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Biomedical subjects

T J Parker

Publications and source records attributed to T J Parker.

At least 19 recordsLinked to original sources

Assessment of Mars Exploration Rover landing site predictions.

Comprehensive analyses of remote sensing data during the three-year effort to select the Mars Exploration Rover landing sites at Gusev crater and at Meridiani Planum correctly predicted the atmospheric density profile during entry and descent and the safe and trafficable surfaces explored by the two rovers. The Gusev crater site was correctly predicted to be a low-relief surface that was less rocky than the Viking landing sites but comparably dusty. A dark, low-albedo, flat plain composed of basaltic sand and haematite with very few rocks was expected and found at Meridiani Planum. These results argue that future efforts to select safe landing sites based on existing and acquired remote sensing data will be successful. In contrast, geological interpretations of the sites based on remote sensing data were less certain and less successful, which emphasizes the inherent ambiguities in understanding surface geology from remotely sensed data and the uncertainty in predicting exactly what materials will be available for study at a landing site.

Journal Article↗

Pancam multispectral imaging results from the Opportunity Rover at Meridiani Planum.

Panoramic Camera (Pancam) images from Meridiani Planum reveal a low-albedo, generally flat, and relatively rock-free surface. Within and around impact craters and fractures, laminated outcrop rocks with higher albedo are observed. Fine-grained materials include dark sand, bright ferric iron-rich dust, angular rock clasts, and millimeter-size spheroidal granules that are eroding out of the laminated rocks. Spectra of sand, clasts, and one dark plains rock are consistent with mafic silicates such as pyroxene and olivine. Spectra of both the spherules and the laminated outcrop materials indicate the presence of crystalline ferric oxides or oxyhydroxides. Atmospheric observations show a steady decline in dust opacity during the mission. Astronomical observations captured solar transits by Phobos and Deimos and time-lapse observations of sunsets.

Atmosphere↗

Pancam multispectral imaging results from the Spirit Rover at Gusev Crater.

Panoramic Camera images at Gusev crater reveal a rock-strewn surface interspersed with high- to moderate-albedo fine-grained deposits occurring in part as drifts or in small circular swales or hollows. Optically thick coatings of fine-grained ferric iron-rich dust dominate most bright soil and rock surfaces. Spectra of some darker rock surfaces and rock regions exposed by brushing or grinding show near-infrared spectral signatures consistent with the presence of mafic silicates such as pyroxene or olivine. Atmospheric observations show a steady decline in dust opacity during the mission, and astronomical observations captured solar transits by the martian moons, Phobos and Deimos, as well as a view of Earth from the martian surface.

Atmosphere↗

Effect of Lactobacillus plantarum 299v on colonic fermentation and symptoms of irritable bowel syndrome.

A number of recent clinical trials have promoted the use of probiotic bacteria as a treatment for irritable bowel syndrome (IBS). The recent demonstration of abnormal colonic fermentation in some patients with this condition provides an opportunity for the objective assessment of the therapeutic value of these bacteria. This study was designed to investigate the effects of Lactobacillus plantarum 299V on colonic fermentation. We conducted a double-blind, placebo-controlled, cross-over, four-week trial of Lactobacillus plantarum 299V in 12 previously untreated patients with IBS. Symptoms were assessed daily by a validated composite score and fermentation by 24-hr indirect calorimetry in a 1.4-m3 canopy followed by breath hydrogen determination for 3 hr after 20 ml of lactulose. On placebo, the median symptom score was 8.5 [6.25-11.25 interquartile range (IQR)], the median maximum rate of gas production was 0.55 ml/min (0.4-1.1 IQR), and the median hydrogen production was 189.7 ml/24 hr (118.3-291.1 IQR). On Lactobacillus plantarum 299V the median symptom score was 8 (6.75-13.5 IQR), the median maximum rate of gas production 0.92 ml/min (0.45-1.5 IQR), and the median hydrogen production 208.2 ml/24 hr (146-350.9 IQR). There was no significant difference. Breath hydrogen excretion after lactulose was reduced by the probiotic (median at 120 min, 6 ppm; placebo, 17 ppm; P = 0.019). In conclusion, Lactobacillus plantarum 299V in this study did not appear to alter colonic fermentation or improve symptoms in patients with the irritable bowel syndrome.

Adult↗

Pharmacokinetic-pharmacodynamic modelling in the early development phase of anti-psychotics: a comparison of the effects of clozapine, S 16924 and S 18327 in the EEG model in rats.

1. The use of pharmacokinetic/pharmacodynamic (PK/PD) analysis in early compound development was investigated in the rat for two developmental anti-psychotic compounds with clozapine as a positive control. 2. Three plasma samples were collected from each of eight animals according to a pre-defined sampling matrix allowing a total of 12 time points for PK analysis. Quantitative electroencephalography (QEEG), particularly the theta and beta frequencies, was used as a measurement of pharmacological effect. 3. PK/KD modelling of the sparse PK data available relative to a rich set of PD data was achieved using a population approach in NONMEM (IV). Individual PK parameter estimates were incorporated into a PK/PD model. 4. Qualitative EEG changes in rat and human were similar for clozapine, but different for the two developmental compounds, suggesting that changes in these PD parameters may not be specifically related to the anti-psychotic activity. 5. Although no definitive data are available concerning the signal specificity of EEG frequency bands with respect to dopaminergic or serotonergic receptor activity, qualitative and quantitative differences seen in EEG parameters are likely to result from the multiple receptor occupancy for these compounds. 6. The results confirm the value of population PK/PD modelling in conjunction with sparse sampling to enable determination of concentration effect relationships in the pre-clinical development programme of CNS-active drugs.

Algorithms↗

Irritable bowel syndrome: is the search for lactose intolerance justified?

OBJECTIVES: To determine if confirmation of hypolactasia offers any benefit to the dietary treatment of patients with irritable bowel syndrome (IBS). METHODS: One hundred and twenty-two consecutive IBS patients (37 male, 85 female) were given lactose hydrogen breath tests (LHBT). Those with positive LHBT followed a low lactose diet for 3 weeks. Those improving on the diet were given double-blind, placebo-controlled challenges (DBPCC) with 5 g, 10 g and 15 g of lactose and a placebo, to confirm lactose intolerance. Those who did not respond to the low lactose diet followed either an exclusion or low fibre diet. Symptoms scores were kept prior to the LHBT, 8 h post-LHBT and daily whilst following any dietary change. Patients with negative LHBT returned to clinic and subsequent dietary interventions were recorded. RESULTS: LHBT was positive in 33/122 (27%) IBS patients. Syrr otom scores prior to LHBT were not significantly different between the two groups, but after LHBT the symptoms in the positive group were significantly worse. Twenty-three patients followed a low-lactose diet of which only nine (39%) improved. Six who did not improve followed an exclusion diet, three improved and all were intolerant of milk. Three tried a low fibre diet with two improving. DBPCC were inconclusive. In the negative LHBT group 35 agreed to try a diet and 24 improved (69%). Eight were intolerant of cow's milk. CONCLUSIONS: Use of a low lactose diet was disappointing in IBS patients with lactose malabsorption. Food intolerance was demonstrated in IBS patients with positive or negative LHBT and milk was identified as a problem in both groups. DBPCC were inconclusive. There appears to be little advantage in trying to separate patients who malabsorb lactose from others with IBS.

Adult↗

Effects of nasal O2 on sleep-related disordered breathing in ambulatory patients with stable heart failure.

OBJECTIVE: The purpose of this study was 1) to determine the effects of nasal O2 on periodic breathing, arterial oxyhemoglobin desaturation and nocturnal ventricular arrhythmias in patients with heart failure and 2) determine the characteristics of patients whose periodic breathing will be reversed by O2 administration; our hypothesis was that patients with more severe periodic breathing and desaturation, will respond more favorably to oxygen. DESIGN: Prospective study. SETTING: Referral sleep laboratory of a Department of Veterans Affairs Medical Center. PARTICIPANTS: 36 ambulatory male patients with heart failure whose initial polysomnograms showed periodic breathing with fifteen or more episodes of apnea (A) and hypopnea (H) per hour (AH index, AHI) were treated with nasal O2 during the subsequent full night polysomnography. INTERVENTIONS: Oxygen. MEASUREMENTS AND RESULTS: Arterial blood gases and hydrogen ion concentrations were measured, and cardiac radionuclide ventriculography, Holter monitoring, and polysomnography were done. The studies were scored blindly. Treatment with O2 resulted in a significant reduction in AHI (49+/-19 vs 29+/-29, means+/-SD), central apnea index (28+/-23 vs 13+/-18 per hour), and the percent of total sleep time below an arterial oxyhemoglobin saturation of 90% (23+/-21% vs 0.8+/-2.3%). In spite of virtual normalization of saturation with O2 therapy, the number of ventricular arrhythmias during sleep did not change significantly. In 39% of the patients (14 out of 36), O2 therapy resulted in reversal of central sleep apnea (defined by a reduction in AHI to less than 15/hr). In this group, the AHI decreased by 78% which was significantly (p=0.0001) more than improved (22%) in AHI of the remaining patients (n=22). The main differences between baseline characteristics of the two groups was a significantly higher mean PaCO2 in patients who did respond fully to O2 (39.3+/-5.4 vs 36.1+/-4.2 mm Hg, p=0.03). In both groups, however, O2 administration resulted in significant and similar improvement in arterial oxyhemoglobin saturation (saturation <90%, percent total sleep time 0.1+/-0.3% vs 1+/-3%). CONCLUSION: In patients with stable heart failure, administration of nasal O2 significantly improves periodic breathing and virtually eliminates clinically significant arterial oxyhemoglobin desaturation. The beneficial effects of O2, however, may be modulated by the level of arterial PCO2. Acute O2 therapy has important benefits on sleep apnea and nocturnal arterial oxyhemoglobin desaturation in heart failure patients. Long term benefits of O2 therapy in heart failure and sleep apnea need to be determined.

Aged↗

Sleep apnea in 81 ambulatory male patients with stable heart failure. Types and their prevalences, consequences, and presentations.

BACKGROUND: Heart failure is a highly prevalent disorder that continues to be associated with repeated hospitalizations, high morbidity, and high mortality. Sleep-related breathing disorders with repetitive episodes of asphyxia may adversely affect heart function. The main aims of this study were to determine the prevalence, consequences, and differences in various sleep-related breathing disorders in ambulatory male patients with stable heart failure. METHODS AND RESULTS: This article reports the results of a prospective study of 81 of 92 eligible patients with heart failure and a left ventricular ejection fraction < 45%. There were 40 patients without (hourly rate of apnea/hypopnea, 4 +/- 4; group 1) and 41 patients with (51% of all patients; hourly rate of apnea/hypopnea, 44 +/- 19; group 2) sleep apnea. Sleep disruption and arterial oxyhemoglobin desaturation were significantly more severe and the prevalence of atrial fibrillation (22% versus 5%) and ventricular arrhythmias were greater in group 2 than in group 1. Forty percent of all patients had central sleep apnea, and 11% had obstructive sleep apnea. The latter patients had significantly greater mean body weight (112 +/- 30 versus 75 +/- 16 kg) and prevalence of habitual snoring (78% versus 28%). However, the hourly rate of episodes of apnea and hypopnea (36 +/- 10 versus 47 +/- 21), episodes of arousal (20 +/- 14 versus 23 +/- 11), and desaturation (lowest saturation, 72 +/- 11% versus 78 +/- 12%) were similar in patients with these different types of apnea. CONCLUSIONS: Fifty-one percent of male patients with stable heart failure suffer from sleep-related breathing disorders: 40% from central and 11% from obstructive sleep apnea. Both obstructive and central types of sleep apnea result in sleep disruption and arterial oxyhemoglobin desaturation. Patients with sleep apnea have a high prevalence of atrial fibrillation and ventricular arrhythmias.

Arrhythmias, Cardiac↗

Overview of the Mars Pathfinder mission and assessment of landing site predictions.

Chemical analyses returned by Mars Pathfinder indicate that some rocks may be high in silica, implying differentiated parent materials. Rounded pebbles and cobbles and a possible conglomerate suggest fluvial processes that imply liquid water in equilibrium with the atmosphere and thus a warmer and wetter past. The moment of inertia indicates a central metallic core of 1300 to 2000 kilometers in radius. Composite airborne dust particles appear magnetized by freeze-dried maghemite stain or cement that may have been leached from crustal materials by an active hydrologic cycle. Remote-sensing data at a scale of generally greater than approximately 1 kilometer and an Earth analog correctly predicted a rocky plain safe for landing and roving with a variety of rocks deposited by catastrophic floods that are relatively dust-free.

Atmosphere↗

Results from the Mars Pathfinder camera.

Images of the martian surface returned by the Imager for Mars Pathfinder (IMP) show a complex surface of ridges and troughs covered by rocks that have been transported and modified by fluvial, aeolian, and impact processes. Analysis of the spectral signatures in the scene (at 440- to 1000-nanometer wavelength) reveal three types of rock and four classes of soil. Upward-looking IMP images of the predawn sky show thin, bluish clouds that probably represent water ice forming on local atmospheric haze (opacity approximately 0.5). Haze particles are about 1 micrometer in radius and the water vapor column abundance is about 10 precipitable micrometers.

Atmosphere↗

A comparative population pharmacokinetic analysis for methylprednisolone following multiple dosing of two prodrugs in patients with acute asthma.

AIMS: To conduct a randomized, parallel group comparison of the population pharmacokinetics of the two methylprednisolone (MP) prodrugs Promedrol (MP suleptanate) and Solu-Medrol (MP succinate) in patients hospitalized with acute asthma. METHODS: Ninety volunteers were included in the pharmacokinetic analysis. Each volunteer received a dosage regimen of 40 mg (MP equivalents) i.v. 6 hourly for 48 h. The bio-conversion and disposition of a 40 mg (MP equivalent) i.v. dose of either MP suleptanate or MP succinate to MP was modelled as a first order input, and a mono-exponential elimination phase. RESULTS: Population modelling indicated that the only difference in MP pharmacokinetics between MP suleptanate and MP succinate was in the input rate constant (66.0 h-1 vs 5.5 h-1 respectively). Based on individual Bayesian estimates, the exposure of patients to MP was marginally lower for MP suleptanate although the parameter estimates were not significantly different for half-life (2.7 h vs 3.0 h), steady-state AUC (2007.0 ng ml-1 h vs 2321.0 ng ml-1 h) and steady-state Cmax (698.4 ng ml-1 vs 647.8 ng ml-1) for MP suleptanate and MP succinate respectively. CONCLUSIONS: It was concluded that for the multiple dosage regimen used in patients with acute asthma the systemic exposure to MP following dosing with MP suleptanate is similar to that arising from MP succinate. In addition the differences in the pharmacokinetics for the prodrugs resulted in only a small difference in the relative bioavailability of MP for MP suleptanate (0.94) compared with MP succinate.

Area Under Curve↗

Simulation of resistance forces acting on surgical needles.

High precision in the manual control of needles and biopsy probes in medical treatment requires high skill and dexterity levels. In anaesthesia, force sensation is an important feedback mechanism, and the practitioner needs to refresh or develop skills to improve on the interpretation of needle progress towards the target site. This paper describes an experimental tactile force simulator for uniaxial needle action for which the force resisting progress of the needle is derived from measured data. As an example, the approach taken to develop the simulation of the insertion of epidural needles is described. Adaptation to other procedures would be possible by adopting new reference models based on appropriate measured force data.

Animals↗

Effect of theophylline on sleep-disordered breathing in heart failure.

BACKGROUND: Theophylline has been used to treat central apnea associated with Cheyne-Stokes respiration (periodic breathing). We studied the effect of short-term oral theophylline therapy on periodic breathing associated with stable heart failure due to systolic dysfunction. METHODS: Fifteen men with compensated heart failure (left ventricular ejection fraction, 45 percent or less) participated in the study. Their base-line polysomnograms showed periodic breathing, with more than 10 episodes of apnea and hypopnea per hour. In a double-blind crossover study, the patients received theophylline or placebo orally twice daily for five days, with one week of washout between the two periods. RESULTS: After five days of treatment, the mean (+/-SD) plasma theophylline concentration was 11 +/- 2 microgram per milliliter. Theophylline therapy resulted in significant decreases in the number of episodes of apnea and hypopnea per hour (18 +/- 17, vs. 37 +/- 23 with placebo and 47 +/- 21 at base line; P<0.001), the number of episodes of central apnea per hour (6 +/- 14, vs. 26 +/- 21 and 26 +/- 20, respectively; P<0.001), and the percentage of total sleep time during which the arterial oxyhemoglobin saturation was less than 90 percent (6 +/- 11 percent, vs., 23 +/- 37 and 14 +/- 14 percent, respectively; P<0.04). There were no significant differences in the characteristics of sleep, the frequency of ventricular arrhythmias, daytime arterial-blood gas values, or the left ventricular ejection fraction during the base-line, placebo, and theophylline phases of the study. CONCLUSIONS: In patients with stable heart failure, oral theophylline therapy reduced the number of episodes of apnea and hypopnea and the duration of arterial oxyhemoglobin desaturation during sleep.

Cardiac Output↗

Project 2000 students' perceptions of their training.

This paper reports on the findings of a study conducted into the perceptions of final year Project 2000 pre-registration students towards their pre-registration education programme. The aim of the research was to discover how students perceive their training in terms of value, relevance, intellectual potency, teaching methods and organization. Data were collected using the Hoste scale which has been developed for the evaluation of educational courses. A convenience sample of students (n = 131) within one college of nursing were invited to participate. Findings include a particularly high level of satisfaction with Project 2000 in terms of value, breadth and relevance. Organization and liveliness of the course were perceived much less satisfactorily. There was a trend for a statistically significant difference between the mean scores of the theoretical and practical components of the course. The findings are discussed with particular reference to the perceptions of theory and practice within the educational programme.

Attitude↗

Occult sleep-disordered breathing in stable congestive heart failure.

OBJECTIVE: To determine the prevalence and effect of sleep-disordered breathing in ambulatory patients with stable, optimally treated congestive heart failure. DESIGN: A prospective, longitudinal study. SETTING: Referral sleep laboratory of a Department of Veterans Affairs medical center. PATIENTS: 42 of the 48 eligible patients with stable congestive heart failure and left ventricular systolic dysfunction (left ventricular ejection fraction < or = 45%). MEASUREMENTS: After an adaptation night, polysomnography and Holter monitoring were done in the sleep laboratory. Arterial blood gases and pH were measured, and cardiac radionuclide ventriculography and pulmonary, renal, and thyroid function tests were done. RESULTS: Patients were divided into two groups. Group I (n = 23) had an hourly rate of apnea and hypopnea (apnea-hypopnea index) of 20 episodes per hour or less; group II (n = 19 [45%; CI, 30% to 60%]) had an index of more than 20 episodes per hour. In group II, the index varied from 26.5 to 82.2 episodes per hour (mean +/- SD, 44 +/- 13 episodes per hour; CI, 38 to 51 episodes per hour). Group II had significantly more arousals (24 +/- 12 compared with 3 +/- 3 in group I) that were directly attributable to episodes of apnea and hypopnea, longer periods of time with an arterial oxyhemoglobin saturation of less than 90% (23% +/- 24% of total sleep time compared with 2% +/- 4%), lower arterial oxyhemoglobin saturation during sleep (74% +/- 13% compared with 87% +/- 4%), lower left ventricular ejection fraction (22% +/- 9% compared with 30% +/- 10%), and a significantly increased number of episodes of nocturnal ventricular arrhythmias. Multiple regression analyses showed that left ventricular systolic dysfunction was an independent risk factor for sleep apnea in patients with congestive heart failure. CONCLUSIONS: The prevalence of severe occult sleep-disordered breathing is high in ambulatory patients with stable, optimally treated chronic congestive heart failure. The breathing episodes are associated with severe nocturnal arterial blood oxyhemoglobin desaturation and excessive arousals. Severe untreated sleep-disordered breathing may adversely affect left ventricular function, resulting in a vicious cycle that could contribute to death in patients with congestive heart failure. Prospective, longitudinal studies on survival are needed.

Aged↗

Ependymal differentiation of a glioblastoma multiforme after heterotransplantation into nude mice.

A glioblastoma multiforme from a 64-year-old man was heterotransplanted sc into nude mice (nu/nu BALB/c out-bred). The subsequent growth of the transplanted tumor featured the appearance and eventual domination by cells with ependymal characteristics. This finding supports the view that the host's influence on heterotransplants may be substantial and should be considered when extrapolating the results of therapeutic trials on such animal models to the clinical situation. The view that ependymal cells and astrocytes share a common precursor is also partly supported by the observations.

Animals↗