Avoparcin and virginiamycin as animal growth promoters: a plea for science in decision-making.
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Animal Feed↗
Biomedical subjects
J Freeman
Publications and source records attributed to J Freeman.
Ropivacaine 0.2% versus bupivacaine 0.1% with fentanyl: a double blind comparison for analgesia during labour.
We have performed a randomized, double-blind comparison of two epidural drug regimens for analgesia in labour. In the bupivacaine group (BUPIV), 101 healthy parturients received 0.1% bupivacaine with fentanyl 2 microg ml(-1). In the ropivacaine group (ROPIV), 102 women received 0.2% ropivacaine. Both groups received an initial loading dose of 15 ml, a continuous infusion of 8 ml h(-1), and top-ups of 10 ml. Breakthrough pain not responding to a routine top-up was treated with an 'escape' top-up of 10 ml 0.25% bupivacaine. The two groups were compared for complete analgesia at 30 min, routine and 'escape' top-up requirements, midwife assessment of analgesic efficacy, delivery mode, patient visual analogue scores (VAS) for first and second stage analgesia, overall satisfaction, and patient assessment of motor blockade. Patients receiving ropivacaine received fewer routine top-ups (median 1.0 vs. 2.0, P=0.001) and fewer escape top-ups (9.8% vs. 21.8%, P=0.02). The ropivacaine group was more likely to be pain free in the first stage (51% vs. 33.7%, P=0.01). There were no significant differences in patients' assessment of motor block or mode of delivery between the groups. Pain relief and satisfaction scores from midwives and patients were consistently better in the ropivacaine group, but did not reach statistical significance.
Adolescent↗
Kurtzke scales revisited: the application of psychometric methods to clinical intuition.
When developing his disability scales for multiple sclerosis, Kurtzke demonstrated perception and insight. However, 45 years later, the evaluation of his clinically derived scales remains limited, particularly for more disabled patients. Indeed, many of Kurtzke's assumptions underpinning the development of the Expanded Disability Status Scale (EDSS) and Functional Systems (FS) are untested. This study aims to build on previous work and provide a more detailed examination using psychometric methods of the EDSS and FS. There are three study objectives: (i) to examine comprehensively the psychometric properties of the EDSS in more disabled people with multiple sclerosis undergoing in-patient rehabilitation; (ii) to examine the reliability of the FS and test Kurtzke's assumptions that they measure different aspects of the neurological examination and measure different constructs from that measured by the EDSS; and (iii) to examine whether the FS can be summed to generate a summary score. The EDSS was examined for its acceptability (score distributions), reliability (inter- and intra-rater reproducibility, standard error of measurement), validity (convergent and discriminant validity, measurement precision, discrimination between individuals) and responsiveness (effect size). The FS were examined for their reliability (inter- and intra-rater reproducibility), intercorrelations, correlations with the EDSS and the extent to which they satisfy Likert's criteria as a summed rating scale. In this more disabled sample of people with multiple sclerosis, the EDSS is an acceptable measure but demonstrates limited variability. Inter-rater reproducibility (intraclass correlation coefficient; ICC = 0.78) is adequate for group comparison studies, but intra-rater reproducibility is variable (ICC = 0.62-0.94). Convergent and discriminant validity for the EDSS is supported, but its measurement precision relative to the Functional Independence Measure is limited (56%). Also, the EDSS has a limited ability to distinguish between individuals in terms of their disability and its responsiveness is poor (effect size = 0.10). Results indicate that the FS measure constructs distinct from each other (intercorrelations = -0.23 to +0. 52) and from the EDSS (correlations = -0.10 to +0.59). Intra-rater, but not inter-rater reproducibility is adequate for group comparison studies. The FS do not satisfy criteria as an eight-, seven- or six-item summed rating scale. Despite being based on sound clinical intuition, the lack of psychometric input into the development of the EDSS and FS has limited their usefulness as evaluative outcome measures in multiple sclerosis.
Adult↗
In vitro activity of new generation fluoroquinolones against genotypically distinct and indistinguishable Clostridium difficile isolates.
We compared the activities of ciprofloxacin and levofloxacin with those of the newer fluoroquinolones grepafloxacin, moxifloxacin, sparfloxacin and trovafloxacin against Clostridium difficile isolates. As there is good evidence of marked clonal spread of C. difficile, we studied both genotypically distinct (n = 26) and indistinguishable (n = 28) isolates as determined by random amplified polymorphic DNA and ribosomal spacer PCR fingerprinting. The indistinguishable strains examined represent the main UK epidemic C. difficile clone. For 17 of 54 strains (31%) we were unable to read MICs following inocula preparation using Mueller-Hinton broth. Using Schaedler's broth for inocula preparation 93% of strains had readable MICs, although geometric mean MICs were uniformly higher (2.5- to 5.4-fold) compared with results using Mueller-Hinton broth. Moxifloxacin and trovafloxacin, followed by grepafloxacin, were the most active fluoroquinolones tested and were 3- to 4-fold more active than older agents such as ciprofloxacin by both MIC methods. Unexpectedly, clonal C. difficile strains had markedly reduced susceptibility compared with the distinct strains to each of the fluoroquinolones tested. Clonal strains were more than seven-fold or 12- to 29-fold less susceptible (according to geometric mean MICs) than distinct strains to both moxifloxacin and trovafloxacin, depending on the MIC method used. It remains to be seen whether the enhanced activity of new fluoroquinolones such as moxifloxacin in comparison with other fluoroquinolones against C. difficile implies that these agents are unlikely to be associated with C. difficile infection. However, clinical use of new generation fluoroquinolones in elderly hospitalized patients where C. difficile is endemic requires further study, particularly given the reduced antibiotic susceptibility to all fluoroquinolones of the readily transmissible UK C. difficile clone.
Anti-Infective Agents↗
Telomerase activity is upregulated in laryngeal squamous cell carcinoma.
OBJECTIVE/HYPOTHESIS: The immortalizing enzyme telomerase has been linked to carcinogenesis and is being targeted as a novel molecular marker. This study investigated telomerase expression in patients with laryngeal squamous cell carcinoma and correlated telomerase activity with conventional prognostic parameters. STUDY DESIGN: A consecutive series of patients with laryngeal squamous cell carcinoma undergoing surgical salvage for persistent or progressive disease after failed radiation therapy. METHODS: Twenty patient samples of laryngeal squamous cell carcinoma and 20 adjacent histologically normal mucosal samples were assayed using the telomeric repeat amplification protocol (TRAP) method for detection of telomerase activity. The leukemic cell line, K562, acted as a positive control and the human fibroblast line, Hs21Fs, as a negative control. A sample was classified as telomerase positive when an RNase-sensitive hexameric repeat ladder was observed. Absence of laddering was considered a negative result. RESULTS: Seventeen of 20 (85%) tumor samples and 4 of 20 (20%) adjacent histologically normal samples were telomerase positive. No statistically significant difference was observed when densitometric readings were compared by T category, tumor grade, or site (by ANOVA). CONCLUSIONS: Although telomerase activity is present in laryngeal cancer, levels of activation do not correlate with conventional parameters used for prognostication. Our study indicates that the marker may be a useful adjunctive method in the diagnosis of malignancy after radiation failure.
Adult↗
Multiple sclerosis: care needs for 2000 and beyond.
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Community Health Nursing↗
The validity of the NART-RSPM index in detecting intellectual decline following traumatic brain injury: a controlled study.
The present study replicated Van den Broek and Bradshaw's (1994) study by developing a multiple regression equation to predict Ravens Standard Progressive Matrices (RSPM) scores from participants' National Adult Reading Test (NART) scores and demographic variables. A test of the validity of this procedure was undertaken by applying both the Van den Broek and Bradshaw equation and the present study's equation to a mixed sample of orthopedic control (OC) and closed head injury (CHI) participants. Premorbid RSPM scores were estimated using both equations and then compared to obtained scores. Results indicated that both equations had good predictive accuracy in estimating RSPM scores and were able to detect significantly higher rates of impairment in general intelligence in the CHI participants (24%) compared to the OC sample (7%).
Adult↗
Vector densities that potentiate dengue outbreaks in a Brazilian city.
To identify the critical vector density that potentiates dengue outbreaks in an endemic site and to identify obstacles to anti-dengue activities, we correlated a series of dengue outbreaks in a Brazilian city with the intensity of its anti-vector source-reduction activities. The proportion of houses infested by vector mosquitoes correlated inversely with intensity of anti-mosquito interventions, and the vector population developed independently of rainfall. Local periods of drought promoted vector abundance in two ways: residents stored water in which vector mosquitoes could breed, and cholera outbreaks due to contaminated water diverted local health workers from routine anti-vector activities. One dengue outbreak became apparent to authorities more than two months after it commenced but would have been identified almost immediately had dengue-like disease in indicator hospitals been monitored. Active surveillance, therefore, offers a window of opportunity for promptly executed anti-dengue interventions. Source-reduction measures that suppress vector infestations to less than 1% of houses effectively avert outbreaks of dengue.
Animals↗
Using treatment failure under effective directly observed short-course chemotherapy programs to identify patients with multidrug-resistant tuberculosis.
SETTING: Public ambulatory care centers in three districts of northern metropolitan Lima, Peru. OBJECTIVE: To document drug resistance patterns of isolates of Mycobacterium tuberculosis from patients identified as treatment failures under a model tuberculosis (TB) control program based on directly observed, short-course chemotherapy (DOT-SCC). DESIGN: Case series. RESULTS: In a referred, consecutive sample of 173 patients identified as treatment failures on DOT-SCC, 160 (92.5%) had culture-positive TB. Of those 160, 150 (93.8%) had active, pulmonary multidrug-resistant TB (MDR-TB, resistance to at least isoniazid [INH] and rifampicin [RIF]). Sixty of the 150 (40.0%) had isolates resistant to at least INH, RIF, ethambutol (EMB) and pyrazinamide (PZA), the initial first-line empiric treatment regimen used locally. Forty-four (29.3%) had isolates resistant to at least INH, RIF, EMB, PZA and streptomycin (SM), the first retreatment regimen. This series of patients had isolates resistant to a mean of 4.5 of the ten drugs tested. The local profile of multidrug resistance is very different from that obtained from national data from Peru. CONCLUSION: In this setting, treatment failure on DOT-SCC is strongly predictive of active MDR-TB. Because of existing local drug resistance patterns in northern Lima, 89.3% of MDR-TB patients identified as treatment failures will receive ineffective therapy with two or fewer secondary TB drugs if they are given the five-drug empiric retreatment regimen endorsed by the World Health Organization. Further short-course chemotherapy for these patients would only serve to amplify ominous existing drug resistance patterns.
Antitubercular Agents↗
Redefining MDR-TB transmission 'hot spots'.
Halting further spread of multidrug-resistant tuberculosis (MDR-TB) requires both new resources and a renewed discussion of priority setting informed by estimates of the existing burden of this disease. The 1997 report of the first phase of the global survey by the World Health Organization (WHO) and the International Union Against Tuberculosis and Lung Disease (IUATLD) uses the indicator of the proportion of TB cases that are MDR-TB to identify MDR-TB 'hot spots'. We sought to refine the definition of MDR-TB transmission 'hot spots'. For this purpose, we obtained estimates of two additional indicators for regions where data are available: MDR-TB incidence per 100,000 population per year, and expected numbers of new patients with MDR-TB per year. There is generally much agreement in the three indicators considered, and some differences also appear. We conclude that it is useful, when defining indicators of MDR-TB transmission 'hot spots', to include estimates of underlying TB incidence rates and of absolute numbers of MDR-TB cases. Estimating the force of morbidity of MDR-TB in a population is important for comparing this burden across settings with very different underlying TB incidence rates; estimating the absolute number of MDR-TB patients will be critical for planning the delivery of directly observed MDR-TB therapy and the rational procurement of second-line drugs. Through this exercise, we aim to initiate discussion about improved methods of quantifying and comparing current MDR-TB transmission 'hot spots' that require intervention.
Antitubercular Agents↗
Barriers to communication about diabetes mellitus. Patients' and physicians' different view of the disease.
BACKGROUND: Management of diabetes mellitus is difficult for both the patient and the clinician, and poor communication resulting from different conceptions of the disease and different treatment goals can exacerbate the problem. METHODS: We used qualitative methods, including semistructured interviews with patients and clinicians and direct observation of clinical precepting sessions by trained observers at an inner-city family practice training site. Transcripts from these sessions were analyzed for content (with the help of Nud.ist software) to identify themes that highlight problem areas in clinician-patient communication. RESULTS: The most important themes revolved around the concept of control, which was used in at least 3 different ways, and the concept of frustration. Frustration resulted from different understandings of the biology, physiology, and natural history of the disease, and approaches to treatment. In the interviews, clinicians often spontaneously acknowledged the multiple physical, psychological, and social obstacles to treatment confronted by their patients, but in observed practice they almost always focused entirely on managing blood sugar numbers. CONCLUSIONS: Different conceptions of the term "control" affect the ability of patients and clinicians to communicate effectively. The tendencies of clinicians to view their own management strategy as scientific truth, and their focus on managing numbers rather than attempting to understand their patient's conception of disease and their treatment goals, lead to frustration and are serious obstacles to effective collaboration.
Aged↗
Sebaceous gland carcinoma of the ocular adnexa.
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Aged↗
Determining clinically meaningful cognitive impairment following traumatic brain injury.
AIMS: To study the reliability and validity of ratings of: neuropsychological impairment with test data from traumatically brain-injured patients. METHODS: Neuropsychological test results from 66 traumatically brain-injured adults and 27 orthopaedic controls were rated for neuropsychological impairment by an experienced neuropsychologist and three undergraduate students provided with brief training in test interpretation. Ratings were based on the discrepancy between a patient's current cognitive level and their estimated premorbid cognitive level. Decision making rules were utilised in making the ratings. The raters, who were blind with respect to the patients diagnostic group membership, independently rated test results. Test results were rerated using the same method approximately two weeks later. RESULTS: The ratings of novice raters were in good to very good agreement with the ratings of an expert. All raters evidenced very good to excellent test-retest reliability. Higher rates of neuropsychological impairment were found in the traumatically brain-injured group than in the orthopaedic control group. Discriminant function analysis suggested that raters employed information from all neuropsychological measures (with the exception of current intellectual level), in making their overall ratings of neuropsychological impairment. CONCLUSION: These findings provide encouraging preliminary evidence in support of the reliability and validity of individual case-based ratings of neuropsychological impairment. The high false positive rate in the control sample may reflect the relatively low specificity of neuropsychological impairment.
Adolescent↗
Language recovery after left hemispherectomy in children with late-onset seizures.
We investigated the language capabilities of the isolated right hemisphere in 6 children (age, 7-14 years) after left hemidecorticectomy for treatment of Rasmussen's syndrome. Patients were right-handed before surgery and had at least 5 years of normal language development before the onset of seizures. Language testing included speech sound (phoneme) discrimination, single word and phrasal comprehension, repetition, and naming. Within 4 to 16 days after surgery, patients showed improved phoneme discrimination compared with their performance shortly before surgery. Other language functions remained severely impaired until at least 6 months after surgery. By 1 year after surgery, receptive functions were comparable with, or surpassed, patient presurgery performance. Although word repetition was intact by 1 year after surgery, naming remained impaired, and patient speech was limited largely to production of single words. These results suggest that the right hemisphere is innately capable of supporting multiple aspects of phoneme processing. Recovery of higher level receptive and, to a lesser extent, expressive language functions is attributed to plasticity of the right hemisphere, which appears to persist beyond the proposed critical period for language acquisition and lateralization.
Adolescent↗
Whose life is it anyway?
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Persons with Disabilities↗
Insulin modulates intestinal response of suckling mice to the Escherichia coli heat-stable enterotoxin.
Effect of insulin on the response of suckling mice to the enterotoxigenic Escherichia coli heat-stable enterotoxin (STa) was studied. Four groups (8-10 in each group) of two day old Swiss Webster suckling mice were used. Five, 10, 25, and 50 micrograms of insulin were given orally to half the mice in each group respectively. The rest of the mice in each group were given normal saline as intra-litter controls. After 7 days, the suckling mouse assay for STa was performed on three mice from each insulin-treated and control groups. Enterocyte suspensions were prepared from mice in all groups. Intestinal tissue samples were taken for electron microscopy. Interaction of STa with its putative receptor on the enterocytes was evaluated using indirect immunofluorescence and flow cytometry. The suckling mouse assay revealed a significant increase in the gut weight to body weight ratio in all mice in the insulin treated groups compared to control mice (p < 0.05). Flow cytometry and indirect immunofluorescence analyses suggested that insulin had an upregulatory effect on the STa receptor level. Similarly, insulin was found to increase intestinal brush border membrane differentiation as indicated by the increase in the inward movement of milk particles through the intestinal mucosa. Insulin seems to modify the structure-function of the brush border membrane including the response of suckling mice to STa. This study may provide further insights into the mechanism of STa/receptor interaction in diarrhea in newborn animals and human infants.
Animals↗
Long-term maintenance of therapeutic cyclosporine levels leads to optimal graft survival without evidence of chronic nephrotoxicity.
Since the introduction of cyclosporine into clinical use, a major area of concern within the transplant community has been the fear of chronic nephrotoxicity. Although progressive renal damage does appear to occur in native kidneys of heart and liver transplant patients receiving cyclosporine, it has been our contention that its use is not a major cause of deterioration in renal allografts. We therefore undertook a study of 91 consecutive renal transplants performed over a three-year period with a minimum graft survival of 1 year and a follow-up of 7-9 years. Serial serum creatinine values, iothalamate clearances and cyclosporine levels were obtained at 3 months after transplantation and yearly thereafter. Biopsies were performed on all grafts that had failed as well as on the majority of patients with deteriorating renal function, and were interpreted by two nephropathologists. As measured by iothalamate clearances, 65% of the patients in this series exhibited absolutely stable renal function despite the maintenance of cyclosporine levels of more than 200 ng/ml for 7-9 years. Since these stable patients did not reveal any decline in renal function, it therefore follows that they did not experience chronic cyclosporine nephrotoxicity. Furthermore, none of the patients with declining renal function or with failed grafts showed any evidence of nephrotoxicity on biopsy. Chronic cyclosporine nephrotoxicity may be a cause of declining function or graft loss with renal transplant recipients, but if so, it is exceedingly rare.
Creatine↗
Antibiotics and Clostridium difficile.
Clostridium difficile is now established as a major nosocomial pathogen. C. difficile infection is seen almost exclusively as a complication of antibiotic therapy, and is particularly associated with clindamycin and third-generation cephalosporins. Depletion of the indigenous gut microflora by antibiotic therapy has long been established as a major factor in the disease. However, the direct influence of antimicrobials upon virulence mechanisms such as toxin production and adhesion in the bowel, and the exact mechanisms by which the organism causes disease remain to be elucidated.
Animals↗