Search PubMed⌕ Search

Biomedical subjects

M Dietz

Publications and source records attributed to M Dietz.

At least 37 records · Page 2Linked to original sources

Intrabacterial sodium-to-potassium ratios and ATP contents of Mycobacterium leprae from ofloxacin-treated patients.

In a clinical trial including 17 multibacillary leprosy patients the in vivo effectiveness of ofloxacin on Mycobacterium leprae was tested via mass spectrometric determination of intrabacterial ratios of the concentrations of the sodium and potassium ions of individual organisms and of the ATP content per 10(6) bacteria isolated from skin biopsies. After 3 months of treatment, the in vivo drug effect could be determined with at least one of the two methods in 14 cases. Both methods revealed that in two cases the bacteria definitely did not respond to a 3-month ofloxacin monotherapy (200 mg twice daily). In three further cases a nonresponse of the M. leprae organisms was suspected from the mass spectrometric measurements. In the responder cases, the M. leprae were severely impaired. From the intrabacterial cation ratios the percentage of viable organisms averaged over all untreated biopsies was determined to be 58% and the percentage-killing during the first 3 months of treatment was 72%.

Adenosine Triphosphate↗

Determination of in vivo and in vitro drug effects of mycobacteria from the mass spectrometric analysis of single organisms.

Laser microprobe mass analysis of single bacterial organisms allows the determination of their intrabacterial ratio of sodium-to-potassium ions and the registration of fragment ions originating from their organic bacterial cell matrices as mass fingerprint spectra. It has been established previously that the intrabacterial cation ratio provides information on the physiological state of an individual bacterial cell. In the present experiments it is also shown, with different cultivable mycobacterial species and strains (drug sensitive and resistant) exposed to various drugs, that data derived from the evaluation of the mass fingerprint spectra reflect changes in the degree of impairment. The analysis of Mycobacterium leprae derived from a limited number of skin biopsies of lepromatous/borderline lepromatous leprosy patients under World Health Organization-recommended multiple-drug therapy (WHO/MDT) showed impairment of the organisms with both of the methods of measurement in proportion to the duration of treatment except in one case. In one M. leprae population from a patient who had been treated for 19 months, the fingerprint evaluation gave the first evidence for an insufficient response to treatment. This was further confirmed by the unusual frequency distribution of the Na+,K+ ratios which revealed the existence of two subpopulations, one impaired and one unimpaired.

Anti-Bacterial Agents↗

Administration of recombinant interleukin-2 reduces the local parasite load of patients with disseminated cutaneous leishmaniasis.

Three patients with disseminated cutaneous leishmaniasis received three intranodular injections of 10 micrograms of recombinant interleukin 2 (rIL-2) at 48-h intervals. After 7 and 14 days, 4-mm punch biopsies were taken of control and injected nodules and processed for histology, electron microscopy, immunocytochemistry, and parasite culture. Control sites exhibited loose infiltrates of parasitized macrophages and T cells predominantly of the CD8+ phenotype. Amastigotes were present in large numbers and were found distributed within tightly apposed endosomes and larger vacuoles. After the administration of rIL-2, there was a prominent influx of T cells, predominantly of the CD4+ phenotype, and an increased number of plasma cells. At 7 days, leishmanial amastigotes were present in either the same or somewhat reduced numbers but predominantly within large, lucent vacuoles. By 14 days the number of amastigotes was strikingly lower. Lymphokine-treated skin sites became sterile in two patients, as evaluated by parasite culture after rIL-2 injection. The results suggest that the local administration of rIL-2 induces a beneficial enhancement of the cellular immunity with a consequent disposal of parasites in the cutaneous site.

Adolescent↗

Intradermal recombinant interleukin 2 enhances peripheral blood T-cell responses to mitogen and antigens in patients with lepromatous leprosy.

Thirty-one patients with lepromatous leprosy received recombinant interleukin 2 (IL-2) intradermally in doses ranging from 10 to 30 micrograms. Before injection and at time intervals of 2-21 days thereafter, samples of peripheral blood mononuclear cells (PBMC) were obtained. Single or multiple injections (1-3) of IL-2 did not modify the total number of circulating lymphocytes or the number of T cells and the CD4/CD8 T-cell ratio. However, IL-2 had a pronounced influence on the [3H]thymidine incorporation in response to various stimuli 4-8 days after intradermal IL-2. Stimulation indices of three- to sevenfold above pre-IL-2 levels were observed with the polyclonal activator phytohaemagglutinin (PHA) and enhanced thymidine incorporation occurred in the presence of antigens to which the patients were already sensitized, such as purified protein derivative and BCG. IL-2 had no effect on the unresponsive state of lepromatous leprosy patient T cells to the antigens of Mycobacterium leprae.

Administration, Cutaneous↗

The reconstitution of cell-mediated immunity in the cutaneous lesions of lepromatous leprosy by recombinant interleukin 2.

Human rIL-2 (10-30 micrograms) was injected intradermally into the skin of patients with lepromatous leprosy with high bacillary loads. All patients responded to the lymphokine with local areas of induration that peaked at 24 h and persisted for 4-7 d irrespective of whether the site was "normal skin" or a nodular lesion. Within 24 h there was an extensive emigration of T cells and monocytes into the site. The percentage of the dermis infiltrated by mononuclear cells increased by more than sevenfold, peaking at 4 d and persisting for greater than 15 d. Both CD4+ and CD8+ T cells entered the site. T cells of CD4+ phenotype predominated at 2-7 d but by 11 d, CD8+ cells were predominant. Considerable numbers of T6+ Langerhans' cells appeared in the dermis by 72 h and persisted for 3 wk. By 4 d the thickness of the overlying epidermis had increased twofold, and keratinocytes were expressing MHC class II antigen and the IFN-gamma-induced peptide IP-10. Starting at 48 h, there was an extensive destruction of mononuclear phagocytes that contained structurally intact or fragmented M. leprae observed at the electron microscope level. The organisms, either free or contained within endocytic vacuoles, were discharged into the extracellular space and then reingested by blood-borne monocytes. This was followed by marked reductions in the number of acid-fast organisms in the injected site, evident as early as 4-7 d and more marked at 2-3 wk after injection. 13 of 15 patients exhibited a disposal of acid-fast bacilli ranging from 5- to 1,000-fold with a mean value of approximately 100-fold. The administration of IL-2 leads to the generation of an effective cell-mediated immune response, recapitulating an antigen-driven event and leading to striking local reductions in M. leprae. In comparison with the purified protein derivative of tuberculin reaction, bacilli are cleared more promptly, although emigratory cells persist for a shorter time.

Adult↗

[Biofeedback training in fecal incontinence].

In 19 patients with incontinence of various causes a treatment programme was instituted in which by biofeedback training they would learn how to increase the force of contraction of the external anal sphincter in response to balloon distension of the rectum. The degree of incontinence was objectified by anorectal manometry before and after training, as well as 3-6 months after the end of training. This programme significantly increased the force of contraction of the sphincter and pelvic-floor musculature. Twelve patients became continent and have remained so at follow-up. The training regimen was especially successful in patients with an organic cause of the incontinence and those most highly motivated. The investigation also demonstrated that anorectal manometry is a suitable method for the diagnosis of and monitoring the response to treatment of anal incontinence.

Adult↗

Glutamate phase shifts circadian activity rhythms in hamsters.

The suprachiasmatic nuclei (SCN) have been identified as a pacemaker for many circadian rhythms in mammals. Photic entrainment of this pacemaker can be accomplished via the direct retino-hypothalamic tract (RHT). Glutamate is a putative transmitter of the RHT. In the present study it is demonstrated that glutamate injections in the SCN cause phase shifts of the circadian activity rhythm of the hamster. In contrast, glutamate injections outside the SCN or vehicle injections inside the SCN did not affect the circadian phase. These data suggest that glutamate could be involved in photic entrainment of the circadian pacemaker.

Animals↗

The effects of intraventricular carbachol injections on the free-running activity rhythm of the hamster.

The effects of light on the circadian pacemaker in the suprachiasmatic nucleus (SCN) are mediated by the retinohypothalamic tract (RHT) and by the retinogeniculosuprachiasmatic tract (RGST). The neurotransmitter of the RGST is neuropeptide Y. The RHT may contain glutamate and aspartate. Recent evidence indicates that acetylcholine could also be involved in phase shifting by light. We determined that intraventricular injections with an acetylcholine agonist, carbachol, induces phase advances during the subjective day and phase delays during the early subjective night. No differences were observed between phase shifts induced in constant darkness and those induced in continuous light. A dose-response curve for carbachol was described at circadian time 6 (CT6). Injections at CT14 with various dosages of carbachol indicated the same dose dependency for this circadian time. Finally, carbachol injections in split animals resulted in similar responses of the two components of the split activity rhythm.

Animals↗

The China diary. AMRA delegation's visit to China. Part I.

In May, 22 AMRA representatives toured the People's Republic of China at the invitation of the Chinese government. Designated delegates kept a diary of the informational exchange between the AMRA delegates and their hosts, as well as a commentary on places seen during their travels. Their diary entries have been compiled into a two-part article. The first part appears in this issue, and the second part will appear in the September issue.

Abstracting and Indexing↗

[Determination of free and conjugated cis-3,3,5-trimethylcyclohexanol in plasma and urine].

A gas chromatographic procedure was developed to determine free and conjugated cis-3,3,5-trimethylcylcohexanol in plasma and urine. The sample is extracted with dichloromethane when free cis-3,3,5-trimethylcyclohexanol is determined, or with hexane after enzymatic hydrolysis, when conjugated cis-3,3,5-trimethylcyclohexanol is determined. An aliquot of the organic extract is injected into a stainless-steel column (packed with Carbowax 20M, 15% on Chromosorb W AW 100-120 mesh) and detected with a flame ionization detector. Extraction recovery from plasma and urine was almost 100% and the limit of quantification was fixed at 100 ng/ml plasma or urine. The procedure was evaluated in a pharmacokinetic study of cyclandelate and its metabolite cis-3,3,5-trimethylcyclohexanol.

Animals↗

The bioavailability and pharmacokinetics of three zinc salts: zinc pantothenate, zinc sulfate and zinc orotate.

In this study the authors compared the pharmacokinetics of three zinc salts after parenteral and oral administration to rabbits: zinc sulfate, a soluble mineral salt; zinc pantothenate, a soluble organic salt; and zinc orotate, an insoluble organic salt. The results obtained with the two soluble salts were not significantly different (p less than 0.05). Therefore they appear to be bioequivalent. The plasma concentration curve for zinc orotate shows a faster distribution (alpha) and elimination phase (beta) after parenteral administration, and a slower absorption phase (Ka) after oral administration, when compared with that of the other two salts. It was shown that the dissolution behaviour of these zinc salts in water does not correlate with the parameters found in vivo.

Administration, Oral↗

Simultaneous determination of cyclandelate and its metabolite in human plasma by capillary column gas-liquid chromatography.

A method was developed for the simultaneous determination of cyclandelate and mandelic acid concentrations in plasma, involving extraction from plasma followed by trimethylsilylation and chromatography of the derivatives on a glass capillary column with hydrogen flame-ionization detection. Calibration graphs were linear down to at least 20 microgram/ml for each substance. The precision was excellent with a pooled relative standard deviation of 6.3% and 6.4% for cyclandelate and mandelic acid serum samples, respectively. Concentrations below 500 ng/ml of each substance could be detected in human plasma. The method was developed for use in bioavailability and metabolism studies.

Animals↗

Spontaneous regression of Friend-virus-induced erythroleukemia. VII. The genetic control of regression.

The genetic control of spontaneous regression of erythroleukemia was studied in parental and hybrid mice in which leukemia was induced by the regressing strain of Friend virus (RFV). Because in previous studies parental regressor mouse strains tested (N/PLCR, SIM, NIH Swiss) all had the FV-1n/n genotype and the progressor mouse strains (SIM.R, BALB/c) had the Fv-1b/b genotype, we detemined the influence of Fv-1 alleles on regression. Genes which influence regression were dominant and had partial penetrance in (progressor x regressor) F1 mice. Regression occurred in hybrid mice which inherited the Fv-1b/b genes of each of the progressor mouse strains. Regression and Fv-1 alleles also segregated independently in (N/PLCR x BALB/c) F2 mice, in random-bred Swiss mice heterozygous for the Fv-1 gene, in partially inbred Swiss recombinant progressor and regressor mouse lines, and in hybrid mice carrying the Fv-1b/b gene of SIM.R mice. Regressor SIM and progressor SIM.R mice, which were bred to be congeneic at the Fv-1 locus, also differ with respect to recovery from viremia, suggesting that their Rfv-3 genes differ and influence regression. Crosses of SIM and SIM.R mice with the A.BY (Rfv-3s/s) mouse strain confirmed that SIM and SIM.R carry Rfv-3r/r and Rfv-3s/s, respectively. We conclude that Fv-1b/b is not inhibitory to regression nor is the Fv-1 gene a genetic deteminant in the process. The data suggest that regression is influenced by several genes, including those (Rfv-1, Rfv-2, Rfv-3) shown to affect recovery from leukemia in other systems.

Alleles↗

Spontaneous regression of Friend virus-induced erythroleukemia. VI. Structural and antigenic differences between the regressing and conventional strains of virus.

The regressing and conventional strains of Friend virus were compared by neutralization assays, sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and tryptic peptide mapping of the individual viral components. Neutralization rates of the two viruses differed in the presence of monospecific anti-gp70 antiserum and sera from regressed or immunized mice. Neutralization of regressing Friend virus, but not conventional Friend virus, occurred when the viruses were incubated with anti-p15(E) and complement. Human serum inactivated conventional Friend virus more rapidly than regressing Friend virus, probably as a result of virolysis induced by the reaction of viral p15(E) with human complement component C1. Structural differences between the viruses were detected in their gp70 viral glycoproteins and p15(E) and p12 proteins. Analysis of different stocks and clonal isolates of the viruses showed that the differences between the gp70 and p15(E), but not the p12 proteins, were associated with the regressing phenotype of the regressing strain of Friend virus.

Animals↗

Hereditary polyposis coli. III. Genetic and evolutionary fitness.

The numbers of progeny born to 355 patients with heritable polyposis of the colon and to 315 related, but normal, subjects, all old enough to have completed their families, are presented, as well as data on 432 subjects still young enough to have more children. Two main indices are used: mean family size ("genetic fitness") and the complement of the extinction probability of the line ("evolutionary fitness"), both of which suppose a steady state. Point- and interval-estimates (the latter derived by an extension of Stigler's method) are furnished. It is estimated that the probability a new mutant gene will persist is one in four for Gardner syndrome, one in 20 for familial polyposis coli, and 0 for Peutz-Jeghers syndrome. There is evidence of bimodality in family size, suggesting voluntary infertility in a proportion of subjects. The data confirm our provisional working assumption that most families are completed by the time women are in their mid-40's and men in their mid-50's.

Adolescent↗