Widespread occurrence of Mycobacterium tuberculosis DNA from 18th-19th century Hungarians

A large number (265) of burials from 1731-1838 were discovered in sealed crypts of the Dominican Church, Vac, Hungary in 1994. Many bodies were naturally mummified, so that both soft tissues and bones were available. Contemporary archives enabled the determination of age at death, and the identification of family groups. In some cases, symptoms before death were described and, occasionally, occupation. Initial radiological examination of a small number of individuals had indicated calcified lung lesions and demonstrable acid-fast bacteria suggestive of tuberculosis infection. Tuberculosis was endemic in 18th-19th century Europe, so human remains should contain detectable Mycobacterium tuberculosis complex (MTB) DNA, enabling comparisons with modern isolates. Therefore, a comprehensive examination of 168 individuals for the presence of MTB DNA was undertaken. Specific DNA amplification methods for MTB showed that 55% of individuals were positive and that the incidence varied according to age at death and sampling site in the body. Radiographs were obtained from 27 individuals and revealed an association between gross pathology and the presence of MTB DNA. There was an inverse relationship between PCR positivity and MTB target sequence size. In some cases, the preservation of MTB DNA was excellent, and several target gene sequences could be detected from the same sample. This information, combined with MTB DNA sequencing data and molecular typing techniques, will enable us to study the past epidemiology of TB infection, and extends the timeframe for studying changes in molecular fingerprints. Am J Phys Anthropol 120:144-152, 2003. (C) 2003 Wiley-Liss, Inc

Detection and characterization of Mycobacterium tuberculosis DNA in 18th Century Hungarians with pulmonary and extra-pulmonary tuberculosis

Skeletal and naturally mummified tissues from a previously archived group of 18th century Hungarian remains were examined for the presence of Mycobacterium tuberculosis complex (MTB) DNA, using specific nested PCR for the IS6110 locus. Paleopathological changes in bones and from radiographs were noted in a minority of cases. Overall, specimens from 157/232 (67.7 %) of individuals proved positive, ranging from 20/43 (46.5 %) in children, 26/29 in middle-age (89.7 %) and 32/46 individuals aged 65-95 years (69.6 %). Single samples gave a positive result in 67/120 of cases (55.8 %). Most were ribs where the surface adjacent to lungs and pleura was sampled. When multiple sites were examined, 73/93 (78.5 %) individuals were positive; most of these had MTB only in the pulmonary region but 26 had disseminated disease (35.6 %) and 12 (16.4 %) had extra-pulmonary disease only. To distinguish M. tuberculosis from Mycobacterium bovis, well-preserved positive samples were examined for several additional genetic loci including the TbD1 deletion – characteristic of modern European strains of M. tuberculosis, and spoligotyped. No evidence other than of human M. tuberculosis was found, but different strains were detected. Tuberculosis was widespread in this community and whilst some individuals succumbed early in life, the majority co-existed with the infection. Therefore, this study may lead to the identification of host alleles and MTB strains associated with active and latent disease

Atypical features of rat dentate granule cells: recurrent basal dendrites and apical axons.

The stereotyped morphology of dentate granule cells in rodents consists of apical dendrites arborizing in the molecular layer and an axon arising from the opposite pole of the soma. Recently, we showed that epilepsy induces the formation of basal dendrites on granule cells and that these dendrites extend into the hilus of the dentate gyrus. The present Golgi study of granule cells from adult rats shows two atypical features for granule cells in control rats. One is the occurrence of recurrent basal dendrites (RBDs) that are defined as basal dendrites arising at or near the hilar pole of the soma and then curving back to the molecular layer. The frequency of granule cells with RBDs was 3.8% in control rats. The second is apical axons of granule cells that were observed to originate from either the apical pole of the soma or an apical dendrite. The incidence of these "apical" axons was about 1%. These morphological findings in the present study suggest that rat granule cells are more heterogeneous than previously indicated. Furthermore, their frequency was not increased in epileptic rats

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

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