Israel Medical Association Journal

Background: Exposure of newborn animals to high concentrations of oxygen leads to diffuse alveolar damage similar to that seen in bronchopulmonary dysplasia in human infants. Therefore, neonatal rats are a suitable practical model of hyperoxic lung damage in human infants.

Objective: To determine the involvement of tumor necrosis factor-alpha and interleukin-6 in lung injury in neonatal rats exposed to 100% O2 concentration.

Methods: A randomized controlled study was designed in which litters of term Sprague-Dawley rat pups were assigned to experimental or control groups. The pups in the experimental group were placed in 100% O2 from birth for 9 days, while the control pups were placed in room air. Twelve to 15 pups from each group were sacrificed on day 1, 3, 6, 9 and 13 after birth for bronchoalveolar lavage collection and lung histologic study. The bronchoalveolar lavage fluid was assayed for TNFα and IL-6.

Results: Newborn rats exposed to 100% O2 for the first 9 days of life showed severe pulmonary edema and hypercellularity on days 1 and 3, which then improved to nearly complete resolution on days 6 and 9. Pulmonary TNFα was produced early on O2 exposure (day 3) and pulmonary IL-6 later (days 6 and 9).

Conclusions: Hyperoxia induces sequential production of pulmonary TNFα and IL-6, which corresponds to the severity of the pathological findings and the known inflammatory and anti-inflammatory role of these cytokines.

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TNFα= tumor necrosis factor-alpha

IL-6= interleukin-6

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: 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.
 

Background: Cholestasis is a frequent problem in patients on total parenteral nutrition. Cisapride has a prokinetic effect on the biliary system, but its effect on hepatic excretory function is unknown.

Objectives: To study the effect of cisapride on TPN-induced cholestasis in a rat model.

Methods: Bile flow and bile salt secretion rate were measured in rats given TPN. There were four groups of 8 to 13 animals each. After a one hour baseline period during which all four groups received i.v. saline infusion, two groups received a TPN solution for another 2 hours, while saline was infused in the two control groups.

At the beginning of the second hour, 2 mg/kg cisapride was injected i.v. as a bolus into one experimental and one control group. Bile was collected from the common bile duct.

Results: At the end of the third hour, TPN caused a significant reduction in bile flow (P<0.02) and bile salt secretion rate (P<0.001) (61.24 vs. 50.74 µl/min/kg, and 1.173 vs. 0.799 µmol/min/kg, respectively). Addition of cisapride abolished the cholestatic effect of TPN.

Conclusions: Cisapride has a protective effect against TPN-associated cholestasis. This may have clinical significance, and further studies are warranted.

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TPN= total parenteral nutrition
 

Background: Previous reports on the behavior of procalcitonin blood levels in diverse clinical conditions suggest that it is part of the activation of cellular immunity and is another acute-phase reactant.

Objective: To compare procalcitonin with C-reactive protein, a well-known acute-phase reactant, in a series of acutely febrile pediatric patients and to review recent literature on procalcitonin.

Methods: Procalcitonin and CRP levels were evaluated in 38 blood samples of pediatric patients who were admitted to the Dana Children’s Hospital for evaluation of unexplained fever or for sepsis work-up.

Results: The parallelism between procalcitonin and CRP was found to be highly significant (P<0.01).

Conclusion: The rise of procalcitonin blood levels in febrile pediatric patients suggests that it is part of the acute-phase reaction, parallel with the CRP reaction.
 

Methods: We attempted to investigate plasma oxidation and plasma and erythrocyte glutathione and glutathione enzymes in 20 patients with NIDDM, compared with euglycemic matched controls. Plasma oxidation was analyzed both basally (without) and as induced by 2,2'-azobis,2-amidopropane hydrochloride measured by the generation of thiobarbituric acid reactive substances and lipid peroxides.

Results: There was a significant increase in oxidation both basally (without) and as induced by AAPH. Plasma glutathione was lowered by 50% (P<0.01) and erythrocyte glutathione peroxidase, glutathione s-transferase and glutathione reductase activities were lower by 30%, 27% and 46%, respectively (P<0.01) in the patients with NIDDM.

Conclusions: Confronted by increased oxidation, patients with NIDDM show an abnormal plasma and erythrocyte antioxidative capacity, which may result in an accelerated rate of complications.

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NIDOM= non-insulin-dependent diabetes mellitus

Objective: To evaluate the contribution of computerized tomography to the diagnosis of Takayasu's arteritis.

Methods: A retrospective analysis of the diagnostic process was recently conducted in three consecutive patients diagnosed over the last 3 years.

Results: Three females of Arab origin with Takayasu's arteritis were recently identified by CT. In two of the three patients the imaging procedure was performed for different working hypotheses, and the radiological findings (wall thickening, perivascular edema, and segmental intraluminal obliteration of the aorta and its major branches) were unexpected. In these two patients, repeated physical examination following the imaging procedure disclosed initially missed findings that could have led to an earlier consideration of Takayasu's arteritis (bruits above the epigastrium, subclavian and carotid arteries, and absent brachial pulses). Retrospective analysis of the patients' symptoms following CT revealed the true nature of the patients' misinterpreted complaints (e.g., typical abdominal angina replaced a faulty obtained history compatible with renal colic or dyspepsia). In the third patient CT was performed for the evaluation of an epigastric bruit associated with constitutional complaints. The diagnosis of aortitis, based upon the presence of diffuse aortic wall thickening and edema of the surrounding fat, without intraluminal narrowing, could have been missed by angiography, the traditional "gold standard" diagnostic procedure. All three patients complained of ill-defined epigastric abdominal pain and had epigastric tenderness during examination.

Conclusions: CT has the potential for detecting Takayasu's disease and may be superior to angiography, particularly at the early non-obliterative stage. Since the diagnosis of Takayasu's disease is rarely considered, the expanding use of CT and MRI technologies may reveal missed cases that are evaluated for other plausible diagnoses. The true incidence of Takayasu's arteritis in Israel may be much higher than reported, particularly in the Arab population. Our findings suggest that epigastric tenderness, originating from active inflammatory reaction in the abdominal aortic wall, should be considered as a diagnostic criterion of Takayasu's aortitis.

Background: Prenatal lead exposure (umbilical cord blood lead concentration 10 (μg/dl) may impair cognitive development. Childhood lead poisoning is infrequent in Israel, and there are no data on lead exposure in immigrants to Israel from the former Soviet Union.

Objectives: To evaluate prenatal blood lead concentrations in Israeli newborns whose mothers were born in Israel and in those whose mothers recently immigrated from Russia, and to compare data of prenatal lead exposure in Israel with those reported from other countries.

Methods: We compared the UCBLC of 35 newborns of new immigrants from Russia with a group of 35 newborns whose mothers were born in Israel. Venous BLC was also measured in 50 mothers. Data are compared with similar reports on prenatal lead exposure internationally.

Results: The UCBLC in all 70 newborns (mean±SD) was 3.53±1.6 μg/dl, and mothers' BLC (mean±SD) was 3.90±1.39 μg/dl. UCBLC and BLC in the 50 mother-newborn pairs correlated (γ=0.36, P<0.01). All newborns except one had UCBLC<8.0 μg/dl. There was no significant difference between UCBLC in the two groups.

Conclusions: Prenatal lead exposure among the study subjects in both groups was low. In this sample the newborns of mothers born in Israel and those whose mothers recently immigrated from Russia were not found to be at risk for lead poisoning. Prenatal lead exposure in this sample was low compared to that reported from various parts of the world.

Background: Although the onset of fever in children often prompts parents to seek immediate treatment, the general level of parental knowledge on pediatric fever and administration of antipyretic medications is unknown. Parents without a basic understanding of treatment principles may give their children incorrect doses of medication. Overdosing may cause drug toxicity, while underdosing may lead to unnecessary, repeated clinic and/or emergency room visits.

Objectives: To assess parental decision-making with regard to treating fever in children, and its effectiveness, and to suggest methods for improving the level of treatment.

Methods: In this cross-sectional self-reported survey, questionnaires were completed by 650 parents who sought medical assistance for a child under the age of 10 years. Parents represented various socioeconomic levels, educational backgrounds and religious affiliations.

Results: Ninety-six percent of parents treated fevers that reached 38.5°C, and 77.6% treated fevers of only 38°C. Acetaminophen was the treatment of choice for 96% and dipyrone for 4%. Parental sources of information for managing and administering antipyretic drugs were medical personnel (40.7%), mother's or grandmother's experience (30%), and the enclosed leaflet or instructions on the bottle (29.3%). Forty-three percent of the parents administered the recommended dosage (10–20 mg/kg), whereas 24.3% used less and 32.7% used more; 11% exceeded a daily dosage of 120 mg/kg. 

Conclusions: A total of 57% of parents treated children with incorrect doses of antipyretic drugs. In 11% of the children treated, the daily dose was at a level that could cause severe toxicity. Parental knowledge of the treatment of fever must be improved.

Objectives: To present a follow-up on tests for use of performance-enhancing drugs among elite Israeli athletes from 1993 until the present.

Methods: Since 1993, 273 drug tests (urine samples) were performed in elite Israeli athletes. These tests were done during major competitions, and at random during the regular training season without prior notice to the athletes. The urine samples were sent for analysis to an official drug laboratory of the Olympic Committee in Cologne, Germany.

Results: Since 1993, seven (2.7%) male Israeli elite athletes (5 weight lifters, a javelin thrower, and a sprinter) tested positive for performance-enhancing drugs — all of them for anabolic steroids, and two for diuretics as well.

Discussion: These findings suggest that the phenomenon of performance-enhancing drug use by elite athletes has also entered Israeli sports, and probably represent the tip of the iceberg among Israeli sportsmen.  Therefore, more drug tests should be performed, especially at random without prior notice and during the regular season. Athletes in the most popular sports such as soccer and basketball should also be tested.  The concern over the use of these agents is both medical and ethical.

Objectives: To report the experience at the first Israeli Linear Accelerator Radiosurgery Unit in the management of 44 patients with acoustic neurinomas.

Methods: We analyzed the clinical records and imaging studies of all patients undergoing radiosurgery for acoustic neurinomas between 1993 and 1997, and quanitified the changes in tumor volume, hearing status, and facial and trigeminal nerve function. The contribution of radiation dose and original tumor volume upon those variables was also studied.

Results: At a mean follow-up of 32 months (range 12–60), 98% of the tumors were controlled (75% had shrunk; 23% had stable volume). The actuarial hearing preservation rate was 71%. New transient facial neuropathy developed in 24% of the patients, persisting in mild degrees in 8%. Neuropathy correlated primarily with tumor volume. Tumors with volumes 4 ml were at high risk when marginal radiation doses were 1,400 cGy. Dose reduction to a maximum of 1,400 cGy produced no neuropathies in the last 20 patients, still preserving tumor control rates.

Conclusions: Radiosurgery is an effective and cost-efficient therapeutic modality for newly diagnosed acoustic neurinomas in the elderly or medically infirm population, and for all residual or recurrent tumors after conventional surgery.