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Biomedical subjects

H Sinclair

Publications and source records attributed to H Sinclair.

At least 19 recordsLinked to original sources
PubMed1996

Agalactosyl IgG [Gal(o)]--an analysis of its clinical utility in the long-term follow-up of patients with rheumatoid arthritis.

This long-term prospective study of patients with newly diagnosed RA assesses the relative value of certain clinical and laboratory measures at first consultation in order to determine factors that help to discriminate between patients likely to go into early remission and those with relapsing/remitting or persistent disease. Validation was sought in a similar group from a separate but comparable prospective study. Measures of clinical activity such as joint score, early morning stiffness (EMS) and acute phase (ESR) improved over 4 yr in both groups, whereas agalactosyl IgG [Gal(o)] levels increased. Using discriminant functional analysis in the first cohort to identify features at entry which would predict outcome at 4 yr, a combination of Gal(o), grip strength, age at onset and gender predicted the course of RA correctly in 95% of the patients. This combination was confirmed in the second cohort, although with reduced power (78% correct). Thus, we show that Gal(o) does not reflect activity of the disease like the ESR, but has greater potential as a prognostic index early in the course of disease.

Arthritis, Rheumatoid↗
PubMed1995

Secular trends in mortality from asthma in children and young adults: Republic of Ireland, 1970-91.

Trends in mortality attributed to asthma in children (0-14 years) and young adults (15-44 years) and the age group 5-34 years were examined for the Republic of Ireland over the period 1970-91. Childhood mortality rates were low with no clear trend. A recent rise in asthma mortality was observed in the 5-34 year olds but not in the 15-44 year age group. More detailed examination of these rates revealed that the rise in mortality in the 5-34 year olds derived from the age band 25-34 years. This increase is masked in the 15-44 year age group by wide fluctuations in mortality in the age band 35-44 years. A similar discrepancy in asthma mortality trends for the 15-44 and 5-34 year age groups has been reported in Britain. Possible reasons for the recent rise in asthma mortality in the 25-34 year age group are discussed.

Adolescent↗
PubMed1995

Functional changes in early child language: the appearance of references to the past and of explanations.

Spontaneous speech samples from children during the period of transition from one word to multi-word utterances in interaction with their French-speaking mothers were explored in order to study the appearance and development of functional changes in their use of language. Two types of such change were noted in the longitudinal records of four children when they were still essentially one-word speakers: the beginnings of references to the past, and the appearance of explanations and justifications, especially in communicative situations of request and refusal. The co-appearance of these behaviours is discussed in relation to two more general developmental changes: a detachment from the immediately perceptible situation linked to a further elaboration of the signifier-signified relation, and a socio-cognitive development leading to a view of the interlocutor as an alter ego, as a person whose psychological states may be different from the child's own.

Child Language↗
PubMed1995

Two cases of Wegener's granulomatosis involving the pituitary.

We describe two patients with Wegener's granulomatosis involving the pituitary. The diagnosis of Wegener's granulomatosis was inferred from the histological appearance of biopsy tissue and the presence of anti-neutrophil cytoplasmic antibodies with cytoplasmic distribution in the first case, in which disease remained confined to the pituitary, causing anterior and posterior pituitary dysfunction. In the second case the diagnosis was made by the progressive involvement of other organ systems, compatible histology and the presence of anti-neutrophil cytoplasmic antibodies with cytoplasmic distribution. In neither patient did posterior pituitary dysfunction respond to immunosuppressive therapy, despite remission of other features of systemic vasculitis. Panhypopituitarism in association with isolated pituitary Wegener's granulomatosis has not previously been described.

Adult↗
PubMed1994

A survey of new attenders at a paediatric accident and emergency department.

A prospective study of one week's new attendances (sampled over three consecutive weeks) at the A&E Department of the National Children's Hospital (NCH) was undertaken. A total of 310 children attended over the composite week. Of these, 307 took part in the study, all but three of which were accompanied by an adult. Almost three-quarters (72%) of the children attended without medical referral. Most children (80%) resided within two miles of the hospital. While 46% of respondents claimed they had used the hospital at least once during the previous twelve months, frequent attendance did not appear to be a problem. The majority of children (83%) were seen by a casualty officer within one hour of arrival. Injuries accounted for over half (53%) of the conditions presented. A fifth (21%) of the attenders were admitted, half (54%) of whom were discharged within 24 hours. The study provides baseline data on paediatric A&E services in Dublin and should assist planning of future services.

Adolescent↗
PubMed1994

Pharmacology of high-threshold calcium currents in GH4C1 pituitary cells and their regulation by activation of human D2 and D4 dopamine receptors.

1. The objective of this study was to characterize the pharmacology of calcium currents in GH4C1 pituitary cells and determine whether activation of heterologously expressed human dopamine receptors can regulate their function. Human D2(short), D3 and D4.2 receptor cDNA's were separately transfected into GH4C1 cells and whole cell calcium currents were recorded by use of nystatin-perforated patch clamp techniques. 2. High-threshold calcium currents were antagonized in a biphasic manner by the dihydropyridine, nisoldipine. The half-maximally effective concentration for each site was 0.2 nM (pIC50 = 9.78 +/- 0.21, n = 4) and 339 nM (pIC50 = 6.47 +/- 0.12, n = 4). The component of current inhibited by 10 nM nisoldipine was also blocked by omega-conotoxin GVIA (30 +/- 9% at 30 nM, n = 6) or by omega-agatoxin IVA (34 +/- 7% at 100 nM, n = 4). 3. Activation of either D2 or D4 receptors by dopamine (10 microM) or quinpirole (0.1 to 10 microM) reduced the peak calcium current by ca. 20% in the majority of cells studied. No inhibition was observed in control or D3 transfected GH4C1 cell lines. 4. The mobilisation of intracellular calcium by thyrotropin releasing hormone in hD4-GH4C1 cells was also studied using Fura-2 AM microspectrofluorimetry. Thyrotropin releasing hormone caused a concentration-dependent increase in calcium mobilisation with an EC50 of 7 nM. D4 receptor activation had no effect upon either basal or hormone-induced [Ca2+]i transients. 5. These results demonstrate that GH4C1 pituitary cells have at least two types of dihydropyridine sensitive high-threshold calcium currents and that like D2 receptors, human D4 receptors can also regulate calcium channel function.

Animals↗
PubMed1994

Depression of high-threshold calcium currents by activation of human D2 (short) dopamine receptors expressed in differentiated NG108-15 cells.

1. This study examined the regulation of calcium currents in differentiated NG108-15 cells that had been stably transfected with cDNA encoding the short isoform of the human D2 dopamine receptor. Whole cell calcium currents were recorded by nystatin-perforated patch clamp recording. 2. Transient low-threshold calcium currents elicited by depolarizations from -100 mV to -20 mV were reversibly depressed by NiCl2 (84 +/- 8% at 30 microM; n = 3) and by omega-agatoxin IVA (15 +/- 5%; 100 nM, n = 7). These currents were unaffected by hD2 receptor activation. 3. High-threshold calcium currents elicited by depolarizations from -80 mV to 0 mV were partly blocked by omega-conotoxin GVIA (67 +/- 6% at 100 nM, n = 4) and by the subsequent addition of the dihydropyridine, nisoldipine (94 +/- 3% at 1 microM). Consistent with the presence of at least two distinct types of high-threshold calcium channels, nisoldipine alone (38 +/- 15% at 1 microM, n = 6) did not preclude the inhibition caused by omega-conotoxin GVIA (69 +/- 13% at 100 nM, n = 4). The residual current was completely blocked by 100 microM CdCl2 (98.8 +/- 0.4%, n = 7). 4. In hD2-transfected cells, but not untransfected cells, high-threshold currents were depressed by quinpirole (30 +/- 4% at 100 nM; n = 15) with a pEC50 of 8.61 +/- 0.22 (n = 5), as well as by (-)-noradrenaline (28 +/- 5% at 1 microM, n = 9). Responses to both agonists were selectively antagonized by S-(-)sulpiride (100 nM) but not by the alpha-adrenoceptor antagonist, phentolamine (1O microM). The depression caused by (-)-noradrenaline was positively correlated with that of quinpirole for each cell(r2 = 0.91, slope = 0.99).5. hD2-receptor-mediated inhibition of high-threshold calcium currents was abolished by pretreatment of cells with omega-conotoxin GVIA (100 nM; n = 4). However, a component of the high-threshold current was reversibly depressed by omega-conotoxin GVIA (67% to 45% depression after 10 min wash). This current was also depressed by hD2 receptor activation (59 +/- 9% depression in 100 nM quinpirole, n = 3),and was completely blocked by nisoldipine (95 +/- 2% at 1 MicroM).6. These data demonstrate that activation of hD2(short) dopamine receptors can regulate both wconotoxinGVIA, and dihydropyridine-sensitive high-threshold calcium currents in neuroblastoma cells.Morever, the ability of human D2 dopamine receptors to regulate more than one type of calcium current supports the notion that these receptors have a diverse functional role in the central nervous system.

Animals↗
PubMed1991

Agalactosyl IgG: an aid to differential diagnosis in early synovitis.

Sixty consecutive patients presenting with early-onset synovitis were studied by measuring rheumatoid factor (RF) titers and the percentage of oligosaccharide chains attached to the C gamma 2 domain of IgG that lack galactose (GAL[0]). After 2 years of followup, 39 patients (65%) had developed rheumatoid arthritis (RA), and 21 had developed a variety of other inflammatory joint diseases. A combination of RF positivity and GAL(0) levels above the age-corrected mean gave a positive predictive value for a diagnosis of RA in 94% of these patients. These observations may well have clinical utility.

Adult↗
PubMed1991

Local injection treatment of tennis elbow--hydrocortisone, triamcinolone and lignocaine compared.

Corticosteroid injections are the mainstay of treating tennis elbow even though their effectiveness has not been well established by controlled studies. A survey of consultant rheumatologists confirmed a widespread preference for this treatment but they varied in their choice of steroid dose and preparation. We examined the value of some practices by comparing local injections of 2 ml 1% lignocaine with either 10 mg triamcinolone or 25 mg hydrocortisone made up to 2 ml with 1% lignocaine (Study 1). The investigation was conducted double blind. Within the first 8 weeks, pain relief was greater for triamcinolone than hydrocortisone although the differences were not statistically significant. The response to both steroid preparations was significantly better than for lignocaine up to this point but at 24 weeks, the degrees of improvement were similar for all three groups and many patients still had pain. Relapse was common. In a separate but similarly designed study, triamcinolone 10 mg was compared with 20 mg of the same agent. Improvements of pain were similar and followed the same time scale. Post-injection worsening of pain occurred in approximately half of all steroid treated patients in both studies and this was sometimes severe and persistent. It was less frequent amongst those given lignocaine alone. Skin atrophy was reported in all groups but was more frequent amongst those given triamcinolone in Study 1. In conclusion, more rapid relief of symptoms was achieved with 10 mg triamcinolone than with 25 mg hydrocortisone or lignocaine alone and there was less needed to repeat injections. Results obtained with 20 mg triamcinolone were similar to those of the smaller dose.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

From one word to two words: repetition patterns on the way to structured speech.

This paper gives an account of the transition from one-word to multi-word utterances based on the productions of one child from age 1; 5.23 to 1; 8.15 in spontaneous interaction with her mother. The authors' interpretation of the observed development emphasizes: (1) the initial dissociation and later co-ordination of temporal chaining of elements on the one hand and meaning-relatedness between elements on the other; and (2) the psychological importance of repetition patterns for the change from single-word functioning to meaning-related and temporally-chained multi-word utterances, i.e. utterances that show the duality of patterning characteristic of human language.

Female↗
PubMed1990

Estimating the prevalence of chronic respiratory disease.

A method is described for estimating the prevalence of chronic respiratory disease in a middle aged and elderly general practice based population, using the prescription of drugs in order to identify the disease. The prevalence estimates ranged from 15 per 1,000 in men aged 45-50 years to 62 per 1,000 in those aged 75-80 years. For women the corresponding values were 11 to 29 per 1,000. The estimates attained displayed the age and sex patterns expected on the basis of other data sources including morbidity surveys in the United Kingdom and the Netherlands. The similarity suggests that this may be a valid method for estimating quickly and cheaply the prevalence of certain diseases in the community.

Aged↗
PubMed1988

Early detection of carpal erosions in patients with rheumatoid arthritis: a pilot study of magnetic resonance imaging.

A pilot study comparing standard radiography to magnetic resonance imaging (MRI) was performed on the wrists of 10 patients with early (anatomic Stage I or II) rheumatoid arthritis (RA). MRI was found to be superior to standard radiographs in 2 respects: (1) synovial inflammation was impressively demonstrated on T2 weighted images, whereas plain films merely suggested soft tissue swelling; and (2) T1 and T2 weighted images clearly revealed erosions of several carpal bones which were not noted on standard radiographs. Although the expense of MRI currently precludes its routine use in clinical practice, the apparent sensitivity of this diagnostic modality for detecting early changes in RA might make it an invaluable tool for therapeutic decision making or for assessing response in interventional trials.

Adult↗