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Biomedical subjects

G Smok

Publications and source records attributed to G Smok.

At least 37 records · Page 2Linked to original sources

[Prevalence and genotypes of hepatitis C virus in blood donors and in patients with chronic liver disease and hepatocarcinoma in a Chilean population].

BACKGROUND: The impact of hepatitis C virus infection in Chile has not been well established. AIM: To assess hepatitis C virus infection in normal Chileans and in patients with liver disease. SUBJECTS AND METHODS: Antibodies against hepatitis C virus were investigated in 21,000 blood donors, 133 patients with non alcoholic chronic liver disease and in 50 patients with hepatocarcinoma. Viral RNA was studied by polymerase chain reaction in all positive blood donors, in 51 patients with chronic liver disease and in all patients with hepatocarcinoma. Hepatitis C virus genotype was established using restriction fragment length polymorphism in 118 RNA positive samples. RESULTS: In blood donors, a 0.3% prevalence of positive antibodies was found. The figure for chronic liver disease was 53% and for hepatocarcinoma, 48%. Viral RNA was detected in 100% of patients with chronic liver disease and hepatocarcinoma and in 68% of blood donors with positive antibodies. Genotype 1b was identified in all infected patients with hepatocarcinoma, in 86% of patients with chronic liver disease and in 46% of blood donors. CONCLUSIONS: Hepatitis C virus infection is an important etiologic agent for chronic liver disease in Chile. The predominance of genotype 1b among patients with the most severe form of liver disease is in agreement with observations made abroad.

Adult↗

The combination of ursodeoxycholic acid and methotrexate for primary biliary cirrhosis is not better than ursodeoxycholic acid alone.

BACKGROUND/AIMS: Many therapies have been tried in primary biliary cirrhosis. It has been suggested that a combination of ursodeoxycholic acid and methotrexate may offer advantages. Because the benefit and safety of this combination is uncertain, we conducted this prospective, randomized, double-blind, controlled trial. METHODS: Twenty-five patients with well-defined primary biliary cirrhosis were randomly assigned to receive either ursodeoxycholic acid (500 mg/day) plus methotrexate (10 mg/week) or ursodeoxycholic acid plus placebo for a period of 48 weeks. Clinical, biochemical and histologic evolution were assessed. RESULTS: In both groups the clinical response was similar and heterogeneous. In patients of ursodeoxycholic acid alone group, biochemical and histologic changes were comparable to those of patients of ursodeoxycholic acid plus methotrexate at 48 weeks. The addition of methotrexate was not associated with substantial adverse affects. CONCLUSIONS: The use of methotrexate in combination with ursodeoxycholic acid was not followed by an additive benefit over ursodeoxycholic acid alone, nor was substantial toxicity added. Unless larger and longer controlled trials with clinical, biochemical and histologic controls show it to be a safe and effective therapy for primary biliary cirrhosis, ursodeoxycholic acid+methotrexate should not be used as a proven and accepted treatment.

Adult↗

Potentiation of ischemia-reperfusion liver injury by hyperthyroidism in the rat.

Parameters related to hepatic oxidative stress, cell injury, and liver histology were determined in control rats and in animals treated with 3,3',5-triiodothyronine (T3), after in vitro perfusion under normoxic or ischemia-reperfusion conditions. Thyroid calorigenesis was found concomitantly with higher rates of hepatic O2 consumption and thiobarbituric acid reactive substances (TBARS) formation, glutathione (GSH) depletion, enhanced TBARS/GSH ratio as indicator of oxidative stress, and higher sinusoidal lactate dehydrogenase (LDH) efflux compared to control values, assessed under normoxic conditions. Perfused livers from control animals subjected to ischemia-reperfusion exhibited significant increases in the TBARS/GSH ratio and in the sinusoidal LDH efflux over values obtained under normoxic conditions, concomitantly with the appearance of small foci of necrotic cells in centrilobular and midzonal areas of the liver lobule. These parameters were further modified in the liver of hyperthyroid rats subjected to ischemia-reperfusion, with elevations in the TBARS/GSH ratio and in the sinusoidal LDH efflux largely exceeding the sum of effects elicited by hyperthyroidism or ischemia-reflow alone. In this situation, liver injury was more pronounced than in control rats, being characterized by multifocal areas of necrotic cells, irregularly distributed in the hepatic lobule, with lymphoid and macrophagic reaction. It is concluded that the concurrence of the hepatic mechanisms related to the oxidative stress underlying thyroid calorigenesis and ischemia-reoxygenation exacerbates liver injury, which seems to be mediated by potentiation of the prooxidant state of the organ.

Animals↗

Prevalence of Helicobacter pylori infection in 190 control subjects and in 236 patients with gastroesophageal reflux, erosive esophagitis or Barrett's esophagus.

A prospective study was performed in 190 control subjects and in 236 patients with different degrees of endoscopic esophagitis in order to determine the prevalence of Helicobacter pylori infection at duodenal gastric and esophageal mucosa and its correlation with histological findings. All patients with pathologic gastroesophageal reflux had 24-h pH monitoring studies confirming the presence of acid reflux into the esophagus. Besides the endoscopic findings, biopsies were taken from the duodenal bulb, gastric antrum, gastric fundus and distal esophagus or at the specialized columnar epithelium in patients with Barrett's esophagus. Patients with pathological gastroesophageal reflux were divided into three groups: 55 with absence of endoscopic esophagitis (gastroesophageal reflux), 81 patients with erosive esophagitis and 100 patients with Barrett's esophagus. There was no H. pylori infection present at duodenal or esophageal mucosa or at the specialized columnar epithelium of the distal esophagus in any case. The prevalence of H. pylori infection at gastric antrum was similar in controls and in any group of patients with reflux disease (20-25% of H. pylori infection). No differences in age and sex distribution were seen. H. pylori infection at gastric fundus was very low (less than 5%). The presence of HP infections was correlated with the finding of chronic active superficial or athrophic gastritis while, in the absence of H. pylori infection, gastric mucosa was normal. In the presence of intestinal metaplasia, no H. pylori infection occurred. Based on these findings, it seems that there is no significant evidence for an important pathogenic role for H. pylori infection in the development of pathologic chronic gastroesophageal reflux, erosive esophagitis or Barrett's esophagus, and the presence of antral gastritis in patients with Barrett's esophagus is closely related to the presence of H. pylori infection, and probably not related to an increased duodenogastric reflux.

Adolescent↗

Kupffer cell function in thyroid hormone-induced liver oxidative stress in the rat.

The influence of thyroid hormone (L-3, 3', 5-triiodothyronine, T3) on Kupffer cell function was studied in the isolated perfused rat liver by colloidal carbon infusion. Rates of carbon uptake were determined from the influent minus effluent concentration difference and the flow rate, and the respective carbon-induced respiratory activity was calculated by integration of the area under the O2 curves during carbon infusion. In the concentration range of 0.2 to 2.0 mg of carbon/ml, livers from euthyroid rats exhibited a sigmoidal-type kinetics of carbon uptake, with a Vmax of 4.8 mg/g liver/min and a concentration of 0.82 mg/ml for half-maximal rate; carbon-induced O2 uptake presented a hyperbolic-type kinetics, with a Vmax of 4.57 mumol of O2/g liver and a K(m) of 0.74 mg of carbon/ml, which significantly correlates with the carbon uptake rates. Light-microscopy showed that carbon was taken up exclusively by non-parenchymal cells, predominantly by Kupffer cells. Thyroid calorigenesis was found in parallel with increased rates of hepatic O2 consumption and thiobarbituric acid reactive substances (TBARS) formation, glutathione (GSH) depletion, and higher sinusoidal lactate dehydrogenase (LDH) efflux compared to control values. In the concentration range of 0.25 to 0.75 mg/ml, carbon infusion did not modify liver LDH efflux in control rats, while it was significantly enhanced in T3-treated animals. In this latter group, higher carbon concentrations (1 and 1.3 mg/ml) led to loss of viability of the liver. At 0.25 to 0.75 mg of carbon/ml, both the rates of carbon uptake and the associated carbon-induced respiratory activities were significantly increased by T3 treatment, effects that were abolished by pretreatment of the rats with gadolinium chloride (GdCl3). In addition, GdCl3 decreased by 50% the changes induced by T3 in hepatic GSH content and TBARS formation. It is concluded that hyperthyroidism enhances Kupffer cell function, correlated with the increased number of liver macrophages observed histologically, which may represent an alternate source of reactive O2 species to that induced in parenchymal cells, thus contributing to the enhanced oxidative stress status developed.

Animals↗

The presence of Helicobacter pylori in nonoperated duodenal ulcer patients compared to patients late after highly selective vagotomy.

There are many recent studies that clearly suggest that Helicobacter pylori (HP) is an etiological agent for duodenal ulcer disease (1-3). Randomized trials have shown that duodenal ulcers treated by omeprazole or H2 blockers heal faster if HP is eradicated concurrently (4-6). Besides, several studies have demonstrated that eradication of HP significantly reduces duodenal ulcer relapses (7-9). Patients followed up to 7 years after eradication of HP demonstrated that 92% remained HP negative, with only 3% recurrence (10). Highly selective vagotomy has been the treatment of choice for duodenal ulcer patients who are candidates for surgical therapy (11, 12). The late results have shown an approximately 10% recurrence rate 8 to 10 years after surgery (13, 14). We hypothesized that in these asymptomatic cases after HSV, HP probably will exist in a minor proportion of cases, similar to what happens after successful medical antiulcer therapy. Therefore the purpose of the present study was to determine the HP status at the antrum in a group of nonoperated duodenal ulcer patients compared to a group submitted to highly selective vagotomy many years prior to the actual study.

Adult↗

[Experience of a single center in liver transplantation in adults and children].

Orthotopic liver transplantation (THO) is the treatment of choice for a variety of liver diseases. The national experience before 1993 has been scarce. In November 1993 we started our experience in THO at Clínica Las Condes, as part of a multiorgan transplant program (liver, kidney, pancreas). Until January 1995 we have performed 14 THO in 13 recipients (one retransplantation), of which 5 were in pediatric cases. The recipients range of age fluctuated between 1 and 61 years. In two pediatric cases a liver allograft reduction was performed. Six recipients (46%) required treatment for acute cellular rejection. One recipient had an hepatic artery thrombosis and had to be retransplanted. There was no operative mortality up to 30 days in cases of primary liver transplants. The retransplanted adult recipient, and another pediatric recipient that died from a late recurrence of a hepatoblastoma, accounted for the mortality of this experience. After an average follow up of 10 months, the actual patient survival in 85%. Of the 11 surviving recipients, 9 are in excellent conditions with a very good quality of life. This experience shows that an active liver transplant program in our country can be successful in obtaining results comparable to those published by very experienced foreign transplant centers.

Adolescent↗

[Hepatic veno-occlusive disease associated to the use of azathioprine in a renal transplant recipient].

We report a 30 years old male, recipient of a kidney allograft and treated with azathioprine, who eighteen days after transplantation had a clinically asymptomatic elevation of total bilirubin and alkaline phosphatases. Nineteen months later, he presented with mild ascites, with a total bilirubin of 3.5 mg/dl, alkaline phosphatases of 308 U/L (normal < 170 U/L) and a prothrombin time at 55% of control. A liver biopsy showed sinusoidal and perivenular fibrosis without inflammation, compatible with chronic venous obstruction. Hepatic veno-occlusive disease is an infrequent complication of azathioprine use.

Adult↗

Influence of hyperthyroidism on lindane-induced hepatotoxicity in the rat.

Parameters related to hepatic oxidative stress, cell injury, phagocytic activity, and liver histology were studied in control rats and in animals subjected to L-3,3',5-triiodothyronine (T3) and/or lindane administration. Hyperthyroidism elicited a calorigenic response and increased rates of hepatic O2 uptake, which were not modified by lindane treatment. T3 diminished serum lindane levels as well as those in the liver and adipose tissue, whereas lindane enhanced serum T3 levels in animals given T3. Compared with control rats, lindane significantly increased the rate of formation of thiobarbituric acid reactants (TBARS) by the liver, with no changes in either the reduced glutathione (GSH) content, the TBARS/GSH ratio as indicator of oxidative stress, or in the fractional rates of lactate dehydrogenase (LDH) and GSH efflux from perfused livers as integrity parameters. Hyperthyroidism induced GSH depletion in the liver, with a significant enhancement in the TBARS formation, the TBARS/GSH ratio, and in the fractional LDH and GSH efflux. These parameters were increased further by joint T3 and lindane administration in a magnitude exceeding the sum of the effects produced by the separate treatments. In addition, hyperthyroidism led to Kupffer cell hyperplasia and significant increases in serum glutamate oxalacetate transaminase (GOT) and in hepatic zymosan-induced chemiluminescence, while liver myeloperoxidase (MPO) activity was found unchanged, compared with controls. Rats treated with lindane presented normal liver histology, with no changes in biochemical parameters related to cell injury. The joint administration of T3 and lindane, however, elicited a marked elevation in serum GOT and glutamate pyruvate transaminase (GPT), concomitantly with extensive liver necrosis and the presence of granulomas containing lymphocytes, Kupffer cells and polymorphonuclear leukocytes (PMN). In this condition, hepatic zymosan-induced light emission and MPO activity were enhanced over control values. It is concluded that hyperthyroidism increases the susceptibility of the liver to the toxic effects of lindane, which seems to be accomplished by potentiation of the hepatic oxidative stress status. The latter effect may be conditioned by an enhanced phagocytic respiratory burst activity due to the observed Kupffer cell hyperplasia and PMN infiltration, in addition to the increased production of reactive oxygen species in parenchymal cells.

Alanine Transaminase↗

[Presence of Helicobacter pylori in the duodenum, antrum, and fundus in control subjects and patients with duodenal ulcer, gastric ulcer, gastritis, or erosive duodenitis. Histological analysis of 357 subjects].

The prevalence of Helicobacter pylori infection was studied in 152 subjects with a normal upper gastrointestinal endoscopy, 125 with duodenal ulcer, 25 with gastric ulcer, 46 with erosive gastritis and 9 with erosive duodenitis. Two biopsies from duodenum, antrum and fundus were obtained from each subject during endoscopy for histological diagnosis and Helicobacter pylori search. None of the patients with normal endoscopy and 2% of patients with duodenal ulcers had Helicobacter pylori in duodenal biopsies. These last patients had a significantly higher frequency of Helicobacter pylori in the antrum (71%) than the rest of the studied groups. Five percent of subjects with normal endoscopy and 5% of those with duodenal ulcers had Helicobacter pylori in the antrum. An active gastritis was demonstrated in almost all patients with Helicobacter infection. Intestinal metaplasia occurred almost exclusively in the absence of Helicobacter pylori infection.

Adolescent↗

Acute fatty liver of pregnancy: a clinical study of 12 episodes in 11 patients.

Twelve episodes of acute fatty liver of pregnancy (AFLP) were diagnosed in 11 patients during the past 18 years in a general hospital in Santiago, Chile, with a prevalence of 1 per 15,900 deliveries. Acute fatty liver of pregnancy started between the 31st and 38th weeks of pregnancy, with malaise, vomiting, jaundice, and lethargy as the main clinical manifestations. Polydipsia (in nine episodes) and skin pruritus (in seven episodes) were unusual clinical findings. In two patients, pruritus started two and four weeks before AFLP, suggesting that an intrahepatic cholestasis of pregnancy preceded AFLP in those patients. Considering the current prevalence of both diseases in Chile, their association should be considered fortuitous. In another patient, two consecutive pregnancies were affected by AFLP, raising to three the number of reported patients with recurrent AFLP. In 11 episodes, liver biopsies supported the diagnosis of AFLP by showing small and midsized vacuolar cytoplasmic transformation as the most prominent histopathological feature. Positive intracellular fat staining was found in the four samples analysed. Studies by electron microscopy showed megamitochondria with paracrystalline inclusions in four samples. All the mothers survived, but fetal mortality was 58.3%. Several extrahepatic complications delayed maternal recovery for up to four weeks after delivery. This study confirms an improvement in maternal prognosis in AFLP, discusses the possibility of an epidemiological association with intrahepatic cholestasis of pregnancy, and increases the number of patients reported with recurrent AFLP.

Acute Disease↗

[Patients with pathologic gastroesophageal reflux without erosive esophagitis: correlation of the endoscopic and histological aspect of the esophagus].

Eighty four patients with chronic gastroesophageal reflux in whom endoscopy showed a normal or minimally altered esophageal mucosa (hyperemia, erythema or mucosal congestion) were prospectively studied. In each patient, two esophageal biopsies were obtained (1 and 3 cm above the mucosal change zone). Histological esophagitis was found in 28% of patients with endoscopically normal mucosa and in 26% of patients with minimal endoscopical mucosal alterations. It is concluded that the description of these minimal esophageal alterations during endoscopy is subjective, unreproducible and do not clearly indicate the presence of esophagitis. A classification of endoscopical findings is proposed, based on the presence of objective lesions such as erosions or Barrett esophagus.

Adult↗

[Long-term survival of patients with stomach cancer treated with subtotal gastrectomy].

The aim of this work was to determine the 5 and 12 years survival of 233 patients with gastric cancer subjected to subtotal gastrectomy. Patients with early gastric cancer (n = 51) had a 95% survival and those with intermediate cancer (n = 19) a 87% survival. Patients with advanced gastric cancer (n = 163) subjected to curative surgery had a 60% survival, whereas none subjected to palliative surgery survived. Those patients that survive more than 24 months after the surgical procedure, have an excellent long term prognosis.

Adult↗

[Intestinal malabsorption in patients treated with total gastrectomy].

Weight loss, chronic diarrhea and fat malabsorption are frequent after total gastrectomy. The aim of this work was to study parameters of intestinal absorption and the histology of jejunal mucosa in 26 patients subjected, at least one year ago, to total gastrectomy and without evidences of tumoral relapse. There was a mean weight loss of 9 kg (range 4 to 20) and 46% of patients had intermittent or episodical diarrhea. Hemoglobin was below 12 g/dl in 4 patients, serum albumin was below 3.5 g/dl in 3, serum carotene was below 40 micrograms/dl in 5 and serum iron was below 80 micrograms/dl in 5. Jejunal biopsies were normal and steatocrit was abnormal in all patients. Present findings suggest that fat malabsorption in these patients is intraluminal and due to an unequal mix of pancreatic and biliary secretions, as a consequence of Y en Roux transit reconstruction.

Adult↗

[Post sinusoidal obstruction of the hepatic venous flow associated with antiphospholipid syndrome in 3 cases].

Three cases of post-sinusoidal hepatic blood flow obstruction as the main feature of antiphospholipid syndrome are reported. Clinically, these patients developed jaundice, malaise, ascites and hepatomegaly. Ultrasonography-Doppler and hepatic venography showed small hepatic vein disease in two and partial occlusion in the suprahepatic segment of inferior vena cava in the remaining patient. In all, anticardiolipin antibodies were positive and activated partial thromboplastin time was prolonged. This experience emphasizes that in patients with post sinusoidal portal hypertension, a systematic search for antiphospholipid syndrome must be carried out.

Adult↗

[Hepatic angiosarcoma: report of 4 cases].

Hepatic angiosarcoma is an infrequent vascular liver tumor of high malignancy. Four patients (two males) are presented, in whom a histopathological study was performed. All patients died and in three a necropsy was executed.

Adult↗

[Morphology of the myenteric plexus of the small intestine in patients with liver cirrhosis].

BACKGROUND: Patients with liver cirrhosis develop small bowel dysmotility of unknown etiology. Morphological features in the enteric nervous system and the intestinal smooth muscle may shed light on pathophysiology of the gut motility disturbances in this disease. AIM: To investigate the morphology of the myenteric plexuses and smooth muscle layers of the small intestine in patients with liver cirrhosis. PATIENTS AND METHODS: Full thickness biopsies of duodenum, jejunum and ileum from seven cirrhotic patients and seven controls were stained with several techniques, including silver impregnation. Neuronal counting and light microscopy studies were stained performed. RESULTS: The neuronal count was not significantly different in patients with cirrhosis compared to controls in duodenal samples (1.6 +/- 0.4 cel/mm vs 1.6 +/- 0.2 cel/mm), jejunal tissue (1.2 +/- 0.3 cel/mm vs 1.4 +/- 0.2 cel/mm), and in ileal specimens (0.8 +/- 0.3 cel/mm vs 0.9 +/- 0.2 cel/mm). In both groups, evidence of fibrosis or inflammation in myenteric plexuses and in smooth muscle was not found. Also, intestinal neuronal dysplasia was absent in cirrhotic patients as in controls. CONCLUSION: These results suggest that small bowel dysmotility in patients with liver cirrhosis is not related to structural changes in myenteric plexuses or in intestinal smooth muscle noted by light microscopy.

Adult↗

Histological studies of Auerbach's plexuses of the oesophagus, stomach, jejunum, and colon in patients with achalasia of the oesophagus: correlation with gastric acid secretion, presence of parietal cells and gastric emptying of solids.

Histological changes in the Auerbach's plexuses of the oesophagus, stomach, jejunum, and colon were analysed in a prospective study in 34 patients with achalasia of the oesophagus. At the distal end of the oesophagus ganglia cells were absent in 91% of cases as well as in the middle third of the stomach (20%). The Auerbach's plexuses were normal in the jejunum and colon. The results of gastric acid secretion showed that the peak acid output was significantly lower in achalasia patients compared with controls (p less than 0.001). There was no correlation between the mean ganglion neuronal count in the gastric plexuses and the rate of gastric acid output (r = 0.33). Gastric emptying of solids was also evaluated, but there was no correlation between gastric emptying and the mean ganglion neuronal count in the gastric Auerbach's plexuses. The rate of gastric emptying of solids was similar in controls and patients with achalasia. These studies suggest that denervation of the oesophagus in patients with achalasia, which is a constant finding in several previous reports may extend beyond the oesophagus to the stomach in nearly half the cases.

Adult↗