Health care provision for illegal immigrants: should public health be concerned?
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Biomedical subjects
Publications and source records attributed to A M Torres.
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INTRODUCTION: The association between infection and growth delay is not well documented in school-age children in developing countries. We conducted a prospective cohort study to examine the association between infectious disease and weight and height gains among Bangladeshi children. METHODS: A one-year follow-up study was performed to elucidate the determinants and consequences of physical growth of children under five years of age. The study included 135 households randomly selected from four villages in the Matlab area. RESULTS: The most frequent infections were upper respiratory infections (mean = 4 episodes or 27 days per year) followed by non-dysenteric diarrhoea (mean = 2.3 episodes or 15 days per year) and dysentery (mean = 0.2 episodes or 2 days per year). The number of episodes and their duration decreased significantly with age. Over a 12-month period the mean weight gain was 1.3 kg and the mean increase in height was 2.9 cm. The total number of days when diarrhoea occurred was negatively associated with annual weight gain (regression coefficient beta = -7 g per day, P = 0.02), with adjustment for age, sex, energy and protein intake, and household land ownership. The incidence of diarrhoeal disease was significantly associated with weight gain in intermediate models but only marginally associated with it in the final multivariate model (P = 0.08). Neither the incidence nor the duration of upper respiratory infections was associated with weight gain. Height gain was not significantly associated with the duration or incidence of either category of illness. Diarrhoea was a significant correlate of retarded weight gain among children above preschool age, whereas upper respiratory infections were not. DISCUSSION: Diarrhoeal morbidity slowed growth in children well beyond the weaning age, suggesting that increased attention should be given to the study of the continuous impact of diarrhoea in children aged over 5 years. An understanding of the determinants of growth in school-age children in developing countries would maximize the health and developmental outcomes that are the target of international child survival strategies at younger ages.
Three defensin-like peptides (DLPs) were isolated from platypus venom and sequenced. One of these peptides, DLP-1, was synthesized chemically and its three-dimensional structure was determined using NMR spectroscopy. The main structural elements of this 42-residue peptide were an anti-parallel beta-sheet comprising residues 15-18 and 37-40 and a small 3(10) helix spanning residues 10-12. The overall three-dimensional fold is similar to that of beta-defensin-12, and similar to the sodium-channel neurotoxin ShI (Stichodactyla helianthus neurotoxin I). However, the side chains known to be functionally important in beta-defensin-12 and ShI are not conserved in DLP-1, suggesting that it has a different biological function. Consistent with this contention, we showed that DLP-1 possesses no anti-microbial properties and has no observable activity on rat dorsal-root-ganglion sodium-channel currents.
NMR q-space plots derived from water diffusing inside and around erythrocytes in a suspension display reproducible and characteristic coherence features. The aim of the present work was to determine which water population gives rise to the respective features. The central experimental strategy was to use choline and choline phosphate which are virtually membrane impermeant on the time scale of the experiment; the former was incorporated into erythrocytes by a lysis-resealing method and the latter was simply added to the suspensions. Dimethyl sulfoxide, which readily but more slowly exchanges across the cell membranes than water, also yielded q-space plots which were similar to those of water, but the differences were able to be accounted for on the basis of its slower transmembrane exchange rate. Random walk simulations using a Monte Carlo procedure, together with a model of an array of biconcave discocytes, helped verify the interpretations of the assignment of the features of the plots to molecules diffusing in the two regions. In addition, the simulations revealed how the presence or absence of transmembrane exchange affects the form of q-space plots.
OBJECTIVE: To describe the current organization of health promoting and preventive activities within the Danish Municipal Dental Health Service and to assess how the service has chosen to comply with the directives as formulated by the National Board of Health. DESIGN: A cross-sectional survey of the municipal dental health services was carried out on a national scale. Postal questionnaires were used to collect information on active and passive preventive care activities and community-orientated health promotion. SETTING: The survey was conducted to aid the reorientation and adjustment of the Municipal Dental Health Services in Denmark. SUBJECTS: All municipal dental health services in Denmark were considered relevant for the survey and 141 services (71%) responded to the questionnaire. OUTCOME MEASURES: Quantitative methods were used to measure recall-intervals for children and adolescents, passive and active prevention, identification of and care for individuals at risk, and health education. Qualitative methods were applied to record the organization of community health activities. RESULTS AND CONCLUSIONS: The majority of dental services stated that preschool children are called at regular intervals (every 3, 6 or 8 months); school-children and adolescents are most often recalled according to individual needs. Chairside assistants, dentists or dental hygienists give oral hygiene instructions systematically to children of grades 0 through to 3. Fluoride is frequently administered through topical application by dentists; fluoride tables are not used. Permanent molars are sealed when this is indicated. Clinical and socio-behavioural criteria are used to identify children at risk. Half of the services reported school-based health education, and in one-quarter of the municipalities community health activities took place. Adjustment of the services should consider population-directed activities and greater use of ancillary personnel.
Invasive aspergillosis has been increasingly recognized as causing significant morbidity and mortality in immunocompromised patients but has never been diagnosed by fine-needle thyroid aspiration. A 24-year-old female with systemic lupus erythematosus presented with cough, shortness of breath, and fever of unknown origin unresponsive to broad-spectrum antibiotics. History and physical examination failed to indicate a source of infection. An 111In white blood cell scan showed thyroid localization. Physical examination revealed a multinodular goiter with a left dominant nodule. Fine-needle aspiration biopsy of a thyroid nodule revealed branching hyphae suggestive of Aspergillus sp. Despite immediate and aggressive treatment with amphotericin B and fluconazole, the patient died of overwhelming infection.
Cellular redox status and membrane protein activities were analyzed in kidneys from rats with ischemic acute renal failure (ARF). ARF was induced by clamping the left renal artery for 50 min. A parallel group of control animals was processed. In the ischemic group urea plasma levels were statistically increased as compared with the control group. Studies employing whole kidney homogenates revealed that ischemia produces an increment in lipid peroxidation levels and a reduction in glutathione concentration and in superoxide dismutase and glutathione peroxidase activities. Since lipid peroxidation may alter the function of membrane proteins we determined succinate cytochrome c reductase (SuccR), sodium-potassium ATPase (Na-K-ATPase), glucose-6-phosphatase (G-6-Pase) and alkaline phosphatase (ALP) activities in whole renal homogenates. Only G-6-Pase and ALP activities were modified by ischemia. Since ALP is a brush border membrane (BBM) enzyme and BBM is one of the main target structures in ARF, we assessed some parameters of BBM functionality. ALP, gamma-glutamyl transferase (gamma-GT) and 5'-nucleotidase (5'-NT) showed diminished activities in BBM from ischemic kidneys. Ischemia also modified the Vmax of paraaminohippuric acid (PAH) uptake without altering Km. An increment of lipid peroxidation and membrane fluidity in BBM was observed after the treatment. Total membrane proteins and protein recoveries in BBM were similar in both experimental groups. Sialic acid and sulfhydryl levels were similar in BBM from ischemic kidney and control ones. In summary, ARF induced by renal artery clamping for 50 min takes place with a significant increase in urea plasma levels. A decrease in the antioxidant defense system is detected. This induces lipid peroxidation in whole renal tissue, which may justify the diminished activities of some membrane enzymes such as G-6-Pase and ALP. A specific analysis of BBM function reveals a significant increment of lipid peroxidation which may be the cause of an increased membrane fluidity. This latter parameter might be, at least in part, responsible for the damaged function of apical ALP, 5'-NT, gamma-GT and PAH carrier.
The fraction of strongly- and weakly-bound water molecules within mitochondrial suspensions, determined using three-quantum filtered 17O NMR relaxation analysis, was found to be large in comparison with that in erythrocytes and concentrated solutions of bovine serum albumen. It is suggested that bound water, together with regulation of mitochondrial matrix volume, may be an important controlling factor in the modulation of enzymic activity in the matrix. A spin I = 5/2 Jeener-Broekaert experiment and a four-quantum filtration experiment were used to demonstrate the absence of orientationally ordered water molecules within the mitochondrion. In contrast, the mitochondrial sodium environment was shown to be highly ordered using a spin I = 3/2 Jeener-Broekaert experiment.
Transverse triple-quantum filtered NMR spectroscopy (TTQF) of 17O-water was used to study the properties of water in insulin solutions at different Zn2+ concentrations and pH values. It was established that strongly bound water molecules are already present in Zn-free insulin. On the assumption that the effective correlation time of a strongly bound water molecule, tau sb, is 10 ns, the apparent number of strongly bound water molecules was approximately 3 to 4 per insulin monomer. Addition of Zn2+ equivalent to approximately 2 g-atoms per hexamer did not produce substantial increases in the overall 17O-water TTQF signal intensity and apparent fraction of bound water. The dramatic enhancement of the TTQF signals observed for samples with a Zn2+/hexamer ratio greater than approximately 2:1 could be attributed to the increase in correlation time of the strongly bound water, due to the formation of higher-order oligomers of the protein.
Vpr, one of the accessory gene products encoded by HIV-1, is a 96-residue protein with a number of functions, including targeting of the viral pre-integration complex to the nucleus and inducing growth arrest of dividing cells. We have characterized by 2D NMR the solution conformations of bioactive synthetic peptide fragments of Vpr encompassing a pair of H(F/S)RIG sequence motifs (residues 71-75 and 78-82 of HIV-1 Vpr) that cause cell membrane permeabilization and death in yeast and mammalian cells. Due to limited solubility of the peptides in water, their structures were studied in aqueous trifluoroethanol. Peptide Vpr59-86 (residues 59-86 of Vpr) formed an alpha-helix encompassing residues 60-77, with a kink in the vicinity of residue 62. The first of the repeated sequence motifs (HFRIG) participated in the well-defined alpha-helical domain whereas the second (HSRIG) lay outside the helical domain and formed a reverse turn followed by a less ordered region. On the other hand, peptides Vpr71-82 and Vpr71-96, in which the sequence motifs were located at the N-terminus, were largely unstructured under similar conditions, as judged by their C(alpha)H chemical shifts. Thus, the HFRIG and HSRIG motifs adopt alpha-helical and turn structures, respectively, when preceded by a helical structure, but are largely unstructured in isolation. The implications of these findings for interpretation of the structure-function relationships of synthetic peptides containing these motifs are discussed.
Two synthetic analogues of murine epidermal growth factor, [Abu6, 20] mEGF4-48 (where Abu denotes amino-butyric acid) and [G1, M3, K21, H40] mEGF1-48, have been investigated by NMR spectroscopy. [Abu6, 20] mEGF4-48 was designed to determine the contribution of the 6-20 disulfide bridge to the structure and function of mEGF. The overall structure of this analogue was similar to that of native mEGF, indicating that the loss of the 6-20 disulfide bridge did not affect the global fold of the molecule. Significant structural differences were observed near the N-terminus, however, with the direction of the polypeptide chain between residues four and nine being altered such that these residues were now located on the opposite face of the main beta-sheet from their position in native mEGF. Thermal denaturation experiments also showed that the structure of [Abu6, 20] mEGF4-48 was less stable than that of mEGF. Removal of this disulfide bridge resulted in a significant loss of both mitogenic activity in Balb/c 3T3 cells and receptor binding on A431 cells compared with native mEGF and mEGF4-48, implying that the structural changes in [Abu6, 20] mEGF4-48, although limited to the N-terminus, were sufficient to interfere with receptor binding. The loss of binding affinity probably arose mainly from steric interactions of the dislocated N-terminal region with part of the receptor binding surface of EGF. [G1, M3, K21, H40] mEGF1-48 was also synthesized in order to compare the synthetic polypeptide with the corresponding product of recombinant expression. Its mitogenic activity in Balb/c 3T3 cells was similar to that of native mEGF and analysis of its 1H chemical shifts suggested that its structure was also very similar to native.
The utility of 1H nuclear magnetic resonance (NMR) diffusion-diffraction of water as a tool for characterising red cell shape was investigated. Experiments were conducted on various cell suspensions which contained different shapes/forms of erythrocytes prepared by manipulating the conditions of the suspension medium, such as osmolality, and altering metabolism to affect the adenosine triphosphate concentration. Abnormal red cells from patients with hereditary stomatocytosis and megaloblastic anemia were also studied in order to assess the practical application of this "new" technique. The results clearly show that NMR diffusion-diffraction is sensitive to very small changes in mean cell dimensions and that a "characteristic" q-space plot/profile can be ascribed to each erythrocyte form. It was also found that the homogeneity of the cell shape and/or size is an important factor that affects the intensity of the diffusion-diffraction peaks. This study demonstrates the potential of the NMR diffusion-diffraction technique as a diagnostic tool in hematology.
Soluble receptors for hormones and cytokines have been described. They can serve as natural blockers of their respective ligands. The natural soluble interferon gamma receptor (sIFN gamma R) has been isolated and characterized only in urine. Chromatography of human (hu) plasma from rheumatoid arthritis (RA) patients and controls on immobilized hu IFN gamma or antibodies against IFN gamma R alpha chain permitted us to isolate the sIFN gamma R. The receptor isolated from one control is a protein with a molecular weight between 60-67 kDa depending on the presence of reducing agents. We detected a significantly higher level of plasma sIFN gamma R in patients with rheumatoid arthritis than in apparently healthy subjects.
Aerobic repression of the hypoxic genes of Saccharomyces cerevisiae is mediated by the DNA-binding protein Rox1 and the Tup1/Ssn6 general repression complex. To determine the DNA sequence requirements for repression, we carried out a mutational analysis of the consensus Rox1-binding site and an analysis of the arrangement of the Rox1 sites into operators in the hypoxic ANB1 gene. We found that single base pair substitutions in the consensus sequence resulted in lower affinities for Rox1, and the decreased affinity of Rox1 for mutant sites correlated with the ability of these sites to repress expression of the hypoxic ANB1 gene. In addition, there was a general but not complete correlation between the strength of repression of a given hypoxic gene and the compliance of the Rox1 sites in that gene to the consensus sequence. An analysis of the ANB1 operators revealed that the two Rox1 sites within an operator acted synergistically in vivo, but that Rox1 did not bind cooperatively in vitro, suggesting the presence of a higher order repression complex in the cell. In addition, the spacing or helical phasing of the Rox1 sites was not important in repression. The differential repression by the two operators of the ANB1 gene was found to be due partly to the location of the operators and partly to the sequences between the two Rox1-binding sites in each. Finally, while Rox1 repression requires the Tup1/Ssn6 general repression complex and this complex has been proposed to require the aminoterminal regions of histones H3 and H4 for full repression of a number of genes, we found that these regions were dispensable for ANB1 repression and the repression of two other hypoxic genes.
AIM: To evaluate the effect of PD Plus on weekly Kt/Vurea and creatinine clearance (Kcr) among patients undergoing CAPD/CCPD (continuous ambulatory peritoneal dialysis/continuous cyclic peritoneal dialysis). METHODS: The kinetic studies of 92 CAPD and 18 CCPD patients who transferred to PD Plus were analyzed. All patients underwent CAPD/CCPD and PD Plus for a minimum of 3 months. Standard collection methods were used and kinetic indices calculated with the Pack PD Kinetic Modeling program. 57 patients had transport data and were modeled for a target weekly Kt/Vurea >/=2.1 using PD Plus with </=15 liters dialysate/day. 6 patients were supervised during the collection periods by research nurses. The actual results for all patients (110) and for the supervised patients were compared against the modeled results. RESULTS: [table] 45% of the patients achieved a Kt/Vurea >/=2.1 and 47% a Kcr >/=60 liters/1.73 m2 with PD Plus, but only 20% did so with CAPD/CCPD. A close correlation between the supervised patients and modeled therapy was observed. CONCLUSIONS: Adequate dialysis is possible by using higher fill volumes, the supine position, and optimal dwell times (PD Plus) in most patients. The discrepancy between modeled and achieved dose is likely due to poor compliance with therapy, inadequate training, or poor specimen collection.
An early stage of diabetic nephropathy was studied. Rat renal function was evaluated by clearance techniques, 7 or 15 days after alloxan administration (groups A7 and A15). Significant diminutions of glomerular filtration rate (inulin clearance) and p-aminohippurate clearance were observed in alloxan-treated rats. Diabetic animals presented glucosuria and enhanced water excretion. A natriuretic response was only observed in A15-rats. Arterial pressure increased along time, and enlarged lipid deposits in glomeruli and vessels of A7-kidney sections were observed. Thus, a vascular compromise at this time was suggested. To better characterize the set up of the renal dysfunction, other studies were performed in A7-group. Urinary protein excretion remained unchanged while a higher level of glycosylation of urinary proteins was observed in A7-rats. Histological studies revealed a normal general morphology in kidneys from diabetic rats. Immunohistochemical analysis in renal sections showed enlarged deposits of fibronectin in glomeruli and interstitium of alloxan-treated rats. Higher myeloperoxidase activity was observed in renal cortex from diabetic animals indicating leukocytes infiltration. These results indicated that 7 days after hyperglycemia induction, the animals presented a renal dysfunction characterized by hemodynamic alterations associated with vascular and glomerular structural impairments, without modifications in tubular function. The higher level of protein glycosylation and the inflammatory process at this early stage could be responsible for the beginning of diabetic nephropathy.
The triple-quantum filtered (TQF) spin-echo signal of (17)O-water, in the presence of proteins, was analysed to yield estimates of the number of weakly, and strongly bound water molecules. The analysis used a constrained direct iterative regression procedure with a three-state model of fast-exchange. Thus, the population size of free, weakly, and strongly bound water were determined simultaneously. The two fractions of the bound water were estimated by using correlation time(s) estimated in other studies. Bovine serum albumin (BSA), basic pancreatic trypsin inhibitor (BPTI), lysozyme and oxyhaemoglobin were studied. Of the four proteins, BSA contained the largest number of strongly and weakly bound water molecules, there being approximately 30 of the former and approximately 3000 of the latter under conditions of high protein concentration. The correlation time of the proteins increases with their concentration in solution, and when this was taken into account for BSA the estimated number of strongly bound water molecules did not change significantly. This NMR technique, and data analysis, will probably also be useful in studies of water binding and mobility in various systems including hydrogels, protein networks, membranes, cells and tissues.
The hepatocytic uptake of cholephilic organic anions occurs by carrier-mediated mechanisms. Electrogenic and electroneutral transport systems have been described. The aim of this study was to determine the dissociation constant (Kd) of the Electrogenic Carrier System(s) (ECS) for tetrabromosulfophthalein (BSP), dibromosulfophthalein (DBSP), tetrabromophthalein (TBP), tetrabromosulfonephthalein (TBS) and thymol blue (TB). Kd (uM) values for ECS-organic anion complexes were: ECS-BSP = 3.61 +/- 0.18; ECS-DBSP = 11.61 +/- 1.32; ECS-TBP = 0.51 +/- 0.08; ECS-TBS = 1.31 +/- 0.25; ECS-TB = 9.44 +/- 1.80. From these data, it is possible to conclude that molecular characteristics of the organic anions are important factors in determining the dissociation constant for the electrogenic hepatic carrier(s). In this sense, the addition of two sulphonic groups on the phenolic ring; the presence of a sulphonic on the benzenic ring and the absence of two or four bromines on the molecule confers a lower affinity for ECS.