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Biomedical subjects

A Polak

Publications and source records attributed to A Polak.

At least 55 records · Page 3Linked to original sources

Pathogenicity and virulence of wild-type and melanin-deficient Wangiella dermatitidis.

Wild-type, dematiaceous Wangiella dermatitidis (DMD 368) and melanin-deficient mutant (Mel 3) strains derived therefrom were compared for pathogenic and virulent effects in Swiss albino mice following intravenous infection. Parameters examined were mouse survival and central nervous system signs of infection, time-course cultures of fungus from brains, lungs, livers, spleens and kidneys, and histopathology of brains. Over a range of concentrations, DMD 368 produced 100% mortality while one Mel 3 strain, DMD 369, produced no mortality by 21 days after inoculation. However, in chronic infections with DMD 369, mice developed ataxia and torticollis. These signs of disease were indistinguishable from those produced by low concentrations of DMD 368. The brain was the most severely affected organ where both DMD 368 and 369 grew exponentially. Histological responses to the two strains appeared to be indistinguishable. However, the mutant appeared not to form the invasive hyphal forms of growth associated with the acute, fatal infections caused by the wild type. Thus, although the absence of melanin was associated with decreased mortality in mice, the chronic neurological signs of mouse phaeohyphomycosis appeared to be unrelated to melanin.

Animals↗

The urinary excretion of albumin in normal pregnancy.

The urinary excretion of albumin was measured in a group of normal pregnant women at 14, 28 and 36 weeks gestation and 6 weeks postpartum. Using 2-h urine collections, the excretion rate was not found to increase during pregnancy or to differ from that in a group of non-pregnant controls. The urinary albumin to creatinine concentration ratio was greater at all stages of pregnancy than in the non-pregnant controls and greater at 36 weeks than at 14 weeks gestation. Correcting for the observed changes in serum albumin and creatinine clearance produced evidence consistent with the hypothesis that mean glomerular permeability to albumin rises progressively during pregnancy. Reasons are given why the measurement of urinary albumin excretion may be a useful screening test in some pregnant women, and may also yield useful information on the effect of multiple pregnancies on renal function. One grand multipara was studied and found to have an increased excretion of albumin at each stage of pregnancy.

Albuminuria↗

5-Fluorocytosine kinetics in patients with acute renal failure undergoing continuous hemofiltration.

The pharmacokinetic disposition of 5-fluorocytosine (5-FC) was studied in 7 patients with acute renal failure undergoing continuous hemofiltration (CH). CH was performed with a high-flux membrane and the average filtration rate (FR) was 16.3 ml/min. Following an intravenous loading dose of 2,500 mg, 5-FC concentrations were measured in plasma and ultrafiltrate. The half-lives of 5-FC were markedly prolonged in all patients, ranging from 15.9 to 37.2 h and longer half-lives corresponded to lower FR. The clearance of 5-FC averaged 97.5% of the FR. Within 48 h, 29-35% of the administered dose was recovered in the ultrafiltrate of 3 patients. The volume of distribution ranged from 0.772 to 0.982 l/kg. We found a linear relationship between the elimination rate constant and the FR, and based on these data, a dosage schedule is proposed regarding the use of 5-FC in patients treated with CH.

Acute Kidney Injury↗

In vitro and in vivo drug studies with three agents of central nervous system phaeohyphomycosis.

Amphotericin B (Amph B), 5-fluorocytosine (5-FC), ketoconazole (KTZ), fluconazole (FLZ), amorolfine (AMOR) and terbinafine (TER) were tested against 3 agents of central nervous system phaeohyphomycosis in vitro and in life-threatening infections in mice. The fungi studied were Cladosporium bantianum, Dactylaria constricta and Wangiella dermatitidis. The broadest protection against this group of fungi in mice was offered by 5-FC followed by Amph B and FLZ, then KTZ. AMOR and TER were inactive in vivo. The results of in vitro susceptibility testing had no predictive value. In contrast, the data obtained from the mouse models should be useful clinically.

Animals↗

Combination therapy of experimental candidiasis, cryptococcosis, aspergillosis and wangiellosis in mice.

Combination pairs of 5-fluorocytosine (5-FC) + itraconazole (Itra), 5-FC + fluconazole (Fluc), and amphotericin B (Amph B) + Itra were administered to mice with experimental candidiasis, cryptococcosis, aspergillosis and wangiellosis with a variety of combination ratios. The life-prolonging effect of the combinations was compared with the effect of each partner administered alone and with a double dosage. Using the U test of Mann and Whitney, the effects of the concentration were classified as synergistic, additive, indifferent or antagonistic; the degree of the interaction was compared with the known effect of Amph B and 5-FC combinations. The combination 5-FC + Itra was definitely synergistic or additive in candidiasis and aspergillosis. The most pronounced synergism occurred in the infection with a 5-FC-resistant strain of Candida albicans. The degree of synergism was the same as with 5-FC + Amph B. In cryptococcosis this combination was indifferent. The combination of 5-FC + Itra merits clinical investigation, especially in candidiasis and aspergillosis. Amph B + Itra was mostly indifferent and weakly antagonistic; the degree of antagonism was significantly weaker than the one observed with Amph B + ketoconazole (Keto). In candidiasis, 5-FC + Fluc was synergistic, but indifferent in cryptococcosis and aspergillosis.

Amphotericin B↗

Retinol binding protein as a small molecular weight marker of renal tubular function in diabetes mellitus.

A radioimmunoassay has been developed for the measurement in urine of retinol-binding protein (alpha 2-microglobulin) and used as an index of renal tubular function in adult Type 1 (insulin-dependent) diabetics and to define reference ranges in non-diabetic controls. There was a significantly greater excretion (P less than 0.001) of retinol-binding protein in the diabetic group compared to the controls in both overnight and daytime samples. There was a weak positive correlation with albumin excretion (r = 0.33; P less than 0.01) but no correlation with HbA1, duration of diabetes or arterial blood pressure. The results indicate that retinol-binding protein excretion may be increased in diabetic subjects without increased albumin excretion. The possibility therefore exists that renal tubular damage may occur early in diabetic nephropathy without apparent glomerular dysfunction.

Adolescent↗

[5-Fluorocytosine and combinations].

The antimycotic and pharmacological properties of 5-fluorocytosine are presented. Especially the aspect of good gastrointestinal absorption, elimination by the kidney, unwanted side effects and appearance of primary and secondary resistance are discussed. The indication of 5 FC monotherapy or combination therapy is shown in various manifestations of deep candidiasis.

Antifungal Agents↗

Dactylaria constricta: another dematiaceous fungus with neurotropic potential in mammals.

Dacylaria constricta, a neurotropic dematiaceous fungal pathogen of poultry, was evaluated for pathogenic potential in mice. Four isolates of D. constricta and two of Scolecobasidium humicola were injected intravenously into groups of mice. Two isolates of a D. constricta group formerly known as Dactylaria gallopava produced signs of central nervous system infection with cerebral microabscesses and death. None of the mice injected with the two remaining isolates of D. constricta from a group formerly known as Scolecobasidium constrictum or with isolates of S. humicola showed any evidence of infection, and none died. Potential pathogenicity can now be added to the previously established physiological differences to separate isolates of D. constricta into two distinct groups.

Animals↗

In vivo and in vitro studies with an atypical, rhinotropic isolate of Cryptococcus neoformans.

An atypical isolate of Cryptococcus neoformans was investigated because of its consistent and reproducible production of gross nasal pathology following i.v. injection in Swiss albino mice. Dose response to graded concentrations ranging from 1 X 10(2)-1 X 10(7) cells/mouse yielded an LD50 of 1.4 X 10(3) cells/mouse for the atypical rhinotropic strain H140 which was significantly less virulent (p less than 0.01) than our reference strain of Cryptococcus neoformans. There was no significant difference in mortality following the injection of in vitro vs. in vivo passed inoculum. As early as two weeks after inoculation, this strain produced gross nasal enlargement to approximately 2-3 X normal dimensions with granulomatous and ulcerated lesions. The LD60 resulted in the greatest percentage of nasal involvement (85%). C. neoformans was demonstrated by culture and histopathology in the noses, brains, lungs, livers and kidneys. A temperature selection was indicated by findings of a lower temperature minimum for subcultures isolated from the noses relative to those isolated from the brain, and by the fact that the most densely populated organs following intraperitoneal injection were the testes. This route of inoculation resulted in cutaneous nasal involvement in a manner analogous to that following i.v. injection. The atypical isolate was unable to assimilate trehalose or raffinose but otherwise was entirely consistent with identification as C. neoformans and produced characteristic CNS and general organ system disease in addition to the rhinotropic cutaneous manifestations. The model characterized here in normal mice may be of value in studies of fungal dermotropism.

Animals↗

Assessment of new radioimmunoassay kit for determining urinary albumin at low concentrations: comparison with radial immunodiffusion.

The assay characteristics of a new radioimmunoassay kit for determining urinary albumin at low concentrations were studied. The sensitivity for urinary albumin was 2 mg/l, the analytical range 2 to 40 mg/l, and interassay coefficient of variation less than 12%. In a method comparison study entailing diabetic urine samples covering an albumin concentration of 2 to 150 mg/l the kit compared adequately with radial immunodiffusion (mean difference between methods = 2 mg/l; residual standard deviation = 4.6 mg/l), absolute variation between methods increasing with the concentration. The kit required much less skill than radial immunodiffusion but its capital and running cost were higher.

Albuminuria↗