Prevalence of hepatitis G virus RNA in a monocentric population of French haemophiliacs.

Hepatitis G virus (HGV) and hepatitis GB virus (GBV-C) have been reported as possible causes of non-A-E transfusional hepatitis. To assess the prevalence of hepatitis G virus infection in haemophiliacs we retrospectively investigated the presence of viral RNA in 92 patients with and without HCV infection. HGV/GBV-C RNA was reverse transcribed and amplified with primers from the 5' non-coding region of the genome. RNA was detected in 16/92 patients (17.4%). Restriction enzyme analysis revealed that the 16 patients belonged to the HGV-like genotype. Serology with E2-specific antibodies demonstrated that HGV viraemia underestimates previous infection by HGV. 33 patients were positive for HGV; all but two have cleared HGV RNA. 47/92 patients had a marker of prior infection by HGV. No difference between HGV RNA positive and negative patients was observed concerning age, diagnosis, HIV and HCV status. Previous HBV infection correlated with the frequency of HGV infection. There was no difference in alanine aminotransferase levels between HGV positive and negative patients. All 18 patients exposed to only virally inactivated plasma-derived concentrates were negative for both HGV RNA and anti E2 antibodies. Prior exposure to untreated concentrates correlated with HGV viraemia (P=0.03), HGV seropositivity (P=0.0002), and markers of HGV infection (P<0.0001). In haemophiliacs with a past exposure to non-inactivated concentrates, persistence of HCV RNA (53/74 patients) was more frequent than HGV RNA persistence (16/74 patients) although HGV viraemia is more frequent than HCV viraemia in blood donors. This may be related to a greater ability of individuals to clear HGV infection and suggests that hepatitis G virus infection in multi-transfused patients has a better outcome than infection with other blood-borne viruses.

Persistent hepatitis C virus RNA replication in haemophiliacs: role of co-infection with human immunodeficiency virus.

In order to evaluate the evolution of transfusional hepatitis C in haemophiliacs, we performed a retrospective study of ALT levels and HCV viraemia with a RNA PCR assay in 57 patients. We found that the vast majority of HCV-infected patients remained viraemic (43/57 = 75%) and higher ALT levels correlated with HCV viraemia. Although indicators of the transfusional viral load (age, severity of haemophilia) and HBV co-infection did not correlate with HCV RNA replication, HIV seropositivity was strongly associated with persistence of HCV viraemia (23/25 = 92% in HIV-positive versus 20/32 = 62% in HIV-negative patients), without any correlation with CD4 counts. Genotyping of HCV in the 43 viraemic patients shows more frequent genotype 1 in the HIV-seropositive group (14/23) than in the seronegative group (6/20). Our data emphasize that besides the role of the immunodeficiency status, the genotypes of HCV might be involved in the differences observed in terms of HCV RNA replication between the HIV-seropositive and seronegative haemophiliacs.

Some aspects of middle molecules toxicity.

Middle molecules can act on several levels of uremic disease. So, this work is a multidisciplinary one with the participation of nephrologists, hematologists and also pharmacologists, chemists and biophysicians. We present here our results on four different toxic effects found with middle molecules: the energy dependant phenomena, the platelet aggregability, the cardiotoxic, and the neurotoxic effects. Middle molecules were isolated from urine of normal subjects and blood of patients with chronic renal insufficiency and treated by hemodialysis. Separation was done according to Furst's procedure.

"In vitro" inhibition of platelet aggregation by uremic middle molecules.

"Uremic middle molecules" are isolated from the urine of normal subjects and the blood in chronic renal insufficiency treated by hemodialysis. Their action is tested in vitro on platelets aggregation induced by ADP. Some fractions of these middle molecules (fractions 7b, 7c and 7 "fg") are without any effect. The 7 "de" fractions give an inhibition of platelets aggregation. The percentage variations of first phase inhibition as a function of the middle molecules concentrations is studied.

[Effect of acetylsalicylic acid on immunologically induced morphologic changes after experimental lung transplantation (light and electron microscopic study)]. / Wirkung von Azetylsalizylsäure auf immuninduzierte, morphologische Thrombozytenveränderungen nach experimenteller Lungentransplantation (Eine licht- und elektronenmikroskopische Studie)

In 3 comparing series the behavior of platelets after experimental lung transplantation was examined in 33 dogs. After allogenic transplantations (21 animals) the ultrastructural findings were pathologic changes of the platelets, such as hyperaggregability with irreversible aggregation prevailing, as well as capillary wall alterations. X-rays showed considerable reduction of functioning parenchyma. Since these findings were absent in animals which underwent merely pulmonary re-implantation (4 animals) and can be considered a controll group, the authors conclude that these alterations are caused by mainly immunologic reactions. Acetylsalicylic acid given to animals with grafted lungs significantly inhibited is specific and certainly immuneinduced pathologic development. Absolutely necessary, therefore, appears the application of such aggregation inhibitor as additional treatment in lung transplantations.

[Appearance of coagulation disorders in the non-healthy newborn infant]. / L'aspect des troubles de la coagulation chez le nouveau-né pathologique

Coagulation abnormalities are particularly frequent in neonatal pathology and justify exploration of hemostasis in the newborn. First of all we established a profile of coagulation in the newborn using our own results and data from the literature. Contrasting with a deficit in numerous factors (II - VII - IX - X - XI - and XII), overall coagulation is normal, or even increased. The fibrinolytic system is characterized by a low plasminogen level but the activity of this system is transitorily increased. Then we recall the known syndromes: avitaminosis K, constitutional deficits in the coagulation factors, isolated thrombopenia, disseminated intravascular clotting. However numerous problems persist. Abnormalities in the clotting factors are frequently difficult to interpret. Correlation between the clinical and laboratory pictures does not always exist. We emphasize the necessity for preventive measures.