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Biomedical subjects

M Nicholson

Publications and source records attributed to M Nicholson.

At least 19 recordsLinked to original sources
PubMed2006

Leucocyte depletion improves renal function during reperfusion using an experimental isolated haemoperfused organ preservation system.

BACKGROUND: Leucocytes have been implicated as mediators of renal ischaemia-reperfusion injury. This study aimed to demonstrate the effect of white cells in early renal reperfusion injury using an isolated haemoperfused porcine kidney model. METHODS: After 2 h cold storage, porcine kidneys were perfused with normothermic autologous blood using an isolated organ preservation system. This was designed using cardiopulmonary bypass technology, and perfusion commenced with a circulating serum creatinine level of 1000 micromol/l. In group 1 (n = 6) a leucocyte filter was included in the circuit and in group 2 (n = 6) non-filtered blood was used. RESULTS: The mean(s.d.) area under the curve for serum creatinine was lower in the leucocyte-depleted experiments (1286(214) versus 2627(418); P = 0.002). Leucocyte depletion also led to improved urine output (191(75) versus 70(32) ml/h; P = 0.002) and higher creatinine clearance (10.6(2.8) versus 1.9(1.0) ml/min; P = 0.002). Renal blood flow, oxygen consumption and acid-base homeostasis were all improved by perfusion with leucocyte-depleted blood, and histological tubular damage was ameliorated. CONCLUSION: These data show that the depletion of leucocytes from blood used to perfuse porcine kidneys improved postschaemic renal function, indicating that white cells play an important role in renal ischaemia-reperfusion injury.

Acid-Base Equilibrium↗
PubMed2002

Phase III randomised trial comparing paclitaxel/carboplatin with paclitaxel/cisplatin in patients with advanced non-small-cell lung cancer: a cooperative multinational trial.

BACKGROUND: The combination of paclitaxel with cisplatin or carboplatin has significant activity in non-small-cell lung cancer (NSCLC). This phase III study of chemotherapy-naïve advanced NSCLC patients was designed to assess whether response rate in patients receiving a paclitaxel/carboplatin combination was similar to that in patients receiving a paclitaxel/cisplatin combination. Paclitaxel was given at a dose of 200 mg/m(2) (3-h intravenous infusion) followed by either carboplatin at an AUC of 6 or cisplatin at a dose of 80 mg/m(2), all repeated every 3 weeks. Survival, toxicity and quality of life were also compared. PATIENTS AND METHODS: Patients were randomised to receive one of the two combinations, stratified according to centre, performance status, disease stage and histology. The primary analyses of response rate and survival were carried out on response-evaluable patients. Survival was also analysed for all randomised patients. Toxicity analyses were carried out on all treated patients. RESULTS: A total of 618 patients were randomised. The two treatment arms were well balanced with regard to gender (83% male), age (median 58 years), performance status (83% ECOG 0-1), stage (68% IV, 32% IIIB) and histology (38% squamous cell carcinoma). In the paclitaxel/carboplatin arm, 306 patients received a total of 1311 courses (median four courses, range 1-10 courses) while in the paclitaxel/cisplatin arm, 302 patients received a total of 1321 courses (median four courses, range 1-10 courses). In only 76% of courses, carboplatin was administered as planned at an AUC of 6, while in 96% of courses, cisplatin was given at the planned dose of 80 mg/m(2). The response rate was 25% (70 of 279) in the paclitaxel/carboplatin arm and 28% (80 of 284) in the paclitaxel/cisplatin arm (P = 0.45). Responses were reviewed by an independent radiological committee. For all randomised patients, median survival was 8.5 months in the paclitaxel/carboplatin arm and 9.8 months in the paclitaxel/cisplatin arm [hazard ratio 1.20, 90% confidence interval (CI) 1.03-1.40]; the 1-year survival rates were 33% and 38%, respectively. On the same dataset, a survival update after 22 months of additional follow-up yielded a median survival of 8.2 months in the paclitaxel/carboplatin arm and 9.8 months in the paclitaxel/cisplatin arm (hazard ratio 1.22, 90% CI 1.06-1.40; P = 0.019); the 2-year survival rates were 9% and 15%, respectively. Excluding neutropenia and thrombocytopenia, which were more frequent in the paclitaxel/carboplatin arm, and nausea/vomiting and nephrotoxicity, which were more frequent in the paclitaxel/cisplatin arm, the rate of severe toxicities was generally low and comparable between the two arms. Overall quality of life (EORTC QLQ-C30 and LC-13) was also similar between the two arms. CONCLUSIONS: This is the first trial comparing carboplatin and cisplatin in the treatment of advanced NSCLC. Although paclitaxel/carboplatin yielded a similar response rate, the significantly longer median survival obtained with paclitaxel/cisplatin indicates that cisplatin-based chemotherapy should be the first treatment option.

Adult↗
PubMed2001

European randomised trial of dual versus triple tacrolimus-based regimens for control of acute rejection in renal allograft recipients.

Two large multicentre studies have shown superiority of tacrolimus-based immunosuppressive regimens compared with standard cyclosporine-based therapy in renal transplantation. In these studies, tacrolimus was used in a triple drug regimen of tacrolimus, corticosteroids, and azathioprine. The present study aimed to determine whether a tacrolimus-based dual regimen achieves a similar efficacy and safety profile compared with conventional triple therapy. In this prospective, open, multicentre trial, 249 patients were randomised to receive either dual therapy (n = 125) of oral tacrolimus (initial daily dose of 0.2 mg/kg) and oral prednisone or additionally, as a triple therapy (n = 124), oral azathioprine. The primary endpoint was the incidence of acute rejection at month 3. In addition, all patients were included into a follow-up evaluation at 1 year after transplantation. Both treatment groups had similar baseline characteristics. At month 3, patient survival was 97.6 % (dual) and 96.7 % (triple); graft survival was 92.7 % (dual) and 91.7 % (triple). The incidence of treated acute rejection confirmed by biopsy was 27.4 % (dual) and 24.8 % (triple); difference 2.6 %, 95 % CI [-9.4 %-12.9 %], P = 0.755. The incidence of corticosteroid-resistant rejection (biopsy-confirmed) was 9.7 % (dual) and 10.7 % (triple). The overall adverse events profile was similar; leukopenia (1.6 % vs 11.6 %, P = 0.002) was more frequent with triple therapy. Between months 4 and 12, six (dual) and eight (triple) patients had a rejection. At month 12, patient survival was 95.6 % (dual) and 93.6 % (triple); graft survival was 91.8 % (dual) and 90.7 % (triple). Tacrolimus proved to be efficacious and safe with both dual and triple low-dose regimens. The addition of azathioprine to a tacrolimus/corticosteroid-based therapy did not result in an increased efficacy.

Acute Disease↗
PubMed2001

The use of high-frequency oscillatory ventilation in adult ARDS patients.

Current ventilatory objectives for adults with ARDS include maximizing gas exchange while minimizing lung injury. To this end, high-frequency oscillatory ventilation (HFOV), a mechanical ventilation strategy that simultaneously avoids end-inspiratory alveolar overdistension and end-expiratory alveolar collapse, has been recommended. HFOV meets these criteria from a theoretical perspective, however, is without the benefit of a prospective randomized clinical trial of CMV versus HFOV to demonstrate that effect. This article provides an overview of high-frequency oscillation, followed by an illustration of how it was applied in the case of a 43-year-old patient who developed respiratory failure 24 hours post-Caesarean section.

Adult↗
PubMed2000

Internet use amongst New Zealand general practitioners.

AIMS: To assess how extensively New Zealand doctors are using medical information on the Internet, and to examine how the new technology is affecting their practice of medicine. METHODS: All general practitioners (GPs) known to be working in Otago and Southland were asked to complete a postal questionnaire regarding their use of the Internet and their impressions of patient use of online medical resources. RESULTS: Of 259 questionnaires mailed out, 168 (65%) were returned by GPs currently in practice. Of those, 114 (68%) said they used the Internet at least monthly. A total of 71% of GPs had patients who indicated they had sought medical information from the Internet. Nearly half of respondents expressed concerns that the Internet could have unwelcome effects on the doctor-patient relationship. CONCLUSIONS: Internet use among New Zealand doctors and patients is widespread, and is likely to have significant impact on medical practice now and in the future. While the potential benefits of the new technology are numerous, the Internet may become a source of conflict between doctors and patients.

Data Collection↗
PubMed2000

Comparison of visual--vestibular interaction in insulin-dependent and non-insulin-dependent diabetes mellitus.

We compared various measures of visual-vestibular interaction in subjects with insulin-dependent diabetes mellitus (IDDM) or non-insulin-dependent diabetes mellitus (NIDDM), as well as non-diabetic controls. Subjects with IDDM exhibited significantly greater postural sway than controls on those conditions in the Clinical Test of Sensory Interaction and Balance (CTSIB) which require greater reliance on the vestibular system (p < 0.005). The IDDM group also exhibited significantly worse gaze-holding in darkness and a significantly higher mean slow phase eye velocity (SPV) of optokinetic nystagmus (OKN; p<0.05 for both comparisons). However, there were no significant differences in latency to circularvection (CV). The NIDDM group showed a significant increase in postural sway across all 12 conditions compared with the controls, as well as a significant decrease in gaze-holding in darkness (p < 0.05 and p < 0.0005, respectively). However, they showed no significant difference in OKN SPV and a significant decrease in latency to CV for anticlockwise trials only (p < 0.05). These results suggest that IDDM and NIDDM are both associated with specific but different changes in visual-vestibular interaction.

Adult↗
PubMed2000

A pilot study: stability of psychiatric diagnoses over 6 months in burning mouth syndrome.

Ten people with burning mouth syndrome (BMS) were interviewed by a psychiatrist using the Schedules of Clinical Assessment in Neuropsychiatry (SCAN) at initial presentation and at 6-month follow-up. A range of psychiatric disorders from the neurotic spectrum was identified using the International Classification of Diseases (ICD-10) criteria, but the diagnoses were unstable. Six of the ten individuals received a psychiatric diagnosis, suggesting that the prevalence of psychiatric morbidity is high in this common dental syndrome. Psychiatric aspects of BMS require further investigation.

Anxiety Disorders↗
PubMed2000

Gemcitabine plus best supportive care (BSC) vs BSC in inoperable non-small cell lung cancer--a randomized trial with quality of life as the primary outcome. UK NSCLC Gemcitabine Group. Non-Small Cell Lung Cancer.

Three hundred patients with symptomatic, locally advanced or metastatic NSCLC not requiring immediate radiotherapy were enrolled into this randomized multicentre trial comparing gemcitabine + BSC vs BSC alone. Patients allocated gemcitabine received 1000 mg/m2 on days 1, 8 and 15 of a 28-day cycle, for a maximum of six cycles. The main aim of this trial was to compare patient assessment of a predefined subset of commonly reported symptoms (SS14) from the EORTC QLQ-C30 and LC13 scales. The primary end-points were defined as (1) the percentage change in mean SS14 score between baseline and 2 months and (2) the proportion of patients with a marked (> or = 25%) improvement in SS14 score between baseline and 2 months sustained for > or =4 weeks. The secondary objectives were to compare treatments with respect to overall survival, and multidimensional QL parameters. The treatment groups were balanced with regard to age, gender, Karnofsky performance status (KPS) and disease stage (40% had metastatic disease). The percentage change in mean SS14 score from baseline to 2 months was a 10% decrease (i.e. improvement) for gemcitabine plus BSC and a 1% increase (i.e. deterioration) for BSC alone (P = 0.113, two-sample t-test). A sustained (> or = 4 weeks) improvement (> or =25%) on SS14 was recorded in a significantly higher proportion of gemcitabine + BSC patients (22%) than in BSC alone patients (9%) (P = 0.0014, Pearson's chi-squared test). The QLQ-C30 and L13 subscales showed greater improvement in the gemcitabine plus BSC arm (in 11 domains) than in the BSC arm (one symptom item). There was greater deterioration in the BSC alone arm (six domains/items) than in the gemcitabine + BSC arm (three QL domains). Tumour response occurred in 19% (95% CI 13-27) of gemcitabine patients. There was no difference in overall survival: median 5.7 months (95% CI 4.6-7.6) for gemcitabine + BSC patients and 5.9 months (95% CI 5.0-7.9) (log-rank, P = 0.84) for BSC patients, and 1 -year survival was 25% for gemcitabine + BSC and 22% for BSC. Overall, 74 (49%) gemcitabine + BSC patients and 119 (79%) BSC patients received palliative radiotherapy. The median time to radiotherapy was 29 weeks for gemcitabine + BSC patients and 3.8 weeks for BSC. Patients treated with gemcitabine + BSC reported better QL and reduced disease-related symptoms compared with those receiving BSC alone. These improvements in patient-assessed QL were significant in magnitude and were sustained.

Adult↗
PubMed1999

The influence of patch test size and design on the distribution of erythema induced by sodium lauryl sulfate.

Patch testing is an invaluable tool for the experimental induction of acute irritant contact dermatitis (ICD), with a variety of chamber systems available for use. Ideally, the inflammatory reactions produced should be of uniform intensity across the test area, thereby facilitating grading of the response and tissue sampling for histopathological studies. Unfortunately, annular, follicular and/or blotchy erythema frequently occur. In this study, we set out to compare the performance of 5 patch test systems (8 mm, 12 mm and 18 mm Finn Chambers; 19 mm and 25 mm Hilltop chambers) when testing normal healthy volunteers with sodium lauryl sulfate at concentrations selected to produce mild, moderate and moderately severe reactions. Visual assessment of the patch test sites revealed good dose responses with all 5 chamber types. Uniformity of erythema across the test site was more closely linked to the actual intensity of response than the delivery system itself, mild reactions being far less likely to display homogeneous erythema than moderately severe reactions. Extra large chambers did not perform significantly better than smaller chambers. Balancing the need for a uniform reaction pattern and adequate tissue sampling area, against the exposure risk, we conclude that 12 mm Finn Chambers represent the optimum patch test system for acute SLS-induced irritation where histopathological investigations are the ultimate aim.

Adult↗
PubMed1998

Diagnosis of early acute renal allograft rejection by evaluation of multiple histological features using a Bayesian belief network.

BACKGROUND AND AIMS: The development of the Banff classification of renal transplant pathology has allowed the standardisation of approaches to transplant biopsy histology and reduced interobserver and interdepartmental variation. The usefulness of the Banff classification in the diagnosis of acute rejection has previously been tested by sending sections from 21 "difficult" biopsies to almost all of the renal transplant pathologists in the UK. Although the Banff classification improved reproducibility, the accuracy of diagnosis of early acute rejection was unchanged from the "conventional" approach. Perhaps this is because in making a diagnosis of acute rejection, the Banff classification uses only two features: tubulitis and intimal arteritis. To include more features on a systematic basis would be laborious for a human observer. Therefore, a Bayesian belief network was developed for this task. METHODS: The network was initialised with observations from 110 transplant biopsies. Its performance was then tested on 21 biopsies that had been seen by 37 different renal transplant pathologists in an earlier study. These biopsies had been selected to represent histologically difficult problems but, in retrospect, they all had clear diagnoses of rejection or non-rejection on clinical grounds. RESULTS: Using the Bayesian belief network, a relatively inexperienced pathologist made 19 of 21 correct diagnoses, better than had been achieved by any of the pathologists who had seen the same sections previously (17 of 21), and considerably better than the average proportion of correct diagnoses provided by all 37 renal transplant pathologists (65%). Application of the system by a second pathologist produced a tendency to overdiagnosis of acute rejection, illustrating the consequences of interobserver variation. CONCLUSIONS: In the diagnosis of acute rejection, further useful information can be extracted from features that are currently not considered in the Banff classification. Integration of data by a computer can give a more reliable diagnosis of early acute rejection, but routine application will require the development of a more sophisticated system that can also accommodate clinical data, perhaps one that can continue to "learn" as more data are entered.

Acute Disease↗
PubMed1998

Campylobacter jejuni lipopolysaccharides in Guillain-Barré syndrome: molecular mimicry and host susceptibility.

OBJECTIVE: This study was designed to determine if the presence of specific ganglioside-like moieties in Campylobacter lipopolysaccharides (LPSs) is related to the development of Guillain-Barré syndrome (GBS), and to discover how frequently such moieties, including GM1, are present in these LPSs. METHODS: We studied Campylobacter isolates and sera from seven patients with GBS (five acute motor axonal neuropathy, one acute inflammatory demyelinating polyneuropathy, and one Fisher's syndrome), and compared them with similar specimens from patients with Campylobacter enteritis alone. RESULTS: All GBS patients had antiganglioside antibodies. Anti-GM1 and anti-GD1a titers were significantly elevated in post-Campylobacter GBS, both axonal and demyelinating, compared with normal control subjects or those with uncomplicated Campylobacter diarrhea. Campylobacter isolated from patients with GBS and with enteritis alone had similar ganglioside-like moieties. CONCLUSIONS: These results indicate that patients who develop GBS respond differently to the ganglioside-like epitopes on Campylobacter than do non-GBS diarrhea patients. Our findings support a role for host susceptibility as a determinant for the outcome following Campylobacter infection. These findings have important implications for the development of vaccines against Campylobacter jejuni.

Adult↗
PubMed1997

Relationship between circulating leptin and energy expenditure in adult men and women aged 18 years to 81 years.

Recent studies suggest that leptin may be an important metabolic signal for energy regulation in rodents, but the role of leptin in human energy regulation remains uncertain. Because adaptive variations in energy expenditure play an important role in human energy regulation, we investigated the relationship between leptin and energy expenditure parameters in 61 weight-stable men and women aged 18 years to 81 years who were not obese. Measurements were made of circulating leptin in the fasting state, body fat and fat free mass, resting metabolic rate (n = 61), free-living total energy expenditure (n = 52), and the thermic effect of feeding (n = 33). After statistically accounting for age, body fat, and fat free mass, there was no association between leptin and any measured energy expenditure parameter. In addition, there was no effect of age on the relationship between circulating leptin and body fat mass. These results indicate that physiological variations in circulating leptin are not linked with adaptive variations in energy expenditure in humans, in contrast to indications of this phenomenon in the ob/ob mouse.

Adipose Tissue↗
PubMed1996

CD4+CD8- thymocytes that express L-selectin protect rats from diabetes upon adoptive transfer.

Previous studies have shown that insulin-dependent diabetes can be induced in normal PVG.RT1u rats by a protocol of adult thymectomy and irradiation. The injection of CD4+ T cells from non-irradiated syngeneic donors prevents the onset of disease in approximately 50% of pre-diabetic recipients but all rats are protected if a particular subset of CD4+ cells is transferred. These protective cells express TCR alpha beta and have a memory phenotype, being CD45RClow RT6+. Further studies have demonstrated that the transfer of CD4+CD8- thymocytes, like that of unfractionated CD4+ peripheral T cells, also protects approximately half of recipients from diabetes suggesting that, as with the peripheral T cells, a functional heterogeneity may exist amongst CD4+CD8- thymocytes. In this study, we show that L-selectin is expressed by 50-60% of all CD4+CD8- thymocytes from 6-week-old rats. Adoptive transfer of these populations into thymectomized and irradiated rats revealed that the protection from diabetes observed by CD4+CD8- thymocytes was mediated almost entirely by the L-selectin+ subset. Cells with this phenotype were also able to mediate both humoral and cell mediated responses, providing primed B cells with help for secondary antibody responses and mediating local graft-versus-host reactions. L-selectin- CD4+CD8- thymocytes failed to mediate these responses. These data indicate that CD4+CD8- thymocytes must mature to the stage of L-selectin expression, before they can mediate normal T cell function. The implications of these results are discussed with respect to the possible role of murine NK1.1+ thymocytes in the control of autoimmunity.

Adoptive Transfer↗
PubMed1996

The beneficial effects of oral nifedipine on cyclosporin-treated renal transplant recipients--a randomised prospective study.

The aim of this study was to test the hypothesis that nifedipine will improve graft survival in cyclosporin A (CyA)-treated renal transplant recipients. One hundred and forty-seven patients were randomised to one of three regimens. Group A received CyA, 7 mg/kg per day, and prednisolone; group B followed the same regimen as group A plus oral nifedipine and group C received CyA, 4 mg/kg per day, prednisolone and azathioprine. Calcium channel blockers were avoided in groups A and C. The crude 2-year (P = 0.0223) and 4-year (P = 0.0181) graft survival was significantly better in group B (86% and 81%, respectively) than in group A (75% and 63%, respectively). Delayed initial function was seen least frequently in group B (10.2%) compared to groups A (31%) and C (28%; P < 0.01). Group B also experienced fewer rejection episodes than groups A and C (P < 0.05). We conclude that the combination of oral nifedipine and CyA significantly improves initial graft function, rejection frequency and long term graft survival.

Administration, Oral↗