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עמוד בית
Sat, 23.11.24

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September 2002
Gisele Zandman-Goddard, MD and Miri Blank, PhD
August 2002
Alla Reitman, MD, Ilana Friedrich, MD, Ami Ben-Amotz, PhD and Yishai Levy, MD

Background: Obesity is among the well-established risk factors for cardiovascular morbidity and mortality. However, the exact mechanisms are not well understood. Low concentrations of vitamins (fat soluble antioxidants and B vitamins) are linked to accelerated atherosclerosis through increased oxidative stress and homocysteine.

Objective: To compare plasma antioxidant vitamins (carotenoids and vitamin E), B vitamins (folic acid and B12) and homocysteine – all linked to increased cardiovascular morbidity – between patients with severe obesity and lean control subjects.

Methods: We investigated plasma carotenoids, vitamin E, folic acid, B12, and homocysteine in 25 obese patients and their age-matched controls (body mass index 38 ± 3 vs. 21 ± 2 kg/m2), respectively), related to BMI[1] and plasma insulin.

Results: Patients with obesity had normal B vitamins and a non-significant decrease in plasma homocysteine as compared to controls (9.4 ± 2.6 vs. 11.4 ± 4.8 mmol/L, P = 0.07). There was a significant decrease in both plasma carotenoids and vitamin E (0.69 ± 0.32 vs. 1.25 ± 0.72 and 24 ± 10 vs. 33 ± 14 mg/ml, respectively; P < 0.01). Both vitamins were inversely related to BMI and plasma insulin, which was significantly increased in patients with obesity (22 ± 21 vs. 6 ± 2 mU/ml, P < 0.01).

Conclusions: Obese patients with BMI above 35 kg/m2 show low plasma antioxidants (carotenoids and vitamin E). This may result in increased oxidative stress and consequently enhanced atherosclerosis in these patients.






[1] BMI = body mass index


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

Rachel Goldwag, MSW, Ayelet Berg, PhD, Dan Yuval, PhD and Jochanan Benbassat, MD

Background: Patient feedback is increasingly being used to assess the quality of healthcare.

Objective: To identify modifiable independent determinants of patient dissatisfaction with hospital emergency care.

Methods: The study group comprised a random sample of 3,152 of the 65,966 adult Israeli citizens discharged during November 1999 from emergency departments in 17 of the 32 acute care hospitals in Israel. A total of 2,543 (81%) responded to a telephone survey tht used a structured questionnaire. The ndependent variables included: hospital characteristics, patient demographic variables, patient perception of care, self-rated health status, problem severity, and outcome of care. The dependent variable was dissatisfaction with overall ED[1] experience on a 1–5 Likert-type scale dichotomized into not satisfied (4 and 5) and satisfied (1,2 and 3).

Results: Eleven percent of the population reported being dissatisfied with their emergency room visit. Univariate analyses revealed that dissatisfaction was significantly related to ethnic group, patient education, hospital identity and geographic location, perceived comfort of ED facilities, registration expediency, waiting times, perceived competence and attitudes of caregivers, explanations provided, self-rated health status, and resolution of the problem that led to referral to the ED. Multivariate analyses using logistic regressions indicated that the four most powerful predictors of dissatisfaction were patient perception of doctor competence and attitudes, outcomes of care, ethnicity, and self-rated health status.

Conclusions: Attempts to reduce dissatisfaction with emergency care should focus on caregiver conduct and attitudes. It may also be useful to improve caregiver communication skills, specifically with ethnic minorities and with patients who rate their health status as poor.


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[1]
ED = emergency department

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

Gerard Espinosa, MD, Ricard Cervera, MD, PhD, Joan-Carles Reverter, MD, PhD, Dolors Tassies, MD, PhD, Josep Font, MD, PhD and Miguel Ingelmo, MD, PhD
Wendy Chen, MSW, Ruth Balaban, MA, RN, Varda Stanger, PhD, Ra’aya Haruvi, MSW, Shmuel Zur, MD and Arie Augarten, MD
Shai Izraeli, MD and Gideon Rechavi, MD, PhD
Bella Bielorai, MD, Hana Golan, MD, Gideon Rechavi, MD, PhD and Amos Toren, MD
July 2002
Manfred S. Green, MD, PhD and Zalman Kaufman, MSc

The appearance of “new” infectious diseases, the reemergence of “old” infectious diseases, and the deliberate introduction of infectious diseases through bioterrorism has highlighted the need for improved and innovative infectious disease surveillance systems. A review of publications reveals that traditional current surveillance systems are generally based on the recognition of a clear increase in diagnosed cases before an outbreak can be identified. For early detection of bioterrorist-initiated outbreaks, the sensitivity and timeliness of the systems need to be improved. Systems based on syndromic surveillance are being developed using technologies such as electronic reporting and the internet. The reporting sources include community physicians, public health laboratories, emergency rooms, intensive care units, district health offices, and hospital admission and discharge systems. The acid test of any system will be the ability to provide analyses and interpretations of the data that will serve the goals of the system. Such analytical methods are still in the early stages of development.

Raymond Kaempfer, PhD, Gila Arad, PhD, Revital Levy, BA and Dalia Hillman, BA

Background: Superantigens produced by Staphylococcus aureus and Streptococcus pyogenes are among the most lethal of toxins. Toxins in this family trigger an excessive cellular immune response leading to toxic shock.

Objectives: To design an antagonist that is effective in vivo against a broad spectrum of superantigen toxins.

Methods: Short peptide antagonists were selected for their ability to inhibit superantigen-induced expression of human genes for cytokines that mediate shock. The ability of these peptides to protect mice against lethal toxin challenge was examined.

Results: Antagonist peptide protected mice against lethal challenge with staphylococcal enterotoxin B and toxic shock syndrome toxin-1, superantigens that share only 6% overall amino acid homology. Moreover, it rescued mice undergoing toxic shock. Antagonist peptides show homology to a β-strand/hinge/a-helix domain that is structurally conserved among superantigens, yet remote from known binding sites for the major histocompatibility class II molecule and T cell receptor that function in toxic T cell hyperactivation.

Conclusions: The lethal effect of superantigens can be blocked with a peptide antagonist that inhibits their action at the top of the toxicity cascade, before activation of T cells occurs. Superantigenic toxin antagonists may serve not only as countermeasures to biologic warfare but may be useful in the treatment of staphylococcal and streptococcal toxic shock, as well as in some cases of septic shock.
 

Shmuel Kron, MD, MPA and Shlomo Mendlovic, PhD, MD
Eyal Robenshtok, MD, Shay Luria, MD, Zeev Tashma, PhD and Ariel Hourvitz, MD

Atropine is the drug of choice for treatment of organophosphate (OP) nerve agent and insecticide intoxication and has been used for this indication for several decades. Adverse reactions to atropine may occur, and are of two types: toxic and allergic. Toxic reaction, the most common form, results from the anti-muscarinic effects of the drug. Since it is most probably related to interpersonal variation in sensitivity to atropine, toxic effects may appear at the usual therapeutic doses. The second type, allergic reaction, includes local manifestations, usually after the administration of eyedrops, and systemic reaction in the form of anaphylaxis. Since most patients manifest only a mild reaction, allergy testing is not performed and the prevalence of allergy to atropine is therefore not known. Severe allergic reaction to atropine is rare, as evidenced by the small number of case reports in the literature despite the drug's extensive use. Alternative anti-muscarinic drugs recommended for OP poisoning include glycopyrrolate and scopolamine. Glycopyrrolate is a peripheral anti-muscarinic drug that has been studied in comparison to atropine for many clinical indications, while scopolamine is an anti-muscarinic drug with both peripheral and central effects. An acceptable alternative regimen for patients with proven allergy to atropine is a combination of glycopyrrolate with centrally active drugs such as benzodiazepines or scopolamine.

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