Joseph Lysy

Childhood hygiene is associated with the risk for inflammatory bowel disease: a population-based study.

OBJECTIVES:The “hygiene hypothesis” postulates that individuals raised in a sanitary environment are more likely to develop inflammatory bowel disease (IBD). Several studies previously demonstrated contradictory results in this regard. We performed for the first time a population-based study on the association of surrogate markers of childhood hygiene with the risk for IBD.METHODS:A cross-sectional population-based study was undertaken. Information on number of siblings, birth order, and living in an urban versus rural environment was obtained for 399,251 Jewish adolescents at the age of 17 yr from 1998 to 2004. The study population included only subjects born in Israel. In order to control for genetic confounding, subjects were also divided according to their ethnic group as being Ashkenazi, Sephardic, or Israeli in origin.RESULTS:In total, 768 cases of inflammatory bowel disease (IBD) were diagnosed (0.19%), with 53.8% of the cases being of Ashkenazi origin. On multivariate analysis, variables significantly associated with IBD were male gender (odds ratio [OR] 1.44, 95% confidence interval [CI] 1.24–1.67), Ashkenazi origin (OR 1.91, 95% CI 1.63–2.22), living in an urban environment (OR 1.38, 95% CI 1.02–1.78), small number of siblings in the family (for 1 sibling vs 5 or more, OR 2.63, 95% CI 1.49–4.62), and higher birth order (for birth order of 5 or higher vs 1, OR 2.35, 95% CI 1.47–3.77), showing for both variables an almost strictly highly significant monotonic association (P value for trend <0.001).CONCLUSIONS:Surrogate markers of childhood hygiene are associated with the risk for IBD, thus reinforcing the “hygiene hypothesis.”

The prevalence of chronic diarrhea among diabetic patients.

OBJECTIVE:The prevalence of chronic diarrhea in patients with type I and type II diabetes is uncertain, most data being available from tertiary referral centers. We report the prevalence and etiology of chronic diarrhea in 861 heterogeneous diabetic patients attending a primary care diabetic outpatient clinic.METHODS:All patients attending the clinic were asked to fill in a questionnaire relating to their bowel habits. Patients who fulfilled the criteria for chronic diarrhea underwent a comprehensive workup to define the cause of the diarrhea. Additional parameters were the mean duration of diabetes, hemoglobin-A1c levels, and the presence of autonomic neuropathy.RESULTS:Chronic diarrhea was diagnosed in 32 patients (overall prevalence of 3.7%). The prevalence of nondiabetic diarrhea was higher among type I diabetic patients than among type II patients (3.29%vs 2.3%), although it did not reach statistical significance. Diabetic diarrhea was more common among type I than type II diabetic patients (5.2%vs 0.4%, respectively, p < 0.01). The most common cause of nondiabetic diarrhea was medication induced (metformin).CONCLUSIONS:Chronic diarrhea is more frequent in type I diabetic patients. The higher prevalence of diarrhea in this population can be attributed to diabetic diarrhea (which is quite rare in type II patients). The most common cause of nondiabetic diarrhea is drug therapy with metformin.

Effect of Long-term, Continuous Versus Alternate-day Omeprazole Therapy on Serum Gastrin in Patients Treated for Reflux Esophagitis

Background Proton pump inhibitors have been proven to have a major role in the management of peptic diseases, especially the long-term control of reflux esophagitis. The potent inhibitory effect of omeprazole on gastric acid secretion is frequently associated with hypergastrinemia, and gastrin and its intermediates have been reported to promote gastrointestinal cellular functions and cell growth. Experimental data suggest that gastrin may affect the proliferation of colon cells and some other cancer cells. However, so far the direct role of gastrin in tumorigenesis is unclear. Although most clinical studies on long-term treatment with omeprazole or other proton pump inhibitors do not report serious adverse effects, the issue of prolonged hypergastrinemia and tissue growth is unsettled, and many clinicians are reluctant to recommend long-term use of omeprazole or of other proton pump inhibitors. Study We examined the effect of long-term omeprazole treatment on serum gastrin levels in patients with reflux esophagitis when given either 20 mg daily (group 1) or on alternate days (group 2). During the follow-up period, clinical remission was monitored and maintained in all patients in group 1 and in the majority of patients in group 2. Results The mean serum gastrin level was significantly elevated in group 1 (mean ± SE, 159 ± 23.6 pg/mL; range, 45–620 pg/mL;n = 31) as compared with the alternate-day treatment group (group 2) (66 ± 4.8 pg/mL; range, 37–115 pg/mL;n = 21) (p < 0.005). In controls, serum gastrin levels showed similar values to those found in group 2 (54 ± 4.3 pg/mL; range, 27–94 pg/mL;n = 20). Fourteen patients (45%) in group 1 had serum gastric ranging from 140 to 620 pg/mL, and 8 (25%) had a 6-fold or greater increase in serum gastrin. The follow-up treatment period ranged between 3 and 60 months (mean ± SE, 16.1 ± 2.1 months) for group 1 and 3–36 months (9.7 ± 1.4 months) for group 2. Upon multivariate adjustment for age and duration of treatment, a significantly lower mean serum gastrin level was observed in the alternate-day group as compared with the daily treated group. Conclusion Alternate-day, long-term treatment with omeprazole may be adequate to maintain remission in patients with reflux esophagitis. This regimen can assure serum gastrin levels within the normal range, thus reducing the potential risk of prolonged, sustained hypergastrinemia and profound hypochlorhydria.

Treatment of chronic anal fissure with Isosorbide dinitrate : Long-term results and dose determination

PURPOSE: Anal fissure is a tear of the anoderm, which eventually can become an ulcer. Chronic anal fissure is perpetuated by contraction of the internal sphincter, believed to reduce perfusion. Nitric oxide is a neurotransmitter mediating vasodilation and internal anal sphincter relaxation. The aim of the present study was to evaluate both the effect and the effective dose regimen of isosorbide dinitrate, a nitric oxide donor, as a treatment for chronic anal fissure. METHODS: Isosorbide dinitrate, Isoket® spray (Schwarz-Pharma, Mannheim, Germany), was used to treat 41 patients with chronic anal fissure. Anal manometry was performed in all patients before they entered the study. The treatment program consisted of digital application of isosorbide dinitrate in a dose of 1.25 mg or 2.5 mg three times each day for four weeks. At the end of the trial, patients were followed up for an average time of 11 ± 1 months. RESULTS: In 34 (83 percent) patients, the fissure healed within one month of treatment (mean, 3 ± 0.1 weeks). The average time for symptoms to disappear was 6.5 ± 0.7 days. In six (14.6 percent) patients the anal fissure did not heal even after four weeks of further treatment, and they underwent lateral sphincterotomy. Six patients relapsed during the follow-up period, but responded to another course of treatment. A dose of 2.5 mg of isosorbide dinitrate caused a greater reduction in maximum anal resting pressure than a dose of 1.25 mg. CONCLUSIONS: Topical isosorbide dinitrate is an effective and safe treatment for chronic anal fissure. In our experience the optimal dose regimen is 2.5 mg three times each day.

Pancreatitis in ulcerative colitis

A 19-year-old man without apparent predisposing factors was found to have chronic pancreatitis and 6 months later developed ulcerative colitis. Is there a real association between pancreatitis and inflammatory bowel disease? We discuss previous reports.

Losartan Reduces Trinitrobenzene Sulphonic Acid-Induced Colorectal Fibrosis in Rats

BACKGROUND Intestinal fibrosis is a challenging clinical condition in several fibrostenosing enteropathies, particularly Crohns disease. Currently, no effective preventive measures or medical therapies are available for intestinal fibrosis. Fibrosis, due to an abnormal accumulation of extracellular matrix proteins, is a chronic and progressive process mediated by cell⁄matrix⁄cytokine and growth factor interactions, but may be a reversible phenomenon. Of the several molecules regulating fibrogenesis, transforming growth factor-beta 1 (TGF-b1) appears to play a pivotal role; it is strongly induced by the local activation of angiotensin II. The levels of both TGF-b1 and angiotensin II are elevated in fibrostenosing Crohns disease. AIMS To evaluate the in vivo effect of losartan - an angiotensin II receptor antagonist - on the course of chronic colitis-associated fibrosis and on TGF-b1 expression. METHODS Colitis was induced by intrarectal instillation of trinitrobenzene sulphonic acid (TNBS) (15 mg⁄mL) while losartan was administered orally daily by gavage (7 mg⁄kg⁄day) for 21 days. Three groups of rats were evaluated: control (n=10); TNBS treated (n=10); and TNBS + losartan treated (n=10). Inflammation and fibrosis of the colon were evaluated by macro- and microscopic score analysis. Colonic TGF-b1 levels was measured using ELISA. RESULTS Twenty-one days after induction, losartan significantly improved the macro- and microscopic scores of fibrosis in the colonic wall and reduced TGF-b1 concentration. CONCLUSIONS Prophylactic oral administration of losartan reduces the colorectal fibrosis complicating the TNBS-induced chronic colitis, an effect that appears to be mediated by a downregulation of TGF-b1 expression.

Sciatic pain after rubber band ligation of haemorrhoids

Dear Editor: Rubber band ligation is probably the most commonly used nonsurgical treatment for haemorrhoidal disease. Tissue destruction by heat delivered in a variety of forms is slightly less effective (needs more re-treatment) but is significantly less painful. During the last 10 years, more than 1,000 patients had rubber band ligation of haemorrhoids in our proctology clinic. Here, we report a 30-year-old female who developed severe sciatic pain and paresthesis of the left leg immediately after rubber band ligation of the left lateral internal haemorrhoids. The pain was severe and localised to the left buttock, radiating through the back of the left thigh down to the ankle. Surprisingly, the anal pain was minimal. Physical examination was unremarkable. The location of the rubber band was 10 mm above the dentate line. Two hours later, the ring was removed due to intolerable “sciatic like pain” and paresthesis. Following the rubber band removal, the pain was immediately alleviated and completely resolved within a few minutes. We do not understand the exact pathogenesis of the phenomenon. Upper anal canal is insensitive to stimuli-like cutting or squeezing, allowing us to band haemorrhoids without anaesthesia. On the other hand, stimuli-like tension and traction are conducted by the sensory nerves, producing visceral dull pain. These sensory fibres run in the parasympathetic nerves and enter the spinal cord at the same segments (S2–S4) like a part of the sciatic nerve, innervating to the buttock area. Due to the proximity of those nerves, we can speculate that impulse delivered by one could be interpreted as delivered by another. The other option is that local inflammatory reaction to rubber band ligation can trigger adjacent nerves and create false sensation as we see sometimes in an infection of the pelvic floor. Interestingly, four out of five patients, reported in literature with this complication, were females, raising the possibility that female pelvic anatomy could be a predisposing factor to this complication. Sciatic-like pain caused by rubber band ligation is extremely rare, and to the best of our knowledge, this is the second report of such a complication. In the previously reported cases, the rubber band was left in place, and the duration of the “sciatic like pain” was 7 days. We preferred to release the rubber band, which resulted in prompt pain resolution, and to refer the patient to argon plasma laser haemorrhoidal treatment.