Changes in mitochondrial function induced in isolated guinea-pig ventricular myocytes by calcium overload.

1. Changes in [Ca2+]i and pHi, mitochondrial membrane potential (psi m) and mitochondrial [NADH] have been measured independently using fluorescent techniques in single isolated guinea-pig ventricular myocytes subjected to Ca2+ overload. 2. The changes in NADH autofluorescence on the inhibition or uncoupling of respiration are consistent with the signal emanating from the mitochondrial NADH. 3. Removal of Ca2+ and Mg2+ from the bathing Tyrode solution induced a modest fall in both [Ca2+]i and pHi, a small slowly developing depolarization of psi m and an initial fall followed by a rise in mitochondrial [NADH]. 4. In myocytes that maintained an intact sarcolemma, return to Ca(2+)-containing fluid elicited a strong but brief intracellular acidification, a rise in [Ca2+]i which generally recovered more slowly to stabilize above the initial level in Tyrode solution, a steep fall in mitochondrial [NADH] and a brief transient recovery followed by a large sustained depolarization of psi m. NADH autofluorescence and mitochondrial depolarization often reached values that were not further increased by uncoupling respiration although recovery of NADH was elicited by inhibitors of respiration. 5. These changes were reduced when the Ca2+ overload was less severe as evidenced by a reduced hypercontracture upon Ca2+ repletion. A similar reduction could be routinely achieved by elevation of [Mg2+]o during the period of Ca2+ depletion. 6. These results suggest that the well-established depletion of energy-rich phosphates that occurs on Ca2+ overload is due to the combined effects of the failure of the citric acid cycle to provide sufficient mitochondrial NADH for the respiratory chain and an uncoupling of respiration from ATP production due to depolarization of psi m. The former effect could result from the depletion of sarcoplasmic amino acids and the latter from increased Ca2+ cycling across the mitochondrial wall provoked by the elevated [Na+]i and [Ca2+]i.     

Microanalyses of lesions and lymph nodes from coalminers'' lungs.

The dust content and composition of lesions and hilar lymph nodes from the lungs of British coalworkers have been examined. Samples of macules, fibrotic nodules, and massive fibrosis (both peripheral and central sites) were dissected from 49 lungs. The highest mean dust concentrations (about 20%) were found in nodules and massive fibrosis. Overall there were no significant differences between the selected lesion types and their respective whole lung dust composition, although the central sites of massive fibrosis were found to contain on average a higher proportion of coal and a lower proportion of ash and its measured constituents, quartz and kaolin plus mica, than the edge of the lesion (p less than 0.001 for each component). There were striking differences between recovered lung and lymph node dusts. An examination of 180 specimens showed a mean quartz in lymph node dust of 20.3% compared with 6.1% in lung dust. As expected the proportion of quartz was greater in lymph nodes and lungs from men who had worked "low" rank (high ash) coal. By contrast with the corresponding figures for lung dusts, however, the mean proportion of quartz in nodes did not increase over the pathological range of pneumoconiotic lung disease. On average the proportions of kaolin and mica in lymph nodes reflect those found in lungs. The lymphotrophic nature of quartz was clearly shown although it was not possible to show an association between this clearance pathway and any particular type of lesion.     

Giant cell granuloma of the orbit with intracranial extension

An 8-year-old boy presented with acute proptosis of the right eye. Examination revealed 8 mm of exophthalmos, limitation of upward gaze, optic disc swelling, and normal visual acuity, but an inferonasal quadrantic visual field defect. Orbital ultrasound and computed tomographic scanning demonstrated a superotemporal tumor of the right orbit with intracranial extension. At operation, this proved to be a "reparative" giant cell granuloma. After partial resection, the remaining mass resolved spontaneously without further specific treatment. There had been no recurrence at the 1-year follow-up examination.     

An odor discrimination model with application to kin recognition in social insects

The problem of discriminating between a number of similar, nonspecific odors is discussed with special reference to the phenomenon of kin and nestmate discrimination in social insects. Guided by the basic physiological and anatomical features of the olfactory sensory receptors and neural pathways in insects, a model is presented for the process of odor discrimination. The model hypothesizes neural processing capabilities that include the logarithmic transformations of electrical potentials to generate a scalar quantity representing the "similarity" of two multivalued signals. The model thereby quantifies the notion of phenotype matching that appears in the kin recognition literature, and makes the concept of a recognition template more precise. The hypotheses underlying the model suggest a number of neurophysiological studies that should be undertaken, while the model itself provides a basis for integrating several areas of research pertaining to kin recognition in particular species of animals.     

Evaluation of the Sydney "Quit. For Life" anti-smoking campaign. Part 1. Achievement of intermediate goals

The "Quit. For Life" campaign was a media-based programme that was aimed at reducing the prevalence of smoking in Sydney. The programme committee set four intermediate goals which it felt had to be met for such a change in prevalence to occur. From households selected at random in Sydney and Melbourne, 5713 people were interviewed to assess whether the campaign attained these goals. The television commercials that were designed for the campaign, their frequency and the timing of their screening produced a higher recall of the commercial's message and the use of campaign back-up services than were specified originally in the goals. During the campaign there was a progressive increase in the number of smokers in Sydney who reported that they were likely to quit; this was significantly different from Melbourne data by the end of the campaign and thus fulfilled another campaign goal. However, shortly after the campaign ended, the proportion of smokers who intended to quit smoking was the same in the two cities. A cohort study of 949 people from the baseline study showed that, during the 12-month period of follow-up, 66% of Sydney smokers tried to stop or to reduce their smoking. In the control city, Melbourne, 60% of smokers reported making such attempts. Of the original smokers, 23% in Sydney and 9% in Melbourne quit during the follow-up period--a statistically significant difference. As well, 10% of the original ex-smokers in Sydney and 11% in Melbourne relapsed, while 4% of nonsmokers in both cities began smoking by the end of the second survey.     

The failure of physician education as a cost containment strategy. Report of a prospective controlled trial at a university hospital

To test the hypothesis that physician education is an effective strategy to reduce total hospital costs, we evaluated three educational interventions at a large university hospital. This prospective controlled study spanned two academic years and involved 1,663 patients and 226 house staff. In the first year, weekly lectures on cost containment (medicine and surgery) and audit with feedback (medicine only) both failed to produce a significant change in total hospital charges. The "dose" of the intervention was increased on medicine in the second year by combining the lecture and audit strategies. Again, total charges did not change significantly. While decreased use occurred for certain selected services, the impact was not great enough to affect total hospital charges significantly. We conclude that, in the absence of other cost containing incentives, physician education alone is not an effective hospital cost containment strategy.     

Hypolipidemic Agents of Phthalimide Derivatives 6. Effects of Aromatic vs. Non-Aromatic Imides

A number of substituted phthalimide, 1, 8-naphthalimide, succinimide and glutarimide derivatives demonstrated significant hypolipidemic activity at 20 mg/kg/ day, I.P. after 16 days dosing. The N-(n-pentyl) succinimide proved to be the most potent analogue of the new compounds, lowering serum triglyceride levels 51 % and serum cholesterol 47 % after 16 days dosing in mice. For the N-substituted derivatives, i. e., n-butyl, butanone, and propionic acid, of these four cyclic imides, there appeared to be no obvious trend in ability to reduce serum lipid levels. In general, the 1,8-naphthalimide and glutarimide derivatives appeared to be less active than phthalimide and succinimide. However, the -phenylsuccinimide afforded less activity than the -phenylglutarimide. Most of the derivatives at 20mg/kg/day demonstrated improved activity over clofibrate at 150mg/kg/day.     

Difficulties in navigating the intersection of generalist and specialist palliative care services: A cross-sectional study of bereaved family's experiences of care at home in New Zealand

A generalist–specialist model of palliative care is well established as a framework for the provision of community care in resource-rich countries. However, evidence is lacking regarding how the model is experienced by family carers and the extent to which access to both generalist and specialist palliative care is equitable. A cross-sectional postal survey was undertaken to explore bereaved family's experiences of generalist palliative care and its intersection with hospice services in the last 3 months of life. A modified version of the Views of Informal Carers—Evaluation of Services survey was sent to 4,778 bereaved family. Data were collected between February 2017 and October 2018. Chi-square was utilised to identify factors that impacted on experiences of generalist palliative care; analysis of free text data comprising 45,823 words was undertaken using a directed content analysis approach. Eight hundred and twenty-six questionnaires were returned (response rate = 21%). Seventy per cent of people (n = 579) spent some time at home in the last 3 months prior to death. People who received support from hospice were more likely to receive support from multiple other services. Those who received no community services were less likely to feel supported by their general practitioner, less likely to spend the last 2 days of life or die at home. Feeling supported had a strong association with services working well together, being involved in decision-making and being aware of the poor prognosis. The provision of palliative care is complicated by a lack of integration with specialist palliative care and may be the basis of continuing inequities in the provision of community care at the end of life. The assumption at a policy level that “generalists” are willing and able to play a key role in palliative care provision needs to be further challenged.