The influence of experimental distemper infection on the distribution of lead in dogs previously subacutely intoxicated with lead carbonate.

The ability of experimental canine distemper infection to mobilize body lead deposits has been studied in Beagle dogs previously subacutely intoxicated with lead carbonate. For comparative purposes dogs were included which had either received lead only or distemper only or remained undosed. It was found that in dogs predosed with lead, distemper infection resulted in a significant increase in lead levels in blood and urine; this coincided with the peak body temperatures reached on the third day post infection. It was also found that the lead content of the liver and bone of these dogs was considerably higher than that of dogs receiving lead alone; at the same time bone phosphorus showed a marked decrease while bone calcium values remained similar to undosed controls.     

Glycosylation is not required for the fusion activity of the G protein of vesicular stomatitis virus in insect cells

The gene encoding the complete glycoprotein of vesicular stomatitis virus (VSV, Indiana serotype G protein) with potential asparagine-linked glycans at amino acid residues 179 and 338 was inserted into a baculovirus transfer vector pAcYM1, derived from the nuclear polyhedrosis virus of Autographa californica (AcNPV). The gene was placed under the control of the AcNPV polyhedrin promotor and expressed by the derived recombinant viruses to high levels in Spodoptera frugiperda cell lines. The principal product was the glycosylated version of the G protein, although some alternative (including probable degradation) forms of the protein were also observed. Similar recombinant viruses were prepared with deletion of one, the other, or both glycosylation sites of the VSV G protein. All forms expressed VSV G protein derivatives and mediated cell fusion and the production of syncytia at low pH. The fusogenic properties of the VSV G protein expressed on the surface of insect cells was prevented using anti-VSV sera, or by elevating the pH above 6.2. A reduction of the pH to 5.5, or 5.0, accelerated the rate of syncytia formation.     

Identification of MEN1 gene mutations in sporadic carcinoid tumors of the lung

Lung carcinoids occur sporadically and rarely in association with multiple endocrine neoplasia type 1 (MEN1). There are no well defined genetic abnormalities known to occur in these tumors. We studied 11 sporadic lung carcinoids for loss of heterozygosity (LOH) at the locus of the MEN1 gene on chromosome 11q13, and for mutations of the MEN1 gene using dideoxy fingerprinting. Additionally, a lung carcinoid from a MEN1 patient was studied. In four of 11 (36%) sporadic tumors, both copies of the MEN1 gene were inactivated. All four tumors showed the presence of a MEN1 gene mutation and loss of the other allele. Observed mutations included a 1 bp insertion, a 1 bp deletion, a 13 bp deletion and a single nucleotide substitution affecting a donor splice site. Each mutation predicts truncation or potentially complete loss of menin. The remaining seven tumors showed neither the presence of a MEN1 gene mutation nor 11q13 LOH. The tumor from the MEN1 patient showed LOH at chromosome 11q13 and a complex germline MEN1 gene mutation. The data implicate the MEN1 gene in the pathogenesis of sporadic lung carcinoids, representing the first defined genetic alteration in these tumors.      

Exploring Differences in Work Disability Duration by Size of Firm in Canada and Australia

Journal of Occupational Rehabilitation - Purpose To identify whether there were differences in work disability duration between injured workers employed by small, medium, large, and self-insured...     

Age Differences in Work-Disability Duration Across Canada: Examining Variations by Follow-Up Time and Context

Journal of Occupational Rehabilitation - Purpose This study aimed to understand age differences in wage-replacement duration by focusing on variations in the relationship across different periods...     

The use of artificial intelligence and robotics in regional anaesthesia

The current fourth industrial revolution is a distinct technological era characterised by the blurring of physics, computing and biology. The driver of change is data, powered by artificial intelligence. The UK National Health Service Topol Report embraced this digital revolution and emphasised the importance of artificial intelligence to the health service. Application of artificial intelligence within regional anaesthesia, however, remains limited. An example of the use of a convoluted neural network applied to visual detection of nerves on ultrasound images is described. New technologies that may impact on regional anaesthesia include robotics and artificial sensing. Robotics in anaesthesia falls into three categories. The first, used commonly, is pharmaceutical, typified by target-controlled anaesthesia using electroencephalography within a feedback loop. Other types include mechanical robots that provide precision and dexterity better than humans, and cognitive robots that act as decision support systems. It is likely that the latter technology will expand considerably over the next decades and provide an autopilot for anaesthesia. Technical robotics will focus on the development of accurate sensors for training that incorporate visual and motion metrics. These will be incorporated into augmented reality and visual reality environments that will provide training at home or the office on life-like simulators. Real-time feedback will be offered that stimulates and rewards performance. In discussing the scope, applications, limitations and barriers to adoption of these technologies, we aimed to stimulate discussion towards a framework for the optimal application of current and emerging technologies in regional anaesthesia.     

Sub-clinical Cushing's syndrome in patients with adrenal gland incidentalomas. Pitfalls in diagnosis and management

Widespread use of contemporary imaging techniques (ultrasound, computerized axial tomography, and magnetic resonance imaging scans) have led to the incidental discovery of asymptomatic adrenal neoplasms with increasing frequency. Patients with such adrenal "incidentalomas" typically have no clinical manifestations of adrenal cortical hyperfunction at the time of discovery. We have studied 122 patients with asymptomatic adrenal masses ranging in size from 2 to 7 cm in diameter from 1978 to 1988. Selected patients, after adrenal metastases, pheochromocytoma, myelolipomas, and cysts were ruled out, were further evaluated for adrenal cortical hyperfunction by measuring urinary 17-hydroxysteroids, 17-ketosteroids, and free cortisol, serum A.M., P.M. cortisol, and plasma ACTH levels. These values were also measured before and after dexamethasone suppression. NP-59 adrenal scintiscans were performed on all patients. Six patients were identified with sub-clinical Cushing's syndrome. Baseline cortisol levels were normal in each of these patients. Loss of diurnal rhythm appeared to be the most sensitive indicator of abnormal adrenal cortical function. When adrenalectomy is performed in such patients, especially when contralateral adrenal gland suppression is evidenced by NP-59 scanning or other biochemical assessment, perioperative steroids should be administered in a manner similar to that used for patients with symptomatic Cushing's syndrome. Unilateral adrenalectomy in a patient with an asymptomatic adrenal adenoma, insufficiently studied, may result in Addisonian crisis.     

Nonhereditary p53 mutations in T-cell acute lymphoblastic leukemia are associated with the relapse phase

We have previously reported that greater than 60% of human leukemic T- cell lines possess mutations in the p53 tumor suppressor gene. To determine whether T-cell acute lymphoblastic leukemia (T-ALL) patient samples possess p53 mutations, we screened peripheral blood-and bone marrow-derived leukemia samples, taken at diagnosis and at relapse, for p53 mutations. Exons 4 through 9 and selected intron regions of the p53 gene were analyzed using polymerase chain reaction-single-strand conformation polymorphism and direct sequencing. p53 mutations were found in 0 of 15 T-ALL diagnosis samples, as compared with 10 of 36 (28%) T-ALL relapse samples. To determine whether p53 mutations play a role in the recurrence (relapse) of T-ALL, two special groups of T-ALL patients were studied: (1) a group of 8 relapse patients whose disease was refractory to chemotherapeutic treatment, and (2) a group of 6 "paired" T-ALL cell samples from patients for whom we possess both diagnosis and relapse samples. Three of 8 relapsed patients (37.5%) whose disease was refractory to the reinduction of remission by chemotherapy possessed missense mutations of the p53 gene. All 3 cases had mutations in exon 5. Among the paired samples, 3 of 6 patients harbored p53 mutations at disease recurrence, but possessed only wild- type p53 alleles at diagnosis. One case had mutation on exon 4, 1 case in exon 5, and 1 case in exon 8 with loss of heterozygosity. These data clearly indicate that recurrence of T-ALL is associated with missense mutations in p53. Our results indicate that (1) mutations of p53 do occur in T-ALL in vivo, and such mutations are associated with the relapse phase of the disease; and (2) p53 mutation is involved in the progression of T-ALL. This conclusion is supported by our observation that the introduction of T-ALL-derived mutant p53 expression constructs into T-ALL cell lines further increases their growth rate in culture, enhances cell cloning in methylcellulose, and increases tumor formation in nude mice.     

The New Zealand Socioeconomic Index: developing and validating an occupationally-derived indicator of socio-economic status

OBJECTIVE: Following revision of the international standard classification (ISCO88), to update and validate on health data an occupationally derived indicator of socio-economic status (SES) adapted to changing occupational and demographic conditions. METHOD: The development of the New Zealand Socioeconomic Index (NZSEI) is based on a 'returns to human capital' model of the stratification process and uses data from the 1991 New Zealand Census (n = 1,051, 926) to generate scores for 97 occupational groups. The construct validation of the scale is carried out on data from the 1992-93 nationwide Household Health Survey (n = 3,000) using three health indicators (self-assessed health, cigarette smoking, general practitioner visits). RESULTS: In general, the results are consistent with expected socio-economic patterns drawn from the literature for the three indicators. CONCLUSIONS: While further work is required on a number of methodological and conceptual issues, the NZSEI provides a robust, standardised and internationally comparable occupational scale of SES for both males and females in either full- or part-time employment. IMPLICATIONS: The NZSEI can be used on routinely collected occupational data. It has a clear conceptual rationale, updates existing SES scales, and provides a link to international standards in SES and occupational classification.