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Biomedical subjects

C G Zaroulis

Publications and source records attributed to C G Zaroulis.

At least 19 recordsLinked to original sources

Two examples of an inseparable antibody that reacts equally well with DW+ and Rh32+ red blood cells.

BACKGROUND AND OBJECTIVES: Anti-DW is a rare specificity that detects an antigen on DVa red blood cells (RBCs). Some anti-DW contain an inseparable component that cross-reacts weakly with RBCs expressing the low-incidence Rh antigen Rh32. RH32 is expressed by RBCs with either the R=Nor the DBT phenotype. CASE REPORT: We describe here an antibody found in the serum of 2 patients that reacts equally well with RBCs possessing either DVa, R=N, or DBT phenotypes. The reactivity for DW and Rh32 antigens could not be separated by adsorption onto and elution from DW+Rh32- or from DW-Rh32+ RBCs. CONCLUSIONS: We suggest that amino acids encoded by nucleotides at the junction of exon 4 of RHD to exon 5 of RHCE may induce a conformation that is recognized by these equally reactive inseparable antibodies. Until such time that the epitope recognized by these antibodies is defined, we recommend use of the descriptive name anti-DW/Rh32.

Agglutinins↗

Idiopathic hemochromatosis presenting as amenorrhea and arthritis.

Idiopathic hemochromatosis in young adults has been increasingly recognized over the last three decades. Younger patients with hemochromatosis frequently have presenting problems other than diabetes, cirrhosis, and hyperpigmentation. A young woman with idiopathic hemochromatosis is described. Arthritis and secondary amenorrhea developed at age 20, and liver biopsy showed hemochromatosis at age 29. Further work-up revealed that the amenorrhea was due to underproduction of pituitary gonadotropins. The patient was treated with phlebotomy. Estrogen and progesterone replacement was begun because of severe osteoporosis. Serum iron studies may be useful in young patients with unexplained amenorrhea and/or arthropathy.

Adult↗

Evaluation of a new microporous filtration membrane system for therapeutic plasma exchange.

A new therapeutic plasma exchange device developed by Sarns Inc./3M was evaluated in plasmapheresis of 20 healthy volunteers and in a multicenter clinical study of therapeutic plasma exchange that included 49 patients. Safety and efficacy of plasma separation from whole blood were assessed for a module that contains Durapore microporous surfactant-free polyvinylidene fluoride membrane (Millipore Corp., Bedford, Mass., USA). The extra-corporeal volume was 80 ml. Citrate and heparin anticoagulants were utilized. Mean plasma separation efficiency was 62% with unhindered passage of plasma proteins through the membrane pores and no hemolysis or activation of complement as measured by total hemolytic complement (CH50) and C3 conversion. Mean decrease in platelet count after procedures was 10%. No severe reactions occurred, and citrate effects (13%) were comparable to values reported with centrifugal instruments. The Sarns Inc./3M Therapore device is a rapid, safe and efficient system for plasma exchange and potentially for source plasma collection. The principal benefits are small extracorporeal volume and cell-free filtrate.

Citrates↗

Neonatal alloimmune thrombocytopenic purpura: a case report.

We report a case of a sibling pair with neonatal alloimmune thrombocytopenic purpura. Serial antepartum platelet alloantibody quantitation by an enzyme-linked immunoabsorbent assay revealed rising antibody titers during advancing gestation. We discuss the implications of this finding in the antepartum diagnosis of neonatal alloimmune thrombocytopenic purpura, a rare, but frequently fatal disorder.

Adult↗

Neonatal alloimmune thrombocytopenic purpura.

We reviewed 58 literature reports of neonatal alloimmune thrombocytopenic purpura (NAITP). The mortality rate was 9%. The total incidence of suspected intracranial hemorrhage was 28%. We reviewed 17 sibship cases for the relation of birth order to treatment and outcome. Among firstborn affected infants (n = 17) the mortality rate and incidence of central nervous system sequelae were 24 and 47%, respectively, compared to rates of 5 and 15%, respectively, in their younger affected siblings (n = 20). The improved outcome in the latter group appeared to be related to more frequent cesarean section delivery and more frequent and earlier use of corticosteroids and maternal platelet transfusions in the neonate. Sensitive assays of maternal platelet alloantibody are now available, but they lack specificity for NAITP affecting the current gestation. There are two reports in which sensitive assays revealed rising titers of maternal platelet alloantibody during advancing gestation. We propose further study to determine if this is specific for the antepartum diagnosis of NAITP.

Adrenal Cortex Hormones↗

The clinical effectiveness and safety of chronic plasmapheresis in patients with primary biliary cirrhosis.

Primary biliary cirrhosis (PBC) is a chronic nonsuppurative, destructive cholangitis, whose etiology is unknown. Morbidity arises early from pruritus and later from hypercholesterolemia with xanthoma formation. Therapy is supportive and directed at the complications of cholestasis. Plasmapheresis has been reported to benefit patients with hyperlipidemia and PBC; thus a pilot study of plasmapheresis utilizing the Haemonetics Model 30 with replacement by albumin and saline was conducted. Five patients (four female and one male) with a mean age of 43 (range 29-58) and a mean duration of illness of 9.5 years (range 6-21) with marked jaundice, xanthomas, xanthelasma, hepatomegaly, fatigability, anorexia, and pruritus, as well as mild nausea were studied. Peripheral neuropathy was present in two patients. Two patients had splenomegaly. Two patients had an associated Sjogren syndrome. All patients had high serum bilirubin, alkaline phosphatase, and cholesterol levels and mild elevations in aspartate amino transferase and alanine amino transferase activities. Immune complexes measured in four patients were present. Antimitochondrial antibody titers were significant in all patients. Patients underwent a mean of 63 plasmapheresis procedures over a mean of 112 weeks removing a mean of 94.7 liters of plasma. No serious toxicity was seen. All patients showed a reduction in pruritus, xanthomas, xanthelasmas, and serum cholesterol values. The two patients who had evidence of Sjogren syndrome noted subjective improvement. All patients who had fatigue, anorexia and nausea also noted moderate improvement. There was no change in hepatomegaly or splenomegaly in patients demonstrating such organomegaly. Liver function did not change significantly. Overall, four patients had improvement in their condition and one patient achieved stability.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Immune thrombocytopenia and Gaucher's disease.

A 35-year-old Ashkenazi woman with Gaucher's disease was evaluated for persistent thrombocytopenia. The diagnosis of Gaucher's disease was made by bone marrow aspiration and confirmed by the determination of glucocerebrosidase levels in leukocytes and cultured skin fibroblasts. Studies of platelet-associated IgG and in vivo platelet survival demonstrated immune-mediated destruction of platelets consistent with immune thrombocytopenic purpura. A trial of prednisone had no effect on the platelet count. Total splenectomy resulted in a complete and prolonged remission. The clinical implications of Gaucher's disease and concurrent immune thrombocytopenic purpura are discussed.

Adult↗

Unfractionated human marrow cell cryopreservation using dimethylsulfoxide and hydroxyethyl starch.

Unfractionated bone marrow (BM) cells were cryopreserved in 1- to 2-ml aliquots using a mixture containing both 5% dimethylsulfoxide (DMSO) and 6% hydroxyethyl starch (HES) in an attempt to increase the viable cell yield and reduce the clumping after thawing, observed when 10% DMSO is used alone. Samples thawed after storage for 6 months in the vapor phase of liquid nitrogen, were assayed. Compared to prefreeze values, there was both a greater number of cells that excluded Trypan Blue (50 +/- 12 vs 28 +/- 12%, P less than .01) and a greater CFU-C Recovery (110 +/- 20 vs 89 +/- 35%, P less than .02) for cells in the DMSO/HES mixture, compared to those in 10% DMSO alone. No macroscopic clumping of the thawed cells was observed for those cryopreserved in the mixture in contrast to those in DMSO alone. Freezing was done without a rate-controlled freezing apparatus by simply placing the samples initially into a -80 degrees C freezer, and then later into a liquid nitrogen freezer. Additional samples stored in the DMSO/HES mixture were kept at only -80 degrees C, and when thawed 12 to 16 months later also gave an excellent CFU-C recovery (105 +/- 39% of prefreeze). The DMSO/HES mixture allows for a simplified BM cryopreservation technique that not only assures excellent recovery of CFU-Cs and eliminates clumping upon thawing, but also does not require either the use of a rate-controlled freezer or liquid nitrogen temperatures for storage up to a year.

Bone Marrow Cells↗

Thrombotic thrombocytopenic purpura in southeastern New England.

Eight patients with thrombotic thrombocytopenic purpura (TTP) originating within a 25-mile radius had their conditions diagnosed in a three-year period at a community teaching hospital in southeastern New England. In the preceding ten years, only one case of TTP had occurred in the same hospital. A niece-uncle relationship was present in two patients, and lymphocyte typing showed that they both shared an HLA haplotype. In the remaining patients, no social, familial, or environmental connection was established. Three patients died, all of whom were female. Six patients received exchange plasmapheresis with excellent responses in five. Autopsies in the three fatal cases showed widespread organ involvement with TTP but did not disclose evidence of any common underlying disease. This unusual occurrence should alert physicians to the possibility of localized outbreaks of TTP and the necessity of considering this diagnosis in all patients with unexplained thrombocytopenia.

Adolescent↗

A microimmunofluorescent assay to detect human granulocyte antigens and antibodies.

Granulocyte antibodies are important in the pathogenesis of neonatal granulocytopenia, in some varieties of idiopathic granulocytopenia, and in transfusion reactions, particularly since the development of leukocyte transfusion therapy for granulocytopenic patients. Previous assays for the detection of granulocyte-specific antigens and antibodies were cumbersome, complex, and unreliable. Thus we have now described a new microimmunofluorescent method to assay human granulocyte antigens and their antibodies. This sensitive and reliable technique allows for the preservation of human granulocyte antigenicity for at least 24 hours. The granulocyte-specific antigens of a Caucasian population, residing in metropolitan New York, were studied by this microimmunofluorescent method. We report the distribution of granulocyte-specific antigens in this population, together with the corresponding gene frequency. This microimmunofluorescent test should improve our understanding of antigenic systems restricted to single cell populations.

Antibodies↗

Serum concentrations of erythropoietin measured by radioimmunoassay in hematologic disorders and chronic renal failure.

Bioassays for human erythropoietin are cumbersome, time-consuming, and insensitive. The purification of human erythropoietin (EP) had provided small quantities of highly bioactive EP (approximately 70,000 U/mg) required for the development of an EP radioimmunoassay (RIA). The RIA for EP described in this investigation, can detect 5 mU/ml of EP in the assay tube; the serum concentration of EP in normal individuals ranged from less than 18 to 81 mU/ml with a mean value of 29 mU/ml. In contrast, nine patients with severe aplastic anemia had markedly elevated serum EP concentrations with a mean value of 3,487 mU/ml, range 984--6,434 mU/ml. In this RIA, patients with Polycythemia vera had consistently undetectable EP concentrations, less than 18 mU/ml. Eleven patients with chronic renal failure had a higher mean serum EP concentration (40.5 mU/ml) than normal individuals, but the range (less than 18-115 mU/ml) overlapped that of normals. By immunologic and gel chromatographic criteria, EP measured in serum was similar to standard urinary EP. The EP immunoassay that we have developed has sufficient sensitivity and specificity not only to quantitate the elevated serum EP levels found in aplastic anemia but also to discriminate decreased from normal serum concentrations of EP in most circumstances. This simple, reliable RIA has provided the necessary framework upon which to increase our understanding of the importance of EP in hematopoiesis.

Adult↗

Evidence that circulating immune complexes remove transfused platelets from the circulation.

Fifteen recently diagnosed patients with acute leukemias admitted for induction chemotherapy were selected for study. When thrombocytopenic (venous platelet count less than 20 X 10(9)/l) these patients received prophylactic platelet transfusions. A total of 67 platelet transfusion therapies were administered and evaluated. Using the Raji cell radioimmunoassay, the serum concentrations of circulating immune complexes (CIC) were measured immediately before and 10-12 hr after each platelet transfusion. In 36 instances, elevated values of CIC were present in the recipient's pretransfusion samples. The corresponding posttransfusion values being significantly lower (P less than 0.05). Furthermore, in those 36 instances the mean percentage for the posttransfusion platelet increment was significantly lower (P less than 0.001) than in the remaining 31 instances in which normal pretransfusion values of CIC were measured. We conclude that CIC were an important factor in rapidly removing transfused platelets from the circulation, thereby, adversely affecting the benefit of platelet transfusions.

Acute Disease↗

Plasma beta-thromboglobulin values in thrombocytopenic patients with acute leukemia.

Plasma beta-thromboglobulin (beta-TG) levels were measured in 14 healthy subjects and in 20 acute leukemia (AL) patients, newly diagnosed, with highly variable values for venous platelet counts. For healthy subjects the plasma beta-TG levels ranged 12-38 (mean 17) ng/ml. In this group of patients with AL, a highly significant positive correlation (P < 0.001) between the values for plasma beta-TG and venous platelet count was present. During a thrombocytopenic period, the plasma beta-TG concentraton was measured in nine of the AL patients immediately before and 10 to 12 hours after platelet transfusion therapy. Fourteen platelet transfusions were administered when the patient's highest temperature of the day was < 38.5 degrees C, and 18 when the highest temperature of the day was greater than or equal to 38.5 degrees C. The mean pre-transfusion and post-transfusion beta-TG values for the 14 platelet transfusions were 7 +/- 2 and 20 +/- 5 ng/ml, respectively. The corresponding means for the 18 transfusions given to febrile patients were 5 +/- 2 ng/ml and 11 +/- 2 ng/ml, respectively. Of the pretransfusion values, 11/14 and 14/18 were below the control range. We conclude that the plasma beta-TG values are considerably lower in thrombocytopenic patients than in subjects with normal platelet counts. Further work should provide reference values for plasma beta-TG over a wide range of venous platelet counts.

Adolescent↗

Platelet transfusion therapy and circulating immune complexes.

30 platelet transfusions were administered to 9 thrombocytopenic patients with acute leukemias. Using the Raji cell radioimmunoassay, the serum concentration for circulating immune complexes (CIC) were determined immediately before and 10--12 h after each transfusion therapy. Elevated serum concentrations for CIC were present in 14 of the pretransfusion samples. After platelet transfusion therapy, a significant (p < 0.02) decrease in the values of CIC occurred. In these 14 transfusion studies the mean percent platelet increment was considerably lower (0.10 > p > 0.05) than the mean for the 16 transfusion studies in which the pretransfusion values for CIC were normal. These results show that CIC probably play an important role in removing transfused platelets from the circulation. Conversely, platelets are able to remove CIC from the circulation.

Acute Disease↗

Plasma levels of beta-thromboglobulin and platelet factor 4 in relation to the venous platelet concentration.

The plasma levels of beta-thromboglobulin (beta-TG) and platelet factor 4 (PF-4) were determined in patients with various hematologic malignancies, and the results were related to simultaneously determined venous platelet counts. All studied patients were in a steady state. The plasma beta-TG concentrations were determined on 69 occasions and the values ranged from 0 to 82 ng/ml. In 33 instances, the venous platelet count was <25 x 10 (9/1) and in two thirds of these samples beta-TG was undedectable. The highest values for plasma beta-TG were found in patients with the highest venous platelet counts. A highly significant correlation (r=0.77, p <0.001) between the values for plasma beta-TG and venous platelet count was present. The plasma concentrations for PF-4 ranged from 0 to 50 ng/ml. Similarly, there was a highly significant relationship (r=0.78, p<0.001) between the values for PF-4 and venous platelet concentration. We conclude, if the plasma levels of beta-TG and PF-4 are used as markers of platelet activation in vivo, it is necessary to simultaneously consider the platelet concentration in the collected blood.

Adolescent↗

beta-Endorphin: analgesic and hormonal effects in humans.

The pharmacokinetics and the hormonal, analgesic, and behavioral effects of several doses of human beta-endorphin were evaluated after intravenous administration to three patients and intracerebroventricular administration to one patient with pain caused by cancer. These effects were compared to the hormonal effects of intravenously administered morphine sulfate in two patients and an enkephalin analog in two baboons. The mean terminal half-life after intravenous administration of 5 or 10 mg of human beta-endorphin to three patients was 37 min; the mean volume of distribution was 178 ml/kg, and the metabolic clearance rate was 3.2 (ml/min)/kg. The half-life of beta-endorphin in cerebrospinal fluid after intracerebroventricular administration was 93 min, and the volume of distribution was 0.74 ml/kg. A rapid rise in plasma prolactin followed both intravenous and intracerebroventricular beta-endorphin. Intravenous administration did not affect plasma growth hormone, but intracerebroventricular administration suppressed plasma growth hormone. No significant change in plasma growth hormone was noted after intravenous administration of morphine to humans, but plasma growth hormone decreased in one baboon after administration of the enkephalin analog. beta-Endorphin-stimulated release of prolactin occurred at doses lower than those required to produce analgesic and other behavioral effects. When both hormonal and analgesic effects were observed (after 7.5 mg were given intracerebroventricularly), the onset of the hormonal response slightly preceded the analgesic and behavioral responses. These studies suggest that the hormonal effects of beta-endorphin are species dependent and are similar to those of morphine. Hormonal and analgesic effects of beta-endorphin appear to result from the activation of opiate receptors that differ in their locations and characteristics.

Adult↗