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Biomedical subjects

H G Klein

Publications and source records attributed to H G Klein.

At least 91 records · Page 5Linked to original sources
PubMed1991

Renal excretory function, atrial natriuretic peptide (ANP) and plasma renin activity (PRA) during long-term sodium loading in rats.

The effect of chronic sodium loading on the level of plasma atrial natriuretic peptide (ANP) and on plasma renin activity (PRA), as well as on the renal excretory function was studied. Fifty-six standardly bred Long Evans rats were divided into three experimental groups: controls, rats drinking 170 mmol NaCl/l solution instead of water, and rats consuming food with high sodium content (850 mmol NaCl/kg) for 21 days. During the study, we measured the amount of fluid intake, the parameters of the renal function: diuresis (VU); sodium, potassium and cloride excretion (UNa V, UKV and UClV), and the dynamics of body mass. On the 21st day the animals were sacrificed by decapitation. Plasma ANP and PRA were determined radioimmunologically. Packed cells volume and plasma Na and Cl concentrations were measured. The data showed a full compensation in sodium balance: the body mass dynamics in the three groups was similar; no changes in packed cells volume and plasma electrolytes were seen; UNaV and UClV were significantly increased in the groups with high sodium intake. PRA was significantly depressed in the two groups while ANP did not show any real changes. We concluded that it is PRA and not ANP that might participate in the regulation of chronic sodium balance.

Animals↗
PubMed1990

Prevalence of human immunodeficiency virus type 1 p24 antigen in U.S. blood donors--an assessment of the efficacy of testing in donor screening. The HIV-Antigen Study Group.

BACKGROUND: We performed a multicenter study in 1989 to determine whether screening whole-blood donors for human immunodeficiency virus type 1 (HIV-1) p24 antigen would improve transfusion safety by identifying carriers of the virus who are seronegative for HIV-1 antibody. METHODS: More than 500,000 donations were tested at 13 U.S. blood centers with test kits from two manufacturers. Units found repeatedly reactive were retested in a central laboratory; if the results were positive, they were confirmed by a neutralization assay. A subgroup of units was also tested for HIV-1 by the polymerase chain reaction. Selected donors confirmed or not confirmed as having p24 antigen were contacted for follow-up interviews to identify risk factors and undergo retesting for HIV-1 markers. RESULTS: Positive tests for p24 antigen were confirmed by neutralization in five donors (0.001 percent of all donations tested), all of whom were also positive for HIV-1 antibody and HIV-1 by polymerase chain reaction. Three of the antigen-positive donors had other markers of infectious disease that would have resulted in the exclusion of their blood; two had risk factors for HIV-1 that should have led to self-exclusion. Of 220 blood units with repeatedly reactive p24 antigen whose presence could not be confirmed by neutralization (0.04 percent of the donations studied), none were positive for HIV-1 antibody, HIV-1 by polymerase chain reaction (120 units tested), or virus culture (76 units tested)--attesting to the specificity of confirmatory neutralization. CONCLUSIONS: The finding that no donation studied was positive for p24 antigen and negative for HIV-1 antibody suggests that screening donors for p24 antigen with tests of the current level of sensitivity would not add substantially to the safety of the U.S. blood supply.

Blood Donors↗
PubMed1990

Syngeneic bone marrow transplantation and adoptive transfer of peripheral blood lymphocytes combined with zidovudine in human immunodeficiency virus (HIV) infection.

OBJECTIVE: To examine the role of syngeneic bone marrow transplantation and peripheral blood lymphocyte infusions combined with zidovudine in the treatment of patients with human immunodeficiency virus (HIV) infection. DESIGN: A partially randomized outpatient trial. SETTING: Outpatient and inpatient facility of the Clinical Center of the National Institutes of Health, a research-based referral facility. PATIENTS: Sixteen patients with HIV infection (15 symptomatic, 1 asymptomatic). INTERVENTIONS: Symptomatic patients were treated with zidovudine, 500 mg orally every 4 hours for 12 weeks, combined with six peripheral blood lymphocyte infusions (four at week 10, two at week 12) and bone marrow transplantation (at week 12) using HIV-seronegative identical twins as donors. After transplantation, patients were randomly assigned to receive either zidovudine, 100 mg every 4 hours, or placebo for 12 months. The asymptomatic patient received zidovudine for the first 12 weeks, discontinuing therapy after transplantation. Immunologic and virologic monitoring were done monthly. MEASUREMENTS AND MAIN RESULTS: Immediately after lymphocyte infusions and bone marrow transplantation, there was an increase in the mean (+/- SE) CD4 cell percent (19.1% +/- 3.1% to 28.1% +/- 3.0%), an increase in the fraction of patients with delayed-type hypersensitivity responses to tetanus toxoid (4 of 13 to 11 of 13) and the development of delayed-type hypersensitivity to keyhole-limpet hemocyanin (a primary immunogen to which only the donor had been immunized) in 8 of 12 patients tested. No significant clinical improvement was noted, however, and there was no overall sustained immunologic improvement. No differences in CD4 cell percents, delayed-hypersensitivity skin tests, HIV cultures, or p24 antigenemia were seen between patients treated with zidovudine or placebo after transplantation. CONCLUSIONS: Although they establish the feasibility of combining zidovudine with cellular immune reconstitution in treating patients with HIV infection, our results show that any benefits from such combination therapy are at best transient. Future attempts at cellular immune reconstitution may need to use improved antiretroviral regimens as well as immunization of donors with HIV-specific antigens.

Adult↗
PubMed1990

Millimolar concentrations of ascorbic acid in purified human mononuclear leukocytes. Depletion and reaccumulation.

Ascorbic acid (vitamin C) was found in isolated human mononuclear leukocytes and their purified components in millimolar concentration. Intracellular ascorbic acid was depleted greater than 96% during cell culture and was rapidly reaccumulated after addition of physiologic concentrations of ascorbic acid to the extracellular medium. Purified cells maintained concentration gradients of ascorbic acid as large as 100-fold across the plasma membrane. The ability to vary intracellular ascorbic acid concentrations over such a wide range makes it possible for the first time in these cells to study ascorbic acid function in direct relationship to intracellular concentration.

Ascorbic Acid↗
PubMed1990

Preparation of IgA-deficient platelets.

The IgA-deficient patient presents a difficult transfusion problem, particularly if he or she has previously been immunized and has formed IgA antibodies. Blood components from IgA-deficient donors may be used safely but are often not accessible to transfusion facilities. A satisfactory red cell component may be obtained by standard freezing and washing methods. There is no comparable platelet concentrate that uniformly affords protection against anti-IgA-mediated reactions. A method has been developed for the preparation of an IgA-deficient platelet concentrate by washing with citrate-buffered saline. Platelets prepared in this manner were transfused successfully to an IgA-deficient patient with a history of anaphylaxis related to transfusion. It was further demonstrated that the removal of IgA is enhanced if platelets are washed within 48 hours of collection. When platelets were stored for more than 48 hours, similar washing techniques resulted in significantly higher levels of IgA in the platelets washed with either buffered (p = 0.004) or unbuffered (p = 0.0002) saline. Platelets washed with unbuffered saline (pH 4.5-5.5) contained substantially more IgA than did platelets washed in a similar manner with citrate-buffered saline (pH 6.5-6.8) (p = 0.001).

Adolescent↗
PubMed1990

Effect of white cells on platelets during storage.

White cells (WBCs) present in stored platelet concentrates have adverse effects on platelet function and on posttransfusion recovery. Although these effects have been attributed to the fall in pH that results from active WBC metabolism, platelets stored in gas-permeable storage bags still exhibit abnormalities, despite maintenance of a stable pH of greater than 6.0. The changes in platelet proteins and function brought about by storage with a controlled number of WBCs were studied. Twelve platelet-pheresis specimens were centrifuged at 180 x g to achieve a WBC count of less than 2 x 10(5) per mL (which contained less than 10% granulocytes). These specimens were split into two aliquots and placed in platelet bags for storage at 22 degrees C with constant horizontal agitation. Neutrophils, obtained from the same donor by centrifugation of 50 mL of whole blood through a discontinuous ficoll gradient, were added to one of the two platelet storage bags to achieve a final neutrophil count of 1 x 10(6) per mL. Platelet aliquots were removed and studied on Days 3 and 5. In platelets stored without neutrophils, the average response to ristocetin, using the mean slope as an index of platelet responsiveness, was 10.3 (n = 9, SD = 11) on Day 3, whereas for the platelets stored with neutrophils, it was 1.25 (n = 12, SD = 0.9, p less than 0.01). Significant differences were also seen on Day 5 (slope = 4.5 for platelets stored without neutrophils, slope = 0.3 for platelets stored with neutrophils, p less than 0.01). Platelet aggregation with 8 microM ADP and 1.5 mg per mL of collagen did not differ significantly.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Diphosphate↗
PubMed1990

Controversies in transfusion medicine. Alanine aminotransferase screening of blood donors: pro.

In my opinion, independent, carefully conducted scientific studies indicate that an accurate, rapid, relatively sensitive, and inexpensive laboratory test substantially reduces the major long-term risk of blood transfusion in the United States; donor ALT has emerged as one of the most effective laboratory determinants for reducing the incidence of NANB PTH. Despite its nonspecificity and limited predictive value, ALT screening may prevent up to 30 percent of cases, one-half of which would progress to chronic liver disease and then possibly to cirrhosis and hepatocellular carcinoma. Blood donors appear to understand and accept the testing rationale as a reasonable precaution. Admittedly, ALT screening is not a perfect solution. It has not been validated by prospective studies and probably never will be. Determination of the proper cutoff value remains controversial. However, the risk of PTH progresses with increasing ALT levels, so that the real issue is not whether to test, but how best to configure the test to exclude the fewest false-positive donors while detecting the most true-positive donors. It is undesirable and expensive to discard safe units of blood, but the primary responsibility of blood collectors is to ensure an adequate supply of safe components. Some still consider the ALT assay technically too demanding for routine use. However, technical concerns regarding performance and interpretation are not insurmountable, and both quality control and proficiency testing are being addressed at the national level. The assay is capable of great precision, and a system employing a national standard and single cutoff has already been described and tested with excellent results. Circumstances have changed since donor screening with ALT was widely implemented in 1986. More thorough screening and testing have eliminated many high-risk donors. Public expectations have changed as well. While it is neither reasonable nor responsible to promise the public blood transfusions without risk, neither is it prudent to propose any major change in management of the blood supply without compelling evidence that such a change will not impair transfusion safety. It is hard to defend discontinuing the ALT screen at this time, especially when the costs of retaining it are minimal and the benefits clearly greater than those of screening for HTLV-I and for Treponema pallidum (in the United States) or HIV-2 (in West Germany). A first-generation assay specific for antibody to hepatitis C will probably be available within a year.(ABSTRACT TRUNCATED AT 400 WORDS)

Alanine Transaminase↗
PubMed1990

Microcirculatory adaptations in sickle cell anemia: reactive hyperemia response.

With the technique of laser-Doppler velocimetry, cutaneous blood flows in the forearm of patients with stable sickle cell disease after graded periods of proximal ischemia were compared with normal subjects matched for age, race, and sex, and with patients with anemia caused by beta(+)-thalassemia. In the sickle cell patients the reactive hyperemia was characterized by an increased time interval between the release of the occlusion and the peak amplitude response (time-to-peak) and by a greater period of blood flow above the base-line value (payback ratio) compared with controls. In addition, prolongation of the occlusion period led to an augmentation in the magnitude of the characteristic basal flow oscillations or an induction of this phenomenon at sites not exhibiting it before ischemia. Base-line or ischemia-provoked flow oscillations of either this magnitude or frequency were only observed in normal or thalassemic controls during brief intervals in the rapidly decaying portion of the hyperemic response and in one subject with homozygous hemoglobin C disease. These results would support a model of a local integrative control of microcirculatory blood flow, which appears to become augmented, synchronized, and sustained in sickle cell subjects.

Adaptation, Physiological↗
PubMed1990

Utilization patterns of frozen autologous red blood cells. Experience in a referral center and a community hospital.

The risks of homologous blood transfusion have motivated some blood centers and private industry to consider providing long-term storage of frozen, autologous red blood cells as a service. The usefulness of this practice is unknown. We performed a retrospective analysis of frozen autologous red blood cell use in two hospitals. Records were available for 21- and 9-year intervals, respectively. A total of 104 autologous units were cryopreserved for 41 patients. Fifteen (37%) of 41 patients received one or more of their stored units of red blood cells. Twenty-two patients had autologous units frozen in anticipation of elective surgery; 11 (50%) of these 22 patients received some or all of their stored units. Sixteen patients had autologous units stored because of potential transfusion problems related to rare blood types or to the presence of multiple blood cell alloantibodies, and another 3 patients had units frozen simply at their personal request. Only 4 (21%) of these latter 19 patients who donated without a specific planned use eventually received their frozen autologous red blood cells. Long-term autologous frozen red blood cell storage can improve medical management of some patients with anticipated surgical procedures or unusual requirements for transfusion. However, our study suggests that most autologous units frozen without specific planned use will not be transfused.

Blood Preservation↗
PubMed1989

Clinical implications of positive tests for antibodies to human immunodeficiency virus type 1 in asymptomatic blood donors.

Of 693,000 volunteer blood donors in Washington, D.C., who were screened for infection with human immunodeficiency virus type 1 (HIV-1) from July 1985 through December 1988, 284 tested positive on both enzyme immunoassay and Western blot assay. To determine the clinical importance of confirmed positive test results in asymptomatic blood donors, we followed 156 donors with positive Western blot assays and 80 donors with positive enzyme immunoassays but negative or indeterminate Western blots at 6-month intervals for a mean of 28 months. As compared with Western blot-negative persons, those with positive Western blots were significantly more likely to be black, male, and first-time donors and to have a history of venereal disease, generalized lymphadenopathy on examination, CD4-cell counts lower than 0.4 x 10(9) per liter, IgG levels higher than 18 g per liter, and antibody to hepatitis B core antigen on initial evaluation. In 17 (11 percent) of the Western blot-positive donors, the disease progressed to Class IV (symptomatic disease), according to the Centers for Disease Control system. CD4 counts below 0.2 x 10(9) per liter, IgA levels above 4 g per liter, abnormal proliferative responses to tetanus toxoid, and positive viral cultures were the strongest predictors of disease progression. Among the 80 donors with repeatedly reactive assay results but either negative or indeterminate Western blot assays, there was no evidence of HIV exposure in their histories, physical examinations, or laboratory evaluations, and manifestations of HIV infection developed in none of them. We conclude that a small number of persons with HIV infection continue to donate blood, despite attempts to exclude them, but that donors who test positive on enzyme immunoassay but persistently negative or indeterminate on Western blot assay probably do not represent a risk for the transmission of HIV.

AIDS-Related Complex↗
PubMed1989

Methylene blue for neutralization of heparin.

Patients with protamine allergy present a difficult dilemma when reversal of heparin is required for excessive bleeding. Premedication with steroids and antihistamines has not been shown to effectively prevent anaphylactic reactions in patients with hypersensitivity to protamine. Other heparin antagonists are either not available or are too toxic for human use. This report describes a patient in whom methylene blue was used effectively to neutralize heparin and decrease bleeding due to heparinization. In vitro testing was then done to further define the interaction of heparin and methylene blue. This testing demonstrated that methylene blue neutralized heparin levels of 1 u/ml as well as 10 u/ml. Methylene blue acted as an anticoagulant when present at levels of 3000 micrograms/ml. However, it acted as a coagulant when present in intermediate levels of 800 micrograms/ml and 1600 micrograms/ml. The plasma levels necessary for neutralization of heparin levels of 1 unit/ml (the levels achieved in patient therapeutically anticoagulated) are easily achieved using doses routinely used in treatment of methemoglobinemia. Although the toxicity of methylene blue has been well defined at the lower doses of 2-4 mg/Kg, work still needs to be done to determine safety of the drug at the higher doses necessary to neutralize heparin levels achieved in bypass patients.

Adult↗
PubMed1989

PGE2 concentrations in renal venous plasma and renal lymph during basal and stimulated conditions in the dog.

PGE2 concentration (pg/ml + SEM) was measured in canine renal lymph (394 +/- 115), renal venous plasma (276 +/- 55), arterial plasma (172 +/- 34) and urine (1290 +/- 934). Control periods were followed by an infusion of the sodium salt of arachidonic acid (AA) (40 micrograms/kg min) into the renal artery to stimulate prostaglandin synthesis. During infusion of AA PGE2 concentrations increased significantly in renal lymph (672 +/- 155) renal venous plasma (549 +/- 123), and urine (6768 +/- 1420), but not in the arterial plasma (176 +/- 31). Concentrations in renal lymph and renal venous plasma were not significantly different under either condition. These findings indicate that PGE2 concentration in renal venous plasma is, by and large, representative of mean PGE2 concentrations in the cortical renal interstitium, although focal inhomogeneities in PGE2 concentration in the different areas of the renal interstitium cannot be excluded. Since flow rate of renal lymph is insignificant in comparison with renal venous plasma flow rate total renal PGE2 output can be estimated from measurements in renal venous plasma and urine.

Animals↗