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Biomedical subjects

W J Hellstrom

Publications and source records attributed to W J Hellstrom.

At least 55 records · Page 3Linked to original sources

Effect of tumour necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) on human sperm motility, viability and motion parameters.

Male genital tract infections and non-specific inflammatory conditions may be associated with unexplained infertility. Previous studies have shown the presence of cytokines such as tumour necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) in the semen of infertile men. However, the mechanism of effect of these cytokines on human sperm function is still controversial. The present study was undertaken to investigate the in-vitro effects of TNF-alpha and IFN-gamma on human sperm motion, viability and the hypoosmotic swelling test (HOST). Washed spermatozoa from normal volunteers (n = 9) were incubated in the presence/absence of TNF-alpha (1 microgram/mL) plus IFN-gamma (0.1 microgram/mL). Sperm motility, viability, HOST, and video sequences were recorded at different time intervals (0, 30, 60 and 180 min). Sperm motion parameters were analysed using computer-assisted semen analysis. There was a time-dependent negative effect of TNF-alpha plus IFN-gamma on sperm motility, viability, HOST, and lateral-head displacement (ALH). The maximum decrease was observed between 60 and 180 min for sperm motility (50.8 +/- 5.6%), viability (52.8 +/- 4.0%), HOST (38 +/- 2%) and ALH (4.7 +/- 0.1 microns) compared to control samples (62.2 +/- 2.8, 62.4 +/- 2.9, 58 +/- 4, and 5.3 +/- 0.4, respectively; All p < 0.05). There was no significant effect on sperm straight-line velocity and mean linearity when compared to control. These data suggest that the common inflammatory cytokines TNF-alpha plus IFN-gamma have only partial detrimental effects on sperm motility, viability, membrane integrity and lateral head displacement, which may contribute to the poor fertilizing potential of human spermatozoa during inflammatory conditions.

Cell Membrane↗

Nociceptin, a novel endogenous ligand for the ORL1 receptor, has potent erectile activity in the cat.

The heptadecapeptide nociceptin, also known as orphanin FQ, is a newly discovered endogenous ligand for the opioid-like G protein-coupled receptor ORL1. The present study was undertaken to investigate the effects of intracavernosal injections of nociceptin on penile erection in anesthetized cats. Responses to nociception were compared with erectile responses elicited by intracavernosal injection of vasoactive intestinal polypeptide (VIP), adrenomedullin (ADM), the novel nitric oxide donor diethylaminenitric oxide complex sodium (DEA/NO), and the control triple-drug combination (papaverine, phentolamine, and prostaglandin E1). The order of potency was VIP > ADM > nociceptin > DEA/NO. Intracavernosal injections of nociceptin in doses of 0.3-30 nmol elicited dose-related increases in cavernosal pressure and penile length that were comparable to those induced by the triple-drug combination, which is used in the treatment of erectile dysfunction. The response to nociceptin was rapid in onset, and the duration of the peak pressure increase and total response was significantly shorter than the response to the control triple-drug combination but longer in duration than responses to VIP and ADM. Intracavernosal injection of the triple-drug combination resulted in a greater decrease in mean systemic arterial blood pressure than did nociceptin. These data demonstrate that intracavernosal injection of this novel endogenous ligand for the ORL1 receptor induces a potent and relatively long-lasting erectile response in the cat.

Animals↗

Human vasal changes after vasectomy: in vitro studies.

UNLABELLED: Failure to impregnate, after successful vasovasostomy, has been attributed to immunologic, testicular, and epididymal factors. OBJECTIVES: To study the effect of vasectomy on human vas innervation and vesicoelastic properties. METHODS: Vas rings were obtained from 8 healthy males during vasectomy as controls and compared to those of 3 vasovasostomy patients. The active and passive properties were determined and the cumulative blocking effects of phenoxybenzamine, propranolol, atropine and tetrodotoxin were studied. RESULTS: There was significantly higher rigidity in the vasovasostomy group as compared to the control group but there were similar active forces between the two groups up to 100-120% of stretch. In the control group, phenoxybenzamine blocked 33.3%, propranolol blocked 15.8%, and atropine blocked 36.5% but tetrodotoxin had no further effect. In the vasovasostomy group, phenoxybenzamine blocked 33.3% (similar to control), propranolol blocked 2%, atropine blocked 11.7% and tetrodotoxin blocked 37.1%. CONCLUSIONS: In vasovasostomy group there was increased rigidity without reduction of the active force. There were also decreased cholinergic and possible existence of nonadrenergic noncholinergic neurotransmitters.

Adrenergic alpha-Antagonists↗

A double-blind, placebo-controlled evaluation of the erectile response to transurethral alprostadil.

OBJECTIVES: Previous studies have indicated that the urethra may provide an effective route for administering vasoactive medication for the treatment of erectile dysfunction. We evaluated the safety and efficacy of alprostadil administered intraurethrally at home for the treatment of this disorder. METHODS: This prospective, multicenter, double-blind, placebo-controlled study evaluated the erectile response to randomly assigned doses of transurethral alprostadil at home in 68 men with long-standing (mean 41 months) erectile dysfunction of primarily organic etiology. Patients completing the study each administered a random sequence of four different doses (125, 250, 500, and 1000 micrograms) and placebo over a 2 to 4-week period. Assessments included the couples' ability to have intercourse, patient ratings of erectile response by both categorical and visual analogue scales, penile volume measurements, and overall assessments of comfort and ease of administration. RESULTS: Overall, 75.4% (49 of 65) of study patients achieved full enlargement of the penis and 49.2% (32 of 65) achieved an erection judged by the patient to be sufficient for intercourse. In addition, 63.6% (42 of 66) of patients reported intercourse. Efficacy was similar across etiologies. The most common side effect was penile pain, which occurred in association with 9.1% to 18.3% of alprostadil administrations, depending on dose. Mean comfort ratings ranged from 79 to 87, depending on dose, where 0 = severe discomfort and 100 = comfortable; ease of administration scores were above 90 for each dose, where 0 = difficult and 100 = easy. There were no episodes of priapism in this study. CONCLUSIONS: Short-term treatment with transurethral alprostadil produced erections resulting in sexual intercourse in most patients with chronic erectile dysfunction. This therapy may be a useful treatment option for patients with erectile dysfunction.

Adult↗

Reconstruction of a total anterior urethral defect using buccal mucosa.

Extensive urethral defects in the presence of insufficient local skin can challenge the reconstructive urologist. We report a case of complete anterior urethral loss due to Fournier's gangrene that was successfully reconstructed using autologous buccal mucosa. A 17.5 x 2.5 cm tube graft was harvested, extending from the left to right buccal regions along the lower labial fold. At long-term follow-up, the patient had an acceptable cosmetic result with maintenance of potency and the ability to urinate. Buccal mucosal grafts are a viable alternative for cases of near-total urethral reconstruction.

Aged↗

Priapism in sickle cell disease: the case for early implantation of the penile prosthesis.

OBJECTIVES: Recurrent ischemic priapism in sickle cell (SS) patients often leads to impotence. Blockage of venous outflow by sickle cells leads to anoxia of the cavernosal smooth muscle with subsequent replacement of the erectile tissue with dense fibrosis. This study evaluates the efficacy of early penile prosthesis implantation in patients with priapism associated with sickle cells disease. METHODS: Our recent experience includes 6 SS patients with impotence resulting from repeated episodes of priapism and 1 SS patient who suffered penile autoamputation from prolonged tricorporeal low flow priapism. The average age was 26 years. Six patients underwent excision of fibrotic cavernosal sinusoidal tissue and placement of a malleable prosthesis. The autoamputation case was managed with a one-stage penile reconstruction using a forearm free-flap and a two-piece inflatable penile prosthesis. RESULTS: All patients in our series are currently potent. Because of infection, 1 patient required removal and subsequent reinsertion of his prosthesis, and another has required revision. CONCLUSION: Potency in the young SS patient with recurrent episodes of ischemic priapism may best be managed by a penile prosthesis. Early implantation may lessen the psychological trauma of repeated priapisms, and reduce the technical difficulties and complications associated with penile prosthetic insertion in the presence of dense fibrosis.

Adolescent↗

Three-piece inflatable penile prosthesis implantation: a comparison of the penoscrotal and infrapubic surgical approaches.

Patient satisfaction with the three-piece inflatable penile prosthesis was evaluated in two surgical subgroups following randomized implantation: those who underwent implantation via an infrapubic (IP) approach and those via a penoscrotal (PS) incision. Follow-up questionnaires were mailed to 86 patients who had undergone implantation of a Mentor alpha-1 or AMS 700CX inflatable penile prosthesis between August 1989 and November 1992. The questionnaire (54 items) was designed to elicit both factual and perceptual information in the areas of general medical information, prosthesis usage, erectile quality, postoperative complications, and general satisfaction. Questionnaire data was enhanced by a review of the clinic and hospital records of each patient who returned the questionnaire. Patients were followed postoperatively at regular intervals for a minimum of 6 months. Results demonstrate an overall patient satisfaction of 85%. Breakdown into the two surgical subgroups revealed similar rates of satisfaction by both groups. Analysis of the 42 questionnaires returned demonstrated no statistical differences in the replies of the two groups in either the factual or perceptual data. The most common sources of dissatisfaction related to penile length, girth, and difficulty with usage. This study demonstrates no compelling advantages in employing one surgical approach over the other.

Humans↗

Penile intracavernosal substance abuse.

A complete workup for a 36-year-old man with unexplained inguinal adenopathy and an indurated, enlarged penis and scrotum included urine cultures for bacteria, fungi, and acid-fast bacilli; scrotal ultrasound; computed tomography of the abdomen and groin; a retrograde urethrogram; a cystogram; duplex penile Doppler blood flow studies; and a surgical inguinal lymph node dissection. Pathologic examination of the excised lymph node revealed lipoid granulomatous lymphadenitis. After receiving definitive treatment for a psychotic condition, the patient acknowledged a 2-year history of intracavernosal injection of gelatinous vitamin E.

Adult↗

Gunshot wounds to the male genitalia.

Fifty consecutive cases of gunshot wounds to the male external genitalia were treated by the Tulane University Urology Service at the Medical Center of Louisiana in New Orleans. Fifty percent of the patients had significant associated injuries. Eight anterior urethral injuries were identified, all by retrograde urethrography. Five of 17 testicular injuries were salvaged with conservative operative technique. Review of this series suggests that good functional integrity of the male genitalia after gunshot injury can be maintained by following a strict diagnostic and therapeutic regimen.

Adolescent↗

Posttraumatic high flow internal pudendal artery-urethral fistula.

A case of posttraumatic fistula of the internal pudendal artery-urethra is reported. The patient was referred with prolonged pulsatile gross hematuria requiring multiple blood transfusions after a motor vehicle accident. Associated injuries included a comminuted pubic ramus fracture. Initial uroradiographic evaluations did not identify the site of origin of hematuria but eventually selective angiography allowed diagnosis. Selective arterial embolization of the internal pudendal artery provided definitive treatment.

Adult↗

Bacterial infection in prostatodynia.

PURPOSE: We investigated a possible bacterial etiology for prostatodynia. MATERIALS AND METHODS: We evaluated segmented urine specimens from 22 patients and 16 controls by bacteriological localization studies. Immunological studies were performed on patient and control sera. RESULTS: Nine patients had positive cultures from prostatic secretions. When compared to controls, this novel finding was statistically significant (p < 0.025). Coagulase-negative staphylococci were the most common isolates (68%). No humoral (IgG) immune differences were found between patients and controls. CONCLUSIONS: In a subset of prostatodynia patients bacteria may have an etiological role. Antibiotic treatment demonstrated clinical efficacy.

Adult↗

Oxidative stress and interleukins in seminal plasma during leukocytospermia.

OBJECTIVE: To quantify the levels of reactive oxygen species, superoxide dismutase (SOD), and interleukins (IL) 2 and 8 in seminal plasma of infertile patients as well as to examine the possible relationship between oxidative stress and proinflammatory cytokines. DESIGN: Semen collected from normal fertile donors, infertile men without symptoms of genitourinary (GU) inflammation, and infertile men with symptoms of infection-inflammation of the GU tract was evaluated for the levels of granulocyte elastase, reactive oxygen species, SOD, IL-2, and IL-8. Any correlation between the levels of reactive oxygen species and other parameters in these population was analyzed statistically. RESULTS: Significantly high levels of granulocyte elastase (18.32 +/- 1.52 U/L), reactive oxygen species (6 x 10(5) cpm), IL-8 (3.7 +/- 0.10 microgram/L), and IL-2 (18.32 +/- 1.47 ng/L) were observed in semen of infertile patients with leukocytospermia compared with the other two groups. In leukocytospermic samples, the activity of SOD was significantly lower (624.89 +/- 41.16 NU/mL) compared with nonleukocytospermic samples (787.85 +/- 24.26 NU/mL) or fertile donors (816.29 +/- 50.16 NU/mL). A significant positive correlation was observed between the levels of reactive oxygen species and IL-8. CONCLUSIONS: These findings suggest that increased oxidative stress observed during leukocytospermia may modulate the level of proinflammatory cytokines. The increased oxidative stress may be due to a defect in the reactive oxygen species scavenging system.

Humans↗

Reproductive capacity of the nucleus of the male gamete after completion of meiosis.

PURPOSE: Our purpose was to investigate the possibility of achieving fertilization and subsequent normal embryonic development by injecting round spermatid nuclei into rabbit oocytes. RESULTS: Two-to four-cell-stage embryos developed after round spermatid nuclear injections into rabbit ooplasma could further develop in vitro up to the expanding blastocyst stage or in vivo up to complete gestation. CONCLUSION: The current findings show that the haploid set of chromosomes of round spermatid can pair with the chromosomes of the ootid to participate in complete fertilization and subsequent embryonic and fetal development. In addition, we suggest that postmeiotic modifications of the round spermatid are not required for the pairing of male gamete chromosomes with those of the ootid.

Animals↗

Effect of sodium nitroprusside on sperm motility, viability, and lipid peroxidation.

OBJECTIVE: To analyze the effect of sodium nitroprusside, a nitric oxide releaser, on sperm motion and lipid peroxidation-induced membrane damage in cryopreserved human sperm. DESIGN: Post-thaw, cryopreserved, human sperm samples were washed and divided into three aliquots. Each aliquot was incubated with either 0, 50, or 100 nM sodium nitroprusside. INTERVENTIONS: Samples were analyzed for lipid peroxidation (measured by malonaldehyde-thiobarbituric acid reactivity) at 3 hours post-thaw. MAIN OUTCOME MEASURES: Percent viability and motion parameters were assessed at 0, 10, and 30 minutes and 2, 3, 5, and 6 hours post-thaw. RESULTS: All results represent a mean +/- SEM, n = 10. Lipid peroxidation in samples incubated with 50 nM sodium nitroprusside (15.1 +/- 2.1 nM malonaldehyde/10(8) sperm) or 100 nM sodium nitroprusside (13.2 +/- 2.1 nM malonaldehyde/10(8) sperm) was significantly lower than in controls (22.7 +/- 3.1 nM malonaldehyde/10(8) sperm). Percent viability was significantly reduced from 0 minutes (60.6% +/- 3.5%) to 6 hours post-thaw in controls (38.0% +/- 5.1%) but not in 50 nM (46.8% +/- 10.4%) or 100 nM (48.8% +/- 6.5%) sodium nitroprusside-treated samples. Compared with controls (18.3% +/- 3.4%), maintenance of percent motility at 3 hours post-thaw was significantly improved in 50 nM (24.5% +/- 2.9%) and in 100 nM (26.3% +/- 3.2%) sodium nitroprusside-treated samples. Straight line velocity maintenance was significantly improved in 50 nM (37.3 +/- 1.3) and in 100 nM (37.0 +/- 1) sodium nitroprusside-treated samples as compared with controls (30.5 +/- 1.7). Significant improvements in curvilinear velocity maintenance compared with controls (56.3 +/- 2.9) also were observed in 50 nM (65.9 +/- 2.1) and 100 nM (72.1 +/- 4.1) sodium nitroprusside-treated samples. Significant differences in the motion parameters of sodium nitroprusside-treated samples were maintained at 5 and 6 hours post-thaw in comparison to controls. CONCLUSION: These results suggest that sodium nitroprusside is beneficial to the maintenance of post-thaw sperm motion and viability for up to 6 hours and that reduction of lipid peroxidative damage to sperm membranes may be the mechanism for these benefits.

Cell Survival↗

Nitric oxide mediates penile erection in cats.

The present study was undertaken to investigate the in vivo effects of nitric oxide (NO) mediating agents injected intracavernosally on penile erection in cats. All NO donors increased the cavernosal pressure and penile length in a dose-dependent manner. The maximal effects on cavernosal pressure and penile length induced by s-nitrosocysteine (NO-CYS) and s-nitroso-n-acetylpenicillamine (SNAP), respectively, were 8-fold and 5-fold increases in pressure, and 45% and 34% increases in length when compared with baseline values. These changes were comparable to that caused by the control drug combination (papaverine, phentolamine and prostaglandin E1). The effects of acetylcholine (ACh) and substance P on cavernosal pressure and penile length were less than those obtained with the control drug combination, NO-CYS (p < 0.01), or SNAP (p < 0.05). N omega-nitro-l-arginine-methyl-ester (L-NAME), a nitric oxide synthase (NOS) inhibitor, significantly decreased the effects of NO-CYS, ACh and substance P on penile erection. This in vivo study with NO donors and an NOS inhibitor suggests that NO is a mediator of penile erection in cats.

Acetylcholine↗

Penile erection in the primate: induction with nitric-oxide donors.

The primate model has been used for investigations on the physiology and pharmacology of erection. Recent in vitro investigations indicate that nitric oxide acts as the mediator of penile erection, but in vivo primate studies are needed to corroborate these findings. Penile erections were induced in a primate model using intracavernosal injections of nitric oxide donors s-nitrocysteine (NO-CYS) and sodium nitroprusside (SNP), and acetylcholine (ACh) which stimulates the formation of nitric oxide. Penile length and intracavernosal pressures following agonist injection were compared with baseline (flaccid) and control erections (elicited by injection of a papaverine/phentolamine/PGE1 standard mixture). Dose-response curves for each drug were determined with respect to maximal intracavernosal pressure, duration of effect and penile length, and systemic arterial pressure was monitored. All three agents induced erections, with dose-dependent increases in cavernosal pressure and penile length. The maximal cavernosal pressure attained was similar for all three agents, but the duration of action was significantly shorter with ACh (p < .05). Injection of L-nitro-arginine-methyl-ester (L-NAME), a nitric oxide synthase inhibitor, before injection of the nitric oxide donor shortened the duration of effect but did not alter maximal cavernosal pressure or penile length attained. Although systemic hypotension was induced by each agent, digital compression at the base of the penis at the time of injection prevented such changes. These results suggest that the primate is a useful model to evaluate the action of substances that induce or inhibit penile erection. The findings provide support for the hypothesis that nitric oxide is a mediator of penile erection and that nitric oxide donors may be useful in the treatment of erectile dysfunction.

Acetylcholine↗

Post-thaw sperm motility, cAMP concentration and membrane lipid peroxidation after stimulation with pentoxifylline and platelet-activating factor.

Earlier studies have demonstrated that pentoxifylline (PTX) and platelet-activating factor (PAF) can significantly improve the motion parameters of post-thaw human spermatozoa. This study has investigated the effects of PAF, PTX and their combination on cyclic adenosine monophosphate (cAMP) concentrations and membrane lipid peroxidation (LPO) in post-thaw human spermatozoa. Washed spermatozoa from normal volunteers (n = 10) were cryopreserved in Test-yolk buffer using a standard protocol. After 2 weeks the sperm samples were thawed, washed and incubated with either 1 microM PAF, 3 mM PTX or 0.5 microM PAF plus 1.5 mM PTX. Video sequences were recorded at 0, 30, 60, and 120 min for analysis of sperm motion parameters using the Cell Track Sperm Analysis System. Concentrations of cAMP were assessed by radioimmunoassay, and LPO levels were measured by malondialdehyde-thiobarbituric acid reactivity. Our studies indicate a time-course stimulatory effect with overall maximal stimulation observed in samples treated with the combination of PAF and PTX. The maximal stimulation of percentage motility compared to control was observed at 60 min in samples treated with PAF, PTX, or PAF plus PTX. PAF plus PTX stimulated straight-line velocity (VSL), curvilinear velocity (VCL) and lateral head displacement (ALH) after 30 min incubation. The primary effect of PAF was observed on VSL, while the main effect of PTX was on VCL. cAMP concentrations were 3-fold higher than controls in samples treated with PTX or PAF plus PTX. cAMP concentrations in PAF-treated samples did not differ significantly from controls. No significant differences were observed between any groups for LPO.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗