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.     

Repeat consultations after antibiotic prescribing for respiratory infection: a study in one general practice.

BACKGROUND. Several new antibacterial drugs have been introduced in the last 10 years with the aim of improved treatment of respiratory tract infection. AIM. The study set out to use repeat consultations as a measure of the outcome of antibiotic treatment for respiratory tract infection, and to develop a simple model for discussion of the cost effectiveness of alternative antibiotic treatments. METHOD. All consultations to one practice during a single winter were reviewed by one general practitioner. RESULTS. A total of 1140 patients had acute symptoms suggestive of respiratory infection. Of these, 899 patients (79%) were prescribed antibiotics at the first consultation and 160 of the 899 patients (18%) returned for one or more repeat consultations; only nine repeat consultations were due to adverse effects of the antibiotics prescribed. Only two patients were admitted to hospital for respiratory symptoms following initial antibiotic therapy and both patients had additional reasons for their admission. Using the highest estimates, the cost of a repeat consultation was found to be 28.54 pounds. These data were used to calculate how much more might be spent on more effective antibiotics at the first consultation. It would be difficult to justify increasing the cost of antibiotic treatment by more than 5 pounds per patient, even if the new treatment were 100% effective and all repeat consultations were due to treatment failure (5 pounds is equal to 28.54 pounds x 0.18, which is the maximum cost of a repeat consultation multiplied by the proportion of patients prescribed antibiotics who make repeat consultations). CONCLUSION. From these results and a review of the literature it can be concluded that new antibacterial drugs will have to be carefully targeted if they are to prove cost effective in practice. Other methods for reducing repeat consultation merit investigation.     

Hydrogen peroxide Modulates Ca2+-Activation of Single permeabilized Fibres from Fast- and Slow-twitch Skeletal Muscles of Rats

We examined the effects of redox modulation on single membrane-permeabilized fibre segments from the fast-twitch extensor digitorum longus (EDL) and slow-twitch soleus muscles of adult rats to determine whether the contractile apparatus was the redox target responsible for the increased contractility of muscles exposed to low concentrations of H₂O₂. The effects of H₂O₂ on maximum Ca²⁺-activated force were dose-dependent with 30 min exposure to 5 mM H₂O₂ causing a progressive decrease by 22 ± 3 and 13 ± 2% in soleus and EDL permeabilized muscle fibres, respectively. Lower concentrations of exogenous H₂O₂ (100 M and 1 mM) had no effect on maximum Ca²⁺-activated force. Subsequent exposure to the reductant dithiothreitol (DTT, 10 mM, 10 min) fully reversed the H₂O₂-induced depression of force in EDL, but not in soleus muscle fibres. Incubation with DTT alone for 10 min did not alter Ca²⁺-activated force in either soleus or EDL muscle fibres. The sensitivity of the contractile filaments to Ca²⁺ (pCa₅₀) was not altered by exposure to any concentration of exogenous H₂O₂. However, all concentrations of H₂O₂ diminished the Hill coefficient in permeabilized fibres from the EDL muscle, indicating that the cooperativity of Ca²⁺ binding to troponin is altered. H₂O₂ (5 mM) did not affect rigor force, which indicates that the number of crossbridges participating in contraction was not reduced. In conclusion, H₂O₂ may reduce the maximum Ca²⁺ activated force production in skinned muscle fibres by decreasing the force per crossbridge.     

Molecular heterogeneity and fine specificity of BALB/c antibodies elicited by isologous myeloma protein.

BALB/c mice immunized with the isologous myeloma protein MOPC-315 (M315; α, λ₂) develop antibodies most of which are directed to idiotypic antigens (Id315) located in or near the CNP binding sites of M315, In order to more precisely establish the fine specificity of anti-Id315 antibodies, and to obtain an estimate of the size of the BALB/c anti-Id315 repertoire, we examined anti-Id315 antibodies from individual mice by analytical isoelectric focusing followed by autoradiography. ¹²⁵I-labeled probes were prepared from purified mildly reduced and alkylated M315 protein (RA315) (7 S monomer), Fab'315, Fv315, L315, H315, DNP affinity-labeled RA315, mildly reduced and alkylated MOPC-460 (RA460; 7 S; α, k, Fab'460, H460, and DNP affinity-labeled RA460. We observed that (a) the majority of BALB/c antibodies elicited by immunization with RA315 are specific for idiotypic antigens in the variable region which are rendered inaccessible in the presence of DNP-hapten; (b) distinctly separate antibodies are specific for idiotypic antigens also located in the variable regions but which are not influenced by DNP hapten; (c) about 30 % of BALB/c mice develop antibodies which appear to be specific for a determinant located in the second or third, homology regions of the constant region of the α chain which is not influenced by DNP hapten, and which is also present in the same region of H460; (d) none of the antibodies elicited by M315 recognize free L315; (e) the total antibody response is quite restricted; (f) shared spectrotypes are common between individual mice; and (g) unique or infrequently shared spectrotypes do occur. These studies demonstrate, by a direct technique, the fine specificity and the clonal and molecular heterogeneity of the B cell response induced by immunization with RA315.