West Nile Virus infection triggering autoimmune encephalitis: Pathophysiological and therapeutic implications.

BACKGROUND: A contributing factor in triggering autoimmune phenomena is pathogen infections. Here we describe a case that expands the spectrum of infection-associated autoimmune encephalitis and discuss plausible pathogenetic mechanisms. DESIGN: Case report and in silico analysis. RESULTS: A patient with West Nile Virus infection developed autoimmune encephalitis with positive anti-glycine receptor antibodies. Combination therapy with corticosteroids and intravenous immunoglobulin resulted in the resolution of encephalitis signs and symptoms. An in silico analysis unveiled certain sequence similarities between viral antigens and receptor sequence fragments suggesting a molecular mimicry autoimmunization process. CONCLUSIONS: Our case indicates that West Nile Virus infections can trigger autoimmune encephalitis. Our finding expands the spectrum of autoimmune conditions that can develop following an infection. Whether the autoimmunization process is due to molecular mimicry or due to the expansion of natural autoantibody clones merits further investigation.

Anastrozole plus leuprorelin in early maturing girls with compromised growth: the "GAIL" study.

PURPOSE: Aromatase inhibitors have been used to increase predicted adult height (PAH) in boys but in girls only in McCune-Albright syndrome. We investigated whether anastrozole combined with leuprorelin for up to 2 years is safe and effective in improving PAH in girls with early puberty and compromised growth, compared to leuprorelin alone. METHODS: The "GAIL" study: girls treated with an aromatase inhibitor and an LHRH analogue, ISRCTN11469487, was a 7-year prospective phase IIa study with parallel design, performed at Athens Medical Center (C-A), and Attikon University Hospital, Athens, Greece (C-B). Forty girls, consecutively referred for early puberty (onset 7.5-9 years) with a PAH <-2 or >1.5 SD lower than their target height (TH), were included. Twenty started on leuprorelin sc/im 0.3 mg/kg/month plus anastrozole 1 mg/d p.o. (group-A, C-A) and 20 on leuprorelin (group-B, C-B) for 2 years or until the age of 10 years. Groups did not differ in age, height, BMI, bone age advancement (BAA), and distance of PAH from TH. Follow-up was at 6, 12, 18, and 24 m. RESULTS: Reduction in BAA was significantly higher in group-A compared to group-B already by 6 m. Despite the transiently significant decrease in height velocity in group-A, gain in PAH SD was almost double by 12 and 18 m vs group-B and reached the maximum of +1.21 ± 0.45 (7.51 cm) vs +0.31 ± 0.37 (1.92 cm, p = 0.001) in group-B at 24 m. Group-A had no clinical or biochemical hyperandrogenism, unchanged normal bone density, and lumbar spine X-rays. CONCLUSION: The co-administration of anastrozole with leuprorelin safely improves PAH in girls with compromised growth.

L-dopa is a potent stimulator of cortisol in short children.

AIMS: In this study, we evaluated the diagnostic usefulness of oral L-dopa as a stimulatory agent for cortisol. METHODS: In 27 short children that were evaluated for possible growth hormone deficiency (GHD), the levels of serum GH and cortisol were determined after oral L-dopa administration and after i.m. glucagon administration. We defined cortisol concentrations >18 µg/dl (496 nmol/l) as adequate response. Peak GH concentration <10 ng/ml in both tests defined GHD. RESULTS: Twenty-five out of the 27 children (93%) studied showed a normal cortisol response, i.e. a peak serum cortisol >18 µg/dl in the L-dopa test, whereas 19 children (70%) had a normal cortisol response after stimulation with glucagon. In the children with normal cortisol response in both tests, the mean peak serum cortisol concentration was 28.7 (SD 1.59) after L-dopa and 26.65 (SD 1.26) µg/dl after glucagon administration. There was no statistically significant difference in peak serum cortisol response to L-dopa between GH-deficient and GH-sufficient children [25.90 (SD 4.9) vs. 29.87 (SD 9.9) µg/dl, respectively]. CONCLUSIONS: These results clearly suggest that L-dopa administration is a potent stimulus for cortisol secretion at least in short children.

Genetic assessment of familial and early-onset Parkinson's disease in a Greek population.

BACKGROUND AND PURPOSE: Although the first mutation associated with Parkinson's disease (PD) was identified several years ago in the alpha-synuclein (SNCA) gene in families of Greek and Italian ancestry, a more systematic study of this and other known PD mutations has not been performed in the Greek population. METHODS: A genetic analysis in 111 familial or sporadic with early-onset (≤50 years, EO) PD patients was performed for the presence of the A53T SNCA mutation. In separate subgroups of these patients, further mutations in the SNCA, LRRK2, Parkin, PINK1 and DJ-1 genes were searched for. Additionally, a subgroup of familial cases was analysed for mutations in the glucocerebrosidase (GBA) gene. RESULTS: In total, five patients (4.5% of our whole population) were identified with the A53T SNCA mutation, two with a heterozygote dosage mutation and one with a heterozygote point mutation in the Parkin gene, and seven patients (10.3% of our familial cohort) with GBA gene mutations. CONCLUSIONS: The A53T mutation in the SNCA gene, although uncommon, does represent a cause of PD in the Greek population, especially of familial EOPD with autosomal dominant inheritance. GBA mutations in the familial cohort tested here were as common as in a cohort of sporadic cases previously examined from the same centres. For the remainder of the genes, genetic defects that could definitively account for the disease were not identified. These results suggest that further Mendelian traits that lead to PD in the Greek population remain to be identified.

A network meta-analysis of randomized controlled trials for comparing the effectiveness and safety profile of treatments with marketing authorization for relapsing multiple sclerosis.

WHAT IS KNOWN AND OBJECTIVE: The relative effectiveness and safety profile of the treatments with marketing authorization for relapsing multiple sclerosis (MS) are not well known because randomized controlled trials with head-to-head comparisons between these treatments do not exist. Thus, a network of multiple-treatments meta-analysis was performed using four clinical outcomes: 'patients free of relapse', 'patients without disease progression', 'patients without MRI progression' and 'patients with adverse events'. METHODS: Randomized controlled trials (RCTs) on MS were systematically searched in PubMed and Cochrane Central Register of Controlled Trial. The network analysis performed pairwise comparisons between the marketed treatments (Betaferon 250mcg, Avonex 30mcg, Rebif 44mcg, Rebif 22mcg, Aubagio 7 mg, Aubagio 14 mg, Copaxone 20 mg, Tysabri 300 mg, Gilenya 0·5 mg and Novantrone 12 mg/m(2)) using direct and indirect analyses. RESULTS AND DISCUSSION: The analysis included 48 articles, involving 20 455 patients with MS. The direct analysis showed better response for more than one outcome for Gilenya compared with Avonex ('patients free of relapse' and 'patients without MRI progression') and for Betaferon compared with Avonex ('patients without disease progression' and 'patients without MRI progression'). The indirect analysis indicated that Tysabri may have better relative effectiveness compared with the other treatments for two outcomes: 'patients free of relapse' and 'patients without MRI progression'. Regarding 'patients with adverse events', no data were available for all comparisons to make fair inferences. WHAT IS NEW AND CONCLUSION: This was an attempt, for the first time, to compare the efficacy and safety profile of existing approved treatments for relapsing MS. Although some treatments have shown better response, the results of the network analysis should be interpreted with caution because of the lack of RCTs with head-to-head comparisons between treatments.

MTHFR C677T polymorphism modifies the effect of HRT on metabolic parameters in postmenopausal women.

OBJECTIVE: To assess the interaction of the MTHFR C677T polymorphism with changes in lipid and glucose metabolism effected by oral hormone replacement therapy (HRT) in postmenopausal women. METHODS: In this open-label, prospective, interventional study, parameters of lipid and glucose metabolism, as well as homocysteine, were assessed in 97 postmenopausal women at baseline and 1 year after the initiation of HRT. Participants were stratified into three subgroups, according to the MTHFR C677T polymorphism (wild-type: CC genotype; heterozygous: CT genotype; homozygous for the mutant variable: TT genotype). RESULTS: The TT genotype was associated with an elevation of total and low density lipoprotein (LDL) cholesterol, while CT and CC genotypes were associated with a reduction of total cholesterol and LDL cholesterol after 1 year of HRT (p = 0.032 for total cholesterol and p = 0.002 for LDL cholesterol). Women with the TT genotype had higher glucose levels in contrast to women with the CC genotype who had lower glucose levels after 1 year of HRT (p = 0.011). Additionally, CC carriers under HRT had a significant elevation of apolipoprotein A1 levels (p = 0.018), contrarily to CT and TT genotypes. CONCLUSION: While HRT was associated with favorable changes in lipid and metabolic parameters in carriers of the CC genotype, this effect was not evident in carriers of the T allele. The MTHFR C677T polymorphism may modify the effect of HRT on lipid and metabolic parameters in postmenopausal women.

The proinflammatory mediator's production from ischemic brain during carotid endarterectomy.

AIM: The aim of the study was to determine the quantity of produced mediators of inflammation (cytokines and eicosanoids), during carotid endarterectomy (CEA), which are factors of ischemic damage of the brain. METHODS: Two groups (A and B) of 15 patients each, with internal carotid backpressure >30 mmHg were operated in our institution. We did not use a shunt in Group A during CEA and group B was operated upon with a shunt. Plasma concentrations of Interleukin-1b (IL-1b), Thromboxane B2 (TXB2), Prostaglandin E2 (PGE2) and tumor necrosis factor-a (TNFa) were measured by enzyme-linked immunosorbent assay (ELISA) technique. RESULTS: We measured gradual increase of levels of IL-1b and TXB2 during cross-clamping and during reperfusion in group A (P<0.05). The levels of TNFa increased only during reperfusion (P<0.05). The concentration of IL-1b and TNFa remained almost stable in group B, whereas the concentration of TXB2 reduced but not significantly (P>0.05). The levels of PGE2 remained stable in both groups. CONCLUSION: We should consider the increase of proinflammatory mediators during carotid cross-clamping when no shunt is used. The critical concentration of these mediators that threaten the brain's vitality is not yet detected. However, the clinical significance of this is unclear, since there were no perioperative strokes.

Effects of buflomedil on skin blood flow in patients with type 2 diabetes mellitus without overt micro- or macroangiopathy.

AIM: The aim of this study was to assess the effects of buflomedil on the peripheral microcirculation in patients with type 2 diabetes mellitus (T2DM) without overt micro- or macroangiopathy. METHODS: Twenty-three patients with T2DM were randomly assigned to receive buflomedil 600 mg/day for six months (N.=12) or no medication (N.=11). Skin blood flow in the lower limbs was assessed at baseline and after 3 and 6 months using Laser Doppler. We measured the following laser Doppler parameters: volume, flow and velocity. RESULTS: In patients treated with buflomedil, there was a significant increase in volume (P=0.039) and a trend for an increase in both flow and velocity (P=0.097 for both parameters). In contrast, significant decreases in volume and flow were observed in the control group (P=0.045 and P=0.027, respectively) whereas velocity did not change (P=0.150). CONCLUSION: In conclusion, buflomedil appears to have a beneficial effect on the peripheral microcirculation in patients with T2DM.

Semapimod a new pretreatment modality of acute intestinal ischemia-reperfusion syndrome: experimental study in rabbits.

AIM: Semapimod is an experimental drug that strongly inhibits macrophages and stimulates the cholinergic anti-inflammatory pathway. The aim of this study was to evaluate the effect of semapimod on experimentally-induced acute intestinal ischemia-reperfusion syndrome in rabbits. METHODS: The experimental protocol included 16 adult male White New Zealand rabbits divided into two equal groups, A and B. Animals were subjected to 150 min of intestinal ischemia, followed by 30 min of reperfusion. At 30, 90 and 150 min after the onset of ischemia the animals in group A received i.v. placebo (2 mg/kg; Cytokine PharmaSciences Inc, PA, USA) and those of group B received i.v. semapimod (2 mg/kg; Cytokine PharmaSciences Inc, PA, USA). Blood samples were taken for plasma measurements of tumor necrosis factor-a (TNF-a), interleukin 1ß (IL-1ß) and interleukin 6 (IL-6) at 0, 60, 120 and 180 min after the onset of ischemia. At the same time points, wedge intestinal biopsies were taken for histopathological evaluation of mucosal injury. All data were analyzed by the non-parametric Mann-Whitney test as appropriate. The power effect of Semapimod was evaluated by mixed between-within Anova statistical analysis. RESULTS: Measurements of TNF-a and IL-1ß levels showed significant differences between groups A and B at 120 min (P=0.004 and P=0.003 respectively) and at 180 min (P=0.001 and p<0.005 respectively). IL-6 values were lower in animals of group B but the differences were not significant. Intestinal mucosal injuries were significantly milder in animals of group B at 120 and 180 min CONCLUSION: Semapimod minimized intestinal mucosa injury and reduced the systemic inflammatory response during acute intestinal ischemia-reperfusion. Further studies are required to investigate the possible value of semapimod as a new pretreatment modality in acute vascular abdomen.

Preoperative withdrawal of antiplatelet treatment in lower limb vascular patients prior to surgical management under epidural or spinal anaesthesia: an evidence based approach and systematic review.

Antiplatelet drugs given to high risk patients for secondary prevention of cardiovascular disease are frequently withdrawn prior to surgical or diagnostic procedures to reduce bleeding complications. This is also the case for many patients undergoing lower limb vascular surgery via spinal or epidural anaesthesia. The aim of this study is to corroborate the clinician's decision for discontinuing or continuing the anti-platelet treatment in these patients perioperatively. We screened MEDLINE and Scopus (January 1980 - July 2007) with additional manual cross-referencing for clinical studies, surveys on the opinions of doctors and guidelines according to Evidence Based Medicine rules. One randomized controlled trial, 2 meta-analyses, 1 prospective and 4 retrospective studies as well as 6 esteemed medical societies'" guidelines all conclude that there is no justification for the discontinuation of aspirin and NSAIDs prior to neuraxial anesthesia. However, for other antiplatelet drugs like ticlopidine, clopidogrel, abciximab, eptifabatide and tirofiban not enough data exist to support their continuation through the procedure. Therefore, their preoperative withdrawal is suggested 8 hours to 14 days prior, accordingly. The existing evidence does not justify the discontinuation of aspirin and NSAIDs before the intended procedure. Anesthesiologists and surgeons should be aware of the cardiovascular risks of withdrawal versus the non - evidence based benefit in hemorrhage complications.

Hemodynamic follow-up of iliofemoral venous thrombosis.

AIM: The aim of this pilot study was to assess the venous hemodynamic changes after deep venous thrombosis (DVT) using air-plethysmography (APG) and to study the rate and magnitude of these changes in relation to those associated with the post-trombotic syndrome. METHODS: Twenty limbs of 19 patients with acute iliofemoral thrombosis have been followed up with APG and Duplex scanning for 24 months. Patients were treated with anticoagulation and elastic stockings. The air-plethysmographic measurements of venous outflow and functional venous volume were measured on admission. These measurements, as well as venous reflux and calf muscle pump ejecting capacity, have been performer after one week, one month and 3, 6, 12, 18 and 24 months. The results were compared with similar measurements of 10 normal limbs and 10 post-thrombotic limbs with chronic venous ulcers. Duplex scanning was performed on admission, in six and 24 months. RESULTS: Plethysmographic parameters showed a dramatic improvement in the first month, fast improvement after three months and slower improvement thereafter, with the exception of the development of marked venous reflux in five of the 20 limbs studied, in the first three months. Popliteal reflux was diagnosed in these limbs. Elastic compression protected the patent veins from overdistention and incompetence and contributed to the relatively good calf muscle pump function during the first year after DVT. By the end of the study no patient had post-thrombotic changes, but four patients needed elastic stockings in order to avoid edema. CONCLUSIONS: The most important hemodynamic alterations occurred during the first three months after DVT. This is the crucial period during which conservative treatment needs to be improved. Further work is required in this field to study the effect of various newly emerging methods. The air-plethysmographic measurements described may become surrogate endpoints for testing different therapies.

Buflomedil: potential new indications for an old agent.

Our understanding of vascular pathophysiology has significantly improved during the past two decades. Patients with type 2 diabetes mellitus have an increased vascular risk and a series of modifiable risk factors play a crucial role in the atherosclerotic process. The microvascular dysfunction in diabetes results in increased vascular permeability and impaired regulation of blood flow and vascular tone. These changes culminate in nephropathy, retinopathy and neuropathy and probably contribute to the increase vascular morbidity and mortality in this population. Moreover, studies in the skin microvasculature suggest that this microvascular dysfunction contributes significantly to the pathogenesis of diabetic foot. Several studies showed a beneficial effect of vasoactive drugs, including buflomedil, in non-diabetic patients. However, it remains to be established whether these drugs could also be beneficial in the diabetic population, especially in the early stages of diabetes.

Stem cell therapy in stroke.

Recent work has focused on cell transplantation as a therapeutic option following ischemic stroke, based on animal studies showing that cells transplanted to the brain not only survive, but also lead to functional improvement. Neural degeneration after ischemia is not selective but involves different neuronal populations, as well as glial and endothelial cell types. In models of stroke, the principal mechanism by which any improvement has been observed, has been attributed to the release of trophic factors, possibly promoting endogenous repair mechanisms, reducing cell death and stimulating neurogenesis and angiogenesis. Initial human studies indicate that stem cell therapy may be technically feasible in stroke patients, however, issues still need to be addressed for use in human subjects.

S-shaped ilio-mesenteric bypass in a young high risk patient.

Symptomatic chronic mesenteric ischemia is a rare condition. Several surgical and endovascular techniques have been described, but treatment is individualized according to the conditions of each patient. We report a successful superior mesenteric artery revascularization by using an S-shaped retrograde polytetrafluoroethylene ilio-mesenteric bypass graft in a young overweight patient with a history of two abdominal vascular operations and several comorbidities.

The use of mice and rats as animal models for cardiopulmonary resuscitation research.

Cardiopulmonary resuscitation (CPR) after the induction of cardiac arrest (CA) has been studied in mice and rats. The anatomical and physiological parameters of the cardiopulmonary system of these two species have been defined during experimental studies and are comparable with those of humans. Moreover, these animal models are more ethical to establish and are easier to manipulate, when compared with larger experimental animals. Accordingly, the effects of successful CPR on the function of vital organs, such as the brain, have been investigated because damage to these vital organs is of concern in CA survivors. Furthermore, the efficacy of several drugs, such as adrenaline (epinephrine), vasopressin and nitroglycerin, has been evaluated for use in CA in these small animal models. The purpose of these studies is not only to increase the rate of survival of CA victims, but also to improve their quality of life by reducing damage to their vital organs after CA and during CPR.

Percutaneous endovascular management of a splenic artery aneurysm.

Splenic artery aneurysms are extremely rare lesions. Elective repair of these aneurysms is justified only if the aneurysm's size is greater than 2 cm and the predicted peri-operative mortality is below 0.5%. Percutaneous techniques minimise the peri-operative morbidity and mortality rates and offer a safe and effective treatment option. We report a coil-embolisation of a 5.1 cm splenic artery aneurysm and a short review of the literature concerning the endovascular treatment options.

Prevalence of overweight and obesity in young Greek men.

We determined the prevalence of overweight and obesity in young Greek men in 2006 and examined variations related to their place of residence and educational level. Body height and weight were measured in 2568 conscripts of the Greek army, aged 19-26 years. The calculated body mass index (BMI, kg m(-2)) was correlated to their socio-demographic characteristics, i.e. level of education and place of residence (urban or rural). Overweight and obesity were defined according to the World Health Organization classification. Mean BMI (standard deviation) of the conscripts was 24.7 (4.2). The prevalence of overweight (30 > BMI > or = 25 kg m(-2)) was 28.5% and correlated positively with a higher educational level, whereas the prevalence of obesity (BMI > or = 30 kg m(-2)) was 10.4% and correlated positively with a lower educational level. Our data were compared with those of similar studies performed in the years 1969: BMI 23.8 (1.4) (P < 0.0001) and 1990: BMI 23.8 (2.9) (P < 0.0001), showing a positive secular trend for BMI in Greek conscripts in the last 16 years. In conclusion, we documented an alarmingly high prevalence of overweight and obesity among young Greek men.