Heterogeneous in vitro effects of doxorubicin on gene expression in primary human liposarcoma cultures

Background  

Doxorubicin is considered one of the most potent established chemotherapeutics in the treatment of liposarcoma; however, the response rates usually below 30%, are still disappointing. This study was performed to identify gene expression changes in liposarcoma after doxorubicin treatment.     

Reduced Neutrophil Sequestration in Lung Tissue after Laparoscopic Lavage in a Rat Peritonitis Model

Laparoscopy to treat abdominal infections is becoming more and more popular. The effects of the CO(2) pneumoperitoneum have not yet been completely clarified. In a rat peritonitis model, therefore, we investigated the influence of laparoscopic lavage in comparison with the conventional technique. A defined multibacterial fecal specimen was installed in the abdominal cavities of 80 rats. These animals were randomized to three groups: group 1 (n = 32), no intervention; group 2 (n = 24), conventional; group 3 (n = 24), laparoscopic lavage. At 1, 2, and 8 hours after the surgical intervention, animals were killed and autopsied. The main outcome measures were bacteremia, interleukin-6 (IL-6) in plasma and ascites, changes in the blood count, and myeloperoxidase (MPO) activity in lung, liver, kidney, and pancreas. Differences of bacteremia were not found. In the ascites a marked increase in IL-6 was observed after 8 hours, which was lower in the treatment groups than in the controls (p <0.025). MPO activity as a measure of the granulocytes present in the tissue showed significant changes only in lung tissue. Two hours after the surgical intervention, the MPO in the lung in the laparoscopy group was significantly lower than that in the controls and the laparotomy group. In conclusion, conventional and laparoscopic lavage reduce inflammation. In this model, laparoscopic lavage with a CO(2) pneumoperitoneum appeared to have no negative influence on the inflammatory reaction during the early postoperative phase. Reduced neutrophil sequestration in lung tissue following laparoscopic lavage reflects the lower level of trauma caused by laparoscopy.     

What predicts incident use of cannabis and progression to abuse and dependence? A 4-year prospective examination of risk factors in a community sample of adolescents and young adults

OBJECTIVES: To determine risk factors of incident onset of use, abuse and dependence of cannabis in a community sample of adolescents and young adults. METHODS: Risk factors were examined in a prospective longitudinal design across 4 years in a representative sample (N = 2,446) aged 14-24 at the outset of the study (EDSP). Patterns of DSM-IV defined cannabis use, abuse and dependence were assessed with the Composite International Diagnostic Interview (M-CIDI). Potential risk factors were assessed at baseline. Incident cannabis use, abuse and dependence at second follow-up (on average 42 months after baseline) were the main outcome measures in this study. Associations were analyzed with logistic and negative binomial regressions. RESULTS: Using 11 of a total of 56 variables examined, the predictive value of the final multiple logistic regression for incident cannabis use was moderately good (area under the ROC curve = 0.78). Cannabis use frequency was predicted in the final model by 18 variables, cannabis abuse by two variables in the younger subsample and nine factors in the older group, and dependence by eight variables (dependence: ROC curve area = 0.97). Incident cannabis use was predicted mainly by availability of drugs, peers' drug use, a more 'positive' attitude towards future drug use, and regular previous use of licit drugs, while cannabis dependence was predicted primarily by parental death before age 15, deprived socio-economic status, and baseline use of other illicit drugs. CONCLUSION: Different factors predict the onset or severity of cannabis use and the progression to abuse and dependence. In addition to well-documented risk factors such as peer group pressure, drug availability, and low self-esteem, findings suggest that family history (e.g. parental mental disorders, early parental death), and prior experiences with legal drugs play a significant role in the initiation of cannabis consumption and the transition to cannabis use disorders in adolescents and young adults. Findings suggest that early intervention and prevention might be improved by better targeted treatment.     

Generalized anxiety disorder: prevalence,burden, and cost to society

Generalized anxiety disorder (GAD) is a prevalent and disabling disorder characterized by persistent worrying, anxiety symptoms, and tension. It is the most frequent anxiety disorder in primary care, being present in 22% of primary care patients who complain of anxiety problems. The high prevalence rate of GAD in primary care (8%) compared to that reported in the general population (12-month prevalence 1.9-5.1%) suggests that GAD patients are high users of primary care resources. GAD affects women more frequently than men and prevalence rates are high in midlife (prevalence in females over age 35: 10%) and older subjects but relatively low in adolescents. The natural course of GAD can be characterized as chronic with few complete remissions, a waxing and waning course of GAD symptoms, and the occurrence of substantial comorbidity particularly with depression. Patients with GAD demonstrate a considerable degree of impairment and disability, even in its pure form, uncomplicated by depression or other mental disorders. The degree of impairment is similar to that of cases with major depression. GAD comorbid with depression usually reveals considerably higher numbers of disability days in the past month than either condition in its pure form. As a result, GAD is associated with a significant economic burden owing to decreased work productivity and increased use of health care services, particularly primary health care. The appropriate use of psychological treatments and antidepressants may improve both anxiety and depression symptoms and may also play a role in preventing comorbid major depression in GAD thus reducing the burden on both the individual and society.     

Management of Benign Biliary Strictures

Benign biliary strictures are most commonly a consequence of injury at laparoscopic cholecystectomy or fibrosis after biliary-enteric anastomosis. These strictures are notoriously difficult to treat and traditionally are managed by resection and fashioning of a choledocho- or hepato-jejunostomy. Promising results are being achieved with newer minimally invasive techniques using endoscopic or percutaneous dilatation and/or stenting and these are likely to play an increasing role in the management. Even low-grade biliary obstruction carries the risks of stone formation, ascending cholangitis and hepatic cirrhosis and it is important to identify and treat this group of patients. There is currently no consensus on which patient should have what type of procedure, and the full range of techniques may not be available in all hospitals. Careful assessment of the risks and likely benefits have to be made on an individual basis. This article reviews the current literature and discusses the options available. The techniques of endoscopic and percutaneous dilatation and stenting are described with evaluation of the likely success and complication rates and compared to the gold standard of biliary-enteric anastomosis.     

Pilzpneumonie

Concomitant with advances in medicine, involving the development and use of antibiotics, immunosuppressive drugs, organ/stem cell transplantation and pre-existing illnesses such as AIDS, the frequency of fungal infection has increased dramatically. These factors determine the susceptibility of the lung for an acute or chronic course of disease. Early detection, characterisation and follow-up of the pulmonary infiltrates is the major task of the radiologist. The correct timing to perform an investigation and adequate technique are an additional essential factor in this setting. Furthermore, radiological procedures support the clinicians in identifying the underlying micro-organism. The radiologist can suggest which micro-organism might cause the infiltrate. Certain findings and patterns can point to a specific causative agent, but experience, local epidemiology and clinical information are necessary for the differential diagnosis of infiltrates in long-term immunocompromised hosts. In addition, radiological techniques are useful in guiding interventions for identification of the underlying micro-organism or for therapeutical procedures. This review summarises useful radiological information of appearance and complications of fungal pneumonia.     

Acetyl-11-keto-β-boswellic acid, a constituent of a herbal medicine from Boswellia serrata resin, attenuates experimental ileitis

The gum resin extract from Boswellia serrata (H15), an herbal product, was recently shown to have positive therapeutic effects in inflammatory bowel disease (IBD). However, the mechanisms and constituents responsible for these effects are poorly understood. This study examined the effect of the Boswellia extract and its single constituent acetyl-11-keto-beta-boswellic acid (AKBA) on leukocyte-endothelial cell interactions in an experimental model of IBD. Ileitis was induced by two subcutaneous injections of indomethacin (7.5 mg/kg) in Sprague-Dawley rats 24 h apart. Rats also received oral treatment with the Boswellia extract (H15) or AKBA at two different doses (low and high) equivalent to recommendations in human disease over 2 days. Controls received only the carriers NaHCO3 (subcutaneously) and tylose (orally). Effects of treatment were assessed by intravital microscopy in ileal submucosal venules for changes in the number of rolling and adherent leukocytes and by macroscopic and histological scoring. Increased leukocyte-endothelial cell adhesive interactions and severe tissue injury accompanied indomethacin-induced ileitis. Treatment with the Boswellia extract or AKBA resulted in a dose-dependent decrease in rolling (up to 90%) and adherent (up to 98%) leukocytes. High-dose Boswellia extract as well as both low- and high-dose AKBA significantly attenuated tissue injury scores. Oral therapy with the Boswellia extract or AKBA significantly reduces macroscopic and microcirculatory inflammatory features normally associated with indomethacin administration, indicating that the anti-inflammatory actions of the Boswellia extract in IBD may be due in part to boswellic acids such as AKBA.