Israel Medical Association Journal

Background: In the last decade the diagnosis of celiac disease has increasingly been made in adults.

Objectives: To determine disease prevalence (including silent and potential disease) in this population group.

Methods: We performed serologic screening of celiac disease in a representative and homogenous sample of a young adult general population in Israel, namely, 18 year old military conscripts, in 2003. Serologic screening was performed on serum samples randomly obtained from 850 healthy recruits (male/female = 1.1). Immunoglobulin A anti-tissue transglutaminase was determined by enzyme-linked immunosorbent assay. In cases of IgA[1] deficiency, IgG anti-endomysial antibodies were determined. A small intestinal biopsy was offered to all patients with positive serology.

Results: The prevalence of overt CD[2] diagnosed prior to recruitment was 0.12% (0.1% in men and 0.14% in women). The overall prevalence based on positive serology was 1.1%. Six of nine subjects with positive serology agreed to undergo endoscopy and intestinal biopsies. In all cases, biopsies were compatible with celiac disease (five biopsies were graded as Marsh 3a and one as Marsh 3b). One subject previously reporting irritable bowel-like symptoms was diagnosed with overt atypical CD. The prevalence of overt CD diagnosed by screening was 0.12%. The ratio of overt to silent CD was 1:8. No cases of potential disease were encountered.

Conclusions: Our findings suggest that CD is highly prevalent in the young adult population in Israel. Serologic screening for CD is a reliable and simple method for diagnosing this disease before symptoms or complications develop. 

[1] Ig = immunoglobulin

[2] CD = celiac disease

Background: Hodgkin’s lymphoma is a distinct primary solid tumor of the immune system that shows wide variation in incidence among different geographic regions and among various races. It was previously suggested that susceptible people living in certain parts of Israel had a higher risk of HL[1] because of exposure to unidentified environmental factors in these regions. Compared with other parts of Israel, these regions were characterized by a higher proportion of Israeli-born Jews.

Objectives: To study time trends in the incidence rate of HL in Israeli-born Jews of all age groups during the years 1960–2005.

Results: A total of 4812 Jewish cases of HL were reported to the Israel Cancer Registry during the study period 1960–2005. There has been a persistent increase in the age-standardized incidence rate of HL, all subtypes pooled, in Israeli-born Jews in both men and women. The age distribution pattern in both genders was bimodal in all periods. The highest incidence was observed in the 20–24 year age group: for women (9.13 per 100,000 per year) during the period 1988–1996, and for men (6.60 per 100,000 per year) during the period 1997–2005.

Conclusions: The reported incidence level of HL in Israeli-born young adult Jews in Israel has increased in recent years to high levels compared with other western countries. Our findings suggest a cohort effect to unidentified factors affecting Israeli-born young adult Jews in Israel.

Background: Stem cell-based therapy is a promising approach for the treatment of neurodegenerative disease. In our laboratory, a novel protocol has been developed to induce bone marrow-derived mesenchymal stem cells into neurotrophic factor-secreting cells. These cells produce and secrete factors such as BDNF (brain-derived neurotrophic factor) and GDNF (glial-derived neurotrophic factor).

Objectives: To evaluate the migratory capacity and efficacy of NTF-SC[1] in animal models of Parkinson's disease and Huntington's disease.

Methods: MSCs[2] underwent two-phase medium-based induction. An efficacy study was conducted on the 6-hydroxydopamine-induced lesion, a rat model for Parkinson's disease. Cells were transplanted on the day of 6-OHDA[3] administration, and amphetamine-induced rotations were measured as a primary behavioral index. In a second experiment, migratory behavior was examined by transplanting cells a distance from a quinolinic acid-induced striatal lesion, a rat model for Huntington's disease. Migration, in vivo, was monitored using longitudinal magnetic resonance imaging scans followed by histology.

Results: NTF-SCs attenuated amphetamine-induced rotations by 45%. HPLC analysis demonstrated a marked decrease in dopamine depletion, post-cellular treatment. Moreover, histological assessments revealed that the engrafted cells migrated and acted to regenerate the damaged striatal dopaminergic nerve terminal network. In a preliminary work on an animal model for Huntington's disease, we demonstrated by high resolution MR images and correlating histology that induced cells migrated along the internal capsule towards the QA[4]-induced lesion.

Conclusions: The induced MSCs are a potential therapy for neurodegenerative diseases, due both to their NTF secretion and their ability to migrate towards the diseased tissue.

Background: High levels of plasma homocysteine constitute a risk for cardiovascular disease. Physical activity, known to reduce CVD[1] risk, has been related to levels of Hcy[2]. Recently, higher Hcy was shown to be associated with lower cardiovascular fitness in women but not in men.

Objectives: To further explore the relationship between cardiorespiratory fitness and plasma total homocysteine levels in a large cohort of adult males and females.

Methods: This cross-sectional study included 2576 fitness and Hcy examinations in adults (62% males) aged 30–59 years, randomly drawn from a population undergoing a periodic health examination in the Sheba Medical Center's Executive Screening Survey. Blood tests were collected for tHcy[3] and a sub-maximal exercise test was performed to estimate cardiorespiratory fitness. Information on CVD/CVD risk factors (coronary heart disease, cerebrovascular accident, diabetes, hypertension or dyslipidemia) was self-reported.

Results: Mean tHcy plasma levels were 14.4 ± 7.7 and 10.2 ± 3.0 µmol/ml, and mean maximal oxygen uptake 36.5 ± 11.7 and 29 2 ± 9.5 ml/kg/min for males and females, respectively. A multiple regression analysis, adjusting for age, body mass index and CVD/CVD risk factors, showed no association between cardiorespiratory fitness and level of tHcy in males (P = 0.09) or in females (P = 0.62).

Conclusions: In this sample no relationship was found between level of cardiorespiratory fitness and plasma tHcy in men or women. The inconsistency of findings and the small number of studies warrant further research of the association between cardiorespiratory fitness and tHcy, an association that may have clinical implications for the modifications of cardiovascular risk factors.

Background: Locally delivered steroids by inhalers or nebulizers have been shown in small trials to be effective in acute asthma attack, but evidence-based data are insufficient to establish their place as routine management of adult asthma attacks.

Objectives: To determine the efficacy of nebulized compared to systemic steroids in adult asthmatics admitted to the emergency department following an acute attack.

Methods: Adult asthmatics admitted to the ED[1] were assigned in random consecutive case fashion to one of three protocol groups: group 1 – nebulized steroid fluticasone (Flixotide Nebules®), group 2 – intravenous methylprednisolone, group 3 – combined treatment by both routes. Objective and subjective parameters, such as peak expiratory flow, oxygen saturation, heart rate, and dyspnea score, were registered before and 2 hours after ED treatment was initiated. Steroids were continued for 1 week following the ED visit according to the protocol arm. Data on hospital admission/discharge rate, ED readmissions in the week after enrollment and other major events related to asthma were registered.

Results: Altogether, 73 adult asthmatics were assigned to receive treatment: 24 patients in group 1, 23 in group 2 and 26 in group 3. Mean age was 44.4 ± 16.8 years (range 17–75 years). Peak expiratory flow and dyspnea score significantly improved in group 1 patients compared with patients in the other groups after 2 hours of ED treatment (P = 0.021 and 0.009, respectively). The discharge rate after ED treatment was significantly higher in groups 1 and 3 than in group 2 (P = 0.05). All 73 patients were alive a week after enrollment. Five patients (20.8%) in the Flixotide treatment arm were hospitalized and required additional systemic steroids. Multivariate analysis of factors affecting hospitalization rate demonstrated that severity of asthma (odds ratio 8.11) and group 2 (OD[2] 4.17) had a negative effect, whereas adherence to chronic anti-asthma therapy (OD 0.49) reduced the hospitalization rate.

Conclusions: Our study cohort showed the advantage of nebulized steroid fluticasone versus systemic corticosteroids in adult asthmatics managed in the ED following an acute attack. Both these and previous results suggest that nebulized steroids should be used, either alone or in combination with systemic steroids, to treat adults with an acute asthma attack.

Background: In view of the rising prevalence of obesity, the identification of young adult populations at risk is important for the formulation of intervention and prevention programs.

Objectives: To assess demographic and behavioral factors associated with an increase in body mass index in young healthy adults and to identify the incidence of overweight/obesity in this population.

Methods: Data on anthropometric measures, demographic characteristics, and health behaviors were collected retrospectively for a representative sample of young Israeli adults (11,391 men, 11,280 women) on their release from military service (age 20–22 years) between 1989 and 2003. The incidence of overweight (BMI[1] < 25-< 30 kg/m²), incidence of obesity (BMI ≥ 30 kg/m²), and increase in BMI during military service were calculated.

Results: The average increase in BMI during military service was 1.11 kg/m² in males and 1.08 kg/m² in females. A greater increase was positively associated with low paternal education and smoking cessation, and negatively associated with high physical activity. Twelve percent of subjects with a normal BMI on recruitment became overweight, and 21.7% of overweight subjects became obese. On multivariate logistic regression analysis, a higher incidence of overweight was associated with low education level (in both the subject and his or her father) in both genders, and non-use of oral contraceptives and low level of physical activity in females.

Conclusions: BMI appears to increase significantly during early adulthood. Intervention programs should be targeted specifically at subjects with low education or who started smoking before age 18, and physical activity (especially among females) should be encouraged.

Background: The new syndrome, known as PFAPA, of periodic fever characterized by abrupt onset of fever, malaise, aphthous stomatitis, tonsillitis, pharyngitis and cervical adenopathy  has been described only in pediatric patients. It usually begins before the age of 5 years and in most cases resolves spontaneously before age 10. 

Objectives: To describe a series of adults with PFAPA syndrome.

Methods: This 6 year retrospective descriptive study includes all newly diagnosed incident adult cases aged 18 years and over referred to our center with symptomatology suggestive of PFAPA syndrome. Patients’ medical records were reviewed for past history of the disease, demographic characteristics, symptoms and signs, course of the disease, laboratory findings, and outcome following corticosteroid therapy. The comparison group included our pediatric cohort children (N=320, age 0–18 years) followed for the last 14 years (1994–2008).

Results: Fifteen adult patients were diagnosed with PFAPA syndrome. Episodes of fever occurred at 4.6 ± 1.3 week intervals, beginning at the age of 20.9 ± 7.5.  All patients had monthly attacks at the peak of the disease, with attacks recurring at 4–8 week intervals over the years. Between episodes the patients were apparently healthy, without any accompanying diseases. Attacks were aborted by a single 60 mg dose of oral prednisone in all patients.

Conclusions: This study reports the presence of PFAPA syndrome in adult patients. Although the disease is rare, an increased awareness by both patients and family physicians of this clinical syndrome has resulted in more frequent diagnosis in adult patients.
 

Background: Posterior glottic stenosis is a complication of prolonged intubation, manifesting as airway stenosis that may mimic bilateral vocal cord paralysis. It presents a variety of features that mandate specific surgical interventions.

Objectives: To summarize our experience with PSG[1] and its working diagnosis.

Methods: We conducted a retrospective review of a cohort of adult patients with PGS operated at the Sheba Medical Center between 1994 and 2006.

Results: Ten patients were diagnosed with PGS, 6 of whom also had stenosis at other sites of the larynx and trachea. Since 2000, all patients underwent laryngeal electromyographic studies and direct laryngoscopy prior to surgery. Surgical interventions included endoscopic laser procedures (in 2 patients), laryngofissure and scar incision (in 1), laryngofissure with buccal mucosa grafting (in 3) or with costal cartilage grafting (in 1), laryngofissure with posterior cricoid split and stenting (in 1); one patient was not suitable for surgery. Postoperative follow-up included periodical fiberoptic endoscopies. Voice analysis was evaluated by the GRBAS grading. Seven patients were successfully decannulated within one to three procedures. Voice quality was defined as good in 7 patients, serviceable in 2 and aphonic in 1.

Conclusions: Posterior glottic stenosis may be isolated or part of complex laryngotracheal pathologies. Electromyographic studies and direct laryngoscopy must be included in the diagnostic workup. Costal cartilage or buccal mucosa grafts are reliable, safe and successful with respect to graft incorporation and subglottic remodeling.