Reconfiguration of the severely fibrotic penis with a penile implant.

PURPOSE: Using evidence based methods we prospectively evaluated the impact of a new surgical procedure on penile deformity caused by severe cavernous fibrosis. MATERIALS AND METHODS: In 10 patients with severe penile curvature, shortening and impaired penile rigidity due to fibrosis of the corpora cavernosa we made multiple relaxing incisions of the tunica albuginea and subsequently placed a 3-piece inflatable penile implant. Patients were evaluated before and after the procedure by the International Index of Erectile Function and several general assessment questions. Preoperatively and postoperatively we measured flaccid and erect penile length. RESULTS: At the 6-month followup all International Index of Erectile Function domains were significantly improved compared with preoperative values. Average penile length was increased 2.3 and 3 cm. while flaccid and erect, respectively, compared with before surgery. Complete penile straightening was achieved in 9 of 10 cases (90%). Surgical reoperation was performed in 1 patient (10%) in whom the implant was removed due to scrotal infection and in another (10%) in whom a further single relaxing incision of the fibrotic plaque was needed to attain complete penile straightening. CONCLUSIONS: Patients with severe penile curvature, shortening and impaired penile rigidity due to penile fibrosis may be offered this surgical alternative, which proved to be effective and safe in our preliminary series.

Vulvodynia: the challenge of "unexplained" genital pain.

Vulvodynia is a clinical syndrome that may include unexplained vulvar pain, sexual dysfunction, and psychological disability. It is a multifactorial syndrome that should be diagnosed, if possible, with an intradisciplinary approach. This article discusses the diagnosis and treatment of vulvodynia, starting with a summary of the complex nervous system within the pelvis. Different clinical pictures and different subtypes of the syndrome have been described in order to identify the etiologic aspects that are essential for diagnosis and subsequent treatment. Clinical evaluation should stress attention to detailed "pain-mapping" and evaluation of past and present history. The gynecological examination should be an overall patient evaluation, incorporating global physical impression, change in posture due to pain and careful examination of the pelvic floor. Examination of the pelvic floor is frequently omitted. Leading to an incorrect diagnosis of psychogenic pain. Such a misdiagnosis can result in the dismissal of appropriate treatment. Proper evaluation requires a comprehensive, multidisciplinary approach that includes medical, rehabilitative, and psychological issues.

Malignant fibrous histiocytoma of soft tissue producing granulocyte colony-stimulating factor.

We treated a rare case of malignant fibrous histiocytoma (MFH) of soft tissue that produced granulocyte colony-stimulating factor (G-CSF). The patient, an 80-year-old woman, was admitted because of a feeling of abdominal fullness and leg edema. An elastic, hard, tender tumor was palpated in the right thigh. Histopathological examinations of the tumor revealed atypical and prominent pleomorphic spindle-shaped cells with funicular arrangement, which were compatible with the diagnosis of MFH. Prominent leukocytosis (up to 84,300/microl), a high serum G-CSF concentration (82 pg/ml) and positive immunohistochemical staining of the tumor tissue for G-CSF indicated that G-CSF was produced by the MFH.

A randomized open trial for comparison of proton pump inhibitors, omeprazole versus rabeprazole, in dual therapy for Helicobacter pylori infection in relation to CYP2C19 genetic polymorphism.

BACKGROUND AND AIM: The genetic polymorphism of cytochrome P450 (CYP) 2C19 has been shown to influence the efficacy of Helicobacter pylori eradication therapy with a proton pump inhibitor (PPI) and amoxicillin (so-called dual therapy). Omeprazole, a widely used PPI, and rabeprazole, a new PPI, are metabolized in different pathways in terms of CYP2C19 genetic polymorphisms. In this study, we compared the efficacy of omeprazole and rabeprazole in a 2-week dual therapy in relation to CYP2C19 polymorphism. METHODS: One hundred and ninety-nine patients with peptic ulcer disease were randomly assigned to receive one of the following regimens: 500 mg t.i.d. amoxicillin together with either 20 mg b.i.d. omeprazole or 10 mg b.i.d rabeprazole. The eradication of H. pylori was evaluated by using a bacterial culture and a [(13)C]-urea breath test at 1--2 months after completion of treatment. Cytochrome P4502C19 polymorphism was analyzed by using polymerase chain reaction-restriction fragment length polymorphism. RESULTS: Intention-to-treat-based cure rates for the omeprazole or rabeprazole regimens were 66.3% (95% CI, 56--75) and 62.4% (95% CI, 52--71), respectively, without significant difference. Cytochrome P4502C19 genetic polymorphism did not influence the cure rates in either of these regimens. We analyzed various factors associated with treatment failure (PPI, CYP2C19 genotype, and smoking habit) by using multiple logistic regression; smoking was the only significant independent factor for treatment failure. CONCLUSION: Omeprazole and rabeprazole were equally effective in combination with amoxicillin in eradicating H. pylori, irrespective of the PPI used (omeprazole or rabeprazole) and CYP2C19 genetic polymorphism. Smoking significantly decreased the cure rate of H. pylori infection in the dual therapy.

A formal framework of knowledge to support rational psychoactive drug selection.

Rational psychoactive drug selection is a data and knowledge intensive task which requires true expertise from clinical, pathophysiological and pharmacotherapeutic knowledge. This paper presents a framework of knowledge, which relates concepts from several disciplines required for psychoactive drug selection in a formal way. A framework, when based on formal semantics, avoids ambiguity and gives conceptual clarity and supports precise use of terminology which is required when many domain experts (clinicians, pharmacologists and basic science researchers) are involved. A formal framework permits linking of existing classification systems. It furthermore can serve as a knowledge base for drug selection decision support systems.

Towards a more rational use of psychoactive substances in clinical practice.

Complex knowledge and data intensive nature of the psychoactive drug selection and prescription process often makes for irrational and inconsistent use of psychoactive drugs in clinical practice. After describing the state of the art with respect to psychoactive drug prescription practices and selection processes, our aim is to analyze the advantages of computer support systems in assisting the clinician in his clinical decisions. Finally, we will review the neuropsychiatric expert systems developed for the neuropsychiatric domain. Suboptimal psychoactive drug therapy is common practice, which leads to hospital admissions, extended length of hospital stay, ineffective therapy and increased costs. Furthermore, the psychoactive drug selection process is a complex decision process, using up-to-date integrative knowledge of drugs from basic sciences to the clinical level. Due to the information load, the lack of appropriate up-to-date information at the point of clinical care and the problem of integrating and weighing all information relatively equally, it is questionable whether any clinician can manage such a complex situation with optimal effectiveness. As has been shown in a number of experiments, clinicians can benefit from computer-based systems that provide access to accurate, up-to-date information. We maintain that more rational use of psychoactive drugs in clinical practice is needed, and conclude that rational psychoactive drug prescription is a knowledge and data-intensive task requiring true expertise derived from clinical, pathophysiological and pharmacotherapeutic knowledge. We will be developing a Multidisciplinary Psychoactive Drug Selection advisor system, M-PADS, to support the integration of various types of biomedical information and deliver that integrated information supportive to evidence-based rational drug prescription in the practice of medicine for the drug treatment of individual patients.

Evidence based assessment of long-term results of plaque incision and vein grafting for Peyronie's disease.

PURPOSE: We assessed the long-term outcome of plaque incision and vein grafting in select patients with Peyronie's disease by extensive preoperative and postoperative subjective and objective analysis. MATERIALS AND METHODS: From January 1995 to June 1998, 50 men 28 to 62 years old (mean age 44) underwent surgery. Patients were evaluated preoperatively, 3 months after surgery and at a mean long-term followup of 32 months by sexual history, physical examination, determination of penile length and degree of curvature, dynamic color power Doppler sonography of the penile vessels and nocturnal RigiScan* evaluation for 3 nights. Study inclusion criteria were penile curvature 45 degrees or greater that made vaginal intromission impossible, stable disease for at least 6 months, patient reported normal penile rigidity, normal penile hemodynamics on color power Doppler ultrasound, normal nocturnal penile rigidity with at least 1 erection nightly (including base and tip rigidity greater than 60%, and a duration of 10 minutes) and absent base-tip discrepancies. Plaque was usually approached via a combined subcoronal and midline sagittal scrotal incision. Maximal rigidity was created intraoperatively and 1 to 3 plaque incisions were made. Saphenous vein patches were then grafted at the incision sites. Postoperatively patients were systemically treated with neurotrophic factors and low molecular weight heparin. Local vacuum supported corporeal stretching was done and weekly alprostadil injections were given to optimize corporeal oxygenation. RESULTS: At long-term followup complete penile straightening was achieved in 40 cases (80%), minor residual curvature of 30 degrees or less persisted in 7 (14%) and significant disease recurred in 3 (6%). Penile rigidity was equal to that preoperatively in 47 patients (94%), while 3 (6%) reported clinically significant decreased potency. Penile length was equal to that preoperatively in 30 patients (60%), while 20 (40%) noticed slight penile shortening. Postoperatively penile color power Doppler sonography showed vascular impairment in 5 men (10%) and nocturnal RigiScan testing revealed a significant decrease in nightly erections in 5 (10%). Surgical complications included penile hypoesthesia in 1 case (2%), penile hematoma in 2 (4%), wound infection in 1 (2%) and glandular ischemia in 1 (2%). CONCLUSIONS: Plaque incision and vein grafting achieved satisfactory clinical results in the majority of patients with severe and stable Peyronie's disease, intact penile rigidity preoperatively, normal penile color power Doppler ultrasound and normal nocturnal RigiScan testing.

Sildenafil taken at bedtime significantly increases nocturnal erections: results of a placebo-controlled study.

OBJECTIVES: Nighttime erections occur at all ages and contribute to the maintenance of the morphodynamic integrity of smooth muscle cells within the corpora cavernosa. This study was aimed at evaluating the effect on nocturnal erections of sildenafil versus a placebo taken at bedtime. METHODS: A double-blind, crossover, placebo-controlled study design was used to examine the effects of sildenafil and placebo on sleep-related erectile activity. Thirty selected patients with erectile dysfunction (vasculogenic etiology, 22 patients [73%]; psychogenic etiology, 8 patients [27%]) were submitted to a polysomnographic recording of nocturnal erections, using a RigiScan device during 3 consecutive nights. After a first night of adaptation, the 2 following nights were used to study patients after the administration of sildenafil (100 mg) or a placebo taken at bedtime. RESULTS: Twenty-three patients (77%) showed a significantly improved nocturnal erectile activity (according to the calculation of rigidity and tumescence activity units) after the administration of sildenafil (P <0.01), 5 patients (17%) showed comparable nocturnal erections with sildenafil and placebo, and 2 patients (6%) showed a significantly improved nocturnal erectile activity after taking the placebo (P <0.05). Overall, mean rigidity and tumescence activity values at the tip and base of the penis were significantly improved after sildenafil rather than placebo administration (P <0.001). The duration of tip rigidity greater than 60% was significantly longer during the night with sildenafil (P <0. 001). Although the number of erectile episodes was greater during the sildenafil night, this did not reach statistical significance. CONCLUSIONS: In most patients with good sleep efficiency and who have erectile dysfunction, sildenafil, rather than a placebo, taken at bedtime produces a significantly improved nocturnal erectile activity. Further studies are needed to verify whether this preliminary finding may constitute the basis for the use of sildenafil as a tool for preventing erectile dysfunction.

Sandimmune to Neoral conversion and value of abbreviated AUC monitoring in stable pediatric kidney transplant recipients.

Neoral is a new microemulsion formulation of cyclosporin A (CsA) that has been reported to have better absorption characteristics than sandimmune. We converted 25 long-term pediatric renal transplant recipients with a mean age of 14.1 yr and a mean follow-up period of 6.4 yr from sandimmune (SIM) to neoral (NEO) on a 1:1 basis. The mean dosage of SIM or NEO required to maintain 'therapeutic range' steady-state trough levels between 100 and 200 ng/mL was similar. We compared 6-h CsA pharmacokinetic profiles taken approximately 6 months after the conversion to NEO with the previous SIM profiles of the same patients. Generally, in the NEO profiles the time to reach the maximum concentration was shorter and the maximum concentration was higher, showing a rapid decline towards the trough-level when compared to the previous SIM profiles. During intake of NEO the AUC0-12 h in the 12-h profiles correlates strongly with the AUC0-6 h in the 6-h profiles (r = 0.98), a similar finding to that which we reported previously for SIM. The median AUC0-6 h for NEO demonstrates a 70% increase compared to the median AUC0-6 h for SIM. Despite the increased drug exposure NEO was well tolerated and did not cause any apparent toxicity within the first 6 months after conversion. The CsA blood level 2 h after intake of NEO showed a higher correlation with the AUC0-12 h (r = 0.91) than the trough level (r = 0.64). The abbreviated profile based on three early sampling points and calculated by AUCPRED = 335.9 + 1.1*(C1) + 1.1*(C2) + 5.4*(C4) correlated well with the full AUC (r2 = 0.98, p < 0.0001). Mean prediction error (+/- SD) was 0.16% (+/- 4.32), and in no patients did the calculated values fall outside the 10% prediction error limit. We therefore conclude that NEO exhibits a higher bioavailability in children compared to SIM without causing apparent toxicity. Monitoring of the C2 might be a better alternative for trough level monitoring in daily clinical practice. A strategy of three early sampling points (C1, C2 and C4) allows a reliable AUC0-12 h prediction and can reduce the length of observation, making it a useful and cost-effective tool in clinical practice.

Functional anatomy of cavernous helicine arterioles in potent subjects.

PURPOSE: We investigated the morphological and functional features of cavernous helicine arterioles in male potent subjects. MATERIALS AND METHODS: Ten young men reporting normal rigid erections which were confirmed by polysomnographic recording underwent power Doppler sonography of the cavernous helicine arterioles during flaccidity, after intracavernous injection of alprostadil, and after subsequent genital and audiovisual sexual stimulation. RESULTS: During flaccidity the helicine arterioles were never detected by power Doppler imaging while they became evident in all cases after alprostadil injection. They usually originated from the cavernous artery forming an acute angle and showed 3 orders of ramifications. Systolic and diastolic flow was present. After genital and audiovisual sexual stimulation, and achievement of maximum rigidity, the helicine arterioles were still evident but with only 1 or 2 orders of distal ramifications. Only systolic flow was present. During penile tumescence the helicine arterioles disappeared in all cases. CONCLUSIONS: Using power Doppler sonography it is possible to investigate the functional anatomy of the cavernous helicine arterioles during the various phases of the erectile cycle. Our preliminary study suggests that the helicine arterioles are functionally inactive during penile flaccidity while they are activated during penile tumescence and continue to supply blood to the corpora also during maximum penile rigidity.

Geranylgeranylacetone and cetraxate hydrochloride increase UDP-galactosyltransferase activity in rat gastric mucosa.

UDP-galactosyltransferase (UDP-Gal-T) is a key enzyme in the synthesis of mucus glycoprotein which plays an important role in gastric mucosal defensive mechanisms. Analysis of gastric UDP-Gal-T activity should clarify the mechanisms of the action of antiulcer drugs regarding gastric defensive factors. Here, we examined UDP-Gal-T activity in rat gastric mucosa treated with the antiulcer drugs geranylgeranylacetone (GGA) and cetraxate hydrochloride (CET). The effects of coadministration of indomethacin and exogenous administration of prostaglandins (PGs) were also studied. GGA and CET significantly increased UDP-Gal-T activity, and coadministration of indomethacin inhibited the increase of enzyme activity. UDP-Gal-T activity level with GGA was significantly higher than the control level, even in the presence of indomethacin. With CET, however, this was not the case. Among PGs, PGE1 significantly increased enzyme activity. Concomitant administration of PGE1 and GGA or CET increased UDP-Gal-T activity even with indomethacin to the levels achieved when these antiulcer drugs were administered without indomethacin. Our findings suggest that GGA and CET exert antiulcer effects by increasing mucus glycoprotein synthesis and that endogenous PG synthesis may be involved in this process. However, mechanisms not mediated by endogenous PGs may also exist in the stimulatory action of GGA on UDP-Gal-T activity.

Use of the methylxanthine derivative A802715 in transplantation immunology: II. In vivo experiments.

BACKGROUND: We have previously demonstrated in vitro that the methylxanthine derivative A802715 suppresses the cyclosporine (CsA)-resistant "signal two"-dependent pathway of T cell activation and hence acts synergistically with CsA. Here, this synergism was further investigated in vivo in rats. METHODS: Primary cardiac allografts were placed in the neck, and secondary grafts were transplanted intra-abdominally. A802715 was given orally for 30 days or by continuous intravenous infusion via a mini-osmotic pump for 2 weeks. CsA was given orally for up to 30 days. T cell responses were examined in vitro using mixed lymphocyte reaction, concanavalin A whole blood, and cell-mediated lympholysis assays. RESULTS: In a major histocompatibility complex incompatible WKAH-->PVG combination, neither oral CsA (7.5 mg/kg/day) nor oral A802715 (100 mg/kg/day) was able to prolong graft survival. However, a combination of both drugs, given at the same dose, sustained graft survival during treatment. A similar synergism was not obtained with pentoxifylline, another methylxanthine derivative. The synergism between A802715 and CsA could be further increased by using a continuous intravenous infusion of A802715, since (1) lower doses of A802715 (20 mg/kg/day) and CsA (5 mg/kg/day) could be used, and (2) six of seven grafts survived permanently. In a major histocompatibility complex compatible Wag/Rij-->R/A combination, similar synergistic effects and permanent graft survival could also be obtained by oral A802715 (100 mg/kg/day) in combination with a low dose of CsA (2.5 mg/kg/day). In both strain combinations, long-term survivors accepted donor-type but rejected third-party second grafts in the absence of immunosuppression. This specific tolerance was not related to clonal deletion nor anergy, as recipient lymphocytes proliferated normally in the anti-donor mixed lymphocyte reaction. Instead, a defect in generating specific cytotoxic T lymphocytes was involved. CONCLUSIONS: A802715 synergizes with CsA in vivo to induce specific transplantation tolerance and hence should be considered as a promising new immunosuppressant.

Assessment of UDP-galactosyl-transferase activity in gastric mucosa of patients with chronic liver disease using an enzyme-linked peanut agglutinin binding assay.

Gastric mucin plays an important role in protecting mucosa from irritants such as acids and pepsin, and UDP-galactosyltransferase is a key enzyme in mucin synthesis. In order to study the synthesis of gastric mucin in patients with chronic liver disease, we developed a new assay using a peanut agglutinin lectin to measure this enzyme in human gastric mucosa obtained by endoscopic biopsy. Enzyme activity correlated well with that determined with a previous method using radiolabeled galactose. The enzyme activity in gastric mucosa of cirrhotic patients was significantly lower than in patients with chronic hepatitis or in normal controls and correlated with the amount of mucin in surface epithelial cells. Our findings suggest that the synthesis of gastric mucin is impaired in patients with liver cirrhosis.

Changes in organ perfusion after brain death in the rat and its relation to circulating catecholamines.

Brain death can have an impact on donor organ function. This is often attributed to an altered hormonal, mainly thyroidal, status after brain death. A second possible explanation is that during the brain death process, blood flow is redistributed, causing ischemic damage in underperfused organs or regions. We investigated blood flow redistribution with colored microspheres in the rat early and late after brain death, induced by inflation of an intracranial balloon, and correlated this with the global hemodynamic situation and plasma catecholamine concentrations. Brain death was proven by the demonstration of lasting absence of brain perfusion in all animals. Myocardial blood flow closely followed the myocardial oxygen need as estimated by the rate-pressure product. The abdominal organs showed intense vasoconstriction early after brain death, which led to significantly decreased perfusion of these organs despite the highly increased perfusion pressure, followed by significant vasodilation. Total plasma catecholamine concentration was 57 times higher at 30 sec after brain death as compared with basal levels. Plasma noradrenaline concentration fell significantly below basal levels late after brain death. We conclude that brain death importantly alters regional perfusion, with possible implications for donor organ function. These changes are probably due to the tremendous alterations in the activity of the sympathetic nervous system.

AMS 700 CX inflatable penile implants for Peyronie's disease: functional results, morbidity and patient-partner satisfaction.

This study was designed to clarify the functional results, morbidity and the patient-partner satisfaction observed with, the American Medical System 700 CX three-piece inflatable prosthesis in the treatment of impotence associated with Peyronie's disease. Thirty-three patients were treated and additional plaque surgery was performed in 13 cases (40%). Within 10 days of surgery, four patients (12%) developed a wound infection which was treated conservatively and one patient (3%) experienced glandular ischemia. At the 6-week follow-up, complete penile straightening was achieved in 23 patients (70%), while penile rigidity was considered optimal by all patients. On the contrary, the penis was considered short by 10 patients (30%). Five diabetic patients (15%) complained of severe scrotal and penile pain during full activation of the implant and in one of these patients (3%) the implant had to be removed. Due to spontaneous erections occurring after implant activation one patient (3%) required replacement of the reservoir from the Retzius space into the peritoneum. At the long-term follow-up (mean +/- SE: 17 +/- 2.2 months), 23 patients were evaluated and all found to be engaging in intercourse with the prosthesis. However, five patients (21%) and three of the 13 partners (25%) assessed were not yet completely satisfied. The American Medical System CX700 inflatable penile prosthesis obtains complete penile straightening in 70% and rigidity in 100% of impotent patients with Peyronie's disease. Patients should be fully informed about possible surgical morbidity and actual post-operative penile length.

Verapamil as prophylactic treatment for atrial fibrillation after lung operations.

BACKGROUND: Atrial fibrillation is a frequently occurring arrhythmia after thoracic operations. Preventive strategies for this complication have been extensively evaluated after cardiac operations. METHODS: We performed a prospective, open randomized study, comparing intravenous verapamil and placebo in 199 patients after pneumonectomy or lobectomy at the University Hospital of Leuven. Verapamil was administered as a bolus of 10 mg over 2 minutes followed by a 30-minute infusion of 0.375 mg/min and then 0.125 mg/min for 3 days. The patients were continuously monitored in the postoperative intensive care unit. RESULTS: Atrial fibrillation occurred in 15% of the patients receiving placebo and in 8% of the patients receiving verapamil (difference not significant). The verapamil infusion was interrupted in 9% of the patients because of bradycardia and in 14% because of hypotension. CONCLUSIONS: If tolerated, continuous intravenous verapamil infusion showed only a modest prophylactic efficacy for the occurrence of atrial fibrillation after lung operations. In the dose employed the verapamil infusion was accompanied with a high incidence of side effects necessitating interruption of the therapy.

Long-term cyclosporin A pharmacokinetic profiles in pediatric renal transplant recipients.

To study the long-term effect of cyclosporin A (CyA), 94 6-h and 29 12-h pharmacokinetic profiles were evaluated in 32 children at least 1 year after renal transplantation. Children weighing less than 25 kg needed significantly higher doses of CyA than those weighing more than 25 kg (9.8 vs 5.3 mg/kg per day; P < 0.001) to achieve similar trough levels (TL). The average dose of CyA required to achieve the target TL declined gradually with time after transplantation. The average area under the curve over 6 h (AUC/6) correlated strongly with the AUC/12 (r = 0.967; P < 0.001). The AUC/6 of patients with biopsy-proven CyA toxicity was significantly higher than for those without toxicity (Mann-Whitney U-test P < 0.05) despite similar TL. We conclude that AUC monitoring for 6 h provides valuable information not only on TL but also on the absorption and elimination characteristics of CyA as well as on the potential for CyA toxicity.