The vanishing vast ventricular thrombus.

A 54-year old man presented with multiple pulmonary emboli and an incidental finding of a huge left ventricular thrombus. Transthoracic echo images demonstrated a globally dilated heart with very poor left ventricular function. It was elected to manage the patient medically, and he was commenced on warfarin therapy, resulting in completed resolution of the thrombus over 10 weeks. No underlying cause was found and he did not experience any further embolic events. This illustrates a rare case of a large ventricular thrombus in a patient with no underlying risk factors.     

Costello syndrome: Clinical phenotype,genotype, and management guidelines

Costello syndrome (CS) is a RASopathy caused by activating germline mutations in HRAS. Due to ubiquitous HRAS gene expression, CS affects multiple organ systems and individuals are predisposed to cancer. Individuals with CS may have distinctive craniofacial features, cardiac anomalies, growth and developmental delays, as well as dermatological, orthopedic, ocular, and neurological issues; however, considerable overlap with other RASopathies exists. Medical evaluation requires an understanding of the multifaceted phenotype. Subspecialists may have limited experience in caring for these individuals because of the rarity of CS. Furthermore, the phenotypic presentation may vary with the underlying genotype. These guidelines were developed by an interdisciplinary team of experts in order to encourage timely health care practices and provide medical management guidelines for the primary and specialty care provider, as well as for the families and affected individuals across their lifespan. These guidelines are based on expert opinion and do not represent evidence‐based guidelines due to the lack of data for this rare condition.     

Effect of Cyclophosphamide on Histoplasma capsulatum Infections in Mice

Mice were injected intraperitoneally (i.p.) with 300 mg of cyclophosphamide (CY)/kg of body weight, and 24 h later were injected i.p. with varying dosages of yeast-phase cells of Histoplasma capsulatum. At specific time intervals organs were removed, ground, and cultured to determine the number of viable organisms contained in the spleen, liver, and lungs. Injection of mice with CY was found to cause a dramatic increase in the numbers of parasites isolated from these organs when compared with non-drug-treated controls. Mice given 10(7) yeast cells showed the largest increase in colony numbers. A greater than fivefold increase in the numbers of organisms isolated from the spleens of CY and 10(3) yeast cell-treated mice, as compared with non-drug-treated animals, was observed at all time periods. The general trend for infected control animals was a decrease in colony numbers. All mice given CY plus 10(7) yeast cells intravenously (i.v.) died by day 20 postinfection. Mice given CY and 10(7) yeast cells i.p. showed no evidence of fatal Histoplasma infection. Deaths occurring by day 5 in CY-treated animals injected with H. capsulatum yeast cells i.v. or i.p. were considered due to bacterial infection or toxicity, or both. Hepatosplenomegaly was observed in mice treated with CY and 10(7) yeast cells of H. capsulatum. Enlarged lungs were also noted. CY control mouse spleens weighed 30% less than normal spleens. Organs of animals injected with H. capsulatum alone did not vary significantly from those of normal mice. Complete drug-induced suppression of humoral antibody response was achieved for 10 days, as determined by hemagglutination titrations.     

Progress in the autosomal segmental aneusomy syndromes (SASs): single or multi-locus disorders?

Based on cytogenetic observations, several syndromes have been previously identified as microdeletion-based disorders. In this review, recent progress is presented regarding whether one or multiple genes can be implicated in the pathogenesis of these segmentally aneusomic syndromes. The syndromes discussed include Angelman, Alagille, Williams, Langer-Giedeon, Prader-Willi, Smith-Magenis, Miller-Dieker, and DiGeorge/velocardiofacial or the 22q11 deletion syndromes. For Angelman and Alagille syndromes, single genes have been identified, whereas for Williams and Langer-Giedion syndromes, more than one gene can be implicated. Although there has been significant progress in dissecting the molecular basis for the other disorders, the ultimate answer regarding one versus several genes remains to be determined.      

Is there a relationship between attention deficit hyperactivity disorder and bipolar disorder?

With the increasing recognition of attention deficit hyperactivity disorder (ADHD) in adults and psychotic disorders in children and adolescents, the possibility of a relationship between bipolar disorder (BP) and ADHD has attracted growing interest. This paper critically reviews the scientific literature concerning this postulated relationship by examining evidence from clinico-epidemiological, follow up, family and laboratory studies, including neuroimaging, neuropsychology and genetic studies. The evidence suggests that although the diagnostic categories of BP and ADHD appear to be unrelated, there is support for a possible relationship between some ADHD and manic-like symptoms. However, several fundamental methodological issues require rectification in future research in order to further elucidate the relationship between these disorders.     

Erythrocyte survival in normal mice and in mice with autoimmune haemolytic anaemia

Erythrocyte survival has been studied in a strain of mice which develop autoimmune haemolytic anaemia in adult life (NZB/B1), and also in CBA and C57B1 mice, using one or both of two radioactive isotope labels, ⁵¹Cr and ³²P.

Erythrocyte survival is customarily expressed as the half-life but this is unsatisfactory for purposes of statistical comparison and we have used instead a parameter `κ' which represents the slope of the line obtained when: log(Counts per unit haemoglobin on day t)/(Counts per unit haemoglobin on day 0) is plotted against time.

Young NZB/B1 mice yield values of κ intermediate between those obtained in CBA and C57B1 mice, and may reasonably be judged to show normal erythrocyte survival. On the other hand, in older NZB/B1 mice which are strongly Coombs positive and show reticulocytosis and anaemia, erythrocyte survival is greatly shortened.

The survival of erythrocytes transfused to NZB/B1 recipients from isogeneic donors was found to be similar to that of the recipient's own erythrocytes, irrespective of whether or not the donor was Coombs positive or showed other evidence of haemolytic activity.

The values of κ obtained in NZB/B1 mice were essentially the same with both labels; in CBA mice, however, a significant difference was observed.

     

HIV-1 RNA levels and development of clinical disease in two different adolescent populations

HIV infection rates in American youth continue to increase unabated. As adolescent-specific therapeutic interventions are planned, information on HIV infection's course and its predictors becomes critically important for valid and precise study design. We report on age-specific disease rates stratified by estimated time since infected and predictors of HIV disease progression through four clinical categories in two distinct adolescent populations. Adolescents with hemophilia infected through contaminated blood products showed disease progression rates of 18 to 23 events per 100 person-years (PYs) by age and years infected. Predictors of first progression included HIV-1 RNA >30,000 copies/ml (rate ratio [RR], 2.4; 95% confidence interval [CI], 1.5-3.9), antiretroviral monotherapy (RR, 2.4; 95% CI, 1.7-3.3); Latino/a ethnicity (RR, 2.2; 95% CI, 1.2-4.2) and initial intermediate clinical status (RR, 1.9; 95% CI, 1.3-2.9). Sexually-infected adolescents >18 years who had been infected >3 to 6 years had a disease progression rate of 16 events per 100 PY. For these youths, the sole predictor of first progression was viral load (VL) (RR for VL >30,000 copies per ml, 8.4; 95% CI, 2.8-25.1). This article examines the predictive capacity of viral load and evaluates other cofactors for disease progression in different adolescent populations. These data will be of value in clinical trial design.     

Missense mutation in a von Willebrand factor type A domain of the alpha 3(VI) collagen gene (COL6A3) in a family with Bethlem myopathy

The Bethlem myopathy is a rare autosomal dominant proximal myopathy characterized by early childhood onset and joint contractures. Evidence for linkage and genetic heterogeneity has been established, with the majority of families linked to 21q22.3 and one large family linked to 2q37, implicating the three type VI collagen subunit genes, COL6A1 (chromosome 21), COL6A2 (chromosome 21) and COL6A3 (chromosome 2) as candidate genes. Mutations of the invariant glycine residues in the triple-helical domain-coding region of COL6A1 and COL6A2 have been reported previously in the chromosome 21-linked families. We report here the identification of a G-->A mutation in the N-terminal globular domain-coding region of COL6A3 in a large American pedigree (19 affected, 12 unaffected), leading to the substitution of glycine by glutamic acid in the N2 motif, which is homologous to the type A domains of the von Willebrand factor. This mutation segregated to all affected family members, to no unaffected family members, and was not identified in 338 unrelated Caucasian control chromosomes. Thus mutations in either the triple-helical domain or the globular domain of type VI collagen appear to cause Bethlem myopathy.