Severe malaria in children and pregnancy: an update and perspective.

This review summarizes progress in preventing and treating severe malaria, which has been accompanied by advances in our understanding of the pathogenesis of severe malaria complications. New drugs such as intravenous artesunate and oral artemisinin combinations, with increased access to insecticide-treated bed nets, are improving outcomes and decreasing malaria deaths. Several groups are beginning to identify characteristics of parasite var genes associated with cerebral malaria.

Suppurative inflammation with microabscess and pseudocyst formation is a characteristic histologic manifestation of cutaneous infections with rapid-growing Mycobacterium species.

Mycobacterial infections of the skin classically cause a granulomatous tissue reaction. We have observed a suppurative pattern of inflammation associated with infections by rapid-growing Mycobacterium species in immunocompromised patients. We report 6 cases in skin and soft tissue with an unusual but consistent lack of a predominance of granulomatous inflammation.

Desmin mediates TNF-alpha-induced aggregate formation and intercalated disk reorganization in heart failure.

We explored the involvement of the muscle-specific intermediate filament protein desmin in the model of tumor necrosis factor alpha (TNF-alpha)-induced cardiomyopathy. We demonstrate that in mice overexpressing TNF-alpha in the heart (alpha-myosin heavy chain promoter-driven secretable TNF-alpha [MHCsTNF]), desmin is modified, loses its intercalated disk (ID) localization, and forms aggregates that colocalize with heat shock protein 25 and ubiquitin. Additionally, other ID proteins such as desmoplakin and beta-catenin show similar localization changes in a desmin-dependent fashion.

Malaria: mechanisms of erythrocytic infection and pathological correlates of severe disease.

Malaria is an ancient disease that continues to cause enormous human morbidity and mortality. The life cycle of the causative parasite involves multiple tissues in two distinct host organisms, mosquitoes and humans. However, all the clinical symptoms of malaria are a consequence of infection of human erythrocytes.

Visually guided reaching depends on motion area MT+.

Visual information is crucial for goal-directed reaching. A number of studies have recently shown that motion in particular is an important source of information for the visuomotor system. For example, when reaching a stationary object, movement of the background can influence the trajectory of the hand, even when the background motion is irrelevant to the object and task.

Alpha7beta1 integrin does not alleviate disease in a mouse model of limb girdle muscular dystrophy type 2F.

Transgenic expression of the alpha7beta1 integrin in the dystrophic mdx/utr-/- mouse decreases development of muscular dystrophy and enhances longevity. To explore the possibility that elevating alpha7beta1 integrin expression could also ameliorate different forms of muscular dystrophy, we used transgenic technology to enhance integrin expression in mice lacking delta-sarcoglycan (delta sgc), a mouse model for human limb girdle muscular dystrophy type 2F. Unlike alpha7 transgenic mdx/utr-/- mice, enhanced alpha7beta1 integrin expression in the delta sgc-null mouse did not alleviate muscular dystrophy in these animals.

A genome-wide map of diversity in Plasmodium falciparum.

Genetic variation allows the malaria parasite Plasmodium falciparum to overcome chemotherapeutic agents, vaccines and vector control strategies and remain a leading cause of global morbidity and mortality. Here we describe an initial survey of genetic variation across the P. falciparum genome.

Confirmation of emergence of mutations associated with atovaquone-proguanil resistance in unexposed Plasmodium falciparum isolates from Africa.

Background: In vitro and in vivo resistance of Plasmodium falciparum to atovaquone or atovaquone-proguanil hydrochloride combination has been associated to two point mutations in the parasite cytochrome b (cytb) gene (Tyr268Ser and Tyr268Asn). However, little is known about the prevalence of codon-268 mutations in natural populations of P. falciparum without previous exposure to the drug in Africa.

Maternal syphilis infection is associated with increased risk of mother-to-child transmission of HIV in Malawi.

Objective: To determine the association between maternal syphilis and HIV mother-to-child transmission (MTCT).

Design: Prospective cohort study.

Methods: Pregnant women admitted at Queen Elizabeth Central Hospital (Malawi) in late third trimester were screened for HIV (by HIV rapid tests) and syphilis (by rapid plasma regain test and Treponema pallidum hemagglutination assay).

The distribution and intensity of parasite sequestration in comatose Malawian children.

Background: The sequestration of Plasmodium falciparum-infected erythrocytes in capillary beds is a characteristic feature of severe malaria and is believed to be central to disease pathogenesis. Sequestration occurs in all P. falciparum infections, including those in asymptomatic individuals.

Genetic analysis of circulating and sequestered populations of Plasmodium falciparum in fatal pediatric malaria.

Falciparum malaria is characterized by cytoadherence of host erythrocytes containing mature asexual-stage parasites and the consequent sequestration of these forms in tissue microvasculature. A postmortem study of pediatric malaria provided us with the opportunity to compare the genetic complexity of circulating and sequestered Plasmodium falciparum populations, in patients with fatal cerebral malaria (CM) versus control subjects with incidental P. falciparum parasitemia who died of causes other than malaria.

Maternal-fetal microtransfusions and HIV-1 mother-to-child transmission in Malawi.

Background: Between 25% and 35% of infants born to HIV-infected mothers become HIV-1 infected. One potential route of mother-to-child transmission (MTCT) could be through a breakdown in the placental barrier (i.e.

Integrative genomic analyses identify MITF as a lineage survival oncogene amplified in malignant melanoma.

Systematic analyses of cancer genomes promise to unveil patterns of genetic alterations linked to the genesis and spread of human cancers. High-density single-nucleotide polymorphism (SNP) arrays enable detailed and genome-wide identification of both loss-of-heterozygosity events and copy-number alterations in cancer. Here, by integrating SNP array-based genetic maps with gene expression signatures derived from NCI60 cell lines, we identified the melanocyte master regulator MITF (microphthalmia-associated transcription factor) as the target of a novel melanoma amplification.

Treatment of human disseminated strongyloidiasis with a parenteral veterinary formulation of ivermectin.

There are no parenteral antihelminthic drugs licensed for use in humans. We report the successful treatment of disseminated strongyloidiasis with a parenteral veterinary formulation of ivermectin in a patient presenting with severe malabsorption and paralytic ileus. To our knowledge, ivermectin levels are reported for the first time in this situation.

Sampling of supraorbital brain tissue after death: improving on the clinical diagnosis of cerebral malaria.

The clinical diagnosis of cerebral malaria in Plasmodium falciparum-endemic regions is strengthened by demonstration of cerebral sequestration at autopsy. Parasitized comatose patients dying of other causes are less likely to have cerebral sequestration but can be difficult to distinguish, on clinical grounds, from patients dying of cerebral malaria. Sequestered parasites in a cytological preparation of a supraorbital brain sample, obtained after death, can be studied by use of standard thin blood-film staining.

Transgenic expression of {alpha}7{beta}1 integrin maintains muscle integrity, increases regenerative capacity, promotes hypertrophy, and reduces cardiomyopathy in dystrophic mice.

We previously reported that enhanced expression of the alpha7beta1 integrin ameliorates the development of muscular dystrophy and extends longevity in alpha7BX2-mdx/utr(-/-) transgenic mice (Burkin DJ, Wallace GQ, Nicol KJ, Kaufman DJ, Kaufman SJ: Enhanced expression of the alpha7beta1 integrin reduces muscular dystrophy and restores viability in dystrophic mice. We now report on the mechanism by which these mice were rescued by the integrin. As a result of increased integrin in alpha7BX2-mdx/utr(-/-) mice the structural integrity of the myotendinous and neuromuscular junctions are maintained.

Risk factors and mechanisms of preterm delivery in Malawi.

Problem: We examined risk factors and mechanisms of preterm delivery (PTD) in malaria-exposed pregnant women in Blantyre, Malawi.

Method Of Study: The human immunodeficiency virus (HIV), malaria, syphilis, and anemia were assessed in a cross-sectional study of 572 pregnant women. In a nested case-control study, chorioamnionitis (CAM) was examined; tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, IL-8, macrophage inflammatory protein (MIP)-1alpha, monocyte chemotactic protein (MCP)-1, transforming growth factor (TGF)-beta, cortisol, and corticotropin-releasing hormone were measured in placental, maternal and/or cord blood.

The physiological effects of smoking on the respiratory system.

Knowledge about the harmful effects of smoking on the lungs is high among the general population. This damage can occur to both active and passive smokers. Although scientific understanding in this area is incomplete we do have some knowledge about how individual toxic substances in cigarette smoke act on the lung tissues.

Mucocutaneous leishmaniasis in a US citizen.

Mucocutaneous leishmaniasis (MCL) is endemic to many areas of Central and South America. A case of MCL in a US citizen is reported here. An ulcer appeared on the patient's left hard palate, years after a working trip to Peru.

Pediatric pericardial tamponade presenting as altered mental status.

The purpose of this case report is to illustrate the diagnostic difficulties of pericardial tamponade and to suggest that focused cardiac ultrasound be included in the resuscitative care of pediatric shock. Three cases of cardiac tamponade are presented. Each patient had a syncopal episode and presented with altered mental status and hypotension.

Prolonged hypothermia following respiratory syncytial viral infection in infancy.

Following proven respiratory syncytial viral infection, a previously healthy 2 year old boy displayed notable persistent hypothermia-the lowest temperature being 34.2 degrees C. No obvious ill effects were observed.

Sarcolemmal organization in skeletal muscle lacking desmin: evidence for cytokeratins associated with the membrane skeleton at costameres.

The sarcolemma of fast-twitch muscle is organized into "costameres," structures that are oriented transversely, over the Z and M lines of nearby myofibrils, and longitudinally, to form a rectilinear lattice. Here we examine the role of desmin, the major intermediate filament protein of muscle in organizing costameres. In control mouse muscle, desmin is enriched at the sarcolemmal domains that lie over nearby Z lines and that also contain beta-spectrin.