Factor VIII:C concentrate purified from plasma using monoclonal antibodies: human studies

Conventional clotting factor concentrates have, until recently, been of intermediate purity, containing less than 1% of the coagulation factor, and greater than 99% extraneous plasma proteins such as fibrinogen, fibronectin, gamma globulins, and traces of many others. We report here the results of a new factor VIII concentrate that is purified from human plasma using a mouse monoclonal antibody to factor VIII:vWF in an affinity chromatography system. The resultant concentrate has an activity of between 3,000 and 5,000 U/mg protein before albumin is added as a stabilizer. Seven patients with severe hemophilia A and no inhibitor who were positive for antibody to human immunodeficiency virus (HIV) have been treated solely with this concentrate for over 24 months. Factor usage in these patients has ranged from 611 U/kg/yr to 2,022 U/kg/yr. These patients have infused approximately once per week on the average, most often for joint hemorrhages. The efficacy of the concentrate is excellent. No allergic reactions have occurred and no factor VIII antibodies have developed. In these seven patients mean CD4 counts stabilized (856 +/- 619 at screen v 778 +/- 686 at 24 months) and there was reversal of skin test anergy. In a comparison group on conventional intermediate purity concentrate chosen retrospectively decreases in mean CD4 cell counts similarly did not occur. However, the number of the comparison patients who were anergic increased over the course of the study. These observations indicate the possibility that more highly purified concentrates may stabilize immune function in HIV seropositive patients

NURTURE: Development and pilot testing of a novel parenting intervention for mothers with histories of an eating disorder: Nurture Pilot Testing

To describe the treatment development and pilot testing of a group parenting intervention, NURTURE (Networking, Uniting, and Reaching out To Upgrade Relationships and Eating), for mothers with histories of eating disorders

Effects of Anacetrapib in Patients with Atherosclerotic Vascular Disease

BACKGROUND: Patients with atherosclerotic vascular disease remain at high risk for cardiovascular events despite effective statin-based treatment of low-density lipoprotein (LDL) cholesterol levels. The inhibition of cholesteryl ester transfer protein (CETP) by anacetrapib reduces LDL cholesterol levels and increases high-density lipoprotein (HDL) cholesterol levels. However, trials of other CETP inhibitors have shown neutral or adverse effects on cardiovascular outcomes. METHODS: We conducted a randomized, double-blind, placebo-controlled trial involving 30,449 adults with atherosclerotic vascular disease who were receiving intensive atorvastatin therapy and who had a mean LDL cholesterol level of 61 mg per deciliter (1.58 mmol per liter), a mean non-HDL cholesterol level of 92 mg per deciliter (2.38 mmol per liter), and a mean HDL cholesterol level of 40 mg per deciliter (1.03 mmol per liter). The patients were assigned to receive either 100 mg of anacetrapib once daily (15,225 patients) or matching placebo (15,224 patients). The primary outcome was the first major coronary event, a composite of coronary death, myocardial infarction, or coronary revascularization. RESULTS: During the median follow-up period of 4.1 years, the primary outcome occurred in significantly fewer patients in the anacetrapib group than in the placebo group (1640 of 15,225 patients [10.8%] vs. 1803 of 15,224 patients [11.8%]; rate ratio, 0.91; 95% confidence interval, 0.85 to 0.97; P=0.004). The relative difference in risk was similar across multiple prespecified subgroups. At the trial midpoint, the mean level of HDL cholesterol was higher by 43 mg per deciliter (1.12 mmol per liter) in the anacetrapib group than in the placebo group (a relative difference of 104%), and the mean level of non-HDL cholesterol was lower by 17 mg per deciliter (0.44 mmol per liter), a relative difference of -18%. There were no significant between-group differences in the risk of death, cancer, or other serious adverse events. CONCLUSIONS: Among patients with atherosclerotic vascular disease who were receiving intensive statin therapy, the use of anacetrapib resulted in a lower incidence of major coronary events than the use of placebo. (Funded by Merck and others; Current Controlled Trials number, ISRCTN48678192 ; ClinicalTrials.gov number, NCT01252953 ; and EudraCT number, 2010-023467-18 .)

Prevalence of hepatitis C virus antibody in a cohort of hemophilia patients

One hundred thirty-one patients followed at the New England Hemophilia Center (Worcester, MA) were tested for antibody to hepatitis C virus (HCV). All but two had used factor concentrate that had not undergone viral inactivation; two patients had used only cryoprecipitate. The overall prevalence of HCV antibody positivity was 76.3%. There was no significant difference in age or the amount of non-heat-treated factor concentrate used between the group that was HCV antibody positive and negative. There was also no significant difference between aminotransferase levels in the two groups. There was a positive association between HCV antibody and the presence of antibody to hepatitis B core antigen and antibody to human immunodeficiency virus. A group of 31 patients were tested twice for HCV antibody at intervals of 35 to 71 months. In this subset, 25 were repeatedly seropositive, 4 were repeatedly seronegative, and 2 went from seropositive to seronegative. These data confirm the previous impression that non-A, non-B hepatitis is a major sequela to the use of pooled coagulation factor concentrates. HCV infection may account for most of the chronic liver disease observed in this population. Anti-HCV testing of plasma donors and improved methods of viral inactivation should prevent new cases from developing

Platelet activation and mitral valve prolapse

Mitral valve prolapse (MVP) is a predisposing factor for cerebral ischemia, especially in young adults. Cerebral embolization of intracardiac thrombi is the probable mechanism in many cases. Platelets play a key role in the development of thrombi. We found that platelet factor 4, a marker protein of platelet activation, was elevated in 12 of 33 MVP patients (36%) without a history of stroke. This finding indicates that platelets are frequently activated in asymptomatic MVP patients and may allow identification of a subgroup of MVP patients with activated platelets who are at increased risk for emboli

Marker proteins of platelet activation in patients with cerebrovascular disease

Platelet activation is assumed to occur in many patients with strokes of transient ischemic attacks (TIAs). Determination of this activity can now be measured by assaying the platelet-specific proteins, platelet factor 4 and beta-thromboglobulin. These proteins are platelet specific and are released during irreversible aggregation. The plasma level of these proteins was measured in patients with strokes and TIAs and both groups had significantly greater values than healthy control subjects. These markers of platelet activation may provide further understanding of the role of platelets in the etiology, diagnosis, and treatment of cerebrovascular disease

The low risk of hepatitis C virus transmission among sexual partners of hepatitis C-infected hemophilic males: an international, multicenter study

To study the transmission rate of hepatitis C virus (HCV) in the female sexual partners of antibody-positive hemophilic males, 106 partners from three hemophilia centers located in Europe, America, and Australia were tested for HCV seropositivity using a first-generation enzyme-linked immunosorbent assay (ELISA-1) and, subsequently, a second-generation ELISA (ELISA-2) and a supplemental recombinant immunoblot assay. Additionally, the cohort was tested for the presence of antibody to the human immunodeficiency virus type-1 and hepatitis B virus markers. No female partner was HCV antibody-positive using the ELISA-1 test, whereas five were seropositive by the ELISA-2 test. Three of these five female partners were seropositive on the supplemental test, the remaining two having indeterminate results, for an overall prevalence of 2.7%. Thus, even with the use of sensitive testing, the prevalence of HCV infection remains low in this cohort, showing that the efficiency of heterosexual transmission of HCV is poor