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Biomedical subjects

J Snelling

Publications and source records attributed to J Snelling.

12 recordsLinked to original sources

How we do it: The role of trans-nasal flexible laryngo-oesophagoscopy (TNFLO) in ENT: one year's experience in a head and neck orientated practice in the UK.

KEYPOINTS: Transnasal flexible laryngo-oesophagoscopy (TNFLO) is a safe and well-tolerated procedure that may be performed in a procedure room in the outpatient or day-case/main theatre setting. It requires a local anaesthetic and no sedation. It may be used to histologically diagnose or exclude pathology from the nose to the gastro-oesophageal junction. It provides a "one stop" diagnosis service, reducing diagnostic delays, the need for endoscopy under general anaesthesia, barium swallows and follow-up outpatient appointments. Therapeutic procedures such as vocal cord medialization, endolaryngeal laser surgery, insertion of speech prostheses and foreign body removal may be performed without general anaesthesia.

Ambulatory Care↗

Attitudes of medical and dental students to dissection.

Guy's, King's, and St. Thomas's School of Medicine encourages students to learn anatomy from human dissection. Today, there is a worldwide move of anatomy-based teaching away from dissection to prosection. This study investigates how attitudes toward dissection vary with gender and ethnicity. We assessed students' reactions and concerns regarding the dissecting room, any coping strategies they use to combat them, and analyzed effective methods of teaching anatomy to medical and dental students. Three questionnaires were distributed amongst 474 first-year medical and dental students before dissection and 1 week and 12 weeks after exposure to the dissecting room. Over the 3 months we found significant changes in the concerns of students about dissection. There were also significant differences (P < 0.05) between medical and dental students, males and females, and students of differing ethnic backgrounds, which persisted over 12 weeks. Both medical and dental students found tutorials and textbooks of most value in learning anatomy. Dental students found prosection more useful than medical students (P < 0.001) though neither group demonstrated a significant preference for prosection over dissection. Of concern, 7% reported recurring images of cadavers and 2% insomnia after commencing dissection. Interest in the subject matter and discussion were the commonest methods used to combat stress. This study contributes to the ongoing debate about the value of the dissecting room in the medical school curriculum.

Adaptation, Psychological↗

Contribution of CYP1A2 in the hepatic metabolism of melatonin: studies with isolated microsomal preparations and liver slices.

The objective of the present studies was to define the enzyme systems catalysing the 6-hydroxylation of melatonin, by monitoring the levels of 6-sulphatoxymelatonin in rat hepatic postmitochondrial preparations and in precision-cut liver slices. Melatonin 6-hydroxylase activity was localized in microsomes and was supported by NADPH, but not NADH. Treatment of rats with beta-naphthoflavone more than tripled 6-sulphatoxymelatonin formation from melatonin, but gave rise only to a moderate increase (25%) in the sulphate conjugation of 6-hydroxymelatonin. Treatment of rats with phenobarbitone, acetone, dexamethasone and clofibrate did not increase 6-sulphatoxymelatonin generation when either melatonin or 6-hydroxymelatonin served as substrates. Of a number of cytochrome P450 inhibitors investigated, only furafylline inhibited markedly the conversion of melatonin to 6-sulphatoxymelatonin without any concomitant effect on the sulphoconjugation of 6-hydroxymelatonin. When liver slices were incubated with melatonin, treatment of rats with beta-naphthoflavone, and to a lesser extent phenobarbitone, elevated the levels of 6-sulphatoxymelatonin in the culture medium. No such increase was seen when slices from beta-naphthoflavone-treated rats were incubated with 6-hydroxymelatonin, whereas a modest increase was seen with slices from phenobarbitone-treated rats. Treatment of rats with acetone, dexamethasone or clofibrate failed to modulate the levels of 6-sulphatoxymelatonin generated from either melatonin or 6-hydroxymelatonin. Molecular modelling analysis revealed that melatonin had a high area/depth(2) ratio, displayed characteristics of CYP1A2 substrates and could be readily accommodated into the human CYP1A2 active site in a position favouring 6-hydroxylation. Collectively, all the above data provide strong experimental evidence that CYP1A2 is an important catalyst of the 6-hydroxylation of melatonin.

Animals↗

Effect of vitamin C supplementation on hepatic cytochrome P450 mixed-function oxidase activity in streptozotocin-diabetic rats.

The effect of vitamin C supplementation on hepatic cytochrome P450 expression was investigated in streptozotocin (STZ) diabetic male Wistar Albino rats. STZ-treated rats displayed the usual characteristics of diabetes including; hyperphagia, polydipsia, decreased body weight gain and also the increased expression and activity of hepatic CYP1A, 2B, 2E and 4A proteins. Vitamin C administration in drinking water (2% w/v) was associated with significant decreases in the levels of hyperglycaemia (P < 0.05), glycosylated haemoglobin (P < 0.05), hyperlipidaemia (P < 0.001), and hyperketonaemia (P < 0.001) associated with STZ-diabetes. Vitamin C-treatment selectively reduced the activity and expression of CYP2E proteins (P < 0.001). These effects on CYP2E expression may be mediated by the reduced levels of circulating ketone bodies, however, a direct effect on CYP2E expression in diabetes cannot be discounted.

Animals↗

Interaction with the aromatic hydrocarbon receptor, CYP1A induction, and mutagenicity of a series of diaminotoluenes: implications for their carcinogenicity.

The present study was undertaken to provide a rationale for the marked difference in carcinogenic potential among isomeric diaminotoluenes, in relation to their ability to induce their own bioactivation through CYP1A induction, their genotoxic potential, and their ability to bind to the cytosolic aromatic hydrocarbon (Ah) receptor. Of the four possible diaminotoluenes only the 2,3- and, to a lesser extent, the 2,4-isomer induced CYP1A activity. Similarly, only these two isomers could displace [3H]T-CDD from the hepatic cytosolic Ah receptor. In the presence of Aroclor 1254- induced microsomes, 2,4- and 2,6-diaminotoluene were potent mutagens in the Ames test. Only 2,4-diaminotoluene could autoinduce its activation. Of the four isomers only 2,4-diaminotoluene is an established carcinogen and this is compatible with the present observations that it is the only isomer that stimulates its own activation through CYP1A induction, is metabolically converted to genotoxic intermediates, and binds to the Ah receptor. 2,6-Diaminotoluene is recognized as a mutagenic noncarcinogen and in the present studies it elicited a positive mutagenic response in the Ames test but failed to induce CYP1A activity and its own activation, and could not bind to the Ah receptor even at concentrations as high as 5 x 10(-4) M. The present findings demonstrate that in vitro studies are very useful tools in predicting the carcinogenic potency of isomeric chemicals.

Animals↗

Induction of hepatic CYP1A2 by the oral administration of caffeine to rats: lack of association with the Ah locus.

Caffeine was administered to male Wistar albino rats for two weeks at three concentrations, namely 0.1, 0.2 and 0.3%, and hepatic cytochrome P450-dependent mixed-function oxidase determined. Caffeine administration gave rise to a marked, dose-dependent increase in the O-deethylation of ethoxyresorufin and, to a lesser extent, in the O-depentylation of pentoxyresorufin. Erythromycin N-demethylase, p-nitrophenol hydroxylase and lauric acid hydroxylase activities, as well as total cytochrome P450 content were unaffected by this treatment. Immunoblot analysis revealed that caffeine gave rise to a dose-dependent increase in the hepatic CYP1A2, and at the highest dose only, CYP2B apoprotein levels. Apoprotein levels of CYP3A and CYP2E1 were not modulated by the treatment with caffeine at all dose levels studied. Caffeine could not displace [3H]TCDD from the rat hepatic cytosolic Ah receptor. Computer analysis showed that caffeine is essentially a planar molecule with an area/depth ratio 4.8, characteristic of CYP1A substrates/inducers. Molecular modelling revealed that the caffeine molecule could orientate itself within the putative CYP1A2 active site so as to facilitate demethylation of the N-1, N-3 and N-7 positions. However, at physiological pH, the N-9 nitrogen atom is likely to be partially protonated, allowing it to participate in an electrostatic interaction with the negatively-charged glutamate 318-residue, favouring N-3 demethylation, the major pathway of metabolism in both humans and animals. In conclusion caffeine, being essentially planar, is an inducer of CYP1A2 in rat liver.

Administration, Oral↗

Species variation in the metabolism of 15,16-dihydro-11-methylcyclopenta[a]phenanthren-17-one to its 3,4-dihydrodiol, the proximate carcinogen.

The title compound is a strong carcinogen, similar in potency to benzo[a]pyrene in mouse skin assay. This paper describes a comparison of its in vitro metabolism by hepatic microsomal preparations from mouse, rat, rabbit, hamster, dog, monkey and man. Metabolites were isolated by preparative high pressure liquid chromatography from the ethyl acetate extractable material and their structures tentatively assigned on the basis of their retention times and ultraviolet spectra, when possible by direct comparison with authentic synthetic specimens. Mass spectrometry was then used to confirm these assignments. All these animals produce the same range of metabolites derived exclusively from oxidation at the benzo-ring A, the five-membered ring D, and at the 11-methyl group. However, the amounts of individual metabolites varied substantially. In particular all the animals yielded the proximate carcinogen 3,4-dihydroxy-11-methyl-3,4,15, 16-tetrahydrocyclopenta[a]phenanthren-17-one, from which it is reasoned that all might be susceptible to its carcinogenic action. A rationalization for the observed distribution of the metabolites is proposed on the basis of a molecular model of the active site of cytochrome P450 1A1, the oxidative enzyme involved.

Animals↗

The effect of chronic pain on the family unit.

The purpose of the study was to examine what kind of effect a relative with chronic pain had on his or her partner and the other members of the family. The methodology used was grounded theory. The sample was a convenience group of 18 chronic pain sufferers, their partners, and one adult child taken from two pain clinics. The subjects were briefed on the purpose of the study, and how their confidentiality would be protected. Informed consent was then obtained. Data were collected through audio-taped interviews, which were conducted on an individual basis in the subject's home environment. Analysis was conducted through the constant comparative method. Findings revealed that two main variables emerged, that of social relationships and coping techniques. The aspects of social relationships affected were the marital partnership, sexual activity, contact with friends and relatives, and roles. This meant that chronic pain caused social isolation, role tension, marital conflict, reduced sexual activity and feelings of anger, anxiety, resentment and despondency in other family members. However, the results also suggested that the extent to which chronic pain negatively affected the chronic pain sufferer's respective partner and other family members was dependent to some extent on how effective the family was in coping with a relative with chronic pain.

Adaptation, Psychological↗

The role of the family in relation to chronic pain: review of the literature.

As families maintain the primary responsibility for the care of the chronic pain sufferer, this paper examines the family's aetiological role in chronic pain, the ways in which the family influences and maintains pain, and the impact that chronic pain has on the family unit. Although some of the research is contentious, it can be concluded that, (a) there is a tendency for patients to come from families which include another member suffering from pain or illness, (b) that it is conceivable that spouses reinforce pain behaviors in their partners, and (c) that it is possible that the chronic pain sufferer may significantly subscribe to poor marital relationships, poor sexual adjustment and high levels of emotional distress.

Chronic Disease↗

Help--toddler at large!

Following an initiative by the staff at the child development centre at Maelor Hospital in Wrexham, a group of mothers with toddlers set up, manage and run self-help discussion groups covering aspects of family life with toddlers.

Child, Preschool↗

Some infectious and parasitic diseases in Oklahoma raptors.

Blood films and sera samples from wild Oklahoma raptors (Strigiformes--36 birds, 3 species; Falconiformes--50 birds, 7 species) were examined for hematozoa and tested for serologic antibody response to Newcastle Disease Virus (NDV), encephalitis (EEE and WEE), ornithosis, and influenza. Twenty-nine of 36 (80.5) Strigiformes and 24 of 50 (48.0%) Falconiformes showed the presence of one or more hematozoa. Serologic testing revealed the serum of one adult male red-tailed hawk positive for antibody to NDV and one additional adult male red-tailed hawk positive for antibody to type-A influenza.

Animals↗