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.

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.

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.

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.

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.

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.

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.

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.

Periodontal and atherosclerosis-induced diseases.

AIM: This article reviews the available studies assessing the association between chronic inflammatory periodontal diseases with atherosclerosis-induced diseases, cardiovascular diseases, and their complications, using standard evidence based criteria. METHODS: This study is based on a literature search using Medline medical database covering the period from 2001 to April 2006 and applying specific inclusion criteria. The authors reviewed randomized controlled trials, systematic reviews, narrative reviews and meta-analyses, which investigated the relationship of periodontal and cardiovascular diseases with clinically derived documentation. The critical evaluation of the studies was performed based on the Impact Factor of the journals, on which they were published. RESULTS: On the basis of clinical aspects, the periodontitis-cardiovascular association was evaluated in 2 randomized controlled trials, 5 systematic reviews, 5 narrative reviews and 2 meta-analyses. The evidence linking periodontitis with an increased risk for cardiovascular disease and atherosclerosis is limited. CONCLUSION: Current evidence supporting the causal, periodontitis-cardiovascular disease, association is weak. There is a clear need for new, well designed observational and intervention studies to confirm that thus far observed associations explore the validity of the associations in diverse populations, to establish whether they are causal in nature and determine potential benefits of periodontal intervention in reducing the risk for these medical conditions.

Hyperhomocysteinemia and hypercoagulable state in carotid plaque evolution. Novel risk factors or coincidental risk predictors?

AIM: The majority of patients with carotid occlusive disease (COD) have one or more of the conventional risk factors of atherosclerosis. In addition, hyperhomocysteinemia (HHCY) and hypercoagulable state (HCGS) are increasingly recognized as potentially ''novel'' risk factors. The aim of this study was to determine the role of these factors in carotid plaque evolution and clinical manifestation of COD. METHODS: Between September 2003 and 2005, 153 patients were admitted in our Department with clinical and duplex ultrasound evidence of severe (>70%) COD as operative candidates and 33 patients with evidence of moderate (50-69%) stenosis included in the protocol of conservative treatment and lifelong observation. Conventional risk factors of atherosclerotic disease and plasma levels of homocysteine (HCY), fibrinogen (FBG), protein C (PC), protein S, antithrombin III and activated protein C resistance were recorded in all patients. The degree of carotid stenosis was measured in a carotid angiogram following North American Symptomatic Carotid Endarterectomy Trial (NASCET) criteria for all operative candidates. Angiographic workup revealed 147 carotid stenoses >70% and 16 internal carotid occlusions in 82 symptomatic and 52 asymptomatic patients, while in 19 patients the carotid stenosis was moderate (50-69%) and these patients included in the conservative treatment group. The study of the ''novel'' and conventional risk factors was performed with univariate and multivariate statistical analysis as well as with correlational analysis of HCY and the other risk factors between patients with severe or moderate COD and between symptomatic and asymptomatic patients with carotid stenosis >70%. RESULTS: Our data showed that HHCY was a strong independent risk factor of symptomatic carotid disease >70%. In addition, the coexistence of high FBG levels and thrombophilia factor deficiency with HHCY was significantly related with the clinical manifestation of COD. CONCLUSION: HHCY and HCGS are often detected among patients with severe and symptomatic carotid stenosis. The early diagnosis and treatment of these deficiencies might be helpful for the management of COD, but their role in future clinical practice is yet to be determined.

Carotid artery disease in octogenarians: endarterectomy or stenting?

AIM: Carotid endarterectomy (CEA) is the gold standard for the treatment of carotid stenosis, but carotid angioplasty and stenting (CAS) has emerged as a potential less invasive therapeutic alternative to patients who would otherwise be considered as high risk for open surgery. The aim of this review was to pool the most current studies of the growing body of literature in which outcomes of CEA or CAS are compared in octogenarians and non-octogenarians to determine the current safety and efficacy of these therapeutic procedures, due to a lack of randomized controlled trials. METHODS: An electronic search of Medline, PubMed and Cochrane databases was supplemented by a review of bibliographies of relevant articles, as well as manual searches of relevant journals. Outcomes included 30-day stroke rate, death rate, combined stroke/death rate and myocardial infarction rate between octogenarians and non-octogenarians. RESULTS: Randomized clinical trials or studies comparing CEA and CAS in the same study population were not identified. CEA and CAS outcomes, in octogenarians compared to younger cohorts, were evaluated in 10 and 5 studies, respectively. Analysis of data indicates no significant difference in adverse events reported in the two groups in the majority of studies of CEA, as opposed to the findings of CAS studies. CONCLUSION: The current review supports the viewpoint that CEA remains the standard of care in octogenarians, towards which other procedures to prevent stroke should be compared. It also challenges the definition of the ''high-risk''/age blanket classification and suggests that until the longevity, safety and efficacy of CAS is established, wide applicability of CAS to such ''high-risk'' patients should be questioned and limited to ongoing controlled clinical trials.

Comparative study of intravenous amiodarone and procainamide in the treatment of atrial fibrillation of recent onset.

AIM: The aim of the present study was to compare the safety and efficacy of amiodarone and procainamide in the acute cardiology setting. METHODS: The study population consisted of 223 patients with symptomatic atrial fibrillation (AF). After administration of digoxin for ventricular rate control, all patients who failed to restore sinus rhythm (SR) were randomized into 2 groups: group A (113 patients) were administered 300 mg amiodarone intravenously over 30 min and, in case of failure to restore SR, amiodarone of 20 mg/kg/24 h was administered intravenously. Group B (110 patients) were intravenously administered a bolus dose of 1 gm procainamide, at an infusion rate 50/mg/min, and, in case of failure to restore SR, 2 mg/min for the next 24 h. RESULTS: The rate of cardioversion to SR was similar between amiodarone (81.4%) and procainamide (82.7%) (P=NS). Procainamide loading recorded faster cardioversion times than amiodarone loading (P=0.02), but there was no significant difference after that. Amiodarone caused a significant decrease on systolic blood pressure compared to procainamide for the first 18 h (P<0.001), and a significant decrease in the diastolic blood pressure for the first 6 h (P<0.001). Side-effects for either medication were sparse. The only real prognostic factor for successful cardioversion remains the size of left atrium. CONCLUSION: Both drugs were equally effective in restoring SR, though procainamide acts quicker in the loading phase. Both medications are safe and side effects develop only in the maintenance phase.

Current therapeutic options in the management of superficial femoral artery occlusive disease.

The management of superficial femoral artery occlusive disease remains challenging for vascular surgeons. Despite the advances and dramatic changes we have seen in modern practice with the development and introduction of new endovascular techniques, long-term results with these interventions remain disappointing when compared to the "gold standard" of a vein bypass with a good run-off. Furthermore, there is little Level 1 evidence to guide us with regards to the best treatment strategy. In this article, we review some of the currently available open surgical and endovascular options for the management of superficial femoral artery disease.

Nuclear reprogramming and adult stem cell potential.

Cell-based therapy may represent a new strategy to treat a vast array of clinical disorders including neurodegenerative diseases. Recent observations indicate that adult somatic stem cells have the capacity to contribute to the regeneration of different tissues, suggesting that differentiative restrictions are not completely irreversible and can be reprogrammed. Cell fusion might account for some changed phenotype of adult cells but it seems to be biologically irrelevant for its extreme rarity. Other experimental evidences are compatible with the hypothesis of wide multipotency of well-defined stem cell populations, but also with transdifferentiation and/or dedifferentiation. Further studies on nuclear reprogramming mechanisms are necessary to fulfil the promise for developing autologous cellular therapies.

Celiac artery aneurysm associated with atherosclerotic common hepatic artery stenosis.

Celiac artery aneurysms are rare vascular lesions and represent 4% of all splanchnic aneurysms. Media degeneration and atherosclerosis are the most common underlying etiologic factors. The risk of rupture and the associated mortality rate are 13% and 40% respectively. In contrast, elective repair carries a low mortality rate of 5%. Most of celiac artery aneurysms are asymptomatic and in the past nearly 80% of the cases were diagnosed when ruptured. Recently, there is an increased recognition of all splanchnic aneurysm types, probably because of better diagnostic techniques. We report a case of celiac artery aneurysm with severe atherosclerotic stenosis of the common hepatic artery. We performed, through a midline supraumbilical laparotomy, extended partial aneurysmectomy and common hepatic artery ostium endarterectomy. For the closure we used Dacron patch. The uncomplicated postoperative patient's course, with no evidence of liver dysfunction and excellent patency of the common hepatic artery, suggests that this technique offered good results and minimized the perioperative risk.

Screening transvaginal uterine ultrasonography for identifying endometrial pathology in postmenopausal women.

BACKGROUND: During the last decade, transvaginal ultrasonography (TVS) has become a widely-used technique for the evaluation of endometrial histology. The purposes of this study were to compare transvaginal sonographic evaluation of the endometrium with histology obtained by endometrial biopsy in asymptomatic postmenopausal women and to determine whether screening transvaginal sonography might be useful in the evaluation of postmenopausal women. MATERIALS AND METHODS: The study included 59 unselected asymptomatic postmenopausal women who attended the outpatients' clinic for annual cervical cytology at Ioannina University Hospital, Greece. The women were evaluated by transvaginal scans, performed immediately before endometrial biopsy. RESULTS: In the 43 women with a histopathological diagnosis of normal endometrium/inadequate for assessment/atrophy, the mean endometrial thickness was 5.1 +/- 3.3 mm (range 0.8-13.8 mm) whereas the corresponding value in the 16 women with abnormal findings was 17.6 +/- 4.3 mm (range 9.4-24.6 mm) (p<0.001). If a 9-mm cut-off limit was used for endometrial thickness, the sensitivity, specificity and positive predictive value were 100%, 90.69% and 80%, respectively. CONCLUSION: TVS is a sensitive test for determining endometrial disease in asymptomatic postmenopausal women. However, well-designed studies should be conducted, completed, analysed and validated before a mass-screening program using TVS is implemented.

Transvaginal uterine ultrasonography compared with endometrial biopsy for the detection of endometrial disease in perimenopausal women with uterine bleeding.

BACKGROUND: Almost 70% of all gynecological consultations in perimenopausal women are related to irregular uterine bleeding. In this prospective study, we compared endometrial assessment by transvaginal ultrasonography (TVS) in perimenopausal women with irregular uterine bleeding to histological assessment and tested whether the TVS was effective as a diagnostic tool for the detection of endometrial pathology in these women. MATERIALS AND METHODS: Eighty consecutive perimenopausal women complaining of irregular uterine bleeding participated in the study. The women were evaluated by transvaginal scans, performed immediately before endometrial biopsy. The ultrasonographic results were compared with the histological diagnosis obtained from the endometrial biopsy. RESULTS: Sixty-seven out of 80 women (83.7%) had normal histological findings, whereas 13 (16.3%) had abnormal findings. No endometrial cancer was diagnosed in this cohort of women. In the 67 women with a histological diagnosis of normal endometrium, mean+/-SD endometrial thickness was 10.5+/-4.0 mm (range 4.0-18.5 mm), whereas the corresponding value in the 13 women with abnormal findings was 18.7+/-3.8 mm (range 13.5-22.5 mm). If a 13 mm cut-off limit was used for endometrial thickness, which would include all abnormal cases, the sensitivity, specificity and positive predictive values were 100%, 71.64% and 40.62%, respectively. CONCLUSION: TVS can identify women with perimenopausal bleeding in which the likelihood of endometrial pathology is high and in which tissue sampling should be performed. Thus, TVS can be a primary method of selecting women with perimenopausal bleeding who must be further investigated with more invasive methods such as endometrial biopsy.