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Biomedical subjects

K Koch

Publications and source records attributed to K Koch.

At least 73 records · Page 4Linked to original sources
PubMed1992

Renal handling of enalaprilat.

Most converting enzyme inhibitors share a predominantly renal dual elimination pathway consisting of glomerular filtration and tubular secretion. Since enalaprilat has two functional acidic groups, it is likely that it may be secreted via the proximal tubule organic acid system and, thus, its clearances would exceed that of glomerular filtration rate markers. We therefore examined the renal clearance of enalaprilat in normal volunteers and compared it with simultaneously measured inulin and creatinine clearances to explore the contribution of tubular secretion to the renal elimination of the drug. Twelve healthy male subjects with an age range of 24 to 58 years (mean +/- SE, 33.1 +/- 2.8) were studied. They had representative height (178.6 +/- 1.99 cm) and weight (73.3 +/- 2.1 kg) and had normal renal function as judged by blood urea nitrogen (BUN) (6 +/- 0.3 mmol/L [17 +/- 0.8 mg/dL]), plasma creatinine (88 +/- 3 mumol/L [1.0 +/- 0.03 mg/dL]), and creatinine clearance determined by a prestudy 24-hour urine collection (123.2 +/- 6.2 mL/min). Results are as follows: mean creatinine clearance, 2.12 mL/s (127 mL/min); mean inulin clearance, 119.1 ml/min mean creatinine clearance/inulin clearance, 1.07 mean enalaprilat protein binding, 37.9% unbound enalaprilat clearance, 222.4 ml/min; and the mean fractional enalaprilat clearances were: enalaprilat clearance/creatinine clearance, 1.72 (P less than 0.05, difference from 1.0); enalaprilat clearance/inulin clearance, 1.85, (P less than 0.05, difference from 1.0). Our results demonstrate that the clearance of free enalaprilat exceeds that of inulin and creatinine, suggesting that elimination of the drug proceeds through two complementary pathways, namely glomerular filtration and tubular secretion.

Adult↗
PubMed1992

Analysis of c-myc, bcl-1 and bcl-2 translocations in human lymphoma by pulsed-field gel electrophoresis.

Translocations of the c-myc, bcl-2 and the putative bcl-1 oncogene are recurrent events in B-cell lymphoma. Since it is likely that the rearranged genes contribute to the malignant phenotype of the tumor cells, such oncogene translocation is of major interest. The molecular detection of translocations using conventional Southern hybridization analysis is complicated by the fact that translocation breakpoints are dispersed over large chromosomal regions. In order to overcome this problem we used pulsed-field gel electrophoresis (PFGE) to detect c-myc, bcl-2 and bcl-1 translocations in 29 lymph node biopsies. C-myc translocation could not be detected in this group, either with standard Southern analysis of PFGE. Translocations of the bcl-2 gene were detected by PFGE in 5 samples and the breakpoints were mapped in all cases to the third exon of bcl-2 by standard Southern analysis. Furthermore, we also found rearrangements of the bcl-1 locus in 3 samples. Mapping of the breakpoint failed in one of these cases, which strongly indicates the existence of a breakpoint outside the bcl-1 major breakpoint region. Thus, PFGE allows the rapid detection of translocations in human lymphomas within large stretches of DNA.

Adult↗
PubMed1992

Use of patient care extenders in critical care nursing.

This article explores the implementation and use of patient care extenders in two critical care units. Experimentation and diversity in changing the care-delivery system were the forces motivating the management team to redesign the existing nursing care-delivery system. The impetuses for the change process were the use of the role of the registered nurse and cost containment. Two case studies will illustrate from a practical perspective how the change occurred. Although the same nurse manager was responsible administratively for the two units, the patient care extender models were implemented differently. This was based on the conviction that each unit is unique with regard to patients and staff needs. The first case study occurred in an 18-bed cardiac telemetry unit in which the patient extender care model was integrated with direct patient care activities of the unit. In the second case study, which occurred in a ten-bed cardiac care unit, the patient care extender was integrated with indirect patient care activities. The approach to this article is practical, and it is intended for units that may be dealing with these issues in these changing times in health care.

Humans↗
PubMed1992

Expression of truncated transcripts of the proto-oncogene c-fps/fes in human lymphoma and lymphoid leukemia cell lines.

The human c-fps/fes proto-oncogene is expressed as a transcript of about 3.0 kb in both normal and leukemic myeloid cells. We have detected truncated c-fps/fes transcripts of about 0.9 kb in a panel of human lymphoma and lymphoid leukemia cell lines, but not in normal untransformed hematopoietic cells. Analysis of the chromatin structure of the c-fps/fes gene revealed DNAase I-hypersensitive sites in the 5' region of the gene and in exon 16. The presence and absence of these sites correlates with the expression of the 3.0 kb and 0.9 kb c-fps/fes RNAs respectively. The truncated transcripts initiate at two distinct sites within exon 16 of the c-fps/fes gene. The genomic region 5' to the transcription initiation sites is G+C rich but does not contain typical promoter consensus sequences. Sequence analysis of a cDNA clone of the truncated c-fps/fes transcripts did not reveal any point mutation and the truncated transcripts are normally spliced using the regular splice donor and acceptor sites. A putative open reading frame encompasses the phosphotransfer motif and the autophosphorylation site of the fps/fes kinase domain. In vitro transcription/translation of a cDNA clone corresponding to the truncated c-fps/fes transcripts revealed a protein of 17 kDa. There are no translocations or rearrangements in or around the c-fps/fes gene in cell lines which express the truncated c-fps/fes transcripts. This alternative transcription of c-fps/fes may indicate a novel activation process of this proto-oncogene.

Base Sequence↗
PubMed1991

Lower incidence of meningeal leukemia when prednisone is replaced by dexamethasone in the treatment of acute lymphocytic leukemia.

In 1971, Cancer and Leukemia Group B (CALGB) mounted a study of acute lymphocytic leukemia (ALL) that compared the effects of the two steroid hormones dexamethasone and prednisone. Six-hundred-forty-six children and adolescents with ALL were randomized to receive either prednisone or dexamethasone as part of their remission induction therapy. The 493 evaluable patients who achieved complete remission received the same steroid as pulses throughout remission. Specific central nervous system (CNS) therapy was randomized to either six injections of intrathecal methotrexate (IT MTX) alone or to six injections of IT MTX with cranial radiation (2,400 cGy). Both cranial radiation and dexamethasone offered increased protection against CNS relapse as the first site of failure over IT MTX alone. There were 30 CNS relapses among 238 patients (12.6%) receiving cranial radiation plus IT MTX, whereas there were 70 CNS relapses among 225 (P less than 0.001) (22.5%) in those who received IT MTX alone. Similarly, there were 33 CNS relapses among 231 (14.3%) children treated with dexamethasone, whereas there were 67 CNS relapses among 262 (25.6%) treated with prednisone (P = 0.017). Both steroids appeared equal in protecting the bone marrow. Recent national studies have shown significant improvements in preventing CNS relapse over the results in the present report. However, this finding warrants further investigation and, with further documentation, could lead to the substitution of prednisone by dexamethasone to aid further in preventing CNS relapse. This may be particularly important in patients at higher risk for CNS relapse.

Adolescent↗
PubMed1991

[Pancreatic penetration of antibiotics].

Antibiotic therapy is indicated in acute pancreatitis because the most common complication and the mean reason for mortality is a bacterial infection. Concentrations of nine antibiotics from various classes were studied in the pancreatic tissue and pancreatic juice of patients and dogs. The volume of distribution is the most valuable parameter for predicting the potential pancreatic penetration of a substance. As a result of our pharmacokinetic studies mezlocillin and cefotiam, especially ciprofloxacin, have the most antiinfectious potential in treatment of acute pancreatitis. Metronidazole is suitable for combination in cases of pancreatic infections covering anaerobic bacteria.

Animals↗
PubMed1991

[Determinant factors and disturbances in controlling power distribution patterns by the hyperthermia-ring system BSD-2000. 2. Measuring techniques and analysis].

Clinical observables and phantom measurements (part 1) have suggested that the control of power deposition patterns can still be improved for the hyperthermia system BSD-2000. This is addressed to system-specific phase errors as well as inadequacies of phase selection (target point method), which might be corrected by modifications of the manufacturer. Furthermore, frequency-dependent physical effects (coupling, mode excitation) are existing, which might cause distortions and asymmetries of current distribution on antennas and consequently deteriorate the power deposition pattern (e.g. focussing capability). The application of a network analyzer system is described in order to determine electrical material constants, phase errors, coupling coefficients, reflection coefficients and current distributions on antennas. The analysis of the measurement datas suggests that ring-applicator has a variable frequency-optimum (supposed around 80 ... 95 MHz) characterized by minimal coupling and asymmetries.

Humans↗
PubMed1990

Growth inhibition of human melanoma tumor xenografts in athymic nude mice by swainsonine.

Swainsonine, an inhibitor of alpha-mannosidases, has been shown to block experimental metastasis of B16F10 melanoma and MDAY-D2 lymphoid tumor cells in syngeneic mice. In this report we demonstrate that swainsonine also reduces the growth rate of human melanoma cells in vitro and in vivo. Graded doses of swainsonine were administered either orally or via implanted Alzet miniosmotic pumps to athymic nude mice bearing subcutaneously implanted human MeWo melanoma cells. Swainsonine at 10 micrograms/ml in the drinking water or 0.5 mg/kg/day administered by miniosmotic pump reduced the growth rate of the MeWo tumors by approximately 50% and inhibited the expression of complex-type oligosaccharides in tumors and host intestine by only 10-20%. Swainsonine doses of 4 mg/kg/day reduced expression of complex-type oligosaccharides by 85% in vivo but afforded no additional inhibitory effect. A glycosylation mutant of MeWo called 3S5 has a defect in the synthesis of complex-type asparagine-linked oligosaccharides resulting in incomplete processing similar to that observed in swainsonine-treated MeWo tumor cells. Swainsonine did not inhibit the proliferation of 3S5 cells in vitro nor the growth of 3S5 tumors in nude mice. The results suggest that expression of highly branched complex-type oligosaccharides commonly associated with the malignant phenotype may provide the tumor cells with a growth advantage.

Alkaloids↗
PubMed1990

[Laser and afterloading therapy of bronchial cancer].

Endobronchial afterloading irradiation by remote control was administered to 304 patients with lung cancer. The use of a highly active 192-Iridium source (740 GBq) is possible; irradiation time lasts only a few minutes. A combined treatment modality with laser was employed in 24%, with chemotherapy in 2%. The response rate of all patients amounted to 67%. There was an improvement in 81% of patients with retrostenotic complications.

Brachytherapy↗
PubMed1990

[The fibrinolytic tissue activity of various brain tumors].

In tissue samples of 45 operated astrocytomas and of 45 meningiomas the fibrinolytic and proteolytic activity was determined by means of fibrin-agar-plate-method. In astrocytomas significant higher values of fibrinolysis were found than in the meningiomas. In the course of tumor cell necrosis or as a result of brain damage caused by the operation, proteins inducing fibrinolysis are liberated. In some cases they can lead to localized or generalized disturbances of haemostasis.

Astrocytoma↗
PubMed1990

[The influencing factors and interfering effects in the control of the power distributions with the BSD-20000 hyperthermia ring system. 1. The clinical observables and phantom measurements].

A new generation of annular-phased-array systems BSD-2000 has been clinically applied in a pilot study. Therapeutic intratumoral temperatures greater than 42 degrees C were obtained in 15/15 sessions with six patients. However, the control of power deposition pattern has to be improved in order to increase the therapeutic gain and to guarantee an efficient therapy. A retrospective analysis of clinical phenomena has been performed by phantom set-ups because the power deposition pattern cannot be determined during therapy. Phantom measurement techniques are outlined, specifically phantom materials and visualization of power distributions. The problem of focus balance and frequency choice is illustrated by self-developed phantoms (liquid crystal sheets, light-emitting-diode-arrays). Especially, the limitation of modeling calculations is demonstrated.

Evaluation Studies as Topic↗