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Biomedical subjects

G Nahler

Publications and source records attributed to G Nahler.

15 recordsLinked to original sources

The Austrian Immunoglobulin in MS (AIMS) study: final analysis.

From observational studies and positive experience in other autoimmune disorders it has been speculated that intravenous immunoglobulin (IVIG) may be effective for the interval treatment of MS. The Austrian Immunoglobulin in Multiple Sclerosis (AIMS) study was the first to test this assumption in a randomized, double-blind, placebo controlled trial of 148 patients with relapsing remitting MS. IVIG given monthly at a dosage of 0. 15-0.2 g/kg bodyweight over 2 years was associated with a significantly more favourable course of disability as measured by the EDSS (- 0.23 vs 0.12; P=0.008) and caused a significant reduction of the frequency of relapses (0.52 vs 1.26; P=0.011). Beneficial effects on these outcome measures were already seen within 6 months of treatment and did not appear to depend on the severity of baseline disability. IVIG treatment also had a positive effect on daily and social living according to patient' self rating on the Incapacity Status and Environmental Status Scales and was associated with a lower, though not significantly different number of hospital admissions and days spent in hospital. These data support IVIG as an alternative treatment option for relapsing-remitting MS and encourage further studies to clarify the optimal usage of this substance for this indication.

Adult↗

Randomised placebo-controlled trial of monthly intravenous immunoglobulin therapy in relapsing-remitting multiple sclerosis. Austrian Immunoglobulin in Multiple Sclerosis Study Group.

BACKGROUND: Multiple sclerosis is an autoimmune disorder characterised by the repeated occurrence of demyelinating lesions within the central nervous system. Uncontrolled studies and experimental evidence suggest beneficial effects of repeated administration of intravenous immunoglobulin (IVIg) by immunomodulating mechanisms and induction or remyelination. We aimed to investigate the efficacy of IVIg in a randomised double-blind multicentre study. METHODS: Patients with relapsing-remitting multiple sclerosis were randomly assigned a monthly dose of IVIg (0.15-0.2 g/kg bodyweight) or placebo. Duration of treatment was 2 years. The primary outcome measures were the effect of treatment on clinical disability-measured by the absolute change in Kurtzke's expanded disability status scale (EDSS) score- and the proportion of patients with improved, stable, or worse clinical disability (> or = 1.0 grade on EDSS score). FINDINGS: Of the 243 patients screened, 150 met our eligibility criteria and were randomly assigned to IVIg or placebo. Before the start of treatment two patients in the placebo group dropped out, so there were 75 patients in the IVIg group and 73 in the placebo group. Intention-to-treat analysis showed that IVIg treatment had a beneficial effect on the course of clinical disability. The EDSS score decreased in the IVIg-treated patients and increased in the placebo group (-0.23 [95% CI -0.43 to -0.03] vs 0.12 [-0.13 to 0.37], p = 0.008). In the IVIg group, the numbers of patients with improved, stable, or worse clinical disability were 23 (31%), 40 (53%), and 12 (16%) compared with ten (14%), 46 (63%), and 17 (23%) in the placebo group. Side-effects were reported in three (4%) IVIg-treated patients and in four (5%) placebo-group patients, but were not directly linked to study medication. INTERPRETATION: Monthly IVIg is an effective and well-tolerated treatment for patients with relapsing-remitting multiple sclerosis.

Adult↗

Treatment effects of monthly intravenous immunoglobulin on patients with relapsing-remitting multiple sclerosis: further analyses of the Austrian Immunoglobulin in MS study.

Recently, the Austrian Immunoglobulin in Multiple Sclerosis (AIMS) study showed patients with relapsing-remitting multiple sclerosis to benefit from repeated administration of intravenous immunoglobulin (IVIg). To provide a more detailed understanding of IVIg's action we performed further analyses on the time course of treatment effects and in regard to the impact of clinical disability at study entry on patients' response to medication. The AIMS trial was a randomized, placebo-controlled, double blind, multicenter trial. It included 148 patients (IVIg: 75; placebo 73) who suffered from relapsing-remitting MS, were 15-65 years old and scored from 1-6 on the Expanded Disability Status Score (EDSS). IVIg was given over 2 years in a monthly dosage of 0.15-0.2 g/kg body weight Within the first 6 months of the trial clinical disability of IVIg treated patients improved significantly from a baseline EDSS of 3.33 +/- 1.38 to a score of 3.05 +/- 1.73 (P=0.002). This improvement was retained over the subsequent 18 months of the trial (final EDSS: 3.09 +/- 1.62). In contrast, placebo-treated patients showed a slight trend for deterioration over the study period (baseline EDSS: 3.37 +/- 1.67; final EDSS: 3.49 +/- 1.83). IVIg treatment was associated with a significant reduction of relapses throughout the study which was independent of the patients' disability at baseline. The observation of clinical improvement in the early phase of IVIg medication may suggest the activation of repair mechanisms such as the promotion of remyelination while immunoregulatory effects would be expected as the cause of fewer exacerbations throughout the AIMS study. These hypotheses need to be tested in future trials.

Adolescent↗

[Hormonal status of the woman and its effect on symptoms and progression of chronic polyarthritis].

In a retrospective study 434 female patients suffering from rheumatoid arthritis (mean age at the onset of disease 45.7 +/- 13.3 years) were asked about information concerning number of deliveries, abortions, hormonal contraception or treatment respectively, and any changes of complaints during pregnancy, after deliveries or hormonal treatment. The effect of oral contraceptives on the progression of the disease was of particular interest. The present results show that the progression of RA is not influenced dramatically by the hormonal situation or hormonal treatment respectively. The worldwide opinion of female sex hormones regarding their influence on symptoms and progression of RA and the risk of developing RA are controversial. Positive and negative studies on the influence of hormonal situation or treatment respectively are depending very much on the individual study conditions. In order to find out more on the effects of hormones on RA, a prospective approach and much more data would be required. This is the reason why no study so far has shown unanimously acceptable results.

Adult↗

[Methodological deficiencies in clinical trials].

In many cases, the results obtained with clinical trials are out of all proportion to the time, money and effort invested by those participating in them. The reasons for this are to be sought, for the most part, in readily avoidable errors at the planning stage, during evaluation and during preparation for publication. Common weak points prove to be the design of the trial, patient numbers, selection of end points, characteristics of case material, blinding, randomization, exclusion from evaluation, test efficiency (power 1-beta), subgroup analyses and interim analyses.

Clinical Trials as Topic↗

Amoxicillin in the treatment of asymptomatic bacteriuria in pregnancy: a single dose of 3 g amoxicillin versus a 4-day course of 3 doses 750 mg amoxicillin.

A prospective, randomized, controlled comparative clinical trial was carried out with the aim of investigating the efficacy and tolerance of two different dosage regimens of amoxicillin in the treatment of asymptomatic bacteriuria during pregnancy. Patients in group A received a single dose of 3 g amoxicillin, which was compared to a 4-day course of 3 X 750 mg amoxicillin tablets taken every 8 h (group B). Significant bacteriuria (CFU greater than or equal to 10(5)/ml clean catch midstream urine and CFU greater than or equal to 10(4)/ml urine obtained by bladder catheterization) was diagnosed using the dip-slide method (Uricult). 91 pregnant women with a mean gestational age of 25 weeks (14-38) were randomly allocated to the two treatment groups. 53 patients were assigned to group A and 38 patients to group B. The treatment groups were comparable in terms of age and duration of pregnancy. Urine culture tests were performed 1 and 4 weeks after completion of therapy. The predominant species was Escherichia coli, which was isolated in 60-65% of the cases. Bacteriological cure rates at 1 and 4 weeks, respectively, were 77 and 74% in group A, and 62 and 62% in group B. These differences were statistically not significant. The incidence of side effects was 4% in group A and 13% in group B. The results obtained in the present study suggest that in the treatment of asymptomatic bacteriuria in pregnancy, a single dose of 3 g amoxicillin is as effective and acceptable as a 4-day course. In addition, the single-dose regimen offers the advantage of a reduction in total dose, lower costs and better patient compliance.

Adolescent↗

Salivary levels of gramicidin after use of a tyrothricin-containing gargle/mouth-wash and tyrothricin lozenges.

Three pharmaceutical preparations for the disinfection of the oropharynx were tested with regard to the gramicidin concentration obtained in the saliva after their appropriate application. Peak values followed a dose-concentration relationship and were highest after sucking a lozenge containing 10 mg tyrothricin (mean 109.3 mg/L) followed by that of a gargle/mouth-wash containing 667 mg tyrothricin/L (mean 21.1 mg/L) and of a lozenge containing 4 mg tyrothricin (mean 14.4 mg/L).

Adult↗

In vitro antibacterial activity of gramicidin and tyrothricin.

815 recent clinical isolates of different species representing pathogenic or saprophytic constituents of human microbial flora were submitted to agar dilution tests. In concentrations above 64 micrograms/ml tyrothricin is in general equally as gramicidin or slightly more effective whereas below 8 micrograms/ml gramicidin is mostly more effective than tyrothricin. Of 401 streptococci all were inhibited by tyrothricin and gramicidin in concentrations up to 96 micrograms/ml; staphylococci were more resistant. The pathogenic species of 130 strains of gram-negative cocci were more susceptible than the saprophytic species. Haemophilus strains were mostly resistant to gramicidin and to a lesser extent to tyrothricin. Enterobacteriaceae were totally resistant to both antibiotics.

Bacteria↗

Salivary levels of gramicidin after use of a tyrothricin lozenge and a tyrothricin gargle/mouth-wash.

Salivary levels and total salivary recovery of gramicidin were determined by high performance liquid chromatography in healthy volunteers after administration of a tyrothricin lozenge and a tyrothricin gargle/mouth-wash. Average peak values of gramicidin after sucking the lozenge were 37.5 mg/l and were usually reached within the five minutes. After use of the lozenge mean total recovery of gramicidin in saliva was 44% within the first 30 minutes. After application of the gargle/mouth-wash about 11% was retained in the oral cavity and excreted with saliva within the following 30 minutes. The implications of these findings are discussed.

Adult↗

Escherichia coli heat-labile enterotoxin: DNA-directed in vitro synthesis and structure.

Escherichia coli heat-labile enterotoxin was synthesized in a cell-free system directed by DNA of the plasmid P307. Synthesis of the toxin, assayed by the elongation induced in Chinese hamster ovary cells, was strongly stimulated by cyclic AMP and occurred at physiological levels of Mg2+ only when the polyamine spermidine was present. Activity was abolished by heat and antisera prepared against the enterotoxins of both E. coli P263 and Vibrio cholera. Tritium-labeled enterotoxin was purified by immunoprecipitation and examined by sodium dodecyl sulfate/polyacrylamide gel electrophoresis. When gel slices were assayed for the ability to stimulate adenylate cyclase [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1] activity in erythrocyte ghosts, two peaks were found, one at Mr 26,000 and frequently, but not always, another at Mr 23,000. Detection of radiolabeled protein by fluorography and scintillation counting of gel slices revealed three prominent polypeptides, two corresponding to the peaks having adenylate cyclase-stimulating activity and a further one of Mr 11,500, identical to that of the cholera subunit B. The data suggest that the E. coli heat-labile enterotoxin synthesized in the cell-free system has a subunit structure.

Animals↗

Amoxycillin in bronchitis. Comparison of two versus three daily doses.

Fifty patients with moderate or severe bronchitis were randomly allocated into groups receiving orally either 1000 mg amoxycillin twice daily or 750 mg three times daily. Overall cure rates (both 92%) and the incidence of side-effects (4% and 8%, respectively) were similar in both groups. A twice daily regimen, therefore, seems to be as effective as conventional treatment and has the advantage of being more convenient for the patient.

Acute Disease↗

Decontamination of the oral cavity. Effect of six local anti-microbial preparations in comparison to water and parafilm as controls.

Six preparations (four liquid and two solid) were tested in a double-blind crossover design for their anti-bacterial effect on aerobic and anaerobic bacteria in saliva of 12 volunteers. The four liquid preparations contained either tyrothricin, hexetidine, hydrogen peroxide or ethanol and were tested against a rinse with water as control. The two solid preparations, in the form of lozenges, contained tyrothricin in doses of 4 or 10 mg and were tested against parafilm. A single rinse with either tyrothricin or hexetidine resulted in a significant reduction of aerobic and anaerobic bacteria in saliva which lasted for the whole 1 h observation period and was considerably more effective than hydrogen peroxide or ethanol. Similar results were seen with the solid preparations. The lozenge containing 10 mg tyrothricin was the most effective and was the only formulation capable of reducing oral aerobic bacterial counts by a factor of approximately 100.

Adult↗

[Amoxicillin in the treatment of asymptomatic bacteriuria in pregnancy--3g single dose versus 3 times 750mg 4-day therapy].

A prospective, randomized, controlled comparative clinical trial was conducted to assess the efficacy and tolerability of 2 regimens of amoxicillin. In group A a single dose of 3 g amoxicillin and in group B a 4-day course of 3 doses of 750 mg amoxicillin tablets were administered 8-hourly. Significant bacteriuria (greater than or equal to 10(5) cfu/ml midstream urine) and of urine samples obtained by bladder catheterization (greater than or equal to 10(4) cfu/ml) was diagnosed with the dip-slide method (Uricult). 91 pregnant women with a mean gestational age of 25 weeks (14-38) were randomly allocated to both treatment groups. Group A consisted of 53 patients, group B of 38. The treatment groups were comparable in terms of age, duration of pregnancy and additional therapy. Control examinations of urine cultures were taken after 1 and 4 weeks following therapy. The predominant bacterial species was E. coli isolated in 60 to 65 percent. Bacteriological cure rates at 1 and 4 weeks were in group A 77% and 74% and in group B 62% each respectively. The differences in cure rates were not significant. Side effects occurred in group A in 4% and in group B in 13%. Our results suggest that for the treatment of asymptomatic bacteriuria in pregnancy a single dose of 3 g of amoxicillin is equally effective and acceptable as a 4-day course with the advantage of a lower total-dose, lower costs and a better compliance.

Adolescent↗