Intestinal parasitic infections among rural farming communities in eastern Sierra Leone

A study carried out in four rural, mainly farming villages in the Gorama Chiefdom, Kono District, Eastern Sierra Leone revealed that intestinal helminth infections are prevalent in this area of Sierra Leone. Out of the 1164 persons of all ages who were examined, 853 (73.5%) proved positive for at least one intestinal helminth infection. Ascaris lumbricoides was the most common helminth encountered (37.5%), followed by hookworms, 12.9%; Trichuris trichiura, 12.6%; Schistosoma mansoni, 5.6%; Strongyloides stercoralis, 3.8%; tapeworms 1.0%, and multiple infections were common. Adults used poorly built pit latrines, while children defecated indiscriminately and unsupervised around houses and in the nearby bush. In addition, in most of the villages, domestic water was obtained from polluted streams and rivers. Only one village had protected pipe borne water supply. The high prevalence of intestinal helminth infections in this area results from constant infection and reinfection caused by poor sewage disposal, poor environmental health, and the low socioeconomic status prevailing in these communities.     

Acute mountain sickness in the Southern Alps of New Zealand

AIM: To assess the incidence and impact of acute mountain sickness in the Southern Alps of New Zealand. METHODS: Over a 22 month period, mountaineers in the Mount Cook region were asked to complete a questionnaire at the completion of their climbing excursions. The questionnaire recorded demographic data and incorporated the Lake Louise scoring system to assess the presence of acute mountain sickness. RESULTS: Of the 114 subjects who completed the questionnaire, 30 (26%) developed acute mountain sickness. The incidence was higher amongst those who slept above 2500 m (50%). Of those with acute mountain sickness, 33% reported that their symptoms resulted in no reduction in activity, while 13% reported a moderate or severe reduction in activity. CONCLUSION: Mountaineers climbing in New Zealand's Southern Alps should be aware of the risk of acute mountain sickness, especially for those sleeping above 2500 m.     

Development of segment specificity in identified lineages of the grasshopper CNS

The purpose of this study was to determine the factors underlying differences in population size and composition between segmentally homologous neuronal lineages. The segmental median neuroblasts (MNBs) of grasshoppers are identified stem cells that each produce a midline group of neurons. We traced the embryonic development of the group in two disparate segments, counting MNB progeny and profiles of dying cells in fixed and stained preparations of staged embryos. In the metathoracic segment (T3), about 95 MNB progeny survive embryonic development, whereas in the next posterior segment, the first abdominal (A1), only about 60 survive. In T3, the MNB arises at 29% of embryogenesis and dies at 78%, whereas in A1 the MNB arises at 30% and dies at 73%. In T3, the number of MNB progeny initially increases at a steady rate, 10 cells being added per 5% of embryogenesis. Between 70% and 78% growth tapers off; although the T3 MNB continues to divide, cells die at the same time, specifically removing last-born progeny. By contrast, in A1 the MNB progeny increase in two phases, one from 30% to 45% and the other from 60% to 73%, again at the rate of 10 cells per 5%. Between the two phases, the number of A1 progeny is stable. The A1 MNB continues to divide, but cells die at the same time, specifically removing earlier-born progeny. The episodes of cell death in A1 and T3 coincide with embryonic molts, and thus may be hormonally triggered. Cell death is greater in A1 than T3, accounting for most of the difference in population size. The difference in MNB longevity makes a lesser contribution. The present data, together with corollary anatomical data (Thompson and Siegler, 1991), support the hypothesis that progeny fated to become certain neuronal types are selectively removed from the two MNB lineages: intersegmental interneurons from T3 and efferent neurons and local interneurons from A1.     

Paleolithic and Neolithic lineages in the European mitochondrial gene pool

PURPOSE: This article presents a new optimization method for stereotactic radiosurgery treatment planning for gamma unit treatment system. METHODS AND MATERIALS: The gamma unit has been utilized in stereotactic radiosurgery for about 30 years, but the usual procedure for a physician-physicist team to design a treatment plan is a trial-and-error approach. Isodose curves are viewed on two-dimensional computed tomography (CT) or magnetic resonance (MR) image planes, which is not only time consuming but also seldom achieves the optimal treatment plan, especially when the isocenter weights are regarded. We developed a treatment-planning system on a computer workstation in which Powell's optimization method is realized. The optimization process starts with the initial parameters (the number of isocenters as well as corresponding 3D isocenters' coordinates, collimator sizes, and weight factors) roughly determined by the physician-physicist team. The objective function can be changed to consider protection of sensitive tissues. RESULTS: We use the plan parameters given by a well-trained physician-physicist team, or ones that the author give roughly as the initial parameters for the optimization procedure. Dosimetric results of optimization show a better high dose-volume conformation to the target volume compared to the doctor's plan. CONCLUSION: This method converges quickly and is not sensitive to the initial parameters. It achieves an excellent conformation of the estimated isodose curves with the contours of the target volume. If the initial parameters are varied, there will be a little difference in parameters' configuration, but the dosimetric results proved almost to be the same.     

Segregation of myogenic lineages in Drosophila requires numb

Terminal divisions of myogenic lineages in the Drosophila embryo generate sibling myoblasts that found larval muscles or form precursors of adult muscles. Alternative fates adopted by sibling myoblasts are associated with distinct patterns of gene expression. Genes expressed in the progenitor cell are maintained in one sibling and repressed in the other. These differences depend on an asymmetric segregation of Numb between sibling cells. In numb mutants, muscle fates associated with repression are duplicated and alternative muscles are lost. If numb is overexpressed the reverse transformation occurs. Numb acts to block Notch-mediated repression of genes expressed in muscle progenitor cells. Thus asymmetric cell divisions are essential determinants of muscle fates during myogenesis in Drosophila     

The embryonic central nervous system lineages of Drosophila melanogaster. I. Neuroblast lineages derived from the ventral half of the neuroectoderm

Central nervous system development in Drosophila starts with the delamination from the neuroectoderm of about 30 neuroblasts (NBs) per hemisegment. Understanding the mechanisms leading to the specification of the individual NBs and their progeny requires the identification of their lineages. Here we describe 17 embryonic NB lineages derived from the ventral half of the neuroectoderm and we assign these lineages to identified medial and intermediate NBs. The lineages are composed of interneurons (NB 1-2, NB 2-1, MP2, NB 4-1, NB 5-1, NB 5-3, NB 6-1, NB 6-2, and NB 7-2), interneurons and motoneurons (NB 3-1, NB 3-2, NB 4-2, NB 5-2, NB 7-1, and NB 7-3), or interneurons, motoneurons, and glial cells (NB 1-1 and NB 2-2). NB 1-1, NB 2-2, and NB 3-1 form segment-specific lineages. Neuroectodermal progenitors forming NB 2-1, NB 5-1, and NB 7-3 divide while still in the ectoderm to give rise to an additional epidermoblast. Expression of segmentation genes is not lineal in the clones of NB 1-2 and NB 7-3 (engrailed), NB 1-1, NB 4-2, and NB 7-1 (even-skipped), and NB 7-1 (gooseberry-proximal). The timing of delamination for individual NBs as well as the number of their progeny is not strictly invariant. The 17 NBs produce about 200 neurons and only three glial cells, corresponding to about 70% of the estimated total number of neurons and 10% of the glial cells per thoracic and abdominal hemisegment. Previously identified neural cell types were linked to particular lineages and we introduce a systematic terminology for the ventral nerve cord neurons. The wild-type clones provide a foundation for the analysis of mutants, expression patterns, and experimental manipulations.     

Cell fates in leech embryos with duplicated lineages

We have examined the fates of the progeny of supernumerary embryonic stem cells (O/P teloblasts) generated by microinjecting polyadenylic acid into newborn O/P teloblasts in embryos of the leech, Helobdella triserialis. In normal development, each O/P teloblast generates a rostrocaudal column of daughter cells (primary blast cells) that contribute distinct segmentally iterated O or P sets of epidermal and neural progeny to the mature leech. Previous results suggest that primary blast cells derived from ipsilateral pairs of O/P teloblasts are equipotent and equivalent at birth; that they and their progeny assume distinct O or P fates according to hierarchical and position-dependent interactions; and that the P fate is the primary, or default, fate and the O fate is the secondary fate. In the work presented here, one O/P teloblast was experimentally induced to undergo a supernumerary equal division, and the developmental fates of the progeny of the three (two "duplicate" and one "nonduplicate") ipsilateral O/P teloblasts were determined at stages 8 and 10. We find that some supernumerary O/P teloblasts produce supernumerary P progeny, whereas others generate supernumerary O progeny. When three O/P-derived bandlets are present, bandlets derived from the duplicate O/P teloblasts give rise to progeny of the same (O or P) fate. When the nonduplicate bandlet is absent, the duplicate bandlets assume distinct O and P fates. These results suggest that ipsilateral sister O/P teloblasts, while equipotent, might not be equivalent.     

Mitochondrial abnormalities in the cells of myeloma patients

Mitochondrial abnormalities in the myeloma cells of 52 patients are described. They included increased number, bizarre shape, alterations in their internal ultrastructure and vacuolization. There was no correlation between the type of myeloma or the severity of the disease and the observed abnormality of the mitochondria. The possible connection between the damaged mitochondria and the function of the tumor cells is discussed.     

Assessment of acute mountain sickness by different score protocols in the Swiss Alps

INTRODUCTION: Purpose of the present study was to evaluate the Lake Louise acute mountain sickness (AMS) score questionnaire at different altitudes and to compare it with the currently used clinical score and the environmental symptoms questionnaire AMS-C score. METHODS: We investigated 490 climbers who stayed over night at 4 huts in the Swiss Alps, located at the altitudes of 2850 m, 3050 m, 3650 m, and 4559 m. AMS was assessed using our previously described clinical score, the Lake Louise consensus AMS score questionnaire and the environmental symptoms questionnaire III. RESULTS: Below 4000 m, the prevalence of AMS, defined by symptoms that force a reduction in activity, was 7%; when assessed with the clinical score (score > or = 3) it was 22%; with the AMS-C score (score > or = 0.7) 4% and with the Lake Louise score (score > 4) 8%. At the altitude of 4559 m, the prevalence of AMS was 30%, 38%, 40%, and 39%, respectively. The standardized regression coefficients from multiple regression analysis (adjusted R2 0.65, p < 0.001) were 0.45 (p < 0.001) for the self-reported Lake Louise score, 0.48 (p < 0.001) for the sum of the points assigned in the clinical section of the Lake Louise questionnaire, and 0.05 (p = 0.27) for the AMS-C score. The sensitivity and specificity of the Lake Louise score > 4 was 78% and 93%, respectively. CONCLUSIONS: The Lake Louise consensus score is adequate and, compared with the AMS-C score, more effective for the assessment of acute altitude illness at different altitudes.     

Childbirth in eastern Europe

OBJECTIVE: Right atrial dilation occurring late after the modified Fontan procedure is frequently associated with low output states, supraventricular arrhythmias, and atrial thrombus formation. We addressed the hypothesis that progressive right atrial dilatation contributes to inefficient right heart flow dynamics. METHODS: Modified atriopulmonary connections were performed on explanted isolated sheep heart preparations with various degrees of surgically induced right atrial dilatation (right atrial volumes 6 to 55 cm3). Flow models were perfused in an in vitro flow loop with the use of a blood analog fluid. A fluid energy balance was performed for six flow rates (1.0 to 6.0 L/min) at each degree of right atrial dilatation, and the rate of total fluid energy loss was calculated and expressed as a function of right atrial volume and flow rate. Effective pressure drop and fluid resistance across the right atrial chamber were also determined for each flow condition. RESULTS: The rate of fluid energy loss increased with increasing right atrial dilatation and flow rate for all conditions studied (p < 0.001). Over the range of right atrial volumes and flow rates examined, the average increase in the rate of energy loss was 3.8- and 117-fold, respectively. Calculated fluid resistance through the right atrium also increased with increasing right atrial volume and flow rate (p < 0.001), exhibiting an average increase of 3.2- and 3.3-fold respectively. CONCLUSIONS: Right atrial dilatation in atriopulmonary connections causes fluid energy losses and increases the energy required to move blood from the venae cavae to the pulmonary arteries. These observations may help explain the progressive nature of late failures of atriopulmonary connections and provide additional rationale for conversion from atriopulmonary connections to lateral tunnel total cavopulmonary connections in selected patients.     

Mitochondrial dysfunction in neurodegenerative diseases

A potential pivotal role for mitochondrial dysfunction in neurodegenerative diseases is gaining increasing acceptance. Mitochondrial dysfunction leads to a number of deleterious consequences including impaired calcium buffering, generation of free radicals, activation of the mitochondrial permeability transition and secondary excitotoxicity. Neurodegenerative diseases of widely disparate genetic etiologies may share mitochondrial dysfunction as a final common pathway. Recent studies using cybrid cell lines suggest that sporadic Alzheimer's disease is associated with a deficiency of cytochrome oxidase. Friedreich's ataxia is caused by an expanded GAA repeat resulting in dysfunction of frataxin, a nuclear encoded mitochondrial protein involved in mitochondrial iron transport. This results in increased mitochondrial iron and oxidative damage. Familial amyotrophic lateral sclerosis is associated with point mutations in superoxide dismutase, which may lead to increased generation of free radicals and thereby contribute to mitochondrial dysfunction. Huntington's disease (HD) is caused by an expanded CAG repeat in an unknown protein termed huntingtin. The means by which this leads to energy impairment is unclear, however studies in both HD patients and a transgenic mouse model show evidence of bioenergetic defects. Mitochondrial dysfunction leads to oxidative damage which is well documented in several neurodegenerative diseases. Therapeutic approaches include methods to buffer intracellular ATP and to scavenge free radicals.     

Mitochondrial dysfunction in neurodegenerative disorders

Left ventricular hypertrophy with adequate wall thickness, preserved adult phenotype and extracellular matrix may be useful in the prevention of heart failure. Because activation of subtype 1 of angiotensin II (AT1) receptors is thought to be involved in the hypertrophic response of cardiomyocytes, we tested the potential of systemic AT1 blockade to modify the development of left ventricular hypertrophy due to pressure overload. Sham-operated rats and rats with ascending aorta constriction were treated with losartan (30 mg/kg/day) for 8 weeks. Left ventricular geometry, dynamics of isovolumic contractions, hydroxyproline concentration as well as myosin isozymes (marker of fetal phenotype) were assessed. Rats with aortic constriction exhibited a marked increase in left ventricular weight and the diastolic pressure-volume relationship was shifted to smaller volumes. An enlarged ventricular pressure-volume area and increased (p < 0.05) peak values of +dP/dtmax and- dP/dtmax demonstrated an enhanced overall ventricular performance. Signs of congestive heart failure were not apparent. In contrast, parameters of myocardial function (normalized length-stress area, +d delta /dtmax and -d delta /dtmax) were depressed (p < 0.05), indicating an impaired myocardial contractility. The hydroxyproline concentration remained unaltered. However, the proportion of beta-myosin heavy chains (MHC) was increased (p < 0.05). Administration of losartan decreased (p < 0.05) blood pressure and body weight in sham operated and pressure overloaded rats. By contrast, neither the concentric left ventricular hypertrophy or depressed myocardial function nor the increased beta-MHC expression were significantly altered. Thus, activation of AT1 receptors appears not to be involved in the initial expression of the fetal phenotype of pressure overloaded heart which may be responsible for the progressive functional deterioration of the hypertrophied ventricle.     

mtDNA variation in the Yanomami: evidence for additional New World founding lineages

Native Americans have been classified into four founding haplogroups with as many as seven founding lineages based on mtDNA RFLPs and DNA sequence data. mtDNA analysis was completed for 83 Yanomami from eight villages in the Surucucu and Catrimani Plateau regions of Roraima in northwestern Brazil. Samples were typed for 15 polymorphic mtDNA sites (14 RFLP sites and 1 deletion site), and a subset was sequenced for both hypervariable regions of the mitochondrial D-loop. Substantial mitochondrial diversity was detected among the Yanomami, five of seven accepted founding haplotypes and three others were observed. Of the 83 samples, 4 (4.8%) were lineage B1, 1 (1.2%) was lineage B2, 31 (37.4%) were lineage C1, 29 (34.9%) were lineage C2, 2 (2.4%) were lineage D1, 6 (7.2%) were lineage D2, 7 (8.4%) were a haplotype we designated "X6," and 3 (3.6%) were a haplotype we designated "X7." Sequence analysis found 43 haplotypes in 50 samples. B2, X6, and X7 are previously unrecognized mitochondrial founding lineage types of Native Americans. The widespread distribution of these haplotypes in the New World and Asia provides support for declaring these lineages to be New World founding types.     

Markers for macrophage and osteoclast lineages in giant cell lesions of the oral cavity

PURPOSE: Giant cell lesions of the oral cavity are a well recognized entity. However, the histogenesis of these lesions is still the subject of controversy, with support for both histiocyte/macrophage and osteoclast origins being found in the literature. This study evaluated a set of peripheral giant cell lesions (PGCLs) and central giant cell lesions (CGCLs) for characteristics of both cell types to address this dilemma. MATERIALS AND METHODS: Detection of histiocyte/macrophage characteristics was accomplished immunohistochemically by evaluating for markers specific for this cell type, namely alpha-1 -antichymotrypsin (1 -ACT) and factor XIIIa antibodies. Detection of osteoclast characteristics made use of the fact that osteoclasts possess a unique enzyme, tartrate-resistant acid phosphatase, which can be appreciated by histochemical procedures. RESULTS: A large percentage of the multinucleated cells stained with the 1-ACT (38.08% in PGCLs and 15.84% in CGCLs), while only isolated cells stained for factor XIIIa (1.20% PGCLs, 0.99% CGCLs). Isolated stromal cells also were stained. Virtually all multinucleated cells reacted with the tartrate-resistant acid phosphatase stain (99.26% PGCLs, 98.34% CGCLs), as did a number of the mononuclear stromal cells. CONCLUSIONS: This study supports the contention that GCLs of the oral cavity may arise from precursor cells related to the granulocyte/macrophage line, and may originate from mononuclear cells that express markers for both macrophages and osteoclasts.     

Mitochondrial DNA in idiopathic cardiomyopathy

143 women treated in 28 departments from 1980 to 1995 were retrospectively analysed to study the impact of prognostic factors in primary carcinoma of the fallopian tube. The mean age of the patients was 62.5 years. Sixty (42%) tumours were FIGO stage I, 28 (20%) stage II, 38 (27%) stage III, 17 (12%) stage IV. Complete radical resection was achieved in 102 (71%) patients. In 122 (85%) women, surgery involved removal of the uterus, the adnexa, and/or the omentum or lymph nodes. Postoperative therapy consisted of either irradiation (n = 40; 28%) or chemotherapy (n = 70; 49%); 33 women (23%) did not receive any treatment after surgery. The 5-year survival rate for all cases was 43%. The 5-year survival rate was 59% for stages I and II and 19% for stages III and IV (P < 0.00001). FIGO stage, histological grade and presence of residual tumour had an independent prognostic impact in multivariate analysis. In order to investigate the role of p53 in primary fallopian tube carcinomas, we analysed the immunohistochemical expression of p53 protein regarding survival and FIGO stage in 63 patients (44%). No statistical significance was observed.     

Drug-resistant Plasmodium falciparum malaria in the eastern Transvaal

In March 1993, a study was undertaken in the Komatipoort/Malelane area to monitor the in vitro sensitivity of Plasmodium falciparum to antimalarial drugs currently in use in South Africa. Of the 12 isolates collected, 7 were successfully tested for sensitivity to chloroquine and quinine, 6 for mefloquine susceptibility, and 5 for sensitivity to Fansidar. Four of the isolates were resistant to chloroquine at RIII level, 1 at RII level, and 2 were sensitive. All isolates were found to be sensitive to both quinine and mefloquine. Results suggested possible resistance to Fansidar. These findings have implications for tourists travelling to this area.