Treatment of MOG antibody associated disorders: results of an international survey.

INTRODUCTION: While monophasic and relapsing forms of myelin oligodendrocyte glycoprotein antibody associated disorders (MOGAD) are increasingly diagnosed world-wide, consensus on management is yet to be developed. OBJECTIVE: To survey the current global clinical practice of clinicians treating MOGAD. METHOD: Neurologists worldwide with expertise in treating MOGAD participated in an online survey (February-April 2019). RESULTS: Fifty-two responses were received (response rate 60.5%) from 86 invited experts, comprising adult (78.8%, 41/52) and paediatric (21.2%, 11/52) neurologists in 22 countries. All treat acute attacks with high dose corticosteroids. If recovery is incomplete, 71.2% (37/52) proceed next to plasma exchange (PE). 45.5% (5/11) of paediatric neurologists use IV immunoglobulin (IVIg) in preference to PE. Following an acute attack, 55.8% (29/52) of respondents typically continue corticosteroids for ≥ 3 months; though less commonly when treating children. After an index event, 60% (31/51) usually start steroid-sparing maintenance therapy (MT); after ≥ 2 attacks 92.3% (48/52) would start MT. Repeat MOG antibody status is used by 52.9% (27/51) to help decide on MT initiation. Commonly used first line MTs in adults are azathioprine (30.8%, 16/52), mycophenolate mofetil (25.0%, 13/52) and rituximab (17.3%, 9/52). In children, IVIg is the preferred first line MT (54.5%; 6/11). Treatment response is monitored by MRI (53.8%; 28/52), optical coherence tomography (23.1%; 12/52) and MOG antibody titres (36.5%; 19/52). Regardless of monitoring results, 25.0% (13/52) would not stop MT. CONCLUSION: Current treatment of MOGAD is highly variable, indicating a need for consensus-based treatment guidelines, while awaiting definitive clinical trials.

Kappa free light chains is a valid tool in the diagnostics of MS: A large multicenter study.

OBJECTIVE: To validate kappa free light chain (KFLC) and lambda free light chain (LFLC) indices as a diagnostic biomarker in multiple sclerosis (MS). METHODS: We performed a multicenter study including 745 patients from 18 centers (219 controls and 526 clinically isolated syndrome (CIS)/MS patients) with a known oligoclonal IgG band (OCB) status. KFLC and LFLC were measured in paired cerebrospinal fluid (CSF) and serum samples. Gaussian mixture modeling was used to define a cut-off for KFLC and LFLC indexes. RESULTS: The cut-off for the KFLC index was 6.6 (95% confidence interval (CI) = 5.2-138.1). The cut-off for the LFLC index was 6.9 (95% CI = 4.5-22.2). For CIS/MS patients, sensitivity of the KFLC index (0.88; 95% CI = 0.85-0.90) was higher than OCB (0.82; 95%CI = 0.79-0.85; p < 0.001), but specificity (0.83; 95% CI = 0.78-0.88) was lower (OCB = 0.92; 95% CI = 0.89-0.96; p < 0.001). Both sensitivity and specificity for the LFLC index were lower than OCB. CONCLUSION: Compared with OCB, the KFLC index is more sensitive but less specific for diagnosing CIS/MS. Lacking an elevated KFLC index is more powerful for excluding MS compared with OCB but the latter is more important for ruling in a diagnosis of CIS/MS.

Is there A Relationship between route of delivery, perinatal characteristics, and neonatal outcome in preterm birth?

BACKGROUND: Preterm birth is one of the most challenging problems in obstetric care and it is closely related to perinatal mortality and morbidity. The aim of the current study was to document our experience with preterm births and to analyze the association between perinatal variables and clinical outcomes. METHODOLOGY: In this retrospective study, data were derived from the medical records of 785 singleton preterm births delivered in the obstetrics and gynecology department of our institution. Variables under investigation were maternal and gestational ages, fetal gender, route of delivery (vaginal vs. cesarean section [C/S]), causes of preterm birth, birth weight, placental weight, umbilical cord length, and Apgar scores at the 1st and 5th min. RESULTS: Pregnant women with advanced age (≥35 years) were more likely to undergo C/S (P < 0.001). Apgar score at the 1st and 5th min was influenced significantly by gestational age (P < 0.001), newborn birth weight (P < 0.001), placental weight (P < 0.001), and umbilical cord length (P < 0.001). Infants delivered due to antepartum fetal distress indication had remarkably lower Apgar scores at the 1st min and the birth weight seemed to be positively correlated with Apgar scores at both 1st (P < 0.001) and 5th min (P < 0.001). Apgar scores both at the 1st and 5th min were positively correlated with placental weight (R: 0.239 and 0.231, respectively, and P < 0.001 for both) and length of umbilical cord (R:0.228 and 0.211, respectively, and P < 0.001 for both). CONCLUSION: Advanced age pregnancies have higher C/S rates, but Apgar scores are significantly correlated with infant characteristics. Umbilical cord length and placental weight might be the new add-on predictors of postpartum well-being in premature infants.

The coexistence of eosinophilic esophagitis with allergic rhinitis.

OBJECTIVE: Eosinophilic esophagitis (EoE) is diagnosed with the presence of characteristic esophageal symptoms and eosinophilic infiltration of the esophageal mucosa after other causes of eosinophilia are excluded. EoE has been reported to co-occur with some allergic diseases. In this study, we evaluated the co-existence of EoE in Ear-Nose-Throat (ENT) outpatient clinic patients with allergic rhinitis (AR). PATIENTS AND METHODS: The study group consists of 67 AR patients (AR group) and the control group (CG) was formed with 53 cases with dyspepsia symptoms. Symptoms of AR and CG groups were compared in terms of endoscopic and histological findings. Moreover, in AR group, accompanying symptoms, immunoglobulin E (IgE), skin prick test (SPT) positivity, Helicobacter pylori (H. pylori) presence, endoscopic findings and biopsy results were compared between patients with EoE and those without. RESULTS: Seven of the cases with AR were diagnosed with EoE. Reflux symptoms were more common in patients with EoE (71.4%). The presence of H. pylori was similar between groups. Blood IgE levels were significantly higher among EoE patients compared to those without EoE (p = 0.003). SPT positivity was present in the 85.7% of patients with EoE and 50% of the patients without EoE (p = 0.113). Allergens were more likely to be mites Dermatophagoides farinae and Dermatophagoides pteronyssinus in patients with EoE (p = 0.042 and p = 0.034 respectively). CONCLUSIONS: The most common symptom among patients with EoE is reflux. In AR patients with EoE, serum IgE levels were higher compared to those without EoE. In AR patients with reflux symptoms, high serum IgE levels, and especially in patients whose tests are positive for allergy to mites, referral to a gastroenterologist for EoE evaluation may be recommended.

Assessment of primary radical hysterectomy and neoadjuvant chemotherapy followed by radical hysterectomy in Stage IB2, IIA bulky cervical cancer.

OBJECTIVE: Uncertainty concerning the treatment of Stage IB2-IIA (bulky) cervical cancer is still continuing. In this study, an analysis of Stage IB2-IIA (bulky) cervical cancer was performed. The efficacy of primary radical surgery and neoadjuvant chemotherapy followed by a radical surgery was investigated. MATERIALS AND METHODS: Medical data of 50 patients who were diagnosed with Stage 1B2-IIA (bulky) cervical cancer and treated between 2002-2009 were retrospectively assessed. In the radical surgery group, radical hysterectomy + bilateral pelvic + para-aortic lymphadenectomy were performed. In the neoadjuvant chemotherapy group, a combination of cisplatin/topotecan or paclitaxel/carboplatin was given to the patients and then radical surgery was performed. Each group was evaluated individually. Prognostic factors were determined and survival rates were compared between the groups. Ap value was taken < 0.05 for the statistical significance level for all results. RESULTS: Radical surgery after neoadjuvant chemotherapy was performed in 21 and primary radical surgery in 29 patients. Median follow-up time was 36.0 +/- 14.0 months. Average of the tumor size before treatment was 50.2 +/- 7.6 mm. In the radical surgery after neoadjuvant chemotherapy group, lymphovascular space invasion (LVSI) and tumor size (before and after treatment) were determined to be significant factors for each of disease-free survival (DFS) and overall survival (OS). On multivariate analysis, tumor size (before treatment) was found to be an independent prognostic factor for both of DFS (p = 0.006) and OS (p = 0.010). No significant difference in survival periods was observed among the groups. CONCLUSION: There was no significant superiority among the two treatment options. Nonetheless, further studies are needed to compare the multimodal approaches in these stages of cervical cancer.

Conversion from clinically isolated syndrome to multiple sclerosis: A large multicentre study.

BACKGROUND AND OBJECTIVE: We explored which clinical and biochemical variables predict conversion from clinically isolated syndrome (CIS) to clinically definite multiple sclerosis (CDMS) in a large international cohort. METHODS: Thirty-three centres provided serum samples from 1047 CIS cases with at least two years' follow-up. Age, sex, clinical presentation, T2-hyperintense lesions, cerebrospinal fluid (CSF) oligoclonal bands (OCBs), CSF IgG index, CSF cell count, serum 25-hydroxyvitamin D3 (25-OH-D), cotinine and IgG titres against Epstein-Barr nuclear antigen 1 (EBNA-1) and cytomegalovirus were tested for association with risk of CDMS. RESULTS: At median follow-up of 4.31 years, 623 CIS cases converted to CDMS. Predictors of conversion in multivariable analyses were OCB (HR = 2.18, 95% CI = 1.71-2.77, p < 0.001), number of T2 lesions (two to nine lesions vs 0/1 lesions: HR = 1.97, 95% CI = 1.52-2.55, p < 0.001; >9 lesions vs 0/1 lesions: HR = 2.74, 95% CI = 2.04-3.68, p < 0.001) and age at CIS (HR per year inversely increase = 0.98, 95% CI = 0.98-0.99, p < 0.001). Lower 25-OH-D levels were associated with CDMS in univariable analysis, but this was attenuated in the multivariable model. OCB positivity was associated with higher EBNA-1 IgG titres. CONCLUSIONS: We validated MRI lesion load, OCB and age at CIS as the strongest independent predictors of conversion to CDMS in this multicentre setting. A role for vitamin D is suggested but requires further investigation.

Evaluation of preoperative and postoperative S-100B levels in children with chronic adenotonsillar hypertrophy: preliminary results.

OBJECTIVES: Upper air obstruction leads hypoxia, it is also known that S-100B levels increase by glial activations indicate cerebral hypoxic injury. This study aimed to evaluate the preoperative and postoperative S-100B levels in children with chronic adenotonsillar hypertrophy. PATIENTS AND METHODS: The study comprised 40 patients with indications for tonsillectomy and/or adenoidectomy following a diagnosis of chronic adenotonsillar hypertrophy and 40 age-gender matched control patients. Blood samples were taken from the patients preoperatively and at four weeks postoperatively. Preoperative and postoperative serum S-100B levels were analyzed. RESULTS: The serum S-100B levels in the preoperative period were found to be significantly higher compared to those of the control group (p < 0.05). The S-100B levels were significantly decreased in the postoperative period (p < 0.05). CONCLUSIONS: The development of chronic adenotonsillar hypertrophy would play a role in increased S-100B levels. This indicates that neuronal damage would exists in patients with chronic adenotonsillar hypertrophy.

Acute effects of splint immobilization of the forearm on in vivo microcirculation and histomorphology of the human skin.

BACKGROUND: Splint immobilization of the forearm is often performed in clinical practice. Previous studies investigated the effect of immobilization on bone, cartilage, muscle, and tendon, however, the acute effects on human skin microcirculation and histomorphology remains elusive. METHODS: In 12 healthy, nonsmoking individuals (aged 29.7 ± 9.1 years) a randomly selected forearm was immobilized by splinting for 72 h, whereas the other forearm served as control. In vivo Reflectance-Mode Confocal-Microscopy (RMCM) was performed prior (baseline value) and postimmobilization to evaluate: quantitative blood cell flow; density of functional dermal capillaries; epidermal thickness; and granular cell size. RESULTS: At 72h forearm immobilization, quantitative blood cell flow was significantly reduced (42.86 ± 3.68 cells/min) compared to the control blood flow (53.11 ± 3.68 cells/min, P < 0.05) and dermal capillaries indicates less functional density (5.73 ± 0.63 capillaries/mm2) compared to the controls (7.04 ± 0.81 capillaries/mm2, P < 0.05). Histometric assessment reveals significantly thinner epidermis following immobilization compared to the control site (40.02 ± 2.91 vs. 46.64±3.09 µm, P < 0.05). Granular cell size was significantly altered at 72 h splinting (730.1 ± 42.53 µm2) compared to the control cell size at 770.2 ± 38.21 µm2. Comparison of baseline values of both forearms indicate statistically insignificance (P > 0.05) for each parameter. CONCLUSION: At 72 h splint immobilization, for the first time, significant adaptive mechanisms were evaluated on human skin microcirculation and histomorphology using in vivo RMCM. These adaptations may be considered as an incipient atrophy of the human skin. Long-term effects of immobilization including the regenerative potential should be evaluated in further RMCM studies.

Characterization of neuromyelitis optica and neuromyelitis optica spectrum disorder patients with a late onset.

BACKGROUND: Few data are available for patients with a late onset (≥ 50 years) of neuromyelitis optica (LONMO) or neuromyelitis optica spectrum disease (LONMOSD), defined by an optic neuritis/longitudinally extensive transverse myelitis with aquaporin-4 antibodies (AQP4-Ab). OBJECTIVE: To characterize LONMO and LONMOSD, and to analyze their predictive factors of disability and death. METHODS: We identified 430 patients from four cohorts of NMO/NMOSD in France, Germany, Turkey and UK. We extracted the late onset patients and analyzed them for predictive factors of disability and death, using the Cox proportional model. RESULTS: We followed up on 63 patients with LONMO and 45 with LONMOSD during a mean of 4.6 years. This LONMO/LONMOSD cohort was mainly of Caucasian origin (93%), women (80%), seropositive for AQP4-Ab (85%) and from 50 to 82.5 years of age at onset. No progressive course was noted. At last follow-up, the median Expanded Disability Status Scale (EDSS) scores were 5.5 and 6 in the LONMO and LONMOSD groups, respectively. Outcome was mainly characterized by motor disability and relatively good visual function. At last follow-up, 14 patients had died, including seven (50%) due to acute myelitis and six (43%) because of opportunistic infections. The EDSS 4 score was independently predicted by an older age at onset, as a continuous variable after 50 years of age. Death was predicted by two independent factors: an older age at onset and a high annualized relapse rate. CONCLUSION: LONMO/LONMOSD is particularly severe, with a high rate of motor impairment and death.

The role of physical activity, body mass index and maturity status in body-related perceptions and self-esteem of adolescents.

BACKGROUND: Adolescence represents a transitional period which is marked by physical, social and psychological changes. Changes in body shape and physical activity especially alter and shape the psychological well-being of adolescents. AIM: The purpose of this study was to determine the role of physical activity level, body mass index and maturity status in body-related perception and self-esteem of 11-18 years old adolescents. SUBJECTS AND METHODS: A total of 1012 adolescents participated in this study. The "Social Physique Anxiety Scale", "Body Image Satisfaction Scale", "Physical Self-Perception Profile for Children" and "Rosenberg Self-Esteem Inventory" were administered. Physical activity level and body mass index were assessed using the "Physical Activity Questionnaire" and "Bioelectrical Impedance Analyzer", respectively. RESULTS: Regression analysis indicated that body mass index was the only predictor of perceived body attractiveness, social physique anxiety, body image satisfaction and self-esteem for female adolescents. For male adolescents, both physical activity and body mass index were correlated with perceived body attractiveness and social physique anxiety. Pubertal status were not correlated with self-esteem and body-related perceptions for both males and females adolescents. CONCLUSION: In summary, body mass index and physical activity plays an important role in body-related perceptions and self-esteem of adolescents.

Clinicopathological features and prognostic factors of the uterine sarcomas: 20 years of experience at Cukurova University.

OBJECTIVE: Uterine sarcomas (US) are rare, malignant, and aggressive tumors of the uterus. In this study the authors aimed to evalu- ate retrospectively the clinical and pathologic features and to investigate the prognostic factors of the U.S. patients who were treated in their department in the last 20 years. MATERIALS AND METHODS: The archive files, medical, and pathological records of the 132 US patients who were operated on and regularly followed up in the clinic between March 1991-March 2011 were reviewed. Clinical features, operation characteristics, pathological findings, adjuvant therapies, and follow-up data of the patients and their effects on survival were investigated. Analysis of disease-free survival (DFS) and overall survival (OS) were calculated using Kaplan-Meier and Cox regression tests. Thep value was taken <0.05 to maintain the statistical significance level for all results. Results: Seventy of the patients were diagnosed with leiomyosarcomas (LMS), 33 were with carcinosarcomas, 12 were with endometrial stromal sarcomas (ESS), nine were with undifferentiated endometrial sarcomas, five were with adenosarcomas, and three were with botryoid rhabdomyosarcomas. The average patients' age was 53.7 +/- 12.6 (17-78). About two-thirds of the patients were in postmenopausal and one-third were in pre- menopausal period. Vaginal bleeding was detected as the most common reason for patients' admission (68.9%). All cases underwent surgery and a procedure of total abdominal hysterectomy + bilateral salpingo-oophorectomy (TAH + BSO) was performed for most of them (88%). The mean duration of follow-up was 36 months (4-198). The two- and five-year OS rates were 65% and 36%, respectively, with a median time of 37 months (95% CI, 28-45). The two- and five-year DFS rates were 59% and 33%, respectively, with a median time of 29 months (95% CI, 18-40). CONCLUSION: As a result of multivariate analysis, while age, stage, lymphovascular space invasion (LVSI), and lymphadenectomy were found to be independent prognostic factors affecting DFS, only stage was detected as an independent prognostic factor for OS.

Acute effects of local cold therapy in superficial burns on pain, in vivo microcirculation, edema formation and histomorphology.

BACKGROUND: Local cold therapy for burns is generally recommended to relief pain and limit tissue damage, however, there is limited data of its physiological benefit. This study aimed to evaluate pathophysiological effects of cold therapy in superficial burn on microcirculation, edema formation, and histomorphology. METHODS: In 12 volunteers (8f, 4m; aged 30.4±14.1 years) circumscribed superficial burn was induced on both hand back and either left untreated as control (control-group) or treated by local-cold-application (cold-treatment-group). Prior to burn (t0), immediately (t1), 15 min (t2), and 30 min (t3) following cold therapy, following parameter was evaluated using intravital-microscopy; epidermal-thickness (ET), granular-cell-size (GCS), individual-blood-cell-flow (IBCF), and functional-capillary-density (FCD). RESULTS: Both ET and GCS increased significantly more in control-group and slightly in cold-treatment-group in t1, while turns to insignificant t2 onwards. IBCF and FCD raised up in control-group compared to dramatically decrease in cold-treatment-group in t1. In t2 both parameter remains in control-group and increased in cold-treatment-group. Comparison of both groups for IBCF and FCD indicates significant difference in t1 and t2, however, insignificant in t0 and t3. CONCLUSIONS: Microcirculation, edema formation, and histomorphology of superficial burn has been significantly influenced through immediate cold therapy, however, this alterations are transient and turns to ineffective after 30 min.

Preoperative evaluation, clinical characteristics, and prognostic factors of nongenital metastatic ovarian tumors: review of 48 patients.

OBJECTIVE: To evaluate the clinicopathologic characteristics, methods for preoperative evaluation, prognostic factors, and overall survival of nongenital ovarian metastases (NGOM). MATERIAL AND METHODS: Forty-eight patients with NGOM followed between January 2001 and January 2009 in Cukurova University Department of Gynecologic Oncology were included in the study. Clinical characteristics including demographics, preoperative imaging methods, endoscopic evaluations, tumor markers, histopathologic findings, prognostic factors, types of surgery, modalities for adjuvant therapy and survival were analyzed. RESULTS: The gastrointestinal tract is the most common location of the primary tumor; colonic origin was found in 41% of the patients (n = 20). All metastatic lesions were adenocarcinoma with 23% of these classified as Krukenberg and 29% as mucinous type adenocarcinoma. When the whole group was evaluated, median survival time was 15.7 months in patients and there were significant differences between the groups according to primary site. Histopathological subtypes and presence of peritoneal carcinomatosis affected the median survival. The significant prognostic factors were primary site and histopathologic subtypes of the NGOM. CONCLUSIONS: NGOM should be kept in mind to avoid inappropriate management and therapy in patients with surgically managed ovarian tumor, especially young patients with gastrointestinal complaints.

Clinical and radiological characteristics of tumefactive demyelinating lesions: follow-up study.

BACKGROUND: Demyelinating lesions over 20 mm in size, referred to as tumefactive demyelinating lesions, can be misdiagnosed as being either a tumor or an abscess. Although some radiological characteristics can help make a differential diagnosis easier, a cerebral biopsy may still be necessary. OBJECTIVE: Our objective was to assess the clinical characteristics of tumefactive lesions, with or without a diagnosis of multiple sclerosis (MS), and present follow-up data for 54 patients with tumefactive lesions. METHODS: Demographic, clinical, radiological and laboratory data were gathered and treatment responses were evaluated in a total of 54 patients from five medical centers. RESULT: Twenty-nine patients were diagnosed with tumefactive lesions at the onset, whereas 25 patients were diagnosed with tumefactive lesions after a diagnosis of MS. Median follow-up was 38.12 months. At final examination, 19 of the patients with a tumefactive lesion diagnosis at the onset eventually developed relapsing-remitting MS, while 10 remained with the condition as a clinically isolated syndrome. The tumefactive lesions studied were mostly focal, with closed-ring enhancement. We found that oligoclonal band positivity was less frequent in the patients with tumefactive onset. CONCLUSION: Although our demographic data were similar to formerly collected Turkish MS data, we found that the distribution of the patients' clinical course differed if there was an absence of primary progressive MS and that there was a lower frequency of secondary progressive MS cases in our group of patients. We believe that less frequent oligoclonal band positivity and the difference we witnessed in the clinical course of disease in our study groups suggest that there is a need for further studies to compare all the biological and immunological differences between MS and tumefactive lesion cases, in order to reveal whether there are different pathogenetic mechanisms involved.

Protective effects of black cumin (Nigella sativa) oil on TNBS-induced experimental colitis in rats.

BACKGROUND: The pathogenesis and treatment of ulcerative colitis remain poorly understood. The aim of the present study is to investigate the effects of black cumin (Nigella sativa) oil on rats with colitis. METHODS: Experimental colitis was induced with 1 mL trinitrobenzene sulfonic acid (TNBS) in 40% ethanol by intracolonic administration with 8-cm-long cannula under ether anesthesia to rats in colitis group and colitis + black cumin oil group. Rats in the control group were given saline at the same volume by intracolonic administration. Black cumin oil (BCO, Origo "100% natural Black Cumin Seed Oil," Turkey) was given to colitis + black cumin oil group by oral administration during 3 days, 5 min after colitis induction. Saline was given to control and colitis groups at the same volume by oral administration. At the end of the experiment, macroscopic lesions were scored and the degree of oxidant damage was evaluated by colonic total protein, sialic acid, malondialdehyde, and glutathione levels, collagen content, and tissue factor, superoxide dismutase, and myeloperoxidase activities. Tissues were also examined by histological and cytological analysis. Proinflammatory cytokines [tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1ß, and IL-6], lactate dehydrogenase activity, and triglyceride and cholesterol levels were analyzed in blood samples. RESULTS: We found that black cumin oil decreased the proinflammatory cytokines, lactate dehydrogenase, triglyceride, and cholesterol, which were increased in colitis. CONCLUSIONS: BCO, by preventing inflammatory status in the blood, partly protected colonic tissue against experimental ulcerative colitis.

Insight in human skin microcirculation using in vivo reflectance-mode confocal laser scanning microscopy.

Reflectance-mode confocal laser scanning microscopy allows in vivo imaging of the human skin. We hypothesized that this high-resolution technique enables observation of dynamic changes of the cutaneous microcirculation. Twenty-two volunteers were randomly divided in two groups. Group 1 was exposed to local heating and group 2 to local cold stress. Confocal microscopy was performed prior t (0) (control), directly t (1) and 5 min t (2) after local temperature changes to evaluate quantitative blood cell flow, capillary loop diameter, and density of dermal capillaries. In group 1, blood flow increased at t (1) (75.82 +/- 2.86/min) and further at t (2) (84.09 +/- 3.39/min) compared to the control (61.09 +/- 3.21/min). The control capillary size was 9.59 +/- 0.25 microm, increased to 11.16 +/- 0.21 microm (t (1)) and 11.57 +/- 0.24 microm (t (2)). The dermal capillary density increased in t (1) (7.26 +/- 0.76/mm(2)) and t (2) (8.16 +/- 0.52/mm(2)), compared to the control (7.04 +/- 0.62/mm(2)). In group 2, blood flow decreased at t (1) (41.73 +/- 2.61/min) and increased at t (2) (83.27 +/- 3.29/min) compared to the control (60.73 +/- 2.90/min). The control capillary size was 9.55 +/- 0.25 microm, decreased at t (1) (7.78 +/- 0.26 microm) and increased at t (2) (11.38 +/- 0.26 microm). Capillary density decreased at t (1) (5.01 +/- 0.49/mm(2)) and increased at t (2) (7.28 +/- 0.53/mm(2)) compared to the control (7.01 +/- 0.52/mm(2)). Confocal microscopy is a sensitive and noninvasive imaging tool for characterizing and quantifying dynamic changes of cutaneous microcirculation on a histomorphological level.

Monitoring of microcirculation in free transferred musculocutaneous latissimus dorsi flaps by confocal laser scanning microscopy--a promising non-invasive methodical approach.

INTRODUCTION: For the survival of a microvascular tissue transfer, early detection of vascular complications is crucial. In vivo confocal laser scanning microscopy allows real-time, non-invasive evaluation of tissue microcirculation with a high cellular resolution. The aim of this study was to evaluate confocal laser scanning microscopy for early recognition of flap failure. METHODS: Fourteen patients (ages: 40.2+/-12.4 years) were monitored postoperatively for a period of 24h following free microvascular M. latissimus dorsi transfer to the lower extremity using confocal laser scanning microscopy (Vivascope1500; Rochester; New York; USA). The following parameters were evaluated: quantitative blood-cell flow, diameter of capillary loops and minimal thickness of the epidermis. RESULTS: Venous congestion was characterised by a decrease in blood-cell flow of up to 41%, accompanied by an increase of the diameter of capillary loops of up to 22% and the minimal thickness of the epidermis up to 32%. By contrast, arterial occlusion was clearly verified by a decrease in blood flow of up to 90%, accompanied by an insignificant change of both capillary loop size and epidermal thickness. CONCLUSION: Confocal laser scanning microscopy appears to be a useful non-invasive tool for early recognition of flap failure during the monitoring of microsurgical tissue transfer prior to its clinical manifestation.

A Turkish newborn infant with cerebellar agenesis/neonatal diabetes mellitus and PTF1A mutation.

Classical neonatal diabetes mellitus is defined as hyperglycemia that occurs within the first month of life in term infants. It can be either permanent or transient. Cerebellar agenesis and permanent neonatal diabetes has been previously reported as a new autosomal recessive disorder. Pancreas Transcription Factor 1 Alpha (PTF1A) mutations have been related with this constellation of abnormalities. Here we report a new case of cerebellar agenesis and neonatal diabetes mellitus whose parents are PTF1A mutation carriers.

CADISP-genetics: an International project searching for genetic risk factors of cervical artery dissections.

BACKGROUND: Cervical artery dissection (CAD) is a frequent cause of ischemic stroke, and occasionally death, in young adults. Several lines of evidence suggest a genetic predisposition to CAD. However, previous genetic studies have been inconclusive mainly due to insufficient numbers of patients. Our hypothesis is that CAD is a multifactorial disease caused by yet largely unidentified genetic variants and environmental factors, which may interact. Our aim is to identify genetic variants associated with an increased risk of CAD and possibly gene-environment interactions. METHODS: We organized a multinational European network, Cervical Artery Dissection and Ischemic Stroke Patients (CADISP), which aims at increasing our knowledge of the pathophysiological mechanisms of this disease in a large group of patients. Within this network, we are aiming to perform a de novo genetic association analysis using both a genome-wide and a candidate gene approach. For this purpose, DNA from approximately 1100 patients with CAD, and 2000 healthy controls is being collected. In addition, detailed clinical, laboratory, diagnostic, therapeutic, and outcome data are being collected from all participants applying predefined criteria and definitions in a standardized way. We are expecting to reach the above numbers of subjects by early 2009. CONCLUSIONS: We present the strategy of a collaborative project searching for the genetic risk factors of CAD. The CADISP network will provide detailed and novel data on environmental risk factors and genetic susceptibility to CAD.

Multiple sclerosis risk in radiologically uncovered asymptomatic possible inflammatory-demyelinating disease.

BACKGROUND: Natural history of patients with incidentally discovered lesions that fulfill magnetic resonance imaging (MRI) criteria for multiple sclerosis (MS) in the absence of objective clinical symptoms suggestive of central nervous system (CNS) inflammatory-demyelinating disease is not well defined. OBJECTIVE: We evaluated the risk of developing symptomatic MS in patients with radiologically uncovered asymptomatic possible inflammatory-demyelinating disease (RAPIDD). METHODS: We identified and longitudinally followed a cohort of 22 patients from two tertiary care MS centers: Istanbul University, Cerrahpasa School of Medicine, Istanbul, Turkey, and Mayo Clinic, Rochester, Minnesota, after an initial MRI study fulfilling the Barkhof-Tintore MRI criteria completed for other reasons unrelated to MS. RESULTS: Eight of 22 patients developed an objective clinical symptom consistent with a CNS inflammatory-demyelinating syndrome and fulfilled dissemination in space and time criteria for definite MS. Median age at the time of diagnosis of MS was 44.8 years (range 28.3-71.4 years). Time taken for the development of definite MS was studied by survival analysis. Cumulative event rates were; 12 months: 9%, 24 months: 15%, 36 months: 30.4%, and 60 months: 44.6%. Six of 22 patients were followed beyond 60 months. Two of these six patients developed MS later (at 66 and 112 months, respectively). Three patients remained asymptomatic despite follow-up of 10 years. PATIENTS: with RAPIDD develop MS at a similar rate to treated patients (and less frequently than placebo groups) with clinically isolated syndromes from prior randomized controlled studies. Some patients with RAPIDD continue to have radiological evolution of subclinical disease without MS symptoms despite long follow-up periods.