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Biomedical subjects

R H Gelber

Publications and source records attributed to R H Gelber.

At least 55 records · Page 3Linked to original sources
PubMed1987

Further studies of the killing of M. leprae by aminoglycosides: reduced dosage and frequency of administration.

The bactericidal activity of the aminoglycoside antibiotics streptomycin and kanamycin for Mycobacterium leprae in mice was assessed, both alone and in combination with rifampin, utilizing various dosage schedules. As in previous studies, 100 mg/kg five times weekly of streptomycin and kanamycin resulted, respectively, in 96% +/- 2% and 89% +/- 6% bactericide. Reducing the dosage of streptomycin to 50 mg/kg, 25 mg/kg, and even 12.5 mg/kg resulted in less but significant bactericidal activity. Such a reduction of kanamycin dosage resulted in no significant bactericidal activity. Reducing the frequency of administration of streptomycin (100 mg/kg) to twice weekly and once weekly resulted in a decreased but still significant killing of M. leprae; for kanamycin such a reduction in frequency of administration resulted in loss of bactericidal activity. Streptomycin when combined with rifampin was found more bactericidal than either drug alone, even when each was administered only once monthly.

Animals↗
PubMed1986

Quantitation of the phenolic glycolipid of Mycobacterium leprae and relevance to glycolipid antigenemia in leprosy.

Chemical and immunologic procedures have been developed for quantitation, in the body fluids of patients with leprosy, of phenolic glycolipid I, the major specific antigen of the leprosy bacillus. Serum samples were extracted with CHCl3/CH3OH and fractionated on columns of silicic acid. Thin-layer chromatography with a sensitivity of about 500 ng allowed detection of the glycolipid in untreated lepromatous and borderline patients, and high-pressure liquid chromatography gave a quantitation of 0.8-3.7 micrograms/ml of serum from four patients. An ELISA-inhibition assay with polyclonal antibodies to glycolipid corroborated these figures. Dot-ELISA on nitrocellulose with polyclonal and monoclonal IgG antibodies allowed for much greater sensitivity (500 pg) and semiquantitative evaluation. Small quantities of glycolipid were present in the urine of patients with lepromatous leprosy. In sera obtained from patients undergoing chemotherapy, the amount of glycolipid declined sooner than did titer of antibody. This experimental approach is applicable to diagnosis of leprosy, bacillary quantification, and standardization of skin-test reagents and vaccines.

Animals↗
PubMed1986

Superiority of the neonatally thymectomized Lewis rat (NTLR) to monitor a clinical trial in lepromatous leprosy of the two regimens of rifampin and dapsone.

The ability of the neonatally thymectomized Lewis rat (NTLR) and the congenitally athymic (nude) rat systems to detect low numbers of viable Mycobacterium leprae in tissues from lepromatous leprosy patients undergoing short-course chemotherapy was compared with that of the commonly employed mouse foot pad assay. Fifteen previously untreated lepromatous patients were randomly assigned to treatment regimens of either a single initial 1500 mg dose of rifampin plus daily doses of 100 mg of dapsone, or weekly doses of 900 mg of rifampin plus daily doses of 100 mg of dapsone. Four skin biopsies from each patient taken sequentially up to one month after initiation of therapy were used as the source of the M. leprae inocula. Only 2 of 57 skin biopsies (2%) proved positive for viable M. leprae following direct inoculation into mouse foot pads. However, 30 of 58 patient biopsies (52%) provided positive for viable M. leprae following direct passage into NTLR foot pads or in subsequent mouse subpassage. In contrast, the nude rat was observed to be a poor monitor of such trials. Although not statistically significant, the regimen consisting of a single dose of rifampin plus daily dapsone resulted in a lower percentage of biopsies found to contain viable M. leprae at each of the four sampling intervals.

Animals↗
PubMed1985

Evaluation of testing modalities for peripheral neuropathy in lepromatous Hansen's disease.

To assess methods for detecting peripheral neuropathy, 28 previously untreated patients with lepromatous Hansen's disease underwent upper extremity manual muscle testing, sensory testing by using monofilaments, and electrophysiological nerve conduction studies (motor and sensory) at their initial examination. All but three patients demonstrated some abnormality identified by at least one of the testing procedures. Sensory testing with monofilaments located the greatest number of abnormalities found in 24 of the 28 patients. Next, electrophysiological testing demonstrated neuropathy in 21 of the 28 patients tested; 20 of these patients had sensory abnormalities and 20 had motor irregularities. The least sensitive method was manual muscle testing, which detected abnormalities in only 12 patients. Furthermore, sensory testing with monofilaments revealed peripheral neuropathy in 5 patients whose electrophysiological studies showed normal sensory patterns, and electrophysiological testing detected abnormalities in 1 patient whose sensory monofilament examination was normal. The results of this study support the usefulness of all three testing modalities.

Adult↗
PubMed1985

Defective cell-mediated immunity in leprosy: failure of T cells from lepromatous leprosy patients to respond to Mycobacterium leprae is associated with defective expression of interleukin 2 receptors and is not reconstituted by interleukin 2.

Patients with lepromatous leprosy (LL) but not borderline tuberculoid leprosy (BT) have defective cell-mediated immune responses to Mycobacterium leprae, despite normal responses to other stimuli, as judged by in vivo skin testing and in vitro lymphocyte transformation. To investigate the basis of the immune defect in LL patients, we studied the ability of patient mononuclear leukocytes to produce interleukin 1 (IL 1) and interleukin 2 (IL 2) upon stimulation with M. leprae, and determined the ability of exogenous IL 1 and IL 2 to reconstitute the LL patient response to this antigen in vitro. Equal numbers of adherent non-T cells from LL and BT patients produced similar amounts of IL 1 upon challenge with M. leprae, and addition of IL 1 to the culture medium failed to reconstitute the response of lymphocytes from LL patients to M. leprae. On the other hand, T cells of LL patients failed to express receptors for IL 2 or to produce IL 2 in response to M. leprae, whereas similarly treated T cells of BT patients both expressed IL 2 receptors and produced IL 2. Finally, recombinant human IL 2 purified to homogeneity as well as crude supernatants of mitogen-activated lymphocytes failed to reconstitute the response of LL patients to M. leprae. These results suggest that T cells of LL patients fail to respond to M. leprae despite an ability to produce IL 1 and that their failure to express receptors for IL 2 may explain both defective proliferation and the failure of exogenous IL 2 to reconstitute the response.

Animals↗
PubMed1984

Use of an artificial antigen containing the 3,6-di-O-methyl-beta-D-glucopyranosyl epitope for the serodiagnosis of leprosy.

The coupling of synthetic 3,6-di-O-methyl-beta-D-glucopyranosyl-(1----4)-2,3-di-O-methyl-alpha-L -rhamnopyranose, the hapten determinant of phenolic glycolipid I from Mycobacterium leprae, to bovine serum albumin (BSA) by reductive amination produced the antigen epsilon-N-1-[1-deoxy-2,3-di-O-methyl-4-O-(3',6'-di-O-methyl-beta -D-glucopyranosyl)-rhamnitol]-lysyl-BSA, which proved highly sensitive in ELISA and showed good concordance with the native glycolipid in analysis of serum samples from 223 leprosy patients. Conjugates prepared from 6-O-methyl-beta-D-glucopyranosyl- or beta-D-glucopyranosyl-containing disaccharides were inactive and those containing noncyclic 3,6-di-O-methyl-glucitol showed little activity. Thus 3,6-di-O-methyl-beta-D-glucopyranose in its cyclic hemiacetal form is necessary for binding anti-glycolipid IgM from leprosy patients. Analysis of serum samples from healthy subjects showed a false-positive rate of 2.4% (four of 169) against the glycolipid and 3.6% (six of 169) against the glycoconjugate. Comparable figures for samples of sera of tuberculosis patients were 3.0% (two of 66) and 9.0% (six of 66), respectively. Alternative synthesizing strategies may diminish this cross-reactivity. The prospects of a fully synthetic specific antigen for the worldwide serodiagnosis of leprosy look promising.

Antigens, Bacterial↗
PubMed1984

Localization of catheter-induced urinary tract infections: interpretation of bladder washout and antibody-coated bacteria tests.

Accurate differentiation of upper from lower urinary tract infection (UTI) has been reported based on the presence or absence of antibody-coated bacteria (ACB) in the urinary sediment. The specificity of ACB localization in adults has been reported to be high based on a strong correlation with localization results obtained with the bladder washout technique. The present study examines the efficacy of ACB testing with respect to accurate anatomic localization of UTI in 20 studies in 14 patients exhibiting bacteriuria as a result of chronic urethral catheterization. 17 studies (85%) demonstrated significant ACB. Localization of UTI was assessed in each study by the bladder washout technique. Following instillation of a washout solution, a normal decrease in colony counts was observed in only 3 studies (15%), a frequency significantly lower than the value of 90% previously reported in noncatheterized bacteriuric patients (p less than 0.001). Each of these 3 patients was ACB-positive, yet anatomic localization indicated lower tract UTI. The observed characteristics of the 14 patients included the absence of upper tract signs and symptoms, and spontaneous clearing of ACB and bacteriuria following catheter removal. These findings suggest that in chronically catheterized patients, both (1) the observed abnormal resistance of bacteria to bladder washout and (2) the high frequency of positive ACB tests are indices of severe chronic tissue invasion and intense antibody production in the lower urinary tract in this condition and thus not of value in localizing infection to the upper tract. Neither ACB nor washout testing with current techniques can reliably localize UTI in chronically catheterized patients.

Adult↗
PubMed1984

Primary dapsone-resistant leprosy in San Francisco.

The dapsone sensitivity of strains of Mycobacterium leprae from 54 multibacilliferous untreated leprosy patients presenting to the United States Public Health Service Hospital in San Francisco, California, U.S.A., from 1978 to 1981 was studied by mouse foot pad inoculation. M. leprae from 53 patients were found fully sensitive to dapsone. M. leprae from one patient were resistant to only the lowest dietary level of dapsone, 0.0001%, since growth of the bacilli was inhibited by higher and clinically easily achievable levels. Mouse plasma dapsone levels confirmed the reliability of the drug-containing diets.

Adolescent↗