Biomedical subjects

D Griffiths

Publications and source records attributed to D Griffiths.

At least 19 recordsLinked to original sources

PubMed2001

A single nocturnal exposure to 2-7 millitesla static magnetic fields does not inhibit the excretion of 6-sulfatoxymelatonin in healthy young men.

The present study sought to evaluate possible acute effects on 6-sulfatoxymelatonin (aMT6s) excretion, a surrogate for melatonin levels in blood, in volunteers exposed to static magnetic fields with flux densities representative for workers in light metal reduction plants and operators of medical MRI in hospitals. Eleven healthy male volunteers (23-43 years) participated. Urine samples were collected for two consecutive 24 h periods from 22:00 hours day 1 (exposure day) through day 2 (day after exposure) and then for 24 h from 07:00 hours on day 7 (control day). On the day of exposure the subjects slept in the MRI room from 22:00 hours until 07:00 hours next morning, thus receiving a 9 h exposure to the magnetic field (2-7 mT). On the day after exposure and on the control day, they slept at home and otherwise performed their ordinary daily activities. Total daily urine production was collected in four parts: 22:00-07:00 hours, 07:00-11:00 hours, 11:00-18:00 hours, 18:00-22:00 hours, and the volume for each interval was measured and recorded. Samples were transferred to coded bottles and frozen for later RIA analysis of aMT6s. Pairs of values of mean hourly aMT6s excretion, both diurnal and for the four daily intervals, were compared using two-sided Wilcoxon signed ranks test. The day of exposure and the day after exposure were not significantly different from the control day, either for the total diurnal secretion or the interval data. In summary, the study shows no association between a single nocturnal exposure to a static magnetic field of strength 2-7 mT and excretion of aMT6s in urine.

Adult↗

PubMed2000

Invasive pneumococcal disease in England and Wales: vaccination implications.

Knowledge of the epidemiology of invasive pneumococcal disease (IPD) will aid in planning the use of pneumococcal vaccines. A United Kingdom (UK)-based surveillance in England and Wales (1995-1997) of 11,528 individuals with IPD and a local enhanced surveillance in the Oxford (UK) area (1995-1999) have been analyzed. IPD has a high attack rate in children, with 37.1-48.1 cases per 100,000 infants <1 year old per year, and in older persons, with 21.2-36.2 cases per 100,000 persons >65 years old per year, for England, Wales, and Oxford. The 7-valent conjugate vaccine includes serotypes causing < or =79% of IPD in children <5 years old, but only 66% in adults >65 years old. The data also indicate that IPD varies by serotype, age, and country, emphasizing that the epidemiology of IPD is heterogeneous and requires continued surveillance.

Adolescent↗

PubMed2000

Carriage of serogroup W-135, ET-37 meningococci in The Gambia: implications for immunisation policy?

We found high levels of symptomless carriage of a hyperinvasive Neisseria meningitidis strain (electrophoretic type 37 [ET-37], serogroup W-135) during a vaccine trial in Gambian children in 1996. Serogroup C, ET-37 complex meningococci cause 30-40% of meningococcal disease in countries such as the UK, and have a point prevalence of 0.5-1.0%. The recent Haj-associated spread of serogroup W-135, ET-37 complex meningococci, which has been accompanied by numerous secondary cases, might be explained by the apparently raised carriage rates reported here.

Bacterial Vaccines↗

PubMed2000

Editorial comment.

Explore the source record for details and available documents.

Journal Article↗

PubMed2000

Molecular typing of bacteria directly from cerebrospinal fluid.

Using Streptococcus pneumoniae as an example, the ability of multilocus sequence typing (MLST) to characterise isolates directly from cerebrospinal fluid (CSF) was investigated. A nested multiplex polymerase chain reaction method that amplifies the seven housekeeping gene fragments used for pneumococcal MLST was applied to 30 CSF samples from suspected cases of bacterial meningitis. The fragments were amplified from all 14 samples from which Streptococcus pneumoniae was cultured, and, after direct sequencing, the allelic profiles obtained from ten of the samples corresponded to those of clones previously associated with invasive pneumococcal disease. MLST could also predict the penicillin susceptibility and serotype of the CSF isolates.

Alleles↗

PubMed2000

Function-based isolation of novel enzymes from a large library.

Here we describe a high-throughput, quantitative method for the isolation of enzymes with novel substrate specificities from large libraries of protein variants. Protein variants are displayed on the surface of microorganisms and incubated with a synthetic substrate consisting of (1) a fluorescent dye (2) a positively charged moiety (3) the target scissile bond, and (4) a fluorescence resonance energy transfer (FRET) quenching partner. Enzymatic cleavage of the scissile bond results in release of the FRET quenching partner while the fluorescent product is retained on the cell surface, allowing isolation of catalytically active clones by fluorescence-activated cell sorting (FACS). Using a synthetic substrate with these characteristics, we enriched Escherichia coli expressing the serine protease OmpT from cells expressing an inactive OmpT variant by over 5,000-fold in a single round. Screening a library of 6 x 10(5) random OmpT variants by FACS using a FRET peptide substrate with a nonpreferred Arg-Val cleavage sequence resulted in the isolation of variant proteases with catalytic activities enhanced by as much as 60-fold. This approach represents a potentially widely applicable method for high-throughput screening of large libraries on the basis of catalytic turnover.

Boron Compounds↗

PubMed2000

Outcome of invasive pneumococcal disease: a UK based study. Oxford Pneumococcal Surveillance Group.

METHODS: The records of 106 children aged less than 5 years with invasive disease caused by Streptococcus pneumoniae were reviewed. RESULTS: The clinical manifestations were meningitis (37%), upper respiratory tract infection (24%), pneumonia (19%), and occult bacteraemia (18%). One child died and seven had persisting neurological impairment. Five serotypes caused 83% of disease and 92% of the serotypes are included in the seven valent conjugate vaccines which are undergoing trials. CONCLUSIONS: These data suggest that S pneumoniae infection is associated with a low case fatality rate but substantial morbidity in the UK.

Child, Preschool↗

PubMed2000

A novel mutant allele of the chromatin-bound fission yeast checkpoint protein Rad17 separates the DNA structure checkpoints.

To further dissect the genetic differences between the checkpoint pathway following S-phase cdc arrest versus DNA damage, a genetic screen was performed for checkpoint mutants that were unable to arrest mitosis following cell-cycle arrest with a temperature-sensitive DNA polymerase delta mutant, cdc20-M10. One such checkpoint mutant, rad17-d14, was found to display the cut phenotype following S-phase arrest by cdc20-M10, but not by the DNA synthesis inhibitor hydroxyurea, reminiscent of the chk1 mutant. Unlike chk1 , rad17-d14 was not sensitive to UV irradiation. Interestingly, the ionising radiation sensitivity of rad17-d14 was only at higher doses, and cells were found to be defective in properly arresting cell division following irradiation in S phase, but not G(2) phase. Biochemical analysis attributes the checkpoint defects of rad17-d14 to the failure to phosphorylate the checkpoint effector Chk1p. To investigate if Rad17p monitors the genome for abnormal DNA structures specifically during DNA synthesis, chromatin association of Rad17p was analysed. Rad17p was found to be chromatin associated throughout the cell cycle, not just during S phase. This interaction occurred irrespective of the arrest with cdc20-M10 and, surprisingly, was also independent of the other checkpoint Rad proteins, and the cell-cycle effectors Chk1p and Cds1p.

Alleles↗

PubMed2000

Epidermoid cysts of the testis: the case for conservative surgery.

The series comprises 6 patients (mean age, 21 years) who presented with an epidermoid cyst of the testis between 1991 and 1998. Pre-operative ultrasonography suggested the presence of a testicular cancer in 3 patients who underwent a radical orchidectomy. The ultrasound successfully predicted the true diagnosis in 3 patients who had a wedge excision of the cyst together with a cuff of normal surrounding tissue. All patients are free of disease with a mean follow-up of 3 years. With increasing awareness of the condition coupled with accurate pre-operative radiological imaging, local excision of an epidermoid cyst with preservation of the remainder of the testis is now a feasible and rational alternative to more radical surgery.

Adolescent↗

PubMed1999

Quinuclidine inhibitors of 2,3-oxidosqualene cyclase-lanosterol synthase: optimization from lipid profiles.

Novel 3-substituted quinuclidine inhibitors of cholesterol biosynthesis are reported. Compounds were optimized against oxidosqualene cyclase-lanosterol synthase (OSC) inhibition in vivo, rather than by the conventional optimization of structure-activity relationship information based on in vitro OSC inhibition. Thus, examination of HPLC lipid profiles from orally dosed rats showed cholesterol biosynthetic intermediates and whether cholesterol levels were reduced. A new substituted quinuclidine pharmacophore 18a-c was rapidly found for the inhibition of OSC, and the most promising inhibitors were validated by the confirmation of potent OSC inhibition. Compound 16 gave an IC50 value of 83 +/- 11 nM for human and an IC50 value of 124 +/- 14 nM, for rat, coupled with oral and selective inhibition of cholesterol biosynthesis derived from OSC inhibition (rat, ED50 = 1.3 +/- 0.7 mg/kg, n = 5; marmoset, 15 mg/kg dose, n = 3, caused complete inhibition). These 3-substituted quinuclidines, which were derived from a quinuclidine series previously known to inhibit cholesterol biosynthesis at the squalene synthase step, may afford a novel series of hypocholesterolemic agents acting by the inhibition of OSC.

Administration, Oral↗

PubMed1999

Retroviruses: ancient and modern.

Retroviruses are transmitted in two distinct ways: as infectious virions and as 'endogenous' proviral DNA integrated in the germ line of their hosts. Modern infectious viruses such as HIV recently infected mankind from simian hosts, whereas human endogenous retroviral genomes have been present throughout old world primate evolution. Recently we have characterised novel retroviruses in humans and pigs. Human retrovirus 5 (HRV-5) is detected as an exogenous genome in association with arthritis and systemic lupus erythematosus. Porcine endogenous retroviruses (PERV) are carried in swine DNA but can be activated to produce virions that are infectious for human cells, which has implications for xenotransplantation. A brief account of HRV-5 and PERV is given here.

Animals↗

PubMed1999

Episodic memory: what can animals remember about their past?

The question of whether episodic memory, the ability to recall unique, personal experiences, is restricted to humans is a matter of current controversy. Recent work on food-storing jays suggests that several features of episodic memory may not be as exclusive to humans as previously thought. In this review we outline the critical features of episodic memory in humans, its relationship to declarative memory, and recent results revealing that jays can learn to perform a task that depends on certain features of episodic memory and can thus be considered 'episodic-like'. Finally, we compare this avian performance with a contemporary definition of human episodic memory and consider the implications for studies of hippocampal function and animal cognition.

Journal Article↗

PubMed1999

Smokers and haemodynamic responses to desflurane.

Changes in basic haemodynamic variables following a sudden increase in the concentration of inspired desflurane administered during anaesthesia were compared in 30 female smokers and 30 nonsmokers. Smokers had significantly greater percentage increases in heart rate (p = 0.02), systolic and diastolic blood pressure (p < 0.005 and = 0.01, respectively) and rate-pressure product (p < 0.005). Such increases were reached faster by smokers for both systolic and diastolic blood pressures (p < 0.01) and for rate-pressure product (p = 0.02). The peak values of rate pressure product reached were sufficient to warrant caution when using desflurane for anaesthesia in smokers.

Adult↗

PubMed1999

A survey of biomedical scientists and consultant pathologists involved in the cervical screening programme.

The past decade has seen a transformation in the National Health Service Cervical Screening Programme (NHSCSP) largely driven by responses to various screening scandals. Independent inquiries into these laboratory failures have identified a number of contributing factors. The aim of this postal survey was to determine how widespread these factors are throughout screening laboratories in England. The results indicate that issues around recruitment and retention of staff, the training of pathologists and low morale appear to be widespread. However, the results do not indicate a widespread breakdown in working relationships between consultants and biomedical scientists, although there is room for improvement in their relationships with hospital management. Finally, there seem to be mixed messages about the commitment of consultants to the screening programme.

Burnout, Professional↗

PubMed1999

Urinary incontinence after radical prostatectomy: a randomized controlled trial comparing pelvic muscle exercises with or without electrical stimulation.

OBJECTIVES: To assess the effectiveness of intensive conservative treatment on and the impact of urinary incontinence after radical retropubic prostatectomy. PATIENTS AND METHODS: Sixty-three men with urinary incontinence >/= 8 weeks after radical prostatectomy were randomized to one of three groups; group 1, standard treatment (control); group 2, intensive pelvic muscle exercises (PME); or group 3, PME plus electrical stimulation (PME+ES). Group 1 received verbal and written instructions about postoperative PME from their urologist and from the nurses at the pre-admission clinic. Groups 2 and 3 were treated by a physiotherapist for 30 min twice a week for 12 weeks and carried out home exercises three times a day on the days when they were not treated. Outcome was assessed using the 24-h pad test, two validated quality-of-life questionnaires and a urine symptom inventory, all obtained at baseline, 12, 16 and 24 weeks after enrolment. The final pad test was carried out approximately 8 months after surgery. RESULTS: Fifty-eight patients completed the study, 21 in group 1, 18 in group 2 and 19 in group 3; five discontinued, three with bladder neck contractures requiring dilatation, one with rectal pain when doing the exercises and one unable to complete therapy while on vacation. The mean (median) time elapsed from surgery to entry into the study was 19 (8) weeks. At 12 weeks from baseline, the mean overall urine loss had decreased from 463 g to 115 g but there were no differences among groups, nor were there significant differences in urine loss at 16 and 24 weeks (F=0. 16, P=0.69). There was a significant impact on quality of life during the early recovery. Despite preoperative instructions, many patients revealed little or no knowledge about catheter care, bladder spasms, rectal pain, incontinence and erectile dysfunction. Little of the preoperative education was retained because of the overwhelming nature of the diagnosis. CONCLUSIONS: From the initial assessment to the final pad-test at approximately 8 months after surgery, incontinence improved greatly in all three groups. This rapid improvement may have masked any treatment benefit. Further research should address incontinence in men whose urine loss has stabilized and who underwent surgery >8 months previously. Moreover, a telephone-based follow-up soon after discharge may alleviate many of the concerns expressed.

Aged↗

PubMed1999

The three major Spanish clones of penicillin-resistant Streptococcus pneumoniae are the most common clones recovered in recent cases of meningitis in Spain.

One hundred six isolates of Streptococcus pneumoniae recovered in Spain from patients with meningitis in 1997 and 1998 were characterized by multilocus sequence typing. A heterogeneous collection of genotypes was associated with meningitis in Spain: 65 different sequence types were resolved and, even at a genetic distance of 0.43, there were 37 distinct lineages. Thirty-eight percent of the isolates, including all isolates of serotypes 6B, 9V, 14, and 23F, were resistant to penicillin, and 24% of the isolates were members of the three major Spanish penicillin-resistant or multidrug-resistant clones of serotypes 6B, 9V, and 23F or serotype variants of these clones. These three clones (MICs, 1 to 2 microg of penicillin/ml) were the most common clones associated with pneumococcal meningitis in Spain during 1997 and 1998. Only two of the other clones associated with meningitis were penicillin resistant (MICs, 0.12 to 0.5 microg/ml). One of the two most prevalent penicillin-susceptible clones causing meningitis (serotype 3) has not been detected outside of Spain, whereas the other (serotype 18C) has been recovered from patients with meningitis in the United Kingdom, The Netherlands, and Denmark. The prevalence of meningitis caused by isolates of the three major Spanish penicillin-resistant or multiply antibiotic-resistant clones, which are now globally distributed, is disturbing and clearly establishes their ability to cause life-threatening disease.

Base Sequence↗

PubMed1999

A psychiatric trainee's guide to the criminal courts.

This article provides a guide on the criminal justice system in England and Wales to assist psychiatrists who are asked to prepare reports on people subject to criminal proceedings. It describes which sections of the Mental Health Act 1983 are relevant at different stages of the criminal justice process.

Criminology↗

PubMed1999

Patterns of respite use by aging mothers of adults with mental retardation.

Use of respite services by 275 aging families of adults with mental retardation was examined over a 4.5-year period. Although more than twice as many families used respite in 1993 compared to 1988, over half never used respite during this period. Most families using respite received in-home services, in moderate amounts, and with high levels of satisfaction. In an analysis of predictors of respite use, the only significant predictor in 1988 was poorer functional abilities of the adult with mental retardation. By 1993, respite use was predicted by three characteristics: poorer functional abilities, better health in the adult with mental retardation, and greater maternal caregiving burden. These findings reflect variability in aging families' needs for support and changing respite policies.

Adult↗