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Biomedical subjects

M J Peters

Publications and source records attributed to M J Peters.

At least 37 records · Page 2Linked to original sources
PubMed1999

Responses to median and tibial nerve stimulation in patients with chronic neuropathic pain.

Somatosensory evoked magnetic fields and electrical potentials were measured in eight patients with unilateral neuropathic pain. After median nerve stimulation on the painful side, the amplitudes of the evoked responses were enhanced 2 to 3 times at a latency of about 100 ms compared to the responses of the contralateral, unaffected side. After posterior tibial nerve stimulation an enhancement was found at latencies around 110 ms and 150 ms. The scalp distribution of the magnetic field at the latencies of "abnormal" responses was dipolar and the responses could be ascribed to a current dipole. Three (of the eight) patients underwent spinal cord stimulation (SCS) for their pain. The enhancement of the evoked responses to stimulation of the painful side decreased after spinal cord stimulation. After a long period of spinal cord stimulation only (e.g., a year) during which the patient reported to be pain free, these "abnormal" responses were no longer observed.

Accidents↗
PubMed1999

Circulating platelet-neutrophil complexes represent a subpopulation of activated neutrophils primed for adhesion, phagocytosis and intracellular killing.

Platelets play a prominent role in linking the processes of inflammation, haemostasis and thrombosis. Recent studies have shown that platelets form heterotypic aggregates with leucocytes via platelet CD62P and leucocyte beta2 integrins. These interactions have been observed in vitro in blood taken from healthy volunteers and in clinical conditions in which thrombosis and inflammation are prominent. This study investigated the properties of platelet-neutrophil complexes (PNCs) in anticoagulated whole blood. At rest, neutrophils in PNCs exhibit a significantly more activated adhesion molecule profile than free neutrophils with increased CD11b expression and activation (increased binding of the CD11b/CD18 'activation reporter' monoclonal antibody 24) and decreased CD62L expression. In addition, neutrophils in PNCs phagocytosed significantly more Neisseria meningitidis and produced more toxic oxygen metabolites than free neutrophils. Stimulation with the platelet agonist adenosine diphosphate (ADP) led to further increases in CD11b expression and activation, loss of CD62L as well as increased phagocytosis and toxic oxygen metabolite production throughout the whole neutrophil population. When these experiments were repeated with the CD62P blocking antibody G1 the effects were inhibited to a variable extent, dependent upon the parameter under investigation. These results indicate that both soluble and contact-dependent factors contribute to platelet-mediated neutrophil activation. Platelet neutrophil complexes represent a large subpopulation of neutrophils with a more activated adhesion molecule profile, and a greater capacity for phagocytosis and toxic oxygen metabolite production. This study provides further support for a role for PNCs in both health and disease.

Blood Platelets↗
PubMed1999

Single versus multiple doses of acetazolamide for metabolic alkalosis in critically ill medical patients: a randomized, double-blind trial.

OBJECTIVE: To compare two dosing regimens of acetazolamide for the reversal of metabolic alkalosis in mechanically ventilated patients with asthma or chronic obstructive pulmonary disease. DESIGN: A randomized, double-blind, placebo-controlled trial. SETTING: A 35-bed medical intensive care unit in a tertiary care teaching hospital. PATIENTS: Forty mechanically ventilated patients with a metabolic alkalosis (arterial pH > or = 7.48 and serum bicarbonate concentration > or = 26 mEq/L) resistant to fluid or potassium therapy (serum potassium concentration, > or = 4 mEq/L) not receiving acetazolamide or sodium bicarbonate in the previous 72 hrs. INTERVENTIONS: Stratified by previous diuretic use and randomized to receive intravenous administration of acetazolamide, one dose of 500 mg or 250 mg every 6 hrs for a total of four doses. MEASUREMENTS AND MAIN RESULTS: Serum bicarbonate and potassium concentrations were drawn every 6 hrs for 72 hrs, arterial blood gases were drawn every 12 hrs for 72 hrs, and both urine chloride and pH were drawn at hours 0, 6, 12, 18, 24, 48, and 72. By using generalized estimating equation techniques, no difference was found between the two dosing regimens at any point over the study period for serum bicarbonate, serum potassium, or urine chloride end points. Results did not differ between diuretic- and nondiuretic-treated patients. Serum bicarbonate concentrations remained significantly decreased in both treatment groups 72 hrs after administration of the first acetazolamide dose (31.8 +/- 4.9-25.3 +/- 3.8 mEq/L, p < .0001 [250 mg x 4]; 31.9 +/- 25.4-25.4 +/- 3.6 mEq/L, p < .0001 [500 mg x 1]). CONCLUSIONS: We conclude that a single 500-mg dose of acetazolamide reverses nonchloride responsive metabolic alkaloses in medical intensive care unit patients as effectively as multiple doses of 250 mg. Studies to examine the prolonged duration of action of acetazolamide observed in this study as well as the effect of acetazolamide on clinical end points, such as duration of mechanical ventilation, are warranted.

Acetazolamide↗
PubMed1998

The volume conductor may act as a temporal filter on the ECG and EEG.

The influence of the volume conductor on the EEG, MEG, fetal ECG and fetal MCG is studied by means of simulations. The assumption that the Maxwell equations can be used in a quasi-static approximation is reconsidered and the fact that the conductivity of human tissue is frequency dependent is taken into account. It is found that displacement currents have a substantial effect on the fetal ECG and to a lesser degree on the fetal MCG. Moreover, the frequency dependence of the conductivity of the tissues within the head may have a considerable effect on the EEG.

Electrocardiography↗
PubMed1998

Combined lung injury, meningitis and cerebral edema: how permissive can hypercapnia be?

We describe a patient with combined meningococcal septicemia and meningitis, cerebral edema and acute respiratory distress syndrome, in whom we balanced the conflicting carbon dioxide strategies for optimal pulmonary and neurological management using jugular oxygen saturation (SjvO2) monitoring to identify the upper limit of "tolerable" hypercapnia. Our observations suggest that significant acidosis was not well tolerated; however, cautious induction of pH down to 7.32 and an arterial carbon dioxide tension (PaCO2) < 5.9 kPa was tolerated acutely without significant cerebral hyperemia. Moreover, with the development of metabolic compensation and normal pH, higher levels of PaCO2 could be permitted. In similar cerebro-pulmonary circumstances we suggest that these findings warrant consideration. Alternatively, invasive monitoring of SjvO2 could be undertaken so that patient-specific criteria for permissive hypercapnia can be determined.

Acidosis, Respiratory↗
PubMed1998

Acute hypoxemic respiratory failure in children: case mix and the utility of respiratory severity indices.

OBJECTIVE: Acute hypoxemic respiratory failure (AHRF) is a common reason for emergency pediatric intensive care. An objective assessment of disease severity from acute physiological parameters would be of value in clinical practice and in the design of clinical trials. We hypothesised that there was a difference in the best early respiratory indices in those who died compared with those who survived. DESIGN: A prospective observational study of 118 consecutive AHRF admissions with data analysis incorporating all blood gases. SETTING: A pediatric intensive care unit in a national children's hospital. INTERVENTIONS: None. RESULTS: Mortality was 26/118, 22% (95 % confidence interval 18-26%). There were no significant differences in the best alveolar-arterial oxygen tension gradient (A-aDO2, torr), oxygenation index (OI), ventilation index (VI), or PaO2/FIO2 during the first 2 days of intensive care between the survivors and non-survivors. Only the mean airway pressure (MAP, cm H2O) used for supportive care was significantly different on days 0 and 1 (p < 0.05) with higher pressure being used in non-survivors. Multiple logistic regression analysis did not identify any gas exchange or ventilator parameter independently associated with mortality. Rather, all deaths were associated with coincident pathology or multi-organ system failure, or perceived treatment futility due to pre-existing diagnoses instead of unsupportable respiratory failure. When using previously published predictors of outcome (VI > 40 and OI > 40; A-aDO2 > 450 for 24 h; A-aDO2 > 470 or MAP > 23; or A-aDO2 > 420) the risk of mortality was overestimated significantly in the current population. CONCLUSION: The original hypothesis was refuted. It appears that the outcome of AHRF in present day pediatric critical care is principally related to the severity of associated pathology and now no longer solely to the severity of respiratory failure. Further studies in larger series are needed to confirm these findings.

Acute Disease↗
PubMed1998

Volume conduction effects in EEG and MEG.

Volume conductor models that are commonly used to describe the EEG and MEG neglect holes in the skull, lesions, the ventricles, and anisotropic conductivity of the skull. To determine the influence of these features, simulations were carried out using the finite element method. The simulations showed that a hole in the skull will have a large effect on the EEG, and as one of the consequences localisation errors up to 15 mm may occur. The effect on the MEG is negligible. The presence of a lesion may cause the shape and magnitude of the EEG and MEG to change. Hence, a lesion has to be taken into account, if the active neurones are close to it. Moreover, a localisation procedure may fail if the lesion is not included in the volume conductor model. Inclusion of the ventricles in the volume conductor model is necessary only if sources are in their vicinity or if their sizes are unusually large. Anisotropic conductivity of the skull has a smearing effect on the EEG but does not influence the MEG.

Algorithms↗
PubMed1998

Determining the number of independent sources of the EEG: a simulation study on information criteria.

The separation of signal and noise is an important problem in the analysis of EEG and MEG data. Furthermore, many source localisation strategies need the number of independent signal components as input parameter (e.g., dipole fit, multiple signal classification). Information criteria offer a relatively objective way to separate the space spanned by the principal components of the data covariance matrix into a signal and a noise part. Eighteen such criteria were extensively tested by simulations. They differ with respect to the statistical model of the data, the assumptions on the noise, and the correction term. In the simulations, different dipole sources were used to generate EEG, which was then distorted by Gaussian correlated or uncorrelated noise. The noise level, the accuracy of the noise covariance matrix used by the criteria, the numbers of channels and time samples, and the stochastic or deterministic nature of the source waveforms were varied. The performance of the criteria was very variable. For each criterion, limits for the noise level and the relative inaccuracy of the noise covariance matrix could be established. Taking more channels or time steps did increase the criteria's ability to tolerate noise, but at the same time, made them more vulnerable to inaccuracies in the (estimated) noise covariance matrices. Out of the eighteen criteria investigated, we recommend two criteria that are best suited for the cases of (1) high noise and accurate covariances and (2) low noise and less accurate covariances.

Artifacts↗
PubMed1998

Stress ulcer prophylaxis in medical ICU patients: annual utilization in relation to the incidence of endoscopically proven stress ulceration.

OBJECTIVE: To measure changes in the proportion of medical intensive care unit (MICU) patients prescribed pharmacologic stress ulcer prophylaxis therapy over a 4-year period in relation to the incidence of stress-related ulceration detected by endoscopy at our institution. DESIGN: Retrospective 4-year review of pharmacy and endoscopy databases. SETTING: A 35-bed MICU. PATIENTS: Patients (n = 2941) admitted to the MICU for longer than 24 hours, between January 1, 1993, and December 31, 1996, without acute gastrointestinal hemorrhage on admission. METHODS: Records were reviewed to identify patients prescribed pharmacologic stress ulcer prophylaxis (> 24 h of sucralfate or a histamine2-receptor antagonist [H2RA]), and patients with evidence of stress ulceration during endoscopy. RESULTS: The number of patients per year receiving stress ulcer prophylaxis significantly (p < 0.001) decreased between 1993 and 1996: 1993, 492/693 (71%); 1994, 478/798 (60%); 1995, 295/670 (44%); 1996, 164/780 (21%). There was no difference between years in the median duration of stress ulcer prophylaxis therapy or the proportion of patients receiving sucralfate versus H2RA therapy. There was no difference (p = 0.91) between years in the annual incidence of definite or possible stress-related ulceration: 1993, 6/693 (0.87%); 1994, 5/798 (0.63%); 1995, 6/670 (0.90%); 1996, 5/780 (0.64%). CONCLUSIONS: The incidence of endoscopically proven stress-related ulceration has remained unchanged over the past 4 years in our MICU despite significantly fewer patients receiving pharmacologic stress ulcer prophylaxis therapy.

Anti-Ulcer Agents↗
PubMed1997

Investigation of platelet-neutrophil interactions in whole blood by flow cytometry.

Evidence is increasing that platelets can initiate and propagate inflammatory processes by interacting with leucocytes and the vascular endothelium. Platelets have been shown to bind to neutrophils, existing as platelet/neutrophil complexes (PNC) within the circulation. We describe a simple flow cytometric method for assessing and investigating platelet interactions with neutrophils in small volumes of whole blood. Twenty-five percent (sd 6%) of circulating neutrophils from healthy adults were associated with platelets. Formation of these platelet-neutrophil complexes was CD62P (P-selectin) and divalent cation dependent. Platelet activation (with ADP or thrombin) caused a rapid and sustained rise in %PNC which differed from the pattern of free platelet activation as assessed by CD62P expression. F-met-leu-phe induced neutrophil activation but did not increase the percentage PNC. Platelet activation also caused increased neutrophil CD11b/CD18 expression which was most marked on neutrophils complexed with platelets. This straightforward technique is simple, reproducible, and allows assessment of platelet-neutrophil interactions and activation of neutrophils. It may also provide a method for estimating platelet activation in whole blood.

Adult↗
PubMed1996

Computation of neuromagnetic fields using finite-element method and Biot-Savart law.

The finite-element method in combination with the Biot-Savart law is described to compute the magnetic field distribution generated by a dipolar source within a homogeneous volume conductor of an arbitrary shape. In order to calculate the three independent components of the magnetic field outside the volume conductor by means of the Biot-Savart law, the distribution of the current throughout the medium is required. A finite-element mesh is constructed using four-node tetrahedral elements. The potential in each node is computed numerically by the finite-element method using the proper continuity conditions across the boundaries. The gradient of the potential denotes the current density within an element. The components of the magnetic induction are calculated by numerical integration, applying the current density within the tetrahedrons. Simulations are carried out to assess the numerical accuracy for a homogeneous spherical volume conductor. Errors of 3% can be obtained with a locally refined spherical mesh containing about 1000 nodes, for dipoles at any depth and any orientation. A homogeneous realistically shaped model with the shape of the inside of the skull is obtained from magnetic resonance images.

Biomedical Engineering↗
PubMed1995

Beta-adrenoceptor agonists interfere with glucocorticoid receptor DNA binding in rat lung.

Inhaled beta 2-adrenoceptor agonists are the most effective bronchodilator treatment in asthma, yet paradoxically high doses may be associated with increased asthma morbidity and mortality. Steroids are the most effective therapy in controlling asthmatic inflammation and act by binding to specific sequences of DNA (GRE), thus modulating gene transcription. We report that in rat lung, the beta 2-adrenoceptor agonists, salbutamol and fenoterol, decrease the binding of glucocorticoid receptors to GRE, by 46 +/- 4% although it has no effect on the affinity or number of glucocorticoid receptors. The inhibition of GRE binding by salbutamol is concentration-dependent, can be blocked by propranolol and is seen following forskolin treatment. This effect appears to be due to an interaction between the glucocorticoid receptor and the transcription factor, cAMP response element binding protein (CREB), which is activated by high concentrations of beta 2-adrenoceptor agonists. We suggest that by this mechanism high doses of inhaled beta 2-adrenoceptor agonists may inhibit the anti-inflammatory effects of endogenous glucocorticoids and exogenous corticosteroids used for asthma therapy.

Albuterol↗
PubMed1995

Differences in binding of glucocorticoid receptor to DNA in steroid-resistant asthma.

Although glucocorticosteroids are a very effective treatment for asthma and other chronic inflammatory diseases, a small proportion of patients are resistant to their therapeutic effects. The molecular mechanism for this steroid resistance is unclear. Steroid resistance cannot be explained by pharmacokinetic mechanisms, by a defect in the binding of steroids to glucocorticoid receptors, nor by defective nuclear translocation of this receptor, thereby suggesting that the molecular abnormality lies distal to nuclear translocation. We examined the ability of nuclear translocated glucocorticoid receptors to bind to their DNA binding sites (GRE) using electrophoretic mobility shift assays in PBMC from patients with steroid-sensitive and steroid-resistant asthma. The binding of the glucocorticoid receptor to DNA in these patients was also studied using Scatchard analysis. Dexamethasone induced a significant rapid and sustained twofold increase in GRE binding in PBMCs from steroid-sensitive asthmatic patients and nonasthmatic individuals, but this was markedly reduced in steroid-resistant asthmatic patients. Scatchard analysis of glucocorticoid receptor-GRE binding showed no change in binding affinity but did show a reduced number of receptors available for DNA binding in the steroid-resistant patients. These results suggest that the ability of the glucocorticoid receptor to bind to GRE is impaired in steroid-resistant patients because of a reduced number of receptors available for binding to DNA.

Adult↗
PubMed1995

Individually shaped volume conductor models of the head in EEG source localisation.

Inverse solution techniques based on electroencephalograph (EEG) measurements have become a powerful means of gaining knowledge about the functioning of the brain. A model of the head and a potential computation method are necessary to describe the EEG problem mathematically. The generation of realistically shaped three-compartment models of the head is discussed. The isolated problem approach for the boundary element method is applied to develop a fast and accurate numerical solution of the EEG forward problem. Accuracy studies with this approach show that dipole positions can be reconstructed within a distance of 3 mm from the original positions. Inverse simulations indicate that the incorporation of the individual head shape may significantly influence the reconstructed dipole position but not its magnitude and orientation, in comparison with the commonly used three-sphere model. However, the presence of noise in the simulated potential data affects the solutions based on realistically shaped models more than those of the simple three-sphere model. The increased sensitivity of the former models to noise in the data remains a serious drawback for their practical application to EEG source localisations.

Electroencephalography↗
PubMed1995

Cytomegalovirus retinitis in AIDS.

Cytomegalovirus retinitis is common in adults with AIDS but has been reported infrequently in children with perinatally acquired HIV infection. The cases are presented of two infants with vertically acquired HIV infection who developed disseminated cytomegalovirus infection and retinitis, and who posed difficult management issues.

Acquired Immunodeficiency Syndrome↗