Endoscopic ultrasonography-guided portal injection chemotherapy for hepatic metastases.

INTRODUCTION: We hypothesized that endoscopic ultrasonography-guided portal injection chemotherapy (EPIC) using irinotecan-loaded microbeads may achieve increased intrahepatic concentrations, while decreasing systemic exposure. This may achieve enhanced efficacy for the treatment of diffuse liver metastases, while decreasing systemic toxicities. MATERIALS AND METHODS: In eight anesthetized 35 kg pigs, EPIC was performed transgastrically using the linear-array echoendoscope and a 22 g fine-needle aspiration. In four animals, irinotecan (100 mg) loaded onto 75-150 micron liquid chromatography (LC) beads was injected. In four animals, saline was injected into the portal vein and unloaded irinotecan (100 mg) was injected into the jugular vein. Plasma (every 15 min), and at 1 h bone marrow, liver and skeletal muscle samples were obtained. Irinotecan and SN-38 (active metabolite) concentrations were assayed by LC/mass spectrometry. RESULTS: The procedure was performed safely in all eight animals. Compared with systemic administration, EPIC resulted in almost twice the hepatic concentration of irinotecan (6242 vs. 3692 ng/g) and half the systemic concentrations in plasma (1092 vs. 2762 ng/mL), bone marrow (815 vs. 1703 ng/mL) and skeletal muscle (521 vs. 1058 ng/g). SN-38 levels were lower with EPIC (liver: 166 vs. 681 ng/g; plasma: 1.8 vs. 2.4 ng/mL; bone marrow: 0.9 vs. 1.4 ng/mL; muscle 4.6 vs. 9.2 ng/g). Liver histology showed the beads within small portal venules. CONCLUSIONS: EPIC using irinotecan-loaded microbeads can enhance hepatic exposure to irinotecan, while decreasing systemic concentrations. SN-38 levels were lower with EPIC indicating that a substantial portion of the irinotecan was still loaded onto beads. The microbeads may act as a reservoir resulting in prolonged hepatic drug exposure.

Risk equations to predict life expectancy of people with Type 2 diabetes mellitus following major complications: a study from Western Australia.

AIMS: To develop a model for predicting life expectancy following major diabetes-related complications and to summarize these results by age and gender in the form of a simple table. METHODS: Equations for forecasting mortality were derived using an observational cohort of 12,792 patients who had one of the following complications of diabetes: myocardial infarction, stroke, heart failure, amputation or renal failure, recorded in administrative health and mortality data from the state of Western Australia between 1990 and 1999. Logistic regression was used to estimate mortality within the first month post-event and a Gompertz proportional hazards model was used to estimate survival over the patients' remaining lifetime. After examining the internal validity over a 5-year period, these equations were used to estimate remaining life expectancy by age and sex following specific complications. RESULTS: Of the complications examined, renal failure had most impact on life expectancy at all ages, followed by heart failure; the best prognosis was following stroke, myocardial infarction and amputation. For a 60-year-old male, life expectancy immediately post-event ranged from 10.1 years (95% CI 9.4-10.8 years) for stroke to 4.3 years (95% CI 3.1-6.1 years) for renal failure. Life expectancies for women at 60 and 70 years of age were significantly lower than men following myocardial infarction and significantly higher than men following heart failure and amputation at 70 and 80 years of age. CONCLUSION: The model allows estimation of both survival probability and life expectancy post-event for men and women of any age. The summary table may provide a useful and simple reference for clinicians and diabetes specialists.

Patterns of analgesic and anti-inflammatory medicine use by Australian veterans.

BACKGROUND: We examined analgesic and anti-inflammatory medicine use by Australian veterans before and after the introduction of selective Cox-2 inhibitors. METHODS: We studied cohorts of Gold Card-holding veterans using prescription data held by the Department of Veterans' Affairs for the period 1 July 1998 to 30 June 2004. Outcomes were volume dispensed, average daily quantity and cumulative incidence of use of paracetamol-containing and aspirin-containing medicines, non-selective and Cox-2-selective non-steroidal anti-inflammatory drugs (NSAIDs), tramadol and dextropropoxyphene. RESULTS: Overall, we found high levels of use of analgesic and anti-inflammatory medicines, which increased by 43% over the study period. Use of paracetamol-containing medicines was overtaken by NSAIDs in 1999/2000, corresponding to the introduction of the Cox-2-selective agents. Between 12 and 17% of Cox-2-selective medicine recipients were supplied amounts indicative of continuous use in relatively high doses and 51% of veterans received at least one relatively Cox-2-selective medicine (celecoxib, rofecoxib, meloxicam, diclofenac) by the end of the study period. Dextropropoxyphene use declined during the study and tramadol use increased 10-fold. CONCLUSION: This study shows very high levels of Cox-2 inhibitor use during the 6-year period. Cox-2-selective agents were more likely to be taken continuously and at higher doses than non-selective NSAIDs. This is relevant in view of the cardiovascular toxicity of this group of medicines. The study shows the value of using unit record dispensing data to assess drug use patterns. Linking dispensing records to hospital separation and mortality data will further enhance our ability to monitor drug safety.

Deep vein thrombosis and air travel: record linkage study.

OBJECTIVE: To investigate the time relations between long haul air travel and venous thromboembolism. DESIGN: Record linkage study using the case crossover approach. SETTING: Western Australia. PARTICIPANTS: 5408 patients admitted to hospital with venous thromboembolism and matched with data for arrivals of international flights during 1981-99. RESULTS: The risk of venous thromboembolism is increased for only two weeks after a long haul flight; 46 Australian citizens and 200 non-Australian citizens had an episode of venous thromboembolism during this so called hazard period. The relative risk during this period for Australian citizens was 4.17 (95% confidence interval, 2.94 to 5.40), with 76% of cases (n = 35) attributable to the preceding flight. A "healthy traveller" effect was observed, particularly for Australian citizens. CONCLUSIONS: The annual risk of venous thromboembolism is increased by 12% if one long haul flight is taken yearly. The average risk of death from flight related venous thromboembolism is small compared with that from motor vehicle crashes and injuries at work. The individual risk of death from flight related venous thromboembolism for people with certain pre-existing medical conditions is, however, likely to be greater than the average risk of 1 per 2 million for passengers arriving from a flight. Airlines and health authorities should continue to advise passengers on how to minimise risk.

Research use of linked health data--a best practice protocol.

OBJECTIVE: This article outlines a protocol for facilitating access to administrative data for the purpose of health services research, when these data are sourced from multiple organisations. This approach is designed to promote confidence in the community and among data custodians that there are benefits of linked health information being used and that individual privacy is being rigorously protected. BACKGROUND: Linked health administration data can provide an unparalleled resource for the monitoring and evaluation of health care services. However, for a number of reasons, these data have not been readily available to researchers. In Australia, an additional barrier to research is the result of health data sets being collected by different levels of government - thus all are not available to any one authority. To improve this situation, a practical blue-print for the conduct of data linkage is proposed. This should provide an approach suitable for most projects that draw large volumes of information from multiple sources, especially when this includes organisations in different jurisdictions. CONCLUSIONS AND IMPLICATIONS: Health data, although widely and diligently collected, continue to be under-utilised for research and evaluation in most countries. This protocol aims to make these data more easily available to researchers by providing a controlled and secure mechanism that guarantees privacy protection.

Egocentric language in deaf children.

Egocentric language is a generalization of Piaget's egocentric speech concept (1926/1969) investigated by Vygotsky (1962). Behaviors of eight children ages 2 to 5 years with profound congenital deafness were analyzed using six classes of egocentric language: motor reaction activity, silent lips articulation, murmur, oral-facial mimics, body expression, and vocalization. No child had received oral or sign language training. All attended videotaped play sessions. Events in which children engaged in "dialogue" with themselves or a toy, while pursuing a specific solution, were observed. Such extralinguistic behavior moves the thinking process toward problem solving like that of hearing children. Consequently, teachers should not interrupt when a deaf child is playing with or signing or vocalizing to a toy, because this behavior may be the manifestation of a reflexive moment and the generator of a decision process fundamental for cognitive development. Vocalization by a deaf child does not indicate willingness to speak; it merely manifests symbolic reasoning. Silent lips articulation and oral-facial mimics have the same effect and can also be interpreted.

The Australian National Death Index: an assessment of accuracy.

OBJECTIVE: The Australian National Death Index (NDI) provides a comprehensive and accessible source of mortality information for epidemiological research. Use of the index requires a probabilistic matching process that inevitably results in some inaccuracy. In this paper, accuracy is assessed. METHODS: Results of a matching process against the NDI performed by the Australian Institute of Health and Welfare in Canberra were compared with information provided by the Medical Device Outcomes study cohort and their families (n = 2,990). Indices of accuracy for the NDI were calculated. RESULTS: For this particular study, the NDI has sensitivity 88.8% (84.9-92.8) and specificity 98.2% (97.4-98.7). CONCLUSIONS AND IMPLICATIONS: The relatively low sensitivity is of some concern to those using the NDI for health outcomes research. The importance of such a national database is evident; however, to improve accuracy the introduction of a national unique patient identifier is necessary.

It's time: record linkage--the vision and the reality.

OBJECTIVE: To examine reasons for the minimal use of Australian administrative health data for research and evaluation. METHOD: Legislative, organisational, social and political barriers in Australia are described. RESULTS: System changes are identified that would support the implementation of an evaluation-oriented health data collection system. A Universal Patient Identifier is essential. Leadership and funding at the federal level will be required to ensure the co-ordinated introduction of a rational and integrated health data system in Australia. CONCLUSIONS: Health data in Australia is not currently collected in a manner that allows the assessment of health outcomes. It is time to change the basis of health data collection from accounting to health outcomes evaluation and to reorganise the system to support this. IMPLICATIONS: If appropriate national health data were available, research and evaluation of services could be undertaken and treatment outcomes and adverse events could be monitored. Such information could provide a basis for targeted clinical trials and provide evidence for best clinical practice.

Metaphyseal undertubulation in gaucher disease: resolution at MRI in a patient undergoing enzyme replacement therapy.

Gaucher disease is a sphingolipid storage disorder that results in the accumulation of Gaucher cells within the reticuloendothelial system. The life span can be near normal in the most common form. Our case illustrates the resolution of the skeletal findings in Gaucher disease following enzyme replacement therapy. We also report the correlation of these findings with clinical improvement.

Xanthomatous infiltration of ankle tendons.

We present a case of type II hyperbetalipoproteinemia in a patient whose diagnosis had been previously unrecognized, and who had previously been misdiagnosed with rheumatoid arthritis and later gout. Radiographic and MR imaging features of the patient's ankles were pronounced but otherwise typical of xanthomatous infiltration. Radiologic assessment can be useful in permitting a specific diagnosis to be made in patients with periarticular and tendinous swelling.

Fat-suppressed three-dimensional spoiled gradient-echo MR imaging of hyaline cartilage defects in the knee: comparison with standard MR imaging and arthroscopy.

OBJECTIVE: The sensitivity of fat-suppressed three-dimensional spoiled gradient-echo (SPGR) images was compared with that of standard MR images for detecting hyaline cartilage defects of the knee, using arthroscopy as the standard of reference. SUBJECTS AND METHODS: We assessed 114 consecutive patients for hyaline cartilage defects of the knee with both standard MR imaging sequences and a sagittal fat-suppressed three-dimensional SPGR sequence. Of these patients, 48 with meniscal or ligament injury, or persistent symptoms, underwent subsequent arthroscopy. The standard MR images and SPGR images of these 48 patients were then retrospectively analyzed for articular defects in a blinded fashion by two independent observers. Sensitivity, specificity, and intraobserver and interobserver agreement were determined for the different imaging techniques. RESULTS: One fourth of the patients who went on to arthroscopy were shown to have isolated hyaline cartilage lesions that were clinically confused with meniscal tears and that were missed on the standard MR images. When looking at all surfaces combined for each reader, the SPGR imaging sequence had a significantly higher sensitivity than the standard MR imaging sequences for detecting hyaline cartilage defects (75-85% versus 29-38%, p < .001 for each comparison). When looking at individual surfaces for each reader, significant differences in sensitivity were shown for each surface except the trochlear and lateral tibial surfaces. We found no difference in specificity (97% versus 97%, p > .99). We also found that combined evaluation of standard MR and SPGR images gave no added diagnostic advantage (sensitivity, 86%; specificity, 97%; p > .42). Except for the lateral tibial surface, the study achieved excellent reproducibility among readings and between readers. CONCLUSION: Fat-suppressed three-dimensional SPGR imaging is more sensitive than standard MR imaging for the detection of hyaline cartilage defects of the knee.

In vivo evaluation of a collagen corneal allograft derived from rabbit dermis.

BACKGROUND: This study evaluates epithelialization, clarity, intraocular inflammation, and fibroblast ingrowth of a collagen corneal allograft derived from rabbit dermis. METHODS: Dermal collagen fibers were dispersed intact and chemically modified to make them soluble. The allografts consisted of a fibrous, opaque peripheral zone and a central clear area. Twelve New Zealand white rabbits underwent penetrating keratoplasty with implantation of an allograft. The grafts were evaluated daily for clarify, anterior segment inflammation, and extent of reepithelialization with a slit-lamp microscope. RESULTS: Epithelialization of the fibrous peripheral zone of the graft ranged from 0% to 90%. The central clear area did not epithelialize in any of the animals. Fibroblasts migrated into the peripheral zone in all eyes. Complications included ulceration of the central clear area in two eyes. There was no ulceration or leakage at the graft-host interface and no synechia, fibrous, or inflammatory retrocorneal membranes in any of the eyes. CONCLUSIONS: Our study is the first to describe the method of modifying dermal type I collagen into a clear corneal allograft. Survival of the corneal collagen allograft beyond 1 month may be limited by several factors including lack of epithelialization of the central clear area.