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Biomedical subjects

M Field

Publications and source records attributed to M Field.

At least 37 records · Page 2Linked to original sources
PubMed2001

A prospective 2-year study of 75 patients with adult-onset septic arthritis.

AIMS AND METHODS: To assess the clinical features of septic arthritis and characterize therapeutic strategies and outcome in a prospective study of 75 patients selected by positive synovial fluid culture. RESULTS: Underlying joint disease was present in 46 patients, 25 of whom had rheumatoid arthritis and 15 osteoarthritis. Eleven patients were i.v. drug abusers. Fifty-six per cent of cases involved the knee, 15% involved two or more joints, and staphylococci and streptococci were cultured in >90%. Seventy-eight per cent of patients lived in areas of high social deprivation. Fever was present in 64% and the white cell count (WCC) was normal in 38%. The C-reactive protein was elevated in 98%. Leg ulcers were present in 11% of all patients but in 38% of patients who died (P<0.006). Median duration of antibiotic therapy was 15 days i.v. with subsequent oral treatment for 21 days. Thirty-seven per cent of cases required surgical intervention. Mortality was 11%. A raised WCC at presentation (P<0.02) and the development of abnormal renal function (P<0.015) were predictors of poor prognosis.

Age of Onset↗
PubMed2001

A polymorphism within the interleukin 1 receptor antagonist (IL-1Ra) gene is associated with ankylosing spondylitis.

OBJECTIVE: Genetic factors that predispose individuals to ankylosing spondylitis (AS) are not fully understood, but are unlikely to be restricted to HLA-B27. Proinflammatory cytokines are implicated in the development of sacroiliitis. We have examined the allele frequencies of three polymorphic sites in the interleukin (IL)-1 genes in AS patients to investigate whether genetic regulation of IL-1 production could be implicated in AS pathogenesis. METHODS: DNA from 188 AS patients, 115 healthy controls and 81 HLA-B27-positive healthy controls, all from the West of Scotland, were examined with the polymerase chain reaction in a case-controlled study. Polymorphic sites in genes of the IL-1 family were examined, including the 86-base pair variable number tandem repeat within intron 2 of the IL-1Ra gene, and the restriction fragment length polymorphisms at positions -889 in the IL-1alpha gene and -511 in the IL-1beta gene. RESULTS: No significant differences were seen at the polymorphic alleles in the IL-1alpha and IL-1beta genes, but there was a significant increase in the carriage of allele 2 in the IL-1Ra in the AS patients compared with local controls (16 vs 8%, odds ratio 2.3, 95% confidence interval 1.2-4.4, P=0.01). CONCLUSION: This report of an association with a polymorphic site within the IL-1 locus and AS suggests that genes other than B27 may well be involved in the pathogenesis of AS.

Adolescent↗
PubMed2001

Smoking expectancy mediates the conditioned responses to arbitrary smoking cues.

Smokers' responses to smoking cues may be the result of a classical conditioning process. There is evidence that classical conditioning may not proceed in human subjects unless subjects are consciously aware of the stimulus (CS)-reinforcer (UCS) contingencies. In two experiments the role of CS<-->UCS contingency awareness in the expression of conditioned responses (craving, salivation, and skin conductance) was studied. A discriminative classical conditioning paradigm was used during which subjects were presented with one stimulus (the CS +) always paired with cigarette smoking (the UCS) and another (the CS -) never paired with cigarette smoking. Half of the subjects were given instructions to discover the CS<-->UCS contingencies (group 'aware', AWR), whereas the other half were not (group 'unaware', UWR). In experiment 1, all subjects responded to the CS + with increased cigarette craving relative to the CS -; this effect was more pronounced in the AWR group compared to the UWR group. A lower amount of salivation in response to the CS + compared to the CS - was found in the UWR group. These between-group differences were interpreted as a consequence of the enhanced expectancies of smoking in the presence of CS + in group AWR compared to group UWR. In experiment 2, the observed craving responses to CS + and CS - were consistent with those seen in experiment 1, but no discriminative salivary response to the stimuli was found. When, after conditioning training, subjects' expectancies of smoking were removed by instructions, and their responses to CS + and CS - were again measured, the discriminative craving response to CS + and CS - was eliminated and all subjects demonstrated a lower amount of salivation in response to the CS + compared to the CS -. These data suggest that presentation of arbitrary cues previously paired with cigarette smoking can elicit CRs and that facilitation of awareness of the CS<-->UCS contingency by instructions can potentiate craving CRs. In addition, these data suggest that craving CRs can be eliminated, whereas compensatory CRs can be facilitated, when cigarette expectancy is removed with instructions.

Adolescent↗
PubMed2001

Comprehensive assessment of hemorrhage risks and outcomes after stereotactic brain biopsy.

OBJECT: Stereotactic brain biopsy has played an integral role in the diagnosis and management of brain lesions. At most centers, imaging studies following biopsy are rarely performed. The authors prospectively determined the acute hemorrhage rate after stereotactic biopsy by performing immediate postbiopsy intraoperative computerized tomography (CT) scanning. They then analyzed factors that may influence the risk of hemorrhage and the diagnostic accuracy rate. METHODS: Five hundred consecutive patients undergoing stereotactic brain biopsy underwent immediate postbiopsy intraoperative CT scanning. Before surgery, routine preoperative coagulation studies were performed in all patients. All medical charts, laboratory results, preoperative imaging studies, and postoperative imaging studies were reviewed. In 40 patients (8%) hemorrhage was detected using immediate postbiopsy intraoperative CT scanning. Neurological deficits developed in six patients (1.2%) and one patient (0.2%) died. Symptomatic delayed neurological deficits developed in two patients (0.4%), despite the fact that the initial postbiopsy CT scans in these cases did not show acute hemorrhage. Both patients had large intracerebral hemorrhages that were confirmed at the time of repeated imaging. The results of a multivariate logistic regression analysis of the risk of postbiopsy hemorrhage of any size showed a significant correlation only with the degree to which the platelet count was below 150,000/mm3 (p = 0.006). The results of a multivariate analysis of a hemorrhage measuring greater than 5 mm in diameter also showed a correlation between the risk of hemorrhage and a lesion location in the pineal region (p = 0.0086). The rate at which a nondiagnostic biopsy specimen was obtained increased as the number of biopsy samples increased (p = 0.0073) and in accordance with younger patient age (p = 0.026). CONCLUSIONS: Stereotactic brain biopsy was associated with a low likelihood of postbiopsy hemorrhage. The risk of hemorrhage increased steadily as the platelet count fell below 150,000/mm3. The authors found a small but definable risk of delayed hemorrhage, despite unremarkable findings on an immediate postbiopsy head CT scan. This risk justifies an overnight hospital observation stay for all patients after having undergone stereotactic brain biopsy.

Adolescent↗
PubMed2000

Management of cancer treatment-related diarrhea. Issues and therapeutic strategies.

The cancer treatment-related diarrhea caused by acute graft-versus-host disease (GVHD) and chemotherapeutic agents, particularly fluoropyrimidines and irinotecan, significantly affects patient morbidity and mortality. The mechanisms causing cancer treatment-related diarrhea are not fully understood, but histopathologic evidence points to a multifactorial process that causes an absorptive and secretory imbalance in the small bowel. Cancer treatment-related diarrhea could be life-threatening, yet assessment and treatment are not currently standardized. Several clinicians participated in a closed roundtable meeting to review the mechanisms of chemotherapy-induced diarrhea (CID) and GVHD-induced diarrhea, management issues in cancer treatment-induced diarrhea, and pharmacologic approaches to treatment. The meeting produced a proposal for new treatment guidelines and an algorithm, which include the use of octreotide for the management of CID- and GVHD-induced diarrhea. The development of diarrhea assessment guidelines that expand on the current National Cancer Institute criteria and allow for better patient management was also proposed.

Antineoplastic Agents↗
PubMed2000

The Consortium of Graduate Medical Schools in Australia: formal and informal collaboration in medical education.

CONTEXT: In 1996-97 three Australian medical schools adopted 4-year graduate medical courses. The schools formed a consortium to establish common admissions processes and to collaborate on curriculum and staff development. OUTCOMES: ADMISSIONS: Outcomes in admissions included the construction of an entry test and agreement on common application procedures. Structured interviews and measures of prior tertiary performance were adopted in each school with some local variations. Formal structures were put into place to manage the development of the test and admissions procedures. OUTCOMES: CURRICULUM AND STAFF DEVELOPMENT: No formal structures were put into place for curriculum and staff development. While the advantages of common approaches were recognised, it was accepted that it was also important to generate local ownership and commitment to the new courses. Outcomes of educational consortia should not be judged solely by the nature of joint ventures but by the way in which membership of the consortium changes the priorities and practices within the institutions. Examples of the operation of this principle within the three schools include: use of visiting experts to refine and modify approaches to problem-based learning; use of staff from partner institutions to facilitate implementation of the courses; sharing information technology expertise; cooperation in the construction of feedback mechanisms, and sharing advice on fulfilling accreditation requirements. CONCLUSION: The Consortium has had an important impact on Australian medical education. There is a need for further analysis of the two methods of operation of the consortium, formal and informal, and their relation to its overall functioning.

Australia↗
PubMed2000

Interferon-gamma downregulates ion transport in murine small intestine cultured in vitro.

Effects of IFN-gamma on mammalian small intestinal ion transport were studied in vitro using incubated sheets of murine small intestine in Ussing chambers. In oxygenated standard culture medium containing hydrocortisone and antibiotics, they maintained their short-circuit current (I(sc)) responses to glucose and theophylline for 48 h. Histological examination revealed a 50% diminution of villus height over 36 h but no change in crypts. Height was better maintained during a 36-h incubation of small intestine from SCID mice, suggesting a role for B or T lymphocytes in villus atrophy. Exposure of small intestine to 100 U/ml IFN-gamma for 36 h decreased basal I(sc) by 40% and I(sc) responses to glucose and theophylline by approximately 70%; at 1,000 U/ml for 36 h, IFN-gamma inhibited these I(sc) responses by 90%. An inhibitor of inducible NO synthase did not reverse these effects, suggesting that they are not mediated by NO. Tissue resistance, mucosal K(+) content, and epithelial morphology were not affected. Ouabain-sensitive ATPase activity in homogenates was inhibited 60% by IFN-gamma (100 U/ml for 36 h). IFN-gamma inhibition of I(sc) responses to glucose and theophylline also occurred in SCID mouse small intestine. Thus murine small intestinal sheets can be maintained viable in vitro for at least 48 h, although villus blunting develops (but less so in SCID mouse small intestine). Also, prolonged exposure to IFN-gamma downregulates Na(+)-coupled glucose absorption, active Cl(-) secretion, and Na(+)-K(+)-ATPase activity, effects unlikely to be mediated by enhanced NO.

Animals↗
PubMed1999

Setup reproducibility in radiation therapy for lung cancer: a comparison between T-bar and expanded foam immobilization devices.

PURPOSE: Physiologic and non-physiologic tumor motion complicates the use of tight margins in three-dimensional (3D) conformal radiotherapy. Setup reproducibility is an important non-physiologic cause of tumor motion. The objective of this study is to evaluate and compare patient setup reproducibility using the reusable T-bar and the disposable expanded foam immobilization device (EFID) in radiation therapy for lung cancer. METHODS AND MATERIALS: Two hundred forty-four portal films were taken from 16 prospectively accrued patients treated for lung cancer. Patients were treated with either a pair of anterior and posterior parallel opposing fields (POF), or a combination of POF and a three-field isocentric technique. Each patient was treated in a supine position using either the T-bar setup or EFID. Six patients were treated in both devices over their treatment courses. Field placement analysis was used to evaluate 3D setup reproducibility, by comparing positions of bony landmarks relative to the radiation field edges in digitized simulator and portal images. Anterior-posterior, lateral, and longitudinal displacements, as well as field rotations along coronal and sagittal planes were measured. Statistical analyses of variance were applied to the deviations among portal films of all patients and the subgroup treated with both immobilization methods. RESULTS: For the T-bar immobilization device, standard deviations of the setup reproducibility were 5.1, 3.7, and 5.1 mm in the anterior-posterior, lateral, and longitudinal dimensions, respectively. Rotations in the coronal plane and the sagittal plane were 0.9 degrees and 1.0 degrees, respectively. For the EFID, corresponding standard deviations of set up reproducibility were 3.6 mm, 5.3 mm, 5.4 mm, 0.7 degrees and 1.4 degrees, respectively. There was no statistically significant difference (p = 0.22) in the 3D setup reproducibility between T-bar and EFID. Subgroup analysis for the patients who were treated with both immobilization devices did not reveal a difference either. There was no consistent systematic error from simulator to treatment unit identified for either immobilization device. CONCLUSION: Although the optimal immobilization technique and patient positioning for thoracic radiotherapy have yet to be determined, this study indicates that T-bar is comparable with EFID in its setup reproducibility. In view of the inherent advantages of T-bar, it has become a standard immobilization device at our institution. The observed range of displacements in field positioning with either immobilization device implies that one cm (two standard deviations [SD] of setup error) will be a more appropriate margin to allow for setup variability in radiation therapy for lung cancer.

Equipment Design↗
PubMed1999

Preparing the ground: contributions of the preclinical years to medical education for care near the end of life. Working Group on the Pre-clinical Years of the National Consensus Conference on Medical Education for Care Near the End of Life.

The preclinical years of medical education have rich potential for preparing medical students to provide optimal end-of-life care. Most of the opportunities and settings for this education already exist in the curricula of most medical schools, although they are underutilized for this purpose. In this report The Working Group on the Pre-clinical Years of the National Consensus Conference on Medical Education for Care Near the End of Life identifies the most promising settings and suggests how they might be used for maximum benefit in end-of-life education. Basic end-of-life care competencies are in five domains: (1) psychological, sociologic, cultural, and spiritual issues; (2) interviewing and communication skills; (3) management of common symptoms; (4) ethical issues; and (5) self-knowledge and self-reflection. A centralized group should oversee educational activities related to end-of-life care at each medical school. This group would identify and facilitate teaching opportunities in the preclinical curriculum: basic science courses; problem-based learning seminars; courses in interviewing, the doctor-patient relationship, and introduction to clinical medicine; courses in ethics, humanities, and the social-behavioral sciences; clinical preceptorships; and longitudinal experiences with patients. The group would also assess the potential impact of the "hidden curriculum."

Attitude to Death↗
PubMed1999

A proinflammatory role for IL-18 in rheumatoid arthritis.

IL-18 is a novel cytokine with pleiotropic activities critical to the development of T-helper 1 (Th1) responses. We detected IL-18 mRNA and protein within rheumatoid arthritis (RA) synovial tissues in significantly higher levels than in osteoarthritis controls. Similarly, IL-18 receptor expression was detected on synovial lymphocytes and macrophages. Together with IL-12 or IL-15, IL-18 induced significant IFN-gamma production by synovial tissues in vitro. IL-18 independently promoted GM-CSF and nitric oxide production, and it induced significant TNF-alpha synthesis by CD14(+) macrophages in synovial cultures; the latter effect was potentiated by IL-12 or IL-15. TNF-alpha and IFN-gamma synthesis was suppressed by IL-10 and TGF-beta. IL-18 production in primary synovial cultures and purified synovial fibroblasts was, in turn, upregulated by TNF-alpha and IL-1beta, suggesting that monokine expression can feed back to promote Th1 cell development in synovial membrane. Finally, IL-18 administration to collagen/incomplete Freund's adjuvant-immunized DBA/1 mice facilitated the development of an erosive, inflammatory arthritis, suggesting that IL-18 can be proinflammatory in vivo. Together, these data indicate that synergistic combinations of IL-18, IL-12, and IL-15 may be of importance in sustaining both Th1 responses and monokine production in RA.

Animals↗
PubMed1999

The -308.1 polymorphism in the promoter region of the tumor necrosis factor gene is associated with ankylosing spondylitis independent of HLA-B27.

OBJECTIVE: To investigate the allele frequencies of 6 polymorphic sites spanning the region of the genome close to the tumor necrosis factor (TNF) gene in a group of HLA-B27 positive patients with ankylosing spondylitis (AS) in the West of Scotland. METHODS: One hundred sixty-seven patients with AS, 93 healthy controls, and 88 HLA-B27 positive healthy controls, all from the West of Scotland, were typed by polymerase chain reaction (PCR) for 3 restriction fragment length polymorphisms (RFLP) and 3 microsatellite polymorphic sites spanning the TNF gene cluster. The distribution of these alleles was correlated with the presence of extraspinal manifestations such as peripheral joint disease and uveitis. RESULTS: The frequency of the Nco-1.2 allele was significantly reduced in patients compared to the genetically unselected control population (p < 0.05), but was no different from the HLA-B27 positive controls. However, the -308.1 allele was significantly increased in the patients compared to the HLA-B27 positive controls (p < 0.03). CONCLUSION: This study confirms the importance of correct matching in genetic analysis in disease association studies, and provides further evidence supporting the involvement of genes other than the MHC class I locus in the pathogenesis and features of AS.

Adolescent↗
PubMed1998

Novel nonpeptide CCK-B antagonists: design and development of quinazolinone derivatives as potent, selective, and orally active CCK-B antagonists.

We have designed a novel series of CCK-B receptor antagonists by combining key pharmacophores, an arylurea moiety of 1 and a quinazolinone ring of 3, from two known series. Our earlier studies showed that compounds with methylene linkers in our "target" produced moderate binding affinity and selectivity for CCK-B receptors, whereas its higher and lower homologues resulted in loss of affinity. Introduction of -NH- as a linker dramatically enhanced binding affinity and selectivity for CCK-B receptors, thus providing several compounds with single-digit nanomolar binding affinity and excellent selectivity. Analogous to the earlier studies of the series of quinazolinone derivatives 3, we also found 3-isopropoxyphenyl as a preferred substitution on the N-3 quinazolinone. Electron-withdrawing substitutions on the urea terminal phenyl ring enhanced the CCK-B potency. Representative compounds of this series were tested in the functional assay and showed pure antagonist profiles. Compounds 51 and 61 were orally active in the elevated rat X-maze test. These compounds were also evaluated for their pharmacokinetic profile. The absolute oral bioavailability of compound 61 was 22% in rats.

Administration, Oral↗
PubMed1998

Evaluation of two media for the membrane filtration enumeration of Clostridium perfringens from water.

Two media (mCP medium and Tryptose Sulphite Cycloserine (TSC) agar) were evaluated for recovery of Clostridium perfringens in environmental and part-treated drinking water. For laboratory strains of Clostridium, mCP was more selective and specific for Cl. perfringens than TSC, but was markedly less efficient for the enumeration of both vegetative cells and spores. For samples of river water and part-treated drinking water, TSC recovered significantly greater numbers of Cl. perfringens than mCP. In contrast to previous reports, there was a significant number of false presumptive positive and negative isolates on mCP. TSC is a more suitable medium for the routine monitoring of water supplies for the presence of Cl. perfringens.

Clostridium perfringens↗
PubMed1998

Mood, cue and gender influences on motivation, craving and liking for alcohol in recreational drinkers.

The effects of exposure to an alcohol-related cue (drinking low-alcohol beer) and a musical depression/elation mood induction procedure, on craving, motivation and liking for alcohol, were studied in male and female recreational drinkers. Alcohol craving was assessed using the multidimensional desires for alcohol questionnaire (DAQ), motivation for alcohol was assessed by performance on a progressive ratio (PR) task reinforced with small volumes (25 ml) of low-alcohol beer, and liking for the reinforcers earned in the PR task was assessed using a visual analogue scale. Consumption of a half-pint of low-alcohol beer increased alcohol craving in male subjects but had no effect or decreased craving in female subjects. Subsequent induction of a depressed mood increased craving scores, relative to elated or neutral mood groups, but these effects were confined to abstinent (non-cued) subjects, both male and female. Performance on the PR task correlated significantly with one of the four factors of the DAQ, negative reinforcement, and was increased by induction of a depressed mood in abstinent female and cued male subjects. Reinforcer liking was unchanged following mood induction in male subjects, but decreased in both groups of female subjects. To summarize, the cue of drinking low-alcohol beer increased alcohol craving in men but not in women, and induction of a depressed mood increased alcohol craving and motivation, but also decreased alcohol liking. These effects were present to different extents in different cue/gender subgroups, and were partially independent.

Adult↗
PubMed1998

Recommended guidelines for the treatment of chemotherapy-induced diarrhea.

PURPOSE: Management of chemotherapy-induced diarrhea (CID) has customarily involved symptomatic treatment with opioids in conjunction with supportive care. Alternatively, patients refractory to conventional therapy have been given octreotide, a somatostatin analogue. Although this agent has been effective against CID, no widely accepted treatment guidelines that incorporate its use currently exist. An expert multidisciplinary panel was convened to formulate clinical practice guidelines for the treatment of CID. METHODS: The panel reviewed clinical data on the management of CID reported in the literature and analyzed currently available tools used to assess CID. Expert consensus was applied when published data were insufficient. Panel members also considered the effect of CID on quality of life and the cost-effectiveness and efficacy of different pharmacologic approaches. Effective resolution of CID and decreases in the need for supportive care or hospitalization were considered to be primary goals in the formulation of the guidelines. RESULTS: The panel formulated suggested practice guidelines for the management of CID that detail recommendations for the assessment and evaluation of diarrhea and the sequence and duration of administration of specific pharmacologic agents. CONCLUSION: The consensus of the panel was that standardized assessment and management of diarrhea is required to effectively control CID. The panel agreed that further data from a National Cancer Institute (NCI)-sponsored intergroup trial is required to determine the optimal dosage of octreotide and its cost in the treatment of cancer. The panel also agreed that further clinical research is warranted to address significant questions about the most effective way to assess and treat CID.

Antineoplastic Agents↗