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Biomedical subjects

R D Jones

Publications and source records attributed to R D Jones.

At least 55 records · Page 3Linked to original sources

Tenoxicam i.v. for major gynaecological surgery--effects on renal function.

Thirty women presenting for major gynaecological oncology surgery under a standardized, combined epidural/general anaesthetic technique received either placebo or tenoxicam 20 mg intravenously, in a randomized double-blinded manner prior to surgery. Plasma and urinary electrolytes, creatinine, prostaglandins PgE2 and PgF1 alpha, and thromboxane (TxB2) were collected 12 hours preoperatively and then for four days postoperatively. There were no significant differences in any of the measured parameters between the groups, at any of the measurement times. Mean (SD) creatinine clearance at baseline, 24 h and 48 h was 100.4 (29.7) and 86.9 (27.5), 128.1 (45.9) and 115.0 (40.3), 137.5 (50.7) and 121.6 (38.6) in the placebo and tenoxicam groups respectively (P = 0.28). Both groups required similar amounts of intraoperative ephedrine and intravenous fluids to maintain blood pressure. The minimal changes in plasma and renal parameters reflect predictable responses to major surgery and rehydration rather than any response to cyclooxygenase inhibition. This may underscore the importance of maintenance of blood pressure during the course of surgery and postoperative care, and perhaps the usefulness of a fluid loading regimen to preserve renal function during surgery. The predicted attenuation of renal prostaglandin-mediated protective mechanisms and enhancement of the catecholamine-mediated renal vasoconstriction by the use of a single 20 mg dose of tenoxicam in this study were not seen. Modulation of renal concentrating mechanisms or excretion of sodium and potassium by tenoxicam was not apparent and a large increase in study size would be required to detect a significant difference in these parameters as a consequence of the drug, over and above any changes in response to surgery and epidural anaesthesia.

Aged↗

The influence of "sputum-like gel" viscosity on crackle characteristics in a mechanically ventilated porcine lung model.

This study investigated the influence of airway secretion viscosity on the characteristics of crackle sounds produced using a mechanically ventilated porcine lung model. Aqueous ultrasonic methylene blue stained gel solutions of viscosity 100, 150 and 200 P were prepared and instilled into 15 isolated, mechanically ventilated, porcine lungs immersed in water. Sound signals recorded by a hydrophone before and after instillation of gel were subjected to both fast Fourier transform and wave-form analysis. At the completion of sound recording, the main bronchi were dissected and the location of the stained gel was photographically recorded. Wave-form analysis demonstrated that expiratory phase crackle incidence and amplitude were both significantly higher than inspiratory phase data. This study demonstrates that crackle duration and amplitude are inversely related to gel viscosity and that electronic lung sound analysis can provide indirect evidence of sputum viscosity.

Animals↗

Real-time detection of epileptiform activity in the EEG: a blinded clinical trial.

The aim of this study was to determine the performance of a PC-based system for real-time detection and topographical mapping of epileptiform activity (EA) in the EEG during routine clinical recordings. The system incorporates a mimetic stage to locate candidate spikes (including sharp-waves) followed by two expert-system-based stages, which utilize spatial and wide-temporal contextual information in deciding whether candidate events are epileptiform or not. The data comprised 521 consecutive routine clinical EEG recordings (173 hours). Performance was evaluated by comparison with three independent electroencephalographers (EEGers-I). A second group of two EEGers (EEGers-II) separately interpreted the spike topographical maps and, for EEGs categorized as containing only questionable EA by the detection system, reviewed 6 sec segments of raw EEG centered on each questionable event. Thirty-eight of the EEGs were considered to contain definite EA by at least two of EEGers-I. The false detection rate of the system was 0.41 per hour. The system was found to have a sensitivity of 76% and a selectivity of 41% for EEGs containing definite EA. However, it only missed detection of EA in 5% of the recordings. EEGers-II agreed with EEGers-I on the distribution (generalized, lateralized, focal, multifocal) of EA in 79% of cases. This is by far the largest clinical evaluation of computerized spike detection reported in the literature and the only one to apply this in routine clinical recordings. The false detection rate is the lowest ever reported, suggesting that this multi-stage rule-based system is a powerful and practical tool in clinical electroencephalography and long-term EEG monitoring.

Adolescent↗

Wavelet analysis of transient biomedical signals and its application to detection of epileptiform activity in the EEG.

Wavelet based signal analysis provides a powerful new means for the analysis of nonstationary signals such as the human EEG. The properties of the discrete wavelet transform are reviewed in illustrated application examples. The continuous wavelet transform is shown to provide better detection and representation of isolated transients. An approach to extract features of edges and transients from the continuous wavelet transform is outlined. Matching pursuit is presented as a more general transform method that covers both transients and oscillation spindles. A statistical model for the continuous wavelet transform of background EEG is found. A spike detection system based on this background model is presented. The performance of this detection system has been assessed in a preliminary clinical study of 11 EEG recordings containing epileptiform activity and shown to have a sensitivity of 84% and a selectivity of 12%. The spatial context of epileptiform activity will be incorporated to improve system performance.

Brain↗

Triclosan: a review of effectiveness and safety in health care settings.

Triclosan is a widely accepted antimicrobial ingredient because of its safety and antimicrobial efficacy. Triclosan is a unique antimicrobial well suited for use in the health care industry in which mildness is a necessity to protect the health care worker during repeated use and antimicrobial activity is a necessity to protect public health. Triclosan has demonstrated immediate, persistent, broad-spectrum antimicrobial effectiveness and utility in clinical health care settings. This review highlights the utility and effectiveness of a 1% triclosan formulation for use in high-risk, high-frequency handwashing.

Anti-Infective Agents, Local↗

Aging reduces the responsiveness of coronary arteries from male Wistar rats to the vasodilatory action of testosterone.

This study was performed to examine whether aging affects the vasodilatory effects of testosterone in the coronary arteries of male rats. Isolated coronary arteries from young mature (3-4 months) and elderly (22-26 months) male Wistar rats were studied in a wire myograph. Contractile function and endothelial function were assessed by measuring vasomotor responses to 10-100 mmol/l KCl, 0.1 mmol/l prostaglandin F(2alpha) (PGF(2alpha)) and 10 micromol/l acetylcholine. Sensitivity to the vasodilatory effects of testosterone was assessed by constructing dose-response curves to concentrations between 1 micromol/l and 1 mmol/l testosterone dissolved in water in vessels maximally preconstricted with PGF(2alpha). The compliance characteristics of each vessel and serum testosterone levels from each animal were measured. Histological sections of myocardium were examined for differences in coronary artery morphology. Vessels from elderly animals were significantly more resistant to the vasodilatory effects of testosterone than vessels from young animals (P=0.001 by analysis of covariance). Vessels from elderly animals were also significantly less compliant (7.32+/-0.43 microm/mN, compared with 10.99+/-1.52 microm/mN in young animals; P=0.011), and the levels of circulating testosterone in elderly animals were lower, but not significantly so (2.04+/-0.63 nmol/l compared with 3.88+/-1.7 nmol/l; P=0.32). Vessels from elderly animals were less contractile in response to KCl than those from young animals (P=0.004 by analysis of covariance). There were no significant differences between the two groups in their responses to PGF(2alpha) or acetylcholine. Thus it is concluded that coronary arteries from elderly rats are significantly less sensitive to the vasodilatory effects of testosterone than those from young animals.

Acetylcholine↗

The NADPH oxidase inhibitors iodonium diphenyl and cadmium sulphate inhibit hypoxic pulmonary vasoconstriction in isolated rat pulmonary arteries.

Interest surrounds the role of an NADPH oxidase-like enzyme in hypoxic pulmonary vasoconstriction (HPV). We have studied the effects of the NADPH oxidase inhibitors iodonium diphenyl (ID) and cadmium sulphate (CdSO4) upon HPV of isolated rat pulmonary arteries (n = 73, internal diameter 545 +/- 23 microm). Vessels were preconstricted with prostaglandin F2alpha (PGF2alpha, 0.5 or 5 microM) prior to a hypoxic challenge. ID (10 or 50 microM), CdSO4 (100 microM) or vehicle (50 microl) was added for 30 min before re-exposure to PGF2alpha and hypoxia. ID and CdSO4 significantly inhibited HPV. In vessels preconstricted with 5 microM PGF2alpha, ID (10 and 50 microM) reduced HPV from 37.4 +/- 5.6 % to 9.67 +/- 4.4 % of the contractile response elicited by 80 mM KCl (P<0.05) and from 30.1 +/- 5.0 % to 0.63 +/- 0.6% 80 mM KCl response (P<0.01), respectively. CdSO4 (100 microM) reduced HPV from 29.4 +/-4.0 % to 17.1 +/- 2.2% 80 mM KCl response (P<0.05). In vessels preconstricted with 0.5 microM PGF2alpha, ID (10 and 50 microM) reduced HPV from 16.0 +/- 3.15% to 3.36 +/- 1.44 % 80 mM KCl response (P<0.01) and from 15.0 +/- 1.67 % to 2.82 +/- 1.40 % 80 mM KCl response (P<0.001), respectively. Constriction to PGF2alpha was potentiated by ID. ID and CdSO4, at concentrations previously shown to inhibit neutrophil NADPH oxidase, attenuate HPV in isolated rat pulmonary arteries. This suggests that an NADPH oxidase-like enzyme is involved in HPV and could act as the pulmonary oxygen sensor.

Animals↗

The effect of the endothelin ET(A) receptor antagonist CI-1020 on hypoxic pulmonary vasoconstriction.

The mechanism of Hypoxic Pulmonary Vasoconstriction is unknown. The role of endothelin-1 in hypoxic pulmonary vasoconstriction was studied in precontracted small and large pulmonary arteries using the endothelin ETA receptor antagonist sodium-2-benzol [1,3]dioxol-5-yl-4-(4-methoxyphenyl)-4-oxo-3-(3,4,5-trimethoxy-ben zyl)-but-2-enoate (CI-1020). Small rat pulmonary arteries exhibit a mixed endothelin ETA receptor and endothelin ETB2 receptor population whereas large rat pulmonary arteries contain only endothelin ETA receptors. CI-1020 inhibited endothelin-1 in small vessels via endothelin ETA receptor blockade (1 and 10 microM) and at high concentrations via endothelin ETA receptor and endothelin ETB2 receptor blockade (100 microM). CI-1020 (0.01, 0.1 and 1 microM) inhibited endothelin-1 in large vessels via endothelin ETA receptor blockade alone. CI-1020 (1, 10 and 100 microM) significantly reduced hypoxic pulmonary vasoconstriction in small vessels, by -9.8+/-1.4, -9.2+/-2.3 and -8.0+/-1.7% 80 mM K+, respectively, compared to +2.5+/-4.2% with vehicle (P < 0.05). CI-1020 (0.01, 0.1 and 1 microM) had no significant effect upon hypoxic pulmonary vasoconstriction in large vessels. In small, but not large, pulmonary arteries hypoxic pulmonary vasoconstriction is due in part to the action of endothelin-1 at the endothelin ETA receptor.

Animals↗

Absence of neurovisual effects due to tissue and blood cholinesterase depression in a chronic disulfoton feeding study in dogs.

Technical grade disulfoton (DiSyston) was fed to Beagle dogs (four animals per sex and treatment level) at nominal concentrations of 0, 0.5, 4 and 12 ppm for 1 year. The purpose of this study was to characterize the potential general and neurovisual toxicity according to routine Environmental Protection Agency (EPA) guideline requirements, and by use of ancillary ocular and neurologic tests established in this Laboratory. Ophthalmological tests included: ocular tissue cholinesterase and histopathology, electroretinography (ERG), tracking, refractivity, intraocular pressure and pachymetry (corneal thickness) measurements. Neurological examinations included; peripheral and cranial reflex tests, task performance tests, gait and behavioral observations, and rectal temperature measurements. Plasma, erythrocyte and corneal cholinesterase were significantly depressed at 4 and 12 ppm in both sexes. Brain cholinesterase was depressed at 4 and 12 ppm in females. Retinal cholinesterase was depressed at 4 ppm in females and at 12 ppm in males. Ciliary body cholinesterase was depressed at 12 ppm in both sexes. Despite these cholinergic effects, there were no ophthalmologic findings in measurements of ERG, tracking, refractivity, intraocular pressure or pachymetry. There were no clinical neurology findings related to compound administration. We conclude that 0.5 ppm was a no-observable effect level (NOEL), and effects were limited to cholinesterase changes that had no detectable physiologic impact. This study demonstrates that special mechanistic investigations incorporated within guideline studies, enhances scientific integrity and can minimize the need for dedicated organ system studies.

Animals↗

The continuous measurement of cerebrospinal fluid gas tensions in critically ill neurosurgical patients: a prospective observational study.

OBJECTIVE: To determine the feasibility and usefulness of continuous cerebrospinal fluid pH and gas tension monitoring in critically ill neurosurgical patients. DESIGN: Prospective, observational study. SETTING: Neurosurgical intensive care unit in a teaching hospital. PATIENTS: Five critically ill neurosurgical patients (GCS < 8) requiring intensive care intracranial pressure monitoring and intermittent positive pressure ventilation. INTERVENTIONS: Placement of a Paratrend 7 sensor into the external ventricular drain. MEASUREMENTS AND MAIN RESULTS: The cerebrospinal fluid (CSF) pH, PCO2 and PO2 were recorded at 1-min intervals. Intracranial pressure (ICP) and cerebral perfusion pressure (CPP) were recorded at 15-min intervals. The mean baseline CSF pH, O2 and PO2 values were 7.28 +/- 0.08 pH units, 44 +/- 6 torr and 43 +/- 27 torr, respectively. The ranges of CSF pH, PCO2 and PO2 observed during the study were 6.3-7.8 pH units, 37-150 torr and 4-150 torr, respectively. A statistically significant correlation between ICP, CPP and CSF gas tensions occurred in patient 3. Significant changes in CSF PO2 and pH were observed with augmentation of CPP and preceded clinical improvement in patient 4. There were no complications attributable to sensor placement. CSF gas tensions and pH values obtained from patients 3 and 4 suggest that these measurements may be an indicator of cerebral perfusion. CONCLUSIONS: Continuous CSF gas tension measurements in critically ill patients are possible and may be an indicator of adequacy of cerebral perfusion. The relative merits and limitations of the technique are discussed.

Adult↗

Physical and biological properties of cationic triesters of phosphatidylcholine.

The properties of a new class of phospholipids, alkyl phosphocholine triesters, are described. These compounds were prepared from phosphatidylcholines through substitution of the phosphate oxygen by reaction with alkyl trifluoromethylsulfonates. Their unusual behavior is ascribed to their net positive charge and absence of intermolecular hydrogen bonding. The O-ethyl, unsaturated derivatives hydrated to generate large, unilamellar liposomes. The phase transition temperature of the saturated derivatives is very similar to that of the precursor phosphatidylcholine and quite insensitive to ionic strength. The dissociation of single molecules from bilayers is unusually facile, as revealed by the surface activity of aqueous liposome dispersions. Vesicles of cationic phospholipids fused with vesicles of anionic lipids. Liquid crystalline cationic phospholipids such as 1, 2-dioleoyl-sn-glycero-3-ethylphosphocholine triflate formed normal lipid bilayers in aqueous phases that interacted with short, linear DNA and supercoiled plasmid DNA to form a sandwich-structured complex in which bilayers were separated by strands of DNA. DNA in a 1:1 (mol) complex with cationic lipid was shielded from the aqueous phase, but was released by neutralizing the cationic charge with anionic lipid. DNA-lipid complexes transfected DNA into cells very effectively. Transfection efficiency depended upon the form of the lipid dispersion used to generate DNA-lipid complexes; in the case of the O-ethyl derivative described here, large vesicle preparations in the liquid crystalline phase were most effective.

3T3 Cells↗

Bacterial resistance and topical antimicrobial wash products.

Current scientific evidence has not shown that a link exists between the use of topical antimicrobial formulations and antiseptic or antibiotic resistance. As a result of the extensive history and varied use of antiseptic products and ingredients, any selective pressure for antibiotic resistance that may be occurring or may be uncovered in the future because of antiseptic use would be expected to be insignificant compared with the selective pressure because of antibiotic use. This review illustrates the effectiveness of topical antimicrobial wash products against antibiotic-resistant and antiseptic-resistant bacteria in use settings as well as the studies performed (antiseptic, deodorant, and oral care) demonstrating the lack of development of resistance in long-term clinical studies. Although these studies illustrate that the use of topical antimicrobial products have not been shown to play a role in the fluctuations of the specific composition or resistance of the skin flora, changes in skin flora have been shown to occur. Based on current knowledge, the benefit from use of topical antimicrobial wash products in combination with standard infection control and personal hygiene practices far outweighs the risk of increased antibiotic resistance.

Anti-Infective Agents, Local↗

Detection of epileptiform discharges in the EEG by a hybrid system comprising mimetic, self-organized artificial neural network, and fuzzy logic stages.

OBJECTIVE: A multi-stage system for automated detection of epileptiform activity in the EEG has been developed and tested on pre-recorded data from 43 patients. METHODS: The system is centred on the use of an artificial neural network, known as the self-organising feature map (SOFM), as a novel pattern classifier. The role of the SOFM is to assign a probability value to incoming candidate epileptiform discharges (on a single channel basis). The multi-stage detection system consists of three major stages: mimetic, SOFM, and fuzzy logic. Fuzzy logic is introduced in order to incorporate spatial contextual information in the detection process. Through fuzzy logic it has been possible to develop an approximate model of the spatial reasoning performed by the electroencephalographer. RESULTS: The system was trained on 35 epileptiform EEGs containing over 3000 epileptiform events and tested on a different set of eight EEGs containing 190 epileptiform events (including one normal EEG). Results show that the system has a sensitivity of 55.3% and a selectivity of 82% with a false detection rate of just over seven per hour. CONCLUSIONS: Based on these initial results the overall performance is favourable when compared with other leading systems in the literature. This encourages us to further test the system on a larger population base with the ultimate aim of introducing it into routine clinical use.

Adult↗

Effect of positioning on recorded lung sound intensities in subjects without pulmonary dysfunction.

BACKGROUND AND PURPOSE: Physical therapists often use positioning to assist in the reexpansion of collapsed lung segments. An increase in lung sound intensity on auscultation is considered indicative of lung expansion. This study was designed to examine whether clinical interpretation of auscultatory findings is warranted. SUBJECTS: The subjects (5 male, 6 female) were young physical therapist students without pulmonary dysfunction (mean age=20.4 years, mean height=166.3 cm, mean weight=57.5 kg). Subjects with lung disease were excluded because pulmonary pathology is difficult to standardize. METHODS: Lung sounds electronically recorded over the posterior chest wall of subjects in sitting and side-lying positions were compared. Measures included peak intensity, frequency at maximum power, and median frequency. RESULTS: In the sitting position, inspiratory sounds recorded over the left posterior chest wall were louder than those recorded on the right side. In the side-lying positions, the sound intensity recorded from the dependent chest wall was louder than that recorded from the nondependent chest wall. In side-lying positions, the upper hemithorax is "nondependent," and the side in contact with the bed is "dependent." Sound intensities recorded over both posterior chest walls in the sitting position were louder than those recorded over the same lung area in the nondependent side-lying position. There was no difference in the sound intensity recorded between the sitting and dependent side-lying postures. CONCLUSION AND DISCUSSION: When comparative auscultation of the chest wall is used by physical therapists to assess the adequacy of pulmonary ventilation, patient posture and regional differences in breath sound intensity can influence clinical interpretation.

Adult↗

Enhancement of deep epileptiform activity in the EEG via 3-D adaptive spatial filtering.

The detection of epileptiform discharges (ED's) in the electroencephalogram (EEG) is an important component in the diagnosis of epilepsy. However, when the epileptogenic source is located deep in the brain, the ED's at the scalp are often masked by more superficial, higher-amplitude EEG activity. A noninvasive technique which uses an adaptive "beamformer" spatial filter has been investigated for the enhancement of signals from deep sources in the brain suspected of containing ED's. A forward three-layer spherical model was used to relate a dipolar source to recorded signals to determine the beamformer's spatial response constraints. The beamformer adapts, using the least-mean-squares (LMS) algorithm, to reduce signals from sources distant to some arbitrarily defined location in the brain. The beamformer produces three outputs, being the orthogonal components of the signal estimated to have arisen at or near the assumed location. Simulations were performed by using the same forward model to superimpose realistic ED's on normal EEG recordings. The simulations show the beamformer's ability to enhance signals emanating from deep foci by way of an enhancement ratio (ER), being the improvement in signal-to-noise ratio (SNR) to that observed at any of the scalp electrodes. The performance of the beamformer has been evaluated for 1) the number of scalp electrodes, 2) the recording montage, 3) dependence on the background EEG, 4) dependence on magnitude, depth, and orientation of epileptogenic focus, and 5) sensitivity to inaccuracies in the estimated location of the focus. Results from the simulations show the beamformer's performance to be dependent on the number of electrodes and moderately sensitive to variations in the EEG background. Conversely, its performance appears to be largely independent of the amplitude and morphology of the ED. The dependence studies indicated that the beamformer's performance was moderately dependent on eccentricity with the ER increasing as the dipolar source and the beamformer were moved from the center to the surface of the brain (1.51-2.26 for radial dipoles and 1.17-2.69 for tangential dipoles). The beamformer was also moderately dependent on variations in polar or azimuthal angle for radial and tangential dipoles. Higher ER's tended to be seen for locations between electrode sites. The beamformer was more sensitive to inaccuracies in both polar and azimuthal location than depth of the dipolar source. For polar locations, an ER > 1.0 was achieved when the beamformer was located within +/- 25 degrees of a radial dipole and +/- 35 degrees of a tangential dipole. Similarly, angular ranges of +/- 37.5 degrees and +/- 45 degrees, respectively, for inaccuracies in azimuthal locations. Preliminary results from real EEG records, comprising 12 definite or questionable epileptiform events, from four patients, demonstrated the beamformer's ability to enhance these events by a mean 100% (52%-215%) for referential data and a mean 104% (50%-145%) for bipolar data.

Algorithms↗

Pseudo-Gaucher cells in myelodysplasia.

A case of myelodysplastic syndrome is reported, in which the bone marrow contained many cells with the typical light microscopic morphology of Gaucher cells. In the absence of any evidence of inherited Gaucher's disease, these cells are considered to be pseudo-Gaucher cells, which have been described previously in association with other haematological diseases. This is the first report of their occurrence in myelodysplastic syndrome.

Aged↗

Electrophysiology and pathology evaluation of the Yucatan pig as a non-rodent animal model for regulatory and mechanistic toxicology studies.

Six male and six female Yucatan pigs were utilized to investigate the feasibility of this species as a non-rodent model for routine regulatory and mechanistic toxicology studies. This study evaluated disease surveillance and computerized electrophysiology, along with possible gross and micropathology changes. Two pigs were used as sentinel animals to evaluate the microbiological status of the vendor upon arrival; the other pigs were maintained as biomonitors and to provide baseline clinical chemistry, urinalysis, pathology and electrophysiology data. The electrophysiology tests conducted included electrocardiography (ECG), electroretinography (ERG) and quantitative electroencephalography (qEEG), which achieved consistent baseline values with acceptable intrasubject variation. Tissue cholinesterase and histochemical staining were done to determine their suitability for testing cholinesterase compounds. Evaluation of the serum chemistry profile demonstrated increased CPK and LDH, which was likely associated with slight haemolysis or minor subclinical muscle stress during handling. There were no additional clinical chemistry changes or findings in haematology, urinalysis parameters or gross pathology. Micropathology found an absence of background lesions which would interfere with routine toxicology studies, except for a mild rhinitis. The aetiological agent was identified by electron microscopy as being consistent with inclusion body rhinitis of swine, previously unreported in miniature swine. This would most notably interfere with inhalation studies. The anatomical and physiological similarities of the Yucatan pig, along with its ability to accept the performance of electrophysiology tests allow this species to be considered as a suitable model for organ system testing in toxicology studies.

Animals↗