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Biomedical subjects

P Klein

Publications and source records attributed to P Klein.

At least 217 records · Page 12Linked to original sources
PubMed1980

Chronopharmacology: a therapeutic frontier.

Chronopharmacology, the study of time-dependent physiological response to drugs, and its relationship to current drug therapy are discussed. The objective of chronotherapy is to apply chronobiologic principles to the treatment of human disease. The appropriate patients for chronotherapy are those who are receiving high-risk drugs, who have a high-risk disease (e.g., cancer) or who are receiving a high-cost drug. Although little is known of the chronobiologic characteristics of many drugs or diseases, researchers should take into account the possible relationship of chronobiology to drug effects when designing therapeutic trials. Drug therapy can be optimized by tailoring dosing schedules and distribution systems to chronobiologic patterns.

Animals↗
PubMed1978

Phase II clinical trial with high-dose methotrexate therapy and citrovorum factor rescue.

One hundred and thirty-four patients with advanced malignant disease were treated with 496 infusions of high-dose methotrexate (HD-MTX) followed by citrovorum factor rescue. Most patients had failed to respond to previous combination chemotherapy. The overall response rate was 29% with 33 partial responses and six complete responses observed in patients with a variety of tumors. Plasma MTX levels were monitored in all patients during each course of therapy in order to identify those patients with delayed plasma MTX clearance. Patients with abnormally slow rates of plasma MTX decay received escalated doses of citrovorum factor rescue in order to prevent drug-induced toxicity. In general, during this study HD-MTX was well-tolerated. Because serious toxicity was neither frequent, severe, nor unpredictable, its use was not limited. HD-MTX should now be evaluated in well-designed controlled clinical trials to compare its antitumor activity to that of conventional- or standard-dose MTX regimens in diseases where HD therapy appears to have efficacy.

Adolescent↗
PubMed1978

[Use of tests based on the analysis of expired air in nutritional studies].

Tests based on the analysis of the gaseous components of expired air have been developed to study intestinal absorption and intermediary metabolism of various nutrients. This paper reviews the breath-analysis tests based on the measurement of CH4, H2, and isotopically-labelled CO2 for studying the intestinal absorption of carbohydrates, fats, and bile salts, and intrahepatic metabolism. New technology employing mass spectrometry allows the use of the stable isotope, carbon-13, instead of the radioactive isotope, carbon-14, for CO2 breath tests. The nutritional application of the breath-analysis tests is discussed, and the advantages of the non-radioactive, non-invasive procedures, especially for use in children and pregnant women in whom standard investigational methods represent a discomfort or a radioactive hazard, are emphasized.

Bile Acids and Salts↗
PubMed1978

Serological and chromatographic analyses of antigenic structures detected in human brain, thymus and lymph nodes.

In the present paper it is shown that the non-species specific determinant of the antigenic thymus-brain system previously detected in murine and human brain also exists in human thymus. However, in contrast to the situation in mice and rats this antigenic structure is not expressed on suspended thymic lymphocytes, but is associated with thymic tissue largely depleted of thymic lymphocytes. Moreover, this determinant is also detectable in human lymph nodes. Besides the non-species-specific antigenic determinant human thymus and brain also share a species-specific determinant. In contrast to the non species specific determinant this structure is also displayed by suspended thymic lymphocytes, certain peripheral blood lymphocytes and bone marrow cells. The non-species-specific determinant detected in human thymus is borne by a structure, which physico-chemically resembles the thymus-brain antigen isolated from murine brain and thymus as well as from human brain. Although the structure bearing the species specific antigenic determinant has a similar apparent molecular weight both antigens could be separated by ion exchange chromotography indicating their molecular diversity.

Animals↗
PubMed1976

[New method for security by colon anastomoses (author's transl)].

After examinaning the vascular supply of the parietal peritoneum helved peritoneal flaps were fixed in wound dehiscent colon anastomoses. If the vascular supply to the peritoneal flap was sufficient all animals survived without signs of stenosis. It was proved by microangiographic studies that there was an additional vascular supply to the anastomosed colon by the artery of the peritoneal flap.

Animals↗
PubMed1976

Solubilization and molecular characterization of membrane-bound antigens shared by thymocytes and brain.

In order to characterize chemically the serologically well-defined antigens shared by thymocytes and nervous tissue of mice and rats, different solubilization procedures have been tested. Treatment of thymocyte membranes with urea-Nonidet-P40 (NP40) proved to be the most valuable method, since nearly 100% of the antigen was solubilized essentially without loss of the antigenicity. By gel filtration in urea-NP40 the molecular weight was estimated to be 35 000 and the Stokes radius in sodium deoxycholate 31.8 A. In gel filtration studies a homogenous peak was obtained, whereas isoelectric focusing yielded two peaks (isoelectric points pH 4.5-5.0 and pH 5.4). The three determinants of this antigenic system were inseparable in gel filtration and isoelectric focusing, supporting the view put forward on the basis of serological studies that they are part of the same molecule. Extraction of murine thymocyte membranes with organic solvents yielded a considerable loss of activity of the thymocyte-brain antigen. There was some residual activity in the protein fraction, but none in the organic phase. Correspondingly, the highly purified ganglioside G Gtet 2b proved unable to absorb any rabbit anti-CBA brain serum. The reduced antigenic activity of the delipidated protein fraction could be restored by addition of lipids, as well as the nonionic detergent NP40. These observations suggest that interaction of protein and lipid is necessary for the antigenicity of the thymocyte-brain antigen.

Animals↗
PubMed1976

[Cultivation of the epithelium in burns].

Comparison of two groups of burned patients shows that patients who were treated by wound solution stayed a significantly shorter time in hospital. The group with healing under the scab (PQB) had indeed slighter skin lesions, but syated a much longer time in hospital. The great advantage of treatment of burned wounds with wound solution is seen in the relief of pain of the patients. Aslo, physical exercises can begin immediately. Wound solution needs no anaesthesia for necrolysis. The shortening of the healing time results in stimulation of the marginal epithelium and growth of autologous transplanted cells on the wound.

Adult↗
PubMed1975

[Antibody differentiation in human toxoplasmosis experiments on model cases (author's transl)].

Human sera with antibodies against Toxoplasma gondii were investigated-before and after gel filtration (Sephadex G 200)-by IgM-and IgG-specific immunofluorescent reactions as well as well by complement fixation tests.-In sera from patients with "latent" infections IgM-antibodies could not be demonstrated neither by the IgM-IFT-nor the CFT technique, although IgG antibodies with IFT titres between 1:50 qnd 1:200 were present.-In sera from patients in the "acute" stage of infection both IgM and IgG antibodies were always found. In some cases the IgG fraction had complement fixing properties only, although IgM antibodies were present as demonstrable by the IFT technique. -These observations leed to the possibility of immunologic differentiation between IgM-IFT and CF-antibodies. The role of the different antibodies in the serodiagnosis of human toxoplasmosis is discussed.

Adolescent↗
PubMed1975

Successful application of prenatal diagnosis in a pregnancy at risk for homozygous beta-thalassemia.

A Sicilian couple whose first child had homozygous beta-+-thalassemia requiring monthly transfusion requested prenatal diagnosis during the second pregnancy. Fully informed consent was obtained. The placenta was localized by ultra-sound at the 20th week of gestation, and was aspirated with a 20-gauge needle. Samples containing fetal red cells were obtained, and studies of globinchain synthesis showed a normal beta/gamma synthesis ratio for this gestational age. The conclusion that the child was not affected by beta-thalassemia was confirmed when an infant not affected with homozygous of heterozygous beta-thalassemia was born at term. Although more experience with this approach is necessary, this study demonstrates that prenatal diagnosis or exclusion of beta-thalassemia and sickle-cell anemia is feasible.

Blood Cell Count↗
PubMed1975

Bile salt metabolism in the human premature infant. Preliminary observations of pool size and synthesis rate following prenatal administration of dexamethasone and phenobarbital.

Bile salt synthesis and bile salt pool size were determined by isotope dilution in two groups of healthy premature infants, utilizing nonradioactive deuterium-labeled bile salts. All 9 infants were between 32 and 36 weeks of gestation; however, in one group (4 infants), the mothers had received either dexamethasone or phenobarbital prior to delivery. The total bile salt pool averaged 20 mg for the infants of untreated mothers and 79 mg for the infants of treated mothers; similarly, the bile salt synthesis of 8 mg per day in the untreated group was increased to 27 mg per day for the treated group. Expressed per sq m of body surface, the cholic acid pool for the treated group was 321 mg per sq m, and the cholic acid synthesis rate equaled 98 mg per sq m per day; values equal to those for full term infants and nearly 4 times those for the untreated prematures. The intraduodenal bile salt concentrations obtained during meals were also low in the untreated group, equaling 1.2 mM as compared to 5.3 mM for the treated group. The reductions of bile salt pool size, synthesis, and intestinal concentration establish that the functional maturity of the liver, and possibly the gastrointestinal tract, is reduced in premature infants. The results further suggest that this maturity may be dramatically influenced by medications administered to the mother prior to delivery.

Bile Acids and Salts↗