TNFα Inhibits Schwann Cell Proliferation, Connexin46 Expression, and Gap Junctional Communication

Schwann cell responses to nerve injury are stimulated, in part, by inflammatory cytokines. This study compares changes in the phenotype of cultured Schwann cells after exposure to the cytokine tumor necrosis factor (TNF)-α or the mitogen neu differentiation factor (NDF)-β. TNFα inhibited proliferation in a dose-dependent manner without altering Schwann cell survival. TNFα also reduced both gap junctional conductance and Lucifer yellow dye coupling between Schwann cells. Moreover, both P₀and glial fibrillary acidic protein (GFAP) immunoreactivity were reduced. By contrast, NDFβ initially had little effect on cell division although it reduced junctional coupling within 8 h. However, by 48 h, NDFβ stimulated proliferation with a concomitant increase in coupling. Dividing Schwann cells (BrdU⁺) were preferentially dye coupled compared to nondividing cells, indicating an association between proliferation and coupling. Moreover, cultured Schwann cells expressed connexin46 mRNA and protein, and changes in the levels of the protein correlated with the degree of proliferation and coupling. The data thus provide evidence for cytokine-induced modulation of Schwann cell antigenic phenotype, proliferation, and gap junction properties. These observations suggest that enhanced gap junctional communication among Schwann cells after nerve injury could help to coordinate cellular responses to the injury, and that TNFα may be a signal which terminates proliferation as well as junctional communication.     

Phylogenetic reconstruction of Mycobacterium tuberculosis within four settings of the Caribbean region: tree comparative analyse and first appraisal on their phylogeography.

In order to compare phylogenetic methods and to reconstruct the evolutionary history of the tubercle bacilli, a set of macro-array-based genotyping data of Mycobacterium tuberculosis clinical isolates (called spoligotyping for spacer oligonucleotide typing, which assays the variability of the Direct Repeat -DR- locus), was analyzed in four settings of the Caribbean region (Guadeloupe, Martinique, Cuba and Haiti). A set of 47 alleles, split into 26 shared and 21 unique alleles) representative of 321 individual M. tuberculosis clinical isolates from patients residing in the above regions was studied. The following methods (and software in brackets) were investigated: numerical taxonomy distance methods (TAXOTRON), maximum parsimony procedure (PAUP), median-joining networks (NETWORK), and nested clade analysis (GEODIS). Results using these methods were analyzed, compared and discussed. The latter method (GEODIS) was investigated in detail by introducing geographical data together with genetic variability results to detect a link between population structure and population history, and to test the null hypothesis of no association between geography and genotypes. Irrespective of the methods used, our findings demonstrate that a core structure of four families (or clades) of M. tuberculosis strains is highly prevalent within the islands studied, indirectly reflecting passed colonization history of these different settings. Specificity of M. tuberculosis genotypes in each of the islands is discussed in the light of their respective colonial and contemporary histories.     

Airbag deployment and improperly restrained children: a lethal combination

BACKGROUND: Airbag deployment is an acknowledged mechanism of serious trauma in children involved in motor vehicle crashes. From a review of national databases, we determined the number and types of fatal and nonfatal injuries to children caused by airbag deployment and child restraint system use. We also reviewed the relevant literature and provide information useful for caregivers and health care professionals in hopes of reducing future injuries. METHODS: We retrospectively reviewed 263 reported cases in which airbag deployment caused fatal or nonfatal injuries in children from reports released by the National Highway and Transportation Safety Administration and the National Pediatric Trauma Registry. Data were collected from January 1993 to December 2002 and imported into a database program for analysis. RESULTS: Of the 263 pediatric injuries caused by airbag deployment, 159 were fatal, and 104 were nonfatal. The peak incidence occurred in 1998, when 58 children were reported injured. Head injuries were most frequent, involving 170 children (64.6%), followed by spinal injuries, involving 100 children (38.0%). For children in their first year of life, head injuries were the sole mechanism of fatality. Of all children studied, only six (2.3%) were properly restrained. CONCLUSION: Airbag deployment in motor vehicle crashes is a well-recognized mechanism of morbidity and mortality in the pediatric population. Most injuries include trauma to the head and spine, which can have significant long-term consequences. Although the reported incidence of such injuries is decreasing, many children are improperly restrained. In our study, only 2.3% of children were properly restrained, suggesting that proper child restraint and seating position could have prevented most injuries.     

A systematic review of the results of surgery and radiotherapy on tumor control for pediatric craniopharyngioma

Objective

Craniopharyngiomas are rare tumors with bimodal incidence in the pediatric and adult age groups. Treatment strategies range from aggressive resection to planned limited resection combined with adjuvant therapies. Currently there is no consensus for standard of care for pediatric craniopharyngioma.

Materials and methods

We performed a systematic review of the published literature on pediatric craniopharyngioma. Patients were grouped based on extent of resection into gross total resection (GTR), subtotal resection (STR), and biopsy procedures. These groups were compared with respect to tumor control. Chi square was used to compare rates of recurrence. Kaplan–Meier was used to generate progression-free survival (PFS) estimates. Cox proportional hazard modeling was used to evaluate risk of progression. Each extent of resection group was also subdivided based on adjuvant therapy and compared.

Results

A total of 109 studies described extent of resection resulting in a cohort of 531 patients. Recurrence data were available for 377 patients. There was no difference in 1- or 5-year PFS between the groups who underwent GTR and STR combined with radiation (XRT; log-rank; p?=?0.76; 1-year PFS 89 vs 84 %; 5-year PFS 77 vs 73 %, respectively). One-year PFS was 84 % for STR+XRT compared to 76 % for STR alone while 5-year PFS was 73 % for STR+XRT compared to 43 % for STR alone (log-rank; p?=?0.003).

Conclusion

Although there are limitations of a systematic review of retrospective data, our results suggest that STR+XRT of pediatric craniopharyngioma is associated with similar rates of tumor control as GTR.     

Responses to medical students' frequently asked questions about family medicine

This article provides answers to many questions medical students ask about the specialty of family medicine. It was developed through the collaborative efforts of several family medicine organizations, including the American Academy of Family Physicians, the Society of Teachers of Family Medicine, the Association of Family Medicine Residency Directors, and the Association of Departments of Family Medicine. The article discusses the benefits of primary care and family medicine, the education and training of family physicians, the scope of medical practice in the specialty, and issues related to lifestyle and medical student debt.     

EML4::ALK fusions in complex lymphatic malformations

Gorham–Stout disease (GSD) and generalized lymphatic anomaly (GLA) are subtypes of complex lymphatic malformations (CLMs) with osseous involvement that cause significant complications, including pain and pathologic fractures. As with other vascular anomalies, somatic mosaic mutations in oncogenes are often present, and the mTOR inhibitor sirolimus alleviates symptoms in some, but not all, patients. We describe two patients, one with GSD and one with GLA, found to have EML4::ALK fusions. This report of a targetable, oncogenic fusion in vascular malformations expands our understanding of the genetic basis for CLMs and suggests additional targeted therapies could be effective.     

Pediatric intracranial aneurysms—our experience and review of literature

Purpose

Intracranial aneurysms in children are not as common as in adults and there are many differences in the etiology, demographic variables, aneurysm location, aneurysm morphological characteristics, clinical presentation, and outcome in pediatric and adult intracranial aneurysms.

Methods

All children (≤18 years) suffering from intracranial aneurysm managed at our center from July 2001 through June 2013 were included in the study, and the details of these patients were retrieved from the computerized database of our hospital.

Observations

A total of 62 pediatric patients were treated for 74 aneurysms during the study period and constituted 2.3 % of all intracranial aneurysms treated during the same period. The mean age at presentation was 13.5 years. Headache (82 %) was the commonest presenting feature; other symptoms included seizures (21 %), ictal loss of consciousness (27 %), and motor/cranial nerve deficits (22.6 %). Computed tomogram revealed subarachnoid hemorrhage in 58 % of patients. Eighty-two percent of aneurysms were in anterior circulation. Sixty-seven percent of aneurysms were complex aneurysms. Fifty-eight percent of patients underwent surgical intervention while 30 % underwent endovascular procedures. Twenty-one percent of the patients developed vasospasm. There was no postoperative mortality. Favorable outcome was seen in 72 % of the patients.

Conclusions

Pediatric intracranial aneurysms are uncommon as compared to in adult patients. Seizures and cranial nerve involvement are seen more often as the presenting features in children. Posterior circulation aneurysms are more common in children, as are the internal carotid artery bifurcation aneurysms. There is high incidence of giant, posttraumatic, and mycotic aneurysms in children.