Use of porcine factor VIII in the treatment of patients with acquired hemophilia

Data have been collected from 47 centers in Europe and North America on the treatment with porcine factor VIII concentrate of 74 acute bleeding episodes in 65 patients with acquired hemophilia. The median initial anti-human factor VIII auto-antibody inhibitor level was 38 Bethesda unit (BU)/mL (range 1.2 to 1,024) whereas that against porcine was 1 BU/mL (range 0 to 15). The mean initial dose of porcine factor VIII infused was 84 IU/kg, which increased the plasma factor VIII:C activity by 0.85 IU/mL. Therapy was continued for a mean of 8.5 days during which time the average number of infusions was 11. Objective clinical responses were rated as good or excellent in 78% of recipients. Side effects were uncommon; only one patient experienced a severe anaphylactic reaction necessitating the discontinuation of porcine FVIII therapy. After therapy, no increase in the median level of anti- human FVIII or anti-porcine antibody was noted in the group as a whole, although 13 patients showed individual increases in either anti-human or anti-porcine antibody levels or both of more than 10 BU/mL. Of the 7 patients who subsequently rebled, 5 were successfully re-treated and 2 did not respond to further porcine factor VIII treatment. Porcine factor VIII is safe and clinically effective treatment for bleeding episodes associated with acquired hemophilia and should be considered as first-line therapy for patients whose acquired anti-factor VIII:C antibody cross-reacts with porcine factor VIII:C at low levels.     

Household Food Insecurity,Maternal Nutritional Status,and Infant Feeding Practices Among HIV-infected Ugandan Women Receiving Combination Antiretroviral Therapy

Household food insecurity (HHFI) may be a barrier to both optimal maternal nutritional status and infant feeding practices, but few studies have tested this relationship quantitatively, and never among HIV-infected individuals. We therefore described the prevalence of HHFI and explored if it was associated with poorer maternal nutritional status, shorter duration of exclusive breastfeeding (EBF) and fewer animal-source complementary foods. We assessed these outcomes using bivariate and multivariate analyses among 178 HIV-infected pregnant and breastfeeding (BF) women receiving combination antiretroviral therapy in the PROMOTE trial (NCT00993031), a prospective, longitudinal cohort study in Tororo, Uganda. HHFI was common; the prevalence of severe, moderate, and little to no household hunger was 7.3, 39.9, and 52.8 %, respectively. Poor maternal nutritional status was common and women in households experiencing moderate to severe household hunger (MSHH) had statistically significantly lower body mass index (BMIs) at enrollment (21.3 vs. 22.5, p < 0.01) and prior to delivery (22.6 vs. 23.8, p < 0.01). BMI across time during pregnancy, but not gestational weight gain, was significantly lower for MSHH [adjusted beta (95 % CI) ?0.79 (?1.56, ?0.02), p = 0.04; ?2.06 (?4.31, 0.19), p = 0.07], respectively. The prevalence (95 % CI) of EBF at 6 months was 67.2 % (59.7–73.5 %), and the proportion of women BF at 12 months was 80.4 % (73.3–85.7 %). MSHH was not associated with prevalence of EBF at 6 months or BF at 12 months. However, among those women still EBF at 4 months (81.4 % of population), those experiencing MSHH were significantly more likely to cease EBF between 4 and 6 months (aHR 2.38, 95 % CI 1.02–5.58). The prevalence of HHFI, maternal malnutrition, and suboptimal infant feeding practices are high and the causal relationships among these phenomena must be further explored.     

Progressive aortic valve inflammation occurring despite apparent remission of relapsing polychondritis

We describe a patient with relapsing polychondritis in whom aortic valve inflammation developed 3 years after diagnosis, when the polychondritis had been in apparent remission for an extended period of time. Infection and cardiac involvement can be significant complications of relapsing polychondritis. Recommendations for monitoring and treatment of patients with this disease are discussed.     

Effect of metoprolol on the submaximal stress test performed early after acute myocardial infarction

To determine the effect of beta-adrenergic blockade on the submaximal stress test after acute myocardial infarction (AMI), 36 post-AMI patients performed their treadmill test on 2 separate days, with and without metoprolol, in a double-blind, placebo-controlled, crossover design study. Rest and peak submaximal exercise heart rate was diminished by 100 mg of metoprolol administered twice daily (from 84 +/- 3 to 68 +/- 2 beats/min, p less than 0.001, and from 126 +/- 3 to 97 +/- 2 beats/min, p less than 0.001, respectively) compared with placebo. Rest and peak submaximal systolic blood pressure was also decreased (from 121 +/- 3 to 108 +/- 2 mm Hg, p less than 0.001, and from 151 +/- 4 to 124 +/- 3 mm Hg, p less than 0.001). Exercise-induced ST-segment depression of 1 mm or more from baseline occurred in 12 patients taking placebo. However, only 4 of these patients had ST depression when they exercised while taking metoprolol (p less than 0.05). Angina pectoris occurred in 4 patients taking placebo but in only 1 of these taking a beta-blocking drug. It is concluded that beta-blocking therapy renders the post-AMI submaximal stress test less sensitive for markers of exercise-induced ischemia than if the test is performed without the drug. Therefore, when using the prognostic information of published studies, it is important to define the conditions surrounding the exercise test.     

Immunoactivating Peptide P4 Augments Alveolar Macrophage Phagocytosis in Two Diverse Human Populations

New treatment strategies are urgently needed to overcome early mortality in acute bacterial infections. Previous studies have shown that administration of a novel immunoactivating peptide (P4) alongside passive immunotherapy prevents the onset of septicemia and rescues mice from lethal invasive disease models of pneumococcal pneumonia and sepsis. In this study, using two diverse populations of adult volunteers, we determined whether P4 treatment of human alveolar macrophages would upregulate phagocytic killing of Streptococcus pneumoniae ex vivo. We also measured macrophage intracellular oxidation, cytokine secretion, and surface marker expression following stimulation. Peptide treatment showed enhanced bacterial killing in the absence of nonspecific inflammation, consistent with therapeutic potential. This is the first demonstration of P4 efficacy on ex vivo-derived human lung cells.