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Biomedical subjects

R T Card

Publications and source records attributed to R T Card.

13 recordsLinked to original sources

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

Alterations in red cell metabolism during and following cardiac bypass surgery.

Reduced concentrations of red cell organic phosphates and increased hemoglobin--oxygen affinity have been reported during and following cardiac bypass surgery. Some have related these changes to low concentrations of ATP and 2,3-diphosphoglycerate (DPG) in stored blood while others have related them to use of the pump oxygenator. There was a 10% decrease in DPG concentration in seven dogs on cardiac bypass although the animals received no transfusions. In 16 patients who received 0 to 7 units of blood during cardiac bypass there was a decrease of 10% in the red cell DPG concentration from the preoperative value, but it did not relate to the concentration of DPG in the transfused blood bags. The magnitude of the decrease was not sufficient to impair oxygen delivery severely. The results suggest that a re-evaluation of indications for the use of fresh red cells in cardiac surgery is necessary.

Adenosine Triphosphate

Portal hypertension complicating myelofibrosis: reversal following splenectomy.

Portal hypertension occurs in approximately 10% of patients with myelofibrosis. Increased portal blood flow secondary to splenomegaly has been proposed to explain its development. In a 60-year-old woman with proven myelofibrosis of 10 years' duration and gross splenomegaly, portal hypertension developed with esophageal varices and ascites. There was no demonstrable obstruction to portal blood flow. Following splenectomy the ascites and esophageal varices disappeared. Despite the presence of splenic myeloid metaplasia, splenectomy did not impair the patient's hematologic status. Portal hypertension complicating myelofibrosis has a poor prognosis, so careful attention should be given to its detection. Splenectomy may be preferable to portal-systemic shunting in the management of this complication.

Ascites

Chronic myelomonocytic leukemia: an ultrastructural study by transmission and scanning electron microscopy.

The hematologic findings in three cases of chronic myelomonocytic leukemia are presented, with results of ultrastructural studies by transmission and scanning electron microscopy on two of the cases. In the peripheral blood there was a dual, non-lymphocytic, markedly increased population of granulocytes and monocytes. The granulocytes showed marked nuclear abnormality and nuclear cytoplasmic organelle asynchrony. In the marrow the majority of the cells appeared granulocytic but atypical forms and intermediate difficult to distinguish from monocyte precursors were evident by electron microscopy. The ultrastructural findings lend some support to the concept that the neoplastic granulocytes and monocytes having a common precursor.

Aged

Determination of hemoglobin-oxygen affinity on micro samples.

The spectrophotometric determination of hemoglobin-oxygen dissociation on dilute red cell suspensions has been modified by the use of a bicarbonate buffer containing bovine serum albumin. The red cell suspension is equillibrated with known ratios of air and nitrogen and 5 per cent carbon dioxide at atmospheric pressure using two gas pumps. The method enables the hemoglobin-oxygen dissociation curve to be measured on 10 to 20 mul of whole blood, and has given values for the P50 (the oxygen tension at 50 per cent hemoglobin-oxygen saturation) of 25.9 plus or minus 1.5 S. D. which are comparable to the value of 26.0 plus or minus 1.0 S. D. obtained by the mixing technique and by other methods. The addition of bovine albumin (35 mg. per cent or greater) increased the P50 by 3 mm. Hg above that obtained with buffer alone. The P50 value has been compared in bis-Tris and phosphate buffers with and without albumin, and in bicarbonate buffers with the addition of approximately equimolar concentrations of either human or bovine serum albumin or polyvinyl-pyrrolidone (PVP), and buffer alone. The effect of albumin on the P50 value was most marked in bicarbonate buffer, and was statistically significantly greater in the presence of human or bovine albumin than in buffer alone or buffer plus PVP. The addition of albumin could not be explained through an alteration of cell shape or volume, but may be an influence on intracellular pH.

Adenosine Triphosphate