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Biomedical subjects

A Lowe

Publications and source records attributed to A Lowe.

At least 19 recordsLinked to original sources
PubMed2001

Phase II study of rituximab in combination with chop chemotherapy in patients with previously untreated, aggressive non-Hodgkin's lymphoma.

PURPOSE: To determine the safety and efficacy of the combination of the chimeric anti-CD20 antibody Rituxan (rituximab, IDEC-C2B8; Genentech Inc, South San Francisco, CA) and cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy in patients with aggressive non-Hodgkin's lymphoma (NHL). PATIENTS AND METHODS: Thirty-three patients with previously untreated advanced aggressive B-cell NHL received six infusions of Rituxan (375 mg/m2 per dose) on day 1 of each cycle in combination with six doses of CHOP chemotherapy given on day 3 of each cycle. RESULTS: The ORR by investigator assessment confirmed by the sponsor was 94% (31 of 33 patients). Twenty patients experienced a complete response (CR) (61%), 11 patients had a partial response (PR) (33%), and two patients were classified as having progressive disease. In the 18 patients with an International Prognostic Index (IPI) score > or = 2, the combination of Rituxan plus CHOP achieved an ORR of 89% and CR of 56%. The median duration of response and time to progression had not been reached after a median observation time of 26 months. Twenty-nine of 31 responding patients remained in remission during this follow-up period, including 15 of 16 patients with an IPI score > or = 2. The most frequent adverse events attributed to Rituxan were fever and chills, primarily during the first infusion. Rituxan did not seem to compromise the ability of patients to tolerate CHOP; all patients completed the entire six courses of the combination. The bcl-2 translocation of blood or bone marrow was positive at baseline in 13 patients; 11 patients had follow-up specimens obtained (eight CR, three PR), and all had a negative bcl-2 status after therapy. Only one patient has reconverted to bcl-2 positivity, and all patients remain in clinical remission. CONCLUSION: This is the first report to demonstrate the safety and efficacy of the Rituxan chimeric anti-CD20 antibody in combination with standard-dose CHOP in the treatment of aggressive B-cell lymphoma. The clinical responses are at least comparable to those achieved with CHOP alone with no significant added toxicity. The presence or absence of the bcl-2 translocation did not affect the ability of patients to achieve a CR with this regimen. The ability to achieve sustained remissions in patients with an IPI score > or = 2 warrants further investigation with a randomized study.

Adult↗
PubMed2001

The graphical presentation of decision support information in an intelligent anaesthesia monitor.

This contribution examines the graphical presentation of decision support information generated by an intelligent monitor, named SENTINEL, developed for use during anaesthesia. Clinicians make diagnoses in real-time during operations by examining clinically significant trends in multiple signals. SENTINEL attempts to mimic this decision process by using a system of fuzzy trend templates. SENTINEL's implementation of fuzzy trend templates is capable of providing the dual fuzzy measures of belief and plausibility, which are derived from the theory of evidence. It is thus capable of generating fairly rich diagnostic decision support information. However, for SENTINEL to be effective, the visual presentation of this information must be intuitive to the anaesthetist, who may not be familiar with the theory of evidence. This paper discusses techniques that are being evaluated to meet the requirements of the SENTINEL anaesthesia monitor. Specifically, the paper presents methods for highlighting clinically significant trends in physiological (or derived) signals by superimposing a coloured band on the signal that reflects fuzzy output from the intelligent monitor. This paper also discusses the intuitive graphical presentation of binary diagnostic fuzzy measures, including their further interpretation and presentation as crisp "alarm" and "warning" conditions.

Anesthesia, General↗
PubMed2000

Genetic variability determinants of Helicobacter pylori: influence of clinical background and geographic origin of isolates.

Helicobacter pylori has an unusual pattern of genetic variation, which complicates research on this organism. To gain a better understanding of the forces behind this phenomenon, the extent to which recombination and single point mutations affect genetic variability in H. pylori was quantified and the influence of both geographical distance and clinical background were assessed. Site-directed restriction-endonuclease digestion of 2 gene fragments was performed on 168 isolates from Montreal and Berlin. Allelic diversity was found to be much higher for H. pylori than for other bacterial species. This finding is consistent with those of previous studies on H. pylori that were conducted using other techniques. However, nucleotide diversity was within the range reported for other bacterial species. Phylogenetic analysis found no grouping of strains with clinical background or geographical origin. Recombination at a rate that resulted in linkage equilibrium within genes can explain these observations.

Alleles↗
PubMed2000

A cholesterol-lowering gene maps to chromosome 13q.

A cholesterol-lowering gene has been postulated from familial hypercholesterolemia (FH) families having heterozygous persons with normal LDL levels and homozygous individuals with LDL levels similar to those in persons with heterozygous FH. We studied such a family with FH that also had members without FH and with lower-than-normal LDL levels. We performed linkage analyses and identified a locus at 13q, defined by markers D13S156 and D13S158. FASTLINK and GENEHUNTER yielded LOD scores >5 and >4, respectively, whereas an affected-sib-pair analysis gave a peak multipoint LOD score of 4.8, corresponding to a P value of 1.26x10-6. A multipoint quantitative-trait-locus (QTL) linkage analysis with maximum-likelihood binomial QTL verified this locus as a QTL for LDL levels. To test the relevance of this QTL in an independent normal population, we studied MZ and DZ twin subjects. An MZ-DZ comparison confirmed genetic variance with regard to lipid concentrations. We then performed an identity-by-descent linkage analysis on the DZ twins, with markers at the 13q locus. We found strong evidence for linkage at this locus with LDL (P<.0002), HDL (P<.004), total cholesterol (P<.0002), and body-mass index (P<.0001). These data provide support for the existence of a new gene influencing lipid concentrations in humans.

Adult↗
PubMed2000

The construction of a network at Health Waikato. The "towards clinical budgeting" project.

The purpose of this paper is to provide an explanation and understanding of developments in casemix and related information systems at a large regional hospital, Health Waikato (HW), in the centre of the North Island of New Zealand. The themes will be explicated and theorised, drawing on the sociology of translation (Latour). A central idea will be the use of accounting techniques to influence decision makers both within and outside the health institutions. The power of accounting in the translation and inscription of data (the fabrication of accounting systems per Preston et al.), will be a central theme in understanding the role of accounting systems as technology. Drawing from Latour has helped to provide a frame of reference to allow an assimilation of disparate changes and influences as they have come to affect the health sector at a national level, within New Zealand, and also at an organisational level, within a large regional health provider. This paper provides a detailed description of events at the research site, a large regional hospital (HW). The paper consists primarily of a descriptive case study of aspects of the change process as it has impacted on the research site.

Accounting↗
PubMed2000

Association of Helicobacter pylori genotype with gastroesophageal reflux disease and other upper gastrointestinal diseases.

OBJECTIVE: Helicobacter pylori (H. pylori) is a recognized pathogen, but it may also have a protective effect for gastroesophageal reflux disease (GERD). We compared the prevalence of potential virulence factors (cagA, cagE, vacA genotypes) in GERD to other upper gastrointestinal diseases and controls. METHODS: A total of 405 patients underwent gastroscopy with H. pylori isolation and serum testing. Patient diagnostic subgroups were prospectively defined. Genotypes were determined by amplification using polymerase chain reaction. CagA antibodies were determined by western blot, enzyme-linked immunosorbent, and flow microsphere immunofluorescent assays. RESULTS: Patients were grouped as follows: nonulcer dyspepsia (26%), GERD (20%), gastric ulcer (17%), duodenal ulcer (12%), gastric cancer (6%), or controls (19%). The cagA gene was present in 94-97% of subjects in all categories, but the cagA antibody was less prevalent in nonulcer dyspepsia (69%, 95% CI: 48-86%, p = 0.02) and GERD (69%, CI: 39-91%, p < 0.05) than in those with gastroduodenal pathology including gastric ulcer, duodenal ulcer, and gastric cancer (92%, CI: 81-98%). The cagE gene and vacA S1 genotype were more frequent in patients with gastroduodenal pathology (p < 0.01). GERD was associated with a significantly lower rate of vacA S1 genotype than controls (29% (CI: 10-56%) versus 80% (CI: 59-93%), p < 0.01). The vacA S1 genotype was associated with the presence of cagA antibodies. CONCLUSIONS: The cagE and vacA S1 genotypes are more prevalent in patients with peptic ulcer or gastric cancer, suggesting a potential function in virulence for these genes. However, the vacA S1 genotype was also more prevalent in controls than GERD, suggesting a potential protective effect against GERD.

Antigens, Bacterial↗
PubMed2000

Physical and chemical evidence remaining after the explosion of large improvised bombs. Part 1: firings of ammonium nitrate/sugar and urea nitrate.

Recent criminal acts in the United Kingdom, United States and other countries have demonstrated the dangers to public safety from the criminal use of improvised explosives on a large scale. Four sets of trials were carried out over four years, partly in collaboration with the United States Federal Bureau of Investigation, involving the firing of large bombs, mostly fertilizer based. The principal objectives of the firings were to measure the physical effects of the explosions upon objects representative of those that would be found at a real bomb scene and to recover any chemical traces deposited on these objects. The results are intended for use as an aid in determining the approximate size and type of an explosive employed in a terrorist attack. This paper describes the background behind the trials, the procedures for preparation of witness materials and charges, and the collection and analysis of physical and chemical evidence.

Criminology↗
PubMed2000

Physical and chemical evidence remaining after the explosion of large improvised bombs. Part 2: Firings of calcium ammonium nitrate/sugar mixtures.

Six test firings of large improvised explosive devices were carried out. The principal objectives of the firings were to measure the physical effects of the explosions upon representative objects placed nearby and to recover any chemical traces deposited on these objects. The results are intended for use as an aid in determining the approximate size and type of an explosive employed in terrorist attacks. Three 454 kg charges of a mixture of calcium ammonium nitrate (CAN) fertilizer and sugar, and three 2268 kg charges of a similar mixture, all confined in cylindrical steel containers were fired. Each charge was surrounded by 19 road signs mounted on posts and four vehicles, to act as witness materials. The analysis of aqueous swab extracts taken from the witness materials after firing showed the recovery of nitrate, ammonium and low levels of glucose. No sucrose was detected. Nitrate was usually recovered in greater quantities than ammonium and recovery generally decreased with increasing distance from the charges in any given direction. Quantities recovered from objects placed at the same distance in different directions varied considerably. Patterns of physical damage to the witness materials could be discerned according to their distance from the charge and the size of the charge. The velocities of detonation and air blast effects were measured.

Criminology↗
PubMed2000

Trend recognition in clinical signals using template-based methods.

The recognition of clinically significant trends in monitored signals plays an important role in many medical diagnostic applications. A template-based system technique to identify characteristic patterns in time-series data is described, based on fuzzy logic. Fuzzy set theory allows the creation of fuzzy templates from linguistic rules. The resulting fuzzy template system can accommodate multiple time signals, relative or absolute trends, and automatically generates a normalised "goodness of fit" score. The template approach was originally developed for monitoring during anaesthesia but has the potential to be useful in other domains that require temporal pattern recognition.

Artificial Intelligence↗
PubMed1999

Diagnostic monitoring in anaesthesia using fuzzy trend templates for matching temporal patterns.

A technique based on the concept of a 'fuzzy trend template' has been developed to identify characteristic patterns in multiple time-series. The method has its foundation in fuzzy logic and allows for the intuitive and transparent description of 'templates', which preserve nuances of vagueness, temporal relationships and quantitative descriptors. Evaluation of fuzzy trend templates can provide both belief and plausibility information for use in diagnostic applications. The technique has been applied to the diagnosis of specific problems in anaesthesia and has demonstrated sensitivity and specificity of 95 and 65%, respectively. Evaluation of fuzzy trend templates is, computationally, relatively efficient and has allowed a real-time implementation. The technique has the potential to be useful in any domain that requires temporal pattern recognition based on linguistic rules.

Anesthesia↗
PubMed1999

Computer-enhanced diagnosis of malignant hyperpyrexia.

A computer program using fuzzy logic templates has been developed to enhance the diagnosis of malignant hyperpyrexia. When tested, retrospectively, against the physiological changes that occurred during the onset of a bona fide malignant hyperpyrexia episode it made the diagnosis about 10 minutes before the anaesthetist. When tested against the changes associated with laparoscopic surgery, which has certain similarities, the diagnosis of malignant hyperpyrexia was very transient. The use of this program may assist the anaesthetist in the diagnosis of this rare event.

Algorithms↗
PubMed1999

Diagnostic image quality of mobile neonatal chest X-rays and the radiation exposure incurred.

A study was undertaken to identify the variation of entrance skin doses (ESDs) in mobile neonatal chest radiography with regard to the European Commission (EC) reference dose and to examine potential relationships with image quality and radiographic techniques. Five sites from the former North West Thames region participated. All mobile neonatal radiographic techniques were surveyed. Dose-area product per examination was directly measured and the ESD calculated. Image quality criteria were developed from those published by the EC. Image quality was graded by two independent observers. Over the five sites, 144 examinations were recorded. Calculated ESDs ranged up to 160 microGy, with an appreciable variation not only between sites but also within sites. A clear relationship between actual rather than nominal speed and dose over all sites was demonstrated (r = -0.95, p = 0.013). No correlation between image quality and dose was noted (r = -0.044, p = 0.665). Neonatal imaging systems at participating sites, within the North Thames region, comply with EC guidelines on patient dose and image quality for mobile chest X-rays. Significant variation in ESDs was encountered between sites with no discernible relationship with image quality or the employed radiographic techniques as described by the EC. The strong inverse relationship between ESDs and actual rather than nominal speed suggests a neglected aspect of radiation protection.

England↗
PubMed1998

Four-year follow-up of Palmaz-Schatz stent revascularization as treatment for atherosclerotic renal artery stenosis.

BACKGROUND: Stent revascularization is perceived as superior to balloon angioplasty and surgical revascularization, but the paucity of stent publications precludes even historical comparison with surgical data. METHODS AND RESULTS: Palmaz-Schatz stent revascularization of renal artery stenosis was successfully performed on 163 consecutive patients for poorly controlled hypertension or preservation of renal function. Of these, 145 were eligible for > or =6-month clinical follow-up of the effect of the procedure on renal function, blood pressure control, number of antihypertensive medications, and survival. At 4 years, systolic and diastolic blood pressures significantly decreased (from 166+/-26 to 148+/-22 mm Hg and from 86+/-14 to 80+/-11 mm Hg, respectively; P<0.05), and blood pressure control was more facile in approximately half of the patients. Creatinine decreased or remained stable in approximately two thirds of the patients. The cumulative probability of survival was 74+/-4% at 3 years, with few deaths related to end-stage renal disease. Survival was good in patients with normal (92+/-4%) baseline renal function, fair (74+/-7%) in those with mildly impaired renal function, and poor (52+/-7%) in patients with elevated baseline creatinine levels (> or =2.0 mg/dL). The combination of impaired renal function and bilateral disease adversely affected survival. CONCLUSIONS: Renal artery stent revascularization in the presence of normal or mildly impaired renal function had a beneficial effect on blood pressure control and a nondeleterious effect on renal function. Survival was adversely affected by renal dysfunction despite adequate revascularization. Early diagnosis and adequate revascularization before the onset of renal dysfunction could beneficially affect blood pressure control, preserve or prevent deterioration of renal function, and improve patient survival.

Actuarial Analysis↗
PubMed1998

A preliminary exploration of the interactional skills of trainee surgeons.

BACKGROUND: The interactional skills of 21 surgical trainees were studied in the areas of breaking bad news to patients and preparing patients for potentially threatening medical procedures. When compared to the established guidelines for dealing with these issues, the trainees performed poorly. METHODS: Trainees were videotaped using clinical histories delivered by simulated patients in simulated consulting rooms. All videos were scored on standard rating scales where the criteria for rating the specific interactional skills were adopted from existing guidelines. RESULTS: The proportion of trainees who could meet the guidelines when breaking bad news was low. The proportion of trainees who met the guidelines were: closing the the consultation (0%), provided patient information about prognosis (43%) and treatment (38%) and when they gave support (10%). There were also low numbers of trainees who could meet the guidelines when they prepared patients for potentially threatening procedures. Ten per cent of trainees followed the guidelines when providing information, 25% could establish treatment goals, 35% could give a prognosis and 0% could deal appropriately with psychosocial issues or close the consultation appropriately. CONCLUSIONS: It is concluded that there is a need for further formal training in interactional skills as part of surgical training.

Clinical Competence↗