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Biomedical subjects

D Hart

Publications and source records attributed to D Hart.

At least 19 recordsLinked to original sources

Comparison between FSS-II scores of two groups of university students sampled 15 yr apart.

Undergraduate students were contacted in classes at Memorial University of Newfoundland during 1975 and asked to complete the FSS-II, on a voluntary basis; 511 students (232 male and 279 female subjects) provided enough data for analyses. In 1990, the same procedure was carried out, resulting in a comparable group of 359 students (161 male and 198 female subjects). Contrary to predictions, the 1990 students were more fearful than the 1975 group and the increase in fearfulness was contributed exclusively by women students. The component of fear contributing most to this increase related to social evaluation and violence.

Adult

Basolateral Na(+)-independent Cl(-)-HCO3- exchange in primary cultures of rat IMCD cells.

The role of anion exchange in the regulation of intracellular pH (pHi) under base load and steady-state conditions was investigated in confluent monolayers of rat inner medullary collecting duct (IMCD) cells in primary culture using the pH-sensitive fluoroprobe 2,7-bis(carboxyethyl)-5(6')-carboxyfluorescein (BCECF). Recovery of pHi after imposition of a base load induced either by replacement of HCO3-/CO2 by N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid (HEPES) at the same extracellular pH (pHo) or deletion of Cl- from a HCO3-/CO2-buffered solution had an absolute requirement for Cl-, was Na+ independent, and was inhibited approximately 90% by 50 microM 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS). When pHo was decreased by lowering HCO3- concentration in the constant presence of 5% CO2, the rate of decrement in pHi was significantly blunted in the absence of Cl-. Imposition of a positive or negative diffusion potential of equal but opposite magnitude did not modify the anion exchange rate, confirming the electroneutrality of the process. Under steady-state conditions, pHi of cells bathed in a HCO3-/CO2-buffered solution was 7.33 +/- 0.06, significantly lower than that of cells bathed in a nominally HCO3-/CO2-free buffer (7.50 +/- 0.04), indicating that under physiological conditions the pathway functions as a base extruder. In studies performed on cells grown on permeable supports, the anion exchange pathway was found to be confined exclusively to the basolateral-equivalent cell surface. In summary, confluent monolayers of rat IMCD cells in primary culture possess a Na(+)-independent, DIDS-inhibitable electroneutral Cl(-)-HCO3- exchange pathway that is confined to the basolateral cell surface. The transporter is an important determinant of steady-state pHi and is the predominant mechanism whereby the cell recovers from imposed elevations in pHi.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid

The distribution of medical X-ray doses amongst individuals in the British population.

This study has estimated the distribution of diagnostic X-ray doses amongst individuals in the British population by sampling the records kept by general practitioners (GPs) on their patients and the records held by the radiology department of a district general hospital. Deceased patients were chosen in the former case in order to evaluate the dose acquired over a complete lifetime. In each case, several hundred records were sampled. The GP data obtained have enabled an estimate to be made of the likelihood of reaching various dose levels in a lifetime. It is estimated that about 1% of the population has received a lifetime effective dose-equivalent of more than 100 mSv. The largest cumulative dose revealed by the samples of GP and radiology department records was about 200 mSv. The GP data have also shown that the last year of life sees a four-fold increase in the number of X-ray examinations experienced compared with the previous 9 years. The hospital data have allowed an estimate to be made of current rates of dose acquisition amongst the population of a District Health Authority.

Adolescent

Immobilization alters cell metabolism in an immature ligament.

This investigation examined the metabolic and cellular effects of immobilization on immature rabbit medial collateral ligaments (MCLs). Thirty-two three-month-old rabbits had their right knee pinned in flexion for intervals of two weeks, one month, two months, or three months before being killed for comparison with MCLs from nonpinned contralateral controls and MCLs from 16 normal age-matched controls. Twelve animals were studied by gait analysis after either one month or three months of immobilization and were killed with the others for in vitro analysis of ligament mass, collagen synthesis, plasminogen activator secretion, or DNA content. Immobilized hindlimbs carried less weight than did contralaterals, and MCLs from those hindlimbs synthesized less collagen and secreted less plasminogen activator than did controls at all intervals. Contralaterals also showed some signs of altered cell metabolism compared with normal controls, suggesting that they are not normal by these assessment criteria. With increasing periods of knee immobilization, immobilized MCLs switched progressively from an anabolic to a more catabolic state, apparently contributing to the failure of immobilized ligaments to increase normally in mass. Knee immobilization alters the metabolic behavior of MCLs in both knees in growing rabbits, and, based on these results, either knee joint motion or hindlimb load bearing could be necessary for normal rabbit medial collateral ligament growth and maturation.

Animals

Polarized distribution of Na+/H+ antiport and Na+/HCO3- cotransport in primary cultures of renal inner medullary collecting duct cells.

Primary cultures of rat renal inner medullary collecting duct cells were grown to confluence on glass coverslips and treated permeant supports, and the pH-sensitive fluorescent probe 2,7-biscarboxyethyl-5,6-carboxyfluorescein was employed to delineate the nature of the transport pathways that allowed for recovery from an imposed acid load in a HCO3-/CO2-buffered solution. The H+ efflux rate of acid-loaded cells was 13.44 +/- 0.94 mM/min. Addition of amiloride, 10(-4) M, to the recovery solution reduced the H+ efflux rate to 4.06 +/- 0.63 mM/min. The amiloride-resistant pHi recovery mechanism displayed an absolute requirement for Na+ but was Cl(-)-independent. Studies performed on permeable supports demonstrated that the latter pathway was located primarily on the basolateral-equivalent (BE) cell surface and was inhibited by 50 microM 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS). In a Na(+)-replete solution containing DIDS (50 microM) and amiloride (10(-4) M), acid-loaded cells failed to return to basal pHi. To delineate further the amiloride-inhibitable component of pHi recovery, monolayers were studied in the nominal absence of HCO3-/CO2. In 70% of monolayers studied, Na(+)-dependent, amiloride-inhibitable H+ efflux was the sole mechanism whereby acid-loaded cells returned to basal pHi. A Na(+)-independent pathway was observed in 30% of monolayers examined and represented only a minor component of the pHi recovery process. In studies performed on permeable supports, the Na(+)-dependent amiloride-inhibitable pathway was found to be confined exclusively to the BE cell surface. In summary, confluent monolayers of rat renal inner medullary collecting duct cells in primary culture possess two major mechanisms that contribute toward recovery from an imposed acid load, namely, Na+/H+ antiport and Na+/HCO3- cotransport. Na(+)-independent pHi recovery mechanisms represent a minor component of the pHi recovery process in the cultured cell. Both the Na+/H+ antiporter and Na+/HCO3- cotransporter are located primarily on the BE cell surface.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid

Carcinogenic ranking of aromatic amines and nitro compounds.

A scheme is proposed for ranking the carcinogenicity of aromatic amines and nitro compounds based on both qualitative (weight of evidence) and quantitative (carcinogenic potency, i.e. the TD50 value) factors. The scheme has been drawn up specifically with a view to linking with workplace hygiene controls. Other essential features are that a reliable database exists for the TD50 values for many compounds and that the scheme is capable of usage by non-toxicologists. Validation of the scheme using 38 aromatic amines or nitro compounds indicates that the main objectives have been met. Extension to different chemical classes should be possible but has not been attempted in this work. An example of a potential hygiene control scheme for use alongside the carcinogenicity ranking is described.

Amines

Spontaneously productive C-type retrovirus infection of fish cell lines.

The spontaneous production and release of morphologically typical, 85 to 90 nm diameter C-type retrovirus particles from four cell lines derived from three species of warmwater fish have been identified. Virus pellets from cell culture supernatants showed high levels of Mn(2+)-dependent reverse transcriptase activity at 24 degrees C. Peak enzyme activity was associated with a 1 x 16 g/ml sucrose gradient fraction. All four isolates induced a cytolytic infection of a bluegill fry cell line within 6 to 10 days.

Animals

Characterization of endothelin 1 receptor and signal transduction mechanisms in rat medullary interstitial cells.

Previous autoradiographic studies have delineated the renal medullas the predominant site of renal endothelin (ET) receptors. Accordingly, cultured rat renal medullary interstitial cells (RMICs) were studied as a target tissue for ET action. Scatchard analysis revealed presence of a single class of high-affinity receptor sites (Kd, 57 +/- 10 pM; receptor density, 749 +/- 124 fmol/mg protein). Relative potency order for displacing 125I-ET-1 was ET-1 greater than ET-2 greater than sarafotoxin greater than big endothelin (human) = big endothelin (porcine). ET-3, unrelated pressor substances, vasodilators, Ca2+ channel antagonists, atrial natriuretic factor, GTP, and GppNHp did not inhibit binding. Challenge of monolayers with ET-1 evoked a biphasic elevation in cytosolic free Ca2+ concentration [Ca2+]i). Initial transient rise in [Ca2+]i observed in absence of extracellular Ca2+ and accumulation of inositol trisphosphate (IP3) was consistent with activation of phosphatidylinositol-specific phospholipase C (PI-PLC). Half-maximal activation concentration of ET-1 for the process was 0.5 and 1 nM for [Ca2+]i and IP3, respectively. The late sustained phase in [Ca2+]i elevation was completely blocked by Ni2+, unperturbed by nimodipine, and accompanied by influx of Mn2+, indicating presence of receptor-operated Ca2+ channels. Ca2+ channel opening was detected at 10(-16) MET-1, whereas greater than 10(-12) M agonist was required to mobilize Ca2+ from intracellular stores and/or stimulate phosphoinositol hydrolysis, indicating that ET activation of PI-PLC and Ca2+ channel opening were independent events. ET-1 markedly stimulated prostaglandin E2 synthesis in a concentration-dependent manner that paralleled PI-PLC activation and mobilization of [Ca2+]i. In summary, cultured rat RMICs possess ET receptors that are linked to PI-PLC, Ca2+ channels, and perhaps phospholipase A2.

Animals

The effects of diet on the incidence of periodontitis in rats.

Four groups of 60 male Alpk:APfSD rats were fed different nutritionally comparable diets for 107 weeks with interim sacrifices at 26, 53 and 77 weeks in order to compare the effect of diet on the incidence of oral disease. Changes in the oral and nasal cavities were assessed by histopathology. Oro-nasal fistulation and severe periodontitis were associated with diets containing fibres originating from oats and barley. An expanded ground diet induced the most severe lesions. Aspects of the pathogenesis of the lesions observed are discussed.

Animal Nutritional Physiological Phenomena

Locomotor disability in very elderly people: value of a programme for screening and provision of aids for daily living.

OBJECTIVE: To assess the prevalence of potentially reversible locomotor disabilities in elderly subjects and the cost effectiveness of providing aids for daily living. DESIGN: Population based randomised controlled trial of subjects aged greater than or equal to 85 living independently in an inner London borough. SETTING: 21 Electoral wards of the London Borough of Hackney. SUBJECTS: 1255 Subjects aged greater than or equal to 85 living in their own home whose names were obtained from general practitioner lists and cross checked against the electoral register, 511 of whom were subsequently found to be ineligible. Of the 744 remaining, those with disability on screening were randomised and allocated to an intervention group (36) or a control group (43), in which intervention was postponed until four weeks, after the follow up assessment. Subjects with aids supplied previously were excluded from the intervention phase. INTERVENTIONS: Provision of raised toilet seat, teapot tipper, tap turner, shoe horn and elastic laces, and double handled saucepan. MAIN OUTCOME MEASURES: Degree of difficulty (grades 1-4) with specific tasks (getting on and off a toilet, pouring from a teapot into a cup, turning taps on and off, carrying a saucepan of standard weight, and putting on shoes) and time taken to perform them. RESULTS: 545 (73%) Of the 744 eligible subjects assessed; 428 had no disability and 118 had difficulty with at least one task. Some had had their disability recognised before the study and already had aids, representing half of those with difficulty getting on and off the toilet but 24% for putting on shoes and 13% for pouring from a teapot and turning on a tap. The mean number of difficulties was similar between the groups (intervention group 1.7, control group 1.6). Time taken to complete the tasks corresponded with the observed grade of difficulty. All aids were associated with reduced difficulty according to observer assessment (% improvement intervention group v control group: raised toilet seat, 71 v 13 teapot tipper 100 v 33; tap turner 100 v 0; saucepan 88 v 0; shoe horn 50 v 13) and time taken to complete the tasks. A cost benefit analysis of this screening-intervention programme suggested a total cost of 32 pounds per individual benefit. CONCLUSIONS: Appreciable degrees of unrecognised locomotor disability are detected on screening of very elderly people living independently. Providing aids offers a feasible and cost effective means of improving function in such people.

Activities of Daily Living

Intracellular pH regulates Na(+)-independent Cl(-)-base exchange in JTC-12 (proximal tubule) cells.

The role of an anion exchange pathway in the regulation of intracellular pH (pHi) under alkaline load and steady-state conditions and the modulation of this transporter by pHi was investigated in confluent monolayers of cloned JTC-12 cells, derived from monkey kidney proximal tubule. Regulation of pHi was fluorometrically monitored using the pH-sensitive probe, 2',7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein (BCECF). Monolayers in which pHi was rapidly elevated by removal of HCO3(-)-CO2 from the bathing medium demonstrated an absolute requirement for Cl- to recover toward base-line pHi. The recovery process proceeded in the absence of Na+, was inhibited 80% by 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid, and was unaffected by 10(-4) M amiloride. When extracellular pH (pHo) was serially lowered from 7.4 to 6.7, recovery from an alkaline load induced by removal of HCO3(-)-CO2 from the medium occurred only when pHi was elevated above approximately 7.25. Below pHi approximately 7.25 no recovery toward initial pHi was observed. When pHi was elevated above approximately 7.25 with pHo maintained at 6.7, the recovery process ceased at pHi approximately 7.25 despite favorably oriented Cl- and OH- chemical gradients. Consistent with these observations, removal of Cl- from the medium of cells buffered with 25 mM HCO3(-)-5% CO2 at pHo 7.4 (in the absence of Na+) resulted in reversible elevation of pHi, whereas in a solution buffered to pHo 6.7 with 5 mM HCO3(-)-5% CO2, removal of Cl- failed to elevate pHi. Under steady-state conditions in the presence of 25 mM HCO3(-)-5% CO2 at pHo 7.4, pHi was 7.40 +/- 0.02 and reversibly decreased to 7.23 +/- 0.01 on removal of Na+ (in the presence of amiloride) from the bathing medium, indicating that the Cl(-)-base exchanger is operative under basal conditions and functions as a base extruder. In summary the JTC-12 cell possesses a Na(+)-independent Cl(-)-base exchange mechanism that is operative under alkaline load and steady-state conditions. pHi but not pHo modulates the activity of this transport pathway, and below pHi approximately 7.25 the exchanger is quiescent.

Animals

Accuracy of electoral registers and Family Practitioner Committee lists for population studies of the very elderly.

STUDY OBJECTIVE: The purpose of the study was to assess the accuracy of Family Practitioner Committee (FPC) lists for identifying very elderly people registered with general practitioners. DESIGN: The accuracy of available FPC lists was checked against the most recent electoral register to determine which recorded individuals were still living at their FPC registered addresses. This was followed by a postal and home visit enquiry to validate the accuracy of the electoral register. SETTING: The study was carried out in the London borough of Hackney. PARTICIPANTS: The investigation was confined to persons aged 85 and over. RESULTS: Of a total of 3018 people listed as being 85 years or over by the FPC, 1183 (39%) were listed on the electoral register. Of these, 751 (63%) were living at their registered address, ie 25% of the people in the original FPC list. A further 154 (5%) of the original list were not recorded on the electoral register but were alive at the FPC recorded address. CONCLUSIONS: the use of FPC lists alone to identify the very elderly in an inner city population is too inaccurate to be of value. The combined use of FPC lists and the electoral register is better but one in six persons will still be missed.

Aged

Consumer satisfaction on a psychiatric ward.

A survey of consumer satisfaction was carried out on one ward of the psychiatric unit of a district general hospital. Data were collected by questionnaire, the content of the questionnaire being guided by a number of semi-structured interviews. The information collected suggested many ways in which the patients' time in hospital could be made more comfortable and relaxed. Areas attracting particular concern were the food, noise, the provision of information and boredom. The various methods which can be used to elicit consumer views are described, and we have discussed the value and possible obstacles to users having more influence in the planning and running of mental health services.

Adolescent

Renal physiology of the prostaglandins and the effects of nonsteroidal anti-inflammatory agents on the kidney.

The prostaglandins are a series of fatty acid products derived from the cellular metabolism of arachidonic acid. The kidney makes prostaglandins and the endogenous renal prostaglandins appear to play a role in the regulation of renal hemodynamics, renal salt and water excretion, and control of the level of activity of the renin-angiotensin system. The administration of nonsteroidal anti-inflammatory drugs blocks cyclooxygenase activity, an early step in the synthesis of prostaglandins. This class of drugs, under certain circumstances, leads to sodium retention, hyperkalemia and several different forms of acute and chronic renal failure. The potential role of altered prostaglandin synthesis in leading to these clinical syndromes is reviewed.

Animals

Suprofen-related nephrotoxicity. A distinct clinical syndrome.

We describe a unique clinical syndrome of flank pain and acute renal failure that is associated with suprofen, a nonsteroidal anti-inflammatory drug that has recently been made available in the United States. In the initial 6 months of the drug's distribution in this country, at least 16 patients developed this syndrome. All 16 had acute flank pain and 13 developed mild reversible renal failure within 12 hours of ingestion of one to three suprofen capsules. This syndrome is unlike other nephrotoxic syndromes related to nonsteroidal anti-inflammatory drugs. The mechanism is not known.

Abdomen