Search PubMed⌕ Search

Biomedical subjects

A Huggett

Publications and source records attributed to A Huggett.

17 recordsLinked to original sources
PubMed2002

Review of the function of a telephone helpline in the treatment of outpatients with rheumatoid arthritis.

OBJECTIVES: To examine the role, acceptability, and cost effectiveness of a telephone helpline organised and run by specialist nurses in a district general hospital outpatient rheumatology department. MATERIAL AND METHODS: Patients accessed the telephone helpline by leaving a taped message on an answer phone with a 24 hour response time. Assessment included an audit of the nature and outcome of helpline calls, patient satisfaction with the helpline, and a health economic analysis of the helpline operation. A postal questionnaire was used to assess patient satisfaction; this was sent to the 87 patients who called the helpline during one month, and overall satisfaction with the helpline was assessed. The nature and outcome of all calls was analysed retrospectively using a helpline record book for February and October of one year and February of the following year. From the results of the retrospective analysis and an estimate of the number of general practitioner consultations avoided by provision of the helpline, the cost effectiveness of the helpline was calculated. RESULTS: Of those returning questionnaires, 61/63 (97%) were satisfied with the response time, 63/63 (100%) with the courtesy, and 60/63 (95%) felt that their questions were answered directly and to their satisfaction in 62 (98%) of cases. Had the helpline not been available, 38/63 (60%) patients would have made an appointment with their GP. When these figures were extrapolated to an annual estimation, a basic cost analysis showed that the helpline produced a cost saving to the NHS, largely as a result of GP consultations avoided. CONCLUSION: Clinical advice and support can be provided by a rheumatology helpline set up as an adjunct to a standard outpatient service. The results of a postal questionnaire suggested more than 95% satisfaction with all aspects of the helpline service and that 99% of callers would call the helpline again. The provision of the helpline service contributes to the quality of care provided by an outpatient department and provides benefit to the NHS.

Adolescent↗
PubMed1997

Induction and reversal of long-term potentiation by repeated high-frequency stimulation in rat hippocampal slices.

Field potential recordings were made from area CA1 of hippocampal slices from young adult rats to study the effects of repeated tetanic stimulation on the development of LTP. Stimulation was applied to the Schaffer collateral afferents, and field excitatory postsynaptic potentials were recorded in stratum radiatum. Theta-burst stimulation (TBS) resulted in variable amounts of long-term potentiation (LTP), depending on how many trains of stimulation were delivered. Peak amounts of LTP occurred after 8-16 trains of TBS, but virtually no LTP occurred after 24 or 32 trains of TBS. There was thus an inverted U-shaped relation between the amount of TBS and the degree of LTP. The temporal spacing of TBS trains was important for observing the lack of LTP after 32 trains ("over-stimulation"). If the trains were grouped into blocks of 8, with 10 min between blocks, LTP occurred normally. This finding suggests that a time-dependent LTP reversal process was occurring during the massed presentation of TBS trains. Over-stimulation inhibited for 60-90 min the subsequent induction of LTP by a normally efficient LTP-inducing protocol. This effect was input specific and dependent on activation of N-methyl-D-aspartate (NMDA) receptors. Lowering extracellular [Ca2+] from 2.5 to 2.0 mM, or adding the L-type calcium channel antagonist nimodipine, had only a small protective effect on the lack of LTP induced by 32 trains of TBS. Addition of an NMDA receptor antagonist to the bath solution shortly after the beginning of the over-stimulation protocol gave significantly more protection. Administration of an adenosine (A1) receptor antagonist during over-stimulation permitted robust LTP to occur, indicating that A1 receptor activation during TBS contributes to the depotentiation process. These findings confirm previous findings in the dentate gyrus that repeated afferent tetanization within a narrow time frame can lead to a loss or reversal of LTP. Activation of adenosine receptors appears to trigger this effect.

Adenosine↗
PubMed1996

The safety assessment of novel foods. Guidelines prepared by ILSI Europe Novel Food Task Force.

The diversity of novel foods and novel ingredients covered by the scope of the EU regulation is such that a check list approach to safety evaluation is inappropriate. Rather, a case-by-case approach is required taking into account the composition of the novel food, its intake, its role in the diet and the intended target group. The SAFEST approach provides a means of targeting the safety evaluation on those aspects, nutritional or toxicological, of a novel food which are of particular concern. Using this approach, novel foods are assigned to one of three classes on the basis of certain background information. For those novel foods which can be shown to be in SAFEST class 1, namely those which are substantially equivalent to a traditional counterpart, no further information is required to demonstrate their safety. For those novel foods in SAFEST class 2, i.e. those sufficiently similar to a traditional counterpart or differing from it only in particular, well defined, characteristics, the evaluation will focus on those differences. Only in the case of novel foods which are not in class 1 or class 2 is extensive testing of the whole food likely to be required. Even in these cases, the testing should follow a scientifically-based hierarchical approach involving: literature reviews; chemical analysis; appropriate in vitro and in vivo tests; and, if necessary, confirmation of safety and nutritional value in humans. Examination of the causes of any adverse effects reported by consumers after the novel food or ingredient has been approved and is introduced into the market may provide additional reassurance of safety.

Animals↗
PubMed1990

Metabolism of 2-acetylaminofluorene and benzo(a)pyrene and activation of food-derived heterocyclic amine mutagens by human cytochromes P-450.

The human P-450 CYP1A1 gene and a P450IA2 complementary DNA have been expressed in Cos-1 cells and the expressed proteins were assayed for their capacity to metabolize the carcinogens 2-acetylaminofluorene (AAF), benzo(a)pyrene, 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), 2-amino-3,4-dimethylimidazo[4,5-f]quinoline, 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline, 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) was determined. The expressed human P450IA1 and P450IA2 proteins, when run on a 7.5% sodium dodecyl sulfate-polyacrylamide gel, migrated with different mobilities, with the former displaying the lower molecular weight. In human liver microsomes from 18 subjects, only a protein band corresponding to P450IA2 was detectable. Cos-1 cell-expressed P450IA1 and P450IA2 were capable of N-hydroxylating AAF and these activities were inhibited by alpha-naphthoflavone. In human liver microsomes, a correlation of r = 0.76 (P less than 0.05; n = 18) was obtained between AAF N-hydroxylase activity and P450IA2 content. AAF N-hydroxylase activity of human liver microsomes was also strongly inhibited by alpha-naphthoflavone. Except in the case of PhIP, where both proteins exhibited similar activities, P450IA2 was at least an order of magnitude more efficient than P450IA1 in activating IQ, 2-amino-3,4-dimethylimidazo[4,5-f]quinoline, 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline, and 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline to mutagens as measured in the Ames test. Statistically significant correlations were obtained between IQ activation and P450IA2 content (r = 0.75, r2 = 0.56) and PhIP activation and P450IA2 content (r = 0.71, r2 = 0.5) in human liver microsomes. The activation of both IQ and PhIP by expressed proteins and human liver microsomes was strongly inhibited by alpha-naphthoflavone. The above data suggest a major role for P450IA2 in activation (N-hydroxylation) of aromatic amides and amines in human liver. When benzo(a)pyrene hydroxylase activity was determined, only Cos-1 cell-expressed P450IA1 exhibited appreciable activity. While alpha-naphthoflavone inhibited Cos-1 cell-expressed P450IA1 benzo(a)pyrene hydroxylase activity, it caused a marked stimulation of this activity in human liver microsomes, which lack P450IA1 protein. The lack of a role for P450IA proteins in benzo(a)pyrene metabolism is further supported by the poor correlation (r = 0.43, P greater than 0.05) between this activity and P450IA2 content of human liver microsomes. However, when P450IIIA3 content of the above human liver microsomes was determined by using the Western blot technique and correlated with benzo(a)pyrene metabolism, an r value of 0.70 (P less than 0.5) was obtained. These data suggest that human P450IIIA proteins are involved in benzo(a)pyrene metabolism.

2-Acetylaminofluorene↗
PubMed1989

Immunochemical and catalytical characterization of the human liver NADPH-cytochrome P450 reductase.

1. The NADPH-cytochrome P450 reductases (EC 1.6.2.4) from human and rabbit liver have been purified to electrophoretic homogeneity. The human reductase had an apparent monomeric molecular weight of 77,500 and the rabbit enzyme of 76,500. 2. Both flavoproteins exhibited typical flavoprotein spectra and contained equimolar quantities of FAD and FMN. The two reductases were catalytically active in reducing cytochrome c, ferricyanide and dichlorophenolindophenol, and in supporting rabbit liver cytochrome P450 Form 4 metabolism of 2-acetylaminofluorene. 3. An antibody raised in the goat against the human enzyme formed a precipitin line with the human reductase in a double-diffusion assay, but did not react with the rabbit reductase. Similarly, an antibody raised in the goat against the rabbit reductase formed a precipitin line with the rabbit enzyme, but did not cross-react with the human reductase. 4. Both antibodies inhibited cytochrome c reduction by the two reductases suggesting some immunochemical recognition. 5. Immunochemical cross-reactivity was confirmed when both reductases were subjected to the more sensitive immunoblot technique using either anti-human or anti-rabbit reductase IgG. 6. The human and rabbit reductases are essentially similar in amino acid composition, except that the former has larger amounts of serine and glycine.

Amino Acids↗
PubMed1983

Hypnotic accumulation and hangover in elderly inpatients: a controlled double-blind study of temazepam and nitrazepam.

The hypnotic and residual sedative effects of the first and seventh of seven regular night-time doses of nitrazepam 5 mg, temazepam 20 mg, and placebo were studied in 58 elderly inpatients. Plasma temazepam and nitrazepam concentrations rose by about 50% and 113% respectively between the mornings of day 1 and day 7. Patients reported sleeping well more often after the first dose of either hypnotic (p less than 0.05), but there was no difference after the seventh dose. Reaction time was unchanged on the morning after the first dose but was significantly prolonged after the seventh dose of both hypnotics (p less than 0.01). The time taken to eliminate the letter E from a page of prose tended to be prolonged after the first dose of both drugs (temazepam v placebo, p less than 0.05; nitrazepam v placebo, not significant) and was further prolonged on the morning after the seventh dose of nitrazepam (nitrazepam v placebo, p less than 0.05). Thus plasma accumulation of the drug was associated with a deterioration in daytime performance. This change in performance did not correlate with age, cerebral blood flow, or plasma concentration, but patients of low intelligence tended to be more severely affected.

Aged↗
PubMed1983

The mechanism of paracetamol-induced hepatotoxicity: implications for therapy.

1 The reactive metabolite responsible for paracetamol-induced hepatotoxicity, postulated to be N-acetyl-p-benzoquinoneimine reacts with N-acetyl cysteine. 2 An adduct is formed by an SN2 mechanism and paracetamol is produced by a redox reaction. 3 The adduct produced is capable of further oxidation by N-acetyl-p-benzoquinoneimine. 4 Methionine does not react with the reactive metabolite to any great extent.

Acetaminophen↗
PubMed1982

Liquid-chromatographic measurement of nitrazepam in plasma.

In this simple and rapid "high-performance" liquid-chromatographic method for determining nitrazepam in plasma, serum, or whole blood, the sample at pH 7.4 is extracted into diethyl ether with an internal standard (prazepam), chromatographed, and detected at 280 nm with a fixed-wavelength ultraviolet detector. A specimen, together with standards and a quality control, can be analyzed in duplicate within 90 min. The limit of sensitivity is 5 micrograms/L (nitrazepam and 7-acetamidonitrazepam) and 50 micrograms/L (7-aminonitrazepam), and no interferents have been found. This method has the advantages of a small sample requirement and complete resolution of nitrazepam and the above-mentioned major metabolites. We have used this method for analysis of therapeutic and overdose concentrations of nitrazepam, and to investigate the stability of the drug in blood.

Chromatography, High Pressure Liquid↗
PubMed1981

Value of toxicological investigation in the diagnosis of acute drug poisoning in children.

In the 2 years 1978 and 1979 specimens from 287 children aged between 10 days and 14 years were received for general toxicological investigations. Of the 95 (33%) cases of confirmed poisoning, the diagnosis was established as a direct result of the analyses in 48 patients. No diagnosis was made in at least 85 (30%) of the remaining cases. Benzodiazepines were the drugs most commonly encountered (33%), followed by barbiturates, glutethimide, and meprobamate (15%), salicylate and paracetamol (15%), tricyclic antidepressants (12%), and ethanol (11%). 36 patients were severely poisoned (grade 3 or 4 coma, or convulsions), although only 1 patent died. There was evidence that drug(s) had been administered without authorisation in at least 7 instances, and in 51 (54%) of the poisoned patients there was sufficient concern about the safety of the child or the mode of administration of the drug(s) to institute legal proceedings (8 cases), involve the social services (25 cases), or arrange further medical appointments (18 cases). Drugs are readily available in most households and offer a means of inflicting injury that is less easily detectable than physical assault. For this reason, comprehensive toxicological investigations should be considered in children not only when they may assist in management but also in the presence of unusual or unexplained symptoms which could be drug-induced.

Adolescent↗
PubMed1981

Rapid micro-method for the measurement of paracetamol in blood plasma or serum using gas-liquid chromatography with flame-ionisation detection.

A simple method for the measurement of plasma paracetamol concentrations using a novel extraction/acetylation procedure prior to gas-liquid chromatographic analysis has been developed. The sample (100 microliters) is vortex-mixed for 30 sec with 0.067 mole/l phosphate buffer, pH 7.4 (50 microliters), internal standard solution (N-butyryl-p-aminophenol (200 mg/l) in chloroform) (50 microliters) and "acetylation reagent" (acetic anhydride--N-methylimidazole (catalyst)--chloroform, 5:1:30) (20 microliters). After centrifugation at 9950 g for 3 min, a portion (5 microliters) of the resulting extract is analysed on a 1.5 m X 4 mm I.D. glass column packed with 3% (w/w) C87 hydrocarbon (Apolane-87) on Chromosorb W HP, 100-120 mesh, maintained at 235 degrees C. A specimen together with a quality control sample can be analysed, in duplicate, within 20 min. The limit of accurate measurement of the assay is 10 mg/l, and few potential sources of interference have been identified. The method has advantages of speed and reproducibility over other gas-liquid chromatographic procedures and, in addition, of selectivity over spectrophotometric techniques. The procedure provides a useful alternative to liquid chromatographic methods for emergency paracetamol measurements.

Acetaminophen↗
PubMed1980

Child abuse.

Explore the source record for details and available documents.

Adolescent↗
PubMed1979

Value of emergency toxicological investigations in differential diagnosis of coma.

Out of 208 cases of coma of unknown aetiology referred to the poisons unit of this hospital during 1978 for emergency toxicological investigations, 108 were found to be due to self-poisoning medical conditions, mainly neurological, accounted for coma in 90 patients; the cause was not ascertained in the remaining 10 cases. More than one preparation had been ingested by 58 (54%) of the poisoned patients, although barbiturates were the drugs most commonly encountered in the severe cases. Toxicological investigations should be considered in the differential diagnosis of coma when history, physical examination, and emergency biochemical measurements yield little diagnostic information.

Acute Disease↗