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עמוד בית
Fri, 01.11.24

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October 2002
Craig Bjinderman, MA, Oren Lapid, MD and Gad Shaked, MD
Arie Shifman, DMD, Shmuel Orenbuch, MA and Mel Rosenberg, PhD
September 2002
Aliza Amiel, PhD, Orit Reish, MD, Elena Gaber, PhD, Ronit Masterman, MD, Tally Tohami, MSc and Moshe D. Fejgin, MD

Background: While most allelic pairs of DNA replicate synchronously during the S phase of the cell cycle, some genes normally replicate asynchronously, i.e., genes on the X chromosome and imprinted genes. The replication control mechanism is unknown but was shown to be impaired in malignancies and chromosomal trisomies where replication pattern becomes asynchronous.

Objectives: To determine the level of asynchronization in replication timing of cells from patients with microdeleted genomes.

Methods: We applied monocolor fluorescent in situ hybridization with different probes on leukocytes from microdeleted genomes.

Results: All samples derived from the microdeleted genomes showed significantly higher levels of an asynchronized pattern compared to normal individuals.

Conclusions: Even a “small” genetic imbalance (microdeletion) can interfere with gene replication and cell cycle progression, as previously shown in full trisomies.
 

Pierre Singer, MD

Pressure sores are a well-recognized problem, with an etiology that is multifactorial and not solely a consequence of pressure itself. Malnutrition is one of the factors involved, namely low calorie and protein intake. Mainly elderly patients, patients after hip fracture, but also patients after trauma, burns or extended surgery require additional nutritional support to reduce the possibility of pressure ulcers developing. Evidence has shown the efficacy of percutaneous endoscopic gastrostomy in elderly patients with malnutrition and dementia. Nutritional support should include sufficient calories, protein, fat, carbohydrates, vitamins and minerals. Arginine is the main amino acid required and is essential for collagen deposition and wound healing. Vitamin A and zinc should be added to nutritional support.

August 2002
Raanan Shamir, MD, Rami Eliakim, MD, Nitza Lahat, PhD, Esther Sobel, MSc and Aaron Lerner, MD, MHA

Background: Celiac disease is common in both children and adults. Small intestinal biopsy is mandatory for establishing a diagnosis. Anti-endomysial antibodies, detected by immunofluorescence, have a sensitivity and specificity close to 100% in the diagnosis of CD[1]. Recently, tissue transglutaminase has been identified as the target autoantigen of antibodies against endomysium, and TTG[2] antibodies are comparable to EMA-IMF[3] in the diagnosis of CD.

Objective: To evaluate a new enzyme-linked immunosorbent assay kit for EMA, compared to EMA-IMF and TTG antibodies in the diagnosis of CD.

Methods: Our study population included all subjects with positive EMA-IMF who underwent intestinal biopsy (n=21). From the same sera, TTG antibodies and EMA-ELISA[4] were determined, and all antibody results were compared to the biopsy findings.

Results: EMA-IMF was able to predict biopsy findings of CD in 19 of 21 cases (90.5%). When patients with biopsy findings compatible with CD and positive EMA-IMF (n=19) were tested for EMA-ELISA and TTG antibodies, 18 of the 19 were positive for both EMA-ELISA and TTG antibodies. A significant correlation was found between EMA-ELISA and TTG antibody titers (r = 0.74, P < 0.001).

Conclusions: Our study demonstrates that EMA-ELISA is comparable to TTG antibodies in the diagnosis of CD, and supports the use of EMA-ELISA as a serologic marker for this disease.


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[1]
CD = celiac disease

[2] TTG = tissue transglutaminase

[3] EMA-IMF = anti-endomysial antibodies measured by immunofluorescence

[4] ELISA = enzyme-linked immunosorbent assay

Fabio Broglio, MD, Emanuela Arvat, MD, Andrea Benso, MD, Cristina Gottero, MD, Flavia Prodam, MD, Riccarda Granata, PhD, Mauro Papotti, MD, Giampiero Muccioli, PhD, Romano Deghenghi, PhD and Ezio Ghigo, MD

Ghrelin, a 28 amino acid acylated peptide predominantly produced by the stomach, displays strong growth hormone-releasing activity mediated by the hypothalamus-pituitary GH[1] secretagogue receptors that were found to be specific for a family of synthetic, orally active GH secretagogues. The discovery of ghrelin brings us to a new understanding of the regulation of GH secretion. However, ghrelin is much more than simply a natural GH secretagogue. It also acts on other central and peripheral receptors and exhibits other actions, including stimulation of lactotroph and corticotroph secretion, orexigenia, influences gastroenteropancreatic functions, and has metabolic, cardiovascular and anti-proliferative effects. Knowledge of the whole spectrum of biologic activities of this new hormone will provide new understanding of some critical aspects of neuroscience, metabolism and internal medicine. In fact, GHS[2] were born more than 20 years ago as synthetic molecules, eliciting the hope that orally active GHS could be used to treat GH deficiency as an alternative to recombinant human GH. However, the dream did not become reality and the usefulness of GHS as an anabolic anti-aging intervention restoring the GH/IGF-I[3] axis in somatopause is still unclear. Instead, we now face the theoretic possibility that GHS analogues acting as agonists or antagonists could become candidate drugs for the treatment of pathophysiologic conditions in internal medicine totally unrelated to disorders of GH secretion. 




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[1]
GH = growth hormone

[2] GHS = GH secretagogues

[3] GH/IGF-1 = growth hormone/insulin-like growth factor-I

Bella Bielorai, MD, Hana Golan, MD, Gideon Rechavi, MD, PhD and Amos Toren, MD
July 2002
Shmuel C. Shapira, MD and Joshua Shemer
Rami Sagi, MD, Eyal Robenshtok, MD, Lior H. Katz, MD, Shmuel Reznikovich, MMHF, Israel Hendler, MD, Lior Poles, MD, Ariel Hourvitz, MD, Boaz Tadmor, MD, Meir Oren, MD, Giora Martonovich, MD and Boaz Lev, MD

The threat of a disease outbreak resulting from biologic warfare has been of concern for the Israeli health system for many years. In order to be prepared for such an event the health system has formulated doctrines for various biologic agents and defined the logistic elements for the procurement of drugs. During the last 4 years, and especially after the West Nile fever epidemic in 2000, efforts to prepare the healthcare system and the relevant organizations were accelerated. The Director-General of the Ministry of Health nominated a Supreme Steering Committee to fill in the gaps and upgrade the preparedness of the health system for an unusual disease outbreak. This committee and its seven subcommittees established appropriate guidelines, communication routes among different organizations, and training programs for medical personnel. The anthrax outbreak in the United States found the healthcare system in the hub of the preparation process, and all modes of action were intensified. Further work by hospitals, primary care clinics and all other institutes should be initiated to maintain a state of proper preparedness.

Jehuda Hiss, MD, Maya Freund, PhD, Uzi Motro, PhD and Tzipi Kahana

Background: The majority (n = 445) of the Israeli and Palestinian fatal victims of the El Aqsa Intifada was examined at the National Center of Forensic Medicine in Tel Aviv. Analysis of the trauma sustained and the anthropologic profile of both the victims and the perpetrators elucidates the trends and contrasts them with the phenomenon in the past.

Objectives: The purpose of the forensic investigation of mass casualty incidents is manifold: establishing the minimal number of individuals involved, identifying the victims and perpetrators, collecting material evidence, and determining the modus operandi.

Methods: The postmortem examination includes external description of the bodies and their injuries, photo-documentation, and sampling of tissues. Radiography, dental examination, and a ten-print card of each cadaver are also recorded.

Results: The modus operandi of the current Intifada is somewhat different from that of the previous wave of terrorism and includes more road shootings and vehicular terrorism. In addition, three suicide bombers using explosive devices detonated within crowded areas were young women, and the age of the perpetrators has increased from up to 35 years to individuals as old as 47, thus greatly enlarging the potential number of suicide terrorists. Virologic and biologic tests have been introduced to examine the tissues of the suicide bombers since they are possible sources of contagion to the wounded victims.

Conclusion: The results of the medico-legal investigation of victims and perpetrators of terrorism enable us to establish the modus operandi and the profile of potential perpetrators, which can help in the prevention of similar attacks. Documentation of the different types of injuries in fatal victims of explosion and shooting contributes to improving the awareness of the medical staff treating the wounded of similar attacks. Further investigation into the reliability of virologic and biologic tests conducted on postmortem tissue is recommended.

June 2002
Shlomo Vinker, MD, Sasson Nakar, MD, Elliot Rosenberg, MD, MPH and Eliezer Kitai, MD

Background: Colorectal cancer is the second leading cause of cancer mortality in Israel. Unfortunately, compliance  with annual fecal occult blood testing is very low.

Objective: To assess the effectiveness of interventions to increase FOBT[1] screening in primary care clinics in Israel.

Methods: A prospective, randomized study included all 50–75 year old enrollees of six family physicians in two primary care clinics. The register of two physicians, one from each clinic, was allocated to one of three groups. Two FOBT reminder strategies were tested: a physician reminder (753 patients), and a patient reminder that was either a phone call (312 patients) or a letter (337 patients). The control group (913 patients) of physicians continued administering their regular level of care. The main outcome measure was the percentage of patients undergoing FOBT screening in each study arm at the conclusion of the one year study period.

Results: In the intervention groups 14.3% (201/1,402) were screened using the FOBT over the course of the study year. Using an intent-to-screen analysis, the screening rate in the physician and patient reminder groups was significantly higher than in the control group(16.5 and 11.9%,vs. 1.2% respectively, P < 0.0001). Phone reminders were significantly more efective as compared to letters (14.7 vs. 9.2%, P = 0.01).

Conclusions: Our study has shown the benefit of various FOBT reminder systems, especially those centered around the family physician. Further research should focus on this area, in conjunction with other novel approaches.

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[1] FOBT = fecal occult blood testing

Eliezer Golan, MD, Bruria Tal, PhD, Yossef Dror, PhD, Ze’ev Korzets, MBBS, Yaffa Vered, PhD, Eliyahu Weiss, MSc and Jacques Bernheim, MD

Background: Multiple factors are involved in the pathogenesis of hypertension in the obese individual.

Objective: To evaluate the role of a decrease in sympathetically mediated thermogenesis and the effect of the correlation between the plasma leptin and daily urinary nitric oxide levels on obesity-related hypertension.

Methods: We evaluated three groups: 25 obese hypertensive patients (age 45.7±1.37 years, body mass index 34.2±1.35 kg/m2, systolic/diastolic blood pressure 155±2.9/105±1.3, mean arterial pressure 122±1.50 mmHg); 21 obese normotensive patients (age 39.6±1.72, BMI[1] 31.3±0.76, SBP/DBP[2] 124±2.1/85.4±1.8, MAP[3] 98.2±1.80); and 17 lean normotensive subjects (age 38.1±2.16, BMI 22.1±0.28, SBP/DBP 117±1.7/76.8±1.5, MAP 90.1±1.50). We determined basal resting metabolic rates, plasma insulin (radioimmunoassay), norepinephrine (high performance liquid chromatography) in all subjects. Thereafter, 14 obese hypertensives underwent a weight reduction diet. At weeks 6 (n=14) and 14 (n=10) of the diet the above determinations were repeated. Plasma leptin (enzyme-linked immunosorbent assay) and UNOx[4] (spectrophotometry) were assayed in 17 obese hypertensives and 17 obese normotensives, and in 19 obese hypertensives versus 11 obese normotensives, respectively.

Results: Obese hypertensive patients had significantly higher basal RMR[5] and plasma NE[6] levels. Insulin levels were lower in the lean group, with no difference between the hypertensive and normotensive obese groups. At weeks 6 and 14, BMI was significantly lower, as were insulin and NE levels. RMR decreased to values of normotensive subjects. MAP normalized but remained significantly higher than that of obese normotensives. Leptin blood levels and the leptin/UNOx ratio were significantly higher in the obese hypertensive compared to the obese normotensive patients. Both these parameters were strongly correlated to BMI, MAP5, RMR, and plasma NE and insulin .Obese hypertensive patients excreted less urinary NO metabolites. A strong correlation was found between MAP and the leptin/UNOx ratio.  

Conclusions: A reduction of sympathetically mediated thermogenesis, as reflected by RMR, results in normalization of obesity-related hypertension. In contrast, insulin does not seem to play a major role in the pathogenesis of hypertension associated with obesity. Increased leptin levels in conjunction with decreased NO production in the presence of enhanced sympathetic activity may contribute to blood pressure elevation in the obese.

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[1] BMI = body mass index

[2] SBP/DBP = systolic blood pressure/diastolic blood pressure

[3] MAP = mean arterial pressure

[4] UNOx = urinary nitric oxide

[5] RMR – resting metabolic rate

[6] NE = norepinephrine

Oren Shibolet, MD, Olga Schatz, MD, Michal Krieger, MD, Alexander Maly, MD and Yoseph Caraco, MD
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