Israel Medical Association Journal

Background: Thyroid-associated ophthalmopathy (TAO) is an inflammatory disease that affects the thyroid gland and the eye orbit. Of patients with TAO, 3%–5% have severe sight-threatening disease due to optic neuropathy Optical coherence tomography (OCT), the non-invasive imaging technology that yields high-resolution cross-sectional images of the retina, provides qualitative and quantitative data on the retina.

Objectives: To apply this technique to quantitatively assess retinal nerve fiber layer (RNFL) and macular ring thicknesses in healthy subjects and in patients with TAO to determine their relationship to the severity of the orbital disease.

Methods: All patients in the ophthalmology clinic who were diagnosed with TAO and underwent OCT imaging as part of their ocular examination comprised the study group, and healthy patients who volunteered to undergo OCT examination served as controls. Results of the complete ophthalmologic examination and OCT findings were collected from medical files, including the thickness of the RNFL and the macula.

Results: The study comprised 21 patients and 41 healthy controls. TAO patients exhibited RNFL thickening and inner macula thinning compared to healthy subjects. Mean RNFL thickness was correlated with the severity of the orbital disease.

Conclusion: The OCT findings suggest that the retina is involved in TAO, probably as early as the subclinical stage. This highlights the ability of OCT to identify retinal changes earlier and far more accurately than is detected today, enabling earlier diagnosis and more timely treatment to prevent severe visual sequelae.

Background: Early prenatal ultrasound is an important part of prenatal screening in Israel. No studies have described the rate of trisomy 21 [T21] identification at 14–17 weeks gestation.

Objectives: To describe the rate of T21 identification by transvaginal sonograms (TVS) at 14–17 weeks gestation. 

Methods: We conducted a historical prospective study. Since 1986, early TVS of 72,000 fetuses at 14–17 weeks gestation have been prospectively recorded together with prenatal screening data at a private ultrasound center (AL-KOL, Haifa). We calculated the fraction of T21 cases by dividing the total number of cases with abnormal sonographic findings by the total number of diagnosed T21 cases. We also examined the percentage of verified T21 cases that had completely normal prenatal screening tests prior to the early prenatal TVS, thus revealing the contribution of this examination to the existing prenatal screening. Fisher’s exact test was used to calculate odds ratios for each sonographic marker. 

Results: Of 137 T21 fetuses, 123 had sonographic markers on early TVS, yielding a prediction capability of at least 89.87%. Of all T21 cases, 14% had completely normal nuchal translucency/first-trimester screening prior to the abnormal 14–17 week TVS findings. Isolated abnormal sonographic findings, which were found to increase the risk for T21, were common atrioventricular septal canal (odds ratio 88.88), duodenal atresia (OR 88.23), nuchal edema (OR 39.14), and hydrocephalus (OR 15.78). Fetal hydronephrosis/pyelectasis was non-significant when isolated (OR 1), and cardiac echogenic focus was associated with a decreased risk (OR 0.13).

Conclusions: Early prenatal TVS at 14–17 weeks may identify almost 90% of T21 and adds 14% to the identification rate at the first-trimester screening.

 

Background: Orofacial clefts are the most common craniofacial congenital malformations, with significant anatomic, ethnical, racial and gender differences.

Objectives: To investigate the prevalence, distribution and characteristic features of various types of non-syndromic clefts among Israeli Jews and Arabs.

Methods: We conducted a retrospective multi-center survey in 13 major hospitals in Israel for the period 1993–2005. To obtain the true prevalence and detailed clinical characteristics, data on liveborn infants with non-syndromic clefts were obtained from the Ministry of Health's National Birth Defect Registry and completed by chart reviews in the 13 surveyed hospitals.

Conclusions: The prevalence of non-syndromic clefts was 7.00/10,000 live births. The markedly higher rate in Arabs is related to the high rate of consanguinity. Both very young and old maternal age represents a higher risk of clefts in their offspring. 

Objectives: To describe the phenotypic and genotypic features in five Bulgarian Jewish patients, from different families, with autosomal dominant OPMD.

Methods: We performed clinical follow-up, electrodiagnostic tests and mutation detection. Blood samples were obtained after informed consent and DNA was extracted; measurement of GCG repeats in both PABPN1 alleles and sequencing of OPMD mutations were performed according to standard techniques.

Results: We identified five patients (four females), aged 58 to 71 years, with bilateral ptosis, dysphagia, dysphonia (n=3) and myopathic motor units by electromyography. In all patients we noticed proximal weakness of the upper limbs with winging scapulae in three of them. All cases shared the (GCG)13-(GCG)10 PABPN1 genotype.

Conclusions: OPMD among Bulgarian Jews is produced by a (GCG)13 expansion, identical to the mutation in Uzbek Jews and French Canadians. In addition to the classical neurological and neuro-ophthalmological features, early shoulder girdle weakness is common in Bulgarian Jewish patients; this is an unusual feature during the early stages of OPMD produced by the same mutation in other populations. We suggest that besides the disease-producing GCG expansion, additional ethnicity-related genetic factors may influence the OPMD phenotype. OPMD is a rare disease, and the identification of five affected families in the rather small Bulgarian Jewish community in Israel probably represents a new cluster; future haplotype studies may elucidate whether a founder effect occurred. 

Background: Hypovitaminosis D is common worldwide, even in sunny regions.

Objectives: To assess the prevalence and determinants of vitamin D deficiency in toddlers.

Methods: A cross-sectional prospective study was conducted in healthy Jewish children aged 1.5–6 years at five primary care pediatric clinics in the Jerusalem area during the period October 2009 to November 2010. Parents were interviewed regarding personal and demographic data and sun exposure. Blood samples were obtained for serum 25-hydroxyvitamin D [25-OHD] level. Vitamin D deficiency and insufficiency were defined as 25-OHD < 20 ng/ml and < 30 ng/ml, respectively.

Results: Of 247 children studied, 188 (76%) were ultra-Orthodox and 59 (24%) were Orthodox, traditional or secular. Mean (± SD) 25-OHD level was 25.7 ± 10 ng/ml. Only 73 children (29.6%) had sufficient 25-OHD levels, 104 (42.1%) had insufficiency, and 70 (28.3%) had 25-OHD deficiency. The difference between ultra-Orthodox and others was insignificant (25 ± 10 vs. 27.8 ± 10.5 ng/ml respectively, P = 0.062). Children aged 1.5–3 years had higher 25-OHD levels than those aged 3–6 years (28.6 ± 10.7 and 24 ± 9.2 ng/ml respectively, P < 0.001). Vitamin D deficiency was more common in winter (53%) and autumn (36%) than in summer (19%) and spring (16%). Toddlers attending long-day kindergartens had higher 25-OHD level than those staying at home or at short-day kindergartens (28.8 ± 11.5 and 24.7 ± 9.6 ng/ml respectively, P < 0.05).

Conclusions: A high prevalence of vitamin D deficiency was found in toddlers in our study, mainly in older children and in the winter and autumn. We recommend routine supplementation of vitamin D for children beyond the agear.

Objectives: To determine the profile of unsaturated fatty acids in the breast milk of two populations in southern Israel, Jewish and rural tent-dwelling Bedouin women.

Methods: This study involved 48 lactating Israeli mothers, 29 Jewish and 19 Bedouin (16–20 weeks postpartum), whose full-term infants were fed exclusively with breast milk. Total milk lipid extracts were transmethylated and analyzed by using an improved gas chromatographic method.

Results: The breast milk of the Bedouin women contained significantly higher levels of total major saturated fatty acids, lauric acid and palmitic acid (45.2 ± 4.7% vs. 41.0 ± 5.6%, P = 0.005; 5.2 ± 2.1 vs. 6.8 ± 2.0%, P = 0.03; and 22.7 ± 2.4 vs. 20.6 ± 3.8%, P = 0.02) respectively. No difference was found in the myristic acid level between the groups. The level of stearic acid was significantly higher in the Jewish group compared to the Bedouin group (5.7 ± 1.1 vs. 5.1 ± 1.1%, P = 0.04). There was a linear correlation between the levels of C14:0 and C12:0 in the Bedouin and Jewish groups respectively (R = 0.87, R = 0.82, P < 0.001).

Conclusions: Higher levels of saturated fatty acids were measured in the breast milk of Bedouin women, an economically weaker population. The results emphasize the importance of diet among lactating women and its influence on milk quality. 

Background: Fatigue is a common complaint in primary care and has a broad differential diagnosis, making the approach complex and often ineffective.

Objectives: To follow the course of adults without a significant known background disease who complain of fatigue for the first time, and to characterize the family physician’s approach.

Methods: The study population comprised a random sample of 299 patients aged 18–45 who presented with fatigue as a first-time single complaint to their family physician. Excluded were patients with chronic diseases or states that may include signs of fatigue. We analyzed the index encounter data, the diagnostic and laboratory tests, the medications prescribed and the one year clinical outcome.

Results: Seventy percent were women, average age 30.5 years, and 69% had no known co-morbidities; 57% of the patients were physically examined at the first visit and most (78.6%) were sent for laboratory analysis. Five percent of laboratory tests were positive. Eighty patients (26.8%) were given a specific diagnosis, with the leading diagnoses being anemia and infectious diseases; 18.7% were given sick leave at the first visit. Fatigue was more common in early summer.

Conclusions: The majority of young healthy patients complaining of fatigue are not diagnosed with an organic physiological disorder. Many of the study patients were sent for laboratory tests but in most cases these tests were not contributory to the diagnosis or management. It seems likely that the most efficient strategy would be watchful follow-up with a minimum of testing.

Background: The "obesity paradox" is defined as an inverse association of good health, survival and obesity. Usually in healthy persons the more obese you are the more metabolic complications you have; however, thin patients with chronic obstructive pulmonary disease (COPD) have more cardiovascular complications and a higher mortality rate.

Objectives: To explore whether atherosclerosis and peripheral artery disease (PAD) contribute to the higher morbidity and mortality of patients with COPD.

Methods: This prospective study included 87 patients with chronic COPD who were treated in the pulmonary outpatient clinic; all signed a consent form before enrollment. We documented their lung function (FEV1%), body mass index (BMI) and ankle brachial index (ABI). The primary endpoints were to find an association between atherosclerosis and BMI in patients with COPD, and between atherosclerosis and severity of lung disease.

Results: Average ABI[1] was 1.01 ± 0.20, BMI[2] was 29.33 ± 7.48 kg/m2, and the abdominal circumference was 107.34 ± 18.87 cm. A positive correlation was found between BMI and ABI (P = 0.001) and between abdominal circumference and ABI (P = 0.000). Patients with peripheral artery disease were older (73.6 ± 11.5 vs. 68.1 ± 11.6 years old, P = 0.04), were thinner (average BMI 25.5 ± 6.2 vs. 31.06 ± 7.3, P = 0.001), and had a lower abdominal circumference (97.7 ± 18.3 vs. 111.7 ± 17.5 cm, P = 0.001). No such difference was observed for years of smoking. Male PAD patients with COPD had a lower BMI (25.2 ± 5.6 vs. 29.9 ± 7.4, P = 0.016), and their abdominal circumference was smaller (96.1 ± 18.0 vs. 110.2 ± 16.5 cm, P = 0.004). Female PAD patients with COPD had a lower BMI (26.3 ± 8.2 vs. 33.1 ± 7.0, P = 0.045), but their abdominal circumference was not different from females without PAD (102.0 ± 19.7 vs. 114.0 ± 19.4 cm, P = 0.162). Patients with PAD had a worse lung disease (FEV1% 34 ± 8% vs. 45 ± 16%, P = 0.01). During the 1 year of follow-up five patients died: two PAD patients due to acute myocardial infarction and three non-PAD patients died from pulmonary insufficiency (two patients) and pulmonary emboli (one patient).

Discussion: We found that COPD patients with PAD were older and thinner and had a lower abdominal circumference and a more progressive lung disease. Extensive atherosclerosis in patients with COPD may partly explain the “obesity paradox” observed in patients with COPD.