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Biomedical subjects

J Gonzalez

Publications and source records attributed to J Gonzalez.

At least 19 recordsLinked to original sources

Conformal prostate brachytherapy: initial experience of a phase I/II dose-escalating trial.

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.

Adenocarcinoma

Ultrasound-guided high dose rate conformal brachytherapy boost in prostate cancer: treatment description and preliminary results of a phase I/II clinical trial.

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.

Adenocarcinoma

Biochemical, immunological, and biological characterization of Trypanosoma cruzi populations of the Andean north of Chile.

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.

Animals

Bioelectric impedance detects fluid retention in patients undergoing cardiopulmonary bypass.

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.

Adult

Effects of indapamide on atherosclerosis development in cholesterol-fed rabbits.

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.

Administration, Oral

The effect of recovery conditions on the apparent heat resistance of Bacillus cereus spores.

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).

Bacillus cereus

Alteration of [3H]MK-801 binding associated with the N-methyl-D-Aspartate receptor complex by acute ethanol in rat cortex and hippocampus in vitro.

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)

Animals

Ceramide mediates tumor necrosis factor effects on P450-aromatase activity in cultured granulosa cells.

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.

Animals

Nutritional assessment with bioelectrical impedance analysis in maintenance hemodialysis patients.

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.

Absorptiometry, Photon

Improved local control and survival for surgically staged patients with locally advanced prostate cancer treated with up-front low dose rate iridium-192 prostate implantation and external beam irradiation.

PURPOSE: In an effort to improve upon the historically poor local control and survival rates for locally advanced prostate carcinoma, a prospective multidisciplinary clinical trial was initiated using low dose rate Iridium-192 prostate implantation and external beam irradiation. METHODS AND MATERIALS: Between January 1983 and September 1989, 57 patients with newly diagnosed bulky prostatic carcinoma (5 Stage B2, 52 Stage C) were treated at the Mayo Clinic (34 patients) and William Beaumont Hospital (23 patients) with (a) 5 Gy delivered preoperatively in one fraction, (b) pelvic lymphadenectomy with interstitial implantation of the prostate using Iridium-192 seeds via a perineal template to 30-35 Gy, and (c) 30.6 Gy external irradiation to prostate only in 17 fractions. RESULTS: After lymphadenectomy, 30/57 (53%) patients had pathologically confirmed positive lymph nodes or "D1" disease. Thirty-four patients (60%) had Gleason scores > or = 7. Mean age at diagnosis was 63.3 years. Median overall follow-up was 72 months. The 5-year actuarial survival rate was 85% and disease-free survival was 63%. The 5-year survival for patients with negative nodes was 93% and with positive nodes was 79%. The corresponding survival for patients with Gleason scores < or = 6 was 96% and > or = 7 was 78%. Multivariate analysis demonstrated that of all covariates considered, only Gleason score had prognostic significance for disease-free survival (p < 0.05) and no covariates were statistically significant for overall survival. Thirty-nine of the 57 patients had a prostatic re-biopsy performed at 18 months. Pathologically confirmed local control was ultimately achieved in 31/39 (79.5%). There was no difference in survival in patients with positive re-biopsies vs. those with negative results. The 5-year actuarial rate of clinical local control was 94%. Three patients clinically failed locally and 21 demonstrated distant progression. The median time to progression was 34 months. Nineteen percent received some form of hormonal manipulation at the time of their treatment course and an additional 42% were treated with hormones during their follow-up period, primarily after distant failure. The grade 4 rectal ulceration rate decreased to 4.5% with modification of the brachytherapy technique. Three patients experienced grade 4 urinary incontinence and three patients experienced grades 3 or 4 chronic perineal pain. CONCLUSION: These results indicate that bulky prostate carcinoma can be successfully controlled locally by this novel and aggressive approach with moderate toxicity and improved survival.

Adenocarcinoma

Bacteraemia caused by Campylobacter spp.

The genus Campylobacter has become increasingly recognised as the cause of various infections. Campylobacter jejuni and C coli cause acute gastroenteritis in man all over the world. C jejuni enteritis can lead to bacteraemia, but its actual incidence remains unknown. Seven cases of bacteraemia caused by C jejuni or C coli are reported, from the blood of seven patients: five immune deficient adults; a newborn baby; and a patient who had had abdominal surgery. Patients who develop diarrhoea as a result of Campylobacter infection are at risk of bacteraemia thereafter.

Adolescent

Validation of different techniques for the diagnosis of ventilator-associated pneumonia. Comparison with immediate postmortem pulmonary biopsy.

To assess the accuracy of clinical parameters for the diagnosis of ventilator-associated (VA) pneumonia, as well as the diagnostic value of several invasive techniques, such as protected specimen brush (PSB), bronchoalveolar lavage (BAL), fiberoptic bronchial aspirates (FBAS), and percutaneous lung needle aspiration (PLNA), we compared the results of these techniques with the histopathology of immediate postmortem pulmonary biopsies, considered the "gold standard" reference test. We studied 30 mechanically ventilated patients (age 52 +/- 21 yr; mechanical ventilation period 9 +/- 7 days) who died in an intensive care unit. All patients received prior antibiotic treatment. The following procedures were performed immediately after death: bilateral PSB, BAL, FBAS, and PLNA, as well as bilateral minithoracotomies to obtain pulmonary biopsies as close as possible to the area sampled with the other techniques. According to the histopathology 18 patients had pneumonia and 12 did not. The presence of fever (sensitivity 55%, specificity 58%), purulent secretions (sensitivity 83%, specificity 33%), and chest radiograph infiltrates (sensitivity 78%, specificity 42%) could not differentiate in all instances presence from absence of pneumonia. Quantitative bacterial cultures of lung biopsies using 10(3) cfu/g as a cutoff point had low sensitivity (40%) and low specificity (45%) and could not differentiate the histologic absence or presence of pneumonia. Considering the histopathology of pulmonary biopsies as a gold standard, we found the following sensitivities for PSB, BAL, FBAS, and PLNA: 36, 50, 44, and 25%. The specificities were 50, 45, 48, and 79%, respectively. The sensitivities and specificities of different invasive techniques are much lower than those reported in clinical studies.(ABSTRACT TRUNCATED AT 250 WORDS)

Anti-Bacterial Agents

Ventilator-associated pneumonia by Staphylococcus aureus. Comparison of methicillin-resistant and methicillin-sensitive episodes.

All episodes of ventilator-associated pneumonia (VAP) caused by Staphylococcus aureus were prospectively analyzed for a 30-mo period. Methicillin-sensitive S. aureus (MSSA) was isolated in 38 episodes and methicillin-resistant S. aureus (MRSA) in 11 others. The two groups were similar regarding sex, severity of underlying diseases, prior surgery, and presence of renal failure, diabetes, cardiopathy, and coma. MRSA-infected persons were more likely to have received steroids before developing infection (relative risk [RR] = 3.45, 95% confidence interval [CI] = 1.38-8.59), to have been ventilated > 6 d (RR = 2.03, 95% CI = 1.36-3.03), to have been older than 25 yr (RR = 1.50, 95% CI = 1.09-2.06), and to have had preceding chronic obstructive pulmonary disease (RR = 2.76, 95% CI = 0.89-8.56) than MSSA-infected patients. MSSA-infected persons were more likely than MRSA-infected patients to have cranioencephalic trauma (RR = 1.94, 95% CI = 1.22-3.09). All patients with MRSA VAP had previously received antibiotics, compared with only 21.1% of those with MSSA infection (p < 0.000001). The incidence of empyema was similar in both groups; nevertheless, the presence of bacteremia and septic shock was more frequent in the MRSA group. Finally, mortality directly related to pneumonia was significantly higher among patients with MRSA episodes (RR = 20.72, 95% CI = 2.78-154.35). This analysis was repeated for monomicrobial episodes, and the difference remained statistically significant. We conclude that MRSA and MSSA strains infect patients with different demographic profiles; previous antibiotic therapy is the most important risk factor for developing MRSA infection.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult