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P Kohler

Publications and source records attributed to P Kohler.

At least 19 recordsLinked to original sources
PubMed2004

Ethnicity and glutathione S-transferase (GSTM1/GSTT1) polymorphisms in a Brazilian population.

The distribution of polymorphisms related to glutathione S-transferases (GST) has been described in different populations, mainly for white individuals. We evaluated the distribution of GST mu (GSTM1) and theta (GSTT1) genotypes in 594 individuals, by multiplex PCR-based methods, using amplification of the exon 7 of CYP1A1 gene as an internal control. In São Paulo, 233 whites, 87 mulattos, and 137 blacks, all healthy blood-donor volunteers, were tested. In Bahia, where black and mulatto populations are more numerous, 137 subjects were evaluated. The frequency of the GSTM1 null genotype was significantly higher among whites (55.4%) than among mulattos (41.4%; P = 0.03) and blacks (32.8%; P < 0.0001) from São Paulo, or Bahian subjects in general (35.7%; P = 0.0003). There was no statistically different distribution among any non-white groups. The distribution of GSTT1 null genotype among groups did not differ significantly. The agreement between self-reported and interviewer classification of skin color in the Bahian group was low. The interviewer classification indicated a gradient of distribution of the GSTM1 null genotype from whites (55.6%) to light mulattos (40.4%), dark mulattos (32.0%) and blacks (28.6%). However, any information about race or ethnicity should be considered with caution regarding the bias introduced by different data collection techniques, specially in countries where racial admixture is intense, and ethnic definition boundaries are loose. Because homozygous deletions of GST gene might be associated with cancer risk, a better understanding of chemical metabolizing gene distribution can contribute to risk assessment of humans exposed to environmental carcinogens.

Adult↗
PubMed2003

Three regulatory regions of the Aedes aegypti glutamine synthetase gene differentially regulate expression: identification of a crucial regulator in the first exon.

Aedes aegyptiglutamine synthetase (GS) is expressed constitutively at various developmental stages and its relative mRNA abundance increases in the midgut following blood feeding in support of the biosynthesis of chitin, a component of the peritrophic matrix. To understand the regulation of GS expression better, GS-luciferase reporter fusion genes were constructed and analysed in transiently transfected C6/36 cells. These studies have identified three GS regions: GS-A, -B and -C (C1, C2) that are required for efficient transcription. The crucial regulatory DNA sequence is located within 140 nucleotides of the GS-C region in the first exon. GS-B region between -209 and +4 contains a negative modulator that represses transcription of the GS-C promoter, but the 5'-GS-A region, between -476 and -282, can negate the transcription inhibition of GS-B and promote GS transcription of the GS-C promoter. Electrophoretic mobility shift assays showed that nuclear proteins for GS-A, GS-B and GS-C1 are present in the C6/36 cells, and therefore that GS-A, GS-B and GS-C1 indeed possess regulatory function. By contrast, nuclear proteins isolated from both cultured cells and midgut tissues bound to GS-C2, suggesting that GS-C2 plays an important role in GS transcription and that GS-C2 is regulated by several different and redundant transcription factors to achieve constitutive expression in a wide variety of tissues.

Aedes↗
PubMed1994

A phase II study of vinblastine in combination with acrivastine in patients with advanced renal cell carcinoma.

Renal cell carcinoma exhibits chemoresistance attributable in part to the P-glycoprotein drug efflux mechanism. Acrivastine is a hydrophylic antihistamine that has been shown in vitro to reverse this form of resistance. After five patients were treated on a dose-finding study, seventeen patients with metastatic or unresectable renal cell carcinoma were entered into a phase II study of vinblastine in combination with acrivastine. Patients received oral acrivastine at doses of 400 mg every 4 hours for 6 days and a 96-hour continuous infusion of vinblastine at a dose of 1.6 mg/m2/24 h. Of 15 evaluable patients, no tumor responses were seen. The regimen was well-tolerated with the majority of toxicities being gastrointestinal and hematologic. Serum levels of acrivastine, its principal metabolite (270C81) and vinblastine were measured during the study. Based on in vitro data, the plasma levels of acrivastine were within a range adequate to block P-glycoprotein activity. High doses of acrivastine were well-tolerated clinically, however, the combination of acrivastine and vinblastine was not active against renal cell carcinoma.

Adult↗
PubMed1994

Effect of hypertonic NaCl-starch-solution on oedema of different pathogenesis.

Small volumes of hypertonic NaCl-solutions have been proven to restore haemodynamics in hypovolemic shock patients. Topic of this study was to investigate whether bolus application of 7.5% NaCl-6.5% starch-solution (HSS) apart from its relevance in shock might be an effective therapy in oedema. Considering differential therapeutic aspects, the volume effects of 7.2 ml HSS were tested in three types of oedema: hydrostatic oedema induced by venous congestion (n = 6), oedema caused by bradykinin injection (n = 6), and proteinase-induced oedema (n = 6). The arterial, venous pressure and weight changes indicating volume shifts between intra- and extravascular space were continuously monitored in 36 isolated perfused rabbit hindlimbs. Oedema formation was induced corresponding to a weight gain of 18-20 g. Subsequently 7.2 ml HSS were injected into the extracorporeal circulation system containing 200 ml cell free, isoosmotic perfusate. Six experiments of each oedema group without HSS-application served as controls. 75-100% of oedema formation could be remobilised via bolus application of HSS within 5 min in all types of oedema. A persisting weight reduction was detectable in the hydrostatic and bradykinin oedema, whereas in the elastase oedema the initial weight loss was followed by a regain of weight up to 180% of initial oedema formation at 120 min after HSS-application. The results show that, due to the osmotic gradient induced by bolus application of HSS, the hydrostatic and bradykinin oedema can be permanently remobilised, whereas the therapeutic effect during proteinase oedema is only short-lasting due to an irreversible damage of barrier function.

Animals↗
PubMed1992

Phase I evaluation of 773U82-HCl in a two-hour infusion repeated daily for three days.

One of a novel series of compounds (AMAPS or arylmethylaminopropanediols), 773U82-HCl has shown significant antitumor activity in in vitro and in in vivo tumor systems, but has less animal CNS toxicity than the lead compound in the same series (crisnatol). This study was designed to evaluate the pharmacokinetics, qualitative and quantitative toxicities of 773U82-HCl and to determine the recommended phase II dose (MTD) of 773U82-HCl given as a short infusion daily for 3 days every 3 weeks. Twenty-nine patients with refractory malignancies received 79 courses over 9 dose levels during this study. Doses ranged from 50 to 1060 mg/m2/d x 3 days. Due to the possibility of local hemolysis with concentrations > 1.5 mg/ml, drug was administered in solutions containing < or = 1.5 mg/ml. Because large volumes were needed at the higher dose levels, the infusion duration was increased from 2 hours to 4 hours. Mild to moderate nausea, vomiting, fatigue, dizziness and headaches were observed. Myelosuppression was the dose limiting toxicity. The recommended phase II dose and schedule was determined to be 800 mg/m2/d x 3d every 3 weeks. 773U82-HCl plasma concentration-time data were analyzed using a two-compartment pharmacokinetic model. The t1/2 beta averaged 6 hours and the total body clearance was 75.9 L/hr/m2. The volume of distribution (Vdss) was large, averaging 470 L/m2.

Adult↗
PubMed1992

[Are humidity filters necessary in the inspired air in the breathing circuit? A new in vivo method of measuring humidity in the air breathed].

Humidification of inspiratory gases under anaesthetic conditions still is a matter of controversial discussion. Physiological humidification and heating of breathing air are preconditions for mucociliary clearance, pulmonary cleaning and defence mechanisms. These functions of the upper respiratory tract are eliminated by application of artificial airways. In general the humidification of inspiratory gases should not remain under 70% of relative air humidity at 37 degrees C. Under clinical conditions it is problematic to ensure sufficiently rapid and reproducible measurements of humidity during breathing cycles. We developed a measuring method that enables to make these measurements without big mechanical device. Aim of this investigation was to measure air humidity in typical semiclosed systems during anaesthesia and semiopen CPAP-respiration. The necessity and efficiency of a heat and moisture exchanger (HME) was to be investigated as well. After approximately 5 minutes there was an inspiratory relative air humidity not below 70% at 28 degrees C (19 mg H2O/l humid air) within the breathing circuit with CO2 double-absorber. By using an HME it is possible to increase relative air humidity within this system to 86% at 29.5 degrees C (25 mg/l). After one hour's respiration with this system without HME a relative humidity of 87% at 30 degrees C (26 mg/l) is reached after replaced HME. Initial relative humidity in a semiopen CPAP-system is about 12% at 28 degrees C (3 mg/l). This is increased to 85% at 29.5 degrees C (25 mg/l) after 15 minutes respiration with HME.(ABSTRACT TRUNCATED AT 250 WORDS)

Air↗
PubMed1990

[Lung imaging in intensive medicine. A comparison of digital storage-screen imaging and conventional film-screen imaging].

Luminescence radiography is a new digital imaging modality, which can be used instead of conventional film radiography for many examinations. Imaging capabilities of luminescence radiography were compared with film radiography by test images and examinations especially in intensive care radiology. The results demonstrate, that luminescence radiography is an advantageous imaging method for intensive care radiology.

Humans↗
PubMed1990

[Adaptation of the left ventricle function to exercise in aortic stenosis. Study with cavitary angioscintigraphy].

Eighteen patients with pure aortic stenosis without coronary artery disease underwent equilibrium radionuclide angiography to evaluate the adaptation of their left ventricular function to exercise. The left ventricular ejection fraction, peak left ventricular ejection, and fillings, and their timing were calculated from time-activity curves and their first derivatives at rest and at the maximum of exercise. There were no clinical complications. The ST segment and T wave changes of 14 patients were accentuated and 3 patients developed anginal pain. The ejection fraction was normal at rest and did not change significantly during exercise. The peak ejection did not vary but peak left ventricular filling was prolonged by exercise. There was a correlation between peak ventricular ejection at rest and the aortic valve surface area at catheterisation. This isotopic parameter was inversely correlated with LVEDP. There was a close correlation between age and peak ventricular filling on exercise. The variation between resting and exercise values of this parameter was inversely correlated with age. This study shows that exercise stress testing can be undertaken without risk in patients with aortic stenosis. The results of radionuclide angiography show that peak left ventricular ejection is a valuable parameter. The interpretation of the diastolic parameters is however more difficult because they are age-related.

Adult↗
PubMed1989

[Detection of coronary restenosis using myocardial tomoscintigraphy with thallium 201. A series of 85 cases].

UNLABELLED: After a successful coronary angioplasty (less than 50 p. 100 residual stenosis and no complication), can restenosis be detected by a non-invasive method? We tested the value of stress thallium 201 myocardial scintigraphy by comparing this method with clinical angina and the conventional exercise-induced angina test. The study was prospective and involved 85 patients (74 men, 11 women; mean age 54.7 years, range 33-78 years). Sixty patients were suffering from angina, 13 had post-infarction angina and 12 had mild necrosis. Angioplasty had been performed on a single vessel (LAD in 57 cases, right in 18 cases and CX in 10 cases). After 6.4 +/- 1.8 months, all patients were re-evaluated under treatment, undergoing successively an exercise test, a stress and recovery myocardial scintigraphy and a coronary angiography. Restenosis was defined as a more than 50 p. 100 reduction of diameter on two orthogonal planes and was observed in 22 cases (26 p. 100). 19 patients were suffering from angina, 12 had restenosis, 10 were asymptomatic but had restenosis. Eighteen exercise tests were pathological; 10 corresponded to restenosis and 12 were normal in spite of restenosis. Myocardial scintigraphy was regarded as positive when, outside a necrotic territory, a lack of uptake at stress was reversible or became worse at redistribution. 27 tests were positive, 18 corresponded to restenosis, 4 were normal in spite of restenosis. The diagnostic values of the three methods were compared: (Table: see text). CONCLUSIONS: (1) stress myocardial scintigraphy has the best sensitivity and specificity; (2) if it is negative, restenosis is very unlikely; (3) coronary angiography may be performed only in case of symptoms and/or of positive stress scintigraphy.

Adult↗
PubMed1985

[A simple system for emergency coniotomy].

The successful clinical application of a new emergency cricothyrotomy device is reported. We used it first in a patient who was in acute respiratory insufficiency and could not be intubated because of a large tumour in the pharynx. Emphasis is placed on the description of the easy handling especially for less experienced physicians and of the atraumatic procedure.

Acute Disease↗