Hemorrhagic transformation after stroke: inter- and intrarater agreement.

BACKGROUND AND PURPOSE: Hemorrhagic transformation (HT) is a complication of stroke that can occur spontaneously or after treatment. We aimed to assess the inter- and intrarater reliability of HT diagnosis. METHODS: Studies assessing the reliability of the European Cooperative Acute Stroke Study (ECASS) classification of HT or of the presence (yes/no) of HT were systematically reviewed. A total of 18 raters independently examined 30 post-thrombectomy computed tomography scans selected from the Aspiration versus STEnt-Retriever (ASTER) trial. They were asked whether there was HT (yes/no), what the ECASS classification of the particular scan (0/HI1/HI2/PH1/PH2) (HI indicates hemorrhagic infarctions and PH indicates parenchymal hematomas) was and whether they would prescribe an antiplatelet agent if it was otherwise indicated. Agreement was measured with Fleiss' and Cohen's κ statistics. RESULTS: The systematic review yielded four studies involving few (≤3) raters with heterogeneous results. In our 18-rater study, agreement for the presence of HT was moderate [κ = 0.55; 95% confidence interval (CI), 0.41-0.68]. Agreement for ECASS classification was only fair for all five categories, but agreement improved to substantial (κ = 0.72; 95% CI, 0.69-0.75) after dichotomizing the ECASS classification into 0/HI1/HI2/PH1 versus PH2. The inter-rater agreement for the decision to reintroduce antiplatelet therapy was moderate for all raters, but substantial among vascular neurologists (κ = 0.70; 95% CI, 0.57-0.84). CONCLUSION: The ECASS classification may involve too many categories and the diagnosis of HT may not be easily replicable, except in the presence of a large parenchymal hematoma.

[Cutaneous adverse events of telaprevir/peginterferon/ribavirin therapy for chronic hepatitis C: A multicenter prospective cohort study]. / Effets secondaires cutanés de l'association télaprévir/peg-interféron/ribavirine pour le traitement de l'hépatite C chronique : étude prospective d'une cohorte multicentrique.

BACKGROUND: Telaprevir, sale of which was suspended, has been approved in combination with pegylated interferon and ribavirin (triple therapy) in the treatment of chronic hepatitis C virus (HCV). Skin eruptions and isolated cases of severe cutaneous adverse reactions (SCAR) have been reported. AIMS: Our aim was to assess the incidence of skin eruption and the clinical characteristics of mucocutaneous adverse events (AE), and to identify potential risk factors for telaprevir-associated skin eruption. PATIENTS AND METHODS: A prospective observational multicenter follow-up cohort study with monthly controls by a dermatologist and additional examinations in case of any undercurrent AE. RESULTS: Among the 48 enrolled patients, the incidence of skin eruption was 58.4%, consisting mainly of maculopapular and eczematous lesions and only one case of SCAR. Telaprevir was discontinued in 6% of patients due to severe rash, whereas peginterferon and ribavirin were continued. The median time to onset of rash following telaprevir initiation was 25 days (range: 3-79 days). The rash was preceded by skin dryness and associated with pruritus in 100% and 90% of patients, respectively. Of those presenting with skin eruption, 37.5% also complained of conjunctival or oral lesions, or of anorectal symptoms. Neither a past history of dermatological conditions nor sociodemographic or viral status was predictive factor for skin rash. CONCLUSIONS: Telaprevir-related dermatitis has a high incidence but is mostly of mild intensity. In most cases, tri-therapy was continued under close dermatological follow-up allowing rapid detection of rare instances of severe drug eruptions. Ribavirin and Interferon were thus continued even in the event of diffuse eruptions, enabling confirmation of the causative role of telaprevir in these eruptions.

Evaluation of immunologic parameters in canine glioma patients treated with an oncolytic herpes virus.

Aim: To molecularly characterize the tumor microenvironment and evaluate immunologic parameters in canine glioma patients before and after treatment with oncolytic human IL-12-expressing herpes simplex virus (M032) and in treatment naïve canine gliomas. Methods: We assessed pet dogs with sporadically occurring gliomas enrolled in Stage 1 of a veterinary clinical trial that was designed to establish the safety of intratumoral oncoviral therapy with M032, a genetically modified oncolytic herpes simplex virus. Specimens from dogs in the trial and dogs not enrolled in the trial were evaluated with immunohistochemistry, NanoString, Luminex cytokine profiling, and multi-parameter flow cytometry. Results: Treatment-naive canine glioma microenvironment had enrichment of Iba1 positive macrophages and minimal numbers of T and B cells, consistent with previous studies identifying these tumors as immunologically "cold". NanoString mRNA profiling revealed enrichment for tumor intrinsic pathways consistent with suppression of tumor-specific immunity and support of tumor progression. Oncolytic viral treatment induced an intratumoral mRNA transcription signature of tumor-specific immune responses in 83% (5/6) of canine glioma patients. Changes included mRNA signatures corresponding with interferon signaling, lymphoid and myeloid cell activation, recruitment, and T and B cell immunity. Multiplexed protein analysis identified a subset of oligodendroglioma subjects with increased concentrations of IL-2, IL-7, IL-6, IL-10, IL-15, TNFα, GM-CSF between 14 and 28 days after treatment, with evidence of CD4+ T cell activation and modulation of IL-4 and IFNγ production in CD4+ and CD8+ T cells isolated from peripheral blood. Conclusion: These findings indicate that M032 modulates the tumor-immune microenvironment in the canine glioma model.

The impact of hypovolaemic shock on the aortic diameter in a porcine model.

OBJECTIVES: To investigate the impact of hypovolaemic shock on the aortic diameter in a porcine model, and to determine the implications for the endovascular management of hypovolaemic patients with traumatic thoracic aortic injury (TTAI). MATERIALS AND METHODS: The circulating blood volume of seven Yorkshire pigs was gradually lowered in 10% increments. At 40% volume loss, an endograft was deployed in the descending thoracic aorta, followed by gradual fluid resuscitation. Potential changes in aortic diameter during the experiment were recorded using intravascular ultrasound (IVUS). RESULTS: The aortic diameter decreased significantly at all evaluated levels during blood loss. The ascending aortic diameter decreased on average with 38% after 40% blood loss (range 24-62%, p = 0.018), the descending thoracic aorta with 32% (range 18-52%, p = 0.018) and the abdominal aorta with 28% (range 15-39%, p = 0.018). The aortic diameters regained their initial size during fluid resuscitation. CONCLUSION: The aortic diameter significantly decreases during blood loss in this porcine model. If these changes take place in hypovolaemic TTAI patients as well, it may have implications for thoracic endovascular aortic repair (TEVAR). Increased oversizing of the endograft, or additional computed tomography (CT) or IVUS imaging after fluid resuscitation for more adequate aortic measurements, may be needed in TTAI patients with considerable blood loss.

A proposed grading system to evaluate the endovascular curability of deep-seated arteriovenous malformations.

BACKGROUND: Aggressive treatment of deep-seated AVMs is paramount because of their high tendency to bleed (or to re-bleed). In the literature concerning endovascular therapy, AVMs of the basal ganglia, the semi-ovale center and the midbrain are always considered as a single entity. In this study, the authors address the anatomical classification of these AVMs and propose a classification that considers factors influencing their endovascular curability. METHODS: From 1995 to 2013, clinical and angiographic data of cerebral AVMs were prospectively collected. We reviewed data from patients treated for a deep-seated AVM with the goal to distinguish factors that influence the curability and the outcome of these AVMs. RESULTS: 134 patients (mean age: 28years) were consecutively treated by endovascular techniques. We describe an anatomical classification concerning the exact location of the nidus and distinguish 5 different sub-types (anterior, lateral, medial, posterior and midbrain). Then, we propose a grading system based on statistical analysis of our series to evaluate the curability of a deep AVM. This comprehensive score is calculated with the Spetzler-Martin grade, the location of the nidus, its type, arterial feeders and venous drainage. CONCLUSIONS: Deep-seated AVMs may be classified according to their exact location; we can distinguish 5 different sub-types (anterior, lateral, medial, posterior and midbrain). Each group presented different arterial supplies and venous drainage that influenced treatment possibilities. The comprehensive grading system that we propose in this study must be tested in another deep-seated AVMs population.

Ocular Signs Caused by Dural Arteriovenous Fistula without Involvement of the Cavernous Sinus: A Case Series with Review of the Literature.

Carotid cavernous fistula is a well-known clinical and angiographic entity responsible for ocular signs and symptoms. On the contrary, ocular signs are unusual in the presentation of cranial dural arteriovenous fistulas at locations other than the cavernous sinus. We retrospectively analyzed data focusing on the pathophysiology of ophthalmologic signs and their angiographic explanations. Thirteen patients were included with a mean age of 50 years. The most common signs were chemosis (61.5%), loss of visual acuity (38.5%), exophthalmia (38.5%), and ocular hypertension (7.7%). Dural arteriovenous fistulas presenting with ocular signs could be classified into 4 types due to their pathologic mechanism (local venous reflux into the superior ophthalmic vein, massive venous engorgement of the cerebrum responsible for intracranial hypertension, compression of an oculomotor nerve by a venous dilation, or intraorbital fistula with drainage into the superior ophthalmic vein).

Molecular cloning and sequencing of the cDNA encoding the catalytic subunit of mouse glutamate-cysteine ligase.

Reverse transcription-polymerase chain reaction (RT-PCR) was used for the enzymatic synthesis of cDNA sequences encompassing the open reading frame for the catalytic subunit of mouse kidney glutamate-cysteine ligase (Glclc). Comparison of the mouse Glclc cDNA sequence and predicted protein sequence with that of rat Glclc and human GLCLC revealed between 94.8% and 88.4% cDNA homology and 98.4% to 95% amino acid identity, respectively.

Molecular cloning and sequencing of the cDNA encoding mouse glutamate-cysteine ligase regulatory subunit.

Reverse transcription-polymerase chain reaction (RT-PCR) was used to amplify and clone the regulatory subunit of mouse glutamate-cysteine ligase (Glclr) using primers adapted from the published rat Glclr cDNA sequence, and from mouse genomic DNA. Amplified cDNA was cloned into a plasmid vector, and additional RT-PCR reactions coupled with 3' RACE were used to amplify and sequence 3' regions covered by the rat primer. Comparison of the mouse Glclr cDNA sequence and predicted protein sequence with that of rat Glclr and human GLCLR revealed extensive homology in cDNA and amino acid sequences among these species.

Evidence for the synthesis and secretion of APF--a bile lipid associated protein--by isolated rat hepatocytes.

Bile lipids are thought to be secreted in a lipoprotein complex in which they are associated with cholesterol and a protein called the anionic polypeptidic fraction (APF). APF is present in both bile and serum HDL. The association of APF with both bile and lipoprotein strongly suggests that hepatocytes may be responsible for the synthesis and secretion of this protein. In the present work we attempted to verify this by studying the incorporation of [14C]leucine into APF in isolated rat hepatocytes and by immunolocalization in cell cultures. Results obtained showed that synthesis of APF by cells follows the same kinetic pattern as albumin and that it was the third most abundant protein in the bile secretion. Immunolocalization confirmed that APF is synthesized in the endoplasmic reticulum of hepatocytes. This protein which appears to be rapidly secreted could be of great value for the specific detection of the lipids destined for bile secretion.

Reconstructive operations for esophagogastric corrosive lesions.

Corrosive esophagogastric lesions are common in Algeria and France. Within the past 14 years, our overall mortality has decreased to 6% as compared to 12% in the best results from elsewhere. This report describes our operative experience with 68 patients from 1974 to 1982. According to a prospective interdisciplinary program, lesions in 351 patients were staged by emergency esophagoscopic findings: Stage I, ulceration; Stage II, hemorrhage and ulceration; Stage III, mucosal necrosis, hemorrhage, and ulceration. Total parenteral nutrition or jejunal feeding was given to patients with Stage II lesions for 3 weeks and to those with Stage III lesions for 3 months before repeat esophagoscopy. Operations were required by 68 patients who had Stage III lesions and severe stenosis. Procedures done included 39 retrosternal colon interpositions, 11 partial or total gastrectomies, nine esophagogastrectomies, four esophagoenteral colonic bypasses, six esophagogastric colonic interpositions following partial gastric resection, and one gastrojejunostomy. Eleven of the cervical anastomoses were to the pharynx. There were no operative deaths and no anastomotic leaks. All patients have satisfactory nutrition and rehabilitation. Our operative experience in the preceding 5 years included an 11% mortality; improved results in the past 8 years are attributed to early and accurate staging, planned multidisciplinary management, good nutritional support, and better timing of operations. Stage III esophagogastric corrosive lesions may be treated within 4 to 5 months of injury with low mortality and good functional outcome.

End-tidal CO2 pressure determinants during hemorrhagic shock.

OBJECTIVES: To examine the relationship between end-tidal CO2 (PETCO2) and its physiological determinants, pulmonary blood flow (cardiac output, CO) and CO2 production (VCO2), in a model of hemorrhagic shock during fixed minute ventilation. DESIGN AND SETTING: Prospective, observational study in a research laboratory at a university center. SUBJECTS AND INTERVENTIONS: Six anesthetized, intubated, and mechanically ventilated mongrel dogs. Progressive stepwise bleeding. MEASUREMENTS AND RESULTS: We continuously measured PETCO2 with a capnograph, pulmonary artery blood flow with an electromagnetic flow probe, arterial oxygen saturation (SaO2) with a fiberoptic catheter, and oxygen consumption (VO2) and VCO2 by expired gases analysis. Oxygen delivery (DO2) was continuously calculated from pulmonary blood flow and SaO2. We studied the correlation of PETCO2 with CO and VCO2 in each individual experiment. We also calculated the critical point in the relationships PETCO2/ DO2 and VO2/DO2 by the polynomial method. As expected, PETCO2 was correlated with CO. The best fit was logarithmic in all experiments (median r2 = 0.90), showing that PETCO2 decrease is greater in lowest flow states. PETCO2 was correlated with VCO2, but the best fit was linear (median r2 = 0.77). Critical DO2 for PETCO2 and VO2 was 8.0 +/- 3.3 and 6.3 +/- 2.5 ml x min(-1) kg(-1), respectively (NS). CONCLUSIONS: Our data reconfirm the relationship between PETCO2 and CO during hemorrhagic shock. The relatively greater decrease in PETCO2 at lowest CO levels could represent diminished CO2 production during the period of VO2 supply dependency.

Peripheral venous complications of a hyperosmolar (960 mOsm) nutritive mixture: The effect of heparin and hydrocortisone. A multicenter double-blinded random study in 98 patients.

Peripheral intravenous nutrition with hyperosmolar solutions usually results in a high rate of venous complications. The aim of this multicenter double blind randomised study in 98 patients has been to measure: (a) tolerance by the peripheral veins being perfused with a protein-glucose-lipid nutritive mixture of 960 mOsm/l (group A, n = 33), (b) the protective effect of the additive to the nutritive mixture of either heparin: 1000 IU/1 (group B, n = 32) or heparin with hydrocortisone (5 mg/l) group C, n = 33). Tolerance by the veins was evaluated on a single vein site during a 48 h perfusion with 21 per day. The following complications: oedema, erythema, induration, thrombophlebitis led to the interruption of the perfusion. The rate of interruptions of perfusions for total venous complications and for thrombophlebitis has been respectively: at 24 h, in group A: 39 and 15%, in group B: 6 and 3%, in group C: 12 and 0%; at 48 h: in group A: 82 and 42%, in group B: 53 and 18%, in group C: 36 and 6%. Venous complication rates for 24 and 48 h were significantly lower in groups B and C (p<0.05) than in group A and there was no inter group difference between groups B and C. These results suggest that peripheral venous nutrition infusing 14.1 g of nitrogen and 8.5 MJ per day can be performed with a hyperosmolar solution of 960 mOsm/1, if that heparin be added to the nutritive mixture and the perfusion site be changed daily. Under these conditions the observed venous complications rate is equal to or less than 6% of cases.

1H NMR spin-spin relaxation and imaging in porous systems: an application to the morphological study of white portland cement during hydration in the presence of organics.

Proton nuclear magnetic resonance (NMR) spin-spin relaxation and imaging have been applied to investigate white Portland cement pastes during hydration in the absence and in the presence of organic solvents. The main organic solvent investigated was methanol, alone or together with the organic waste 2-chloroaniline (2-CA), an aromatic amine representative of an important class of highly toxic compounds. For all the analysed samples, prepared with a solvent-to-cement ratio of 0.4, the decay of the echo magnetization has been fitted by adopting a model that combines an exponential component with a gaussian one. The calculated independent relaxation parameters have been discussed in terms of morphological and dynamical changes that occur during the cement hardening process and pore formation. Three kinds of water molecules: "solid-like" (chemically and physically bound), "liquid-like" (porous trapped) and "free" water, endowed with anisotropic, near isotropic and isotropic motion, respectively, were identified. Spin-echo images collected on the same samples during the hydration kinetics, allowed the changes of water and solvents spatial distribution in the porous network to be monitored, showing percolation phenomena and confirming the multimodal open channels structure of the hardened cement system. Both T(2) relaxation and imaging data indicated that a pronounced delay occurs in the cement hardening when organics are present.

[Pharmacology of male sexual dysfunction]. / Farmacologia delle disfunzioni sessuali maschili.

The understanding of pharmacology of impotence has shown a steady improvement over the last 15 years which has resulted in a better appreciation of the neurovascular mechanisms of the erectile process especially at the level of the corpora cavernosa; however, central mechanisms which control libido and erection are not yet completely elucidated. Frequent diseases most commonly encountered in elderly patients--i.e. diabetes, hypertension, atherosclerosis, depression, etc--represent a frequent cause of erectile dysfunction (ED) and are treated with medications that can interfere with sexual functioning at the central and/or peripheral level. Antidepressants, including the tricyclics and the monoamine oxidase inhibitors, have been implicated in ED, decreased libido, and impaired ejaculation. Most antihypertensives have been associated with some erectile impairment, but diuretics seem to have little effect on erectile function. The calcium channel blockers and ACE inhibitors are associated with a low incidence of ED. Sympatholytic antihypertensives seldom cause importence but can cause retrograde ejaculation because of the relaxation of the smooth muscles in the prostatic urethra and bladder neck. The most commonly prescription drugs that can affect sexual function are briefly discussed and an integrated pharmacological approach to the patient with drug-induced ED is proposed.

Modulating effects of bile salt hydrophobicity on bile secretion of the major protein of the bile lipoprotein complex.

Bile lipids are secreted in association with a newly identified major apoprotein called anionic polypeptide fraction-calcium binding protein (APF-CBP), which is synthesized in the hepatocytes and has been detected in both bile and plasma and characterized. The secretion of the lipids in bile depends both on the concentration and the hydrophobicity of the bile salts (BS) secreted. The present study was undertaken to determine whether the synthesis and the secretion of APF-CBP are similarly regulated by BS, using two methods. The synthesis and secretion of labelled, newly synthesized APF-CBP by isolated rat hepatocytes were monitored by solid-phase immunoassay. For this purpose, hepatocytes were incubated with either glycodeoxycholate (GDC) or taurocholate (TC). The synthesis and secretion of labelled, newly synthesized APF-CBP by perfused rat liver were measured by immunological enzyme-linked assay (ELISA) upon perfusing the liver with either GDC or TC. We found that (i) the synthesis and the secretion of APF-CBP were increased during either TC or GDC perfusion, but the increase was more pronounced with TC; (ii) in GDC perfusion the APF-CBP levels measured were more closely related to the levels of bile salts and not to phospholipid levels, (iii) when the two bile salts were perfused in reverse order, i.e., first GDC and then TC, the secretion of APF-CBP in bile decreased when GDC was perfused, but increased when TC was perfused. Similar results were obtained in experiments with isolated hepatocytes.(ABSTRACT TRUNCATED AT 250 WORDS)

Post-menopausal breast cancer risk: oral estrogen treatment and abdominal obesity induce opposite changes in possibly important biological variables.

Almost all of the epidemiological studies on the consequences of estrogen replacement treatment (ERT) refer to subjects treated with oral conjugated equine estrogens (CEE). These studies suggest that breast cancer (BC) risk is limited and can only be seen after long-term and/or high dosage use. Orally administered estrogens present a number of metabolic and endocrine peculiarities, some of which could be important in reducing the risk to the breast. Actually, these peculiarities are opposite to those observed in post-menopausal women with abdominal obesity (AO), a group which has recently been identified to be at high risk. AO (as other situations in which an increase in BC risk does exist) shows a sex-hormone-binding-globulin (SHBG) level reduction, which causes an increase of both estrogenic and androgenic activity. Further features of AO, possibly involved in BC risk, could be: i) increased free fatty acid (FFA) levels; ii) hyperinsulinemia; iii) increase of circulating insulin-like growth-factor-I (IGF-I) activity. On the contrary oral estrogens, through their hepatocellular effects, cause: i) a clearcut SHBG increase; ii) a trend to reduced circulating IGF-I activity. As a consequence, the possibility that oral estrogens are characterized by a favourable balance between estrogenic activity and biological modifications protective to the breast, is worth consideration. Even non-oral estradiol have a possible protective action through FFA level reduction; however, due to the absence of hepatocellular effect, it does not influence SHBG levels and IGF-I activity. It seems difficult to extend data on the relationship between BC and oral CEE to other types of types of ERT. For the latter, further study will be necessary.

[Budd-Chiari syndrome and Behçet's disease. A case treated by mesenterico-atrial prosthesis]. / Syndrome de Budd-Chiari et maladie de Behçet. Une observation traitée par prothèse mésentérico-atriale.

A 36 year-old North African man, with Behçet's syndrome complicated by an inferior vena caval thrombosis, developed a chronic Budd-Chiari syndrome associated with bleeding esophageal varices. He was treated by an emergency mesoatrial shunt. Results at 2 years were good. Analysis of this case and the 13 other similar cases with associated Budd-Chiari syndrome and Behçet's syndrome found in the literature showed that hepatic veins thrombosis: a) is often due to inferior vena caval thrombosis or membranous obstruction; b) has a high spontaneous mortality rate by acute liver failure; c) remains a potential indication for porto-systemic shunt, as are other causes of Budd-Chiari syndrome.

[Evaluation of ultrasonography in the diagnosis of cirrhosis. Retrospective studies of 100 consecutive tests]. / Evaluation de l'ultrasonographie dans le diagnostic des cirrhoses. Etude rétrospective de 100 examens consécutifs.

This study was carried out in order to assess the value of ultrasonography in the diagnosis of cirrhosis. One hundred patients were studied within 2 weeks of the histological diagnosis of the liver disease (cirrhosis 49, acute or chronic hepatitis: 23, fatty liver: 16, normal liver: 12). Ultrasonic patterns were classified by a second examiner according to 5 hepatic criteria (volume, outline, echogenicity, attenuation of the ultrasound beam, enlargement of caudate lobe) and 3 extrahepatic criteria (dilatation of the portal vein, ascites, splenomegaly), leading to a ultrasonic diagnosis. Cirrhosis was diagnosed in 36 out of 49 patients (73 p. 100) by the echographist whereas clinical and biological data lead to diagnosis in only 27 out of these 49 patients (P = 0.057). Hepatocellular carcinoma was diagnosed only in 2 out of 5 patients. Splenomegaly (0.60) and caudate lobe enlargement (0.59) were the signs whose predictive value was the best for this group of patients. The ratio thickness of caudate lobe/global hepatic thickness (as measured on a sagittal cut through the inferior vena cava) allowed for easy assessment of caudate lobe size. The mean value of this ratio was significantly different (P less than 0.001) in the cirrhotic group (0.38 +/- 0.07) when compared to the non-cirrhotic one (0.28 +/- 0.06). Ratios greater than 0.35 were not seen in subjects with normal livers, nor were ratios greater than 0.40 seen in non-cirrhotic patients.(ABSTRACT TRUNCATED AT 250 WORDS)