Liver metastases from colorectal cancer: regional intra-arterial treatment following failure of systemic chemotherapy

This study was designed to determine response rate, survival and toxicity associated with combination chemotherapy delivered intra-arterially to liver in patients with hepatic metastases of colorectal origin refractory to standard systemic treatment. A total of 28 patients who failed prior systemic treatment with fluoropyrimidines received a median of 5 cycles of intra-arterial treatment consisting of 5-fluorouracil 700 mg/m2/d, leucovorin 120 mg/m2/d, and cisplatin 20 mg/m2/d for 5 consecutive days. Cycles were repeated at intervals of 5–6 weeks. A major response was achieved in 48% of patients: complete response in 8% and partial response in 40%. The median duration of response was 11.5 months. Median survival was 12 months at a median follow up of 12 months. On multivariate analysis, the only variables with a significant impact on survival were response to treatment and performance status. Toxicity was moderate: grades III–IV neutropenia occurred in 29% of patients. Most of the patients complained of fatigue lasting for a few days following each cycle. There were no cases of hepatobiliary toxicity. These findings indicate that regional intra-arterial treatment should be considered in selected patients with predominantly liver disease following failure of standard treatment. © 2001 Cancer Research Campaign http://www.bjcancer.co

Normal Gallbladder Visualization during Post-Ablative Iodine-131 Scan of Thyroid Cancer

Whole body iodine-131 scan is a well-established imaging method for the detection of metastatic or residual tumor sites in patients with well-differentiated thyroid cancer. Many false-positive iodine-131 scan findings mimicking metastatic thyroid cancer have long been reported. The authors describe a false positive uptake in normal gallbladder on post-ablative iodine-131 scan in a patient with papillary thyroid cancer. This finding should be considered to be another possible false-positive finding on iodine-131 whole body scan

Health professionals' and managers' definitions of developmentally appropriate healthcare for young people:Conceptual dimensions and embedded controversies

Objectives: We aimed to (i) explore how health professionals and managers who work with young people seek to define developmentally appropriate healthcare (DAH), (ii) identify the range of conceptual dimensions present in their definitions and (iii) explore the controversies embedded in their characterisations of DAH. Methods: A qualitative multisite ethnographic study was conducted across three hospitals in England. We undertook face-to-face semi-structured interviews with health professionals and managers; and non-participant observation in clinics, wards and meetings. Anonymised field notes and interview transcripts were analysed using thematic analysis. The theme conceptualisations of DAH' was then further analysed, and the resulting themes categorised to form conceptual dimensions. Results: We recruited 192 participants and conducted 65 interviews (41 with health professionals and 24 with managers) and approximately 1600 hours of non-participant observations (involving 103 health professionals and 72 managers). Despite the wide range of definitions provided by participants, five conceptual dimensions of DAH were identified: (i) biopsychosocial development and holistic care, (ii) acknowledgement of young people as a distinct group, (iii) adjustment of care as the young person develops, (iv) empowerment of the young person by embedding health education and health promotion and (v) interdisciplinary and interorganisational work. Also, some controversies were identified within most dimensions. Conclusions: This study illustrates the lack of a generalised definition of DAH for young people among UK health professionals and managers, and presents a set of five core dimensions that can inform future research to help define and evaluate DAH for young people

Gastrointestinal Dysfunction in a Parkinson’s Disease Rat Model and the Changes of Dopaminergic, Nitric Oxidergic, and Cholinergic Neurotransmitters in Myenteric Plexus

This study aims to explore the gastrointestinal dysfunction and the changes of dopaminergic, nitric oxidergic, and cholinergic neurons in the myenteric plexus of a Parkinson’s disease (PD) rat model. A PD rat model was induced through unilateral substantia nigra administration of 6-hydroxydopamine. Four weeks later, the feces in 1 h and residual solid food in stomach at 2 h after feeding were measured. Changes in tyrosine hydroxylase (TH) in substantial nigra, TH, choline acetyltransferase (ChAT), and neuronal nitric oxide synthase (nNOS) in gastric antrum and colon tissue were examined by immunohistochemistry. Reverse transcription (RT) polymerase chain reaction (PCR) and Western blot were used to evaluate and compare the levels of messenger RNA (mRNA) and protein expression of TH, ChAT, and nNOS in the GI tract between normal and 6-hydroxydopamine-lesioned rats. Compared with control samples, the number of TH+ cells in the damaged side of substantia nigra of 6-hydroxydopamine-lesioned rats decreased significantly (P < 0.01). The weight and water content of the fecal matter decreased (P < 0.01), and the percentage of residual solid food increased (P < 0.01). The average integrated optical densities of TH-positive areas in the gastric antrum and colon tissue increased significantly (P < 0.01), nNOS decreased significantly (P < 0.01), and there were no significant changes in ChAT (P > 0.05). TH and nNOS mRNA levels in the gastric antrum and proximal colon decreased (P < 0.01), there were no significant changes in ChAT mRNA levels (P > 0.05). The protein levels of TH in the GI tract were significantly increased (P < 0.01), nNOS significantly decreased (P < 0.01), and ChAT had no significant changes (P > 0.05). 6-Hydroxydopamine-lesioned rats had delayed gastric emptying and constipation that might be related to the gastrointestinal TH increase and nNOS decrease. These symptoms were not related to changes in cholinergic transmitters

Biopharmaceutical considerations in paediatrics with a view to the evaluation of orally administered drug products – a PEARRL review.

Objectives: In this review, the current biopharmaceutical approaches for evaluation of oral formulation performance in paediatrics are discussed. Key findings: The paediatric gastrointestinal (GI) tract undergoes numerous morphological and physiological changes throughout its development and growth. Some physiological parameters are yet to be investigated, limiting the use of the existing in vitro biopharmaceutical tools to predict the in vivo performance of paediatric formulations. Meals and frequencies of their administration evolve during childhood and affect oral drug absorption. Furthermore, the establishment of a paediatric Biopharmaceutics Classification System (pBCS), based on the adult Biopharmaceutics Classification System (BCS), requires criteria adjustments. The usefulness of computational simulation and modeling for extrapolation of adult data to paediatrics has been confirmed as a tool for predicting drug formulation performance. Despite the great number of successful physiologically based pharmacokinetic models to simulate drug disposition, the simulation of drug absorption from the GI tract is a complicating issue in paediatric populations. Summary: The biopharmaceutics tools for investigation of oral drug absorption in paediatrics need further development, refinement and validation. A combination of in vitro and in silico methods could compensate for the uncertainties accompanying each method on its own