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Biomedical subjects

D J Read

Publications and source records attributed to D J Read.

At least 37 records · Page 2Linked to original sources
PubMed1988

Distribution of substance P-immunoreactive structures in the developing cat carotid body.

The distribution of substance P immunoreactivity in the cat carotid body was examined at 4 different stages of development. Although substance P-immunoreactive fibers were present in the carotid body from before birth through to adulthood, glomus cells did not display substance P-immunoreactivity until the period between birth and 6 weeks postnatally. The time course of these morphological differences in substance P distribution in the cat carotid body parallel the maturational changes in the hypoxic ventilatory response, suggesting that substance P may play a role in these changes.

Aging↗
PubMed1988

High doses of soman protect against organophosphorus-induced delayed polyneuropathy but tabun does not.

Organophosphorus-induced delayed polyneuropathy (OPIDP) is thought to result from organophosphorylation of neuropathy target esterase (NTE; formerly known as neurotoxic esterase), followed by an "aging" of the phosphorylated NTE. Protection against OPIDP should thus be achieved by production of an inhibited but "nonaging" NTE. Inhibited NTE produced in vitro by interaction with any of the four resolved isomers of soman aged negligibly (M. K. Johnson, D. J. Read, and H. P. Benschop, 1985a, Biochem. Pharmacol., 34, 1945-1951). Therefore both unresolved soman and the most inhibitory isomer (C(-)P(+)) were tested in adult hens for effects on NTE and for ability to produce OPIDP. With improved prophylaxis and therapy of acute intoxication, birds survived greater than 100 X LD50 of unresolved soman and did not develop OPIDP. One day after dosing, about half of brain and spinal cord NTE was in an unmodified (unaged) inhibited form; at this time eight survivors were challenged with a neuropathic dose of diisopropyl phosphorofluoridate (DFP). No neuropathy developed in four out of eight birds and mild to moderate signs were seen in the other four. Nine challenge control birds receiving DFP after solvent all developed severe neuropathy. Partial protection was seen in three out of three birds dosed prior to DFP challenge with sufficient C(-)P(+) isomer of soman (1.2 mg/kg sc) to convert about half of the spinal cord NTE to unaged inhibited form. Protection was not related to cholinergic shock. Two birds which survived out of eight pretreated with tabun (12 mg/kg sc) had about as much NTE inhibited as after soman administration but it was all in the modified (aged) inhibited form; these birds were not protected against DFP-induced neuropathy. A limited histopathologic examination showed that typical neurodegenerative lesions were seen only in birds with clear clinical neuropathy.

Animals↗
PubMed1987

The influence of chirality on the delayed neuropathic potential of some organophosphorus esters: neuropathic and prophylactic effects of stereoisomeric esters of ethyl phenylphosphonic acid (EPN oxon and EPN) correlate with quantities of aged and unaged neuropathy target esterase in vivo.

Organophosphate-induced delayed polyneuropathy (OPIDP) is thought to result from organophosphorylation of neuropathy target esterase (NTE), followed by an "aging" of the phosphorylated NTE. Prophylactic against OPIDP should thus be achieved by production of an inhibited but "nonaging" NTE. Resolved stereoisomers of ethyl phenylphosphonic acid esters produce two forms of inhibited NTE; in vitro one form ages rapidly and the other only negligibly. The present study examined the in vivo effects of two preparations of incompletely resolved isomers of EPN oxon (ethyl 4-nitrophenyl phenylphosphonate) and its thionate on adult hen brain and spinal cord NTE and the relationship of inhibition and aging to the development of OPIDP. Single doses of the L-(-)-isomers (Preparation A, 7:3 proportion of isomers, or Preparation B, 9:1) caused severe neuropathy after doses which produced 70% aged inhibited NTE and mild effects after 50-60%. Single doses of the D-(+)-isomers produced either equal amounts of aged and unaged inhibited NTE (Preparation A) or predominantly unaged (Preparation B): the amount of aged was never more than 50% and no clinical OPIDP occurred. Doses of D-(+) which produced 50% unaged inhibited NTE were protective: challenge with the highly neuropathic phenyl saligenin cyclic phosphate did not cause OPIDP. All effects are consistent with the two-stage initiation process which requires both inhibition of NTE and subsequent modification of the protein by an "aging" process. Previously reported neuropathic effects of D-(+)-EPN probably reflect a substantial proportion of L-(-)-isomer present in the test material. Neuropathic studies with chiral OP esters should consider the possibility of production of protective unaged inhibited NTE in test animals.

Animals↗
PubMed1986

Influences of endogenous dopamine on carotid body discharge and ventilation.

Ventilatory and carotid body responses to hypoxia have been related to the endogenous release of dopamine by use of the antagonist drug haloperidol. The published studies have produced conflicting data for ventilation. However, antagonist drugs can act at multiple anatomical sites, on multiple pharmacological receptors, often at different dosages, and have nonspecific actions at high dosage. For these reasons, we have undertaken a systematic study of haloperidol dose-response curves with particular emphasis on the lowest possible concentrations of drug. In five cats anesthetized with pentobarbital sodium (30-35 mg/kg), single- or few-fiber afferent recordings of the carotid body showed that haloperidol increased the discharge during both basal and asphyxic conditions, the increments being proportional to haloperidol dosage (0.1-1,000 micrograms/kg). Increments of ventilation were also produced, these increments increasing only over the lower range of dosage; at the highest haloperidol dosage, the dose response showed a tendency to plateau or inflect downward, suggesting the appearance of an opposing inhibitory mechanism.

Animals↗
PubMed1985

Interaction of the four stereoisomers of soman (pinacolyl methylphosphonofluoridate) with acetylcholinesterase and neuropathy target esterase of hen brain.

Dilute solutions in cold dry ethyl acetate of 98-100% pure specimens of each of the four stereoisomers of soman were tested against enzymes in hen brain homogenate at 37 degrees and pH 8.0. Rate constants for progressive inhibition of acetylcholinesterase were 10(7)-10(8)/mole/min for both P(-) isomers and less than 10(5) for both P(+) isomers. All isomers inhibited neuropathy target esterase non-progressively to some degree. Rate constants for progressive inhibition of neuropathy target esterase were 2.7-3.8 X 10(5)/mole/min for C(-) P(+) and 2-6 X 10(4) for the others. Forced reactivation by KF was 90% initially and aging was slow in each case. Spontaneous reactivation of inhibited neuropathy target esterase was substantial during 18 hr for both P(-) isomers but not for P(+). By comparison of rate constants for the two enzymes we predict that pure P(+) isomers may cause delayed neuropathy in hens dosed at about unprotected LD50: prophylaxis and therapy against acute cholinergic effects would have to raise LD50 1000-fold before birds could tolerate potentially neuropathic doses of P(-) isomers.

Acetylcholinesterase↗
PubMed1985

Thiamine deficiency--a neglected problem of infants and mothers--possible relationships to sudden infant death syndrome.

An unexpectedly high incidence of biochemical thiamine deficiency (erythrocyte transketolase) was found in groups of mothers and infants, selected for apparent health from a westernized Caucasian community in Australia. Deficiency was common in mothers at term but not their infants, and in apparently healthy older infants but not their mothers. These findings can be explained by preferential delivery of thiamine to the fetus, at the expense of the pregnant mother; after delivery the mother recovers, and the infant becomes depleted. The incidence of thiamine deficiency was high in 'near-miss' sudden infant death syndrome (SIDS) infants and their mothers, and in siblings of SIDS. The thiamine deficient infants had a high familial incidence of SIDS deaths. These 'high risk families' might reflect poor nutrition or genetic defects of thiamine uptake and metabolism. Since apparently thriving infants with thiamine deficiency can sometimes die unexpectedly, thiamine status deserves more attention in clinical practice and research.

Adult↗
PubMed1984

Effects of naloxone on the hering-breuer apnea in sleeping kittens.

The modulatory role of endogenous opiates on the Hering -Breuer inflation reflex was examined in 11 newborn kittens, aged 10-31 days, during active and quite sleep. The Hering -Breuer apnea duration was significantly shortened by naloxone (1 mg/kg, intraperitoneally; P less than 0.05). This effect was abolished by 100% O2 breathing. The duration of apnea, and its shortening by naloxone, did not differ significantly in the two sleep states. Hering -Breuer apnea is a result of the inspiratory inhibition and expiratory excitation of medullary neurons in response to lung stretch; the apnea is terminated by the opposing influences of chemoreceptors, which respond to hypercapnia and hypoxia. The results suggest that opioid influences on the Hering -Breuer reflex are due to an opioid modulation of the carotid body discharge in hypoxia, or of its central integration, and that sleep state is not implicated in such modulation in kittens.

Animals↗
PubMed1983

Multiple causes of asphyxia in infants at high risk for sudden infant death.

A wide range of clinical findings was present in 58 near-miss sudden infant death syndrome (SIDS) infants and 6 surviving twins of SIDS siblings. Specific investigations included: studies of gastro-oesophageal reflux and aspiration (24-hour oesophageal pH recordings, barium swallow, radionuclide 'milk-scan'); polygraphic studies of breathing, reflux, and sleep state; studies of upper airways disease (lateral airways radiography and endoscopy); detection of seizure activity by electroencephalography; evaluation of thiamine status by erythrocyte transketolase activity of venous blood. Thiamine deficiency was found in 12 of 43 tested infants; 5 of the deficient infants had a familial history of SIDS. Many potential mechanisms for asphyxia were found: idiopathic central apnoea (7 infants), tracheal obstruction from minimal tracheomalacia or aberrant innominate artery (4 infants), temporal lobe or generalised seizures (6 infants), gastro-oesophageal reflux (55 infants) with intrapulmonary aspiration (11 infants). The high incidence, severity, and timing of reflux were new findings. Reflux occurred in active and indeterminate sleep, but not in quiet sleep. The depression of respiratory reflexes by active sleep stresses the vulnerability to asphyxia. Two factors suggest that near-miss episodes are related to SIDS: the similar age distribution but earlier occurrence of near-miss episodes compared with age at death of SIDS infants, and the subsequent sudden death of 2 infants whose necropsies were consistent with SIDS.

Age Factors↗
PubMed1983

Spinal cord stimulation in the United Kingdom.

All the medical, surgical and engineering personnel in the UK who have used spinal cord stimulation (SCS) in patients, attended a workshop to discuss their results. The major use of SCS has been for multiple sclerosis and intractable pain. It was concluded that the technique benefited up to two thirds of patients with bladder dysfunction, and that pain and possibly spasticity also responded to SCS, but other manifestations of multiple sclerosis did not. Further information on long term benefit is needed and the use of SCS in other conditions, such as spinal injury and peripheral vascular disease, is not yet established. SCS cannot be recommended for use outside large centres as x-ray screening, urodynamic and neurophysiological assessment facilities are required as well as biological engineering assistance.

Electric Stimulation Therapy↗
PubMed1983

Idiopathic hypercalcaemia of chronic dialysis.

Three women on different forms of maintenance dialysis developed persistent steroid-responsive idiopathic hypercalcaemia, with low calcium absorption, severe skeletal decalcification, multiple fractures, and severe clinical problems. Bone histology showed osteomalacia with suppression of osteoblast activity and no hyperparathyroidism. The disease persists at least six months after transplantation. The features are compatible with poisoning by a toxin with many similar properties to aluminium: we only found significant aluminium overload in one of these cases.

Adult↗
PubMed1983

Vibration sensory threshold: a guide to adequacy of dialysis?

The vibration sensory threshold (VST) is an easy non-invasive reproducible and sensitive bedside test of peripheral nerve function. It is impaired in pre-dialysis uraemic patients with no clinical evidence of peripheral neuropathy; tends to deteriorate during the first year of dialysis after which it remains relatively constant, and returns towards normal within one week of kidney allograft function. It is unrelated to type of dialysis, acetylator status, average serum creatinine values or serum aluminium. VST may be a valuable monitor of the adequacy of dialysis.

Female↗