Effect of biotherapeutics on antitoxin IgG in experimentally induced Clostridium difficile infection.

Purpose: Recurrent diarrhoea after successful treatment of primary Clostridium difficile associated disease (CDAD) occurs due to bowel flora alterations and failure to mount an effective antibody response. Apart from antibiotics, risk factors include immunosuppressive and acid-suppressive drug administration. Biotherapeutics such as probiotic and epidermal growth factor (EGF) may offer potential effective therapy for CDAD. Materials and Methods: The effect of biotherapeutics in mounting an antibody response against C. difficile toxins was studied in BALB/c mice challenged with C. difficile after pre-treatment with ampicillin, lansoprazole or cyclosporin. Sera from sacrificed animals were estimated for antitoxin IgG by enzyme linked immunosorbent assay. Results: Antitoxin IgG was significantly higher (P<0.05) in C. difficile challenged groups compared to unchallenged controls, but insignificant (P>0.05) in animals in which C. difficile was given after pre-treatment with cyclosporin compared to those without any pre-treatment, or pre-treatment with antibiotic or lansoprazole. In inter-subgroup comparisons also significant anomaly in production of antitoxin IgG was found. The antitoxin IgG levels were raised in animals administered C. difficile after pre-treatment with ampicillin, but lower in animals administered cyclosporin. High levels of antitoxin IgG were also found in the serum samples of animals receiving lansoprazole and C. difficile. Conclusions: Probiotics showed their beneficial effect by boosting the immune response as seen by production of antitoxin IgG. Oral administration of EGF did not affect the immune response to C. difficile toxins as significant increase was not observed in the serum antitoxin IgG levels in any of the groups investigated.

Benign gastric outlet obstruction – spectrum and management.

Intrinsic or extrinsic obstruction of the pyloric channel or duodenum either by benign or malignant diseases leads to gastric outlet obstruction. With improvement in science and technology, the spectrum of gastric outlet obstruction has changed from peptic ulcer disease to corrosives and malignant diseases. Newer investigations like computerized tomography and endoscopy have supplemented the previous clinical tests like saline load test and barium series. Improvised treatment modalities like endoscopic balloon dilatation and endoscopic incision have circumvented the use of surgery which was the gold standard for management of gastric outlet obstruction. Newer modalities like biodegradable stents have an upcoming role in the management.

Importance of CYP2C19 genetic polymorphism in the eradication of Helicobacter pylori in north Indians.

Background & objectives: Genetic polymorphism of CYP2C19 is known to occur with a frequency of 12 per cent in north Indian population. But no study correlated CYP2C19 genetic polymorphism with eradication of Helicobacter pylori in north Indian gastritis patients positive for H. pylori and hence this study. Methods: Ninety one consecutive patients positive for H. pylori fulfilling the study criteria were phenotyped and genotyped for CYP2C19. They were given 20 mg omeprazole (OPZ), 750 mg amoxicillin (AMC) and 500 mg tinidazole (TNZ) (bid) for 7 days followed by 20 mg OPZ (qd) for 21 days. Non eradicated extensive metabolizers (EMs) were retreated with 40 mg OPZ (bid) and 500 mg AMC (qid) for 14 days. Results: EMs and poor metabolizers (PMs) excreted 4.26 ± 0.34 (95% CI 3.59-4.92) and 0.73 ± 0.05 (95% CI 0.63-0.82) μmol 5-OH-OPZ in 8 h, respectively. After initial therapy, EMs demonstrated 37 per cent (95% CI: 24.5-49.5) and PMs 92 per cent (95% CI: 77-107) eradication of H. pylori. Non eradicated EMs after retreatment demonstrated 90 per cent (95% CI: 79-101) eradication. Interpretation & conclusions: This study demonstrated a direct correlation between CYP2C19 genetic polymorphism and H. pylori eradication in north Indian patients with gastritis. Knowing the CYP2C19 phenotype of a patient may help in prescribing optimum dose of proton pump inhibitor to achieve better therapeutic outcome.

Coexistent hepatic and pulmonary epitheloid hemangioendothelioma.

Epitheloid hemangioendothelioma (EHE) is a rare neoplasm of vascular origin known to arise in soft tissue, liver and lung. We describe a case of coexistent hepatic and pulmonary epitheloid hemangioendothelioma, proven on autopsy, and review the histological and radiological features of epitheloid hemangioendothelioma. The coexistence of hepatic with pulmonary EHE has been reported in only a few cases. Large confluent masses, peripheral location with capsular retraction, hypertrophy of uninvolved liver, invasion of portal and hepatic veins, enhancing margins and delayed enhancement and dense calcification are the typical features which provide a clue to diagnosis of hepatic EHE. In patients with both hepatic and pulmonary EHE it is difficult to say whether the tumor arose primarily in the lung or liver, or began simultaneously in both organs.

Genetic polymorphism of CYP2C19 & therapeutic response to proton pump inhibitors.

Proton pump inhibitors (PPIs) are extensively metabolized in the liver by CYP2C19, that demonstrates genetic polymorphism with 21 mutant alleles. The subjects can be divided into 2 groups with respect to CYP2C19 phenotypes viz., extensive metabolizers (EMs) and poor metabolizers (PMs) of PPIs. This division results in marked interindividual variations in the pharmacokinetics and pharmacodynamics of PPIs in the population. Intragastric pH values and the plasma concentration of PPIs after oral ingestion were significantly lower in EMs namely normal homozygotes (CYP2C19*1/*1) and heterozygotes (CYP2C19*1/*X) compared to PMs namely mutant homozygotes (CYP2C19*X/*X) where 'X' represents the mutant allele. Hence, association has been found between the genetic polymorphism of CYP2C19 and therapeutic response to PPIs. CYP2C19 polymorphism affected eradication of Helicobacter pylori using diferent PPI based eradication therapies as PM patients demonstrated significantly higher eradication rates compared to EMs. CYP2C19 genetic polymorphism also affects the therapeutic outcome of gastroesophageal reflux disease (GERD), reflux oesophagitis and duodenal ulcers. For optimal therapeutic response with PPIs, CYP2C19 pharmacogenetics should be taken into consideration. This shall help in the prescription of optimal doses of PPIs, thus paving the way for personalized medication.

Radiation Schedules for Palliation in Carcinoma Esophagus.

This study was undertaken to compare the three different radiation schedules for their efficacy in symptom relief, dysphagia free survival and radiation morbidity (if any), in carcinoma oesophagus. A total of 116 inoperable patients were prospectively randomized to three different arms of radiation. Arm-A received external beam radiation (EBRT) to a dose of 30Gy/10 #/2 weeks along with two sessions of intraluminal brachytherapy (ILBT), 600cGy each, one week apart, after a gap of two weeks from EBRT. Arm-B received only EBRT to a dose of 30Gy/10 #/2 weeks. Arm-C received EBRT to a dose of 20Gy/5#/1week without brachytherapy. The age of the patients ranged from 30 - 70 years. Improvement in dysphagia was seen in 76% of patients in Arm-A, 56% in Arm-B & 54% in Arm-C at 1 month. The dysphagia progression free survival was 10.6+0.6 months in Arm-A, 9.8+0.8 months in Arm-B and 9.9+0.6 months in Arm-C respectively. Grade 1 & 2 acute radiation toxicity was seen in 50% of patients in Arm-A, 55% patients in Arm-B & 30% patients in Arm-C. It is concluded that all the three radiation schedules achieved good palliation with similar dysphagia free survival.

Severe acute bleeding from portal colopathy controlled by somatostatin: a case report.

Portal hypertensive colopathy (PHC) is a recently described entity in patients with portal hypertension which can cause even life-threatening lower gastrointestinal bleeding. In contrast to variceal bleed, there is no standardized treatment for the control of bleeding from these lesions. We report a case of alcoholic cirrhosis with portal hypertension, in whom bleeding from colonic angiodysplasia-like lesions was effectively controlled by somatostatin infusion.

Transendoscopic fine needle aspiration cytology in the diagnosis of hepatocellular carcinoma.

This report describes the use of transendoscopic fine needle aspiration cytology in the diagnosis of three cases of hepatocellular carcinoma who had presented with large nodular liver and mass impression on the left border of the stomach at endoscopy. Using a 21G, 1.0 cm needle catheter, transendoscopic fine needle aspiration was done under direct endoscopic vision. The aspirate confirmed the diagnosis of hepatocellular carcinoma in all of them.

Celiac disease presenting as iron-deficiency anemia in northern India.

BACKGROUND: Adult celiac disease is infrequent in India. Iron-deficiency anemia as its presenting manifestation is still rarer. METHODS: We investigated patients with refractory iron-deficiency anemia attending the hematology clinic of a tertiary-care hospital for celiac disease. The diagnosis of celiac disease was based on histology, serology and response to treatment. RESULTS: Of 19 patients with refractory iron-deficiency anemia seen from April 1998 to March 2000, 11 were diagnosed to have celiac disease. Four of these had abnormal D-xylose test and 3 had fat malabsorption. All 11 patients responded to gluten-free diet with improvement in hematological parameters. CONCLUSION: Patients with refractory iron-deficiency anemia of unknown cause should be investigated for subclinical celiac disease.

Lactose intolerance in different types of irritable bowel syndrome in north Indians.

BACKGROUND: Twenty-five patients of irritable bowel syndrome (IBS) and 25 normal healthy individuals serving as controls, were studied for lactose intolerance. METHODS: Hydrogen breath test was used as an investigation after giving 50 g of oral lactose. Clinically, the patients were classified into 3 types of IBS. RESULTS: Eleven (44%) out of 25 patients belonged to diarrhoeal type of IBS, 7 (28%) of 25 patients to spastic and rest 7 (28%) of 25 patients had features of both types of symptoms. Lactose hydrogen breath test was abnormal in 9 cases (82%) of 11 diarrhoeal type of IBS which was significantly higher (p < 0.02) than controls. However, the difference of abnormal hydrogen breath test between spastic type of IBS and patients with features of both types was not significant as compared to controls. CONCLUSIONS: These results suggest that patients with diarrhoeal type of IBS have a higher incidence of lactose intolerance as compared to spastic type as well as patients with features of both types.

Paterson-Kelly syndrome and celiac disease--a rare combination.

Paterson-Kelly syndrome is characterized by an association of iron deficiency with dysphagia. We describe a patient with this syndrome who was later diagnosed to have celiac disease.

Intestinal pseudo-obstruction due to neurofibromatosis responding to cisapride.

Gastrointestinal involvement in neurofibromatosis presenting with mechanical obstruction, hemorrhage or intussusception is known. Small bowel dysmotility and intestinal pseudo-obstruction due to neurofibromatosis is rare. A 23-year-old man with classical neurofibromatosis presented with intermittent episodes of intestinal pseudo-obstruction, small bowel bacterial overgrowth and steatorrhea. The patient had good symptomatic improvement with cisapride.

Concurrent renal transitional cell carcinoma and right colon cancer.

A 45-year-old man who had undergone right radical nephrectomy for transitional cell carcinoma 3 months earlier was admitted with right colonic tumor. Review of CT done for right kidney tumor was suggestive of right colon pathology. Right hemicolectomy was performed, followed by a course of chemotherapy for mucinous adenocarcinoma, and he is well a year later.

Teratocarcinoma presenting with duodenal metastases diagnosed on endoscopic fine needle aspiration.

Upper gastrointestinal bleed as the first symptom of metastatic testicular tumors is rare. We describe a 17-year-old man who presented with upper gastrointestinal bleed; endoscopic fine needle aspiration cytology from a duodenal mass suggested germ cell tumor, which was later confirmed on histology of the testis.

Watermelon stomach: a rare cause of upper gastrointestinal bleeding.

Watermelon stomach is a rare cause of upper gastrointestinal bleeding. We report a middle-aged woman who had been having recurrent bleeding from watermelon stomach. She was treated surgically by gastrectomy and Billroth II anastomosis.

Retained surgical sponge: an unusual cause of malabsorption.

Retained surgical sponge is an unpleasant surprise in clinical practice. Intraluminal migration of the retained sponge, though rare, can lead to intestinal obstruction and other complications. We describe two cases of retained surgical sponge, both following gynaecological surgery, presenting several years after surgery with features of subacute intestinal obstruction, malabsorption and several years after surgery with features of subacute intestinal obstruction, malabsorption and sever hypoproteinemia which reverted after surgical removal.