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Biomedical subjects

D Sinclair

Publications and source records attributed to D Sinclair.

At least 19 recordsLinked to original sources
PubMed2006

Do we need to measure total serum IgA to exclude IgA deficiency in coeliac disease?

BACKGROUND: Screening for IgA deficiency in patients with coeliac disease is essential because of the increased incidence of IgA deficiency associated with the disease, which usually relies on the estimation of IgA levels in each case. AIM: To devise a method of excluding IgA deficiency without measuring total serum IgA in each case. MATERIALS AND METHODS: The optical density readings on enzyme-linked immunosorbent assay (ELISA) of 608 routine samples received for tissue transglutaminase (TTG) antibody testing for coeliac disease were compared with their total IgA concentrations. Dilution experiments were also carried out to ensure linear relationships between optical density on ELISA and IgA concentrations and to compare the sensitivities for TTG and endomysium antibodies in TTG-positive samples. RESULTS AND DISCUSSION: A clear relationship was shown between total IgA concentration and TTG optical density readings by ELISA. To ensure a positive TTG result if antibodies are present, it was possible to recommend an optical density level above which all samples have sufficient IgA. Samples with optical density <0.05 should be investigated further by estimating total IgA and, if low, samples should be subjected to immunofluorescence microscopy testing for IgA and IgG endomysium antibodies. CONCLUSIONS: An easier, more cost-effective and practical way of excluding IgA deficiency in the investigation on coeliac disease is reported.

Autoantibodies↗
PubMed2006

Can the laboratory affect the investigation and diagnosis of primary biliary cirrhosis?

BACKGROUND: Primary biliary cirrhosis (PBC) is an autoimmune liver disease characterised by the presence of various laboratory abnormalities but the precise role of laboratory staff in initiating clinical referral and subsequent biopsy is not clear. OBJECTIVE: To examine the impact of laboratory abnormalities in the investigation of PBC. METHODS: In a retrospective study of laboratory results over nine years from 1996, computer records were reviewed to identify how many referrals for biopsy were initiated and subsequent diagnoses made as a result of clinical signs, raised serum alkaline phosphatase activity (ALP), raised IgM concentration, or positive mitochondrial antibodies accompanied by a clinical comment from the laboratory suggesting further action. RESULTS: 22 diagnoses of PBC were confirmed by histopathology. Eleven had high ALP activity which had follow up tests initiated by the laboratory (mitochondrial antibodies or IgM or both) and a comment added suggesting further investigation into the possibility of PBC. Seven had abnormal liver antibodies and one had a high polyclonal IgM concentration which prompted the relevant follow on testing and comments. One had an earlier diagnosis made on serological/clinical grounds and the biopsy was a confirmatory measure. One had no liver related antibodies. One had a request by laboratory staff for follow on tests but these were not asked for in subsequent samples by the requesting clinician. CONCLUSIONS: There is a positive role for laboratory staff in the diagnosis of PBC. Unexplained rises in ALP activity, positive mitochondrial antibodies, or raised IgM concentrations should be investigated more fully by laboratory staff and advice given to prompt a clinical referral for review and biopsy.

Adult↗
PubMed2005

Occurrence of autoantibodies in chronic graft vs. host disease after allogeneic stem cell transplantation.

Chronic graft vs. host disease (GVHD) remains a major cause of morbidity and mortality after allogeneic stem cell transplantation (SCT). Chronic GVHD (cGVHD) has many similarities to de novo autoimmune disorders. While the presence and association of autoantibodies is well reported in these disorders, their role and clinical use remains a less studied area after SCT. We report the presence of autoantibodies in SCT recipients and a possible association with presence of cGVHD. During routine follow-up visits peripheral blood samples were tested for: rheumatoid factor (RF), antinuclear antibody (ANA), double stranded DNA (dsDNA), antimitochondrial antibody, antismooth muscle antibody (Anti Sm), antiendomysial, antireticulin antibodies, antithyroid peroxidase antibodies and an extractable nuclear antigen screen, in 13 SCT recipients. Six of 13 (46%) patients had one or more autoantibodies. All the patients with antibodies had cGVHD where as none of the patients without cGVHD had any autoantibodies (P = 0.025). Three (23%) patients had only one autoantibody and three (23%) of them had more than one autoantibody. ANA was positive in three (23.3%) patients, double stranded DNA in four (30.7%) patients, RF in one (7.6%) and Anti Sm muscle in two (15.3%) patients. In the present study, autoantibodies were detected predominantly in patients with presence of cGVHD. They also appeared to be more frequent in an unmanipulated graft and so less in patients with a T-cell depleted allograft. In two of 13 patients only there appeared to be an association between the antibody titre and flare up in skin symptoms. In conclusion, this small series raises interesting questions about the presence and role of autoantibodies after SCT and their association with cGVHD.

Autoantibodies↗
PubMed2004

Acquired C1 esterase inhibitor deficiency or serendipity? The chance finding of a paraprotein after an apparently low C1 esterase inhibitor concentration.

Acquired C1 esterase inhibitor deficiency is a rare condition, usually presenting after the 2nd decade of life, and is often related to underlying conditions such as autoimmune and lymphoproliferative disorders. This case report describes a man whose initial clinical presentation with acute angioedema and whose initial estimation of a low C1 esterase inhibitor concentration indicated that he had an acquired angioedema, possibly secondary to a B cell neoplasm. A paraprotein was detected, and although its detection was serendipitous because it hinged on a spurious C1 esterase inhibitor result, this case confirms the role of C4 concentrations in the investigation of C1 esterase inhibitor deficiency. It also confirms the need to obtain repeat confirmatory samples before arriving at a diagnosis, however convincing the clinical signs may be.

Acute Disease↗
PubMed2004

The effect of a symptom related "gating policy" on ANCA requests in routine clinical practice.

BACKGROUND: Most positive antineutrophil cytoplasmic antibody (ANCA) results are associated with non-vasculitic conditions, and guidelines have been proposed for the judicious use of this test. The outcome of applying similar guidelines in a routine laboratory is reported. METHODS: All immunology requests (6500) over six months were selected, and those requesting ANCA were studied for the appropriateness of the clinical data supporting the request, the presence of ANCA in those samples tested, and the final diagnosis. Antibodies were detected by indirect immunofluorescence. RESULTS: ANCA testing was requested in 287 samples. Application of a "gating policy", which refuses analysis on requests that are not supported by clinical data suggestive of systemic vasculitis, made clinicians more selective about the patients for whom they requested ANCA testing. The percentage of "appropriate" screens for systemic vasculitis was relatively high (212 of 287 requests: 72.5%). Only one of the remainder, for whom ANCA testing was initially refused, developed an ANCA related systemic vasculitis in the two years after the study, but the delay in reporting her positive ANCA was only two days. Most of the samples tested were negative (155 of 212), but most (42 of 57) of the patients with positive ANCA results were found to have a systemic vasculitis. CONCLUSIONS: A gating policy to select requests supported by clinical data suggestive of systemic vasculitis makes ANCA testing more clinically relevant and cost effective. Studies where guidelines can be proposed and their effects measured are important in the light of clinical governance and evidence based medicine.

Antibodies, Antineutrophil Cytoplasmic↗
PubMed2004

What happens to patients with positive tissue transglutaminase and endomysium antibody results in general practice?

BACKGROUND: A previous study showed that many patients with positive gut related antibodies (anti-tissue transglutaminase (TTG) and/or anti-endomysium (EMA) antibodies), indicative of coeliac disease, were not offered a duodenal biopsy, despite the recommendation of the British Society for Gastroenterology guidelines. AIMS/METHODS: To investigate whether the addition of a comment on the advisability of referral to a gastroenterologist and biopsy to each positive gut related antibody result would improve the referral rate to investigate possible coeliac disease. RESULTS: The referral rate improved from 30.1% of patients who were referred and 18% subsequently biopsied before the addition of the comment, to 79.8% who were referred after the introduction of a specific laboratory comment attached to positive antibodies to TTG and/or EMA. All patients with these positive antibodies who were referred for consultant opinion were subsequently biopsied. CONCLUSIONS: To ensure that British Society for Gastroenterology guidelines are followed, laboratories should incorporate more explicit details on the recommended course of action for general practitioners on their receipt of positive gut antibodies to TTG/EMA.

Autoantibodies↗
PubMed2004

The predictive value of total serum IgE for a positive allergen specific IgE result.

BACKGROUND: Measurement of total serum IgE and allergen specific IgE is often requested to assess possible allergy. As public awareness increases, so do requests for allergy assessment; unless there is a clear "allergen suspect" in the history, several allergen specific IgE requests may be made. This increases the likelihood of detecting borderline increases in allergen specific IgE of uncertain relevance, and has important cost implications for the service. AIMS: To provide an evidence base for this observation. METHODS: In this retrospective observational study, results from 301 patients under 16 years of age from whom blood was taken for "allergy testing" from March 2001 to February 2003 were studied. RESULTS: Allergen specific IgE testing in children with low total serum IgE concentrations (<10 IU/litre) yielded very few positive results (three of 73 children), except in those being investigated for an acute reaction to a single food; when IgE was 11-20 kU/litre, 13 of 73 children had positive allergen specific IgE; in the 21-40 kU/litre IgE group, 16 of 74 children had positive allergen specific IgE and in the 41-80 kU/litre group, 22 of 81 had positive allergen specific IgE. CONCLUSIONS: Allergen specific IgE testing in children with low IgE concentrations (<10 kU/litre) produces few positive results in patients with non-specific symptoms. Laboratories should perform allergy testing for specific allergens regardless of total IgE concentration only when there are convincing clinical reasons to do so, and should not proceed with this if the total IgE is <10 kU/litre and the presenting symptoms are non-specific.

Adolescent↗
PubMed2003

Seasonal pseudohyperkalaemia.

AIMS: To investigate the relation between ambient temperature and serum potassium concentrations in samples from primary care. METHODS: Potassium concentrations were estimated on general practitioner and hospital ward samples taken over a two year period using serum obtained from gel separator samples. The number of samples analysed from general practice during each month varied from 5093 to 8978 (mean of 7068 samples/month). RESULTS: As the temperature fell in winter, the mean daily serum potassium concentration rose in samples from general practice, with the inverse occurring during the warmer summer months. This effect was restricted to samples coming from general practice, with inpatient samples seemingly unaffected. CONCLUSIONS: These results indicate that exposure of the samples to variations in ambient temperature during their transport to the laboratory profoundly affects measured serum potassium concentrations.

Blood Preservation↗
PubMed2001

Spinal anesthesia improves the early recovery profile of patients undergoing ambulatory knee arthroscopy.

PURPOSE: We compared the recovery profiles, postoperative complications, perioperative OR utilization times, and times to discharge of patients undergoing ambulatory knee arthroscopy under spinal anesthesia (SA) or general anesthesia (GA). METHODS: In this randomized, prospective study, 84 ASA I-II patients were randomized to receive either SA with 50 mg of 1% lidocaine, or a standardized GA. Postoperative pain, nausea and vomiting, sedation, OR utilization, postanesthesia care unit (PACU), and ambulatory surgical unit (ASU) recovery were compared. RESULTS: Patients in the GA group had more pain in the PACU than the SA group (61% vs 15%, P <0.01), and a higher incidence of PACU analgesic use (59% vs 7.5%, P <0.01). Patients in the SA group were able to drink and eat sooner than the GA group (83 +/- 23 vs 95 +/- 22 min, P <0.05 and 88 +/- 27 vs 105 +/- 29 min, P <0.01, respectively). The times to sit, walk, and void were similar. The length of PACU and ASU stay between the GA and SA groups were similar (67 +/- 17 vs 60 +/- 19 min, P >0.05 and 122 +/- 27 vs 127.9 +/- 31 min, P >0.05, respectively). The incidence of backache was higher in the SA group (35 vs 13.6%, P <0.05) than the GA group. However, the incidence of sore throat was higher in the GA compared to the SA group (25% vs 2.5%, P <0.01). CONCLUSIONS: SA with 50 mg of 1% lidocaine provides an improved recovery profile for ambulatory knee arthroscopy. Discharge times were similar, and with the exception of backache and sore throat, the incidence of complications was similar.

Adult↗
PubMed2001

Pharmacological relapse prevention in alcohol dependence: from animal models to clinical trials.

This article represents the proceedings of a symposium at the 2000 ISBRA Meeting in Yokohama, Japan. The chairs were Jobst August-Ludwig Boening and Otto Michel Lesch. The presentations were (1) Pharmacological validation of a new animal model of alcoholism, by Rainer Spanagel; (2) Persisting loss of control as main criterion for alcohol addiction in rats and mice, by Jochen Wolffgramm; (3) Role of NMDA receptor subunits associated with protein kinase C in the prevention of alcohol dependence, by Minoru Narita; (4) Long-term follow up of continued naltrexone treatment, by David Sinclair; (5) Pharmacological treatment trials with dopaminergic and serotonergic substances: Myths or facts? by Gerhard A. Wiesbeck; and (6) Methodology and behavioral therapy of the U.S. acamprosate study, by Barbara J. Mason.

Acamprosate↗
PubMed2001

IgD myeloma: a potential missed diagnosis.

This report describes a case of IgD lambda myeloma which was discovered only following investigation of a suspicious 'low gamma region'. If anti-IgD investigations had not been carried out, it may have been misinterpreted as Bence Jones myeloma. The case illustrates that evaluation of serum and urine in cases of suspected myeloma is mandatory and that the possibility of IgD myeloma in cases that appear to be 'free light chain' paraproteins only should be investigated.

Female↗
PubMed2000

Does expression of inducible nitric oxide synthase correlate with severity of oral epithelial dysplasia?

The small molecule nitric oxide (NO) has generated an exponential amount of research since its discovery as a biological messenger in 1987. It has a vast number of actions, many of which are poorly understood. It has been studied in a variety of human cancers and has been implicated both in tumour promotion and inhibition. Although NO is produced by three distinct isoforms of the enzyme nitric oxide synthase (NOS), most cancer research is directed towards the calcium-independent form, iNOS which following induction, produces much higher quantities of NO than the other two. In this study the expression of iNOS is assessed by immunohistochemistry in 26 cases of oral epithelial dysplasia ranging in severity from mild to severe. iNOS staining was found in all 26 cases of dysplasia with the degree of staining correlating to the severity of dysplasia (p < 0.001). There was no iNOS staining seen in adjacent normal epithelium. The possible role of iNOS in the complex transformation from dysplasia to invasive oral cancer and the clinical applications are discussed.

Adult↗
PubMed2000

Home care and emergency medicine: a pilot project to discharge patients safely from the emergency department.

OBJECTIVES: To describe in detail the implementation of an acute care home care program (quick response program; QRP) for the emergency department (ED). METHODS: A prospective observational study with key process and outcome indicators, including number of referrals, time to initiate service, type of home care provided, number of return patients to the ED, and outcome for all patients, defined at the beginning of the project. Patients are identified for the QRP and services are in place within four hours of patient discharge. RESULTS: Of 177 eligible patients, 121 were entered into the program. Sixty-eight percent were more than 65 years old, and 54% lived alone. All patients met the time target of services in place within four hours of discharge from the ED. Patient satisfaction was high as measured by an independent survey instrument. Fifty percent of the patients required no further service after the QRP, but 20% were admitted to hospital within 30 days. CONCLUSIONS: A QRP can be successfully implemented in the ED to discharge patients home, most of whom would have been admitted to hospital.

Adult↗