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Biomedical subjects

J K Brown

Publications and source records attributed to J K Brown.

At least 19 recordsLinked to original sources
PubMed1992

Neurological outcome following neonatal post-haemorrhagic hydrocephalus: the effects of maximum raised intracranial pressure and ventriculo-peritoneal shunting.

UNLABELLED: The neuromotor outcome of 33 survivors of grade 3 or 4 neonatal post-haemorrhagic hydrocephalus born between 1975 and 1988 was assessed at a mean age of 4.7 years (9 months to 13 years). Two outcomes were determined: 12 patients were either normal (10 or had neurological signs without functional impairments (2), while 21/33 were moderately (16), severely (2), or profoundly impaired (3). Intracranial pressure (ICP) was measured in 26/33 patients (4-40 mm Hg): 2 had normal pressures (< 5.6 mm Hg) and were normal. Raised ICP was not significantly different between outcome groups. Twenty-seven children were shunted; 10/27 had five or more operations (up to 14) and all of these had abnormal neurological outcomes, whereas the number of children with 1-4 shunt procedures was equal in both outcome groups. The rise in morbidity after the fourth shunt procedure may be associated with the ventriculitis suffered by 9 of the 10 patients with more than four shunts (P < 0.01): this compares with 4/14 cases of ventriculitis in the children with 2-4 shunts and no cases of infection in the 3/27 who were shunted once. Outcome was independent of antenatal and perinatal factors including the age at or mode of presentation, and was unrelated to grade of intraventricular haemorrhage or parenchymal changes on ultrasound or CT scanning. CONCLUSION: for these small numbers, adverse outcome is statistically related to more than four shunt procedures and ventriculitis but independent of maximum ICP or other perinatal factors.

Birth Weight↗
PubMed1992

Peripheral and central mechanisms of hindfoot equinus in childhood hemiplegia.

A detailed clinical examination of 24 hemiplegic children at a mean age of 9.9 years showed that nine had an obligate toe-strike when walking at a self-selected speed and this was maintained throughout stance. None of the 24 children had a fixed equinus. No association could be found between this pattern of gait equinus and lower-limb atrophy, reduced ankle-joint range, muscle extensibilite, power of dorsiflexors and plantarflexors or actual muscle imbalance at the ankle joint. Gait equinus was independent of reduced compliance of the calf muscles, of a clinical diagnosis of tonic spasticity, of fine-motor dexterity of the toes, and of the side of the hemiplegia. Gait equinus cannot be explained merely in terms of a central paralytic foot-drop. A developmental model of equinus is advanced.

Ankle Joint↗
PubMed1992

Direct measurement of acetylcholine release in guinea pig trachea.

In this study, we applied high-performance liquid chromatography with electrochemical detection (HPLC-EC) to the measurement of acetylcholine (ACh) release from nerve endings in guinea pig tracheal smooth muscle. We also tested for muscarinic inhibitory regulation of ACh release in this species, which is widely used for studies of airway neural control. Clip-connected segments of the posterior membrane of the guinea pig trachea were mounted in organ baths between stimulating electrodes and incubated in Krebs-Henseleit buffer containing (in microM) 10 indomethacin, 1 neostigmine, 1 phentolamine, and 1 propranolol. To measure ACh, the bath was emptied and aliquots of buffer were injected directly into the HPLC-EC; the lower limit of detection was 1 pmol/200 microliters sample. Electrical field stimulation (EFS) at 5 Hz for 10 or 30 min increased ACh release from 1.8 +/- 1.4 (SE) to 6.2 +/- 1.3 pmol.mg protein-1.min-1 (n = 15). The effect of atropine was examined by comparing amounts of ACh released by EFS before and after exposure to either atropine (0.3 microM) or vehicle. Before atropine treatment, EFS-evoked ACh release was 4.9 +/- 0.6 pmol.mg protein-1.min-1; after atropine exposure, EFS-evoked release of ACh increased significantly to 15.0 +/- 2.2 pmol.mg protein-1.min-1 (n = 11; P less than 0.05). Corresponding values before and during exposure to vehicle were 9.3 +/- 4.4 and 10.7 +/- 4.7 pmol.mg protein-1.min-1, respectively. The ratios of the changes in EFS-evoked ACh release were 3.1 +/- 0.3 and 1.3 +/- 0.1 in atropine-treated and vehicle-treated groups, respectively (P less than 0.05). We conclude that HPLC-EC is a reliable and sensitive technique for the detection of EFS-evoked release of ACh from clip-connected segments of guinea pig tracheal smooth muscle.

Acetylcholine↗
PubMed1992

Oxygen may improve dyspnea and endurance in patients with chronic obstructive pulmonary disease and only mild hypoxemia.

Oxygen (O2) has been reported to improve exercise tolerance in some patients with chronic obstructive pulmonary disease (COPD) despite only mild resting hypoxemia (PaO2 greater than 60 mm Hg). To confirm these prior studies and evaluate potential mechanisms of benefit, we measured dyspnea scores by numeric rating scale during cycle ergometry endurance testing and correlated the severity of dyspnea with right ventricular systolic pressure (RVSP) measured by Doppler echocardiography during a separate supine incremental exercise test. Both sets of exercise were performed according to a randomized double-blind crossover protocol in which patients breathed compressed air or 40% O2. We studied 12 patients with severe COPD (FEV1 0.89 +/- 0.09 L [mean +/- SEM], FEV1/FVC 37 +/- 2%, DLCO 9.8 +/- 1.5 ml/min/mm Hg[47% of predicted], PaO2 71 +/- 2.6 mm Hg). With endurance testing on compressed air, PaO2 did not change significantly in the group as whole (postexercise PaO2 63 +/- 5.1 mm Hg, p = NS), but did fall to less than 55 mm Hg in four patients from this group. Duration of exercise increased on 40% O2 from 10.3 +/- 1.6 to 14.2 +/- 1.5 min (p = 0.005), and the rise in dyspnea scores was delayed. Oxygen delayed the rise in RVSP with incremental exercise in all patients and lowered the mean RVSP at maximum exercise from 71 +/- 8 to 64 +/- 7 mm Hg (p less than 0.03). Improvement in duration of exercise correlated with decrease in dyspnea (r2 = 0.66, p = 0.001) but not with decreases in heart rate, minute ventilation, or RVSP.(ABSTRACT TRUNCATED AT 250 WORDS)

Double-Blind Method↗
PubMed1992

Description of a prototype emission-transmission computed tomography imaging system.

We have developed a prototype imaging system that can perform simultaneous x-ray transmission CT and SPECT phantom studies. This system employs a 23-element high-purity-germanium detector array. The detector array is coupled to a collimator with septa angled toward the focal spot of an x-ray tube. During image acquisition, the x-ray fan beam and the detector array move synchronously along an arc pivoted at the x-ray source. Multiple projections are obtained by rotating the object, which is mounted at the center of rotation of the system. The detector array and electronics can count up to 10(6) cps/element with sufficient energy-resolution to discriminate between x-rays at 100-120 kVp and gamma rays from 99mTc. We have used this device to acquire x-ray CT and SPECT images of a three-dimensional Hoffman brain phantom. The emission and transmission images may be superimposed in order to localize the emission image on the transmission map.

Algorithms↗
PubMed1991

Chromosome arrangements in human fibroblasts at mitosis.

The positions of the centromeres of all 46 human chromosomes were analysed in three dimensional reconstructions of electron micrographs of 10 serially sectioned unpretreated human male fibroblast cells. The reconstructions show that the spatial positioning of the chromosomes during division is not random. The centromeres were arranged on a metaphase plate that was ellipsoidal and that tended to be flat. The distance of centromeres from the centre of the mitotic figure was correlated with chromosome size; small chromosomes tended to be central in all the metaphases. Large chromosomes were more peripheral, especially in cells that were more advanced in mitosis. Thus, there is a tendency for larger chromosomes to move outwards as metaphase advances. In many cells, the A group centromeres were overdispersed, whereas G group centromeres tended to be clustered. The acrocentric chromosomes (D and G groups) also tended to be clustered when analysed together, probably reflecting associations in nucleoli at the previous interphase. The results show that chromosome disposition is non-random and that it changes during division.

Chromosomes↗
PubMed1991

Interrelationships of liver and brain with special reference to Reye syndrome.

Reye syndrome is an acute non-inflammatory encephalopathy that can be precipitated by toxic, infective, metabolic or hypoxic upsets. The biochemical changes point to mitochondrial dysfunction and this is substantiated by structural changes in mitochondria on electron microscopy. The toxic metabolites that accumulate are similar to those incriminated in hepatic encephalopathy and other metabolic diseases. These metabolites exert their deleterious effects by direct neuronal damage, neurotransmitter blockade, vascular damage, cerebral oedema, hypoxic ischaemic damage, demyelination, retardation of brain growth and neuronal storage. Brain capillary endothelial cells are very rich in mitochondria and mitochondrial disorders can effect the central nervous system primarily, and not just as a consequence of systemic metabolic upset.

Animals↗
PubMed1991

Neurophysiology of lower-limb function in hemiplegic children.

Equinus in hemiplegic children is multifactorial. In some cases it is due to a short muscle, in others to simple foot-drop, tonic spasticity, rigidity, compensation for a short limb, fixed flexion contracture at the hip, dominantly inherited forefoot deformity, forefoot equinus secondary to chronic toe-walking, or abnormalities of the visco-elastic properties of the muscle, with true intramuscular contracture. This neurophysiological study confirms that hemiplegia in children is not a homogeneous condition. Some have tonic spasticity; some, although stiff, show electrical silence on stretching; some appear to have a short muscle, with no hypertonicity; and others have hypertonicity in relation to position (i.e. rigidity). A short muscle is not always associated with tonic spasticity with reciprocal inhibition. Weakness can occur without spasticity. Speed of movement of toes, ankle and hip is also significantly reduced.

Adolescent↗
PubMed1990

Receptors on airway gland cells.

Airway submucosal glands are by volume the most important source of macromolecules in airway secretions. These secretions, containing gel-forming mucins, antibacterial proteins, and antiproteases, comprise the major defensive barrier protecting the host against airborne pathogens. The identification of the mechanisms regulating secretion from the submucosal glands is key to understanding the genesis of this barrier and how it is altered by disease processes. Using a variety of methods, we and others have identified on the gland cells of several species receptors specific for ACh, norepinephrine, substance P, VIP, PGE1, PGE2, PGA1, PGD2, histamine and bradykinin. These receptors all participate in modulating the secretory activity of the airway submucosal glands. Studies of homogeneous cultures of bovine airway serous cells have yielded detailed information regarding the beta-adrenergic receptor on these cells. Using radioligand binding techniques, we found evidence for the presence of a single high affinity beta receptor of beta-2 subtype. Occupancy of this receptor by isoproterenol causes an elevation in the concentration of intracellular cAMP, which in turn stimulates the phosphorylation of a subset of cytoplasmic and membrane proteins. Based on the kinetics and pharmacology of these effects, it is likely that cAMP functions as a second messenger in the serous cell secretory pathway, probably acting through protein kinases. Current efforts are directed at identification of those phosphoproteins whose phosphorylation and dephosphorylation times are consistent with their possible roles in secretion.

Animals↗
PubMed1989

Neuro-developmental study of profoundly mentally handicapped children in hospital care.

Swedish estimates of the need for long-term intensive health care provision for profoundly mentally handicapped children were compared with an Edinburgh survey, and the neurodevelopment and health characteristics of Edinburgh children with profound mental handicap who required prolonged admission are described. The extent of their disabilities indicates the complexity of the task of designing alternatives to their present hospital provision which will adequately meet their health needs.

Abnormalities, Multiple↗
PubMed1989

Cerebrospinal fluid nucleotide metabolites following short febrile convulsions.

Cerebrospinal fluid (CSF) markers of cerebral energy depletion were measured in 32 infants and children following short (less than 10 minutes) febrile convulsions, and in 19 controls. Specific and sensitive indices of high-energy phosphate compound depletion (hypoxanthine, xanthine and uridine) showed no marked changes. Values for patients and febrile controls were significantly higher than for afebrile controls, which is consistent with increased cerebral metabolism in febrile patients. There were no differences in pH, lactate or creatine kinase levels in the CSF of patients and controls. The results suggest that short febrile convulsions are benign and that in the absence of risk factors for the subsequent development of epilepsy, prophylactic anticonvulsant treatment is not indicated.

Child Development↗
PubMed1989

Cerebrospinal fluid nucleotide metabolites following non-convulsive status epilepticus.

The authors studied specific and sensitive indicators of neuronal adenosine triphosphate (ATP) depletion--hypoxanthine, xanthine and uridine levels--in the cerebrospinal fluid (CSF) of nine children during non-convulsive status epilepticus. No evidence of ATP depletion was found and CSF pH and creatine kinase levels were similar to those of controls. Hypoxanthine, xanthine and uridine had a tendency to be low, but this was significant only for xanthine. The authors speculatively link this reduction to a reduction in neuronal protein synthesis. This might be a mechanism whereby non-convulsive status epilepticus could lead to intellectual deterioration and dementia.

Child↗