Clinical impact of recreational drug use among people living with HIV in southern Taiwan

BackgroundIt is unclear about the impact of recreational drug use on the adherence, drug–drug interaction and the occurrence of sexual transmitted diseases (STDs) among people living with HIV.Material and methodsA retrospective study was conducted between Dec 2016, and July 2018 to assess the clinical impact of recreational drug consumption in people living with HIV with antiretroviral therapy. We collected data of the demographics, recreational drug use, laboratory results and STDs diagnoses. Potential drug–drug interactions were checked with reference databases. The association between recreational drug use and STDs, HIV viral load suppression and drug interactions were evaluated.ResultsA total of 462 participants were enrolled, included 384 recreational drug users and 78 non-recreational drug users. Younger age (adjusted odds ratio [aOR], 0.94; 95% CI: 0.91–0.98; p = 0.001), longer HIV infection period (aOR, 1.11; 95% CI: 1.03–1.20; p = 0.009) and poor antiretroviral drug adherence (1–2 pills missing per month: aOR, 6.82; 95% CI: 3.50–13.27; p < 0.001; >2 pills missing per month: aOR, 3.50; 95% CI: 1.28–9.61; p = 0.015) were factors associated with recreational drug use. Methamphetamine and nitrites were two most common recreational drugs. Recreational drug use was significantly associated with STDs in one-year follow-up period (aOR, 2.43; 95% CI: 1.11–5.32; p = 0.027) but was not significantly associated with unsuppressed viral load, though a trend was observed (OR, 2.23; 95% CI: 0.92–5.37; p = 0.074). Potential interactions with recreational drugs included 33.1% antiretroviral drugs and 31.3% medications for comorbidities.ConclusionRecreational drug was associated with STDs. A great proportion of the patients consuming recreational drugs had potential interactions with antiretroviral drugs and medications for comorbidities. The association of recreational drug use and unsuppressed viral load warrants further investigation.     

Web-Based Cognitive Behavioral Self-Help Intervention to Reduce Cocaine Consumption in Problematic Cocaine Users: Randomized Controlled Trial

Background

Web-based self-help programs that reduce problematic substance use are able to reach hidden consumer groups in the general population. These programs are characterized by their low treatment threshold and nonrestrictive intervention settings. They are also cost effective, making them of interest to both low-income and high-income industrialized countries with ever-increasing health costs.

Objective

To test the feasibility and effectiveness of an anonymous, fully automated, Web-based self-help intervention as an alternative to outpatient treatment services for cocaine users.

Methods

A total of 196 cocaine-using participants were recruited through various online and offline media for a randomized controlled trial. Participants in the intervention group received interactive cognitive behavioral modules and a consumption diary to reduce cocaine use, whereas participants in the control group received online psychoeducative information modules. Web-based follow-up assessments were conducted after 4 weeks, 6 weeks, and 6 months. Treatment retention was examined and compared between the intervention and control groups. Severity of cocaine dependence was the main outcome measure. Secondary outcomes were cocaine craving, depression symptoms, and alcohol and other substance use.

Results

This Web-based intervention attracted older and more educated participants than existing outpatient treatment programs for which cocaine is the primary substance of abuse. Participants in the intervention group showed greater treatment retention compared with the control group (P = .04). Low response rates at the follow-up assessments restricted the explanatory power of the analyses. At the follow-up assessments, the severity of cocaine dependence did not differ between the intervention and control groups (P = .75). Furthermore, there were no differences in cocaine craving, depression, or alcohol and other substance use. Using the consumption diaries, the average number of cocaine-free days per week did not change significantly, whereas the weekly quantity of cocaine used decreased equally in both groups (P = .009).

Conclusions

For cocaine users with low dependence severity, a fully automated Web-based cognitive behavioral self-help intervention is a feasible alternative with limited effectiveness in outpatient treatment services. However, this type of intervention may attract specific user groups that are rarely reached by existing outpatient treatment and may help them to control their cocaine consumption anonymously.

Trial Registration

ISRCTN93702927; http://www.controlled-trials.com/ISRCTN93702927 (Archived by WebCite at http://www.webcitation.org/6CTMM10MR)     

Clinical and microbiological features associated with group B <Emphasis Type="Italic">Streptococcus</Emphasis> bone and joint infections,France 2004–2014

This study describes the clinical and microbiological features associated with group B Streptococcus (GBS) bone and joint infections (BJIs). It was a retrospective analysis of adult cases of GBS BJIs reported to the French National Reference Center for Streptococci from January 2004 to December 2014. Clinical data and GBS molecular characteristics are reported. Strains were collected from 163 patients. The most frequent comorbidities were: solid organ cancer (n = 21, 21%) and diabetes mellitus (n = 20, 20%). The main infection sites were knee (47/155 = 30%) and hip (43/155 = 27%), and occurred on orthopedic devices in 71/148 cases (48%). CPS III (n = 47, 29%), Ia (n = 26, 16%) and V (n = 40, 25%) were predominant. Resistance to erythromycin, clindamycin and tetracycline was detected in 55/163 (34%), 35/163 (21%) and 132/163 (81%) strains, respectively. The most frequent sequence types were ST-1 (n = 21, 25%), ST-17 (n = 17, 20%) and ST-23 (n = 11, 13%). The rate of resistance to erythromycin was 0% for ST-17 strains, 52% (n = 11) for ST-1 and 44% (n = 7) for ST-23 (p < 0.001). GBS bone and joint infections predominantly occur in patients aged >50 years and/or with comorbidities such as cancer and diabetes mellitus. CPS type distribution and MLST are very similar to that of other adult GBS invasive infections.     

The effects of aging on postural control and selective attention when stepping down while performing a concurrent auditory response task

Purpose

To investigate the effects of aging on postural control and cognitive performance in single- and dual-tasking.

Methods

A cross-sectional comparative design was conducted in a university motion analysis laboratory. Young adults (n = 30; age 21.9 ± 2.4 years) and older adults (n = 30; age 71.9 ± 6.4 years) were recruited. Postural control after stepping down was measured with and without performing a concurrent auditory response task. Measurement included: (1) reaction time and (2) error rate in performing the cognitive task; (3) total sway path and (4) total sway area after stepping down.

Results

Our findings showed that the older adults had significantly longer reaction times and higher error rates than the younger subjects in both the single-tasking and dual-tasking conditions. The older adults had significantly longer reaction times and higher error rates when dual-tasking compared with single-tasking, but the younger adults did not. The older adults demonstrated significantly less total sway path, but larger total sway area in single-leg stance after stepping down than the young adults. The older adults showed no significant change in total sway path and area between the dual-tasking and when compared with single-tasking conditions, while the younger adults showed significant decreases in sway.

Conclusion

Older adults prioritize postural control by sacrificing cognitive performance when faced with dual-tasking.     

Effects of physical fitness on relaxed G-tolerance and the exercise pressor response

Fighter pilots are commonly recommended strength training as a means of improving the tolerance to withstand high gravitoinertial (G) loads. Previous studies on the effect of short-term strength-training regimens on G-endurance show equivocal results, with a majority of the studies suggesting improved G-endurance. The mechanisms underlying such improvement are unknown. Presumably, any change in G-tolerance induced by physical training habits should be manifest following long-term training. We also reasoned that during repeated straining maneuvers—as during certain G-endurance protocols—the relaxed G-tolerance and the exercise pressure response may play a significant role in maintaining adequate arterial pressure, and hence that different training modalities might alter G-endurance, by altering the exercise pressor response. Three groups of males were studied, long-term (>6 months) endurance-trained (E; n = 17), strength-trained (S; n = 16) and untrained (U; n = 17) individuals. The pressor response was studied during sustained (40 s) isometric knee extensions at 50 % of the maximal contraction level. Relaxed gradual onset-rate G-tolerance was determined. G-tolerance was similar in the E (4.6 ± 0.5 G), S (4.9 ± 0.8 G) and U (4.6 ± 0.8 G) groups. The mean arterial pressure increase during isometric exercise was higher in the S (36 ± 7 mmHg = mean ± SD) and U (35 ± 16 mmHg) groups than in the E group (28 ± 8 mmHg). The results suggest that relaxed G-tolerance is unaffected by physical training habits, and that the training modality affects the magnitude of the exercise pressor response. However, it seems that the response is blunted by endurance training rather than enhanced by strength training.     

The effects of recreational sport on VO2peak, VO2 kinetics and submaximal exercise performance in males and females

The purpose of the present study was to examine changes in VO_2peak, VO₂ kinetics and steady-state exercise performance following 4 weeks of participation in recreational sport. Subjects (male n = 8, female n = 9) participated in recreational sport (basketball, floor hockey and soccer) four times per week for 4 weeks. Both before and after training, VO_2peak was measured on a cycle ergometer, VO₂ kinetics was determined as the average of three transitions to 80 W, and heart rate (HR) and respiratory exchange ratio (RER) were measured during 60 min at a work rate corresponding to 50 % of pre-training VO_2peak. HR was also monitored during all training sessions. After training, VO_2peak was increased in females, but not males, while VO₂ kinetics (τVO₂) were sped in both males and females. HR during constant load exercise was reduced in both males and females, but exercise RER was only reduced in females. Mean HR during participation in sport was higher in males than females and higher during basketball than both floor hockey and soccer. These results demonstrate that training adaptations traditionally associated with endurance exercise can also be obtained through regular participation in recreational sport.     

Mid-term results of 17-mm St. Jude Medical Regent prosthetic valves in elder patients with small aortic annuli: comparison with 19-mm bioprosthetic valves

This study was designed to compare the mid-term outcomes after aortic valve replacement (AVR) between 17-mm mechanical heart valves (MV) and 19-mm bioprosthetic valves (BV) in elderly patients with small aortic annuli. Between 2000 and 2011, 127 consecutive patients (mean age 79 years; 87 % female) underwent AVR for aortic valve stenosis with a small aortic annulus. 19-mm BV (n = 67) was implanted. When the 19-mm BV did not fit the annulus, 17-mm St. Jude Medical Regent prosthetic mechanical valve (n = 60) was used instead of an aortic root-enlargement procedure. The follow-up rate was 94.0 % in the BV group, and 98.5 % in the MV group. No significant differences in survival rate and valve-related complications were found between the 2 groups. In-hospital mortality rates were 1.5 % (n = 1) in the BV group and 5.0 % (n = 3) in the MV group. Late mortality rates were 3.9 % per patient-years (p-y; n = 8) in the BV group, and 6.0 % per p-y (n = 10) in the MV group. Five-year Kaplan–Meier survival rates were 62 % in the BV group, and 72 % in the MV group (log-rank P = 0.280). Freedom from major adverse valve-related stroke and cerebral bleeding events was 92.5 and 98.5 % in the BV group, and 94.7 and 100 % in the MV group. AVR using 17-mm MV in elder patients with small aortic annuli provided equivalent mid-term clinical results to that with 19-mm BV.     

The Association Between Weight Status,Weight History,Physical Activity,and Cognitive Task Performance

Purpose

Physical activity has been shown to attenuate the association between overweight/obesity and deleterious cardiovascular health-related outcomes, with emerging work also taking the duration of overweight/obesity into consideration. No previous work, however, has explored the interrelationships between physical activity, obesity, and obesity duration in the context of cognitive task performance, which was the purpose of this study.

Method

Data from the 1999–2002 National Health and Nutrition Examination Survey were used (N = 2322 adults 60–85 yrs). Physical activity was assessed via self-report, with body mass index (BMI) directly measured. Participants were classified into one of eight mutually exclusive groups: (0) normal weight now and 10 years ago and active now (n = 195), (1) normal weight and 10 years ago and inactive now (n = 265), (2) normal weight now but not 10 years ago and active now (n = 46), (3) normal weight now but not 10 years ago and inactive now (n = 123), (4) overweight/obese now but not 10 years ago and active now (n = 117), (5) overweight/obese now but not 10 years ago and inactive now (n = 168), (6) overweight/obese now and 10 years ago and active now (n = 435), and (7) overweight/obese now and 10 years ago and inactive now (n = 973). The digit symbol substitution test (DSST) was employed to assess cognitive task performance.

Results

After adjustments, only individuals who were inactive (groups 1, 3, 5, and 7) had significantly lower cognitive task performance.

Conclusion

Being inactive, regardless of weight classification and duration of overweight/obesity, was inversely associated with cognitive task performance in this national sample of older adults.

     

Relationship between IL-27 and coronary arterial lesions in children with Kawasaki disease

Kawasaki disease (KD) arises due to the disorder of the inflammation response and faulty immune regulation. Interleukin-27 (IL-27) is a novel cytokine with both pro-inflammatory and anti-inflammatory effects. This study investigated the relationship between serum levels of IL-27, Interleukin-17A (IL-17A), Interleukin-10 (IL-10), Interleukin-6 (IL-6), Interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α) and coronary artery lesions (CALs) in patients with KD. We obtained blood samples from 81 children with KD before intravenous immunoglobulin (IVIG) therapy. Levels of IL-27, IL-17A, IL-10, IL-6, IL-1β and TNF-α were measured in 251 cases, including 4 groups: the normal control group, NC (n = 90), febrile control, FC (n = 80), KD without coronary arteries (n = 41) and KD with coronary arterial lesions (n = 40). White blood cells counts (WBC), red blood cells counts (RBC), hemoglobin, C-reactive protein (CRP), erythrocyte sedimentation rate and procalcitonin (PCT) were tested in all subjects. Levels of IL-27, IL-10, IL-17A, IL-6, IL-1β and TNF-α were significantly elevated, and RBC and hemoglobin significantly decreased in the group of KD group compared with febrile and control groups. IL-27, IL-6, IL-1β and TNF-α serum levels are even higher in KD children with CALs. There was positive relationship between serum levels of IL-27 and WBC, CRP, PCT, IL-10, IL-17A, IL-6 and TNF-α in children with KD. The up-regulation of IL-27 may be closely linked to up-regulation of systemic pro-inflammatory markers in acute KD. Morover, IL-27 may be involved in the development of CALs in acute KD.     

Project DyAdd: classical eyeblink conditioning in adults with dyslexia and ADHD

In this study of the project DyAdd (Adult Dyslexia and Attention Deficit Disorder in Finland), classical eyeblink conditioning (EBC) was investigated in both delay and trace paradigms in adults (18–55 years) with dyslexia (n = 37), attention deficit-hyperactivity disorder (ADHD; n = 21), their comorbid combination (n = 8), and healthy controls (n = 35). In addition, the profiles of three participants with a rare autosomal dominant cerebellar disease were assessed (episodic ataxia type 2, EA-2). We found that participants with dyslexia were overall slower learners than controls in eyeblink conditioning. Further, they were the only group that had a reduced number of CRs in mediotemporal-dependent trace paradigm compared to the more cerebellum-dependent delay paradigm. Second, ADHD was found to be related to larger CR amplitude. Third, those with a comorbid condition learned faster and manifested CRs that were not well timed. Fourth, the cerebellar patients showed nearly no conditioning at all. Correlations between EBC and various neuropsychological domains (phonological processing, reading, spelling, arithmetic, executive functions, attention, and fine motor control) over all participants resulted in significant relations only for the delay paradigm: Increased amount of reading errors related with later peak latency and increased amount of self-corrections in fine motor control related with larger response magnitude. Within those who conditioned, relations emerged only for the trace paradigm: better spelling was related to larger response magnitude. These results do not lend support to the cerebellar hypothesis of dyslexia. On the contrary, dyslexia in its pure form seems to be related to a relative dysfunction of a larger hippocampal–cerebellar network. Further, larger responses in the ADHD group are suggested to result from their lowered responding threshold.     

Continuous theta-burst stimulation of the right superior temporal gyrus impairs self-motion perception

Sensory input from the semicircular canals (SCC) and otolith organs is centrally combined with signals from other sensory modalities to continuously update the internal estimate of self-motion. Constant velocity vertical on-axis rotation leads to decay of the nystagmus response from the horizontal SCC and of perceived angular velocity (PAV), and when the rotation stops, a similar oppositely directed post-rotatory response occurs. Case reports and electrical stimulation studies suggest an involvement of the temporo-peri-Sylvian vestibular cortex in generating the PAV. Here, we transiently inhibited the right superior temporal gyrus (STG) by use of continuous theta-burst stimulation (cTBS) and predicted an accelerated decay of PAV compared to controls (n = 5 control session first, n = 1 cTBS session first). Constant velocity (100°/s) vertical on-axis rotations were applied over 75 s before (1 block) and after (3 blocks) cTBS over the right STG in six subjects. Breaks between the rotations (75 s) were initiated by abrupt stops. By use of a rotating potentiometer, subjects indicated the PAV during and after the chair rotations. Simultaneously eye positions were recorded using a scleral search coil. One subject was excluded for per-rotary analysis. Early after cTBS, the post-rotary PAV decay time constant (DTC) was significantly (9.4 ± 5.7 vs. 13.6 ± 5.9 s; p = 0.049) reduced (no directionality to this effect observed). Overall, post-rotary PAV showed a trend toward shortened DTC compared to the control trials (p = 0.086) in the first 25 min after cTBS, while per-rotary PAV was not significantly changed. Per-rotary and post-rotary aVOR DTC were not significantly changed after cTBS (p > 0.05). These findings support the hypothesis that the right STG is involved in mediating self-motion perception and can be modulated by cTBS.     

Experiences of carriers of multidrug-resistant organisms: a systematic review

Objectives

A comprehensive overview of the ways control measures directed at carriers of multidrug-resistant organisms (MDRO) affect daily life of carriers is lacking. In this systematic literature review, we sought to explore how carriers experience being a carrier and how they experience being subjected to control measures by looking at the impact on basic capabilities.

Poly-2-methoxyethylacrylate-coated cardiopulmonary bypass circuit can reduce transfusion of platelet products compared to heparin-coated circuit during aortic arch surgery

Several coating techniques for extracorporeal circulation have been developed to reduce the systemic inflammatory response during cardiopulmonary bypass (CPB). We compared the clinical effectiveness and biocompatibility of poly-2-methoxyethylacrylate (PMEA)- and heparin-coated CPB circuits in total aortic arch replacement (TAR) with the prolonged use of the bypass technique. Twenty patients who underwent elective TAR were divided randomly into two equal groups: group P (n = 10) to use PMEA-coated circuits and group H (n = 10) to use heparin-coated circuits. Clinical outcomes, hematological variables, and acute phase inflammatory response were analyzed perioperatively. Demographic, CPB, and clinical outcome data were similar for both groups. Hemoglobin and platelet count showed similar time-course curves. However, the amount of platelet products transfused intraoperatively was significantly larger in group H (group P 26.0 ± 7.0 units; group H 33.0 ± 6.7 units, p = 0.04). Total protein, and albumin levels were significantly higher in group P during and after the operation (total protein, p = 0.04; albumin, p = 0.02). The use of PMEA-coated circuit is associated with retainment of perioperative plasma proteins levels and may help to reduce transfusion of platelet products in TAR in comparison with the heparin-coated circuit.     

Psoriasis risk SNPs and their association with HIV-1 control

Human evolution has resulted in selection for genetic polymorphisms beneficial in the defense against pathogens. However, such polymorphisms may have the potential to heighten the risk of autoimmune disease. Here, we investigated whether psoriasis-associated single nucleotide polymorphisms influence host control of HIV-1 infection. We studied psoriasis and viral immune response variants in three HIV-positive cohorts: (1) HIV-1 controllers and non-controllers in the Study of the Consequences of the Protease Inhibitor Era (SCOPE) cohort (n = 366), (2) Individuals with primary HIV infection in the Options cohort (n = 675), and (3) HIV-positive injection drug users from the Urban Health Study (UHS) (n = 987). We found a strong association of two psoriasis MHC variants, rs9264942 and rs3021366, with both HIV-1 controller status and viral load, and identified another Class III MHC variant rs9368699 to be strongly associated with viral load. A number of genetic variants outside the MHC (SOX5, TLR9, SDC4, PROX1, IL12B, TLR4, MBL-2, TYK2, IFIH1) demonstrated nominal significance. Overall, our data suggest that several psoriasis variants within the MHC have a robust impact on HIV-1 control, while variants outside the MHC require further investigation.     

Characterization of the inflammatory response to solid cancer metastases in the human brain

New immunomodulatory agents showed promising activity in brain metastases (BM). However, little is known about the inflammatory response in BM. New insights are needed to further guide the development of treatment strategies. We investigated 17 human autoptic tissue specimens of BM from breast cancer (n = 3), non-small cell lung cancer (NSCLC; n = 5), small cell lung cancer (n = 3) and melanoma (n = 6). Immunohistochemical staining for a comprehensive panel of 21 inflammation-associated markers was performed. Results were quantified by manual counting of the various cell populations in three areas of 0.5 mm² (intratumoral, peritumoral, control region). Profound microglia activation with marked peritumoral accumulation and some intratumoral infiltration of HLA-DR-positive microglia/macrophages was found. A high proportion of these cells showed strong immunoreactivity for phagocytosis associated markers and MHC class 1, while a smaller subgroup of cells expressed molecules involved in radical production. Only few B- and T-lymphocytes were observed in and around BM. The number of CD8-positive T-cells was not correlated to MHC class 1 expression on tumor cells and only a fraction of T-cells showed Granzym B expression. Melanoma BM had significantly less accumulation of peritumoral microglia than NSCLC BM. The inflammatory pattern was independent from treatment of patients with glucocorticoids or radiation. The inflammatory reaction to BM is mainly characterized by activation of microglia/macrophages and shows pronounced upregulation of markers involved in phagocytosis, but seem to be insufficient in activating adaptive immunity. Treatment strategies aimed at activating specific immunity may potentiate immune attack on tumor cells.     

Ultra-endurance sports have no negative impact on indices of arterial stiffness

Purpose

Marathon running has been linked with higher arterial stiffness. Blood pressure is a major contributor to pulse wave velocity (PWV). We examined indices of arterial stiffness with a blood pressure-independent method in marathon runners and ultra-endurance athletes.

Methods

Male normotensive amateur runners were allocated to three groups according to former participation in competitions: group I (recreational athletes), group II (marathon runners) and group III (ultra-endurance athletes). Indices of arterial stiffness were measured with a non-invasive device (VaSera VS-1500N, Fukuda Denshi, Japan) to determine the cardio-ankle vascular index (CAVI, primary endpoint) and brachial-ankle PWV (baPWV). Lifetime training hours were calculated. Cumulative competitions were expressed as marathon equivalents. Linear regression analysis was performed to determine predictors for CAVI and baPWV.

Results

Measurements of arterial stiffness were performed in 51 subjects (mean age 44.6 ± 1.2 years): group I (n = 16), group II (n = 19) and group III (n = 16). No between-group differences existed in age, anthropometric characteristics and resting BP. CAVI and baPWV were comparable between all groups (P = 0.604 and P = 0.947, respectively). In linear regression analysis, age was the only independent predictor for CAVI (R ² = 0.239, β = 0.455, P = 0.001). Systolic BP was significantly associated with baPWV (R ² = 0.225, β = 0.403, P = 0.004).

Conclusions

In middle-aged normotensive athletes marathon running and ultra-endurance sports had no negative impact on arterial stiffness.     

Exercise volume and intensity: a dose–response relationship with health benefits

Introduction

The health benefits of exercise are well established. However, the relationship between exercise volume and intensity and health benefits remains unclear, particularly the benefits of low-volume and intensity exercise.

Purpose

The primary purpose of this investigation was, therefore, to examine the dose–response relationship between exercise volume and intensity with derived health benefits including volumes and intensity of activity well below international recommendations.

Methods

Generally healthy, active participants (n = 72; age = 44 ± 13 years) were assigned randomly to control (n = 10) or one of five 13-week exercise programs: (1) 10-min brisk walking 1×/week (n = 10), (2) 10-min brisk walking 3×/week (n = 10), (3) 30-min brisk walking 3×/week (n = 18), (4) 60-min brisk walking 3×/week (n = 10), and (5) 30-min running 3×/week (n = 14), in addition to their regular physical activity. Health measures evaluated pre- and post-training including blood pressure, body composition, fasting lipids and glucose, and maximal aerobic power (VO₂max).

Results

Health improvements were observed among programs at least 30 min in duration, including body composition and VO₂max: 30-min walking 28.8–34.5 mL kg^?1 min^?1, 60-min walking 25.1–28.9 mL kg^?1 min^?1, and 30-min running 32.4–36.4 mL kg^?1 min^?1. The greater intensity running program also demonstrated improvements in triglycerides.

Conclusion

In healthy active individuals, a physical activity program of at least 30 min in duration for three sessions/per week is associated with consistent improvements in health status.     

E-Cadherin in human brain tumours: loss of immunoreactivity in malignant meningiomas

Cadherins are a family of glycoproteins that are associated with cell adhesion mechanisms. They are divided into subclasses. The E- and P-cadherins are regarded as the epithelial subtype. Their expression has been demonstrated in many different carcinoma types. Using immunomorphological techniques, we studied the expression of E-cadherin in a series of 145 human brain tumours with the monoclonal antibody 5H9. Western blot analysis was used to confirm the immunohistochemical data. The tumour types represented were astrocytoma WHO I (n = 7), astrocytoma WHO II (n = 6), astrocytoma WHO III (n = 14), glioblastoma WHO IV (n = 8), oligodendroglioma WHO II (n = 5), ependymoma WHO II (n = 5), choroid plexus papilloma WHO I (n = 5), pineoblastoma WHO IV (n = 5), medulloblastoma WHO IV (n = 5), neurinoma WHO I (n = 5), meningioma WHO I and WHO III (n = 75) and pituitary adenoma WHO I (n = 5). Only choroid plexus papillomas (5/5) and meningiomas showed E-cadherin expression. In benign meningiomas (n = 45; 100%), positive E-cadherin immunoreactivity was found regardless of the histomorphological subtype. E-Cadherin was also expressed in 21 WHO I meningiomas (100%) invading dura, bone, brain, and muscle. In contrast, E-cadherin was absent from the majority of morphologically malignant meningiomas (6/9, 66.6%). In addition, in recurrent meningiomas (n = 9), E-cadherin expression in the recurrent tumours was identical to that in the primary neoplasm except in cases with malignant progression, where the malignant recurrent tumour was E-cadherin negative. In 2 cases of metastasizing meningiomas, no E-cadherin immunoreactivity was found in the primary tumours or their metastases.     

Reactive oxygen and nitrogen species in sepsis-induced hepatic microvascular dysfunction

Objective and design

Hepatic microvascular dysfunction is a critical event in the development of liver failure during sepsis. Activated blood cells and reactive oxygen and nitrogen species (RONS) have been implicated in the pathogenesis of sepsis.

Methods

Intravital-videomicroscopy was used to determine whether RONS contribute to the recruitment of leukocytes/platelets in the hepatic microvasculature during sepsis. Six hours following cecal-ligation and puncture (CLP), disturbances of the hepatic microvasculature were assessed in WT-mice (C57Bl/6 J; n = 8), in mice lacking gp91^phox(n = 5), overexpressing superoxide-dismutase (SOD, n = 8), in WT-mice treated with a NOS-inhibitor (l-NAME, n = 5), lacking nNOS, eNOS or iNOS (n = 5 each), treated with the NO-donor DetaNO (n = 5), in WT-mice treated with gadolinium-chloride (GdCl₂, n = 5) and compared to a group of WT-mice following a sham operation (n = 8). Six hours post-CLP, the adhesion of leukocytes and platelets in terminal hepatic venules (THV) and sinusoids was quantified.

Results

In WT-mice, CLP elicited increases in the number of adherent leukocytes and platelets. Similar responses to CLP were noted in mice overexpressing SOD or lacking either eNOS or gp91^phox. The blood-cell recruitment was significantly blunted in septic iNOS-knockout mice and this response was reversed by pre-treatment with DetaNO.

Conclusion

These findings suggest that iNOS-derived NO is a determinant of the pro-inflammatory phenotype assumed by the hepatic microvasculature during sepsis.