Malaria epidemiology in the Pakaanóva (Wari') Indians, Brazilian Amazon

This paper reports the results of a longitudinal study of malaria incidence (1998-2002) among the Pakaanóva (Wari') Indians, Brazilian southwest Amazon region, based on data routinely gathered by Brazilian National Health Foundation outposts network in conjunction with the Indian health service. Malaria is present yearlong in the Pakaanóva. Statistically significant differences between seasons or months were not noticed. A total of 1933 cases of malaria were diagnosed in the Pakaanóva during this period. The P. vivax / P. falciparum ratio was 3.4. P. vivax accounted for 76.5% of the cases. Infections with P. malariae were not recorded. Incidence rates did not differ by sex. Most malaria cases were reported in children < 10 years old (45%). About one fourth of all cases were diagnosed on women 10-40 years old. An entomological survey carried out at two Pakaanóva villages yielded a total of 3.232 specimens of anophelines. Anopheles darlingi predominated (94.4%). Most specimens were captured outdoors and peak activity hours were noted at early evening and just before sunrise. It was observed that Pakaanóva cultural practices may facilitate outdoor exposure of individuals of both sexes and all age groups during peak hours of mosquito activities (e.g., coming to the river early in the morning for bathing or to draw water, fishing, engaging in hunting camps, etc). In a context in which anophelines are ubiquitous and predominantly exophilic, and humans of both sexes and all ages are prone to outdoor activities during peak mosquito activity hours, malaria is likely to remain endemic in the Pakaanóva, thus requiring the development of alternative control strategies that are culturally and ecologically sensitive.     

Pulmonary and mediastinal "sarcoidosis" following surgical resection of cancer

Previous reports indicate that enlarged hilar and mediastinal lymph nodes caused by sarcoid-like reactions may develop after curative resection of cancer, and their presence does not necessarily denote neoplastic recurrence. Reports further suggest that coexisting pulmonary infiltrates in this setting may be related to sarcoidosis. In this study, we describe two patients who had resected lung and gastric cancer and who later developed pulmonary interstitial infiltrate, concurrent with progressive mediastinal lymphadenopathy initially thought to be caused by intrathoracic dissemination of their cancer. These changes were shown by open lung biopsy to be a benign, granulomatous reaction interpreted as sarcoidosis. Thus, it is important to recognize this clinical pattern when pulmonary infiltrates develop after complete treatment of cancer in an otherwise relapse-free patient and to encourage lung or lymph node biopsy in these particular settings in order to confirm a sarcoid-like reaction, thereby avoiding unnecessary chemotherapy for presumed tumor recurrence.     

Autonomic nervous control of the heart rate response to dynamic incremental exercise: evaluation of the Rosenblueth-Simeone model

Summary To evaluate the validity of the Rosenblueth-Simeone model for the heart rate response to incremental dynamic exercise, 11 healthy men performed maximal exercise tests on a cycle ergometer after administration of placebo, propranolol, atropine or both propranolol and atropine. The model showed that the influence of sympathetic activity on heart rate increased at intensities up to those which resulted in a heart rate 70% maximal heart rate on placebo, and levelled off at higher intensities, while there was a progressive withdrawal of the parasympathetic activity. The ratio between heart rate predicted by the model and the recorded heart rate following placebo treatment tended to be less than 1.0 at lower exercise intensities, and approached the unit at intensities above those which resulted in a heart rate higher than 70% of maximal heart rate on placebo. There was a strong correlation (r=0.94,P<0.01) between the heart rate on placebo and the heart rate estimated by the model. Nevertheless, there was some scattering of the data around the identity line, with a standard error of the estimate for the regression line of 11 beats · min^–1. Thus, during incremental exercise, the influence of sympathetic activity on heart rate does not become progressively more important at higher exercise intensities. The application of the Rosenblueth-Simeone model shows limitations during incremental exercise, particularly at low exercise intensities.     

Variable dystrophin expression in different muscles of a Duchenne muscular dystrophy carrier

The majority of Duchenne muscular dystrophy (DMD) female carriers show dystrophin immunostaining abnormalities, although a significant proportion of clinically non-manifesting carriers are normal following this analysis. We had the opportunity to study dystrophin immunostaining in two different muscles, the vastus lateralis and the rectus abdominis of a possible DMD carrier. While the vastus showed normal dystrophin immunostaining, pathological staining was detected in her rectus abdominis. These findings seem to indicate that dystrophin expression can vary in different muscle groups of a DMD carrier. The implications of these findings in DMD carrier detection and possible dystrophin function are discussed.     

Biallelic somatic inactivation of the mismatch repair gene MLH1 in a primary skin melanoma

Inactivation of mismatch repair (MMR) genes has been linked to the hereditary nonpolyposis colon cancer syndrome and to a subset of sporadic cancers. A phenotypic characteristic of tumors with defective MMR is microsatellite instability (MSI). Although MSI has been reported in a proportion of cutaneous melanomas, inactivation of MMR genes in this tumor type has not been detected thus far. We recently described a human melanoma cell line, PR-Mel, and a cutaneous metastasis from the same patient, which displayed a MMR defect, and showed high MSI. Here we report that in the PR-Mel cell line both MLH1 alleles are somatically inactivated. One allele is lost through a chromosomal deletion of the region 3p21-24, whereas the remaining allele harbors a G --> A transition at position -1 of the acceptor splice site of intron 15, leading to the in-frame skipping of exon 16. The primary melanoma of the PR patient shows loss of heterozygosity at the BAT21 microsatellite marker, located in the MLH1 gene, and does not express the MLH1 and PMS2 proteins. Moreover, it harbors the same mutation detected in the PR-Mel cells. These results demonstrate that biallelic inactivation of MLH1 had occurred in the primary melanoma of the PR patient and suggest that disruption of MMR might have had a role in the development of the melanoma. This is the first report in which genetic defects leading to disruption of MMR function in a human melanoma have been identified.     

ABCA1 gene deletion protects against cerebral malaria: potential pathogenic role of microparticles in neuropathology

The ATP-binding cassette transporter A1 (ABCA1) modulates the transbilayer distribution of phosphatidylserine at the outer leaflet of the plasma membrane. This external exposure of phosphatidylserine is a hallmark of microparticle production and is impaired in ABCA1(-/-) mice. In this study, we report about the complete resistance to cerebral malaria of these mice. On analysis of histological and systemic parameters we evidenced an impairment of cellular responses to Plasmodium berghei ANKA infection in ABCA1(-/-) mice, as shown by lower plasma tumor necrosis factor levels, a weaker up-regulation of endothelial adhesion molecules in brain microvessels, a reduced leukocyte sequestration, as well as an ablated platelet accumulation. Besides, the number and the procoagulant activity of microparticles were dramatically reduced in the plasma of ABCA1(-/-) compared to ABCA1(+/+) mice. Moreover, microparticles derived from Plasmodium berghei ANKA-infected ABCA1(+/+) mice induced a significant increase of tumor necrosis factor release by noninfected macrophages. In ABCA1(-/-) mice platelet and macrophage responses to vesiculation agonists were ablated and reduced, respectively. Altogether, by pointing out the ABCA1 transporter as a major element controlling cerebral malaria susceptibility, these data provide a novel insight into its pathophysiological mechanisms and are consistent with a pathogenic role of microparticles in this neurological syndrome.