Longitudinal Changes in CT Body Composition in Patients Undergoing Surgery for Colorectal Cancer and Associations With Peri-Operative Clinicopathological Characteristics.

There is evidence for the direct association between body composition, the magnitude of the systemic inflammatory response, and outcomes in patients with colorectal cancer. Patients with a primary operable disease with and without follow-up CT scans were examined in this study. CT scans were used to define the presence and changes in subcutaneous fat, visceral fat, skeletal muscle mass, and skeletal muscle density (SMD). In total, 804 patients had follow-up scans and 83 patients did not. Furthermore, 783 (97%) patients with follow-up scans and 60 (72%) patients without follow-up scans were alive at 1 year. Patients with follow-up scans were younger (p < 0.001), had a lower American Society of Anaesthesiology Grade (p < 0.01), underwent a laparoscopic surgery (p < 0.05), had a higher BMI (p < 0.05), a higher skeletal muscle index (SMI) (p < 0.01), a higher SMD (p < 0.01), and a better 1-year survival (p < 0.001). Overall only 20% of the patients showed changes in their SMI (n = 161) and an even lower percentage of patients showed relative changes of 10% (n = 82) or more. In conclusion, over the period of ~12 months, a low-skeletal muscle mass was associated with a systemic inflammatory response and was largely maintained following surgical resection.

The relationship between computed tomography-derived body composition, systemic inflammatory response, and survival in patients undergoing surgery for colorectal cancer.

INTRODUCTION: Colorectal cancer is the fourth leading cause of cancer mortality in developed countries. There is evidence supporting a disproportionate loss of skeletal muscle as an independent prognostic factor. The importance of the systemic inflammatory response as a unifying mechanism for specific loss of skeletal muscle mass in patients with cancer is increasingly recognized. The aim of the present study was to delineate the relationship between the systemic inflammatory response, skeletal muscle index (SMI), skeletal muscle density (SMD), and overall survival in patients with colorectal cancer. MATERIALS AND METHODS: The study included 650 patients with primary operable colorectal cancer. Computed tomography scans were used to define the presence of visceral obesity, sarcopenia (low SMI), and myosteatosis (low SMD). Tumour and patient characteristics were recorded. Survival analysis was carried out using univariate and multivariate Cox regression. RESULTS: A total of 650 patients (354 men and 296 women) were included. The majority of patients were over 65 years of age (64%) and overweight or obese (68%). On univariate survival analysis, age, ASA, TNM stage, modified Glasgow Prognostic Score (mGPS), body mass index, subcutaneous fat index, visceral obesity, SMI, and SMD were significantly associated with overall survival (all P < 0.05). A low SMI and SMD were significantly associated with an elevated mGPS (<0.05). On multivariate analysis, SMI (Martin) [hazard ratio (HR) 1.50, 95% confidence interval (CI) 1.04-2.18, P = 0.031], SMD (Xiao) (HR 1.42, 95% CI 0.98-2.05, P = 0.061), and mGPS (HR 1.44, 95% CI 1.15-1.79, P = 0.001) were independently associated with overall survival. SMD but not SMI was significantly associated with ASA (P < 0.001). CONCLUSIONS: This study delineates the relationship between the loss of quantity and quality of skeletal muscle mass, the systemic inflammatory response, and survival in patients with operable colorectal cancer.

Role of the kinesin neck linker and catalytic core in microtubule-based motility.

Kinesin motor proteins execute a variety of intracellular microtubule-based transport functions [1]. Kinesin motor domains contain a catalytic core, which is conserved throughout the kinesin superfamily, followed by a neck region, which is conserved within subfamilies and has been implicated in controlling the direction of motion along a microtubule [2] [3]. Here, we have used mutational analysis to determine the functions of the catalytic core and the approximately 15 amino acid 'neck linker' (a sequence contained within the neck region) of human conventional kinesin. Replacement of the neck linker with a designed random coil resulted in a 200-500-fold decrease in microtubule velocity, although basal and microtubule-stimulated ATPase rates were within threefold of wild-type levels. The catalytic core of kinesin, without any additional kinesin sequence, displayed microtubule-stimulated ATPase activity, nucleotide-dependent microtubule binding, and very slow plus-end-directed motor activity. On the basis of these results, we propose that the catalytic core is sufficient for allosteric regulation of microtubule binding and ATPase activity and that the kinesin neck linker functions as a mechanical amplifier for motion. Given that the neck linker undergoes a nucleotide-dependent conformational change [4], this region might act in an analogous fashion to the myosin converter, which amplifies small conformational changes in the myosin catalytic core [5,6].

Determinants of Physicians' Intention to Collect Data Exhaustively in Registries: an Exploratory Study in Bamako's Community Health Centres.

BACKGROUND: The incomplete collection of health data is a prevalent problem in healthcare systems around the world, especially in developing countries. Missing data hinders progress in population health and perpetuates inefficiencies in healthcare systems. OBJECTIVE: This study aims to identify the factors that predict the intention of physicians practicing in community health centres of Bamako, Mali, to collect data exhaustively in medical registries. DESIGN: A cross sectional study. METHOD: In January and February 2011, we conducted a study with a random sample of thirty two physicians practicing in community health centres of Bamako, using a questionnaire. Data was analyzed by using descriptive statistics, correlations and linear regression. MAIN OUTCOMES MEASURES: Trained investigators administered a questionnaire measuring physicians' sociodemographic and professional characteristics as well as constructs from the Theory of Planned Behaviour. RESULTS: Our results showed that physicians' intention to collect data exhaustively is influenced by subjective norms and by the physician's number of years in practice. CONCLUSIONS: the results of this study could be used as a guide for health workers and decision makers to improve the quality of health information collected in community health centers.

An enzyme immunoassay design using labelled antibodies for the determination of haptens. Application to methotrexate assay.

A competitive enzyme immunoassay with labelled antibodies has been developed for methotrexate (MTX). Methotrexate in the sample and a constant quantity of this hapten physically absorbed to polystyrene spheres through a methylated bovine albumin carrier were allowed to compete for a limiting amount of peroxidase labelled antibody. After washing, the residual enzyme activity bound to the solid phase was measured. This test was able to detect 10 fm of MTX per sample. A comparative study of this test with a commercial radioimmunoassay kit using the same antiserum and a high pressure liquid chromatography method showed that the sensitivity, specificity and precision of this test were as good as of the radioimmunoassay. The high pressure liquid chromatography method was 500 times less sensitive. Good agreement was found among the 3 methods on 83 serum samples from patients receiving methotrexate therapy.

A new case of total kininogen deficiency.

Six families with total kininogen deficiency have been described in the literature. We report herein an additional case in a Pakistanese woman. The defect was discovered accidentally due to lack of normal clot formation in a preoperative routine blood sample. She had a borderline prolonged bleeding time, and reported occasional hematuria, but was otherwise without symptoms. Absence of both kininogen species was proven by functional and immunological methods, and by lack of kinin formation both by plasma kallikrein and hog pancreas kallikrein. Prekallikrein was reduced, probably because the main part circulates complexed to high molecular kininogen. Activation of intrinsic fibrinolysis was grossly hampered, and cold activation of coagulation absent with epsilonaminocaproic acid and greatly retarded by dextran sulfate, kaolin and ellagic acid. Together with other evidence the findings indicate the following order of importance for contact activation in plasma--F.XII, high molecular weight kininogen, prekallikrein.

A case of withdrawal from the GHB precursors gamma-butyrolactone and 1,4-butanediol.

We describe a case of withdrawal from the gamma hydroxybutyric acid (GHB) precursors gamma butyrolactone and 1,4-butanediol. Symptoms included visual hallucinations, tachycardia, tremor, nystagmus, and diaphoresis. Administration of benzodiazepines and phenobarbital successfully treated the withdrawal symptoms. As predicted from the metabolism of gamma butyrolactone and 1,4-butanediol to GHB, the symptoms were nearly identical to those reported from GHB withdrawal. Because GHB is now illegal in the United States, individuals have begun abusing the legal and easier to acquire GHB precursors. More frequent cases of both abuse and withdrawal from these GHB precursors can be expected.

Comprehensive analysis of "bath salts" purchased from California stores and the internet.

STUDY OBJECTIVE: To analyze the contents of "bath salt" products purchased from California stores and the Internet qualitatively and quantitatively in a comprehensive manner. METHODS: A convenience sample of "bath salt" products were purchased in person by multiple authors at retail stores in six California cities and over the Internet (U.S. sites only), between August 11, 2011 and December 15, 2011. Liquid chromatography-time-of-flight mass spectrometry was utilized to identify and quantify all substances in the purchased products. RESULTS: Thirty-five "bath salt" products were purchased and analyzed. Prices ranged from $9.95 to 49.99 (U.S. dollars). Most products had a warning against use. The majority (32/35, 91%) had one (n = 15) or multiple cathinones (n = 17) present. Fourteen different cathinones were identified, 3,4-methylenedioxypyrovalerone (MDPV) being the most common. Multiple drugs found including cathinones (buphedrone, ethcathinone, ethylone, MDPBP, and PBP), other designer amines (ethylamphetamine, fluoramphetamine, and 5-IAI), and the antihistamine doxylamine had not been previously identified in U.S. "bath salt" products. Quantification revealed high stimulant content and in some cases dramatic differences in either total cathinone or synthetic stimulant content between products with the same declared weight and even between identically named and outwardly appearing products. CONCLUSION: Comprehensive analysis of "bath salts" purchased from California stores and the Internet revealed the products to consistently contain cathinones, alone, or in different combinations, sometimes in high quantity. Multiple cathinones and other drugs found had not been previously identified in U.S. "bath salt" products. High total stimulant content in some products and variable qualitative and quantitative composition amongst products were demonstrated.

Human papillomavirus-associated oropharyngeal cancer: a new clinical entity.

The incidence of oropharyngeal cancers is rising worldwide in both nonsmokers and nondrinkers. Epidemiology studies suggest a strong association between human papillomavirus (HPV) 16 infection, changing sexual behavior and cancer development. Despite initial presentation with locally advanced disease and poorly differentiated histology, HPV-associated oropharyngeal carcinoma is associated with a good prognosis because its response to chemotherapy and radiation. Clinicians should be aware of the risk of oropharyngeal cancer in young people to avoid unnecessary delay in diagnosis and treatment. A history of oral sex should be elicited in young patients with enlarged neck nodes and/or tonsillar masses.

Complications after therapeutic splenectomy for hematologic disease in adults.

221 patients were treated by splenectomy for various hematologic disorders, including immunologic thrombocytopenia (80 cases), hereditary spherocytosis (15 cases), immune hemolytic anemia (25 cases), chronic lymphatic leukemia (27 cases), lymphosarcoma (27 cases), myelofibrosis (11 cases) and pancytopenia/aplastic anemia (14 cases). There were 8 postoperative deaths (3.6%), and 49 patients (22%) had postoperative complications, mainly infections and bleeding. Complications were more frequent in cases of massive splenomegaly (greater than or equal to 1 000 g) (65 cases), severe thrombocytopenia (less than 20 X 10(6)/1) (51 cases), and leukemia. Late postsplenectomy fulminant infection was seen in 8 patients (3.6%) for a mean follow up of 5.3 years. We conclude that splenectomy is sufficiently well tolerated even by severely ill patients to make it applicable as a therapeutic modality in the various hematologic disorders presently studied.

Immunological typing of acute leukemias: immunoenzymatic staining of fixed cells compared with immunofluorescence staining of unfixed cells in suspension.

A panel of 14 monoclonal antibodies (McAb) against hematopoietic cell surface antigens was applied on mononuclear blood or bone marrow cells from 40 cases of acute leukemia in order to compare immunoenzymatic staining (IE) (alkaline phosphatase) of fixed cells with immunofluorescence staining (IF) of unfixed suspended cells. According to the immunological results, 25 cases were phenotyped as ALL and 15 cases as AML. Cases with blast crisis secondary to chronic myelogenous leukemia (CML-BC) were not represented in this series. In all ALL cases the two methods gave an identical antigenic distribution. In 20 our of 21 cases of non-T-cell ALL, a B-cell progenitor origin was demonstrated by a positive staining reaction with the anti-CD19 McAb AB1 or HD37, and in 10 cases additionally with the anti-CD20 McAb B1 or 1F5. In contrast to the results obtained with IF, IE revealed a poor preservation of the AB1 epitope on CD19, whereas the HD37 epitope was equally well demonstrated by both methods. In 15 cases of AML the distribution of positive versus negative cells with IE or IF was identical for all McAb except J5 (anti-CALLA) (CD10) and B1 (CD20). Thus, 10/15 AML cases expressed CALLA with IE compared to 2/15 with IF. The corresponding figures for B1 were 5/15 and 0/15, respectively. Accordingly, normal myeloid precursor cells were CALLA-positive with IE but negative with IF. The discrepancy probably reflects the fact that, whereas both intracytoplasmatic and membrane-bound antigens are exposed in IE, only the latter are in IF. If the alteration of antigenic accessibility after fixation is considered, IE can safely be used for immunophenotyping of acute leukemia.

[Folic acid deficiency can cause severe anemia and pancytopenia]. / Folsyremangel kan gi alvorlig anemi og pancytopeni.

Pancytopenia is occasionally a consequence of folate deficiency. The most important differential diagnostic considerations are haematologic malignancies, aplastic anaemia and vitamin B12 deficiency. We discuss the problem as exemplified by three patients. Bone marrow examination and determination of blood concentrations of vitamin B12 and folate will give the correct diagnosis.