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Biomedical subjects

M Campbell

Publications and source records attributed to M Campbell.

At least 199 records · Page 11Linked to original sources

Intra-articular morphine and/or bupivacaine in the management of pain after total knee arthroplasty.

The purpose of this study was to determine if intra-articular injection of morphine or bupivacaine significantly decreased postoperative pain as well as the use of intravenous narcotics for pain relief in patients undergoing total knee arthroplasty (TKA). In a prospective, double-blind, randomized fashion, 105 patients undergoing TKA were divided into the following 4 groups defined by the intra-articular injection they received: group 1 (n = 27) received saline solution, group 2 (n = 26) received morphine sulfate (5 mg), group 3 (n = 24) received bupivacaine (50 mg), and group 4 (n = 28) received a combination of morphine sulfate and bupivacaine. The injections were administered immediately after wound closure by the Hemovac drainage tubing that remained clamped for 45 minutes after surgery to allow for absorption. Before surgery and at 2, 4, 6, 24, and 48 hours after surgery, pain intensity was recorded using a visual analog scale. Postoperative supplemental intravenous morphine and/or meperidine was administered via a patient-controlled analgesia device, and 24-hour drug usage was tabulated. Results were suggestive of a modest short-term reduction in pain scores in the morphine and bupivacaine treatment groups compared with placebo (saline); however, results were statistically significant only at 4 hours because of the great variability in the pain score data. The total amount of postoperative pain medication used in the first 24 hours after surgery was not statistically significant between the 4 treatment groups. Thus, the results put into question the benefit of postoperative intra-articular administration of morphine or bupivacaine in patients undergoing TKA.

Adult↗

Using aspects of study design in sample size estimation.

The basis of sample size calculations is usually needed in protocols for clinical trials and when publishing results in respected journals. Although a large amount of research has been undertaken on sample size estimation for different trial designs, in practice the methods are rarely used. This paper describes some useful theory that has practical relevance.

Clinical Trials as Topic↗

Nonpharmacological response in hospitalized children with conduct disorder.

OBJECTIVE: There is a paucity of research regarding the effects of hospitalization and/or the response to placebo in children with conduct disorder who are hospitalized for chronic and severe aggression. However, many children with this problem are hospitalized and immediately begin pharmacotherapy. In this report, the effects of hospitalization and placebo administration were examined. METHOD: Subjects were forty-four children (37 males, 7 females) with conduct disorder, aged 9.83 to 17.14 years, who were hospitalized for chronic and severe aggression. This was a 4-week double-blind and placebo-controlled study with a 2-week single-blind placebo lead-in period. During the 2-week placebo baseline period, aggression was measured on a 24-hour basis, using the Overt Aggression Scale. Only subjects meeting a specific aggression criterion were randomized to the treatment period of the trial. RESULTS: Of the 44 subjects enrolled, 23 (52.3%) met the aggression criteria for entering the treatment period (baseline nonresponders), while 21 (47.7%) did not (baseline responders). Thus, almost half of the subjects, while taking no active medication, benefited from the inpatient milieu/structure and/or placebo. CONCLUSION: This finding has important treatment and research implications. Medication to treat aggression should not be initiated immediately upon hospitalization because improvements associated with hospitalization may be attributed inaccurately to pharmacotherapy, resulting in unnecessarily medicating children. A placebo baseline period is essential to decrease the risk of a type II error in pharmacological research concerning aggression.

Adolescent↗

Neuroleptic-related dyskinesias in autistic children: a prospective, longitudinal study.

OBJECTIVE: To report results from a long-term prospective study of safety of haloperidol treatment and prevalence of haloperidol-related dyskinesias. METHOD: Subjects were children with autism requiring pharmacotherapy for target symptoms. After baseline assessments, children received haloperidol treatment; responders requiring further treatment were considered for enrollment into the present study. Six-month haloperidol treatment periods were followed by a 4-week placebo period. The procedure was repeated if further haloperidol treatment was required. At specified times children were evaluated by using multiple instruments. RESULTS: Between 1979 and 1994, 118 children aged 2.3 to 8.2 years participated in the study. The mean dose of haloperidol was 1.75 mg/day. Mainly withdrawal dyskinesias (WD) developed in 40 (33.9%) children; 20 had more than one dyskinetic episode. A subgroup that remained significantly longer in the study and had a significantly higher cumulative dose of haloperidol evidenced a significantly higher incidence of WD. Occurrence rates of tardive dyskinesia (TD) and multiple episodes of TD/WD were higher among girls. CONCLUSION: Female gender and pre- and perinatal complications may be involved in susceptibility to dyskinesias; greater cumulative haloperidol dose and/or longer exposure to haloperidol may increase the risk.

Antipsychotic Agents↗

Intravenous regional analgesia using morphine. The effect on postoperative pain following total knee arthroplasty.

BACKGROUND: We hypothesised that any peripheral action of morphine may contribute to improved postoperative analgesia. The aim of this study was to evaluate the analgesic efficacy of morphine administered preoperatively into an exsanguinated limb prior to total knee arthroplasty. METHODS: A randomised, double-blind, controlled study was performed in 50 patients having total knee arthroplasty surgery. Patients were divided into two groups. In the study group, 0.125 mg/kg morphine in 60 ml of saline was administered intravenously (iv) into the exsanguinated operative limb via a cannula in the foot. A saline intramuscular (im) injection was administered into the opposite leg. The control group received 60 ml saline iv into the operative leg and 0.125 mg/kg morphine im into the opposite leg. Pain was assessed postoperatively using a 10-point visual analogue scale and by comparing morphine requirements and demand:delivery ratios from a patient-controlled analgesic pump. RESULTS: We found no statistically significant difference between the groups in relation to any of the analgesic measures employed. CONCLUSIONS: Intravenous regional analgesia using morphine provides no analgesic advantage over the intramuscular route from 6-24 h postoperatively.

Analgesia, Patient-Controlled↗

Prevalence of bacterial enteropathogens in pet dogs in Trinidad.

The rectal swabs of diarrhoeic and apparently healthy non-diarrhoeic dogs presented to a Small Animal Clinic were cultured for Escherichia coli, Salmonella and Campylobacter and the enteropathogens were characterized. Overall, of 130 dogs divided equally into two groups consisting of 65 diarrhoeic and 65 non-diarrhoeic dogs, 99 (76.2%), 6 (4.6%) and 18 (13.8%) were positive for E. coli, Salmonella and Campylobacter, respectively. The differences were statistically significant (P < or = 0.05; chi 2). The prevalences of the enteropathogens in diarrhoeic and non-diarrhoeic dogs were not statistically significant (P > or = 0.05; chi 2). Diarrhoea was significantly (P < or = 0.01; chi 2) more prevalent in dogs less than 6 months of age and 7 months to 1 year old than in dogs older than 1 year. The prevalences of Salmonella, E. coli and enteropathogenic E. coli (EPEC) strains were not significantly (P > or = 0.05; chi 2) associated with age but the prevalence of Campylobacter infection was significantly (P < or = 0.01; chi 2) higher in dogs less than 1 year old (25.0%) than in older dogs (5.4%). Of 99 E. coli strains tested, three (3.0%), four (4.0%), five (5.1%) and 20 (20.2%) were haemolytic, non-sorbitol fermenters, verocytotoxigenic (VT) and EPEC strains, respectively. Resistance to tetracycline (59.6%) and ampicillin (50.5%) was most prevalent and significantly (P < or = 0.01; chi 2) higher than to six other antimicrobial agents.

Ampicillin↗

A study of treatment failures following large loop excision of the transformation zone for the treatment of cervical intraepithelial neoplasia.

OBJECTIVE: To examine the long term efficacy of large loop excision of the transformation zone (LLETZ) in the treatment of cervical intraepithelial neoplasia (CIN) and to evaluate the relative diagnostic merits of colposcopy and cytology in the follow up of these women. DESIGN: A retrospective examination of cytology, colposcopy and histology records of the first 1000 women treated with LLETZ in Aberdeen from 1989 to 1991. SETTING: Colposcopy Clinic Aberdeen Royal Infirmary, Grampian Region, Scotland. RESULTS: Nine hundred and seventy-seven women (97.7%) were seen for follow up at least once and 317 were followed for as long as four years. This comprises 2812 woman years of follow up. The incidence of recurrent CIN was 27/1000 woman years and the cumulative rate of recurrence at four years was 10.1 per 100 women. Twenty-eight of the 59 women (47%) with abnormal colposcopy and proven CIN had a concurrent smear that did not show dyskaryosis. CONCLUSIONS: LLETZ is an effective from of treatment for CIN. Colposcopy was useful in the follow up of these women and expedited the treatment of persistent disease. We recommend that any follow up protocol should include a colposcopic assessment and cytological follow up for at least four years following treatment. Further data are required to determine the risk of recurrence beyond this time.

Adolescent↗

The UPDRS scale as a means of identifying extrapyramidal signs in patients suffering from dementia with Lewy bodies.

The study aimed to evaluate the merits of the Unified Parkinson's Disease Rating Scale (UPDRS) in the assessment of parkinsonism in patients suffering from Dementia with Lewy Bodies (DLB). Parkinsonian symptoms were assessed in 73 dementia patients using the UPDRS and staged using the Hoehn & Yahr system. A staging of 1 or greater was taken to indicate significant parkinsonism. DLB (n=42) was diagnosed using the McKeith et al. criteria, Alzheimer's disease (n=30) was diagnosed using the NINCDS ADRDA criteria. The inability of some patients to comply with some of the more complicated tasks meant that the full UPDRS assessment could only be completed in 35 (83%) of the DLB patients, 23 (66%) of whom had significant parkinsonism. Patients with parkinsonism were significantly younger than those without. A Principal Components Analysis derived a sub-scale including the items tremor at rest, action tremor, bradykinesia, facial expression and rigidity. These items had a specificity of 100% and a sensitivity of 85% for significant parkinsonism using a cut-off of 7/8. The brief scale had several advantages over the complete UPDRS. Unlike the full scale it was independent of the severity of cognitive impairment and the 5 key items could be assessed in 41 (98%) of the DLB patients. Autopsies have been completed on 31 patients, with a specificity of greater than 90% for the operationalized clinical diagnosis of DLB. It is suggested that a 5 item subscale of the UPDRS provides a reliable and generally applicable instrument for the assessment of parkinsonism in DLB patients.

Aged↗

Inactivation of the human immunodeficiency virus type 1 inhibitory elements allows Rev-independent expression of Gag and Gag/protease and particle formation.

The expression of gag, pol, and env of human immunodeficiency virus type 1 (HIV-1) depends on the presence of the viral Rev protein. This dependence is, at least in part, due to the presence of negatively acting sequences (inhibitory or instability elements [INS]) located within unspliced and partially spliced mRNAs. The positive interaction of Rev with the Rev-responsive element in these mRNAs counteracts the negative effects of the inhibitory sequences. Here, we demonstrate that in addition to the previously identified INS1 within p17gag, several other INS elements exist within the gag/pol region of HIV-1. These elements act independently of each other and were eliminated by mutagenesis after the introduction of multiple point mutations not affecting the coding region, leading to constitutive high levels of Gag expression. Expression vectors containing an intact or nearly intact p55gag region allowed the production of immature viral particles in mammalian cells in the absence of any other HIV proteins. The introduction of additional mutations in the protease region allowed efficient production of Gag/protease, which resulted in processing of the Pr55gag precursor and production of mature Gag particles with a lentivirus-like conical-core structure. The elimination of a newly identified INS element within pol and the previously identified CRS located within int was accomplished by the same methodology. Sequence comparisons of the identified inhibitory elements revealed no apparent homologies and demonstrated that these sequences are not splice sites. These results demonstrate that the elimination of INS elements leads to efficient expression of HIV-1 mRNAs in the absence of Rev or any posttranscriptional activating mechanisms.

Amino Acid Sequence↗

Correlation of Pseudomonas aeruginosa virulence factors from clinical and environmental isolates with pathogenicity in the neutropenic mouse.

The potential pathogenicity of a microorganism is a major concern for Health Canada evaluators, who will be processing new biotechnology products under the Canadian Environmental Protection Act. Potential pathogenicity is generally predicted by the results of animal pathogenicity studies. In an attempt to define surrogate data for an animal model, this study was initiated. Pseudomonas aeruginosa isolates from clinical and environmental sources were screened for their pilus type, serotype, lipopolysaccharide type, ability to evade host responses, and production of toxin A, exoenzyme S, elastase, phospholipase C, and total protease. The 50% lethal dose (LD50) of the same isolates was determined in the neutropenic mouse model of infection. An attempted correlation was drawn between each (or combinations) of the virulence determinants and the LD50. Stepwise linear regression showed that the presence of high levels of exoenzyme S in association with elastase or phospholipase C, or to a minor extent toxin A, was correlated with low numbers of bacteria required to elicit an LD50. No correlation between any of the other factors examined and virulence was detected. The data suggest that an in vitro high level of exoenzyme S production could be used as surrogate information for neutropenic mouse modelling; however, the levels of all of the extracellular enzymes should be considered when making such an assessment.

ADP Ribose Transferases↗

Unequal randomisation can improve the economic efficiency of clinical trials.

OBJECTIVES: In the majority of clinical trials patients are randomised equally between treatment groups. This approach maximises statistical power for a given total sample size. The objectives of this paper were to determine if, when research costs between treatments differ, it is more economically efficient to randomise additional patients to the cheaper treatment, and how the optimum randomisation ratio can be estimated. METHODS: Estimation of the most economically efficient randomisation ratio for four hypothetical clinical trials using cost-effectiveness analysis. RESULTS: When research costs differ between treatments, and there is no constraint on total sample size, it is always more cost-effective to randomise more patients to the cheaper treatment. For example, a cost ratio between the lesser and more expensive treatment of ten, results in a randomisation ratio of 3.2:1. CONCLUSIONS: Unequal randomisation ratios should be more widely used as this will achieve optimum statistical power for the lowest expenditure of research resources.

Budgets↗

Women married to men with myocardial infarction are at increased risk of coronary heart disease.

AIM: To measure the prevalence of coronary heart disease (CHD) risk factors in the female partners of men with acute myocardial infarction (AMI). METHOD: Consecutive incident cases of men under 65 years of age with AMI surviving to 3 months, their female partners and female healthy controls matched for age and marital status drawn from the general population were investigated. RESULTS: One-hundred and seventeen cases of AMI in men under 65 years of age and 89 female partners were identified; 133 age- and sex-matched controls were examined for CHD risk factors. Cigarette smoking was more common among the younger partners (25-44 years of age) compared with controls. A body mass index > 28 kg/m2, systolic blood pressure > 150 mmHg, diastolic blood pressure > 90 mmHg and cholesterol > 6.5 mmol/l were all significantly more common in partners compared with controls. In a logistic regression of age, smoking habit, blood pressure, cholesterol and body mass index, based on 89 female partners and 132 controls with complete data, body mass index > 28 kg/m2 (odds ratio 2, 17, 95% CI 1.11-4.23) and cholesterol > 6.5 mmol/l (odds ratio 2.21, 95% CI 1.08-4.49) were both significantly more common in the female partners compared with controls. CONCLUSIONS: Women married to men with AMI have a higher frequency of CHD risk factors compared with married women in the general population, consistent with a shared family lifestyle putting both adults at higher risk of CHD. Screening blood relatives in families prematurely affected by CHD is widely advocated; such screening should include partners.

Adult↗

PET scanning and the human immunodeficiency virus-positive patient.

UNLABELLED: The use of PET scanning in patients with human immunodeficiency virus infection and fever of unknown origin, confusion and/or weight loss was investigated. METHODS: Eighty patients were examined using PET. Fifty-seven patients had half-body scans with [18F]fluorodeoxyglucose (FDG), and 23 patients had brain studies performed with FDG. Fourteen patients also had [11C]methionine studies (2 chest, 1 abdomen and 11 brain) performed. RESULTS: Thirteen patients with lymphoma had the extent of the disease clearly identified in both nodal and extranodal sites. Patients with a variety of infections (Cryptococcus neoformans, Pseudomonas aeruginosa, Mycobacterium tuberculosis and Mycobacterium avium intracellulare) had disease localized for appropriate biopsy or sampling procedures. A half-body FDG-PET scan had a sensitivity of 92% and a specificity of 94% for localization of focal pathology that needed treatment. High uptake of FDG (greater than liver) had a positive predictive value for pathology needing treatment of 95%. FDG brain studies showed that 16 patients with CD4 T-lymphocyte counts less than 200 cells/ml had reduced cortical uptake compared with that in basal ganglia. FDG scans were abnormal in all 19 patients with focal space occupying lesions identified by magnetic resonance scans. The standardized uptake values (SUVs) over cerebral lesions due to toxoplasma were in the range of 0.14-3.7 (13 patients) and due to lymphoma were in the range of 3.9-8.7 (6 patients). Three more patients with progressive multifocal leukoencephalopathy had SUVs in the range of 1.0-1.5 over the lesions. Another patient had a low-grade oligodendroglioma (SUV = 2.9). Carbon-11-methionine uptake also was high in patients with cerebral lymphoma but did not add to the discrimination between toxoplasmosis and lymphoma in these patients obtained with the FDG scan. CONCLUSION: In hospitals with access to PET facilities, FDG scanning allows the rapid evaluation of the whole body, including the brain, of patients with human immunodeficiency virus infection, with a report potentially available within 4 hr of injection. Sites of infection and tumor were identified, and discrimination between cerebral pathologies was possible.

AIDS-Related Opportunistic Infections↗

A prescribing incentive scheme for non-fundholding general practices: an observational study.

OBJECTIVE: To examine the effects of a financial incentive scheme on prescribing in non-fundholding general practices. DESIGN: Observational study. SETTING: Non-fundholding general practices in former Northern region in 1993-4. INTERVENTION: Target savings were set for each group of practices; those that achieved them were paid a portion of the savings. MAIN OUTCOME MEASURES: Financial performance; prescribing patterns in major therapeutic groups and some specific therapeutic areas; rates of generic prescribing; and performance against a measure of prescribing quality. SUBJECTS: 459 non-fundholding general practices, grouped into three bands according to the ratio of their indicative prescribing amount to the local average (band A > or = 10% above average, B between average and 10% above, C below average). RESULTS: 102 (23%) of 442 practices achieved their target savings (18%, 19%, and 27% of bands A, B, and C respectively). Band C practices that achieved their target had a lower per capita prescribing frequency for gastrointestinal drugs, inhaled steroids, antidepressants, and hormone replacement therapy. There were no other significant differences in prescribing frequency, and no reduction in the quality of prescribing in achieving practices. Total savings of pounds 1.54 m on indicative prescribing amounts were achieved. Payments from the incentive scheme and discretionary quality awards resulted in pounds 463,000 being returned to practices for investment in primary care. CONCLUSIONS: The prescribing behaviour of non-fundholding general practitioners responded to financial incentives in a similar way to that of fundholding practitioners. The incentive scheme did not seem to reduce the quality of prescribing.

Budgets↗