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Biomedical subjects

T Mandalaki

Publications and source records attributed to T Mandalaki.

At least 19 recordsLinked to original sources

Early plasmapheresis in patients with thrombotic thrombocytopenic purpura.

OBJECTIVES: To investigate the relationship of thrombotic thrombocytopenic purpura to adult respiratory distress syndrome (ARDS) and study the responses of thrombotic thrombocytopenic purpura patients to early plasmapheresis. DESIGN: Case series. SETTING: ICU of a university hospital. PATIENTS: Twenty-four consecutive patients with thrombotic thrombocytopenic purpura, with various periods of time (1 to 18 days) having elapsed since the onset of this condition. Patients ranged in age from 17 to 66 yrs. INTERVENTIONS: Plasmapheresis, using intermittent flow separators, was instituted soon after the patients' ICU admission. The retinoscopic findings on admission and the relationship of Pao2 to platelet counts before and after plasmapheresis therapy were recorded. Antiplatelet agents were given to the survivors to prevent relapses. MEASUREMENTS AND MAIN RESULTS: Eighteen patients survived and six died. Plasmapheresis was administered for a range of 1 to 5 days (mean 3) and 3 to 18 days (mean 9.8) in survivors and nonsurvivors, respectively (p less than .001). Four patients with confluent fundus hemorrhages died and seven without these fundoscopic findings had easily controlled disease. Increases in Pao2 paralleled increases in platelet counts after plasmapheresis (p less than .001) in this small series of patients. Three of 18 discharged survivors relapsed over a period of 3 to 56 months of follow-up. CONCLUSIONS: Early introduction of plasmapheresis in thrombotic thrombocytopenic purpura seems to increase the survival rate and to halt the development of ARDS. Fundus findings may be a prognostic factor in thrombotic thrombocytopenic purpura. The antiplatelet agents seem to be efficacious in the prevention of relapses.

Adolescent

Antibody responses to hepatitis C virus by second-generation immunoassays in a cohort of patients with bleeding disorders.

The antibody responses and the prevalence patterns of antibodies to hepatitis C virus (anti-HCV) in a cohort of patients (n = 210) with bleeding disorders were studied using a first-generation and a second-generation enzyme immunoassays (EIA-1, EIA-2) as well as a second-generation recombinant immunoblot assay (RIBA-2). The anti-HCV prevalence as determined by EIA-1 and EIA-2 was 183/210 (87.1%) and 197/210 (93.8%), respectively (p = 0.0026). None of the 17 EIA-2(+)/EIA-1(-) samples was scored nonreactive by RIBA-2. At follow-up, samples of 123 patients were tested. Twenty-nine out of 111 patients reactive by EIA-1 seroreverted according to EIA-1 while the seroreversion rate with EIA-2 was 0 out of the 121 (p < 10(-8)). The anti-HCV prevalence by EIA-2 was 150/154 (97.4%) in anti-HIV-1-positive individuals and 47/56 (83.9%) in the anti-HIV-1-negative ones (p = 0.001). However, high assay signals (OD 492 nm > 2.0) were observed in 94/150 (62.7%) and 45/47 (95.7%) of the anti-HIV-1-positive and -negative patients, respectively (p = 10(-5)). The decreasing anti-HCV reactivity among anti-HIV-1-positive individuals was mainly due to diminishing c33c reactivity. Seroconversion to anti-HCV was observed in 3/7 (42.9%) cases with acute icteric non-A, non-B hepatitis by both EIA-1 and EIA-2, while the remaining 4 cases had detectable levels of anti-HCV 1-18 months before the acute episode.

Acquired Immunodeficiency Syndrome

Neuropsychological assessment of HIV-seropositive haemophiliacs.

Neuropsychological findings from investigation of 46 HIV-seropositive asymptomatic and 14 HIV-seropositive symptomatic haemophiliacs without AIDS-related complex (ARC) or AIDS, with known duration of HIV seropositivity were compared with 29 seronegative controls. Subjects were assessed blindly using a battery of sensitive computerized neuropsychological tests. They underwent a thorough neurological examination, were assessed for mood and screened for psychopathology. Symptomatic HIV-positive haemophiliacs without ARC or AIDS showed statistically significant decreased performances compared with HIV-negatives in choice reaction, visuomotor coordination and global attentional performance (P = 0.018, 0.039 and 0.044, respectively). HIV-positive asymptomatic subjects gave lower performances than HIV-negative subjects in all tests, although these differences were not statistically significant. However, there was a statistically significant trend for these findings between seronegative, asymptomatic and symptomatic groups. Impairment was not associated with mood factors. Duration of seropositivity was found to be a more important factor than Centers for Disease Control stage in the choice reaction test (P less than 0.01). These findings indicate that mild cognitive impairment observed during the natural history of HIV infection in haemophiliacs without ARC or AIDS may be a progressive phenomenon not necessarily associated with the clinical expression of HIV infection.

Anxiety Disorders

Two novel point mutations correlate with an altered developmental expression of blood coagulation factor IX (hemophilia B Leyden phenotype).

Hemophilia B Leyden is characterized by low levels of factor IX antigen and activity before the age of 15 years, whereas after puberty factor IX levels rise at a rate of about 5% per year. Two distinct point mutations (deletion of A, A----G) were identified at position +13 of the factor IX gene of a Greek and an American patient with hemophilia B Leyden. The nucleotide changes have occurred 32 basepairs downstream of a previously reported point mutation in a Dutch kindred with the same hemophilic phenotype. The results point to the importance of sequences surrounding the putative start site for the constitutive expression of the factor IX gene and to the possible significance of an imperfect direct repeat of DNA.

Age Factors

Carrier detection in hemophilia using pedigree analysis coagulation tests and DNA probes.

Hemophilia A and B are hereditary X-linked recessive bleeding disorders due to an anomaly or absence of the gene coding for coagulation factors VIII or IX. Until recently, carrier detection was performed on standard pedigree analysis and clotting factor assays. Due to lyonisation, the results obtained by these methods were only probabilistic. Recombinant DNA procedures have now been applied to the identification of molecular defects and carrier detection in inherited diseases. Because of the great heterogeneity of the molecular defects in hemophilia, the diagnosis of carrier status has to be made by the study of restriction fragment length polymorphisms (RFLP) genetically linked to factor VIII or factor IX genes. In a large number of cases, gene probing provides certain diagnosis. We studied some 300 individuals belonging to 70 families with hemophilia A or B. We used two probes to explore hemophilia A: an intragenic probe, p114.12, which detects an RFLP with the enzyme BclI and the extragenic polymorphic probe, St 14, which reveals an RFLP with the enzyme TaqI. For hemophilia B a genomic probe comprising exons b, c, d was used to detect an RFLP linked to a TaqI site. Despite the risk of recombination due to its extragenic location, the St 14 probe proved to be very useful because of the high informativity obtained in the families with hemophilia A. In contrast, the low informativity of the factor IX probe necessitates a search for other RFLPs in or near the factor IX gene. A comparison of the different methods used for carrier detection showed the possibility of misdiagnosis when using only pedigree analysis and biologic data and the improved certainty of diagnosis by gene probing.

Blood Coagulation Tests

Heterosexual transmission of HIV in Greece.

To provide further evidence for the heterosexual transmission of the acquired immunodeficiency syndrome (AIDS) in Greece we examined 53 Greek female steady heterosexual partners of 53 anti-HIV-positive men. Human immunodeficiency virus (HIV) transmission was estimated by the detection of anti-HIV antibodies. Our results showed that 27.8% (5 of 18) of the female partners of bisexuals, 33.3% (2 of 6) of intravenous drug abusers (IVDA), and 100% (4 of 4) of those who had lived for a long time in Africa were found anti-HIV positive. In contrast, only 4% (1 of 25) of the studied sexual partners of hemophiliac carriers were found to be HIV seropositive. The use of condoms seemed to be the most important factor in reducing HIV transmission. According to our results the duration of sexual relationships and the practice of anal intercourse did not increase the possibility of seroconversion. These results confirm the heterosexual transmission of HIV. However, further studies should be conducted to evaluate the relative role of various risk factors and the overall importance of heterosexual spread of HIV infections.

Acquired Immunodeficiency Syndrome

Antibody responses in early human immunodeficiency virus type 1 infection in hemophiliacs.

Sera from hemophiliacs were analyzed for antibodies to human immunodeficiency virus type 1 (HIV-1) by using radioimmunoprecipitation (RIP), western blotting (WB) with nonreducing buffer (NR), and WB with reducing buffer (R). We analyzed envelope gp160, gp120, and gp41; pol gene proteins p64, p53, and p34; and gag gene protein p24. Of 215 samples positive for reactivity to gp160 and gp120(RIP), antibodies to p24 were undetectable in 2 (0.9%), to gp41 in 9 (4.2%), to the pol antigens in 5 (2.3%), to gp120(NR) in 3 (1.4%), and to gp120(R) in 55 (25.6%). By sequential analysis of samples, antibodies to gp120(NR), gp120(R), p24, gp41, p64/53, and p34 were observed later in the course of infection than were antibodies to gp120(RIP) or gp160. This result suggests caution against reliance on WB as the "gold standard." A significantly higher rate of progression to AIDS-related complex was found for individuals lacking antibodies to gp120(R). It is possible that antigenic domains represented by gp120(R) may play a role in the pathogenesis of HIV-1 infection.

AIDS-Related Complex

Extracorporeal lithotripsy in patients with hemophilia.

Two hemophiliac patients with nephrolithiasis were treated with extracorporeal lithotripsy. Both patients were followed up by the 2nd Hemophilia Center of Athens. One is registered as severe hemophilia A and the other one suffers from hemophilia B. With the cooperation of the specialized center they were prepared as for a major operation by administration of substitution therapy. The least possible number of shock waves at low voltage was administered in order to minimize renal damage. Both patients had an uneventful postoperative course.

Adult

Haemophilia B Leyden in Greece.

In this paper, a five generation Greek family is described with haemophilia B. The disease is characterized by a normal ox-brain prothrombin time, normal levels of the vitamin-K dependent clotting factors VII and X and a proportional reduction of factor IX activity and antigen levels all of which is consistent with the cross-reacting material negative form of haemophilia B. However, in this family the factor IX levels in the three patients of generation V are around 1 U/dl while the three older patients in generation III have factor IX levels ranging from 28 to 44 U/dl. In the oldest patient of generation V we observed a rise of the factor IX level from 1 U/dl up to the age of 13 to 10 U/dl at age 14. In addition, the older patients have very mild bleeding symptoms or none at all, while the young ones have occasional spontaneous haemorrhages in muscles and joints, compatible with severe or moderately severe haemophilia. The disease appears to be similar to haemophilia B Leyden which has been described in a Dutch family.

Aging

Abnormalities of lymphocyte subsets and anti-LAV/HTLV-III status in Greek hemophiliacs.

Peripheral blood lymphocyte subsets and the incidence of LAV/HTLV-III antibodies were studied in 63 patients with hemophilia A who had been transfused with a low dose regimen of commercial (U.S.A.) factor VIII concentrates. Five patients with hemophilia B were also included in this study. In hemophilia A patients a significant reduction in the percentage and absolute numbers of T4+ cells and of the T4/T8 ratio and a significant increase in the percentage of T8+ and Leu-7+ cells were observed. These abnormalities were independent of the presence of anti-LAV/HTLV-III. In hemophilia B patients a significant increase of T8+ cells and a decrease of T4/T8 ratio was noted while the percentage of Leu-7+ cells was normal. A significant negative correlation of F VIII units transfused and T4/T8 ratio was seen only in LAV/HTLV (-) patients, suggesting that F VIII per se could cause immunodysregulation. Seropositive patients were found to have consumed a larger amount of F VIII units than seronegative patients during the period 1980-1984 (p less than 0.005).

Acquired Immunodeficiency Syndrome

High frequency of HLA-DR5 in Greek patients with haemophilia A and haemophilia B.

Sixty unrelated Greek patients with haemophilia (46 with haemophilia A and 14 with haemophilia B) were typed for HLA-A, B and DR antigens. A highly significant increase in the frequency of HLA-DR5 was observed in both groups of patients (58.6% vs 30.0%, chi 2 = 10.47, pc less than 0.03, RR = 3.31 for haemophilia A and 78.5% vs 30.0%, chi 2 = 12.32, pc less than 0.007, RR = 8.5 for haemophilia B). An increased frequency of HLA-B13 was also observed in patients with haemophilia A (15.2% vs 5.7%, chi 2 = 5.74, pc less than 0.4, RR = 2.9). Thirty of the 60 patients (50.0%) were positive for LAV/HTLVIII antibodies. HLA-DR5 was equally distributed in patients with and without these antibodies (63.3% and 63.3%, respectively). The presence of DR5 did not correlate with the severity of haemophilia A or B. These results may suggest an influence of gene(s) on chromosome 6 in haemophilia A and haemophilia B and no effect of HLA antigens in the susceptibility to LAV/ HTLVIII infection among haemophiliac patients.

Acquired Immunodeficiency Syndrome

Raynaud's phenomenon: primary and secondary causes.

The terms "Raynaud's disease" and "Raynaud's phenomenon" are often used interchangeably, as if they were a single problem. Because prognosis and therapy are different with each of these entities, 86 patients with episodic digit ischemia were evaluated over the past five years. All patients were evaluated similarly with plethysmography, angiography, and other studies for underlying causes of the digital ischemia. From the study, it was concluded that the majority of the patients had an underlying cause for the problem even though they satisfied the commonly accepted criteria for the diagnosis of Raynaud's disease. It is clear that the diagnosis of Raynaud's disease must be one of exclusion, because it is more uncommon than is generally appreciated by the medical community.

Cold Temperature

Marathon run I: effects on blood coagulation and fibrinolysis.

Blood coagulation and fibrinolysis were assessed in 13 Finnish amateur runners aged 31 to 48, and one 65-year old taking part in a non-competitive marathon (42.2 km). After the run the mean values of partial thromboplastin time showed a very significant shortening, whereas the mean values of the prothrombin time and of plasma fibrinogen were not significantly altered. The mean values of euglobulin lysis time were significantly shorter and the mean values of fibrin degradation products increased highly significantly. After the run, protamine sulphate was positive or strongly positive in all subjects, whereas the ethanol gelation test was negative in all runners; no cryofibrinogen was detected in any participant. Thus, running a marathon race affects the haemostatic balance and activates the fibrinolytic mechanism. The effects of training and physical fitness on the above parameters are discussed.

Adult

Marathon run II: Effects on platelet aggregation.

Platelet count and aggregation were assessed in 9 Finnish amateur runners aged 34 to 48, and one 65-year old taking part in a non-competitive marathon race (42.2 km). After the run the mean value of platelet count showed a very significant rise (p less than 0.001). The platelets were markedly more sensitive to both ADP and collagen-induced aggregation. A highly significant increase (p less than 0.001) was noted for both the intensity and velocity of platelet aggregation. The finding of platelet by hyperaggregability after prolonged strenous exercise even in trained subjects is discussed. It is concluded that a through medical examination of the haemostatic balance is recommended before a marathon race.

Adenosine Diphosphate

Jaundice and hepatitis B surface antigen and antibody in Greek haemophiliacs.

The incidence of hepatitis B surface antigen (HBsAg) and antibody (HBsAb) in 101 Greek multitransfused haemophiliacs with or without a previous history of jaundice was studied. Using the haemagglutination inhibition assay, HbsAg was detected in 9.9%, HBsAb in 61.3% and HBsAg plus Ab in 11.8% of the cases. The incidence of jaundice was 14.8%. Liver function was tested by means of Normotest, SGOT, SGPT and serum protein electrophoresis. Abnormal values of liver function tests were found in 47% of the patients. The abnormal findings were related to the presence of HBsAg or Ab and to the history of jaundice. There was no significant difference between the various groups of patients.

Antibodies