PubMed HealthSearch

Biomedical subjects

R Rodriguez

Publications and source records attributed to R Rodriguez.

At least 73 records · Page 4Linked to original sources

Vinorelbine as first-line chemotherapy for metastatic breast carcinoma.

PURPOSE: A phase II trial was performed to evaluate the efficacy and toxicity of vinorelbine (VNB) as first-line chemotherapy for metastatic breast carcinoma. PATIENTS AND METHODS: Between August 1991 and February 1993, 45 patients with metastatic breast cancer were entered onto the study. Therapy consisted of VNB 30 mg/m2 diluted in 500 mL of normal saline administered as a 1-hour intravenous infusion. Injections were repeated weekly until evidence of progressive disease (PD) or severe toxicity developed. RESULTS: One patient was considered not assessable for response. An objective response (OR) was observed in 18 of 44 patients (41%; 95% confidence interval, 26% to 56%). Three patients (7%) had a complete response (CR) and 15 (34%) had a partial response (PR). The median time to treatment failure for the entire group was 6 months (range, 1 to 15), and the median duration of response was 9 months (range, 1 to 15). The median survival duration has not been reached yet. There were no treatment-related deaths. The dose-limiting toxicity was myelosuppression. Leukopenia occurred in 35 patients (78%) and was grade 3 or 4 in 16 (36%). Phlebitis was observed in 19 of 29 patients (66%) who did not have central implantable venous systems. Fifteen patients (33%) developed peripheral neurotoxicity. Myalgia occurred in 20 patients (44%). CONCLUSION: VNB is an active drug against metastatic breast cancer with moderate toxicity, which justifies further evaluation in association with other agents.

Adult

Paromomycin resistance in Leishmania tropica: lack of correlation with mutation in the small subunit ribosomal RNA gene.

The aminoglycoside antibiotic paromomycin is a potentially useful anti-leishmanial chemotherapeutic agent. Resistance to this antibiotic was studied using Leishmania tropica. Promastigotes resistant to 210 micrograms/ml of paromomycin were selected by exposing them to gradual increments of this drug. Previous work in Escherichia coli, Tetrahymena, and yeast mitochondrial mutants has demonstrated mutations in the E. coli small subunit ribosomal RNA at the 1409:1491 basepair position, or equivalent positions in other organisms, resulting in basepair disruption. When the nucleotide sequence at both the DNA and RNA levels of the resistant L. tropica promastigotes cultured in the presence of paromomycin was compared with those of the drug-sensitive parent, there was no sequence change at the putative mutation site. Paromomycin resistance in L. tropica is apparently due to other mechanisms.

Animals

Physiological studies on gentamicin: phosphate repression of antibiotic formation.

The effect of inorganic phosphate on the fermentative production of gentamicin by Micromonospora purpurea has been studied using a chemically defined medium. Phosphate concentrations higher than 5.75 mM (1 g/liter-1) did not inhibit growth but specifically prevented antibiotic formation. Changes in the pH medium and carbon or nitrogen depletion were excluded as the cause of antibiotic underproduction. The use of a phosphate analogue, a protein synthesis inhibitor and the profiles of differential rate of antibiotic production suggested that phosphate itself transiently repressed gentamicin formation. Phosphate affected the formation of 2-deoxystreptamine from 2-deoxyinosose, a none phosphorylated substrate.

Arsenates

Hypocholesterolemia, hypertriglyceridemia, suicide, and suicide ideation in children hospitalized for psychiatric diseases.

To assess relationships of total plasma cholesterol (TC) and triglyceride (TG) values to suicide, suicide ideation, and hospitalization for psychiatric disease, we studied 220 children, ages 5 to 18 y, hospitalized with affective, adjustment, disruptive, anxiety, schizophrenic, other, and organic psychiatric disorders. The 135 male and 85 female patients had higher TG values (p = 0.0001 and 0.0003, respectively) and higher Quetelet Indices (p = 0.0001 and 0.003, respectively) than the 732 male and 316 female schoolchild controls; male patients had higher TC values than male controls (p = 0.014). Substance abuse in patients was an independent inverse determinant of TC value (p = 0.05); TG value correlated positively with alcohol use (p < or = 0.1) and substance abuse (p < 0.05). After covariance adjustment for age, race, sex, and Quetelet, children having adjustment disorders with depression had much lower covariance-adjusted TC value than control schoolchildren (3.91 versus 4.29 mmol/L, p = 0.003), whereas those with disruptive behavior with oppositional defiant disorder had much higher adjusted TC value (5.09 mmol/L, p = 0.0001). After covariance adjusting for age, race, sex, Quetelet, cigarette smoking, alcohol use, and substance abuse, children having adjustment disorders with concomitant depression had the highest group suicide tendencies (attempts and ideation) and the lowest covariance-adjusted TC value (4.03 mmol/L). Conversely, children having disruptive behavior with attention deficit hyperactivity disorder or disruptive behavior with oppoistional defiant disorder had 50% lower suicide index than those with adjustment disorders with concomitant depression and higher adjusted TC levels (4.45 and 5.12 mmol/L, p = 0.0003).(ABSTRACT TRUNCATED AT 250 WORDS)

Adjustment Disorders

Capillary electrophoresis of abnormal hemoglobins associated with alpha-thalassemias.

Capillary electrophoresis was evaluated for separation of hemoglobin species associated with alpha-thalassemias, and for identification of hemoglobin variants commonly found in the same human populations. Separation of hemoglobins was achieved using capillary isoelectric focusing with chemical mobilization; visible-wavelength absorbance detection was used to identify hemoglobins against a background of nonheme-containing proteins. This technique could easily differentiate hemoglobins Bart's and H (associated with alpha-thalassemias) from hemoglobin variants. Analysis of globin chains derived from intact hemoglobins was performed by free zone capillary electrophoresis under denaturing conditions. This technique was useful for distinguishing Hb Bart's and Hb H, and for confirming the identity of hemoglobin variants.

Electrophoresis

Characterization of a new oriental-mustard (Brassica juncea) allergen, Bra j IE: detection of an allergenic epitope.

Bra j IE, a major allergen from oriental-mustard (Brassica juncea) seeds, has been isolated and characterized. Its primary structure has been elucidated. This protein is composed of two chains (37 and 92 amino acids) linked by disulphide bridges. The amino acid sequence obtained is closely related to that previously determined for Sin a I, an allergen isolated from yellow mustard (Sinapis alba). A common epitope has been detected in the large chain of both Bra j IE and Sin a I by means of electroblotting and immunodetection with 2B3, which is a monoclonal antibody raised against the yellow-mustard allergen. A histidine residue of the large chain of both mustard allergens has been found to be essential for the recognition by 2B3 antibody. A synthetic multiantigenic peptide containing this His was recognized by 2B3 as well as by sera of mustard-hypersensitive individuals. Therefore this antigenic determinant must be involved in the allergenicity of these proteins.

2S Albumins, Plant

Stochastic dynamical aspects of neuronal activity.

A stochastic model of neuronal activity is proposed. Some stochastic differential equations based on jump processes are used to investigate the behavior of the membrane potential at a time scale small with respect to the neuronal states time evolution. A model for learning, implying short memory effects, is described.

Animals

Diffuse leptomeningeal melanomatosis of the spinal cord: a case report.

A rare case of diffuse leptomeningeal melanosis presenting with symptoms of spinal cord compression due to the presence of anterolateral arachnoid cyst and treated with Spetzler's drainage system is reported. The diagnosis of diffuse melanosis of the leptomeninges is rarely possible during life. In the present case MRI was of great help in the definition of the limits of the pathological process and the presence of the anterior compressing cyst. After laminectomy and a biopsy of the pathological tissue which achieved the histological diagnosis, an external drainage was inserted to reduce the cyst extension and to exclude the presence of melanocytes in the cystic fluid before a peritoneal shunt was placed. At 8th month of follow-up the patient is doing well with a dramatic reduction of symptoms and a significant reduction of spinal cord compression. The diagnostic role of MRI and the relationship between leptomeningeal melanosis and arachnoid cyst are discussed.

Adult

Synthesis of beta 2-microglobulin in lymphocyte culture: role of hemodialysis, dialysis membranes, dialysis-amyloidosis, and lymphokines.

Dialysis-amyloidosis (A beta 2M) is a recently recognized chronic complication in long-term dialysis patients, apparently effecting 5% to 10% of all dialysis patients. In 1985, Gejyo et al (Biochem Biophys Res Commun 129:701-706, 1085) and Shirahama et al (Lab Invest 53:705-709, 1985) identified beta 2-microglobulin (beta 2-M) as the major constituent protein of this unique type of systemic amyloidosis. The specific pathogenesis of A beta 2M remains unknown, although beta 2-M has been clearly identified as playing a central role as the amyloidogenic protein. To investigate the factors responsible for in vitro beta 2-M synthesis, we studied beta 2-M production by lymphocyte cultures obtained from dialysis patients and grown under a variety of different conditions, and compared the results to a control group of subjects with normal renal function. We could not demonstrate any stimulatory influence on beta 2-M synthesis by the hemodialysis treatment, the type of dialysis membrane used, or the clinical presence of A beta 2M. Rather, dialysis membranes, sterilized with ethylene oxide or gamma rays, added to the lymphocyte cultures exerted a strong dose-dependent inhibitory effect on beta 2-M synthesis. From the results of this study, we conclude that peripheral blood lymphocytes in uremic patients synthesize beta 2-M normally and that the direct interaction between circulating lymphocytes and the dialysis membrane that occurs during hemodialysis does not seem to contribute directly to beta 2-M synthesis.

Adult

Endoscopic and bioptic findings in the upper gastrointestinal tract in patients with Crohn's disease.

A prospective study was carried out on 41 patients diagnosed as having Crohn's disease (CD) to evaluate the degree of upper gastrointestinal tract involvement. In 23 patients (56%), endoscopic alterations were found most frequently affecting the antrum and duodenum. Lesions encountered were: Aphthoid erosions, ulcers, thickening of folds, nodules, erythema and stenosis. Granulomas were found in biopsies in 19.5% of the patients: They were more frequent in those demonstrating endoscopic alterations (26%) than in those with normal endoscopic findings (11%). Clinical evolution was favorable with conventional treatment for CD and ranitidine, although the endoscopic lesions did not totally disappear in any cases. We conclude that upper gastrointestinal endoscopy with biopsies is useful in evaluating the extension of disease and can be of diagnostic value in cases of indeterminate colitis.

Adult

Metastatic pattern and DNA ploidy in stage IV breast cancer at initial diagnosis. Relation to response and survival.

Sixty-nine patients with metastatic breast cancer (MBC) at initial diagnosis were analyzed to verify if metastatic pattern and clinical outcome are related to DNA ploidy determined by flow cytometry (FCM). Characteristics of 55 fully evaluable patients were as follows: median age: 61 years; postmenopausal: 75%; bone-only metastases (BM): 60%; extraosseous-only metastases (EM): 40%. Overall response rates (CR + PR) obtained with different chemotherapies and/or hormonal therapies were 58% and 68% for patients with BM and EM, respectively. Sixty percent of specimens resulted aneuploid, and the mean coefficient of variation of the complete series was 5.1%. In the whole group of patients DNA ploidy of primary tumor did not predict the metastatic pattern and had no influence upon response to treatment, duration of response, time to progression, and overall survival. When analyses were carried out according to metastatic pattern, those patients with BM showed similar results. However, within the group with EM, those with diploid tumors presented a significantly better survival (median 18 vs 13 months, p = .04). FCM-DNA analysis seems to identify a subgroup of patients with poor prognosis constituted by those who had aneuploid primary tumors and metastases to extraosseous sites.

Adenocarcinoma

Effects of accidental trauma on cytokine and endotoxin production.

OBJECTIVE: To determine the effects of accidental injury of varying severity on interleukin (IL)-1 alpha, IL-6, IL-8, tumor necrosis factor-alpha (TNF-alpha), and endotoxin release. DESIGN: Prospective, multi-unit, longitudinal study. SETTING: Emergency Departments and intensive care units of two university hospitals. PATIENTS: Trauma patients after mild, moderate, and severe injury (Injury Severity Score of < or = 10, 11 to 24, and > or = 25, respectively). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Plasma cytokine and endotoxin concentrations were measured over a 5-day period, starting within 2 hrs of accidental injury. An enzyme-linked immunosorbent assay was used to determine plasma concentrations of IL-1 alpha, IL-6, IL-8, and TNF-alpha. Plasma endotoxin concentrations were measured using a chromogenic limulus amebocyte assay. Preresuscitation samples obtained immediately on arrival in the Emergency Department, and within 2 hrs of injury, demonstrated significant increases of IL-6 and IL-8 concentrations in the severe injury group, in contrast to minimal increases seen after mild or moderate injury. Analysis of serial postresuscitation samples demonstrated rapid increases in IL-6 and IL-8 concentrations within 12 hrs of injury. IL-6 and IL-8 remained increased for 24 hrs after injury, then decreased markedly from their peak values during the next 24 hrs. Increased circulating concentrations of these cytokines continued to be present for > 5 days in the severely injured patients. IL-6 and IL-8 concentrations were only minimally increased in patients 8 and 24 hrs after moderate injury. Endotoxin and IL-1 alpha were not found in any samples, including those samples obtained serially from severely injured patients. No patient at any time point had TNF-alpha concentrations of > 35 pg/mL. CONCLUSIONS: These results demonstrate that severe injury produces rapid, large increases in circulating concentrations of IL-6 and IL-8 that may contribute to the frequent development of the adult respiratory distress syndrome and multiple organ system failure in this clinical setting.

Adult

Effects of the novel potassium channel opener, UR-8225, on contractile responses in rat isolated smooth muscle.

1. The effects of UR-8225 [(1,2-dihydro-4-(1,2-dihydro-2-oxo-1-pyridyl)-2,2-dimethyl-1-oxonapht halen-6- carbonitrile)] and levcromakalim were studied on the electrical and contractile responses induced by noradrenaline and KCl and on 86Rb+ efflux in rat aortic rings and on spontaneous mechanical activity in rat portal vein segments. 2. UR-8225 and levcromakalim, 10(-9) M-10(-5) M, relaxed the contractile responses induced by noradrenaline (IC50 = 2.7 +/- 0.4 x 10(-6) M and 6.6 +/- 1.3 x 10(-7) M, respectively) or 30 mM KCl (IC50 = 1.4 +/- 0.2 x 10(-7) M and 9.4 +/- 1.3 x 10(-8) M, respectively) more effectively than those induced by 80 mM KCl. The relaxant effect on noradrenaline-induced contractions was independent of the presence or absence of functional endothelium. 3. The vasorelaxant effect of UR-8225 and levcromakalim can be competitively antagonized by glibenclamide, an ATP-sensitive K+ channel blocker. There were no differences in the calculated pA2 values for glibenclamide to inhibit UR-8225- and levcromakalim-induced relaxations (7.61 +/- 0.08 and 7.69 +/- 0.10, respectively). The slope of the Schild plot yielded values not significantly different from unity (0.95 +/- 0.06 and 0.96 +/- 0.05, respectively). 4. UR-8225 (10(-5) M) hyperpolarized the resting aortic membrane potential from -50.7 +/- 0.7 mV to -66.0 +/- 2.0 mV and stimulated 86Rb+ efflux. 5. UR-8225 and levcromakalim inhibited the contractions induced by Ca2+ in aortae incubated in Ca(2+)-free PSS containing methoxyverapamil in the presence of noradrenaline. 6. Both drugs inhibited the amplitude of spontaneous activity in portal veins (IC50 = 5.1 +/- 1.4 x 10-8 M and 1.5 +/- 0.7 x 10-8 M, respectively), this effect being competitively antagonized by glibenclamide.7. These results indicated that UR-8225 exhibited qualitatively similar, but slightly less potent,vasorelaxant effects than those exerted by levcromakalim, which suggests that they can be related to its ability to activate ATP-sensitive K+ channels in vascular smooth muscle cells.

Animals

Ifosfamide and mitoxantrone as first-line chemotherapy for metastatic breast cancer.

PURPOSE: A phase II trial was performed to evaluate the efficacy and toxicity of a combination of ifosfamide (IFX) and mitoxantrone (MXN) as first-line chemotherapy for metastatic breast carcinoma. PATIENTS AND METHODS: Between January 1990 and August 1991, 48 patients with metastatic breast cancer were entered onto the study. Therapy consisted of IFX 2 g/m2 given as a 1-hour intravenous (IV) infusion on days 1 to 3; mesna 400 mg/m2 as an IV bolus immediately before and 4 hours after IFX administration and 2,000 mg orally 8 hours after IFX administration on days 1 to 3; and MXN 12 mg/m2 as an i.v. bolus on day 3. Cycles were repeated every 21 days until progressive disease (PD) or severe toxicity developed. RESULTS: One patient was considered not assessable for response. Objective regression (OR) was observed in 28 of 47 patients (60%; 95% confidence interval, 46% to 74%). Six patients (13%) had a complete response (CR) and 22 (47%) had a partial response (PR). The median time to treatment failure for the whole group was 9 months (range, 1 to 28); median survival was 19 months (range, 2 to 28). There were no treatment-related deaths. The limiting toxicity was myelosuppression. Leukopenia occurred in 37 patients (77%) and was grade 3 or 4 in 19 patients (40%). Nausea and vomiting were observed in 38 patients (80%), mucositis in 16 patients (33%), and grade 2 hematuria in two patients (4%). Eight patients (16%) developed mild neurotoxicity. CONCLUSION: The combination of IFX plus MXN is an active regimen against metastatic breast cancer with moderate toxicity that deserves further evaluation.

Adult

Auditory system degeneration in Alzheimer's disease.

We observed a highly topographically specific and consistent pattern of degeneration in the auditory system of Alzheimer's disease (AD) patients. Senile plaques (SP) and neurofibrillary tangles (NFT) were distributed throughout the ventral nucleus of the medial geniculate body (MGB) and the central nucleus of the inferior colliculus (IC) in nine of nine AD patients. Adjacent nuclei within the MGB and IC were consistently spared. NFT and SP were also present in the primary auditory and the auditory association cortices. In all control tissues, there were neither SP nor NFT in any of the above sites. The cochlear nuclei were normal in tissues from both AD and control patients. The ventral nucleus of the MGB is the major thalamic relay station for auditory function and receives fibers from neurons of the central nucleus of the IC, with projections arranged tonotopically in a laminar pattern corresponding to a gradient of high-to-low frequency ranges. The degenerative changes distributed throughout these nuclei suggest that neuronal loss may include all frequency ranges in AD. In contrast, the clinical features of presbycusis in elderly patients include only high-frequency loss due to lesions peripherally in the cochlea or auditory nerves, rather than in the central auditory nuclei. These histologic changes in the brains of AD patients may provide an additional basis for altered cognitive function due to primary sensory deafferentation.

Aged

Community health organizing: whom are we empowering?

Current strategies for initiating and operating community health programs rely on one of two approaches. One is a predetermined, operational process. The other comes from the grassroots, beginning with involvement of the recipients of the program. This editorial chronicles how one grassroots program, begun by volunteer mothers and one community health nurse, developed into a partnership for primary health care that advocates and empowers the entire community. In the end, the editorial challenges community health organizers to ask whom their programs are empowering--the community or the organizers themselves?

Community Health Services