Biomedical subjects

J A Hunt

Publications and source records attributed to J A Hunt.

At least 73 records · Page 4Linked to original sources

PubMed1996

Is the mid-inguinal point an accurate landmark for the common femoral artery in vascular patients?

BACKGROUND: An accurate guide to the common femoral artery (CFA) is important in vascular patients as the CFA pulse may not me palpable. At least four different descriptions of the surface anatomy of the CFA are given in standard anatomic texts. This study was undertaken to determine the accuracy of the mid-inguinal point as a guide to the CFA in patients undergoing femoral arteriography. METHODS: The surface anatomy of the CFA was determined using true anteroposterior arteriograms of 30 patients [20 men, 10 women, age (mean +/- s.d.) 67 +/- 6.8 years, range 56-82]. RESULTS: The distance between the anterior superior iliac spine (ASIS) and the symphysis pubis was measured with callipers and defined as the inguinal distance [(mean +/- s.d.) 16.03 +/- 1.06 cm, range 14.00-18.50]. The midpoint of this line defined the mid-inguinal point. Similarly, the distance was measured from the symphysis pubis to the midpoint of the CFA where it crossed the inguinal line on the arteriogram, and was defined as the femoral distance [(mean +/- s.d.) 7.99 +/- 0.51 cm, range 6.80-9.00]. The location of the CFA coincided with the mid-inguinal point in only six (10%) of the 60 measurements. The difference between the CFA and mid-inguinal point varied from 1.25 to 1.50 cm either side of the mid-inguinal point, and in six (10%), the difference was 1 cm more, and therefore of clinical significance. CONCLUSIONS: On the basis of these findings we conclude that the relationship between the mid-inguinal point, found using bony landmarks, is an appropriate guide to the CFA as it can be expected to lie within 1.5 cm either side of the mid-inguinal point. The natural variability observed could account for the different anatomical descriptions of the surface anatomy of the CFA. No exact definition may be possible.

Aged↗

PubMed1995

Fibroblast adhesion onto methyl-silica gradients with and without preadsorbed protein.

This study was designed to evaluate the interfacial interactions between proteins and cells and a model surface which varied in its surface energy. The adsorption of proteins from single and binary solutions was studied using ellipsometry and the adhesion and spreading of L929 fibroblasts has been quantified using image analysis. The results demonstrated that after 24 h incubation, multilayer adsorbed fibrinogen appeared to produce a surface most conductive to cell adhesion and spreading on both the hydrophilic and hydrophobic regions of the material. Fibronectin on its own did not produce an optimal surface for cell spreading. Albumin produced a suitable surface for cell spreading on the hydrophilic part of the surface, but created a highly unsuitable surface on the hydrophobic region of the specimens. Competition between proteins for adsorption to the surface and changes in protein conformation was evident, particularly on the hydrophobic part of the material, and this was shown to influence cell adhesion and spreading.

Adsorption↗

PubMed1995

Quantifying the soft tissue response to implanted materials.

As the diversity of biomaterials increases, new developments are aimed at these materials becoming interactive rather than passive with respect to the environment they are placed in. The need accurately and reproducibly to assess the response of the body to these materials increases. Historically, quantification of tissue responses has taken many forms but with the continuing development of powerful computers, our ability to quantify the tissue response to implanted materials has become a reality. Computer systems can now analyse sections automatically and then go on to sort the huge quantities of data created, into in depth patterns and cross comparisons so that subtle changes in tissue responses can be detected and understood.

Biocompatible Materials↗

PubMed1995

The paediatric oncology community nurse specialist: the influence of employment location and funders on models of practice.

A specialist nursing service has evolved in recent years, to care for children with cancer or leukaemia and their families, and co-ordinate care in the community. These paediatric oncology community nurse specialists (POCNS) are mostly based at regional children's cancer treatment centres, although some are based within paediatric units of district general hospitals. In addition to the National Health Service (NHS), a major source of funding has been provided from a range of charities. This paper examines the impact that the employment location (regional or district) and funding sources have on the process, practice and structure of nursing within the speciality. All 43 POCNSs were interviewed from 28 different hospitals across the United Kingdom and Eire. Thirty-one were based at regional treatment centres, whilst 12 were from district general hospitals. Funding was provided by: the NHS (9); Cancer and Leukaemia in Childhood (CLIC) (10); Cancer Relief Macmillan Fund (5); and other charities (19). Major differences were found according to the location of POCNSs, i.e. the regional model and the district model, and according to funders, i.e. the Macmillan model, the CLIC model and the 'other funders' model. This research suggests that both funding source and location of POCNSs have implications for nursing practice.

Community Health Nursing↗

PubMed1995

Studies of possible mechanisms for the effect of urokinase therapy in small cell carcinoma of the lung.

Urokinase-type plasminogen activator has been administered by other investigators to patients with small cell carcinoma of the lung (SCCL) in an attempt to induce lysis of fibrin that is known to exist in the connective tissue stroma of this tumour type and that may support tumour growth. To study the fate of infused urokinase in this disease, a biopsy of a scalp metastasis was obtained from a patient with SCCL (entered on a phase I clinical trial of urokinase plus combination chemotherapy) immediately following urokinase infusion during the fourth course of therapy a time when this tumour mass had decreased to approximately 25% of its original size. Immunohistochemical procedures revealed abundant stromal fibrin in accord with previous observations from this laboratory. By contrast, urokinase, that is not a feature of small cell tumour cells, was present on the tumour cells in this specimen. Urokinase infusion was associated with a rapid increase in the amount of this enzyme associated with isolated peripheral blood monocytes. These results are consistent with uptake of infused urokinase onto monocytes and possibly tumour cells. It is postulated that substantial tumour fibrinolysis may not accompany such therapy and that urokinase, or its amino terminal fragment that bears the growth factor domain of this molecule, may bind to and alter the growth of the tumour cells.

Aged↗

PubMed1995

Quantitative water mapping of cryosectioned cells by electron energy-loss spectroscopy.

A direct technique based on electron energy-loss spectroscopy (EELS) in the scanning transmission electron microscope (STEM) has been developed to map subcellular distributions of water in frozen-hydrated biological cryosections. Previously, methods for water determination have been indirect in that they have required the cryosections to be dehydrated first. The new approach makes use of spectrum-imaging, where EELS data are collected in parallel at each pixel. Several operations are required to process the spectra including: subtraction of the detector dark current, deconvolution by the detector point-spread function, removal of plural inelastic scattering and correction for the support film. The resulting single scattering distributions are fitted to standard reference spectra at each pixel, and water content can be determined from the fitting coefficients. Although the darkfield or brightfield image from a hydrated cryosection shows minimal structure, the processed EELS image reveals strong contrast due to variations in water content. Reference spectra have been recorded from the major biomolecules (protein, lipid, carbohydrate, nucleic acid) as well as from vitrified water and crystalline ice. It has been found that quantitative results can be obtained for the majority of subcellular compartments by fitting only water and protein reference spectra, and the accuracy of the method for these compartments has been estimated as +/- 3.5%. With the present instrumentation the maximum allowed dose of 2 x 10(3) e/nm2 limits the useful spatial resolution to around 80 nm for +/- 5% precision at a single pixel. By averaging pixel intensities a value of 56.8% with a precision of +/- 2.0% has been determined for the water content of liver mitochondria. The water mapping technique may prove useful for applications to cell physiology and pathophysiology.

Animals↗

PubMed1995

One-year acarbose treatment raises fasting serum acetate in diabetic patients.

alpha-Glucosidase inhibitors such as acarbose improve blood glucose control in diabetes by delaying or reducing carbohydrate absorption. The fermentation of malabsorbed carbohydrate in the colon is associated with the production of gas, leading to flatulence, and short chain fatty acids such as acetate, which may have systemic effects. To see if acarbose raised fasting serum acetate in diabetic patients, we studied 85 subjects selected from the 267 who had completed a 1-year, double-blind, placebo-controlled, parallel design study of the effects of acarbose in the treatment of diabetes. At baseline, there was no significant difference between the 44 subjects subsequently randomized to placebo and the 41 randomized to acarbose, respectively, in fasting serum acetate (80 +/- 5 vs 71 +/- 4 mumoll-1) or glycosylated haemoglobin (HbA1C; 7.2 +/- 0.3 vs 7.4 +/- 0.3%). Compared to placebo, acarbose treatment significantly increased fasting serum acetate by 11 +/- 4 vs 2 +/- 3 mumoll-1 (p < 0.02) and reduced HbA1C by -0.59 +/- 0.16 vs -0.13 +/- 0.20% (p < 0.02). Acarbose treatment had no significant effect on serum cholesterol or non-esterified fatty acids, but was associated with a significant increase in flatulence. There was no relationship between changes in serum acetate and changes in HbA1C, serum cholesterol or symptoms. We conclude, in subjects with diabetes who tolerate therapy for a 1-year period, that acarbose treatment increases serum acetate. The magnitude of change in acetate was unrelated to side-effects or changes in blood glucose control or serum lipids.

Acarbose↗

PubMed1995

Accelerated gastric epithelial proliferation.

Gastric body mucosal proliferation was quantified and localised under conditions of increased gastrin drive using a variety of techniques. Rats were given omeprazole 400 mumol/kg/day by gavage and after 30 days mean serum gastrin rose 11-fold (p < 0.001). Total mucosal polyamines rose 220% from 15.9 to 50.9 nmol/mg protein (p < 0.001). This was associated with a 238% increase in crypt cell production rate from 0.541 to 1.83 crypt cells/h by vincristine metaphase arrest (p < 0.02). Using computer aided counting of proliferating cell nuclear antigen (PCNA) immunostained nuclei to assess epithelial proliferation in hypergastrinaemia rat stomach: mucus neck cell PCNA labelling was increased by 41% (p < 0.001) and gland cell PCNA labelling was increased by 222% (p < 0.001). PCNA/AgNOR (argyrophilic nuclear organiser regions) co-stained sections were used to assess proliferative activity in cycling and non-cycling cell populations. Data from these experiments suggest that, in addition to increasing the number of mucosal cells in cycle, cell life and cell cycle duration may be reduced in hypergastrinaemia.

Animals↗

PubMed1995

A double-blind placebo-controlled trial evaluating the safety and efficacy of acarbose for the treatment of patients with insulin-requiring type II diabetes.

OBJECTIVE: To determine whether a forced titration of acarbose (from 50 to 300 mg three times daily) administered over a 24-week period, in conjunction with diet and insulin therapy, improves glycemic control and reduces daily insulin requirements in insulin-requiring type II diabetes. RESEARCH DESIGN AND METHODS: This multicenter, randomized, double-blind, placebo-controlled trial was 36 weeks in duration. The trial consisted of a 6-week pretreatment period, a 24-week double-blind treatment period, and a 6-week post-treatment follow-up period. The primary efficacy variables were the mean change from baseline in HbA1c levels and the mean percentage change from baseline in total daily insulin dose. RESULTS: Treatment with acarbose was associated with significant reductions in HbA1c levels of 0.40% (P = 0.0001) and in total daily insulin dose of 8.3% (P = 0.0015). There were also significant reductions in all plasma glucose variables measured, including a 0.9 mmol/l reduction in fasting glucose (P = 0.0440), a 2.6 mmol/l reduction in glucose Cmax (P = 0.0001) and a 270 mmol.min-1.l-1 reduction in glucose area under the curve (P = 0.0002). Although acarbose treatment was associated with a greater incidence of adverse events than was placebo treatment, primarily flatulence and diarrhea, these events did not generally prevent patients from completing the study. CONCLUSIONS: The results of this study suggest that acarbose is a safe and effective adjunct to diet and insulin therapy for the management of insulin-requiring type II diabetes.

Acarbose↗

PubMed1995

Clinical experience with acarbose: results of a Canadian multicentre study.

Current therapeutic options for the treatment of non-insulin-dependent diabetes mellitus (NIDDM) focus on regimens that primarily lower fasting blood glucose concentrations. In several short-term studies, the alpha-glucosidase inhibitor, acarbose, has been reported to significantly lower post-prandial plasma glucose levels as well as HbA1c. The primary objective of this present study was to assess the long-term efficacy of adjunctive acarbose therapy to improve metabolic control. Over a 1-y period, acarbose or placebo was administered to 4 groups of patients: those managed by diet only, diet and sulfonylurea, diet and biguanide, and diet and insulin. In all treatment groups, the addition of acarbose resulted in significant reductions in postprandial blood glucose levels. Additionally, HbA1C was significantly lower after 12 months of acarbose therapy, compared with placebo, in all groups except the diet and insulin group. The addition of acarbose consequently expands the armamentarium available to clinicians for the optimization of glycemic control in patients with NIDDM.

Acarbose↗

PubMed1994

The efficacy of acarbose in the treatment of patients with non-insulin-dependent diabetes mellitus. A multicenter controlled clinical trial.

OBJECTIVE: To evaluate the long-term efficacy of acarbose, an alpha-glucosidase inhibitor, in improving glycemic control in patients with non-insulin-dependent diabetes mellitus. DESIGN: A 1-year, multicenter, randomized, double-blind, placebo-controlled study. SETTING: Seven university-affiliated, community-based, tertiary care diabetes clinics. PATIENTS: 354 patients with non-insulin-dependent diabetes mellitus were recruited; 77 were being treated with diet alone, 83 with diet and metformin, 103 with diet and sulfonylurea, and 91 with diet and insulin. Patients in each treatment group were randomly assigned to either acarbose or placebo for 1 year. Eighty-seven percent of patients receiving acarbose and 92% of those receiving placebo were included in the efficacy analysis (n = 316). MEASUREMENTS: At baseline and at 3-month intervals, levels of hemoglobin A1c (HbA1c), fasting and postprandial plasma glucose, fasting and postprandial serum C-peptide, and fasting serum lipids were measured. RESULTS: Compared with placebo, acarbose treatment caused a significant decrease in the mean postprandial plasma glucose peak (90 minutes) in all four groups (19.0 +/- 0.4 mmol/L to 15.5 +/- 0.4 mmol/L; P < 0.001). Analysis of the postprandial plasma glucose incremental area under the curve showed that the change from baseline to the end of the treatment period differed for placebo and acarbose recipients by 4.73 mmol.h/L in the diet alone group (P < 0.001), 2.06 mmol.h/L in the metformin group (P = 0.01), 2.65 mmol.h/L in the sulfonylurea group (P < 0.001), and 3.13 mmol.h/L in the insulin group (P = 0.001). Corresponding decreases in HbA1c levels occurred; these were 0.9% in the diet alone group (P = 0.005), 0.8% in the metformin group (P = 0.011), 0.9% in the sulfonylurea group (P = 0.002), and 0.4% in the insulin group (P = 0.077). Acarbose did not significantly affect mean serum C-peptide or mean serum lipid levels. CONCLUSIONS: Acarbose improved long-term glycemic control in patients with non-insulin-dependent diabetes mellitus regardless of concomitant antidiabetic medication.

Acarbose↗

PubMed1994

Hairy cell interactions with extracellular matrix: expression of specific integrin receptors and their role in the cell's response to specific adhesive proteins.

Integrin/extracellular-matrix interactions are central to the migration, localization, and subsequent function of lymphocytes within tissues. In hairy cell leukemia (HCL) the malignant cells display a highly characteristic tissue distribution in which interactions with extracellular matrix (ECM) are often prominent. Therefore, we used HCL as a model in which to investigate the poorly understood integrin/ECM interactions that underlie the migratory behavior of malignant B lymphocytes. Using a combined approach involving immunocytochemistry, flow cytometry, and immunoprecipitation analysis, hairy cells (HCs) were shown to have a consistent and distinctive phenotype (mainly alpha 4 beta 1, alpha 5 beta 1, alpha v beta 1, and alpha v beta 3). Furthermore, functional studies utilising adhesion assays, time-lapse video-microscopy and image analysis showed that the HCs displayed very specific adhesive behaviour in response to relevant adhesive protein ligands. HCs were able to adhere to different extents on all the adhesive proteins examined, but, on laminin and collagen, binding was weak with little cytoplasmic spreading. In contrast, the cells showed strong adhesion both to fibronectin (FN) and to vitronectin (VN). On FN, the cells spread extensively with nonpolarized cytoplasmic projections, whereas on VN cytoplasmic projections were markedly polarized. This polarized morphology was shown to reflect cell motility. Investigation of the role of individual integrin receptors in the cell movement response suggested that alpha v beta 3 is the major integrin responsible for this motile behavior. These results are discussed in relation to the limited previous data on leukemic and activated B-cell integrins, and we suggest that the HC integrins play a significant role in the characteristic behavior of HCs within tissues.

Actin Cytoskeleton↗

PubMed1994

The function of c-fms in hairy-cell leukemia: macrophage colony-stimulating factor stimulates hairy-cell movement.

Hairy cells (HCs) and some activated B cells express high levels of macrophage colony-stimulating factor (M-CSF) (CSF-1) receptor, but the functional effects of the cytokine on B cells have not been previously identified. Using video microscopy, image analysis, and migration assays, M-CSF was shown to induce chemokinetic and chemotactic movement of HCs. This movement response involved transition to a highly mobile, rounded cell form and was accompanied by distinctive changes in F-actin polymerization and distribution. Furthermore, the M-CSF-induced motility was substantially modified by the adhesive protein used as a substratum and involved qualitative changes in the function of the alpha v beta 3 integrin of HCs. It is suggested that the findings are relevant to the pathophysiology of hairy-cell leukemia (HCL) in particular, and to the biology of B-cell migration in general.

Actins↗

PubMed1994

Filipino beta-thalassemia due to a large deletion: identification of the deletion endpoints and polymerase chain reaction (PCR)-based diagnosis.

The gene frequency of beta-thalassemia among Filipinos is estimated to be 0.02, although little is known about the mutations involved. Recently, an extensive beta-thalassemia deletion was reported in several unrelated individuals of Filipino descent. The deletion begins approximately 4 kb upstream of the beta-globin gene, and extends 3' beyond the beta-globin gene. In this report, we identify the 5' and 3' deletion endpoints and present a polymerase chain reaction (PCR) strategy for rapid DNA diagnosis of the Filipino beta-thalassemia deletion.

Base Sequence↗

PubMed1994

Determinants of diet glycemic index calculated retrospectively from diet records of 342 individuals with non-insulin-dependent diabetes mellitus.

Controlled trials have shown that a diet with a low glycemic index improves blood glucose and lipid control in patients with diabetes. To study the distribution and determinants of diet glycemic index, we obtained two 3-d diet records from 342 free-living subjects with non-insulin-dependent diabetes. Mean +/- SD 24-h intakes were as follows: energy, 7170 +/- 1890 kJ; fat, 33.6 +/- 6.5% of energy; protein, 20.1 +/- 3.2% of energy; available carbohydrate, 45.3 +/- 7.2% of energy; and dietary fiber, 17.2 +/- 6.4 g. Diet glycemic index values (85.4 +/- 4.55, range, 70-97.8) were normally distributed. Diet glycemic index was inversely associated with intake of simple sugars, whether expressed in grams (r = -0.426), percent of energy (r = -0.446), or percent of carbohydrate (r = -0.453, P < 0.001). By step-wise-multiple-linear regression, grams carbohydrate and percent protein were also independently related to diet glycemic index. Differences in diet glycemic index between men and women, and between subjects on different types of diabetes therapy were explained by differences in intake of simple sugars.

Blood Glucose↗

PubMed1994

Biological electron energy loss spectroscopy in the field-emission scanning transmission electron microscope.

The dedicated scanning transmission electron microscope (STEM) combined with parallel electron energy loss spectroscopy (EELS) provides a very sensitive means of detecting specific elements in small structures. EELS is more sensitive than optimized energy-dispersive X-ray spectroscopy by a factor of about three for calcium. Measurement of such low concentrations requires special processing methods such as difference-acquisition techniques and multiple least squares procedures for fitting reference spectra. By analyzing data recorded at each pixel in a spectrum-image it is possible to map quantitatively the elemental distributions in a specimen. It is possible to prepare cryosections that are sufficiently thin to avoid excessive plural inelastic scattering so analysis can be performed at 100 keV beam energy. Under optimal conditions, a resolution of 10 nm and detection limits of a few atoms are achievable for elements such as calcium, phosphorus and iron. In the field emission STEM certain types of chemical information can be extracted from biological specimens. Valence EELS has been exploited to measure water distributions in frozen hydrated cryosections.

Animals↗

PubMed1994

Urokinase inhibits HL-60 cell proliferation in vitro.

The binding of urokinase-type plasminogen activator (u-PA) to its receptor (u-PA-R) is required for morphological and functional maturation during monocyte differentiation of the promyelocytic leukaemia line HL-60. This paper reports that monocyte differentiation of HL-60 cells induced by 1,25 dihydroxyvitamin D2 (vitamin D2) results in a marked increase in expression of u-PA and u-PA-R. This increase in u-PA expression is of greater magnitude than is observed after culture with interferon-gamma (IFN gamma), another potent inducer of monocytic differentiation. Dimethyl sulphoxide (DMSO), an agent that induces granulocytic differentiation, also increased expression of u-PA. However, culture with the granulocyte-inducing all-trans retinoic acid (RA) did not induce an increase in surface expression of u-PA or u-PA-R. The vitamin D2-induced increase in cell-surface u-PA was not coincident with an increase in steady-state levels of u-PA mRNA, suggesting that intracellular stores of this protein, translational or post-translational mechanisms of regulation, or some other regulatory mechanism may be responsible for the increase in u-PA during differentiation. To ascertain an association between the increased expression of cell-surface u-PA and reduced proliferation that accompanies differentiation, the effect of u-PA on cellular proliferation of HL-60 cells was measured. Both pro-u-PA (whole molecule) and fragments of u-PA that retained receptor-binding capability caused a marked inhibition of HL-60 proliferation in the absence of vitamin D2.(ABSTRACT TRUNCATED AT 250 WORDS)

Autoreceptors↗

PubMed1994

Modelling the pattern of cell distribution around implanted materials.

The analysis of the cellular soft tissue response has traditionally focused on using highly skilled human assessment to determine the severity or presence of a particular type of response. This has taken the form of many different assessment criteria, some even attempting some form of 'quantitative' grading index. With the complexity of this response and the availability of high performance computer systems it is not sufficient and no longer necessary to describe a tissue response subjectively. The soft tissue response to a number of implanted materials has been analysed using a combination of immunohistochemistry and image analysis to reproducibly stain and count the cells involved in a soft tissue response to implanted materials, as well as measure their position relative to the implanted material. The combination of cell count and pattern of cell distribution revealed that although the magnitude of the cellular responses changes with respect to time the position of cells with respect to an implanted material does not change significantly over time. The position of cells is controlled more by the type of implant material and the change in subject the material is implanted in.

Animals↗