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Biomedical subjects

M J Peters

Publications and source records attributed to M J Peters.

At least 19 recordsLinked to original sources
PubMed1992

Effects of inhalation of N-formyl-methionyl-leucyl-phenylalanine in the well elderly and in patients with chronic bronchitis.

BACKGROUND: Inhalation of the bacterial peptide N-formyl-methionyl-leucyl-phenylalanine (FMLP) produces bronchoconstriction in normal subjects. FMLP thus has a putative role as a mediator of bronchoconstriction associated with bacterial bronchial infection. METHODS: The effects of FMLP inhalation were examined in ten subjects with a history of chronic bronchitis and ten age matched control subjects. Each subject inhaled FMLP doses from 0.025 to 0.8 mumol to determine the provocative dose of FMLP causing a 20% fall in FEV1(PD20FMLP). FEV1 was recorded every five minutes after the final FMLP inhalation until it had returned to 95% of baseline FEV1 or 60 minutes had elapsed. The time to return to 95% baseline FEV1 was recorded or extrapolated from the recovery curve as an index of rapidity of recovery. Total and differential white cell counts were performed on each subject at baseline and five and 15 minutes after the final FMLP inhalation. RESULTS: The geometric mean PD20 FMLP in the patients with chronic bronchitis was 0.06 mumol (95% confidence interval 0.015-0.26), which was significantly lower than that in the control subjects (0.21 mumol (0.02-1.9)). PD20 FMLP in the patients with chronic bronchitis but not age matched controls (p = 0.35) was lower than that found previously in young normal subjects (0.35 mumol (0.07-1.8). The return to 95% baseline FEV1 occurred after 86(10) minutes in subjects with chronic bronchitis and in 81(23) minutes in their age matched controls, in both cases being much slower than that seen in young subjects (29(9) minutes). CONCLUSION: Patients with chronic bronchitis may be especially susceptible to formyl peptides elaborated by bacteria during bacterial bronchial infection.

Administration, Inhalation↗
PubMed1992

Haematological effects of inhalation of N-formyl-methionyl-leucyl-phenylalanine in man.

BACKGROUND: N-Formyl-methionyl-leucyl-phenylalanine (FMLP) is a bacterial oligopeptide which stimulates neutrophil chemotaxis, degranulation and superoxide generation. Inhalation of FMLP produces bronchoconstriction in man; in the rabbit this is in part neutrophil dependent. The effects of inhalation of FMLP on peripheral blood leucocytes in normal subjects has been studied. METHODS: This was an open study in non-asthmatic subjects. Change in total peripheral white cell count were studied for 15 minutes after inhalation of 0.4 mumol FMLP in six subjects. Change in total and differential white cell count and spontaneous neutrophil chemiluminescence were then studied five and 30 minutes after inhalation of 0.4 mumol FMLP (n = 7) or diluent (n = 4). Finally, leucocytes from three subjects were labelled ex vivo with technetium-99m labelled sulphur colloid and reinfused. The effect of inhalation of FMLP or diluent on pulmonary neutrophil flux was studied by continuous gamma scanning of a pulmonary window. RESULTS: Leucopenia occurs rapidly after inhalation of FMLP, the nadir of the white cell count (53% of baseline) occurring at four minutes. This was followed by a rebound increase in white cell count evident at 15 minutes (154% of baseline). Five minutes after inhalation of 0.4 mumol FMLP, neutropenia (17% of baseline) and monocytopenia (40% of baseline) were seen followed again by a neutrophilia (213% of baseline at 30 minutes). The eosinophil count was significantly reduced at 30 minutes (24% of baseline). Neutrophil chemiluminescence was elevated (186% of baseline) at the time of the neutropenia. There was no influx of labelled cells to the lung during the period of neutropenia. CONCLUSION: FMLP inhalation activates circulating leucocytes. In vivo production of FMLP in the airway could contribute to bronchial inflammation during bacterial infection.

Administration, Inhalation↗
PubMed1991

Source localization of EEG versus MEG: empirical comparison using visually evoked responses and theoretical considerations.

Theoretically, the information we can obtain about the functional localization of a source of brain activity from the scalp, for instance evoked by a sensory stimulus, is the same whether one uses EEG or MEG recordings. However, the nature of the sources and, especially of the volume conductor, poses constraints such that appreciable differences between both types of data may exist. We present here empirical and theoretical data that illustrate which are the main constraints and to what extent they may affect electric potential and magnetic field maps. The empirical data consists of visual evoked potential and magnetic fields to the appearance of a checkerboard pattern (half-visual field stimulation). The concept of equivalent dipole is presented and its limitations are discussed. It is considered that the concept of equivalent dipole (ED) yields only an approximate description of the activity of a patch of cortex. A main difference between EEG and MEG recordings is the fact that radially oriented dipoles can hardly be seen in the MEG in contrast with the EEG. Accordingly, a weak tangential dipole component is difficult to distinguish in the EEG if a strong radial component is also present. However, a combination of both methods can give useful complementary information in such cases. A factor that influences largely such differences is the model of volume conductor used. A four concentric spheres model, as commonly used for solving the inverse problem of source localization, causes appreciable errors when EEG data are used but much less in case of the MEG. The use of a model consisting of eccentric spheres fitting the four compartments, brain, CSF, skull and scalp, provides a better approximation of the real geometry of the head and allows to obtain comparable results for visual evoked potentials and magnetic fields. It is emphasized that for precise localization of EDs, especially based on EEG recordings, a realistic model of the different compartments of the head is necessary. The latter must be tailor made to a given subject using MRI-scans, in view of the large variability in head geometry between subjects.

Adult↗
PubMed1991

The use of the asymptotic expansion to speed up the computation of a series of spherical harmonics.

When a function is expressed as an infinite series of spherical harmonics the convergence can be accelerated by subtracting its asymptotic expansion and adding it in analytically closed form. In the present article this technique is applied to two biophysical cases: to the potential distribution in a spherically symmetric volume conductor and to the covariance matrix of biomagnetic measurements.

Brain↗
PubMed1991

Effect of neutral endopeptidase inhibition of f-Met-Leu-Phe-induced bronchoconstriction in the rabbit.

Inhalation of f-Met-Leu-Phe (FMLP) produces dose-dependent increases in pulmonary resistance (RL) in rabbits. We hypothesized that inhibition of neutral endopeptidase (NEP), which has high affinity for FMLP, would augment the response to FMLP inhalation. We found the increase in RL above baseline in response to FMLP to be reduced from 56 +/- 18 to 8 +/- 10% (P less than 0.01) by phosphoramidon (1 mg/kg) and to 15 +/- 6% (P less than 0.02) by thiorphan (3 mg/kg). The geometric mean dose of FMLP producing a 20% rise in RL (PC20RL FMLP) was increased by phosphoramidon from 1.1 to 4.5 mg/ml (P less than 0.05). Enkephalins, which are also NEP substrates, modulate cholinergic neurotransmission in the airway. Inhibition of the FMLP response by phosphoramidon was reversed by coadministration of naloxone (0.1 mg/kg); after atropine (2 mg/kg) the change in RL in response to FMLP was reduced to 7 +/- 4% (P less than 0.01), whereas morphine (0.15 mg/kg) increased PC20RL FMLP to 5.1 mg/ml (P less than 0.05). FMLP-induced bronchoconstriction in the rabbit is vagally mediated, and reduced responses after NEP inhibition may reflect modulation of cholinergic bronchoconstriction by enkephalins. Changes in airway NEP activity may influence the activity of a wide range of its substrates, of which some are bronchoconstrictors and others bronchodilators.

Airway Resistance↗
PubMed1991

Effects of prolonged inhalation of N-formyl-methionyl-leucyl-phenylalanine in rabbits.

On the basis of its potent proinflammatory and spasmogenic effects, N-formyl-methionyl-leucyl-phenylalanine (FMLP), a bacterial oligopeptide, is a putative mediator of bronchoconstriction and airway inflammation during bacterial bronchial infection. However, after an FMLP dose-response curve in rabbits, tachyphylaxis to a second challenge was seen in some rabbits and airway inflammation was absent. This study was designed to reproduce the more prolonged airway exposure to FMLP that may occur during bacterial infection. Two groups of rabbits received FMLP [5 mg/ml in 66% dimethyl sulfoxide- (DMSO) saline] or DMSO diluent alone by nebulization every 15 min for 2 h. Pulmonary resistance (RL) was measured at 1 and 2 h. Recovery from bronchoconstriction was also assessed by measuring RL every 30 min for 2 h after the final FMLP administration. Sections of trachea and large bronchi were prepared and graded by quadrant from 0 to 3 for inflammation, a total score from 0 to 12 being given for each section. There was a progressive increase in RL in FMLP-treated rabbits, reaching 68 +/- 9% above baseline after 120 min, a significantly greater change than after diluent, 8 +/- 12% (P less than 0.01). RL remained elevated above baseline for 90 min after the final FMLP dose. Inflammation scores were greater after FMLP than DMSO: 9.3 +/- 0.5 vs. 4.3 +/- 0.7 (P less than 0.01) in trachea and 5.2 +/- 0.4 vs. 1.7 +/- 0.5 (P less than 0.01) in lobar bronchi. We conclude that prolonged exposure of airways to FMLP produces a sustained increase in RL and airway inflammation, the cardinal features of infective exacerbations of chronic airflow limitation.

Administration, Inhalation↗
PubMed1991

The influence of model parameters on the inverse solution based on MEGs and EEGs.

The influence of parameters describing the head on the localization of two simultaneous active dipoles is studied. The head is described by a set of five concentric anisotropic spheres. The uncertainties in the conductivity parameters and their effects on the dipole parameters are discussed. Finally the applicability of EEG and MEG is compared.

Adult↗
PubMed1990

Sarcoidosis presenting as recurrent alcohol-induced pancreatitis.

A previously well 27-year-old Caucasian woman presented with five episodes of alcohol-induced abdominal pain over two years culminating in severe acute pancreatitis. Chest x-ray showed bilateral hilar lymphadenopathy and nodular pulmonary infiltrates. In hospital she developed a unilateral facial nerve palsy and other features of sarcoidosis, which was confirmed by biopsy of a pretracheal lymph node. No previous case is reported of sarcoidosis presenting with recurrent pancreatitis apparently induced on each occasion by moderate alcohol consumption and in the absence of other risk factors. Pancreatic involvement as part of sarcoidosis is uncommon but is treatable if recognized and has a good prognosis.

Adult↗
PubMed1989

On the numerical accuracy of the boundary element method.

The numerical accuracy of the boundary element (BE) method used to solve the volume conduction problem of nested compartments, each having a homogeneous conductivity, is studied. The following techniques for improving this accuracy are discussed: the handling of the auto solid angle element omega ii, the overall refinement of the level of discreteness, the use of a locally refined discrete grid, the isolated problem approach, and an adaptive refined computation of the discrete surface integrals involved in the BE method. The effects of these techniques on the numerical accuracy of the computed electrical potentials are illustrated by taking a volume conductor consisting of four concentric spheres representing the head since for this model an analytical (exact) solution is available. The techniques are of importance for numerically computed electroencephalograms (EEG's) since the numerically computed surface EEG's are severely affected by the relatively low conductivity of the compartment representing the skull.

Brain↗
PubMed1989

Comparison of STIR and spin-echo MR imaging at 1.5 T in 90 lesions of the chest, liver, and pelvis.

Short TI inversion recovery (STIR) produces both fat suppression and the additive effect of T1 and T2 mechanisms on tissue brightening, in contrast to the subtractive effect of these two mechanisms on spin-echo sequences. In order to compare STIR and spin-echo imaging, we reviewed 90 lesions detected in 76 consecutive MR studies of the chest, liver, or pelvis performed at 1.5 T with both STIR and double-echo spin-echo techniques. Images were compared for the number of individual lesions detected. Lesion conspicuity was scored by using a subjective scale for each sequence. Lesion size was measured with hand-held calipers, and volume was calculated assuming a prolate ellipse. Because of inherent error in such calculations, lesions were judged to be similar in size (within 20%) or dissimilar (more than 20% difference). The presence of a lesion was proved by direct biopsy in 36 (40%), by tissue pathology from some other focus plus follow-up of the lesion in 37 (41%), or by other imaging plus follow-up in 12 (13%). STIR images detected five (6%) more lesions than spin echo and did not miss any of the lesions detected by spin echo. Conspicuity was greater on STIR images than on spin-echo images in 82 (91%) of the lesions. Twenty-six (29%) of the lesions appeared larger on STIR images than on spin-echo images. For these reasons, STIR may be a useful adjunct to spin echo for body MR in some cases. However, STIR images typically display lower signal-to-noise than spin-echo images do, and all abnormalities (tumor or edema) may appear equally bright on STIR.

Adolescent↗
PubMed1989

The effect of anticholinergic and beta-agonist pretreatment on bronchoconstriction induced by N-formyl-methionyl-leucyl-phenylalanine.

N-Formyl-methionyl-leucyl-phenylalanine (FMLP), an acylated tripeptide bacterial neutrophil chemotactic factor, has been shown to be a bronchoconstrictor by inhalation in man in vivo. It thus has a putative role in the generation of bronchoconstriction associated with bacterial bronchial infection. We have investigated the effect of pretreatment with the anticholinergic agent, ipratropium bromide (IB), and the beta 2-agonist, fenoterol (F), on FMLP-induced bronchoconstriction. Ten non-asthmatic subjects aged 21-28 yrs performed dose-response curves to nebulized FMLP on 3 study days after pretreatment with saline, F or IB. Amongst the 8 subjects who bronchoconstricted by 20% to FMLP there was a significant increase in the provocative concentration causing a 20% fall in forced expiratory volume in one second (FEV1) (PC20FMLP) after both IB and F. F was significantly better than IB. When comparison was made using absolute fall in FEV1 and including all 10 subjects the same results were found. Partial inhibition of FMLP-induced bronchoconstriction by IB suggests that part of the effect of FMLP is vagally mediated. We suggest that F is acting via modulation of FMLP-induced rises in intracellular free calcium.

Adult↗
PubMed1988

Effect of inhaled formyl-methionyl-leucyl-phenylalanine on airway function.

Formyl-methionyl-leucyl-phenylalanine (FMLP), a synthetic, acylated tripeptide analogous to bacterial chemotactic factors, has been shown to cause bronchoconstriction in guinea pig, rabbit, and human airways in vitro. To determine whether FMLP causes bronchoconstriction in man in vivo, a preliminary study was undertaken in which five non-smokers (mean age 35 years, FEV1 94% (SEM 5%) predicted) and five smokers (mean age 34 years, FEV1 93% (6%) predicted) inhaled aerosols of FMLP. None of the subjects showed airway hyperresponsiveness to histamine (the provocative concentrations of histamine causing a fall of greater than or equal to 20% in FEV1 (PC20) were over 8 mg/ml). FMLP dissolved in 50% dimethylsulphoxide and 50% saline in concentrations of 0, 0.06, 0.12, 0.25, 0.5, 1.0, 2.0, and 4.0 mg/ml was administered to the subjects by means of a French-Rosenthal dosimeter, FEV1 being recorded after inhalation of each concentration. Dose dependent falls in FEV1 occurred in five non-smokers (geometric mean 1.76, 95% confidence limits 0.87-3.53 mg/ml) and three smokers (0.23, 0.07-0.78 mg/ml), with two smokers not responding by 20% to the highest concentration of FMLP. On a separate day the FMLP dose-response curves were repeated after nebulisation of 500 micrograms of ipratropium bromide. The PC20 FMLP in the responders more than doubled. In six additional normal subjects a histamine inhalation test was performed before and four and 24 hours after inhalation of FMLP. All subjects remained unresponsive to histamine. These results show that FMLP is a potent bronchoconstrictor in some non-asthmatic individuals in vivo and this may be important in bronchoconstriction related to infection in patients with chronic obstructive lung disease.

Adult↗
PubMed1987

On the magnetic field distribution generated by a dipolar current source situated in a realistically shaped compartment model of the head.

The magnetic field distribution around the head is simulated using a realistically shaped compartment model of the head. The model is based on magnetic resonance images. The 3 compartments describe the brain, the skull and the scalp. The source is represented by a current dipole situated in the visual cortex. The magnetic field distribution due to the source and that due to the volume currents are calculated separately. The simulations are carried out in order to ascertain which matrix of grid points is suitable as a measuring grid. The possibilities studied are grid points situated in a plane, in a surface which follows the contours of the head and in a sphere. This sphere is taken concentric to the sphere which is the best possible fit for the head. Taking into account the relative contribution of the volume currents and the possible accuracy in the positioning of the magnetic field detector, it can be concluded that the best choice is to measure the normal component of the magnetic field at points which are situated in the spherical surface. The results of this study also show that the magnetic field distribution based on a realistically shaped compartment model differs from that based on a compartment model consisting of concentric spheres. In the spherical model of the head no contribution of the volume currents to the component of the field normal to the sphere can be expected. The difference between the results obtained with these two volume conductor models increases with source depth.

Brain↗