Risk of colorectal neoplasia associated with the adenomatous polyposis coli E1317Q variant.

BACKGROUND: Reports of the risk of colorectal neoplasia associated with a variant of the adenomatous polyposis coli (APC E1317Q) gene are conflicting. Using a case-control design, we investigated this relationship within a clinic-based cohort followed through the Integrated Cancer Prevention Center and the Tel-Aviv Sourasky Medical Center. MATERIALS AND METHODS: All study subjects were tested for the APC E1317Q variant at enrollment. Subjects underwent colonoscopic evaluation (+/-biopsy and/or polypectomy) and had cancer history and colorectal neoplasia risk factors assessed. The crude and adjusted risks of neoplasia associated with the E1317Q variant were calculated. RESULTS: The prevalence of the E1317Q variant was 1.4% in the entire study sample and 3.2% in Sephardic Jews. E1317Q was more prevalent among cases: 15 of 458 (3.3%) cases were carriers compared with 11 of 1431 (0.8%) controls [odds ratio (OR) 4.4, 95% CI 2.0-9.6]. When stratified by neoplasia type, adenoma risk was significantly elevated in carriers (OR 4.1, 95% CI 1.8-9.4) but colorectal cancer risk was not (OR 2.1, 95% CI 0.8-5.3). After adjustment, the E1317Q variant remained a significant predictor of colorectal adenoma (OR 4.6, 95% CI 2.0-10.8). CONCLUSIONS: The APC E1317Q variant is associated with colorectal neoplasia, particularly colorectal adenomas, but further studies are still needed. Variant prevalence is elevated in Sephardic Jews.

Regulation of PGLYRP1 and TREM-1 during Progression and Resolution of Gingival Inflammation.

INTRODUCTION: The triggering receptor expressed on myeloid cells 1 (TREM-1) signaling pathway is stimulated by bacteria and, together with its putative ligand peptidoglycan recognition protein 1 (PGLYRP1), propagates proinflammatory responses. OBJECTIVES: We aimed to evaluate the TREM-1/PGLYRP1/interleukin (IL)-1ß regulation in response to biofilm accumulation and removal in an experimental human gingivitis model. METHODS: The study (n = 42 participants, mean age: 23.8 ± 3.7 y) comprised a recruitment step (day -14) followed by experimentally induced biofilm formation (induction [I] phase, day 0 to +21) and a 2-wk resolution (R) phase (day +21 to +35). Plaque was recorded by the Modified Quigley and Hein Plaque Index (TQHPI), while records of gingival inflammation were based on the Modified Gingival Index (MGI). Unstimulated whole saliva supernatants (n = 210, 5 time points) were tested for TREM-1, PGLYRP1, and IL-1ß by enzyme-linked immunosorbent assay. RESULTS: During the I-phase, concentrations of all analytes showed a tendency for downregulation at day +7 compared to day 0. TREM-1 (P = 0.019) and PGLYRP1 (P = 0.007) increased significantly between day +7 and day +21. Although all analyte levels decreased during the R-phase, the difference was not significant except TREM-1 being at borderline significance (P = 0.058). Moreover, TREM-1, PGLYRP1, and IL-1ß showed significant positive correlations (P < 0.0001) with each other. The study participants were grouped into "fast" and "slow" responders based on clinical gingival inflammation scores. At each time point, fast responders showed significantly higher concentrations of TREM-1 (P < 0.025), PGLYRP1 (P < 0.007), and IL-1ß (P < 0.025) compared to slow responders. Mixed-effects multilevel regression analyses revealed that PGLYRP1 (P = 0.047) and IL-1ß (P = 0.005) showed a significant positive association with the MGI scores. CONCLUSION: The study demonstrated that TREM-1 and PGLYRP1 are regulated in response to biofilm accumulation and removal, and fast responders demonstrated higher levels of these analytes compared to slow responders. KNOWLEDGE TRANSFER STATEMENT: The results of this study demonstrated the suitability of salivary TREM-1 and PGLYRP1 to reflect biofilm accumulation and removal and PGLYRP1 to monitor the progression and resolution of inflammation in gingivitis-susceptible individuals (fast responders). Combined with conventional risk factors, the molecular toolbox proposed here should be further validated in future studies to confirm whether it can be used for population-based monitoring and prevention of gingivitis.

Low-dose heparin for the prevention of post-ERCP pancreatitis: a randomized placebo-controlled trial.

BACKGROUND: As suggested by observational and animal studies, heparin has antiinflammatory effects that could prevent acute post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis. Low-molecular-weight heparin did not reduce the incidence of post-ERCP pancreatitis in a controlled study. The current study aimed to determine whether prophylactic administration of low-dose unfractionated heparin, which has potentially more antiinflammatory capability, can prevent acute post-ERCP pancreatitis. METHODS: Patients scheduled for ERCP in the authors' department were randomized to receive unfractionated heparin (5,000 IU) or placebo (saline solution 0.5 ml) administered subcutaneously 20 to 30 min before the ERCP. Patients who had undergone endoscopic sphincterotomy in the past were excluded from the study. Post-ERCP pancreatitis was defined according to criteria established by Cotton: abdominal pain combined with a threefold elevation of blood amylase 24 h after the ERCP. RESULTS: The study enrolled 106 patients. One patient was excluded from the analysis due to inaccessible papilla of Vater, leaving 51 patients in the heparin group and 54 in the placebo group, for a total of 105 patients (62 women and 43 men) with a mean age of 64.6 years. The rate of post-ERCP pancreatitis was not different between the groups (heparin, 4 patients, 7.8%; placebo, 4 patients, 7.4%). Two patients in each group experienced mild bleeding. CONCLUSIONS: The study did not demonstrate a significant effect of low-dose unfractionated heparin in the prevention of post-ERCP pancreatitis. A multicenter trial with a larger number of patients is needed to demonstrate a benefit from this drug.

Proton pump inhibitors reduce cell cycle abnormalities in Barrett's esophagus.

Neoplastic progression in Barrett's esophagus is a multi-step process in which the metaplastic columnar epithelium sequentially evolves through a metaplasia-dysplasia-carcinoma sequence. The expression and DNA copy number of key cell cycle regulatory genes in paired normal and Barrett's esophagus samples was evaluated. Protein levels were evaluated in 60 formalin-fixed, paraffin-embedded human tissues by immunohistochemistry. DNA copy number from 20 fresh tissue pairs was analysed by Southern blot analysis. All normal mucosal samples expressed the p27(kip1) protein, but did not display appreciable nuclear staining for p16(kip4), p21(cip1) or cyclins D1 and E. Barrett's metaplastic specimens displayed increased expression levels of p16(kip4) (74%), p21(cip1) (89%) and cyclins D1 (43%) and E (37%). p27 protein was absent in three cases. There was a significant correlation between the expression of p16(kip4) and cyclin E, and p21(cip1) and p27(kip4) with cyclin D1. DNA analysis did not reveal any amplification or deletion of these genes. Acid suppression, however, was associated with significantly lower expression levels of key cell cycle proteins. Increased expression of key cell cycle regulatory genes appears to occur early in the neoplastic progression associated with Barrett's esophagus. Treatment with proton pump inhibitors appears to alter this increased expression.

Malabsorption syndrome, coccidiosis, combined immune deficiency, and fulminant lymphoproliferative disease.

Coccidia were found in a patient suffering from malabsorption syndrome. In addition, immunologic investigation showed combined humoral and cellular immunodeficiency. Treatment with metronidazole induced the disappearance of coccidia from the stool and clinical remission. Six months later, the patient was seen with acute lymphoproliferative disease and died thereafter. The possible relationship between malabsorption, immunodeficiency, coccidiosis, metronidazole, and malignancy is reviewed.

One week triple therapy with omeprazole, clarithromycin and tinidazole for Helicobacter pylori: differing efficacy in previously treated and untreated patients.

BACKGROUND: Triple therapy with omeprazole, clarithromycin, and tinidazole (OCT) has been found to be highly effective against Helicobacter pylori infection. However, its efficacy as a second line regimen for patients who failed metronidazole-based triple therapy has not been evaluated. AIM: The aim of this study was to evaluate the efficacy of low-dose, short-term OCT therapy in an Israeli population, and to compare results obtained in previously treated and untreated patients. METHODS: Patients with duodenal or gastric ulcers and chronic antral gastritis with H. pylori infection as assessed by rapid urease test and/or 14C urea breath test (14C-UBT), were studied. All patients received omeprazole 20 mg b.d., clarithromycin 250 mg b.d. and tinidazole 500 mg b.d. for 7 days. Eradication was assessed by 14C-UBT 4 weeks after treatment. RESULTS: One hundred and fourty-four patients (M/F = 81/63) were enrolled (mean age 48.1 years, range 12-78). Eradication of H. pylori was significantly different between patients who were initially treated with this regimen (90/94, 96%) and patients who had previously failed to eradicate H. pylori with standard triple therapy (27/50, 54%). Moreover, the eradication rate was significantly decreased in patients with more than one previous failure (9/22, 41%) compared to that in patients with only one failure (18/29, 62%). No other differences such as age, gastric pathology, ethnic origin, smoking habits, or pre-treatment urease activity were found to influence the eradication rate. CONCLUSIONS: One-week low-dose triple therapy with OCT is highly effective as an initial therapy in eradicating H. pylori infection. The efficacy is significantly lower when given as a second line treatment in patients who have previously failed to eradicate H. pylori with bismuth-based standard triple therapy.

A modified, solid phase radioimmunoassay for the differential diagnosis of acute and convalescent phases of hepatitis A infection.

The commercial assays for diagnosing the presence of hepatitis A antibodies (HAVAB; Abbott Laboratories, North Chicago, IL) or the presence of IgM class anti-hepatitis A virus antibodies (HAVAB-M; Abbott) do not provide precise information as to the timing of the acute infection. IgM class antibodies are detected as late as six months after the acute infection. In this study the authors describe a modified HAVAB test that inactivates the IgM class antibodies. It thus measures the proportion of IgG antibodies out of the total anti-hepatitis A virus antibodies. In a study of 139 patients with impaired liver function, the available and modified tests showed good agreement except for the convalescent phase of hepatitis A. During serial testing for three months after the acute infection, the commercial tests continuously detected IgM class antibodies. The modified test detected predominantly IgG class antibodies from four weeks on. By six weeks, 85% of the patients had predominantly IgG class antibodies. The modified test thus provides information on the timing of recent hepatitis A infection.

Clinical and angiographic findings in black patients with suspected coronary artery disease.

To determine the clinical variables and coronary angiographic findings in black patients with suspected coronary artery disease, we analyzed the data on consecutive black patients undergoing their first coronary angiogram over a three year period at the Cook County Hospital, Chicago, Illinois. We compared these findings to those of black and white patients from previous studies. There were 654 patients with a mean age+/-standard deviation of 56+/-10 years; 309 (47%) were men. Two hundred nineteen patients (33%) presented with unstable angina, 75 patients (12%) with acute myocardial infarction and 338 patients (52%) with chronic stable angina. Three hundred forty-six patients (53%) had 50% or greater stenosis in at least one of the major vessels. Among the patients with coronary artery disease, 128 patients (37%) had one vessel disease, 102 patients (29%) had two-vessel disease, and 116 patients (34%) had three-vessel disease. Black patients who undergo coronary angiography for suspected coronary artery disease have a high frequency of normal coronary angiogram or non-obstructive coronary artery disease. The frequency of 1-, 2- and 3-vessel disease in blacks with coronary artery disease is comparable to those observed in whites in previous reports.

Prostaglandin E2 in duodenal ulcer complications.

Prostaglandins are presumed to have cytoprotective properties and may play a role in the pathogenesis of duodenal ulcer and its complications. To evaluate this hypothesis, 35 patients with either duodenal ulcer bleeding (18 patients) or gastric outlet obstruction (17 patients) were investigated. Biopsies were taken from gastroduodenal tissues and secretions for prostaglandin E2 (PGE2) levels. These levels were compared to those taken from the same areas during a later endoscopy. A correlation was found between the severity of the clinical endoscopic findings and PGE2 levels. Increased levels of PGE2 were found in the quiescent phase and decreased levels found during the deteriorated phase. These differences of PGE2 levels were found to be of significant value (P less than 0.002). Furthermore, the patients in which the PGE2 levels were decreased at second endoscopy needed surgery. PGE2 may, thus, be a factor in duodenal ulcer pathogenesis and its complications, and be used as a prognostic marker and guide.

Laparoscopic herniorrhaphy: review of complications and recurrence.

Laparoscopic hernia repair has evolved considerably since its introduction. Different methods have been described, and multiple studies have been performed reporting widely varying outcomes. This study was undertaken to review all the major publications on laparoscopic herniorrhaphy from 1993 to 1996 and evaluate the rates of recurrence and complications involved in the various techniques. In a total of 11,222 laparoscopic hernia repairs, the procedure performed most frequently was the transabdominal preperitoneal patch (TAPP), followed by the total extraperitoneal patch (TEP). There were 300 (2.7%) recurrences. From 9,955 hernia repairs, there were 1,534 (15.4%) complications. Hematoma/seroma (456), neuralgia (199), urinary retention (150), and chronic pain (39) were the most frequently reported complications. Laparoscopic herniorrhaphy is a higher effective method of hernia repair with results comparable with the open technique. TAPP is still the most widely performed technique. TEP is becoming more popular, mainly because of its excellent outcome. The major drawback of TEP is the difficulty of reproducibility by different general surgeons with comparable results. Other techniques such as plug and patch carry a high rate of recurrence and complications and should probably be completely abandoned.

Laparoscopic staging of Hodgkin's disease.

With recent advances in laparoscopy, specifically the development of laparoscopic splenectomy, a complete laparoscopic Hodgkin's staging procedure is now possible. Using five trocars and the patient in the right semidecubitus position, six laparoscopic staging procedures were performed. All were stages IIA or IIB pre-operatively, and none were upgraded to stage III or IV as a result of the procedure. Operative time was from 185-255 min. (mean 210 min.) There were no operative morbidities or mortalities associated with the procedure. We believe this procedure will be adopted by more surgeons as they become more comfortable in performing laparoscopic splenectomies.

[Early postoperative constrictive pericarditis: value of echocardiography. Report of 4 cases]. / Péricardite constrictive postopératoire précoce: intérêt de l'échocardiographie. A propos de quatre observations.

In the present study, four cases of early postoperative constrictive pericarditis have been described which serve as a basis for recalling the current main echographic features of this disorder: pericardial thickening, abnormal septal movement with inspiratory expansion of the right ventricle, respiratory variations in ventricular filling, characteristic modifications in the supra-hepatic pulmonary venous flow, and pulmonary insufficiency. Some hypotheses have also been presented on the possible etiology of this disease. The necessity of making a precise and rapid diagnosis, which should also be confirmed by catheterization to ensure the appropriateness of therapy, has been emphasized. Pericardectomy can determine the long-term prognosis.

[Prediction of intolerance to beta blocker therapy in chronic heart failure patients using BNP]. / Prédiction du risque d'intolérance du traitement bêtabloquant chez l'insuffisant cardiaque chronique par le dosage du BNP.

Beta-blocker therapy is actually recommended as first line therapy for systolic heart failure. However, beta-blocker have a low prescription rate comparatively to ACEI. Beta-blocker potential side effects as bradycardia, hypotension and especially acute decompensation could explain this under prescription. Clinical data could easily identify high-risk patients for hypotension or bradycardia but not high-risk patients for induced decompensation linked to beta-blocker therapy. BNP could identify these patients with a high sensitivity. Patients with BNP above 1000 pg/ml had a 40% risk of acute decompensation after introduction or increase of beta-blocker therapy. As a conclusion, clinicians must be very cautious for introducing or increasing Carvedilol therapy in patients with high BNP levels.

[Antimicrobial sensitivity and treatment of Helicobacter pylori infections].

Helicobacter pylori (HP) is considered the etiological agent of chronic active gastritis and suspicion is strong that it plays an important role in duodenal ulcer. Recently, several clinical studies reported that eradication of HP markedly reduces the frequency of ulcer relapse. Triple-drug treatment, including a bismuth salt and 2 antibiotics (usually metronidazole with either amoxycillin or tetracycline) is considered the treatment of choice. It has been shown that the most important factor for predicting success of treatment is the sensitivity of HP to metronidazole, which varies considerably. In the present study we evaluated antimicrobial susceptibility of 18 HP clinical isolates, as well as effectiveness of triple therapy for eradicating HP infections in 65 patients. In vitro, HP was highly sensitive to amoxycillin, erythromycin and tetracycline (100%), and also to metronidazole and tinidazole (94%). Sensitivity to chloramphenicol was low (50%). In our clinical study, the overall eradication rate was 66%; it was higher among women (80%) than men (54%), probably due to better compliance. It is concluded that HP strains in Israel are highly sensitive to metronidazole and that triple therapy is effective, providing compliance is good.

[Treatment of Crohn's disease with anti TNF alpha antibodies--the experience in the Tel Aviv Medical Center].

TNF alpha is a pro-inflammatory cytokine in Crohn's disease and it's neutralization is beneficial in patients with active disease. Remicade is a chimeric monoclonal anti-TNF antibody. Remicade is used in our center since December 1998 in 13 patients who were treated for active disease or fistula. We followed the patients and treatment results in order to estimate the efficacy and safety of this preparation. Response to treatment was measured by the Crohn's Disease Activity Index (CDAI) in patients treated due to active disease, or by the presence of discharge from external fistulae. Five out of seven patients with fistulae had less or no discharge after completing a course of 3 infusions. Four out of 6 patients treated due to active disease improved significantly after a single infusion. Five out of the six needed additional injections due to symptom recurrence. Intervals between infusions were 2 weeks--for fistulae patients to 32 weeks for patients with active disease. Adverse events for the 13 patients were usually mild except for 4 patients that suffered from anaphylactic shock, disseminated eruption (2) and eosinophilic pneumonitis. In summary, treatment of patients with active Crohn's disease or fistulae with monoclonal anti-TNF antibodies is an effective and relatively safe option after established treatment has failed. Analyzing the results of on going clinical trials and of the patients treated off-protocol will enable to establish new treatment strategies for patients with active Crohn's disease and fistulae.

Sarcoidosis presenting with acute pleurisy, hemoptysis, pruritus and eosinophilia.

Sarcoidosis carries a low prevalence in Israel, and acute pleural involvement in sarcoidosis is uncommon throughout the world. We report a case of a young Israeli male of Yemenite origin who presented with atypical manifestations of sarcoidosis: pleuritic pain, hemoptysis, pruritus and alcohol-induced pain. The differential diagnosis from Hodgkin's disease was involved. Various aspects of diagnosis are discussed.

Supernumerary nostrils: a case report and review.

Supernumerary or accessory nostrils are a very rare type of congenital nasal anomaly, with only a few cases reported in the literature. They can be associated with such malformations as facial clefts and they can be unilateral or bilateral, with most cases reported being unilateral. The accessory nostril may or may not communicate with the ipsilateral nasal cavity, probably depending on the degree of embryological progression of the anomaly. A case of simple supernumerary left nostril with no nasal cavity communication and with a normally developed nose is presented. The surgical treatment is described and the different speculative theories related to the embryogenesis of supernumerary nostrils are also reviewed.