Detection of circulating anodic antigen before and after specific chemotherapy in experimental murine Schistosomiasis mansoni.

In two groups of mice infected with 60 (group I) and 120 (group II) Schistosoma mansoni cercariae, respectively, the effects of intensity and duration of infection, and of praziquantel therapy (curative vs subcurative dose) on the levels of circulating anodic antigen (CAA), were studied. CAA was measured in trichloracetic acid-treated serum samples with an avidin-biotin enzyme-linked immunosorbent assay (AB-ELISA) using the monoclonal anti-CAA antibody. Total worm burdens, oogram patterns and ova counts/g liver and intestine were followed up. The lowest detectable level of CAA was about 1.0 ng/ml, and was positive with a worm load of 3-5/mouse. CAA levels became already detectable as early as 1-2 weeks post-infection (pi) before any parasitological parameter and showed a significant drop from the 11th-12th week pi onwards. A positive correlation was demonstrated between the CAA level and worm load. Following successful praziquantel therapy, CAA disappeared earlier than any of the other parameters studied.     

Outcome of Microscopic Incomplete Resection (R1) of Colorectal Liver Metastases in the Era of Neoadjuvant Chemotherapy

Background  

Data from patients with colorectal liver metastases (CRLM) who received neoadjuvant chemotherapy before resection were reviewed and evaluated to see whether neoadjuvant chemotherapy influences the predictive outcome of R1 resections (margin is 0 mm) in patients with CRLM.     

Quantitative 3D elemental microtomography of Cyclotella meneghiniana at 400-nm resolution

X-ray fluorescence tomography promises to map elemental distributions in unstained and unfixed biological specimens in three dimensions at high resolution and sensitivity, offering unparalleled insight in medical, biological, and environmental sciences. X-ray fluorescence tomography of biological specimens has been viewed as impractical—and perhaps even impossible for routine application—due to the large time required for scanning tomography and significant radiation dose delivered to the specimen during the imaging process. Here, we demonstrate submicron resolution X-ray fluorescence tomography of a whole unstained biological specimen, quantifying three-dimensional distributions of the elements Si, P, S, Cl, K, Ca, Mn, Fe, Cu, and Zn in the freshwater diatom Cyclotella meneghiniana with 400-nm resolution, improving the spatial resolution by over an order of magnitude. The resulting maps faithfully reproduce cellular structure revealing unexpected patterns that may elucidate the role of metals in diatom biology and of diatoms in global element cycles. With anticipated improvements in data acquisition and detector sensitivity, such measurements could become routine in the near future.     

Timing of psychiatric consultations: the impact of social vulnerability and level of psychiatric dysfunction

The authors examined the timing of patient referrals to a psychiatric consultation-liaison service in relation to the patient's social vulnerability and level of psychiatric dysfunction. One hundred consecutive patients were assessed with the INTERMED, a method to document biopsychosocial and health care-related aspects of disease. Although 30% of patients were referred within the first day of admission, 19% of requests for referrals were made after 2 weeks. Late referral was associated with high social vulnerability and early referral with severe psychiatric dysfunction. The authors illustrate the disadvantages of a psychiatric liaison model focusing on psychopathology alone and demonstrate the need for an integrated patient assessment in the general hospital, focusing on detecting frail elderly patients.     

Preconditioning of rat hearts by adenosine A1 or A3 receptor activation

A reduction in airway beta-adrenoceptor density has been reported in cystic fibrosis lung but the mechanism underlying this defect remains unclear. In this study, we have investigated whether the decrease in beta2-adrenoceptor associates with altered G protein-coupled receptor kinase (GRK) levels. We assessed GRK activity by rhodopsin phosphorylation, and beta2-adrenoceptor and GRK at the mRNA and protein levels by Northern and Western blotting in peripheral lung samples from normal donors and patients with cystic fibrosis. GRK activity was significantly increased in peripheral cystic fibrosis lung with parallel increases in GRK2/5 mRNAs and protein expression. Functionally, isoproterenol-stimulated adenylyl cyclase activity was also diminished by 65% in cystic fibrosis lung homogenates. These data suggest that the increase in GRK activity may be one of the mechanisms underlying alterations in the coupling between beta2-adrenoceptor and adenylyl cyclase via G-protein and may thus contribute to the downregulation of beta2-adrenoceptor in cystic fibrosis lung.     

Effects of impaired renal function on the pharmacokinetics and toxicity of i.v. ZD9331, a novel non-polyglutamated thymidylate synthase inhibitor,in adult patients with solid tumors

ZD9331 is a potent thymidylate synthase inhibitor. Renal and hepatic clearances were found to be important routes of elimination. The objectives of this pharmacologic trial were to investigate the effect of renal impairment on the pharmacokinetics of ZD9331, to study the toxicity profile and to document any antitumor effects of ZD9331 when administered i.v. to patients with different degrees of renal impairment. Patients were treated with ZD9331 130 mg/m2 given as an i.v. infusion on day 1 of a 4-week cycle to allow full pharmacokinetic assessment. Subsequent cycles involved the administration of ZD9331 on days 1 and 8, every 3 weeks. Patients were stratified according to their renal function assessed by the creatinine clearance: normal renal function (creatinine clearance > or =60 ml/min), mildly impaired renal function (creatinine clearance > or =40 to <60 ml/min) and moderately impaired renal function (creatinine clearance >25 to <40 ml/min). For pharmacokinetic analysis plasma sampling was performed during the first course and assayed using a validated liquid chromatographic tandem mass spectrometry assay. Twenty-three patients were entered on the study, of whom 21 received 130 mg/m2 ZD9331 in the first treatment cycle. No relationship was seen between renal impairment and plasma clearance nor with the area under the concentration-time curve of free ZD9331. Increasing renal impairment was associated with a greater incidence of myelosuppression. No predictive relationship between the clearance of free ZD9331 and the degree of renal impairment as determined by creatinine clearance could be assessed. However, data from this trial indicate that increased renal impairment may be associated with greater ZD9331-induced toxicity, particularly myelosuppression, although this cannot be attributed to any alteration in the plasma pharmacokinetics of ZD9331. Therefore, it may be necessary to administer a reduced dose of ZD9331 to patients with impaired renal function.     

The INTERMED: a screening instrument to identify multiple sclerosis patients in need of multidisciplinary treatment

OBJECTIVE: To analyse the value of the INTERMED, a screening instrument to assess case complexity, compared with the Expanded Disability Status Scale (EDSS) and the Guy's Neurological Disability Scale (GNDS) to identify multiple sclerosis (MS) patients in need of multidisciplinary treatment. METHODS: One hundred MS patients underwent INTERMED, EDSS, and GNDS examinations. Patient care needs were assessed by a multidisciplinary team and a goal oriented treatment plan was defined. Correlations between INTERMED, individual INTERMED domains, EDSS, GNDS sum score, and total number of proposed disciplines involved in the treatment plan were studied. RESULTS: Mean (SD) age was 40.6 (10.1) years. Median scores were 14.0 for the INTERMED, 4.0 for the EDSS, and 13.5 for the GNDS sum score. Moderate correlations were found between the INTERMED sum score and EDSS (r=0.59) and GNDS sum score (r=0.60). The number of disciplines as proposed by the multidisciplinary team showed the highest statistically significant correlation with the INTERMED sum score (r=0.41) compared with EDSS (r=0.32) and GNDS sum score (r=0.34). No significant or only weak correlations were found between the psychological domain of the INTERMED and EDSS or GNDS. CONCLUSION: The findings in this study show that there is an additional value of the INTERMED compared with the EDSS and GNDS in identifying MS patients in need of multidisciplinary treatment. The INTERMED domains show the area of the patient's vulnerability and care needs: especially the INTERMED's psychological and social domains may guide the clinician to deal with specific problems that complicate healthcare delivery.