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Biomedical subjects

I Smith

Publications and source records attributed to I Smith.

At least 55 records · Page 3Linked to original sources
PubMed2001

Thrombocytosis in intensive care.

We conducted a retrospective study of platelet count in 226 patients admitted for critical care over a 5-month period, to explore the incidence of thrombocytosis and its relation to admission category, duration of ICU stay and outcome. Our findings indicate that thrombocytosis is not rare in ICU patients. At least one platelet count greater than 450x10(9) litre(-1) was found in 21.7% of patients and was associated with lower ICU mortality (P=0.003), lower hospital mortality (P=0.006), but longer duration of ICU stay (P<0.0001). Thrombocytosis may serve as an independent predictor of favourable outcome in ICU patients.

Adult↗
PubMed2001

Coverage of neonatal screening: failure of coverage or failure of information system.

OBJECTIVES: To evaluate neonatal screening coverage using data routinely collected on the laboratory computer. SUBJECTS: 90 850 births in 14 North East Thames community provider districts over a 21 month period. METHODS: Births notified to local child health computers are electronically copied to the neonatal laboratory computer system, and incoming Guthrie cards are matched against these birth records before testing. The computer records for the study period were processed to estimate the coverage of the screening programme. RESULTS: Out of an estimated 90 850 births notified to child health computers, all but 746 (0.82%) appeared to have been screened or could be otherwise accounted for (0.14% in non-metropolitan districts, 0.39% in suburban districts, and 1.68% in inner city districts). A further 893 resident infants had been tested, but could not be matched to the list of notified resident births. The calculated programme coverage already exceeds the 99.5% National Audit Programme standard in 7/14 districts. Elsewhere it is not clear whether it is coverage or recording of coverage that is low. CONCLUSION: Previous reports of low coverage may have been exaggerated. High coverage can be shown using routine information systems. Design of information systems that deliver accurate measures of coverage would be more useful than comparison of inadequately measured coverage with a national standard. The new NHS number project will create an opportunity to achieve this.

Birth Certificates↗
PubMed2001

Role of Herceptin in primary breast cancer: views from North America and Europe.

Current therapeutic strategies for primary breast cancer aim to provide improvements in outcome with minimal toxicity to the patient. However, annual relapse rates of up to 12 to 13% during the first 10 years after treatment are seen, and although toxicity has been reduced, it remains a problem in a patient population that is largely asymptomatic. Thus, there is a clear need for more effective therapies. Amplification/overexpression of the human epidermal growth factor receptor-2 (HER2) is an early event in the development of a significant proportion of breast tumors. This abnormality has been shown to have a detrimental effect on prognosis, may predict the outcome of therapies such as tamoxifen and anthracyclines, and provides a target for the novel therapy, Herceptin. Herceptin is effective and well tolerated in the metastatic setting, making it an ideal candidate for use in adjuvant breast cancer therapy. This has led to the design of a number of trials that aim to provide conclusive evidence as rapidly as possible that Herceptin is well tolerated and effective in the adjuvant setting while also addressing the question of which regimen provides greatest benefit. This review describes these trials and explains how differences in practice between North America and Europe have influenced trial design.

Adult↗
PubMed2001

Cost considerations in the use of anaesthetic drugs.

Anaesthetic drugs typically comprise approximately 5% or less of a hospital pharmacy budget, yet they are a common target for cost reduction measures. In particular, there is considerable pressure to use less costly products where alternatives exist and to limit the introduction of expensive new items. In considering strategies to reduce a departmental drug budget, or in defending against restrictions imposed from outside, it is important to consider all of the costs associated with anaesthetic drug delivery. These costs comprise not only the expense of the anaesthetic drugs themselves, but also fixed and variable costs associated with their delivery and related to their effects. Elimination of drug waste will always be beneficial, since it has no direct effect on the patient yet clearly reduces cost. Waste is by no means confined to anaesthetic drugs, however. Using less expensive drugs may appear an attractive option and can reduce costs, provided that patient outcome is in no way affected. Rarely is this the case. Once patient care is modified, through changes in recovery times or complication rates, determining the true cost of the intervention becomes essential; there may be increases in indirect costs which dwarf the apparent savings. Sometimes indirect costs will rise by a lesser amount than savings in direct costs, such that there is still an overall benefit but less than that originally anticipated. Exactly how indirect effects result in indirect costs is highly variable. The requirement for additional drugs or supplies to treat an adverse event, such as emesis, will always have an associated cost. Delayed recovery or prolonged hospital stay will waste operating room time or increase the amount of time that a patient requires nursing care, but whether this carries an associated cost depends on what the staff would otherwise have been doing. Depending on the employment method, staff may have been sent home early (with less pay) or employed at identical cost but with less to do. Many studies which purport to consider all costs either ignore such issues, or make invalid assumptions. These issues are complex, but anyone involved with decisions concerning anaesthetic costs should be familiar with the underlying principles and be able to make a rational assessment of the likely indirect costs in their own institution.

Anesthesia↗
PubMed2001

Determinants of drug-resistant tuberculosis: analysis of 11 countries.

SETTING: Eleven countries/territories. OBJECTIVES: Global information on the determinants of drug-resistant tuberculosis (TB) based on representative data is not available. We therefore studied the relationship between demographic characteristics, prior TB treatment, and human immunodeficiency virus (HIV) infection with anti-tuberculosis drug resistance. METHODS: Population-based representative data on new and previously treated patients with TB collected within an international drug resistance surveillance network. RESULTS: Of 9,615 patients, 8,222 (85.5%) were new cases of TB and 1,393 (14.5%) were previously treated cases. Compared with new cases, previously treated cases were significantly more likely to have resistance to one (OR = 2.5,95% CI 2.1-3.0; P < 0.001), two (OR = 4.6, 95%CI 3.7-5.6; P < 0.001), three (OR = 11.5, 95%CI 8.6-15.3; P < 0.001), and four (OR = 18.5, 95% CI 12.0-28.5; P < 0.001) drugs. An approximately linear increase in the likelihood of having multidrug-resistant tuberculosis (MDR-TB) was observed as the total time (measured in months) of prior anti-tuberculosis treatment increased (P < 0.001, chi2 for trend). In multivariate analysis, prior TB treatment for 6-11 months (OR = 7.6, 95% CI 2.6, 22.4; P < 0.001) and > or = 12 months (OR 13.7, 95% CI 4.5-41.6; P < 0.001), but not HIV positivity, was associated with MDR-TB. CONCLUSION: This study shows that prior but ineffective treatment is a strong predictor of drug resistance, and that HIV is not an independent risk factor for MDR-TB. The association between length of treatment and drug resistance may reflect longer treatment as a result of treatment failure in patients with drug resistance; it may also reflect irregular prior treatment for TB, leading to drug resistance.

Adolescent↗
PubMed2001

Tuberculosis treatment in nepal: a rapid assessment of government centers using different types of patient supervision.

SETTING: Urban and periurban government tuberculosis (TB) treatment clinics in Nepal. OBJECTIVE: To assess TB treatment supervision strategies and outcomes. DESIGN: Three types of treatment centers were selected according to intensity of treatment supervision: Group A-all patients supervised by directly observed therapy (DOT) at the treatment center during the intensive phase; Group B-flexible DOT where patient-nominated treatment supervisors include community or family members; Group C-drugs dispensed monthly and no supervised treatment. The cohort studied comprised all new patients starting treatment during a 5-month period in 1996 (n = 759). RESULTS: At group A treatment centers, 100% of patients had daily DOT supervised by treatment center staff during the intensive phase. At group B sites, 75% of nominated supervisors were family or community members and 13% of patients had no supervisor. At group C sites 93% of patients were unsupervised. Bacteriologically confirmed cure rates for smear-positive patients were 91% (95%CI 80.3-97.2) for A sites, 57% (95%CI 48.8-64.0) for B, and 34% (95%CI 25.1-40.4) for C. Treatment centers with the best results had good access to laboratory facilities, uninterrupted drug supply, longer clinic hours, standardized TB case management, and support from a non-governmental organization. CONCLUSION: At government facilities in Nepal, only group A treatment centers achieved World Health Organization global targets for cure. Group B treatment centers showed better outcomes than unsupervised therapy but did not achieve cure targets. Rapid low-cost assessments to collect data that are not routinely reported can improve the evaluation of program aspects such as supervision strategies.

Adolescent↗
PubMed2000

Development and characterization of novel potent and stable inhibitors of endopeptidase EC 3.4.24.15.

Solid-phase synthesis was used to prepare a series of modifications to the selective and potent inhibitor of endopeptidase EC 3.4.24.15 (EP24.15), N-[1(R, S)-carboxy-3-phenylpropyl]-Ala-Ala-Tyr-p-aminobenzoate (cFP), which is degraded at the Ala-Tyr bond, thus severely limiting its utility in vivo. Reducing the amide bond between the Ala and Tyr decreased the potency of the inhibitor to 1/1000. However, the replacement of the second alanine residue immediately adjacent to the tyrosine with alpha-aminoisobutyric acid gave a compound (JA-2) that was equipotent with cFP, with a K(i) of 23 nM. Like cFP, JA-2 inhibited the closely related endopeptidase EC 3.4.24.16 1/20 to 1/30 as potently as it did EP24.15, and did not inhibit the other thermolysin-like endopeptidases angiotensin-converting enzyme, endothelin-converting enzyme and neutral endopeptidase. The biological stability of JA-2 was investigated by incubation with a number of membrane and soluble sheep tissue extracts. In contrast with cFP, JA-2 remained intact after 48 h of incubation with all tissues examined. Further modifications to the JA-2 compound failed to improve the potency of this inhibitor. Hence JA-2 is a potent, EP24.15-preferential and biologically stable inhibitor, therefore providing a valuable tool for further assessing the biological functions of EP24.15.

Metalloendopeptidases↗
PubMed2000

ASCA Observation of the Quiescent X-Ray Counterpart to SGR 1627-41.

We present a 2-10 keV ASCA observation of the field around the soft gamma repeater SGR 1627-41. A quiescent X-ray source, whose position is consistent both with that of a recently discovered BeppoSAX X-ray source and with the Interplanetary Network localization for this soft gamma repeater, was detected in this observation. In 2-10 keV X-rays, the spectrum of the X-ray source may be fit equally well by a power-law, blackbody, or bremsstrahlung function, with unabsorbed flux approximately 5x10-12 ergs cm-2 s-1. We do not confirm a continuation of a fading trend in the flux, and we find no evidence for periodicity, both of which were noted in the earlier BeppoSAX observations.

Journal Article↗
PubMed2000

Concurrent measurement of antigen- and antibody-dependent oxidative burst and phagocytosis in monocytes and neutrophils.

The current study aims to review flow cytometric (FCM) parameters for the quantification of phagocytosis. A limitation of existing methods is their difficulty with accurate quantification of the phagocytic index, i.e., number of beads per phagocyte, in individual cell lines in mixed cell suspensions. We have quantified phagocytosis and the oxidative burst simultaneously using fluorescent beads coated with meningococcal outer membrane vesicles (OMV beads) by the conversion of dihydrorhodamine 123 (DHR-123) to rhodamine 123 (R-123). Both these processes depend on specific serum opsonins. After the incubation, staining with a fluorescent anti-CD14 monoclonal antibody succeeded in discriminating phagocytosing monocytes from neutrophils. The spectral overlaps between OMV beads, R-123, and anti-CD14 could be completely compensated. Percentage of phagocytosis and the phagocytic index were similar in monocytes and neutrophils, but the oxidative burst behaved differently. Two monocyte subpopulations were observed. Both subpopulations spontaneously converted some DHR-123 into R-123, whereas the reaction was triggered by phagocytosis in neutrophils. The total oxidative response increased with increasing phagocytic index in both cell types, but the oxidative burst in monocytes was about twice that of neutrophils. The oxidative ratio (mean R-123 fluorescence value divided by the phagocytic index) declined with time in monocytes, but increased in neutrophils. Our results demonstrate the need for careful attention to technical details. This single-laser, three-color FCM method facilitates the comparative research of phagocytosis and the oxidative burst in monocytes and neutrophils and provides a basis for a number of applications in hematology, infectious medicine, and immunology.

Antibodies, Monoclonal↗
PubMed2000

Behaviour in early treated phenylketonuria: a systematic review.

UNLABELLED: A search was made of the literature on behaviour in early treated phenylketonuria (PKU). Some 34 publications were selected for systematic review in order to answer the following questions: (1) does behaviour in early treated subjects with PKU differ from that in the general population?, (2) if so, do the differences show any consistent pattern?, matter in real life?, relate to intellectual status, phenylalanine (Phe) control or social factors? and (3) can behavioural problems be precipitated or reversed by changes in Phe control?. Eleven reports based on four studies of > 20 subjects provided the most useful data. There was good evidence of differences between subjects with PKU and their unaffected peers in behaviour and perception of self. The pattern of results was consistent across nations and age groups (higher scores on emotional/neurotic items and lower scores on anti-social/aggressive items) and suggested that subjects with PKU are more prone to depression, anxiety, phobic tendencies, isolation from their peers and a less "masculine" self image. Features of attention deficit hyperactivity disorder and associations between behaviour problems and both lower IQ and a worse quality of Phe control were well documented in several studies. CONCLUSION: The literature did not allow for definite conclusions on the cause of the behavioural problems but, taken together, the findings suggest that both the stressful dietary intervention and a degree of neurobiological impairment are likely to play a part.

Adolescent↗
PubMed2000

Oxygenated mycolic acids are necessary for virulence of Mycobacterium tuberculosis in mice.

Members of the Mycobacterium tuberculosis group synthesize a family of long-chain fatty acids, mycolic acids, which are located in the cell envelope. These include the non-oxygenated alpha-mycolic acid and the oxygenated keto- and methoxymycolic acids. The function in bacterial virulence, if any, of these various types of mycolic acids is unknown. We have constructed a mutant strain of M. tuberculosis with an inactivated hma (cmaA, mma4) gene; this mutant strain no longer synthesizes oxygenated mycolic acids, has profound alterations in its envelope permeability and is attenuated in mice.

Animals↗
PubMed2000

Acceptable levels of digital image compression in chest radiology.

The introduction of picture archival and communications systems (PACS) and teleradiology has prompted an examination of techniques that optimize the storage capacity and speed of digital storage and distribution networks. The general acceptance of the move to replace conventional screen-film capture with computed radiography (CR) is an indication that clinicians within the radiology community are willing to accept images that have been 'compressed'. The question to be answered, therefore, is what level of compression is acceptable. The purpose of the present study is to provide an assessment of the ability of a group of imaging professionals to determine whether an image has been compressed. To undertake this study a single mobile chest image, selected for the presence of some subtle pathology in the form of a number of septal lines in both costphrenic angles, was compressed to levels of 10:1, 20:1 and 30:1. These images were randomly ordered and shown to the observers for interpretation. Analysis of the responses indicates that in general it was not possible to distinguish the original image from its compressed counterparts. Furthermore, a preference appeared to be shown for images that have undergone low levels of compression. This preference can most likely be attributed to the 'de-noising' effect of the compression algorithm at low levels.

Humans↗
PubMed2000

Detoxification from alcohol: a comparison of home detoxification and hospital-based day patient care.

An uncontrolled study was carried out to examine two types of ambulatory care for patients undergoing detoxification from alcohol. The safety, efficacy, and acceptability of home detoxification was compared to detoxification within a day hospital setting. Seventy-nine per cent of home detoxification patients, many of whom had major alcohol-related problems and were severely dependent on alcohol, were successfully detoxified at 10 days. The day hospital group overlapped in severity with the home group and 78% completed detoxification. At 60 days, 45% of home detoxification patients and 31% of the day hospital group showed significant improvements in a range of alcohol-related difficulties. Improved outcome was associated with attendance for further treatment for both groups. Both home and day hospital detoxifications were viable alternatives to in-patient detoxification for selected groups of patients.

Adult↗
PubMed2000

Analysis of tnrA alleles which result in a glucose-resistant sporulation phenotype in Bacillus subtilis.

Bacillus subtilis cells cannot sporulate in the presence of catabolites such as glucose. During the analysis of Tn10-generated mutants, we found that deletion of the C-terminal region of the tnrA gene, which encodes a global regulator that positively regulates a number of genes in response to nitrogen limitation, results in a catabolite-resistant sporulation phenotype. Analyses of nrg-lacZ and nasB-lacZ, which are activated by TnrA under nitrogen limitation, showed that C-terminally truncated TnrA activates nitrogen-regulated genes constitutively. The relief of catabolite repression of sporulation may result from the uncontrolled expression of the TnrA-regulated genes.

Alleles↗
PubMed2000

Indomethacin induced avascular necrosis of head of femur.

Chemically induced avascular necrosis of bone is a well documented entity. Indomethacin is one of the causes of this condition but is often difficult to recognise. Review of the literature shows that only one case of indomethacin induced avascular necrosis has been reported in the English language between 1966 and the present. The case of a young healthy man, who developed avascular necrosis of head of femur after prolonged administration of indomethacin, is reported here.

Adult↗