An enhanced chemiluminescent enzyme immunoassay for follicle stimulating hormone

An enhanced chemiluminescent enzyme immunoassay for serum follicle stimulating hormone is described which involves sequential reaction of anti-follicle stimulating hormone antibody immobilised to the inside surface of an opaque microtitre plate with sample, monoclonal anti-alpha thyroid stimulating hormone antibody, and an anti-mouse IgG - horseradish peroxidase conjungate. Bound peroxidase activity was measured using a p-hydroxycinnamic acid enhanced chemiluminescent luminol-hydrogen peroxide reaction. The assay was sensitive (detection limit 0.01 mU/well) precise (intra-assay precision 2.5-8.1%, inter-assay precision 6.7-11.9%) and results obtained with this assay and a competitive radioimmunoassay were in good agreement (correlation coefficient 0.98).     

Morbidity data collection in general practice: experience in the South Eastern Health Board 1998-1999

A joint project between general practitioners and the South Eastern Health Board resulted in the establishment of a network of computerised practices collecting morbidity data in 1998 - 1999. Five practices established age sex registers for public and private patients. The International Classification of Primary Care 2 (ICPC-2) was used to define inclusion criteria for a range of illnesses relevant to primary care and public health. Problems arose in validating and extracting data in three practices. Disease prevalence for 17 illnesses was established for two practices only. The project clearly established the problems associated with morbidity data collection in general practice which include absence of a national patient registration system, absence of a national electronic messaging standard, difficulties extracting data from practice software systems and the need for a high level of dedicated staff and resources to implement such a project.     

The effect of celecoxib, a cyclooxygenase-2 inhibitor, in familial adenomatous polyposis

BACKGROUND: Patients with familial adenomatous polyposis have a nearly 100 percent risk of colorectal cancer. In this disease, the chemopreventive effects of nonsteroidal antiinflammatory drugs may be related to their inhibition of cyclooxygenase-2. METHODS: We studied the effect of celecoxib, a selective cyclooxygenase-2 inhibitor, on colorectal polyps in patients with familial adenomatous polyposis. In a double-blind, placebo-controlled study, we randomly assigned 77 patients to treatment with celecoxib (100 or 400 mg twice daily) or placebo for six months. Patients underwent endoscopy at the beginning and end of the study. We determined the number and size of polyps from photographs and videotapes; the response to treatment was expressed as the mean percent change from base line. RESULTS: At base line, the mean (+/-SD) number of polyps in focal areas where polyps were counted was 15.5+/-13.4 in the 15 patients assigned to placebo, 11.5+/-8.5 in the 32 patients assigned to 100 mg of celecoxib twice a day, and 12.3+/-8.2 in the 30 patients assigned to 400 mg of celecoxib twice a day (P=0.66 for the comparison among groups). After six months, the patients receiving 400 mg of celecoxib twice a day had a 28.0 percent reduction in the mean number of colorectal polyps (P=0.003 for the comparison with placebo) and a 30.7 percent reduction in the polyp burden (the sum of polyp diameters) (P=0.001), as compared with reductions of 4.5 and 4.9 percent, respectively, in the placebo group. The improvement in the extent of colorectal polyposis in the group receiving 400 mg twice a day was confirmed by a panel of endoscopists who reviewed the videotapes. The reductions in the group receiving 100 mg of celecoxib twice a day were 11.9 percent (P=0.33 for the comparison with placebo) and 14.6 percent (P=0.09), respectively. The incidence of adverse events was similar among the groups. CONCLUSIONS: In patients with familial adenomatous polyposis, six months of twice-daily treatment with 400 mg of celecoxib, a cyclooxygenase-2 inhibitor, leads to a significant reduction in the number of colorectal polyps.     

Association of stress proteins with autoantigens: a possible mechanism for triggering autoimmunity?

Patterns of autoantibody production are diagnostic of many autoimmune disorders; the recent observation of additional autospecificities towards stress-induced proteins may also provide insight into the mechanisms by which such responses arise. Grp78 (also known as BiP) is a target of autoaggressive B and T cell responses in our murine model of anti-Ro (SS-A) autoimmunity and also in rheumatoid arthritis. In this report we demonstrate reciprocal intermolecular spreading occurs between Ro52 and Grp78 in immunized mice, reflecting physiological association of these molecules in vivo. Moreover, we provide direct biochemical evidence that Grp78 associates with the clinically relevant autoantigen, Ro52 (SS-A). Due to the discrete compartmentalization of Ro52 (nucleocytoplasmic) and Grp78 (endoplasmic reticulum; ER) we propose that association of these molecules occurs either in apoptotic cells, where they have been demonstrated indirectly to co-localize in discrete apoptotic bodies, or in B cells themselves where both Ro52 and Grp78 are known to bind to immunoglobulin heavy chains. Tagging of molecules by association with Grp78 may facilitate receptor mediated phagocytotsis of the complex; we show evidence that exogenous Grp78 can associate with cell surface receptors on a subpopulation of murine splenocytes. Given the likelihood that Grp78 will associate with viral glycoproteins in the ER it is possible that it may become a bystander target of the spreading antiviral immune response. Thus, we propose a model whereby immunity elicited towards Grp78 leads to the selection of responses towards the Ro polypeptides and the subsequent cascade of responses observed in human disease.     

Audit of an inpatient neurology consultation service in a tertiary referral centre: value of the consulting neurologist

The Mater Misericordiae Hospital is a 575-bed tertiary referral centre with busy medical and surgical subspecialty services (including the national cardiac, cardiothoracic, spinal cord injury and pulmonary hypertension units). An audit of in-patient referrals to a neurology service was carried out over the twelve-month period of January to December 2002 inclusively. Five hundred and seventy seven inpatients were evaluated and managed in conjunction with the referring services. Consultation by the neurological service led to a significant contribution in the management of clinical cases in one of three ways: establishing a de novo diagnosis in patients admitted with active neurological symptoms where no working diagnosis exists (40.7% of referrals), significant alteration in diagnosis where the referring service have already established a specific working diagnosis (11.1% of referrals), or offering advice in the ongoing management of active neurological symptoms when the diagnosis is historically established and secure (48.2% of referrals). In order of frequency the most common reason for referral was stroke (131 cases (22.7%)), seizures unrelated to alcohol (59 cases (10.2%)), alcohol-related neurological problems (55 cases (9.5%)), movement disorders (41 cases (7.1%)), neuromuscular (40 cases (6.9%)), coma (35 cases (6%)), disorders of cognition (31 cases (5.3%)), acute headache (28 case (4.8%)) and functional neurological syndromes (26 cases (4.5%)). This audit highlights the value of a consulting neurology service in a multidisciplinary tertiary referral setting.