Search

Chronic arsenic toxicity (CAT) manifests predominantly as cutaneous lesions in the form of melanosis, keratosis and neoplastic changes. We have studied skin biopsies from 42 patients of CAT. Histological study of H/E stained sections showed--hyperkeratosis in 13, parakeratosis in 13, acanthosis in 12, papillomatosis in 24, elongation of reteridges in 21, increased basal pigmentation in 27 and dysplastic changes in 8 cases. Squamous cell carcinoma was present in 2, basisquamous in 1 and basal cell carcinoma in 1 case. Changes of skin lesions after drug DMSA and DMPS therapy compared to placebo were studied. The result was inconclusive. Proliferative activity of skin lesions in CAT were studied by AgNOR stain to assess the biological behaviour of the lesions. AgNOR score showed--normal control 1.08, benign changes (e.g. Hyperkeratosis, parakeratosis, acanthosis, papillomatosis etc.) without dysplasia--1.35, mild to moderate dysplasia--1.735, severe dysplasia--3.0 and carcinoma--3.56. Thus, AgNOR score gives some idea on the biological behaviour of CAT lesions. It is suggested that AgNOR staining should be done regularly along with HE staining for proper assessment of the cases.

The pathophysiology of non ulcer dyspepsia is poorly understood. Data on gastrointestinal motility alterations in this condition in the Indian population are scanty. We studied esophageal and gastric motility in patients with non ulcer dyspepsia.58 consecutive patients with non ulcer dyspepsia (according to the Rome criteria) were studied; 10 healthy volunteers were studied as controls. Esophageal transit of solid and liquid boluses (in all patients) and solid-phase gastric emptying (in 20 patients) were studied using scintigraphic techniques.Delayed esophageal transit and delayed gastric emptying were observed in 32 (55%) and 9 (45%) patients, respectively. Delay of both esophageal and gastric transit was found in 5 patients. Mean (SD) esophageal transit for liquid bolus was significantly delayed in patients (9.3 [3.7] s) compared to controls (7.0 [2.0] s; p0.01). Mean (SD) gastric emptying time (T50) was significantly delayed in patients (61.6 [13.6] min) compared to controls (50.0 [5.0] min; p0.001). Esophageal and gastric delayed transit was found in about two thirds of patients with dysmotility-like dyspepsia, but there were no significant difference in these abnormalities among different subgroups of dyspepsia.High prevalence of esophageal and gastric transit delay was found in non ulcer dyspepsia, particularly in the dysmotility subgroup.

Oxidative stress has been implicated in the initiation of hepatic damage caused by various agents. Not much data on oxidative stress in liver in chronic arsenic exposure are available in the literature. We therefore studied this aspect in a murine model.BALB/c mice were given arsenic-contaminated (3.2 mg/L) or arsenic-free (0.01 mg/L, control) drinking water ad libitum. Batches of mice were sacrificed after 2 and 4 months, and blood samples and liver tissue were collected. Liver histology was examined and levels of hepatic reduced glutathione (GSH), malondialdehyde, and enzymes of the antioxidant defense system in the liver tissue were determined. Arsenic content in liver tissues obtained at 4 months was estimated.Two-month exposure to arsenic caused significant elevation of hepatic GSH (11.4 [0.8] micrograms/mg protein) compared to control mice (9.3 [0.4]; p0.01). Levels of enzymes related to GSH homeostasis were also elevated. At 4 months, hepatic GSH was significantly reduced (8.4 [0.5] micrograms/mg protein) when compared to control mice (9.3 [0.4]; p0.01). Arsenic content in the liver tissue after 4 months of exposure was significantly higher (0.40 [0.05] microgram/g) as compared to control mice (0.04 [0.04]; p0.01).The results suggest that the antioxidant defense system in the liver of mice is activated after exposure to arsenic for 2 months. However, prolonged exposure to arsenic probably causes overuse failure of this system, which might result in initiation of biochemical injury to the liver.

The excretory-secretory (ES) antigens of Ascaris suum are known to cause hepatic damage in animals. The present study was aimed at developing an animal model of hepatic fibrosis with these antigens.Three doses of ES antigens of A. suum were injected into 24 golden hamsters on days 0, 10 and 20. Batches of 8 animals each were sacrificed at 3 days, 45 days and 90 days after the third injection, after collection of blood. Three groups of 6 control animals each were injected with normal saline and were sacrificed similarly. Liver biochemistry, leukocyte migration inhibition test on cells separated from spleen, and liver histology were carried out.Serum ALT levels in experimental animals were significantly higher than those in control animals at days 3, 45 and 90 after the last antigen dose; AST levels were elevated 45 and 90 days after the last dose of ES antigen. Leukocyte migration inhibition in experimental animals was 58.2 (8.5)%, 51.6 (11.2)% and 50.5 (12.8)% at days 3, 45 and 90 after the last antigen dose. Marked centrivenular degeneration and necrosis were observed in liver tissue in all the experimental animals sacrificed 72 h after the last antigen dose. Condensation of reticulin around the portal zone with extension into the liver lobule was observed in 4 of 8 and 7 of 8 experimental animals sacrificed 45 and 90 days, respectively, after the last dose. Control animals did not have such lesions.An animal model of hepatic fibrosis could be produced by repeated injection of ES antigens of A. suum.

Immunoproliferative small intestinal disease (IPSID) is commonly reported from developing countries with poor socioeconomic conditions, hygiene, and high frequency of gastrointestinal infections and infestations. The disease requires anti-malignant chemotherapy in lymphomatous stage. Reported here is a 20-year old man with IPSID lymphoma who responded to anti-malignant chemotherapy initially, but later deteriorated due to Strongyloides stercoralis infestation, which was treated successfully with mebendazole. Importance of an early recognition and adequate treatment for gastrointestinal infections and infestations before anti-malignant chemotherapy for this disease is highlighted considering the occurrence of this disease in the developing world. The patient developed alternate brown black and white lines in the finger nails after combination chemotherapy, which has not been reported earlier in this disease; the nail changes disappeared 6 months after the withdrawal of doxorubicin suggesting this drug as the cause for such nail changes during anti-malignant combination chemotherapy.

Infection with Helicobacter pylori is believed to be associated with generation of reactive oxygen molecules which leads to oxidative stress in the gastric mucosa; but the relation between oxidative stress and gastrointestinal mucosal damage has not been documented.To look for evidence of oxidative stress and lipid peroxidation in the gastric mucosa in H. pylori-associated peptic ulcer.34 duodenal ulcer (DU) patients with H. pylori infection, 14 DU patients without H. pylori infection and 10 healthy subjects without H. pylori infection were studied. H. pylori infection was diagnosed by histology and rapid urease test on endoscopic biopsies from the gastric body and antrum. Reduced glutathione (GSH) and malondialdehyde (MDA) content were measured in biopsies taken from the gastric antrum. Statistical analysis was done using Student's t test.Tissue levels of GSH were significantly lower (91.7 [35.4] nmole/100 mg versus 147.3 [41.2] nmole/100 mg; p0.001) and MDA higher (163.0 [83.4] nmole/100 mg versus 109.2 [51.3] nmole/100 mg; p0.01) in patients with DU associated with H. pylori infection as compared to those without H. pylori infection. GSH levels were significantly lower and MDA levels higher in DU patients with or without H. pylori infection as compared to control subjects. Serum MDA levels in DU patients with H. pylori infection were also significantly higher than in patients without H. pylori infection.Depletion of gastric mucosal glutathione in H. pylori-infected DU patients may be due to failure of the antioxidant defense system. Failure of the glutathione-dependent defense system results in accumulation of free radicals which can initiate membrane damage by lipid peroxidation.

Since 1983 large number of people are being encountered with arsenic toxicity due to drinking of arsenic contaminated water (0.05-3.2 mg/l) in 6 districts of West Bengal. Clinical and various laboratory investigations were carried out on 156 patients to ascertain the nature and degree of morbidity and mortality that occurred due to chronic arsenic toxicity. All the patients studied had typical rain drop like skin pigmentation (being inclusion criteria) while thickening of palm and sole were found in 65.5% patients. Other features included weakness (70%), gastro-intestinal symptoms (58.6%), involvement of respiratory system (57.08%) and nervous system (50.6%). Lung function tests showed restrictive lung disease in 53% (9/17) and combined obstructive and restrictive lung disease in 41% (7/17) of patients. Abnormal electromyography was found in 34.8% (10/29) and altered nerve conduction velocity in 34.8% (10/29) of cases. Enlargement of liver was found in 120 cases (76.9%) while splenomegaly in 31.4% cases. Liver function test showed elevated globulin level in 15.8% and alkaline phosphatase in 51.3%, alanine amino transferase (ALT) in 11.8% and aspartate amino transferase (AST) in 27.6% of cases. Evidence of portal hypertension was found in 33.3% patients. Liver biopsy reports of 45 patients showed non-cirrhotic portal fibrosis in 41, cirrhosis in 2 and normal histology in 2 cases. There was no correlation between the quantity of arsenic taken through water and the level of arsenic in hair, nail, liver tissues and the degree of fibrosis. There were 5 deaths of which one had skin cancer. The various non-cancer manifestations which were observed in these patients were much severe than those reported in similar cases in other parts of the world.

A subset of patients with chronic duodenal ulcer has severe ulcer diathesis in the form of frequent relapses and complications like perforation and hemorrhage. We observed the effect of drug treatment on the natural history of this subset.Of 526 patients diagnosed to have chronic duodenal ulcer by endoscopy, 23 patients with severe diathesis were available for long follow-up (mean period 36 months). Each patient was assessed clinically and endoscopically every 2 months for at least 12 months and then every 3 months or when symptomatic. Helicobacter pylori status was assessed during endoscopy. The effect of antisecretory drugs and anti-H. pylori therapy on natural history was determined.Thirteen of 23 patients (56%) had refractory ulcers; six responded to double dose of H2-receptor antagonists (H2RA) for 8 weeks and six to omeprazole 40 mg daily for 4-8 weeks. Of 20 patients (87%) who were H. pylori-positive, 15 completed triple-drug therapy; of these, 10 patients eradicated H. pylori. These 10 patients were followed up for 24 months; there were no ulcer relapses within the first 12 months but 8 of them relapsed between 12 and 24 months (total number of relapses 8). Reinfection with H. pylori occurred in 3 patients. In the other 10 patients who remained H. pylori-positive, there were 19 episodes of ulcer relapse in 7 patients over 24 months, in spite of maintenance therapy with H2RA (p0.05).Refractoriness in patients with severe ulcer disease is usually episodic and amenable to larger doses of omeprazole or H2RA. Anti-H. pylori therapy improves the natural history but its effect in preventing ulcer relapse is short lasting (less than 12 months). Recurrence of infection is a problem in our population.

To evaluate the frequency and clinical importance of portal hypertensive gastropathy (PHG) and gastric varices (GV) before endoscopic sclerotherapy (EST) and after esophageal variceal obliteration.Patients with portal hypertension (PHT) with variceal bleed were prospectively evaluated for PHG and GV before EST with intravariceal injection of absolute alcohol and after esophageal variceal obliteration. Gastric varices and PHG were characterized and graded according to previously established criteria. Patients were followed up for 12-48 (mean 37) months after variceal obliteration.Of 70 patients with PHT 26 had PHG before (severe in two) [18/37 in cirrhosis, 6/20 in non-cirrhotic portal fibrosis (NCPF), and 2/13 in extrahepatic portal vein obstruction (EHPVO)] and 50 had PHG after variceal obliteration (severe in 22) (27/37 in cirrhosis, p = 0.03 before versus after esophageal variceal obliteration; 16/20 in NCPF, p0.01; and 7/13 in EHPVO, p = ns). Type I GV (continuation of esophageal varix into the stomach) was found in 25/70 before and 5/70 after esophageal variceal obliteration (p0.001); in contrast, other types of GV were seen in 14/70 before and 29/70 after (p0.01). Overt bleeding from GV and PHG during follow-up after variceal obliteration occurred in 6 and 4 patients, respectively.Esophageal variceal obliteration by EST increases the frequency of PHG and GV (except type I GV which get obliterated); both PHG and GV have potential to cause rebleeding.

Picrorhiza kurrooa (Pk) has been used in liver diseases in the Indian indigenous system of medicine. We undertook this study to determine whether Pk extract possesses hepatoprotective function and if so to determine its nature and mechanism.Liver injury was induced in 16 mice by thrice-a-week injection of carbon tetrachloride (CCl4) for nine weeks. Eight of them were given daily feeding of Pk extract (12 mg/Kg) 10 days prior to CCl4 injection. Control mice (n = 6) were injected with olive oil for the same period. Serum markers of liver injury and histology of liver tissues were studied. Hepatic glutathione (GSH), total thiol (-SH), glucose 6-phosphate dehydrogenase (G6PD), catalase, lipid peroxidation and plasma membrane-bound Na+/K+ ATPase were also determined.CCl4 treatment resulted in significant elevation of serum ALT and AST. Liver GSH [6.3 (0.7) vs control 10.5 (1.1) micrograms/mg protein], -SH, G6PD, catalase and membrane-bound Na+/K+ AT-Pase [164.3 (23.2) vs control 358.4 (12.9) nmole pi released/min/mg protein] were significantly reduced. Significant increase of lipid peroxidation [3.0 (0.6) vs control 1.0 (0.3) nmole MDA/mg protein] and histologic changes characteristic of liver injury were also seen. Feeding of Pk extract in CCl4-treated mice caused significantly less alteration of serum ALT, AST, liver GSH [8.9 (0.7) micrograms/mg protein], -SH, G6PD, catalase and membrane-bound Na+/K+ ATPase [270.8 (21.3) nmole pi released/min/mg protein]. Histologic lesions of liver and lipid peroxidation [1.7 (0.4) nmole MDA/mg protein] were also significantly less in these animals.The extract of Pk appears to offer significant protection against liver damage by CCl4. It probably acts as free-radical scavenger and inhibitor of lipid peroxidation of liver plasma membrane.

Portal Hypertension (PH) is the commonest cause of upper gastrointestinal bleeding in children. Most Indian studies have highlighted extrahepatic portal venous obstruction (EHPVO) as the major cause of PH in children. As there is paucity of data from the eastern part of the country we decided to study the major causes of PH in children in this region and to ascertain the efficacy of sclerotherapy for its management. Fifty children aged 14 months to 10 years with PH were studied from April 1990 to April 1995. Thorough examination and relevant investigations showed non-cirrhotic portal fibrosis (NCPF) in 24 (48%), EHPVO in 18 (36%) and cirrhosis of liver in 8 (16%) children. Forty six children had hematemesis and melaena of whom endoscopic sclerotherapy (EST) was done in 45 cases. One child having type 2 gastric varices was referred for surgery. Following eradication of varices the patients were followed-up at 3 monthly intervals. Number of sittings of sclerotherapy required for obliteration of varices was 5.9 +/- 1.6. A variceal state was achieved in 35 (78%) cases and varices were reduced to Grade I in 6 cases (13%). Two cases underwent surgery for EST failure. One patient of cirrhosis died within two weeks of bleeding episode due to hepatic encephalpathy. Rebleeding (13%) and recurrences (13%) were noted during the follow-up period. Retrosternal discomfort (22%), dysphagia (22%), stricture (13%), oesophageal ulceration (13%) and fever (11%) were the complications noted but these could be managed conservatively. The present study highlights that NCPF is an important cause of PH in eastern India. EST is useful in controlling variceal bleeding in children irrespective of their aetiology.

Hepatitis A is usually thought to be innocuous. We report a woman who developed subacute hepatic failure due to hepatitis A and died of the disease.

Nosocomial infection is a major problem in hospitalized patients, particularly those who are debilitated. These infections may manifest as diarrhea. The spectrum of infections agents causing nosocomial diarrhea in our country is not known.Thirty-two patients, admitted to the hospital with various complaints, who developed diarrhea during their hospital stay, were studied to identify the causative agents of diarrhea. Hospital food samples were also processed for pathogens.The bacteria isolated from patients included established enteropathogens like Salmonella, enteropathogenic Escherichia coli, Campylobacter species and organisms with low pathogenicity like Serratia marsescens, Pseudomonas aeruginosa and Morganella morganii. The bacterial pathogens isolated were resistant to most antibiotics, suggesting their nosocomial character. Hospital food samples contained Salmonella typhimurium, Campylobacter jejuni (biotype 1) and enteropathogenic Escherichia coli, suggesting that food might have been the vehicle for these infections.Nosocomial infection was found to be an important cause of diarrhea (34%), EPEC and Salmonell being the predominant pathogens. Water, egg and milk were the source of infection in these cases. Special measures to obtain uneffected items will prevent occurrence of nosocomial diarrhea in our hospitals.

A rare combination of multiple adenomatous polyps of the colon and carcinoid tumor of the ileum in a 54-year-old man is reported.

We describe three patients with nephrotic syndrome and non-cirrhotic portal fibrosis. In two of them, the liver disorder preceded the nephrotic syndrome while in the third patient the two conditions presented together. All three patients achieved remission of nephrotic syndrome with prednisolone and cyclophosphamide.

To ascertain the role of excretory and secretory (ES) products of Ascaris lumbricoides in liver damage.The ES products of A lumbricoides were collected in vitro and their SDS-PAGE analysis was done. Feeding and subcutaneous injection of ES products were done in hamsters. Estimation of serum proteins, alkaline phosphatase and alanine aminotransferase and histology of liver were carried out. Control animal experiments were done concurrently.The ES products of A lumbricoides contained several proteins ranging in molecular weight from 14 to 205 Kd. Prolonged feeding of ES products caused elevation of ALT and amyloid deposition in the liver, whereas short term feeding or subcutaneous challenge caused focal cell necrosis and granuloma formation in the liver.ES products of A lumbricoides can produce liver damage.

Immunological status of 14 women taking oral contraceptive for prolonged period (more than 6 months, low dose pill) was studied. Phytohaemagglutinin induced lymphocytes stimulation (PILT) was found to be significantly depressed in these subjects though T-lymphocyte subpopulation was found to be normal. Serum IgA and IgG levels in these cases were found to be normal but IgM level was increased. Though incidence of G lamblia infection was reported to be high in immunocompromised subjects, it was found only one out of 14 subjects taking oral contraceptive harboured the protozoa.Whether use of oral contraceptives depresses the immune system in Indian women, and whether they affect the prevalence of giardiasis in users, was explored by testing immune function and stools for Giardia lamblia in 14 pill users and 10 controls. The subjects were aged 18-40 and had taken a low dose oral contraceptive for at least 6 months. The immune functions examined were quantitative serum IgG, IgA and IgM levels by radial immunodiffusion, cell-mediated response to phytohemagglutinin, and peripheral T-cell counts. 1 pill user had signs of giardia infection. Immunoglobin levels in the other were not significantly different from controls, except for IgM, which was 415.34 mg/dl in pill users, vs. 251.69 in controls. T-cells were normal in 1 pill user tested. The mean blastogenic index, or lymphocyte transformation index, was significantly depressed at 6.6 in pill users as well as the woman with giardia, compared to 17.6 in controls. The reported incidence of giardiasis in an adult Indian population was 4.4%, thus the incidence in these pill users was not increased. The significance of the immunologic findings was unknown.

The paper presents clinical observations on 1 233 persons with smallpox who were admitted to the Infectious Diseases Hospital, Calcutta, in 1973. The disease was of the modified type in 53 patients (4.3%), the ordinary type in 717 (58.2%), the flat type in 249 (20.2%), and the haemorrhagic type in 214 (17.3%). The fatality of these types of smallpox was found to be 5.7%, 26.8%, 88.4%, and 98.1%, respectively, and the overall case fatality was 50.7%. The haemorrhagic type was found mainly among older patients and affected males more often than females. The vaccination status of 1 218 patients was known. Of these, 901 (73.9%) were unvaccinated and had a fatality rate of 53.4%, whereas the 317 (26.1%) vaccinated patients had a fatality rate of 36.5%. Among the 201 haemorrhagic cases, 145 patients were unvaccinated (16.09% of the total number unvaccinated) and 56 (17.67%) had been vaccinated. Of 34 patients vaccinated during the incubation period, 19 (41.1%) died, whereas of 18 patients who had been vaccinated after the onset of fever, but before the appearance of rash, 9 (50%) died.

Gastric acid production, unstimulated and following stimulation with betazole hydrochloride, was measured in Indian men with cholera or acute vibrio-negative diarrhoea-Measurements were made during acute illness and after different periods of convalescence. Men from the same socioeconomic group and from a higher one served as controls. Stimulated acid production was severely reduced during diarrhoea caused by V. cholerae and related vibrios but not during acute vibrio-negative diarrhoea. Acid production returned to stable convalescent values 1-3 days after cessation of diarrhoea. Stimulated acid production was significantly lower in controls from the lower socioeconomic group than in those from the higher socioeconomic group. Achlorhydria that did not respond to betazole administration occurred in 32% of the convalescent cholera patients but in none of the controls or convalescent vibrio-negative diarrhoea patients. It is concluded from these results that diarrhoea produced by V. cholerae and related vibrios is accompanied by transient inhibition of gastric acid secretion, that cholera occurs largely in a population with impaired acid secretion, and that preexisting achlorhydria may predispose to infection with V. cholerae.