Endotoxin-induced cytokine and chemokine expression in the HIV-1 transgenic rat

Background  

Repeated exposure to a low dose of a bacterial endotoxin such as lipopolysaccharide (LPS) causes immune cells to become refractory to a subsequent endotoxin challenge, a phenomenon known as endotoxin tolerance (ET). During ET, there is an imbalance in pro- and anti-inflammatory cytokine and chemokine production, leading to a dysregulated immune response. HIV-1 viral proteins are known to have an adverse effect on the immune system. However, the effects of HIV-1 viral proteins during ET have not been investigated.     

Consensus on melanonychia nail plate dermoscopy

This statement, focused on melanonychia and nail plate dermoscopy, is intended to guide medical professionals working with melanonychia and to assist choosing appropriate management for melanonychia patients. The International Study Group on Melanonychia was founded in 2007 and currently has 30 members, including nail experts and dermatopathologists with special expertise in nails. The need for common definitions of nail plate dermoscopy was addressed during the Second Meeting of this Group held in February 2008. Prior to this meeting and to date (2010) there have been no evidence-based guidelines on the use of dermoscopy in the management of nail pigmentation.     

The Association between the Low Muscle Mass and Osteoporosis in Elderly Korean People

The purpose of this study was to predict osteoporosis risk as decreasing muscle mass and to declare the cut-off value of low muscle mass in an elderly Korean population. This study was based on data from the 2008-2010 Korea National Health and Nutritional Examination Surveys (KNHANES). The subjects included 1,308 men and 1,171 women over 65 yr. Bone mineral density (BMD) and appendicular skeletal muscle (ASM) were measured by dual energy X-ray absorptiometry (DXA), and appendicular skeletal muscle was adjusted by height as a marker of sarcopenia. After confirming the correlation between low muscle mass and BMD, the best cut-off value of muscle mass to estimate osteoporosis was suggested through the receiver operating characteristic (ROC) curve. For both men and women, BMD correlated positively with low muscle mass when ASM/Ht² was used as a marker for sarcopenia. The ROC curve showed that ASM/Ht² was the best marker for osteoporosis at a cut-off value of 6.85 kg/m² for men and 5.96 kg/m² for women. When these cut-off values were used to determine sarcopenia, the risk of osteoporosis increased 4.14 times in men and 1.88 times in women. In particular, men (OR 2.12) with sarcopenia were more greatly affected than women (OR 1.15), even after adjusting for osteoporosis risk factors. In elderly Korean people, sarcopenia is positively correlated with BMD and there is a strong correlation between sarcopenia and osteoporosis with risk of bone fracture.     

Significance of COX‐2 and VEGF expression in histopathologic grading and invasiveness of meningiomas

Meningiomas are slow‐growing neoplasms that recur locally. Their morphologic grading does not always correlate with patient outcome. We evaluated the status of several immunohistochemical markers with histopathologic parameters in various grades of meningioma.Eighty‐eight meningioma specimens were examined immunohistochemically to determine the status of Ki‐67, cyclin D1, epidermal growth factor receptor (EGFR), cyclooxygenase‐2 (COX‐2), vascular endothelial growth factor (VEGF), and bcl‐2. Several clinical and pathological parameters were investigated.Forty‐nine Grade I, 33 Grade II, and 6 Grade III meningiomas were observed. VEGF and Ki‐67 expression was correlated with higher tumor grade. The association between grade and other immunohistochemical markers expression was not significant. A correlation was observed between COX‐2 expression and invasiveness to the brain or adjacent soft tissue. Tumor recurrence was correlated with brain or adjacent soft tissue invasion. We also observed a relationship between VEGF level and COX‐2 expression, and they were both correlated with necrosis.Immunohistochemical evaluation of VEGF, COX‐2, and Ki‐67 expression can provide information regarding the behavior of meningiomas, particularly for cases in which histological grading is not straightforward.     

The pharmacological mechanisms of omalizumab in patients with very high IgE levels—Clues from studies on atopic dermatitis

Seventeen case series investigating the effects of omalizumab on patients with atopic dermatitis included patients whose pretreatment serum IgE was above 700 IU/ml, the upper inclusion limit specified in the product label. In all, 107 patients received omalizumab at doses of ≤375 mg every 2 weeks, which is recommended for patients with IgE <700 IU/ml. Among them, 87 improved in clinical symptoms and some did so after the first dose. Among these 87 patients, 35 and 12 had pretreatment serum IgE in the range 700–7000 IU/ml and 7000–121,000 IU/ml, respectively. These results not only suggest the pathogenic roles of IgE and the potential utility of omalizumab in atopic dermatitis, but also raise questions concerning the pharmacological mechanisms of omalizumab in patients with very high IgE levels. If omalizumab at regular doses is proven to treat patients with ultra high IgE (e.g. above 7000 IU/ml) effectively, it probably achieves this without neutralizing most of the IgE produced in the patients and downregulating the high-affinity IgE-Fc receptors on basophils and mast cells. Herein, we propose that a potential main pharmacological mechanism of omalizumab in patients with ultra high IgE is the ability of the rapidly accumulated IgE:omalizumab complexes to trap allergens.     

Development and preliminary validation of the PC‐SAD5, a screener‐derived short depression severity measure

Background The prevalence of depressive disorders is high among patients with skin disease. The PC‐SAD is a 37‐item self‐administered depression screening questionnaire that has been validated in dermatological patients. Objective The aim of this study was to develop and validate a brief depression severity instrument derived from the PC‐SAD that can be used to assess severity and monitor ongoing clinical course. Methods Two patient samples participated in the study: 72 adult dermatological inpatients and 73 adults attending six primary care practices. Psychiatric assessment included the Structured Clinical Interview for DSM‐IV and an 18‐item version of the PC‐SAD; moreover, dermatological patients completed the Patient Health Questionnaire depression scale (PHQ‐9), while primary care patients were administered the Montgomery‐Asberg Depression Rating Scale (MADRS). A subset of five PC‐SAD items showing the best psychometric properties were selected, and the reliability and validity of the resulting instrument (PC‐SAD5) were examined. Results The PC‐SAD5 showed satisfactory internal consistency in both samples. There was a high correlation between PC‐SAD5 and PHQ‐9 and MADRS scores. Multiple regression analysis revealed a gradient of PC‐SAD5 scores from patients with no mental disorder, those with milder forms of depression, to those with Major Depressive Disorder. Similar results were observed for the 18‐item version of the PC‐SAD. Conclusion The availability of valid and reliable continuous measures of depression severity derived from the PC‐SAD extends its field of application from depression screening to use as a follow‐up measure of depression severity in routine clinical practice. A validated very short instrument such as the PC‐SAD5 may have substantial clinical value.