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R Metcalfe

Publications and source records attributed to R Metcalfe.

At least 19 recordsLinked to original sources
PubMed2006

Hemodynamics in a cerebral artery before and after the formation of an aneurysm.

Using data obtained from 3D digital subtraction angiography acquisitions, computational fluid dynamics techniques were used first to assess hemodynamic factors in geometrically correct models of 3 paraclinoid aneurysms and then again for assessment after virtual removal of the aneurysms and reconstruction of the parent artery. Simulations revealed an area of relatively low and rotating wall shear stresses at the location at which each aneurysm had developed. This phenomenon, to our knowledge, has not been previously described.

Angiography, Digital Subtraction↗
PubMed2005

New Zealand national incidence of bronchiectasis "too high" for a developed country.

AIMS: To prospectively estimate the incidence of bronchiectasis among New Zealand (NZ) children, to consider aetiology and severity, and to evaluate regional and ethnic variation. METHODOLOGY: NZ paediatricians were surveyed monthly for new cases of bronchiectasis during 2001 and 2002 via the NZ paediatric surveillance unit (with coverage of >94% of NZ paediatricians). Notified cases had their computed tomography scans reviewed and scored for severity. Confirmed cases were followed up by postal questionnaire one year after diagnosis. Demographic, aetiological, and severity data were collected. RESULTS: Ninety nine notifications were received. Sixty five cases were confirmed. An overall incidence of 3.7 per 100,000 under 15 year old children per year was estimated. Incidence was highest in Pacific children at 17.8 compared with 4.8 in Maori, 1.5 in NZ European, and 2.4 other per 100,000 per year. Incidence varied significantly by region. The median age at diagnosis was 5.2 years; the majority had symptoms for more than two years. Eighty three per cent had bilateral disease, with a median of three lobes affected, mean FEV1 of 77% predicted, and modified Bhalla HRCT score of 18. CONCLUSIONS: The incidence of bronchiectasis is high in NZ children, nearly twice the rate for cystic fibrosis and seven times that of Finland, the only other country reporting a childhood national rate. Incidence varied substantially between ethnicities. Most cases developed disease in early childhood and had delayed diagnosis.

Adolescent↗
PubMed2003

Retrospective review of children presenting with non cystic fibrosis bronchiectasis: HRCT features and clinical relationships.

Non cystic fibrosis (CF) bronchiectasis in children presents with a spectrum of disease severity. Our aims were to document the extent and severity of disease in children with non-CF bronchiectasis, to review the inter- and intraobserver agreement for the high-resolution computed tomography (HRCT) features examined, and to assess correlations between HRCT features and clinical measures of severity. We performed a retrospective review of 56 children from the Starship Children's Hospital. HRCT scans were scored by a modified Bhalla system, and the chest X-rays using the Brasfield score. Scores were correlated with demographics, number of hospitalizations, disease duration, pulmonary function, clinical examination, and chronic sputum infection. The bronchiectasis seen was widespread and severe, particularly in Maori and Pacific Island children. The kappa coefficient for intraobserver agreement was better than that for interobserver agreement. Comparisons between HRCT scan and lung function parameters showed that the strongest relationships were between forced expiratory volume in 1 sec (FEV(1)) and forced expiratory flow between 25-75% of forced vital capacity (FEF(25-75)) with the extent of bronchiectasis, bronchial wall thickening, and air trapping. Children with digital clubbing and chest deformity showed significantly higher scores for extent of bronchiectasis, bronchial wall dilatation and thickness, and overall computed tomography (CT) score. No relationship was demonstrated between chronic sputum infection and CT score. The HRCT score demonstrated a stronger correlation between the extent and severity of bronchiectasis, and spirometry values, than the chest X-ray score. In conclusion, pediatric non-CF bronchiectasis in Auckland is extensive and severe. The good intraobserver ratings mean that consistency of scoring is possible on repeated scans. This study cannot comment on the relationships of CT and less severe disease.

Adolescent↗
PubMed1998

Vitiligo melanocytes in long-term culture show normal constitutive and cytokine-induced expression of intercellular adhesion molecule-1 and major histocompatibility complex class I and class II molecules.

The aetiology of vitiligo remains unclear. An autoimmune involvement has been suggested and, in this study, we examine whether melanocytes cultured from unaffected regions of the skin of vitiligo patients are more susceptible to immune attack by investigating constitutive and cytokine-stimulated expression of intercellular adhesion molecule-1 (ICAM-1) (under three media variants) and major histocompatibility complex (MHC) class I and class II (under one medium). Both normal and vitiligo melanocytes had similarly low constitutive expression of ICAM-1 and MHC class II molecules, whereas > 95% of cells had high constitutive expression of MHC class I. Normal and vitiligo melanocytes showed similar and significant increases in the expression of all three immune-related molecules in response to the cytokine, interferon-gamma. The expression of ICAM-1 was also similarly increased by the cytokine, tumour necrosis factor-alpha in both cells. Additionally, it was noted that, once the melanocyte cultures were established under experimental conditions, the rate of proliferation of vitiligo melanocytes did not differ significantly from that of normal melanocytes. In conclusion, we suggest that vitiligo melanocytes, once in culture, do not have intrinsic differences from normal melanocytes with respect to the expression of immune-related molecules.

Adult↗
PubMed1998

A new chemiluminescent assay for the rapid detection of thyroid stimulating antibodies in Graves' disease.

OBJECTIVE: Thyroid stimulating antibodies (TSAb) are the cause of Graves' disease (GD). At present, these antibodies can only be measured using bioassays, which are generally time consuming and difficult to apply to whole serum. Here we describe a new chemiluminescent assay for the detection of TSAb in serum samples. METHODS: A Chinese hamster ovary (CHO) cell line, stably transformed with a reporter plasmid containing the firefly luciferase gene under the transcriptional control of multiple cAMP responsive elements (CRE), was transfected with the human thyroid stimulating hormone (TSH) receptor. A clonal cell line, (NA-4), was obtained which showed a dose-dependent increase in luciferase activity in response to bovine and human TSH stimulation. NA-4 was subsequently used to study TSAb activity in 42 GD sera. RESULTS: Of the GD sera 25 (60%) produced an increase in luciferase activity of 1.4-9 fold that obtained with control sera. Results were compared with an established bioassay for TSAb, based on the direct measurement of intracellular cAMP, and there was a significant correlation between the two assays (r = 0.8; P < 0.0001). IgG from GD patients, but not controls, also increased luciferase activity in NA-4 cells using concentrations as low as 3 mg/l in selected samples. CONCLUSION: The present report describes a simple, sensitive and rapid assay for the detection of TSAb, with application both in the clinical analysis of GD patient sera and as a potential research tool for use in the isolation of TSAb monoclonal antibodies.

Animals↗
PubMed1998

Are autoimmune thyroid dysfunction and depression related?

The objective of this study was to examine the relationship between autoimmune thyroid disease and depression in perimenopausal women. Thyroid function [TSH, free T4, and thyroid peroxidase antibodies (TPO-Ab)] and depression (using the Edinburgh Depression Scale) were assessed cross-sectionally together with other determinants of depression. The subjects were 583 randomly selected perimenopausal women (aged 47-54 yr) from a community cohort of 6846 women. The main outcome measures were the occurrence of thyroid dysfunction (abnormal free T4 and/or TSH or elevated levels of TPO-Ab) and the concomitant presence of depression according to the Edinburgh Depression Scale. Neither biochemical thyroid dysfunction nor menopausal status was related to depression. Apart from several psycho-social determinants (the occurrence of a major life event, a previous episode of depression, or financial problems), an elevated level of TPO-Ab (> or = 100 U/mL) was significantly associated with depression (odds ratio, 3.0, 95% confidence interval, 1.3-6.8). We conclude that women with elevated TPO-Ab levels are especially vulnerable to depression, whereas postmenopausal status does not increase the risk of depression.

Autoantibodies↗
PubMed1998

Common mutations in autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy patients of different origins.

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED; OMIM *240300, also called APS 1,) is a rare autosomal recessive disorder that is more frequent in certain isolated populations. It is generally characterized by two of the three major clinical symptoms that may be present, Addison's disease and/or hypoparathyroidism and/or chronic mucocutaneous candidiasis. Patients may also have a number of other clinical symptoms including chronic gastritis, gonadal failure, and rarely, autoimmune thyroid disease and insulin-dependent diabetes mellitus. We and others have recently identified the gene for APECED, which we termed AIRE (for autoimmune regulator). AIRE is expressed in thymus, lymph nodes, and fetal liver and encodes a protein containing motifs suggestive of a transcriptional regulator, including two zinc finger motifs (PHD finger), a proline-rich region, and three LXXLL motifs. Six mutations, in cluding R257X, the predominant Finnish APECED allele, have been defined. R257X was also observed in non-Finnish APECED patients occurring on different chromosomal haplotypes suggesting different mutational origins. Here we present mutation analyses in an extended series of patients, mainly of Northern Italian origin. We have detected 12 polymorphisms, including one amino acid substitution, and two additional mutations, R203X and X546C, in addition to the previously described mutations, R257X, 1096-1097insCCTG, and a 13-bp deletion (1094-1106del). R257X was also the common mutation in the Northern Italian patients (10 of 18 alleles), and 1094-1106del accounted for 5 of 18 Northern Italian alleles. Both R257X and 1094-1106del were both observed in patients of four different geo-ethnic origins, and both were associated with multiple different haplotypes using closely flanking polymorphic markers showing likely multiple mutation events (six and four, respectively). The identification of common AIRE mutations in different APECED patient groups will facilitate its genetic diagnosis. In addition, the polymorphisms presented provide the tools for investigation of the involvement of AIRE in other autoimmune diseases, particularly those affecting the endocrine system.

Female↗
PubMed1998

Involvement of calcium in retinal pigment epithelial cell proliferation and pigmentation.

PURPOSE: The aim of this study is to explore the role of intracellular calcium in the mechanism of co-regulation of retinal pigment epithelial cells (RPE) by vitreous fluid and platelet mitogens, in order to evaluate the use of calcium modulating drugs in preventing RPE cell proliferation and contraction of fibrocellular membranes. METHODS: Monolayers of human RPE cells were loaded with Fura-2-AM and examined in a fluorimeter for changes in intracellular free calcium in response to platelet mitogens (PDGFAB or TGFbeta1) and vitreous fluid (containing vitreous substrate proteins), both alone or in combination. The effect of the calcium antagonists TMB8 and verapamil and the calmodulin antagonists J8 and tamoxifen were then examined on RPE cell proliferation and pigmentation, both in the presence and absence of vitreous substrate and platelet mitogens. RESULTS: We report that co-exposure of RPE cells to platelet mitogens and vitreous fluid produces an increase in intracellular free calcium of greater duration than that with either PDG-FAB, TGFbeta1 or vitreous fluid alone. Calcium and calmodulin antagonists significantly reduce RPE cell proliferation in both the presence and absence of vitreous substrate and platelet mitogens. Calcium antagonists also stimulate the accumulation of autofluorescent granules within RPE cells. CONCLUSIONS: Calcium signalling plays a role in the co-regulation of RPE cells by vitreous substrate and platelet mitogens. Drugs that lower intracellular calcium or inhibit calmodulin may offer an additional approach to preventing the hyperproliferation of RPE cells in PVR.

Adult↗
PubMed1995

Immunoglobulin A class fibroblast antibodies in patients with Graves' disease and pretibial myxedema.

The involvement of autoantibodies in the extrathyroidal manifestations of Graves' disease has been the subject of extensive investigation, with fairly inconclusive results to date. We investigated the presence of immunoglobulin A (IgA) and IgG antibodies in patients with Graves' disease and pretibial myxedema (PTM; n = 21) as well as those with Graves' disease with thyroid-associated ophthalmopathy (TAO; n = 10), Graves' disease with no clinical evidence of extrathyroidal manifestations (n = 11), Hashimoto's thyroiditis (n = 9), type 1 diabetes mellitus (n = 10), systemic lupus erythematosus (n = 9) and normal individuals (n = 17). We looked for antibodies to both retroocular muscle and dermal fibroblasts as well as to thyroid peroxidase, thyroid microsomal antigen, thyroglobulin, and human eye muscle membranes. IgA class antibodies to microsomal antigen (30-50% of patients), thyroid peroxidase (5-20%), and human eye muscle membrane (0-26%) antigens were found in the various groups of patients with Graves' disease. With each of these antigens, serum from patients with PTM showed the greatest binding. Highly significant IgA binding was shown by PTM serum to both dermal (P < 0.001) and retroocular muscle (P < 0.001) fibroblasts from 12 different donors. Serum from Graves' patients with and without TAO and that from Hashimoto's thyroiditis patients reacted significantly with 4 of the 12 fibroblasts lines. In contrast, IgG binding was only found for 3 of the 12 fibroblast lines using patient serum. The IgA binding to fibroblasts shown by PTM patients was predominantly of the IgA2 subclass. The activity was absorbed out by both fibroblasts and thyroid cells. In immunoblotting studies, PTM patient serum reacted with a 54-kilodalton dermal fibroblast antigen and a 66-kilodalton retroocular fibroblast antigen. No binding to these antigens was seen with serum from normal controls or patients without PTM. Further elucidation of the nature of this fibroblast antigen will help to determine the role of IgA autoantibodies in the extrathyroidal manifestations of Graves' disease.

Adult↗
PubMed1994

An investigation of the ability of TSH and Graves' immunoglobulin G to increase intracellular calcium in human thyroid cells, rat FRTL-5 thyroid cells and eukaryotic cells transfected with the human TSH receptor.

The purpose of this study was to determine if immunoglobulin G preparations (IgGs) from patients with Graves' disease can increase intracellular calcium in thyroid cells, as has been reported for TSH. Both TSH and Graves' IgGs (prepared by protein G affinity chromatography) increased calcium in a range of thyroid cells; however, the response seen, using Fura-2-loaded coverslips of cell monolayers, varied considerably. Chinese hamster ovary (CHO/JPO9) cells transfected with a high number of human TSH receptors showed the greatest response: TSH (10 mU/ml) increased calcium in 46% of experiments and 18 out of 25 (72%) Graves' IgGs increased calcium at 0.1 mg/ml (significantly greater, P < 0.001, than for control IgGs where cells responded to 2 out of 13 preparations). Rat FRTL-5 cells only responded to TSH in 22% of experiments and to 2 out of 8 (25%) of Graves' IgGs. Similarly, human thyroid cells responded to TSH in 22% of experiments and to 2 out of 9 (22%) of Graves' IgGs. (When studying cyclic AMP responses in JPO9 cells, much higher concentrations of Graves' IgGs were required (1-3 mg/ml). However, higher concentrations (0.3 mg/ml) of both Graves' IgGs, and to a lesser extent of control IgGs, were capable of increasing calcium in cells both with and without TSH receptors (control CHO cells and normal human dermal fibroblasts). We conclude that relatively low concentrations of patient IgGs can be distinguished from control IgGs in JPO9 cells on the basis of their ability to increase calcium, but that additionally all IgG preparations possibly contain another factor which can increase calcium in a range of cells independent of the presence of the TSH receptor.

Adolescent↗
PubMed1990

Somatization and illness behaviour in a neurology ward.

One hundred and thirty-three female patients admitted to a neurological ward were fully investigated for the presence of organic neurological disease, and assessed for psychiatric disorder and illness behaviour, using the Clinical Interview Schedule (CIS) and the Illness Behaviour Questionnaire (IBQ). The likelihood of the presenting symptoms being due to organic disease was expressed by the neurologists on a visual analogue scale and the psychiatrists used a similar technique to describe whether the symptoms could be the result of psychiatric disorder. Many patients either had clear organic disease or somatic presentation of psychiatric disorder 'somatization', but one-third fell between these two extremes and either had a complex mixture of the two types of illness or could not be accurately diagnosed. The IBQ scores were raised in those with psychiatric disorder but did not help to explain why some patients present to the neurologists with symptoms that are unexplained by either organic disease or psychiatric disorder. Close liaison between neurologists and psychiatrists increases the detection of psychiatric disorder but some patients would require long-term follow-up to understand the true nature of the underlying disorder.

Adolescent↗
PubMed1988

Gadolinium-DTPA as a contrast agent in magnetic resonance imaging of the brain.

One hundred patients with CT-proven intracranial disease have been studied by magnetic resonance imaging (MRI) before and after intravenous injection with Gadolinium-DTPA (Gd-DTPA), in order to assess the role and clinical efficacy of Gd-DTPA. T2-weighted spin echo sequences, although sensitive to the detection of intracranial disease, in general fail to differentiate macroscopic tumor from oedema. Following Gd-DTPA, T1-weighted spin echo sequences in primary tumours demonstrated a variable degree of contrast enhancement unrelated to histological type. Small tumours, especially acoustic neuromas and meningiomas in the posterior fossa, were rendered more conspicuous. Optimum time for scanning was between five and 25 min following injection for all lesions except those adjacent to normal enhancing structures such as nasal/sinus mucosa and pituitary gland when delayed scans up to 45 min were necessary. No differences were observed between the 0.1 and 0.2 mmol/kg Gd-DTPA concentrations used and no complications attributable to Gd-DTPA were detected. Clinical advantages of Gd-DTPA include shorter scan times, macroscopic tumour/oedema separation and improved detection of certain tumours, particularly acoustic neuromas.

Adolescent↗
PubMed1988

Psychiatric morbidity and illness behaviour in female neurological in-patients.

Ninety three female neurological in-patients were assessed in a collaborative neurological and psychiatric study. An overall prevalence of definite psychiatric disorder of 34% was found, depression being the most common diagnosis. Psychiatric morbidity was most common when the neurologist felt that the presentation could not be explained by a neurological disorder. The majority of such patients had symptoms which could be explained by the psychiatric disorder but a substantial number could not be given a definite diagnosis. The General Health Questionnaire was not found to be a useful screening instrument in this setting.

Cerebrovascular Disorders↗
PubMed1988

Extracellular calmodulin and its association with epidermal growth factor in normal human body fluids.

In this study we describe the occurrence of a calmodulin-like protein in normal human biological fluids. Extraction of the calmodulin-like protein from breast milk, saliva, serum and urine provided an extract with enhanced calmodulin immunoreactivity which, in the case of milk and saliva, showed a protein band comigrating with authentic calmodulin (Mr 17,000) on sodium dodecylsulphate-polyacrylamide gel electrophoresis. However, in milk, saliva and serum a major protein band of Mr 14,000-15,000 was always observed, which we speculate may be related to calmodulin, possibly as a partially degraded form. Estimates of biologically active calmodulin in most normal extracellular fluids were of the order which we have found will stimulate cell division when added to the extracellular medium of cells in culture. Levels ranged from 0.03 nmol/l in urine to 18.6 nmol/l in breast milk, and exhibited a quantitative relationship (r = 0.79, P less than 0.01) to epidermal growth factor (EGF) levels in fluids. Where EGF concentrations varied from normal (increased in saliva 24 h after oral surgery and reduced in the urine of patients with renal failure) calmodulin concentrations were similarly affected. The presence of calmodulin in serum may in part be attributable to its release from platelets which are particularly rich in calmodulin. Release of calmodulin from the platelet was associated with that of EGF and other platelet products.

Blood Platelets↗
PubMed1986

Antibody levels to Mycoplasma pneumoniae in sera collected from healthy blood donors of Wellington, New Zealand, during 1976-80.

The sera of healthy blood donors from the Wellington area of New Zealand, collected between 1976 and 1980, were analysed by the complement fixation test for antibody to Mycoplasma pneumoniae. A high prevalence of antibody to this organism was demonstrated and the occurrence of an M. pneumoniae epidemic in New Zealand within the survey period was shown to be reflected in the immune status of this healthy adult population. This would suggest that during an epidemic many people within the Wellington community may have M. pneumoniae infections involving little overt illness.

Adolescent↗