Biliary pain, no gallstones--remove the gallbladder, anyway?

As these 2 cases show, cholecystectomy may be helpful for such patients, even those with a high ejection fraction.

Is treatment with 6-mercaptopurine for colitis associated with the development of colorectal cancer?

BACKGROUND: Patients with ulcerative colitis and Crohn's colitis have an increased risk of colon cancer influenced by the duration, extent, and severity of disease. Surveillance colonoscopy serves to detect cancer and precancerous dysplasia at the earliest possible time. Reduction of inflammation should theoretically reduce the development of cancer. Immunosuppressives should do so, but there is a fear that indeed the risk of cancer might be increased with their use. Our study was conducted to determine whether a relationship exists between receiving treatment with 6-MP for ulcerative and Crohn's colitis and increasing or decreasing the incidence of colorectal cancer (CRC). METHODS: We conducted a single-center, retrospective cohort study of patients with long standing colitis (ulcerative and Crohn's) using the database of the senior investigator (B.I.K.). Two groups were matched based on their propensity to receive treatment with 6-MP; one group received 6-MP treatment, the other did not. Both groups were compared on the incidence of colon cancer. RESULTS: No significant differences existed between the two cohorts with regard to type of disease, duration, extent, age, and sex. Six out of 27 patients not on 6-MP and seven out of 27 patients on 6-MP developed CRC (P= 1). CONCLUSIONS: We conclude that there is neither sufficient evidence currently to state that 6-MP is associated with an increased development of CRC, nor that it has a chemopreventive effect.

Desensitization of patients with allergic reactions to immunosuppressives in the treatment of inflammatory bowel disease.

Crohn's disease and ulcerative colitis are chronic, immune-mediated inflammatory bowel diseases (IBDs) of unknown etiology with high morbidity in patients who are not receiving adequate medical treatment. A variety of medical therapies are currently available, and much progress has been made to alleviate symptoms and restore quality of life. The mainstay of treatment in those with moderate to severe disease consists of medications that alter or suppress the body's immunologic attack on its own gastrointestinal tract. The medications currently in use are highly effective when given in the appropriate clinical context, but side effects are not uncommon and must be treated expeditiously when they occur. One class of immunosuppressive medication, 6-mercaptopurine and its prodrug azathioprine, is effective at inducing remission and improving the lives of patients with IBD. The most common side effects of these drugs are allergic reactions and rarely can they be severe and life threatening. These reactions can sometimes be overcome by desensitizing the immune system to the drug. This review emphasizes allergy to 6-mercaptopurine and azathioprine and the process of desensitization when these allergic reactions occur in order to continue use of this important class of medication in the total treatment of IBD.

Choledochoscopy-assisted intraductal shock wave lithotripsy.

In more than 90% of choledocholithiasis cases, endoscopic retrograde cholangiopancreatography with sphincterotomy and stone extraction are successful therapeutic options for clearance of the bile duct with the use of a stone retrieval balloon or basket. However, these techniques fail in a small percentage of patients with biliary stones, and advanced techniques for fragmentation must be used. Intraductal shock wave lithotripsy offers the endoscopist a therapeutic option that may be effective despite the difficulties of a large, impacted stone that cannot be captured by a basket, or a stricture that prohibits delivery of a stone beyond it. This article reviews the use of electrohydraulic lithotripsy and laser lithotripsy in the clinical setting.

The prevalence of pantoprozole associated thrombocytopenia in a community hospital.

OBJECTIVE: Proton pump inhibitors (PPIs) are widely used in the treatment of gastritis, gastroesophageal reflux disease and peptic ulcer disease. Thrombocytopenia is not listed as one of the main side effects of PPI therapy. However, there have been documented cases of thrombocytopenia with the use of PPIs in the literature. Our objective was to determine whether exposure to PPIs leads to an increased incidence of thrombocytopenia in hospitalized patients. METHODS: This retrospective cohort study examined the platelet counts of 468 hospitalized patients who were 18 - 80 years of age, were prescribed pantoprazole for a minimum of 3 days and were matched to 468 non-medicated controls. The primary outcome was defined as either a drop in the platelet count by >/= 50% relative to baseline, or a drop to < 150,000/ml. Exclusion criteria were baseline thrombocytopenia and hospitalization for < 3 days. RESULTS: No difference was found in the occurrence of thrombocytopenia between the two groups (6.2%; 95% CI = 4.1 - 8.7%) in the study group versus (6.6%; 95% CI = 4.5 - 9.2%) in the control group (p = 0.90). Post-hoc analysis revealed a higher incidence of > 20% drop in platelet count in the study group compared with the controls (23%; 95% CI = 19 - 27% versus 11%; 95% CI = 8 - 14%, respectively; p < 0.001). CONCLUSION: This study failed to demonstrate an increased incidence of thrombocytopenia for patients treated with pantoprazole. Our study adds support to the favorable safety profile of PPI therapy in hospitalized patients. Further investigation is needed to evaluate the effects of PPI use in the outpatient setting.

Abnormalities of uterine cervix in women with inflammatory bowel disease.

AIM: To evaluate the prevalence of abnormalities of the uterine cervix in women with inflammatory bowel disease (IBD) when compared to healthy controls. METHODS: One hundred and sixteen patients with IBD [64 with Crohn's disease (CD) and 52 with ulcerative colitis (UC)] were matched to 116 healthy controls by age (+/- 2 years) at the time of most recent papanicolaou (Pap) smear. Data collected consisted of age, race, marital status, number of pregnancies, abortions/miscarriages, duration and severity of IBD, Pap smear results within five years of enrollment, and treatment with immunosuppressive drugs. Pap smear results were categorized as normal or abnormal including atypical squamous cells of undetermined significance (ASCUS), low-grade squamous intraepithelial lesion (LGSIL), and high-grade squamous intraepithelial lesion (HGSIL). RESULTS: The median age at the time of Pap smear was 46 (range: 17-74) years for the IBD group and matched controls (range: 19-72 years). There were more Caucasian subjects than other ethnicities in the IBD patient group (P = 0.025), as well as fewer abortions (P = 0.008), but there was no significant difference regarding marital status. Eighteen percent of IBD patients had abnormal Pap smears compared to 5% of controls (P = 0.004). Subgroup analysis of the IBD patients revealed no significant differences between CD and UC patients in age, ethnicity, marital status, number of abortions, disease severity, family history of IBD, or disease duration. No significant difference was observed in the number of abnormal Pap smears or the use of immunosuppressive medications between CD and UC patients (P = 0.793). No definitive observation could be made regarding HPV status, as this was not routinely investigated during the timeframe of our study. CONCLUSION: Diagnosis of IBD in women is related to an increased risk of abnormal Pap smear, while type of IBD and exposure to immunosuppressive medications are not. This has significant implications for women with IBD in that Pap smear screening protocols should be conscientiously followed, with appropriate investigation of abnormal results.

Developmental regulation of cardiac MAP4 protein expression.

It has been shown that the level of expression of microtubule-associated protein 4 (MAP4) mRNAs changes throughout neonatal heart development [Chapin SJ, et al. 1995. Biochemistry 34:2289]. In the present study, both immunofluorescence and western blotting methods were used to monitor MAP4 protein expression levels in the developing heart. By both methods, it was shown that the levels of total MAP4 protein were maximal during the first postnatal week, and then declined progressively to adulthood. In addition, four major electrophoretic species that reacted with MAP4-specific antibodies (called bands 1-4) were observed in all heart tissue samples. Three of the four bands decreased in abundance throughout postnatal development, but at different rates. The fourth band remained relatively constant in abundance with increasing postnatal age. To determine if phosphorylation events might contribute to this heterogeneity, western blotting experiments using phospho-specific antibodies and phosphatase digestion of extract samples were performed. No phosphorylation-specific antibody staining was observed and no significant changes were demonstrated in the bands after phosphatase treatment, implying that the observed complexity was due mainly to alternative start site or differential isoform expression. Finally, it was discovered that cardiomyocyte MAP4 associated with drug- and cold-stable microtubules in early neonatal myocytes. Thus, the complex regulation of MAP4 protein expression may play a key role in the functional differentiation of myocyte microtubules during heart development.

Incidence of neoplasms in patients who develop sustained leukopenia during or after treatment with 6-mercaptopurine for inflammatory bowel disease.

BACKGROUND & AIMS: Studies to date have not confirmed an association between neoplasms and inflammatory bowel disease (IBD) treated with 6-mercaptopurine (6-MP). We have observed the occurrence of some neoplasms in IBD patients who developed sustained leukopenia as a result of treatment with 6-MP. As a result, we sought to compare the incidence of neoplasms in patients who developed sustained leukopenia after taking 6-MP compared with patients treated with 6-MP without sustained leukopenia. METHODS: A database containing the medical records of more than 600 patients treated with 6-MP for IBD at 1 center between 1965 and 2002 was searched. The patients were divided into 2 groups. The study group consisted of patients who developed sustained leukopenia, defined as a white blood cell count of less than 4000 for 20 or more days. The control group patients matched those in the study group for age and sex. There were 3 matched controls for each patient in the study group. RESULTS: Eighteen patients developed sustained leukopenia and, of these, 4 developed neoplasms (22%)-2 leukemias, 1 non-Hodgkin's lymphoma, and 1 breast cancer. Of the 54 patients in the control group, 4 developed neoplasms (7%) (P = .10). Post hoc analysis revealed a statistically significant difference in the number of hematologic malignancies in the group with sustained leukopenia (P = .014). There was no significant difference between the 2 groups for all confounding variables examined. CONCLUSIONS: There was a trend toward a greater number of total malignancies in the sustained leukopenic patients. The data suggest that it is those patients who develop sustained leukopenia while taking 6-MP/azathioprine who are most at risk.

Toxicity of infliximab in the course of treatment of Crohn's disease.

Infliximab is a monoclonal antibody directed against the pro-inflammatory mediator TNF-alpha, which was approved in the US in 1998 for treatment-resistant Crohn's disease. Since that time, the indications have dramatically expanded to include rheumatoid arthritis, ankylosing spondylitis, psoriasis and most recently, active ulcerative colitis. Although the safety profile in the initial studies was quite favourable, subsequent studies have shown that a small percentage of patients reported severe side effects, including pneumonia, tuberculosis, lymphoma, drug-induced lupus and hepatotoxicity. Although these complications are rare, it is important to properly screen patients for predisposing conditions before beginning treatment. Furthermore, concurrent use of other immunosuppresive agents, such as 6-mercaptopurine, may reduce the incidence of less serious side effects, such as arthralgias, myopathies and other antibody-associated diseases. Since its approval, infliximab has revolutionised the treatment of Crohn's disease and has shown benefit in a variety of other inflammatory conditions, but significant toxicities can occur that necessitate thorough screening protocols and periodic clinical evaluation.