Mouse homologues of the human AZF candidate gene RBM are expressed in spermatogonia and spermatids, and map to a Y chromosome deletion interval associated with a high incidence of sperm abnormalities

An RNA-binding motif (RBM) gene family has been identified on the human Y chromosome that maps to the same deletion interval as the 'azoospermia factor' (AZF). We have identified the homologous gene family (Rbm) on the mouse Y with a view to investigating the proposal that this gene family plays a role in spermatogenesis. At least 25 and probably >50 copies of Rbm are present on the mouse Y chromosome short arm located between Sry and the centromere. As in the human, a role in spermatogenesis is indicated by a germ cell-specific pattern of expression in the testis, but there are distinct differences in the pattern of expression between the two species. Mice carrying the deletion Yd1, that maps to the proximal Y short arm, are female due to a position effect resulting in non-expression of Sry ; sex-reversing such mice with an Sry transgene produces males with a high incidence of abnormal sperm, making this the third deletion interval on the mouse Y that affects some aspect of spermatogenesis. Most of the copies of Rbm map to this deletion interval, and the Yd1males have markedly reduced Rbm expression, suggesting that RBM deficiency may be responsible for, or contribute to, the abnormal sperm development. In man, deletion of the functional copies of RBM is associated with meiotic arrest rather than sperm anomalies; however, the different effects of deletion are consistent with the differences in expression between the two species.      

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.     

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.