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Biomedical subjects

R M Douglas

Publications and source records attributed to R M Douglas.

At least 55 records · Page 3Linked to original sources
PubMed1997

Mutations in the glutathione-gated KefC K+ efflux system of Escherichia coli that cause constitutive activation.

The kefC gene of Escherichia coli encodes a potassium efflux system that is gated by glutathione (GSH) and by GSH adducts. Independently isolated kefC mutations that result in spontaneous activation of the efflux system have been analyzed. Three mutations affect residues located adjacent to the conserved Rossman fold in the carboxyl-terminal domain. Two mutations lie in a sequence predicted to form a cytoplasmically located loop in the membrane domain of KefC. All of the mutants retain normal regulation by the YabF protein and by GSH adducts. A mutation in the Rossman fold, R416S, alters the normal regulation of KefC by GSH. In contrast to the wild-type protein, which is inactive in the presence of GSH, the R416S mutant is only active in the presence of GSH or its analogue, ophthalmic acid. Other mutations in this region or elsewhere in the protein have their spontaneous activity augmented by depletion of the GSH pool. These data identify a specific role for the carboxyl-terminal domain of KefC in regulating KefC activity and are discussed in the light of recent data that suggest that GSH adducts can bind within a Rossman fold.

Bacterial Proteins↗
PubMed1997

Serotonin facilitates synaptic plasticity in kitten visual cortex: an in vitro study.

We have addressed the role of serotonin-2C (5-HT2C) receptors in the development and maintenance of synaptic plasticity in the kitten visual cortex. In visual cortical slices, taken from 40- to 80-day-old kittens, bath application of serotonin markedly facilitated the induction of both long-term depression (LTD) and long-term potentiation (LTP). Field potential responses to white matter stimulation were recorded from layer IV after a regime of low frequency stimulation (LFS; 1 Hz, 15 min), which reliably induced LTP or LTD in younger kittens (less than 30 days of age). At 40-80 days, this protocol almost never induced LTD or LTP in layer IV. However, in 50% of the visual cortical slices studied in 40-80-day-old kittens, LTD or LTP was induced, if serotonin (1 or 10 microM) was co-applied with LFS. No such serotonin facilitation of long-term plasticity was ever detected in > 120-day-old animals, indicating that serotonin facilitates synaptic plasticity within a defined period of visual cortical development. Serotonergic 5-HT2C receptors are likely to contribute to the synaptic plasticity observed in layer IV, since mesulergine, an antagonist of the 5-HT2C receptor, completely blocked synaptic modifications induced by the combination of low frequency stimulation and serotonin application.

Aging↗
PubMed1997

Respiratory effects associated with indoor nitrogen dioxide exposure in children.

BACKGROUND: The human health effects of exposure to indoor nitrogen dioxide (NO2) are unclear, and few studies have examined the effects of short-term peak levels of exposure. METHODS: The association between indoor exposure to NO2 and respiratory illness was examined in 388 children aged 6-11 years. The NO2 levels were monitored during winter in 41 classrooms, from four schools with unflued gas heating and four schools with electric heating. Each classroom was monitored daily with 6-hour passive diffusion badge monitors over nine alternate weeks, and with hourly monitors over two of those weeks. Children living in homes with unflued gas appliances were also monitored daily over four evenings during times of gas use. RESULTS: Exposure to NO2 at hourly peak levels of the order of > or = 80 ppb, compared with background levels of 20 ppb, was associated with a significant increase in sore throat, colds and absences from school. An increase in cough with phlegm was marginally significant. Significant dose-response relationships were demonstrated for these four measures with increasing levels of NO2 exposure. CONCLUSIONS: Short-term peak levels of exposure are important to consider in relation to adverse respiratory effects associated with NO2 exposure.

Air Pollution, Indoor↗
PubMed1997

Health effects of exposure to cyanobacteria (blue-green algae) during recreational water-related activities.

The aim of this study was to investigate effects on health of exposure to cyanobacteria as a result of recreational water activities. Participants, who were aged six years and over, were interviewed at water recreation sites in South Australia, New South Wales and Victoria on selected Sundays during January and February 1995. Telephone follow-up was conducted two and seven days later to record any subsequent diarrhoea, vomiting, flu-like symptoms, skin rashes, mouth ulcers, fevers and eye or ear irritations. On the Sundays of interview, water samples from the sites were collected for cyanobacterial cell counts and toxin analysis. There were 852 participants, of whom 75 did not have water contact on the day of interview and were considered unexposed. The 777 who had water contact were considered exposed. No significant differences in overall symptoms were found between the unexposed and exposed after two days. At seven days, there was a significant trend to increasing symptom occurrence with duration of exposure (P = 0.03). There was a significant trend to increasing symptom occurrence with increase in cell count (P = 0.04). Participants exposed to more than 5000 cells per mL for more than one hour had a significantly higher symptom occurrence rate than the unexposed. Symptoms were not correlated with the presence of hepatotoxins. These results suggest symptom occurrence was associated with duration of contact with water containing cyanobacteria, and with cyanobacterial cell density. The findings suggest that the current safety threshold for exposure of 20,000 cells per mL may be too high.

Adult↗
PubMed1997

General practitioners' perceptions regarding coordinated care.

OBJECTIVE: To explore the attitudes of general practitioners to the changing roles in the coordination of complex patient care. METHOD: A questionnaire survey was distributed with Australian Doctor. RESULTS: GPs were found to fall into four broad groups in relation to care coordination: those who do not want to expand their role in coordination of care (30%); those who would like to expand their role in coordination of care, but do not want to take costs into account when making decisions about patient care (34%); those who would like to expand their role in coordination of care, do think costs should be taken into account, but do not wish to be involved in budget management (21%); and those who would like to expand their role in coordination of care and be involved in budget management (22%). CONCLUSION: In the context of the introduction of managed care in Australia, this survey highlights the potential for GPs to take on a range of roles and responsibilities under these arrangements.

Adult↗
PubMed1996

Dosimetric results from a feasibility study of a novel radiosurgical source for irradiation of intracranial metastases.

PURPOSE: A feasibility study addressing the role of a new miniature x-ray device, the Photon Radiosurgery System (PRS), for interstitial radiosurgical treatment of intracranial metastatic neoplasms, was conducted at our institution. To gain insight into the role of PRS vis-à-vis other currently available radiosurgical treatment modalities, dosimetric comparisons of Linac Radiosurgery and proton beam therapy were performed in the treatment of a small approximately spherical metastasis. METHODS AND MATERIALS: The photon radiosurgery system is a miniature, battery operated, high-voltage x-ray generator that produces low-energy x-rays with an effective energy of 10-20 keV emanating from the tip of a probe stereotactically inserted into small tumors (< 3 cm in diameter) in humans. Patients, 18 years or older, with supratentorial mass lesions less than 3 cm in diameter were eligible if they were likely to survive their systemic cancer and be capable of self-care for more than 4 months. Patients were ineligible if presenting with infratentorial lesions, contraindications for biopsy, or receipt of chemotherapy or radiotherapy within 4 weeks were ineligible. RESULTS: Fourteen patients with metastatic supratentorial lesions were treated from December 1992 to December 1993 for metastatic tumors to the brain. Single doses of 10-20 Gy were delivered to spherical targets of 10 to 35 mm in diameter. Treatment, including biopsy, pathologic review and radiation treatment, generally took less than 3 h. One patient, later found to have an ischemic stroke, developed a small hemorrhage from the biopsy that preceded interstitial irradiation. There were no other complications. Median survival was 10 months. Three locally recurrent lesions failed at 3.5, 4, and 10 months after treatment. All patients had stable or improved Karnofsky status for 2 weeks to 21 months after treatment. The PRS dosimetry appears at least as good as that obtained using 6 MV Linac or 160 MeV protons. Analyses of dose-volume histograms comparing the volumes of normal CNS tissue irradiated employing each of the respective modalities suggest a small sparing of normal tissue with PRS, as opposed to linac or protons, in this patient population with small, approximately spherical tumors. CONCLUSIONS: The PRS device provides a unique cost and time efficient procedure for providing interstitial radiation therapy immediately following histologic confirmation of malignancy in patients undergoing biopsy of intracranial lesions. The PRS treatment appears safe, and preliminary data suggest no evidence of treatment-related morbidity within the life span of the selected patient population. When treating small, spherical lesions, PRS appears to offer a modest dosimetric advantage over Linac or proton beam therapy in sparing normal tissue. These encouraging results have prompted a Phase II trial that is currently underway. Further efforts are necessary in the design of a clinically relevant trial addressing the role of fractionated external beam radiation therapy with boost vs. PRS treatment with WBRT in the treatment of single metastases.

Adult↗
PubMed1996

The public health impact of minor injury.

The mortality and hospital morbidity data usually used to quantify the burden of injury are generally considered to represent only the tip of the iceberg. This article documents the population-based morbidity arising from non-hospitalised injuries and demonstrates the public health importance of this group of injuries. A prospective cohort study was conducted in an Australian population using a sample of injured adults to identify the health outcomes arising from the range of injuries. The total health loss caused by injury experienced by these subjects over the period of injury recovery was calculated and then weighted to provide population estimates. This study has shown that minor injuries are responsible for the greater part of the injury-related health burden in the adult community. Injuries that can be coded as 1 on the Abbreviated Injury Scale account for 80% of the morbidity arising over the first six months after injury and about 75% of the estimated lifetime morbidity. The lifetime estimates of morbidity resulting from injuries not considered serious enough to admit to hospital were of an order of magnitude higher than those that resulted in either death or hospitalisation. Sprains contributed as much to the total morbidity as all other injuries types combined and limb injuries contributed more to the total morbidity than injuries to the more central structures. The results of this study provide a strong argument for the recognition of the public health importance of minor injury. Strategies for the prevention and management of minor injury must be included in national programmes for injury control.

Abbreviated Injury Scale↗
PubMed1996

Conservative surgery, patient selection, and chemoradiation as organ-preserving treatment for muscle-invading bladder cancer.

Multimodality organ-sparing treatment has, during the last decade, become the standard of care for many common malignancies. In appropriately selected patients with muscle-invading bladder cancer, bladder-preserving treatment combining surgical transurethral resection (TUR) with chemoradiation therapy offers a chance for long-term cure and survival equal to cystectomy, while also affording a 60% to 70% chance of maintaining a normally functioning bladder. Selection criteria helpful in determining appropriate patients for bladder preservation include such variables as small tumor size, that a visibly complete TUR is possible, the absence of hydronephrosis and that a complete response (CR) to induction chemoradiotherapy was achieved. Selecting patients based on response to induction therapy allows for prompt cystectomy if residual disease is found or for prompt consolidation chemoradiotherapy if a CR with induction therapy is achieved. Bladder-preserving treatment usually results in a normally functioning bladder without incontinence or hematuria for stage T2 and T3a patients. Stage T3b-T4 patients are locally controlled less frequently using these techniques. However, no data exist to suggest that patients with more advanced disease are in any way disadvantaged by preoperative chemoradiotherapy as an attempt at bladder conservation. Patients require close urological surveillance as do any patients with superficial bladder cancer who are being treated conservatively. As studies addressing the possibility of organ preservation continue to show positive results, more patients will become informed about and will be offered selective bladder-sparing approaches as one-treatment option.

Combined Modality Therapy↗
PubMed1995

Consumer use of multiple general practitioners: an Australian epidemiological study.

The aim of this Australian study was to explore the reasons for peoples' choice of general practitioner (GP) in an environment where they have freedom of choice of doctor on every occasion of attendance. A questionnaire was administered by trained research assistants to 555 people during an hour-long interview. Utilization of more than one general practitioner was examined in terms of sociodemographic factors, health status and satisfaction with the last general practice visit. Respondents were more likely to see more than one general practitioner if they had more visits; were dissatisfied with their last consultation with a general practitioner; were younger; were female; and were highly qualified. Further, respondents who described good communication as the rationale for their satisfaction rating for their last general practitioner visit were less likely to have seen more than one general practitioner.

Adult↗
PubMed1994

A prospective study of proneness to acute respiratory illness in the first two years of life.

BACKGROUND: This study sought explanations for the proneness to respiratory events in young Australian children. METHODS: Prospective respiratory symptom diaries on 836 children collected data on respiratory symptoms and episodes. Questionnaires to mothers and birth and pregnancy records provided 56 known and possible predictors which were tested against two summary respiratory outcomes in each of the first and second years of life. RESULTS: The two summary respiratory variables recorded for first and second year of life give four outcome variables. In fitting multivariate regression models to predict outcomes, use of child care in early childhood and mothers' experience of respiratory illness in the 12 months before birth were significant predictors for all four outcomes. Number of siblings was a predictor for three of the four outcomes. Sleep difficulty during pregnancy in the mother, and respiratory hospitalization of the infant in the first year, were significant predictors for both first-year outcomes. Unexpected and unexplained findings emerged for alcohol intake during pregnancy, passive smoking and breastfeeding in relation to the second year respiratory outcomes. Less than 9% of variance in outcome scores was explained in any of the four multiple regression models but this rose to between 24% and 31% when a corresponding score from the other year was added to the model. CONCLUSIONS: Proneness to respiratory illness is an important entity; its determinants are largely unknown and events in pregnancy or the perinatal period explain only a small proportion of the between-infant variability.

Acute Disease↗