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Biomedical subjects

G Rios

Publications and source records attributed to G Rios.

At least 19 recordsLinked to original sources

Early posttransplant lymphoproliferative disease in pediatric liver transplant recipients.

Among 23 pediatric patients who underwent orthotopic liver transplant (OLT), we report two (11 and 26 months old) with posttransplant lymphoproliferative disease (PTLD) that occurred in the early posttransplantation period. They were Epstein-Barr Virus (EBV)-negative and received graft from EBV-positive donors. The surveillance for EBV viremia using serial EBV polymerase chain reaction determinations in the peripheral blood was positive at 10 and 90 days after OLT concomitant with symptoms of primary infection, both patients were treated with gancyclovir. The patients should progression to a Burkitt's and a non-Hodgkin's lymphoma that appeared 3 months posttransplantation. They were treated by withdrawal of immunosuppression and six courses of cyclophosphamide as well as anti-CD20 monoclonal antibody (Rituximab) every 21 days. One patient experienced acute graft rejection, which resolved with steroids and low doses of tacrolimus, she is free of disease at 24 months after the end of treatment. The other patient relapsed with a cerebral lymphoma, receiving aggressive chemotherapy, but died due to sepsis. In conclusion, PTLD occurred among in 2/23 patients who underwent OLT and appeared in the first quarter post OLT. The risk factors associated with early PTLD were primary EBV infection after OLT, young age, and EBV-negative recipient receiving a transplant from an EBV-positive donor. Antiviral treatment alone was inefficient; withdrawal of immunosuppression and courses of Rituximab and cyclophosphamide were well tolerated and controlled PTLD. The risk of graft rejection was increased by withdrawal of immunosuppression. One patient died.

Biliary Atresia↗

Celiac disease in a Chilean population carrying Amerindian traits.

BACKGROUND: Although clinical manifestations of celiac disease may change throughout life, clinical, histologic, immunologic, and genetic studies show that there are incomplete forms of this condition, making it difficult to define the disease at a given moment. Because there is no information published in the Latin American-Amerindian population, this study was conducted to assess relations between these parameters in Chileans with celiac disease and their first-degree relatives. METHODS: Sixty-two persons with confirmed celiac disease (mean age, 17.9 +/- 5.1 years; 78.3% females) and 126 relatives (mean age, 27.9 +/- 17.2 years; 65.1% females) were evaluated. Clinical manifestations, antiendomysial antibodies (EMAs), and human leukocyte antigen (HLA) haplotypes were studied in patients. Additionally, jejunal biopsy specimens were assessed (light microscopy) in EMA-positive (EMA+) relatives. RESULTS: Of the patients, 24.1% adhered to a strict gluten-free diet; 26% were oligosymptomatic, and none were malnourished; 45% were EMA+; 13.8% who ingested gluten were EMA-negative (EMA-); one patient consuming a strict gluten-free diet was EMA+. The DQA1*0501 allele was present in the highest frequency (48%, P < 0.0005), whereas combinations of DQ8 were predominant. Of the relatives, 4.8% were EMA+; they had a significantly higher frequency of diarrhea, weight loss, and anorexia (P < 0.03); and all had abnormal histology in biopsy specimens. CONCLUSIONS: After childhood, celiac disease is oligosymptomatic and is often unrecognized by patients. Disease in 13.8% of patients and in 4.8% relatives appeared as incomplete forms of celiac disease. Predominance of DQ8 HLA haplotypes reflects the genetic Spanish-Mapuche heritage of this population.

Adolescent↗

Endoscopic injection of bleeding esophageal varices with a poly-N-acetyl glucosamine gel formulation in the canine portal hypertension model.

BACKGROUND: It has been shown that poly-N-acetyl glucosamine produces rapid hemostasis by stimulating erythrocyte aggregation. Endoscopic injection of this substance may be effective in the treatment of bleeding varices. METHODS: In eight heparinized dogs with a bleeding esophageal varix greater than 2 mm in diameter, 2.5% to 3.5% poly-N-acetyl glucosamine gel was injected intravariceally and paravariceally. Endoscopy, endosonography, and histopathology were performed at 1, 7, 21, and 90 days after injection. RESULTS: In all cases, the variceal hemorrhage was stopped with three to four injections of a mean total gel volume of 1.9 mL. No recurrence of bleeding, ulceration, or stricture formation occurred. Through replacement of the gel by connective tissue, the varix was permanently obliterated in its whole course in five cases and in more than 70% of its length in three cases. No embolization and no poly-N-acetyl glucosamine antibodies were detected. CONCLUSIONS: Endoscopic injection of bleeding esophageal varices in this animal model with the use of poly-N-acetyl glucosamine gel was an effective and safe method for stopping the hemorrhage and inducing permanent varix obliteration.

Acetylglucosamine↗

A novel mechanism of ion homeostasis and salt tolerance in yeast: the Hal4 and Hal5 protein kinases modulate the Trk1-Trk2 potassium transporter.

The regulation of intracellular ion concentrations is a fundamental property of living cells. Although many ion transporters have been identified, the systems that modulate their activity remain largely unknown. We have characterized two partially redundant genes from Saccharomyces cerevisiae, HAL4/SAT4 and HAL5, that encode homologous protein kinases implicated in the regulation of cation uptake. Overexpression of these genes increases the tolerance of yeast cells to sodium and lithium, whereas gene disruptions result in greater cation sensitivity. These phenotypic effects of the mutations correlate with changes in cation uptake and are dependent on a functional Trk1-Trk2 potassium transport system. In addition, hal4 hal5 and trk1 trk2 mutants exhibit similar phenotypes: (i) they are deficient in potassium uptake; (ii) their growth is sensitive to a variety of toxic cations, including lithium, sodium, calcium, tetramethylammonium, hygromycin B, and low pH; and (iii) they exhibit increased uptake of methylammonium, an indicator of membrane potential. These results suggest that the Hal4 and Hal5 protein kinases activate the Trk1-Trk2 potassium transporter, increasing the influx of potassium and decreasing the membrane potential. The resulting loss in electrical driving force reduces the uptake of toxic cations and improves salt tolerance. Our data support a role for regulation of membrane potential in adaptation to salt stress that is mediated by the Hal4 and Hal5 kinases.

Biological Transport↗

Trends in indications and outcomes in the Whipple procedure over a 40-year period.

There have been increasing changes in the role of pancreatoduodenectomy (PD) in the management of benign and malignant pancreatic disease. The aim of this paper was to compare the current role of PD with that of our earlier experience. The records of patients undergoing PD at our institution between 1983 and 1996 (Group A) were reviewed and compared with cases between 1956 and 1982 (Group B). Student's t test was used to analyze differences between groups. A total of 153 PDs were performed with 98 (64%) in Group A (88% of these in the last 6 years) and 55 (36%) in Group B. Carcinoma of the head of the pancreas was the most common indication for surgery in both periods (43% and 47% for Groups A and B, respectively). In Group A, the next most common indication was chronic pancreatitis, accounting for 28 per cent versus 13 per cent in Group B. Carcinoma of ampulla of Vater was also a common indication, making up 21 per cent of the cases in Group A and 20 per cent in Group B. Preoperative biliary drainage was performed in 62 per cent of Group A and 3 per cent of Group B patients (P < 0.001). Postoperative complications were comparable in both groups: delayed gastric emptying (22%), wound infection (17%), pancreatic fistula (13%), gastrointestinal bleeding (8%), and intestinal obstruction (3%). The perioperative mortality rate was significantly different between the two groups: 1 per cent in Group A versus 16 per cent in Group B (P < 0.001). Mean postoperative length of stay was 17 days in Group A (22 days for benign disease) and 25 days for Group B (P < 0.01). In the last 40 years, there has been a rise in the use of PD for chronic pancreatitis and a significant decrease in postoperative mortality and hospital length of stay. These data support the safety of PD in the management of patients with both benign and malignant periampullary disease.

Adult↗

Yeast putative transcription factors involved in salt tolerance.

Four putative yeast transcription factors (Hal6-9p) have been identified which upon overexpression in multicopy plasmids increase sodium and lithium tolerance. This effect is mediated, at least in part, by increased expression of the Enalp Na+/Li+ extrusion pump. Hal6p and Hal7p are bZIP proteins and their gene disruptions affected neither salt tolerance nor ENA1 expression. Hal8p and Hal9p are putative zinc fingers and their gene disruptions decreased both salt tolerance and ENA1 expression. Therefore, Hal8p and Hal9p, but not Hal6p and Hal7p, qualify as transcriptional activators of ENA1 under physiological conditions. Hal8p seems to mediate the calcineurin-dependent part of ENA1 expression.

Adaptation, Physiological↗

AT1 angiotensin II receptor inhibition in pacing-induced heart failure: effects on left ventricular performance and regional blood flow patterns.

BACKGROUND: AT1 angiotensin II (AT1 Ang II) receptor activation has been shown to cause increased vascular resistance in the systemic (SVR), pulmonary (PVR), and coronary vasculature which may be of particular importance in the setting of congestive heart failure (CHF). The overall goal of this study was to examine the effects of acute AT1 Ang II receptor inhibition on left ventricular (LV) pump function, systemic hemodynamics, and regional blood flow patterns in the normal state and with CHF, both at rest and with treadmill-induced exercise. METHODS AND RESULTS: Pigs (25 kg) were instrumented to measure cardiac output (CO), SVR, and PVR, and LV myocardial blood flow distribution in the conscious state and were assigned to one of two groups: (1) pacing-induced CHF (240 bpm for 3 weeks, n = 6) or (2) sham controls (n = 5). Measurements were obtained at rest and after treadmill exercise (15 degrees for 10 minutes). Studies were repeated 30 minutes after intravenous infusion of a low (1.1 mg/kg) or high (125 mg/kg) dose of the AT1 Ang II antagonist, valsartan. The low dose of valsartan reduced the Ang II pressor response by approximately 50% but had a minimal effect on arterial pressure, whereas the high dose eliminated the Ang II pressor response and reduced resting blood pressure by approximately 20%. With CHF, CO was reduced at rest (2.5+/-0.2 v 3.9+/-0.1 L/min) and with exercise (6.4+/-0.5 v 7.8+/-0.5 L/min) compared with controls (P < .05). Valsartan at the low and high dose increased resting CO by 28% in the control and CHF groups, but did not affect CO with exercise. Resting SVR in the CHF group was higher than controls (2,479+/-222 v 1,877+/-65 dyne x s x cm(-5), P < .05), but SVR fell to a similar degree with exercise (1,043+/-98 v 1,000+/-77 dyne x s x cm(-5)). The low and high dose of valsartan reduced resting SVR by more than 30% in both the control and CHF groups. PVR was increased by more than twofold in the CHF group at rest. The high dose of valsartan reduced resting PVR with CHF, but had no further effect with exercise. LV myocardial blood flow was reduced with pacing CHF, particularly with exercise. With exercise and CHF, a low or high dose of valsartan reduced coronary vascular resistance, but LV myocardial blood flow remained reduced from normal values. CONCLUSIONS: Heightened AT1 Ang II receptor activity occurred in this model of CHF, which contributed to alterations in systemic hemodynamics and vascular resistive properties. By using a low dose of a selective AT1 Ang II receptor antagonist reduced SVR, PVR, and coronary vascular resistive properties and therefore may provide beneficial effects in a setting of CHF.

Angiotensin II↗

Mechanisms of salt tolerance conferred by overexpression of the HAL1 gene in Saccharomyces cerevisiae.

Overexpression of the HAL1 gene improves the tolerance of Saccharomyces cerevisiae to NaCl by increasing intracellular K+ and decreasing intracellular Na+. The effect of HAL1 on intracellular Na+ was mediated by the PMR2/ENA1 gene, corresponding to a major Na+ efflux system. The expression level of ENA1 was dependent on the gene dosage of HAL1 and overexpression of HAL1 suppressed the salt sensitivity of null mutants in calcineurin and Hal3p, other known regulators of ENA1 expression. The effect of HAL1 on intracellular K+ was independent of the TRK1 and TOK1 genes, corresponding to a major K+ uptake system and to a K+ efflux system activated by depolarization, respectively. Overexpression of HAL1 reduces K+ loss from the cells upon salt stress, a phenomenon mediated by an unidentified K+ efflux system. Overexpression of HAL1 did not increase NaCl tolerance in galactose medium. NaCl poses two types of stress, osmotic and ionic, counteracted by glycerol synthesis and sodium extrusion, respectively. As compared to glucose, with galactose as carbon source glycerol synthesis is reduced and the expression of ENA1 is increased. As a consequence, osmotic adjustment through glycerolsynthesis, a process not affected by HAL1, is the limiting factor for growth on galactose under NaCl stressed.

Adaptation, Physiological↗

Accuracy of MR angiography compared with radionuclide scanning in identifying the cause of pulmonary arterial hypertension.

OBJECTIVE: MR imaging has proven accurate in identifying patients with chronic thromboembolic pulmonary hypertension (CTEPH). However, we know of no attempt to distinguish patients with CTEPH from patients with other causes of pulmonary arterial hypertension (PAH). Primary pulmonary hypertension (PPH) is the disease most frequently confused with CTEPH. We examined patients with CTEPH or PPH and control subjects to identify MR imaging features that might distinguish CTEPH from PPH, to compare the accuracy of MR angiography (MRA) with that of radionuclide scanning, and to determine the cardiac and pulmonary vascular measurements in these groups. SUBJECTS AND METHODS: T1-weighted and two-dimensional multiplanar spoiled gradient-recalled scans were obtained in 30 patients with CTEPH who had undergone conventional pulmonary angiography, 10 patients with PPH, and 13 control subjects with no known vascular disease. Ventilation-perfusion scans were available in all patients with CTEPH and in six of the 10 patients with PPH. The MR scans were assessed independently by two radiologists who evaluated the appearance of segmental vessels and noted the presence of mosaic perfusion. Cardiac chambers and pulmonary vessels were measured on T1-weighted spin-echo scans. RESULTS: The two radiologists used MR angiograms to reliably distinguish between patients with CTEPH and those with PPH. The accuracy of MR angiograms matched that of ventilation-perfusion scans (92%). On T1-weighted scans, the two radiologists used cardiac and pulmonary vascular measurements to distinguish patients with PAH from control subjects but failed to distinguish between patients with CTEPH and those with PPH. CONCLUSION: MRA is useful in distinguishing patients with CTEPH from those with PPH. In this population, MRA had an accuracy that was identical to that of radionuclide scanning. Vascular and cardiac measurements made on MR scans reliably identified patients with PAH but did not distinguish between patients with CTEPH and those with PPH.

Adult↗

Accuracy of high-resolution CT in identifying chronic pulmonary thromboembolic disease.

OBJECTIVE: The aims of this study were to determine the reliability of the high-resolution CT (HRCT) appearance of the lung parenchyma in distinguishing patients with chronic pulmonary thromboembolism (CPTE) from those with other pulmonary diseases and to compare HRCT with radionuclide scanning. SUBJECTS AND METHODS: Sixty-seven patients for whom HRCT scans were available for review were included in the study. Twenty-eight had proven pulmonary arterial hypertension (PAH), 17 cases of which were caused by CPTE, and 39 had other pulmonary abnormalities. Diagnosis based on the HRCT appearance was attempted by two radiologists, who independently evaluated pulmonary parenchyma for a mosaic pattern of variable attenuation, for a measurable disparity in the size of pulmonary vessels, and for the presence of peripheral scars. HRCT findings were compared with radionuclide scan findings and pulmonary angiography findings. RESULTS: For both readers (readers 1 and 2), sensitivity (94% and 100%, respectively) and specificity (96% and 98%, respectively) were high for distinguishing patients with CPTE from patients with other pulmonary abnormalities, including those with nonthromboembolic PAH. The average ratios of segmental vessel size were 2.2 for patients with CPTE and 1.1 for those with nonthromboembolic diseases. Mosaic attenuation was identified in all patients with CPTE but was also seen in 22% (reader 1) and 14% (reader 2) of patients with no evidence of CPTE. Radionuclide scans revealed a high probability for pulmonary emboli for all but one patient with CPTE but also revealed a high probability for three patients who had no emboli. CONCLUSION: HRCT findings of disparity in the size of segmental vessels and a mosaic pattern of variable attenuation reliably distinguished patients with CPTE from those with nonthromboembolic PAH and from those with other pulmonary abnormalities. In addition, HRCT was more specific than radionuclide scanning in identifying patients with CPTE.

Adolescent↗

Immediate and reversible platelet inhibition after intravenous administration of a peptide glycoprotein IIb/IIIa inhibitor during percutaneous coronary intervention.

We studied the pharmacokinetic and pharmacodynamic properties of integrelin, a novel platelet glycoprotein IIb/IIIa receptor inhibitor, in patients undergoing elective percutaneous coronary intervention. Patients were randomized to placebo (n = 19) or to 1 of 4 integrelin dosing regimens (total n = 54) that were studied sequentially. All patients received aspirin and heparin. Patients were followed until discharge for the occurrence of adverse clinical events: death, myocardial infarction, coronary artery bypass surgery, repeat intervention, or recurrent ischemia. Bleeding was the primary safety end point. Frequent blood sampling was performed for adenosine diphosphate-induced platelet aggregations. Simplate bleeding times were performed. Adverse clinical events occurred less often in the integrelin-treated patients, although the overall numbers were too small to make a definitive statement as to clinical efficacy. There was no significant increase in serious bleeding among integrelin-treated patients. The 2 highest integrelin boluses (180 and 135 micrograms/kg) immediately (15 minutes after the bolus) provided > 80% inhibition of adenosine diphosphate-induced platelet aggregation in > 75% of treated patients. A constant integrelin infusion of 0.75 micrograms/kg/min maintained this marked antiplatelet effect, whereas an infusion of 0.50 micrograms/kg/min allowed gradual recovery of platelet function. Elective coronary intervention was performed safely and with no significant increase in serious bleeding events using integrelin with aspirin and heparin as an antithrombotic regimen. Integrelin provided rapid, intense, and persistent ex vivo platelet inhibition during coronary intervention. This new antiplatelet agent may be beneficial in reducing platelet-mediated ischemic complications of percutaneous coronary intervention.

Aged↗

Regulation of cation transport in Saccharomyces cerevisiae by the salt tolerance gene HAL3.

Dynamic regulation of ion transport is essential for homeostasis as cells confront changes in their environment. The gene HAL3 encodes a novel component of this regulatory circuit in the yeast Saccharomyces cerevisiae. Overexpression of HAL3 improves growth of wild-type cells exposed to toxic concentrations of sodium and lithium and suppresses the salt sensitivity conferred by mutation of the calcium-dependent protein phosphatase calcineurin. Null mutants of HAL3 display salt sensitivity. The sequence of HAL3 gives little clue to its function. However, alterations in intracellular cation concentrations associated with changes in HAL3 expression suggest that HAL3 activity may directly increase cytoplasmic K+ and decrease Na+ and Li+. Cation efflux in S. cerevisiae is mediated by the P-type ATPase encoded by the ENA1/PMR24 gene, a putative plasma membrane Na+ pump whose expression is salt induced. Acting in concert with calcineurin, HAL3 is necessary for full activation of ENA1 expression. This functional complementarity is also reflected in the participation of both proteins in recovery from alpha-factor-induced growth arrest. Recently, HAL3 was isolated as a gene (named SIS2) which when overexpressed partially relieves loss of transcription of G1 cyclins in mutants lacking the protein phosphatase Sit4p. Therefore, HAL3 influences cell cycle control and ion homeostasis, acting in parallel to the protein phosphatases Sit4p and calcineurin.

Adenosine Triphosphatases↗

Combination of platelet fibrinogen receptor antagonist and direct thrombin inhibitor at low doses markedly improves thrombolysis.

BACKGROUND: We evaluated the effects of a novel platelet fibrinogen receptor antagonist, Integrelin, and a direct thrombin inhibitor, recombinant hirudin, given together with recombinant tissue plasminogen activator (rTPA) in a canine experimental model of intracoronary thrombosis. We tested the hypothesis that combination of both agents at low doses would have an additive antithrombotic effect, resulting in a significant improvement in the efficacy of rTPA. METHODS AND RESULTS: Thirty-two dogs with an electrically induced coronary thrombus were treated with rTPA (1 mg/kg over 20 minutes) together with one of the following adjunctive treatments in a random fashion. Eight dogs received saline for 90 minutes; Integrelin (5 micrograms.kg-1.min-1 for 90 minutes) was given to 8 dogs; 8 dogs received recombinant hirudin (20 micrograms.kg-1.min-1 for 90 minutes); and 8 dogs were treated with a low-dose combination of Integrelin (2.5 micrograms.kg-1.min-1) plus recombinant hirudin (10 micrograms.kg-1.min-1) for 90 minutes. Integrelin or recombinant hirudin, when given as single adjunct to rTPA, enhanced the lysis of the occlusive thrombus, causing full restoration of coronary blood flow (100% of its baseline value) for 29 +/- 16 and 26 +/- 5 minutes, respectively, whereas coronary blood flow was fully restored for only 5 +/- 1 minutes in dogs receiving rTPA plus saline (both P < .05). However, either Integrelin or recombinant hirudin failed to modify the reocclusion rate (57% and 63%, respectively) compared with saline (83%; all P = NS). Conversely, the low-dose combination therapy led to complete restoration of coronary blood flow for 92 +/- 19 minutes (P < .01 versus all treatments) and significantly reduced the reocclusion rate (25%; P < .05 versus saline). CONCLUSIONS: These data show that inhibition of specific pathways of platelet and thrombin activity improves the extent and duration of rTPA-induced thrombolysis in the electrolytic canine model. Furthermore, our findings suggest that low doses of platelet IIb/IIIa and direct thrombin antagonists in combination may be used successfully during thrombolysis.

Animals↗

Electrohydraulic and ultrasonic lithotripsy in 100 consecutive cases of primary ureteral stones.

We have performed, between May 1985 and December 1988, in situ lithotripsy in 100 consecutive cases of primary ureteral stones, using electrohydraulic lithotripsy in 33 patients and ultrasonic lithotripsy in the remaining 67. After using similar instruments and surgical techniques in both groups, we have comparatively evaluated the complications encountered and the results obtained. With the electrohydraulic lithotripsy we have obtained a complication rate of 42% (operative and postoperative) and favorable results in 72.7% of the patients; using ultrasonic lithotripsy, the complication rate was 10.4%, and favorable results were obtained in 92.5%. We conclude that, at least in our experience, ultrasonic lithotripsy is less invasive and more successful than electrohydraulic lithotripsy in the treatment of primary stone disease.

Calcium Oxalate↗

Intravesical formalin for the treatment of massive hemorrhagic cystitis: retrospective review of 25 cases.

Between 1980 and 1988 25 patients with massive bladder hemorrhage were treated with intravesical instillation of 4% formalin in 19 cases and 10% in the remaining 6 cases; the contact time was 15 min in 20 cases. The etiology of the hemorrhage was cyclophosphamide therapy (1 case), pelvic radiotherapy (15 cases) and infiltrating bladder cancer in the remaining 9 cases. In 10 cases, the instillation of formalin was performed in bladders with a prior supravesical diversion. Complications included 1 case of vesicorectal fistula, 1 case of uretero-hydronephrosis and 1 case of vesical extravasation of formalin when a concentration of 10% was used at a volume superior to 50 ml. The only complication seen with 4% formalin was 1 case of upper urinary tract dilatation. Good results were obtained in 88% of cases, who achieved correct hemostasis during a mean of 4 months.

Administration, Intravesical↗