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Biomedical subjects

R Meadows

Publications and source records attributed to R Meadows.

At least 19 recordsLinked to original sources
PubMed2006

Investigation into the suitability of a portable psychometric device to be used in the field: an illicit drugs field investigation.

RATIONALE: Driving performance is easily disrupted as a direct consequence of the use of alcohol, licit and illicit drugs. The use of such drugs has a high degree of correlation with increased accident risk. Europe wide research projects into drugged driving have called for the development of a portable objective device capable of screening those impaired through drug use which can be used at the roadside. OBJECTIVE: This study investigated the cognitive and psychomotor performance of a cohort of polydrug drug users in field conditions. Volunteers completed a psychometric test battery on a hand held device in music festival conditions. The test battery comprised a critical tracking task (CTT) and a sustained attention to response task (SART). Volunteers also took a breathanalyser and provided a saliva sample for a DOA screen. RESULTS: On the CTT significance was observed for tracking error following response to a peripheral stimulus in the high alcohol (>80 mg/100 ml) illicit drug group (p=0.0090) and approached significance for the low alcohol (<80 mg/100 ml) illicit drug group (p=0.088). For the SART, incorrect presses to the target stimulus was impaired for volunteers in both the low (<80 mg/100 ml) alcohol illicit drug group (p=0.0080) and the high alcohol (>80 mg/100 ml) illicit drug group (p=0.0415). Discrimination analysis demonstrated that the impairment device was able to discriminate between those individuals who had consumed neither alcohol nor drugs (94.12%), those in the low alcohol drug group (46.67%) and those in the high alcohol drug group (60.00%). CONCLUSION: It is possible to derive an impairment ratio. Further research will demonstrate whether this device could significantly contribute to drug driving detection and road traffic safety.

Adolescent↗
PubMed2005

Investigating couples' sleep: an evaluation of actigraphic analysis techniques.

'Blip' analysis, fast wavelet transformations (FWT) and correlation analysis have all been used to actigraphically assess the impact one person is having on another's sleep, yet no review exists as to the differences between, and applicability of, these methods for investigating couples' sleep. Using actigraphy data and audio sleep diaries collected from 18 couples, this paper provides such a review. This paper constructs and assesses two novel, analytical methods: Lotjonen's sleep/wake algorithm, and the partner impact on sleep wake analysis (PISWA). Both 'blip' analysis and correlation suggest that the strongest relationship between bed partners occurs on an epoch-to-epoch basis. However, 'blips' deal strictly with onset of movement and fail to incorporate strength and duration of movement. Conversely, correlation analysis incorporates some elements of strength and duration of movement but makes identification of onset problematic. FWT offer useful 'relativistic' pattern recognition, identifying onset, strength and duration of movement, but are difficult to quantify. Although audio diary data support the potential of Lotjonen's sleep/wake algorithm to identify sleep non-movement, sleep movement, wake non-movement (or quiet wakefulness) and wake movement, the problem remains that this method also relies on visualization. Of most promise, we argue, is the PISWA, which examines 'impact' of bed partners through incorporating elements of 'blip' analysis and the sleep/wake algorithm.

Adult↗
PubMed2003

A placebo controlled investigation into the effects of paroxetine and mirtazapine on measures related to car driving performance.

OBJECTIVE: To assess the effects of paroxetine and mirtazapine on psychometric performance related to car driving, including an on-the-road test of BRT. METHOD: In a 4-way, double blind randomised crossover study, 12 healthy volunteers received paroxetine 20mg mane, mirtazapine 15mg/30mg nocte (comparator), mirtazapine 15mg mane/15 mg b.i.d.(verum) and placebo over a 5 day period with a washout period of 7 days between treatments. Psychometric assessments included 'on-the-road' BRT (BRT), CFF (CFF), CRT (CRT) and subjective measures of sedation and sleep parameters. RESULTS: Paroxetine had no significant effect on BRT compared with placebo. Although subjective ratings of sleep quality and sedation were impaired, there were significant improvements in both CFF and the recognition reaction component of CRT with paroxetine. Mirtazapine 15mg/30mg nocte impaired laboratory performance and some subjective tests. Mirtazapine 15mg mane/15mg b.i.d. improved sleep, but significantly impaired all other measures. CONCLUSION: Paroxetine 20 mg/day has no psychomotor or behavioural toxicity and has no negative impact on BRT. Further research into the chronic and sub-chronic effects of mirtazapine is needed to establish the clinical significance of these results.

Adrenergic alpha-Antagonists↗
PubMed2001

The acute and sub-chronic effects of levocetirizine, cetirizine, loratadine, promethazine and placebo on cognitive function, psychomotor performance, and weal and flare.

AIM: To compare the central and peripheral H1 inhibitory effects of acute and sub-chronic doses of levocetirizine (L-CTZ), cetirizine (CTZ), loratadine (LOR) and promethazine (PRM) versus placebo, using a battery of psychomotor and cognitive tests together with measures of the weal and flare reaction. PRM was included in the study as a positive internal control to validate the sensitivity of the psychometric test battery to the CNS effects of the various treatments. METHODS: Twenty healthy volunteers (18-50 years) received L-CTZ 5mg, CTZ 10 mg, LOR 10 mg, PRM 30 mg and placebo once daily for four days in a five-way, double-blind, crossover study. For each treatment condition, subjects were assessed using a psychometric test system and a pinprick weal and flare response to 100 mg/ml histamine solution at baseline and at 1, 2, 3 ,4, 6, 8, 10 and 122 hours post-dose on days 1 and 4. The psychometrics comprised critical flicker fusion (CFF), choice reaction time (CRT), a continuous tracking task (CTT) and subjective rating scales for sedation (LARS). On days 2 and 3, subjects took their medication at pre-designated times while out of the unit. RESULTS: The verum (PRM) established the sensitivity of the test battery: a significant overall reduction in CFF thresholds on both days 1 and 4 (p < 0.05); an overall significant increase (impairment) in recognition, motor and total reaction times on day 1 (p < 0.05); a significant impairment of both the tracking accuracy and reaction time aspects of the CTT task on day 1 (p < 0.005) and significantly higher ratings of subjective sedation on day 1 (p < 0.05). L-CTZ, CTZ and LOR were not distinguishable from placebo in any of the objective and subjective tests at any time point on either day 1 or day 4. With regards to the peripheral inhibitory effects, L-CTZ inhibited both the weal and flare reaction, with maximum inhibition (almost 100%) occurring within two hours of drug ingestion. CTZ also showed evidence of potent peripheral inhibition of histamine, whereas PRM, and especially LOR, showed only a weak weal and flare reaction which had completely attenuated at day 4. CONCLUSIONS: In a study where the psychometric assessments were shown to be sensitive to impairment, L-CTZ 5 mg was found following both initial and repeated doses, but also to be demonstrably free from disruptive and sedative effects on objective measures of psychomotor and cognitive function. Similarly, CTZ showed evidence of pronounced antihistaminic activity and significantly reduced weal and flare scores after both acute and repeated doses, again without evidence of cognitive or psychomotor impairment. LOR also was non-sedative but the antihistaminic reaction was demonstrably weak.

Adult↗
PubMed1996

Medical complications of glue sniffing.

Glue sniffing refers to the deliberate inhalation of volatile solvents, commonly found in adhesives, for the purpose of intoxication. The increasing prevalence of inhalant use suggests that many physicians will encounter a glue-sniffing patient at some time during their practice. Knowledge of the epidemiology, toxicology, and medical complications associated with glue sniffing is essential in obtaining an accurate history of substance abuse and in clinically managing these patients. This review of sources is intended to aid clinicians in the recognition of glue-sniffing patients and in the diagnosis of acute and chronic medical complications associated with the abuse of glues, solvents, and related substances. Glue sniffing has been linked to sudden death and chronic damage to the heart, lungs, kidneys, liver, peripheral nerves, and brain. Inhalant abuse in general is associated with mortality and morbidity, including social, educational, and economic deprivation in adolescents and young adults.

Acute Disease↗
PubMed1996

Growing pains.

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Air Pollutants, Radioactive↗
PubMed1995

Livestock legacy.

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Air Pollution↗
PubMed1993

Solution structure of the cyclosporin A/cyclophilin complex by NMR.

Cyclosporin A, a cyclic undecapeptide, is a potent immunosuppressant that binds to a peptidyl-prolyl cis-trans isomerase of 165 amino acids, cyclophilin. The cyclosporin A/cyclophilin complex inhibits the calcium- and calmodulin-dependent phosphatase, calcineurin, resulting in a failure to activate genes encoding interleukin-2 and other lymphokines. The three-dimensional structures of uncomplexed cyclophilin, a tetrapeptide/cyclophilin complex, and cyclosporin A when bound to cyclophilin have been reported. However, the structure of the cyclosporin A/cyclophilin complex has not been determined. Here we present the solution structure of the cyclosporin A/cyclophilin complex obtained by heteronuclear three-dimensional NMR spectroscopy. The structure, one of the largest determined by NMR, differs from proposed models of the complex and is analysed in terms of the binding interactions and structure/activity relationships for CsA analogues.

Amino Acid Isomerases↗
PubMed1993

1H, 13C, and 15N assignments and secondary structure of the FK506 binding protein when bound to ascomycin.

The 1H, 13C, and 15N resonances of FKBP when bound to the immunosuppressant, ascomycin, were assigned using a computer-aided analysis of heteronuclear double and triple resonance three-dimensional nmr spectra of [U-15N]FKBP/ascomycin and [U-15N,13C]FKBP/ascomycin. In addition, from a preliminary analysis of two heteronuclear four-dimensional data sets, 3JHN,H alpha coupling constants, amide exchange data, and the differences between the C alpha and C beta chemical shifts of FKBP to random coil values, the secondary structure of FKBP when bound to ascomycin was determined. The secondary structure of FKBP when bound to ascomycin in solution closely resembled the x-ray structure of the FKBP/FK506 complex but differed in some aspects from the structure of uncomplexed FKBP in solution.

Amino Acid Sequence↗
PubMed1991

1H, 13C and 15N backbone assignments of cyclophilin when bound to cyclosporin A (CsA) and preliminary structural characterization of the CsA binding site.

The backbone 1H, 13C and 15N chemical shifts of cyclophilin (CyP) when bound to cyclosporin A (CsA) have been assigned from heteronuclear two- and three-dimensional NMR experiments involving selectively 15N- and uniformly 15N- and 15N,13C-labeled cyclophilin. From an analysis of the 1H and 15N chemical shifts of CyP that change upon binding to CsA and from CyP/CsA NOEs, we have determined the regions of cyclophilin involved in binding to CsA.

Amino Acid Isomerases↗
PubMed1985

Cell cycle perturbations following DNA damage in the presence of ADP-ribosylation inhibitors.

Cell cycle analysis by DNA flow cytofluorimetry and autoradiography has been utilized to investigate the effects of 3-methoxybenzamide (MBA), a potent inhibitor of ADP-ribosylation reactions, on cell cycle progression in N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-treated C3H10T1/2 cells. Following a dose of 6.8 microM MNNG, the presence of MBA resulted in an increased length of S phase from approximately 6.5 h to 10 h and in an accumulation of cells in G2 with a mitosis delay of 12 h. Progression to the next S phase occurred 5-10 times more slowly and the cells ultimately accumulated in G2. Increasing the dose of MNNG resulted in a complete block in cell division in the absence of ADP-ribosylation. These results suggest that ADP-ribosylation reactions, which do not seem to be necessary for DNA excision repair in nondividing cells, are essential for coordinating the events of DNA excision repair with DNA replication and events related to progression through the cell cycle.

Animals↗
PubMed1984

Effect of nicotinamide analogues on recovery from DNA damage in C3H10T1/2 cells.

The effects of nicotinamide analogues on cellular recovery following N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) treatment have been characterized in the transformable cell line, C3H10T1/2. The recovery of cell division potential was measured under conditions which allow simultaneous quantification of intracellular levels of poly(adenosine diphosphate ribose), nicotinamide adenine dinucleotide, and rates of RNA, DNA, and protein synthesis. 3- Methoxybenzamide (MBA), 3-aminobenzamide, and benzamide, which are effective inhibitors of adenosine diphosphate ribosyltransferases , blocked recovery of cell division following treatment with 34 microM MNNG, while the noninhibitors , 3- methoxybenzoate and benzoate, had no effect. In the presence of MBA, cells progressively lost the ability to resume cell division during the first 24 to 36 hr following DNA damage. The intracellular levels of poly(adenosine diphosphate ribose) increased approximately 7-fold within 20 min following MNNG treatment, and 1 mM MBA inhibited this increase by approximately 82%. In the presence of MBA, a dramatic decrease in the rate of DNA synthesis occurred approximately 16 hr after MNNG treatment, while RNA and protein synthesis continued at rates similar to those in cells treated with MNNG alone.

Animals↗
PubMed1979

Acute post-streptococcal glomerulonephritis in adults: a long-term study.

The long-term outcome after acute post-streptococcal glomerulonephritis was studied in 57 patients (52 aged 16 or over) followed for a period of one to 14 years (mean seven years). All patients presented with hypertension, haematuria and proteinuria. The antistreptolysin-0 titre was raised or the serum complement was low in all cases at the initial episode. All patients had histological evidence of a diffuse proliferative and exudative glomerulonephritis at onset. Follow-up renal biopsy was performed in 33 patients; in 18 patients this was carried out five years or more after the initial illness. Five patients died beyond two years, only two having had abnormal renal function at the time or death. Four patients were found to be mildly hypertensive without other clinical abnormalities. Eleven patients had proteinuria, haematuria or abnormal renal function; in three of these repeat renal biopsy was normal, incomplete resolution was reported in five, obsolescent glomeruli in one, and two others were not biopsied. No patient who had normal renal function at the time of follow-up had abnormal renal histology on biopsy. Obsolescent glomeruli were present in two other biopsies in association with evidence of incomplete resolution. It was concluded that the majority of patients with acute PSGN have a good prognosis. Histological resolution of the renal lesion may not occur for nine years.

Acute Disease↗
PubMed1975

Acute interstitial nephritis following ampicillin hypersensitivity.

A case of acute anuric renal failure following hypersensitivity to ampicillin is presented. Renal biopsy showed severe interstitial nephritis. Treatment with prednisolone and heparin, together with supportive measures and peritoneal dialysis, was followed by rapid recovery of renal function. It is concluded that hypersensitivity to ampicillin can cause acute interstitial nephritis, analogous to that seen with penicillin and methicillin.

Acute Disease↗