Multicentre analysis of treatment planning information: Technical requirements,possible applications and a proposal

Digital data from 3‐D treatment planning computers is generally used for patient planning and then never considered again. However, such data contains enormous quantities of information regarding patient geometries, tissue outlining, treatment approaches and dose distributions. Were such data accessible from planning systems from multiple manufacturers, there would be substantial opportunities for undertaking quality assurance of radiotherapy clinical trials, prospective assessment of trial outcomes and basic treatment planning research and development. The technicalities of data exchange between planning systems are outlined, and previous attempts at producing systems capable of viewing and/or manipulating imaging and radiotherapy digital data reviewed. Development of a software system for enhancing the quality of Australasian clinical trials is proposed.     

Loss of beta-catenin expression in metastatic gastric cancer.

PURPOSE: Beta-catenin (beta-catenin) participates in intercellular adhesion and is an integral part of the Wnt signaling pathway. The role of beta-catenin in the pathogenesis of gastric cancer and its metastasis is largely unknown. PATIENTS AND METHODS: Immunohistochemistry and Western blot analysis were used to analyze the expression of beta-catenin in 87 human gastric cancers, in metastasis and cancer cell lines. The beta-catenin and the adenomatous polyposis coli (APC) genes were analyzed for gene mutations. Furthermore, methylation of the beta-catenin promoter in cell lines was assessed by treatment with 5'-azadeoxycytidine and sodium bisulfite genomic sequencing. RESULTS: beta-Catenin expression was present at either the cell membrane or the cytoplasm in 34 of 75 primary gastric cancers. Expression of beta-catenin was significantly more frequent in intestinal-type (P =.0049) and well-differentiated gastric cancers (P <.001). There were no quantitative differences between gastric cancers and the nonmalignant gastric tissues, as determined by Western blot analysis. One of 18 metastatic cancer lesions and four of five gastric cancer cell lines expressed beta-catenin protein. N87 cells, derived from the liver metastasis of a gastric cancer, did not express beta-catenin. Treatment with 5'-azadeoxycytidine restored beta-catenin protein levels in this cell line, which exhibited significantly more 5-methylcytosines in the beta-catenin promoter compared with the other cell lines. CONCLUSION: beta-Catenin expression is lost in a subgroup of primary gastric cancers, is frequently absent in metastases, and exhibits nuclear localization in cancers with either beta-catenin or APC gene mutations. Interestingly, the loss of beta-catenin expression in metastatic gastric cancers may result from hypermethylation of the beta-catenin promoter.     

Auditing paediatric diabetes care and the impact of a specialist nurse trained in paediatric diabetes

AIMS: To define outcome measures for auditing the clinical care of children and adolescents with insulin dependent diabetes mellitus (IDDM) and to assess the benefit of appointing a dedicated paediatric trained diabetes specialist nurse (PDSN). METHODS: Retrospective analysis of medical notes and hospital records. Glycaemic control, growth, weight gain, microvascular complications, school absence, and the proportion of children undergoing an annual clinical review and diabetes education session were assessed. The effect of the appointment of a PDSN on the frequency of hospital admission, length of inpatient stay, and outpatient attendance was evaluated. RESULTS: Children with IDDM were of normal height and grew well for three years after diagnosis, but grew suboptimally thereafter. Weight gain was above average every year after diagnosis. Glycaemic control was poor at all ages with only 16% of children having an acceptable glycated haemoglobin. Eighty five per cent of patients underwent a formal annual clinical review, of whom 16% had background retinopathy and 20% microalbuminuria in one or more samples. After appointing the PDSN the median length of hospital stay for newly diagnosed patients decreased from five days to one day, with 10 of 24 children not admitted. None of the latter was admitted during the next year. There was no evidence of the PDSN affecting the frequency of readmission or length of stay of children with established IDDM. Non-attendance at the outpatient clinic was reduced from a median of 19 to 10%. CONCLUSIONS: Outcome measures for evaluating the care of children with IDDM can be defined and evaluated. Specialist nursing support markedly reduces the length of hospital stay of newly diagnosed patients without sacrificing the quality of care.     

Inflammatory bowel disease and predisposition to osteopenia

The prevalence of osteopenia in children with inflammatory bowel disease (IBD) is unknown. The effect of nutritional state, disease activity, and steroid therapy on bone mineral content (BMC) of whole body, lumbar spine, and left femoral neck measured by dual energy x ray absorptiometry in 32 children with IBD was assessed by comparison with 58 healthy local school children. Using the control data, a predicted BMC was calculated taking into account bone area, age, height, weight, and pubertal stage. The measured BMC in children with IBD was expressed as a percentage of this predicted value (% BMC). Mean (SD) % BMC was significantly reduced for the whole body and left femoral neck in the children with IBD (97.0 (4.5)% and 93.1 (12.0)% respectively, p < 0.05). Of the children with IBD, 41% had a % BMC less than 1 SD below the mean for the whole body and 47% at the femoral neck. Reduction in % BMC was associated with steroid usage but not with the magnitude of steroid dose, disease activity, or biochemical markers of bone metabolism. In conclusion, osteopenia is relatively common in childhood IBD and may be partly related to the previous use of steroids.     

Phenotypic diversity in siblings with partial androgen insensitivity syndrome

The androgen insensitivity syndrome is a heterogeneous disorder with a wide spectrum of phenotypic abnormalities, ranging from complete female to ambiguous forms that more closely resemble males. The primary abnormality is a defective androgen receptor protein due to a mutation of the androgen receptor gene. This prevents normal androgen action and thus leads to impaired virilisation. A point mutation of the androgen receptor gene affecting two siblings with partial androgen insensitivity syndrome is described. One had cliteromegaly and labial fusion and was raised as a girl, whereas the other sibling had micropenis and penoscrotal hypospadias and was raised as a boy. Both were shown to have the arginine 840 to cysteine mutation. The phenotypic variation in this family is thus dependent on factors other than abnormalities of the androgen receptor gene alone.     

Immunobiology of T helper cells and antigen-presenting cells in autoimmune thrombocytopenic purpura (ITP)

Autoimmune thrombocytopenic purpura (AITP) is a bleeding disease in which autoantibodies are directed against the individual's own platelets, resulting in enhanced Fc-mediated platelet destruction by macrophages in the reticuloendothelial system. Most research in AITP has focused on characterization of the autoantibodies, while little has been devoted to the cellular immune mechanisms leading to autoantibody production. This report summarizes the current state of the literature and argues that enhanced T helper cell/antigen-presenting cell interactions in patients with AITP are the primary stimulus for the development of antiplatelet autoantibody production. Understanding these events is important for eventually identifying disease-initiating platelet autoantigens and ultimately developing specific immunotherapies for AITP.     

Anticonvulsant efficacy of topiramate in phenytoin-resistant kindled rats

PURPOSE: We evaluated the anticonvulsant efficacy of topiramate (TPM), a structurally novel antiepileptic drug (AED), in amygdala kindled rats that had been preselected with respect to their response to phenytoin (PHT). METHODS: Anticonvulsant response was tested by determining the afterdischarge threshold (ADT; i.e., a sensitive measure for drug effects on focal seizure activity). By repeated testing with the PHT prodrug fosphenytoin (FOS) three groups of kindled rats were separated: rats in which consistent anticonvulsant effects were obtained (PHT responders), rats that showed no anticonvulsant response (PHT nonresponders), and rats with variable responses (variable PHT responders). The latter, largest group was used to evaluate at which doses and pretreatment times TPM exerted significant anticonvulsant effects on ADT. For this purpose, TPM was tested at four doses (20, 40, 80, 160 mg/kg i.p.) and two pretreatment times (1 and 4 h). The most effective treatment protocol was then used for TPM testing in PHT responders and nonresponders. RESULTS: TPM proved to be an effective AED in the kindling model. At 40 mg/kg, significant ADT increases were obtained after both 1 and 4 h after administration. In addition to the effect on focal seizure threshold, seizure severity and duration recorded at ADT were decreased by TPM, indicating that this drug acts on both seizure threshold and seizure spread. In PHT nonresponders, TPM significantly increased ADT, which is in line with its proven efficacy in patients with refractory partial epilepsy in whom phenytoin has failed. However, TPM was more efficacious in increasing ADT in PHT responders than in nonresponders, substantiating that the difference between these groups of kindled rats extends to other AEDs. Repeated testing of kindled rats with TPM indicated that, similar to PHT, there are individual kindled rats without anticonvulsant response to TPM (i.e., TPM nonresponders). CONCLUSIONS: The data of this study substantiate that PHT nonresponders are a unique model for the search of new AEDs with improved efficacy in refractory partial epilepsy.     

Frontal-executive dysfunction in early onset cerebellar ataxia of Holmes' type

We report the case of a 29-year-old male patient with cerebellar ataxia of Holmes' type. The combination of progressive cerebellar ataxia and hypogonadotrophic hypogonadism is a rare distinctive syndrome which was first described by Holmes in 1907. Early diagnosis is desirable because replacement of testosterone may allow normal sexual development. MRI showed severe combined superior vermian and cerebellar hemisphere atrophy. Comprehensive neuropsychological testing pointed to a more widespread cerebellar mediated functional CNS involvement in the earlier stages of this ataxic syndrome than previously described in mentally not retarded subjects.     

Renal responses to low-flow desflurane, sevoflurane, and propofol in patients

BACKGROUND: The contributing factors that result in significant, postoperative proteinuria and glucosuria after low-flow isoflurane and sevoflurane anesthesia are unknown. The present study compared renal responses after anesthesia with desflurane (negligible metabolism), sevoflurane, or intravenous propofol. METHODS: Informed consent was obtained from 52 patients with American Society of Anesthesiologists physical status I-III (aged 36-81 yr). Patients with diabetes or renal insufficiency were excluded. Desflurane (n = 20) or sevoflurane (n = 22), without nitrous oxide, was given at 1 l/min fresh gas flow for elective surgical procedures lasting more than 2 h; 10 patients received propofol without nitrous oxide as the primary anesthetic. Blood and urine chemistries were obtained before surgery. Blood and 24-h urine collections were obtained for 3 days after surgery and were analyzed for liver and renal indices. RESULTS: Length of surgery averaged approximately 300 min (range, 136-750 min), minimum alveolar concentration-hour averaged 4.3 (range, 1.2-11.0), and infusion rates of propofol were 99-168 microg x kg(-1) x min(-1). Plasma creatinine concentration did not change, plasma blood urea nitrogen decreased significantly, and significant increases in urine glucose, protein, and albumin occurred similarly in all groups. Mean (+/- SD) postoperative urine glucose values for day 1 after desflurane, sevoflurane, and propofol were 1.4 +/- 3.0, 1.1 +/- 2.1, and 1.9 +/- 2.6 g/d (normal, < 0.5 g/d). The average daily protein/creatinine ratios for postoperative days 2-3 after desflurane, sevoflurane, and propofol were 240 +/- 187, 272 +/- 234, and 344 +/- 243 (normal, < 150 mg/g). Regardless of anesthetic, there were significantly greater urine protein concentrations after surgical procedures in central versus peripheral regions. CONCLUSIONS: Alterations in postoperative renal function were common and unrelated to the choice of anesthetic. These findings implicate nonanesthetic factors in producing changes in biochemical indices of renal excretory function.