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Biomedical subjects

C K Kasper

Publications and source records attributed to C K Kasper.

At least 91 records · Page 5Linked to original sources
PubMed1985

Poor response to danazol in hemophilia.

We gave danazol (600 mg/day orally for 14 days) to eight adults with mild or moderate hemophilia A, one with severe hemophilia A, and one with moderate hemophilia B. In the patient with severe hemophilia A, the levels of factor VIII two to four days after an infusion of factor VIII concentrate were higher than expected, suggesting a prolonged half-life. In one patient with mild hemophilia A, a questionable slight increase in factor VIII was noted at the end of the study. No change was seen in factor levels of other subjects. Therapy was terminated early, at eight days, in a patient who developed severe muscle cramps, and at ten days in a patient with a severe rash. Another patient developed hepatic dysfunction three days after completing the 14-day trial. In this trial, the side effects of danazol outweighed its meager and questionable benefits.

Adult↗
PubMed1985

Distinctive lymphocyte subpopulation abnormalities in patients with congenital coagulation disorders who exhibit lymph node enlargement.

The majority of patients with congenital clotting disorders who use clotting factor concentrate exhibit lymphocyte subpopulation abnormalities. A subset of these patients develop lymph node enlargement (LNE), part of the spectrum of clinical disease associated with the acquired immune deficiency syndrome (AIDS). It is therefore important to determine if these patients with LNE exhibit specific immune alterations suggestive of early infection with the AIDS agent. We used one- and two-color immunofluorescence to distinguish the lymphocyte subpopulation alterations associated with concentrate use from those associated with LNE. Patients who use concentrate had elevated levels of Leu-2+ (T suppressor phenotype) cells and Leu-7+ (phenotype of some natural killer) cells. These increased levels were largely caused by a dramatic (2.6-fold) increase in the number of lymphocytes co-expressing Leu-2 and Leu-7 (2+7+). A dose-response effect between amount of concentrate infused during the preceding year and level of 2+7+ cells was observed. Concentrate recipients, as a group, also showed increased levels of T cells expressing Dr antigen (T+Dr+ phenotype, characteristic of activated or immature T cells) and cells expressing the T10 antigen (phenotype of some null cells and activated/immature T cells). Patients with LNE showed a further increase in T10+ cells as well as a distinctive decrease in Leu-3+ (T helper phenotype) lymphocytes. All LNE patients exhibited either low Leu-3+ levels, high T10+ levels, or both. Thus, concentrate use was associated with increased levels of Leu-2+ (particularly 2+7+) cells and T+Dr+ cells, whereas LNE was associated with decreased levels of Leu-3+ cells and high levels of T10+ cells.

Acquired Immunodeficiency Syndrome↗
PubMed1985

Comprehensive management of haemophilia.

Haemophilia is a congenital, life-long disorder that may cause major disabilities. The goal of comprehensive care is to prevent problems when possible, to treat early in order to minimize morbidity, and to restore function to disabled patients. The co-ordinated efforts of many experts are needed for success.

Aminocaproic Acid↗
PubMed1985

Long-term follow-up of hemophiliacs with lymphocytopenia or thrombocytopenia.

Immunologic abnormalities resembling those seen in patients with the acquired immunodeficiency syndrome (AIDS) are frequently observed in multitransfused but otherwise healthy individuals with hemophilia. To determine whether there was clinical or laboratory evidence to suggest an abnormality of immunoregulation in persons with hemophilia before the recognition of AIDS, we examined data collected by the Hemophilia Study Group from 1975 to 1979 on 1,551 patients with factor VIII deficiency. The prevalence of lymphocytopenia and thrombocytopenia in patients over 5 years of age on entry was found to be 9.3% (94/1,013) and 5.0% (26/518), respectively. These rates were significantly different from a normal population (P less than .00001 and less than .0003). No cases meeting the definition of AIDS were noted during the study. However, on follow-up in 1984 of a cohort of 79 patients with thrombocytopenia or lymphocytopenia on two or more occasions during the study, eight patients (10%) with AIDS-related abnormalities, including idiopathic thrombocytopenic purpura, non-Hodgkin's lymphoma, generalized lymphadenopathy, and oral moniliasis without obvious cause were identified. Of the 79 patients, liver disease accounted for five of the ten deaths (12.6% mortality) observed during a minimum follow-up of five years after detection of cytopenia. Only one death was attributed to bleeding in the absence of liver disease. We conclude that (a) the frequency of lymphocytopenia and thrombocytopenia was increased in multitransfused factor VIII-deficient hemophiliacs before the advent of AIDS, and (b) persistent lymphocytopenia and thrombocytopenia appear to be strongly associated with liver disease, which was the leading cause of death in a cohort of hemophiliacs followed five or more years.

Acute Kidney Injury↗
PubMed1984

Nontransmission of T-cell subset abnormalities from hemophiliacs to their spouses.

Hemophiliacs who are exposed to pooled clotting factor concentrate constitute one group at increased risk for development of acquired immune deficiency syndrome. To determine the prevalence of cellular immune aberrations in asymptomatic hemophiliacs, we studied a group of 65 adult hemophiliacs for T-cell subset abnormalities. Sixty-five percent of concentrate recipients had an abnormal T-helper to T-suppressor cell ratio, 40% had a depressed absolute T-helper cell level, and 29% had an elevated absolute T-suppressor cell count. To determine whether horizontal transmission of T-cell subset abnormalities from hemophiliacs to their female sexual partners occurred, we studied 41 spouses. We found no correlation between paired husband and wife values for T-cell ratio or any other immune parameter studied. There were no significant differences found between wives of hemophiliacs with reversed T-cell ratios and wives of hemophiliacs with T-cell ratios of 1.0 or greater, with respect to immunologic tests. We conclude that there is no evidence to date for heterosexual or household-contact transmission of T-cell subset abnormalities from hemophiliacs to their spouses in our study population.

Adolescent↗
PubMed1984

Antibody to human T-cell leukemia virus membrane antigens, beta 2-microglobulin levels, and thymosin alpha 1 levels in hemophiliacs and their spouses.

Recently, antibodies to human T-cell leukemia virus membrane antigens (HTLV-MA) and elevated levels of beta 2-microglobulin and thymosin alpha 1 have been found with high frequency in patients with the acquired immunodeficiency syndrome. Prospective studies of asymptomatic persons at high risk for this syndrome will ascertain whether any of these findings is a predictive marker for the disease. In this study, antibodies to HTLV-MA, beta 2-microglobulin levels, and thymosin alpha 1 levels were determined for a group of asymptomatic adult hemophiliacs and their wives. Five of thirty-nine hemophiliacs had HTLV-MA antibody, compared with none of 21 wives tested. The mean beta 2-microglobulin level for hemophiliacs was significantly higher than the control value (p less than 0.001), whereas the wives had a normal mean value. The mean thymosin alpha 1 values were normal for hemophiliacs and their wives; however, 3 of 22 hemophiliacs and 1 of 16 wives had abnormally high levels. Whether any of these abnormalities correlate with subsequent development of the acquired immunodeficiency syndrome will be ascertained by longitudinal follow-up of this population.

Acquired Immunodeficiency Syndrome↗
PubMed1983

Reproduction in hemophilia.

Reproduction rates in 294 men with severe hemophilia, 327 of their mothers, and 215 of their sisters were compared with Vital Statistics data for the general US population matched for exact age, calendar year between 1940 and 1977, and, for women, parity. Before 1950, reproduction rates in hemophiliacs and in mothers did not differ from those of the general population, but thereafter the rates fell notably. Births to sisters who were para 0 were lower than expected beginning in 1965, but births to sisters who had had one or more nonhemophiliac children were similar to those expected of the general population. The decline in fecundity may be caused by greater availability of genetic counseling and birth control measures and by social changes. Many prospective parents would welcome the opportunity to have unafflicted children but refuse selective abortion. Preconception gender selection would be appropriate for this sex-linked disorder.

Adult↗
PubMed1983

Antibodies to human T-cell leukemia virus membrane antigens (HTLV-MA) in hemophiliacs.

Along with homosexual men, Haitians, and intravenous drug abusers, hemophiliacs are at high risk of contracting acquired immunodeficiency syndrome (AIDS). An earlier study revealed that 36 percent of a group of the AIDS patients had antibodies to cell membrane antigens associated with the human T-cell leukemia virus (HTLV-MA), whereas only 1.2 percent of matched asymptomatic homosexual controls had these antibodies. In the present experiments, serum samples from 172 asymptomatic hemophiliacs were examined for the presence of antibodies to HTLV-MA. Such antibodies were detected in 5 to 19 percent of the hemophiliacs examined from four geographical locations, but in only 1 percent or less of laboratory workers, normal blood donors, donors on hemodialysis, or donors with chronic active hepatitis.

Antibodies, Viral↗
PubMed1982

In vitro detection of mild inhibitors to factor VIII in hemophilia.

Plasma samples from patients with severe classic hemophilia, suspected of having mild inhibitors not detected in the standard Bethesda inhibitor test, were examined in modified Bethesda tests and in a screening test based on the activated partial thromboplastin time (APTT). The APTT test was more sensitive to mild inhibitors than any modification of the Bethesda method. Increasing the ratio of patient to normal plasma in either the APTT or the Bethesda test improved the sensitivity to mild inhibitors. If a patient's plasma is used as its own control in the APTT test, results are more consistent as minor fluctuations in the APTT occur over time.

Factor VIII↗
PubMed1981

Purification and properties of an abnormal blood coagulation factor IX (factor IXBm)/kinetics of its inhibition of factor X activation by factor VII and bovine tissue factor.

An abnormal blood coagulation factor IX has been isolated from the blood of a hemophilia B patient with a variant of the disease (hemophilia Bm) characterized by a normal concentration of factor IX antigen, negligible factor IX coagulant activity, and a prolonged prothrombin time with bovine tissue factor. The isolated protein (factor IXBm) had the same apparent molecular weight as normal factor IX (55,000) and the same mobility on two dimensional immunoelectrophoresis as normal factor IX. Factor IXBm underwent limited proteolysis induced by activated factor XI, in the presence of Ca2+ ions, or induced by the reaction product of tissue factor, factor VII and Ca2+ ions. A timecourse study showed that activated factor XI cleaved factor IXBm and factor IX at similar rates. However, in contrast to normal factor IX, the limited protelysis of factor IXBm did not generate procoagulant activity. In kinetic experiments purified factor IXBm behaved like a competitive inhibitor (Ki of 0.017 muM) of the activation of factor X by bovine tissue factor and factor VII. Normal factor IX was also found to inhibit the reaction but required a four-fold higher concentration to activate the same inhibitory effects as factor IXBm.

Animals↗