic control of testicular descent is based upon the assumption that testosterone regulates the development of the sexually dimorphic genitofemoral nucleus and nerve (GFN). To investigate whether or not alterations in the genitofemoral nerve are indeed androgen dependent and associated with testicular undescent, we administered flutamide in a time-specific manner to pregnant Sprague-Dawley rats. The GFN of ten animals with unilateral intra-abdominal testicular undescent was compared with the contralateral GFN associated with the descended testicle. Digital microscopic evaluations found that the GFN associated with testicular undescent did express altered morphologic abnormalities. Specifically, the GFN associated with the cryptorchid testicle had significant reductions in the neural diameter (.0169 +/- .0024 mm.2 versus .0275 +/- .0079 mm.2; p < .01), the number of large myelinated fibers per mm.2 (8.4 +/- 3.3 versus 18.8 +/- 5; p < .001) and the number of small myelinated nerve fibers per mm.2 (632 +/- 87.4 versus 1090.7 +/- 104.3; p < .001). These data suggest that testicular undescent in the rat is associated with morphologic alterations in the ipsilateral genitofemoral nerve. The exact mechanism of how these alterations are related to cryptorchidism remains to be elucidated.

Age Factors↗

PubMed1994

Hydronephrosis in renal ectopia: incidence, etiology and significance.

The incidence, cause and significance of hydronephrosis in patients with renal ectopia are unknown. Therefore, we conducted a retrospective review of 77 patients with 82 ectopic kidneys. Of 82 kidneys 46 (56%) had hydronephrosis. Dilatation of the renal pelvis was the result of primary ureteropelvic or ureterovesical obstruction in 52%, grade 3, 4 or 5 vesicoureteral reflux in 26% and extrarenal collecting systems with malrotation that produced apparent ureteropelvic junction obstruction in 22%. Surgery was performed in 41 patients, including primary nephrectomy in 18, ureteral reimplantation in 14 and ureteropelvic junction repair in 8. Hydronephrosis was present in 15 of 58 contralateral nonectopic kidneys, and 11 required surgery mostly for vesicoureteral reflux. Solitary ectopic kidneys with no associated obstruction or reflux demonstrated normal renal function. Our data indicate that the prognosis in renal ectopia relates directly to the associated urological disease and timely surgical intervention, not to ectopia alone.

Adolescent↗

PubMed1993

Altered brain and pituitary androgen metabolism by prenatal, perinatal or pre- and postnatal finasteride, flutamide or dihydrotestosterone treatment in juvenile male rats.

1. The authors investigated the administration of finasteride, a 5 alpha-reductase inhibitor; flutamide, an androgen receptor blocker and; exogenous dihydrotestosterone (DHT) during intervals covering different portions of the "critical period" of neural development (i.e. prenatal, perinatal or pre- and postnatal development) to determine the long-term effects of these agents on altering androgen metabolism in hypothalamic and pituitary tissue of juvenile (30 day-old) male rats. 2. The efficacy of the treatments and hypothalamic-pituitary axis function was monitored by measuring luteinizing hormone levels by radioimmunoassay. 5 alpha-Reductase and aromatase activity was determined in hypothalamic and pituitary tissue. 3. Significant alterations in pituitary 5 alpha-reductase activity was detected in DHT-treated animals, whereas, hypothalamic 5 alpha-reductase activity was significantly decreased by finasteride treatment and significantly increased by DHT treatment. Hypothalamic aromatase activity was significantly decreased in flutamide-treated animals. 4. These results suggest that: a) prenatal exposure to exogenous DHT stimulates hypothalamic (but inhibits pituitary) 5 alpha-reductase activity long-term and b) basal 5 alpha-reductase activity levels can be inhibited by finasteride treatment in hypothalamic but not in pituitary tissue, suggesting that a different regulatory mechanism exists for 5 alpha-reductase in hypothalamic versus pituitary tissue.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗