Biomedical subjects
Publications and source records attributed to G Silva.
Overdose of paracetamol is associated to varying degrees of hepatic necrosis and may lead to severe hepatic failure. In this paper, we report 2 patients with paracetamol overdose for suicidal purposes who were successfully treated using the antidote N-acetyl-cysteine orally. A brief analysis of the literature follows.
A controlled trial on the use of Silymarin in patients with alcoholic liver disease was performed. Seventy two patients were admitted to the trial and randomly assigned to an experimental or controls group. Experimentals received 280 mg/day of Silymarin and controls an equal number of placebo tablets. Three patients on placebo and nine on Silymarin were lost from control (p = 0.035), remaining in control 34 patients receiving placebo and 25 patients receiving the drug. Both groups did not differ in their initial laboratory assessment and were followed up for an average of 15 months. Ten patients died during the follow up (5 in placebo and 5 in Silymarin); life table analysis did not show significant differences in mortality. Patients who died had lower serum albumin and prothrombin time and higher total bilirubin, alkaline phosphatases and CCLI on the initial clinical and laboratory assessment. Final laboratory values and their changes in those who survived did not differ between Silymarin and placebo. Twenty two patients on placebo (65%) and 14 on Silymarin (58%) recognized alcohol ingestion or had a positive urine sample analysis for alcohol during follow up. Those who abstained from alcohol had a significant fall in gamma glutamyl transferase during follow up. No other significant differences were observed between these two groups. It is concluded that in this trial, Silymarin did not change the evolution or mortality of alcoholic liver disease.
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To evaluate the clinical usefulness of the ultrasonographic (echo-Doppler) measurements of portal blood flow their results were compared with several clinical and biochemical parameters in alcoholic cirrhotic patients. The technique was standardized and its reproducibility was checked in 30 cirrhotics and in 20 control subjects. In controls, portal area was greater when measured on its transversal axis and in deep inspiration. In cirrhotics the area did not change neither according to the axis nor the respiratory movements. The estimated velocity of blood flow was dependent on the angle of insonation. Measurements performed on longitudinal axis, at 50 degrees in expiratory apnea showed, in the same subject, an interday variability of 7%. In cirrhotic patients portal blood flow was higher than in controls (0.93 +/- 0.32 L/min vs 0.64 +/- 0.12, p < 0.001) being the difference due to a greater area. Considering controls and Child's A and B cirrhotic patients, portal blood flow correlated with the severity of disease (r = 0.738, p < 0.001). In Child C, portal blood flow was decreased, compared to Child's B patients. The presence and size of esophageal varices was also correlated to portal blood flow (r = 0.461, p < 0.05). However no differences were observed between the groups with or without previous variceal bleeding. It is concluded that echo-doppler measurement of portal blood flow is a reproducible technic in standardized conditions, detecting changes related to global liver function and the presence and size of esophageal varices.
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It has been suggested that glucagon contributes to the pathogenesis of portal hypertension by increasing portal blood flow. This study examined this issue by assessing the hemodynamic effects of a pharmacological dose of glucagon (1 mg, intravenously) in patients with cirrhosis and portal hypertension (n = 10) and in subjects without significant liver disease (controls = n = 5). Patients with cirrhosis had much higher glucagon levels than control subjects (875 +/- 167 vs. 186 +/- 25 pg/ml, p less than 0.01) and showed blunted hemodynamic responses after glucagon administration. This occurred despite greater circulating glucagon levels, probably because of a significant prolongation of the plasma half-life of exogenously administered glucagon (4.9 +/- 0.4 vs. 2.7 +/- 0.1 min, p less than 0.1). Control subjects had marked increases in heart rate (+ 19% +/- 4%, p less than 0.01), cardiac index (+ 16% +/- 4%, p = 0.01) and arterial pressure (+ 10% +/- 3%, p less than 0.05), but corresponding changes in patients with cirrhosis (+ 7% +/- 1%, + 6% +/- 1%, and + 6% +/- 2%, respectively) were significantly less pronounced (p = 0.05), and there was a negative correlation between basal glucagon levels and the response of heart rate to glucagon injection (r = -0.804, p less than 0.001). Resistance to the systemic effects of glucagon in cirrhosis may thus be caused by a down-regulation of vascular glucagon receptors. In addition, glucagon administration caused a significant increase in portal pressure (from 18.1 +/- 1.1 to 19.0 +/- 1.2 mm Hg, p less than 0.01), as well as in azygos blood flow (from 0.54 +/- 0.03 to 0.64 +/- 0.04 L/min, + 19% +/- 4%, p less than 0.02), reflecting increased portocollateral blood flow. These findings are consistent with the hypothesis that glucagon is one of the factors contributing to the splanchnic vasodilatation and increased portal pressure of cirrhosis.
The anticoagulant and estrogenic effects of hexolame, N-(3-hydroxy-1,3,5(10)-estratrien-17 beta-yl)-6-hydroxyhexylamine, are described. A single subcutaneous injection of hexolame in adult and infant male mice produced dose-dependent increases in blood clotting time which could be observed even after 2 days. In ovariectomized mice, hexolame produced vaginal cornification (estrogenic response). The data suggested that if used in the treatment of prostatic cancer, hexolame, like prolame, would not induce cardiovascular accidents. It could also be useful in the prevention of thrombosis.
In patients with low-back and radiating leg pain, a clinical phenomenon has been described known as "centralization," which occurs during a mechanical evaluation protocol described by McKenzie. Relocation of the most distal pain in a proximal or central direction characterizes the pain behavior when patients are assessed in this fashion. Centralization typically occurs rapidly and can be maintained. In a review of 87 such patients, centralization occurred in 76 (87%). Its occurrence during initial mechanical evaluation is a very accurate predictor of successful treatment outcome and reliably determines the appropriate direction of treatment exercise. Nonoccurrence of centralization accurately predicts poor treatment outcome and was a helpful early predictor of the need for surgical treatment.
We studied the effects of indoprofen on urea and creatinine clearance and on protein loss in 6 patients submitted to intermittent peritoneal dialysis. The patients had no evidence of peritonitis. Dialysis fluid contained indoprofen (50 mg/l) or no drug. Mean protein loss into dialysis solution was 51.2 g without and 44.7 g with indoprofen (NS). Urea clearance was 33.3 and 33.6 ml/min and creatinine clearance 24.7 and 36.0 ml/min, respectively (NS). Levels of PGF2 alpha in the dialysate, measured in 2 subjects, were not affected by indoprofen. These results suggest that prostaglandins are not the main factors involved in control of urea and creatinine clearance and protein loss during intermittent peritoneal dialysis.
The effects of a nutritional support in hospitalized patients with alcoholic cirrhosis and liver failure were studied in a controlled protocol. Thirty-six patients were included, 17 were randomly assigned to an experimental group and the rest to a control group. Experimentals received a diet aiming at 50 kcal (209 kJ)/kg bodyweight/d and 1.5 g protein/kg bodyweight/d (as proteins of high biological value). Controls received the standard diet prescribed by the attending physician. The severity of liver failure and the nutritional status on admission were similar in both groups. The measured energy intake in controls was 1813 +/- 121 kcal/d (7589 +/- 506 kJ/d) and 2707 +/- 71 kcal/d (1131 +/- 297 kJ/d) in experimentals (P less than 0.001). The protein intake in controls was 47 +/- 3.8 g/d and in experimentals 80 +/- 3 g/d (P less than 0.001). There were seven deaths during the study period (two experimentals and five controls). No differences were observed in the evolution of liver failure, hepatic encephalopathy or nutritional status between both study groups. It is concluded that a higher energy and protein intake in these patients does not have adverse effects and is associated with a non-significant reduction in mortality.
The value of ultrasound in the diagnosis of choledocholithiasis is controversial, sensitivity figures ranging from 22 to 75%. We correlated the ultrasound study with operative findings in 38 patients. A diagnosis of common bile duct stone was made upon finding an echogenic image with or without acoustic shadow in the common bile duct; no attention was paid to the dilatation of the biliary tree. The sensitivity was 68% and the positive predictive value was 85%. Therefore, our results approach the highest reported figures for the value of this diagnostic technique.
Propranolol, a non-selective beta-blocker, is known to decrease glucagon release in normal subjects. The present study was aimed at investigating the effects of propranolol on the hyperglucagonism commonly observed in patients with cirrhosis. Eight cirrhotic patients and 6 matched healthy controls were studied. The plasma concentrations of glucagon, insulin, c-peptide and glucose were measured in basal conditions and after stimulating glucagon secretion by an i.v. infusion of arginine (0.4 g/kg/30 min). The study was repeated 24 h later after inducing beta-blockade by the i.v. infusion of propranolol (10 mg). In baseline conditions, patients with cirrhosis, despite normal levels of insulin and glucose, had a marked hyperglucagonism (654 +/- 303 pg/ml vs. 269 +/- 90 in controls, P less than 0.01). Prior to propranolol, arginine infusion caused greater glucagon release in cirrhotics (71 +/- 31 ng.h.ml-1) than in controls (33 +/- 17 ng.h.ml-1, P less than 0.02), but despite a similar insulin secretion (assessed from c-peptide), blood glucose did not increase. After propranolol, glucagon secretion decreased as expected in controls (29 +/- 12 ng.h.ml-1, P less than 0.05) but experienced a paradoxical increase in cirrhotics (113 +/- 64 ng.h.ml-1, P less than 0.05). Again, despite the marked increase in glucagon release, there was no increase in glucose production, providing further evidence of the glucagon resistance that accompanies hyperglucagonism in cirrhosis. Our results suggest that hyperglucagonism with glucagon resistance might be the initial disturbance in carbohydrate metabolism in patients with cirrhosis. Contrary to what could be expected, propranolol does not correct but further accentuates this disturbance.
Portal hypertension is a common complication of chronic liver disease. Conventional therapy consists of surgery and palliative measures for the hemodynamic problem. It has been recently reported that somatostatin may reduce portal pressure without altering the systemic circulation and so reducing hepatic blood flow. This peptide also causes a significant fall in azygos circulation in patients with esophageal varices. The mechanism of this effect is unclear although suppression of intestinal vasodilating hormones and of glucagon have been claimed to play a role. Comparative clinical studies have shown somatostatin to be superior to the standard vasopressin treatment. Recent findings suggest that the efficacy of somatostatin can be increased by administering this peptide in repeated intravenous bolus injections. New derivatives, specially long-acting peptides, may eventually prove beneficial in the chronic treatment of this complication.
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1. Rat kidney extracts obtained at successive stages of a purification procedure, which allows the separation of renin and kallikrein, were used in order to investigate their effect upon urinary excretion of kallikrein, sodium, potassium and water in hyperhydrated rats. 2. Only the purified fraction containing renin reduced kallikrein excretion. The decrease of kallikrein coincided with a considerable increase in sodium, potassium and water excretion. 3. The natriuretic effect of renin extract did not depend on the presence of kallikrein. The injection of a mixture of renin and kallikrein attenuated the effect of renin alone, indicating that both enzymes exert antagonistic actions on the excretion of electrolytes and water by the kidneys. 4. A purified fraction of kidney extract containing no kallikrein and only traces of renin activity, had a stimulatory effect on kallikrein, water and electrolyte excretion.