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Biomedical subjects

C C Butler

Publications and source records attributed to C C Butler.

At least 19 recordsLinked to original sources
PubMed2006

Oral or topical nasal steroids for hearing loss associated with otitis media with effusion in children.

BACKGROUND: Otitis media with effusion (OME) is common and may cause hearing loss with associated developmental delay. Treatment remains controversial. OBJECTIVES: To examine evidence for or against treating children with hearing loss associated with OME with systemic or topical intranasal steroids. SEARCH STRATEGY: We searched the Cochrane Ear, Nose and Throat Disorders Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library Issue 4 2005, MEDLINE (1966 to 2006), EMBASE (1974 to 2006), and the CINAHL, LILACS, Zetoc, IndMED, SAMED, KoreaMed, MEDCARIB and Cambridge Scientific Abstracts databases in January 2006. SELECTION CRITERIA: Randomised controlled trials of oral and topical intranasal steroids, either alone or in combination with another agent such as an antibiotic, were included. EXCLUSIONS: publications in abstract form only; uncontrolled, non-randomised or retrospective studies; studies reporting outcomes with ears (rather than children). DATA COLLECTION AND ANALYSIS: Data were extracted from the published reports by the authors independently using standardised data extraction forms and methods. The methodological quality of the included studies was independently assessed by the authors as described in the Cochrane Handbook. Dichotomous results were expressed as an odds ratio using a fixed-effect model together with the 95% confidence intervals. Continuous data were analysed using the weighted mean difference in a fixed-effect model. Tests for heterogeneity between studies were performed using a Mantel-Haenszel approach. In trials with a cross-over design, post cross-over treatment data were not used. MAIN RESULTS: No study prospectively documented hearing loss associated with OME prior to randomisation. Follow up was mainly short term. The odds ratio for OME persisting after short-term follow up in children treated with oral steroids compared to control was 0.22 (95% CI 0.08 to 0.63). The odds ratio for OME persisting after short-term follow up for children treated with oral steroids plus antibiotic compared to control plus antibiotic was 0.37 (95% CI 0.25 to 0.56). However, there was significant heterogeneity between studies included in the latter comparison (P < 0.01). Trends favoured steroids for most other comparisons, but confidence intervals included unity. There was no evidence of benefit for steroid treatment for OME or hearing loss associated with OME in the longer term. AUTHORS' CONCLUSIONS: Both oral and topical intranasal steroids alone or in combination with an antibiotic lead to a quicker resolution of OME in the short term, however, there is no evidence of longer term benefit.

Administration, Intranasal↗
PubMed2006

Prognostic factors and clinical outcome in acute lower respiratory tract infections: a prospective study in general practice.

BACKGROUND: Unrealistic expectations about illness duration are likely to result in reconsultations and associated unnecessary antibiotic prescriptions. An evidence-based account of clinical outcomes in patients with lower respiratory tract infection (LRTI) may help avoid unnecessary antibiotic prescriptions and reconsultations. OBJECTIVES: We aimed to identify clinical factors that may predict a prolonged clinical course or poor outcome for patients with LRTI and to provide an evidence-based account of duration of an LRTI and the impact of the illness on daily activities in patients consulting in general practice. METHODS: A prospective cohort study of 247 adult patients with a clinical diagnosis of LRTI presenting to 25 GPs in The Netherlands was carried out. Multivariable Cox regression analysis was used to identify baseline clinical and infection parameters that predicted the time taken for symptoms to resolve. A Kaplan-Meier curve was used to analyse time-to-symptom resolution. Clinical cure was recorded by the GPs at 28 days after the initial consultation and by the patients at 27 days. RESULTS: Co-morbidity of asthma was a statistically significant predictor of delayed symptom resolution, whereas the presence of fever, perspiring and the prescription of an antibiotic weakly predicted enhanced symptom resolution. The GPs considered 89% of the patients clinically cured at 28 days, but 43% of these nevertheless reported ongoing symptoms. Patient-reported cure was much lower (51%), and usual daily activities were limited in 73% of the patients at baseline, and 19% at final follow-up. CONCLUSIONS: The course of LRTI was generally uncomplicated, but the morbidity of this illness was considerable with a longer duration than generally reported, especially for patients with co-existent asthma. These results underline once again the importance of providing GPs with an evidence-based account of outcomes to share with patients in order to set realistic expectations and of enhancing their communication skills within the consultation.

Acute Disease↗
PubMed2006

Interventions for cutaneous molluscum contagiosum.

BACKGROUND: Molluscum contagiosum is a common skin infection, caused by a virus, which will usually resolve within months in people with a normal immune system. Many treatments have been promoted for molluscum contagiosum but a clear evidence base supporting them is lacking. OBJECTIVES: To assess the effects of management strategies (including waiting for natural resolution) for cutaneous, non-genital molluscum contagiosum in healthy people. SEARCH STRATEGY: We searched the Skin Group Specialised Register (March 2004), the Cochrane Central Register of Controlled Trials (2004, Issue 2), MEDLINE (from 1966 to March 2004), EMBASE (from 1980 to March 2004) and LILACS (from 1982 to March 2004) databases. We also searched reference lists and contacted pharmaceutical companies and experts in the field. SELECTION CRITERIA: Randomised controlled trials for treatment of molluscum contagiosum were investigated. Trials on sexually transmitted molluscum contagiosum and in people with lowered immunity (including those with HIV infection) were excluded. DATA COLLECTION AND ANALYSIS: Study selection and assessment of methodological quality were carried out by two independent authors. As similar comparisons between two interventions were not made in more than one study, statistical pooling was not performed. MAIN RESULTS: Five studies, with a total number of 137 participants, examined the effects of topical (three studies), systemic and homoeopathic interventions (one study each). Limited evidence was found for sodium nitrite co-applied with salicylic acid compared to salicylic acid alone (risk ratio (RR) 3.50, 95% confidence interval (CI) 1.23 to 9.92). No statistically significant differences were found for topical povidone iodine plus salicylic acid compared to povidone iodine alone (RR of cure 1.67, 95% CI 0.81 to 3.41) or compared to salicylic acid alone. Also no statistically significant differences were found for potassium hydroxide compared to placebo; systemic treatment with cimetidine versus placebo or systemic treatment with calcarea carbonica, a homoeopathic drug, versus placebo (RR 5.57, 95% CI 0.93 to 33.54). Study limitations included no blinding (two studies), many dropouts (three studies) and no intention-to-treat analysis (two studies); small study sizes may have led to important differences being missed. None of the evaluated treatment options were associated with serious adverse effects. AUTHORS' CONCLUSIONS: No single intervention has been shown to be convincingly effective in treating molluscum contagiosum.

Anti-Infective Agents, Local↗
PubMed2005

Oral vitamin B12 versus intramuscular vitamin B12 for vitamin B12 deficiency.

BACKGROUND: Vitamin B12 deficiency is common and rises with age. Most people with vitamin B12 deficiency are treated in primary care with intramuscular vitamin B12 which is a considerable source of work for health care professionals. Several case control and case series studies have reported equal efficacy of oral administration of vitamin B12 but it is rarely prescribed in this form, other than in Sweden and Canada. Doctors may not be prescribing oral formulations because they are unaware of this option or have concerns regarding effectiveness. OBJECTIVES: To assess the effectiveness of oral vitamin B12 versus intramuscular vitamin B12 for vitamin B12 deficiency. SEARCH STRATEGY: Searches were undertaken of The Cochrane Library, MEDLINE, EMBASE and Lilacs in early 2005. The bibliographies of all relevant papers identified using this strategy were searched. In addition we contacted authors of relevant identified studies and Vitamin B12 research and pharmaceutical companies to enquire about other published or unpublished studies and ongoing trials. SELECTION CRITERIA: Randomised controlled trials (RCTs) examining the use of oral or intramuscular vitamin B12 to treat vitamin B12 deficiency. DATA COLLECTION AND ANALYSIS: All abstracts or titles identified by the electronic searches were independently scrutinised by two reviewers. When a difference between reviewers arose, we obtained and reviewed a hard copy of the papers and made decisions by consensus. We obtained a copy of all pre-selected papers and two researchers independently extracted the data from these studies using piloted data extraction forms. The whole group checked whether inclusion and exclusion criteria were met, and disagreement was decided by consensus. The methodological quality of the included studies was independently assessed by two researchers and disagreements were brought back to the whole group and resolved by consensus. MAIN RESULTS: Two RCT's comparing oral with intramuscular administration of vitamin B12 met our inclusion criteria. The trials recruited a total of 108 participants and followed up 93 of these from 90 days to four months. High oral doses of B12 (1000 mcg and 2000 mcg) were as effective as intramuscular administration in achieving haematological and neurological responses. AUTHORS' CONCLUSIONS: The evidence derived from these limited studies suggests that 2000 mcg doses of oral vitamin B12 daily and 1000 mcg doses initially daily and thereafter weekly and then monthly may be as effective as intramuscular administration in obtaining short term haematological and neurological responses in vitamin B12 deficient patients.

Administration, Oral↗
PubMed2004

Interventions for impetigo.

BACKGROUND: Impetigo is a common superficial bacterial skin infection, most frequently encountered in children. There is no standard therapy and guidelines for treatment differ widely. Treatment options include many different oral and topical antibiotics as well as disinfectants. OBJECTIVES: To assess the effects of treatments for impetigo, including waiting for natural resolution. SEARCH STRATEGY: We searched the Skin Group Specialised Trials Register (March 2002), Cochrane Central Register of Controlled Trials (CENTRAL, Issue 1 2002), the National Research Register (2002), MEDLINE (from 1966 to January 2003), EMBASE (from 1980 to March 2000) and LILACS (November 2001). We handsearched the Yearbook of Dermatology (1938-1966), the Yearbook of Drug Therapy (1949-1966), used reference lists of articles and contacted pharmaceutical companies. SELECTION CRITERIA: Randomised controlled trials of treatments for non-bullous and bullous, primary and secondary impetigo. DATA COLLECTION AND ANALYSIS: All steps in data collection were done by two independent reviewers. We performed quality assessments and data collection in two separate stages. MAIN RESULTS: We included 57 trials including 3533 participants in total which studied 20 different oral and 18 different topical treatments. CURE OR IMPROVEMENT: Topical antibiotics showed better cure rates than placebo (pooled odds ratio (OR) 6.49, 95% confidence interval (CI) 3.93 to 10.73), and no topical antibiotic was superior (pooled OR of mupirocin versus fusidic acid 1.76, 95% CI 0.69 to 2.16). Topical mupirocin was superior to oral erythromycin (pooled OR 1.22, 95% CI 1.05 to 2.97). In most other comparisons, topical and oral antibiotics did not show significantly different cure rates, nor did most trials comparing oral antibiotics. Penicillin was inferior to erythromycin and cloxacillin and there is little evidence that using disinfectant solutions improves impetigo. SIDE EFFECTS: The reported number of side effects was low. Oral antibiotic treatment caused more side effects, especially gastrointestinal ones, than topical treatment. REVIEWERS' CONCLUSIONS: Data on the natural course of impetigo are lacking. Placebo controlled trials are scarce. There is little evidence about the value of disinfecting measures. There is good evidence that topical mupirocin and topical fusidic acid are equally, or more effective than oral treatment for people with limited disease. It is unclear if oral antibiotics are superior to topical antibiotics for people with extensive impetigo. Fusidic acid and mupirocin are of similar efficacy. Penicillin was not as effective as most other antibiotics. Resistance patterns against antibiotics change and should be taken into account in the choice of therapy.

Administration, Oral↗
PubMed2003

Screening children in the first four years of life to undergo early treatment for otitis media with effusion.

BACKGROUND: Otitis media with effusion (OME) is the most common cause of acquired hearing loss in childhood and has been associated with delayed language development and behavioural problems. This condition has a prevalence of about 20% at the age of two years, a time of rapid language development. It is most often asymptomatic. Effective treatment exists for clearing effusions. Some have argued, therefore, that children should be screened and treated early if found to have clinically important OME. However, there is a high rate of spontaneous resolution of effusions and for some children, effusions may represent a physiological response that does not reduce hearing significantly or impact negatively on language development or behaviour. Previous reviews of the effect of screening and treatment have included studies using non-randomised designs. OBJECTIVES: The aim of this review was to assess evidence from randomised controlled trials about the effectiveness, on language and behavioural outcomes, of screening and treating children with clinically important OME in the first four years of their life. The focus was on the first four years of life because this is the time of most rapid language development. The consequences of hearing loss are likely to be most serious during this time. In addition, children of this age are least likely to be able to report or seek help for impaired hearing, particularly if these problems have a slow onset and are subtle. SEARCH STRATEGY: We searched the Cochrane Controlled Trials Register (the Cochrane Library Issue 1, 2002), MEDLINE (1966-2002) and EMBASE (1974-2002) (all in February 2002) and reference lists of all studies. We also contacted the first authors of the studies we included in this review. SELECTION CRITERIA: 1. Randomised controlled trials evaluating interventions for OME among children with OME identified through screening. 2. Comparison of outcomes for children randomised to be screened for OME and outcomes for children who were not randomised to be screened for OME. DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted data and assessed trial quality. MAIN RESULTS: We identified no trials comparing outcomes for children randomised to be screened for OME with outcomes for children who were not randomised to be screened for OME. We identified three trials evaluating interventions for OME among children with OME identified through screening. From these trials, we found no evidence of clinically important benefit in language development from screening and treating children with clinically important OME. Although there was a beneficial effect on the resolution of OME and improved hearing in the short-term (six months), this effect largely disappeared in the long-term (12 months). REVIEWER'S CONCLUSIONS: The identified randomised trials do not show an important benefit from screening of the general population of asymptomatic children in the first four years of life for OME on language development and behaviour.

Child, Preschool↗
PubMed2003

Should children be screened to undergo early treatment for otitis media with effusion? A systematic review of randomized trials.

BACKGROUND: Otitis media with effusion (OME) is the most common cause of acquired hearing loss in childhood and has been associated with delayed language development and behavioural problems. Some have argued that children should be screened and treated early if found to have clinically important OME. The aim of this review was to assess evidence from randomized controlled trials about the effectiveness of screening and treating children with clinically important OME in the first 4 years of their life. The primary outcome was language development. METHODS: We searched the Cochrane Controlled Trials Register, MEDLINE and EMBASE and reference lists of all included studies in February 2003. We also contacted the first authors of the studies included in this review. Search terms included otitis media; otitis media with effusion; glue ear; OME; screen; children; treatment; language; and behaviour. Data extraction and methodological quality assessment were performed by at least two of us for each study independently, using methods described in the Cochrane Collaboration Handbook. RESULTS: From the three included randomized controlled trials evaluating interventions among children with OME identified through screening, we found no evidence of clinically important benefit in language development. CONCLUSIONS: The identified randomized trials do not show an important benefit on language development from screening the general population of asymptomatic children in the first 4 years of life to undergo early treatment for OME. Screening asymptomatic children in the first 4 years of life for OME is not recommended.

Child↗
PubMed2001

Steroids for otitis media with effusion: a systematic review.

BACKGROUND: Otitis media with effusion (OME) is common and may cause hearing loss with associated delayed language development in children. Treatment remains controversial. OBJECTIVE: To examine evidence for or against treating OME with systemic or topical nasal steroids. DATA SOURCES: We searched the Cochrane Controlled Trials Register using the terms otitis media; otitis media with effusion; glue ear; or OME and steroids; glucocorticoids; glucocorticoids, synthetic; glucocorticoids, topical; or anti-inflammatory agents, steroidal; or various combinations of these terms. EMBASE and MEDLINE were also searched. STUDY SELECTION: Randomized controlled trials of oral and topical nasal steroids, either alone or in combination with another agent such as an antibiotic, were included. Ten studies met the inclusion criteria. DATA EXTRACTION: Data extraction and methodological quality assessment were performed by the 2 of us (C.C.B. and J.H.v.d.V.) independently, using standardized methods described in the Cochrane Collaboration Handbook. DATA SYNTHESIS: The odds ratio for OME persisting after short-term follow-up in children treated with oral steroids compared with a control was 0.22 (95% confidence interval, 0.08 = 0.63), and was 0.32 (95% confidence interval, 0.20 = 0.52) for children treated with oral steroids plus an antibiotic compared with a control plus an antibiotic. Trends favored steroids for most other comparisons, but confidence intervals included unity. Trends favored steroids for most other comparisons, but confidence intervals included unity. CONCLUSIONS: Steroids alone or combined with an antibiotic lead to a quicker resolution of OME in the short-term. However, there is no evidence for a long-term benefit from treating hearing loss associated with OME with either oral or topical nasal steroids. These treatments are, therefore, not recommended.

Anti-Bacterial Agents↗
PubMed2001

A case study of nurse management of upper respiratory tract infections in general practice.

BACKGROUND: Nurses increasingly manage acute illness in United Kingdom (UK) general practice. Few data exist about patients routinely consulting with these nurses. There are concerns that providing this additional service will lower thresholds for consulting with an overall increase in workload. Upper respiratory tract infection (URTI) is the commonest reason for consulting. Inappropriate antibiotics promote resistant bacteria. Nurse management of URTI is an ideal opportunity to promote self-care and nonantibiotic management. AIMS: To describe the effects of a specially trained practice nurse managing URTI in a general practice in Cardiff, UK. METHODS: Descriptive study. RESULTS: Data were collected on 132 patients consulting with the nurse. We also collected data on 234 patients consulting general practitioners (GPs) in the same practice. Patients seen by the nurse were younger and less likely to be given antibiotics at the time of their index illness than those who saw GPs (7% vs. 93%; P < 0.001). During the year following the consultation with the nurse, patients consulted slightly less often and received antibiotics for URTI less often compared with the year preceding this consultation (P=0.02). Their consultation rate for all conditions did not change. The consultation rates for URTI of the patients managed by the GPs remained constant and consultations for all conditions increased (P < 0.01). CONCLUSIONS: Nurse management of URTI did not lower patients' threshold for future consulting, and patients who saw her were prescribed antibiotics less often.

Adolescent↗
PubMed2001

Antibiotics and shared decision-making in primary care.

Antibiotics are often prescribed to patients with respiratory tract infections who are unlikely to benefit. Models of physician-patient interaction may help understanding of this problem and inform the design of communication skills interventions to enhance appropriate prescribing. The 'paternalistic model' of the consultation remains common in the setting of acute respiratory tract infections. However, the four assumptions that could support this model are not valid for most of these patients, because: best treatment is controversial; management is inconsistent; physicians are not in the best position to evaluate trade-offs between management options without understanding patients' perspectives; and many pressures (apart from patients' agendas) intrude into the consultation. One alternative is the 'informed model' of consulting, but this does not take society's interests into account. The 'shared decision-making model', however, provides a framework for addressing both clinicians' and patients' agendas, and could guide the development and evaluation of specific consultation strategies to promote more appropriate use of antibiotics in primary care.

Anti-Bacterial Agents↗
PubMed2001

Does early detection of otitis media with effusion prevent delayed language development?

OBJECTIVE: To consider whether earlier detection of otitis media with effusion (OME) in asymptomatic children in the first 4 years of life prevents delayed language development. METHODS: MEDLINE and other databases were searched and relevant references from articles reviewed. Critical appraisal and consensus development were in accordance with the methods of the Canadian Task Force on Preventive Health Care. RESULTS: No randomised controlled trials assessing the overall screening for OME and early intervention to prevent delay in acquiring language were identified, although one trial evaluated treatment in a screened population and found no benefit. The "analytic pathway" approach was therefore used, where evidence is evaluated for individual steps in a screening process. The evidence supporting the use of tools for early detection such as tympanometry, microtympanometry, acoustic reflectometry, and pneumatic otoscopy in the first 4 years of life is unclear. Some treatments (mucolytics, antibiotics, steroids) resulted in the short term resolution of effusions as measured by tympanometry. Ventilation tubes resolved effusions and improved hearing. Ventilation tubes in children with hearing loss associated with OME benefited children in the short term, but after 18 months there was no difference in comparison with those assigned to watchful waiting. Most prospective cohort studies that evaluated the association between OME and language development lacked adequate measurement of exposure or outcome, or suffered from attrition bias. Findings with regard to the association were inconsistent. CONCLUSIONS: There is insufficient evidence to support attempts at early detection of OME in the first 4 years of life in the asymptomatic child to prevent delayed language development.

Acoustic Impedance Tests↗
PubMed2000

Randomised controlled trial of nurse practitioner versus general practitioner care for patients requesting "same day" consultations in primary care.

OBJECTIVE: To ascertain any differences between care from nurse practitioners and that from general practitioners for patients seeking "same day" consultations in primary care. DESIGN: Randomised controlled trial with patients allocated by one of two randomisation schemes (by day or within day). SETTING: 10 general practices in south Wales and south west England. SUBJECTS: 1368 patients requesting same day consultations. MAIN OUTCOME MEASURES: Patient satisfaction, resolution of symptoms and concerns, care provided (prescriptions, investigations, referrals, recall, and length of consultation), information provided to patients, and patients' intentions for seeking care in the future. RESULTS: Generally patients consulting nurse practitioners were significantly more satisfied with their care, although for adults this difference was not observed in all practices. For children, the mean difference between general and nurse practitioner in percentage satisfaction score was -4.8 (95% confidence interval -6.8 to -2.8), and for adults the differences ranged from -8.8 (-13.6 to -3.9) to 3.8 (-3.3 to 10.8) across the practices. Resolution of symptoms and concerns did not differ between the two groups (odds ratio 1.2 (95% confidence interval 0.8 to 1.8) for symptoms and 1.03 (0.8 to 1.4) for concerns). The number of prescriptions issued, investigations ordered, referrals to secondary care, and reattendances were similar between the two groups. However, patients managed by nurse practitioners reported receiving significantly more information about their illnesses and, in all but one practice, their consultations were significantly longer. CONCLUSION: This study supports the wider acceptance of the role of nurse practitioners in providing care to patients requesting same day consultations.

Acute Disease↗
PubMed2000

Oral or topical nasal steroids for hearing loss associated with otitis media with effusion in children.

BACKGROUND: OME is common and may cause hearing loss with associated developmental delay. Treatment remains controversial. The effect of both systemic and intra-nasal steroids on effusions has been assessed by randomised controlled trials. OBJECTIVES: To examine evidence for or against treating children with hearing loss associated with OME with systemic or topical nasal steroids. SEARCH STRATEGY: Searches were conducted in February 2000. We searched the Cochrane Controlled Trials Register using the terms 'otitis-media', 'otitis media with effusion', 'glue ear', or 'OME', and 'steroids', 'glucocorticoids, synthetic', 'glucocorticoids, topical', 'anti-inflammatory agents, steroidal'. EMBASE and MEDLINE were also searched for additional information. SELECTION CRITERIA: Randomised controlled trials of oral and topical nasal steroids, either alone or in combination with another agent such as an antibiotic, were included. EXCLUSIONS: publications in abstract form only since adequate appraisal was not possible; uncontrolled, non-randomised or retrospective studies; studies reporting outcomes with ears (rather than children) as the unit of analysis. DATA COLLECTION AND ANALYSIS: Data were extracted from the published reports by the two authors independently (CCB and JH van der V) using standardised data extraction forms and methodology. The methodological quality of the included studies were independently assessed by the two authors using the scheme described in the Cochrane Handbook. Dichotomous results were expressed as an odds ratio using a fixed effects model together with the 95% confidence intervals. Continuous data were analysed using the weighted mean difference in a fixed effects model. Tests for heterogeneity between studies were performed using a Mantel-Haenszel approach. In trials with a cross over design, post-crossover treatment data were not used. MAIN RESULTS: No study prospectively documented hearing loss associated with OME prior to randomisation. Follow up was short term. No serious or lasting side effects were reported in the four studies that did mention side effects. Most comparisons involved small numbers of subjects. The odds ratio for OME persisting after short term follow up for children treated with oral steroids plus antibiotic compared to control plus antibiotic was 0.32 (95% CI 0.20 to 0.52). However there was significant heterogeneity between studies (p<0.01). Trends favoured steroids for most other comparisons, but confidence intervals included unity. There was no evidence of benefit for steroid treatment in the longer term, and no study assessed effect of steroid treatment on language development. REVIEWER'S CONCLUSIONS: There is evidence that steroids combined with an antibiotic lead to a quicker resolution of OME in the short term. However, there is not evidence for long term benefit from treating hearing loss associated with OME with either oral or topical nasal steroids. These treatments are therefore not recommended at the present time. Future studies should document hearing loss associated with OME before the start of study treatment. Follow up should be longer and ideally include symptom, audiometry and developmental outcomes. Data should not be presented with ears as the unit of analysis.

Administration, Intranasal↗
PubMed2000

Fluorescent microplate assay for cancer cell-associated cathepsin B.

Cathepsin B and in particular cell-surface and secreted cathepsin B has been implicated in the invasive and metastatic phenotype of numerous types of cancer. We describe here a method to easily survey cancer cell lines for cathepsin B activity using the highly selective substrate Z-Arg-Arg-AMC. Intact human U87 glioma cells hydrolyze Z-Arg-Arg-AMC with a Km of 460 microM at pH 7.0 and 37 degrees C. This is nearly the same as the Km of 430 microM obtained with purified cathepsin B assayed under the same conditions. The pericellular (i.e. both cell-surface and released) cathepsin B activity was inhibited by the cysteine protease inhibitors E-64, leupeptin, Mu-Np2-HphVS-2Np, Mu-Leu-HpHVSPh and the cathepsin B selective inhibitor Mu-Tyr(3,5 I2)-HphVSPh with IC50 values similar to those observed for the inhibition of purified human liver cathepsin B. Other human cancer cell lines with measurable pericellular cathepsin B activity included HT-1080 fibrosarcoma, MiaPaCa pancreatic, PC-3 prostate and HCT-116 colon. Cathepsin B activity correlated with protein levels of cathepsin B as determined by immunoblot analysis. Pericellular cathepsin B activity was also detected in the rat cell lines MatLyLu prostate and Mat B III adenocarcinoma and in the murine lines B16a melanoma and Lewis lung carcinoma. The ability to determine pericellular cathepsin B activity will be useful in selecting appropriate cell lines for use in vivo when analyzing the effects of inhibiting cathepsin B activity on tumor growth and metastasis.

Animals↗
PubMed2000

Estimating the prevalence of diagnosed diabetes in a health district of Wales: the importance of using primary and secondary care sources of ascertainment with adjustment for death and migration.

AIMS: To determine diagnosed diabetic prevalence within our district (population 434398) in 1996 using data from two sources. METHODS: A general practice audit comprising data on patients with diabetes from 61 (82%) of 74 general practices was linked to a record linkage-derived patient index in which data from secondary care and other sources underwent a process of probability matching to identify records relating to the same patient and to flag those with diabetes. By linking this dataset to a mortality dataset, patients known to have died before 1996 could be excluded. Age and sex-stratified emigration rates were applied to those identified by the hospital dataset for each year from 1991 onwards. RESULTS: A total of 386988 residents (89.1%) were listed with a general practitioner participating in the audit, of whom 6050 patients were identified as having diabetes in 1996; a prevalence rate of 1.56%. From the hospital-based source, 7639 patients were identified who were alive in 1996, a period prevalence of 1.76%. By combining the two sources, and extrapolating the general practice audit to the population as a whole, a total of 10 530 patients were identified of whom 8735 were confirmed as still resident within South Glamorgan during 1996. This represented a period prevalence of between 2.01% to 2.42%. By applying age and sex-stratified migration rates to the diabetic population identified by hospital sources, a diagnosed diabetic population of 10,004 was identified, a prevalence of 2.3%. CONCLUSIONS: This study demonstrates that to calculate the true prevalence of diagnosed diabetes from health sources, it is necessary to use both primary and secondary care sources.

Adolescent↗
PubMed2000

The prevalence of multiple diabetes-related complications.

AIMS: To determine the prevalence of the complications of diabetes and the interrelationship between them within a United Kingdom district health authority population. METHODS: Data extracted from a general practice diabetes audit were combined with data for patients with diabetes derived from a patient index constructed using record linkage techniques. RESULTS: A total of 10709 patients were identified as having diabetes (prevalence 2.47%). Coronary heart disease was present in 25.2%, cerebrovascular disease in 9.6%, complications of the 'diabetic foot' in 18.1%, retinopathy in 16.5% and nephropathy in 2.0%. Over a half of the patients (52.1%) had none of the studied complications, 30.2% had one, 12.7% had two, 4.1% had three, 0.8% had four and 0.1% had all five. All complications were related to both age and duration of diabetes but duration was particularly apparent for the microvascular complications (retinopathy and nephropathy). Macrovascular complications in the Type 2 diabetic population appear advanced in onset compared with Type 1. CONCLUSIONS: Multiple complications are apparent in almost one fifth of patients with diabetes. Macrovascular morbidity in Type 2 diabetes of early onset indicates that a targeted approach to treatment may prove most beneficial in both patient and health service terms.

Adolescent↗