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Biomedical subjects

M Nicol

Publications and source records attributed to M Nicol.

At least 19 recordsLinked to original sources
PubMed2003

A glycine to aspartic acid substitution of COL2A1 in a family with the Strudwick variant of spondyloepimetaphyseal dysplasia.

BACKGROUND: Spondyloepimetaphyseal dysplasia (SEMD) is one of a clinically heterogeneous group of skeletal disorders, characterized by defective growth and modelling of the spine and long bones. Common clinical features include disproportionate short stature, malformed vertebrae and abnormal epiphyses or metaphyses. Some cases have been associated with mutations in the COL2A1 gene. AIM: To determine whether the autosomal dominant Strudwick-type SEMD in a three-generation family, showing specific phenotypical features such as chest deformity, limb shortening, myopia and early-onset degenerative osteoarthrosis, might be caused by a novel COL2A1 mutation. DESIGN: Genetic testing and clinical examination of family members. METHODS: Direct sequencing of PCR-amplified genomic DNA from the COL2A1 gene. RESULTS: A point mutation within exon 20 of the COL2A1 gene was identified that substituted a glycine for an aspartic acid residue at codon 262. DISCUSSION: All previously reported autosomal dominant mutations causing SEMD have substituted an obligate glycine within the triple helix, in particular at codons 292, 304 and 709 in the three reported Strudwick-type patients. Additionally, a recurrent glycine substitution at codon 154 has been identified in two unrelated Finnish cases with radiological features consistent with the Strudwick subtype. Our sixth helical glycine substitution extends the mutational spectrum and genotype/phenotype correlations of Strudwick-type SEMD.

Aspartic Acid↗
PubMed2001

Martensitic fcc-to-hcp transformation observed in xenon at high pressure.

Angle-resolved x-ray diffraction patterns of Xe to 127 GPa indicate that the fcc-to-hcp transition occurs martensitically between 3 and 70 GPa in diamond-anvil cells without an intermediate phase. These data also reveal that the transition occurs by the introduction of stacking disorder in the fcc lattice at low pressure, which grows into hcp domains with increasing pressure. The small energy difference between the hcp and the fcc structures may allow the two phases to coexist over a wide pressure range. Evidence of similar stacking disorder and incipient growth of an hcp phase are also observed in solid Kr.

Journal Article↗
PubMed2000

Variation in the vitreous phenotype of Stickler syndrome can be caused by different amino acid substitutions in the X position of the type II collagen Gly-X-Y triple helix.

Stickler syndrome is a dominantly inherited disorder characterized by arthropathy, midline clefting, hearing loss, midfacial hypoplasia, myopia, and retinal detachment. These features are highly variable both between and within families. Mutations causing the disorder have been found in the COL2A1 and COL11A1 genes. Premature termination codons in COL2A1 that result in haploinsufficiency of type II collagen are a common finding. These produce a characteristic congenital "membranous" anomaly of the vitreous of all affected individuals. Experience has shown that vitreous slit-lamp biomicroscopy can distinguish between patients with COL2A1 mutations and those with dominant negative mutations in COL11A1, who produce a different "beaded" vitreous phenotype. Here we characterize novel dominant negative mutations in COL2A1 that result in Stickler syndrome. Both alter amino acids in the X position of the Gly-X-Y triple-helical region. A recurrent R365C mutation occurred in two unrelated sporadic cases and resulted in the membranous vitreous anomaly associated with haploinsufficiency. In a large family with linkage to COL2A1, with a LOD score of 2.8, a unique L467F mutation produced a novel "afibrillar" vitreous gel devoid of all normal lamella structure. These data extend the mutation spectrum of the COL2A1 gene and help explain the basis for the different vitreous phenotypes seen in Stickler syndrome.

Abnormalities, Multiple↗
PubMed2000

Value of cerebrospinal fluid leukocyte aggregation in distinguishing the causes of meningitis in children.

BACKGROUND: Current laboratory tests often cannot distinguish between bacterial and aseptic meningitis rapidly and accurately. The ability to make a prompt diagnosis has important implications for the management and outcome of children with meningitis. The observation that leukocytes aggregate in the cerebrospinal fluid (CSF) has been previously reported, and it has been advocated as a reliable method to distinguish the causes of meningitis in children. OBJECTIVE: To investigate the utility of CSF leukocyte aggregation as a screening test to distinguish between bacterial and aseptic meningitis. METHODS: We compared the clinical and laboratory indices of 109 prospectively enrolled patients with meningitis (67 bacterial, 23 viral, 19 undefined etiology) and evaluated the validity of the CSF leukocyte aggregation test. The predefined leukocyte aggregation scores (LAS) were compared among the types of meningitis, and correlations with other markers of inflammation were calculated. RESULTS: The median LAS was significantly higher (P < 0.001) in the bacterial (32.1%; range, 0 to 84.1%) than in the viral (0%; range, 0 to 16.6%) or undefined (0%; range, 0 to 20.7%) groups. The optimal sensitivity of the leukocyte aggregation test, 98.5 to 92.5%, was demonstrated with LAS values of 0 to 3%. The corresponding specificity was 64.3 to 88.1%. The peripheral white blood cell (WBC) count, serum C-reactive protein, CSF WBC count, blood culture, CSF Gram stain and CSF culture were inferior to the LAS as screening tests when compared individually. The LAS was as effective as CSF protein, TNF-alpha, IL-1-beta, IL-6 and IL-8 to predict bacterial meningitis. In a logistic regression model that included routine laboratory tests, the best predictor of bacterial meningitis was the LAS (odds ratio, 1.6 to 3.7). Significant correlations were demonstrated between the LAS and CSF protein, CSF WBC count, IL-1-beta, IL-6 and IL-8. Duration of symptoms before diagnosis, pretreatment with antibiotics, HIV-1 infection status and CSF red blood cell count did not significantly alter the LAS. CONCLUSIONS: There is no single test to diagnose the etiology of meningitis in children promptly and accurately. The finding of leukocyte aggregation in CSF might be of value as a sensitive adjunctive screening tool for the timely diagnosis of bacterial meningitis, recognizing that it has low specificity and potential practical limitations.

Adolescent↗
PubMed2000

Reduction in episodes of self harm/harm to others in severely mentally ill population through assertive outreach.

This article aims to apply the process of clinical governance to the management of patients with a major mental illness, living in the community, with a history of self harm and/or harm to others; and to design an early warning system to drive rapid intervention if patients miss a clinic appointment. This follows the recommendations of good clinical practice for this vulnerable group.

Adult↗
PubMed2000

Acute regulation of the bovine gene for the steroidogenic acute regulatory protein in ovarian theca and adrenocortical cells.

Upregulation of the steroidogenic acute regulatory protein (StAR) is implicated in the rapid synthesis and secretion of steroidogenic cells to produce steroids in response to stimulation by trophic hormones of the gonadal and stress axes. In the present study, we have assessed the kinetics of both StAR gene transcription and protein biosynthesis in primary cell cultures of bovine adrenocortical and ovarian theca cells, under conditions of acute stimulation by corticotrophin (ACTH) and luteinizing hormone (LH), respectively. In both cell systems, detectable upregulation of StAR gene transcription occurred within 1-2 h, reaching maxima at 4 h (theca cells) or 6 h (adrenocortical cells). mRNA levels returned rapidly to baseline, by 12 h or 24 h, respectively. Specific StAR protein levels were assessed by western blotting using a novel antibody raised against a bovine StAR peptide, and showed a similar fast upregulation, albeit delayed by 1-2 h compared with the mRNA. The response of the cultured theca cells was more acute than that of the adrenocortical cells, possibly reflecting the propensity of the LH receptor to desensitize rapidly, unlike the ACTH receptor. The primary bovine theca cell cultures were also used for fully homologous transfection studies using various deletion promoter-reporter constructs of the bovine StAR gene. Kinetic analysis of the results indicated that the acute transcriptional response resides within the proximal (-315 bp) promoter region, which includes two putative responsive elements for the steroidogenic factor-1. More distal promoter regions may be involved in modulating the specificity of expression by combining enhancer and inhibitory functions.

Adrenal Cortex↗
PubMed2000

Effects of cellular mediator agonists on cortisol and steroid acute regulatory (StAR) protein in bovine zona fasciculata (ZF) cells.

Primary cultures of bovine ZF cells were incubated for 1 h or 6h with the agonists 8-bromo-cyclic AMP (8-Br-cAMP) an activator of protein kinase A (PKA), the phorbol ester phorbol 12-myristate 13-acetate (PMA) a protein kinase C (PKC) activator, the Ca2+ ionophore, A23187, or the L-type Ca2+ channel agonist Bay K8644. Both cortisol secretion (determined by radioimmunoassay of cell medium) and cellular StAR protein levels (quantified by western blotting) were significantly increased at 6h, by all agonists. However, while all agonists stimulated cortisol secretion at 1h, StAR protein levels remained unchanged by these treatments. We conclude that in bovine ZF cells, StAR protein synthesis can be regulated by mechanisms involving activation of PKA, PKC and Ca2+ influx. However, a net increase in cellular StAR protein does not appear to be essential for the initiation for the first stage of acute steroidogenesis.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1998

Assessment of clinical skills: a new approach to an old problem.

The changed nature of clinical placements, with shorter in-patient episodes and staff in clinical areas carrying increasingly high workloads, has prompted changes in the teaching learning and assessment of clinical skills. The 'Bart's Nursing OSCE' is an innovative approach to the assessment of clinical skills, through the medium of simulated professional practice. The antecedents of this educational development are discussed before detailed description of the Bart's Nursing OSCE. Discussion focuses upon: the rationale, authenticity, validity and reliability of the assessment; the roles of assessors and simulated patients; feedback to and from students and other stakeholders; the educational impact of the innovation; and management issues.

Clinical Competence↗
PubMed1998

Learning clinical skills: an interprofessional approach.

The professions of nursing and medicine are committed to interprofessional education, in the belief that through this, patient care and satisfaction will be improved. Most initiatives involving nurses have been at post-qualification level, in primary health care, and concerning interpersonal or information management skills. Much of this collaboration has been with professions allied to medicine or social services. This paper discusses an innovative programme of shared learning in acute care, involving final year medical students and newly qualified staff nurses. The programme, developed in response to the blurring of professional roles between nurses and junior doctors, took place in our interprofessional Clinical Skills Centre. It was based around a developing patient scenario which was pertinent to the participants' area of practice. Each session was led by an experienced nurse lecturer and doctor, supported by specialist contributors. The style of learning was participative, with small interprofessional groups addressing a range of patient management issues. In this way, relevant clinical and communication skills were integrated within the context of holistic patient care. The course was well evaluated by both professional groups of participants and their managers. Subsequent research and curriculum development are leading to the expansion of this successful initiative.

Clinical Competence↗
PubMed1997

IL-6, DHEA and the ageing process.

The age-related increase in circulating IL-6 levels in humans which has been attributed to a decline in DHEA production by the adrenal gland is currently attracting attention because of its possible relevance to the aetiology and management of a number of age-related clinical disorders. The potential importance of these observations and suggestions has prompted us to perform more detailed studies on the relationship between IL-6 and DHEA. Using immunoassay techniques we have found in normal healthy individuals over the age of 40 an inverse relationship between plasma DHEA levels and the presence of detectable levels of IL-6 (more than 1 pg/ml). In vitro, studies also revealed that low dose (10(-6)-10(-8) M) of DHEA and DHEAS inhibited the production of IL-6 in unstimulated human spleen cell suspension cultures whilst enhancing its release by explant cultures of the same tissue. In contrast they had no effect on immunoglobulin production. These studies suggest that there is a real, but complex relationship between IL-6 production and DHEA levels which warrants further investigation.

Adult↗
PubMed1996

Discharge of elderly people from an accident and emergency department: evaluation of health visitor follow-up.

Elderly people discharged directly home from an accident and emergency department are known to be a vulnerable group. The value of health visitor follow-up in patients aged 75 years and over was assessed in a random controlled trail; 222 intervention patients were seen at home by a research health visitor shortly after discharge and screened for new dependency and support needs, appropriate community services then being offered. These patients, and 192 controls for whom no special arrangements were made, were followed up four weeks later by a research occupational therapist. New dependency, most commonly trauma-related, was found in approximately 50%, and in the majority proved transient. Advice and/or referral to a wide range of services was offered to 92% of the intervention group. Service refusal rates were high in both groups. Compared to controls, intervention patients received more services and were significantly more independent at four weeks. Health visitor assessment was seen as helpful. In order to identify elderly accident and emergency department patients at risk following discharge, study data were used to derive a short questionnaire. In follow-up visits to 48 patients the use of this questionnaire was piloted, and its validity demonstrated. A number of study limitations and areas for development of discharge planning are discussed.

Activities of Daily Living↗
PubMed1996

Liver transglutaminases and vitamin-A deficiency in hairless mice.

In hairless mice, a moderate vitamin-A deficiency, without any clinical signs or weight changes, reduces the activity of soluble cytoplasmic hepatic transglutaminase without affecting the membrane form of the enzyme. This attack of soluble transglutaminase appears to be a biological marker of early deficiency. The relations between this disturbance and the hepatocyte sensitivity to aggressors at this stage are discussed.

Animals↗