Biomedical subjects
J Gonzalez
Publications and source records attributed to J Gonzalez.
Increased prevalence of genotype F hepatitis B virus isolates in Buenos Aires, Argentina.
The genomic coding region of the hepatitis B surface antigen (HBsAg) was partially sequenced from 12 HBsAg-positive sera of carriers residing in Buenos Aires, Argentina. A phylogenetic analysis groups the 12 isolates into genotypes A (n = 4), B (n = 1), D (n = 2), and F (n = 5). The occurrence of genotypes A and D is not unexpected, considering the mainly European origin of the studied population. The high prevalence of genotype F and its genetic composition support the suggestion that F strains originated in native populations of the New World.
Reversible high rate atrial fibrillation dilated cardiomyopathy.
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Plasma membrane calcium ATPase isoform expression in cultured rat mesangial cells.
The maintenance of intracellular ionized calcium (iCa2+) in the submicromolar range is important for mesangial cell (MC) function, and, as in most mammalian cells, plasma membrane Ca(2+)-ATPases (PMCA) play an important role in the homeostatic process. Molecular studies have demonstrated four PMCA isoforms, each with multiple splice variants. The present study examines the expression of PMCA isoforms and calmodulin-binding region splice variants in cultured MC from Sprague-Dawley rats and from spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats before and after the onset of hypertension in SHR. Using reverse transcription-polymerase chain reaction (RT-PCR) and Southern blot analyses, we have demonstrated PMCA1, -3, and -4, but not PMCA2, to be present in MC from these rat strains. Splice variant analysis revealed PMCA1a and -1b, PMCA3a, -3b, and -3c, and PMCA4a and -4b to be expressed in MC from all three strains. The relative quantities of PMCA1 and PMCA4 mRNA were not different in age-matched SHR vs. WKY rats, correlating with similar iCa2+ measurements. The expression of all three isoforms declined with age in SHR and WKY.
Unique CD8+ T cell-rich lymphoid aggregates in human uterine endometrium.
Using confocal scanning laser microscopy of viable tissue sections, we have demonstrated organized lymphoid aggregates (LA), that have a unique structure, in the stratum basalis of uterine endometrium. These LA consist of a core of B cells surrounded by more numerous T cells and an outer halo of monocytes/ macrophages. The T cells in the LA were almost exclusively CD8+CD4-. These CD8+ LA, in terms of both their T cell and B cell components, were either small or absent during the early proliferative stage of the menstrual cycle, significantly larger in size at mid-cycle and during the secretory phase, and absent in post-menopausal women, suggesting that their development is hormonally influenced. This new finding of a menstrual cycle-dependent, phenotypically unique, organized immune cell structure may lead to new insights into the mechanisms by which the endometrium accepts a semiallogeneic graft while providing resistance to infectious organisms.
The efficacy of intravesical Tice strain bacillus Calmette-Guerin in the treatment of interstitial cystitis: a double-blind, prospective, placebo controlled trial.
PURPOSE: Interstitial cystitis is a debilitating bladder disease of unknown etiology with no cure. A recent report suggested that bacillus Calmette-Guerin (BCG) may be effective in the treatment of interstitial cystitis. A randomized, prospective, double-blind, placebo controlled trial to evaluate the safety and efficacy of intravesical BCG in treating interstitial cystitis was done. MATERIALS AND METHODS: Patients meeting the National Institute of Arthritis, Diabetes and Digestive and Kidney Diseases criteria for interstitial cystitis received 6 weekly instillations of Tice strain BCG or placebo. Periodic questionnaires, voiding diaries and cystometrograms were obtained. A total of 30 evaluable subjects was enrolled in the study with a mean followup of 8 months (range 6 to 13). Based on an exit questionnaire a responder was defined as one who rated the interstitial cystitis symptoms as moderately improved or better. RESULTS: A 60% BCG response rate was noted, compared to a 27% placebo response rate. Minimum voided volume and quality of life improved in the BCG group compared to placebo. Adverse events were similar in each group, mostly irritative in nature, and no significant systemic events were noted. CONCLUSIONS: Intravesical Tice strain BCG appears to be safe and efficacious in the treatment of interstitial cystitis. Additional studies must be performed to confirm the results of this pilot study.
Treatment options for localized prostate cancer based on pretreatment serum prostate specific antigen levels.
PURPOSE: We reviewed all available literature on early stage prostate cancer treatment in which pretreatment serum prostate specific antigen (PSA) levels were used to stratify patients. We determined if any conclusions could be reached regarding the optimal therapy of this disease. MATERIALS AND METHODS: A MEDLINE search was conducted to obtain all articles in English on prostate cancer treatment from 1986 to 1996 in which PSA levels were used to stratify patients and evaluate outcome. Studies were considered eligible only if they met all criteria of pretreatment PSA values recorded and grouped for subsequent evaluation, posttreatment PSA values monitored continuously, definitions of biochemical control stated and median followup given. RESULTS: Of the 16 surgical studies identified only 3 met the inclusion criteria. Of the 30 radiation therapy articles identified 15 met the inclusion criteria, including 2 on conformal external beam radiotherapy, 8 on conventional external beam radiotherapy and 5 on interstitial brachytherapy. No studies using neutrons or combined hormonal therapy with surgery or radiotherapy were identified in which patients were stratified by pretreatment PSA. Results for all therapies were extremely variable with the 3 to 5-year rates of biochemical control ranging from 48 to 100% for patients with a pretreatment PSA of less than 4 ng./ml., 44 to 90% for PSA more than 4 to 10 ng./ml. and 27 to 89% for PSA more than 10 to 20 ng./ml. Even using the same treatment modality, a wide range of results were obtained. No treatment option consistently produced superior results. CONCLUSIONS: When data were reviewed from studies using pretreatment serum PSA to stratify patients, no consistently superior treatment option in the radiotherapy or surgical literature emerged. These data suggest that standard definitions of disease stage and biochemical cure must be adopted to evaluate treatment efficacy and advise patients on the most appropriate treatment option for the disease.
CD4+ T-lymphocytopenia in severe pulmonary tuberculosis without evidence of human immunodeficiency virus infection.
SETTING: A large public hospital in Buenos Aires, Argentina. OBJECTIVE: To determine the number of blood CD4 and CD8 T-lymphocytes in male human immunodeficiency virus (HIV) negative patients with severe pulmonary tuberculosis. DESIGN: Seventeen patients with severe pulmonary tuberculosis (SPT), with a mean age of 44.1 years, all HIV negative, had on admission lost 20% or more of their normal weight. Ten male HIV negative pulmonary tuberculosis patients (PT), with a mean age of 25.2 years, in good general condition, acted as a control group. Patients from both groups had a blood CD4/CD8 count before treatment. RESULTS: In the SPT patients, the CD4/CD8 count before treatment yielded a mean of 341.25 +/- 142.73/ mm3 for CD4 and 259.33 +/- 100.89/mm3 for CD8. Three patients died a few weeks after starting treatment; on admission they had 180,220 and 280 CD4/ mm3, respectively. Patients in good general condition yielded 721.40 +/- 272.20 for CD4 (P < 0.01, t = 4.216) and 416.67 for CD8. At the same time, five normal volunteers, with a mean age of 35.60 +/- 10.45 years, had mean CD4 and CD8 counts of 906 +/- 75.37 and 360 +/- 190.79, respectively. CONCLUSION: Based on the findings of this study, we feel that it is of value to measure the CD4 and CD8 T-lymphocyte counts in STP patients with a compromised general condition and with significant weight loss at the beginning of treatment. Those patients with a CD4 count of < 300/mm3 have a very poor prognosis and, in addition to the regular antituberculosis drugs, will require intensive care during the first weeks of treatment.
[Hepatitis A virus infection in children in Argentina: a pilot study].
UNLABELLED: The severity and/or the prognostic of infections with the hepatitis A virus (HAV) is related to the age at which the infection occurs. Since transmission of the virus occurs by the fecal-oral route, the prevalence and age-relate incidence of infection is determined by the adequacy of sanitation hygienic measures and the socio economic level of exposed populations. Thus, the disease is having an increasing impact in developing countries with improving sanitary standards whereas inhabitants of industrialized countries are particularly at risk while visiting under-developed countries. We have established a cooperative group for the serologic study of children range between six months to ten years old, without sintomatology of acute hepatitis. The patients live in Buenos Aires, San Justo, Trelew, Rosario and Tucumán cities. We studied 3699 children. The specific Ab-antiHAV IgG were measured by enzyme immunoassay with commercial available kits (Organon and-or Abbott). The variable of study were age, sex and water quality. RESULTS: 45.19% were of San Justo, 26.15% of Rosario, 13% of Buenos Aires, 8.37% of Trelew and 7.29% of Tucumán. We observed the highest of possibility percentage (%POS) in Tucumán (81.4%), followed by San Justo (57.8%), Rosario (46.5%), Trelew (41.99%) and Buenos Aires (29.4%). In all the cities the lowest %POS was found in children under three years old. Between three and six years old the results were variable and an increase in %POS was observed related to the growth. The global %POS was 51.56%. CONCLUSIONS: This study confirms Argentina as a high endemic country for HAV infection. A global vaccination program is the only strategy that has the potential to prevent recurrent epidemics of hepatitis A and its erradication.
Assessing the variability of outcome for patients treated with localized prostate irradiation using different definitions of biochemical control.
PURPOSE: Biochemical control using serial posttreatment serum prostate specific antigen (PSA) levels is being increasingly used to assess treatment efficacy for localized prostate cancer. However, no standardized definition of biochemical control has been established. We reviewed our experience treating patients with localized prostate cancer and applied three different commonly used definitions of biochemical control to determine if differences in therapeutic outcome would be observed. METHODS AND MATERIALS: Between January 1987 and December 1991, 480 patients with clinically localized prostate cancer received external beam irradiation (RT) using localized prostate fields at William Beaumont Hospital. The median dose to the prostate was 66.6 Gy (range 58-70.4) using a four-field or arc technique. Pretreatment and posttreatment serum PSA levels were recorded. Over 86% (414 of 480) of patients had a pretreatment PSA level available. Three different definitions of biochemical control were used: (a) PSA nadir < 1 ng/ml within 1 year of treatment completion. After achieving nadir, if two consecutive increases of PSA were noted, the patient was scored a failure at the time of the first increase; (b) PSA nadir < 1.5 ng/ml within 1 year of treatment completion. After achieving nadir, if two consecutive increases of PSA were noted, the patient was scored a failure at the time of the first increase; (c) Posttreatment PSA nadir < 4 ng/ml without a time limit. Once the nadir was achieved, if it did not rise above normal the patient was considered to be biochemically controlled. Clinical local control was defined as no palpable prostate nodularity beyond 18 months, no new prostate nodularity, or a negative prostate biopsy. RESULTS: Median follow-up was 48 months (range 3-112). Pretreatment PSA values were correlated with treatment outcome using the three definitions of biochemical control as well as clinical local control. Pretreatment PSA values were stratified into five groups (Group 1: PSA < 4; Group 2: PSA 4-10; Group 3: PSA 10-15; Group 4: PSA 15-20; and Group 5: PSA > 20), and 5-year actuarial rates of biochemical control were calculated using the three biochemical control and one clinical local control definitions. For Group 1, 5-year actuarial rates of biochemical control were 84%, 90%, 91%, and 96% for Definitions 1-3 and clinical local control, respectively. For Group 2, 5-year actuarial control rates were 45%, 54%, 74%, and 92% for the four definitions, respectively. For Group 3, 5-year actuarial control rates were 26%, 31%, 63%, and 100% for the four definitions, respectively. For Group 4, 5-year actuarial control rates were 24%, 24%, 50%, and 100% for the four definitions, respectively. Finally, for Group 5, 5-year actuarial control rates were 5%, 14%, 15%, and 89% for the four definitions, respectively. Depending on the definition used, statistically significant differences overall in outcome rates were observed. Differences between all four definitions for all pairwise comparisons ranged from 5 to 53% (p < 0.001). CONCLUSION: When different definitions of biochemical control are used in assessing treatment outcome, significantly different rates of success are noted. Until a standardized definition of biochemical control is adopted, differences in treatment outcome cannot be meaningfully compared.
Effect of the position of a basic amino acid on C-terminal rearrangement of protonated peptides upon collision-induced dissociation.
Internal rearrangement involving the loss of the C-terminal amino acid residue upon collision-induced dissociation (CID) or metastable decomposition was studied for protonated peptides. To investigate the structural characteristics of peptides responsible for this rearrangement, a series of synthetic peptides were prepared and subjected to B/E-linked scan or tandem mass spectrometric analyses using a four-sector instrument. The results showed that the position of a basic amino acid in the peptide sequence and its basicity have a significant influence on the rearrangement. Arginine (Arg) located at the n-1 position facilitates the rearrangement with about twice as many rearrangement ions as is observed for the other Arg-containing peptides. This can be attributed to the interaction of a positively charged guanidino group of Arg with its own carbonyl group via a salt bridge which is tightly formed in vacuo between a guanidino and carboxylate groups, the mechanism of which is analogous to that previously proposed for the formation of similar rearrangement ions observed in the spectra of metal-cationized peptides. This association would result in the facile attack of the C-terminal hydroxyl group on the penultimate carbonyl group, leading to the rearrangement. In addition, the rearrangement ion was observed both in metastable decomposition and high-energy CID spectra obtained by B/E-linked scan analyses without or with gas, respectively, but in a sequence dependent manner.
Remission of hypercalciuria in patients with tuberculosis after treatment.
The hypercalciuria evolution and other bone metabolism parameters were evaluated in patients with tuberculosis after treatment. Twenty-two patients with tuberculosis and 54 normal subjects were studied; they consumed an average diet (calcium intake 1000 mg/day). Ten of these patients and nine normal subjects were also studied after a low calcium diet (400 mg/calcium/day) and after a load of oral calcium of 1000 mg (calcium absorption test). The study with an average diet was performed after 1 week (basal) and 3, 6, and 12 months after the antituberculosis treatment was started; the calcium absorption test was carried out 2 weeks, 3 and 12 months after the treatment was started. On an average diet, patients with tuberculosis presented, at baseline state, lower calcidiol levels than normal controls. Serum calcitriol levels at baseline were higher than at 6 and 12 months. Serum parathyroid hormone (PTH) levels in patients with tuberculosis were lower than in normal controls at baseline, but these levels were similar to controls at 3, 6, and 12 months after treatment. During the calcium absorption test and under basal conditions, patients with tuberculosis showed lower serum PTH and calcidiol levels in all the dietetic situations than in normal controls. However, serum calcitriol levels were higher than in controls after the restrictive diet. After 3 months of treatment, urinary calcium excretion was normal in patients with tuberculosis during the average and low diets, but higher than in control group after calcium load. After 12 months of treatment, all the biochemical parameters of the patients with tuberculosis were similar to the control group under all the dietetic situations. These data indicate that antituberculous treatment, although it may contribute to the production of some alteration in the calcium and vitamin D metabolism, basically favors the correction of disturbances associated with tuberculosis.
Relationship between ventilator-associated pneumonia and intramucosal gastric pHi: a case-control study.
PURPOSE: Prior investigations have suggested a clear relationship between nosocomial pneumonia and intramucosal gastric pH (pHi), a probable marker of bacterial translocation. METHODS: We studied 33 patients (18 with pneumonia and 15 without) admitted to an intensive care unit and hospitalized longer than 72 hours with the aim of assessing the relationship between nosocomial pneumonia, pHi, and outcome. pHi was estimated at the time of inclusion of patients into the study. Arterial pH (pHa) and bicarbonate and stomach pH and tonometer PtCO2 were also recorded. Values of < 7.32 or delta pHa-pHi of > +0.06 were used to differentiate between normal and low pHi. Quantitative cultures of pharyngeal swabs, gastric lumen, and protected specimen brush from lower airways were also done. RESULTS: The mean pHi values were 7.397 +/- 0.105 (range, 7.14 to 7.53) and 7.452 +/- 0.059 (range, 7.37 to 7.56) for patients with and without pneumonia, respectively (P = .073). Five patients, all with pneumonia, had pHi < 7.32. No patients without pneumonia had pHi < 7.32 (P = .04). The mean delta pHa-pHi was 0.04 +/- 0.07 (range, -0.11 to 0.13) and 0.05 +/- 0.09 (range, -0.09 to 0.28; P = .72) for patients with and without pneumonia, respectively. However, there were significant differences when tonometer PtCO2 values of both groups were compared (38.9 +/- 8.3 and 30.6 +/- 4.7 mm Hg, respectively; P = .025). Patients with pneumonia had higher alkaline gastric lumen pH (5.2 +/- 1.0) than those without pneumonia (3.8 +/- 1.4; P = .006). Nonsurvivors (n = 7) had more acidic pHi (7.33 +/- 0.11) than survivors (7.44 +/- 0.06; P = .045). The mean gastric lumen bacterial concentration was 4.14 +/- 1.01 Log10 CFU/mL in patients with pneumonia and 4.28 +/- 1.22 Log10 CFU/mL in patients without pneumonia (P = NS). When patients with and without intramucosal gastric acidosis (pHi < 7.32) were compared, the gastric bacterial burden was 4.42 +/- 0.82 Log10CFU/mL and 4.32 +/- 1.03 Log10 CFU/mL (P = .08), respectively. CONCLUSIONS: Most patients with nosocomial pneumonia had no associated intramucosal gastric acidosis. However, low pHi was associated with increased mortality.
Cutaneous T-cell lymphoma, tropical spastic paraparesis, cerebral vasculitis, and protein S deficiency in a patient with HTLV-I.
The clinical spectrum of retroviruses is expanding rapidly. Human T-cell lymphotropic virus type I (HTLV-I) was the first retrovirus to be described, and its role had been established in adult T-cell leukemia/lymphoma and tropical spastic paraparesis. We report the case of a 35-year-old woman with HTLV-I and the unusual combination of cutaneous T-cell lymphoma, tropical spastic paraparesis, cerebral vasculitis, and protein S deficiency. We discuss the relationship of all her diseases to HTLV-I.
Cytolytic response to HIV in patients with HIV disease treated with extracorporeal photochemotherapy: preliminary study.
Extracorporeal photochemotherapy (photopheresis), an immunomodulatory therapy that targets circulating T helper lymphocytes, has been applied to the management of human immunodeficiency virus (HIV) disease. Any therapy that exerts its actions on CD4+ T cells has the potential of exacerbating HIV infection. Therefore, it was necessary to observe immune function during treatment. Because cytotoxic T lymphocytes (CTL) and natural-killer cells are thought to play an important role in the response against HIV infection, we examined the effect of photopheresis on HIV cytolytic activity. The study group consisted of seven patients with late-stage HIV disease who had not received any previous treatment for HIV infection. Patients were treated exclusively with photopheresis on two consecutive days each month for 14-32 months (average, 25 months). Peripheral lymphocytes, collected at various points during treatment, were used as effectors in a 51Cr release assay. Epstein-Barr virus (EBV)-transformed autologous B cell lines transfected with recombinant vaccinia vectors that expressed the HIV env (gp120, gp41) and gag (p24) proteins were used as target cells. All seven patients demonstrated relatively constant levels of cytolysis (>10% above controls) during treatment in the context of stable CD4+ T cell counts and a stable clinical status. These results suggest that extracorporeal photochemotherapy did not impair the cytolytic response to HIV infection and may have enhanced it in some patients.
Nosocomial pneumonia during mechanical ventilation.
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Chronic central nervous system exposure to interleukin-1 beta causes catabolism in the rat.
Interleukin-1 (IL-1) and interleukin-6 (IL-6) are thought to play a role in mediating weight loss, net protein catabolism, anorexia, and fever after infection or injury. Because IL-1 and IL-6 can be synthesized in the brain and have been shown to be increased in central nervous system (CNS) infections, we investigated the metabolic consequences of prolonged CNS exposure to these cytokines. At equivalent doses, intracerebroventricular infusion of IL-1, but not IL-6, caused negative nitrogen balance, weight loss, and anorexia. Intracerebroventricular infusion of IL-1 also caused adrenocortical activation, as indicated by increased adrenal weight and plasma corticosterone, and decreased thymus weight. However, clamping plasma glucocorticoids at low levels by adrenalectomy and corticosterone pellet replacement did not attenuate IL-1-induced losses of body weight and nitrogen. We conclude that centrally produced IL-1 could play an important role in the metabolic alterations associated with CNS injury or infection and that these effects may not be solely attributable to increased secretion of glucocorticoids.