A Haemodynamic Analysis to Assess the Safe Dose of Carvedilol across Different Child Class of Liver Disease.

Background: Literature regarding safe dose of carvedilol is limited and also safe dose across different child classes of chronic liver disease is not very clear. Aim: We aimed primarily to study, the effect of reasonably safe dose (12.5 mg) of carvedilol in acute reduction of portal pressure and compared it with chronic reduction of portal pressure, after proper optimization of dose of carvedilol. Second aim of our study was to define predictors of response for acute and chronic reduction of portal pressure and to assess difference in dose tolerated and response across different child class on chronic basis. Methods: One hundred two consecutive patients of cirrhosis of liver with significant portal hypertension were included and hepatic venous pressure gradient was measured at the base line and after 90 minutes of administration of 12.5 mg carvedilol. After proper dose optimization of carvedilol, hepatic venous pressure gradient was again measured after 3 months to assess the chronic response. Results: The mean age of study population was 58.3±6.6 years. A total of 42.2%, 31.9% and 26.6% patients had child class A, child class B and Child class C cirrhosis, respectively. Mean pre-drug hepatic venous pressure gradient was 16.75±2.12 mmHg which dropped to 13.07±2.32 mmHg after 90 minutes of administration of 12.5 mg of carvedilol. The mean drop of hepatic venous pressure gradient was 4.5±2.2 mmHg and 2.4±1.9 mmHg among responders and non-responders, respectively. Overall, 51% showed acute response while 49% were nonresponders. Low cardiac output and high mean arterial pressure were significantly predicting the acute response, while, low baseline cardiac output was found as an independent predictor. After dose optimization, number of responders increased from 52 to 62. Mean dose of carvedilol was higher in non–responders as compared to responders, though statistically insignificant (p>0.05). Mean reduction of hepatic venous pressure gradient from baseline and after 3 months was 5.5±1.7 mmHg and 2.8±1.6 mmHg among responders and non responders on chronic basis, respectively (p<0.001). Absence of any adverse events (OR 11.3, 95% CI; 1.9-67.8), and more than 2.5 mmHg fall in hepatic venous pressure gradient during acute response (OR 8.7, 95% CI; 3.1-25.3) were found as independent predictors of chronic response (p<0.05). Univariate analysis found that no adverse events, no ascites, low baseline cardiac output, more than 2.5 mmHg fall in hepatic venous pressure gradient during acute response, as predictors of chronic response. However, etiology, child class, variceal size (large vs small) and gender were not significantly associated with chronic response Conclusion: At safe dose and with proper optimization of dose, carvedilol may achieve greater response with minimum side effects among different child classes of liver disease.

A six-nucleotide deletion polymorphism in the casp8 promoter is associated with reduced risk of esophageal and gastric cancers in Kashmir valley.

BACKGROUND: Caspase-8 (CASP8) is a key regulator of apoptosis or programmed cell death, an essential defense mechanism against hyperproliferation and malignancy. To evaluate the role of CASP8 polymorphisms in esophageal (EC) and gastric cancers (GC) in the Kashmir valley, we examined the risk due to -652 6N ins/del polymorphism (rs3834129) in the promoter of CASP8 in a case–control study. MATERIALS AND METHODS: Genotypes of the CASP8 polymorphisms (-652 6N ins/del; rs3834129) were determined for 315 patients (135 EC and 108 GC) and 195 healthy controls by polymerase chain reaction. Data was statistically analyzed using Chi-square test and logistic regression model by using the SPSS software. RESULTS: Carriers for the del allele of rs3834129 single nucleotide polymorphism were associated with decreased risk for both EC (odds ratio [OR] = 0.278; 95% confidence interval [95% CI] = 0.090–0.853; P = 0.025) and GC (OR = 0.397; 95% CI = 0.164–0.962; P = 0.041). Also, in a recessive model, our results showed that CASP8 -652 6N ins/del “del/del” allele was conferring significant low risk for both EC (OR = 0.380; 95% CI = 0.161–0.896; P = 0.027) and GC (OR = 0.293; 95% CI = 0.098–0.879; P = 0.029). However, interaction of CASP8 -652 6N ins/del genotypes with smoking and high consumption of salted tea did not further modulate the risk of EC and GC. CONCLUSIONS: Polymorphism in CASP8 -652 6N ins/del polymorphism modulates the risk of EC and GC in Kashmir valley.

Incidence of colorectal cancer in Kashmir valley, India.

Background There is wide variation in the incidence of colorectal cancer globally and also within the same country among different racial or ethnic groups. The present population-based study was undertaken to determine the incidence of colorectal cancer in Kashmiri population which is non-migratory and ethnically homogeneous having stable food habits. Methods Over a period of one year, all newly diagnosed and histological proved cases of colorectal cancer in all possible areas, where such patients are diagnosed and treated were prospectively registered. Results A total of 212 cases of colorectal cancers were registered; of them 113 (53.3%) originated in the colon and other 99 (46.7%) in rectum. Male to female ratio was 1.2:1. The crude incidence rate of colorectal cancer was 3.65/ 100,000; it was 3.78 in males, and 3.50/100,000 in females. The incidence rates for colorectal cancer in Muslims and Hindus were different. The crude incidence rate for colorectal carcinoma was highest for district Srinagar 6.19/100,000 (urban area) and lowest for district Kupwara (rural area) 1.59/100,000. The highest numbers of cases were detected in the age group 55–59 years (n=34). The agespecific rate for colorectal carcinoma was highest in the age group 55–59 years (17.21/100,000), followed by 65–69 years (14.86/100,000). The age standardized incidence rate was 4.52/100,000 per year. The truncated age adjusted incidence rates in age group 35–64 years was 8.31/100,000; while that for colorectal carcinoma was 8.77/100,000 in males and 7.66/100,000 in females. Conclusion We conclude that the incidence of colorectal cancer in Kashmir valley is similar to that reported in the rest of India.

Predictors of intestinal parasitosis in school children of Kashmir : A prospective study.

Objectives: To identify the factors associated with intestinal parasitosis in rural and urban school children of Kashmir. Methods: Single fresh stool samples from rural and urban school children in three age groups: a)5 to < 8 years ,b) 8 to <11 years and c)11-14 years were taken .Various demographic characteristics considered were source of drinking water, type of toilet used and social classes as per the Kuppuswamy social scale. Personal hygiene was assessed by the visiting physician based on length of nails, hair and frequency of bathing. Stool samples were analyzed for detection of motile forms of E. histolytica and microscopic examination under low power detected eggs of intestinal helminths. Concentration methods were used if egg count was low. Results: 274 stool samples from rural school children and 240 samples were taken from urban school children respectively. 214 (46.7%) students had stool tests positive for parasitosis. Ascariasis was the most prevalent parasitosis ( 28%) followed by Giardiasis ( 7%) , Trichuriasis( 5%) and Taeniasis( 4%). There was higher prevalence of parasitosis among rural orphanage children compared to urban orphanage students (76% vs. 48% p <0.05). Highest prevalence of 70% was seen in the age group 8-11years. Students using river/stream water had higher rates of parasitosis compared to those who were using tap water. 202 students were found to have poor personal hygiene and parasitosis was higher in them compared to students with good personal hygiene (p<0.05). Conclusion: Poor environmental sanitation, personal hygiene, type of toilet and water used were associated with recurrent intestinal infestation besides socio economic status. Regular deworming programmes need to be adopted at school level especially in 8-11 years old children to check the surge of intestinal parasites and their subsequent morbidities.

Correlation of hepatic venous pressure gradient with variceal bleeding, size of esophageal varices, etiology, ascites and degree of liver dysfunction in cirrhosis of liver.

An elevated hepatic venous pressure gradient (HVPG) has been associated with risk of variceal bleeding, and outcome and survival after variceal bleeding. In this pilot study, we measured HVPG in 40 patients with liver cirrhosis and studied its relationship with etiology of liver disease, esophageal variceal size, history of variceal bleeding or ascites, biochemical liver tests and Child-Pugh class. There was no procedurerelated complication. The mean (SD) HVPG was similar in patients who had history of variceal bleeding as compared to those who did not (15.4 [2.8] mmHg vs. 13.9 [2.7] mmHg, p=0.1); HVPG had no significant association with etiology of cirrhosis (p=0.4). HVPG levels were significantly higher in patients with larger esophageal varices (grade III/IV vs. I/II: 15.2 [2.7] mmHg vs.13.1 [2.8] mmHg, p=0.04), poorer Child- Pugh class (B or C versus A), and presence of ascites (p=0.04). Thus, HVPG correlated with variceal size, Child-Pugh class, and presence of ascites, but not with variceal bleeding status.

Effect of bending exercise on gastroesophageal reflux in symptomatic patients.

BACKGROUND: Recumbency and bending are thought to provoke symptoms of reflux in patients with gastroesophageal reflux disease (GERD). The effect of exercise which involved bending and abdominal contractions was evaluated in symptomatic patients of GERD using continuous 24-hour ambulatory esophageal pH test. METHODS: Twenty-five patients with GERD, confirmed by abnormal 24-hour esophageal pH study, performed exercise for 30 minutes consisting of 5 sessions of 6 minutes each. The exercise involved toe touching from supine, sitting and standing position of 2 minutes' duration each. Each 2 minutes' period included 8 repetitions of the same exercise of 15 seconds' duration. 24-hour esophageal pHmetry was done on day 1 without exercise and on day 2 with 30-minute exercise. Reflux time percent (RT%) pH <4 was compared between days 1 and 2 and 30 minutes before and during exercise. RESULTS: Fourteen patients were upright refluxers and 11 patients were combined refluxers, which included 4 patients with supine reflux and 7 patients who refluxed both in supine and upright positions. The median (range) 24-hour RT% on day 1 and day 2 was 7 (5-40) and 7 (4-46), respectively (p=0.15). RT% during 30 minutes exercise compared with 30 minutes before exercise was 6.6 (0-60) and 0.0 (0.0-80) (p=0.02), respectively. In combined and upright refluxers, RT% during and before exercise was 13 (0-53) and 0.0 (0.0-42) (p=0.008), respectively and 0.0 (0-60) and 0.0 (0-80), (p=0.71), respectively. RT% between upright and combined refluxers during exercise was 0.0 (0-60) and 13 (0-53), respectively (p=0.004). The mean (SD) LES pressure in mmHg in combined and upright refluxers was 7 (2.9) and 19.6 (6.8), respectively (p=0.008). Esophagitis in combined and upright refluxers was seen in 8 patients (72.7%) and 2 patients (14.3%), respectively. Two patients (8%) developed symptoms during exercise. CONCLUSION: Exercise which involves bending precipitates reflux in patients with moderate-to-severe GERD.

Vesicoperitoneal fistula--an unusual cause of tense ascites.

We report a 55-year-old man who developed tense ascites due to vesicoperitoneal fistula. He had undergone surgery 32 years ago for excision of an infected urachal cyst, the tract and the umbilicus.