Thiopurines treatment for inflammatory bowel disease in current clinical practice

Thiopurines, or purine analogues, are immunomodulators used in the treatment of malignancies, rheumatic diseases, dermatologic conditions, inflammatory bowel disease and in solid organ transplantation. These agents include azathioprine [AZA], mercaptopurine [6-MP] and thioguanine [6- TG]. Thiopurines are converted by the enzyme thiopurine methyltransferase [TPMT] into metabolites. Measurement of TPMT activity may help identify patients at risk for excessive toxicity, most often myelosuppression, after receiving standard doses of thiopurine medications. Measurement of metabolites [metabolite markers] may help tailor individualized drug therapy. Azathioprine, which is a prodrug of 6-mercaptopurine [6-MP], is considered an effective immunosuppressive treatment of inflammatory bowel disease, particularly in patients with steroidresistant disease. For example, in the course of 1 year, 50% of patients with Crohn's disease will require steroids for its treatment; of these, 50% will either be steroid resistant or steroid dependent, and thus candidates for immunosuppressive therapy. Azathioprine therapy eliminates the need for corticosteroids in about 75% of patients; azathioprine is also considered an effective therapy for fistulizing disease. A recent randomized clinical trial of children with Crohn's disease suggests that compared to prednisone alone, the inclusion of azathioprine with prednisone at the time of initial diagnosis is associated with improved maintenance of remission, while simultaneously decreasing the dose of prednisone. However, the use of azathioprine is limited by both its long onset of action [3-4 months] and drug toxicities, which include hepatotoxicity, bone marrow suppression, pancreatitis and allergic reactions. Long-term drug use has been associated with neoplasia. The purpose of this comprehensive review is to suggest guidelines for the application of azathioprine and 6-mercaptopurine in the treatment of inflammatory bowel disease

Oesophageal carcinoma in Jordanian field hospital in Afghanistan

Mazzar-I-Shariff in Afghanistan, is a poor wartorn city with only one gastrointestinal endoscopist in the region. It was noticed by previous gastroenterologists working in Jordanian Field Hospital in Afghanistan that oesophageal carcinoma is seen more frequant than that in Jordan. The objectives of the study were to determine the spectrum of upper gastrointestinal diseases in patients who undergone upper endoscopy in the Jordanian Field Hospital in Afghanistan and to estimat the incidence,age of diagnosis, clinical presentations and the endoscopic appearanace of the oesophageal carcinoma. Between 20 Decumber 2003 and March 3, 2004, 289 gastroscopies were performed in Jordanian field Hospital/Afghanistan on patients aged 16 years or more. Biopsies were taken from any suspected lesion. Data for each patient were kept to correlate with the histopathological results. Thirty three [11.4%] endoscopies gave normal results. The most common major single findings in the other 256 were oseophageal carcinoma [22.5%] duodenal ulcers [13.5%], and oesophagitis [13%]. About one third of the patients had more than one endoscopic finding. Oseophageal carcinoma was found in 22.5% of patients and it was more common in men than women. The most common presenting symptom for oseophageal carcinoma were dysphagia and weight loss. It was more frequent in age group of 60-72 years. The most common endoscopic findings were mass or ulcerative lesion. Oesophageal carcinoma is a common finding in patients who had upper endoscopy in the Jordanian Field Hospital in the north of Afghanistan.Mazzar-I-Sharif needs well equiped gastrointestinal unit and a multi disciplinary team [Gastroenterologist, Histopathologist, Surgeon and Dietitian] to deal with patients with oesophageal carcinoma and more research is needed to establish the possible etiology

Nonalcoholic steatohepatitis [NASH]

Nonalcoholic steatohepatitis [NASH] is a chronic liver disease that is attracting increasing significance characterized by diffuse fatty infiltration and inflammation.The exact prevalence of NASH is unclear, but it is becoming more evident that the disease is much more common than previously thought, although originally believed to be a benign clinical entity, NASH is now recognized as a cause of progressive fibrotic liver disease with adverse clinical sequelae. Clinical characteristics associated with NASH include obesity, hyperlipidemia, and diabetes mellitus, all of which have been associated with underlying insulin resistance. Typically, this disease becomes evident in the fourth or fifth decade of life with an equal sex predilection. NASH is thought to be caused, in part, by impaired insulin signaling, leading to elevated circulating insulin levels and subsequent altered lipid homeostasis. This process is likely multifactorial and includes both genetic and environmental factors. Treatment options to date are limited and are based on very small clinical trials. Current investigations are focusing on improving the underlying insulin resistance that has been associated with NASH as well as other therapies that decrease oxidative stress or improve hepatocyte survival

comparison of four different regimens in the treatment of acute brucellosis

To evaluate the efficacy and safety of four combinations in the treatment of brucellosis. All drugs were administered orally for six weeks except streptomycin intra-muscular for 14 days. One hundred and forty eight patients were enrolled in the study. Ninety three [66.4%] patients of them had blood and or marrow culture positive for Brucella. Brucella melitensis was identified in 92 [98.9%] patients and Brucella abortus only in one [1.1%] patient. The significant side effect for the four combinations was gastric discomfort. From 88 patients received Doxycycline-Rifampicin, there were five [5.7%] relapses, and 29 [32.9%] patients had gastric discomfort of the twenty eight patients received Doxycycline-Streptomycin; there were two [7.1%] relapses and six [21.4%] patients had gastric discomfort. From the twenty one patients received Rifampicin- Co-trimoxazol, there were two [9.5%] therapeutic failure, six [28.5%] relapses and seven [33.3%] patients developed gastric discomfort. There were no relapses among the eleven patients received Rifampicin-Ciprofloxacin, and two [18.2%] patients had gastric discomfort. The combination of Rifampicin plus Ciprofloxacin or Rifampicin plus Doxycycline adminstred for six weeks are convenient, safe and effective. The next choice is Doxycycline-Streptomycin, and Rifampicin-Co-trimoxazol is the least effective in the treatment of acute brucellosis

Hepatic manifestations of human brucellosis

No data on the frequency and diversity of hepatic abnormalities occurring in brucellosis in Jordan have been reported. In the present study 175 patients with proven brucellosis were investigated to determine the hepatic changes during the active course of this infection. Two hundred and seventeen adult patients were studied prospectively during the years between 1987-1996 at the Jordan University Hospital, and those [211 patients] who had clinical picture suggestive of brucellosis were admitted to the hospital for investigations. From 175 cases proved to have brucellosis, elevated aspartate aminotransferase [AST] was detected in 20.6% patients, elevated alanine aminotransferase [ALT] 14.6% patients, elevated alkaline phosphatase in 31.4% patients. Total protein below 60 gm/L was found in 3.4% patients, albumin below 35 gm/L in 19.5% patients, elevated bilirubin in 29.1% patients. Hepatomegaly in 31.4% patients. Liver cirrhosis was observed in 2 patients, liver abscess in one patient. The commonest hepatic function profile abnormalities are elevation of transaminases and bilirubin. Liver abscess and cirrhosis may occur. Hepatic non caseating granuloma is characteristic for brucellosis and so liver biopsy may be done as a diagnostic test when clinical picture is consistent with brucellosis and other tests for brucellosis are negative

diagnostic value of various laboratory tests in human brucellosis

To determine the accuracy and reliability of various laboratory tests in the diagnosis of human brucellosis. Method: 217 adult patients were studied prospectively during the years between 1987-1996 at the Jordan University Hospital. Of these, 211 patients with the clinical picture suggestive of brucellosis were admitted to the hospital for investigations. Of the 175 patients proved to have brucellosis, 91.4% were found to have a brucella titer of >/= 1/160, 32.5% revealed positive blood culture and 40.3% had positive bone marrow culture. 8.57% patients were found to have negative brucella agglutination test, and the diagnosis was based on positive blood culture, bone marrow culture, the presence of non-caseating granuloma in bone marrow or liver biopsy in association with the suggestive clinical picture and combined with complete response to antibrucella drugs. Six patients were found to have brucella titers >/= 1: 160 without the accompanying suggestive clinical picture. Follow up titers of those patients at the outpatient clinic were decreasing, all had previous antimicrobial therapy and were excluded from the study. Brucella agglutination test and titer in association with the suggestive clinical picture is sensitive, rapid, inexpensive and less contagious than other available laboratory methods in the diagnosis of human brucellosis