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Biomedical subjects

I Fraser

Publications and source records attributed to I Fraser.

At least 19 recordsLinked to original sources
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↗
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↗
PubMed1994

Use of surface molecules and receptors for studying macrophages and mononuclear phagocytes.

Members of the mononuclear phagocyte system use their extensive repertoire of cell surface receptors to interact with their external environment. A number of different assays are available for the study of these molecules and their many functions. In this paper we describe how monoclonal antibodies may be generated against macrophage molecules, and discuss how screening strategies aimed at producing functionally active reagents may be devised. Using the macrophage mannose and scavenger receptors as examples, we describe assays for determining macrophage adhesion to culture plastic surfaces, endocytosis of soluble ligands and phagocytosis of particles in vitro. These assays may be used in the production of inhibitory monoclonal antibodies, as well as in studies of the regulation of macrophage phenotype and activity.

Animals↗
PubMed1994

Intestinal anastomosis with a skin stapler: a safe and efficient method in humans.

A method of intestinal anastomosis with a skin stapler has been used successfully in 39 patients to form 40 anastomoses. The method has been employed in elective and emergency surgery, in small and large intestine, for a variety of pathological conditions and in the presence of obstruction, sepsis and soiling. Bowel anastomosis with a skin stapler is safe, simple and efficient in time and materials.

Adult↗
PubMed1994

Upregulation of the macrophage scavenger receptor in response to different forms of injury in the CNS.

The monoclonal antibody 2F8 was used to localize the macrophage scavenger receptor by immunohistochemistry. In control adult mice, macrophage scavenger receptor expression in the brain was restricted to stromal and epiplexus macrophages of the choroid plexus, meningeal macrophages and to perivascular sites. Microglia did not express the receptor. In the developing mouse brain, macrophage scavenger receptor expression was high on meningeal macrophages and detectable on immature microglia in the supraventricular corpus callosum, cingulum, cavum septum and the periaqueductal area. In the aged mouse brain, the pattern of macrophage scavenger receptor expression was no different from that in the young adult brain. Macrophage scavenger receptor expression on resident microglia and recruited macrophages was detected 24 h after an intrahippocampal injection of either lipopolysaccharide or kainic acid. Macrophage scavenger receptor expression was also detected in microglia 3 days after optic nerve crush both in the nerve segment distal to the crush site and in the superior colliculus. These studies indicate a potential role for the macrophage scavenger receptor in the CNS in the clearance of debris during acute neuronal degeneration.

Animals↗