A Review and Update on Tourette Syndrome: Where Is the Field Headed?

Tourette syndrome (TS) is a childhood onset neurologic disorder with manifestations including multiple motor and phonic tics, and in most cases a variety of behavioral comorbidities such as attention deficit hyperactivity disorder, obsessive compulsive disorder, and other impulse control disorders. Although it is considered a hereditary disorder, likely modified by environmental factors, genetic studies have yet to uncover relevant causative genes and there is no animal model that mimics the broad clinical phenomenology of TS. There has been a marked increase in the number of neurophysiological, neuroimaging, and other studies on TS. The findings from these studies, however, have been difficult to interpret because of small sample sizes, variability of symptoms across patients, and comorbidities. Although anti-dopaminergic drugs are the most widely used medications in the treatment of TS, there has been increasing interest in other drugs, behavioral therapies, and surgical approaches including deep brain stimulation. Herein, we review the current literature and discuss the complexities of TS and the challenges in understanding its pathophysiology and in selecting the most appropriate treatment. We also offer an expert’s view of where the field of TS may be headed.     

Chromogenic in situ hybridization for alpha6beta4 integrin in breast cancer: correlation with protein expression

The α6β4 integrin is the receptor for the basement membrane protein laminin-5. Recent studies suggest that α6β4 integrin expression in invasive breast carcinomas may be a poor prognostic factor. Because we have not had reliable results with commercially available antibodies for the immunohistochemical detection of α6β4 integrin in archival paraffin-embedded tissues, we designed a probe to detect β4 integrin subunit mRNA in paraffin sections. In situ hybridization for β4 mRNA was performed on paraffin-embedded tissue sections of 25 invasive breast carcinomas using a hyperbiotinylated oligonucleotide DNA probe. Immunohistochemical staining was performed on corrresponding frozen tumor sections using two commercially available antibodies to the β4 integrin subunit. All cases positive for β4 protein by one or both antibodies were also positive for β4 mRNA by in situ hybridization, but three cases with β4 mRNA expression were negative by immunohistochemistry with both antibodies. These findings suggest that in situ hybridization appears to be a sensitive method for detecting β4 integrin mRNA, but it appears to identify some cases that either lack β4 protein or express variants not recognized with commercial antibodies directed to particular extracellular or cytoplasmic domains.     

Mechanisms of hematopoietic stem cell aging

New blood cells are continually produced from the hematopoietic stem cells (HSCs) that reside in the bone marrow. Throughout the life-span of the organism, this stem cell reservoir sustains life. Although HSCs can persist in vivo longer than one life-span (Harrison et al., 1978), with aging, HSC regenerative potential diminishes and skewing from lymphopoiesis toward myelopoiesis occurs. The expansion in the HSC pool with aging provides sufficient, yet abnormal, blood production. Examination of gene expression changes in aged HSCs has provided a link between aging and genomic instability. Furthermore, studies on the effects of reactive oxygen species (ROS) on HSC aging has given more insight into the reasons for HSC failure. Understanding of the interactions between niche cells and HSCs and changes in them with aging, may give us insights into the lineage skewing phenotype observed in the aged, and also other immune dysfunctions.     

Professional Experiences of International Medical Graduates Practicing Primary Care in the United States

Background  

International medical graduates (IMGs) comprise approximately 25% of the US physician workforce, with significant representation in primary care and care of vulnerable populations. Despite the central role of IMGs in the US healthcare system, understanding of their professional experiences is limited.     

Cell cycle markers have different expression and localization patterns in neuron-like PC12 cells and primary hippocampal neurons

Recent studies have indicated that bone marrow stromal cells (BMSCs) have significant tropism towards glioma which makes them play an important role in carrying genes/drugs to inhibit the growth of glioma as cell vehicles. But BMSCs may differentiate into neural cells under entocranial environment and few researches support the idea that neurally differentiated bone marrow stromal cells (N-D-BMSCs) still hold the capacity of migrating to the tumor sites. The aim of our study was to investigate the tropism of N-D-BMSCs towards C6 glioma. In vitro migration assay was employed by transwell co-culture system and Student's t-test analysis indicated that N-D-BMSCs had the significant tropism towards C6 glioma-conditioned medium (GCM) (P < 0.01). Furthermore, the vascular endothelial growth factor (VEGF) bioactivity of the C6 GCM was neutralized by the anti-rat VEGF antibody and our data suggested that the VEGF from C6 GCM hold chemoattraction for N-D-BMSCs and some other cytokines from the C6 GCM may be responsible for the chemoattraction for N-D-BMSCs. In vivo migration assay was carried out with cells transplantation and one way ANOVA analysis indicated that the tropism of N-D-BMSCs towards C6 glioma sites presented time variation (P-value = 2.9E−20). Moreover, multiple comparisons for the time variables with the Student's t-test and the results suggested that the migration capacity of N-D-BMSCs towards C6 glioma sites reach the peak on the 7th day after transplantation. These results demonstrate that N-D-BMSCs as well as BMSCs have significant tropism towards C6 glioma.     

A new variation: An anterior cruciate ligament attached to the accessory ossicle

Anatomic variations of the anterior cruciate ligament (ACL) are very rare. The prevalence of congenital aplasia or hypoplasia of the ACL is 0.017 per 1,000 live births. The normal ACL consists of the anteromedial (AMB) and posterolateral bundles (PLB). Together, they attach to a fossa on the posteromedial aspect of the lateral femoral condyle. The PLB fibrils are smaller and shorter than those of the AMB. We report an ACL variation that had not been previously described, in which the PLB was attached to an intraarticular accessory ossicle, without causing knee instability. The large accessory ossicle caused pain. We reviewed the anatomy, anomalies, and variation in the ACL.     

The presence of Epstein-Barr virus (EBV) in diffuse large B-cell lymphomas (DLBCLs) in Turkey: special emphasis on 'EBV-positive DLBCL of the elderly'

Accumulated evidence has shown the importance of Epstein-Barr virus in the pathogenesis of various lymphomas. This study aimed to determine the prevalence of Epstein-Barr virus expression and its effect on survival amongst diffuse large B-cell lymphoma (DLBCL) cases from two large tertiary care centres in Turkey with a particular interest in identifying cases of 'Epstein-Barr virus-positive DLBCL of the elderly'. Diffuse large B-cell lymphoma cases diagnosed between 1999 and 2009 were retrieved and 340 cases were used to construct tissue microarrays. The presence of Epstein-Barr virus small ribonucleic acids was examined by in situ hybridization using Epstein-Barr virus (EBV)-encoded small RNA (EBER) oligonucleotides. A total of 18 cases (5.3%) showed Epstein-Barr virus expression. Twelve cases were classified as Epstein-Barr virus-positive DLBCL of the elderly. Epstein-Barr virus-positive DLBCL cases showed a significantly inferior overall survival as compared with Epstein-Barr virus-negative cases (p < 0.001). In our study group Epstein-Barr virus expression is not prevalent in DLBCLs. Epstein-Barr virus-positive DLBCL of the elderly is also rare in the Turkish population. The presence of Epstein-Barr virus, however, is associated with poor prognosis.     

Crimean-Congo haemorrhagic fever cases in Turkey

Crimean-Congo haemorrhagic fever (CCHF) is an arbovirus infection, which is transmitted through ticks or via blood and secretions. Until recently, human cases of CCHF were unknown in Turkey; however, several acute disease cases were reported in 2002. We report on the investigation of a cluster of suspected CCHF cases in the middle part of the Black Sea from May 2002 to October 2003. The medical charts that we reviewed were obtained from all local physicians and our field investigations. 'Suspected case' was defined with regard to time, place, and both clinical and laboratory characteristics. A total of 108 patients were defined as suspected case. Among them 36 patients were reached and blood samples taken for examination for CCHF by using ELISA and RT-PCR. According to the laboratory analysis, 80.6% (29/36) were acute cases and 8.3% (3/36) were past CCHF infections. The overall mortality rate was 5.6%. There was no nosocomial infection; however, there were 2 family clusters. Tick exposure was the most prevalent risk factor (74.2%). A multidisciplinary collaboration should be developed in order to understand the magnitude of the disease and also to keep it under control.     

A Ten-Month Program in Curriculum Development for Medical Educators: 16 Years of Experience

BACKGROUND Despite increased demand for new curricula in medical education, most academic medical centers have few faculty with training in curriculum development. OBJECTIVE To describe and evaluate a longitudinal mentored faculty development program in curriculum development. DESIGN A 10-month curriculum development program operating one half-day per week of each academic year from 1987 through 2003. The program was designed to provide participants with the knowledge, attitudes, skills, and experience to design, implement, evaluate, and disseminate curricula in medical education using a 6-step model. PARTICIPANTS One-hundred thirty-eight faculty and fellows from Johns Hopkins and other institutions and 63 matched nonparticipants. MEASUREMENTS Pre- and post-surveys from participants and nonparticipants assessed skills in curriculum development, implementation, and evaluation, as well as enjoyment in curriculum development and evaluation. Participants rated program quality, educational methods, and facilitation in a post-program survey. RESULTS Sixty-four curricula were produced addressing gaps in undergraduate, graduate, or postgraduate medical education. At least 54 curricula (84%) were implemented. Participant self-reported skills in curricular development, implementation, and evaluation improved from baseline (p < .0001), whereas no improvement occurred in the comparison group. In multivariable analyses, participants rated their skills and enjoyment at the end of the program significantly higher than nonparticipants (all p < .05). Eighty percent of participants felt that they would use the 6-step model again, and 80% would recommend the program highly to others. CONCLUSIONS This model for training in curriculum development has long-term sustainability and is associated with participant satisfaction, improvement in self-rated skills, and implementation of curricula on important topics.     

Fluoxetine in posttraumatic eating disorder in two-year-old twins

Feeding disorders of infancy or early childhood are relatively uncommon in the pediatric population. In posttraumatic eating disorder, the infant demonstrates food refusal after a traumatic event or repeated traumatic events to the oropharynx or esophagus. We present case reports of 24-month-old twin girls, A and B, who presented to our clinic with food refusal and fear of feeding. Several invasive gastrointestinal procedures were performed when they were 3 months old, and they started to refuse all solid food and some liquids soon after hospitalization. Fluoxetine 0.3 mg/kg per day (5 mg/day) was started to target their anxiety and fear about feeding. In the second month of weekly follow up, the children began to be fed without a nasogastric catheter. A significant decrease in anxiety and fear was observed during feeding. Although the use of serotonin-selective reuptake inhibitors (SSRIs) in preschool children is controversial due to the lack of empirical data in this age group, we observed clinical improvements in anxiety in these two cases. Furthermore, fluoxetine was well tolerated and no side effects were observed.