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עמוד בית
Sat, 14.06.25

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September 2000
Edna Ben-Asher, PhD, Vered Chalifa-Caspi, PhD, Shirley Horn-Saban, PhD, Nili Avidan, PhD, Zviya Olender, PhD, Avital Adato, PhD, Gustavo Glusman, Marilyn Safran, Menachem Rubinstein, PhD and Doron Lancet, PhD
Pesach Shvartzman, MD, Elena Rivkind, MD, Anat Neville, MBA, Michael Friger, PhD and Ami D. Sperber, MD, MSPH,

Background: First-degree relatives of colorectal cancer patients are the largest groups of individuals at increased risk for colorectal cancer.

Objective: To assess the knowledge, attitudes and behavior to disease prevention and colorectal cancer screening among first-degree relatives of colon cancer patients.

Methods: A descriptive, point-prevalence epidemiological study was conducted among 215 first-degree relatives of survivors of colorectal cancer in the southern (Negev) region of Israel. Variables included perceived health status, knowledge about cancer screening, compliance rates with colorectal cancer screening, and interest in participation in early detection programs in the future.

Results: The mean age of the respondents was 47.9111.2 years, and 54% were males. Only 58 (27%) remembered having been encouraged to undergo an early detection test. In the previous year only 15% underwent fecal occult blood tests, while 9% had a barium enema and 14% an endoscopic examination of the colon by sigmoidoscopy or colonoscopy. A total of 49% of the asymptomatic respondents were unaware of recommendations for screening, and only 38.3% expressed any interest in participating in early detection programs in the future. Only 19% of respondents over the age of 50 and 8% of respondents over age 60 were interested in participating compared with 49% under the age of 50 (P0.0001).

Conclusion: A minority of first-degree relatives of colorectal cancer patients reported having been counseled to undergo screening, although most had seen their family physician in the previous 3 years. Primary care physicians should be more active in informing at-risk patients and encouraging them to undergo periodic screening.

Channa Maayan, MD, Onit Sela, MD, Felicia Axelrod, MD, D'vorah Kidron, MD and Drorith Hochner-Celnikier, MD

Background: Familial dysautonomia is a genetic disease in which there is a defect in the autonomic and sensory nervous systems. These systems have a major role in the reproductive system.

Objective: To study the inter-relationship of autonomic and sensory dysfunction and gynecological function.

Methods: The gynecological histories of 48 women with familial dysautonomia were analyzed retrospectively. Their mean age was 22.25 years (range 12-47). Thirty-three women (65%) were available for further questioning and investigation of hormonal status.

Results: Menarche had occurred in 32 of the 48 (66.7%). Their average age of menarche was significantly delayed as compared to their unaffected mothers (15.5 vs. 13.6 years respectively, P=0.002). The most prominent finding was the very high prevalence, 81.2%, of premenstrual symptoms. Seven of 26 had premenstrual syndrome symptoms of dysautonomic crisis. Blood sex hormone levels were normal in 27 of the 33 patients studied. None reached natural menopause. One patient had adenomyosis, and another, dysgerminoma. Three patients became pregnant and delivered healthy infants.

Conclusion: Menarche is delayed in women with FD, and the physiological monthly hormonal fluctuations may disturb autonomic homeostasis sufficiently to precipitate dysautonomic crisis.

Hana Strul MD and Nadir Arber MD

There is increasing evidence to suggest that aspirin and other non-steroidal anti-inflammatory drugs reduce the risk of colorectal cancer. This observation is supported by animal studies that show fewer tumors per animal and fewer animals with tumors after administration of several different NSAIDs. Intervention data in familial adenomatous polyposis have established that the effect is exerted on the process of human colonic adenoma formation. Supportive evidence in sporadic colorectal neoplasia, derived from 22 of 24 studies (both case-control and cohort), found a reduced risk in men and women for cancers of the colon and the rectum and for both aspirin and the other NSAIDs. Earlier detection of lesions as a result of drug-induced bleeding does not seem to account for these findings. Although the molecular mechanism responsible for the chemopreventive action of this class of drugs is not yet completely understood, the protection may affect several pathways including both cell cycle arrest and induction of apoptosis.

In the third millennium the question is not if but how. Based on the consistency of epidemiological, clinical and experimental data, the association between regular long-term aspirin or NSAIDs intake and a decreased death rate from colorectal cancer is sound and there is no need for further placebo trials. At the same time, despite this consistency there is no clear data on the dose, duration or frequency of use for cancer-preventive activity.

Jacob Urkin, MD and Manuel Katz, MD
August 2000
Haim Hammerman MD and Michael Kapeliovich MD PhD

Background: Iatrogenic illness, defined as a disease that results from a diagnostic procedure or from any form of therapy, is a well-recognized phenomenon in clinical practice.

Objectives: To study and evaluate major car-diac iatrogenic disease as the cause of admission to the intensive cardiac care unit in the modern era.

Methods: We assessed 64 critically ill patients suffering from major cardiac iatrogenic problems among a total of 2,559 patients admitted to the intensive cardiac care unit during 3 years. Iatro-genic illness was defined as any problem that resulted from therapy. Only cardiac problems were included in the study. Complications of interventional cardiovascular procedures, suicide attempts or accidental intoxications were ex-cluded.

Results: There was evidence of a major cardiac iatrogenic problem as the cause for admission in 64 patients (2.5%): 58 (91%) suffered from ar-rhythmias (mainly bradyarrhythmias) secondary to beta-blockers, amiodarone, calcium antago-nists, electrolyte imbalance or a combination, and 6 (9%) had non-arrhythmic events (hypotension, syncope or acute heart failure). In 41 patients (64%) the iatrogenic event was considered pre-ventable

Conclusions: Major cardiac iatrogenic compli-cations are an important factor among patients admitted to the intensive cardiac care unit. Most of the events are bradyarrhythmias related to anti-arrhythmic agents. Almost two-thirds of events are preventable.

Robert Goldstein PhD, Dan Braverman MD and Halina Stankiewicz MSc

Background: Carbohydrate malabsorption of lactose, fructose and sorbitol has already been described in normal volunteers and in patients with functional bowel complaints including irritable bowel syndrome. Elimination of the offending sugar(s) should result in clinical improvement.

Objective: To examine the importance of carbohydrate malabsorption in outpatients previously diagnosed as having functional bowel disorders, and to estimate the degree of clinical improvement following dietary restriction of the malabsorbed sugar(s).

Methods: A cohort of 239 patients defined as functional bowel complaints was divided into a group of 94 patients who met the Rome criteria for irritable bowel syndrome and a second group of 145 patients who did not fulfill these criteria and were defined as functional complaints. Lactose (18 g), fructose (25 g) and a mixture of fructose (25 g) plus sorbitol (5 g) solutions were administered at weekly intervals. End-expiratory hydrogen and methane breath samples were collected at 30 minute intervals for 4 hours. Incomplete absorption was defined as an increment in breath hydrogen of at least 20 ppm, or its equivalent in methane of at least 5 ppm. All patients received a diet without the offending sugar(s) for one month.

Results: Only 7% of patients with IBS and 8% of patients with FC absorbed all three sugars normally. The frequency of isolated lactose malabsorption was 16% and 12% respectively. The association of lactose and fructose-sorbitol malabsorption occurred in 61% of both patient groups. The frequency of sugar malabsorption among patients in both groups was 78% for lactose malabsorption (IBS 82%, FC 75%), 44% for fructose malabsorption and 73% for fructose-sorbitol malabsorption (IBS 70%, FC 75%). A marked improvement occurred in 56% of IBS and 60% of FC patients following dietary restriction. The number of symptoms decreased significantly in both groups (P<0.01) and correlated with the improvement index (IBS P<0.05, FC P<0.025).

Conclusions: Combined sugar malabsorption patterns are common in functional bowel disorders and may contribute to symptomatology in most patients. Dietary restriction of the offending sugar(s) should be implemented before the institution of drug therapy.

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IBS = irritable bowel syndrome

FC = functional complaints

Timna Naftali MD, Ben Novis MD, Itamar Pomeranz MD, George Leichtman MD, Yaakov Maor MD, Rivka Shapiro MD, Menachem Moskowitz MD, Beni Avidan MD, Yona Avni MD, Yoram Bujanover MD and Zvi Fireman MD

Background: About one-third of patients with severe ulcerative colitis do not respond to conventional therapy and require urgent colectomy. It was recently shown that cyclosporin is effective in some of these patients.

Objectives: To review the current experience of six hospitals in central Israel that used cyc-losporin in patients with severe ulcerative colitis.

Methods: The files of all 32 patients treated with cyclosporin for corticosteroid-resistant ulcerative colitis were reviewed. Activity of disease was measured by a clinical activity, index colonoscopy and laboratory tests.

Results: The average duration of treatment with intravenous cyclosporin was 12.7 days (range 9–28) after which the disease activity index dropped from an average of 14.22 to 4.74. The mean time for response was 7.5 days (4–14). Twelve patients (40%) required surgery within 6 months and another 6 patients (18.8%) were operated on after more than 6 months. Twelve patients (37%) maintained remission for at least 6 months and did not require surgery. In one patient treatment was stopped because of non-compliance and one was lost to follow-up. There were numerous side effects, but in only one case with neurotoxicity was treatment withdrawn.

Conclusions: Cyclosporin is a relatively safe and effective treatment for severe ulcerative colitis. It induced long-term remission in 37% of the patients, and in those who required surgery the treatment resulted in an improved clinical condition before the operation.

Aharon Klar MD, Eva Gross-Kieselstein MD, Gila Shazberg MD, Talia Israeli MD, Shoshana Revel-Vilk MD and Haggit Hurvitz MD

Background: Concomitant bacterial and viral infection is a well-known phenomenon, however only very rarely has a bacterial infection been reported during hepatitis A virus infection.

Objective: To evaluate retrospectively the clinical records of children hospitalized with HAV infection for a concomitant infection proved or presumed to be bacterial.

Method: A retrospective study was conducted on all the children hospitalized with hepatitis A infection from 1988–96 in our center. The records were evaluated for a concomitant infection.

Results: Of 40 children hospitalized with HAV infection, 13 were found to have a concomitant infection: these included 6 with pneumonia, 4 with pyelonephritis and 1 case each of purulent otitis media, osteomyelitis and staphylococcal bacteremia.

Conclusion: In areas where hepatitis A is endemic, a simultaneous infection with hepatitis A and other common bacterial infection during childhood may co-exist. A permissive role for HAV infection is suggested.

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HAV = hepatitis A virus

Tzipora C. Falik-Zaccai MD, Elena Shachak MSc, Devora Abeliovitch PhD, Israela Lerer MSc, Ruth Shefer MD, Rivka Carmi MD, Liat Ries MSc, Moshe Friedman MD, Mordechai Shohat MD and Zvi Borochowitz MD

Background: Achondroplasia is the most frequent form of disproportionate short stature, characterized by rhizomelic shortening of the limbs. This disorder is inherited as an autosomal dominant trait, although most of the cases are sporadic, a result of a de novo mutation. A recurrent glycine to arginine mutation at codon 380 (G380R) in the transmembrane domain of the fibroblast growth factor receptor 3 gene was found to cause achondroplasia among different populations. This is most uncommon in other autosomal dominant genetic diseases.

Objectives: To determine whether this mutation is also common among Jewish patients from diverse ethnic groups and among the Arab population in Israel.

Methods: We examined the G380R mutation (G>A and G>C transition) and the mutation G375C (G>T transition at codon 375) in 31 sporadic patients and in one family diagnosed clinically to have achondroplasia.

Results: We found the G>A transition at codon 380 in 30 of our patients and the G>C transition in one patient. We were not able to detect any of the three mutations in two patients with an atypical form of achondroplasia.

Conclusions: Our results further support the unusual observation that nucleotide 1138 of the FGFR3 gene is the most mutable nucleotide discovered to date across different populations.

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FGFR3 = fibroblast growth factor receptor 3

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