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Biomedical subjects

R Stephenson

Publications and source records attributed to R Stephenson.

At least 19 recordsLinked to original sources
PubMed2006

Sustained high levels of stored drinking water treatment and retention of hand-washing knowledge in rural Kenyan households following a clinic-based intervention.

Nyanza Province, Kenya is characterized by poor water quality and high diarrhoea prevalence. To address these problems, nurses in a maternal and child health clinic in Homa Bay, Kenya were trained in household water chlorination with a locally available, social marketed product, and in six steps of proper hand washing. They were asked to communicate this information to their clients. Interviews immediately following the training by nurses were conducted on 220 clients, of whom 168 (76%) reported being taught both procedures during their clinic visit. After 2 weeks, free chlorine residuals were present in stored drinking water in 67 out of 98 (68%) clients' homes and, 1 year later, in 36 out of 51 (71%) clients' homes. After 2 weeks, all six hand-washing steps were correctly demonstrated by 41 (44%) out of 93 clients, and by 17 out of 51 (34%) 1 year later. This brief, practical intervention shows promise for vulnerable populations.

Adolescent↗
PubMed2005

The PETRRA positron camera: design, characterization and results of a physical evaluation.

The PETRRA positron camera is a large-area (600 mm x 400 mm sensitive area) prototype system that has been developed through a collaboration between the Rutherford Appleton Laboratory and the Institute of Cancer Research/Royal Marsden Hospital. The camera uses novel technology involving the coupling of 10 mm thick barium fluoride scintillating crystals to multi-wire proportional chambers filled with a photosensitive gas. The performance of the camera is reported here and shows that the present system has a 3D spatial resolution of approximately 7.5 mm full-width-half-maximum (FWHM), a timing resolution of approximately 3.5 ns (FWHM), a total coincidence count-rate performance of at least 80-90 kcps and a randoms-corrected sensitivity of approximately 8-10 kcps kBq(-1) ml. For an average concentration of 3 kBq ml(-1) as expected in a patient it is shown that, for the present prototype, approximately 20% of the data would be true events. The count-rate performance is presently limited by the obsolete off-camera read-out electronics and computer system and the sensitivity by the use of thin (10 mm thick) crystals. The prototype camera has limited scatter rejection and no intrinsic shielding and is, therefore, susceptible to high levels of scatter and out-of-field activity when imaging patients. All these factors are being addressed to improve the performance of the camera. The large axial field-of-view of 400 mm makes the camera ideally suited to whole-body PET imaging. We present examples of preliminary clinical images taken with the prototype camera. Overall, the results show the potential for this alternative technology justifying further development.

Equipment Design↗
PubMed2003

A gas microstrip detector for XAS studies in the photon energy region 300-1500 eV.

The ability to perform X-ray absorption spectroscopy (XAS) in the 300-1500 eV energy range allows measurements to be made on transition metal compounds. This paper describes a detector and the technique used to perform fluorescent measurements on such materials. A variety of test sample results are shown to illustrate the low energy and energy-resolving capabilities of the detector (based on gas microstrip technology). Two possible applications are also demonstrated. The first shows how the detector can be used to gather X-ray absorption spectra for the L edges of transition metals and K edges of light elements (C, O and N). The other shows how the magnetic immunity of the detector can be exploited to study the magnetic properties of materials.

Absorptiometry, Photon↗
PubMed2001

Circadian rhythms and sleep have additive effects on respiration in the rat.

1. We tested two hypotheses: that respiration and metabolism are subject to circadian modulation in wakefulness, non-rapid-eye-movement (NREM) sleep and rapid-eye-movement (REM) sleep; and that the effects of sleep on breathing vary as a function of time of day. 2. Electroencephalogram (EEG), neck electromyogram (EMG) and abdominal body temperature (T(b)) were measured by telemetry in six male Sprague-Dawley rats. The EEG and EMG were used to identify sleep-wake states. Ventilation (V(I)) and metabolic rate (V(CO2)) were measured by plethysmography. Recordings were made over 24 h (12:12 h light:dark) when rats were in established states of wakefulness, NREM sleep and REM sleep. 3. Statistically significant circadian rhythms were observed in V(I) and V(CO2) in each of the wakefulness, NREM sleep and REM sleep states. Amplitudes and phases of the circadian rhythms were similar across sleep-wake states. 4. The circadian rhythm in V(I) was mediated by a circadian rhythm in respiratory frequency (f(R)). Tidal volume (V(T)) was unaffected by time of day in all three sleep-wake states. 5. The 24 h mean V(I) was significantly greater during wakefulness (363.5 +/- 18.5 ml min(-1)) than during NREM sleep (284.8 +/- 11.1 ml min(-1)) and REM sleep (276.1 +/- 13.9 ml min(-1)). V(CO2) and V(T) each significantly decreased from wakefulness to NREM sleep to REM sleep. f(R) was significantly lower in NREM sleep than in wakefulness and REM sleep. 6. These data confirm that ventilation and metabolism exhibit circadian rhythms during wakefulness, and NREM and REM sleep, and refute the hypothesis that state-related effects on breathing vary as a function of time of day. We conclude that the effects of circadian rhythms and sleep-wake state on respiration and metabolic rate are additive in the rat.

Animals↗
PubMed2001

Inhibition of prolyl 4-hydroxylase in vitro and in vivo by members of a novel series of phenanthrolinones.

Examples of a novel series of phenanthrolinones are shown to be potent competitive inhibitors of avian prolyl 4-hydroxylase, and of collagen hydroxylation, in embryonic chick tendon cells and human foreskin fibroblasts in vitro and in the oestradiol-stimulated rat uterus in vivo. Two compounds, Compound 1 (1,4-dihydrophenanthrolin-4-one-3-carboxylic acid) and Compound 5 [8-(N-butyl-N-ethylcarbamoyl)-1,4-dihydrophenathrolin-4-one-3-carboxylic acid], with comparable potencies in vivo, were chosen to investigate the effect of the inhibition of the hydroxylation of newly synthesized uterine collagen on the turnover of this protein in vivo. Inhibition of hydroxylation by more than 50% for approx. 8 h following single oral doses of the compounds was associated with significant losses of radiolabelled proline and 4-hydroxyproline from collagen during this period. Progressive hydroxylation of collagen over 48 h, as the inhibitory action of the compounds declined, was accompanied by a decreased loss of radiolabel from the uterine collagen. Earlier reports indicated that underhydroxylated collagen, accumulating within the endoplasmic reticulum in cells where prolyl 4-hydroxylase is inactivated, is slowly degraded, but is then rapidly hydroxylated and secreted when the activity of prolyl 4-hydroxylase is restored. Taken with the present results, this suggests that the potential use of inhibitors of prolyl 4-hydroxylase to control excessive collagen deposition in pathological fibrosis may be limited by the need to maintain continuous inhibition of collagen hydroxylation so as to facilitate intracellular degradation of the accumulated protein.

Animals↗
PubMed2001

Respiratory control in neonatal mice with NADPH oxidase deficiency.

A membrane bound cytochrome b(558) (NADPH oxidase) is a candidate for the oxygen sensor in pulmonary neuroepithelial bodies (NEBs) - putative airway chemoreceptors. Recent electrophysiological studies on NEB from mice with NADPH oxidase deficiency (OD; gp(91phox) knock-out) have shown lack of response of O(2) sensitive K(+) current to hypoxia challenge compared with wild-type (WT) control mice. To assess the effects of oxidase deficiency on the control of ventilation at the whole animal level, respiratory measurements were conducted under normoxic and hypoxic conditions in neonatal OD mice and compared that with the WT control group. Five-day-old OD mice were faster and shallower breathers during normoxia as well as hypoxia. In addition, the maximum hypoxic ventilatory response of the OD mice was lower than that of the WT control group and the peak increase in minute ventilation (.V(max)-.V(normoxia)) was greater in WT control than the OD mice (P=0.02). Since the lung development and NEB morphology in OD mice were comparable to the WT control mice, the observed differences implicate NADPH oxidase as an O(2) sensor involved in neonatal ventilatory control, possibly modulated via pulmonary NEBs.

Animals↗
PubMed2001

Understanding users' perspectives of barriers to maternal health care use in Maharashtra, India.

This paper uses data collected using in-depth, semi-structured interviews to examine utilization of maternal health care services among two rural and urban populations of Pune and Mumbai in Maharashtra, India. The study aims to identify key social, economic and cultural factors influencing women's decisions to use maternal health care and the places used for child delivery, whilst considering the accessibility of facilities available in the local area. Socioeconomic status was not found to be a barrier to service use when women perceived the benefits of the service to outweigh the cost, and when the service was within reasonable distance of the respondent's place of residence. A large number of women perceived private services to be superior to those provided by the government, although cost often meant they were unable to use them. The provision of services did not ensure that women used them; they had to first perceive them to be beneficial to their health and that of their unborn child. Respondents identified the poor quality of services offered at government institutions to be a motivating factor for delivering at home. Thus further investigation is needed into the quality of services provided by government facilities in the area. A number of respondents who had received antenatal care went on to deliver in the home environment without a trained birth attendant. Further research is needed to establish the types of care provided during an antenatal consultation to establish the feasibility of using these visits to encourage women, particularly those with high-risk pregnancies, to be linked to a trained attendant for delivery.

Attitude to Health↗
PubMed2001

Selected Contribution: Regulation of sleep-wake states in response to intermittent hypoxic stimuli applied only in sleep.

Recurrent sleep-related hypoxia occurs in common disorders such as obstructive sleep apnea (OSA). The marked changes in sleep after treatment suggest that stimuli associated with OSA (e.g., intermittent hypoxia) may significantly modulate sleep regulation. However, no studies have investigated the independent effects of intermittent sleep-related hypoxia on sleep regulation and recovery sleep after removal of intermittent hypoxia. Ten rats were implanted with telemetry units to record the electroencephalogram (EEG), neck electromyogram, and body temperature. After >7 days recovery, a computer algorithm detected sleep-wake states and triggered hypoxic stimuli (10% O2) or room air stimuli only during sleep for a 3-h period. Sleep-wake states were also recorded for a 3-h recovery period after the stimuli. Each rat received an average of 69.0 +/- 6.9 hypoxic stimuli during sleep. The non-rapid eye movement (non-REM) and rapid-eye-movement (REM) sleep episodes averaged 50.1 +/- 3.2 and 58.9 +/- 6.6 s, respectively, with the hypoxic stimuli, with 32.3 +/- 3.2 and 58.6 +/- 4.8 s of these periods being spent in hypoxia. Compared with results for room air controls, hypoxic stimuli led to increased wakefulness (P < 0.005), nonsignificant changes in non-REM sleep, and reduced REM sleep (P < 0.001). With hypoxic stimuli, wakefulness episodes were longer and more frequent, non-REM periods were shorter and more frequent, and REM episodes were shorter and less frequent (P < 0.015). Hypoxic stimuli also increased faster frequencies in the EEG (P < 0.005). These effects of hypoxic stimuli were reversed on return to room air. There was a rebound increase in REM sleep, increased slower non-REM EEG frequencies, and decreased wakefulness (P < 0.001). The results show that sleep-specific hypoxia leads to significant modulation of sleep-wake regulation both during and after application of the intermittent hypoxic stimuli. This study is the first to determine the independent effects of sleep-related hypoxia on sleep regulation that approximates OSA before and after treatment.

Animals↗
PubMed2001

Diving accidents in sports divers in Orkney waters.

Scapa Flow in Orkney is one of the major world centres for wreck diving. Because of the geography of Orkney and the nature of the diving, it is possible to make relatively accurate estimates of the number of dives taking place. The denominator of dive activity allows the unusual opportunity of precise calculation of accident rates. In 1999, one in every 178 sports divers visiting Orkney was involved in a significant accident, in 2000 the figure was one in 102. Some of these accidents appear to have been predictable and could be avoided by better education and preparation of visiting divers.

Athletic Injuries↗
PubMed2000

A model of the chemoreflex control of breathing in humans: model parameters measurement.

We reviewed the ventilatory responses obtained from rebreathing experiments on a population of 22 subjects. Our aim was to derive parameter estimates for an 'average subject' so as to model the respiratory chemoreflex control system. The rebreathing technique used was modified to include a prior hyperventilation, so that rebreathing started at a hypocapnic P(CO2) and ended at a hypercapnic P(CO2). In addition, oxygen was added to the rebreathing bag in a controlled manner to maintain iso-oxia during rebreathing, which allowed determination of the response at several iso-oxic P(O2) levels. The breath-by-breath responses were analysed in terms of tidal volume, breathing frequency and ventilation. As P(CO2) rose, ventilation was first steady at a basal value, then increased as P(CO2) exceeded a breakpoint. We interpreted this first breakpoint as the threshold of the combined central and peripheral chemoreflex responses. Above, ventilation increased linearly with P(CO2), with tidal volume usually contributing more than frequency to the increase. When breathing was driven strongly, such as in hypoxia, a second breakpoint P(CO2) was often observed. Beyond the second breakpoint, ventilation continued to increase linearly with P(CO2) at a different slope, with frequency usually contributing more than tidal volume to the increase. We defined the parameters of the variation of tidal volume, frequency and ventilation with P(O2) and P(CO2) for an average subject based on a three-segment linear fit of the individual responses. These were incorporated into a model of the respiratory chemoreflex control system based on the general scheme of the 'Oxford' model. However, instead of considering ventilatory responses alone, the model also incorporates tidal volume and frequency responses.

Adolescent↗
PubMed2000

Heart rate and rate of oxygen consumption during flight of the barnacle goose, Branta leucopsis.

We report the first measurements of heart rate (f(H)) and the rate of oxygen consumption (V(O(2))) during flights from a species of bird larger than 500 g. V(O(2))was obtained from nine forward flapping flights of 8.9 min mean duration at a mean speed of 13.2 m s(-1) performed by three barnacle geese of mean mass 1.68 kg. Mean V(O(2))was 332 ml min(-1)or 201 ml min(-1) kg(-1). Sixteen flights were obtained from two of these birds equipped with heart rate data loggers, both when they were wearing a V(O(2)) mask and when they were not. During flights with the mask (mean duration 7.4 min), mean f(H) was 472 beats per min and during flights without the mask (mean duration 8.0 min) it was 391 beats per min. Heart rate was also measured in another goose flying without a respiratory mask and mean f(H) for all the three birds (mean mass 1.7 kg) flying without a mask for an average of 7.9 min at 13 m s(-1) was 378 beats per min. Resting f(H) for these three birds was 79 beats per min. The values of f(H) during flight are greater than those obtained from the same species during their autumn migration from Spitsbergen to southern Scotland. The possible reasons for this are discussed.

Animals↗
PubMed2000

Circadian rhythms in the chemoreflex control of breathing.

Mechanisms underlying the circadian rhythm in lung ventilation were investigated. Ten healthy male subjects were studied for 36 h using a constant routine protocol to minimize potentially confounding variables. Laboratory light, humidity, and temperature remained constant, subjects did not sleep, and their meals and activities were held to a strict schedule. Respiratory chemoreflex responses were measured every 3 h using an iso-oxic rebreathing technique incorporating prior hyperventilation. Subjects exhibited circadian rhythms in oral temperature and respiratory chemoreflex responses, but not in metabolic rate. Basal ventilation [i.e., at subthreshold end-tidal carbon dioxide partial pressure (PET(CO(2)))] did not vary with time of day, but the ventilatory response to suprathreshold PET(CO(2)) exhibited a rhythm amplitude of approximately 25%, mediated mainly by circadian variations in the CO(2) threshold for tidal volume. We conclude that the circadian rhythm in lung ventilation is not a simple consequence of circadian variations in arousal state and metabolic rate. By raising the chemoreflex threshold, the circadian timing system may increase the propensity for respiratory instability at night.

Adult↗
PubMed2000

Effects of hypoxia and hypercapnia on circadian rhythms in the golden hamster (Mesocricetus auratus).

This study was designed to determine whether respiratory stimuli can influence the mammalian circadian timing system. Three-hour pulses of hypoxia (inspired O(2) concentration = 8%) or hypercapnia (inspired CO(2) concentration = 11%) were presented for 7 days at mid-subjective day (circadian time 6-9) under constant darkness. Hypoxic and hypercapnic pulses caused cumulative phase delays of 46. 4 +/- 6.9 and 25.9 +/- 12.3 min, respectively. Distance run per day was significantly reduced on hypoxic and hypercapnic pulse days, compared with nonpulsed days. Phase shifts were correlated with the reduction in daily running activity (multiple r(2) = 0.521, P = 0.036), metabolic depression (multiple r(2) = 0.772, P < 0.001), and reduction in body temperature (multiple r(2) = 0.539, P = 0.027), but not lung ventilation (multiple r(2) = 0.306, P = 0.414) during pulses. We conclude that hypoxia and hypercapnia can influence the phase and quantity of activity in free-running hamsters.

Animals↗
PubMed2000

Oestradiol is a potent mitogen and modulator of GnRH signalling in alphaT3-1 cells: are these effects causally related?

GnRH acts via phospholipase C (PLC) activating G-protein coupled receptors to stimulate secretion of gonadotrophins from gonadotrophs. These cells are also regulated by gonadal steroids, which act centrally to influence GnRH secretion, and peripherally to modulate GnRH action. We have shown that oestradiol can stimulate proliferation and modulate GnRH-stimulated [(3)H]inositol phosphate ([(3)H]IP(x)) accumulation (used as a measure of PLC activity) in a gonadotroph-derived cell line (alphaT3-1). Here we show that when alphaT3-1 cells were incubated in medium with 2% foetal calf serum (FCS), [(3)H]thymidine incorporation was not stimulated by oestradiol but was reduced to <2% of control by the oestrogen antagonist, raloxifene. The inhibitory effect of 10 or 1000 nM raloxifene was reversed competitively by oestradiol. A similar pattern of effects was seen when effects of oestradiol and raloxifene on the proportion of cells in the S-phase of the cell cycle (as measured by flow cytometry of propidium iodide-labelled cells) and on oestrogen receptor activity (as measured by trans-activation of the oestrogen-response elements in the vitellogenin promoter) were quantified. In addition, RT-PCR revealed expression of alpha and beta (but not beta2) subtypes of oestrogen receptors. Thus, oestrogen is an essential mitogen for alphaT3-1 cells, its mitogenic effect is oestrogen receptor mediated and is associated with a marked alteration of cell cycle distribution, and the full extent of these effects are best revealed in the presence of raloxifene. Using this strategy, we found that cells cultured for 4 days with 10 nM raloxifene expressed GnRH receptors (K(d) for (125)I-buserelin 4.33 nM) and that their activation by GnRH caused a concentration-dependent increase in [(3)H]IP(x) (in cells labelled with [(3)H]inositol) and inositol 1,4,5 trisphophate (in unlabelled cells). Addition of 10 nM oestradiol (to overcome receptor blockade by raloxifene) reduced GnRH receptor number by 31% but increased maximal effects on [(3)H]IP(x) and Ins(1,4,5)P(3) approximately 4-fold. The effects of oestradiol on GnRH receptor number and signalling were not, however, mimicked by culture for 2 days in medium with 10% FCS and the S-phase blocker, thymidine (15 mM). This treatment increased the proportion of cells in the S-phase 2- to 3-fold but did not alter GnRH receptor number or signalling. Other treatments which altered cell cycle transition (hydroxyurea, colcemid, methotrexate) also failed to alter GnRH receptor number or signalling and no correlation was seen between GnRH receptor number or GnRH-stimulated [(3)H]IP(x) accumulation and the proportion of cells in the S-phase or G2/M-phases of the cell cycle. Thus, oestradiol has pronounced effects on GnRH signalling, proliferation and cell cycle distribution in alphaT3-1 cells, but these trophic effects do not underlie the modulation of GnRH signalling.

Animals↗
PubMed1998

Circadian rhythms in diving behavior and ventilatory response to asphyxia in canvasback ducks.

Underwater feeding behavior was measured in 10 captive canvasback ducks (Aythya valisineria) for 12 days under a 12:12-h light-dark photoperiod. Feeding activity exhibited a daily rhythm, with 76% of dives occurring at night. In separate experiments on six of these ducks, a circadian rhythm was observed in the duration of voluntary dives. Dives at night (14.7 +/- 0.7 s) were significantly longer than those during the day (10.7 +/- 0.7 s). These day-night differences in diving behavior were accompanied by day-night differences in respiratory responses to progressive asphyxia. In the same six ducks, ventilation increased exponentially as a function of inspired CO2 concentration during rebreathing in a closed-circuit barometric plethysmograph. The exponential rate constant for inspired ventilation was significantly smaller at night (0.23 +/- 0.02) than during the day (0.26 +/- 0.01). We suggest that intermittent apneic exercise is facilitated by reduced respiratory chemosensitivity and that the respiratory and behavioral control systems are synchronized by the circadian timing system in diving ducks.

Animals↗
PubMed1998

Lifetime exposure to traumatic events among a sample of city bus drivers.

Lifetime exposure to traumatic events was assessed retrospectively among a representative sample of city bus drivers (228 men and 54 women) from Montréal, Canada. Among them, 68.1% reported at least one exposure to a traumatic event of any type. Among the 68% exposed. 70.4% reported multiple traumatic exposures (M = 2.6, SD = 1.67), with ratings ranging from 0 to 12. This report underlines the fact that the prevalence of traumatic events is not yet well known. Epidemiological research should devote more effort to assess fully the lifetime prevalence of traumatic events and not only cases of PTSD.

Adult↗