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Biomedical subjects

G Frost

Publications and source records attributed to G Frost.

At least 55 records · Page 3Linked to original sources

Development of an enzyme-linked immunosorbent assay for isoproturon in water.

A competitive enzyme-linked immunosorbent assay (ELISA) suitable for the determination of the urea herbicide isoproturon [3-(4-isopropylphenyl)-1,1-dimethyl urea] in water has been developed. A derivative of isoproturon [3-(4-isopropylphenyl)-1-carboxypropyl-1-methyl urea] has been synthesized and linked to thyroglobulin using the N-hydrosuccinimide reaction. The immunogen was used to immunize two sheep, which both responded by producing specific antibodies to isoproturon with little cross-reactivity to various structurally related and unrelated pesticides. The enzyme label was prepared by coupling the hapten to horseradish peroxidase using the above reaction. The coated-antibody competitive ELISA, which has a sensitivity of 0.03 microgram l-1, permits the direct determination of isoproturon in various water matrices and can facilitate the monitoring of water quality in drinking-water supplies.

Animals↗

Dietary advice based on the glycaemic index improves dietary profile and metabolic control in type 2 diabetic patients.

The effect of dietary education incorporating information about the glycaemic index of carbohydrate was tested against standard dietary advice in a randomized controlled study in 51 newly diagnosed patients with Type 2 diabetes treated as out-patients with diet only over a 12-week study period. Outcome was assessed by dietary analysis of 3-day diet diaries, fasting blood glucose, fructosamine, total cholesterol, LDL-cholesterol, HDL-cholesterol, and triglycerides. Dietary analysis indicated that the group who received low glycaemic advice not only had a significantly lower calculated mean diet glycaemic index intake (77 +/- 1.1 (SEM) vs 82 +/- 1%, p < 0.01) but also had a lower fat intake (25 +/- 1 vs 32 +/- 2% of total energy day-1, p < 0.001), a higher carbohydrate intake (49 +/- 2% vs 44 +/- 1% of total energy day-1, p < 0.05) and non-starch polysaccharide intake (21 +/- 1.5 vs 14 +/- 1 g, p < 0.01). There was a significantly greater within-group fall in fructosamine (3.8 +/- 0.2 to 3.2 +/- 0.2 mmol-1 vs 3.6 +/- 0.2 to 3.6 +/- 0.3 mmol-1, p < 0.05) and cholesterol (6.1 +/- 0.3 to 5.4 +/- 0.3 mmol-1 vs. 5.6 +/- 0.2 to 5.3 +/- 0.1 mmol-1, p < 0.05) in the low glycaemic index group.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Glucose↗

Response to rest and exercise in the cold: effects of age and aerobic fitness.

The aim of this study was to determine whether age-related differences in the response to cold exposure are due to aging per se or are caused by a reduced maximal oxygen uptake (VO2max) often observed with aging. Three groups of men, 8 young adults (YA), 8 well-trained seniors (TS), and 11 untrained seniors (US), were tested on a cycle ergometer in thermoneutral (22 degrees C) and cold (5 degrees C) conditions during rest and then during exercise (approximately 50 W). In the thermoneutral conditions, 10 min of rest were followed by 10 min of exercise. After 60 min of rest, subjects entered the cold where 30 min of rest were followed by 30 min exercise. The subjects of the three groups had similar body surface area and subcutaneous fat thickness. It was found that rectal temperature (Tre) decreased during rest in the cold and continued to decrease at a higher rate during exercise in TS and US but not in YA. The mean skin temperature was similar in all the groups, except for the thigh temperature, which was lower in YA than in TS and US. Oxygen uptake (VO2) increased during cold, significantly more so at rest than during exercise. YA displayed the highest VO2 during the first 10 min of rest in the cold, whereas TS displayed the highest VO2 during exercise in the cold. Neither aging nor VO2max appeared to affect thermal comfort or cold sensation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Effects of lisinopril on cardiorespiratory, neuroendocrine, and renal function in patients with asymptomatic left ventricular dysfunction.

OBJECTIVE: To determine the cardiac, renal, and neuroendocrine effects of lisinopril in men with untreated, symptom free left ventricular systolic dysfunction. DESIGN: A randomised, double blind cross over trial with six week treatment periods to compare lisinopril (10 mg/day) and matching placebo. SETTING: Hospital outpatient department. PATIENTS: Patients with pronounced systolic dysfunction on cross sectional echocardiography due to myocardial infarction at least six months previously, without angina and with no or minimal breathlessness. Eighteen men were identified of whom 15 completed the study. INTERVENTIONS: Lisinopril (10 mg) or placebo given once daily by mouth. MAIN OUTCOME MEASURES: Primary: oxygen consumption at peak exercise. Secondary: resting cardiac function as measured by radionuclide ventriculography and echocardiography, renal function estimated radioisotopically, and plasma indices of neuroendocrine activity. RESULTS: Compared with placebo, lisinopril increased (mean (SD)) peak oxygen consumption during exercise (19.8(3.1) ml/kg/min v 21.4(3.2) ml/kg/min; p < 0.003). Lisinopril did not improve indices of cardiac function at rest. It reduced plasma concentrations of angiotensin II (median values 7 pg/ml to 5 pg/ml; p < 0.02), aldosterone (median values 113 pg/ml to 66 pg/ml; p < 0.05) and atrial natriuretic peptide (median values 69 pg/ml to 40 pg/ml; p < 0.04), but noradrenaline and antidiuretic hormone concentrations did not change. Renal blood flow increased and glomerular filtration rate declined. CONCLUSIONS: Even before the onset of heart failure lisinopril improves the cardiopulmonary response to exercise in patients with systolic ventricular dysfunction.

Angiotensin-Converting Enzyme Inhibitors↗

Angiotensin-converting enzyme inhibitors, left ventricular dysfunction, and early heart failure.

A study was undertaken to examine the effects of the angiotensin-converting enzyme inhibitor lisinopril on exercise performance in 18 patients with major impairment of left ventricular systolic function. The study was a randomized, double-blind, crossover design, and patients received treatment with either once-daily lisinopril (2.5-10 mg) or placebo for a period of 6 weeks. A total of 15 patients completed the study. Compared with placebo, lisinopril had no significant effect on supine or standing blood pressure or heart rate. Although lisinopril had no effect on exercise duration during a low-intensity exercise protocol, in patients undergoing a high-intensity exercise protocol, there was a trend toward improved exercise time and peak oxygen consumption improved significantly. In addition, treatment with lisinopril resulted in an increase in renal blood flow and a reduction in glomerular filtration rate. Moreover, administration of once-daily lisinopril 10 mg resulted in a decrease in plasma concentrations of angiotensin II, aldosterone, and atrial natriuretic peptide, and an increase in plasma concentrations of active renin.

Aldosterone↗

Expression of the neural cell adhesion molecule (NCAM) on the haemopoietic cell line Nalm-16.

The Nalm-16 cell line was originally described as being of the null acute lymphoblastic leukaemia (ALL) phenotype. Using phenotypic and genotypic markers, we have demonstrated the line carries markers associated with cells of the B lineage. In addition, Nalm-16 binds a series of monoclonal antibodies characterized as predominantly recognising neuroectodermal tissues. Amongst these antibodies, UJ13A, 5.1.H11 and ERIC-1 have been shown to recognise the neural cell adhesion molecule (NCAM). Expression of the NCAM molecule is highly complex, with several isoforms of the protein resulting from the differential splicing of the NCAM mRNA transcript. Western-blot analysis of Nalm-16 cell extracts indicates that cells express the heavily polysialylated form of the molecule found on many embryonic tumours. Neuraminidase digestion indicates that the 140 kD isoform is predominantly expressed on Nalm-16, although the 120 kD isoform is present to a lesser degree. These findings have been confirmed using Northern-blot analysis.

Antibodies, Monoclonal↗

Hirschsprung disease in infants and children.

Hirschsprung disease (HD) is a disorder of motility in the bowel caused by the absence of parasympathetic ganglion cells. This article will discuss the symptoms, diagnostic tests, methods of surgical management and complications of HD with an emphasis on enterocolitis. HD is a treatable condition and with proper management, the child can return to a normal life.

Child↗

The renal effects of dopamine and dobutamine in stable chronic heart failure.

Although an extensive literature exists on factors controlling sodium excretion in animal experimental models of heart failure, the relevance of these to the human condition remains largely unexplored. Increased renal sympathetic stimulation is considered responsible for heightened urinary sodium retention. Stimulation of dopamine receptors is believed to cause a diuresis. Accordingly, we sought to explore the influence of dobutamine (a beta-1 receptor agonist) and dopamine in high and low doses on a frusemide-induced diuresis in patients with chronic stable heart failure. Preliminary results indicate that low doses of dobutamine and dopamine do not increase a moderate, frusemide-induced diuresis. With higher doses dobutamine, but not dopamine, increased urine volume and sodium excretion. These results suggest that direct stimulation of beta-1 receptors increases urinary sodium excretion, either by a direct effect on the kidney or by altering systemic and renal haemodynamics.

Aged↗

Expression of alternative isoforms of the neural cell adhesion molecule (NCAM) on normal brain and a variety of brain tumours.

A panel of monoclonal antibodies, including a reagent designated ERIC-1, have been characterized as binding to the human neural cell adhesion molecule (NCAM). These monoclonal antibodies bind in a relatively uniform manner to a variety of normal and neoplastic tissues arising from the neuroectoderm. However, multiple forms of the protein are known to arise from the differential splicing of exons within the NCAM gene located on chromosome 11 at q23. On human adult brain, four isoforms of 180, 170, 145 and 120 kDa have been identified. Here, we report the identification of another NCAM isoform of 95 kDa that is apparent on tissues following either N-glycanase or neuraminidase treatment to remove carbohydrate and sialic acid residues from the molecule respectively. NCAM expression is further complicated by differential post-translational modification of the molecule which is developmentally regulated. In general, fetal NCAM is more heavily polysialylated than the adult forms of the molecule. Human fetal brain has been shown to express the heavily sialylated embryonic form of NCAM, but following neuraminidase digestion, a similar pattern of NCAM expression is seen to that in adult brain. A variety of human brain tumours examined also show different patterns of NCAM expression, despite their uniform staining with monoclonal antibodies. The significance of these observations for designing new molecular and immunological approaches to the diagnosis of a variety of primary tumours is reviewed.

Adult↗

Expression of the cluster 1 antigen (neural cell adhesion molecule) in neuroectodermal tumours.

In this study, we have investigated the expression of the neural cell adhesion molecule (NCAM) in the human brain, primary brain tumours and neuroblastoma. Adult brain was found to express discrete isoforms of 180, 170, 140 and 120 kDa, which on neuraminidase treatment resolved into bands of 180, 170, 140, 120 and 95 kDa. Primary brain tumours such as Schwannoma and medulloblastoma expressed embryonic NCAM characterised by a high level of glycosylation, whereas other tumours, e.g. astrocytoma, meningioma, glioma and oligodendroglioma expressed adult NCAM. Post-neuraminidase treatment, differential expression of the 180, 170, 140, 120 and 95 kDa isoforms were noted in these various tumour types. On the other hand, neuroblastoma cell lines were found to express only embryonic NCAM, which after neuraminidase treatment resulted in differential presence of only 180, 140 and 120 kDa proteins.

Astrocytoma↗

Saturation of fat and cholecystokinin release: implications for pancreatic carcinogenesis.

In a study to determine the effect of saturation of fats on their ability to stimulate cholecystokinin (CCK) release six normal volunteers ate five test meals containing different fats with intervals of 1 week. Plasma CCK levels were measured by a specific radioimmunoassay and the gallbladder volume was calculated from ultrasound measurements. The sodium salt of the monounsaturated fatty acid oleic acid (3.5 g) produced a significantly greater integrated CCK response than that of the saturated fatty acid stearic acid (mean [SEM] 103 [41] vs 8[41] pmol.l-1.min). The gallbladder contracted to 42 (3)% of its initial volume after oleate but remained at 89 (8)% of its initial volume after stearate. Integrated CCK responses to dietary triglycerides (30 g) also differed significantly according to the degree of saturation--277 (58) pmol.l-1.min after corn oil (predominantly diunsaturated), 143 (14) pmol.l-1.min after olive oil (predominantly monounsaturated), and 44 (12) pmol.l-1.min after suet (predominantly saturated). The finding that unsaturated fats are stronger stimulants of CCK release than saturated fats may explain the promotion of pancreatic carcinogenesis in rats by unsaturated but not saturated fats and may support the role of CCK in this effect.

Adult↗

Meal frequency and nutritional intake during Ramadan: a pilot study.

A study was carried out to compare the nutritional intake and meal pattern during and after Ramadan. It was found that in a sample group of 15 young Saudis there was a significant increase in caloric, fat, carbohydrate and protein intake. Although there was a significant reduction in meal frequency and the number of meals taken outside the family, a significant increase in body weight was noted during Ramadan.

Adolescent↗

Congenital hypothyroidism and HLA.

HLA-A, B and C antigens tested in 97 patients treated for congenital hypothyroidism, and in members of their families, are compared with normal frequencies from 635 controls. After adjustment for the number of tests, there remains in the patients only a negative association with A11, with a relative risk of .190, and no significant association in the relatives. Patients show no excess homozygosity and no deviations in haplotype frequency. Congenital hypothyroidism thus appears to show a different relationship with HLA from other thyroid disorders.

Adolescent↗

Management of hypertension newly detected by health screening.

An attempt was made, through a hospital-based health screening service, to ensure proper longterm care of clients with hypertension and other cardiovascular risk factors. Of 8755 subjects screened on one occasion, 1274 (14.6%) had a blood pressure reading above defined limits; of these, 1058 were not receiving antihypertensive drugs. Apparently hypertensive subjects were rescreened within one week or were referred to their local doctors. At their second visits, over half of the 716 rescreened subjects had reading consistently below the defined limits. Those with intermittent blood pressure elevation (89 patients) were designated as having labile hypertension, and were reviewed regularly. The remainder, with persisting hypertension, were sent to their local doctors or to the hospital's hypertension clinic. After six months, the group ith labile hypertension showed no change in mean left cardiac ventricular voltage, and more than 50% the group had normal blood pressure; 14 patients were receiving antihypertensive drugs. Subjects referred to the hypertension clinic had a high prevalence of cardiovascular risk factors and a low prevalence of clinically evident organ damage. Only half of this group were deemed to require drug therapy. In a postal survey of clients referred to private doctors, 35% of respondents reported that they had started taking anti-hypertensive drugs. Thorough rescreening of blood pressure is essential in preventing the unnecessary use of antihypertensive drugs, and this can be facilitated by providing management streams appropriate to the needs of the individual subject.

Adolescent↗