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Biomedical subjects

S Rodriguez

Publications and source records attributed to S Rodriguez.

At least 55 records · Page 3Linked to original sources
PubMed1997

Effects of oral rabeprazole on oesophageal and gastric pH in patients with gastro-oesophageal reflux disease.

BACKGROUND: This study examined the dose-response effects of the new proton-pump inhibitor rabeprazole on oesophageal and gastric pH in patients with gastro-oesophageal reflux disease. METHODS: This study had a single-centre, double-blind, randomized, two-way crossover design. Twenty patients were treated for two 7-day periods separated by a 7-10-day washout period. Patients were randomly assigned to receive either 20 mg of rabeprazole once daily during the first treatment period and 40 mg once daily during the second treatment period, or 40 mg during the first treatment period and 20 mg during the second treatment period. The primary efficacy variable was oesophageal acid exposure determined by 24-hour ambulatory pH monitoring. Acid-reflux time was defined as the percentage of time over 24 h that oesophageal pH was < 4. A dosage was considered effective if reflux time was reduced to < 6%, a number which has been our internal laboratory reference. RESULTS: Both rabeprazole 20 mg and 40 mg, given once daily, normalized reflux time, with decreases of 79% and 92% in acid exposure by day 7. Both dosages also decreased the mean total number of reflux episodes and the number of episodes lasting > 5 min, with no significant differences between dosages for any reflux parameter. Mean gastric pH increased with 20 mg from 1.86 at baseline to 3.71 on day 1 and 4.17 on day 7. Rabeprazole 40 mg once daily increased gastric pH from 2.01 to 4.37 on day 1, and to 4.65 on day 7. Safety analyses revealed no significant acute side-effects for either dosage. CONCLUSIONS: Pathological oesophageal acid exposure was normalized with both 20 mg and 40 mg dosages of rabeprazole, and the effects of these two doses did not differ. Rabeprazole was well-tolerated in this short-term study.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1996

Randomized, double-blind, placebo-controlled dose-ranging study of tirofiban (MK-383) platelet IIb/IIIa blockade in high risk patients undergoing coronary angioplasty.

OBJECTIVES: The objectives of this double-blind, placebo-controlled, randomized dose-ranging study were 1) to examine the safety and tolerability of tirofiban (MK-383), a new nonpeptide platelet IIb/IIIa receptor antagonist, on a background of intravenous heparin and aspirin therapy; 2) to study the pharmacodynamics and pharmacokinetics of tirofiban; and 3) to evaluate the incidence of adverse cardiac outcomes (urgent repeat revascularization, myocardial infarction and death) with tirofiban versus placebo in a high risk subset of patients undergoing coronary angioplasty. BACKGROUND: Abrupt vessel closure complicates 4% to 8% of angioplasty procedures. Recent data have suggested that agents that antagonize the platelet glycoprotein IIb/IIIa receptor may reduce the incidence of adverse ischemic outcomes after coronary angioplasty. METHODS: Seventy-three patients received tirofiban in three sequential dose panels and 20 patients received placebo. Patients within each panel were randomized to receive either tirofiban or placebo in a 3:1 randomization design. Bolus doses of 5, 10 and 10 microg/kg and continuous infusion (16 to 24 h) doses of 0.05, 0.10 and 0.15 microg/kg per min were administered in panels I, II and III, respectively. Patients received concomitant heparin and aspirin for the angioplasty procedure. Data on patients receiving placebo (heparin and aspirin only) were pooled across panels for comparisons. The pharmacodynamic effect of tirofiban on ex vivo platelet aggregation to 5 micromol/liter adenosine diphosphate (ADP) and bleeding times were measured. Clinical outcomes were assessed in all patients, but the power to detect clinically meaningful differences (a one-third reduction in clinical events) between groups was limited (5%). RESULTS: Tirofiban was associated with a dose-dependent inhibition of ex vivo ADP-mediated platelet aggregation that was sustained during intravenous infusion and resolved rapidly after drug cessation. Adverse bleeding events, largely related to vascular access site hemorrhage, were slightly increased at the highest dose. Adverse clinical outcomes were infrequent in all patients and were not different among the small number of patients within each group. CONCLUSIONS: This study establishes a rational and generally well tolerated dosing regimen for administration of tirofiban as adjunctive therapy in high risk angioplasty patients. The impact of tirofiban on adverse clinical outcomes after angioplasty awaits definition by a larger clinical trial.

Angioplasty, Balloon, Coronary↗
PubMed1996

Characterization of the glycolipid associated with Alzheimer paired helical filaments.

In the present study, analytical techniques including gas chromatography/mass spectrometry (GC/MS)-assisted carbohydrate linkage-analysis, one- and two-dimensional NMR, and matrix-assisted laser desorption/ionization time of flight mass spectroscopy (MALDI-MS) have been used to characterize the structure of the glycolipid associated with the paired helical filaments (PHF) isolated from the neurofibrillary tangles of Alzheimer's diseased brain. The 1H NMR spectrum of acid-hydrolyzed protein-resistant core PHF (prcPHF) displays resonances that can be assigned to fatty acid and glucose. There are no resonances present that would indicate the presence of protein, amino acids, or a sphingosine base. Using two-dimensional homonuclear correlated spectroscopy, homonuclear Hartmann-Hahn, and heteronuclear multiple quantum coherence experiments, resonances in the 1H and 13C NMR spectrum of native PHF were assigned to a nonreducing terminal alpha-1,6-glycosidically linked glucose, an internal alpha-1,6-linked glucose, and an alpha-1,2,6-linked glucose. The narrow line-widths observed for these residues suggest that they arise from glucose residues undergoing rapid segmental motion. The carbohydrate portion of the PHF-associated glycolipid was analyzed using GC/MS linkage analysis and confirmed the presence of terminal and internal alpha-1,6-linked glucose and alpha-1,2,6-linked glucose in a molar ratio of 2:1:1. Three components of the PHF-associated glycolipid fraction having masses 2,416, 2,325, and 2,237 Da were observed using MALDI-MS. The least abundant, heavier mass component (2,416 Da) was best fit to a structure with a tridecamer of glucose having a single esterified C20 fatty acid (Glc13 + C20 or Glc13 + C20:1), whereas the more abundant, lower mass components were best fit to noncovalently associated glycolipid dimers, each with a glucose pentamer or hexamer having two C14, C16, or C18 esterified fatty acids {D[(Glc5 + C18) + (Glc6 + C16)] or D[(Glc5 + C14) + (Glc6 + C14)]}. The ratio of glucose to fatty acid calculated from these best-fit structures of the more abundant mass components (5.5 +/- 1.1:1.0) is in reasonable agreement with the same ratio calculated from peak integrations in the NMR spectra of acid-hydrolyzed prcPHF (6.2 +/- 1.6). Structural similarities between PHF-associated glycolipid and other glycolipid amphiphiles known to form PHF-like filaments indirectly suggest that this unique glycolipid may be an integral component of the PHF suprastructure.

Alzheimer Disease↗
PubMed1996

Antimitochondrial antibody-negative chronic nonsuppurative destructive cholangitis. Atypical primary biliary cirrhosis or autoimmune cholangitis?

We investigated whether autoimmune cholangitis (AC) has specific features that constitute an entity other than primary biliary cirrhosis (PBC). We compared clinical, laboratory, and liver biopsy features; response to treatment; and the follow-up of two groups of patients. The first group comprised seven patients with AC criteria-PBC with negative antimitochondrial antibodies (AMAs) and positive antinuclear antibodies (ANAs)-termed the PBC AMA-negative group; the second was made up of another seven PBC patients with positive AMA, labeled the PBC AMA-positive group. We found that the PBC AMA-negative group had, besides negative AMAs and positive ANAs, a significantly higher incidence of asthenia, a higher and earlier incidence of liver failure, and higher ANA titers and serum immunoglobulin G levels than the PBC AMA-positive group. There were no significant differences in the other laboratory tests, although the PBC AMA-negative group showed higher serum bilirubin and aminotransferase and lower serum alkaline phosphatase and immunoglobulin M levels. Liver histological data were similar in both groups. Patients in the PBC AMA-negative group, with more markedly abnormal liver tests, responded to immunosuppressive therapy. We concluded that patients with criteria for PBC but with negative AMAs and positive ANAs have a few specific features that fall between PBC and autoimmune chronic hepatitis. This finding suggests that these patients have a different disease, for which autoimmune cholangitis seems to be an appropriate name.

Adult↗
PubMed1996

Irritable bowel syndrome: a study to investigate the mechanism(s) of visceral hypersensitivity.

Irritable bowel syndrome (IBS), is characterized by gastrointestinal hyperalgesia. In this study we investigated mucosal application of dyclonine on urge to defecate and pain threshold in volunteers and IBS patients (n = 10). Either saline or dyclonine (40 ml enema) was administered 10 minutes prior to rectosigmoid distension or cutaneous cold water pressor test. In IBS patients and volunteers no differences in cutaneous pain thresholds were noted. However, IBS patients had a lower pain threshold in the rectosigmoid than volunteers. In volunteers there was a significant difference between the threshold for urge to defecate and the threshold for rectosigmoid pain that was not apparent in IBS patients. Dyclonine administered directly into the rectosigmoid did not alter urge to defecate or pain threshold induced by distension in volunteers or IBS patients. These data suggest that the origin of pain perception is localized in deeper structures within the wall of the rectosigmoid colon.

Adult↗
PubMed1995

Analysis of the core components of Alzheimer paired helical filaments. A gas chromatography/mass spectrometry characterization of fatty acids, carbohydrates and long-chain bases.

We have carried out a fatty acid and carbohydrate compositional analysis of the protease-resistant core of paired helical filaments (prcPHF) isolated from six Alzheimer's diseased brains. Fatty acids, long-chain bases and monosaccharides were characterized by gas chromatography/mass spectrometry (GC/MS) of fatty acid methyl esters, trimethylsilylated long-chain bases, peracetylated alditol acetates and trimethylsilyl methyl glycosides. Glucose and mannose were found to be the only carbohydrate components. Four of the six prcPHF samples contained only glucose while the remaining two samples contained between 30-40% mannose in addition to glucose. None of the samples were found to contain either hydroxylated fatty acids or long-chain bases. The average fatty acid profile of prcPHF was highest in stearic (C18:0) and palmitic acids (C16:0) with less than 10% unsaturated fatty acids. By comparing the carbohydrate and lipid composition of prcPHF to similar data for other brain glycolipids, it was determined that prcPHF is a unique glycolipid, distinct from cerebrosides, gangliosides or brain phospholipids. The fatty acid and carbohydrate composition of a glycolipid isolated from a population of normal brains according to the prcPHF protocol was found to be identical to that of prcPHF glycolipid. It is possible that subtle differences in structure or indigenous factors are responsible for the initiation of PHF formation in vivo.

Aged↗
PubMed1995

Fibrinogen Guarenas I: partial characterization of a new dysfibrinogenemia with an altered rate of fibrinopeptide release and an impaired polymerization.

A congenitally abnormal fibrinogen was isolated from the blood of a young woman with a severe bleeding diathesis. Coagulation tests showed a prolonged Thrombin and Reptilase time partially corrected by Ca2+. Polymerization of thrombin induced preformed fibrin monomers was severely impaired. Thrombin caused the release of fibrinopeptides with normal retention times on HPLC. However, the rate of release was abnormally slow and the total amount of fibrinopeptide A (FpA) released reached only approximately 50% of the theoretical maximum. The rate and quantity of FpA release was normal when Reptilase was used. Transmission Electron Microscopy (TEM) of Thrombin induced clots showed an altered clot structure characterized by a reduced mean fiber diameter. The mother has a polymerization defect similar to the propositus, her fibrinopeptide release is unaffected however. The father has a minor fibrinopeptide release defect suggesting the presence of two populations of fibrinogen. This study supports the idea that the fibrinogen isolated from the propositus has two defects inherited as separate genetic traits. This fibrinogen has been named Fibrinogen Guarenas I.

Adolescent↗
PubMed1995

The influence of angiographically demonstrated coronary collaterals on the results of stress echocardiography.

Previous studies using thallium-201 scintigraphy have suggested that angiographic coronary collaterals can protect against the development of stress-induced perfusion abnormalities, but the effect of collaterals on stress echocardiography (SECHO) has not been determined. In this study, 21 consecutive patients referred for cardiac catheterization underwent SECHO and coronary angiography. Of the 21 study patients, there was a total of 16 significantly obstructed coronary arteries (> or = 70% stenosis) in 14 patients. SECHO revealed stress-induced wall motion abnormalities in the distribution of seven of nine obstructed coronary vessels without angiographic collaterals, but in only one of seven vessels with collaterals (p < 0.05). Six of eight obstructed vessels not associated with a stress-induced wall motion abnormality had collaterals, whereas only one of eight obstructed vessels associated with a stress-induced wall motion abnormality had collaterals. We conclude that (1) angiographically demonstrated coronary collaterals can protect against the development of stress-induced wall motion abnormalities despite the presence of a high-grade coronary artery obstruction, and (2) the lack of a stress-induced wall motion abnormality on SECHO in the perfusion territory of an obstructed vessel may suggest the presence of adequate collateral perfusion.

Aged↗
PubMed1995

Nature and outcome of febrile episodes in patients with pancreatic and hepatobiliary cancer.

Fifty febrile episodes in patients with hepatobiliary and pancreatic cancer were reviewed. Biliary obstruction often resulting in cholangitis was an important predisposing factor, whereas neutropenia (< 500 PMN/mm3) was uncommon (10%). Microbiologically documented infections originating from the gastrointestinal tract were predominant, with Enterococcus faecalis and Escherichia coli being isolated most often. Non-infectious causes of fever occurred in 16% of patients. Only one patient developed a fungal infection. The overall response rate to therapy was 94%, with 32% being eligible for outpatient management. These data are quite different from those generated from patients with hematologic malignancies and indicate that disease-site specific management guidelines need to be developed for febrile episodes in patients with various underlying neoplasms.

Adult↗
PubMed1995

Latent autoimmune hepatitis triggered during interferon therapy in patients with chronic hepatitis C.

BACKGROUND/AIMS: Interferon can induce autoantibodies and autoimmune reactions. This study reviewed the clinical, serological, and HLA phenotypical features of patients who developed autoimmune hepatitis during interferon therapy for chronic hepatitis C, analyzing their response to immunosuppressive treatment. METHODS: The diagnosis of chronic hepatitis C was based on positivity for viral RNA and a liver biopsy specimen obtained before interferon treatment. Sera were tested for autoantibodies by indirect immunofluorescence assay. HLA typing was performed by applying a standard microlymphocytotoxicity method. RESULTS: Of 144 patients with chronic hepatitis C treated with interferon, 7 women deteriorated during treatment; serum transaminase, gamma-globulin, and immunoglobulin G levels increased; and serum autoantibodies became positive. Interferon was interrupted, a diagnosis of autoimmune hepatitis was established, and immunosuppressive therapy was initiated. All patients responded to this treatment. The 7 patients had similar HLA typing to those with autoimmune hepatitis, with DR4 in 2 patients (67%) with type 2 autoimmune hepatitis, and with DR3 and DR52 in 2 (50%) and 4 (100%) patients, respectively, with type 1 autoimmune hepatitis; additionally, 5 patients (71%) had DQ2, and 4 (57%) had both DR52 and DQ2. CONCLUSIONS: In female patients with chronic hepatitis C, a genetic susceptibility to autoimmune hepatitis may exist, possibly triggered by immunostimulating effects during interferon therapy. Immunosuppressive treatment has been well tolerated and seems to be effective.

Adult↗