Israel Medical Association Journal

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: Severe hearing impairment can have devastating effects on social integration and vocational opportunities.

Objectives: To investigate how well – or poorly – individuals who underwent cochlear implantation as children integrated into the general Israeli hearing community.

Method: We sent a questionnaire to the 30 subjects ≥ 18 years old who underwent cochlear implants our department from 1990 to 2004 when they were < 18 years of age and had used their device for at least 3 years before replying.

Results: Eighteen implant users responded (14 males), yielding a 60% response rate. Their mean age was 13.3 ± 7.0 years (range 6–17) at implantation and 21.1 ± 3.6 years (range 18–34) when they filled in the questionnaire. Five were attending rabbinical school (yeshiva students), four were in regular military service, five were university students (three also held jobs), two were attending high school, one was employed (and had a university degree), and one had left the yeshiva and was unemployed when he returned the questionnaire. Fourteen respondents use the oral communication mode for conversation and the other 4 use both oral and sign languages. Longer daily implant use was significantly associated with coping with the difficulties in the setting in which they were currently active, with a higher level of satisfaction with their current lifestyle and with recognition of the implant’s contribution to this satisfaction (P = 0.037, P = 0.019 and P = 0.001, respectively).

Conclusions: Advances in cochlear implant technologies enable profoundly deaf implanted children to integrate well into the Israeli hearing society, albeit with a large inter-subject variability.

Background: Aural cholesteatoma is an epidermal cyst of the middle ear or mastoid that can only be eradicated by surgical resection. It is usually managed with radical or modified radical mastoidectomy. Clinical diagnosis of recurrent cholesteatoma in a closed postoperative cavity is difficult. Thus, the accepted protocol in most otologic centers for suspected recurrence consists of second-look procedures performed approximately 1 year after the initial surgery. Brain herniation into a post-mastoidectomy cavity is not rare and can be radiologically confused with cholesteatoma on the high resolution computed tomographic images of temporal bones that are carried out before second-look surgery.

Objectives: To present our experience with meningoceles that were confused with recurrent disease in patients who had undergone primary mastoidectomy for cholesteatoma and to support the use of magnetic resonance imaging as more suitable than CT in postoperative follow-up protocols for cholesteatoma.

Methods: We conducted a retrospective chart review of four patients.

Results: Axial CT sections demonstrated a soft tissue mass in the middle ear and mastoid in all four patients. Coronal reconstructions of CT scans showed a tympanic tegmen defect in two patients. CT failed to exclude cholesteatoma in any patient. Each underwent a second-look mastoidectomy and the only finding at surgery was meningocele in all four patients.

Conclusions: Echo-planar diffusion-weighted MRI can differentiate between brain tissue and cholesteatoma more accurately than CT. We recommend that otolaryngologists avoid unnecessary revision procedures by using the newest imaging modalities for more precise diagnosis of the patients who had undergone mastoidectomy for cholesteatoma in the past.
 

Background: Infections with blood-borne viruses are a major health problem among illicit drug users. There is little information about infection rates and risk factors for hepatitis virus B, C or the human immunodeficiency virus in drug users in Israel.

Objectives: To determine the prevalence of HCV[1], HBV[2] and HIV[3] infections in a large cohort of drug users in Israel; to compare rates of HCV, HBV and HIV between injecting versus non-injecting drug users and between different origin countries; and to identify risk factors for HCV among illicit drug users.

Methods: We conducted a cross-sectional interviewer-administered questionnaire and serological screening for HCV, HBV and HIV in 1443 consecutive drug users diagnosed at the Israeli National Center for Diagnosis of Drug Addicts between January 2003 and December 2005.

Results: Fourteen (0.9%), 51 (3.5%) and 515 (35.7%) subjects tested positive for HIV, HBV and HCV, respectively. All three infections (HIV, HBV and HCV) were significantly more common among injecting drug users and immigrants from the former Soviet Union and other East European countries compared to native Israelis. Multivariate analysis showed that HCV infection was associated with age (> 40 years) (OR=2.06, 95% CI 1.40–3.03), immigration from East European countries and the former Soviet Union (OR=4.54, 95% CI 3.28–6.28), and injecting drug use (OR=16.44, 95% CI 10.79–25.05).

Conclusions: HIV, HBV and HCV prevalence among drug users in Israel is significantly lower than in North America and West Europe. Risk factors for HCV infection in this population include injecting drug use, older age, and immigration from the former Soviet Union.

Background: Ocular hypotony is a common unexplained feature of myotonic dystrophy type 1. Spuriously low applanation tonometric readings can be caused by thin corneas, flat corneal curvature and corneal edema.

Objectives: To determine whether structure abnormalities of the cornea cause spuriously low readings in applanation tonometry.

Methods: We utilized a TMS-2N corneal topographer, a NonconRobo SP-6000 Specular microscope and a Corneo-Gage Plus 1A Pachymeter to examine seven patients with DM1[1] and eight healthy controls. Intraocular pressure, central corneal thickness, and endothelial cell density were measured, and simulated keratometry readings were made. Cornea guttata and irregularity of corneal topography patterns were also sought.

Results: The mean intraocular pressure was 9.86 ± 1.29 mmHg for all patients (intraocular operated and non‑operated eyes) and 12.88 ± 1.89 mmHg for the controls (P = 0.000021, two-tailed t-test). Central corneal thickness was 530.57 ± 35.30 micron for all patients and 535.00 ± 39.62 micron for the controls (P = 0.75, two-tailed t-test). Endothelial cell density was 3164 ± 761 cells/mm² for all patients and 3148 ± 395 cells/mm² for the controls (P = 0.94, two-tailed t-test). Simulated keratometry readings were similar in both groups when the operated eyes were excluded. Cornea guttata and irregularity of corneal topography patterns were also noted in the study group.

Conclusions: Corneal thickness, corneal curvature and corneal hydration were within normal limits and thus were not the cause for the low applanation tonometry reading in DM1. The presence of cornea guttata and irregularity of corneal topography patterns in DM1 warrants further investigation. 

Background: Seasickness is thought to result from conflicting inputs from the vestibular, visual and somatosensory systems. The otolithic organs, which are responsible for the sensation of linear acceleration and tilt, are important in the pathogenesis of seasickness. Vestibular evoked myogenic potentials test is an objective evaluation of saccular function.

Objective: To examine whether saccular function is related to the pathogenesis of seasickness.

Methods: VEMP1 was performed in 10 subjects susceptible to seasickness and in 14 non-susceptible subjects.

Results: Bilateral VEMP responses were obtained in 7 (50%) of the non-susceptible subjects and 1 (10%) of the susceptible subjects. No differences were found between the groups in P13 and N23 wave latencies, amplitudes, N13-P23 inter-peak latencies, and peak-to-peak asymmetry ratios. More subjects in the susceptible group had asymmetry ratios > 35%.   

Conclusions: The attenuated saccular response might be explained in the context of the neural-mismatch theory and/or the subjective vertical theory, as reflecting an adaptation effort to sea conditions. A larger study is necessary to determine whether a statistically significant difference in VEMP responses exists between seasickness-susceptible and non-susceptible subjects.
 

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.