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Biomedical subjects

H G Klein

Publications and source records attributed to H G Klein.

At least 109 records · Page 6Linked to original sources
PubMed1989

Effect of atrial natriuretic peptide on the release of rat renal kallikrein.

The effect of atrial natriuretic peptide (ANP) on renal kallikrein release was investigated in barbiturate anesthetized rats. ANP injections in a pharmacological dose (1 microgram i.v.) increased kallikrein excretion for about 15 min. The effect of ANP on kallikrein excretion was abolished when amiloride (2.5 mg i.v.) was administered prior to the injection of the peptide. Intravenous infusion of ANP (1 or 5 micrograms/h) or of isotonic saline (2 or 4 ml/h) did not alter urinary kallikrein output. When the ANP infusion was discontinued, the excretory rate of the enzyme tended to decrease. This decrease was prevented by the administration of 0.1 mg/h desoxycorticosterone-glucoside. A transient increase in kallikrein excretion, coincident with the appearance of diuresis, was observed during ANP infusion in the mineralocorticoid-treated animals. The rate of kallikrein release into the incubation medium by rat kidney slices was not affected by the presence of ANP (10(-9)M). These results can be interpreted as effects following an increased distal sodium delivery rather than a direct effect of ANP on connecting tubule cells (CNT cells).

Amiloride↗
PubMed1988

Technical aspects of lymphokine-activated killer cell production.

Adoptive immunotherapy is a novel approach to treating patients with cancer, utilizing as therapy a patient's own peripheral blood lymphocytes that have been activated by incubation with interleukin-2 (IL-2). These cells develop the ability to mediate tumor regression in vivo and are referred to as lymphokine-activated killer (LAK) cells. The production of LAK cells is a complex and labor-intensive process. Lymphocytes are collected by continuous-flow centrifugation, purified on Ficoll-Hypaque (FH) density gradients, incubated in vitro with IL-2, and then harvested for infusion into the patient. An automated approach to LAK cell generation has been developed using the Fenwal CS-3000 cell separator and polyolefin PL-732 blood storage bags. Lymphocyte concentrates (LC) containing 6.5 x 10(9) mononuclear cells per pack were obtained using standard leukapheresis techniques. Disposable apheresis kits were then modified to allow the LC to be pumped into the separation chamber along with a counter-centrifugal flow of saline, removing the platelets and plasma by elutriation. The remaining cells were underlaid with FH, displacing the lymphocytes into a collection bag, where they were washed and concentrated. Mean leukocyte recovery was 59.2% (99.9% lymphocytes, n = 14). The final product contained 6.7% of the initial platelets and had a hematocrit of less than 1%.(ABSTRACT TRUNCATED AT 250 WORDS)

Automation↗
PubMed1988

Adoptive immunotherapy: novel applications of blood cell separators.

Animal models have demonstrated that syngeneic lymphocytes activated ex vivo and infused into animals with experimentally induced tumors can mediate tumor regression. This "adoptive immunotherapy" has been applied to patients with end-stage malignancy refractory to standard therapy. Lymphocytes are collected with the blood cell separator, expanded in culture under the influence of cytokines such as interleukin-2 (IL-2), and reinfused into the patient under conditions similar to those used in the animal models. Studies from several centers using lymphokine-activated killer (LAK) cells, involving more than 300 patients, have shown an overall response rate of greater than 15% and a complete response rate of approximately 10%. Renal cell carcinoma, melanoma, and lymphoma appear to be the cell types that respond best to such therapy. Toxicity in these phase 1 studies has been substantial, related primarily to high doses of intravenous IL-2, and treatment-related deaths have been reported. Adoptive immunotherapy using lymphocytes derived from surgically excised tumors, tumor-infiltrating lymphocytes (TIL), is in the early stages of clinical trials, but this appears to offer a potentially more potent and specific approach than does LAK cell therapy. TIL have been shown to traffic to tumor sites and mediate tumor regression. The mechanisms of adoptive immunotherapy are poorly understood, but blood cell separators and storage technology are playing a critical role in the collection and processing of cells for these research applications.

Blood Component Removal↗
PubMed1988

Transfusion therapy in emergency medicine.

Volume replacement is critical to the resuscitation of the hemorrhaging patient, but this usually can be accomplished quickly and safely with crystalloid and/or colloid solutions. Red cells should be used in addition to asanguinous fluids in the treatment of tissue hypoxia due to anemia. The need for whole blood as opposed to packed red blood cells is controversial. However, plasma should not be used as a volume expander, and its use to supplement coagulation factors during the massive transfusion of red cells should be guided by laboratory tests that document a coagulopathy. Similarly, platelet transfusions are indicated to correct documented thrombocytopenia or platelet dysfunction, and routine prophylaxis after fixed volumes of red cells results is unwarranted. Many anticipated complications of massive transfusions, including hemostatic abnormalities, acid-base imbalances, hyperkalemia, and hypocalcemia, are uncommon or of limited clinical significance. The risks of immune hemolysis and transfusion-transmitted diseases, on the other hand, are significant, and argue for judicious use of blood components. In emergencies in which blood is required immediately before compatibility testing can be completed, O-negative uncrossmatched blood can be requested. Careful blood specimen collection and patient identification prior to transfusion are critical. Practices that emphasize blood conservation, including the use of autologous salvaged blood, are always to the patient's advantage.

Blood Grouping and Crossmatching↗
PubMed1987

'Blood doping'.

Explore the source record for details and available documents.

Blood Transfusion↗
PubMed1987

Development of an automated closed system for generation of human lymphokine-activated killer (LAK) cells for use in adoptive immunotherapy.

Immunotherapy utilizing the adoptive transfer of lymphokine-activated killer (LAK) cells in conjunction with recombinant interleukin-2 (IL-2) can mediate tumor regression in some patients with advanced cancer. The activation of large numbers of LAK cells was performed in roller bottles in a research laboratory setting and required meticulous aseptic technique, at least one skilled technician per patient and one laminar flow hood per patient. To reduce the complexity and expense of LAK cell generation for human immunotherapy trials we have developed a closed-system automated procedure using a continuous flow blood cell separator. PBL were obtained by standard apheresis techniques. Platelets and plasma were elutriated using countercentrifugal flow of saline in the cell separator machine. The washed PBL were underlaid with Ficoll-Hypaque (FH) in the original separation bag. Lymphocytes were then flushed into a collection bag where they were concentrated and washed with 2 liters of saline. Mean recovery from the automated FH technique was 54.6 +/- 4.3% compared to 62.3 +/- 4.0% using manual methods in 50 ml tubes (P greater than 0.05). Cells were diluted in the collection bag with RPMI 1640 +/- 2% human AB serum and could be dispensed in an automated fashion to polyolefin bags via a sample port with 1000-1500 U/ml IL-2. After 3-4 days of culture in 5% CO2 at 37 degrees C, activated cells from the bags were harvested and washed in a closed system using the continuous flow cell separator. Cell yield from the harvest was 79.2 +/- 5.4% in the automated system compared to 64.9 +/- 5.0% in the standard procedure using manual harvest of roller bottles (P less than 0.01). Lytic capacity of the cells against fresh human tumor in a 4 h 51Cr release assay was equivalent in cells processed either by the automated or the conventional manual method. The advantages of a closed system include decreased potential for microbial contamination and reduced labor and capital equipment costs. This technique may be easily adapted for use with other cell collection and culture systems.

Cell Separation↗
PubMed1987

A new technique for the cannulation of small lymph vessels.

A method is described which allows rapid cannulation of small lymph vessels using a modified, in-dwelling cannula and a tissue glue. The method was used to cannulate hilar lymph vessels of the kidney but should but appropriate to cannulate small lymph vessels at other locations as well.

Animals↗
PubMed1986

Optimization of parameters for maximization of plateletpheresis and lymphocytapheresis yields on the Haemonetics Model V50.

Automated apheresis techniques afford the opportunity of tailoring collection parameters for each donor's hematologic profile. This study investigated the effect of various settings of the volume offset parameter as utilized in the Haemonetics Model V50 instrumentation during platelet- and lymphocytapheresis to optimize product yield, purity, and collection efficiency. In both types of procedures, increased product yield could be obtained by using an increased volume offset for donors having lower hematocrits. This improvement was related to an increase in collection efficiency. Platelet products also contained fewer contaminating lymphocytes with this approach. Adjustment of the volume offset parameter can be utilized to make the most efficient use of donors and provide higher-quality products.

Automation↗
PubMed1985

Effects of hemodilution on O2 transport in high-altitude polycythemia.

A native of the Peruvian Andes (4,250 m) was studied before and after isovolemic hemodilution of the hematocrit from 62 to 42%. O2 transport was studied with newly developed catheters in the radial and pulmonary arteries. These catheters allowed continuous measurement of arteriovenous O2 content and intermittent cardiac output by thermodilution. During exercise tests, breath-by-breath gas exchange measurements also allowed cardiac output to be calculated by the O2-Fick technique. A complex series of interrelated physiological changes occurred in response to hemodilution. These included increased ventilation, increased arterial and mixed venous PO2, increased cardiac output (both heart rate and stroke volume), and improved ventilation-flow match. The general improvement in symptoms that followed hemodilution correlated well with increased anaerobic threshold and mixed venous PO2 during exercise.

Altitude↗
PubMed1984

Periodic microcirculatory flow in patients with sickle-cell disease.

We have applied the technique of laser-Doppler velocimetry to compare patterns of cutaneous blood flow in the forearms of patients with stable sickle-cell disease, with the patterns in normal subjects matched for age, race, and sex, and in patients with anemia due to beta+-thalassemia. The mean resting blood flow in the patients with sickle-cell disease was comparable to that of the control groups but was associated with large, local oscillations in flow with periods of 7 to 10 seconds and peak-to-trough magnitudes about half the mean flow. Oscillations occurred simultaneously at sites separated by 1 cm but were independent in phase and frequency. Since these laser-Doppler measurements represent the average flow pattern in about 1 mm3 of skin (i.e., in approximately 50 to 70 capillary loops), these results suggest that microcirculatory flow in patients with sickle-cell disease proceeds by synchronization of rhythmic flow in large domains of microvessels. These findings indicate that periodic flow may be a compensatory mechanism to offset the deleterious altered rheology of erythrocytes containing polymerized hemoglobin S, and suggest that laser-Doppler velocimetry may be a useful method to investigate microvascular physiology in patients with sickle-cell disease.

Adult↗