Israel Medical Association Journal

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: Skin basal and squamous cell carcinomas together account for over half of all newly diagnosed cancer cases. Frozen  section control of surgical margins is often required in the head and neck region. A paraffin permanent section does not always confirm the results of a frozen section.

Objectives: To test the diagnostic accuracy of frozen section histopathological analysis in determining the free margins of excised tumors.

Methods: This was a retrospective study of 169 cutaneous basal and squamous cell carcinomas excised with surgical margins diagnosed by frozen section and confirmed by permanent paraffin sections. The data included patients' age, gender, clinical and histopathological diagnosis, as well as characteristics of the lesions.

Results: There were 149 (88%) basal cell carcinomas and 20 (12%) squamous cell carcinomas. False negative margins were found in 19 cases (11.2%) and false positive margins in 11 cases (6.6%). We did not find any correlation between false positive or false negative margins and patients' age, gender, tumor size, tumor location, or the presence of sun-damaged skin. A significantly lower rate of false negative results was found in the residual tumor group.

Conclusions: Our findings show support the use of frozen section margin control in selected patients suffering from non-melanoma skin cancer of the head and neck.
 

Stem cell research offers great hope to patients suffering from neuronal damage. Stem cell-based regenerative medicine holds huge potential to provide a true cure for patients affected by a neurodegenerative disease or who have suffered a stroke.

Progressive neurodegenerative disorders share common mechanisms of cell death, and in all likelihood multiple factors are involved in every disease. Therefore, several neuroprotective agents are being investigated with the purpose of slowing or preventing further deterioration of cell loss. These include experimental animal and clinical studies on the neuroprotective effects of caspase inhibitors, antioxitands, glutamate antagonists, anti-inflammatory agents and trophic factors in several neurodegenerative diseases. At present there is limited clinical evidence for direct neuroprotective effects against these diseases, but much effort is being invested in research on novel technologies and compounds.

Background: Some studies have indicated a possible link between cigarette smoking and hearing loss.

Objectives: To analyze the association between smoking and hearing loss, other than that induced by noise, and to characterize the type of HL impairment found in smokers.

Methods: We conducted a retrospective cross-sectional study in 13,308 men aged 20±68 (median 34.6 years) who underwent a hearing test as part of a routine periodic examination. For each subject, age, smoking status (current, past or non-smokers) and number of cigarettes per day were noted and a hearing test was performed. The test was performed in a sealed, soundproof room by an experienced audiologist and included pure tone audiometry of 250±8,000 Hz. The audiograms were analyzed and subjects were accordingly divided into two groups: those with HL and at least one of the following impairments in at least one ear: sensorineural, conductive or mixed; and those with no hearing loss (control). Audiograms showing HL typical to noise exposure were excluded.

Results: The prevalence of any type of HL among subjects <35 years was 4.5%, compared to 10.5% among those >35 years (P < 0.0001). A significantly higher incidence of any type of HL was found in current (11.8%) and past smokers (11.7%) than in non-smokers (8.1%) (P < 0.0001). The risk increment of the smoking status for developing HL among subjects under age 35 was 43%, and 17% among those above 35 years. Both mild, flat, sensorineural impairment and conductive impairment were found to be associated particularly with smoking (odds ratio 2.2 and 1.9, respectively).

Conclusions: The incidence of HL unrelated to noise exposure is higher in smokers than in non-smokers, and in young adults the effect is greater.
 

Background: The most frequent cause of defect in the mandible is tumor-related surgery. Larger defects or anterior arch defects cause severe morbidity due to disturbances in function and aesthetics.

Objectives: To assess the outcome of free tissue transfer for mandible reconstruction.

Methods: Since 1998 we operated on 11 patients with mandible defects using the fibula flap as the reconstruction method. We performed immediate reconstruction in eight patients after ablative surgery, and late reconstruction due to radiation-induced complications in three.

Results: All patients achieved good functional and aesthetic outcome. During the follow-up period two patients died of their malignant disease and one patient died from a non-related cause. Although two patients underwent reoperation in the first 3 months after their primary operation due to fixation failure, there were no other major complications.

Conclusions: According to the literature and our limited experience, the fibula flap is a safe and reliable option for mandible reconstruction.
 

Background: Familial Mediterranean fever is an autosomal recessive disease characterized by sporadic attacks of inflammation affecting the serosal spaces. The gene associated with FMF[1] (MEFV), mainly expressed in neutrophils, was recently found to be expressed also in primary cultures of serosal origin (peritoneal and synovial fibroblasts). A C5a inhibitor, previously detected in normal serosal fluids, was recently identified in serosal cultures as well, and was found to be deficient in serosal fluids and cultures obtained from FMF patients.

Objective: To investigate the effect of colchicine (the main therapeutic agent for FMF patients) and certain inflammatory cytokines (IL-1b, TNF-a, IFN-a, IFN-g) on MEFV expression and C5a inhibitor activity in neutrophils and primary peritoneal fibroblast cultures.

Methods: Human primary peritoneal fibroblast cultures and neutrophils were studied for MEFV expression and C5a inhibitor activity, using reverse transcription-polymerase chain reaction and C5a-induced myeloperoxidase assay, respectively, in the presence and absence of colchicine and cytokines.

Results: MEFV expression in neutrophils was high and could not be induced further. Its expression in the peritoneal fibroblasts was lower than in neutrophils and could be induced using colchicine and cytokines parallel with induction of C5a inhibitor activity. Semi-quantitative RT-PCR[2] assays enabled estimation of MEFV induction by the cytokines at 10–100-fold and could not be further increased by concomitant addition of colchicine.

Conclusion: Serosal tissues, which are afflicted in FMF, express colchicine and cytokine-inducible MEFV and contain inducible C5a inhibitor activity. The relation between colchicine ability to induce MEFV and C5a inhibitor activity, and its efficacy in FMF treatment, require further investigation.

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[1] RT-PCR = reverse transcription-polymerase chain reaction

[2] FMF = familial Mediterranean fever