Influence of cerebral embolism on brain monoamines

In baboons the right cerebral hemisphere was embolised by a shower of microemboli, immediately followed by one large embolus designed to occlude the middle cerebral artery (MCA). One hour after embolism a significant, though small, reduction in blood flow and oxygen consumption of the embolised hemisphere was recorded, at which time the animals were killed and brain monoamines measured. Dopamine was reduced in the ipsilateral caudate nucleus, the reported site of maximal ischaemic damage in this model. Dopamine levels were increased in frontal and occipital grey matter sampled from areas surrounding the occluded MCA territory and in similar brain areas of the opposite non-embolised hemisphere. Noradrenaline was increased in grey matter from both cerebral hemispheres, as well as subcortical structures bilaterally. Brain 5-hydroxytryptamine levels were unaltered, but increased 5-hydroxyindoleacetic acid in cisternal cerebrospinal fluid suggested transient alteration in 5-hydroxytryptamine metabolism after embolism. The effects of cerebral embolism on brain monoamine metabolism appear to be different from the effects of permanent surgical occlusion of major cerebral vessels. The bilaterality of effects after unilateral hemispheric embolism might be related to diaschisis. The mechanisms of the observed changes, as well as their relevance to the progression of cerebral ischaemia and the complications associated with cerebral embolism, still require to be established.     

Medical treatments of hyperactive child: about the new pharmaceutical forms of methylphenidate marketed in France]

Multimodal treatment of hyperactive child includes psychostimulant medication, methylphenidate (MPH) marketed in France in its short-acting form since about ten years. We report our clinical experience about the first fifty methylphenidate responders who received one of the two sustained-release forms available since summer 2004, tablets of oros-methyphenidate (Concerta LP) or microgranule-filled capsules (Ritaline LP).     

Psychosis, migration and social environment: an age--and--gender controlled study.

PURPOSE: Adverse social experiences are frequently invoked to explain the higher rate of psychosis among migrant groups. The aim of the present study was to establish the socio-environmental factors distinguishing migrant psychotic patients from autochthonous patients. SUBJECTS AND METHOD: We conducted a cross-sectional survey involving 341 migrant psychotic patients matched for age and gender with 341 autochthonous psychotic patients. RESULTS: Migrant patients lived more often with their parental family, were less often enrolled with a referral psychiatrist, presented a lower rate of employment, a lower percentage of alcohol misuse and of suicide attempts. DISCUSSION: Our findings add to the growing body of results showing that more attention needs to be focused on socio-environmental variables in psychosis research. However, several limitations have to be taken into account, particularly with regard to selection biases and age of onset of the psychotic illness. CONCLUSION: Our results are compatible with the hypothesis that unemployment is a contributing factor in the risk for psychosis among migrant groups. Migrants' families are an important keystone in the mental health care process of their sick relatives. Our service models need to be adapted with the aim to make the treatment easier for migrant patients.     

Sindbis virus replicon particles encoding calreticulin linked to a tumor antigen generate long-term tumor-specific immunity

Alphavirus vectors have emerged as a promising strategy for the development of cancer vaccines and gene therapy applications. In this study, we used the replication-defective vaccine vector SIN replicon particles from a new packaging cell line (PCL) to develop SIN replicon particles encoding calreticulin (CRT) linked to a model tumor antigen, human papillomavirus type 16 (HPV16) E7 protein. The linkage of CRT to E7 in SIN replicon particles resulted in a significant increase in E7-specific CD8(+) T-cell precursors and a strong antitumor effect against E7-expressing tumors in vaccinated mice. SINrep5-CRT/E7 replicon particles enhanced presentation of E7 through the major histocompatibility complex (MHC) class I pathway by infecting dendritic cells (DCs) directly and pulsing DCs with lysates of cells infected by SINrep5-CRT/E7 replicons. Vaccination of immunocompromised (BALB/c nu/nu) mice with SINrep5-CRT/E7 replicon particles also generated significant reduction of lung tumor nodules, suggesting that antiangiogenesis may contribute to the antitumor effect of SINrep5-CRT/E7 replicon particles. Furthermore, SINrep5-CRT/E7 replicon particles generated long-term in vivo tumor protection effects and antigen-specific memory immunities. We concluded that the CRT strategy used in the context of SIN replicon particles facilitated the generation of a highly effective vaccine for cancer prophylaxis and immunotherapy.     

The stereotactic body radiation therapy: initiation and clinical program]

We fully describe an innovative radiotherapy technique called Stereotactic Body Radiation Therapy (SBRT), and explain how this technique is commonly used for clinical purpose at the anticancer center Léon-Bérard (Lyon, France). In this technique, a non-invasive stereotactic body frame is used to locate the tumor site with a great precision. This frame is combined with a system, which enables to track the respiratory motions (Active Breathing Control (ABC) or diaphragmatic compression (DC)) in order to reduce the treatment margins for organ motion due to breathing. Thus, the volume of normal tissues that will be irradiated is considerably reduced. The dosimetry is realized with 3 CT exams performed in treatment conditions. The 3D patient "repositioning" is done with a volume CT acquisition (kV) combined with orthogonal images (kV and MV). The SBRT requires a system to limit the organ motions. Although the ABC seems to be more fastidious for patient, it would enable to use smaller margins than with DC technique. Nevertheless, the ABC is not compatible with volume CT acquisitions, which considerably improve the patient repositioning. In conclusion, the quality of repositioning and the high level of conformation enable to deliver high equivalent doses (>100 Gy) in hypofractionated mode, without increasing the treatment toxicity. The SBRT employs the last technologic innovations in radiotherapy and is therefore considered as a new efficient tool for solid tumors treatment.     

Hydroxyethylstarch microcapsules: a preliminary study for tumor immunotherapy application

The objective of this work was to prepare microcapsules which would allow protection and slow release of antigens used for melanoma immunotherapy treatment. Hydroxyethylstarch (HES) microcapsules were prepared using interfacial cross-linking with terephthaloyl chloride (TC). They were characterized with respect to morphology (microscopy) and size (in the 4-15 microm range). Bovine serum albumin (BSA) was used as model protein for loading and release studies. Microcapsules were loaded with solutions at different protein concentrations (0.5-5%). The maximum loading efficiency (20%) was observed with the concentration of 2.5%, which allowed a loading capacity near 100%. Confocal laser scanning microscopy (CLSM) visualization showed that BSA was entrapped within the microcapsules and not only associated to their outer surface. BSA-release studies showed a 20% BSA release within 30 min while 80% remained entrapped in the microcapsules for 4 days. Microcapsules were degraded by alpha-amylase and addition of esterase to alpha-amylase enhanced slightly their degradation. In vitro studies on melanoma cells showed that HES microcapsules were non-toxic. Preliminary in vivo studies demonstrated that microcapsules were biodegradable after intraperitoneal injection (i.p.). The observation of peritoneal wash showed a complete degradation within 7 days, indicating a possible application as an in vivo drug delivery system especially to enhance the presentation of antigens.     

Long-term outcome of combined penetrating keratoplasty and vitreoretinal surgery using temporary keratoprosthesis

PURPOSE: To evaluate the long-term outcome of combined penetrating keratoplasty (PKP) and vitreoretinal surgery using temporary keratoprosthesis (TKP). METHODS: A retrospective study of 107 eyes with coexisting corneal and vitreoretinal diseases that underwent combined PKP and vitreoretinal surgery using TKP. Corneal graft clarity, intraocular pressure, and anatomical reattachment of retina were followed. RESULTS: The mean follow-up time was 25 months, the longest being 8 years. Successful surgical outcome was defined as maintenance of clear graft, anatomic reattachment of retina, and controlled intraocular pressure. A total of 78 eyes (72.9%) fulfilled these criteria. Surgical intervention within 1 month of ocular injury was associated with higher success rate (81.9%) than intervention at 1 month or more after injury (54.3%). Success rate for reattachment of retina was 95.8% when preoperative proliferative vitreoretinal retinopathy (PVR) was absent compared with 83.1% when preoperative PVR was present. Unsatisfactory postoperative visual acuity was due to graft failure, recurrent PVR, or secondary glaucoma. CONCLUSION: Combined PKP and vitreoretinal surgery is best performed within 1 month of ocular injury for best surgical outcome. Careful selection of cases plays an important role in reducing the risks of complications. TKP is a useful adjunct in the surgery.     

Sweet hyperopia: refractive changes in acute hyperglycemia

PURPOSE: A prospective study was performed to evaluate refractive and ocular biometric changes in acute hyperglycemic status in patients with diabetes mellitus. METHODS: From January to August 2002, 48 eyes of 24 patients with persistent diabetes and a plasma glucose level>or=17 mmol/L or HbA1c>or=10.0% on admission were enrolled in this prospective study. Upon admission to Tri-Service General Hospital in Taipei, Taiwan, these patients underwent intensive glycemic control. The basic ophthalmic examinations, including visual acuity, intraocular pressure measurement, slit lamp, and fundus examinations, were conducted. The ocular parameters including refraction, anterior chamber depth, lens thickness, axial length, mean keratometry, and thinnest corneal thickness were evaluated by A-mode scan and Orbscan II. Each patient underwent clinical follow-up visits at 1, 2, and 4 weeks after the acute hyperglycemic episode. RESULTS: Of the 24 patients, 18 were male and 6 were female. The mean age of the patients was 55 years (range: 38 to 69). Comparing the refractive status on admission and at week 4, the authors found that 8 cases (16 eyes, 33%) showed hyperopia during hyperglycemia (+1.9+/-0.8 D), but in the other 16 cases (32 eyes, 67%), there were no significant changes. In addition, there were also no significant changes in anterior chamber depth, lens thickness, axial length, thinnest corneal thickness, or mean keratometry in the follow-up period. CONCLUSIONS: Transitory hyperglycemia produces hyperopia. The alteration in refractive index in the lens may contribute to the hyperopic change, but no change of ocular biometrics in lens or cornea is observed.     

Plasma and dietary carotenoid, retinol and tocopherol levels and the risk of gastric adenocarcinomas in the European prospective investigation into cancer and nutrition

Despite declining incidence rates, gastric cancer (GC) is a major cause of death worldwide. Its aetiology may involve dietary antioxidant micronutrients such as carotenoids and tocopherols. The objective of this study was to determine the association of plasma levels of seven common carotenoids, their total plasma concentration, retinol and alpha- and gamma-tocopherol, with the risk of gastric adenocarcinoma in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC), a large cohort involving 10 countries. A secondary objective was to determine the association of total sum of carotenoids, retinol and alpha-tocopherol on GCs by anatomical subsite (cardia/noncardia) and histological subtype (diffuse/intestinal). Analytes were measured by high-performance liquid chromatography in prediagnostic plasma from 244 GC cases and 645 controls matched by age, gender, study centre and date of blood donation. Conditional logistic regression models adjusted by body mass index, total energy intake, smoking and Helicobacter pylori infection status were used to estimate relative cancer risks. After an average 3.2 years of follow-up, a negative association with GC risk was observed in the highest vs the lowest quartiles of plasma beta-cryptoxanthin (odds ratio (OR) = 0.53, 95% confidence intervals (CI) = 0.30-0.94, P(trend) = 0.006), zeaxanthin (OR = 0.39, 95% CI = 0.22-0.69, P(trend) = 0.005), retinol (OR = 0.55, 95% CI = 0.33-0.93, P(trend) = 0.005) and lipid-unadjusted alpha-tocopherol (OR = 0.59, 95% CI = 0.37-0.94, P(trend) = 0.022). For all analytes, no heterogeneity of risk estimates or significant associations were observed by anatomical subsite. In the diffuse histological subtype, an inverse association was observed with the highest vs lowest quartile of lipid-unadjusted alpha-tocopherol (OR = 0.26, 95% CI = 0.11-0.65, P(trend) = 0.003). These results show that higher plasma concentrations of some carotenoids, retinol and alpha-tocopherol are associated with reduced risk of GC.     

Cardiac perforation and tamponade during TIPS placement

A patient developed an acute severe haemodynamic compromise immediately after a transjugular intrahepatic portosystemic shunt (TIPS) procedure for intractable ascites. Rapid clinical and echographic evaluation disclosed pericardial blood and cardiac tamponade, probably due to right heart perforation from guidewire and catheter manipulation. Needle drainage of pericardial fluid restored the haemodynamic status. A right ventricular perforation was then successfully treated (sternotomy and closure of right ventricle perforation) and the patient survived. Cardiac tamponade should be considered in the differential diagnosis of patients who develop hypotension and haemodynamic impairment during or immediately after TIPS placement.