Israel Medical Association Journal

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.

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.

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

Background: Trauma is the leading cause of death in children. In abdominal lesions the spleen is the most commonly involved organ. During the last two decades much effort has focused on spleen tissue conservation.

Objectives: To analyze the rationale of a multimodality management policy that includes autotransfusion and mesh wrapping.

Methods: Data gathered over 14 years illustrate the introduction of new techniques and their impact on cases of severe spleen rupture.

Results: A total of 122 children were treated during the 14 year period, 1985-98. In 16 children an absorbable mesh wrapping, alone or in combination with other techniques, was used to obtain hemostatis and save spleen tissue.

Conclusions: Mesh wrapping, partial splenectomy and autotransfusion can be used, alone or in combination, to preserve severely injured spleens. According to our records, all children survived with a functional spleen. There were no cases of rebleeding. In only one case of prolonged postoperative fever could the cause be traced to an infected spleen hematoma that was drained transcutaneously. Autotransfusion is performed simply and without the use of a "cell saver." Its use can be crucial in small or field hospitals or in a situation of mass casualty.

Objective: To report a unique hereditary, juvenile onset, craniocervical predominant, generalized dystonia and parkinsonism affecting four members of one family.

Family Description: A father and three of his four daughters presented to us over the past 30 years with a similar picture of generalized dystonia, starting in the craniocervical region in the second or third decade of life. They later developed moderate parkinsonism, mainly manifesting bradykinesia, rigidity and abnormal postural reflexes. Biochemical and genetic tests excluded Wilson's disease, Huntington's disease and Oppenheim's dystonia.

Conclusion: This is a new type of familial dystonia-parkinsonism where the craniocervical dystonic symptoms are most prominent in the early stages while parkinsonism becomes the predominant problem later in life. A search for the genetic mutation in this family is underway.

Background: A high rate of consanguineous marriages exists within the Israeli Arab community, with approximately half occurring between first cousins. This contributes towards a high incidence of congenital malformations and autosomal recessive diseases, many of which are detectable at prenatal diagnosis.

Objectives: To assess the levels of both awareness and acceptance regarding prenatal diagnosis and termination of pregnancy among a group of Arab women in order to devise the optimal means of providing genetic counseling and general health services.

Methods: A total of 231 Arab women of childbearing age were interviewed 3 days postpartum to assess their knowledge of prenatal diagnosis and termination of pregnancy, their willingness to undergo prenatal diagnosis, and their opinions on termination of pregnancy in the event of a severely affected fetus.

Results: Half the women believed that prenatal testing is not an effective (or accurate) tool for diagnosing an affected fetus. A quarter had poor knowledge on prenatal diagnosis, and a quarter believed that prenatal diagnosis does provide the correct diagnosis. Ninety-five percent said they would agree to undergo prenatal diagnosis; and in the event of a severely affected fetus, 36% said they would agree to a termination of pregnancy, 57% said they would not, and 7% were undecided.

Conclusions: There is a need for special intervention programs, with guidance by health professionals, geneticists and religious authorities, that will inform this population on the increased risk associated with consanguinity, stress the importance and effectiveness of prenatal testing to identify severe congenital malformations, and help them to accept prenatal diagnosis and termination of pregnancy if indicated.

Background: Cell-mediated immunity is impaired in uremia. Cell-matrix interactions of immune cells such as CD4+T lymphocytes with extracellular matrix are an important requirement for an intact immune response. The adherence of CD4+T cells of healthy subjects (normal T cells) to ECM components is inhibited in the presence of uremic serum. Such decreased adhesive capacity is also found in T cells of dialysis patients. Various chemokines and cytokines affect the attachment of CD4+T cells to ECM.

Objective: To evaluate chemokine (MIP-1β and RANTES) and tumor necrosis factor α-induced adhesion of CD4+T cells to ECM in a uremic milieu.

Methods: We examined adhesion of normal CD4+T cells (resting and activated) to intact ECM in response to soluble or bound chemokines (MIP-1β and RANTES) and to TNF-α following incubation in uremic versus normal serum. Thereafter, we evaluated the adhesion of resting CD4+T cells from dialysis patients in a similar fashion and compared it to that obtained from a healthy control group.

Results: Addition of uremic serum diminished soluble and anchored chemokine-induced attachment of normal resting and activated CD4+T cells to ECM compared to a normal milieu (a peak response of 10–11% vs. 24–29% for soluble chemokines, P<0.001; 12–13% vs. 37–39% for bound chemokines on resting cells, P<0.01; and 18–20% vs. 45–47% for bound chemokines on activated cells, P<0.02). The same pattern of response was noted following stimulation with immobilized TNF-α (7 vs. 12% for resting cells, P<0.05; 17 vs. 51% for activated cells, P<0.01).  Adherence of dialysis patients’ cells to ECM following stimulation with both bound chemokines was reduced compared to control T cells (15–17% vs. 25–32%, P<0.0000). In contrast, adherence following stimulation by TNF-α was of equal magnitude.

Conclusions: Abnormal adhesive capacity of T lymphocytes to ECM in uremia may, in part, be related to a diminished response to MIP-1β, RANTES and TNF-α. However, whereas reduced adhesion to chemokines was present in both normal CD4+T cells in a uremic environment and in dialysis patients’ T cells, TNF-α-induced adhesion was found to be inhibited only in normal cells in a uremic milieu.

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ECM = extracellular matrix

TNF-α = tumor necrosis factor-a

Background: Over a 12 month period, the Israel Transplant Center doubled the number of donors by assigning a nurse coordinator to each of 22 hospitals around the country and by using kidneys from elderly donors.

Objective: To evaluate the impact of our "marginal donors" policy on the results immediately following transplantation.

Methods: Between October 1997 and September 1998, 140 cadaveric kidney transplantations from 72 donors were performed in Israel. We defined two groups of recipients: patients with immediate graft function and patients with either delayed graft function requiring >1 week of dialysis post-transplant or with primary graft non-function. We compared the following parameters between groups: donor and recipient age and gender, cause of donor’s death, length of stay in the intensive care unit, vasopressor dosage and creatinine levels before harvesting, cold ischemic time, and the number of recipient grafts.

Results: There were 102 recipients (72.8%) with immediate graft function and 38 with either PNF (n=13, 9.3%) or DGF (n=25, 17.9%). On regression analysis, donor age >50 year and retransplantation were significant risk factors for PNF or DGF (odds ratio 4.4 and 2.8, respectively). Of the 56 kidneys from donors >50 years old, 21 (37.5%) developed either PNF (n=9) or DGF (n=12).

Conclusions: We conclude that kidneys from donors over age 50 are at increased risk for graft non-function or delayed function. Better assessment of functional capacity of kidneys from “aged” donors may help to choose appropriate donors from that pool.

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PNF = primary graft non-function

DGF = delayed graft function

Background: Chickenpox is a highly contagious childhood infection caused by varicella zoster virus, a virus of the herpes family. Although a mild and self-limiting disease in otherwise healthy children, chickenpox can be a complicated and even life-threatening disease in adults, pregnant women and immunosuppressed individuals. Among infants whose mothers had varicella during the first trimester of pregnancy, 2-3% will develop a congenital VZV syndrome that includes a combination of scarring, limb deformation, central nervous system impairment and ocular injury. In 1974, a live attenuated virus vaccine against VZV was developed in Japan and has been thoroughly tested for safety, efficacy and long-term effects. In March 1995 the vaccine was licensed in the U.S. for use in healthy children only.

Objectives: To determine the rate of immunity to VZV in young Israeli adults.

Methods: On the assumption that a randomly picked sample of 18-year-old army recruits in Israel is representative of the general Jewish population, 900 sera samples were taken for 3 years (1985,1988,1992). The sera were analyzed for IgG to VZV with a commercial ELISA kit using microwells coated with VZV antigens.

Results: A total of 98% of the samples tested positive for VZV antibodies. The difference in serologic values between the recruitment years was not statistically significant.

Conclusion: The majority of the Israeli population reaches adulthood already immunized against VZV, with immigrants having slightly lower immunity rates. Nonetheless, a few dozen cases of chickenpox are diagnosed in the IDF annually. These data should be taken into account when a vaccination program is devised. Should such a program be implemented, it would be interesting to repeat the serosurvey for comparison. A shift in the peak occurrence age might necessitate the administration of a booster vaccine at an older age.

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VZV= varicella zoster virus

IDF= Israel Defense Forces

Background: Dyslipidemia and obesity serve as risk factors for the development of atherosclerotic cardiovascular disease. Fasting is sometimes recommended for treating these conditions. This study was undertaken to try to resolve conflicting results reported in the literature.

Objectives: To study the effect of fasting (0 calories, with free intake of fluids) for 3-5 days on plasma concentration of triglyceride, cholesterol and apolipoprotein B.

Methods: Physicians, about to begin a hunger strike, were divided into four groups: normolipidemic non-obese men (group 1), two moderately obese men and two men with type IV hyperlipidemia (group 2), healthy non-obese women (group 3), and healthy non-obese women on oral contraceptives (group 4). Adherence to fasting was monitored daily by detailed interviews, loss of weight, drop in plasma glucose, presence of ketonuria, progressive rise in serum creatinine and uric acid, and decrease in plasma pH. We monitored their serum glucose, electrolytes, liver function, lipids, lipoproteins and apolipoprotein B on days 0, 3, and 5.

Results: Physicians who adhered to complete fasting lost more than 1.5% of their body weight after 3 days of fasting (n=12), and more than 3.2% at 5 days (n=5). All non-obese normolipidemic males and females (groups 1 and 3) showed an increase in plasma triglyceride (by 28-162%) and very low density lipoprotein cholesterol (by 22-316%) after 3 days of fasting. The obese and hyperlipidemic men (group 2) showed a decrease of 17-63% in their VLDL cholesterol, and the women on oral contraceptives (group 4) showed a 20% decrease in their plasma triglyceride on day 3. Low density lipoprotein cholesterol increased by 13% in group 2, decreased by 7.3% in group 4, and remained unchanged in group 1 and 3. Apolipoprotein B level correlated well with LDL cholesterol in all groups. High density lipoprotein cholesterol changes were inconsistent.

Conclusions: These results help to explain and reconcile previous published reports. The metabolic background of the individual together with the amount of energy consumed affect the behavior of plasma lipids and lipoproteins levels during fasting.

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VLDL= very low density lipoprotein

LDL= low density lipoprotein
 

Background: The pathogenesis of neurological symptoms, the most common extraintestinal complication ofchildhood shigellosis, is unclear. To elucidate the mechanisms involved, we developed an animal model and demonstrated that TNF alpha and IL-1 beta play a role.

Objectives: To determine whether TNF alpha and IL-1 beta genes are expressed in the brain following peripheral administration of Shigella dysenteriae 60R.

Methods: Expression of mRNA for TNF alpha and IL-1 beta was examined in the brain structures (hypothalamus and hippocampus) and peripheral organs by reverse transcriptase polymerase chain reaction, at different time points after intraperitoneal injection of S. dysenteriae sonicate.

Results: In our animal model of Shigella related seizures, TNF alpha and IL-1 beta mRNA were induced in the brain, spleen and liver already 1 hour after injection of S. dysenteriae sonicate. The expression of TNF alpha and IL-1 beta mRNA in spleen, hippocampus and hypothalamus decreased after 6 h and increased again at 18 h post-injection.

Conclusions: Local production of TNF alpha and IL-1 beta in the brain may be involved in the enhanced seizure response of mice after administration of S. dysenteriae. It is possible that intracerebral production of TNF alpha and IL-1 beta plays a role in neurological disturbances of human shigellosis.