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Biomedical subjects

P Harvey

Publications and source records attributed to P Harvey.

At least 37 records · Page 2Linked to original sources

Preferences for different sources of information about cancer.

A wide range of cancer information resources is available to patients and their relatives, who are increasingly acting as independent learners. In order to examine preferences for different types of information and to establish the appropriateness of providing a Web-based cancer information resource (CancerHelp UK) a questionnaire survey was undertaken. Of 258 questionnaires distributed to patients attending for oncology outpatient or general practice appointments, 205 (80%) were suitable for analysis. 74% (95% confidence interval 68% to 80%) of participants wanted as much information as possible. All participants cited people most frequently as a future source of cancer information. All participants frequently cited television as a source of both general and cancer-specific information. Despite a lack of computer experience patients were significantly more likely than other groups to say that they would like to use the Web-based resource. It is suggested that such resources are likely to be increasingly well used, particularly by cancer patients, given the growth in health information on the Web and developments in delivery of digital information into the home via television.

Adult↗

Oestrogen and vascular disease.

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in postmenopausal women. Epidemiological studies consistently suggest that oestrogen administered to postmenopausal women confers an estimated 30-50% reduction in risk of development and progression of CVD. The long term effect on the cardiovascular system of the addition of a progestogen to the replacement regimen is currently unknown. In addition, it may be argued that it remains to be proven whether the magnitude of the oestrogen-induced cardioprotective effect demonstrated in these observational studies is a real biological phenomenon. No prospective, randomised, controlled studies examining the effect of oestrogen on primary and secondary prevention of CVD have been completed. However, a large number of biologically plausible mechanisms have been identified which provide evidence to support the proposed oestrogen-induced cardioprotection. These include oestrogen mediated favourable changes in metabolic profile, in particular changes in lipid metabolism, insulin resistance and the fibrinolytic system. In addition, recent data have shown that oestrogen may affect vascular structure and function by a variety of mechanisms. It has been shown that oestrogen may induce acute and chronic coronary and cerebral vasodilation through both direct (vascular smooth muscle) and indirect (endothelium dependent) mechanisms. Oestrogen also has recently been shown to have complex anti-atherogenic and antioxidant properties. Much less is known of the vascular effects of progestogens. Progestogens currently in clinical use have androgenic properties and may attenuate the beneficial effects of oestrogen by neutralising or opposing the lipid lowering, vasodilatory and anti-atherogenic actions of oestrogen. Thus further studies are required to elucidate the effects on arterial physiology and CVD outcome of the oestrogens and progestogens of different types, doses and routes of administration which are collectively referred to as postmenopausal 'hormone replacement therapy'.

Blood Pressure↗

Survival after massive ethylene glycol poisoning: role of an ethanol enriched, bicarbonate-based dialysate.

A 38-year old man presented with drowsiness 14 hours after ingesting about 1200 mls (40 ounces) of antifreeze in a suicide attempt. He was successfully treated with an ethanol enriched, bicarbonate based-dialysate. With a concomitant peripheral intravenous infusion of ethanol, this enrichment of the dialysate helped maintain the intradialytic ethanol concentration between 97-135 mg/dl over an 8 hour dialysis session. The patient developed acute tubular necrosis and required further dialysis. He made a complete recovery after three weeks and was discharged with a serum creatinine of 1.4 mg/dl.

Adult↗

Ileal-lymphoid-nodular hyperplasia, non-specific colitis, and pervasive developmental disorder in children.

BACKGROUND: We investigated a consecutive series of children with chronic enterocolitis and regressive developmental disorder. METHODS: 12 children (mean age 6 years [range 3-10], 11 boys) were referred to a paediatric gastroenterology unit with a history of normal development followed by loss of acquired skills, including language, together with diarrhoea and abdominal pain. Children underwent gastroenterological, neurological, and developmental assessment and review of developmental records. Ileocolonoscopy and biopsy sampling, magnetic-resonance imaging (MRI), electroencephalography (EEG), and lumbar puncture were done under sedation. Barium follow-through radiography was done where possible. Biochemical, haematological, and immunological profiles were examined. FINDINGS: Onset of behavioural symptoms was associated, by the parents, with measles, mumps, and rubella vaccination in eight of the 12 children, with measles infection in one child, and otitis media in another. All 12 children had intestinal abnormalities, ranging from lymphoid nodular hyperplasia to aphthoid ulceration. Histology showed patchy chronic inflammation in the colon in 11 children and reactive ileal lymphoid hyperplasia in seven, but no granulomas. Behavioural disorders included autism (nine), disintegrative psychosis (one), and possible postviral or vaccinal encephalitis (two). There were no focal neurological abnormalities and MRI and EEG tests were normal. Abnormal laboratory results were significantly raised urinary methylmalonic acid compared with age-matched controls (p=0.003), low haemoglobin in four children, and a low serum IgA in four children. INTERPRETATION: We identified associated gastrointestinal disease and developmental regression in a group of previously normal children, which was generally associated in time with possible environmental triggers.

Child↗

An intensive weight loss programme in established type 2 diabetes and controls: effects on weight and atherosclerosis risk factors at 1 year.

The efficacy, safety, and effect on cardiovascular risk factors of two intensive weight loss programmes in overweight Type 2 diabetic subjects were studied. The patients were recruited from hospital diabetic clinics and control obese subjects from the community. Obese (BMI >30) patients with Type 2 diabetes mellitus and controls were offered intensive conventional diabetic advice or a very low calorie diet. Weekly 2 h sessions were conducted in two day-room areas of adjacent medical wards of Torbay Hospital. Non-diabetic and diabetic very low calorie diet groups reduced BMI by 6 and 5 kg m(-2), respectively, at 1 year. Waist-hip ratios (-0.06 and -0.05) were also reduced (p = 0.04 and p = 0.01), while HDL/total cholesterol ratios increased (+0.04 and +0.06, p = <0.01). Transient changes in blood pressure and antioxidant vitamin status occurred in the intensive conventional diet group. Fourteen of diabetic very low calorie diet subjects discontinued insulin and oral hypoglycaemic agents for the whole year, and psychological well-being transiently improved. Substantial weight loss and improvement in cardiovascular risk factors could be maintained for 1 year in Type 2 diabetic patients by the use of a very low calorie diet.

Adult↗

Expression of HGF/SF in mesothelioma cell lines and its effects on cell motility, proliferation and morphology.

The expression of hepatocyte growth factor/scatter factor (HGF/SF) was studied in 12 mesothelioma cell lines characterized by either an epithelioid or a fibroblast-like phenotype. Conditioned media from these lines were analysed by bioassay and ELISA, and HGF/SF was detected in three cell lines, all with a fibroblast-like or mixed morphology. None of eight epithelioid cell lines expressed the factor. Thus, for these cell lines, the ability to secrete HGF/SF correlated with the cell phenotype. Following on from these observations, two cell lines, BR and BT, with a fibroblast-like and an epithelioid phenotype, respectively, were further investigated. Both cell lines expressed the Met receptor but only BR secreted HGF/SF. Both cell lines responded to exogenous HGF/SF treatment by a change of morphology but in different ways: BR became more elongated and bipolar, while BT formed more spread-out cell colonies. HGF/SF acted as a paracrine effector on the epithelioid BT cells and stimulated both cell-spreading and proliferation. Interestingly, BT cells spread but did not scatter in response to exogenous HGF/SF. In contrast BR cells showed only some stimulation of cell motility with HGF/SF and no increase in cell proliferation was observed. Because HGF/SF was previously found in the pleural effusion fluids of patients with malignant mesothelioma and in paraffin-embedded tumour tissues, it is concluded that HGF/SF may well stimulate the growth and spread of malignant mesothelioma in vivo by paracrine and/or autocrine mechanisms.

Cell Division↗

Analysis of coccal cell formation by Campylobacter jejuni using continuous culture techniques, and the importance of oxidative stress.

Campylobacter jejuni is an important human gastrointestinal pathogen. In hostile environments it may adapt its physiology to prolong survival, potentially including the adoption of a viable, non-culturable form and a change to coccal cell morphology. By independently controlling the individual parameters of continuous cultures of Camp. jejuni (e.g. pH, nutrient limitation, growth rate, etc.), coccal cell formation was shown to be elicited only be high oxygen tension in conjunction with reduced carbon concentration. Electron microscopy revealed degradative changes in these cells. This occurred as a transient response over 48 h coincident with a large reduction in maximum growth rate and viable count. Kinetic analysis of the biomass reduction of the cultures demonstrated that significant underlying growth was maintained, with the subsequent selection of a more oxygen-resistant population of cells and reversion to spiral morphology. Coccal cells appear to be predominantly a degenerate form of Camp. jejuni resulting from oxidative damage. While some of these coccal cells may recover, the more interesting population of cells is probably that which retains, or regains, spiral morphology during adaptation to oxidative stress.

Campylobacter jejuni↗

Rehabilitation in complex political emergencies: is rebuilding civil society the answer?

The paper examines the challenge of rehabilitation from complex political emergencies (CPEs) and identifies a strategy that is characterized as a civil society rebuilding approach. It focuses on Somalia and a case study of CARE project that aims to build the capacity of local NGOs. The paper argues that civil society in CPEs is simultaneously being undermined and contested by warring parties and emerging after state collapse. The scope of the paper is limited to one case study and that case study examines only a single aspect of civil society: national and international NGOs The paper therefore presents tentative and preliminary results based on limited research. However, in reviewing the literature and presenting a way of approaching the subject, it aims to suggest a starting-point for developing a theoretical framework for such research. The paper finds that international agencies have tended to focus on civil society institutions simply as conduits for aid money and that this has tended to create organisations which lack downward accountability, are dependent on donors and are not addressing the wider roles for civil society envisaged in the approach. Rebuilding civil society does hold out the promise of giving non-military interests a stronger voice and starting a process of changing the aid delivery culture. Achieving these objectives, however, will be a slow and largely indigenous process and there is a need for lowered expectations about what outside assistance can achieve.

Civil Disorders↗

Mivacurium compared with three different doses of suxamethonium for nasotracheal intubation.

Suxamethonium in the doses of 1.0, 0.5 and 0.25 mg/kg was compared with mivacurium 0.15 mg/kg in 80 patients requiring nasotracheal intubation for maxillofacial surgery in a double-blind randomized controlled trial. Anaesthesia was induced with thiopentone 5 mg/kg and alfentanil 15 micrograms/kg. Patients were randomly allocated to one of the four relaxant groups. Anaesthesia was maintained with enflurane in 70% nitrous oxide and 30% oxygen and analgesia provided with intravenous pethidine 0.5 to 1.5 mg/kg and rectal indomethacin 100mg. All patients given mivacurium or suxamethonium 1 mg/kg had acceptable intubating conditions. Significantly fewer patients given suxamethonium 0.5 mg or 0.25 mg/kg had acceptable intubating conditions (90% and 70% respectively) (P = 0.003). Poor intubating conditions requiring additional relaxation were seen in two patients given suxamethonium 0.25 mg/kg and two given 0.5 mg/kg, while no patients given suxamethonium 1.0 mg/kg or mivacurium 0.15 mg/kg required additional relaxation (P = 0.004). Only four patients had postoperative myalgia, all of whom were given suxamethonium 0.5 mg/kg or more but no significant difference between groups could be demonstrated.

Adult↗

Estimation of relative skin sensitizing potency using the local lymph node assay: a comparison of formaldehyde with glutaraldehyde.

BACKGROUND: Chemicals vary considerably in their intrinsic ability to cause allergic contact dermatitis. Presently, there are no experimental methods available for the quantitative assessment of the relative sensitizing potency of chemical allergens. OBJECTIVE: The objective of the investigations described here was to evaluate the use of the local lymph node assay for determining the relative skin sensitizing potential of chemicals. This has been addressed by comparing the sensitizing potency of formaldehyde with glutaraldehyde. METHODS: Dose responses induced by formaldehyde and glutaraldehyde in the local lymph node assay, using either acetone or dimethylformamide (DMF) as the application vehicle, have been measured. Relative skin sensitizing potency was estimated as a function of the amount of chemical required to induce a threefold increase in lymph node cell proliferative activity, a mathematically derived EC3 value (estimated concentration required to induce a stimulation index of 3). RESULTS: In both vehicles, glutaraldehyde induced substantially more vigorous responses in the local lymph node assay (EC3 values of 0.006mol/L in acetone and 0.002mol/L in DMF) than did formaldehyde (EC3 values of 0.18mol/L in acetone and 0.11mol/L in DMF). CONCLUSIONS: These results demonstrate that glutaraldehyde has a considerably greater potential to induce skin sensitization than does formaldehyde; the data are consistent with what is known of the ability of these chemicals to cause allergic contact dermatitis in humans. Using formaldehyde and glutaraldehyde as examples, the results here illustrate the utility of EC3 values derived from local lymph node assay responses for the estimation of the relative potency of skin sensitizing chemicals.

Allergens↗

Cancer services. Minding body and soul.

The psychosocial impact of cancer on patients' families and carers, as well as patients themselves, needs to be considered at all stages of diagnosis and treatment. The Calman-Hine report specified this principle but did not state how it should be put into action. Everyone who comes into contact with people with cancer should have the confidence to ask: 'How do you feel?' Standards should be incorporated into contracts.

Caregivers↗

A new class of anti-HIV-1 agents targeted toward the nucleocapsid protein NCp7: the 2,2'-dithiobisbenzamides.

As part of the National Cancer Institute's Drug Screening Program, a new class of antiretrovirals active against the human immunodeficiency virus HIV-1 has been identified, and the HIV-1 nucleocapsid protein NCp7 was proposed as the target of antiviral action. The 2,2'-dithiobis-[4'-(sulfamoyl)benzanilide] (3x) and the 2,2'-dithiobis(5-acetylamino)benzamide (10) represented the prototypic lead structures. A wide variety of 2,2'-dithiobisbenzamides were prepared and tested for anti-HIV-1 activity, cytotoxicity, and their ability to extrude zinc from the zinc fingers for NCp7. The structure-activity relationships demonstrated that the ability to extrude zinc from NCp7 resided in the 2,2'-dithiobisbenzamide core structure. The 3,3' and the 4,4' isomers were inactive. While many analogs based upon the core structure retained the zinc extrusion activity, the best overall anti-HIV-1 activity was only found in a narrow set of derivatives possessing carboxylic acid, carboxamide, or phenylsulfonamide functional groups. These functional groups were more important for reducing cytotoxicity than improving antiviral potency or activity vs NCp7. All of the compounds with antiviral activity also extruded zinc from NCp7. From this study several classes of low microM anti-HIV agents with simple chemical structures were identified as possible chemotherapeutic agents for the treatment of AIDS.

Anti-HIV Agents↗

Changes with growth rate in the membrane lipid composition of and amino acid utilization by continuous cultures of Campylobacter jejuni.

Methods and media (defined and complex) are described which permit studies designed to determine the influence of single environmental factors on the survival and virulence of Campylobacter jejuni. The effect of growth rate on selected physiological traits (amino acid utilization, membrane lipid composition, motility, cell morphology) was studied in continuous culture. In both media, growth was at the expense of amino acid (serine, aspartate, glutamate and proline) catabolism. Slow growth in the complex medium shifted amino acid utilization from more (serine and aspartate) to less preferred substrates (glutamate, proline and possibly amino acids from the proteolysis of peptones). Low growth rates promoted the conversion of unsaturated 11-octadecenoic acid substituted phosphatidyl ethanolamines to corresponding 11-methylene substituted species, a feature correlated with stationary phase and exposure to environmental stress in other organisms. During continuous growth, cells lost motility although they still possessed flagella. Slow growth resulted in longer cells. Future studies will investigate the independent effects of nutrient stress and growth rate on the virulence and persistence of cells.

Acetates↗

Correspondence of self-reported fruit and vegetable intake with dietary intake data.

The association between greater fruit and vegetable intake and better health outcomes is now well established, and dietary guidelines and recommendations promote increased intake of fruit and vegetables. The correspondence of self-assessed change in, and adequacy of, fruit and vegetable intake with dietary intake data was investigated using data from a food frequency questionnaire administered in 1989 and again in 1992 to 453 randomly selected adults from Dalby, Queensland. There was some accuracy in self-reported increased intake of fruit for women, although the dietary data for 44 per cent of women who reported an increase in intake did not show such an increase. Self-reported increased intake did not correspond with dietary data for men or for vegetable intake for women. Self-assessed adequacy of fruit and vegetable intake was associated significantly with mean intake and intake frequency data. The association was stronger for men for fruit and for women for vegetables. Nonetheless, high percentages of people who consumed less than two servings of fruit or three servings of vegetables daily assessed their intake as 'about right'. There is a need for clear, consistent and widely promoted messages recommending intake of two fruit and five vegetable servings daily to increase awareness of the amounts of fruit and vegetables Australians should consume.

Adult↗

2,2'-Dithiobisbenzamides and 2-benzisothiazolones, two new classes of antiretroviral agents: SAR and mechanistic considerations.

Substituted 2,2'-dithiobisbenzamides and 2-benzisothiazolones were prepared and shown to possess low microM activity with high therapeutic indices against HIV-1, HIV-2 and SIV in cell culture. The mechanism of antiviral action was determined to be directed toward the nucleocapsid protein (NCp7), which contains two zinc fingers and plays vital roles in the viral life cycle. The "active sulfides" of this study cause the extrusion of zinc from these zinc fingers. Structure-activity relationships of the 2,2'-dithiobisbenzamides reveal that the disulfide bond and the ortho benzamide functional groups are essential for activity, with the best compounds having a carboxylic acid, carboxamide, or sulfonamide substituent. The 2-benzisothiazolones are formed from the disulfides both chemically and in vivo and their SAR mimics that of the 2,2'-dithiobisbenzamides. The antiviral activity of the disulfides may require cyclization to the isothiazolones. Two agents, PD 159206 and PD 161374, which showed good antiviral activity, physical properties, and excellent pharmacokinetics in mice, were selected for advanced studies.

Alkylation↗