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Biomedical subjects

H G Klein

Publications and source records attributed to H G Klein.

At least 19 recordsLinked to original sources
PubMed2005

Pathogen inactivation technology: cleansing the blood supply.

The calculated residual infectious risk of HIV, hepatitis B virus (HBV) and hepatitis C virus (HCV) from blood transfusion is extremely low. However, the risk of bacterial contamination remains and a variety of other agents including emerging viruses, protozoa and tick-borne agents threaten blood supplies and undermine public confidence in blood safety. Traditional methods of donor screening and testing have limited ability to further reduce disease transmission and cannot prevent an emerging infectious agent from entering the blood supply. Pathogen inactivation technologies have all but eliminated the infectious risks of plasma-derived protein fractions, but as yet no technique has proved sufficiently safe and effective for traditional blood components. Half-way technologies can reduce the risk of pathogen transmission from fresh frozen plasma and cryoprecipitate. Traditional methods of mechanical removal such as washing and filtration have limited success in reducing the risk of cell-associated agents, but methods aimed at sterilizing blood have either proved toxic to the cells or to the recipients of blood components. Several promising methods that target pathogen nucleic acid have recently entered clinical testing.

Acquired Immunodeficiency Syndrome↗
PubMed2005

Blood substitutes: how close to a solution?

The term "blood substitute" is commonly misused when "red cell substitute (RCS) is meant. The ideal RCS should deliver (i) oxygen; (ii) require no compatibility testing; (iii) cause few side effects; (iv) have prolonged storage qualities; (v) persist in the circulation and (vi) be available at reasonable cost. While no drug with all these qualities is on the near horizon, several early generation RCS are approaching submission for licensing, at least for limited indications. Haemoglobin-derived RCS from human, bovine and recombinant sources, as well as perfluorochemicals that dissolve 02 are in different stages of development. While each formulation has its own physical characteristics, biological activities, and adverse reaction profile, all share one characteristic: the physiological consequences of delivering 02 with small molecules is poorly understood and may both account for problems seen in the clinical trials and provide therapeutic opportunities for the cancer patient. Those RCS in phase III trials all have a half-life measured in hours and are unlikely to replace transfusions or drugs that stimulate erythropoiesis for chronic anaemia, but they may play a role (i) in military and civilian trauma as resuscitation solutions, (ii) as a bridge to transfusion when no compatible blood is immediately available, (iii) as an adjunct to the autologous haemodilution management of surgery, or even (iv) in radiation therapy or the management of cancer-related vascular occlusive syndromes.

Blood Substitutes↗
PubMed2004

Association of highly active antiretroviral therapy failure with chemokine receptor 5 wild type.

OBJECTIVES: Approximately 10% of HIV-infected patients fail to respond properly to highly active antiretroviral therapy (HAART). Among other factors, genetic variants of chemokine receptors have been shown to modify the course and outcome of HIV infection. Our objective was to investigate whether a failure of virological response is associated with polymorphisms of the chemokine receptors or cofactors. METHODS: A total of 256 HIV-infected patients receiving HAART and 221 healthy controls were analysed for the chemokine receptor 5 (CCR5)-Delta32-bp, stromal derived factor 1 (SDF1)-3'A and chemokine receptor 2 (CCR2)-64I polymorphisms. Treatment failure was defined as failure to lower the viral load below 50 HIV-1 RNA copies/mL within the first year of treatment despite good adherence. Genomic DNA was extracted from peripheral blood lymphocytes (PBL) and amplified by polymerase chain reaction (PCR). RESULTS: Successful treatment was associated with heterozygosity for the CCR5-Delta32-bp variant found in 24 of 184 responders (13%) vs. one of 72 nonresponders (1.4%; P=0.004). Eighty-four of 184 responders (45.7%) vs. 25 of 72 nonresponders (34.7%) were heterozygous for the SDF1-3'A allele (P=0.073). The CCR2-64I polymorphism was rare in both groups: 4.9% in responders vs. 1.4% in nonresponders (P=0.175). The odds ratio for successful treatment was 4.7 for individuals who tested positive for at least one variant allele of the three polymorphisms. Comparison of genotype frequencies between HIV-infected and healthy individuals showed highly significant differences (P<0.001). CONCLUSIONS: Chemokine receptor polymorphisms have a modifying effect on the virological response to HAART. Multivariate analysis demonstrated that heterozygosity for the CCR5-Delta32-bp variant is an independent prognostic factor for treatment outcome.

Adult↗
PubMed2001

Autoantibody formation in the alloimmunized red blood cell recipient: clinical and laboratory implications.

Alloimmunization to erythrocyte antigens is a well-characterized complication in heavily transfused patients. Less well recognized, however, is the frequency of autoantibody formation in these previously alloimmunized patients. The autoantibodies are heterogeneous and of variable clinical significance. We describe the clinical history, laboratory evaluation, diagnosis, and treatment in 4 patients who developed autoantibodies in temporal association with alloantibody formation. In one case, the autoantibody found on routine screening had no clinical significance. In another case, the autoantibody made accurate blood typing and subsequent transfusion exceedingly difficult. Two patients experienced hemolysis as a consequence of the autoantibody. The management of both patients included supportive measures, while one patient required glucocorticosteroids and red blood cell transfusion. We review the published literature concerning autoimmunization in the transfused alloimmunized host. The spectrum of clinical consequences is important for the general practitioner to recognize, as these complications may occur during routine blood transfusions.

Adult↗
PubMed2001

Preserving the national blood supply.

This paper examines the current state of the blood supply in the US and focuses on the potential for augmenting blood availability by attention to the iron status of donors. Increasing demands are being made upon the national blood supply as rates of blood donation are declining, in part because of the loss of blood donors as a result of enhanced screening and testing procedures. Iron-related means of expanding the blood supply include the use of blood from individuals undergoing therapeutic phlebotomy for hereditary hemochromatosis and enhancing the retention and commitment of women of childbearing age as donors by using iron supplementation to prevent iron deficiency. In Section I, Dr. Klein discuss the circumstances responsible for a decline in the population of eligible donors, including public attitudes toward donation, factors influencing the retention of donors by blood centers, and the effects of increased screening and testing to maintain the safety of the blood supply. In Section II, Drs. Kushner and Ajioka focus on the consequences of the decision by the US Food and Drug Administration (FDA) to develop recommendations to permit blood centers to collect blood from patients with hereditary hemochromatosis and to distribute this blood obtained without disease labeling if all other screening and testing procedures are passed. After summarizing the pathophysiology of hereditary hemochromatosis, the use by blood centers of blood obtained from heterozygotes and homozygotes for hereditary hemochromatosis is considered. In Section III, Dr. Brittenham reviews the use of low dose, short-term carbonyl iron supplementation for women donors of childbearing age. Replacing the iron lost at donation can help prevent iron deficiency in women of childbearing age and, by decreasing deferral, enhance the retention and commitment of women who give blood regularly. He emphasizes the use by blood centers of iron-related means to enhance recruitment and retention of blood donors.

Anemia, Iron-Deficiency↗
PubMed2001

Intravenous Rh immune globulin prevents alloimmunization in D- granulocyte recipients but obscures the detection of an allo-anti-K.

Rh immune globulin (RhIG) has been used to prevent alloimmunization in D(-) recipients of apheresis platelet transfusions from D(+) donors that may contain up to 5 mL of D(+) red blood cells (RBCs). Granulocyte concentrates contain approximately 30 mL of RBCs and it has been necessary to give D(-) recipients granulocyte transfusions from D(+) donors. Intravenous RhIG has not yet been demonstrated to be effective in preventing D alloimmunization with granulocyte transfusions. Four D(-) recipients received multiple D(+) granulocyte transfusions from D(+) donors and multiple injections of intravenous RhIG at a standard dose of 600 microg for each D(+) transfusion. Two D(-) males with chronic granulomatous disease were given 32 and 13 daily granulocyte transfusions, 18 and 2 of which, respectively, were D(+). After the first dose of intravenous RhIG, both patients exhibited circulating anti-D that was undetectable 3 to 4 years later. Two patients with severe aplastic anemia were given 5 and 14 granulocyte transfusions, 4 and 7 of which, respectively, were D(+). Both patients died before the effectiveness of RhIG could be assessed. In one of these patients the indirect and direct antiglobulin tests became positive after the first dose of intravenous RhIG, which required that subsequent granulocyte transfusions from D(+) donors be crossmatched by immediate spin (IS) testing only. A delayed hemolytic reaction attributed to allo-anti-K occurred after granulocytes from a K(+) donor were given to this patient. These results suggest that intravenous RhIG can be used to prevent alloimmunization to D in D(-) patients receiving large quantities of RBCs from D(+) granulocyte transfusions. However, anti-D and other passive antibodies from RhIG prohibit the use of the antiglobulin crossmatch with antigen-positive granulocyte donor samples. It may be important to frequently collect new samples to screen for newly formed allo-antibodies when IS crossmatches are used in place of the antiglobulin crossmatch.

Journal Article↗
PubMed2000

From leukocyte reduction to leukocyte transfusion: the immunological effects of transfused leukocytes.

In transfusion medicine, mononuclear leukocytes have been studied more often as contaminants of red blood cells or platelets responsible for adverse transfusion outcomes than as therapeutic cells; leukocyte transfusion has been effective in augmenting recipient immunity only in limited clinical situations. Studies in leukocyte reduction and leukocyte transfusion have progressed separately as if the leukocytes' adverse and therapeutic effects result from different immunological mechanisms. With growing clinical experience, however, it is increasingly clear that some adverse immune effects may be exploited for therapeutic benefit. Advances in clinical immunology, understanding of the variety of cells and functions in the leukocyte fraction of blood, and blood component preparation technology may lead to new ways of deriving immunological benefit from transfused blood leukocytes while minimizing their adverse effects. This chapter reviews the current uses of leukocyte reduction and mononuclear leukocyte transfusion, with an emphasis on the relationship between transfusion-associated graft-versus-host disease and donor lymphocyte infusion in controlling relapsed leukaemias.

Antigen-Presenting Cells↗
PubMed1999

Trypanosoma cruzi meningoencephalitis in HIV-infected patients.

Five cases of Trypanosoma cruzi meningoencephalitis in HIV-infected patients are reported. All patients presented with mass lesions on head computed tomographic scan, trypanosomes in the cerebrospinal fluid and failure to respond to antitoxoplasmosis therapy. Benznidazole therapy was associated with clinical improvement in 1 patient. Another 4 patients had T cruzi identified in a peripheral smear. T cruzi needs to be considered in the differential diagnosis of HIV-infected patients with central nervous system mass lesions if they have a history of appropriate exposure.

AIDS-Related Opportunistic Infections↗