Nf1+/- mice have increased neointima formation via hyperactivation of a Gleevec sensitive molecular pathway

Neurofibromatosis type I (NF1) is a genetic disorder caused by mutations in the NF1 tumor suppressor gene. Neurofibromin is encoded by NF1 and functions as a negative regulator of Ras activity. Somatic mutations in the residual normal NF1 allele within cancers of NF1 patients is consistent with NF1 functioning as a tumor-suppressor. However, the prevalent non-malignant manifestations of NF1, including learning and bone disorders emphasize the importance of dissecting the cellular and biochemical effects of NF1 haploinsufficiency in multiple cell lineages. One of the least studied complications of NF1 involves cardiovascular disorders, including arterial occlusions that result in cerebral and visceral infarcts. NF1 vasculopathy is characterized by vascular smooth muscle cell (VSMC) accumulation in the intima area of vessels resulting in lumen occlusion. We recently showed that Nf1 haploinsufficiency increases VSMC proliferation and migration via hyperactivation of the Ras-Erk pathway, which is a signaling axis directly linked to neointima formation in diverse animal models of vasculopathy. Given this observation, we tested whether heterozygosity of Nf1 would lead to vaso-occlusive disease in genetically engineered mice in vivo. Strikingly, Nf1+/- mice have increased neointima formation, excessive vessel wall cell proliferation and Erk activation after vascular injury in vivo. Further, this effect is directly dependent on a Gleevec sensitive molecular pathway. Therefore, these studies establish an Nf1 model of vasculopathy, which mirrors features of human NF1 vaso-occlusive disease, identifies a potential therapeutic target and provides a platform to further dissect the effect of Nf1 haploinsufficiency in cardiovascular disease.     

Ileal inflammatory fibroid polyp causing chronic ileocolic intussusception and mimicking cecal carcinoma

Inflammatory fibroid polyp (IFP) is a rare, idiopathic pseudotumorous lesion of the gastrointestinal tract. While mostly reported as solitary gastric lesions, multiple cases of small bowel IFPs are also reported. It is a documented cause of intussusception in adults. In the case reports of ileal inflammatory fibroid polyps with intussusception, an emergent presentation with small bowel obstruction has been most often described. Here we depict a case of ileal inflammatory fibroid polyp presenting with chronic intermittent ileocolic intussusception, anemia and weight loss with an endoscopic appearance mimicking necrotic cecal carcinoma.     

Fatty acid transport in multiple carboxylase deficiency fibroblasts

Summary Holocarboxylase synthetase (HS) and biotinidase deficiencies have been identified as causes of biotin-responsive multiple carboxylase deficiency. Acetyl-CoA carboxylase (ACC) deficiency has been shown to occur in multiple carboxylase deficiency, and HS(–) fibroblasts are being employed to investigate compensatory regulatory responses in cells deficient in ACC. In previous studies, biotin starved HS(–) fibroblasts showed a reduced fatty acid content, an abnormal percentage composition of fatty acids, and a preservation of longerchain fatty acid contents of cells. We herein ask whether the mutant cells show compensatory increases in the transport of longer-chain fatty acids from the medium into fibroblasts. In the present experiments there was no change in the uptake of arachidonate, palmitate or oleate following growth of mutant and control fibroblasts in (+) or (–) biotin conditions. Differential fatty acid uptake from the medium is therefore not a compensatory mechanism in HS(–) cells, and cannot account for the specific changes in fatty acid composition produced by biotin restriction.     

Aluminum chloride hexahydrate in a salicylic acid gel base: a case series of combination therapy with botulinum toxin type A for moderate to severe hyperhidrosis

Hyperhidrosis is a common condition that has a tremendous impact on the quality of life of patients. For moderate to severe hyperhidrosis, topical aluminum chloride hexahydrate (AC), iontophoresis, and botulinum toxin type A injections are first-line therapies. Botulinum toxin type A has been a useful addition to the hyperhidrosis armamentarium and typically is utilized when topical therapy or iontophoresis have failed. Although highly effective for most patients, there remains a subset of patients who do not completely respond to botulinum toxin type A injections. For these patients, combination therapy with AC can greatly improve patient response. We present a case series of 10 patients with hyperhidrosis and a history of partial response to botulinum toxin type A monotherapy. With the addition of AC 15% in a salicylic acid 2% gel base, 5 patients achieved 75% to 100% reduction in sweating and 5 patients achieved 100% reduction in sweating. Aluminum chloride hexahydrate in a salicylic acid gel base offers a novel and effective topical therapy in combination with botulinum toxin type A for patients with moderate to severe hyperhidrosis.     

Dietary Patterns and Body Mass Index in Children with Autism and Typically Developing Children

To determine whether dietary patterns (juice and sweetened non-dairy beverages, fruits, vegetables, fruits and vegetables, snack foods, and kid's meals) and associations between dietary patterns and body mass index (BMI) differed between 53 children with autism spectrum disorders (ASD) and 58 typically developing children, ages 3-11, multivariate regression models including interaction terms were estimated. Children with ASD were found to consume significantly more daily servings of sweetened beverages (2.6 versus 1.7, p = 0.03) and snack foods (4.0 versus 3.0, p = 0.01) and significantly fewer daily servings of fruits and vegetables (3.1 versus 4.4, p = 0.006) than typically developing children. There was no evidence of statistical interaction between any of the dietary patterns and BMI z-score with autism status. Among all children, fruits and vegetables (p = 0.004) and fruits alone (p = 0.005) were positively associated with BMI z-score in our multivariate models. Children with ASD consume more energy-dense foods than typically developing children; however, in our sample, only fruits and vegetables were positively associated with BMI z-score.     

The International Infections in Pregnancy Study: group B streptococcal colonization in pregnant women

Background: Heavy colonization with group B streptococcus (GBS) has been associated with increased risk of preterm birth and neonatal sepsis; the burden of neonatal GBS disease varies geographically. To determine whether variation in heavy colonization and GBS serotypes could contribute to geographic differences in disease burden, we assessed the prevalence of heavy colonization and the distribution of serotypes in asymptomatic pregnant women in multiple countries.

Methods: Cervical, lower vaginal and urine samples were collected from women attending seven prenatal clinics in six countries. Light colonization was defined as GBS isolation from Lim broth only; heavy colonization was isolation from urine or sheep blood agar plates. Isolates were serotyped using capillary precipitation.

Results: GBS was present in 11.3% of 1308 participants (range 7.1–21.7%); 5.0% were heavily colonized (0.4–18.8%) and 6.4% were lightly colonized (2.9–8.0%). Serotypes III and V were most common (both 17.2%). Serotypes VII and VIII were found in one study center.

Conclusions: The prevalence of heavy colonization and GBS serotypes varied significantly among our study centers. Whether this variation could in part explain geographic differences in neonatal morbidity and mortality is a hypothesis that needs further study.