The varying role of the GP in the pathway between colonoscopy and surgery for colorectal cancer: a retrospective cohort study

Extent: 11p.Objectives: To describe general practitioner (GP) involvement in the treatment referral pathway for colorectal cancer (CRC) patients. Design: A retrospective cohort analysis of linked data. Setting: A population-based sample of CRC patients diagnosed from August 2004 to December 2007 in New South Wales, Australia, using the 45 and Up Study, cancer registry diagnosis records, inpatient hospital records and Medicare claims records. Participants: 407 CRC patients who had a colonoscopy followed by surgery. Primary outcome measures: Patterns of GP consultations between colonoscopy and surgery (ie, between diagnosis and treatment). We investigated whether consulting a GP presurgery was associated with time to surgery, postsurgical GP consultations or rectal cancer cases having surgery in a centre with radiotherapy facilities. Results: Of the 407 patients, 43% (n=175) had at least one GP consultation between colonoscopy and surgery. The median time from colonoscopy to surgery was 27 days for those with an intervening GP consultation and 15 days for those without the consultation. 55% (n=223) had a GP consultation up to 30 days postsurgery; it was more common in cases of patients who consulted a GP presurgery than for those who did not (65% and 47%, respectively, adjusted OR 2.71, 95% CI 1.50 to 4.89, p=0.001). Of the 142 rectal cancer cases, 23% (n=33) had their surgery in a centre with radiotherapy facilities, with no difference between those who did and did not consult a GP presurgery (21% and 25% respectively, adjusted OR 0.84, 95% CI 0.27 to 2.63, p=0.76). Conclusions: Consulting a GP between colonoscopy and surgery was associated with a longer interval between diagnosis and treatment, and with further GP consultations postsurgery, but for rectal cancer cases it was not associated with treatment in a centre with radiotherapy facilities. GPs might require a more defined and systematic approach to CRC management.David Goldsbury, Mark Harris, Shane Pascoe, Michael Barton, Ian Olver, Allan Spigelman, Justin Beilby, Craig Veitch, David Weller, Dianne L O'Connel

Microglia-associated granule cell death in the normal adult dentate gyrus

Microglial cells are constantly monitoring the central nervous system for sick or dying cells and pathogens. Previous studies showed that the microglial cells in the dentate gyrus have a heterogeneous morphology with multipolar cells in the hilus and fusiform cells apposed to the granule cell layer both at the hilar and at the molecular layer borders. Although previous studies showed that the microglia in the dentate gyrus were not activated, the data in the present study show dying granule cells apposed by Iba1-immunolabeled microglial cell bodies and their processes both at hilar and at molecular layer borders of the granule cell layer. Initially, these Iba1-labeled microglial cells surround individual, intact granule cell bodies. When small openings in the plasma membrane of granule cells are observed, microglial cells are apposed to these openings. When larger openings in the plasma membrane occur at this site of apposition, the granule cells display watery perikaryal cytoplasm, watery nucleoplasm and damaged organelles. Such morphological features are characteristic of neuronal edema. The data also show that following this localized disintegration of the granule cell’s plasma membrane, the Iba1-labeled microglial cell body is found within the electron-lucent perikaryal cytoplasm of the granule cell, where it is adjacent to the granule cell’s nucleus which is deformed. We propose that granule cells are dying by a novel microglia-associated mechanism that involves lysis of their plasma membranes followed by neuronal edema and nuclear phagocytosis. Based on the morphological evidence, this type of cell death differs from either apoptosis or necrosis

Dentate granule cells form novel basal dendrites in a rat model of temporal lobe epilepsy.

Mossy fibre sprouting and re-organization in the inner molecular layer of the dentate gyrus is a characteristic of many models of temporal lobe epilepsy including that induced by perforant-path stimulation. However, neuroplastic changes on the dendrites of granule cells have been less-well studied. Basal dendrites are a transient morphological feature of rodent granule cells during development. The goal of the present study was to examine whether granule cell basal dendrites are generated in rats with epilepsy induced by perforant-path stimulation. Adult Wistar rats were stimulated for 24 h at 2 Hz and with intermittent (1/min) trains (10 s duration) of single stimuli at 20 Hz (20 V, 0.1 ms) delivered 1/min via an electrode placed in the angular bundle. The brains of these experimental rats and age- and litter-matched control animals were processed for the rapid Golgi method. All rats with perforant-path stimulation displayed basal dendrites on many Golgi-impregnated granule cells. These basal dendrites mainly originated from their somata at the hilar side and then extended into the hilus. Quantitative analysis of more than 800 granule cells in the experimental and matched control brains showed that 6-15% (mean=8.7%) of the impregnated granule cells have spiny basal dendrites on the stimulated side, as well as the contralateral side (mean=3.1%, range=2.9-3.9%) of experimental rats, whereas no basal dendrites were observed in the dentate gyrus from control animals. The formation of basal dendrites appears to be an adaptive morphological change for granule cells in addition to the previously described mossy fibre sprouting, as well as dendritic and somatic spine formation observed in the dentate gyrus of animal and human epileptic brains. The presence of these dendrites in the subgranular region of the hilus suggests that they may be postsynaptic targets of the mossy fibre collaterals

The intention to hasten death: a survey of attitudes and practices of surgeons in Australia

Objective: To determine attitudes among surgeons in Australia to assisted death, and the proportion of surgeons who have intentionally hastened death with or without an explicit request. Design: Anonymous, cross-sectional, mail-out survey between August and November 1999. Participants: 683 out of 992 eligible general surgeons (68.9% response rate). Main outcome measures: Proportion of respondents answering affirmatively to questions about administering excessive doses of medication with an intention to hasten death. Results: 247 respondents (36.2%; 95% CI, 32.6%-39.9%) reported that, for the purpose of relieving a patient's suffering, they have given drugs in doses that they perceived to be greater than those required to relieve symptoms with the intention of hastening death. More than half of these (139 respondents; 20.4% of all respondents; 95% CI, 17.4%-23.6%) reported that they had never received an unambiguous request for a lethal dose of medication. Of all respondents, only 36 (5.3%; 95% CI, 2.9%-6.1%) reported that they had given a bolus lethal injection, or had provided the means to commit suicide, in response to an unambiguous request. Conclusions: More than a third of surgeons surveyed reported giving drugs with an intention to hasten death, often in the absence of an explicit request. However, in many instances, this may involve the use of an infusion of analgesics or sedatives, and such actions may be difficult to distinguish from accepted palliative care, except on the basis of the doctor's self-reported intention. Legal and moral distinctions based solely on a doctor's intention are problematic

The intention to hasten death: a survey of attitudes and practices of surgeons in Australia

Objective: To determine attitudes among surgeons in Australia to assisted death, and the proportion of surgeons who have intentionally hastened death with or without an explicit request. Design: Anonymous, cross-sectional, mail-out survey between August and November 1999. Participants: 683 out of 992 eligible general surgeons (68.9% response rate). Main outcome measures: Proportion of respondents answering affirmatively to questions about administering excessive doses of medication with an intention to hasten death. Results: 247 respondents (36.2%; 95% CI, 32.6%-39.9%) reported that, for the purpose of relieving a patient's suffering, they have given drugs in doses that they perceived to be greater than those required to relieve symptoms with the intention of hastening death. More than half of these (139 respondents; 20.4% of all respondents; 95% CI, 17.4%-23.6%) reported that they had never received an unambiguous request for a lethal dose of medication. Of all respondents, only 36 (5.3%; 95% CI, 2.9%-6.1%) reported that they had given a bolus lethal injection, or had provided the means to commit suicide, in response to an unambiguous request. Conclusions: More than a third of surgeons surveyed reported giving drugs with an intention to hasten death, often in the absence of an explicit request. However, in many instances, this may involve the use of an infusion of analgesics or sedatives, and such actions may be difficult to distinguish from accepted palliative care, except on the basis of the doctor's self-reported intention. Legal and moral distinctions based solely on a doctor's intention are problematic

Seizure-induced basal dendrites on granule cells

Seizure-induced hilar basal dendrites on dentate granule cells are observed in several rodent models of temporal lobe epilepsy. Ultrastructural evidence showed that basal dendrites receive predominantly excitatory synapses, including many from mossy fibers. Such highly interconnected granule cells with basal dendrites are suggested to enhance hyperexcitability within the dentate network. For an expanded treatment of this topic see Jasper's Basic Mechanisms of the Epilepsies, Fourth Edition (Noebels JL, Avoli M, Rogawski MA, Olsen RW, Delgado-Escueta AV, eds) published by Oxford University Press (available on the National Library of Medicine Bookshelf [NCBI] at). © 2010 International League Against Epilepsy

Tuberculosis in Dr Granville's mummy: a molecular re-examination of the earliest known Egyptian mummy to be scientifically examined and given a medical diagnosis

‘Dr Granville's mummy’ was described to the Royal Society of London in 1825 and was the first ancient Egyptian mummy to be subjected to a scientific autopsy. The remains are those of a woman, Irtyersenu, aged about 50, from the necropolis of Thebes and dated to about 600 BC. Augustus Bozzi Granville (1783–1872), an eminent physician and obstetrician, described many organs still in situ and attributed the cause of death to a tumour of the ovary. However, subsequent histological investigations indicate that the tumour is a benign cystadenoma. Histology of the lungs demonstrated a potentially fatal pulmonary exudate and earlier studies attempted to associate this with particular disease conditions. Palaeopathology and ancient DNA analyses show that tuberculosis was widespread in ancient Egypt, so a systematic search for tuberculosis was made, using specific DNA and lipid biomarker analyses. Clear evidence for Mycobacterium tuberculosis complex DNA was obtained in lung tissue and gall bladder samples, based on nested PCR of the IS6110 locus. Lung and femurs were positive for specific M. tuberculosis complex cell-wall mycolic acids, demonstrated by high-performance liquid chromatography of pyrenebutyric acid–pentafluorobenzyl mycolates. Therefore, tuberculosis is likely to have been the major cause of death of Irtyersenu

Treatment of Highly Drug-Resistant Pulmonary Tuberculosis

BACKGROUND Patients with highly drug-resistant forms of tuberculosis have limited treatment options and historically have had poor outcomes. METHODS In an open-label, single-group study in which follow-up is ongoing at three South African sites, we investigated treatment with three oral drugs — bedaquiline, pretomanid, and linezolid — that have bactericidal activity against tuberculosis and to which there is little preexisting resistance. We evaluated the safety and efficacy of the drug combination for 26 weeks in patients with extensively drug-resistant tuberculosis and patients with multidrug-resistant tuberculosis that was not responsive to treatment or for which a second-line regimen had been discontinued because of side effects. The primary end point was the incidence of an unfavorable outcome, defined as treatment failure (bacteriologic or clinical) or relapse during follow-up, which continued until 6 months after the end of treatment. Patients were classified as having a favorable outcome at 6 months if they had resolution of clinical disease, a negative culture status, and had not already been classified as having had an unfavorable outcome. Other efficacy end points and safety were also evaluated. RESULTS A total of 109 patients were enrolled in the study and were included in the evaluation of efficacy and safety end points. At 6 months after the end of treatment in the intention-to-treat analysis, 11 patients (10%) had an unfavorable outcome and 98 patients (90%; 95% confidence interval, 83 to 95) had a favorable outcome. The 11 unfavorable outcomes were 7 deaths (6 during treatment and 1 from an unknown cause during follow-up), 1 withdrawal of consent during treatment, 2 relapses during follow-up, and 1 loss to follow-up. The expected linezolid toxic effects of peripheral neuropathy (occurring in 81% of patients) and myelosuppression (48%), although common, were manageable, often leading to dose reductions or interruptions in treatment with linezolid. CONCLUSIONS The combination of bedaquiline, pretomanid, and linezolid led to a favorable outcome at 6 months after the end of therapy in a high percentage of patients with highly drug-resistant forms of tuberculosis; some associated toxic effects were observed. (Funded by the TB Alliance and others; ClinicalTrials.gov number, NCT02333799. opens in new tab.