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Biomedical subjects

I Fraser

Publications and source records attributed to I Fraser.

At least 37 records · Page 2Linked to original sources
PubMed1999

Children and managed care: what research can, can't, and should tell us about impact.

The speed and ubiquity of the move from fee-for-service to managed care raises questions about how these changes affect children. This article examines (1) the pace and context of the move to managed care for children, (2) potential opportunities and challenges emerging from these changes, (3) research findings on how managed care affects children, and (4) next steps for learning more. The research review provides a consistent answer to whether managed care is good for children: it depends on what kind of managed care, which children, and under what circumstances. This finding suggests lessons for future research: (1) focus on particular features of managed care, (2) get inside the "black box" of managed care and examine providers, (3) expand the portfolio of research on children: research on adults cannot "trickle down" to children, (4) foster research partnerships and networks, and (5) focus on poor and chronically ill children.

Child↗
PubMed1998

Structural interactions between actin, tropomyosin, caldesmon and calcium binding protein and the regulation of smooth muscle thin filaments.

The basic structure and functional properties of smooth muscle thin filaments were established about 10 years ago. Since then we and others have been working on the details of how tropomyosin, caldesmon and the Ca(2+)-binding protein regulate actin interaction with myosin. Our work has tended to emphasize the similarities between caldesmon and troponin function whilst others have been more concerned with the differences. The need to resolve the resulting differences has stimulated us to find new and more direct ways of investigating the mechanism of thin filament regulation. In recent years an apparent divergence has opened up between functional measurements, which indicate an allosteric-cooperative regulatory mechanism in which caldesmon and Ca(2+)-binding protein control actin-tropomyosin state in the same way as troponin, and structural measurements which show thin filament structures unlike striated muscle thin filaments. The challenge is to interpret function in terms of structure. We have combined functional studies with expression and mutagenesis of caldesmon and with structural methods including X-ray crystalography of tropomyosin-caldesmon crystals, electron microscopy and helical reconstruction of actin-tropomyosin-caldesmon complexes and high resolution nuclear magnetic resonance spectroscopy of the C-terminus of caldesmon in interaction with actin and calmodulin. We have used this information to propose a structural mechanism for caldesmon regulation of the smooth muscle thin filament.

Actins↗
PubMed1997

Myofibroblasts and arteriolar sclerosis in human diabetic nephropathy.

We examined the biopsy specimens of 62 patients with diabetic nephropathy to establish whether the myofibroblast (MF) has a role in progressive interstitial fibrosis and to ascertain whether a relationship existed between MF activity and severity of arteriolosclerosis. MF were identified by morphology and alpha smooth muscle actin (alpha SMA) immunostaining. Analysis of vascular injury was performed by counting the number of interstitial arterioles after staining endothelial cells with von Willebrand factor (VWF) antibody. Arteriosclerosis was quantified by using a computer-aided image analyzer to measure the arteriolar wall surface and total arteriolar surface area, and the ratio of wall to total surface area was expressed as the index of arteriosclerosis (IA). Fractional area of interstitium (IFA), alpha SMA, and collagen III (Coll III) were quantitated by point counting. Results were related to structural and functional parameters using rank correlation coefficients. There was a strong correlation between IFA and Coll III staining (r = 0.83; P < 0.001). The alpha SMA staining correlated with IFA (r = 0.56; P < 0.001) and Coll III (r = 0.47; P < 0.001), and there were significant correlations between alpha SMA and total urinary protein (r = 0.47; P < 0.001), renal function (plasma creatinine) at time of biopsy (r = 0.51; P < 0.001), and the percent change in plasma creatinine after 4 years (delta Cr) (r = 0.37; P = 0.01). The IA correlated significantly with Coll III (r = 0.29; P = 0.02), glomerular filtration rate (GFR) (r = 0.39; P = 0.008), and creatinine (r = 0.33; P = 0.01), but no correlation was observed between alpha SMA and IA (r = 0.16; P = 0.23) or IA and delta Cr (r = -0.04; P = 0.6). Strong correlations could be shown between arteriolar density, IFA (r = 0.75; P < 0.001), alpha SMA (r = -0.36; P = 0.034), and Coll III (r = -0.66; P < 0.0001). The MF appears to have a significant role in the progression of diabetic nephropathy. Ischemia secondary to arteriosclerosis may contribute to interstitial fibrosis through fibroblast modulation into MF.

Adult↗
PubMed1997

Cancer of the pyriform fossa: hyperfractionated radiotherapy as a primary treatment modality.

Carcinoma of the pyriform fossa carries one of the worst prognoses of all head and neck cancers. A prospective trial was set up to study the efficacy of hyperfractionated radiotherapy as a primary treatment modality in the management of these patients. Seventeen patients entered the trial and were followed for up to 3 years. Results for local control, regional control and survival compare favourably with patients treated primarily with surgery with or without radiotherapy. Hyperfractionated radiotherapy offers a logical and standardized approach to the management of this tumour and reduces the significant morbidity associated with the use of surgery as a primary treatment.

Carcinoma, Squamous Cell↗
PubMed1997

Blood lead levels in preschool children in eastern Sydney.

A blood lead study of 1-4-year-old children attending child care centres in eastern Sydney was conducted from November 1992 until May 1993 to determine the distribution of blood lead levels (PbBs). A total of 191 children were tested during the survey, constituting a participation rate of 67%. The geometric mean PbB was 0.34 mumol/L (7.2 micrograms/dL); 13.6% of children had PbBs equal to or greater than the National Health and Medical Research Council (NHMRC) upper goal of 0.48 mumol/L (10 micrograms/dL). Traffic flow at home, the presence of pets at home and thumb-sucking in females were all highly associated with blood lead. In particular, the association between PbB and traffic volume indicated a positive dose-response type relationship. Removal of paint from a pre-1960s house and having a smoker in the house had a non-significant effect on variation in blood lead. These results suggest that recent government and industry actions to reduce lead in petrol should have a beneficial effect in lowering PbBs in children. Widespread public education on sources of lead around the home and on appropriate control measures to minimise exposure is warranted.

Air Pollution, Indoor↗
PubMed1996

Involvement of specific macrophage-lineage cells surrounding arterioles in barrier and scavenger function in brain cortex.

The transport of solutes between blood and brain is regulated by a specific barrier. Capillary endothelial cells of brain are known to mediate barrier function and facilitate transport. Here we report that specific cells surrounding arterioles, known as Mato's fluorescent granular perithelial (FGP) cells or perivascular microglial cells, contribute to the barrier function. Immunohistochemical and in situ hybridization studies indicate that, in normal brain cortex, type I and type II macrophage scavenger receptors are expressed only in FGP/perivascular microglial cells, and surface markers of macrophage lineage are also detected on them. These cells mediate the uptake of macromolecules, including modified low density lipoprotein, horseradish peroxidase, and ferritin injected either into the blood or into the cerebral ventricles. Accumulation of scavenged materials with aging or after the administration of a high-fat diet results in the formation of honeycomb-like foam cells and the narrowing of the lumen of arterioles in the brain cortex. These results indicate involvement of FGP/perivascular microglial cells in the barrier and scavenger functions in the central nervous system.

Adult↗
PubMed1996

Inhibition of dihydropyrimidine dehydrogenase by 5-propynyluracil, a metabolite of the anti-varicella zoster virus agent netivudine.

OBJECTIVE: To study the effects of the anti-herpetic drug netivudine on dihydropyrimidine dehydrogenase activity in elderly volunteers and to relate them to concentrations of netivudine and its metabolite 5-propynyluracil. METHODS: Three groups of eight elderly volunteers received 400 or 800 mg netivudine or placebo once daily for 8 days. Plasma netivudine, 5-propynyluracil, and uracil, an indirect measure of dihydropyrimidine dehydrogenase activity, were assayed before the first dose and on days 2, 3, 5, 7 and 8. Full plasma profiles of netivudine and 5-propynyluracil were determined after the last dose. RESULTS: Plasma uracil was unquantifiable in all subjects before the first dose and at all time points in the placebo group. In recipients of netivudine it reached a plateau between days 3 and 5, with mean values of 23.2 and 23.5 mumol/L on day 8 in the subjects who received 400 and 800 mg. Plasma netivudine concentrations were approximately dose proportional, but 5-propynyluracil concentrations were similar in both groups. The half-maximal rise in plasma uracil occurred after a cumulative 5-propynyluracil exposure of 120 mumol/L.hr; such exposures will be achieved even after doses as low as 50 to 100 mg daily. CONCLUSIONS: Netivudine dosing produces complete inhibition of plasma dihydropyrimidine dehydrogenase. Coadministration with the antimetabolite 5-fluorouracil will require a substantial reduction in 5-fluorouracil dose to avoid toxicity but may also improve the therapeutic index of 5-fluorouracil.

Aged↗
PubMed1996

Endometrial vasculature in Norplant users: preliminary results from a hysteroscopic study.

Long-acting progestogenic contraceptives are frequently associated with disturbances of menstrual bleeding patterns. In particular, irregular, frequent and prolonged bleeding are commonly seen. The mechanism of this irregular bleeding is unknown, but changes in the endometrial vasculature are thought to be of importance. In endometrial biopsies from Norplant users, an increase in endometrial microvascular density has been observed after 3-12 months. Morphological changes in endometrial capillaries following progestogen exposure have suggested an increase in vascular fragility. Little is known about the structure and function of the endometrial vasculature in vivo following exposure to exogenous contraceptive steroids. This study has developed techniques for the assessment of vascular fragility by imposing a mechanical stress on the endometrium and observing subsequent bleeding under direct vision. The techniques were used in a preliminary examination between 1 and 9 months after Norplant insertion, and the study identified a number of morphological and functional characteristics of Norplant-exposed endometrium.

Adolescent↗
PubMed1996

Training and accreditation in endoscopic surgery.

Increasing concerns following the rapid uptake of endoscopic procedures into routine use and a small number of serious adverse patient outcomes have precipitated calls for guidelines on training and accreditation. A number of international colleges and societies have produced recommendations, although a number of inherent problems remain in the implementation of these. The published literature in the field is quite limited at present, but will undoubtedly expand rapidly.

Certification↗
PubMed1995

Chondroradionecrosis of the larynx: still a diagnostic dilemma.

Following radiation treatment for carcinoma of the larynx it may be very difficult to differentiate between persistent or recurrent tumour and severe radiation effects particularly chondroradionecrosis. Despite repeated negative biopsy it may be necessary to perform total laryngectomy where the concern about persistent cancer remains and the larynx is non-functioning. We report nine cases presenting as chondroradionecrosis over a five-year period. Two patients settled on medical treatment. Of seven patients treated with laryngectomy the histology on two revealed residual or recurrent carcinoma. We outline the dilemmas in diagnosis and propose management strategies to deal with this condition including recommendations for prevention and treatment.

Adult↗
PubMed1995

The inter-relationship of premenstrual symptoms.

The prospective symptom reports of women seeking treatment for premenstrual symptoms and control subjects was investigated. In order to compare symptom reports from premenstrual symptom sufferers and control subjects a method of combining and analysing prospectively collected menstrual cycle symptom data is required. A technique that uses the time of onset of menses and the time of ovulation (as measured by urinary luteinizing hormone excretion) to standardize each cycle into 14 time points was developed. Summary factors were then empirically derived from data collected prospectively from 30 premenstrual symptom sufferers and 19 control subjects. Twenty-two mood symptoms were summarized into a single factor and the 29 most frequently occurring physical symptoms were summarized into two factors. Factor scores were calculated on the basis of these factors and the effect of time during the menstrual cycle on these scores examined. Both physical symptom factor scores increased significantly in the luteal phase for both the premenstrual symptom sufferer group and the control group. The single mood factor score increased significantly in the luteal phase for the premenstrual sufferer group but not for the control group, suggesting that the only qualitative difference between the groups was the presence of cyclic mood symptoms in the premenstrual symptom sufferer group. The premenstrual symptom sufferer group recorded significantly higher scores on each of the three factors than the control group. The correlation between the scores on each of the factors over three cycles was high both in the follicular and luteal phase suggesting that these factor scores provide a reproducible measure of menstrual cycle symptomatology.

Adult↗
PubMed1995

Activation by interferon-gamma of expression of ICAM-1 and MHC class II antigens in tumour cells from colorectal carcinomas.

Aims-To determine whether lack of MHC class II antigen and intercellular adhesion molecule-1 (ICAM-1) expression in some tumours is due to the inability of the tumour cells to respond to the cytokine interferon-gamma (IFN-gamma), an important activator of these surface molecules.Methods-Cells from 40 colorectal tumours which did not constitutively express class II MHC antigens or ICAM-1 were kept in short term culture after disaggregation for a few days to two weeks without significant loss of viability. These were treated with IFN-gamma. Expression of class II MHC antigens and ICAM-1 was determined using immunohistological techniques.Results-There was clear induction in vitro of both MHC class II antigens and ICAM-1 in cells from eight of the tumours, with between 50 and 80% of the tumour cells in the cultures staining positively. The staining was apparent within 24 hours, appeared maximal at about three days, and declined thereafter. There were no obvious differences in cell morphology or viability between the cultures which were inducible and those which were not, nor were there obvious differences between the tumours from which they were derived.Conclusions-Expression of MHC class II antigens and ICAM-1 may be induced by IFN-gamma in a small proportion of colorectal tumours which do not constitutively express these antigens, showing that only a minority of tumours are capable of responding to this cytokine.

Journal Article↗