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Biomedical subjects

J Freedman

Publications and source records attributed to J Freedman.

At least 145 records · Page 8Linked to original sources
PubMed1987

Humoral and cellular immune abnormalities in adult hemophiliacs followed over a 2-year period.

Immune function was assessed in 93 adult hemophiliacs in the 2 years prior to HTLV-III antibody testing of blood donors and routine heat treatment of coagulation factor concentrates. Parameters of humoral and cellular immunity studied included serum complements, immunoglobulins, immune complexes, blood cell counts, lymphocyte subsets, lymphocyte transformation, 2-5A synthetase, serology for HTLV-III and hepatitis B, skin tests, and clinical status. HTLV-III seropositivity was significantly more prevalent in patients treated with factor VIII concentrate; seropositive patients had a higher proportion of abnormal test results and were more symptomatic. Although many subjects had abnormal test results, specific test results generally did not correlate with type of blood component received or time of preceding treatment. The proportion of tests abnormal in individual patients was correlated with the intensity of factor replacement therapy when the time interval from the last treatment was a covariate. While T8+ lymphocytes were increased and T4/T8 ratios were decreased in many patients, significantly reduced T4+ lymphocytes were seen only in seropositive patients and in those treated with factor VIII concentrate. Neither seropositivity nor presence of symptoms correlated with abnormal lymphocyte mitogenic response or 2-5A synthetase levels, but synthetase levels were increased in 65% of patients tested. Over the 2-year study period, no significant deterioration of clinical or laboratory variables was observed in the patients. Abnormalities of immune function were found to be common in hemophiliacs regardless of type of treatment or of evidence of HTLV-III infection.

Antibodies, Viral↗
PubMed1987

Antinociceptive effects and spinal cord tissue concentrations after intrathecal injection of guanfacine or clonidine into rats.

In the present study, the antinociceptive effects of intrathecal injections of the alpha 2-adrenoceptor agonists clonidine and guanfacine in rats was determined to establish their dose-response curves. Spinal cord tissue concentrations were also determined in a separate group of animals. Guanfacine was found to be more potent than clonidine and had a considerably longer duration of action. Thus, whereas the analgesic effect of clonidine declined to baseline by 4 hr after injecting doses of up to 50 micrograms, guanfacine still showed a considerable effect 18 hr after injecting both 25 and 50 micrograms. With both compounds, concentration gradients existed within the spinal cord. In the experiments with guanfacine, the region in the spinal cord tissue with the highest concentrations 10 min after injection contained around 30 pmol/mg wet weight. At 3 hr, this figure was around 20 pmol/mg. With clonidine, on the other hand, the concentration decreased from the maximal level of 200 pmol/mg at 10 min to 10 pmol/mg at 3 hr. On all occasions, except 10 min after injecting clonidine, it was found that the maximal tissue concentrations for both drugs remained below the cervical spinal cord, i.e., the rostral spread was less than expected, especially with drugs with such a long duration of action. The present investigation demonstrates analgesic effects of both clonidine and guanfacine after intrathecal administration, with guanfacine proving more potent and longer acting; the difference in duration of action is probably attributable to differences in rates of elimination of the drugs from spinal cord tissue.

Adrenergic alpha-Agonists↗
PubMed1987

Flap selection in glaucoma filtration surgery.

Glaucoma surgery requires the fashioning of conjunctival flaps with or without scleral flaps. The advantages and use of fornix-based conjunctival flaps are presented. Methods to decrease complications of limbal-based conjunctival flaps are discussed. The use of scleral flaps and their modification to assist in enhancing filtration and to prevent complications of filtering surgery is shown.

Conjunctiva↗
PubMed1986

Unexplained periparturient thrombocytopenia.

Since the advent of routine automated platelet counting we have observed unexplained periparturient thrombocytopenia (PPT) in an unexpected number of periparturient women, ie, during labor or within 24 hr postpartum. Mean +/- SD platelet count in 686 random blood donors was 236 +/- 50 X 10(9)/L and 1.02% had a platelet count less than 136 X 10(9)/L; in 2,204 random prenatal and postpartum women mean count was significantly higher (275 +/- 86 X 10(9)/L; p less than 0.001). Of 1,621 periparturient women, 74 (4.6%) had unexplained PPT (mean +/- SD platelet count 122 +/- 24 X 10(9)/L, range 21-135 X 10(9)/L, N = 74). Platelet count in PPT usually rose to normal within 1 week of delivery; in 10% thrombocytopenia persisted greater than 6 months. PPT occurred in successive pregnancies with normal intervening platelet counts. Nine of 34 newborns of mothers with PPT were thrombocytopenic; there was no correlation between mother's and baby's platelet counts. In no case of PPT was there excessive bleeding in mother or infant. Positive indirect platelet radioactive antiglobulin tests (PRAT) were seen in 11% of normal postpartum women and in 90% of 22 women with PPT; 65% of the positive tests in PPT were due to reactions with anti-C3 only. In contrast, pregnant women with autoimmune thrombocytopenic purpura (AITP) had positive PRAT primarily because of anti-IgG (+/- anti-C3); only 10% were positive only with anti-C3. Results were concordant in all of eight women with PPT tested by both indirect and direct PRAT. Amount of C3 bound per platelet in direct or indirect PRAT was not predictive of degree of thrombocytopenia, but there was correlation of fg C3 per platelet detected by the two assays in individual patients (r = 0.8). Mean levels of serum C3, C4, and factor B in women with PPT did not differ from normal; individual patients had abnormal serum complements but no characteristic pattern was observed. Increased immune complexes were observed in 6% of normal subjects and 33% of women with PPT. Etiology and mechanism of PPT is unclear. Despite lack of clinical evidence in women with PPT of syndromes associated with increased platelet destruction, the presence of preeclampsia cannot be absolutely excluded. Similarly, although the pattern of antiglobulin sensitization in PPT differed markedly from that seen in AITP, autoimmune disorder cannot be excluded. Alloantibodies did not appear to be responsible for PPT. While PPT is usually benign, some patients had a markedly reduced platelet count. Recognition of the phenomenon may be important in obstetrics.

Antigen-Antibody Complex↗
PubMed1986

Changing patterns of transfusion practice in a tertiary care hospital from 1977 to 1984.

Patterns of blood transfusion practice over an eight-year-period (1977-1984) are described. Use of blood and blood products increased annually as did the number of patients crossmatched and transfused. Programs such as the "Blood Group & Antibody Screen" and the "Maximum Surgical Blood Order Schedule" were important in improving transfusion practices. There was improvement in blood use by all subspecialties; the overall C:T (crossmatched:transfused blood) ratio declined from 4.4 to 2.8. Approximately a quarter of both crossmatches performed and transfusions of red cells were associated with cardiac surgery. Incidence of outdated units of blood declined markedly (2.6 per cent in 1984), as did requests for and administration of single unit transfusions. Seven per cent of patients received one unit of blood during hospitalization; since 85 per cent of these were associated with surgery (57 per cent cardiac surgery), it is suggested that single unit transfusions may sometimes be more appropriate than inappropriate. Two per cent of patients had clinically significant alloantibodies. About two per cent of patients had positive direct antiglobulin tests; nine per cent of the sera of these patients contained both auto and alloantibodies. Such data are important for transfusion quality assurance as well as for optimal logistical use of facilities both at hospital Blood Bank and blood collection agency levels.

Antibodies↗
PubMed1986

Purification and characterization of human platelet glutathione-S-transferase.

A glutathione-S-transferase was isolated and purified to homogeneity from human platelets. With a combination of ammonium sulfate fractionation and chromatographic methods, 0.2 mg of pure enzyme was obtained from 9 X 10(11) platelets with a 12% recovery. The purified enzyme had a specific activity of 7.5 U per milligram, representing an approximately 1,100-fold purification. The enzyme was found to be anionic, with an isoelectric point of 4.6. With reduced glutathione as a co-substrate, platelet glutathione-S-transferase was most active with the synthetic substrate, 1-chloro-2,4-dinitrobenzene, less active with 1,2-dichloro-4-nitrobenzene, and essentially inactive with nitroglycerin and 1,2-epoxy-3-(p-nitrophenoxy)-propane. The pH optimum for activity with glutathione and 1-chloro-2,4-dinitrobenzene was 7.0. Indomethacin (1-(p-chlorobenzoyl)-5-methoxy-2-methyindole-3-acetic acid), a chlorobenzene derivative, noncompetitively inhibited human platelet glutathione-S-transferase with an apparent KI of 0.23 mmol/L. This study represents the first complete purification and characterization of a glutathione-S-transferase from platelets. The presence of this enzyme in the platelet, within which high concentrations of reduced glutathione coexist, suggests the potential importance of the platelet in detoxification reactions and in the synthesis of the glutathione adducts of leukotriene metabolism.

Blood Platelets↗
PubMed1986

Indirect platelet radioactive antiglobulin test in patients with lymphoproliferative disease.

An indirect platelet radioactive antiglobulin test (PRAT) was used to evaluate serum antiplatelet antibody and complement activation in 114 patients with lymphoproliferative disease. Overall, 60% of serum samples gave a positive indirect PRAT. Positive PRAT was observed in 85% of patients with chronic lymphocytic leukemia (CLL) and megakaryocytic thrombocytopenia, as well as in about half the patients with CLL and a normal platelet count or amegakaryocytic thrombocytopenia. In contrast to findings in patients with idiopathic autoimmune thrombocytopenic purpura or in those with leukemia who were alloimmunized, positive PRAT in patients with lymphoproliferative disease was predominantly caused by C3-only sensitization of platelets. Results were analyzed in relation to other clinical and laboratory findings. There was no significant difference in antiglobulin sensitization pattern between CLL and other lymphomas, different cell type, stage of disease, presence or absence of splenomegaly, recent or distant chemotherapy, sex, or history of pregnancy. Previous transfusion did affect antiglobulin sensitization patterns, as did presence of autoimmune hemolytic anemia. A high frequency of low serum complements (CH50, C3, C4, and factor B) and increased circulating immune complexes was observed; these did not correlate with frequency or sensitization pattern of positive PRAT. Amounts of bound anti-C3 and anti-IgG were significantly higher in patients with lymphoproliferative disease and positive antiglobulin test than in normal individuals; there was, however, no correlation between amount of antiglobulin serum bound and platelet counts. There was an 87% correlation in direct and indirect PRAT in 24 patients tested.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Use of the indirect platelet radioactive antiglobulin test with anti-IgG and anti-C3 in immune and nonimmune thrombocytopenias.

Indirect platelet radioactive antiglobulin tests using anti-IgG and anti-C3 were performed in 483 individuals. The subjects' diagnoses and clinical states were correlated with sensitizing protein (IgG and/or C3). Sensitivity of the technique was increased by increasing the serum to cell ratio and there was good correlation between direct and indirect antiglobulin tests in 56 patients. Seven percent of normal healthy non-thrombocytopenic untransfused males and 88% of patients in whom autoimmune thrombocytopenia was clinically suspected showed a positive test result. In the indirect antiglobulin test, mean +/- SD fg anti-C3d/platelet was 1.75 +/- 0.28 (N = 58) with serum from normal subjects, 3.91 +/- 1.86 (N = 123) with serum from patients with idiopathic thrombocytopenic purpura and systemic lupus erythematosus, and 2.78 +/- 0.91 (N = 52) with serum from patients with lymphoproliferative disease. The differences were significant with P less than 0.001. Levels of bound anti-IgG were in general accord with those of other reports; there was no significant relationship with serum immunoglobulin levels. When the indirect antiglobulin tests were positive for both IgG and C3, there was a significant correlation between IgG and C3 bound to normal platelets (r = 0.671; P less than 0.01). Although sera from 39% of patients whose thrombocytopenia was not initially suspected to be on an autoimmune basis gave a positive test result, indirect platelet radioactive antiglobulin tests using anti-IgG and anti-C3 may be convenient tools in the evaluation and follow-up of immune thrombocytopenias.

Adult↗
PubMed1985

Redistribution of lidocaine and bupivacaine after intrathecal injection in mice.

Redistribution of lidocaine and bupivacaine was studied after intrathecal injection in mice qualitatively by whole-body autoradiography or quantitatively by determining spinal cord concentration of the drugs. The composition of the drug solutions then were changed to see if drug distribution could be altered. Changing the pH of the lidocaine solution from 7.5 to 5.0 by adding hydrochloric acid had no effect on spinal cord distribution. Simultaneous injection of bupivacaine and epinephrine increased the bupivacaine concentration in the spinal cord. By adding sucrose to a lidocaine solution, rostral spread of lidocaine was considerably less when the animals were restrained in a vertical position as compared with those injected with a plain solution. When lidocaine and bupivacaine were injected simultaneously, the spinal cord concentration was only changed to a small extent as compared with when the drugs were given separately. Whole body autoradiography revealed that both lidocaine and bupivacaine were rapidly redistributed rostrally from the lumbar area, but quantitatively the rostral redistribution is small. Whole body autoradiography also illustrated the elimination pathways from the spinal subarachnoid space. The authors conclude that alterations in the composition of the injected drug solution can affect rostral redistribution in the spinal cord tissue.

Anesthesia, Local↗
PubMed1985

Effect of complement on the viscoelastic properties of human erythrocyte membrane.

Using the micropipette technique, we examined the viscoelastic properties of the red blood cell (RBC) membrane which had been strongly coated with various components of complement (primary C3b, C3d, C4b, C4d) in vitro. The membrane elastic modulus (E), the viscosity index of the initial rapid phase of deformation (eta D1), the viscosity of the later slow phase of deformation (eta D2) and the viscosity of the recovery phase (eta R) were determined. Compared to control non-complement coated RBCs, RBCs coated with C3d, either alone or with other complement components, showed significant increase in the values for elasticity and viscosities. Thus C3d fixation resulted in decreased membrane deformability. Changes in membrane viscoelasticity due to bound C3d were not enhanced by bound C4b, C4d, C5, factor Bb or p; presence on RBC membrane of the latter two complement components may partially reverse the effect of C3d fixation. Lipid fluidity of RBC membrane, examined by fluorescence depolarization, increased with fixation of all complement components except C5. These complement-induced changes in membrane viscoelastic properties have potential pathophysiological and clinical implications. The data suggest that extravascular sequestration of human RBCs may be explained in part by increased membrane rigidity resulting from C3d fixation.

Complement C3↗