[Recent data on Rift Valley Fever epidemiology in Senegal].
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Biomedical subjects
Publications and source records attributed to J Gonzalez.
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A 57-year-old man with Ki-1 anaplastic large-cell lymphoma treated with extracorporeal photochemotherapy is described.
Post-transfusion purpura (PTP) is a rare disorder characterized by the abrupt onset of severe thrombocytopenia following a blood transfusion. We describe a case of PTP in a patient treated with plasmapheresis, noting that this is an uncommon but treatable disease entity.
The proper selection of a wheelchair requires making several critical decisions, not the least of which is what type of wheelchair is appropriate. The International Organization for Standards (ISO) continues to develop and refine wheelchair standards. Standards allow the objective comparison of products from various sources, permitting consumers or clinicians to assess wheelchairs with which they are not familiar by comparing test results. This study consisted of three components: 1) the comparison of fatigue test results with a planar ANSI/RESNA test dummy to a HERL contoured test dummy; 2) the comparison of fatigue test results for common depot versus common rehabilitation manual wheelchairs; and 3) the comparison of fatigue test results for manual rehabilitation wheelchairs with solid 8-inch casters versus those with pneumatic 8-inch casters. Rehabilitation wheelchairs lasted on average 13.2 times longer than the depot wheelchairs. Both types, tested with the standard ISO-ANSI/RESNA dummy, lasted on average 2.1 times longer than those wheelchairs tested using the contoured dummy. The three rehabilitation wheelchairs equipped with 8-inch pneumatic casters lasted on average 3.2 times longer than the 6 rehabilitation wheelchairs equipped with solid 8-inch casters. The depot wheelchairs cost about 3.4 times as much to operate per cycle or per meter than the rehabilitation wheelchairs. The rehabilitation wheelchairs tended to experience component failures, while the depot wheelchairs tended to experience frame failures. Our testing indicates that the tests in the ISO-ANSI/RESNA standards can relate design features to fatigue test results and durability. Rehabilitation wheelchairs tend to use higher quality materials and better manufacturing practices, and they provide greater mobility for wheelchair users. Purchasers and prescribers of wheelchairs should consider the life-cycle cost and not just the purchase price for wheelchairs.
PURPOSE: To improve treatment results on prostatic adenocarcinoma, conformal radiation therapy (CRT) has been used. Two major drawbacks of external CRT are: (a) internal organ motion/daily set-up variations, and (b) exclusion of several patients for CRT based on poor geometrical relationships as identified by three dimensional (3D) treatment planning. To overcome the above problems, we began the first prospective Phase I/II dose-escalating clinical trial of conformal brachytherapy (CB) and concurrent external beam irradiation. METHODS AND MATERIALS: Fifty-nine patients with T2b-T3c prostatic adenocarcinoma received 176 transperineal ultrasound-guided conformal high-dose rate (HDR) boost implants. All patients received concomitant external beam pelvic irradiation. Dose escalation of the three HDR-CB fractions proceeded as follows: 5.5 Gy (30 patients), 6 Gy (20 patients), and 6.5 Gy (9 patients). The CB dose was prescribed to the prostate contour as outlined using an online biplanar transrectal ultrasound probe. The urethra, anterior rectal wall, and prostate boundaries were identified individually and outlined at 5 mm intervals from the base to the apex of the gland. The CB using real-time ultrasound guidance with interactive online isodose distributions was performed on an outpatient basis. As needles were placed into the prostate, corrections for prostate displacement were recorded and the isodose distributions were recalculated to represent the new relationship between the needles, prostate, and normal structures. No computerized tomography (CT) planning or implant preplanning was required. RESULTS: No patient was rejected based on poor geometrical relation of pelvic structures. In every implant performed, prostate displacement was noted. Craniocaudal motion of the gland ranged from 0.5-2.0 cm (mean = 1.0 cm), whereas lateral displacement was 0.1-0.4 cm. With the interactive online planning system, organ motion was immediately detected, accounted for, and corrected prior to each HDR treatment. The rectal dose has ranged from 45 to 87%, and the urethral dose from 97 to 112% of the prostate dose. It is significant to note that operator dependence has been completely removed because the interactive online planning system uniformly guides the physicians. CONCLUSIONS: With ultrasound guidance and the interactive online dosimetry system, organ motion (as compared to external beam) is insignificant because it can be corrected during the procedure without increasing target volume margins. Common pitfalls of brachytherapy, including operator dependence and difficulty with reproducibility, have been eliminated with the intraoperative online planning system.
PURPOSE: To improve results for locally advanced prostate cancer, a prospective clinical trial of concurrent external beam irradiation and fractionated iridium-192 (Ir-192) high dose rate (HDR) conformal boost brachytherapy was initiated. METHODS AND MATERIALS: Between November 1991 and February 1994, 99 implants were performed on 33 patients with prostatic adenocarcinoma at William Beaumont Hospital. Using AJCC staging criteria, 9 patients had T2b tumors, 17 patients had T2c tumors, and 7 patients had T3 disease. Patients were treated with (a) 45.6 Gy whole pelvis external irradiation and (b) three HDR fractions of 5.5 Gy each (18 patients) or 6 Gy each (15 patients) to the prostate. Transperineal needle implants using real-time ultrasound guidance with interactive on-line isodose distributions were performed on an outpatient basis during weeks 1, 2, and 3 of external irradiation. Acute toxicity was scored using the Radiation Therapy Oncology Group (RTOG) morbidity grading system. RESULTS: This technique of concurrent external pelvic irradiation and conformal HDR brachytherapy was well tolerated. No significant intraoperative or perioperative complications occurred. Three patients (9%) experienced Grade 3 acute toxicity (two dysuria and one diarrhea). All toxicities were otherwise Grades 1 or 2 and were primarily as expected from pelvic external irradiation. Persistent implant-related toxicities included Grades 1-2 perineal pain (12%) and hematospermia (15%). Median follow-up time was 13 months. Serum prostatic-specific antigen (PSA) levels normalized in 91% of patients (29 out of 32) within 1-14 months (median 2.8 months) after irradiation. PSA levels were progressively decreasing in the other three patients at last measurement. Prospectively planned prostatic rebiopsies done at 18 months in the first 10 patients were negative in 9 out of 10 (90%). CONCLUSIONS: Acute toxicity has been acceptable with this unique approach using conformal high dose rate Ir-192 boost brachytherapy with concurrent external irradiation. The initial tumor response as assessed by serial PSA measurement and rebiopsy is extremely encouraging. Dose escalation will proceed in accordance with the protocol guidelines. Further patient accrual and longer follow-up will allow comparison to other techniques.
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Twenty-one Trypanosoma cruzi stocks isolated from Triatoma infestans and humans of the Chilean Andean highlands were studied at the genotypic level by schizodeme and molecular karyotype analyses, which allowed a clear distinction of the parasites from those hosts. A phenotypical characterization was performed by proteolytic activity after electrophoretic fractionation without discrimination among the stocks. Metacyclic trypomastigotes obtained in vitro proved to be infective to Swiss mice and the study of immune response and biological behavior was assessed. Of a total of 21 T. cruzi stocks, only 11 proved to be infective in mice due to difficulties in obtaining metacyclic trypomastigotes with the parasite populations isolated from humans. Western blot analysis revealed a complex immune response even in the first days postinfection with each T. cruzi strain studied. Antigenic recognition by each immune serum is characteristic, although several major and common antigens were detected. Lytic antibodies were studied by the in vitro complement-mediated lytic assay using purified metacyclic trypomastigotes as target cells. All the T. cruzi isolates tested induced lytic antibodies in this experimental model. Parasitemias were moderate and characteristic for each T. cruzi strain. Results are compared with metacyclic forms of the infective and pathogenic Tulahuen strain.
The oxidizing capacity of phagocytic cells is suspected to play a major role in the generation of immunogenic drug metabolites, in particular those that cause extrahepatic immunopathological lesions. In the case of the antirheumatic drug gold(I) disodium thiomalate (Na2Au(I)TM), oxidation of the Au(I) ion to Au(III) appears to be responsible for the adverse immune reactions which may develop during gold therapy. Here, we show that the reactive metabolite Au(III) may be generated by mononuclear phagocytes (M phi) exposed to Au(I). The generation of Au(III) was analyzed by means of the adoptive transfer popliteal lymph node assay (PLNA) in mice, using T lymphocytes previously sensitized to Au(III) as a detection probe. Donors of the Au(III)-primed T cells were either directly sensitized to Au(III) by injection of tetrachloroauric acid (HAu(III)Cl4), or indirectly via chronic treatment with Na2Au(I)TM. As donors of peritoneal cells (PC), we used mice which had received weekly i.m. injections of Na2Au(I)TM for 12 weeks and contained increased numbers of activated B cells. The PC of these mice were found to elicit a significant secondary response when used as antigenic material for the restimulation of Au(III)-primed T cells. The immunogenicity of PC obtained from Na2Au(I)TM-treated mice paralleled the total gold content of these cells. Noteworthily, M phi exposed to Au(I) in vitro also proved capable of eliciting a specific secondary response of Au(III)-primed T cells. Hence, M phi exposed to Au(I) generate the reactive intermediate Au(III) which, apparently via oxidation of self proteins, sensitizes T cells. As M phi are constituents of many different organs and, moreover, communicate with T cells, their capacity to generate Au(III) may account for the various extrahepatic adverse immune reactions induced by Au(I) drugs.
Excessive fluid accumulation is associated with increased morbidity and prolonged convalescence after cardiopulmonary bypass. However, water fluctuations are difficult to assess solely on the basis of changes in body weight and fluid balance. Bioelectric impedance analysis is a simple, rapid, noninvasive bedside technique that measures the resistance of the body to a weak alternating current (50 kHz). The change in resistance is inversely proportional to the change in total body water. To investigate the relationship between body weight, fluid balance, and resistance, 18 patients who had cardiopulmonary bypass (9 men, 9 women, aged 61 +/- 3 years, weighing 80 +/- 4 kg, with ejection fraction 54% +/- 3% and bypass time 113 +/- 8 minutes [mean plus or minus standard error of the mean]) were followed up for 7 postoperative days. Body weight, fluid balance, and whole body and regional resistance were determined at 24-hour intervals. In the immediate postoperative period, fluid retention was accurately detected by simultaneous measurements of weight gain and decreased resistance (p < 0.001). Both measurements detected the initiation of diuresis by postoperative day 2 (p < 0.01). Whole body resistance returned to baseline values by day 7 (p > 0.05), and body weight returned to baseline on day 4 (p > 0.05). Change in weight and change in whole body resistance were highly correlated with cumulative fluid balance (r = 0.84, p < 0.001, and r = -0.81, p < 0.001, respectively), and these two measures were also related to each other throughout the study (r = -0.89, p < 0.001). The initial change in resistance was the best measurement associated with postoperative outcome (p < or = 0.01). The data suggest that the measurement of electric resistance across the body can accurately detect acute changes in total body water and in fluid redistribution through the body. However, determining the relative day-to-day change in whole body resistance seems more appropriate than calculating absolute fluid changes over time. Bioelectric impedance offers a simple, rapid, noninvasive method to monitor serial changes in total body water. This technique can be useful in situations in which rapid alterations in water compartments occur, and it may be useful in predicting outcome after cardiopulmonary bypass.
A computer program named MSEQ, based on graph theory has been implemented to aid the sequencing of peptides from collision-activated decomposition (CAD) spectra. Input data required by this program are: the molecular weight of the peptide, the list of the masses of the daughter ions and the masses of the N- and C-terminal groups. The output comprises a list of the most likely sequences with their respective scores and the assignments of the daughter ions. A set of probabilities for each fragment ion was computed from hundreds of CAD spectra obtained from our mass spectrometer. To date many peptides have been sequenced in our laboratory with the help of this program, and in most of them the real sequence ranks among the five top sequences. The program is able to differentiate isobaric amino acids such as leucine and isoleucine when the side-chain fragmentation appears in the spectrum. A criterion is used to discard those sequences that match the spectrum poorly from the earliest steps. The program is fast and consumes no memory.
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We examined the effect of indapamide (IND) on the development of atherosclerosis lesions in rabbits maintained on a 1% (wt/wt) cholesterol-enriched diet for a 16-week period. IND was supplemented to the diet at three different levels to correspond to doses of 0.1, 0.3, and 1 mg/kg/day. Throughout the treatment, dietary consumption and body weight gains were comparable among the experimental and control groups. IND had no significant effect on plasma cholesterol, triglycerides, or phospholipids concentrations. Despite the lack of effect of the drug on these parameters, its administration produced a tendency toward a reduction in the aortic content of cholesterol and a dose-dependent and significant decrease in aortic damage. In the aortic arch, the extent of intimal aortic surface covered by grossly discernible atherosclerotic lesions was decreased by IND 1 mg/kg/day from 11.02 +/- 1.10 to 6.00 +/- 1.00% (p < 0.05) and from 9.72 +/- 1.39 to 5.37 +/- 1.20% (p < 0.05) in the remaining thoracic sections. In addition, the former dose also reduced the number of lesions per square centimeter from 3.69 +/- 0.68 to 1.72 +/- 0.53% (p < 0.05), and from 3.37 +/- 0.85 to 1.55 +/- 0.46% (p < 0.05) in aortic arch and in thoracic sections, respectively. The possibility that IND reduces the development of atherosclerotic lesions produced by diet-induced hypercholesterolemia through a mechanism involving its calcium antagonist and/or its antioxidant activity is discussed.
The effect of recovery media and incubation temperature on the apparent heat resistance of three ATCC strains (4342, 7004 and 9818) of Bacillus cereus spores were studied. Nutrient Agar (NA), Tryptic Soy Agar (TSA), Plate Count Agar (PCA) and Milk Agar (MA) as the media and temperatures in the range of 15-40 degrees C were used to recover heated spores. Higher counts of heat injured spores were obtained on PCA and NA. The optimum subculture temperature was about 5 degrees C below the optimum temperature for unheated spores. No significant differences in heat resistance were observed with the different recovery conditions except for strains 4342 and 9818 when MA was used as plating medium. Large differences in D-values were found among the strains (D100 = 0.28 min for 7004; D100 = 0.99 min for 4342; D100 = 4.57 min for 9818). The 7004 strain showed a sub-population with a greater heat resistance. The z values obtained for the three strains studied under the different recovery conditions were similar (7.64 degrees C +/- 0.25).
We investigated the effect of ethanol on specific binding of [3H]MK-801 to the intrachannel phencyclidine (PCP) receptor site, as an index of change in the functional response of the N-methyl-D-Aspartate (NMDA)-associated ion channel. Saturation binding experiments were performed on synaptic membrane homogenates from adult rat cortex and hippocampus. [3H]MK-801 binding assays were conducted under conditions of basal, 10 microM glutamate, or 10 microM glutamate + 30 microM D-serine, with and without 50 or 100 mM ethanol. Association experiments of [3H]MK-801 binding (5 nM) were conducted under conditions of 0 or 10 microM glutamate, with varying concentrations of glycine (0.01, 0.10, and 10 microM) with and without 100 mM ethanol. Ethanol (50 and 100 mM) significantly decreased the percentage of high-affinity (open-channel state) MK-801 receptors with a concomitant increase in percentage of low-affinity receptors, but did not change high- and low-affinity constants of the two binding states. An ethanol-induced increase in the closed-channel receptor density in basal and activated conditions was suggested by the saturation experiments. Association experiments further explained this finding, in that ethanol (100 mM) significantly decreased fast component (open-channel) [3H]MK-801 binding in conditions of glycine (0.01-10 microM) only and activated conditions of glutamate + glycine (0.01-0.10 microM). However, the observed fast and slow kinetic rate constants of [3h]MK-801 binding, as well as total specific binding (fast + slow components), were not altered.(ABSTRACT TRUNCATED AT 250 WORDS)
Multifrequency bioelectrical impedance analysis was used to estimate the ratio of extracellular water (ECW) to total body water in subjects with end-stage renal disease. The body's resistance was measured at frequencies ranging from 1 kHz to 1 MHz. The impedance index (height2/resistance) determined at low frequency (5 kHz) correlated most closely with ECW (r = 0.886) using sodium bromide dilution as the standard of comparison. In contrast, the ratio of height squared to resistance determined at high frequency (500 kHz) correlated most closely with total body water (r = 0.974) using deuterium oxide dilution as the standard of comparison. The ratio of resistance at 500 kHz to resistance at 5 kHz was directly correlated (r = 0.767) with the ratio of ECW to total body water. Multifrequency bioelectrical impedance analysis may assist in the evaluation of body water distribution in endstage renal disease and other clinical disorders of fluid volume and/or distribution.
In [3H]serine-labelled granulosa cells treatment with TNF alpha (10 ng/ml) resulted in a transient decrease in cellular [3H]sphingomyelin and generation of [3H]ceramide that remained elevated 60 min later. In cells labelled with [methyl-14C]choline, TNF alpha induced a similar reduction in [14C]sphingomyelin content that was accompanied by a sustained elevation in [14C]phosphorylcholine levels. In FSH-primed cells, TNF alpha inhibited P450-AROM activity in a dose-dependent manner, an effect that was also observed in cells treated with bacterial sphingomyelinase (SMase 0.003-0.3 U/ml) or increasing concentrations (0.1-10 microM) of N-acetylsphingosine (C2-cer) a membrane-permeable analogue of ceramide. These results support the notion that sphingomyelin degradation to a bioeffector molecule ceramide, may be an early event involved in TNF alpha-induced signal transduction in granulosa cells.
Protein energy malnutrition is common among persons with ESRD and contributes substantially to morbidity and mortality. The usual methods of nutritional assessment, such as anthropometry, can be misleading because of altered tissue hydration. Bioelectrical impedance analysis (BIA) has been recommended by some as a practical nutritional assessment tool but has not been validated in patients with ESRD. Thirty-three stable patients on maintenance hemodialysis were evaluated in an ambulatory clinical research center with simultaneous BIA, dual-energy x-ray absorptiometry, and deuterium oxide (D2O) and sodium bromide (NaBr) isotope dilution studies. Standard determinations of total body water (TBW) and body cell mass (BCM) were obtained and compared with values estimated by BIA. Two separate outpatient BIA measurements were also obtained approximately 2 wk before and after the clinical research center evaluation. BCM estimated by BIA was directly correlated (r = 0.92, P < 0.0001) with BCM determined by DEXA and NaBr. TBW estimated by BIA was directly correlated (r = 0.96, P < 0.0001) with TBW determined by deuterium oxide dilution. The reactance to resistance ratio (Xc/R) derived from BIA was inversely correlated (r = -0.73, P < 0.0001) with the extracellular water/TBW ratio determined by NaBr/D2O. Bland-Altman analyses showed that for TBW, BIA was in excellent agreement with D2O dilution. BCM was modestly underestimated by BIA compared with the dual-energy x-ray absorptiometry/NaBr standard and was adjusted by linear regression. The coefficients of variation on repeated BIA measurements were below 4%, demonstrating test-retest reliability. BIA is a valid and reliable method of nutritional assessment in maintenance hemodialysis patients.