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Biomedical subjects

J Goldfarb

Publications and source records attributed to J Goldfarb.

At least 91 records · Page 5Linked to original sources

Randomized clinical trial of topical mupirocin versus oral erythromycin for impetigo.

The safety and efficacy of a new topical antiinfective agent, mupirocin, was compared with that of oral erythromycin ethylsuccinate in the treatment of impetigo in children. Sixty-two children aged 5 months to 13 years with impetigo were assigned to be treated with either mupirocin in three daily applications or erythromycin ethylsuccinate (40 mg/kg of body weight per day divided into four doses) according to a randomized treatment schedule. On the initial visit, exudate or cleansed infected sites or both were cultured and therapy was begun. All patients were treated for 8 days. Patients were seen again on days 4 to 5 of therapy, at the end of therapy, and 7 days after the end of therapy. Sites of infection were comparable between the groups, as were bacteriologic responses. At the first visit, 24 of 30 children in the mupirocin group and 14 of 32 children in the erythromycin group were cured or had at least a 75% reduction in size of the lesions. At the end of the study, all 29 of the children in the mupirocin group who came to follow-up, compared with 27 of 29 in the erythromycin group, were cured. Side effects were few. Five children in the erythromycin group developed mild diarrhea. Thus, mupirocin appears to be safe and effective in treating impetigo in children. Our data show a trend toward more rapid clinical response with mupirocin than with erythromycin.

Administration, Oral↗

Lack of effect of oral acyclovir on prevention of aphthous stomatitis.

Aphthous stomatitis (canker sores) is a common cause of recurrent mouth ulceration. The effect of long-term oral acyclovir therapy on aphthous stomatitis recurrences was evaluated in 44 patients who were in a double-blind treatment trial for recurrent genital Herpes simplex infections. Twenty-five subjects received oral acyclovir daily for one year, while 19 received the drug only during outbreaks of herpes. The number of patients who experienced recurrences of aphthous stomatitis and the frequency and duration of attacks per patient were not significantly different between groups. Furthermore, no consistent change in attack rate was observed in members of either group compared to that reported before they had entered the trial. We conclude that oral acyclovir is not effective for prevention of recurrent aphthous stomatitis in most patients.

Acyclovir↗

Once-daily cefadroxil versus oral penicillin in the pediatric treatment of streptococcal pharyngitis.

Thirty-two patients with pharyngitis were randomly assigned to receive either 30 mg/kg of cefadroxil every 24 hours orally or 15 mg/kg of penicillin V potassium every eight hours orally for ten days. Sera for antistreptolysin-O, streptozyme, and anti-DNAase were compared before and after treatment. Twenty patients finished the study and had a confirmed throat culture for the group A streptococcus and at least one fourfold antibody rise. Of these 20 patients, seven of eight in the penicillin group and all 12 in the cefadroxil group were cured at the end of therapy. One patient in the penicillin group had a positive culture at the end of therapy; one patient in each group was recolonized at follow-up culture 10 to 20 days after ending therapy. Seven other patients who finished the study had a positive throat culture but no antibody response and were presumed carriers; these included five in the penicillin and two in the cefadroxil group. One of these presumed carriers had a persistent infection and relapsed two days after the end of therapy. Both therapies appeared to be equally successful and no serious side effects occurred.

Adolescent↗

Intracerebroventricular infusion of inhibitors of endopeptidase-24.11 ('enkephalinase') increases the spontaneous firing frequency of an identifiable set of cells in the substantia nigra.

The effect of inhibitors of the membrane-bound metalloendopeptidase-24.11 ('enkephalinase') on the activity of electrophysiologically identifiable neurons in the substantia nigra is described. Dopaminergic and non-dopaminergic cells were examined. Cells were classified by their responses to striatal stimulation. Only those cells in which the stimulation evoked excitation (alone or mixed with inhibition) responded to the inhibitors. Those cells in which the evoked response was only inhibition did not respond to the drugs. Infusion of 1 mumol of N-[1-(R,S)-carboxy-2-phenyl-ethyl]Phe-pAB (CPAB), 1 or 2 mumol of N-[1-(R,S)-carboxy-3-phenylpropyl]Phe-pAB (CPPAB) into the lateral ventricle produced statistically significant increases (pre- to post-drug treatment) in the spontaneous activity of cells exhibiting excitatory evoked responses: average increases were 33.3%. The increase in spontaneous activity reached an apparent maximum 20 min after the end of the infusion. The increased firing frequency was shown to result from the inhibition of the enzyme, rather than a non-specific effect, as the infusion of 2 mumol of N-[1-(R,S)-carboxy-2-phenyl-ethyl]Leu-pAB, an inhibitor structurally related to CPAB and CPPAB yet two orders of magnitude less potent, was without effect on the activity of nigral neurons. The inhibition of the enzyme by 1 mumol CPAB was verified through in vitro assay. We hypothesize that inhibition of the enzyme enhances peptide-modulated (tachykinin and/or enkephalin) excitation in select neurons of the substantia nigra.

Animals↗

Opsonophagocytic killing antibody to Pseudomonas aeruginosa mucoid exopolysaccharide in older noncolonized patients with cystic fibrosis.

The principal cause of morbidity and mortality in cystic fibrosis is persistent respiratory colonization with mucoid strains of Pseudomonas aeruginosa. To investigate possible mechanisms of resistance to this organism, we studied serum from 16 older (greater than or equal to 12 years) patients not colonized with mucoid P. aeruginosa, 11 older (greater than or equal to 14 years) colonized patients, 10 younger (less than or equal to 11 years) noncolonized patients, and 20 healthy adults. The samples from the older patients not colonized with mucoid P. aeruginosa contained antibody specific to the mucoid-exopolysaccharide antigen, which could mediate bacterial killing in conjunction with complement and white cells (titers of 4 to 80). These opsonophagocytic killing antibodies were not detected in samples from the 20 normal controls (P less than 0.0001 vs. noncolonized older patients) or 9 of 10 younger (less than or equal to 11 years) noncolonized patients (P = 0.0072 vs. noncolonized older patients). Although the patients with chronic colonization had higher titers of serum opsonophagocytic killing antibody than did the older noncolonized patients (P = 0.0005), these antibodies were not specific to the mucoid-exopolysaccharide antigen. We conclude that there is an association between mucoid-exopolysaccharide-specific opsonophagocytic killing antibody and a lack of detectable P. aeruginosa colonization in a subset of older, relatively healthy patients with cystic fibrosis.

Adolescent↗

Serotonin decreases population spike amplitude in hippocampal cells through a pertussis toxin substrate.

Activation of the serotonin1A receptor decreases CA1 population spike amplitude and inhibits forskolin-stimulated adenylate cyclase in rat hippocampus. Pretreatment of rats with pertussis toxin blocked both responses. Because the electrophysiological and biochemical responses to serotonin were correlated after pertussis toxin treatment, we conclude that both responses are mediated by a common regulatory protein, presumably Gi.

Action Potentials↗

Ciprofloxacin monotherapy for acute pulmonary exacerbations of cystic fibrosis.

Ciprofloxacin has potent in vitro activity against Pseudomonas aeruginosa and Pseudomonas cepacia strains isolated from cystic fibrosis patients. Our previous single-dose pharmacokinetic and pharmacodynamic studies identified important differences between cystic fibrosis patients and age- and sex-matched controls. Based on these data, 30 acutely ill cystic fibrosis patients (aged 18 to 44 years) received 750 mg of ciprofloxacin orally every eight hours for 21 days. Multiple timed serum, urine, and sputum samples for pharmacokinetic analysis were obtained on Days 3, 12, 14, and 21 of the study. Estimates of steady-state pharmacokinetic parameters averaged (+/- SD): t1/2 beta, 3.8 (1) hours; Vd/F, 4.4 (2) liters/kg; Cl/F, 772.9 (301) ml/minute/1.73 m2; Fe, 46 percent; peak, 5.4 (2) mg/liter; and trough, 1.8 (0.8) mg/liter. Serum ciprofloxacin concentrations and pharmacokinetic estimates remained unchanged throughout the study. Sputum ciprofloxacin concentrations exceeded those observed in serum. Sputum cultures revealed 43 P. aeruginosa (MIC90 = 2 micrograms/ml) and 15 P. cepacia (MIC90 = 16 micrograms/ml) strains. Sputum ciprofloxacin concentrations exceeded the MIC90 for P. aeruginosa approximately fivefold, yet only eight isolates were fully suppressed. Posttreatment sputum cultures revealed 35 P. aeruginosa (MIC90 = 16 micrograms/ml) and 15 P. cepacia (MIC90 = 16 micrograms/ml). All patients showed clinical improvement based upon the results of pulmonary function tests and an acute clinical efficacy score (median pre 49/post 60). No patients experienced drug-related toxicity. Ciprofloxacin monotherapy is effective for the acute treatment of cystic fibrosis patients. The development of pathogen resistance during oral therapy may limit its utility in ambulatory patients.

Adolescent↗

Sultamicillin in the treatment of superficial skin and soft tissue infections in children.

Fifty-two children with superficial skin and soft tissue infections were randomized to receive sultamicillin or cloxacillin for 7 days. Twenty-one children in each group finished the study. A total of 16 of 21 in the sultamicillin group and 13 of 21 in the cloxacillin group were cured. One child in the sultamicillin group and two in the cloxacillin group failed therapy. Four children who received sultamicillin and six who received cloxacillin had recurrences of lesions. Differences were not statistically significant.

Abscess↗

Single-dose pharmacokinetics of oral ciprofloxacin in patients with cystic fibrosis.

The single-dose pharmacokinetics of oral ciprofloxacin were studied in ten patients with cystic fibrosis aged 18 to 34 years. Each patient received three different drug doses (500 mg, 750 mg, and 1,000 mg) at successive one-week intervals. Dosing and drug assays were double blinded. Blood and urine were assayed over the 48 hours following each dose. Ciprofloxacin was absorbed from the gastrointestinal tract. Peak serum concentrations averaged 2.8, 4.5, and 4.6 micrograms/mL respectively at the three doses, well above the mean inhibitory concentrations of most isolates of Pseudomonas aeruginosa. Time to peak concentration was approximately two hours. The range of sputum levels in three patients was 1.1-2.1 micrograms/mL at four hours after the three doses. The serum elimination half-life was 3.7 hours and was independent of dose. Urinary recovery was 26%; greater than 90% of urinary excretion occurred within the first 12 hours. The results of this study indicate that ciprofloxacin has potential for use in the treatment of P aeruginosa infections in patients with cystic fibrosis.

Administration, Oral↗

EMG biofeedback training, relaxation training, and placebo for the relief of chronic back pain.

24 patients with chronic low back pain were randomly assigned to three treatment conditions: EMG biofeedback, relaxation training, and a placebo condition. Patients were seen for eight sessions and were evaluated before Session 1 and after Session 8. Eight analyses of covariance which were adjusted for age and pretest scores were computed on the final scores to find which variables could detect significant difference between treatments. Age was included as a covariate because the differences in age between conditions were significant. Four variables with significant and nearly significant differences were chosen for analysis. The second set of analyses identified the nature of the differences among the three conditions. These included a priori planned comparisons among conditions, and paired t tests. Relaxation-trained subjects were significantly superior to subjects in the placebo condition, in decreasing pain during the function test, increasing relaxation, and decreasing Upper Trapezius EMG. They were superior to EMG Biofeedback training in increasing reported activity. Both Relaxation and EMG trained subjects were able to reduce Upper Trapezius EMG by Session 8. Relaxation-trained subjects showed significant change on eight of the 14 possible comparisons for each treatment condition. EMG biofeedback training showed significant favorable results in only one condition; the placebo condition showed no significant results. Relaxation training gave better results in reducing EMG and pain, and in increasing relaxation and activity than either EMG biofeedback alone or a placebo condition.

Back Pain↗

Serotonin produces a reversible concentration dependent decrease of population spikes in rat hippocampal slices.

Superfusion of slices of rat dorsal hippocampus in vitro with serotonin (5-HT) reversibly decreases the amplitude of the CA1 population spike evoked by stimulation of stratum radiatum. The magnitude of the drug effect is concentration dependent and is greater on submaximal than on maximal population spikes. Concentration-response curves were generated using population spikes 30-60% of maximum by superfusion with increasing concentrations of 5-HT interspersed with perfusion of drug free medium. The EC50 for 5-HT was 3.2 microM. Repeated applications of a maximal dose of 5-HT did not produce tachyphylaxis. The reversibility, reproducibility and concentration dependence of the 5-HT response in the rat hippocampal slice makes this preparation useful for rigorous pharmacological classification of the receptor(s) involved.

Animals↗

Meningitis caused by multiply antibiotic-resistant viridans streptococci.

Two patients are described with meningitis caused by multiply antibiotic-resistant strains of viridans streptococci; both isolates were resistant to penicillin (MIC greater than 3 micrograms/ml) (4.8 U/ml) and to several other antimicrobial agents. Our findings underscore the importance of doing in vitro sensitivity testing with clinical isolates of viridans streptococci to determine appropriate therapy for infected patients. Multiply antibiotic-resistant strains of viridans streptococci have also been recently isolated in the same populations in South Africa in which the prevalence of resistant Streptococcus pneumoniae is high. Therefore, isolation of resistant clinical strains of viridans streptococci may suggest the need for in vitro surveillance of emerging antibiotic resistance in both streptococcal species.

Anti-Bacterial Agents↗

The penetration of gentamicin into the vitreous humor in man.

Twenty-two patients received gentamicin intramuscularly or subconjunctivally 35-220 min prior to undergoing ocular surgery. There were no detectable gentamicin levels in the vitreous humor of patients who received the drug systemically. Of the patients who received gentamicin subconjunctivally, three quarters had no detectable gentamicin levels, only three of these patients had therapeutic concentrations in their vitreous humor. These results confirm kinetic drug studies performed in animals in which low or absent vitreal gentamicin levels were observed following systemic and subconjunctival administrations. It is suggested that intravitreal injection of aminoglycosides is required in the treatment of bacterial endophthalmitis.

Adult↗