Gastroduodenal manifestations in patients with skeletal fluorosis.

A prospective case-controlled study was performed to evaluate the gastrointestinal symptoms and mucosal abnormalities occurring in patients with osteofluorosis. Ten patients with documented osteofluorosis and ten age- and sex-matched healthy volunteers were included in the study. Clinical evaluation, real-time ultrasound, and upper gastrointestinal endoscopy and biopsy from the gastric antrum and duodenum were performed in all subjects. The biopsies were subjected to a rapid urease test and light and electron microscopic examinations. Ionic fluoride levels were estimated in the drinking water, serum, and urine using an ION 85 ion analyzer. All patients with osteofluorosis had gastrointestinal symptoms, the most common being abdominal pain. Endoscopic abnormalities were found in seven patients with osteofluorosis. In all 7 of these patients, chronic atrophic gastritis was seen on histology. Electron microscopic abnormalities were observed in all 10 patients with osteofluorosis. These included loss of microvilli, cracked-clay appearance, and the presence of surface abrasions on the mucosal cells. None of the control subjects had any clinical symptoms or mucosal abnormalities. It was concluded that gastrointestinal symptoms as well as mucosal abnormalities are common in patients with osteofluorosis.

Toxic effects of chronic fluoride ingestion on the upper gastrointestinal tract.

In a prospective case controlled study, we evaluated the adverse effects of long-term fluoride ingestion on the gastrointestinal tract. Ten patients with otosclerosis who were receiving sodium fluoride 30 mg/day for a period of 3-12 months, and 10 age- and sex-matched healthy volunteers were included. They were all evaluated clinically and subjected to a real time ultrasound examination, upper gastrointestinal endoscopy, and biopsies from the gastric antrum and duodenum. The biopsies were subjected to a rapid urease test as well as light and electron microscopic examinations. Ionic fluoride was estimated in the serum, urine, and drinking water using an ION 85 Ion Analyzer. Seven subjects (70%) ingesting fluoride had abdominal pain, vomiting, and nausea. Petechiae, erosions, and erythema were seen on endoscopy in all the subjects, but not in the controls. Histological examination of the gastric antral biopsy showed chronic atrophic gastritis in all the subjects but in only one (10%) healthy volunteer. Scanning electron microscopic examination showed "cracked-clay" appearance, scanty microvilli, surface abrasions, and desquamated epithelium in the subjects ingesting fluoride, but not in the controls. We conclude that long-term fluoride ingestion is associated with a high incidence of dyspeptic symptoms as well as histological and electron microscopic abnormalities.

Deuterium oxide normalizes blood pressure and elevated cytosolic calcium in rats with ethanol-induced hypertension.

This study examined the effect of 10% deuterium oxide (D2O) in drinking water on systolic blood pressure, platelet cytosolic free calcium, aortic calcium uptake and renal vascular changes in rats with ethanol-induced hypertension. Eighteen male Wistar-Kyoto rats, age seven weeks, were divided into three groups of six animals each. Group I was given water and groups II and III, 5% ethanol in drinking water for the next seven weeks. After one week, systolic blood pressure in the ethanol-treated rats was significantly higher (P < 0.01) than in rats drinking water. After seven weeks, animals in group I were continued on water, group II on 5% ethanol, group III on 5% ethanol but with the addition of 10% D2O in their drinking water for the next seven weeks. After 14 weeks, systolic blood pressure, platelet cytosolic free calcium and aortic calcium uptake was significantly higher (P < 0.01) in group II rats (given ethanol for 14 weeks) compared with rats from other groups. Ethanol-treated rats also showed smooth muscle hyperplasia with some thickening of the wall and narrowing of the lumen in small arteries and arterioles of the kidney. D2O given to ethanol-treated rats normalized their blood pressure, platelet cytosolic free calcium, aortic calcium uptake and attenuated renal vascular changes.

Ethanol induced hypertension in rats: reversibility and role of intracellular cytosolic calcium.

This study examined the reversibility of chronic ethanol induced increase in systolic blood pressure, elevated platelet cytosolic free calcium and aortic calcium uptake in rats and the effect of a calcium channel blocker on these changes. Twenty-four male Wistar-Kyoto rats, age 7 weeks, were divided into 4 groups of 6 animals each. Animals in group I were given water and group II, III and IV, 5% ethanol in drinking water for the next 7 weeks. Systolic blood pressure in the ethanol treated rats was significantly higher (p < 0.01) than in controls after 1 week and remained higher. After 7 weeks, group I was continued on water, group II on ethanol, group III was continued on ethanol but with the addition of verapamil 5 mg/100 ml in their drinking water and group IV was returned to normal drinking water for the next 7 weeks. After 14 weeks, systolic blood pressure, platelet cytosolic free calcium and aortic calcium uptake was significantly higher (p < 0.01) in rats given ethanol for 14 weeks and also in rats given ethanol for 7 weeks followed by water for 7 weeks as compared to controls. These two groups also showed smooth muscle cell hyperplasia with some thickening of the wall and narrowing of the lumen in small arteries and arterioles of kidney. Verapamil given to the ethanol treated rats normalized their blood pressure, platelet cytosolic free calcium, aortic calcium uptake and attenuated renal vascular changes. Discontinuation of ethanol treatment for 7 weeks did not reverse the hypertension or the adverse renal vascular changes in ethanol induced hypertensive rats.

Fluoride as a possible aetiological factor in non-ulcer dyspepsia.

A prospective case controlled study was conducted to evaluate the role of fluoride as a possible aetiological factor for non-ulcer dyspepsia (NUD). Twenty patients with NUD and 10 age and sex matched healthy controls were subjected to clinical evaluation, upper gastrointestinal endoscopy and biopsies from the gastric antrum and duodenum. The antral and duodenal mucosa was subjected to a rapid urease test for Helicobacter pylori and histological and electron microscopic examinations. Fluoride levels in the drinking water, serum and urine were estimated using a ION 85 ion-analyser. These levels were significantly higher in patients with NUD than in controls (P less than 0.05). Histological abnormalities in the antral and duodenal mucosa were seen in 14 patients (70%) with NUD and 1 control subject (10%) (P less than 0.05). Electron microscopic abnormalities in the mucosal cells were seen in all patients with NUD but in none of the controls (P less than 0.01). The fluoride levels in serum and urine correlated with the symptoms, histological and electron microscopic abnormalities (P less than 0.05). It was concluded that chronic exposure to fluoride may result in NUD and should be considered in patients where other known cause of dyspepsia have been excluded.

Control of variceal bleed with metoclopramide.

The efficacy of parenteral metoclopramide in the control of active variceal bleeding was assessed in a prospective, randomized, double blind, placebo controlled trial. Patients with portal hypertension due to different etiologies (cirrhosis, non cirrhotic portal fibrosis and extrahepatic portal venous obstruction) with endoscopically documented active variceal bleeding entered the study. Forty nine consecutive patients were randomized after pre-entry stratification for Child's scores. Intravenous metoclopramide (20 mg) or 2 ml dextrose was administered in all patients while the first endoscopy documented an active variceal bleeding. All patients were subjected to a second endoscopy 15 minutes later to determine control of bleeding. Rebleeding rate, transfusion requirement, adverse effects and mortality were analysed. Twenty of the 25 patients treated with metoclopramide stopped bleeding compared to 5 of 24 in the control group (p less than 0.05). Rebleeding occurred in 4 of 20 in the metoclopramide group and 4 of 5 in the control group within 72 hours (p less than 0.05). The number of patients requiring blood transfusion (10 vs 16) and the transfusion requirement (1.8 +/- 2.2 vs 3.6 +/- 2.1 units) were significantly lower (p less than 0.01) in the metoclopramide group than in the control group. Mortality was similar and there were no complications due to therapy. We conclude that intravenous metoclopramide is a safe and effective agent for the control of acute esophageal variceal bleeding.