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Biomedical subjects

S Kozak

Publications and source records attributed to S Kozak.

14 recordsLinked to original sources
PubMed2006

Headache patients in primary care and a tertiary care unit in Zürich, Switzerland.

The Headache and Pain Clinic (HPC) is a unit of the Zürich Neurology Department, established in 1966. In the present study demographic features, clinical characteristics and medical management of primary and tertiary care patients were compared in two groups of 181 patients each, seen by general practitioners (GPs) or the HPC, respectively, for primary headaches in 1998. There was a preponderance of women and the socially underprivileged in both samples. Chronic headache was overrepresented in the HPC (44.7%). Loss of work for >2 months was found exclusively in the HPC (9.9%). Of the GP patients, 40% were using triptans and 26.5% in the HPC. One-third of both groups had had complementary and alternative medical treatment. Differences in management strategies reflected differences in headache severity and chronicity. Results indicated that remaining shortcomings of diagnosis and treatment of headache in primary care could be minimized by involving GPs in similar non-commercial studies.

Demography↗
PubMed1994

Epidural butorphanol does not reduce side effects from epidural morphine after cesarean birth.

In this prospective, double-blind, randomized study of women undergoing elective cesarean birth, the hypothesis that epidural butorphanol in various doses could effectively reduce or eliminate the side effects caused by epidural morphine was tested. Patients were randomly assigned to one of four groups. All received a standard epidural anesthetic and 20 min after delivery each received 3 mg epidural morphine with either 1 mg butorphanol (Group A), 2 mg butorphanol (Group B), 3 mg butorphanol (Group C), or 3 mL normal saline (Group D). Patient evaluations were made preoperatively and 2, 8, and 24 h after delivery. These consisted of visual analog scores for pain, satisfaction, nausea, itch, and somnolence. At each evaluation, a CO2 challenge test, using portable equipment, was performed. Data from 71 patients were analyzed and all four groups were comparable in terms of age, height, weight, level of sensory block, and volume of local anesthetic used. There were no significant differences among groups in terms of pain, satisfaction, nausea, or pruritus. Groups A, B, and C had significantly higher somnolence scores at 8 h compared to Group D (P < 0.001). There were no significant differences among groups in CO2 challenge test data at any point during the study, but overall a reduced sensitivity to CO2 after opioid administration was observed across all groups. There were no clinically significant incidents of respiratory depression. Epidural butorphanol, in doses of 1-3 mg, failed to reduce the side effects from 3 mg epidural morphine given after cesarean birth. Patients who received epidural butorphanol reported significantly higher levels of somnolence.

Anesthesia, Epidural↗
PubMed1993

The impact of the pre-treatment interval on antimicrobial efficacy in a biological model.

The impact of pre-treatment intervals on the antipseudomonal efficacy of gentamicin, ticarcillin and ceftazidime was studied in an experimental thigh infection model in normal and granulocytopenic mice. Human-equivalent doses were used for simulating human pharmacokinetic profiles of the two study beta-lactam drugs. A lethal inoculum of a virulent strain of Pseudomonas aeruginosa was injected into the thigh muscle. Treatment was started at various post-infection intervals. Antimicrobial efficacy was assessed by determinations of surviving organisms at the site of infection, and plasma drug concentrations were determined in the same mice. The age of infection had a substantial impact on antipseudomonal efficacy of the three study drugs even though high, brief supra-MIC concentrations of gentamicin and persistent supra-MIC concentrations of the beta-lactam drugs were obtained. A pre-treatment interval of six or more hours abolished the bactericidal effect of all three study drugs despite accumulation of the drugs to multiple-MBC plasma concentrations. We believe that the impact of pre-treatment intervals on antimicrobial efficacy is of paramount importance for the interpretation of antimicrobial activity studies in experimental models of infection, although the mechanisms remain to be elucidated.

Agranulocytosis↗
PubMed1992

Mutations in the env gene of friend spleen focus-forming virus overcome Fv-2r-mediated resistance to Friend virus-induced erythroleukemia.

Although Fv-2r homozygous mice are resistant to leukemias induced either by an erythropoietin-encoding virus or by wild-type Friend virus (FV) (M. E. Hoatlin, S. L. Kozak, F. Lilly, A. Chakraborti, C. A. Kozak, and D. Kabat, Proc. Natl. Acad. Sci. USA 87:9985-9989, 1990), they are susceptible to some variants of FV (R. A. Steeves, E. A. Mirand, A. Bulba, and P. J. Trudel, Int. J. Cancer 5:349-356, 1970; R. W. Geib, M. B. Seaward, M. L. Stevens, C.-L. Cho, and M. Majumdar, Virus Res. 14:161-174, 1989). To localize the virus gene involved in influencing the host range, we cloned and sequenced the env gene of the BB6 variant of FV (Steeves et al., Int. J. Cancer 5:349-356, 1970). In comparison with the wild-type env gene, the BB6 variant contains a 159-bp deletion that eliminates the membrane-proximal portion of the extracellular domain and 58 point mutations resulting in 13 amino acid changes. Substitution of the variant env gene for the wild-type env gene resulted in a recombinant virus that produced a Friend virus-like disease in Fv-2r homozygotes. Our results identify the spleen focus-forming virus env gene as the viral gene involved in this virus-host interaction. Additionally, they suggest that the product of the Fv-2r gene modifies the interaction between the spleen focus-forming virus envelope protein and the erythropoietin receptor.

Amino Acid Sequence↗
PubMed1989

Once-daily versus thrice-daily administration of netilmicin in combination therapy of Pseudomonas aeruginosa infection in a man-adapted neutropenic animal model.

A granulocytopenic mouse model was used to elucidate the impact of dose spacing on the activity of netilmicin against Pseudomonas aeruginosa. A thigh infection was produced and then treated with netilmicin combined with azlocillin. Netilmicin was injected subcutaneously at decreasing doses every 20 min to result in plasma-concentration-time curves similar to those observed in patients on intravenous netilmicin treatment. A once-daily regimen was simulated and compared to a simulated conventional schedule of every 8 h. Identical total amounts of drug were used in both groups of comparatively treated mice. Therapeutic efficacy was quantitated by repeated determinations of surviving organisms in thigh homogenates. Combination therapy was significantly more effective than azlocillin treatment alone. In combination regimens the simulated once-daily netilmicin schedule killed the target organisms faster than the simulated thrice-daily regimen and was significantly more efficacious by 24 and 32 h in two out of three strains of Pseudomonas aeruginosa tested. It is concluded that the results of combination therapy of severe Pseudomonas aeruginosa infections in the immunocompromised host might be improved by choosing an aminoglycoside dosage interval of 24 h instead of the conventional 8 h.

Animals↗
PubMed1987

Effect of a single injection of two new bisphosphonates on the hypercalcemia and hypercalciuria induced by Walker carcinosarcoma 256/B in thyroparathyroidectomized rats.

The effect of one single injection of two new bisphosphonates, 4-amino-1-hydroxybutylidene-1,1-bisphosphonate and 2-(2-pyridyl)ethylidene-1,1-bisphosphonate, and of dichloromethylenebisphosphonate on the hypercalcemia and hypercalciuria induced by the Walker carcinosarcoma 256/B in the thyroparathyroidectomized rat was evaluated. When given either before or after the development of hypercalcemia and hypercalciuria, 16.1 mumol/kg 4-amino-1-hydroxybutylidene-1,1-bisphosphonate or 2-(2-pyridyl)ethylidene-1,1-bisphosphonate totally inhibited hypercalciuria, whereas hypercalcemia was only partially reduced over the 14 days of the experiment. At 10 and 100 times lower doses, the effect was strongest the first days, but still partially present 14 days later. The difference of activity on calcemia and calciuria appears to be due to the fact that the tumor increased both bone resorption and renal reabsorption of calcium. Only the former was altered by the bisphosphonates. The two new compounds appeared to be of similar potency and more active than dichloromethylenebisphosphonate. These compounds could be promising for the treatment of malignant hypercalcemia and other conditions with increased bone resorption in humans, even when given only over short periods of time.

Alendronate↗
PubMed1983

Studies on the therapeutic effect of Wratizolin in selected dermatoses.

Clinical investigations of ITCL drug ("Polfa") were carried out on 50 patients (15 women, 16 men, 19 children, at the age of 4-80). ITCL has been successful in non-specific inflammations accompanying some virus dermatoses (zoster, herpes simplex), in streptococcal pyoderma (impetigo, ecthyma), and in some allergic dermatoses (disseminated eczema and atopic dermatitis). Encouraging results were obtained with ITCL in the treatment of psoriasis. It seems that the further attempts with this should be continued in psoriasis. The capillaroscopic examinations in 6 patients revealed ITCL to have vasoconstrictive effect on the nail wall cutis capillaries 6 h after its application. This may be associated with the anti-inflammatory effect of the drug.

Administration, Topical↗
PubMed1981

Activation of sodium cyanate for selective inhibition of protein synthesis in cultured tumor cells.

Sodium cyanate, a selective inhibitor of protein synthesis in animal tumors in situ, has no comparable effect when added to tumor cells in culture. However, a rapid inhibition of protein synthesis in cultured tumor cells can be achieved by reaction of cyanate with the drug-metabolizing system of liver microsomes. Procedures are described for the induction, preparation, and testing of an active cytochrome P-450 fraction which converts cyanate to a short-lived dialyzable metabolite that selectively inhibits amino acid incorporation in tumor cells without a corresponding effect on protein synthesis in normal cells. The suppression of tumor protein synthesis is not due to a general toxicity reaction because thymidine incorporation into the DNA of tumor cells is not inhibited by the cyanate metabolite. When HeLa cells are exposed to sodium butyrate, a substance reported to suppress the malignant phenotype in several tumor cell lines, they lose their sensitivity to the cyanate metabolite. Chick fibroblasts which are normally insensitive to the cyanate metabolite become cyanate sensitive after transformation by the Schmidt-Ruppin strain of the Rous sarcoma virus.

Adenocarcinoma↗
PubMed1979

Transformation of mercuric chloride and methylmercury by the rumen microflora.

The microflora in strained rumen fluid did not methylate or volatilize 203Hg2+ at detectable rates. However, there was an exponential decay in the concentration of added CH3Hg+, which was attributed to demethylation. The major product of demethylation was metallic mercury (Hg0), and it was released as a volatile product from the reaction mixture. Demethylation occurred under both anaerobic and aerobic conditions. The rate of demethylation was proportional to the concentration of added CH3Hg+-Hg from 0.02 to 100 microgram of Hg per ml. The presence of HgCl2 had almost no inhibitory effect on the rate of cleavage of the carbon-mercury bond of CH2HgCl, but it completely inhibited volatilization of the Hg formed, when the concentration of HgCl2-Hg reached 100 micrograms/ml. Three of 11 species of anaerobic rumen bacteria catalyzed demethylation. These were Desulfovibrio desulfuricans, Selenomonas ruminantium, and Megasphaera elsdenii. None of the 11 species caused detectable methylation, and only two caused limited volatilization of Hg2+. Three species of bacteria out of 90 fresh aerobic isolates from rumen contents were demethylators: two were identified as Pseudomonas sp., and the third was a Micrococcus sp. Demethylation by the rumen microflora appeared to be carried out by both aerobic and anaerobic bacteria and, on the basis of Hg2+ sensitivity, probably resulted from the activity of two enzymes, a CH3-Hg+ hydrolase and a Hg2+ reductase.

Aerobiosis↗