Israel Medical Association Journal

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.

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.

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. 

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.

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.

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

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

Background: Genetic factors have been shown to play a major role in the development of peak bone mass, with hereditability accounting for about 50-85% of the variance in bone mass. Numerous candidate genes were proposed to be involved in osteoporosis, but the precise genes and their relative contribution remain unknown.

Objectives: To gain insight into the genetic basis of idiopathic low bone mineral density in Israeli patients by analyzing the impact of two candidate genes: polymorphism of the vitamin D receptor gene and polymorphism A986s in the calcium-sensing receptor gene.

Methods: We analyzed 86 Jewish Israeli patients with LBMD[1]: 38 premenopausal women and 48 men, and compared the allelic pattern distribution with that of the general population (126 men and 112 women). Genotyping of the VDR[2] gene was performed in three polymorphic sites using restriction enzymes, and allelic analysis of A986s polymorphism in the CaSR[3] gene was performed using the denaturing gradient gel electrophoresis technique.  

Reaults: In LBMD women the distributions of VDR alleres in Apal polymorphism were AA=7/28, Aa=16/28 and aa=5/28; in TaqI polymorphism TT=10/31, Tt=16/31 and tt=5/31; and in BsmI polymorphism BB=7/32, Bb=14/32 and 11/32. In LBMD men the distributions were AA=17/39, Aa=21/39 and aa=1/39; in TaqI polymorphism TT=12/42, Tt=23/42 and tt=7/42; and in BsmI polymorphism BB=12/41 Bb=18/41 and bb=11/41. The distributions of all these polymorphisms in the control groups were not significantly different. Adjusting for the independent age and gender parameters confirmed that these three polymorphisms of the VDR gene did not have a significant effect on bone mineral density. Thirty percent (24/79) of LBMD patients of either sex displayed heterozygosity of the CaSR A986s polymorphism, compared with 40 of 203 controls (19.7%) (P=0.059). Adjusting for age and gender in these patients revealed a significant difference in the femoral neck BMD[4] between homozygotes and heterozygotes (P=0.002). The age at menarche of the LBMD women was found to predict 61% of the variance of femoral neck BMD.

Conclusions: In Israeli Jewish men and premenopausal women VDR gene alleles do not seem to be associated with lower lumbar spine or femoral neck BMD. A trend towards heterozygosity for a CaSR polymorphism missense mutation was noted in the LBMD patients. Age at menarche in the LBMD women was found to be an important predictor of BMD. A significant difference was found between LBMD women and healthy control women towards heterozygosity for a CaSR polymorphism, as well between homozygotes and heterozygotes for a CaSR polymorphism in BMD. The significance of these findings and their applicability to a larger population awaits further studies.

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Background: Matrix metalloproteinases are proteolytic enzymes that degrade extracellular matrix components. Numerous studies have demonstrated that individual MMPs[1] play a crucial role in tumor invasion and metastasis.

Objective: To examine the expression of MMPs and their inhibitor TIMP-2 in neoplastic and normal thyroid tissues.

Methods: We examined 33 cases of thyroid tumor (papillary, follicular and medullary carcinoma, follicular adenoma and multinodular goiter). MMP protein content and activity were measured by enzyme-linked immunosorbent assay and gel zymography. Immunohistochemistry was also performed.

Results: The thyroid tissues examined secreted MMP-2 and 9 as well as TIMP-2, but only MMP-2 was significantly higher in papillary carcinoma cases compared to the adjacent normal tissue or to the other tumor entities. Increased MMP-2 immunohistochemical staining was demonstrated in the neoplastic papillary epithelial component. No significant difference was seen between papillary carcinomas with lymph node metastases and those without.

Conclusions: Increased MMP-2 expression may be useful as a diagnostic marker to differentiate papillary carcinoma from other thyroid neoplasms, but it cannot serve as a useful prognostic marker.