Israel Medical Association Journal

Background: The forced oscillation technique is a non-invasive and effort-independent technique and is well suited for lung function measurement in young children. FOT[1] employs small-amplitude pressure oscillations superimposed on normal breathing. Therefore, it has the advantage over conventional lung function techniques in that it does not require patient cooperation for conducting respiratory maneuvers.

Objectives: To test the feasibility of the FOT test in preschool children and to compare the results to the commonly used spirometry before and after the administration of bronchodilator therapy.

Methods: Forty-six children (median age 4.9 years, range 1.8–18.3) attending the Pulmonary Clinic at Schneider Children's Medical Center tried to perform FOT and routine spirometry. Results were retrospectively analyzed. 

Results: Of the 46 children 40 succeeded in performing FOT and only 29 succeeded in performing simple spirometry. All but one of the 32 children aged 4 years and above (97%) could perform both tests. Nine of 14 children (64%) aged 4 and less could perform the FOT but only 3 (21%) could perform spirometry. Baseline values of respiratory resistance measured at 6 Hz (R6) negatively correlated with body length (r² = 0.68, P < 0.005). Twenty-four children performed both tests before and after bronchodilator therapy. A significant concordance was found between the measured responses to bronchodilators by FOT and spirometry (P < 0.01). Only one child had a negative response by FOT but a positive response by spirometry.

Conclusions: The FOT is a simple, non-invasive technique that does not require subject cooperation and thus can be utilized for measuring lung function in children as young as 2 years of age. Furthermore, the FOT was shown to reliably measure response to bronchodilator therapy.

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.

Mesenchymal stem cells, or mesenchymal stromal cells, have emerged as a major new cell technology with a diverse spectrum of potential clinical applications. MSCs[1] were originally conceived as stem/progenitor cells to rebuild diseased or damaged tissues. Over the last 14 years, since the first report of MSC infusions in patients, the cells have been shown to suppress graft vs. host disease, stimulate linear growth in a genetic disorder of bone, and foster engraftment of haplo-identical hematopoietic stem cells. In all cases, few, if any, MSCs were identified at the site of clinical activity. This experience suggests a remarkable clinical potential, but a different general mechanism of action. Systemically infused MSCs seem to exert a therapeutic effect effect through the release of cytokines that act on local, or perhaps distant, target tissues. Rather than serving as stem cells to repair tissues, they serve as cellular factories that secrete mediators to stimulate the repair of tissues or other beneficial effects. Since both the tissue source of MSCs and the ex vivo expansion system may significantly impact the cytokine expression profile, these parameters may be critically important determinants of clinical activity. Furthermore, cell processing protocols may be developed to optimize the cell product for a specific clinical indication. For example, MSC-like cells isolated from placenta and expanded in a three-dimensional bioreactor have recently been shown to increase blood flow in critical limb ischemia. Future efforts to understand the cytokine expression profile will undoubtedly expand the range of MSC clinical applications.

The incidence of aortic valve stenosis is growing rapidly in the elderly. Nonetheless, many symptomatic patients are not referred for surgery usually because of high surgical risk. Unfortunately, percutaneous balloon valvuloplasty is unsatisfactory due to high recurrence rates. In 2002, Cribier and colleagues were the first to describe percutaneous aortic valve implantation, opening a new era of aortic stenosis management. In the present review we report a patient treated by this novel method, discuss and assess how it is implanated, report the findings of studies conducted to date, and suggest future directions for percutaneous treatment of aortic valve disease.
 

Background: Early-onset neonatal sepsis is a major cause of morbidity and mortality among newborn infants.

Objectives: To determine the incidence, type of pathogens and resistance to antibiotics among newborns with early-onset neonatal sepsis, and to identify the risk factors predisposing infants to resistant pathogens in order to reevaluate antibiotic regimens appropriate for resistant bacteria in these high risk neonates.

Methods: We retrospectively studied maternal and neonatal variables of 73 term and near-term infants and 30 preterm infants, born over a period of 10.5 years and exhibiting early-onset neonatal sepsis (positive blood cultures in the first 72 hours of life).

Results: Predominant pathogens in term and near-term infants were gram-positive compared with gram-negative organisms (mostly Escherichia coli) in preterm infants. Mothers of infants with antibiotic-resistant organisms were more likely to have prolonged rupture of membranes and prolonged hospitalization before delivery and to be treated with antibiotics. No trends towards more resistant strains of pathogens were recorded over the 10.5 years of the study period.

Conclusions: Early-onset neonatal sepsis in term infants differs in bacterial species from that in preterm infants, with predominantly gram-positive organisms in term and near-term infants and gram-negative organisms in preterms. Rates of bacterial resistance to the combination of ampicillin and gentamicin, though higher among infants born to mothers with prolonged hospitalization who had been treated with antibiotics, still remained very low in our department. Thus, it seems that our classic antibiotic regimen is still appropriate for both term and preterm newborns.
 

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: West Nile virus, the etiologic agent of West Nile fever, is an emerging mosquito-borne disease. WNV[1] was recognized as a cause of severe human meningo-encephalitis in elderly patients during outbreaks in various parts of the world.

Objectives: To analyze WNV encephalitis therapy and its outcome after prescribing hyperimmune gammaglobulin therapy.

Methods: Eight subjects with WNV encephalitis were treated with supportive therapy and 5 days of IVIG[2] 0.4 g/kg/day containing high WNV antibodies obtained from healthy blood donors.

Results: Patients who were treated with IVIG as soon as possible exhibited an improvement in their symptoms. All subjects presented with high fever, progressive confusion and headaches, nausea and vomining. The Glasgow Coma Screen for six patients ranged between 8 and 13 and all were discharged with a score of 15. The remaining two subjects died during their hospitalization.

Conclusions: In severe WNV infection, where the disease affects the central and/or peripheral nervous system, early intervention with IVIG together with supportive treatment is recommended.

Background: Although unprotected left main coronary artery disease is considered by contemporary guidelines to be an indication for surgery, percutaneous coronary intervention may be necessary in patients at high surgical risk.

Objectives: To assess the outcome of angioplasty in the treatment of unprotected LMCA[1] disease.

Methods: Angiographic and clinical data were collected prospectively for all patients who underwent emergent or non-emergent (planned) therapeutic PCI[2] for unprotected LMCA disease at our center from 2003 to 2007. Baseline values were compared with findings at 1, 6 and 12 months after the procedure.

Results: The study group comprised 71 consecutive patients with a mean age of 74 ± 12 years; 63% were men, and 31% had diabetes. Forty-three patients had a planned procedure and 28 an emergent procedure. Mean EuroScore was 7.3 ± 3.6 (range 5–12). Forty-nine percent of the procedures were performed with bare metal stents and 51% with drug-eluting stents. Procedural success was achieved in 100% of cases. The overall mortality rate was 11.3% at 1 month, 18.3% at 6 months and 19.7% at 12 months. Elective PCI was associated with significantly lower mortality (2.3% vs. 25% at 1 month, 4.6% vs. 39% at 6 months and 6.9% vs. 39% at 12 months), and the use of drug-eluting stents was associated with lower rates of target vessel revascularization and major adverse cardiac events than use of bare metal stents (2.8% vs. 14% at 1 month, 8.3% vs. 43% at 6 and 12 months). Variables that correlated with increased mortality or MACE[3] at 6 and 12 months were cardiogenic shock, emergent PCI, ejection fraction < 35%, renal failure, distal left main stenosis location, and reference diameter < 3 mm.

Conclusions: PCI is a feasible and relatively safe therapeutic option for unprotected LMCA. The less favorable outcome of emergent compared to planned PCI is probably attributable to the overwhelming acute myocardial ischemic injury in emergent cases. The use of drug-eluting stents may improve the intermediate-term restenosis rate.

[1] LMCA = left main coronary artery

[2] PCI = percutaneous coronary intervention

Background: Uncorrected refractive error is the leading cause of visual impairment in children. In 2002 a screening project was launched in Israel to provide data on the effectiveness of the illiterate E-chart in identifying Jewish and Arab schoolchildren in need of a comprehensive eye examination.

Objectives: To present the aims, design and initial results of the visual screening project and the prevalence of vision abnormality in the study population.

Methods: A cross-sectional population-based study was conducted during 2002–2003 among first- and eighth-graders in 70 schools in northern Israel. The nurse's test included use of the illiterate E-chart to measure visual acuity. The medical examination included vision history, clinical eye examination, VA[1] and retinoscopy. The ophthalmologist's evaluation as to whether a child needed a referral for diagnostic procedures, treatment and/or follow-up was recorded and compared with explicit referral criteria formulated after data collection.

Results: Of 1975 schoolchildren, 31% had abnormal VA, defined as VA worse than 6/6 in at least one eye, and a quarter had VA equal or worse than 6/12 in both eyes. The prevalence of vision abnormality among the children was 22.4% when based on the evaluation of the field ophthalmologist and 26.1% when based on two sets of explicit severity scores and referral criteria.

Conclusions: Vision abnormality is a significant health problem among northern Israeli schoolchildren. This project is unique in scope and importance, providing evidence to assist policy making with regard to vision screening for schoolchildren (including data on test reliability and validity) and optimal VA cutoff level, and confirming the need for clinical guidelines regarding referral criteria.

Background: The role of endoscopic ultrasound in evaluating the response of esophageal cancer to neoadjuvant chemotherapy is controversial.

Objectives: To evaluate the accuracy of EUS[1] in restaging patients who underwent NAC[2].

Methods: The disease stage of patients with esophageal cancer was established by means of the TNM classification system. The initial staging was determined by chest and abdominal computed tomography and EUS. Patients who needed NAC underwent a preoperative regimen consisting of cisplatin and fluouracil. Upon completion of the chemotherapy, patients were restaged and then underwent esophagectomy. The results of the EUS staging were compared with the results of the surgical pathology staging. This comparison was done in two groups of patients: the study group (all patients who received NAC) and the control group (all patients who underwent primary esophagectomy without NAC).

Results: NAC was conducted in 20 patients with initial stage IIB and III carcinoma of the esophagus (study group). Post-chemotherapy EUS accurately predicted the surgical pathology stage in 6 patients (30%). Pathological down-staging was noted in 8 patients (40%). However, the EUS was able to observe it in only 2 patients (25%). The accuracy of EUS in determining the T status alone was 80%. The accuracy for N status alone was 35%. In 65% of examinations the EUS either overestimated (35%) or underestimated (30%) the N status. Thirteen patients with initial stage I-IIA underwent primary esophagectomy after the initial staging (control group). EUS accurately predicted the surgical pathology disease stage in 11 patients (85%).

Conclusions: EUS is an accurate modality for initial staging of esophageal carcinoma. However, it is not a reliable tool for restaging esophageal cancer after NAC and it cannot predict response to chemotherapy.