Effects of Difaprost® on voiding dysfunction, histology and inflammation markers in patients with benign prostatic hyperplasia who are candidates for surgical treatment.

AIM: Although previous studies assessed the effects of Serenoa repens, quercetin and ß-sitosterol on inflammatory parameters, no randomized studies have tested the combination of these agents neither on BPH symptoms nor on the inflammatory pattern. The aim of this trial was to evaluate the effects of Difaprost® on voiding dysfunction, histological inflammatory alterations and apoptotic molecular mechanisms in BPH patients. METHODS: We included 36 patients affected by BPH with obstructive symptoms eligible for surgery. Patients were randomly assigned to two groups: 18 patients received Difaprost® for three months before surgery, and 18 patients did not receive any additional therapy and were scheduled for surgery. All patients receiving Difaprost® were evaluated with uroflowmetry with post-void residual volume (PVR) evaluation, serum PSA, and IPSS questionnaire before and after treatment. Moreover, we evaluated inflammatory patterns in prostatic specimens at final pathology. RESULTS: Even without statistically significant differences on inflammatory pattern between patients receiving Difaprost® and controls, patients receiving Difaprost® had lower presence of edema and angiectasia at histological evaluation of prostate specimens. Moreover, patients included in the treatment group had a clinically significant reduction of PVR (46.1 vs. 25.2 mL; P=0.1) and a slight increase in Qmed (5.6 vs. 6.5 mL/s; P=0.9) after three months of chronic treatment with Difaprost®. No statistically significant differences were recorded in other clinical parameters between patients receiving Difaprost® and controls. CONCLUSION: Although not statistically significant, patients treated with Difaprost® showed an improvement in voiding function compared to controls (namely, an increase in Qmed and a reduction of PVR). Future trials with a larger number of patients and a longer treatment period could be necessary to evaluate the clinical efficacy of Difaprost®.

Autonomous online health assessment questionnaire registry in daily clinical practice.

OBJECTIVE: Tight control in RA necessitates frequent disease monitoring; patients might participate by self-assessment of their functional status. Therefore, we assessed the feasibility and acceptability of autonomous online registry of physical functioning. METHODS: In two tertiary-care centres (in The Netherlands and France), consecutive RA patients were approached to perform autonomous registry of the HAQ in an electronic medical record. Feasibility and acceptability of autonomous HAQ registry was assessed through: (i) the percentage of acceptances; (ii) the time needed to register the HAQ (the Netherlands); (iii) patient satisfaction with autonomous registry; and (iv) willingness for future home-based HAQ completion, either self-declared (The Netherlands) or actual file access from home within 6 months (France). RESULTS: In all, 214 patients were approached; 163 agreed to participate; 137 (64% of 214) had complete data that were analysed. Median age was 56 years (range 20-78 years), 80% were female, median disease duration was 9 years. The median time needed to fill in the HAQ in the waiting room was 5.8 min; patient satisfaction was high (mean score 4.1 out of 5), self-declared willingness for autonomous registry at home was 73%. In the 6-month follow-up period, 46% of patients accessed their medical file from home at least once. CONCLUSION: Many RA patients reported willingness to self-monitor their disease online, but fewer than half of the patients actually did. To enhance patient autonomous monitoring, progress is needed in terms of Internet access, continuous patient support and, importantly, convincing patients that they will benefit from autonomous monitoring.

Near-infrared spectroscopy for evaluation of peripheral vascular disease. A systematic review of literature.

OBJECTIVES: To assess near-infrared spectroscopy (NIRS) as a method for the diagnosis and evaluation of peripheral vascular disease. SEARCH STRATEGY: MEDLINE and CENTRAL were searched with a search protocol presented below. Handsearching through reference lists of the retrieved articles and reviews was conducted. MAIN RESULTS: 224 and 57 abstracts from MEDLINE and CENTRAL respectively were retrieved from which 21 studies were selected. NIRS was evaluated for the diagnosis and severity evaluation in patients with peripheral vascular disease. Its parameters were shown to reflect the clinical status of patients, with good correlation to existing methods. CONCLUSIONS: Currently NIRS technology can serve as an adjunct method for the diagnosis and evaluation of patients with peripheral vascular disease.

Relative contributions of testosterone and estrogen in regulating bone resorption and formation in normal elderly men.

Young adult males who cannot produce or respond to estrogen (E) are osteopenic, suggesting that E may regulate bone turnover in men, as well as in women. Both bioavailable E and testosterone (T) decrease substantially in aging men, but it is unclear which deficiency is the more important factor contributing to the increased bone resorption and impaired bone formation that leads to their bone loss. Thus, we addressed this issue directly by eliminating endogenous T and E production in 59 elderly men (mean age 68 years), studying them first under conditions of physiologic T and E replacement and then assessing the impact on bone turnover of withdrawing both T and E, withdrawing only T, or only E, or continuing both. Bone resorption markers increased significantly in the absence of both hormones and were unchanged in men receiving both hormones. By two-factor ANOVA, E played the major role in preventing the increase in the bone resorption markers, whereas T had no significant effect. By contrast, serum osteocalcin, a bone formation marker, decreased in the absence of both hormones, and both E and T maintained osteocalcin levels. We conclude that in aging men, E is the dominant sex steroid regulating bone resorption, whereas both E and T are important in maintaining bone formation.

Phosphodiesterase inhibitors for erectile dysfunction in patients with diabetes mellitus.

BACKGROUND: Erectile dysfunction is a common multi-factorial complication of diabetes mellitus. Numerous strategies have been tried to overcome this diabetic complication. In recent years, phosphodiesterase type 5 (PDE-5) inhibitors have been introduced in the management of erectile dysfunction. OBJECTIVES: The objective of this review was to assess the effect of PDE-5 inhibitors on the management of erectile dysfunction in diabetic men. SEARCH STRATEGY: Studies were obtained from computerised searches of MEDLINE, EMBASE and The Cochrane Library. SELECTION CRITERIA: Randomised controlled trials, in which treatment with PDE-5 inhibitors was compared to control, in diabetic patients with erectile dysfunction. DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted data and assessed trial quality. MAIN RESULTS: Eight randomised controlled trials were identified. A total 976 men were allocated to receive a PDE-5 inhibitor and 741 were randomised to the control groups. Overall, 80% of the participants suffered from type 2 diabetes mellitus. The weighted mean difference (WMD) for the International Index of Erectile Function (IIEF) questions 3 and 4 (frequency of penetration during and maintaining erection to completion of intercourse) was 0.9 (95% CI 0.8 to 1.1) and 1.1 (95% CI 1.0 to 1.2) at the end of the study period, in favour of the intervention group. The WMD for the IIEF erectile dysfunction domain at the end of the study period was 6.6 (95% CI 5.2 to 7.9) in favour of the PDE-5 inhibitors arm. The relative risk (RR) for answering "yes" to a global efficacy question ( "did the treatment improve your erections?") was 3.8 (CI 95% 3.1 to 4.5) in the PDE-5 inhibitors compared with the control arm. The WMD between the percentage of successful attempts in the PDE-5 inhibitors and in the control arm was 26.7 (95% CI 23.1 to 30.3). Mortality was not reported in any of the included trials. Adverse cardiovascular effects were reported in one study. Headache was the most frequent adverse event reported, flushing was the second most common event, with upper respiratory tract complaints and flu like syndromes, dyspepsia, myalgia, abnormal vision and back pain also reported in a descending order of frequency. The overall risk ratio for developing any adverse reaction was 4.8 (CI 95% 3.74 to 6.16) in the PDE-5 inhibitors arm as compared to the control. AUTHORS' CONCLUSIONS: Sufficient evidence exists that PDE-5 inhibitors form a care that improves erectile dysfunction in diabetic men.

Physiological aspects of information processing in the basal ganglia of normal and parkinsonian primates.

There are two views as to the character of basal-ganglia processing - processing by segregated parallel circuits or by information sharing. To distinguish between these views, we studied the simultaneous activity of neurons in the output stage of the basal ganglia with cross-correlation techniques. The firing of neurons in the globus pallidus of normal monkeys is almost always uncorrelated. However, after dopamine depletion and induction of parkinsonism by treatment with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), oscillatory activity appeared and the firing of many neurons became correlated. We conclude that the normal dopaminergic system supports segregation of the functional subcircuits of the basal ganglia, and that a breakdown of this independent processing is a hallmark of Parkinson's disease.

[Gamma hydroxy butyrate intoxication].

Gamma Hydroxybutirate (GHB) is unfamiliar to many physicians in Israel. Recently GHB has emerged as an illicit drug of misuse for its purported euphoric and aphrodisiac effect. The clinical effects can progress rapidly to respiratory arrest and death. We provide a description of a case of GHB poisoning, with a comprehensive review of the literature emphasizing the pharmacodynamics, clinical effect, and suggestions for management. Physicians are urged to become familiar with GHB.

Preoperative erectile function is the only predictor of the use of a high number of phosphodiesterase type-5 inhibitors after bilateral nerve-sparing radical prostatectomy.

It is well known that the administration of phosphodiesterase type-5 inhibitors (PDE5-Is) may improve erectile function (EF) recovery after bilateral nerve-sparing radical prostatectomy (BNSRP). The aim of our study was to identify predictors of the use of a high number of PDE5-Is (one or more per week) after surgery among 184 patients taking proerectile medications on demand. At a mean follow-up of 22.7 months, 116 patients (63%) recovered EF. Overall, EF recovery rates at 1- and 2- year follow-up were 47.3% and 65.4%, respectively. Overall, 43 (23.4%) patients used one or more PDE5-Is per week. Preoperative EF was the only predictor of the use of one or more PDE5-Is per week after BNSRP. This held true even after adjusting our analyses for age at surgery, body mass index and EF at 1 month after surgery. Particularly, patients fully potent before surgery had roughly 2.1-fold higher probability of using one or more pills per week compared with their counterparts with some degree of preoperative erectile dysfunction (ED; odds ratio: 2.16; 95% confidence interval: 1.03-4.37). In conclusion, preoperative EF represents the only determinant of the use of a higher number of PDE5-Is after surgery. Patients with better preoperative EF might represent individuals more motivated to achieve satisfactory sexual function after surgery. These observations should provide physicians with better preoperative patient counseling and management of postoperative ED.

Neurons in the globus pallidus do not show correlated activity in the normal monkey, but phase-locked oscillations appear in the MPTP model of parkinsonism.

1. To test the mode of functional connectivity in the basal ganglia circuitry, we studied the activity of simultaneously recorded neurons in the globus pallidus (GP) of a behaving rhesus monkey. The cross-correlograms of pairs of neurons in the GP were compared with those of neurons in the thalamus and frontal cortex and to the cross-correlograms of pallidal pairs after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) treatment. 2. In contrast with cortical and thalamic neuronal activity, almost all pairs (n = 76/81 pairs; 93.8%, 1,629/1,651 histograms; 98.7%) of GP neurons in the normal monkey were not driven by a common input. 3. The monkey was systemically treated with MPTP until the appearance of parkinsonian signs and an intermittent 7- to 11-Hz action/postural tremor. After the MPTP treatment, many pallidal neurons (49/140; 35%) became oscillatory, and 19% (n = 31/162) of pallidal pairs had oscillatory cross-correlograms. 4. These results support the model of parallel processing in the basal ganglia of normal monkeys and suggest a breakdown of the independent activity in the parkinsonian state.

Physiology of MPTP tremor.

Rhesus and vervet monkeys respond differently to treatment with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride neurotoxin (MPTP). Both species develop akinesia, rigidity, and severe postural instability. However, rhesus monkeys only develop infrequent, short episodes of high-frequency tremor, whereas vervet monkeys have many prolonged episodes of low-frequency tremor. After MPTP treatment, the spiking activity of many pallidal neurons became oscillatory and highly correlated. Oscillatory autocorrelation functions were dominated by lower frequencies, cross-correlograms by higher frequencies. The phase shift distribution of the oscillatory cross-correlograms of pallidal cells in MPTP-treated vervet monkey were clustered around 0 phase shift, unlike the oscillatory correlograms in the MPTP-treated rhesus monkey, which were widely distributed between 0 degrees and 180 degrees. Analysis of the instantaneous phase differences between tremors of two limbs in the MPTP monkeys and human parkinsonian patients showed short periods of tremor synchronization. We thus concluded that the rhesus and the vervet models of MPTP-induced parkinsonism may represent the tremulous and nontremulous variants of human parkinsonism. We suggest that the tremor phenomena of Parkinson's disease (PD) are related to the emergence of synchronous neuronal oscillations in the basal ganglia. Finally, the oscillating neuronal assemblies in the pallidum of tremulous parkinsonian primates are more stable (in time and in space) than those of parkinsonian primates without overt tremor.