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Biomedical subjects

R T Card

Publications and source records attributed to R T Card.

At least 19 recordsLinked to original sources

Effect of splenectomy on slowing human immunodeficiency virus disease progression.

BACKGROUND: Lymphoreticular tissue is the most important site for human immunodeficiency virus (HIV) replication in HIV-infected individuals. OBJECTIVE: To compare the long-term effect of splenectomy on survival and time to development of acquired immunodeficiency syndrome in subjects who had undergone splenectomy with subjects who had not undergone splenectomy. DESIGN: A cohort study with a follow-up of up to 13.4 years. SETTING: Subjects were recruited from a hospital outpatient clinic population and a multicenter study of patients with hemophilia. PARTICIPANTS: Forty-five HIV-infected individuals were observed prospectively for up to 13.4 years (17 had undergone splenectomy and 28 had not undergone splenectomy). Five subjects underwent splenectomy before acquiring HIV infection and 12 underwent splenectomy during the asymptomatic phase of HIV infection. The group who did not undergo splenectomy consisted of HIV-infected individuals who were asymptomatic at study enrollment. MAIN OUTCOME MEASURES: A Cox proportional hazards model was used to test the effects of splenectomy on survival and time to development of acquired immunodeficiency syndrome when adjusting for potential confounders (age, initial CD4+ cell count, and treatment with antiretroviral drugs). Splenectomy was treated as a time-dependent covariate to account for the variation in its timing. RESULTS: During the average follow-up of 8.6 years, 9 (53%) of the 17 subjects who underwent splenectomy and 23 (82%) of the 28 subjects who did not undergo splenectomy died; acquired immunodeficiency syndrome developed in 6 (35%) of the subjects who underwent splenectomy and 23 (82%) of the subjects who did not undergo splenectomy. Splenectomy was associated with a significant reduction of risk of developing acquired immunodeficiency syndrome (adjusted relative risk [RR] <0.4, P<.05), whereas the effect on risk of mortality approached, although it did not reach, significance (adjusted RR approximately 0.5, P approximately .10). CONCLUSION: The absence of a spleen during the asymptomatic phase of HIV infection seems to have a beneficial effect on HIV disease progression.

Acquired Immunodeficiency Syndrome↗

Biologic and clinical significance of CD7 expression in acute myeloid leukemia.

CD7 antigen, a T-cell lineage associated antigen, is expressed in a minority of patients with acute myeloid leukemia (AML). The biologic and clinical significance of this finding is not clearly established. In this retrospective study of patients with de novo acute myeloid leukemia, we have identified CD7 expression and analyzed its association with markers expressed early in hemopoietic ontogeny and clinical parameters. Among 60 consecutive AML patients, we found six (10%) expressing CD7 on leukemic cells. There were five males and one female and the mean age was 59.6 years (age range: 32-76 years) with no demographic peculiarities. The FAB subtypes were: M0 (2), M1 (1), M2 (1), and M4 (2). CD7 expression was associated with immature antigens CD34, HLA-DR, and terminal deoxynucleotidyl transferase (TdT) and antigen receptor gene rearrangements (rearrangements of T-cell receptor gamma chain in 6/6 and immunoglobulin heavy chain in 2/6). Hepatomegaly was present in three and this was associated with splenomegaly with lymphadenopathy in one patient. Mediastinal or central nervous system involvement was absent. Complete remission was achieved in two patients with standard chemotherapy; one of these is in remission and alive (5 years later), while one died following relapse 9 months later. Three patients had significantly lower response to standard therapeutic regimen (two died during induction and one died 7 months later without ever achieving complete remission). One patient has been excluded in determining the prognostic significance of CD7 due to early death. Our results suggest origin of CD7+ AML from early hemopoietic precursors and indicate biologic aggressiveness in a significant proportion of patients. We suggest evaluation of CD7 in all patients with AML at the time of diagnosis in view of poor clinical outcome.

Acute Disease↗

Use of desmopressin acetate to reduce blood transfusion requirements during cardiac surgery in patients with acetylsalicylic-acid-induced platelet dysfunction.

OBJECTIVE: To determine whether desmopressin acetate (DDAVP) has the ability to reduce blood loss in patients with a known bleeding tendency. DESIGN: A randomized, double-blind, placebo controlled study. SETTING: A university teaching hospital. PATIENTS: Men under the age of 70 years who had taken acetylsalicylic acid within 7 days of scheduled coronary artery bypass surgery. Patients with an abnormal hematologic profile or a history of bleeding or who were receiving heparin or undergoing repeat coronary bypass surgery were excluded. Forty-four patients were randomized with restriction in blocks of 10; 20 received DDAVP and 24 received a placebo. MAIN OUTCOME MEASURES: Blood loss and blood transfusion requirements. RESULTS: Patients treated with DDAVP lost significantly (p < 0.01) less blood than those receiving a placebo (1543 mL versus 2376 mL respectively). Nineteen patients had a blood loss of more than 2000 mL; 15 of these were in the placebo group. Significantly (p < 0.02) fewer patients receiving DDAVP required blood transfusion (9 versus 18). CONCLUSIONS: DDAVP reduces blood loss during cardiac bypass surgery in patients who have taken acetylsalicylic acid within 7 days before operation.

Aspirin↗

Avascular necrosis of bone in bone marrow transplant patients.

Avascular necrosis of the hips occurred in two patients after allogeneic bone marrow transplantation. One had been receiving steroid therapy for prophylaxis of graft-versus-host disease, the other for the treatment of this condition. This complication has been reported infrequently, but the incidence could be as high as 10% in long-term survivors of bone marrow transplantation. While other drugs and irradiation may also contribute to this condition, it is likely that steroids are the major cause. An awareness of this risk should encourage minimizing the use of steroid therapy after bone marrow transplantation.

Adrenal Cortex Hormones↗

Human immunodeficiency virus infection and porphyria cutanea tarda.

A recent report documents three homosexual men with porphyria cutanea tarda associated with acquired immune deficiency syndrome (AIDS). We report two brothers with hemophilia and human immunodeficiency virus (HIV) exposure who developed porphyria cutanea tarda. These brothers are heterosexual, have familial porphyria cutanea tarda, and developed overt familial porphyria cutanea tarda in their early twenties. One brother's symptoms were provoked by attending an ultraviolet A suntanning parlor. Our two patients, unlike the previously reported three patients, have not developed AIDS, though one patient has evidence of defective cell-mediated immunity. Three of the five cases of porphyria cutanea tarda associated with HIV infection involved familial porphyria cutanea tarda. It now may be advisable to order HIV serology tests in patients who have porphyria cutanea tarda. We recommend that HIV-positive individuals avoid ultraviolet A radiation because of its immunosuppressive effects in persons already at risk of immunosuppression. Such exposure is further contraindicated in those individuals with porphyria cutanea tarda.

Adult↗

Red cell membrane changes during storage.

A great deal is known about the red cell membrane and its abnormalities in various pathologic states. During red cell storage there is a progressive development of spheroechniocytosis with eventual production of irreversibly nondeformable red cells. The loss of membrane function is most likely related to some abnormality in maintenance of the cytoskeleton of the red cell. These changes appear to occur independent of ATP levels. Despite the increasing knowledge of the structure and function of the red cell membrane very little as yet is known about the specific abnormality in the red cell membrane that occurs during storage in the blood bank. Recent evidence for abnormal spectrin-actin interaction and abnormal spectrin oxidation has been the most promising. Areas of interest for research include studies of the specific mechanisms by which the plasticizer DEHP interacts with the membrane, specific definition of the molecular defect in membrane proteins that occurs during storage, and means to prevent these. If such deterioration and membrane stiffening could be prevented then the quality of the red cells that are transfused would be improved both in their function and ability to survive in the microcirculation. A final need, while not of specific value to the red cell itself, is the development of media and additives that will allow for increased plasma and Factor VIII yields, one of the driving forces in the blood transfusion system.

Blood Preservation↗

Effects of blood and crystalloid cardioplegia on cardiac function at organ and cellular levels during hypothermic cardiac arrest.

The present investigation was undertaken to compare the effects of cold crystalloid and blood cardioplegia on the functional recovery of the heart; on Ca++ binding and uptake, Ca++-ATPase of the sarcoplasmic reticulum (SR), and sarcolemmal (SL) ATPase; and on serum MB fraction of creatine kinase (MBCK) after one and half hours of reperfusion following one hour of ischemic cardiac arrest in dog. This study was made also to determine if the functional changes are related to the changes in biochemistry at the molecular level. The dogs were divided into three groups: sham bypass (SB), cold crystalloid cardioplegia (CC), and pump blood cardioplegia (PB). There was a decrease in the cardiac index (CI), left ventricular work index (LVWI), and mean aortic pressure (MAP) in all three groups. The index of myocardial contractility [dp/dt)/IIP) and CI were lower in the CC group as compared with the SB and PB groups. All the hemodynamic values for the PB group were similar to those of the SB group except total systemic vascular resistance (TSVR) and left ventricular end-diastolic pressure (LVEDP) which were lower in the PB group. The index of myocardial contractility and cardiac index appeared to be greater in the PB group than in the CC group. There was a decrease in the Ca++ uptake by SR from both the CC and PB groups. Ca++ binding and Ca++,-ATPase of SR from the PB group were depressed. The sarcolemmal ATPase was unaffected in both groups. The serum MBCK increased in both PB and CC groups, though the increase was smaller in the PB group. These results indicate that the functional recovery of the heart was slightly better with pump blood cardioplegia than with cold crystalloid cardioplegia. The depressed myocardial contractility and cardiac function in the CC group were associated with a decrease in the Ca++ uptake by SR. However, the decreases in the Ca++ binding, Ca++ uptake, and Ca++ ATPase by SR from the pump blood cardioplegic group were not accompanied by decreases in the cardiac contractility and cardiac function. Myocardial damage as assessed by serum MBCK was smaller in the PB group than in the CC group.

Animals↗

High 2,3-DPG blood cardioplegia and myocardial preservation during cardiopulmonary bypass.

Blood may provide superior cardioplegia compared with crystalloid cardioplegic solution. However, the results are controversial. This may be due to a leftward shift of the hemoglobin (Hb)-O2 dissociation curve induced by hypothermia, increasing the oxygen affinity for Hb. This effect may negate the potential benefit of blood cardioplegia. The oxygen affinity for Hb can be decreased by increasing the red cell 2,3-diphosphoglycerate (2,3-DPG), and hence, more oxygen can be delivered to the myocardium. The present investigation was undertaken to study the effects of 2,3-DPG-enriched blood cardioplegia on the functional recovery of the myocardium and changes in the coronary sinus red blood cell (RBC) adenosine-triphosphate (ATP), lactate, and RBC DPG after one and a half hours of reperfusion following one hour of ischemic cardiac arrest in dogs. The dogs were divided into three groups: crystalloid (CR); stored blood (SB), and high 2,3-DPG blood (HDPG) cardioplegic groups. Incubation of canine RBC in phosphoenal pyruvate (PEP) led to a 36% increase in DPG and a rightward shift in the Hb-O2 dissociation curve. There was a 4 mm Hg shift in the P50. When compared with the CR group, there was a significant decrease in the cardiac index (CI) and left ventricular work index (LVWI) and a significant increase in the total systemic vascular resistance (TSVR) in the SB group. The CI and LVWI of the HDPG group were similar to those of the CR group, but the TSVR was significantly greater in the former group. The LVWI was significantly greater and the TSVR smaller in the HDPG group as compared with those in the SB group.(ABSTRACT TRUNCATED AT 250 WORDS)

2,3-Diphosphoglycerate↗

The effect of the plasticizer di(2-ethylhexyl)phthalate on red cell deformability.

Red cell concentrates (RCC) are stored for 35 to 42 days in plastic containers manufactured with the liquid plasticizer di(2-ethylhexyl)phthalate (DEHP). DEHP leaches from the polyvinylchloride (PVC) plastic bag, then binds to and stabilizes the RC membrane. This study was undertaken to determine the deformability of the RC membrane using an osmotic gradient ektacytometer and to relate these measurements to the concentration of DEHP in the stored RCC. Pooled RCC was aliquoted into PL146 (PVC), PL732 (polyolefin), and PL732 (with added DEHP) bags with samples removed weekly for analysis of osmotic fragility, deformability, and DEHP concentration. The adenosine triphosphate (ATP) content was also measured. The increase in osmotic fragility during storage was greater when RCC was stored without DEHP. In addition, there was a decrease in the maximum elongation index (El max) when there was decreased DEHP in the storage bag. The osmolarity (Omax) at which El max occurred, as well as the Omin, the osmolarity at which minimum elongation (El min) occurred was higher in the PL732 container than in the PL146 or in the PL732 to which DEHP had been added. These changes could be reversed by addition of DEHP at the beginning of the storage period, showing a direct correlation between DEHP concentration during storage and RC membrane flexibility. By a better understanding of the mechanism of DEHP protection, it might be possible to substitute a less toxic stabilizing compound.

Adenosine Triphosphate↗

Prehemolytic erythrocyte deformability changes caused by trichothecene T-2 toxin: an ektacytometer study.

The trichothecene mycotoxin, T-2, is responsible for a wide range of human diseases and animal toxicoses and is known to cause hemolysis of erythrocytes, over time. In order to determine the initial, prehemolytic effect of T-2 toxin on the red cell, we analysed the osmotic deformability pattern using the ektacytometer. After a lag period of 10-60 minutes, hemolysis of T-2 treated red cells is associated with a loss of deformability. During this lag phase there is echinocytosis but no hemolysis. Concurrent with production of echinocytosis there is an initial left shift of the osmotic deformability profile so that the points of maximum and minimum deformability occur in solutions of lower osmolality than normal. The elongation index is also increased. This pattern, one of increased surface area and/or reduced volume (cellular dehydration), represents the initial effect of T-2 toxin on the red cell and is transient. Very quickly, the deformability profile returns to normal, then shifts to the right with a subsequent decrease in elongation index as hemolysis ensues. These changes are independent of the presence of Ca++ and Mg++ and reduced cellular levels of ATP. The findings are consistent with T-2 toxin interacting directly with the cell membrane.

Adenosine Triphosphate↗

Felty's syndrome in a child.

The occurrence of the triad of leukopenia, splenomegaly and rheumatoid arthritis (RA) (Felty's syndrome) during childhood has not been reported previously. We describe an adolescent with onset during childhood of seropositive, nodular, erosive, polyarticular RA in whom both leukopenia and splenomegaly were accompanying features. Neither nonsteroidal antiinflammatory agents nor plasmapheresis were therapeutically beneficial, but low dose oral prednisone therapy resulted in both clinical and hematological improvement.

Anti-Inflammatory Agents↗

Growth of malignant histiocytic cells induced by phorbol myristate acetate.

Cells from the spleen of a patient with malignant histiocytosis were cultured in methyl cellulose with and without 100 ng/mL of phorbol myristate acetate (PMA). Colony growth occurred only with PMA; comparing surface marker studies of the cells before and after culture, it was evident that proliferation had occurred among the histiocytic cells as well as the lymphocytes. After exposure to PMA in organ culture for ten days, the histiocytes appeared to be differentiated and showed evidence of continuing phagocytosis by electron microscopy. This suggests that PMA is a mitogen for the histiocytes in this condition and maintains differentiation of the cells.

Adult↗

Chronic immune thrombocytopenic purpura in hemophilia A.

Chronic immune thrombocytopenic purpura resistant to steroid therapy occurred in a 30-year-old patient with severe hemophilia A. This association has recently been reported in other patients, and a possible relation to the acquired immune deficiency syndrome (AIDS) has been suggested. Although this patient had been treated with factor VIII concentrate for 4 years, the proportions of helper and suppressor T cells were normal, and there was no evidence of AIDS. An uncomplicated splenectomy gave excellent results. All patients with hemophilia should have their platelet counts monitored closely and should report any unusual pattern of bleeding.

Adult↗

Waldenström macroglobulinemia terminating in acute leukemia: a report of three cases.

Acute leukemia was observed to develop in three patients with Waldenstöm macroglobulinemia. Each patient had been treated with cytotoxic drug therapy. Pancytopenia preceded the onset of the terminal leukemia in two of the three cases. The acute leukemias were all of acute myelogenous type. All of the patients died soon after the development of the terminal leukemia. A number of recent reports have documented acute terminal leukemia in patients with macroglobulinemias and multiple myeloma, as well as other malignant and nonmalignant diseases. The role of the cytotoxic drugs, especially chlorambucil, cyclophosphamide, and melphalan, in leukemogenesis has been raised by these recent reports.

Aged↗

Coagulation factor therapy for hemophilia: relation to hepatitis B and to liver function.

Therapy with concentrated coagulation factors has greatly improved the management of hemophilia, but the consequence of repeated infusion of these blood products are unknown. Hepatic dysfunction is frequent in patients with hemophilia, and the use of these products may be responsible. The relation between liver function and both the frequency and type of therapy with coagulation factors was studied in a group of patients with hemophilia. Of the 36 patients studied, 75% were found to have antibody to hepatitis B surface antigen in their serum and 44% had high levels of serum glutamic oxaloacetic transaminase (SGOT). The infusion of concentrated coagulation factor more than once per year was significantly associated with the presence of antibody to hepatitis B surface antigen and with a high SGOT level. The patients treated with concentrates prepared from blood obtained from large donor pools were significantly more likely to have antibody to hepatitis B surface antigen in their serum but no more likely to have a high H-SGOT level than the patients treated exclusively with cryoprecipitate, plasma or whole blood. These findings suggest that in patients with hemophilia the frequency of coagulation factor treatment may be a more important determinant of hepatic dysfunction than the type of treatment.

Adolescent↗