A Study of Autologous Non-Cultured Epidermal Suspension (NCES) Transplant in Patients with Stable Vitiligo without the Use of NB-UVB.

Introduction:Vitiligo is a common form of localized depigmentation and an important public health problem which affects around one percent of the global population and about two percent of the population in India. The present study aimed to document the results and side effects of non-cultured melanocyte transplant in patients with stable vitiligo without post-procedure use of NB UVB. Methods:The present study was a prospective interventional study conducted among patients with stable vitiligo who were attending the outpatient department (OPD) of dermatology of a tertiary center of Delhi. Patients with stable vitiligo aged >10 years who gave their consent for non-cultured epidermal suspension (NCES) were included in the study. Autologous skin graft of size 0.2 mm was taken from the donor site and a melanocyte cell suspension was prepared using standardized procedure, which was later transplanted to the recipient area. All patients were asked to come for follow-up at the OPD after seven days, 15 days, one month, followed by every month till six months post-transplantation, and repigmentation was assessed visually by both graph paper and photography. Data was analyzed using SPSS vs. 21. Results:In our study, the majority of patients had vitiligo vulgaris (27 subjects with 47 patches). A total number of 59 patches were transplanted, of which 38 (64.4%) achieved excellent repigmentation, 28.8% good repigmentation, 3.4% fair repigmentation and 3.39% poor repigmentation. A total of 1302.5 cm² of the depigmented area was operated by NCES and the repigmentation of 874.5 cm2 (67.14%) was achieved by six months. Conclusion:The present study found that the majority of patients (93%) with vitiligo achieved excellent or good repigmentation after NCES and the rate of complication was very low.

The clinical and cost impact of switching to fingolimod versus other first line injectable disease-modifying therapies in patients with relapsing multiple sclerosis.

BACKGROUND: There is limited evidence on the effectiveness and healthcare costs of switching to fingolimod versus another first line injectable therapy (FLIT) in patients with relapsing multiple sclerosis (RMS) who have already been treated with FLIT. OBJECTIVE: The objectives of the study were to assess the annualized relapse rate (ARR), socio-demographic and clinical characteristics, persistence and adherence rates, healthcare resource utilization and cost among patients with RMS who either switch to fingolimod or another FLIT in routine clinical practice. METHODS: A multicenter, observational, retrospective chart review was conducted across eight clinics in Canada between 1 May 2011 and 30 June 2013. The data was collected from two cohorts: patients who switched to fingolimod and patients who switched to FLIT from a previous FLIT. RESULTS AND CONCLUSIONS: A total of 124 patients were included in the study: 82 and 42 switched to fingolimod and FLIT, respectively. There were no significant differences in the patient characteristics at the date of switch except for number of previous disease-modifying therapies (DMTs) which was higher in the fingolimod cohort (fingolimod: 1.52; FLIT: 1.10, p < .001). The ARR during the first year of switching was numerically higher in the FLIT cohort compared to the fingolimod cohort (FLIT: 0.9 [95% CI 0.3-1.6]; fingolimod: 0.3 [95% CI 0.1-0.5]). The negative binomial model adjusted for the number of previous DMTs confirmed a statistically significant difference in ARR between the fingolimod and FLIT cohorts at 12 months of follow-up (p = .012). In the fingolimod cohort, 20.7% of patients experienced at least one relapse compared to 38.1% in the FLIT cohort. In both groups, a high proportion of patients (>90%) showed good treatment adherence (≥80% of prescribed doses).

Eruptive Vellus Hair Cyst: An Uncommon and Underdiagnosed Entity.

Eruptive vellus hair cyst (EVHC) is a rare follicular developmental abnormality of the vellus hair follicles. They are usually seen in children, adolescents, or young adults and manifest as reddish-brown smooth papules most commonly involving the chest, limbs, and abdomen. An 18-year-old male presented with asymptomatic papules on the trunk and flexor aspect of both forearms for the past 2 years. There was no family history of similar lesions. His medical history was also not contributory. A clinical diagnosis of steatocystoma multiplex and chronic folliculitis was given, and a punch biopsy from the papule was performed and sent for histopathological examination. On microscopic examination, a final diagnosis of EVHC was rendered. The patient was advised topical treatment of retinoic acid cream (0.05%) for 6 months, and he is currently under follow-up period. Due to its rarity and resemblance to many similar entities, histopathological examination plays a major role in establishing a definite diagnosis and further proper management of the patient. We report this unusual case to generate awareness about this rarely diagnosed condition.

Patient-reported outcomes in multiple sclerosis: a systematic comparison of available measures.

Multiple patient-reported outcomes (PROs) are currently being used in multiple sclerosis (MS) but their application is inconsistent and guidance on the appropriateness of each tool is lacking. The objective of our study was to identify MS-specific PROs and systematically to assess the development process and the reliability and validity of various instruments. A systematic literature search was conducted on multiple data sources, including MEDLINE, Embase (using the Ovid platform) and Google Scholar, from 1996 to March 2015. Search terms included combinations of MS, PROs and quality of life. Randomized controlled trials or observational studies conducted on patients with MS and published in English were included. In addition, the PROQOLID database was explored. The MS-specific PROs were systematically assessed using the Evaluating the Measurement of Patient-Reported Outcomes tool. In total, 8094 articles were screened and 405 PROs were identified from 1102 relevant articles. PROs were classified into MS-specific (n = 82) and non-MS-specific (n = 323). The results for the eight PROs that are most commonly used in MS clinical trials are presented here. For these eight PROs, the overall summary scores ranged between 50.1 and 68.7. The Multiple Sclerosis Impact Scale-29 had the best overall mean score (68.7), followed by the Leeds Multiple Sclerosis Quality of Life (67.0). This is the first study to provide a standardized assessment of all PROs for MS. There is a lack of data on content validity for PROs used in MS research, which indicates the need for a robust instrument in MS developed according to the US Food and Drug Administration guidelines.

Preoperative magnetic resonance spectroscopy improves diagnostic accuracy in a series of neurosurgical dilemmas.

OBJECT: The purpose of this study was to evaluate the usefulness of preoperative magnetic resonance spectroscopy (MRS) in neurosurgical patients with diagnostically challenging intracranial lesions. METHODS: Included in this study are twenty-three consecutive patients presenting to the neurosurgery service with diagnostically challenging intracranial lesions and who were investigated by conventional MR imaging and proton ((1)H) MRS, followed by surgery with subsequent histopathological diagnosis. An experienced neuroradiologist (RJ) blinded to the final histopathology evaluated the imaging studies retrospectively. Provisional diagnoses based on preoperative clinical and conventional MR data versus preoperative MRS data were compared with definitive histopathological diagnoses. RESULTS: Compared with preoperative clinical and conventional MR data, (1)H MRS improved the accuracy of MR imaging from 60.9% to 83%. We found (1)H MRS reliably distinguished between abscess and high-grade tumour, and between high-grade glioma and low-grade glioma, but was not able to reliably distinguish between recurrent glioma and radiation necrosis. In 12/23 cases (52%) the (1)H MRS findings positively altered our clinical management. Two representative cases are presented. CONCLUSIONS: Our study supports a beneficial role for (1)H MRS in certain diagnostic intracranial dilemmas presenting to neurosurgeons. The information gleaned from preoperative (1)H MRS can be a useful adjunct to clinical and conventional MR imaging data in guiding the management of patients with intracranial pathologies, particularly high-grade tumour versus abscess, and high-grade versus low-grade glioma. Further larger prospective studies are needed to clearly define the utility of (1)H MRS in diagnostically challenging intracranial lesions in neurosurgery.

Congenital miliaria crystallina - A diagnostic dilemma.

Miliaria crystallina is a transient, superficial obstruction of eccrine sweat ducts resulting in rapidly evolving noninflammatory vesicles. The disease is observed frequently in hot, humid, tropical climates and in the neonatal period, most likely due to lack of maturation of the sweat duct during the first few days following birth. It is rarely present at delivery and remains a diagnostic dilemma for the neonatologists. We report a rare case of "Congenital miliaria crystallina" that was present at birth.

Intra-operative transit time flowmetry reduces the risk of ischemic neurological deficits in neurosurgery.

Intra-operative transit time flowmetry (ITTF) can be used to quantify blood flow in local at risk vessels before and after surgical intervention. As inadvertent vessel compromise represents a major cause of neurological deficit following neurovascular surgery, the purpose of this study was to assess this technology in terms of its indications, ease of implementation and interpretation, safety and reliability. Patients were prospectively invited to participate. ITTF was recorded from at-risk vessels before and after surgical intervention, along with blood pressure and PaCO(2). Any episodes of flow compromise or change in surgical procedure were noted and correlated with post-operative neurological deficits and imaging. Twenty-eight patients undergoing 30 craniotomies were enrolled. Operations included n = 21 aneurysm clipping or exploration, 2 AVM excision, 2 dural AV fistula disconnections, 2 EC-IC bypass and 3 tumor resections. ITTF led to an alteration in surgery in 8 of the 30 cases (27%). In patients undergoing aneurysmal surgery, inadvertent vessel occlusion was identified in 3 cases, which led to immediate repositioning of the aneurysm clips. In 2 AV fistulae and 2 AVM surgeries, markedly reduced draining vein flow rates were confirmed quantitatively immediately before final surgical disconnection was carried out. In 1 EC-IC bypass patient, the measurement suggested graft vasospasm then treated with papaverine. One aneurysm person awoke with a stroke presumably from an embolic event undetected by ultrasonography. ITTF provides immediate feedback regarding vessel patency. Clip-related arterial compromise and local vasospasm are detected by this technology, but an embolic event may escape detection. This technology was found to have a broad utility in intra-cranial surgery, and was safe, rapidly performed, easy to interpret and generally reliable.

mRNA expression in rabbit experimental aneurysms: a study using gene chip microarrays.

BACKGROUND AND PURPOSE: The molecular characteristics of intracranial aneurysms are still poorly documented. A rabbit elastase aneurysm model has been helpful in the evaluation of devices and strategies involved in endovascular treatment of aneurysms. The goal of this project was to document the molecular changes, assessed by gene chip microarrays, associated with the creation of aneurysms in this model compared with the contralateral carotid artery. MATERIALS AND METHODS: A microarray of rabbit genes of interest was constructed using rabbit nucleotide sequences from GenBank. Elastase-induced saccular aneurysms were created at the origin of the right common carotid artery in 4 rabbits. Twelve weeks after aneurysm creation, RNA was isolated from the aneurysm as well as the contralateral common carotid artery and used for microarray experiments. Reverse transcription-polymerase chain reaction (RT-PCR) was performed on 1 animal as a confirmatory test. RESULTS: Ninety-six (46%) of 209 genes in the microarray were differentially expressed in the rabbit aneurysm compared with the contralateral common carotid artery. In general, differential gene expression followed specific molecular pathways. Similarities were found between rabbit aneurysms and human intracranial aneurysms, including increased metalloproteinase activity and decreased production of the extracellular matrix. RT-PCR results confirmed the differential expression found by the gene chip microarray. CONCLUSIONS: The molecular characteristics of the rabbit elastase-induced saccular aneurysm are described. The rabbit aneurysm model shares some molecular features with human intracranial aneurysms. Future studies can use the rabbit model and the new rabbit gene chip microarray to study the molecular aspects of saccular aneurysms.

Gastric mucosal fibrosis: a novel explanation for dyspepsia.

The etiology of functional dyspepsia has not been discerned yet which has led to inadequate treatment of this disease. It remains a common disorder with expensive and yet often ineffective therapy. We propose that the pathogenesis of this disease lies in the histological and ultrastructural changes inflicted on the gastric mucosa in chronic gastritis and fibrosis. This hypothesis, if substantiated will provide for therapy which will be based on the pathogenesis of the disease and which will be cheaper and easily available to most. It will also add impetus to the early eradication of Helicobacter pylori, which would prevent chronic gastritis and hence gastric fibrosis.

A direct mechanical method for accurate and efficient adenoviral vector delivery to tissues.

We describe a mechanical method for delivery of adenoviral vector to the adventitial surface of arteries and to other tissues. Our goal was to characterize, principally in intact carotid artery, the morphological, biochemical, and functional effects of mechanical delivery of a recombinant beta-galactosidase-expressing adenoviral vector following its direct application using a small paintbrush. Our ex vivo and in vivo data demonstrate efficient, accurate, and rapid transduction of arteries without compromise of their morphological, biochemical, and functional integrity. We also demonstrate the general applicability of this technique in vivo via transduction of skeletal muscle, fibrotendinous tissue, peritoneum, serosal surface of bowel, and wounded skin. We conclude that direct mechanical delivery of an adenoviral vector to tissues using a suitable paintbrush represents an intuitive, accurate, and effective means of augmenting gene transfer efficiency, and may be a useful adjunct to other delivery methods.

Occult rupture of a giant vertebral artery aneurysm following proximal occlusion and intrasaccular thrombosis. Case report.

The authors describe a unique clinicopathological phenomenon in a patient who presented with an unruptured giant vertebral artery aneurysm and who underwent endovascular proximal occlusion of the parent artery followed, several days later, by surgical trapping of the aneurysm after delayed subarachnoid hemorrhage (SAH). The intraoperative finding of a thrombus extruding from the wall of the aneurysm at a site remote from the origin of the SAH underscores the possibility that occult rupture of an aneurysmal sac can occur in patients with thrombosed giant aneurysms.

Gene transfer for cerebrovascular disease.

Gene transfer is a powerful, evolving technique that uses a biologic vehicle (eg, an engineered adenovirus) to introduce a specific gene of interest (ie, a recombinant gene) into a target tissue. This approach, which has considerable therapeutic potential, underlies the concept of gene therapy. Several studies have characterized the morphologic, biochemical, and functional effects of recombinant gene expression in animal and human cerebral arteries, and support the possibility of gene therapy for cerebrovascular disease. However, for successful integration into future clinical practice, key issues concerning vector safety, delivery methods, and transduction specificity need to be addressed. Alongside completion of the Human Genome Project, transfer of novel genes into the central nervous system is likely to impact greatly on our ability to favorably modify diseased human tissue. Knowledge of the fundamental concepts of cerebrovascular gene transfer is therefore useful to understanding both its molecular basis and potential clinical utility.

Functional interdependence and colocalization of endothelial nitric oxide synthase and heat shock protein 90 in cerebral arteries.

Heat shock protein 90 (HSP90), an essential component of several signal transduction systems, participates in the activation of endothelial nitric oxide synthase (eNOS) in cells. The objective of the current study was to determine if HSP90 and eNOS were functionally interdependent and colocalized in the cerebral circulation. The authors used isometric force recording, cyclic 3'5'-guanosine monophosphate (cGMP) radioimmunoassay (RIA), and immunogold electron microscopy (EM) to study canine basilar artery. They found that geldanamycin (0.1 to 10 microg/mL), a selective HSP90 inhibitor, caused concentration-dependent contractions in arterial rings (n = 6 dogs). Contractions to geldanamycin were unaffected by a cyclooxygenase inhibitor, indomethacin (10 micromol/L; P < 0.05, n = 6). Functional evidence for interaction between HSP90 and nitric oxide (NO)-mediated signaling included observations that the contractile effect of geldanamycin was the following: (1) endothelium-dependent, (2) abolished by Ng-nitro-L-arginine methylester (L-NAME; 0.3 mmol/L), and (3) non-additive with the contractile effect of this NOS inhibitor (P < 0.01, n = 6 for each). Furthermore, RIA showed significant reduction in cGMP levels in arteries treated with geldanamycin (3 microg/mL; P < 0.02, n = 8), whereas immunogold EM demonstrated areas of colocalization of HSP90 and eNOS selectively in the cytoplasm of endothelial cells. The current findings suggest that in cerebral arteries, endothelial HSP90 plays an important role in modulation of basal NO-mediated signaling. This interaction may be particularly important in stress-induced up-regulation of HSP90 with subsequent alteration of vasomotor function.

Adenovirus-mediated gene transfer to human cerebral arteries.

Gene therapy is being investigated as a putative treatment option for cardiovascular diseases, including cerebral vasospasm. Because there is presently no information regarding gene transfer to human cerebral arteries, the principal objective of this study was to characterize adenovirus-mediated expression and function of recombinant endothelial nitric oxide synthase (eNOS) gene in human pial arteries. Pial arteries (outer diameter 500 to 1,000 microm) were isolated from 30 patients undergoing temporal lobectomy for intractable seizures and were studied using histologic staining, histochemistry, electron microscopy, and isometric force recording. Gene transfer experiments were performed ex vivo using adenoviral vectors encoding genes for bovine eNOS (AdCMVeNOS) and Escherichia coli beta-galactosidase (AdCMVLacZ). In transduced arteries, studied 24 hours after exposure to vectors, expression of recombinant beta-galactosidase and eNOS was detected by histochemistry, localizing mainly to the adventitia (n = 4). Immunoelectron microscopy localized recombinant eNOS in adventitial fibroblasts. During contractions to U46619, bradykinin-induced relaxations were significantly augmented in AdCMVeNOS-transduced rings compared with control and AdCMVLacZ-transduced rings (P < 0.01; n = 6). The NOS inhibitor L-nitroarginine methylester (L-NAME) caused significantly greater contraction in AdCMVeNOS-transduced rings (P < 0.001; n = 4) and inhibited bradykinin-induced relaxations in control and transduced rings (P < 0.001; n = 6). The current findings suggest that in AdCMVeNOS-transduced human pial arteries, expression of recombinant eNOS occurs mainly in adventitial fibroblasts where it augments relaxations to NO-dependent agonists such as bradykinin. Findings from the current study might be beneficial in future clinical applications of gene therapy for the treatment or prevention of cerebral vasospasm.