Identification of (+)-erythro-mefloquine as an active enantiomer with greater efficacy than mefloquine against Mycobacterium avium infection in mice.

Infection caused by Mycobacterium avium is common in AIDS patients who do not receive treatment with highly active antiretroviral therapy (HAART) or who develop resistance to anti-HIV therapy. Mefloquine, a racemic mixture used for malaria prophylaxis and treatment, is bactericidal against M. avium in mice. MICs of (+)-erythro-, (-)-erythro-, (+)-threo-, and (-)-threo-mefloquine were 32 µg/ml, 32 µg/ml, 64 µg/ml, and 64 µg/ml, respectively. The postantibiotic effect for (+)-erythro-mefloquine was 36 h (MIC) and 41 h for a concentration of 4× MIC. The mefloquine postantibiotic effect was 25 h (MIC and 4× MIC). After baseline infection was established (7 days), the (+)- and (-)-isomers of the diastereomeric threo- and erythro-α-(2-piperidyl)-2,8-bis(trifluoromethyl)-4-quinolinemethanol were individually used to orally treat C57BL/6 bg(+)/bg(+) beige mice that were infected intravenously with M. avium. Mice were also treated with commercial mefloquine and diluent as controls. After 4 weeks of treatment, the mice were harvested, and the number of bacteria in spleen and liver was determined. Mice receiving (+)- or (-)-threo-mefloquine or (-)-erythro-mefloquine had numbers of bacterial load in tissues similar to those of untreated control mice at 4 weeks. Commercial mefloquine had a bactericidal effect. However, mice given the (+)-erythro-enantiomer for 4 weeks had a significantly greater reduction of bacterial load than those given mefloquine. Thus, (+)-erythro-mefloquine is the active enantiomer of mefloquine against M. avium and perhaps other mycobacteria.

Improving the quality of suicide risk assessments in the psychiatric emergency setting: physician documentation of process indicators.

CONTEXT: Suicide risk assessment in the emergency department is a challenging task for psychiatrists and is further complicated when patients are admitted involuntarily. OBJECTIVE: To evaluate the quality of suicide risk assessments in the psychiatric emergency setting by reviewing physician documentation of process indicators. METHODS: A retrospective review of medical records for patients who were admitted involuntarily to the Kern Medical Center Psychiatric Emergency Service in Bakersfield, Calif. All patients were deemed a "danger to self" as defined by California Law and were admitted for evaluation in June 2006. Medical records were reviewed for 19 process indicators, which were identified from risk factors and treatment guidelines described in the literature. Documentation that a process indicator was not met by a patient was included in the data. Patients were then separated into two study groups: those who were admitted to the inpatient psychiatric unit, and those who were released. Data were analyzed using t tests for continuous variables and chi(2) tests for categorical variables. RESULTS: The medical records of 145 patients were reviewed. None of the suicide risk assessments documented all 19 process indicators. The three most commonly documented process indicators were access to firearms (75.9%), recent stressful life events (75.2%), and "contract for safety" (74.5%). According to medical records, patients admitted to the inpatient unit were more likely than patients released to home care to have been assessed for command auditory hallucinations (P=.02) or prior psychiatric diagnoses (P=.001). Discharged patients were more likely to have been assessed for a family history of suicide (P=.001) or symptoms of major depressive disorder (P=.02). CONCLUSION: Many important risk factors for suicide were not documented in emergency department assessments, suggesting that overall quality of psychiatric risk assessments was not optimal. This lack of documentation has important implications from a treatment and medicolegal perspective.

Terazosin therapy for patients with female lower urinary tract symptoms: a randomized, double-blind, placebo controlled trial.

PURPOSE: We determined the clinical efficacy and safety of terazosin in the treatment of patients with female lower urinary tract symptoms. MATERIALS AND METHODS: A total of 100 females 20 to 70 years old who met the inclusion criteria of total International Prostate Symptom Score 8 or greater, symptom duration 1 or more months, and did not meet any exclusion criteria were entered into the study. Subjects were randomized to receive terazosin or placebo in titrated dose from 1 mg od, 1 mg twice daily to 2 mg twice daily during 14 weeks. Successful treatment outcomes use primary end point of International Prostate Symptom Score quality of life 2 or less and secondary end point of total International Prostate Symptom Score 7 or less. Other outcome measures included International Prostate Symptom Score individual item scores, King's Health Questionnaire quality of life domains, objective assessment parameters of 24-hour frequency volume chart, maximum flow rate and post-void residual urine. RESULTS: Using a primary end point, 32 of 40 (80%) evaluable terazosin subjects responded in contrast to 22 of 40 (55%) evaluable placebo subjects (p <0.02). The secondary end point revealed a successful outcome in 85% of terazosin subjects vs 55% in placebo (p <0.01). Of the 7 International Prostate Symptom Score individual item scores, only item scores of frequency and straining showed statistically significant reductions with terazosin (p <0.01). All King's Health Questionnaire quality of life domains except domain of severity measures showed statistically significant improvement with terazosin (p <0.05). There were no differences between treatment groups in all objective assessment parameters. Of all evaluable subjects 23 of 40 (58%) on placebo experienced adverse events vs 16 of 40 (40%) on terazosin (p >0.05). CONCLUSIONS: Terazosin proved to be more effective and safe than placebo in patients with female lower urinary tract symptoms.

Acupuncture versus sham acupuncture for chronic prostatitis/chronic pelvic pain.

BACKGROUND: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) afflicts 2%-10% of adult men. Available therapies offer little or no proven benefit. Because acupuncture represents an attractive "natural" therapy, we compared the efficacy of acupuncture to sham acupuncture for CP/CPPS. METHODS: Participants met US National Institutes of Health (NIH) consensus criteria for CP/CPPS, were aged > or = 20 years old, and had a total score > or = 15 on the NIH Chronic Prostatitis Symptom Index (NIH-CPSI) and symptoms for at least 3 of the preceding 6 months. They were randomized 1:1 to acupuncture or sham acupuncture. Treatment consisted of twice-weekly 30-minute sessions for 10 weeks (20 sessions total) without needle stimulation, herbs, or adjuvants. The primary response criterion was a 6-point decrease from baseline to week 10 in NIH-CPSI total score (range 0-43). RESULTS: Thirty-two (73%) of 44 participants responded in the acupuncture group compared with 21 (47%) of 45 sham group participants (relative risk 1.81, 95% confidence interval, 1.3-3.1, P = .02). Long-term responses 24 weeks after completing therapy without additional treatment occurred in 14 (32%) of 44 acupuncture group participants and in 6 (13%) of 45 sham group participants (relative risk 2.39, 95% confidence interval, 1.0-5.6, P = .04). CONCLUSIONS: After 10 weeks of treatment, acupuncture proved almost twice as likely as sham treatment to improve CP/CPPS symptoms. Participants receiving acupuncture were 2.4-fold more likely to experience long-term benefit than were participants receiving sham acupuncture.

Efficacy and safety of sildenafil in Asian males with erectile dysfunction and cardiovascular risk.

OBJECTIVE: Assess the effectiveness of sildenafil in Asian males with erectile dysfunction (ED) and one or more of the co-morbidities, mild-to-moderate hypertension, dyslipidemia, and diabetes. MATERIAL AND METHOD: A six-week, double-blind, randomized, placebo-controlled, multicenter study was carried out in Thailand, Malaysia and Singapore. One hundred and fifty five male subjects were randomized (2:1) to sildenafil (n = 104) or placebo (n = 51). Sildenafil was started at 50 mg and increased (100 mg) or decreased (25 mg) at week 2 if necessary. RESULTS: On the primary efficacy endpoint, sildenafil-treated subjects had significantly better scores on the International Index of Erectile Function (IIEF) questions 3 and 4 than placebo (p < 0.001, both questions). When accumulated into IIEF domains, all five domains were significant in favor of sildenafil. In addition, sildenafil-treated subjects were more satisfied with treatment and had a higher intercourse success rate. The majority of adverse events were mild in severity; the most commonly reported treatment-related events were dizziness (7.7%) and tinnitus (2.9%). CONCLUSION: Sildenafil (25, 50, and 100 mg) was found to be an effective, safe, and well-tolerated treatment for ED in the present study population of Thai, Malaysian, and Singaporean males who also had increased cardiovascular risk

EDP-420, a bicyclolide (bridged bicyclic macrolide), is active against Mycobacterium avium.

Infection caused by Mycobacterium avium complex (MAC) is common in patients with immunosuppression, such as AIDS, and deficiencies of gamma interferon and interleukin-12, as well as patients with chronic lung diseases. Treatment of MAC disease is limited since few drugs show in vivo activity. We tested a new bridged bicyclic macrolide, EDP-420, against MAC in vitro and in beige mice. EDP-420 was inhibitory in vitro at a concentration ranging from 2 to 8 microg/ml (MIC(50) of 4 microg/ml and MIC(90) of 8 microg/ml). In macrophages, EDP-420 was inhibitory at 0.5 microg/ml, suggesting that the drug concentrates intracellularly. Mice infected with macrolide-susceptible MAC strain 101 were given 100 mg of EDP-420/kg of body weight daily for 4 weeks and showed a significant reduction in the number of bacteria in both liver and spleen which was greater than the reduction observed with clarithromycin treatment at the same dose (P < 0.05). However, macrolide-resistant MAC 101 did not respond to EDP-420 treatment. A combination of EDP-420 with mefloquine was shown to be indifferent; mefloquine alone was active against macrolide-resistant MAC. The frequency of resistance to EDP-420 in MAC 101 was 10(-9), which is significantly less than the emergence of resistance to clarithromycin, approximately 10(-7) (P < 0.05). Further evaluation of EDP-420 in the treatment of MAC disease is warranted.

Study of prevalence, treatment-seeking behavior, and risk factors of women with lower urinary tract symptoms in Northern Malaysia.

OBJECTIVES: To determine the prevalence, severity, and quality-of-life (QOL) impact of female lower urinary tract symptoms (FLUTS); to determine the patterns, reasons, and factors contributing to the women's treatment-seeking behavior; and to describe the relationship between the social demographic characteristics and FLUTS. METHODS: A total of 2732 women older than 19 years of age were recruited by a series of FLUTS Awareness Campaigns held within Northern Malaysia from January to August 2004. Trained interviewers used surveys to collect information on social demographic characteristics, International Prostate Symptom Score, and King's Health Questionnaire to determine the prevalence, severity, QOL impact, treatment-seeking behavior, and risk factors of FLUTS. RESULTS: The prevalence of FLUTS was 19.0% (n = 519), with 88.6% having moderate and 11.4% severe FLUTS. Using the International Prostate Symptom Score QOL assessment index, 55.3% (n = 287) scored 4 or greater. Using the King's Health Questionnaire, the most affected QOL domain was sleep/energy. The patterns of treatment-seeking behavior revealed that only 23.1% (n = 120) of patients with FLUTS actively sought treatment. The major reason for those (76.9%) who failed to seek treatment was that they did not perceive FLUTS as a major health problem (29.1%). Factors that warranted treatment were the severity, bother, and QOL impact of FLUTS (all P <0.001), hematuria (P <0.001), age (P <0.005), parity, body mass index, and suprapubic pain (all P <0.05). The risk factors for FLUTS (defined as an odds ratio of 2 or more) included age 50 years or older, parity of 4 or more, illiteracy, postmenopausal status, and the presence of one or more concomitant chronic medical illness. CONCLUSIONS: Despite the high prevalence of FLUTS in Northern Malaysia (19.0%), many patients do not seek treatment, with ignorance being the major reason.

Routine vascular control using the Hem-o-lok clip in laparoscopic nephrectomy: animal study and clinical application.

BACKGROUND AND PURPOSE: During laparoscopic nephrectomy (LPN), a stapling device is often used for vascular control, especially of the renal vein. Herein, we report our experience using a polymer clip (Hem-o-lok) for routine control of the vessels during LPN in the animal and clinical setting. PATIENTS AND METHODS: Fifty ablative and fifteen live-donor nephrectomies were performed in domestic pigs. Hem-o-lok clips (10 mm; Weck Closure System, Research Triangle Park, NC) were routinely used for vascular control. In addition, from January 2001 to July 2002, 46 patients underwent hand-assisted laparoscopic (HAL) (N=40) or laparoscopic (N=6) nephrectomy for renal disease or donor nephrectomy. Venous control was achieved solely by the Hem-o-lok clips where at least two clips were applied on the patient side. Arterial control was obtained by the Hem-o-lok clips either alone or in combination with the metal clips. The technical difficulty in obtaining vascular control, transfusion requirement, and clinical outcome were evaluated. RESULTS: In the animal study (total 65 nephrectomies), individual vascular control was obtained by the Hem-o-lok clip in all cases except two, where vascular injury during dissection necessitated endoscopic stapling of renal hilum or open conversion. The warm ischemic time for animal donor kidney harvest was uniformly <2 minutes. In the clinical study, arterial control was obtained mostly by a combination of Hem-o-lok and metal clips. Venous control using the Hem-o-lok was successful in all 46 cases without any slipping of clips or uncontrolled bleeding. The mean operating time was 148 minutes. No open conversion was required. The transfusion rate was 6.5% (N=3), with none of the transfusions being related to inadequacy of vascular control using the Hem-o-lok. Major complications included deep vein thrombosis and postoperative retroperitoneal hemorrhage (same patient) and acute respiratory distress syndrome (N = 1). The mean postoperative stay was 5.2 days (range 1-20 days). CONCLUSION: The Hem-o-lok is a reliable and economical device for vascular control in laparoscopic renal surgery.