A 50% reduction in cyclosporine exposure in stable renal transplant recipients: renal function benefits.

BACKGROUND: Although cyclosporine maintenance therapy reduces the risk of acute rejection and increases short-term graft survival in renal transplant recipients, its associated nephrotoxicity increases the risk of chronic graft dysfunction. The dose that allows an optimal risk-to-benefit ratio has not been established. METHODS: This multicentre study enrolled stable renal allograft recipients receiving cyclosporine and mycophenolate mofetil without corticosteroids in their second year post-transplant. Patients were randomized to a cyclosporine dose targeted to a standard area under the concentration-time curve (AUC)(0-12 h) (usual exposure, n = 104) or 50% of the study standard AUC(0-12 h) (low exposure, n = 108) using a three-point pharmacokinetic sampling. The primary endpoint was the percentage of patients with treatment failure at 24 months (graft loss/acute rejection/nephrotoxicity/>15% serum creatinine level increase). RESULTS: Treatment failure was reported in 37 out of 101 (37%) patients in the usual-exposure and 19 out of 106 (18%) patients in the low-exposure groups (P = 0.003). Mean estimated glomerular filtration rate decreased from baseline to 2 years with usual exposure and increased with low exposure (P < 0.001). Mean systolic and diastolic blood pressures were lower with low exposure (P = 0.03 and P = 0.008, respectively). CONCLUSION: In renal transplant recipients receiving maintenance therapy without corticosteroids, a minimization strategy using three-point pharmacokinetic sampling to reduce and maintain cyclosporine exposure to 50% of the usual levels is safe and reduces the risk of graft dysfunction.

A comparison of two regimens of topical corticosteroids in the treatment of patients with bullous pemphigoid: a multicenter randomized study.

Superpotent topical corticosteroids (CS) have been demonstrated to improve bullous pemphigoid (BP) patients' survival. We assessed whether a mild regimen using lower doses of topical CS and a shorter duration could improve the outcome of BP patients even more. Three-hundred and twelve BP patients were included in a multicenter randomized controlled trial and stratified depending on the extent of BP as moderate (n=134) or extensive (n=178). Patients were randomly assigned to the standard regimen (clobetasol propionate cream, 40 g per day initially, with CS tapering over 12 months) or the mild regimen (10-30 g per day), with CS tapering over 4 months. A noninferior rate of BP control was obtained with the mild regimen 156/159 (98%) as compared with the standard regimen 150/150 (100%; P=0.005). Event-free survival, that is, the combined outcome of deaths and life-threatening adverse events did not differ between the two treatment groups (P=0.77). However, upon adjusting through the Cox model for age and Karnofsky score, a strong beneficial effect of the mild regimen was observed in patients with moderate BP, with an almost twofold decrease in the risk of death or life-threatening adverse events relative to the standard regimen (hazard ratio=0.54; 95% confidence interval, 0.30-0.97; P=0.039). This mild regimen allows a 70% reduction of the cumulative doses of CS and improves BP patients' outcome.

Interface strategy during noninvasive positive pressure ventilation for hypercapnic acute respiratory failure.

OBJECTIVE: To assess the influence of initial mask choice on the clinical effectiveness and tolerance of noninvasive positive pressure ventilation (NIPPV) in the management of hypercapnic acute respiratory failure. DESIGN: A prospective randomized controlled clinical study. SETTING: A medical intensive care unit at a university hospital. INTERVENTION: Randomization between two NIPPV interfaces. PATIENTS: Initial mask choice was randomized between two standard masks: face (NIPPVf group) and nasal (NIPPVn group). The main end point was mask failure (i.e., mask change and/or intubation). Secondary end points were tolerance of NIPPV, change in respiratory parameters during the first 3 days, and patient outcome. Results were analyzed on an intent to treat basis. A per protocol analysis was also conducted. MAIN RESULTS: Ninety patients with underlying chronic lung disease were included, 46 in the NIPPVf group and 44 in the NIPPVn group. The overall success rate of NIPPV was 83%. Mask failure occurred significantly more often in the NIPPVn group (32/44 vs. 9/46; p < 0.0001), mainly because of the need for mask change (32/44 vs. 0/46; p < 0.0001) because of the occurrence of major buccal air-leaks in 94% of cases. Improvement in respiratory parameters was similar in the two groups. Whereas air-leaks were more frequent in the NIPPVn group (p < 0.05), respiratory comfort was assessed as lower and complications more frequent by the staff in the NIPPVf group from day 2 (p < 0.05). CONCLUSIONS: A face mask should be the first-line strategy in the initial management of hypercapnic acute respiratory failure with NIPPV. However, if NIPPV has to be prolonged, switching to a nasal mask may improve comfort by reducing face mask complications.

CXCR4 membrane expression in node-negative breast cancer.

CXC chemokine receptor 4 (CXCR4) has been reported to be involved in organ-specific homing of breast cancer-derived metastasis. We investigated CXCR4 expression by immunohistochemistry as a possible new prognostic factor for primary breast cancer. Two groups of women treated for breast cancer in 1991 at the Centre for the fight against cancer of Upper Normandy-France (Centre de Lutte contre le Cancer de Haute Normandie) were assessed retrospectively. CXCR4 expression was evaluated using standard immunohistochemistry. Usual prognostic factors were recorded in the computer database. Final date of follow-up was December 31, 2001. Tissues were available for 110 node-positive and 84 node-negative breast cancer patients treated in 1991. CXCR4 membrane staining was considered a strong prognostic factor for both 10-year metastasis-free- (p < 0.0001) and overall survival (p < 0.0001) in node-negative but not in node-positive breast cancer patients. CXCR4 cytoplasmic staining was not considered a significant prognostic factor. Our results suggest that CXCR4 membrane staining could be considered a new prognostic factor. Moreover, targeting CXCR4 in primary breast cancer patients may be a new therapeutic concept. However, these results warrant further investigation.

Neutrophil but not eosinophil inflammation is related to the severity of a first acute epidemic bronchiolitis in young infants.

Acute bronchiolitis is the main cause of emergency visits and hospitalizations in infants. Recent data suggest that neutrophil- and eosinophil-mediated inflammations were part of bronchiolitis pathophysiology. Apart from the defined risk factors, few was known on the underlying pathophysiology, which might point out the differences observed in the severity of the disease. The aim of this study was to assess whether the clinical severity of acute epidemic bronchiolitis in young infants might be related to a specific underlying inflammatory process. Total and differential cell counts, IL-8, eotaxin, eosinophil cationic protein (ECP) and albumin levels were assessed at the time of admission in bronchial secretions from 37 infants (median age 17 wk) with acute bronchiolitis. Outcome severity variables were: hypoxemia, Silverman score, tachypnea, feeding alteration, and duration of hospitalization. Neutrophils predominated, and eosinophils were present in 54% of the infants. IL-8 levels strongly correlated with ECP and albumin levels. Albumin levels were correlated with ECP and eotaxin levels. IL-8 levels were higher in infants with hypoxemia and inversely related with SaO(2) levels. IL-8 and albumin levels significantly rose with respiratory rate, and Silverman score. IL-8, albumin and ECP levels were significantly higher in infants hospitalized >/=7 days. Furthermore, IL-8 levels were correlated with the duration of hospitalization. Neither cell counts nor eotaxin levels were related to the severity criteria studied. This study suggests that IL-8-associated airway inflammation significantly contributed to the severity of acute epidemic bronchiolitis.

Continuous positive airway pressure versus bilevel noninvasive ventilation in acute cardiogenic pulmonary edema: a randomized multicenter trial.

STUDY OBJECTIVE: Patients with acute cardiogenic pulmonary edema may develop respiratory failure. Noninvasive respiratory support should be initiated rapidly to avoid tracheal intubation. The aim of this study is to compare the efficacy of continuous positive airway pressure (CPAP) delivered by the Boussignac CPAP device and bilevel positive airway pressure (bilevel PAP) in patients with acute respiratory failure caused by acute cardiogenic pulmonary edema. METHODS: This prospective multicenter randomized study was conducted in 3 emergency departments. Patients were assigned to Boussignac CPAP through a facemask or to bilevel PAP, in addition to standard therapy. The main outcome was a combined criterion (tracheal intubation, death, or acute myocardial infarction). Complications, durations of ventilation, and hospitalization were also assessed. RESULTS: After 1 hour of ventilation and at the end of the ventilation period, clinical parameters of respiratory distress and blood gas exchange significantly improved in each treatment arm. No significant differences were observed between the Boussignac CPAP and bilevel PAP arms for the combined criterion (5% versus 12%, respectively; odds ratio [OR] 0.4; 95% confidence interval [CI] 0.0 to 1.9) and also for severe complications (9% versus 6%; OR 1.5; 95% CI 0.3 to 9.9), duration of ventilation (median for both groups 2 hours; interquartile range [IQR] 1.2 to 3.0 hours), duration of hospitalization (CPAP 8.5 [IQR 6 to 14] days; bilevel PAP 10 [IQR 7 to 16] days), or intrahospital mortality (8% versus 14%; OR 1.8 [IQR 0.4 to 8.8]). Similar results were obtained among hypercapnic patients (PaCO2 >45 mm Hg). Whatever the ventilation support used, the combined criterion and severe complications were more frequently observed among hypercapnic patients. CONCLUSION: Both Boussignac CPAP and bilevel PAP appeared effective in rapidly improving respiratory distress even in hypercapnic patients, but they were not different in terms of patient outcome.

Neurological disorders in patients with bullous pemphigoid.

BACKGROUND: Unexpected cases of bullous pemphigoid (BP) have been reported in adult patients with various neurological disorders suggesting a possible relationship between these diseases. OBJECTIVES: (1) To determine the prevalence and types of neurological disorders in patients with BP, (2) to assess patients' functional impairment, and (3) to compare the clinical and biological findings as well as prognosis of BP patients presenting with or without neurological disorders. METHODS: BP patients with neurological disorders were selected in a series of 341 consecutive BP patients treated in 20 French Dermatology Departments. Functional impairment was prospectively assessed using the Karnofsky score which is a measure of patients' general condition. RESULTS: At least one neurological disorder was present in 123 of the 341 BP patients (36%). They primarily consisted of dementia (n = 68; 20%; 95% CI: 16-25%), cerebral stroke (n = 52; 15%; 95% CI: 4-19%), and/or Parkinson's disease or parkinsonism (n = 32; 9%; 95% CI: 7-13%). BP patients with neurological disease were older than patients without neurological disease (83.8 +/- 7.5 years vs. 79.3 +/- 10.3 years, p < 10(-4)). They also had a lower Karnofsky score (47 +/- 19% vs. 74 +/- 20%, p < 10(-4)). One-year overall survival rates of the two groups were 50.8% (95% CI: 41.8-59.7) and 78.7% (95% CI: 73.0-84.2), respectively (p < 10(-4)). In contrast, the number of bullae and main biological features at baseline were not different between the two groups of patients. CONCLUSION: This study demonstrated a high frequency of neurological disorders, particularly dementia, in BP patients. Most of these patients had a severe functional impairment and a poor prognosis.

Stressful life events as a risk factor for inflammatory bowel disease onset: A population-based case-control study.

BACKGROUND AND AIMS: Stress is often perceived by patients with inflammatory bowel disease (IBD) as the leading cause of their disease. The aim of this study was to assess whether stress, evaluated through life event (LE) occurrence, is associated with IBD onset. METHODS: Incident cases of IBD, including 167 patients with Crohn's disease (CD) and 74 with ulcerative colitis (UC), were compared with two control groups, one of 69 patients with acute self-limited colitis (ASLC) and another of 255 blood donors (BDs). Stress was assessed using Paykel's self-questionnaire of LEs. Only LEs occurring within 6 months before the onset of symptoms in IBD cases and ASLC controls and before blood donation in BD controls were registered. Anxiety and depression were assessed using Bate's and Beck's questionnaires, respectively. RESULTS: In univariate analysis, occurrence of LEs was more frequent in the 6-month period prior to diagnosis in CD cases than in UC cases or either control group. After adjustment for depression and anxiety scores as well as other characteristics such as smoking status and sociodemographic features, this association appeared no longer significant. No associations were noted between occurrence of LEs and onset of UC relative to controls. CONCLUSIONS: Despite its separate association with CD, LE occurrence does not appear to be an independent risk factor for IBD onset.

Undernutrition is predictive of early mortality after palliative self-expanding metal stent insertion in patients with inoperable or recurrent esophageal cancer.

BACKGROUND: Self-expanding metallic stents (SEMS) are a first-line therapeutic procedure in the palliative treatment of dysphagia in patients with esophageal cancer. However, the impact of SEMS insertion on patient nutritional status has never been assessed. OBJECTIVE: To evaluate the nutritional status of patients after insertion of a SEMS and the impact of a preexisting undernutrition status on survival. DESIGN: Retrospective observational study. PATIENTS: A total of 120 patients treated in a single center by insertion of a SEMS for relief of dysphagia in the palliative treatment of esophageal cancer were retrospectively included. MAIN OUTCOME MEASUREMENTS: Efficacy of SEMS was assessed by the Ogilvie's dysphagia score. Patient nutritional and clinical statuses were evaluated at SEMS insertion, and patients were regularly followed until death. Independent predictive factors of early 30-day mortality were researched. RESULTS: Dysphagia scores decreased after SEMS insertion in 89.1% of patients, with median scores decreasing from 3.0 to 1.0 (P < .05). There was a significant decrease in body mass index (BMI) (P < .04), serum albumin level (P < .01), and World Health Organization (WHO) performance index (P < .02) at a 1-month evaluation. Serum albumin level, BMI <18 kg/m(2), and WHO performance index >2 at SEMS insertion were independent predictive factors of 30-day mortality. CONCLUSIONS: This study suggested that palliative stent placement in esophageal cancer was effective to relieve dysphagia but was not followed by an improvement of nutritional parameters. Moreover, it underlined the key role played by undernutrition on survival.

On line clinical reasoning assessment with Script Concordance test in urology: results of a French pilot study.

BACKGROUND: The Script Concordance test (SC) test is an assessment tool that measures the capacity to solve ill-defined problems, that is, reasoning in a context of uncertainty. This study assesses the feasibility, reliability and validity of the SC test made available on the Web to French urologists. METHODS: A 97 items SC test was developed based on major educational objectives of French urology training programmes. A secure Web site was created with two sequential modules: a) The first one for the reference panel to elaborate the scoring system; b) The second for candidates with different levels of experience in urology: Board certified urologists, chief-residents, residents, medical students. All participants were recruited on a voluntary basis. Statistical analysis included descriptive statistics of the participants' scores and factorial analysis of variance (ANOVA) to study differences between groups' means. Reliability was evaluated with Cronbach's alpha coefficient. RESULTS: The on line SC test has been operational since June 2004. Twenty-six faculty members constituted the reference panel. During the following 10 months, 207 participants took the test online (124 urologists, 29 chief-residents, 38 residents, 16 students). No technical problem was encountered. Forty-five percent of the participants completed the test partially only. Differences between the means scores for the 4 groups were statistically significant (P = 0.0123). The Bonferroni post-hoc correction indicated that significant differences were present between students and chief-residents, between students and urologists. There were no differences between chief-residents and urologists. Reliability coefficient was 0.734 for the total group of participants. CONCLUSION: Feasibility of Web-based SC test was proved successful by the large number of participants who participated in a few months. This Web site has permitted to quickly confirm reliability of the SC test and develop strategy to improve construct validity of the test when applied in the field of urology. Nevertheless, optimisation of the SC test content, with a smaller number of items will be necessary. Virtual medical education initiative such as this SC test delivered on the Internet warrants consideration in the current context of national pre-residency certification examination in France.

A keratitis rat model for evaluation of anti-Acanthamoeba polyphaga agents.

PURPOSE: To develop a rat model of chronic Acanthamoeba polyphaga keratitis suitable for pharmacologic assessment of therapeutic agents. METHODS: An A. polyphaga isolate (ATCC #50495) was grown in peptone-yeast extract-glucose medium. Five-weeks-old, Sprague-Dawley male rats were injected with 10(3) or 10(4) trophozoites in the left cornea stromal layer. A subconjunctival injection of 0.14, 0.28, or 0.57 mg long-acting betamethasone was performed weekly. At the end of experiments, rats were killed; the superficial corneal epithelium gently scraped and cultured; and globes histologically examined. Topical polyhexamethylene biguanide (PHMB), hexamidine diisethionate, and miltefosine (hexadecylphosphocholine) were administered topically as eye drops 3 times a day at concentrations of 0.02%, 0.1%, and 0.01% respectively. In vitro minimal inhibitory concentration (MIC) and fractional inhibitory concentration values were measured in A. polyphaga cultures. RESULTS: In infected eyes, lesions consisted of the sequential appearance within 2 weeks of edema, infiltrates, and/or abscesses. On day 35 postinfection, a combination of 10(4) parasites with a regimen of 0.28 mg/week betamethasone resulted in the highest ratio of rats with abscesses. Presence of A. polyphaga was confirmed histologically and inconsistently in cultures. In rats optimally prepared as said earlier, agents were administered on day 6 postinfection. A combination of PHMB and hexamidine diisethionate exerted a synergistic effect and was more effective than PHMB, hexamidine diisethionate, or miltefosine alone. In vitro, PHMB (MIC = 14.6 microM) and hexamidine diisethionate (MIC = 555 microM) exerted a synergistic effect (fractional inhibitory concentration = 0.06), and miltefosine exhibited antiamoebal activity (MIC = 27.4 microM). CONCLUSIONS: In this study, a rat model of chronic A. polyphaga keratitis was obtained and found suitable for assessment of pharmacologic agents. It provides an in vivo approach of drug resistance, pathogenicity, and physiopathologic mechanisms of chronic amoebic keratitis.

Prediction of survival for patients with bullous pemphigoid: a prospective study.

OBJECTIVE: To identify the prognostic factors of bullous pemphigoid (BP). DESIGN: Prospective study of patients with BP included in a randomized, controlled trial. SETTING: Twenty dermatology departments in France. Patients One hundred seventy patients with BP initially treated with a 40-g/d dosage of clobetasol propionate cream (testing sample) and 171 patients initially treated with oral corticosteroids at a dosage of 0.5 or of 1.0 mg/kg per day, depending on the extent of BP (validation samples). MAIN OUTCOME MEASURES: The end point was overall survival during the first year after BP diagnosis. From the testing sample, associations of clinical and biological variables with overall survival were assessed using univariate and multivariate analyses. Selected predictors were included in a prognostic model. To verify that these predictors were not dependent on the treatment used, the model was then validated independently on the 2 series of BP patients treated with oral corticosteroids. RESULTS: Median age of the BP patients included in the testing sample was 83 years. The 1-year Kaplan-Meier survival rate was 74%. From univariate analysis, the main deleterious predictors were demographic factors (ie, older age and female sex), associated medical conditions (ie, cardiac insufficiency, history of stroke, and dementia), and low Karnofsky score, which is a measure of the patient's general condition. No factors directly related to BP, in particular extent of cutaneous lesions, were shown to be related to the patients' prognosis. From multivariate analysis, only older age (P = .02) and low Karnofsky score (P<.001) appeared independently predictive of death. From the Cox model including these 2 predictors, the predicted 1-year survival rates were 90% (95% confidence interval [CI], 85%-96%) for patients 83 years or younger with Karnofsky score greater than 40, 79% (95% CI, 69%-90%) for patients older than 83 years with Karnofsky score greater than 40, 65% (95% CI, 50%-86%) for patients 83 years or younger with Karnofsky score of 40 or less, and 38% (95% CI, 26%-57%) for patients older than 83 years with Karnofsky score of 40 or less. Kaplan-Meier survival distributions of patients from the validation samples appeared clearly separated according to these 4 categories and were in close agreement with corresponding predicted 1-year survival rates obtained from the testing sample. CONCLUSIONS: The prognosis of patients with BP is influenced by age and Karnofsky score. These predictors are easy to use and should facilitate the management of BP.

Opportunistic infections in polymyositis and dermatomyositis.

OBJECTIVE: To assess prevalence and characteristics of opportunistic infections in patients with polymyositis/dermatomyositis (PM/DM). To determine the predictive values for opportunistic infections on clinical presentation, biochemical findings, and paraclinical features of PM/DM to detect patients at risk of opportunistic infections. METHODS: The medical records of 156 consecutive PM/DM patients in 3 medical centers were reviewed. RESULTS: Eighteen PM/DM patients (11.5%) developed opportunistic infections. The majority of patients exhibited an opportunistic infection after the onset of PM/DM (89% of cases). Opportunistic infections occurred most frequently during the first year following PM/DM diagnosis (62.5%). The pathogen microorganisms responsible for opportunistic infections were various, i.e., Candida albicans, Pneumocystis carinii, Aspergillus fumigatus, Geotrichum capitatum, Mycobacterium avium-intracellulare complex, M. xenopi, M. marinum, M. tuberculosis, Helicobacter heilmanii, cytomegalovirus, and herpes simplex virus. Mortality rates were as high as 27.7% in these PM/DM patients. Higher mean daily doses of steroids, lymphopenia, and lower serum total protein levels were significantly more frequent in the group of PM/DM patients with opportunistic infections. CONCLUSION: Our study underscores the high frequency of opportunistic infections in PM/DM, resulting in an increased mortality rate. It also indicates that a great variety of microorganisms are responsible for opportunistic infections, although they were more often due to fungi (>50% of cases). Our series highlights a predominance of both lung and digestive opportunistic infections (89% of cases). In addition, our results suggest that PM/DM patients presenting with factors predictive of opportunistic infection may require closer monitoring.

Clonal T cells in the blood of patients with systemic sclerosis.

BACKGROUND: It has been suggested that clonal T cells may play a critical role in the pathogenesis of systemic sclerosis. OBSERVATIONS: A monoclonal population of T cells was found in blood samples from 13 (34%) of 38 consecutive patients with a definite diagnosis of systemic sclerosis who were prospectively examined by T-cell receptor gamma gene rearrangement using polymerase chain reaction analysis and denaturating gradient gel electrophoresis. In the healthy control group, the same type of examination revealed a monoclonal population of T cells in the blood samples from only 3 healthy subjects (4%)(odds ratio, 12.28; 95% confidence interval, 2.76-54.64; P = .001). Patients who had a circulating clonal population of T cells were older than those who did not (67 years vs 48 years; P = .04). There was a marked relationship between systemic sclerosis subtypes and the presence of a circulating clonal population of T cells. Twelve (43%) of 28 patients with limited cutaneous sclerosis exhibited a circulating clonal population of T cells, whereas only 1 (10%) of the 10 patients with diffuse cutanous sclerosis had evidence of T-cell clonality (P<.01). CONCLUSIONS: Clonally expanded T cells were more commonly detected in patients with limited cutaneous sclerosis than in those with diffuse cutaneous sclerosis, which is also in accordance with a possible role of clonal T cells in patients with limited cutaneous sclerosis.

[Cytokeratins 7 and 20 immunohistochemistry in ampullary carcinomas]. / Expression immunohistochimique des cytokératines 7 et 20 dans les carcinomes ampullaires.

UNLABELLED: Ampullary carcinomas (AC) account for 33% of all surgically operable pancreatoduodenal tumors. The 5-year relative survival rate is 50% and tumoral stage is the main prognostic factor. However, among the three AC histological subtypes (intestinal, pancreatobiliary and mixed), a favorable prognostic has been reported for the intestinal subtype. BACKGROUND: The aims of this study were to determine the prognostic impact of AC histologic subtype and of cytokeratins (CK) 7 and 20 immunostaining profile in these tumors. PATIENTS AND METHODS: Clinical data of 54 AC were obtained retrospectively. Macroscopic and histologic documents were reviewed and immunostainings for CK7 and CK20 were performed. RESULTS: The classification of tumors, according to histological subtype, was: intestinal 26%, pancreatobiliary 65% and mixed 9%. No correlation was found between histological subtype and tumor stage. The 5-year survival rate varied from 100% for intestinal subtype to 35% for pancreatobiliary subtype. A strong correlation (p < 0.0001) was found between histological subtype and CK7/CK20 immunostaining profile. The 5-year survival rate varied from 100% for CK7-/CK20 + AC to 40% for CK7 + /CK20- AC. CONCLUSION: In our study, the intestinal histological subtype had a favorable prognostic value. CK7/CK20 immunostaining profile was helpful for the identification of histological subtype and appears to provide additional prognostic information.

Changes in mesenteric vascular reactivity and inflammatory response after cardiopulmonary bypass in a rat model.

BACKGROUND: Mesenteric ischemia and acidosis leading to intestinal ischemia has been observed during cardiopulmonary bypass (CPB) despite normal flow in the mesenteric vessels. The aim of this study was to assess mesenteric endothelium-dependent reactivity and vasoconstrictor responses of small mesenteric arteries in a rat model of CPB without aortic cross-clamping. METHODS: After femoral cannulation a partial 90 minutes CPB was performed with hemodynamics and blood gas parameters monitoring. Blood samples and segments of small mesenteric arteries were obtained in rats sacrificed 2.5 hours (CPBH2.5) or 6 hours (CPBH6) after femoral cannulation. Sham surgery (sham H2.5, sham H6) was performed with femoral cannulation only. Segments of small mesenteric arteries were placed in a myograph in order to assess the contractile response to phenylephrine (with or without NO synthase inhibitor) or the endothelium-dependent relaxation to acetylcholine. Systemic inflammation was evaluated by measuring plasma concentrations of TNFalpha. Pulmonary and intestinal infiltration of activated leukocytes was assessed by immunohistochemistry. RESULTS: CPB induced increased contractile response to phenylephrine which persisted after blockade of NO synthesis as well as transient impairment of endothelium-dependent relaxations. CPB also led to early and marked release of TNFalpha. CONCLUSIONS: CPB was responsible for mesenteric endothelial dysfunction and direct increase in the contractile response to alpha1-adrenergic agonist with increased systemic inflammatory response. This phenomenon might contribute to an increase in the risk of mesenteric ischemic events during cardiac surgery especially when vasopressor agents are used.

Boussignac continuous positive airway pressure device in the emergency care of acute cardiogenic pulmonary oedema: a randomized pilot study.

This study aimed to assess the short-term respiratory effects of a new portable device that delivers a continuous positive airway pressure via a face mask (Boussignac-CPAP) in patients with severe acute cardiogenic pulmonary oedema, and the feasibility of using this technique in an emergency department. We prospectively studied 30 consecutive patients with acute cardiogenic pulmonary oedema. They were randomly assigned either to the Boussignac-CPAP valve, which delivered oxygen, or to standard oxygen delivery for a duration of 30 min. The end-expiratory pressure reached 9.3+/-0.3 cm H2O with the Boussignac-CPAP valve. At the end of the 30 min period, the decreases in respiratory rate and muscular activity were significantly greater among patients assigned to the Boussignac-CPAP valve compared with those on standard oxygen delivery [24+/-1.6 breaths/min, median 24 (15-37) versus 28.5+/-1.9, median 27 (16-38) and 1.3+/-0.2, median 1 (0-4) versus 2.7+/-0.3, median 2 (0-4), respectively]. Moreover, the arterial oxygen tension to inspired oxygen concentration ratio and tidal volume were improved at the end of the 30 min Boussignac-CPAP period compared with baseline. Boussignac-CPAP was easily implemented and no side-effects were reported. Continuous positive pressure delivered using the Boussignac-CPAP device is feasible in an emergency care setting. It can quickly improve respiratory distress in acute cardiogenic pulmonary oedema patients. A larger trial should be initiated in such an emergency care setting to demonstrate the effectiveness of the Boussignac-CPAP device.

Hepatocyte growth factor, transforming growth factor alpha, and their receptors as combined markers of prognosis in hepatocellular carcinoma.

A change in the balance between proliferation and apoptosis in the course of hepatocellular carcinoma (HCC) development and progression has been suspected. We wanted to identify related genes whose mRNA levels could provide markers of severity and prognosis after resection. The extent of cell apoptosis, proliferation, and differentiation was measured with a terminal deoxynucleotidyl transferase-mediated deoxyuridine 5-triphosphate-biotin nick-end labeling assay, and the Ki-67 index was determined in paired tumor and cirrhotic tissue samples from patients who had undergone HCC resection after diagnosis of hepatitis C-related or alcoholism-related cirrhosis. These patients included two groups with highly versus poorly differentiated tumor cells, and the latter was split into two subgroups of those with versus without early recurrence. The mRNA levels for various apoptosis-related or proliferation-related genes and those for the growth factor/receptor systems were measured by quantitative reverse transcriptase-polymerase chain reaction in paired tumor and cirrhotic liver samples from every patient, and some of the corresponding proteins were detected by immunohistochemistry. In all instances, protein expression was highly heterogeneous within groups and similar between groups. In contrast, some differences in mRNA level between tumor and cirrhotic tissues were quite informative. Low levels of hepatocyte growth factor and transforming growth factor alpha mRNAs were found concomitantly in highly differentiated tumors, whereas overexpression of mRNAs for the cognate receptors c-met and epidermal growth factor receptor were found in poorly differentiated tumors and primarily in patients with early tumor recurrence. These results argue for growth factor-dependent HCC development and provide novel and combined prognosis markers after HCC surgery.

PAS inclusions, immunoreactive tenascin and proliferative activity in low-grade chondrosarcomas.

To distinguish between chondrosarcoma (grade 1--borderline histology) and enchondroma, we examined six chondrosarcomas (grade 1--borderline histology) which looked like benign lesions. Their diagnosis, albeit based on clinical, radiologic and pathologic examinations, was not easily reached. Moreover, we examined six enchondromas and 11 chondrosarcomas, the diagnoses of which were straightforward. All cartilaginous tumors were studied, placing emphasis on PAS-positive intracytoplasmic globules. Anti-Ki67 proliferation-associated nuclear antigen antibody and tenascin antibody were applied. The following features were observed in low-grade chondrosarcomas: (1) masses of hyalin and/or myxoid cartilage invading spaces around the tumor, (2) host lamellar bone trabeculae surrounded by cartilage on all sides, (3) tumoral resorption of bone trabeculae. Intracytopasmic hyalin globules (ICG) were more frequently found in malignant than in benign neoplasm (p = 0.042). Moreover, tenascin matrix immunoreactivity was more likely to be observed in benign than in malignant neoplasm (p = 0.029). Ki67 immunoreactivity was more frequent in characterized than in low-grade chondrosarcomas or in enchondromas, where it was null (p = 0.0044).