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Biomedical subjects

M A Lynch

Publications and source records attributed to M A Lynch.

At least 127 records · Page 7Linked to original sources

Enhanced [3H]-noradrenaline release in synaptosomes from ethanol-tolerant animals: the role of nerve terminal calcium ion concentrations.

Cortical slices from brains of ethanol-tolerant rats have previously been shown to release a greater fraction of uptake [3H]-noradrenaline ([3H]-NA) on K+-depolarisation than slices from control animals. In the present experiments, when stimulated with the Ca2+ ionophore A23187 (30 microM), untreated cortical synaptosomes release only a very small fraction of uptaken [3H]-NA. Under these conditions synaptosomal preparations from ethanol-tolerant animals released a greater fraction of uptaken [3H]-NA but the difference was not significant. However, after incubation with ouabain (100 microM, to increase intrasynaptosomal [Ca2+]) A23187 now produced a much greater enhancement of [3H]-NA release in preparations from ethanol-tolerant rats. Further, after superfusion of the synaptosomal preparation with 1mM EGTA and A23187 for 30 min (a procedure which should reduce intrasynaptosomal [Ca2+]) the reintroduction of Ca2+ to the superfusing fluid caused a marked release of [3H]-NA which was also significantly greater in preparations from ethanol-tolerant animals. Ca2+/Mg2+-ATPase activity was also higher in these synaptosomes but no difference could be detected in the release of [3H]-NA from a combined synaptic vesicle: synaptic plasma membrane preparation. The results suggest that the development of ethanol tolerance is associated with a fundamental change in the dynamic control of Ca2+ concentrations within the nerve terminal which potentiates the depolarisation-induced release of neurotransmitters.

Alcoholism↗

Current concepts of meniscal function and pathology.

The advantages of preserving the menisci are reduced degenerative changes and improved stability. At long-term follow-up, even arthroscopic partial meniscectomy in the anterior cruciate ligament-deficient knee results in more than twice the incidence of Fairbank's changes compared with a normal meniscus, stable meniscus tears left alone, or meniscus repair.

Biomechanical Phenomena↗

Is there a link between cot death and child abuse?

Forty five babies delivered in Oxford obstetric units who subsequently died unexpectedly in infancy were compared with 134 controls matched for maternal age, social class, parity, and year of birth to see whether five factors identified in an earlier study as predictive of subsequent child abuse would also predict the sudden infant death syndrome. Epidemiological findings had suggested certain similarities between the two events. In contrast with babies who were abused, four of the five factors did not distinguish between babies who died suddenly and unexpectedly and their controls, but there was a slight increase in the proportion of mothers of babies who died suddenly and unexpectedly for whom nursing staff thought that support and advice on feeding the baby were needed. Factors predictive of child abuse did not predict sudden infant death in this study.

Affective Symptoms↗

Interactions of ethanol with ionophore A23187 in human platelets and erythrocytes and in rat brain slices.

The aggregation of gel-filtered human platelets induced by A23187 is very sensitive to inhibition by ethanol. Similarly when platelets preloaded with [3H]5-hydroxytryptamine ([3H]5HT) are studied in a superfusion system under conditions where aggregation is likely (high platelet density, presence of Ca2+) the rate of release of [3H]5HT induced by A23187 is reduced by the presence of ethanol. However when platelet aggregation is less likely (low platelet density, absence of Ca2+) ethanol does not reduce the rate of [3H]5HT efflux induced by A23187 in superfused platelets. In addition, in contrast to the effects of ethanol on platelet aggregation, the transformation of human red cells to echinocytes induced by A23187 is accelerated by the presence of ethanol. Similarly the increased efflux of 3H from superfused rat striatal slices preloaded with [3H]dopamine which is produced by A23187 is potentiated by ethanol. It is concluded that the inhibitory effect of ethanol on the action of A23187 may be confined to platelet aggregation. This may be because the mechanisms of action of either A23187 or ethanol on platelet aggregation differ from those on other cell functions.

Animals↗

Picrotoxin inhibits the effect of ethanol on the spontaneous efflux of [3H]-dopamine from superfused slices of rat corpus striatum.

The presence of ethanol, 100 microM, in the superfusate enhanced the spontaneous release of previously uptaken [3H]-dopamine from slices of rat corpus striatum, but produced a small inhibition of K+-stimulated release. The concomitant presence of picrotoxin, 10 microM, in the superfusate prevented the enhancement of spontaneous release of [3H]-dopamine by ethanol with equivocal effects on K+-stimulated release. When present in the superfusate alone picrotoxin had no effect on [3H]-dopamine release.

Animals↗

Comparison of effects of ethanol on platelet function and synaptic transmission.

Ethanol, at concentrations tolerated by man, is generally inhibitory to platelet function in vitro, producing significant inhibition of aggregation in response to most chemical aggregating agents. The calcium ionophore, A23187, is the agent which is most inhibited by ethanol, whereas aggregation induced by arachidonic acid is not inhibited even by concentrations of ethanol far in excess of the lethal range. This spectrum of inhibition found suggests that ethanol inhibits the platelet release reaction by a mechanism involving inhibition of Ca2+-activated phospholipase A2. These effects can be observed in superfused human platelets as well as in those suspended in buffer or in plasma. In superfused rat brain slices however, ethanol does not inhibit the A23187-induced release of radiolabelled neurotransmitter, although it can be shown to inhibit Ca2+-activated phospholipase A2 activity in rat synaptosomal preparations. It is concluded that, although there are many similarities between the effects of ethanol on the platelet and the synapse there may be differences between the way in which ethanol modifies release of intracellular contents in the two situations.

Adenosine Triphosphate↗

Sexual abuse of children in the United Kingdom.

Questionnaires were circulated to 1,599 family doctors, police surgeons, paediatricians, and child psychiatrists to determine the frequency and nature of child sexual abuse in the United Kingdom. At least three per 1,000 children are currently being recognized as sexually abused sometime during their childhood. The majority of cases reported involved actual or attempted intercourse, and 74% of the perpetrators were known to the child. Family disturbance was noted in 56% of the cases. The most common outcome (43%) was criminal prosecution of the perpetrator. Area Review Committees had no clear policy for the management of sexual abuse. Before it is possible to protect children and to develop therapeutic services for the family, it will be necessary to acknowledge that sexual abuse is part of the child abuse spectrum.

Adolescent↗

Moxalactam for the treatment of bacterial meningitis in children.

Increasing resistance to antibiotics in meningeal pathogens has stimulated a search for new antimicrobial agents for the treatment of bacterial meningitis. Moxalactam penetrates well into infected cerebrospinal fluid (CSF) and is highly active against most gram-negative bacteria. The clinical efficacy and safety of moxalactam in the treatment of childhood meningitis caused by Haemophilus influenzae (25 patients) or Neisseria meningitidis (five patients) was evaluated in a random, uncontrolled study. The penetration of the antibiotic into CSF was also evaluated in these patients and in another five children with bacterial meningitis. The clinical results were excellent, with 29 of 30 cases cured. The single adverse clinical reaction noted was the development of a wound hematoma in a postoperative patient; this problem may have been related to moxalactam therapy. The levels of moxalactam achieved in CSF greatly exceeded the minimal bactericidal concentrations for the infecting organisms. Moxalactam appears to be safe and effective as primary therapy for meningitis caused by H influenzae or N meningitidis.

Adolescent↗

Enzymatic methylation of microsomal metabolites of benzo(a)pyrene.

These studies suggest that the microsomal metabolism of benzo(a)pyrene (BP) produces metabolites which can be methylated by the catechol-o-methyltransferase (COMT)/S-adenosylmethionine (SAM) enzyme/donor combination. Induced microsomes converted 12 to 15% of substrate BP to polar products. Approximately 0.06% of substrate BP was recovered as COMT/SAM-reactive substances. In tests for specificity, COMT/SAM was found to react with catechols, but not with dihydrodiols, quinones, a phenol, an epoxide, or 1,4-hydroquinone. Organic extracts of COMT/[14C]SAM incubations with BP were fractionated by high-performance liquid chromatography. The appearance of radiolabeled chromatographic bands required the presence of substrate BP, microsomes, and COMT/[14C]SAM. When the Ames mutagenesis assay was supplemented with COMT/SAM, a 36% reduction was observed in the number of revertant colonies induced by the microsomal oxidation of BP. In contrast, the mutagenic properties of 2-aminofluorene were not affected by COMT/SAM. These observations indicate that COMT/SAM does not generally inhibit mixed-function oxidase activity but rather reacts with substances which are activated by ring oxygenations.

Animals↗

Postneonatal mortality in children from abusing families.

The postneonatal death rate was studied for 332 infants from 160 families, ascertained through an abused proband. There were nine deaths compared with 2.9 expected from the legitimacy, social class, age, and parity distribution (p = 0.003). All but one of the babies died at home, and all were referred to a coroner or procurator fiscal. No adequate explanation of death could be found in four cases. Bonding problems probably existed in most of the nine families before death occurred.

Child Abuse↗

Lost to follow up: a study of nonattendance at a general paediatric outpatient clinic.

50 children defined as persistent outpatient nonattenders were compared with 50 children who regularly attended the same clinics. Several factors were often found in the group of nonattenders: (a) initial referral via casualty without a letter from the family doctor, (b) hospital admission before the first outpatient appointment, (c) recognition of multiple medical problems, and (d) evidence of diffuse social problems affecting the family. 34 of the nonattenders had at least 2 of these factors, compared with only 9 children in the other group. Many of these problems can be identified at the initial consultation, and perhaps other methods of continuing health care should be provided for these children.

Adolescent↗

Recognizing a child at increased risk of abuse.

Data from two studies are presented. Both highlight characteristics which help identify children at increased risk of child abuse. The first study demonstrates that the abused child when compared with unharmed children in the same family is more likely to have been the product of an abnormal pregnancy, labor, delivery and neonatal period. He is more likely to have been separated from his mother and to have been ill in the first year of life. His mother too is more likely to have been sick during that year. The second study shows that it is possible to identify 'at risk' families around the time the baby is born. When compared with controls, five factors are more common: mother aged under 20 at birth of first child, evidence of emotional disturbance, referral to the social worker, admission of baby to special care nursery, and early concern over mothering.

Child↗