Israel Medical Association Journal

Background: Alteration of innate and acquired immunity can play a role in the mechanism involved in the development of dementia. Epidemiologic studies indicate that the use of non-steroidal anti-inflammatory drugs can delay the onset or slow progression of Alzheimer disease.

Objectives: To determine whether the use of NSAIDs[1] is associated with natural killer activity alteration in AD[2] and multi-infarct vascular dementia patients, as compared with non-demented elderly and healthy young people.

Methods: In this prospective open study four groups of subjects (AD, VD[3], non-demented elderly, and healthy young people) were treated with an NSAID drug (rofecoxib 12.5 mg/day or ibuprofen 400 mg twice daily) for 7 days. Natural killer cell cytotoxicity was measured after flow cytometry analysis before and after treatment.

Results: Of the 49 subjects studied, 15 had a diagnosis of AD (3 men, 12 women; mean age 83.5 ± 8.1 years), 15 had a diagnosis of multi-infarct VD (7 men, 8 women; mean age 75.5 ± 8.4), 13 were non-demented elderly (1 man, 12 women; mean age 80.2 ± 7.2), and 6 were healthy young volunteers (3 men, 3 women; mean age 36.8 ± 4.4). While all examined subjects showed decreased NK[4] cell cytotoxicity after treatment, this decrease was most prominent and statistically significant in elderly patients suffering from vascular dementia –  from an average of 30.5 ± 11.8% before treatment to 22.5 ± 16% after treatment (P = 0.04). The decrease in NK cell cytotoxicity was only moderate and not statistically significant in all other elderly and young subjects. Young healthy volunteers exhibited a significantly higher total NK cytotoxicity before and after treatment compared to all age groups (P < 0.001).

Conclusion: These findings suggest that NSAIDs decrease NK activity in vascular dementia patients. Our findings also suggest that natural killer activity alteration cannot explain the ability of anti-inflammatory drugs to delay the onset or slow the progression of AD.

Background: With the introduction of surgery and percutaneous balloon valvuloplasty for relieving severe mitral stenosis the natural history of the disease has markedly altered.

Objectives: To determine the natural history of patients with moderate mitral valve stenosis.

Methods: Demographic, clinical and echocardiographic data were evaluated in 36 patients with moderate mitral stenosis during a follow-up of 71 ± 15 months.

Results: The 36 patients comprised 32 women and 4 men with a mean age of 43.7 ± 12.2 years; 28 were Jewish and 8 were of Arab origin. During follow-up, there was a significant decrease in mitral valve area, with an increase in mean mitral valve gradient and score. Mean loss of mitral valve area was 0.04 ± 0.11 cm²/year. No correlation was found between disease progression and age, past mitral valve commissurotomy, baseline mean gradient or mitral valve score. Larger baseline mitral valve area (P = 0.007) and Arab origin (P = 0.03) had an independent correlation to loss of mitral valve area. Fifteen patients (42%) did demonstrate any loss in mitral valve area during the follow-up period.

Conclusions: The rate of mitral valve narrowing in patients with moderate mitral stenosis is variable and cannot be predicted by patient’s age, past commissurotomy, valve score or gradient. Secondly, larger baseline mitral valve area and Arab origin showed an independent correlation to loss of mitral valve area; and finally, in many patients valve area did not change over a long observation period.
 

Background: Head louse infestations are prevalent worldwide. Over the past 20-25 years, 15-20% of all children in Israel between 4 and 13 years of age have been infested with head lice; This is mainly due to the existence of ineffective pediculicides on the market.

Objective: To examine the pediculicidal efficacy and safety of a natural remedy (”Chick-Chack") and to compare it in an open clinical study with a known pesticide spray.

Methods: The natural remedy, which contains coconut oil, anise ail and ylang ylang oil:, was applied to the hair of infested.children three times at 5 day intervals. Each treatment lasted for 15 minutes. The control pediculicide was a spray, formulation containing permethrin, malathion, piperonyl butoxide, isododecane and propellant gas, which was applied twice for 10 minutes with a 10 day interva1 between applications.

Results: Of 940 Children, aged 6-14 years, from six schools in Jerusalem who were examined for head louse infestastion,199 (21:.2÷/) were infested with lice and eggs, while 164 (17.4% ) were infested only  with nits. Altogether, 119 children were randomly treated with either the natural remedy or the control product. Treatment was successful with the natural remedy  in 60 children (92.3%) and with the control pediculicide in 59 children (92.2%). There were no significant side effects associated with either formulation.

Conclusions: The natural remedy was very effective in controlling  louse infestations under clinical conditions and caused no serious side effects.
 

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. 

Background: Long-term follow-up in apical hypertrophic cardiomyopathy is rare.

Objective: To study the natural history of the disease.

Methods: We followed 11 patients, 5 women and 6 men, for 5-20 years.

Results: At presentation all 11 patients had typical features of apical hypertrophic cardiomyopathy, with dyspnea in 3 and chest pains in 8, of whom 5 were typical of angina and 3 had myocardial infarction. R-wave voltage and T-wave negativity progressively decreased in magnitude at serial electrocardiograms in four patients. Perfusion defects were detected on thallium myocardial scintigraphy in three, increased apical uptake in two, and normal in one patient. Apical aneurysm with normal coronary arteries developed in a patient who had sustained ventricular tachycardia. All of the 10 catheterized patients had normal coronaries except for one with significant left anterior descending artery stenosis and another with a minor lesion. Symptomatic sustained ventricular tachycardia was found in two patients, one of whom required the implantation of an internal cardioverter-defibrillator.

Conclusions: Apical hypertrophic cardiomyopathy may develop morphologic and electrocardiographic changes with life-threatening arrhythmias necessitating close follow-up and treatment.

The hepatitis C virus is an enveloped positive-sense single-stranded RNA virus, which has been classified into 6 major genotypes and over 100 subtypes. HCV replicates mainly in the hepatocyte. Recently, infectious HCV cDNA clones have been generated. Despite evidence that innate and adaptative humoral and cellular immune responses are activated as part of an antiviral defense, HCV has a remarkable ability to establish persistent infection. The analysis of viral kinetics using mathematical modeling shows a relative steady state without treatment, while an immediate biphasic HCV decline occurs in blood during successful treatment, the latter being predictive of clearance of HCV by the end of treatment.

Background: Differentiating between benign and malignant submucosal tumors is difficult. Moreover, the natural course of benign-appearing SMTs is not clearly elucidated.

Objectives: To evaluate the natural course of upper gastrointestinal SMTs by endoscopic endosonography.

Methods: We followed 25 consecutive patients with small (<40 mm) SMTs for a mean period of 19 months. Evaluation included maximal tumor diameter, internal echo pattern, and outer margin of lesions.

Results: Follow-up revealed no change in echo features in 24 of 25 patients (96%). In only one patient a homogenous hypoechoic smooth margin lesion converted to a non-homogenous tumor with an irregular outer margin. This lesion also increased in size from 30 to 38 mm. On surgical removal this tumor was found to be a stromal tumor with high malignant potential.

Conclusions: Most small SMTs do not change during a period of 19 months and a conservative policy of surveillance is warranted.

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SMTs= submucosal tumors

Background: According to studies from different countries, the prevalence of natural rubber latex sensitization in healthcare workers ranges from 2.9 to 17%.

Objective: To estimate the prevalence of NRL-specific IgE antibodies in healthcare workers in Israel.

Methods: Three hundred healthcare workers, mostly from a major pediatric tertiary care facility, and 15 non-healthcare workers completed a questionnaire on signs and symptoms of NRL allergy and other respiratory and food allergies. NRL-specific IgE antibodies were assayed with the DPC AlaSTAT-ELISA method.

Results: Seventy of the 300 workers (23.3%) reported symptoms of NRL allergy: hand eczema and pruritus in 63, upper respiratory tract and ocular symptoms in 10, shortness of breath in 2, and generalized rash in 6. None had anaphylaxis due to latex exposure. There was a significant correlation of symptoms of NRL allergy with atopy and job category (nurses, laboratory technicians, nurse assistants and dental medicine workers), but not with gender, age, or years of employment. The in vitro tests for specific IgE antibodies against NRL were positive (≥0.70 IU/ml) in five workers (1.66%).

Conclusions: This is the first study of the prevalence of NRL-specific IgE antibodies in healthcare workers in Israel. Our 1.66% sensitization rate is much lower than that reported for healthcare workers in other countries. This difference may be due to our inclusion of a study population with a relatively low exposure to latex gloves (pediatricians compared to surgeons). Further studies are needed in this and other high risk populations in Israel.  

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NRL = natural rubber latex

Background: Growth retardation in childhood was only recently recognized as a prominent feature of Gaucher disease type 1, but there are few data on both the pubertal development and the final outcome of growth and sexual maturation.

Objective: To investigate the natural pattern of growth and puberty in patients with Gaucher disease type 1 and the effect of splenectomy and enzyme replacement therapy.

Methods: We retrospectively analyzed growth and puberty in 57 patients with Gaucher disease type 1; 52 were followed since childhood and/or prepuberty and 42 have reached sexual maturity and final height. In the analysis we considered severity of disease, time of splenectomy, and start of enzyme replacement therapy.

Results: Deceleration of growth at age 3–5 years was observed in 30 of 57 patients followed since early childhood while untreated: height-SDS decreased from -0.34±0.42 at age 0–3 years to -1.93±0.95 (P<0.01) at age 7–10 years and was more pronounced with severe disease. A high prevalence (59.6%) of delayed puberty, which was more frequent with severe disease, was observed in 47 patients followed before and throughout puberty. No primary endocrine pathology was found. All patients, untreated as well as treated, with growth and pubertal delay had a spontaneous catch-up, achieved full sexual maturation, and most (83.3%) reached a final height within the range of parental height–standard deviation score. Splenectomy (partial and/or total) performed in 20 patients while still growing had a beneficial effect on growth, which was temporary in some and did not affect puberty. ERT improved growth in 11 patients who started therapy before puberty, as evidenced by a progressive increase in the height-SDS, and seemed to normalize the onset of puberty.

Conclusions: Growth retardation in childhood and delay of puberty are characteristic of Gaucher disease type 1 and are more frequent with severe disease. There is a spontaneous catch-up later in life and most patients reach a final height within their genetic growth potential. Enzyme replacement therapy apparently normalizes growth and possibly also the onset of puberty.

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ERT = enzyme replacement therapy

SDS = standard deviation score