Peyronie's disease: a review

PURPOSE: We provide a current review of Peyronie's disease. MATERIALS AND METHODS: We reviewed the world peer reviewed literature on the pathology, pathogenesis, diagnosis and treatment of Peyronie's disease. RESULTS: The incidence of Peyronie's disease has continuously increased during the last 30 years. However, fewer patients need prosthesis surgery as the sole treatment option because of earlier diagnosis, improved medical therapy, refinement in surgical technique and better understanding of the basic sciences of the disease. CONCLUSIONS: Currently patients with Peyronie's disease have had improvements in prognosis and experienced an expansion of the available therapeutic options.     

Key apoptotic pathways for heat-induced programmed germ cell death in the testis

Short-term exposure (43 C for 15 min) of the rat testis to mild heat results within 6 h in stage- and cell-specific activation of germ cell apoptosis. Initiation of apoptosis was preceded by a redistribution of Bax from a cytoplasmic to paranuclear localization in heat-susceptible germ cells. Here we show that the relocation of Bax is accompanied by cytosolic translocation of cytochrome c and is associated with activation of the initiator caspase 9 and the executioner caspases 3, 6, and 7 and cleavage of poly(ADP) ribose polymerase. Furthermore, early in apoptosis, a significant amount of Bax also accumulates in endoplasmic reticulum, as assessed by Western blot analyses of fractionated testicular lysates. In additional studies using the FasL-defective gld mice, we have shown that heat-induced germ cell apoptosis is not blocked, thus providing evidence that the Fas signaling system may be dispensable for heat-induced germ cell apoptosis in the testis. Taken together, these results demonstrate that the mitochondria- and possibly also endoplasmic reticulum-dependent pathways are the key apoptotic pathways for heat-induced germ cell death in the testis.     

Do impotent men with diabetes have more severe erectile dysfunction and worse quality of life than the general population of impotent patients? Results from the Exploratory Comprehensive Evaluation of Erectile Dysfunction (ExCEED) database

OBJECTIVE: Little is known regarding how diabetic men with erectile dysfunction (ED) differ from the general population of impotent men. The primary objective of this study was to compare disease-specific health-related quality of life (HRQOL) and severity of ED in impotent men with and without diabetes. RESEARCH DESIGN AND METHODS: Validated functional and HRQOL questionnaires (including the International Index of Erectile Function, the Sexual Self-Efficacy Scale, and the Psychological Impact of Erectile Dysfunction scales) were administered to patients in an ED disease registry. Men with ED and a history of diabetes (n = 20) were compared with men with ED and no history of diabetes (n = 90) at baseline and at the 12-month follow-up. RESULTS: Diabetic impotent men reported worse erectile function and intercourse satisfaction at baseline, and ED had a greater impact on their emotional life. Diabetic men with ED had significantly different trends over time in the Erectile Function (P < 0.001), Intercourse Satisfaction (P < 0.013), Sexual Desire (P < 0.016), Overall Satisfaction (P < 0.023), and the Sexual Experience-Psychological Impact domains (P < 0.002). In addition, there was a trend toward a difference over time in the Emotional Life-Psychological Impact domain (P < 0.067). CONCLUSIONS: Impotent men with diabetes present with worse ED than nondiabetic men with ED, resulting in worse disease-specific HRQOL in the diabetic men. Although diabetic patients initially respond well to ED treatment, responses do not appear to be durable over time. Therefore, clinicians must provide longer-term follow-up when treating ED in diabetic patients.     

Afferent synaptic contacts on glycine-immunoreactive neurons in the rat cuneate nucleus

This study was aimed to clarify whether the primary afferent terminals (PATs), GABAergic terminals, and glutamatergic terminals made direct synaptic contacts with glycine-IR neurons in the cuneate nucleus of rats. In this connection, injection of the anterograde tracer WGA-HRP into brachial plexus, antiglycine preembedding immunoperoxidase, and anti-GABA, along with antiglutamate postembedding immunogold labeling, were used to identify the PATs, glycine-IR neurons, GABA-IR terminals, and glutamate-IR terminals, respectively. The present results showed that HRP-labeled PATs, immunoperoxidase-labeled glycine-IR terminals, immunogold-labeled GABA-IR, and glutamate-IR terminals made axodendritic synaptic contacts with immunoperoxidase-labeled glycine-IR neurons. The latter three presynaptic elements also formed axosomatic synapses with glycine-IR neurons. Statistical analysis has shown that the minimum diameter of the glycine-IR dendrites postsynaptic to the above-mentioned four presynaptic elements did not differ significantly. In addition, the synaptic ratio of the glutamate-IR terminals on the glycine-IR dendrites was higher than that of GABA-IR terminals. The synaptic ratio of the GABA-IR terminals on glycine-IR dendrite was in turn higher than that of the PATs and glycine-IR terminals. It is suggested that the PATs and glutamate-IR terminals on the glycine-IR neurons may be involved in subsequent postsynaptic inhibition for spatial precision of lateral inhibition. On the other hand, the GABA-IR and glycine-IR terminals which make synaptic contacts with the dendrites of glycine-IR neurons may provide a putative means for disinhibition or facilitation to maintain the baseline neuronal activity in the rat cuneate nucleus. The results of quantitative analysis suggest that glutamate act as the primary excitatory neurotransmitter, while GABA, when compared with glycine, may serve as a more powerful inhibitory neurotransmitter on glycine-IR neurons in the rat cuneate nucleus.     

Strength and functional performance of patients with limb-girdle muscular dystrophy

This study was design to reach a better understanding of muscle strength, motor function and activity of daily living in patients of limb-girdle muscular dystrophy. Forty-eight patients diagnosed as cases of limb-girdle muscular dystrophy were included in this study. Manual muscle testing was used to evaluate muscle strength. The Brooke and Vignos scales were used to grade upper and lower extremities function, respectively, and the ability of daily living activity was measured by Barthel index. Our patients showed progressive symmetrical limb-girdle muscular weakness. Upon regression analysis we found that mean muscle strength was inversely related to disease duration (years) as follows: mean muscle strength = 0.6052 + (0.6309/disease duration). According to the Brooke functional scale, 89.6% of our patients were graded as 1-3 and 10.4% were graded as 5. On the Vignos functional scale, 79.1% of patients fell into the grades 1-5, one person (2.1%) in grade 6 and 18.8% in grade 9 category. The average Barthel index was 85.3 +/- 20.7. Mean muscle strength was significantly correlated with the average Barthel, Vignos and Brooke functional scales. Our study could offer the strength and functional performance of limb-girdle muscular dystrophy on natural history. The muscle strength declined in Taiwanese patients of limb-girdle muscular dystrophy in a typical pattern. Regression analysis showed that the strength was inversely related to disease duration. These findings demonstrate that most of our patients suffered from mild or moderate physical disability.     

Outcomes of transcatheter valvotomy in patients with pulmonary atresia and intact ventricular septum

The results of transcatheter valvotomy in pulmonary atresia with intact ventricular septum (PA-IVS) patients are presented with an attempt to identify the predictive factors for pulmonary valvotomy alone as definitive treatment. Between June 1995 and December 1997, 14 PA-IVS neonates with tripartite right ventricle underwent an attempted pulmonary valvotomy. For perforation of the pulmonary valve, a guidewire was used in 4, and a radiofrequency guidewire in 10 patients. Two outcome groups were identified. Group I included those in whom transcatheter treatment achieved a definitive success; group II patients required surgery despite an initial successful valvotomy. The attempt failed in 3 patients, 1 of whom had pericardial effusion. Perforation of the pulmonary valve was achieved in 11 patients: 2 with a guidewire and 9 with a radiofrequency guidewire. A subsequent balloon valvuloplasty was performed in these 11 patients. After valvuloplasty, mean right ventricular pressure decreased from 124 +/- 24 to 60 +/- 15 mm Hg (p <0.01). One died of heart failure and infection 10 days later, despite successful weaning from prostaglandin E1. Group I patients (n = 6) were treated with transcatheter valvotomy alone. Group II patients (n = 4) required right ventricular outflow patch. Significant differences between the 2 groups (group I vs II) were identified in tricuspid valve Z value (0.52 +/- 0.37 vs -1.25 +/- 0.48, p <0.05), pulmonary valve Z value (-3.47 +/- 0.59 vs -5.43 +/- 0.94, p <0.05), and ratio of right-to-left ventricular area on the apical 4-chamber view (0.73 +/- 0.06 vs 0.49 +/- 0.03, p <0.05). There were no significant differences in hemodynamic characteristics between the 2 groups. After a follow-up period ranging from 7 to 35 months (mean 18 +/- 10.3), the most recent echocardiograms in the 10 patients showed a mean pressure gradient across the pulmonary valve of 17 +/- 15 mm Hg. All 10 patients had an oxygen saturation of >92%. Transcatheter valvotomy using a radiofrequency guidewire is a safe and effective treatment in selected patients with PA-IVS. Transcatheter valvotomy can be a definitive treatment in PA-IVS patients with a tricuspid valve Z value > or = -0.1, pulmonary valve Z value > or = -4.1 and ratio of right-to-left ventricular area > or = 0.65.     

CT and MRI Findings in a Child with Constrictive Pericarditis

Constrictive pericarditis is rare in children. We report computed tomography (CT) and magnetic resonance imaging (MRI) findings in a 3-year-old girl. She had a swollen abdomen that increased in two months. CT and MRI showed a thickened pericardium (5.2 mm) without calcification. Both atria were enlarged and ventricles were relatively small. The engorged inferior vena cava had 2.8× the diameter of the descending aorta at the same level. Symptoms were dramatically improved after pericardiectomy. The histopathological features confirmed chronic pericarditis.     

Celecoxib enhances radiosensitivity of hypoxic glioblastoma cells through endoplasmic reticulum stress

Background

Refractoriness of glioblastoma multiforme (GBM) largely depends on its radioresistance. We investigated the radiosensitizing effects of celecoxib on GBM cell lines under both normoxic and hypoxic conditions.

Methods

Two human GBM cell lines, U87MG and U251MG, and a mouse GBM cell line, GL261, were treated with celecoxib or γ-irradiation either alone or in combination under normoxic and hypoxic conditions. Radiosensitizing effects were analyzed by clonogenic survival assays and cell growth assays and by assessing apoptosis and autophagy. Expression of apoptosis-, autophagy-, and endoplasmic reticulum (ER) stress–related genes was analyzed by immunoblotting.

Results

Celecoxib significantly enhanced the radiosensitivity of GBM cells under both normoxic and hypoxic conditions. In addition, combined treatment with celecoxib and γ-irradiation induced marked autophagy, particularly in hypoxic cells. The mechanism underlying the radiosensitizing effect of celecoxib was determined to be ER stress loading on GBM cells.

Conclusion

Celecoxib enhances the radiosensitivity of GBM cells by a mechanism that is different from cyclooxygenase-2 inhibition. Our results indicate that celecoxib may be a promising radiosensitizing drug for clinical use in patients with GBM.     

Effect of extended-term estrogen on voiding in a postpartum ovariectomized rat model

Introduction

We tested the hypothesis that extended-term (5-week) estrogen therapy would negatively impact voiding function in a postpartum, ovariectomized rat model.

Methods

Immediately after delivery, 30 primiparous Sprague–Dawley rats underwent intravaginal balloon dilation, followed by ovariectomy 1 week later. Cystometry at postpartum week 2 determined normal or abnormal voiding patterns. After randomization, one-half the normal and abnormal voiding rats received 5 weeks of estrogen therapy, while the remainder received placebo. Estrogen effect was determined by repeat cystometry and immunohistochemical analysis of the urethra and vagina.

Results

Abnormal voiding increased from 60.0% to 73.3% in the estrogen- treated group and declined from 60% to 33% for the placebo group. Rats were then divided into 4 groups for comparison: normal voiding versus placebo (group 1), abnormal voiding versus placebo (group 2), normal voiding versus estrogen (group 3) and abnormal voiding versus estrogen (group 4). Bladder capacity, leak point pressure and maximum voiding pressure were most depressed in group 4. Estrogen treatment was associated with a significant downregulation of α_1A and α_1D-adrenoceptors in the urethral submucosa but an upregulation of nNOS in the urethral smooth muscle.

Conclusion

Extended-term estrogen therapy in a rat model of simulated birth trauma and ovariectomy resulted in a higher rate of incontinence. Immunohistochemical examination demonstrated significant downregulation of urethral α_1A- and α_1D-adrenoceptors and upregulation of neuronal nitric oxide synthase (nNOS) in the urethra of estrogen-treated groups. These studies question the use of hormone replacement therapy in the treatment of postmenopausal incontinence.