Malignancy Associated Type B Lactic Acidosis: A Rare, yet Fascinating Oncological Emergency.

Type B lactic acidosis has been described infrequently in hematologic malignancies, but even less often in solid tumors. Since 1978, there have been only 58 cases of solid tumor associated Type B lactic acidosis described in the literature. Lung cancer (neuroendocrine) is the most common tumor; others frequently have a poorly/undifferentiated histology. The prognosis is dismal. Malignancy associated type B lactic acidosis is not associated with hypoxemia. The most highlighted pathogenetic mechanism is the Warburg effect (aerobic glycolysis of tumor cells causing excess lactate). We describe a patient with metastatic GI neuroendocrine carcinoma with profound lactic acidosis, who died within 24 hours. When extremely ill cancer patients present with lactic acidosis, sepsis is usually a primary concern. This case highlights the need for providers to consider malignancy associated lactic acidosis (MA-LA) in the differential diagnosis, particularly in patients with advanced malignancies, of lung origin, of neuroendocrine or poorly/undifferentiated histologic subtypes. The implications and approach are distinct from Type A/D lactic acidosis, and would involve treatment of the underlying malignancy at the earliest.

The 'Eyes' Have It: Mantle Cell Lymphoma.

Lymphomas presenting as a conjunctival mass/es is a rare occurrence. The symptoms can be vague including eye itchiness and dryness. Biopsy and comparative pathological review with a prior lymph node biopsy (if a prior diagnosis exists) is key to the diagnosis. Failure of prompt recognition and referral to biopsy may lead to underdiagnosis and unnecessary delays in management.

Multi-site study of the Childhood Autism Rating Scale (CARS) in five clinical groups of young children.

This study examined several questions pertaining to the Childhood Autism Rating Scale (CARS) in a sample of 274 preschool children (aged 2-6 years) clinically diagnosed as falling in one of five groups: Autistic Disorder, PDD-NOS, MR, Delayed, and Other. In addition to diagnosis and the CARS, all children were given standardized cognitive and adaptive behavior measures. Results indicated high concordance between the CARS and clinical diagnosis using DSM-IV (including excellent sensitivity and specificity). There was a moderate negative correlation of CARS scores and developmental level (both cognitive and adaptive), indicating significant shared variance. There were significant and sensible differences in mean CARS score for different diagnostic groups, including a substantial difference between the Autistic Disorder and PDD-NOS groups.

Brief report: the Vineland Adaptive Behavior Scales in young children with autism spectrum disorders at different cognitive levels.

Vineland Adaptive Behavior Scales (VABS) data were examined in a large sample of young children with ASD (n = 290) of varying cognitive levels. IQ was higher than VABS composite score among high functioning children only; the opposite pattern was found in lower IQ subgroups. Profile analysis of VABS domains across cognitive levels demonstrated different profiles in different subgroups. A characteristic "autism profile" was found for most subgroups for Age Equivalents but not Standard Scores. In a small set of matched pairs (n = 28) of children with autism versus MR, significantly different profiles were found, with Socialization and Communication lower in autism, but no differences were found between matched pairs of children with autism and PDD-NOS (n = 48). Correlations between age, cognitive level, and adaptive level were also reported, and regression analyses indicated that autism severity accounts for a modest amount of unique variance in Socialization and Daily Living Skills.

How to build a myofibril.

Building a myofibril from its component proteins requires the interactions of many different proteins in a process whose details are not understood. Several models have been proposed to provide a framework for understanding the increasing data on new myofibrillar proteins and their localizations during muscle development. In this article we discuss four current models that seek to explain how the assembly occurs in vertebrate cross-striated muscles. The models hypothesize: (a) stress fiber-like structures as templates for the assembly of myofibrils, (b) assembly in which the actin filaments and Z-bands form subunits independently from A-band subunits, with the two subsequently joined together to form a myofibril, (c) premyofibrils as precursors of myofibrils, or (d) assembly occurring without any intermediary structures. The premyofibril model, proposed by the authors, is discussed in more detail as it could explain myofibrillogenesis under a variety of different conditions: in ovo, in explants, and in tissue culture studies on cardiac and skeletal muscles.

Genetic and genomic tools for zebrafish research: the NIH zebrafish initiative.

The National Institutes of Health (NIH) has been a leading advocate of the zebrafish as a model organism for the study of vertebrate development, physiology, and disease. Genomic tools, developed with the support of NIH funding, have made zebrafish even more attractive as a genetic system and have stimulated research using this model. The NIH continues to provide support for new and existing community resources, such as the Zebrafish International Resource Center and the Zebrafish Information Network, research tool development and mutant screens, and a wide array of investigator-initiated studies that are using zebrafish to elucidate many aspects of vertebrate biology.

Myofibrillogenesis in skeletal muscle cells.

How are myofibrils assembled in skeletal muscles? The current authors present evidence that myofibrils assemble through a three-step model: premyofibrils to nascent myofibrils to mature myofibrils. This three-step sequence was based initially on studies of living and fixed cultured cells from cardiac muscle. Data from avian primary muscle cells and from a transgenic skeletal mouse cell line indicate that a premyofibril model for myofibrillogenesis also holds for skeletal muscle cells. Premyofibrils are characterized by minisarcomeres bounded by Z-bodies composed of the muscle isoform of alpha-actinin. Actin filaments are connected to these Z-bodies and to the mini-A-bands composed of nonmuscle myosin II filaments. Nascent myofibrils are formed when premyofibrils align and are modified by the addition of titin and muscle myosin II filaments. Mature myofibrils result when nonmuscle myosin II is eliminated from the myofibrils and the alpha-actinin rich Z-bodies fuse as the distance between them increases from 0.5 microm in premyofibrils to 2 to 2.5 microm in the mature myofibrils.