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עמוד בית
Fri, 03.05.24

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May 2018
Ido Laish MD, Amir Mari MD, Batya Mannasse MSc, Ruth Hadary MD, Fred Meir Konikoff PhD, Aliza Amiel PhD and Yona Kitay-Cohen MD

Background: Shortened telomeres were found in patients with cirrhosis, probably reflecting chronic liver injury, continuous regeneration, and destruction of hepatic nodules.

Objectives: To test whether telomere shortening is a general marker of cirrhosis, independent of disease etiology.

Methods: We evaluated telomere length in patients with cryptogenic cirrhosis (largely a late sequela of steatohepatitis) compared to patients with cirrhosis caused by chronic hepatitis B and C (HBV/HCV). We also evaluated telomere aggregates, a sensitive parameter of telomere dysfunction and genetic instability. We analyzed peripheral lymphocytes from 25 patients with cryptogenic cirrhosis, 15 patients with cirrhosis due to chronic viral hepatitis, and 20 age-matched controls. Telomere length was analyzed using quantitative fluorescence in situ hybridization. Aggregate size was divided into three fusion groups of 2–5, 6–10, and 11–15 telomeres, relative to the size of a single telomere.

Results: Shorter telomere length was found in patients with cirrhosis from all three etiologies (mean 121.3 ± 24.1) compared to controls (mean 63.5 ± 23.5). In contrast, there was significantly more fusion of > 5 telomeres only in the HBV/HCV cirrhosis group compared to healthy controls (P = 0.023), but not in the cryptogenic cirrhosis group.

Conclusions: While shortened telomeres in peripheral lymphocytes are a general marker of liver cirrhosis, telomere aggregates may signify a more sensitive genetic instability parameter for the diverse, etiology-based malignant potential of cirrhosis. This finding is in agreement with the well-known higher tendency toward developing hepatocellular carcinoma with cirrhosis caused by chronic hepatitis relative to steatohepatitis.

August 2011
T. Naftali, L. Bar Lev, D. Yablekovitz, E. Half and F.M. Konikoff

Background: The marijuana plant cannabis is known to have therapeutic effects, including improvement of inflammatory processes. However, no report of patients using cannabis for Crohn’s disease (CD) was ever published.

Objectives: To describe the effects of cannabis use in patients suffering from CD.

Methods: In this retrospective observational study we examined disease activity, use of medication, need for surgery, and hospitalization before and after cannabis use in 30 patients (26 males) with CD. Disease activity was assessed by the Harvey Bradshaw index for Crohn’s disease.

Results: Of the 30 patients 21 improved significantly after treatment with cannabis. The average Harvey Bradshaw index improved from 14 ± 6.7 to 7 ± 4.7 (P < 0.001). The need for other medication was significantly reduced. Fifteen of the patients had 19 surgeries during an average period of 9 years before cannabis use, but only 2 required surgery during an average period of 3 years of cannabis use.

Conclusions: This is the first report of cannabis use in Crohn’s disease in humans. The results indicate that cannabis may have a positive effect on disease activity, as reflected by reduction in disease activity index, and in the need for other drugs and surgery. Prospective placebo-controlled studies are warranted to fully evaluate the efficacy and side effects of cannabis in CD.
 

April 2004
M. Moshkowitz, E. Ben Baruch, Z. Kline, M. Gelber, Z. Shimoni and F. Konikoff

Background: Pseudomembranous colitis is a well-recognized cause of diarrhea in patients receiving antibiotics and has significant consequences in terms of morbidity, mortality and cost. Clostridium difficile infection is the single most important infectious cause of PMC[1]. PMC is frequently nosocomial, with an increased risk of spread among institutionalized patients, both in hospitals and nursing homes.

Objective: To investigate the demographic, clinical and laboratory characteristics of PMC patients in an Israeli elderly population.

Methods: We studied 72 hospitalized patients with endoscopically proven PMC. The medical records of all patients including clinical history and laboratory data were reviewed, such as: age, pre-hospitalization status (dependency or not, in the community as compared to the nursing home), background medical history, presenting symptoms, antibiotic history, physical examination on admission, hematologic and biochemical parameters, treatment, duration of hospitalization, complications, mortality and recurrence of disease.

Results: Of the 72 patients (34 males and 38 females, mean age 77 years) 47% were nursing home residents. Pre-hospitalization antibiotic treatment was given to 91.4% for infections of the upper respiratory tract (45%) and urinary tract (45%). The most common antibiotics were cephalosporin (64%), penicillins (42%) and quinolones (28%). Sixty-four percent of the patients were treated with more than one antibiotic, 26% of patients received anti-acid therapy and 36% had been fed with a nasogastric tube. On admission, leukocytosis was found in 79% of patients, >20,000/mm3 in half of them; 60% were anemic, 60% had elevated erythrocyte sedimentation rate, and 78% had hypoalbuminemia. Treatment consisted of metronidazole (41%) or a combination of metronidazole and vancomycin (56%). Overall, 31% of patients recovered without complications, 29% died within 30 days of hospitalization, and 24% were re-hospitalized due to recurrence of PMC.

Conclusion: The most common antibiotics implicated in PMC are cephalosporin, penicillins and quinolones. The disease is associated with high mortality and recurrence rates.






[1] PMC = pseudomembranous colitis


December 2002
Ada Kessler MD, Annat Blank MD, Hadar Merhav MD, Dan Orron MD, Fred Konikoff MD, Ran Oren MD, Arie Figer MD, Nissim Marouani MD, Judith Weiss MD, Mordechai Gutman MD, and Moshe Graif MD.

Background: Despite advances in cancer therapy the treatment of liver tumors remains a challenge. Most patients are poor candidates for surgical resection; both chemotherapy and irradiation have a low success rate and neither is without complications. New minimally invasive techniques for ablation of unresectable tumors have gained attention as effective treatment alternatives. Among these are percutaneous ethanol injection and radiofrequency ablation; both are effective for primary liver tumors and RFA is also effective for hepatic metastases.

Objective: To report our experience with PEI and RFA in the treatment of hepatic lesions.

Methods: The study included 49 lesions in 27 patients: 23 primary lesions in 13 patients treated with PEI and 26 lesions (22 secondary and 4 primary) in 14 patients treated with RFA. PEI was performed on an outpatient basis in the ultrasound suite; RFA was done in hospitalized patients (9 in the ultrasound suite and 4 in the operating room). Patients were followed with triphasic spiral computerized tomography 1 month after treatment and every 3±6 months thereafter.

Results: Complete necrosis was achieved with PEI on the first attempt in 11 of 23 primary lesions (91.3%). In 8.7% (2/23) a second series of treatments was required. Using RFA, complete necrosis was achieved in 85% of lesions (22/26) and partial necrosis in 15% (4/26). Complications included low fever (3 patients), high fever and abscess formation (1 patient), peri-tumoral necrosis (1 patient ) and portal vein thrombosis (1 patient ).

Conclusions: Our preliminary results confirm that PEI and RFA are an effective and safe option for treating hepatic tumors in patients unfit for surgery.
 

April 2001
Hana Strul, MD, Michal Carmiel, MD and Fred Konikoff, MD
December 2000
Menachem Moshkowitz, MD, Shlomo Brill, MD, Fred M. Konikoff, MD, Mordechai Averbuch, MD, Nadir Arber, MD and Zamir Halpern, MD
 Background: Cigarette smoking has long beenregarded as an important factor in the pathogenesis of peptic ulcer disease.

Objective: To investigate whether cigarette smoking has an additive effect on the clinical presentation and course of disease in Helicobacter pylori-positive dyspeptic patients.

Patients and Methods: The study group comprised 596 consecutive H. pylori-positive dyspeptic patients (334 males and 262 females, mean age 50.6, range 12--81 years). Following upper gastrointestinal endoscopy, patients were subdivided by diagnosis as follows: Non-ulcer patient group (n=312: gastritis 193, duodenitis 119), gastric ulcer (n=19), and duodenal ulcer (n=265). H. pylori infection was confirmed by histology and/or rapid urease test. In addition, 244 patients had a positive 14C-urea breath test prior to antimicrobial treatment. The patients' medical history and smoking habits were obtained using a detailed questionnaire completed by the patients and their referring physicians.

Results: There were 337 non-smoking patients, 148 current smokers and 111 past smokers. Gastric and duodenal ulcers were significantly less prevalent in non-smokers than in current or past smokers (gastric 1.8%, 4.1%, 6.3%; duodenal 39.8%, 50%, 51.4%, respectively) (P0.05). The incidence of gastrointestinal bleeding was significantly lower in non-smokers than in current or past smokers (7.1%, 8.1% and 20.7%, respectively) (P0.05). Bacterial density, as assessed by the UBT value in 244 patients, was higher in non-smokers (mean 352.3273 units) than in past smokers (mean 320.8199) or current-smokers (mean 229.9162) (P0.05). Logistic regression analysis revealed that male gender, current smoking, and immigration from developing countries were all significant independent risks for developing duodenal ulcer, while only past smoking was associated with a higher rate of upper gastrointestinal bleeding in the past.

Conclusions: In H. pylori-positive dyspeptic patients, current smoking as well as male gender and immigration from developing countries are associated with an increased risk for duodenal ulcer. This effect does not seem to be related to the bacterial density or increased urease activity of H. pylori organisms.

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