Search PubMed⌕ Search

Biomedical subjects

P Milner

Publications and source records attributed to P Milner.

At least 37 records · Page 2Linked to original sources
PubMed1997

A cost effective, community based heart health promotion project in England: prospective comparative study.

OBJECTIVE: To determine whether a community based coronary heart disease health promotion project, undertaken over four years, was associated with changes in the prevalence in adults of lifestyle risk factors known to affect the development of coronary heart disease, and to estimate whether such an approach was cost effective. DESIGN: Prospective, comparative study of the effects of a health promotion intervention on coronary heart disease lifestyle risk factors, assessed by postal questionnaire sent to a randomly chosen sample, both at baseline and after four years. SUBJECTS: Intervention and control populations of adults aged 18-64 in Rotherham, both from areas with a high incidence of coronary heart disease and similar socioeconomic composition. MAIN OUTCOME MEASURES: Changes in prevalence of lifestyle risk factors between the control and intervention communities from 1991 to 1995. The effect of the intervention on certain lifestyle behaviours was evaluated using multiple logistic regression to model the proportion with a particular behaviour in the study communities as a function of age (18-40 or 41-64 years), sex, the year of observation (1991 or 1995), and area (intervention of control). RESULTS: 6.9% fewer people smoked and 8.7% more drank low fat milk in the intervention area, but no other statistically significant changes between the areas were detected. The estimated cost per life year gained was pounds 31. CONCLUSIONS: It is possible to have a cost effective impact on coronary heart disease lifestyle risk factors in a population of adults over four years using only modest resources.

Adolescent↗
PubMed1997

Synthesis and biological evaluation of the enantiomers of the potent and selective A1-adenosine antagonist 1,3-dipropyl-8-[2-(5,6-epoxynorbonyl)]-xanthine.

The individual enantiomers 8 and 12 of the potent and highly selective racemic A1-adenosine antagonist 1,3-dipropyl-8-[2-(5,6-epoxynorbornyl)]xanthine (ENX, 4) were synthesized utilizing asymmetric Diels-Alder cycloadditions for the construction of the norbornane moieties. The absolute configuration of 12 was determined by X-ray crystallography of the 4-bromobenzoate 14, which was derived from the bridged secondary alcohol 13. The latter was obtained from 12 by an acid-catalyzed intramolecular rearrangement. The binding affinities of the enantiomers 8 and 12 and the racemate 4 at guinea pig, rat, and cloned human A1- and A2a-adenosine receptor subtypes were determined. The S-enantiomer 12 (CVT-124) appears to be one of the more potent and clearly the most A1-selective antagonist reported to date, with K1 values of 0.67 and 0.45 nM, respectively, at the rat and cloned human A1-receptors and with 1800-fold (rat) and 2400-fold (human) subtype selectivity. Both enantiomers, administered intravenously to saline-loaded rats, induced diuresis via antagonism of renal A1-adenosine receptors.

Animals↗
PubMed1997

Ultrastructural localisation of nitric oxide synthase, endothelin and binding sites of lectin (from Bandeirea simplicifolia) in the rat carotid artery after balloon catheter injury.

An immunocytochemical and cytochemical study has been made on the ultrastructural localisation of type III (endothelial) nitric oxide synthase, endothelin-1 and the binding sites of lectin from Bandeirea simplicifolia to the endothelium surface-associated glycoproteins in the rat left common carotid artery at 1 and 28 d after Fogarty embolectomy balloon catheter-induced injury. Controls were carotid arteries from sham operated rats. In the controls, the immunoreactivity to nitric oxide synthase-III and endothelin-1 was localised in different proportions in vascular endothelial cells (36.9% +/- 4.3 and 7.6% +/- 2.7, respectively); immunoreactivity was confined to the cytoplasm and the membranes of intracellular organelles and structures. In contrast, staining with lectin was localised on the luminal surface of all endothelial cells. 1 d after injury, platelets were adherent to the endothelium-denuded intima. Some of the platelets displayed, immunoreactivity to nitric oxide synthase-III and endothelin-1 and were stained with lectin. 28 d after injury, a neointimal thickening of substantial size was present. Subpopulations of the regrown endothelial cells covering the luminal surface of the neointima showed positive immunoreactivity to nitric oxide synthase-III and endothelin-1 but there was a significant decrease in the proportion of nitric oxide synthase-III-containing endothelial cells (17.2% +/- 1.9; P < 0.001) and a significant increase in the proportion of endothelin-1-containing endothelial cells (36.9% +/- 4.7; P < 0.001) compared with the controls. Staining with lectin was associated with the cell membrane of all endothelial cells and in addition with cells located 'deeper' in the neointima which showed lectin-positive plasmalemma, Golgi complex and multivesicular bodies/lysosomes. In conclusion, regenerated endothelial cells of the neointima showed reduced population (2-fold) of nitric oxide synthase-III-and increased population (5-fold) endothelin-1-positive cells. The subendothelial location of some lectin-stained cells after balloon catheter injury indicates the heterogeneity of the neointima and suggests that some of these cells are involved in early angiogenesis. 24 h and 28 d after injury some platelets showed positive immunoreactivity for nitric oxide synthase-III and endothelin-1.

Animals↗
PubMed1997

The effects of early antibiotic treatment following diagnosis of mastitis detected by a change in the electrical conductivity of milk.

Mastitis was induced experimentally by infusion of Streptococcus uberis or Staphylococcus aureus into the mammary glands of lactating dairy cows. Clinical mastitis was identified when clots appeared in foremilk (conventional diagnosis) or was predicted by changes in the electrical conductivity of foremilk (early diagnosis). The responses to intramammary antibiotic treatment that was initiated after early diagnosis of mastitis and after conventional diagnosis were compared. Early treatment significantly limited the severity of the disease and, in many cases, prevented the appearance of any visible signs of infection. Milk yield was less depressed, and the somatic cell count (SCC) was lower, when treatment was initiated earlier. The SCC of the quarter at the time mastitis was predicted was approximately 2 x 10(6) cells/ml for both pathogens, which was significantly less than when clots appeared at conventional diagnosis, approximately 4 x 10(6) and 12 x 10(6) cells/ml for Staph. aureus and Strep. uberis, respectively. The time required for SCC to recover to < 4 x 10(5) cells/ml was significantly less, approximately half, for both pathogens following early detection and early initiation of treatment. When treatment was administered in response to early detection, the bacteriological and clinical cure was almost complete, and the amount of antibiotic used was < or = 50% less. Obvious benefits for milk yield and quality and the health of the cow would result when changes in the electrical conductivity of milk are used to predict clinical mastitis and when treatment is initiated early.

Animals↗
PubMed1997

An evaluation of a nurse-led ear care service in primary care: benefits and costs.

BACKGROUND: Nurses trained in ear care provide a new model for the provision of services in general practice, with the aim of cost-effective treatment of minor ear and hearing problems that affect well-being and quality of life. AIM: To compare a prospective observational cohort study measuring health outcomes and resource use for patients with ear or hearing problems treated by nurses trained in ear care with similar patients treated by standard practice. METHOD: A total of 438 Rotherham and 196 Barnsley patients aged 16 years or over received two self-completion questionnaires: questionnaire 1 (Q1) on the day of consultation and questionnaire 2 (Q2) after three weeks. Primary measured outcomes were changes in discomfort and pain; secondary outcomes included the effect on normal life, health status, patient satisfaction, and resources used. RESULTS: After adjusting for differences at Q1, by Q2 there was no statistical evidence of a difference in discomfort and pain reduction, or differential change in health status between areas. Satisfaction with treatment was significantly higher (P = 0.0001) in Rotherham (91%) than in Barnsley (82%). Average total general practitioner (GP) consultations were lower in Rotherham at 0.4 per patient with an average cost of 6.28 Pounds compared with Barnsley at 1.4 per patient and an average cost of 22.53 Pounds (P = 0.04). Barnsley GPs prescribed more drugs per case (6% of total costs compared with 1.5%) and used more systemic antibiotics (P = 0.001). CONCLUSIONS: Nurses trained in ear care reduce costs, GP workload, and the use of systemic antibiotics, while increasing patient satisfaction with care. With understanding and support from GPs, such nurses are an example of how expanded nursing roles bring benefits to general practice. Nurses trained in ear care reduce treatment costs, reduce the use of antibiotics, educate patients in ear care, increase patient satisfaction, and raise ear awareness.

Adult↗
PubMed1996

Development of a simple chemically defined medium for Porphyromonas gingivalis: requirement for alpha-ketoglutarate.

The aim of this study was the development of a simple, defined medium for the growth of laboratory and clinical isolates of Porphyromonas gingivalis. A medium was designed in which the carbon and nitrogen requirements were provided by a single protein source--bovine serum albumin. High cell yields were achieved in this medium but growth was accompanied by a heavy blackening of the cells due to the deposition of metal sulfide(s), most probably iron(II) sulfide, at the cell surface. Good growth in the absence of blackening was achieved when the iron salt in the medium was substituted with alpha-ketoglutarate. The resultant alpha-ketoglutarate/BSA medium was able to support the growth of all laboratory and clinical P. gingivalis strains examined and should prove useful in the investigation of the physiology and nutritional regulation of virulence of this organism.

Animals↗
PubMed1996

Chronic sensory denervation reduces thrombin-stimulated endothelin release from aortic endothelial cells.

The long-term (trophic) influence of perivascular nerves on the endothelium was investigated by measuring changes in thrombin-stimulated release of the potent vasoconstrictor, endothelin, after selective chronic denervation. Rat pups were treated with either guanethidine or capsaicin to destroy sympathetic or sensory nerves, respectively. The abdominal aortas from the rats at three months of age (5 pooled per experiment) were incubated with 4U thrombin/ml in medium for 24 h at 37 degrees C, and the amount of endothelin released from the preparation determined by immunoassay. After neonatal sensory denervation there was a significant reduction in the thrombin-stimulated release of endothelin compared to the controls (0.012 +/ -0.012 (4) compared to 0.063 +/- 0.012 (6), pmol/cm2/24 h, p < 0.02). There was no change in endothelin release after sympathetic denervation. In summary, sensory nerves play a trophic role in the expression of endothelin in endothelial cells of the intima.

Animals↗
PubMed1996

Enteric innervation in idiopathic megarectum and megacolon.

We have studied the resection specimens from 5 patients with idiopathic megarectum and megacolon and 10 control subjects with non-obstructing colonic cancer. Histological staining with haematoxylin and eosin, and immunocytochemical staining for protein gene product 9.5 (PGP9.5), S100 protein, vasoactive intestinal polypeptide (VIP) and calcitonin gene-related peptide (CGRP), and histochemical localization of NADPH diaphorase was performed. The amount of VIP and CGRP present in samples was measured using an enzyme-linked immunosorbent assay. Patients with idiopathic megarectum and megacolon showed hypertrophy of the muscularis mucosae and muscularis externa. The architecture of the innervation as assessed by immunoreactivity for PGP9.5 and S100 protein appeared normal. There was a decrease in the density of innervation of the longitudinal muscle in rectal tissue from patients with idiopathic megarectum, with fewer VIP- and NADPH-diaphorase-containing nerves. In the muscularis mucosae and lamina propria of the rectal samples of patients with idiopathic megarectum, VIP immunoreactivity was higher and more NADPH-diaphorase-containing nerves were seen. CGRP-immunoreactive nerve fibres were only seen in the myenteric plexus. No CGRP-immunoreactive cell bodies were seen. In summary, there is an increase in VIP and nitric oxide containing fibres in the muscularis mucosae and lamina propria and a decrease in the longitudinal muscle in rectal tissue of patients with idiopathic megarectum. Both are NANC (nonadrenergic noncholinergic) inhibitory transmitters in the gut and the possible relationship of the changes in their density with gut function is discussed.

Adolescent↗
PubMed1996

Release of vasoactive agents from the isolated perfused human ovary.

OBJECTIVE: To investigate local vascular control in the isolated perfused premenopausal human ovary by measuring flow-induced release of vasoactive substances. DESIGN: Release of adenosine 5' triphosphate (ATP), substance P (SP), endothelin (ET), and vasopressin (AVP) from the ovarian vascular endothelium was estimated in perfusate under basal conditions and during two periods of increased flow. MAIN OUTCOME MEASURES: Vascular resistance; ATP, SP, ET and AVP release. RESULTS: The mean ratio (pressure/flow during increased flow):(pressure/flow at basal flow) was 1.27 +/- 0.04 for the first, and 1.15 +/- 0.05 for the second period of increased flow (n = 10), indicating significant vasoconstriction (P < 0.01 and 0.05, respectively), present to a greater extent during the first period of increased flow compared to the second (P < 0.05). ATP release was seen in response to increased flow (n = 8, P < 0.05). From 12 ovarian bed preparations, five released ET and SP and three of these released AVP. Four of the five perfused ovaries that released peptides contained either a developing follicle or a corpus luteum while all those that showed no peptide release were inactive. CONCLUSIONS: ATP release may play a role in the local control of the human premenopausal ovarian vasculature independent of ovulatory status. Peptides may also contribute to local vascular control in the ovary and their release from predominantly active ovaries suggests a relationship between ovulation and vascular endothelial function.

Adenosine Triphosphate↗
PubMed1996

Selective damage to sensorimotor perivascular nerves in the mesenteric vessels of diabetic rats.

The perivascular innervation of the superior mesenteric artery and vein was examined using immunohistochemical and immunoassay techniques in rats 8 weeks after induction of diabetes with streptozotocin (STZ). Increased density of innervation and fluorescence intensity was noted for substance P- and calcitonin gene-related peptide-immunoreactive nerves in the diabetic vessels. A slight increase in the density of vasoactive intestinal polypeptide-immunoreactive nerve fibers innervating the mesenteric artery was also noted. However, there was no change in the density of neuropeptide Y- and dopamine beta-hydroxylase-immunoreactive nerve fibers, although the fluorescence intensity of neuropeptide Y-immunoreactive nerve fibers was reduced in diabetic rat vessels. Immunoassays showed that the levels of substance P- and calcitonin gene-related peptide were increased > 10-fold in the diabetic mesenteric vein, while levels of neuropeptide Y and vasoactive intestinal polypeptide were unchanged. In summary, there is a marked increase in nerve fibers containing sensory neuropeptides in mesenteric vessels of STZ-induced diabetic rats, which, in view of the reported impaired sensorimotor function in these vessels, is likely to reflect a neuropathic change.

Animals↗
PubMed1996

Detection of clinical mastitis by changes in electrical conductivity of foremilk before visible changes in milk.

Mastitis was induced by the direct infusion of Staphylococcus aureus or Streptococcus uberis into the mammary gland of lactating cows. Changes in electrical conductivity of foremilk indicated the establishment of bacteria, increased SCC, increased clotting of milk, and, hence, disease, in advance of visible changes in the milk that could be diagnosed by a herdsperson. Clinical mastitis was detectable by changes in electrical conductivity of foremilk, 90% of cases were detectable when clots first appeared in foremilk, and 55% of cases were detectable up to 2 milkings prior to the appearance of clots. All subclinical infections from Staph. aureus were detected, but subclinical infections from Strep. uberis were not detected. The results suggested that clinical mastitis caused by these two major pathogens could be detected earlier by measuring changes in electrical conductivity of milk than by waiting for a herdsperson to detect visible changes in milk. Earlier detection would permit earlier treatment. However, the handheld sensor used in this experiment is impractical for commercial application, and reliable automated sensors and decision-making algorithms are required.

Animals↗
PubMed1995

Cytokines suppress the shear stress-stimulated release of vasoactive peptides from human endothelial cells.

Endothelial cells from human umbilical vein perfused at 0.5 ml/min released vasopressin, endothelin, and substance P. Upon perfusion of the cells at 3.0 ml/min, the release of endothelin and vasopressin was significantly increased whereas the release of substance P was significantly decreased. Endothelial cells precultured for 24 h with interleukin-1 (IL-1) and interferon-gamma (IFN-gamma) released more endothelin and less substance P at low flow and there was no further increase in release at high flow rate. These results suggest that cytokines suppress the normal responses of endothelial cells to increased fluid shear stress.

Cells, Cultured↗