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Biomedical subjects

J Berman

Publications and source records attributed to J Berman.

At least 37 records · Page 2Linked to original sources
PubMed2001

Phase 2 trial of WR6026, an orally administered 8-aminoquinoline, in the treatment of visceral leishmaniasis caused by Leishmania chagasi.

There are no recognized orally administered treatments for any of the leishmaniases. The 8-aminoquinoline WR6026 is an orally administered analog of primaquine that cured 50% of patients with kala-azar in Kenya at a dose of 1 mg/kg/day for 28 days. A further phase 2, open-label, dose-escalating safety and efficacy study was performed for kala-azar in Brazil. Cure rates for Brazilian patients treated for 28 days were as follows: 1 mg/kg/day: 0 of 4 (0%); 1.5 mg/kg/day: 1 of 6 (17%); 2.0 mg/kg/day: 4 of 6 (67%); 2.5 mg/kg/day: 1 of 5 (20%); and 3.25 mg/kg/day: 0 of 1 (0%). Nephrotoxicity that was not anticipated from preclinical animal studies or from phase 1 studies was seen at 2.5 mg/kg/day in 2 patients and in the single patient administered 3.25 mg/kg/day. WR6026 demonstrated the unusual clinical features of lack of increased efficacy against Brazilian kala-azar with increased dosing above 2 mg/kg/day and toxicity that was not present in previous investigations.

Administration, Oral↗
PubMed2001

Plasmodium vivax clinically resistant to chloroquine in Colombia.

Chloroquine-resistant Plasmodium vivax has been the subject of numerous case reports and prospective studies from Oceania and Asia. In contrast, only case reports exist from the Americas. We performed a prospective study with 28-day follow-up of clinical responses to chloroquine in 2 P. vivax-endemic regions of Colombia. Three (11%) of 27 patients failed to respond to treatment with the standard regimen of chloroquine (1,500 mg of base over 3 days). One patient demonstrated RI resistance on Day 26; one patient demonstrated RI resistance due to recrudescence of blood stages on Day 11; and one patient demonstrated RII resistance of blood stages by never displaying clearing of peripheral parasitemia. All patients were successfully treated with primaquine, which has some blood stage efficacy against P. vivax, combined with a second course of chloroquine. Clinical resistance of P. vivax to chloroquine is present in Colombia and should be monitored in the Americas.

Animals↗
PubMed2001

Polypropylene sling for treatment of stress urinary incontinence: an alternative to tension-free vaginal tape.

PURPOSE: Sling procedures have been used successfully to treat stress urinary incontinence (SUI). We report our initial experience with the use of a synthetic polypropylene mesh for treatment of SUI. Based on similar surgical principles of cadaveric fascia sling, we describe placement of a thinly woven polypropylene mesh under the distal urethra. We describe our technique and report our initial results. MATERIALS AND METHODS: There were 146 consecutive patients evaluated. All patients had clinical evidence of SUI. Patients underwent preoperative evaluation with video urodynamics, symptom questionnaire, and cystoscopy. Postoperatively the patients were evaluated at 3-month intervals by symptom questionnaire, physical examination, and postvoid residuals (PVR). One year after the procedure, all patients were asked to fill out a voiding dysfunction and incontinence symptom questionnaire and a validated quality-of-life questionnaire. A flow and PVR also were obtained. RESULTS: Average intraoperative time was 27 minutes for the sling procedure. There were no intraoperative complications and one major postoperative complication. There was no permanent retention and no erosions. Ninety-two percent of patients had either no or rare stress incontinence. Postoperatively, 7% of patients developed de novo urge incontinence. CONCLUSION: We describe excellent results with a new simple, quick, and inexpensive method to correct SUI by placing a polypropylene mesh under the distal urethra.

Cystoscopy↗
PubMed2000

Filamentous growth of Saccharomyces cerevisiae is regulated by manganese.

The Candida albicans INT1 gene is a virulence factor that contributes to both adhesion and filamentous growth of the fungus. Expression of INT1 in the budding yeast Saccharomyces cerevisiae directs both adhesion and filamentous growth. Because Int1p contains two predicted divalent cation-binding motifs, we asked whether divalent cations are important for the role of Int1p in filament formation. In this study, we found that INT1-induced filamentous growth (I-IFG) is sensitive to the divalent cation chelator EDTA and that this EDTA sensitivity can be ameliorated by the addition of Mn(2+), but not Mg(2+) or Ca(2+) ions. The addition of MnCl(2) restored both the proportion of cells forming filaments and the length of filaments formed. Expression of INT1 in S. cerevisiae mutants that reduce the intracellular concentration of Mn(2+) did not affect I-IFG. Interestingly, the Mn(2+) dependence of I-IFG is not dependent upon the presence of the putative divalent cation-binding domains found in INT1. Rather, we found that polarized growth induced by mutations in CDC12 and CLA4 or by expression of excess SWE1 was also sensitive to EDTA treatment and was restored by the addition of MnCl(2) but not by the addition of CaCl(2). Thus, our results suggest that in S. cerevisiae polarized growth is dependent upon the presence of Mn(2+) ions.

Amino Acid Motifs↗
PubMed2000

Angiogenic therapy for the chronically ischemic lower limb in a rabbit model.

The purpose of this study was to evaluate the long-term effectiveness of basic fibroblast growth factor (bFGF) in achieving neovascularization following ischemia from arterial ligation and to determine an optimal dosage level. We used an Ameroid constrictor to produce progressive occlusion of the left femoral artery of rabbits. At 2 weeks, the rabbits were randomized to receive intravenous injection of vehicle (group A, n = 15); 3 microg/kg/day bFGF (group B, n = 12); 10 microg/kg/day bFGF (group C, n = 12); or 16 microg/kg/day bFGF (group D, n = 15) for 3 days. At 1 to 37 days after surgery, we assessed limb neovascularization by transcutaneous oximetry (TCPO(2)), angiography, heart rate, arterial pressure, peripheral vascular resistance (PRU), and muscle blood flow (MBF) during steady-state intra-arterial infusion of saline (basal), acetylcholine, papaverine, or serotonin under anesthesia and capillary density (cap/mm(2)) and capillary per muscle fiber ratio (cap/F). Groups B and C showed significantly greater change in TCPO(2) over time than groups A and D (P < 0.0001). Group D showed the lowest TCPO(2) values from days 14 to 37 and group C the highest. Groups B and C showed a higher number of vessels filled with contrast agent than groups A and D (P < 0.0001). Calf cap/mm(2) and cap/F were significantly higher in groups B and C than groups A and D (P < 0.0001). Calf basal MBF values were higher in groups B and C than in groups A and D, but were not statistically significant. Group D showed the highest level in basal PRU. There were no significant differences in heart rate or blood pressure among the groups. These results show (1) treatment with bFGF has no adverse hemodynamic effects, (2) bFGF enhances angiogenesis and circulation at moderate doses, and these effects persist at least several weeks, and (3) high doses of bFGF may inhibit angiogenesis and collateral circulation.

Animals↗
PubMed2000

Hysteroscopic endometrial ablation using free heated saline for the treatment of menorrhagia.

STUDY OBJECTIVE: To assess the safety and efficacy of hysteroscopic endometrial ablation using controlled intrauterine instillation and circulation of heated (90 degrees C) saline. DESIGN: Phase II clinical study (Canadian Task Force classification II-2). SETTING: Preliminary study performed in an outpatient ambulatory surgery center of a university hospital. PATIENTS: Twenty women with menorrhagia of benign causes. INTERVENTION: Hysteroscopic endometrial ablation. MEASUREMENTS AND MAIN RESULTS: There were no complications. At no time did fluid leak from the fallopian tubes or cervix during treatment. Six patients had concurrent laparoscopy to measure serosal temperatures and to observe fimbriae directly during the 10-minute treatment. Serosal and endocervical temperatures were not elevated. Eighteen women kept evaluable menstrual diaries for 2 months before and 12 months after surgery. Ten women (55.6%) became amenorrheic, four (22.1%) hypomenorrheic, and three (16.7%) returned to normal periods after 12 months of follow-up. One woman (5.6%) reported a 75% decrease in menstrual flow but continued to be menorrhagic by definition. One patient subsequently underwent hysterectomy for simple endometrial hyperplasia. CONCLUSION: This procedure appears to be a safe method of globally ablating the endometrium, resulting in effective treatment of menorrhagia.

Adult↗
PubMed2000

The efficacy of surgically placed epidural catheters for analgesia after posterior spinal surgery.

Posterior spinal fusion for correction of scoliosis is a major procedure for which the provision of satisfactory, safe postoperative analgesia is often a problem. One possible solution involves the placement of epidural catheters under direct vision by the surgeon at the end of the procedure, followed by an epidural infusion of local anaesthetic with or without an opioid. Despite its simplicity, this technique has not been reported as being consistently successful. We report an observational study of the analgesia achieved with surgically placed epidural catheters and of the reasons for the failure of the technique. Fourteen consecutive patients undergoing posterior spinal fusion had epidural catheters placed by the surgeon and had radio-opaque dye injected down the catheter 15 min before their routine postoperative chest X-ray. Analgesia was assessed at 0, 6, 12 and 24 h after surgery using visual analogue scores. Five patients had inadequate pain control; none of these patients had dye visible in the epidural space. Seven patients had dye visible in the epidural space; all of these cases had satisfactory analgesia. In two cases, dye was observed in the paravertebral gutters; both of these patients had satisfactory postoperative analgesia. This small pilot study suggests that correctly placed 'surgical' epidural catheters are capable of providing good analgesia after posterior spinal fusion and that misplaced catheters, seen in a large proportion of patients, are associated with inadequate analgesia.

Adolescent↗
PubMed2000

Identification of a novel allele of SIR3 defective in the maintenance, but not the establishment, of silencing in Saccharomyces cerevisiae.

Using a screen for genes that affect telomere function, we isolated sir3-P898R, an allele of SIR3 that reduces telomeric silencing yet does not affect mating. While sir3-P898R mutations cause no detectable mating defect in quantitative assays, they result in synergistic mating defects in combination with mutations such as sir1 that affect the establishment of silencing. In contrast, sir3-P898R in combination with a cac1 mutation, which affects the maintenance of silencing, does not result in synergistic mating defects. MATa sir3-P898R mutants form shmoo clusters in response to alpha-factor, and sir3-P898R strains are capable of establishing silencing at a previously derepressed HML locus with kinetics like that of wild-type SIR3 strains. These results imply that Sir3-P898Rp is defective in the maintenance, but not the establishment of silencing. In addition, overexpression of a C-terminal fragment of Sir3-P898R results in a dominant nonmating phenotype: HM silencing is completely lost at both HML and HMR. Furthermore, HM silencing is most vulnerable to disruption by the Sir3-P898R C terminus immediately after S-phase, the time when new silent chromatin is assembled onto newly replicated DNA.

Alleles↗
PubMed2000

beta-adrenergic desensitization after burn excision not affected by the use of epinephrine to limit blood loss.

BACKGROUND: Burn patients have impaired myocardial function and decreased beta-adrenergic responsiveness. Further beta-adrenergic dysfunction from systemic absorption of topically administered epinephrine that is given to limit blood loss during burn excision could affect perioperative management. The authors evaluated the effect of topical epinephrine administration to patients during burn excision on the lymphocytic beta-adrenergic response. METHODS: Fifty-five patients (age, 2-18 yr) with 20-90% body surface area burns received a standardized anesthetic for a burn excision procedure. Lymphocyte samples were taken at baseline and 1 and 3 h after the initial use of epinephrine (n = 43) or thrombin (controls, n = 12). Plasma epinephrine levels were measured by high-performance liquid chromatography. Lymphocyte beta-adrenergic responsiveness was assessed by measuring production of cyclic adenosine monophosphate (cAMP) after stimulation with isoproterenol, prostaglandin E1 (PGE1), and forskolin. beta-adrenergic receptor binding assays using iodopindolol and CGP12177 yielded beta-adrenergic receptor density. RESULTS: Epinephrine levels were elevated at 1 h (P < 0.01) and 3 h (P < 0.01) after epinephrine use but not in control patients. Production of cAMP in lymphocytes 1 h after epinephrine was greater in patients receiving epinephrine than in control patients on stimulation with isoproterenol (P < 0.05) and PGE1 (P < 0.05). Three hours after epinephrine administration, production of cAMP decreased when compared with baseline in both control patients and those receiving epinephrine after stimulation with isoproterenol (P < 0. 05), PGE1(P < 0.05), and forskolin (P < 0.05). Lymphocytic beta-adrenergic receptor content was not changed. CONCLUSIONS: Topical epinephrine to limit blood loss during burn excision resulted in significant systemic absorption and increased plasma epinephrine levels. Acute sensitization of the lymphocytic beta-adrenergic cascade was induced by the administration of epinephrine reflected by increased cAMP production after stimulation with isoproterenol and PGE1. The lymphocytic beta-adrenergic cascade exhibited homologous and heterologous desensitization 3 h after the use of epinephrine or thrombin, indicating that epinephrine administration was not a causative factor.

Administration, Topical↗
PubMed2000

Duodenojejunitis: is it idiopathic or is it Henoch-Schönlein purpura without the purpura?

BACKGROUND: Henoch-Schönlein purpura is a small-vessel vasculitic disease that most often affects the skin. Gastrointestinal manifestations have been well described, including duodenojejunal inflammation (DJI). METHODS: Four children with DJI and clinical features of HSP are described, in whom the rash was either not present or appeared atypically late in the illness. RESULTS: The characteristic rash did not develop in three children, and it developed much later in one. The patients (three boys and one girl) were aged between 7 and 9 years (mean, 7.5 years). Growth characteristics were normal. In all patients, pain occurred acutely with colicky abdominal pain in the spring or fall of the year, and all stools were positive for occult blood. No infectious cause was identified. Upper gastrointestinal endoscopic examinations demonstrated significant visual and histologic duodenitis in a pattern consistent with previous reports in children with known HSP. Factor XIII activity was absent. Immunoglobulin A levels were increased in three of four children. All children made a prompt recovery with the administration of intravenous glucocorticoids. In one child, the characteristic rash of HSP developed 18 weeks after the initial examination. CONCLUSION: Duodenojejunal inflammation may be the primary manifestation of HSP, even in the absence of the characteristic rash.

Anti-Inflammatory Agents↗
PubMed2000

Report of the international consensus development conference on female sexual dysfunction: definitions and classifications.

PURPOSE: Female sexual dysfunction is highly prevalent but not well defined or understood. We evaluated and revised existing definitions and classifications of female sexual dysfunction. MATERIALS AND METHODS: An interdisciplinary consensus conference panel consisting of 19 experts in female sexual dysfunction selected from 5 countries was convened by the Sexual Function Health Council of the American Foundation for Urologic Disease. A modified Delphi method was used to develop consensus definitions and classifications, and build on the existing framework of the International Classification of Diseases-10 and DSM-IV: Diagnostic and Statistical Manual of Mental Disorders of the American Psychiatric Association, which were limited to consideration of psychiatric disorders. RESULTS: Classifications were expanded to include psychogenic and organic causes of desire, arousal, orgasm and sexual pain disorders. An essential element of the new diagnostic system is the "personal distress" criterion. In particular, new definitions of sexual arousal and hypoactive sexual desire disorders were developed, and a new category of noncoital sexual pain disorder was added. In addition, a new subtyping system for clinical diagnosis was devised. Guidelines for clinical end points and outcomes were proposed, and important research goals and priorities were identified. CONCLUSIONS: We recommend use of the new female sexual dysfunction diagnostic and classification system based on physiological as well as psychological pathophysiologies, and a personal distress criterion for most diagnostic categories.

Female↗
PubMed1999

Miltefosine, an oral agent, for the treatment of Indian visceral leishmaniasis.

BACKGROUND: There is no effective orally administered medication for any leishmania infection. We investigated miltefosine, which can be taken orally, for the treatment of Indian visceral leishmaniasis. Miltefosine is a phosphocholine analogue that affects cell-signaling pathways and membrane synthesis. METHODS: The study was an open-label, multicenter, phase 2 trial in which four 30-person cohorts received 50, 100, or 150 mg of miltefosine per day for four or six weeks. The 120 patients, who ranged in age from 12 to 50 years, had anorexia, fever, and splenomegaly with at least moderate (2+) leishmania in a splenic aspirate. A parasitologic cure was defined by the absence of parasites in a splenic aspirate obtained two weeks after completion of treatment. The clinical response was assessed at six months. RESULTS: In all 120 patients there was an initial parasitologic cure. Six patients had clinical and parasitologic relapses; the remaining 114 patients had not relapsed by six months after treatment, for a cure rate of 95 percent (95 percent confidence interval, 89 to 98 percent). With the regimen of 100 mg of miltefosine per day (approximately 2.5 mg per kilogram of body weight per day) for four weeks, 29 of 30 patients (97 percent) were cured. Gastrointestinal side effects were frequent (occurring in 62 percent of patients) but mild to moderate in severity, and no patient discontinued therapy because of gastrointestinal side effects. In two patients, treatment was discontinued because of elevated levels of aspartate aminotransferase or creatinine; in both patients the levels rapidly returned to normal. In 12 other patients, the level of aspartate aminotransferase increased to 100 to 150 U per liter during treatment. CONCLUSIONS: Orally administered miltefosine appears to be an effective treatment for Indian visceral leishmaniasis.

Administration, Oral↗
PubMed1999

Development of human and rabbit vaginal smooth muscle cell cultures: effects of vasoactive agents on intracellular levels of cyclic nucleotides.

In this study, we subcultured and characterized human and rabbit vaginal smooth muscle cells and investigated the synthesis of second messenger cyclic nucleotides in response to vasodilators and determined the activity and kinetics of phosphodiesterase (PDE) type 5 (EC 3.1.4.35 3',5'-cyclic GMP phosphodiesterase). Cultured vaginal cells exhibited growth characteristics typical of smooth muscle cells and immunostained with antibodies against alpha smooth muscle actin. The cells retained functional prostaglandin E and beta-adrenergic receptors as demonstrated by increased intracellular cAMP synthesis in response to PGE1, or isoproterenol. The response to these vasoactive substances was augmented with forskolin, suggesting stabilization of G-protein-activated adenylyl cyclases. Treatment with the nitric oxide donor, sodium nitroprusside, in the presence of sildenafil, a PDE type 5 inhibitor, enhanced intracellular cGMP synthesis and accumulation. Incubation of rabbit vaginal tissue with sildenafil, sodium nitroprusside, and PGE1 or forskolin produced a marked increase in intracellular cGMP. These observations were similar to findings with cultured cells and suggest that subcultured cells retain functional characteristics exhibited in intact tissue. The cells retained phosphodiesterase type 5 expression as shown by specific cGMP hydrolytic activity. Sildenafil and zaprinast inhibited cGMP hydrolysis competitively and bound with high affinity (Ki = 7 and 250 nM, respectively). These observations suggest that cultured human and rabbit vaginal smooth muscle cells retained their metabolic functional integrity and this experimental system should prove useful in investigating the pathway of nitric oxide and PDE type 5 inhibitors in modulating vaginal smooth muscle tone.

1-Methyl-3-isobutylxanthine↗
PubMed1999

Use of "N-in-One" dosing to create an in vivo pharmacokinetics database for use in developing structure-pharmacokinetic relationships.

The purpose of this work was (1) to determine if useful in vivo pharmacokinetic data could be obtained after simultaneous administration of 5-22 compounds of a chemically congeneric series to dogs and (2) to determine if structure-pharmacokinetic relationships could be derived from such studies. Mixtures of structurally related alpha-1 antagonist compounds (5-22) were administered intravenously to conscious dogs. Blood samples were taken over the next 24 h and analyzed by LC/MS to determine plasma levels and pharmacokinetics of each compound. The pharmacokinetics of 17 of these compounds were also determined after individual administration. Results obtained in the N-in-One format for 17 compounds correlated well with results obtained when these same compounds were administered individually. The N-in-One method is a useful method for obtaining pharmacokinetic data on 5-20 molecules in a single animal at one time. The increased throughput in obtaining important pharmacokinetic information should enhance the drug discovery process. In addition, it was possible to determine the extent to which various chemical substitutions did or did not affect pharmacokinetic parameters.

Adrenergic alpha-Antagonists↗
PubMed1999

Costimulation of CD28- T cells through CD3 and beta1-integrins induces a limited Th1 cytokine response.

The costimulatory molecule CD28 regulates antigen-specific T-cell proliferation and the synthesis of multiple cytokines. The absence of CD28 on a subset of CD8bright+ T cells suggests that these cells may utilize alternative costimulatory pathways or have a limited cytokine response to presented antigen. We used fibronectin, a ligand for the beta1-integrins alpha4beta1 and alpha5beta1, as an alternate costimulatory ligand to assess the functional phenotype of CD8bright+CD28- T cells. CD25 expression was significantly up-regulated in CD8bright+CD28- T cells by immobilized anti-CD3i with fibronectin. Costimulation with fibronectin also significantly augmented anti-CD3i-induced IFN-gamma production only among CD8bright+CD28- T cells. The CD8bright+CD28- T cells did not produce significant IL-2 and IL-10 even in response to maximal stimulation with phorbol myristate acetate and ionomycin. These data support a costimulatory role for ss1-integrins in CD8bright+CD28- T cells and indicate that CD8bright+ CD28- T cells have a restricted Th1 cytokine repertoire.

CD28 Antigens↗
PubMed1999

Malaria prophylaxis using azithromycin: a double-blind, placebo-controlled trial in Irian Jaya, Indonesia.

New drugs are needed for preventing drug-resistant Plasmodium falciparum malaria. The prophylactic efficacy of azithromycin against P. falciparum in malaria-immune Kenyans was 83%. We conducted a double-blind, placebo-controlled trial to determine the prophylactic efficacy of azithromycin against multidrug-resistant P. falciparum malaria and chloroquine-resistant Plasmodium vivax malaria in Indonesian adults with limited immunity. After radical cure therapy, 300 randomized subjects received azithromycin (148 subjects, 750-mg loading dose followed by 250 mg/d), placebo (77), or doxycycline (75, 100 mg/d). The end point was slide-proven parasitemia. There were 58 P. falciparum and 29 P. vivax prophylaxis failures over 20 weeks. Using incidence rates, the protective efficacy of azithromycin relative to placebo was 71.6% (95% confidence interval [CI], 50.3-83.8) against P. falciparum malaria and 98.9% (95% CI, 93.1-99.9) against P. vivax malaria. Corresponding figures for doxycycline were 96.3% (95% CI, 85.4-99.6) and 98% (95% CI, 88.0-99.9), respectively. Daily azithromycin offered excellent protection against P. vivax malaria but modest protection against P. falciparum malaria.

Adolescent↗