Patterns of care for malignant pleural mesothelioma patients compensated by the Dust Diseases Board in New South Wales, Australia.

BACKGROUND: The silent epidemic of mesothelioma in Australia is steadily increasing, and 30% of cases occur in New South Wales (NSW). AIM: To describe the patterns of care and outcomes of patients with malignant pleural mesothelioma (MPM) in NSW. METHODS: MPM patients in NSW applying for compensation at the NSW Dust Diseases Board from 2007 to 2009 were included. Survival from time of diagnosis was determined by the Kaplan-Meier method. The Chi-squared test was used to determine if there was an association between utilisation of treatment and geographical location. RESULTS: A total of 138 patients was included: median age was 72.5; 91.3% male; 60.1% epithelial subtype; and 65.2% lived in major cities. All patients had at least one chest X-ray and computed tomography scan, and 21% had a positron emission tomography scan; 93.5% and 4.3% had histological or cytological confirmation respectively. Thoracoscopy (59.4%) was the most commonly used diagnostic procedure. Treatment utilisation: 53.6% chemotherapy; 35.5% radiotherapy; 9.4% extrapleural pneumonectomy (EPP); and 72.5% had palliative care involvement. There were no major differences in treatment utilisation between patients living in major cities and those in regional NSW (chemotherapy P = 0.42; radiotherapy P = 0.13 and palliative care P = 0.60), except for a higher rate of EPP in regional patients (16.7% vs 5.6%; P = 0.03). Median survival was 9.7 versus 12.3 months for city and regional patients respectively (P = 0.22). CONCLUSION: Survival and treatment utilisation was not significantly different between MPM patients living in major cities and regional NSW, except for a higher rate of EPP in patients in regional NSW.

The eligibility of advanced non-small-cell lung cancer patients for targeted therapy clinical trials.

BACKGROUND: The selection criteria for phase III trials are often stringent. We aimed to determine how many advanced non-small-cell lung cancer (NSCLC) patients would have been eligible for phase III targeted therapy trials and the proportion receiving anticancer treatment. PATIENTS AND METHODS: From March 2007 to May 2008, all advanced NSCLC patients presented at our lung cancer multidisciplinary team meeting were included to assess eligibility for the targeted therapy trials: ECOG-4599, AVAiL, FLEX, TALENT, INTACT-1, INTACT-2, ESCAPE, NEXUS and MONET1. Medical records were examined to determine treatment utilisation and overall survival. RESULTS: A total of 62 patients were registered: 63% male; median age 71 years; 61% stage IIIB disease. Percentages that met criteria were: ECOG-4599 31%, AVAiL 24%, FLEX 69%, TALENT 27%, INTACT-1 50%, INTACT-2 42%, ESCAPE 39%, NEXUS 63% and MONET1 34%. Common reasons for ineligibility were insufficient life expectancy, poor performance status, abnormal bloods, proteinuria and associated cancer problems. Systemic therapies were received by 66% of patients and median survival was 10.3 months. CONCLUSION: Only 24%-69% were eligible for targeted therapy trials but 66% received anticancer treatment. Clinical trials in patients with advanced NSCLC need to be more representative of the majority of patients.

Malignant mesothelioma.

Malignant mesothelioma (MM) is an aggressive tumour that commonly affects the mesothelial surfaces of the pleural and peritoneal cavities, and occasionally, the tunica vaginalis and the pericardium. Formerly a rare tumour, MM is increasing in incidence in Australia due to the heavy nationwide use of asbestos from 1940 until the 1980s. The incidence is expected to peak in Australia in the next decade, mirroring the long latency period between asbestos exposure and development of MM. Diagnosis of MM can be difficult. Definitive pathological diagnosis is required and it often requires an experienced pathologist to differentiate MM from other benign or malignant processes. Treatment of MM requires a multidisciplinary approach, regardless of palliative or curative intent. Treatment options, such as surgery, chemotherapy, radiotherapy and active symptom control or a combination of these, may be used. Further research is needed to advance the therapeutic options for MM, and strategies to realize personalisation of therapy through discovery of predictive markers. In the Australian society where asbestos contamination of the built environment is very high, education and stringent public health measures are required to prevent a second wave of increased MM incidence.

Altered nociception and morphine tolerance in neuropeptide FF receptor type 2 over-expressing mice.

BACKGROUND: The neuropeptide FF system is thought to act as an anti-opioid modulator and plays a role in nociception, morphine antinociception and dependence. Two receptor subtypes, NPFFR1 and NPFFR2, have been identified, but their respective roles in these processes remain uncertain. METHODS: In the present study, the role of NPFFR2 was investigated using transgenic mice over-expressing NPFFR2 in addition to a NPFFR2 agonist AC-263093. RESULTS: NPFFR2 Tg mice exhibited increased sensitivity to both mechanical and thermal noxious stimuli compared to the WT mice, while the antinociceptive effects of morphine at three different doses (6.25, 12.5 and 25 mg/kg, s.c.) were similar in both strains. The development of tolerance to morphine antinociception after chronic morphine treatment (12.5 mg/kg, s.c.; twice daily × 5 days) was attenuated in NPFFR2 Tg mice when compared to WT mice. Similarly, WT mice receiving AC-263093 pretreatment (2.5 mg/kg, i.p.) showed attenuated morphine tolerance compared to vehicle controls. Most naloxone-precipitated morphine withdrawal symptoms were not attenuated in NPFFR2 Tg mice, with the exception of wet dog shake that was significantly reduced. Both NPFFR2 Tg and WT mice displayed similar degree of morphine rewarding. CONCLUSIONS: Our results suggest that neuropeptide FF R2 is mainly involved in the modulation of nociception and tolerance to morphine antinociception.

beta-Amyloid stimulation of microglia and monocytes results in TNFalpha-dependent expression of inducible nitric oxide synthase and neuronal apoptosis.

Reactive microglia associated with the beta-amyloid plaques in Alzheimer's disease (AD) brains initiate a sequence of inflammatory events integral to the disease process. We have observed that fibrillar beta-amyloid peptides activate a tyrosine kinase-based signaling response in primary mouse microglia and the human monocytic cell line, THP-1, resulting in production of neurotoxic secretory products, proinflammatory cytokines, and reactive oxygen species. We report that most of the amyloid-induced tyrosine kinase activity was stimulated after activation of Src family members such as Lyn. However, transduction of the signaling response required for increased production of the cytokines TNFalpha and IL1-beta was mediated by the nonreceptor tyrosine kinase, Syk. Additionally, beta-amyloid stimulated an NFkappaB-dependent pathway in parallel that was required for cytokine production. Importantly, TNFalpha generated by the monocytes and microglia was responsible for the majority of the neuorotoxic activity secreted by these cells after beta-amyloid stimulation but must act in concert with other factors elaborated by microglia to elicit neuronal death. Moreover, we observed that the neuronal loss was apoptotic in nature and involved increased neuronal expression of inducible nitric oxide synthase and subsequent peroxynitrite production. Selective inhibitors of inducible nitric oxide synthase effectively protected cells from toxicity associated with the microglial and monocytic secretory products. This study demonstrates a functional linkage between beta-amyloid-dependent activation of microglia and several characteristic markers of neuronal death occurring in Alzheimer's disease brains.

Dipsticking the major groove of DNA with enzymatically incorporated spin-labeled deoxyuridines by electron spin resonance spectroscopy.

Site-specifically spin-labeled deoxyuridine triphosphates with tethers of different lengths were synthesized and then enzymatically incorporated with terminal transferase to form a spin-labeled poly(dT) copolymer. The spin-labeled copolymers were annealed with poly(dA) to form a duplex, which was analyzed by electron spin resonance spectroscopy in a solution of low ionic strength. The spin labels are attached in position 5 of the deoxyuridine and protrude into the major groove. Based on the correlation between tether length of the spin label and the electron spin resonance lineshape, we show that the depth of the major groove of a DNA in its B-form is about 8 A in solution, which is in good agreement with X-ray fiber studies. We also conclude, based on electron spin resonance lineshape simulation data, that the correlation time of the bases in a DNA duplex is of the order of nanoseconds.

Surgical coverage of exposed hydroxyapatite implant with retroauricular myoperiosteal graft.

BACKGROUND: With the increasing use of hydroxyapatite orbital implants, the complication of exposure has become apparent to oculoplastic surgeons. Many kinds of patch grafts, such as sclera, dermis, and hard palate mucosa, have been used to cover exposed hydroxyapatite implants with inconsistent results. In this study, the authors use a newly developed technique, autogenous retroauricular myoperiosteal graft, and the results are reported. METHODS: A piece of retroauricular muscle together with its underlying periosteum was carefully harvested. This myoperiosteal graft was patched to the debrided hydroxyapatite exposure area with the periosteal surface facing outward. The margin of periosteal surface was secured with conjunctiva and left uncovered for the surrounding conjunctiva to epithelialise. RESULTS: Nine eyes with hydroxyapatite exposure more than 3 mm were managed with autogenous retroauricular myoperiosteal grafts. Seven cases were successfully treated with single graft surgery. The other two cases needed an additional graft surgery, and there was no re-exposure noted thereafter. Five patients received a successful insertion of the motility peg. All nine patients have been fitted with prosthesis with reasonable motility. There were no complication noted during more than 1 year of follow up. CONCLUSION: The thick composite nature of the myoperiosteal graft provides a durable and vascularised coverage for exposed hydroxyapatite implants. This technique offers an encouraging alternative for the management of exposed hydroxyapatite implants.

Indium-111-leukocyte/technetium-99m-MDP bone and magnetic resonance imaging: difficulty of diagnosing osteomyelitis in patients with neuropathic osteoarthropathy.

Fourteen patients (16 sites) with clinical and/or radiographic evidence of neuropathic osteoarthropathy (Charcot joints) were evaluated with combined indium-111-leukocyte (111In-WBC) and technetium-99m-methylene diphosphonate (99mTc-MDP) bone imaging for suspected osteomyelitis. Magnetic resonance (MR) images were obtained in seven patients. Using a positive bone culture as the criterion for the presence of osteomyelitis, there were four true-positive studies, six true-negative sites, and one false-negative 111In-WBC study. Five of 16 sites (31%) had false-positive 111In-WBC uptake at noninfected sites. There were four true-positive and three false-positive MR studies. All false-positives showed at least moderately abnormal findings by both techniques at sites of rapidly progressing osteoarthropathy of recent onset. In this preliminary study, both techniques appear to be sensitive for detection of osteomyelitis, and a negative study makes osteomyelitis unlikely. However, the findings of 111In-WBC/99mTc-MDP and MR images at sites of rapidly progressing, noninfected neuropathic osteoarthropathy may be indistinguishable from those of osteomyelitis.

Evaluation of a digital workstation for interpreting neonatal examinations. A receiver operating characteristic study.

RATIONALE AND OBJECTIVES: The purpose of this study is to compare the diagnostic accuracy of interpreting clinical neonatal radiographs using a commercially available digital workstation versus conventional radiographic images. METHODS: The case sample consists of 100 chest or abdominal radiographs from the neonatal intensive care unit in which diagnosis was confirmed. Four radiologists served as observers. During two initial reading sessions, half of the studies were viewed on digital radiography monitors and the other half by plain film. Observers indicated whether each patient had normal or abnormal findings and their degree of confidence in this judgment. Six weeks later, observers viewed cases on the alternate presentation system. Two statistical analyses were performed: the data from each observer were treated as a separate experiment in the first analysis; the data from all observers were combined using a new method in the second analysis. RESULTS: No differences between areas under receiver operating characteristic (ROC) curves for viewing on the picture archiving and communication system (PACS) console and plain film were found for any observer (0.86 versus 0.86, 0.89 versus 0.86, 0.88 versus 0.85, 0.83 versus 0.82). CONCLUSIONS: The study suggests that for pediatric plain film images, video images offer diagnostic information comparable with that of conventional radiographs for neonatal examinations.

Time course of satisfaction of search.

"Satisfaction of search" (SOS) refers to the effect in which a second lesion remains undetected after detection of another lesion on the same radiograph. The objective of this study was to clarify our understanding of SOS by relating it to total time of inspection and time intervals before, between, and after discovery of lesions. Detection accuracy of native lesions in chest radiographs, before and after the addition of a simulated nodular lesion, was measured for ten observers. Analysis of data from this and a previous experiment showed that average perceptual accuracy of individual receiver operating characteristic curves was significantly reduced with the addition of the nodules. Plots and analyses of search time revealed that, on average, during a typical 46-second inspection of a case, simulated nodules were found at 18 seconds, native abnormalities at 25 seconds, and false positives occurred at 33 seconds. Time needed to find nodules did not depend on whether native lesions were present; time to find native lesions did not change with addition of nodules; and total search time was the same for images with one, two, or no lesions. The detection results show that the SOS effect was obtained, but that interrupting search in order to measure it also diminishes accuracy. Analysis of the time course data relates SOS to perceptual capture and strategic halting of search.

Radiotherapy in the management of thyroid orbitopathy. Computed tomography and clinical outcomes.

OBJECTIVE: We investigated the long-term outcome of patients with thyroid orbitopathy treated with orbital radiotherapy using quantitative clinical measurements and orbital computed tomographic morphometric changes. DESIGN: Patients who had undergone orbital radiotherapy for thyroid orbitopathy at least 1 year previously were retrospectively recalled for follow-up examination and computed tomography. Controls were patients with similar disease activity but who had not undergone radiotherapy. SETTING: Subspecialty clinic in a university teaching hospital. PATIENTS: Twenty-one patients (42 orbits) who underwent radiotherapy and six clinically comparable patients who had not undergone radiotherapy (12 orbits). INTERVENTION: Standardized, super-voltage, orbital radiotherapy. MEASUREMENTS: Five clinical indexes of orbitopathy and six computed tomographic indexes were examined for interval changes. RESULTS: The orbital computed tomographic muscle-diameter index enlargement ratio did not change in either group (radiotherapy group, 1.54 to 1.51, not significant; nonradiotherapy group, 1.37 to 1.36, not significant). The mean (+/- SEM) number of muscles with low-density areas increased in both groups (radiotherapy group, 1.1 [+/- 1.9] muscles per orbit; P < .001). Soft-tissue signs improved significantly with lesser improvements in extraocular muscle function in both groups. Proptosis, visual acuity, and intraocular pressure rise on upgaze did not improve significantly in either group. CONCLUSIONS: No changes in muscle size measured with computed tomography were found in either patients undergoing radiotherapy or patients not undergoing radiotherapy after long-term follow-up. Clinical indexes of thyroid orbitopathy, especially soft-tissue signs, improved on follow-up, but this was not influenced by the method of treatment.

Lack of mutations of BCL6 and BCL10 genes in mucosa-associated lymphoid tissue lymphomas of the orbital adnexa.

Knowledge regarding the molecular pathogenesis and progression of mucosa-associated lymphoid tissue (MALT) lymphomas of ocular adnexa is limited. Eleven cases of ocular MALT lymphoma were analyzed by clonal rearrangement of antigen receptor genes using Southern blot hybridization. Polymerase chain reaction-single stranded conformational polymorphism analysis and DNA sequencing was utilized to analyze the mutations of BCL6 and BCL10 genes. Clonal rearrangement of immunoglobulin heavy genes was found in all 11 patients. No point mutation was found in BCL6 or BCL10 genes in any of the samples analyzed. We suggest that mutations of BCL6 and BCL10 genes are rare in low-grade MALT lymphoma of ocular adnexa and are unlikely to be involved in the pathogenesis of the disease. But the role of alterations of both BCL6 and BCL10 genes in the disease progression of low-grade MALT lymphoma require additional study.

Molecular analysis of mucosa-associated lymphoid tissue (MALT) lymphoma of ocular adnexa.

Lymphomas of mucosa-associated lymphoid tissue (MALT) are a distinct subgroup of extranodal B-cell non-Hodgkin's lymphomas. Most studies have failed to demonstrate the clonal rearrangement of BCL-1, BCL-2 or c-MYC genes for MALT lymphomas. Further, alteration of the p53 gene is rarely demonstrated in low-grade MALT lymphomas, but can be detected in high-grade disease. Lymphomas of the ocular adnexa represent approximately eight percent of all extranodal lymphomas, most of which are MALT lymphomas, but few studies had explored the alterations of BCL-1, BCL-2, c-MYC and p53 genes specifically for ocular MALT lymphomas. We investigated the changes to BCL-1, BCL-2, c-MYC and p53 genes in these lymphomas for Taiwanese patients. Clonal rearrangement for immunoglobulin heavy-chain (IgH), BCL-1, BCL-2, c-MYC and p53 genes was examined for 16 cases of ocular MALT lymphoma. Restriction-length polymorphism and polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) of the DNA, corresponding to exons 5 through 9, followed by DNA sequencing, were utilized to analyze the possible mutations of the p53 gene for these tumors. Thirteen of the cases revealed rearranged IgH genes using Southern blotting or PCR. No rearrangement of BCL-1, BCL-2, c-MYC or p53 genes was discovered, with point mutation of the p53 gene in one case. As for other types of MALT lymphomas, BCL-1, BCL-2 and c-MYC genes are not implicated in the pathogenesis of the ocular sub-group. Although alteration of the p53 gene is rare for low-grade ocular MALT lymphoma, its role in disease progression merits further research.

Synthesis and properties of novel bis(triarylamines) based on a 3,3'-diphenyl-2,2'-bithiophene core.

An efficient synthesis of 3,3'-diphenyl-2,2'-bithiophene based bis(triarylamines) and their physical properties are reported.

MR of fetal central nervous system abnormalities.

PURPOSE: To investigate whether MR can provide additional information on fetuses with central nervous system abnormalities as demonstrated by ultrasonography. METHODS: Fetal MR examinations were studied prospectively in 22 pregnant women whose fetuses showed evidence of anomalies on ultrasound performed in the High-Risk Obstetric Clinic. RESULTS: In 19 of 22 cases, postpartum confirmatory diagnoses were obtained by MR or CT examinations, autopsy, or surgery. In general, the image quality of MR is comparable with that of ultrasound. However, in six of 22 cases (27%), MR provided additional information that altered the ultrasound diagnosis; these included cases of infarction, diastematomyelia, normal hemimegalencephaly with early myelination, Dandy-Walker variant, and lipoma. All of these cases had postpartum confirmation. The additional information changed the treatment in three of six patients (no intervention or elective abortion). CONCLUSIONS: In certain situations MR can add valuable information to that obtained by sonography in the evaluation of the fetal central nervous system.

Skeletal injuries in the pediatric patient.

Immature skeleton is different from adult skeleton with unique vulnerability to acute and chronic injuries at the growth plate. Recognition and differential diagnosis of inflicted skeletal injury are important. Familiarity with the dynamic changes of growing skeleton in normal children is key to the recognition of pathologic states.

Radiographic manifestations of anomalies of the brain.

Congenital brain anomalies are classified as developmental anomalies, effects of teratogens, errors of histogenesis, or sequelae of infections. The imaging options for delineation of these anomalies are many; a basic understanding of the disorder is central to the effective choice of imaging modality. This review begins with a brief overview of embryogenesis then reviews the common congenital brain anomalies encountered in infants.

Ultrafast computed tomography of the chest.

Improvements in scan speed and resolution are changing the role of the pulmonary imager. An understanding of airway mechanics and blood flow physiology is required to take full advantage of the new technology. Assessment of regional airflow and blood flow provides information that is currently unavailable from clinical tools.

Results of intraoperative mitomycin C application in dacryocystorhinostomy.

AIMS: To evaluate the long term results of intraoperative mitomycin C application in dacryocystorhinostomy (DCR) surgery compared with results of the conventional procedure. METHODS: In this prospective randomised controlled study, a total of 88 eyes diagnosed with acquired nasolacrimal duct obstruction were randomly divided into a conventional DCR group and a mitomycin C group in which mitomycin C was used during DCR surgery. The surgical procedures in both groups were exactly the same, except that in the patients in the mitomycin C group, a piece of neurosurgical cottonoid soaked with 0.2 mg/ml mitomycin C was applied to the osteotomy site for 30 minutes. The results of the DCR surgeries were evaluated by objective findings such as irrigation and the height of tear meniscus and subjective symptoms by asking patients the condition of tearing improvement. RESULTS: Among the 44 eyes in the mitomycin C group, 95.5% of patients remained totally symptom free after 10 months of follow up; while in the conventional group, 70.5% of patients were reported to be symptom free and 18% of patients to have an improvement in their symptoms. There was a significant difference between these two groups. As far as objective findings were concerned, there were 41 eyes in the mitomycin C group classified as having a normal and one eye with moderate tear meniscus level, compared with 32 eyes and seven eyes, respectively, in the conventional group. There was also a significant difference between these two groups. The non-patency rate in the mitomycin C group is 4.5% compared with 11.4% in the conventional group. There were no complications such as abnormal nasal bleeding, mucosal necrosis, or infection except one patient with delayed wound healing. CONCLUSIONS: Intraoperative mitomycin C application is effective in increasing the success rate of DCR surgery in standard nasolacrimal duct obstruction, and no significant complications resulted from its use.