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.

Management of haemophilia in Greece.

A short review is given on several aspects of the management of haemophilia in Greece. A total number of 429 patients with congenital haemorrhagic disorders has been registered. The incidence of F. VIII deficiency is 85.9% and that of F. IX 12.9%. Information concerning distribution throughout the country, age, social standard, financial position and education is given too. Haemophiliacs are systematically treated by Athens specialized Haemophilia Treatment Centres. The most widely therapeutic material still used, is fresh frozen plasma. Lyophilized cryoprecipitate and F. IX (prothrombincomplex) concentrate are also prepared but they are not for every day use. Imported concentrates are used only for very serious cases. Home therapy is attempted in limited scale and it is largely discussed. Consultation, out-patients treatment and hospitalization, if needed, are free of charge for haemophiliacs regardless of their financial position or their national insurance.

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.

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.

Marathon Run III: effects on coagulation, fibrinolysis, platelet aggregation and serum cortisol levels. A 3-year study.

Blood coagulation, fibrinolysis, platelet count-aggregation and cortisol were assessed in 35 Finnish amateur runners aged 27 to 56 years (mean 40) and three aged 65, 67, and 82 who had run a non-competitive Marathon in 1975, 1976 and 1977 over the classical itinerary. After the run, in all 3 years, APTT showed shortening (p < 0.001); prothrombin time and plasma fibrinogen were not significantly altered; euglobulin lysis time was shorter (p < 0.001) and FDP increased (p < 0.001); PSPT became positive in all subjects, whereas the ehtanol gelation test remained negative; no cryofibrinogen was detected. Platelet count and aggregation showed increase (p < 0.001) in 1975 (extreme heat, 25 degrees C) but remained unaltered in 1976, 1977 (15-18 degrees C). Cortisol levels were always significantly increased -- more markedly in 1975. Women's responses were similar to those of men. A possible correlation between physical fitness and the responses of haemostatic balance is suggested and the influence of weather is discussed.

Long lasting sitting position and haemostasis.

Blood coagulation, fibrinolysis and platelet aggregability were assessed in 8 physicians aged 30-40 years, who had travelled non-stop by car from Salonica to Athens (510 km) and returned to Salonica after 48 h of rest and after administration of 1 g of aspirin. At the end of journey A, platelet aggregability was found to be increased (6 out of 8 persons), AT III was decreased by 30% (p less than 0.001), the F VIII:C / F VIIIR: Ag ratio was decreased (p less than 0.02) and ELT was prolonged. At the end of journey B the findings were the following: platelet aggregation was not affected, the decrease of AT III was not statistically significant and ELT was significantly shortened (p less than 0.005). A common finding of both journeys was the increase of platelet counts at the end (p less than 0.005). The correlation between long lasting sitting and the response of the haemostatic balance is suggested. The influence of aspirin is discussed.

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.

Epidemiology of haemophilia in Greece: an overview.

Demographic data of the Greek haemophilia A and B population for the period 1972-1993 were analyzed. Prevalence at birth including known not-registered patients was calculated at 23.1 per 100,000 male births. However, the observed prevalence in 1993 was only 61% of the expected. Since 1975 the proportion of mild cases had significantly increased. Adjusted by age, severity and HIV status reproductive fitness of haemophiliacs was 0.62. Overall mortality was 2.6 times higher than in the general population, but 7.9 times among patients with severe haemophilia and 16.4 among HIV(+) haemophiliacs. Fifty out of 78 deaths occurred among HIV(+) patients and 28 of these were caused by AIDS. Inhibitor patients did not show excess mortality due to bleeding. Cancer mortality was equal to normal, but the number of deaths from ischaemic heart disease was 0.25 of the expected. Risk of death due to cerebral haemorrhage was 3.8 times higher in HIV(+) haemophiliacs than in HIV(-).

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.

PIP: A serologic study of the 53 female partners of Greek men with confirmed human immunodeficiency virus (HIV) infection, conducted from January 1986-May 1987 in Athens, provided additional evidence for a heterosexual mode of transmission. All 53 females tested had had a steady sexual relationship that exceeded 6 months with their male partner and a limited prior sexual history. Among the seropositive males were 18 bisexuals, 6 intravenous drug abusers, 4 heterosexuals who had resided previously in Africa, and 25 hemophiliacs. 12 (23%) of the 53 female partners were seropositive for antibodies to HIV. The lowest frequency of infection was found among spouses of hemophiliacs (4%); the other prevalence rates were 28% for partners of bisexual men, 33% for partners of intravenous drug abusers, and 100% among the spouses of men who had lived in Africa for a significant time period. The duration of the sexual relationship averaged 32 months among seronegative women and 40 months among seropositive female partners. None of the 12 carriers whose spouses were found to be seropositive had used condoms; in contrast, 37 (90%) of carriers of seronegative spouses had used condoms regularly in the 6-month period preceding the study. The practice of anal intercourse was reported more frequently by seropositive female partners (33%) than seronegative women (24%), but this difference was not significant.

A comparison of the availability and content of genetic counseling as perceived by hemophilic men and carriers in the U.S.A., Canada, Scotland, and Greece.

A survey study was carried out with 211 hemophilic men and 205 carriers of hemophilia at four hemophilia centers in New York; London, Ontario; the West of Scotland; and Athens, Greece. The participants responded to a questionnaire exploring socio-demographic and medical information, attitudes toward hemophilia, and experience of and attitudes toward genetic counseling. The study shows differences between attitudes of hemophilic men and carriers, differences in perceived problems among patients and carriers in the four centers, and differences in opinions between consumers and professionals. Comprehensive services for hemophilic families available in the New York center facilitate both patient education and satisfaction.

Association between HLA antigens and progression of HIV infection in Greek haemophiliacs.

The frequencies of HLA antigens in 33 HIV seronegative and in 88 HIV seropositive haemophiliacs, who have been followed for at least 6 years since seroconversion or first HIV positive test, were evaluated in relation to disease susceptibility and disease progression. A high frequency of HLA-A2 and -DR2 antigens and a low frequency of HLA-A9 were found to characterize HIV seropositive patients (p < 0.05). Progressors to symptomatic CDC stage IV had a higher frequency of HLA-A9 (p < 0.01) and DR3. Rapid decline of CD4+ T cells in these patients was associated with HLA-A9, -DR1 and DR3. Our data suggest that HLA antigens may contribute to susceptibility to HIV infection and disease progression in Greek haemophiliacs.

Resistance to activated protein C and FV leiden mutation in patients with a history of acute myocardial infarction or primary hypertension.

This study was designed to investigate both resistance to activated protein C (APC-R) and the factor FV Q506 mutation incidence in patients with a history of acute myocardial infarction (AMI) and patients with primary hypertension (PH), a high-risk group for arterial thrombosis. Eighty patients with a history of AMI (group A), 160 patients with a history of PH (group B), and 124 age-matched controls without arterial disease (group C) were studied. APC-R was determined using the Coatest APC Resistance Kit of Chromagenix, Sweden. The prevalence of the FV Q506 mutation was estimated by DNA analysis (Bertina method). The prevalence of the FV Q506 mutation was 20%, 13.75%, and 8% in groups A, B, and C, respectively (A v C P = .0466). The prevalence of APC-R was 47.5% in group A v 13% in group C (P < .0001) and 36.25% in group B v 13% in group C (P < .0001). The response to activated protein C expressed as mean value +/- SD was 2.05 +/- 0.33 in group A v 2.56 +/- 0.46 in group C (P < .05) and 2 +/- 0.22 in group B v 2.56 +/- 0.46 in group C (P < .05). These findings suggest that patients with a history of AMI or PH have a significantly increased incidence of both APC-R and FV Q506 mutation compared with the control group. These findings support the hypothesis that these anticoagulant defects may be risk factors for arterial thrombosis.

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.

Haemostasis balance disorders in patients with essential hypertension.

This study was aimed at investigating haemostasis parameters in patients (pts) with arterial hypertension (AH) before any medical treatment and to correlate these findings with those in healthy normal Greek population 83 pts (48 m, 35 w) mean age 49.8 +/- 10.1 yrs, body mass index 23.4 +/- 1.5 with mild to moderate AH and 42 healthy volunteers matched for sex (24 m, 18 w), age 51.2 +/- 10.5 yrs and body mass index 22.8 +/- 1.46 were studied. Fibrinogen, vWF, plasminogen, ECLT, a2 antiplasmin, tPA-Ag, PAI-1 in all pts and in the control group were measured. Mean age and BMI did not significantly differ between the two groups. The hypertensive patients had significantly higher levels of fibrinogen (327.75 +/- 51.36 vs. 272.84 +/- 46.8 mg/dl), tPA-Ag (8.81 +/- 3.32 vs. 5.76 +/- 2.54 ng/ml) and PAI-1 (11.8 +/- 10.9 vs. 7.91 +/- 5.5 IU/ml), whereas a2 antiplasmin level was significantly lower (98.71 +/- 15.40 vs. 107.84 +/- 17.52%). No differences were found between hypertensives and normal subjects in vWF, plasminogen and ECLT. These preliminary data suggest that in pts with mild to moderate AH, before any medical treatment, there are significantly higher levels of fibrinogen, tPA-Ag and PAI-1 compared with normal volunteers, whereas there are significantly lower a antiplasmin levels. These findings indicate a disturbance in the haemostasis balance with hypercoagulability and fibrinolytic deficiency.

A novel insertion mutation (1286insC) in exon 9 of the factor XIII-A subunit gene.

Molecular studies have been performed on a Greek family with factor XIII-A subunit deficiency. The 15 exons of the A subunit gene were amplified by polymerase chain reaction and analysed by direct nucleotide sequencing. A homozygous single base insertion (1286insC) in exon 9 of the gene was identified in three affected family members. The insertion results in a frameshift and a premature stop signal a short distance downstream at codon 403. Any A subunit protein expressed is likely to be unstable and lack part of the catalytic core domain together with both beta barrel domains towards the C-terminal of the molecule. This study contributes to our knowledge of the mutational spectrum in patients with factor XIII-A deficiency.