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Biomedical subjects

A Polak

Publications and source records attributed to A Polak.

At least 73 records · Page 4Linked to original sources
PubMed1986

Assessment of immunochemical methods for determining low concentrations of albumin in urine.

Four immunochemical methods (radioimmunoassay, RIA; radial immunodiffusion, RID; immunoturbidimetry, IT; enzyme-linked immunosorbent assay, ELISA) for measuring urinary albumin at low concentrations were assessed for their assay characteristics and practicability. Precision and accuracy were comparable between the methods when studied individually. We made a method comparison, with RIA as reference, using urine samples from diabetic patients with albumin concentrations ranging from 1 to 120 mg/L. There was no significant systematic difference between RID and RIA, but IT and ELISA gave consistently lower values than RIA, the mean differences being 1.8 (p less than 0.01) and 9.7 mg/L (p less than 0.001), respectively. Random error, compared with that for RIA, was in increasing order: RID (residual SD = 3.8 mg/L); IT (4.3 mg/L); ELISA (7.3 mg/L). The difference between the methods increased with the albumin concentration. Operational cost was highest with IT, lowest with RIA. Capital cost was highest with RIA and lowest with RID, which required most technical skill. ELISA had intermediate overall costs.

Albuminuria↗
PubMed1985

Correlation of susceptibility test results in vitro with response in vivo: ketoconazole therapy in a systemic candidiasis model.

In a previous study with flucytosine (5-FC) susceptibility of 40 Candida albicans isolates in vitro proved statistically correlated with response in systemic murine candidiasis in vivo, although exceptions occurred with individual isolates. For the present analogous study with ketoconazole, 58 C. albicans isolates were used of which 38 were from the 5-FC study and 20 were added to equalize the numbers of serotype A (n = 30) and B (n = 28) and to make the range of susceptibility in vitro to ketoconazole continuous and wide. The widest range of ketoconazole susceptibility was noted for the minimal inhibitory concentrations on Kimmig and Casitone agars (0.015-256 micrograms/ml) and disk zone diameters on YNB agar (0-54 mm), whereas with disk tests on other media, the range of 50% inhibitory concentrations, relative inhibition factors and MICs on serum agar remained narrow and/or showed strong ties. The Spearman's rank correlation between the in vitro activities determined with the various parameters showed wide variation consistent with p values from less than 0.001 to greater than 0.05. The serotype B isolates generally were more susceptible than the A isolates (p less than 0.02 for the majority of parameters). Evaluation of response in vivo was hampered by the low activity of ketoconazole on the murine infection with any of the isolates, the range of the ED50's being only 10- greater than 100 mg/kg. The serotype B infections exhibited significantly better response (p less than 0.05) than the serotype A infections. The overall correlation (Spearman's rank) of the susceptibility test results in vitro with the response in vivo was poor (p less than 0.05 for almost all parameters) suggesting very limited if any precise predictive values of the susceptibility tests in vitro with ketoconazole against C. albicans. However, the narrow range of the ED50 suggests relatively little variation in the response of the different isolates in vivo and similarly small variation was also noted in some of the tests in vitro.

Animals↗
PubMed1985

Neuroleptics, lithium and renal function.

Renal function test results in 26 patients on neuroleptic treatment, who had never received lithium or antidepressants, were compared with those in a matched group, treated with lithium; also, their tubular response to DDAVP was compared with that of 25 control subjects. Measurements of serum creatinine, creatinine clearance, and urinary albumin excretion showed no abnormality attributable to either neuroleptics or lithium. The maximum urine concentrating ability after DDAVP was significantly lower in the neuroleptic group than in controls, but significantly higher than in the lithium-treated patients. There was a significant correlation between excretion of urinary beta 2-microglobulin and duration of neuroleptic treatment, but mean excretion rates were the same in both treatment groups. The results suggest that neuroleptics as well as lithium impair urine concentrating ability.

Acetylglucosaminidase↗
PubMed1984

Specific thromboxane synthetase inhibition and albumin excretion rate in insulin-dependent diabetes.

Albumin excretion rates (AER) were measured in 30 insulin-dependent diabetics during a 16-week double-blind, randomised, placebo-controlled study of the specific thromboxane synthetase inhibitor UK-38,485.6 of 15 subjects in the active group had microalbuminuria (defined as mean pretreatment AER 20-150 micrograms/min); in these patients AER fell from 32 +/- 3 micrograms/min to 11 +/- 1 micrograms/min at 8 weeks and 9 +/- 1 micrograms/min at 16 weeks. The AER rose again (to 29 +/- 8 micrograms/min) within 12 weeks of stopping the drug. There was no significant change in the 10 patients with microalbuminuria who received placebo. There was a strong correlation between change from baseline values and the baseline values themselves in the active, but not in the placebo group, and the change from baseline differed significantly between the two groups. There was no change in glycosylated haemoglobin or mean blood glucose levels during the study. In a separate study UK-38,485 caused significant suppression of thromboxane B2 synthesis in diabetic and non-diabetic subjects.

Adult↗
PubMed1984

Cyclic AMP responses to parathyroid hormone and glucagon during lithium treatment.

Inhibition of adenylate cyclase has been proposed as a mechanism for hypothyroidism and nephrogenic diabetes insipidus occurring during lithium treatment, but these disorders are rarely found in the same patients. We have measured plasma levels of adenosine 3':5'-cyclic monophosphate (cyclic AMP) after an intravenous injection of glucagon in eight patients receiving long term lithium treatment and in six control subjects. Urinary cyclic AMP levels after an intravenous injection of bovine parathyroid hormone (PTH) were also measured in the patients. The plasma cyclic AMP response to glucagon in the patient group was significantly lower than that of the controls. No correlation was demonstrated between the plasma cyclic AMP response after glucagon and the urinary cyclic AMP response after PTH. We have previously shown that impairment of the response to PTH correlates with reduced urine concentrating ability during lithium treatment. In contrast, there was no correlation between the responses to PTH and glucagon in individual patients. These results are consistent with the hypothesis that inhibition of adenylate cyclase is an important factor in lithium-induced endocrine dysfunction.

Adult↗
PubMed1984

Mucormycotic infection in mice following prolonged incubation of spores in vivo and the role of spore agglutinating antibodies on spore germination.

Following intranasal inoculation of mice, Rhizomucor pusillus spores are gradually cleared from the lung, with the clearance complete at 30 days. Incubation of R. pusillus spores in vivo for up to 14 days after intranasal inoculation resulted in pulmonary mucormycosis when the mice were then treated with cortisone. Spore-agglutinating IgM antibodies were detected in normal adult mice and R. pusillus-inoculated but not cortisone-treated mice. There was no correlation between antispore antibody titers and spore germination in vitro. The absence of germinated R. pusillus in inoculated but non-cortisone-treated mice appears to be due to a reversible inhibition of spore germination rather than destruction of spores by the host. The factor(s) that restrict spore germination are reversible and do not appear to be spore agglutinating antibodies.

Agglutinins↗
PubMed1984

Antimycotic therapy of experimental infections caused by dematiaceous fungi.

Experimental infections of mice with Wangiella dermatitidis and Fonsecaea pedrosoi provided a model for evaluating new antifungal agents or new combination therapy. In our models flucytosine exerted a dose-related therapeutic effect on the acute and on the more chronic infection. In the acute Wangiella infection amphotericin B also showed therapeutic activity whereas in the Fonsecaea model the effect was weak. The azole derivative ICI 153066 was the most efficacious drug in the Wangiella model whereas ketoconazole was inactive. The effect on colony-forming units of fungi in the brain was stronger with all drugs tested than the effect on survival time. Combination therapy with flucytosine + amphotericin B showed reproducible potentiating effects whereas the combination of flucytosine + ketoconazole was only additive and amphotericin B + ketoconazole showed no synergistic effect.

Amphotericin B↗
PubMed1984

Antifungal activity of four antifungal drugs in the cutaneous retention time test.

The protective prophylactic activity of tolciclate, bifonazole, oxiconazole and Ro 14-4767/002 which may reflect their presence in the horny layer was examined in guinea pigs. Guinea pigs were topically treated with the drug and infected on the application site with Trichophyton mentagrophytes spores at various time intervals. Tolciclate showed the highest prophylactic activity, followed by oxiconazole, Ro 14-4767/002 and bifonazole.

Animals↗
PubMed1984

Renal function during lithium treatment.

Renal function tests were performed in 101 unselected patients who had been on lithium for two weeks to 12 years. None had a recorded episode of lithium intoxication. The glomerular filtration rate (GFR), was not correlated with the cumulative dose of lithium or the duration of use of other psychotropic drugs. Nine patients had creatinine clearances lower than predicted; in six of these, no cause was identified and the small reductions in GFR may have been related to lithium use. Urinary concentrating ability (Umax) declined with age, and total dose of lithium received. Although the concurrent use of neuroleptics did not significantly reduce the Umax, the total duration of treatment with these drugs showed a negative correlation. The results suggest that prolonged use of neuroleptics, particularly in patients treated with lithium, may be responsible for an irreversible reduction in urine concentrating ability. Microalbuminuria was present in 40 per cent of the patients, although the rate of albumin excretion was not correlated with duration of use of psychotropic drugs. beta 2 microglobulin excretion was only raised in nine of these patients, suggesting that increased glomerular permeability rather than impaired proximal tubular protein reabsorption was responsible for the proteinuria. The urinary excretion of beta 2 microglobulin and N-acetyl-beta-glucosaminidase were slightly increased in small numbers of patients, indicating little evidence for proximal tubular damage. Increased NAG excretion did not correlate with reduced distal tubular function. However, there was a tendency to higher urinary beta 2 microglobulin excretion in patients with a reduced Umax.

Adult↗
PubMed1984

Experimental infection of mice by Fonsecaea pedrosoi and Wangiella dermatitidis.

After i.v. inoculation in cortisone-pretreated mice Fonsecaea pedrosoi produced a chronic infection characterized by black lesions in the skin and subcutis with sclerotic bodies resembling the tissue form of human chromomycosis in addition to lesions in the brain and other organs. Wangiella dermatitidis inoculated into unpretreated mice produced an acute, fatal cerebral infection closely resembling human phaeohyphomycosis. Abundant hyphal growth was observed in the brain tissue.

Animals↗
PubMed1983

Impairment of cyclic AMP response to bovine parathyroid hormone in patients on chronic lithium therapy with diminished renal urine-concentrating ability.

1. Urinary and plasma levels of adenosine 3':5'-cyclic monophosphate (cyclic AMP) after an intravenous injection of bovine parathyroid hormone (PTH) were measured in 12 patients on long-term lithium treatment and in nine control subjects. The maximum urine osmolality (Umax.) after an intravenous injection of desamino-D-arginine vasopressin (DDAVP) was also measured. 2. In all the control subjects and six of the patients, the Umax. after DDAVP exceeded 700 mosmol/kg. The cyclic AMP responses in these two groups did not differ significantly. 3. In the remaining six patients whose Umax. did not reach 700 mosmol/kg, the cyclic AMP response to PTH was significantly less than that of the controls. 4. A strong correlation was demonstrated in the patients between the urinary cyclic AMP response after PTH and the maximum osmolality after the administration of DDAVP. 5. These observations are consistent with the hypothesis that reduced adenylate cyclase activity contributes to the development of nephrogenic diabetes insipidus in patients on long-term lithium treatment.

Adult↗
PubMed1983

Mode of action of 5-fluorocytosine and 5-fluorouracil in dematiaceous fungi.

The mode of action of 5-fluorocytosine (5FC) and 5-fluorouracil (5FU) in dematiaceous fungi was studied and compared with results of experiments in yeasts and Aspergillus species. In dematiaceous fungi 5FU is more potent than 5FC. The high activity of 5FU is related to a good and rapid uptake of this compound into the fungus cell. Both compounds exert fungistatic and fungicidal activity. A correlation exists between the amount of 5FU incorporated into RNA and its antifungal activity. The resistance frequency to 5FC varies from 2 x 10(-3) to 1 x 10(-7); resistance frequency to 5FU is generally lower. Addition of 5FC and 5FU to logarithmically multiplying cells inhibits increases of cell numbers and cell constituents after a delay period. The effects on the increase of protein and carbohydrate are more delayed than on the increase of DNA and RNA, indicating unbalanced growth. The concept of a dual biochemical mechanism, i.e. incorporation of 5FU into RNA and formation of 5-fluorodeoxy UMP leading to inhibition of DNA synthesis, previously proposed for the antifungal action of 5FC is also applicable to the action of 5FC and 5FU on the dematiaceous fungi.

Cytosine↗
PubMed1983

Correlation of in vitro susceptibility test results with in vivo response: flucytosine therapy in a systemic candidiasis model.

The in vitro susceptibility of Candida albicans isolates to flucytosine was compared to therapeutic effect in experimental murine candidiasis (candidosis). Four groups of 10 isolates were chosen, based upon their broth dilution minimal inhibitory concentrations (MICs), from a group of 402 isolates from patients without prior flucytosine therapy. Group I MICs were less than 12.5 micrograms/ml after seven days, whereas group II, III, and IV MICs exceeded 12.5 micrograms/ml on days 7, 2, and 1, respectively. Pilot experiments selected challenge inocula of similar virulence. Mice were infected intravenously and given various flucytosine doses. Significant prolongation of survival correlated with MICs and with agar disk-diffusion zone diameters (P less than 0.05). In vivo response to therapy was more favorable for group I isolates compared with group IV isolates (P less than 0.01). The present study demonstrates in this animal model that in vitro susceptibility does correlate with in vivo response to therapy, although exceptions occur with individual isolates.

Animals↗
PubMed1983

Mechanisms of action of 5-fluorocytosine.

5-Fluorouracil and 5-fluorodeoxyuridine monophosphate levels were estimated in 75 isolates of Candida albicans to determine whether 5-fluorocytosine susceptibility could be ideally correlated with the intrafungal formation of both 5-fluorodeoxyuridine monophosphate and 5-fluorouridine triphosphate or a reciprocal formation of the two metabolites to prove the mechanism of 5-fluorocytosine activity. Using the results of four in vitro susceptibility tests, we separated isolates of C. albicans into susceptibility groups. For most strains, there was a positive correlation between the degree of 5-fluorocytosine susceptibility and the inhibition of biosynthesis of both RNA and DNA, incorporation of 5-fluorouracil into RNA, inhibition of ribosomal protein synthesis, and levels of 5-fluorodeoxyuridine monophosphate. However, in some strains with a similar degree of 5-fluorocytosine resistance, either reduced incorporation of 5-fluorouracil or reduced 5-fluorodeoxyuridine monophosphate levels occurred, suggesting that these two mechanisms are not necessarily linked to each other and that both may be responsible for 5-fluorocytosine activity.

Candida albicans↗
PubMed1983

Analysis of Candida albicans phenotypes from different geographical and anatomical sources.

Strain phenotypes of 330 Candida albicans isolates from five areas in the United States were determined on the basis of nine biochemical tests. Statistical analysis of the distribution of phenotypes revealed no significant differences among types from different anatomical sources. However, there were some differences among the phenotypes of strains from the different geographical areas, and there were substantial differences in biochemical phenotypes associated with strains susceptible and resistant to 5-fluorocytosine and between strains of serotypes A and B. Geographical differences in phenotypes of C. albicans were also noted between the 330 U.S. isolates and 247 isolates from Britain. Cluster analysis of the U.S. strains alone and of all of the U.S. and U.K. strains showed that C. albicans phenotypes can be grouped into fewer than 20 clusters with common biochemical properties.

Candida albicans↗
PubMed1983

Antifungal activity in vitro of Ro 14-4767/002, a phenylpropyl-morpholine.

Minimal inhibitory concentrations (MICs) of Ro 14-4767/002 for pathogenic yeasts, Aspergillus spp., dermatophytes and other filamentous fungi were determined in dilution tests under a variety of experimental conditions and, for the most of the species and a number of different isolates. Ro 14-4767/002 showed the highest effect against dermatophytes and Cryptococcus neoformans, followed by Candida spp., whereas its activity against Aspergillus spp. was weak. Its activity against most pathogens compared favourably with antifungals of the imidazole class. The activity of Ro 14-4767/002 not only differed between the species but there was also a significant intra-species variation. The MICs were influenced by the inoculum size, the incubation time, and by the composition of the medium. The activity of the compound was significantly higher on Casitone agar than on a chemically defined medium (Yeast Nitrogen Base + glucose). Ro 14-4767/002 was also found to exert fungicidal activity which was time- and concentration-dependent.

Antifungal Agents↗
PubMed1982

Laboratory diagnosis and oral treatment of CAPD peritonitis.

The laboratory diagnosis of 50 consecutive episodes of peritonitis in patients undergoing continuous ambulatory peritoneal dialysis (CAPD) was studied. The technique which yielded the highest rate (84%) of positive bacteriological diagnoses was inoculation and subculture of thioglycollate broth. Cloudiness of fluid to the naked eye was an accurate predictor of a raised white cell count. A minimum laboratory protocol for the bacteriological diagnosis of CAPD peritonitis was devised and has been in use satisfactorily since the completion of the study. Antibiotic treatment was given orally in the first instance in 43 episodes and was successful in 34.

Administration, Oral↗