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Biomedical subjects

D Currie

Publications and source records attributed to D Currie.

At least 19 recordsLinked to original sources

Comparison of risk factors for cerebral palsy in twins and singletons.

The aim of this study was to investigate the difference in rates of cerebral palsy (CP) between singletons and twins by considering factors that may be predictive of CP. Data were taken from the Scottish Register of Children with a Motor Deficit of Central Origin and the Scottish Morbidity Record series. All children born in Scotland between 1984 and 1990 inclusive comprised the cohort. There were 646 children with CP (370 males, 276 females) of whom 57 were from twin pregnancies. Prevalence of CP was higher in twins than in singletons. Also, for singleton and twin births, the prevalence of CP was higher for infants who had low birthweight for gestational age (GA), were preterm, and who were male. Prevalence of CP by GA followed a different pattern for twins than for singletons, being lower for twins in the middle range of GAs than for singletons. After allowing for GA and birthweight, twins appeared to be at increased risk for CP compared with singletons. The type of CP in singletons and twins also differed with 64.9% of twins having spastic bilateral CP compared with 48.5% for singletons. The aetiology of CP in twins and singletons may differ.

Birth Weight↗

Hierarchical recognition of CpG motifs expressed by immunostimulatory oligodeoxynucleotides.

Synthetic oligodeoxynucleotides (ODN) containing unmethylated CpG motifs trigger human PBMC to proliferate and secrete Ig, cytokines and chemokines. CpG ODN have entered clinical trials, and show promise as vaccine adjuvants, antiallergens, and for the treatment of infectious diseases and cancer. ODNs under consideration for human use vary in the sequence, number and location of the CpG motifs they contain. Yet little is known of the magnitude of the immune response elicited by these diverse ODNs, or the rules governing their interaction with immune cells. This work compares the proliferative, IgM, IL-6 and IP-10 response of PBMC from normal donors to a diverse panel of CpG ODNs. Results indicate that ODNs expressing 3-4 different CpG motifs are strongly stimulatory. The location of these motifs is important, with those at the 5' end exerting the greatest influence on ODN activity. These findings provide a basis for the rational design of ODNs optimized for clinical use.

Cell Division↗

Inevitable risk of high-order multiple pregnancies following IUI, the need for strict criteria for its prevention: two case reports.

Intrauterine insemination with controlled super-ovulation (IUI/SO) is appropriate management of subfertility where the Fallopian tubes are healthy and patent and the sperm quality is satisfactory. The treatment is monitored by intermittent transvaginal ultrasound scans to assess follicular development. There is an unavoidable increased risk of multiple pregnancy including higher order pregnancy. These two case reports suggest the need for national standards regarding the abandonment of the treatment cycle to further reduce the risk of high order multiple implantations.

Adult↗

Assessment of aspiration in patients with tracheostomies: comparison of the bedside colored dye assessment with videofluoroscopic examination.

BACKGROUND: Aspiration is a serious clinical concern in patients with long-term artificial airways. The purpose of this study was to determine the reliability of a bedside colored dye assessment of aspiration in tracheostomized patients and to determine its comparability to a more sophisticated videofluoroscopic study. METHODS: This was a prospective, blinded comparison study conducted in a large, urban, university teaching hospital. We studied 20 consecutive patients who underwent tracheostomy for bronchial hygiene needs and who were referred for videofluorographic evaluation for suspected oropharyngeal dysphagia and possible aspiration. Excluded were patients unable to follow verbal commands and those requiring mechanical ventilatory support. All patients were brought to the videofluorography suite for colored dye assessment for aspiration and videofluorographic assessment of oropharyngeal swallow. A nurse, blinded to the results of videofluorographic swallow study, performed colored dye assessments for aspiration. Speech-language pathologists, blinded to the results of the colored dye assessments, interpreted simultaneous (preliminary) and subsequent complete (final) videofluorographic evaluations of swallow. RESULTS: The colored dye aspiration assessments and the videofluoroscopic studies were compared for the frequency of aspiration detection. Sensitivity and specificity were determined using standard methods. Seven patients showed no aspiration on either the colored dye test or videofluoroscopic examination. Eight patients were judged to aspirate by videofluorography but not by the colored dye test. Five patients were judged to aspirate by both the colored dye test and videofluorography. The data indicate that the colored dye test for aspiration carries a low sensitivity of 38% (95% confidence interval = +/- 7%), but a high specificity of 100%. The videofluoroscopic study detected a significantly greater frequency of aspiration than did the colored dye test (p < 0.01). CONCLUSIONS: The colored dye test for aspiration can provide useful information when positive, but because there is a significant false negative rate, decisions made on the basis of a negative test must be made with caution.

Adult↗

The effect of experimental male removals on extrapair paternity in the wheatear, Oenanthe oenanthe.

To examine the role of the pair male in ensuring paternity in the wheatear, we removed pair males for 24 h during the fertile period (days 0 to +1 in 1992 and days -5 to -1 in 1993, where day 0=first egg date). Control males were removed during incubation. The frequency and duration of intrusions, and the frequency of extrapair copulations (EPCs), increased during removals in the fertile period, but not during incubation. The frequency of extrapair paternity (EPP) was marginally higher (25%) in experimental than control broods and the presence of the pair male seemed particularly important in ensuring paternity in those days immediately preceding laying. Females were selective over which males they copulated with in the absence of their mate and rejected the majority of attempted EPCs. Only extrapair males in better body condition than the removed pair male eventually gained successful matings. Experimental males in poorer body condition were also more likely to have EPP in their brood than experimental males in better body condition. Female copulatory behaviour was the most important factor in determining patterns of paternity, and mate-guarding behaviours by the pair male appeared to limit the females' opportunities to engage in EPCs by reducing the frequency and duration of intrusions, rather than to control female behaviour directly. Copyright 1999 The Association for the Study of Animal Behaviour.

Journal Article↗

Prosthetic reconstruction of the femur for primary bone sarcoma.

The survival of patients and implants, complications and functional outcome were reviewed in 25 consecutive femoral endoprosthetic reconstructions for treatment of primary bone sarcoma. The diagnosis was chondrosarcoma in 11, osteosarcoma in 10, MFH in 3 and Ewing's tumour in 1. Median follow up was 64 months (34 to 219) and median age at operation was 29 years (10 to 70). Twelve remained disease free at review. One had amputation for local recurrence and another was alive with metastases. 11 patients died at a median of 13 months (5 to 128); 8 from metastatic disease and 3 from other causes. Four implants were revised, at a median of 95 months (53 to 136); two for fractures of the stem and two for aseptic loosening. Three implants had radiological evidence of loosening at a median of 43 months (34 to 49). Fourteen patients had significant complications. The median functional score using the Musculoskeletal Tumour Society system was 68%. In our experience, prosthetic reconstruction of the femur does not compromise survival, although there is a significant complication rate.

Adolescent↗

Limited effects of heavy metal pollution on foraging and breeding success in the curlew (Numenius arquata).

We examined the effect of heavy metal pollution on the foraging success and breeding performance of the curlew (Numenius arquata) along a documented pollution gradient from a point source, and also by comparing foraging and breeding parameters between the polluted site and two non-polluted areas. Prey biomass and abundance, and foraging success did not vary along the pollution gradient, and were no less at the polluted site than in the non-polluted areas. Furthermore, there was no difference in adult weight during incubation between the polluted and non-polluted areas. There were also no differences in measures of breeding success along the pollution gradient, or between areas, which could be attributed to pollution per se. Egg shells from the polluted area had higher concentrations of heavy metals than in the non-polluted areas, and egg shells close to the pollution source were contaminated more than those further from it. However, there was no difference in calcium concentrations of egg shells or egg-shell thickness between areas. We conclude that in this study there were minimal immediate effects of heavy metal pollution on foraging and breeding success in the curlew.

Journal Article↗

Screening for chloramphenicol residues in the tissues and fluids of treated cattle by the four plate test, Charm II radioimmunoassay and Ridascreen CAP-Glucuronid enzyme immunoassay.

The administration of chloramphenicol (CAP) is banned in food animals in the European Union (EU). It is, therefore, important to have adequate screening methods to determine if residues of CAP and its major metabolite, chloramphenicol-glucuronide (CAP-Gluc), are present in samples taken for monitoring purposes. Six castrated male cattle were treated with a single intramuscular injection of 10 mg kg-1 CAP. Animals were sampled once daily for urine and were slaughtered at 3 and 6 d post-injection. Samples of bile, kidney, liver and diaphragmatic muscle were removed at slaughter. All matrices were analysed using the four plate test (FPT) bioassay, the Charm II radioimmunoassay and a Ridascreen CAP-Glucuronid competitive enzyme immunoassay (EIA). The FPT detected CAP residues in urine samples taken up to 2 d post-treatment. The Charm assay detected CAP in the urine for up to 4 d post-treatment. The EIA detected CAP throughout the 6 d sampling period. Samples of bile were positive by both the EIA and the Charm assay at day 3 and day 6. No zones of inhibition were obtained using the FPT in bile or diaphragm either with or without sample pre-treatment with beta-glucuronidase. However, the kidney and the liver from one animal killed at day 6 gave larger zones of inhibition after treatment with beta-glucuronidase, indicating the presence of CAP. The kidneys of all treated animals slaughtered at day 3 were positive by both the EIA and the Charm assay but none of the kidneys at day 6 tested positive by either method. Owing to technical difficulties, the Charm assay was not suitable for the analysis of liver. The EIA failed to detect CAP in the liver of any treated animal. It is concluded that urine appears to be the best matrix for screening purposes. The sensitivity of the FPT is inadequate for the determination of CAP residues were minimal withdrawal periods have been observed. The Charm assay and the EIA were suitable for the detection of both CAP and CAP-Gluc in tissues and body fluids for longer periods post-administration. The EIA was more sensitive for the determination of low concentrations of CAP and its metabolite.

Animals↗

The management of patients with advanced cancer (III).

In this third article in the series, the management of patients with symptoms arising as a consequence of metastatic disease involving peripheral nerves, the spinal cord and the brain are discussed. In particular, pain, spinal cord compression and symptoms due to either raised intracranial pressure or specific neurological deficits may substantially impair the quality of life in patients with advanced cancer. Pain control, using both medical and surgical treatments, are discussed. The principles underlying the diagnosis and treatment of metastases to the vertebral column and spinal cord, as well as intracranial deposits, are outlined.

Analgesia↗

The use of anti-depressants and benzodiazepines in the perpetrators and victims of accidents.

The objective of this study was to determine whether there is a greater incidence of psychotropic drugs in the blood of those 'responsible' for an accident compared with those not 'responsible' for an accident. Blood samples were taken from people involved in accidents presenting at the accident and emergency departments of two teaching hospitals over a five-month period and analysed for the presence of alcohol, tricyclic anti-depressants (TCAs) and benzodiazepines (BZs). Details of the accident were used to produce a test group (accidents where a drug may have contributed) and a control group (accidents where the presence of a drug could not have been a factor). In total, 229 samples were collected. The only criterion for inclusion in the study was that the accident was of sufficient severity to merit the routine taking of a blood sample, in which case an additional amount was taken for the purposes of this investigation. In all, 63 samples (27.5%) were positive for at least one of alcohol, TCA or BZ. Of the accidents represented by these samples, 48 could have been caused by the presence of the drug (responsible group) and 15 could not (not responsible group). There was a significantly greater representation of TCAs and BZs in the blood taken from the responsible group compared with the not responsible group (P < 0.0045).

Accidents↗

Central effects of repeated administration of atenolol and captopril in healthy volunteers.

The central effects of atenolol (50 mg tds) and captopril (50 mg tds) ingested for a period of seven days were studied in ten healthy volunteers. A placebo and two active control drugs, methyldopa (250 mg tds) and oxazepam (10 mg), were included in the design. Oxazepam was ingested on the seventh day only, with a placebo being taken on the preceding six days. On the seventh day, central effects of the drugs were tested at 10.00-11.00 h (session 1), immediately before the subjects' last dose of each drug and at 2.5-3.5 h after the final dose of each drug (1330-1430 h, session 2). Performance was assessed using digit symbol substitution, continuous attention, letter cancellation, choice reaction time, finger tapping, immediate and short-term memory, critical flicker fusion and two flash fusion. Subjects assessed their mood and well-being on a series of 12 visual analogue scales. Recordings of the EEG and body sway were carried out. Neither atenolol nor captopril altered performance at any of the skills tested. There were no effects on subjectively assessed alertness or mood with captopril, while atenolol significantly increased wakefulness in session 2 and when the two sessions were meaned. Similarly, captopril did not modify body sway, while with atenolol there was a significant decrease in activity in the frequency range 1.0-2.75 Hz from session 1 to session 2.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Random mating in a natural population of the malaria parasite Plasmodium falciparum.

The genetic structure of a population of the malaria parasite Plasmodium falciparum has been examined in a village in Tanzania. Seventeen alleles of the merozoite surface protein MSP-1 and 23 of MSP-2 were detected by the polymerase chain reaction (PCR) among the blood parasites of the inhabitants. Most infections contained mixtures of genetically distinct parasite clones. PCR was then used to examine individual P. falciparum oocysts, the products of fertilization events, in wild-caught mosquitoes. Forty-five out of 71 oocysts were heterozygous for one or both genes, showing that crossing between clones was taking place frequently, following uptake of mixtures of gametocytes by the mosquitoes. The frequency of heterozygous forms showed that random mating events probably occurred within mosquito bloodmeals between gametes belonging to different parasite clones.

Adolescent↗

Functional significance of different human CYP1A1 genotypes.

At least two different polymorphisms in the human CYP1A1 gene have been associated with an increased risk for tobacco-related lung cancer; however, the functional significance of these polymorphisms has not been determined. We measured CYP1A1 genotypes, gene expression levels and enzymatic activity levels in mitogen-stimulated lymphocytes to determine whether genetic polymorphisms in CYP1A1 alter transcriptional and/or post-transcriptional regulation of the gene. Genotypes were determined at two sites previously associated with lung cancer: a point mutation in exon 7 near the catalytic region of the enzyme and an Msp1 RFLP in the 3' non-coding region of the gene. Variant genotypes at the Msp1 site had no effect on CYP1A1 gene induction, however, variant genotypes at the exon 7 site were significantly associated with increased CYP1A1 gene inducibility. We also observed a significant interaction between the exon 7 polymorphism and smoking on mRNA levels. There was a 3-fold elevation in CYP1A1 enzymatic activity in exon 7 variant genotypes. When Msp1 and exon 7 genotypes were combined, there was an increased CYP1A1 inducibility and enzymatic activity in subjects with the exon 7 polymorphism, and in subjects with both polymorphisms.

Adult↗

Central effects of the diuretic, bendrofluazide.

1. Central effects of the diuretic, bendrofluazide (2.5, 5 and 10 mg) were studied in 12 healthy volunteers. Two placebos and an active control drug, oxazepam (15 mg), were included. Single doses were administered double-blind at 10.00 h. The effects of drugs on performance and subjective feelings were assessed before and from 1.5-2.5 and 3.5-4.5 h after ingestion, and recording of the electrical activity of the brain (EEG) and body sway carried out. 2. Performance was assessed using digit symbol substitution, continuous attention, letter cancellation, choice reaction time, finger tapping, immediate and short-term memory, together with critical flicker fusion and two flash fusion. Subjects assessed their mood and well-being on a series of 12 visual analogue scales. The EEG was recorded with eyes open while the subjects carried out a mental arithmetic task, and with eyes closed, when they were required to relax. Body sway was recorded with eyes open and with eyes closed. 3. Bendrofluazide (10 mg) increased the number of errors at letter cancellation and reduced the rate of finger tapping (P < 0.05), while oxazepam increased the number of errors and reduced accuracy at continuous attention (P < 0.01), and increased the number of involuntary rest pauses during tapping (P < 0.05). 4. There were no effects of drugs on subjective assessment of mood. 5. No changes in the electrical activity of the brain were observed with bendrofluazide. In recordings with eyes open, oxazepam reduced delta (0.5-3 Hz), theta (3.5-7 Hz) and alpha 2 (10.5-13 Hz) while increasing beta 1 (13.5-21 Hz) activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Lead exposure during recreational use of small bore rifle ranges.

AIMS: Following detection of symptomatic lead toxicity in two users of an indoor small bore rifle range, we studied users of several similar facilities to determine if significant recreational lead exposure occurred. METHOD: Red cell lead levels were measured at the end of a six month (winter) indoor shooting season and prior to commencement of shooting in the following year. Lead levels in air and dust sampled at one range were also measured. RESULTS: REd cell lead levels were elevated at the end of season (mean 2.64 mumol/L) and lower (mean 1.60 mumol/L) in the preseason samples. The average red cell lead level of the male shooters was 2.4 times normal and is comparable to the levels found in many occupationally exposed groups. Maximum air lead levels were 210 micrograms/m3, more than 2 times the Department of Labour OSH workplace exposure standard TWA of 100 micrograms/m3. Analysis of dust samples showed that dust at this range contained 24% to 36% lead. CONCLUSION: Although the mean time spent shooting was only 70 minutes per week the blood lead levels are similar to those previously reported for full time instructors at pistol ranges. This data confirms that lead exposure in recreational users of indoor small bore rifle ranges is a significant problem.

Adolescent↗

A novel CYP1A1 gene polymorphism in African-Americans.

A new Msp1 RFLP in the CYP1A1 gene has been found in genomic DNA from African-Americans. The polymorphism results from a single A-T to G-C transition in the 3' noncoding region approximately 300 bp upstream from the polyadenylation site. This mutation leads to cleavage of the normal 2.3 kb MspI restriction fragment into 1.3 and 1.0 kb fragments. The heterozygous mutation has been seen in 8 of 47 African-Americans, but was not detected in 191 Caucasians or 30 Asians. No linkage was observed with either of the two previously described polymorphisms in this gene.

Asia↗

Detection of cadmium exposure in rats by induction of lymphocyte metallothionein gene expression.

The induction of metallothionein (MT) gene expression in lymphocytes of rats was determined in order to detect exposure in vivo to cadmium. Both acute and chronic CdCl2 exposures resulted in the induction of the MT-1 gene in lymphocytes as measured by standard RNA Northern blot analysis. Twenty-four hours following an ip injection of 3.4 mg/kg CdCl2, a ninefold increase in MT gene expression was observed in lymphocytes, as well as five- and sevenfold increases in liver and kidney, respectively. Oral exposure of rats to 1-100 ppm CdCl2 via drinking water resulted in an approximate twofold enhanced MT signal in lymphocytes after 6 wk, and a threefold increase after 13 wk of exposure to 100 ppm Cd. No increases in lymphocyte MT gene expression were observed after 3 wk of Cd exposure. Liver MT gene expression was substantially induced following chronic Cd exposure, while kidney was not, although this organ had a higher basal expression of the MT-1 gene. Analysis of tissue Cd burdens demonstrated a dose-response Cd accumulation in liver and kidney, but only kidney burdens increased substantially with prolonged Cd exposure. These results demonstrate the utility of lymphocyte gene expression assays to detect in vivo toxicant exposure, and thus their applicability as molecular biomarker assays for human exposure assessment.

Animals↗