Israel Medical Association Journal

Background: Overlap syndrome is an entity that satisfies the criteria of at least two connective tissue diseases. These conditions include systemic sclerosis, dermatomyositis or polymyositis, Sjogren's syndrome, rheumatoid arthritis and systemic lupus erythematosus. A combined pathology has impact on the clinical features, diagnosis and treatment.

Objectives: To analyze the features of SSc[1] patients with overlap syndrome registered in the European (EUSTAR) database at our center and to review the literature focusing on clinical and diagnostic issues and new treatments.

Methods: We studied the medical records of 165 consecutive SSc patients and reviewed cases with scleroderma overlap syndrome. Using the key words “overlap syndrome," "systemic sclerosis," “connective tissue disease” and “biological agents” we conducted a PubMed search for the period 1977 to 2009.

Results: Forty patients satisfied the criteria for scleroderma overlap syndrome. The incidence of additional connective tissue diseases in the whole group and in the overlap syndrome group respectively was: dermatomyositis or polymyositis 11.5% and 47.5%, Sjogren's syndrome 10.3% and 42.5%, rheumatoid arthritis 3.6% and 15.4%, and systemic lupus erythematosus 1.2% and 5.0%. Coexistence of SSc and another CTD[2] aggravated the clinical course, especially lung, kidney, digestive, vascular and articular involvement. Non-rheumatic complications mimicked SSc complications. An additional rheumatic or non-rheumatic disease affected treatment choice.

Conclusions: The definition of scleroderma overlap syndrome is important, especially in patients who need high-dose corticosteroids for complications of a CTD. The use of novel biological therapies may be advocated in these patients to avoid the hazardous influences of high-dose steroids, especially renal crisis. In some overlap syndrome cases, biological agents serve both conditions; in others one of the conditions may limit their use. In the absence of formal clinical trials in these patients a cautious approach is preferred.

Background: The rate of brain abnormalities in asymptomatic term neonates varies substantially in previous studies. Some of these rates may justify general screening of healthy newborns by head ultrasound.

Objectives: To assess the incidence of intracranial abnormalities among asymptomatic term newborns with HUS[1] and to detect high-risk populations that might need such screening.

Methods: This was a prospective study in 493 term newborns who underwent HUS and a neurological evaluation during the first 3 days of life. The neurological examination results were unknown to the sonographist and the examiner was blinded to the HUS findings. The abnormal HUS findings were classified as significant or non-significant according to the current literature.

Results: Abnormal HUS was found in 11.2% of the neonates. Significant findings were noted in 3.8% of the infants. There was no association between non-structural HUS findings (hemorrhage or echogenicity) and mode of delivery. There was no relationship between any HUS abnormality and birth weight, head circumference and maternal age, ethnicity, education or morbidity. The rate of abnormal neurological, hearing or vision evaluation in infants with a significant abnormal HUS (5.2%) was comparable to the rate in infants with normal or non-significant findings on HUS (3.1%).

Conclusions: There is no indication for routine HUS screening in apparently healthy term neonates due to the relatively low incidence of significant brain abnormalities in these infants in our population.

Background: In infants, small volume nebulizers with a face mask are commonly used to facilitate aerosol therapy. However, infants may be disturbed by mask application, causing poor mask-to-face seal and thus reducing the dose delivered.

Objectives: To compare lung function response to bronchodilator nebulization via two delivery devices: hood versus mask.

Methods: We studied 26 recurrently wheezy infants aged 45.8 weeks (95% confidence interval 39.6–52.0). Inhalations of 0.30 mg/kg salbutamol were administered in two alliqots 30 minutes apart using mask and hood in alternating order (M+H or H+M). Response to inhalations was measured by maximal expiratory flows at functional residual capacity at 5 minute intervals after each dose, and area under the VmaxFRC[1] curve was documented.

Results: A small but significant response to salbutamol was observed following the second inhalation with VmaxFRC, improving by 31.7% (7.2–56.2, P < 0.02) and AUC[2] by 425 %•min (-154, 1004; P < 0.02). The improvement following salbutamol was similar by both delivery modalities but with a small but significantly better response when H was used after M (P < 0.01).

Conclusions: Nebulized salbutamol induced a variable but positive response in wheezy infants. Salbutamol via hood was as effective as conventional face mask delivery. Since it is simple and patient-friendly, it could replace the face mask method particularly with uncooperative infants.

Background: The term chronic multi-symptom illness refers to a spectrum of pain disorders, such as fibromyalgia and chronic fatigue syndrome, that are characterized by unexplained chronic pain, fatigue, and cognitive and mood complaints

Objectives: To examine the hypothesis that exercise cessation is associated with symptoms similar to CMI[1] in well-trained amateur athletes.

Methods: The study, conducted in running and triathlon clubs in Israel, involved 26 asymptomatic healthy athletes who regularly exercise 6.75 ± 3.65 hours a week. All athletes were instructed to refrain from physical activity for 7 days. All underwent a complete physical exam, rheumatological assessment including non-articular tenderness threshold (using dolorimeter) and tender points. In addition they completed the SF-36 quality of life questionnaire. Assessments were conducted before exercise cessation and 7 days later.

Results: Seven days after sports deprivation all subjects were significantly more tender by all tender measures (P < 0.001) (dolorimeter thresholds and tender point count). There was also a significant reduction in the scores for physical role function (P < 0.001), emotional role function (P < 0.001) and summary subscales of the SF-36 questionnaire after exercise cessation.

Conclusions: Exercise deprivation is associated with change in non-articular tenderness threshold and reduction in quality of life scores. This may be associated with the development of chronic multi-symptom illness.

Background: Concomitant human immunodeficiency virus and human papillomavirus infection increases both HPV[1] persistence and the risk of invasive cervical cancer. An estimation of HPV prevalence among HIV[2]-positive women in Israel would contribute to improving care for this population and preventing morbidity and mortality related to cervical cancer.

Objectives: To determine the prevalence of HPV infection and cervical cytology abnormalities, and to assess the possible influence of HIV infection on HPV carriage in HIV-positive women attending the Infectious Disease Clinic at Soroka University Medical Center.

Methods: The study population included 84 HIV-seropositive women. They were examined by a gynecologist and screened for HPV genotyping, and Pap smears were obtained for cervical cytology. Demographic, behavioral, and HIV infection variables were also recorded and analyzed.

Results: Forty-nine (58.3%) of the study participants were HPV-positive; 34 of them had oncogenic genotypes. Young age (< 16 years) at first sexual intercourse was the only variable significantly associated with HPV infection (P < 0.05). Abnormal cervical cytology was present in 17 women (20.3%); 21 women were referred to colposcopy, which was abnormal in 9 (10.7%).

Conclusions: The prevalence of HPV carriage among HIV-positive woman in our study was slightly higher than published elsewhere. The prevalence of pathological cervical cytology was much higher than in the general population. An extremely high prevalence of pathological colposcopies requiring further treatment was found. Screening for HPV and premalignant changes in the uterine cervix is highly recommended in the HIV-seropositive population. We suggest that colposcopy be considered part of the routine workup in HIV-seropositive woman.

Background: Major advances in the treatment of perinatal asphyxial–hypoxic ischemic encephalopathy followed the translation of hypothermia animal studies into successful randomized controlled clinical trials that substantially influenced the current standard of care.

Objectives: To present our preliminary experience with the first cases of clinical application of therapeutic hypothermia for PA-HIE[1] in what we believe is the first report on non-experimental hypothermia for PA-HIE from Israel.

Methods: We reviewed the medical records, imaging scans, electroencephalograms and outcome data of the six identified asphyxiated newborns who were managed with hypothermia in our services in 2008–2009.

Results: All asphyxiated newborns required resuscitation and were encephalopathic. Systemic hypothermia (33.5ºC) was begun at a median age of 4.2 hours of life (range 2.5–6 hours) and continued for 3 days. All six infants showed a significantly depressed amplitude integrated electroencephalography background, and five had electrographic seizures. One infant died (16%) after 3.5 days. Major complications included fat necrosis and hypercalcemia (n=1), pneumothorax (n=1), and meconium aspiration syndrome (n=2). None of the infants developed major bleeding. Neurodevelopmental follow-up of the five surviving infants at median age 7.2 months (4.1–18.5 months) revealed developmental delays (Battelle screening), with their motor scores ranging from -1 to +1 standard deviation (Bayley scale). None developed feeding problems, oculomotor abnormalities, spasticity or seizures.

Conclusions: Our preliminary experience with this novel modality in a large Tel Aviv neonatal service is consistent with the clinical findings of published trials.

Background: The fish-eating habits of Israelis who present with impacted fish bones in the aerodigestive tract are unknown.

Objectives: To retrospectively investigate the relation between an impacted fish bone in the aerodigestive tract, the species of fish, and the place of occurrence in an Israeli population.

Methods: The current prospective observational study included all patients with aerodigestive impacted fish bones who were treated in our emergency department from 1 September 2008 to 30 September 2009. The data retrieved from their medical records included age, gender, place of event (at home or elsewhere), species of fish, and method of removing the bone.

Results: A total of 108 patients aged 1.5–87 years (median 48 years), 52.8% female, met the study criteria. Most (87%) of the events occurred at home, and 50.9% occurred during the weekend (Friday- Saturday). The bones were from low-priced fish (e.g., carp, hake) in 62% of the cases, high-priced fish (e.g., salmon, red snapper) in 30.5%, and of unknown species in 10.2%. The proportion of cases in which the fish bone belonged to a high-priced fish eaten out of the home was significantly higher than the cases in which a low-priced fish was eaten at home (64.3% vs. 22.3%, P = 0.04). One hundred bones were removed during direct oral inspection and 8 bones were removed under general anesthesia by endoscopy.

Conclusions: Most fish bone impactions in the aerodigestive tract in central Israel involve low-priced fish and take place at home over the weekend.
 

Background: The European Quality of Life 5-Dimensions questionnaire is one of the most commonly used measures of health-related quality of life.

Objectives: To present the feasibility, reliability, and validity of the Hebrew version of the EQ-5D[1].

Methods: We conducted face-to-face interviews with a representative sample (n=1666) of the Israeli Jewish population. The data collected included demographic and medical information, and self-valuation of health using the EQ-5D descriptive system, Visual Analogue Scale and Time Trade-Off. Construct validity was assessed by assuming that older individuals, those with a greater burden of diseases, and those reporting experience with their own severe illness would have lower EQ-5D indexes, VAS[2] and TTO[3] values. Test-retest reliability was assessed in a small sample (n=50) that was reevaluated after a 3 week interval.

Results: Test-retest reliability of the EQ-5D and VAS was very high (r ≥ 0.85). Reliability of the TTO was moderate (r = 0.48). There were significant differences in the EQ-5D index, profiles, VAS and TTO between healthy and sick respondents and younger and older respondents, indicating good validity of the instrument.

Conclusions: The Hebrew translation of the EQ-5D is a practical, reliable and valid instrument for assessing the health-related quality of life of the general Israeli Jewish population.

Background: Traditionally, medication dosage was based on clinical and demographic parameters, but drug metabolism was recently recognized as an important factor for proper dosing and prediction of side effects. Metabolic considerations are crucial when administering drugs with a narrow therapeutic index, such as those of the thioguanides family (azathioprine and 6-MP). These can cause life-threatening myelosuppression due to low activity of a critical metabolic enzyme, thiopurine S-methyl transferase. A number of single nucleotide substitutions encoding variant enzymes account for most enzyme deficiencies.

Objectives: To determine the frequency of individuals from different Israeli ethnic groups who may be at risk for drug toxicity from drugs of the thioguanide family due to enzymatic variants.

Methods: DNA analysis was performed using polymerase chain reaction methods. We tested TPMT[1] allelic variants TPMT*3A (G460A, A719G), TPMT*3B (G460A) and TPMT*3C (A719G) in five subpopulations in Israel: mixed-origin Israeli Jews, Arabs, Druze, Jews of Kurdish extraction, and Ethiopian Jews.

Results: The Druze (P = 0.0002) and Ethiopian Jewish (P = 0.015) subpopulations had a significantly unique distribution of allelic variants compared to the rest of the Israeli population. The Druze subpopulation showed a high number of TPMT variants with decreased activity, and a homozygote for TPMT*3A/ *3A was detected.  Ethiopian Jews were found to carry mainly the TPMT*3C variant, also observed in other studies of African populations.

Conclusions: It is advisable that Druze patients be tested for the TPMT enzyme before starting treatment with 6-MP or azathioprine. Such testing may also be considered for other Israeli ethnic subgroups.

Background: Gastric cancer continues to be a leading cause of cancer death. The treatment approach varies, and preoperative staging is therefore crucial since an exploratory laparotomy for unresectable gastric cancer will be followed by an unacceptably high morbidity and mortality rate.

Objectives: To assess the added value of diagnostic laparoscopy to conventional methods of diagnosis such as computed tomography in avoiding unnecessary laparotomies.

Methods: A retrospective study on 78 patients scheduled for curative gastrectomy based on CT staging was conducted. DL[1] was performed prior to exploratory laparotomy.

Results: In 23 of 78 patients (29.5%), unexpected peritoneal spread not detected on preoperative CT was found. Fifty-five patients underwent radical gastrectomy, 15 patients were referred for downstaging and 8 patients underwent a palliative procedure.

Conclusions: Based on our results, DL should be considered in all gastric cancer patients scheduled for curative gastrectomy.

Background: Familial dysautonomia is a hereditary disease characterized by dysfunction of the sensory and autonomic nervous systems. Studies in patients with familial dysautonomia have shown that abnormal cardiac autonomic denervation might influence repolarization. Autonomic tone also affects atrial conduction parameters and P-wave dispersion, which are predictive of atrial fibrillation.

Objectives: To examine the possible association of familial dysautonomia with abnormal atrial conduction and P-wave dispersion.

Methods: The study population included 12 patients with familial dysautonomia and age and sex-matched control subjects. All participants underwent a 12-lead electrocardiogram under strict conditions. P-wave lengths and P-wave dispersion were computed from a randomly selected beat and an averaged beat using designated computer software.

Results: There were no statistically significant differences between the groups in minimal, maximal, and average P-wave duration or P-wave dispersion for a randomly selected beat. P-wave dispersion for an averaged beat was also similar. During 6 months follow-up, no supraventricular arrhythmias were documented in either group.

Conclusions: We found that patients with familial dysautonomia had P-wave dispersion parameters not significantly different from those of controls. Further research is required to clarify the effects of dysautonomia on atrial conduction in familial dysautonomia.