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Biomedical subjects

I Goldstein

Publications and source records attributed to I Goldstein.

At least 127 records · Page 7Linked to original sources

Relationship between cavernosal ischemia and corporal veno-occlusive dysfunction in an animal model.

PURPOSE: It has been postulated that cavernosal tissue ischemia secondary to arterial occlusive disease is associated with corporal veno-occlusive dysfunction. The goal was to correlate, for the first time, direct local intracavernosal blood flow measurements as a measure of cavernosal tissue perfusion with the integrity of corporal veno-occlusion in an animal model of vasculogenic impotence. MATERIALS AND METHODS: The New Zealand White rabbit model of vasculogenic impotence was utilized (7 control, 9 atherosclerotic). After 16 weeks, intracavernosal blood flow was recorded directly by laser Doppler flowmetry. The relationships among peak intracavernosal blood flow, equilibrium intracavernosal pressure and corporal veno-occlusive function (as determined by intracavernosal pressure decay) were examined. RESULTS: Significant differences in the atherosclerotic compared to control animals were noted in iliac artery blood flow (12 +/- 4 vs 31 +/- 7 ml./min.), peak intracavernosal blood flow during erection (16 +/- 7 vs 25 +/- 4 ml./min./100 gm. tissue), equilibrium intracavernosal pressure (48 +/- 11 vs 72 +/- 6 mm. Hg) and intracavernosal pressure decay (57 +/- 17 vs 36 +/- 8 mm. Hg). Peak intracavernosal blood flow during erection was found significantly related to both equilibrium pressure (r = 0.75) and cavernosal pressure decay (r = -0.8). CONCLUSIONS: Abnormal intracavernosal blood flow (cavernosal ischemia) secondary to arterial occlusive disease predicts abnormal veno-occlusive function and poor erection quality.

Animals↗

Safety and efficacy outcome of mentor alpha-1 inflatable penile prosthesis implantation for impotence treatment.

PURPOSE: We investigated safety and efficacy outcome pertaining to the Mentor Alpha-1, 3-piece inflatable penile prosthesis for impotence treatment. MATERIALS AND METHODS: A 2-phase, multi-institutional, large scale retrospective study, with independently analyzed medical record (phase I) and questionnaire (phase II) data from consecutive eligible patients of 7 physician investigators was performed from March to October 1993. RESULTS: In phase I there were no morbidities of any type in 394 of the 434 patients (90.8%) (mean age 61 years, range 24 to 88) who underwent Alpha-1 implantation (mean followup 22.2 months, range 0.67 to 44.5). The risk of prosthesis malfunction (fluid leak and auto-inflation) was 2.5%. No cylinder aneurysms were reported. A total of 93.1% of Alpha-1 devices was free from explantation (4.4%) or revision surgery (2.5%) for approximately 2 years from the original implant date. Kaplan-Meier actuarial analyses revealed that cumulative survival of the Alpha-1 prostheses at 12, 24 and 36 months was 98 +/- 1%, 93 +/- 2% and 85 +/- 7% until device malfunction, and 91 +/- 2% 83 +/- 4% and 75 +/- 7% until surgical intervention (revision or explantation). In phase II 89% of the men claimed fulfilled expectations with the Alpha-1 prosthesis as impotence treatment. Satisfaction responses 80% or greater were noted with regard to intercourse ability and confidence, and device rigidity and function. Implantation did not result in greater than 80% satisfaction in partner relationships or feelings (as judged by the patient), social or work confidence, or intercourse frequency. Factors adversely affecting satisfaction included partner feelings of dissatisfaction (as judged by the patient), specific physician investigators and need for explantation/revision surgery. CONCLUSIONS: In 1 of the largest multi-institutional implant outcome studies thus far performed, safety and efficacy data concerning the Alpha-1 contemporary inflatable device were found markedly improved over earlier inflatable prostheses and now compare favorably with historical data from noninflatable rod type devices.

Actuarial Analysis↗

Expression of functional alpha2-adrenergic receptor subtypes in human corpus cavernosum and in cultured trabecular smooth muscle cells.

In this study, we have identified and characterized functional alpha2-adrenergic receptor (alpha2-AR) subtypes in human corpus cavernosum and in cultured human corpus cavernosum smooth muscle cells. Analysis of total RNA, isolated from whole corpus cavernosum tissue and smooth muscle cells, by RNase protection assays, demonstrated expression of mRNA for alpha2A, alpha2B, and alpha2C adrenergic receptor subtypes in whole tissue and alpha2A and alpha2C subtypes in cultured smooth muscle cells. Binding studies with [3H]RX821002 (a highly selective and specific ligand for alpha2-adrenergic receptor) in isolated membrane fractions of human corpus cavernosum smooth muscle cells, demonstrated specific alpha2-AR binding sites with high affinity (Kd = 0.63 nM) and limited capacity (25-30 fmol/mg protein). Binding of [3H]RX821002 was displaced with the nonselective alpha-AR antagonist, phentolamine, and with the alpha-AR agonist, norepinephrine, in a dose-dependent manner, but not by the selective alpha1-AR agonist, phenylephrine. Binding of [3H]rauwolscine was also displaced by phentolamine. UK 14,304, a selective alpha2-AR agonist, inhibited forskolin-induced cyclic adenosine monophosphate (cAMP) synthesis in cultured human corpus cavernosum smooth muscle cells and induced dose-dependent contractions of tissue strips in organ bath chambers. UK 14,304-induced contractions were inhibited with alpha2-AR selective antagonists, rauwolscine and delquamine (RS 15385-197). These observations suggest that in human corpus cavernosum, norepinephrine (NE) and epinephrine may activate postsynaptic alpha2-AR subtypes, in addition to activating alpha1-AR subtypes, on smooth muscle cells, contributing to local control of human corpus cavernosum smooth muscle tone, in vivo.

Adrenergic alpha-Agonists↗

Sexual health for the man at midlife: in-office workup.

Normal physiologic changes occur with age that affect male sexuality. The etiology of these problems is often vascular but may be influenced by medications, neurologic conditions, or endocrinopathies, and/or iatrogenic factors. Penile sensitivity and erectile responses decline with age, and patients may present with concerns about ejaculatory disorders and erectile dysfunction. Physicians need to know the pharmacologic, surgical, and educational solutions. Treatment modalities for erectile dysfunction include vacuum erection, devices, intracavernosal or intraurethral alprostadi injections, and penile implants.

Adult↗

G-protein-coupled receptor agonists augment adenylyl cyclase activity induced by forskolin in human corpus cavernosum smooth muscle cells.

The goal of this study was to investigate the synergistic effects between G-protein-coupled receptor agonists and forskolin-induced activation of adenylyl cyclases, in cultured human corpus cavernosum smooth-muscle cells. Treatment of human corpus cavernosum smooth-muscle cells with forskolin (0.1-10 microM) produced an increase in cAMP synthesis in a concentration-dependent manner. Forskolin-induced adenylyl cyclase activity was markedly augmented by prostaglandin E1 (PGE1) and its metabolite, PGE0, isoproterenol, carbachol, and phenylephrine. Augmentation of forskolin-induced cAMP by PGE1, and PGE0 is probably mediated by prostaglandin E receptors (EP). Enhancement of forskolin-induced cAMP synthesis by isoproterenol is mediated by beta-adrenergic receptors (beta-AR), since this activity was inhibited by propranolol. Stimulation of forskolin-induced cAMP synthesis by carbachol is attributed to activation of muscarinic acetylcholine receptors (mAChR), as demonstrated by inhibition with atropine. The augmentation of forskolin-induced cAMP synthesis by phenylephrine, an alpha1-adrenergic receptor (AR) agonist, however, was unexpected and cannot be attributed to increased intracellular Ca2+, since treatment of cells with either the Ca2+ ionophore, A23187, or 80 mM KCl did not affect forskolin-induced cAMP synthesis. Stimulation of forskolin-induced cAMP synthesis by phenylephrine is explained by its binding to beta-AR and activation of Gs protein, since this augmentation was inhibited by the beta-AR antagonist, propranolol. This observation was further supported by physiological studies in organ bath chambers, in which forskolin-induced relaxation of precontracted corpus cavernosum strips was enhanced by phenylephrine. These studies suggest that synergism between agonist-induced cAMP synthesis and forskolin is attributed to increased conformational stabilization of activated adenylyl cyclase catalytic domains by forskolin and the Gs(alpha)-subunit of activated Gs proteins.

Adenylyl Cyclases↗

Intracranial fetus-in-fetu.

Fetus-in-fetu is an extremely rare tumor diagnosed in utero. We present a case report of prenatal diagnosis of intracranial fetus-in-fetu.

Adult↗

Mechanisms of venous leakage: a prospective clinicopathological correlation of corporeal function and structure.

PURPOSE: We investigated the pathophysiology of structurally based corporeal veno-occlusive dysfunction. MATERIALS AND METHODS: We prospectively evaluated 24 impotent patients (mean age plus or minus standard error 46 +/- 3 years) who had exposure to vascular risk factors and/or disorders inducing diffuse trabecular structure alterations and who underwent penile prosthesis insertion. Preoperative indexes of veno-occlusive function (flow to maintain, venous outflow resistance and pressure decay measurements using repeat dosing pharmacocavernosometry) were correlated with postoperative erectile tissue computer assisted color histomorphometry (percent trabecular smooth muscle to total erectile tissue area). To develop further study findings and correlate histomorphometric findings with molecular biological properties molecular biological studies (ribonuclease protection analysis, reverse transcription-polymerase chain reaction assay for expression of transforming growth factor-beta 1 messenger [m] ribonucleic acid [RNA] and protein affinity labeling techniques for specific transforming growth factor-beta receptors) were performed in representative patients with high (39 to 43%), intermediate (30 to 37%) and low (13 to 29%) trabecular smooth muscle content (normal 42 to 50%). RESULTS: Flow to maintain, venous outflow resistance and pressure decay values significantly correlated with trabecular smooth muscle cell content (r = -0.89, 0.82 and -0.85, respectively). In the high, intermediate and low smooth muscle content subgroups flow to maintain, venous outflow resistance and pressure decay values were 1 to 5, 9 to 30 and 50 to 120 ml. per minute, 17 to 84, 3 to 9 and 1 to 2 mm. Hg/ml. per minute, and 40 to 60, 48 to 80 and 110 to 120 mm. Hg decrease in 30 seconds from 150 mm. Hg, respectively. There were no significant differences in patient age or prevalence of risk factors among the 3 subgroups. Patients representative of all 3 subgroups had transforming growth factor-beta 1 mRNA, auto-induction of transforming growth factor-beta 1 mRNA and induction and/or increased availability of all 3 types of transforming growth factor-beta receptors. CONCLUSIONS: The pathophysiology of structurally based corporeal veno-occlusive dysfunction is related to elevated corporeal connective tissue content. Based on our data and those in the literature corporeal fibrosis is hypothesized to develop secondary to abnormalities in the regulation of normal collagen synthesis and degradation, most likely associated with adverse influences of chronic ischemia.

Adult↗

Perineal abscess after embolization for high-flow priapism.

High-flow priapism is unusual and is most often due to blunt perineal trauma with resultant laceration of the cavernosal artery, creating an arteriocavernosal fistula. Although few cases have been reported, the consensus on management appears to be embolization of the fistula with autologous clot, alone or in combination with Gelfoam. We present a case of high-flow priapism treated in this manner. The embolized pseudoaneurysm evolved into an abscess that eventually spread to the perineum. The rarity of this entity and the postprocedural morbidity are reported.

Abscess↗

Diabetic sexual dysfunction.

Although the overall incidence of erectile dysfunction in the general population between the ages of 40 and 70 years is 52%, men with diabetes mellitus have impotence at an earlier age and with a significantly higher prevalence, ranging as high as 75%. Numerous advances have been made in understanding the physiologic and biochemical mechanisms controlling penile erection. Improved clinical techniques for the diagnosis and treatment of impotence, including dynamic vascular testing, intracavernosal pharmacotherapy, and microsurgical revascularization, have allowed us to enter a new and exciting era in the quest for a more complete understanding of erectile dysfunction.

Adult↗

Seven-year follow-up of child survivors of a bus-train collision.

OBJECTIVE: To assess the long-term effects of a traumatic bus-train collision and to examine the effect of levels of exposure and immediate reactions on long-term adjustment. METHOD: Seven years after the accident, 389 subjects, all doing compulsory army service, filled out self-report questionnaires assessing symptoms of posttraumatic stress disorder (PTSD), psychiatric symptomatology, and military functioning. In addition, subjects were questioned about their immediate reactions to the traumatic event. RESULTS: The most highly exposed subjects reported the highest levels of somatization, depression, phobic anxiety, and psychoticism and more PTSD symptoms. Acute stress symptoms and manifestations of fear immediately after the accident were strongly related to long-term maladjustment CONCLUSIONS: The results suggest that the investigation and assessment of long-term adjustment after traumatic events should take into account both contextual factors, such as the level of exposure to the event, and personal factors, such as the victims' immediate reactions.

Accidents, Traffic↗

Parameters that influence the results of in vitro fertilization/embryo transfer: a study of an egg donation model.

A retrospective analysis was carried out after ovulation induction in donors, and treatment outcome in donors and recipients, relating to variables such as: age, protocol of ovarian stimulation, transfer of fresh or cryopreserved embryos, number of embryos transferred including quality and etiology of donor and recipient infertility. The recipients underwent 214 cycles of embryo transfer from 82 different donors. Forty-five (21%) pregnancies were recorded. The age of the recipients significantly affected the conception rate (pregnancy rate of 30% in those aged < 30 years, compared to 9.7% in those aged > 44 years) and the donors were contributed more to pregnancies were also younger. The pregnancy rate was significantly higher when fresh embryos were transferred to recipients (28%, compared to 15% when cryopreserved embryos were transferred). In addition, the number of embryos transferred affected the pregnancy rate if > or = 3 embryos were transferred and, if they were of good quality, the success was significantly higher. Ultimately, when the ovarian stimulation protocol was clomiphene citrate and human menopausal gonadotropin or gonadotropin-releasing hormone agonist/follicle-stimulating hormone/human menopausal gonadotropin, and the etiology of infertility was polycystic ovarian disease in the donors, the success rate was significantly increased in the recipients.

Abortion, Spontaneous↗

Vacuum erection associated impotence and Peyronie's disease.

PURPOSE: Use of a nonmedical, catalogue type vacuum erection device resulted in a case of vacuum induced vasculogenic impotence and Peyronie's disease. MATERIALS AND METHODS: A 66-year-old potent man used a nonmedical vacuum erection device (cylinder plus a hand pump without a pressure-release valve and a doughnut-shaped ring at the base without tension bands) after having achieved a spontaneous rigid erection. The resultant excessive overinflation of the penis was followed by dorsal curvature, diminished rigidity and decreased erectile maintenance. RESULTS: Physical examination revealed a dorsal mid shaft Peyronie's plaque. Nocturnal penile tumescence testing and office injection testing were abnormal and demonstrated partial, short-lived, dorsally curved erections. Dynamic pharmaco-cavernosometry and pharmaco-cavernosography established vasculogenic impotence with site-specific crural (unrelated to the Peyronie's plaque) veno-occlusive dysfunction and dorsal penile curvature. CONCLUSIONS: Vacuum erection devices create pulling forces on the penis. We estimate that the pulling forces in this case were prohibitively high (approximately 29 pounds) due to absence of a pressure-release valve and to the preexistent erection at vacuum application. These intense pulling forces are hypothesized to have damaged the tunica in the mid shaft (Peyronie's disease) and the crus (veno-occlusive dysfunction), the latter being the site of attachment of the corpora to the ischiopubic ramus and a most likely location for high magnitude pulling forces to exert an abnormal injury effect. The patient underwent a Nesbit plication procedure and presently performs self-injection for satisfactory sexual activity.

Aged↗

Evolving concepts in the diagnosis and treatment of arterial high flow priapism.

PURPOSE: We investigated 2 evolving concepts in the management of arterial priapism: 1) the efficacy of perineal duplex Doppler ultrasound as a diagnostic alternative to arteriography and 2) the therapeutic alternative of expectant management. MATERIALS AND METHODS: We evaluated 10 patients with high flow arterial priapism. RESULTS: Compared to selective internal pudendal arteriography, perineal duplex Doppler ultrasonography was associated with 100% sensitivity and 73% specificity rates. Compared to physical examination, followup duplex ultrasonography had a sensitivity of 75% and specificity of 100%. Followup penile duplex ultrasound demonstrated restoration of antegrade flow in the cavernous artery after embolization. Patients on expectant management remained potent as long as 31 years. CONCLUSIONS: Diagnostic perineal duplex Doppler ultrasonography and expectant management are valuable tools for the treatment of arterial priapism. A new algorithm for patient care is presented.

Adolescent↗

A guide to safe corporotomy incisions in the presence of underlying inflatable penile cylinders: results of in vitro and in vivo studies.

PURPOSE: Because iatrogenic injury to an underlying inflatable implant may be induced by electrocautery incision of the tunica during tunical release or cylinder reexploration, safe electrocautery guidelines are needed. MATERIALS AND METHODS: For the in vitro model silicone and polyurethane elastomer lined inflatable penile prosthetic cylinders were used, and cutting and coagulation electrocautery was applied directly on the device, on a tissue-implant interface, and at minimal, partial or full inflation with saline. For the in vivo study 10 patients with underlying inflatable prosthetic cylinders underwent tunical releases for treatment of secondary penile curvature (7) and reexploration for a malpositioned device (3) with a minimum 1 year of followup. RESULTS: In the in vitro study electrocautery injuries either did not occur when applied directly to silicone and polyurethane elastomer lined devices, occurred in both devices in the presence of a tissue-implant interface, occurred in polyurethane elastomer lined devices at a far less thermal energy setting than with silicone, occurred in both implants at lower wattages with increasing saline inflation or did not occur in 100% of polyurethane elastomer lined devices when coagulation electrocautery was less than 65 watts. In the in vivo study, by adhering to the aforementioned principles and using novel surgical techniques, no device malfunctions were created intraoperatively or observed within a mean followup of 22 months. CONCLUSIONS: Electrocautery can be used safely to create a tunical incision with any underlying inflatable cylinder. To avoid electrocautery injury, based on the clinical study results in polyurethane elastomer lined devices, one should deflate the cylinder before electrocautery, use coagulation current at 35 watts, apply the electrocautery only to the outer longitudinal tunical layer, bluntly dissect through the inner circular layer, and elevate the tunica, protect the device and incise the tissue under direct vision.

Adult↗

Study of etiologic relationship of arterial atherosclerosis to corporal veno-occlusive dysfunction in the rabbit.

PURPOSE: The aim of this study was to explore the possible etiologic relationship of hypercholesterolemia and atherosclerosis to corporal veno-occlusive dysfunction. MATERIALS AND METHODS: In the New Zealand White rabbit, the competence of the corporal veno-occlusive mechanism was examined at various intervals after exposure to control diet, high cholesterol diet, or aortoiliac atherosclerosis. RESULTS: Initially, all animals showed normal erectile function and corporal veno-occlusion. After 8 weeks and 16 weeks, the control animals preserved normal erection and corporal veno-occlusion, while most of the hypercholesterolemic and atherosclerotic animals developed corporal veno-occlusive dysfunction. The incidence of corporal veno-occlusive dysfunction in the hypercholesterolemia and atherosclerotic animals increased with time. CONCLUSIONS: This study suggests that a close relationship exists between prolonged atherosclerotic occlusion of major penile arteries and the development of corporal veno-occlusive dysfunction. Ischemia-induced corporal veno-occlusive dysfunction may be the result of alterations in corporal smooth muscle relaxation or changes in the structure and fibroelastic properties of erectile tissue.

Animals↗

Normal nuchal thickness in the midtrimester indicates reduced risk of Down syndrome in pregnancies with abnormal triple-screen results.

OBJECTIVE: Our purpose was to determine whether nuchal thickness measurement can identify the euploid fetuses in midtrimester pregnancies at increased risk for Down syndrome on the basis of maternal age and serum screening. STUDY DESIGN: Nuchal thickness was obtained prospectively in 651 consecutive fetuses at 14 to 21 weeks' gestation and at > or = 1:270 risk for Down syndrome on the basis of unconjugated estriol, alpha-fetoprotein, and human chorionic gonadotropin levels. The risk of Down syndrome with a normal nuchal thickness was determined. A receiver-operator characteristic curve was used to determine a serum-based risk threshold below which the risk for Down syndrome was low. The prevalence of Down syndrome in fetuses with both a normal nuchal thickness and a below-serum-risk threshold was compared with prevalence in either those above threshold risk or with an abnormal nuchal thickness. RESULTS: There were eight cases of trisomy 21 and one case each of 46,XX/47,XXX, 46,XY/47,XY, +7, and 46,XX, 11q-. The sensitivity of an abnormal nuchal thickness (> or = 6 mm) for detecting Down syndrome was four in eight (50%) (95%) confidence interval 15.3% to 84.6%). The risk of Down syndrome was significantly increased with an abnormal compared with a normal nuchal thickness, four in 13 (30.8%) versus four in 638 (0.6%), p < 0.0001. A risk threshold was defined at > or = 1:100 on the basis of the receiver-operator characteristic plot. Of 390 cases with a normal nuchal thickness and a serum risk estimate < 1:100, there were no cases of Down syndrome (0/390 vs 8/253, p = 0.002). CONCLUSION: Normal nuchal thickness significantly reduces the risk of Down syndrome and may help reduce the number of amniocenteses done for abnormal triple screen results.

Adult↗

Cerebellar growth in normal and growth-restricted fetuses of multiple gestations.

OBJECTIVE: Our purpose was to evaluate growth of the cerebellum in growth-restricted fetuses of twin and triplet gestations versus growth in normal in utero sibling(s) and in singleton gestations. STUDY DESIGN: An ultrasonographic study was conducted in a population of pregnant women with twin and triplet gestations. The control group was either the normal in utero sibling(s) when one fetus was growth restricted or normal twin and singleton pregnancies. Standard biometric measurements were obtained on all fetuses throughout pregnancy, including the transverse cerebellar diameter. However, only the last measurement was used for the analysis. Statistical analyses were conducted comparing growth of the transverse cerebellar diameter among the growth-restricted fetuses versus growth in the normal in utero fetal sibling(s) or other normal twin and singleton gestations. RESULTS: Pregnancies were categorized on the basis of the growth status of women with twin and triplet gestations: Group 1 (151) contained women with two fetuses appropriately grown for gestational age; group 2 (52) had one appropriately grown fetus and one with intrauterine growth restriction; group 3 (19) had two fetuses with intrauterine growth restriction. In addition, there were 30 triplet gestations (group 4), five of which had growth-restricted fetuses, and group 5 contained 1405 singleton pregnancies. In all five groups there was a statistically significant relationship between transverse cerebellar diameter and gestational age (p < 0.0001). There was also no significant difference between growth of the transverse cerebellar diameter in the appropriately grown and growth-restricted siblings and among normal singleton and twin pregnancy groups. In most cases of growth-restricted fetuses, except for the transverse cerebellar diameter measurements, all other biometric parameters were < 10th percentile. CONCLUSION: These data confirm the relative preservation of normal cerebellar growth in growth-restricted fetuses and a similar rate of growth in singleton and multifetal gestations. The transverse cerebellar diameter therefore represents an independent biometric parameter that can be used in both singleton and multifetal pregnancies to assess normal and deviant fetal growth.

Biometry↗