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Biomedical subjects

D Robson

Publications and source records attributed to D Robson.

At least 19 recordsLinked to original sources

Spinal cord compression and dorsal root injury cause up-regulation of activating transcription factor-3 in large-diameter dorsal root ganglion neurons.

Spinal cord injury causes damage to ascending and descending tracts, as well as to local circuits, but relatively little is known about the effect of such injury on sensory neurons located within adjoining ganglia. We have therefore used immunocytochemistry for activating transcription factor-3 (ATF3), a sensitive marker of axonal damage, in order to examine the effects of spinal cord injury in rats on dorsal root ganglion (DRG) neurons. A 50-g static compression injury applied to the dorsal surface of the T12 thoracic spinal cord led to an up-regulation of ATF3 that was maximal at 1 day and affected 12-14% of DRG neurons in ganglia caudal to the injury (T13-L3). A similar response was seen after a T12 hemisection that transected the dorsal columns except that compression injury, but not hemisection, also evoked ATF3 expression in ganglia just rostral to the injury (T10, T11). ATF3 was up-regulated exclusively in DRG neurons that were of large diameter and immunoreactive for heavy neurofilament. Small-diameter cells, including the population that binds the lectin Grifffonia simplicifolia IB4, did not express ATF3 immunoreactivity. A similar pattern of ATF3 expression was induced by dorsal rhizotomy. The data show for the first time that ATF3 is up-regulated after spinal cord and dorsal root injury, but that this up-regulation is confined to the large-diameter cell population.

Activating Transcription Factor 3↗

Improved outcome for children with disseminated adenoviral infection following allogeneic stem cell transplantation.

Adenovirus (AdV) infections are a frequent cause of morbidity and mortality following allogeneic stem cell transplantation (SCT), and disseminated infection is associated with high mortality, particularly in paediatric SCT. Here, we describe an approach to reduce mortality from adenoviraemia by combining prospective monitoring for the occurrence of adenoviraemia using a sensitive polymerase chain reaction method, early antiviral therapy and prompt withdrawal of immunosuppression. A total of 155 consecutive paediatric SCT procedures were prospectively monitored, of which 113 (73%) transplants involved donors other than matched siblings and 126 (83%) employed T-cell depletion. Adenoviraemia was detected in 26/155 (17%) transplants and developed exclusively in patients who had received T-cell-depleted grafts. Withdrawal of immunosuppression coupled with early antiviral therapy led to resolution of adenoviraemia in 19/26 (81%) patients with only five patients succumbing to disseminate AdV infection. Survival from adenoviraemia was associated with lymphocyte recovery to above 0.3x10(9)/l. Mortality was closely linked with the absence of lymphocyte recovery because of profound T-cell depletion of the graft with CD34+ magnetic-activated cell sorting. Mortality from disseminated AdV infection was 5/26 (19%) in this study, which is significantly lower than previously reported.

Adenoviridae↗

Efficacy of cyclosporin in the treatment of atopic dermatitis in dogs--combined results from two veterinary dermatology referral centres.

OBJECTIVE: To evaluate the efficacy of cyclosporin in controlling the clinical signs associated with atopic dermatitis in dogs under Australian field conditions. DESIGN: A multicentre prospective clinical investigation of the use of cyclosporin in 41 dogs with atopic dermatitis. PROCEDURE: Dogs were treated with cyclosporin (5 mg/kg orally once daily with food) for 6 weeks. Four clinical parameters of severity of atopic dermatitis were measured on Day 0 and on Day 42 using a 0 to 4 scoring system. Individual variables were then combined to form a Global Score. Both client and clinician observed pruritus scores were combined to form a Pruritus Score. Pre- and post-treatment scores were statistically analysed. The difference in results between the two investigators was also recorded and analysed. RESULTS: All dogs showed a marked reduction in pruritus and erythema during the 6-week treatment period. All dogs showed a significant (P < 0.001) improvement in clinical lesion scores and Global Score (P < 0.001). The mean percentage improvement in Global Score from Day 0 to Day 42 was 83.9%. The mean percentage improvement in Pruritus Score from Day 0 to Day 42 was 83%. The medication was well tolerated. Side effects such as vomiting, diarrhoea and soft stools were observed in four dogs. Another four dogs developed bacterial pyoderma during the trial period. There was no significant difference in results between the two centres. CONCLUSION: Cyclosporin was well tolerated and efficacious in the symptomatic treatment of atopic dermatitis in dogs attending two veterinary dermatology referral centres in Australia, under Australian field conditions, when administered at 5 mg/kg/day for 6 weeks.

Administration, Oral↗

Review of the properties and mechanisms of action of cyclosporine with an emphasis on dermatological therapy in dogs, cats and people.

Cyclosporine is being increasingly used in veterinary medicine. It is a potent suppressor of T cell induction and proliferation, and has a wide variety of anti-inflammatory and antiproliferative effects, downregulating effects on antigen presentation, and variable effects on parasites. This paper reviews its properties and mechanisms of action with particular reference to its use in the treatment of dermatological conditions in dogs, cats and people.

Animals↗

Review of the pharmacokinetics, interactions and adverse reactions of cyclosporine in people, dogs and cats.

Cyclosporine is being increasingly used in veterinary medicine. Oral formulations of the drug have found many therapeutic uses, but topical formulations have met with only limited success, probably owing to their poor penetration through the stratum corneum. The concurrent use of ketoconazole to inhibit cyclosporine metabolism has been shown to reduce the required dose and hence the cost of cyclosporine therapy. In human medicine, adverse reactions to the drug, especially nephrotoxicity, are common but in dogs given the commonly used oral dose of 5 mg/kg per day there have been few adverse reactions. However, no toxicity studies lasting longer than 12 months have been carried out in this species. This paper reviews the pharmacokinetics, drug and procedural interactions, contraindications and the adverse reactions to cyclosporine, with particular reference to its use in the treatment of dermatological conditions in dogs, cats and people.

Animals↗

Influences of wind flow on stopover decisions: the case of the reed warbler Acrocephalus scirpaceus in the Western Mediterranean.

Wind directions measured at two different heights (850 hPa and 700 hPa) and at different hours of the night were analysed during the spring migration passage at a bird stopover site located in the western Mediterranean, in order to evaluate the importance of wind components for a stopover decision. From a huge ringing campaign of bird migration in north-east Spain, data from the reed warbler Acrocephalus scirpaceus have been used for the analysis. From a total of 2,478 reed warblers captured between 1993 and 1997 data recording significant days, with a high number of captures, and decrease days, with few captures, have been selected to develop an analysis of wind direction in relation to stopover and flight resumption. On days with a high capture the winds had mainly a fourth-quadrant flow (from the north, north-west and west), these being mainly head winds. Winds with westerly component (from the north-west, west and south-west), which enhance the flight, account for the majority of the days when there was a low capture of reed warblers. Wind direction therefore appears to be a determining factor for stopover decisions and resumption of flight for the reed warblers at an intermediate stage of their spring migration where topographical characteristics govern the winds.

Animals↗

Canadian male farm residents, pesticide safety handling practices, exposure to animals and non-Hodgkin's lymphoma (NHL).

BACKGROUND: A majority of published studies indicate that farmers have an elevated risk of developing non-Hodgkin's lymphoma (NHL) compared to other workers. METHODS: We evaluated accidental exposure to pesticides, the use of personal protective equipment, and exposure to animals among male farm residents in a Canadian population-based, multi-centre, NHL-control questionnaire study. RESULTS: In a multivariate model, the following variables had statistically significant adjusted odds ratios (OR) using 95% confidence intervals (95% CI) (a) higher risk: having more than 13 head of swine, raising bison, elk or ostriches, a personal history of cancer, > 4 and < or = 15 years of farm residence and occupational exposure to diesel fuel and exhaust; (b) lower risk: raising cattle and a personal history of measles. CONCLUSIONS: Future multidisciplinary studies of NHL should include a comprehensive review of exposure to animals in sufficient detail to assess etiological mechanisms to explain the putative associations between exposure to farm animals and NHL.

Adult↗

Reliable long-term non-pulsatile circulatory support without anticoagulation.

OBJECTIVE: The Terumo implantable left ventricular assist system (T-ILVAS) consists of a titanium centrifugal pump with a unique magnetically suspended impeller producing continuous (non-pulsatile) flow up to 10 l/min. The interior surface is heparin-coated and there is no purge system. We implanted the device into six sheep to ascertain in-vivo haemodynamic function, mechanical reliability and biocompatibility. METHODS: The T-ILVAS was implanted via left thoracotomy without cardiopulmonary bypass. The inflow cannula was placed in the left ventricular apex and a Dacron outflow graft anastomosed to the descending aorta. All animals recovered well. No anticoagulation (heparin or warfarin) was given after the surgery. Suspension position, motor current, impeller speed and pump flow were continuously monitored and stored by on-line computer. Serial blood samples were collected to determine haematological and biochemical indices of renal function, liver function and haemolysis. All animals were electively euthanized between 3 and 7 months postoperatively. The explanted pumps were examined for mechanical reliability and thrombus formation. Major organs were examined macroscopically and histologically for thromboembolism. RESULTS: All animals appeared completely normal for up to 210 days. At speeds between 1500 and 2000 rev./min the device pumped up to 8 l/min capturing all mitral flow. There were no major complications (pump failure, thromboembolism, haemorrhage, or driveline infection). Indices of haemolysis, liver and renal function remained within normal limits. All pumps were mechanically sound and free from thrombus. One embolus was found in a sectioned kidney. CONCLUSION: The T-ILVAS successfully supported the systemic circulation without anticoagulation for up to 210 days. Mechanical reliability and biocompatibility were demonstrated. Organ function remained within normal limits during continuous non-pulsatile flow.

Animals↗

Does extubation result in haemodynamic instability in patients following coronary artery bypass grafts?

Coronary heart disease and its management continue to be at the centre of Government health policy. The present political climate demands clinical effectiveness and best practice should be established, while maintaining the philosophy of cost-effectiveness and resource management. These directives have led practitioners to question the care of patients following coronary artery bypass surgery, in particular the role of mechanical ventilation and the subsequent act of extubation. A retrospective study of 89 patients who had coronary artery bypass grafts (emergency and elective) was undertaken, to establish if extubation had a significant effect on the haemodynamic status of patients with variable degrees of left ventricular function (19% with poor left ventricular function). The study found that extubation was achieved within a mean time of 4.97 hours following return from surgery. Extubation resulted in a significant increase in heart rate (P = 0.001), as well as a respiratory acidosis (pCO2: P = 0.000; pH: P = 0.000). However, the stability of the patient was not compromised, with neither mean arterial blood pressure (P = 0.825) nor oxygenation levels (P = 0.267) being significantly altered by extubation. On multivariate analysis, the act of extubation had no significant effect on any of the dependent variables. These results suggest that it is not extubation alone that has an impact on the haemodynamic stability of patients following coronary artery bypass grafts, but that this is indeed multifactorial. Therefore extubation is 'safe' practice for patients with varying degrees of left ventricular function following coronary artery bypass grafts. Limitations of the study are acknowledged.

Adult↗

Non-Hodgkin's lymphoma and specific pesticide exposures in men: cross-Canada study of pesticides and health.

Our objective in the study was to investigate the putative associations of specific pesticides with non-Hodgkin's Lymphoma [NHL; International Classification of Diseases, version 9 (ICD-9) 200, 202]. We conducted a Canadian multicenter population-based incident, case (n = 517)-control (n = 1506) study among men in a diversity of occupations using an initial postal questionnaire followed by a telephone interview for those reporting pesticide exposure of 10 h/year or more, and a 15% random sample of the remainder. Adjusted odds ratios (ORs) were computed using conditional logistic regression stratified by the matching variables of age and province of residence, and subsequently adjusted for statistically significant medical variables (history of measles, mumps, cancer, allergy desensitization treatment, and a positive history of cancer in first-degree relatives). We found that among major chemical classes of herbicides, the risk of NHL was statistically significantly increased by exposure to phenoxyherbicides [OR, 1.38; 95% confidence interval (CI), 1.06-1.81] and to dicamba (OR, 1.88; 95% CI, 1.32-2.68). Exposure to carbamate (OR, 1.92; 95% CI, 1.22-3.04) and to organophosphorus insecticides (OR, 1.73; 95% CI, 1.27-2.36), amide fungicides, and the fumigant carbon tetrachloride (OR, 2.42; 95% CI, 1.19-5.14) statistically significantly increased risk. Among individual compounds, in multivariate analyses, the risk of NHL was statistically significantly increased by exposure to the herbicides 2,4-dichlorophenoxyacetic acid (2,4-D; OR, 1.32; 95% CI, 1.01-1.73), mecoprop (OR, 2.33; 95% CI, 1.58-3.44), and dicamba (OR, 1.68; 95% CI, 1.00-2.81); to the insecticides malathion (OR, 1.83; 95% CI, 1.31-2.55), 1,1,1-trichloro-2,2-bis (4-chlorophenyl) ethane (DDT), carbaryl (OR, 2.11; 95% CI, 1.21-3.69), aldrin, and lindane; and to the fungicides captan and sulfur compounds. In additional multivariate models, which included exposure to other major chemical classes or individual pesticides, personal antecedent cancer, a history of cancer among first-degree relatives, and exposure to mixtures containing dicamba (OR, 1.96; 95% CI, 1.40-2.75) or to mecoprop (OR, 2.22; 95% CI, 1.49-3.29) and to aldrin (OR, 3.42; 95% CI, 1.18-9.95) were significant independent predictors of an increased risk for NHL, whereas a personal history of measles and of allergy desensitization treatments lowered the risk. We concluded that NHL was associated with specific pesticides after adjustment for other independent predictors.

Adult↗

First permanent implant of the Jarvik 2000 Heart.

BACKGROUND: Heart failure is a major public-health concern. Quality and duration of life on maximum medical therapy are poor. The availability of donor hearts is severely limited, therefore an alternative approach is necessary. We have explored the use of a new type of left-ventricular assist device intended as a long-term solution to end-stage heart failure. METHODS: As part of a prospective clinical trial, we implanted the first permanent Jarvik 2000 Heart--an intraventricular device with an innovative power delivery system--into a 61-year-old man (New York Heart Association functional class IV) with dilated cardiomyopathy. We assessed the effect of this left-ventricular assist device on both native heart function and the symptoms and systemic characteristics of heart failure. FINDINGS: The Jarvik 2000 Heart sustained the patient's circulation, and was practical and user-friendly. After 6 weeks, exercise tolerance, myocardial function, and end-organ function improved. Symptoms of heart failure have resolved, and continuous decreased pulse-pressure perfusion has had no adverse effects in the short term. There has been no significant haemolysis and no device-related complications. The skull-mounted pedestal is unobtrusive and has healed well. CONCLUSIONS: The initial success of this procedure raises the possibility of a new treatment for end-stage heart failure. In the longer term, its role will be determined by mechanical reliability.

Blood Pressure↗

Surgical and nonsurgical management of lumbar spinal stenosis: four-year outcomes from the maine lumbar spine study.

STUDY DESIGN: A prospective cohort study of patients with lumbar spinal stenosis recruited from the practices of orthopedic surgeons and neurosurgeons throughout Maine. OBJECTIVE: To assess 4-year outcomes for patients with lumbar spinal stenosis treated surgically or nonsurgically. SUMMARY OF BACKGROUND DATA: Surgery for lumbar spinal stenosis has increased dramatically despite the lack of randomized trials comparing surgical with nonsurgical treatments. Long-term evaluation of surgical series has documented deterioration in initial symptomatic improvement, but few studies have compared long-term outcomes of surgical and nonsurgical treatment. METHODS: Eligible, consenting patients had baseline interviews with mailed follow-up questionnaires at 3, 6, and 12 months, then annually thereafter. Clinical data were obtained at baseline from a physician questionnaire. Outcomes included patient-reported symptoms of leg and back pain, functional status, and satisfaction. RESULTS: Of 148 patients with lumbar spinal stenosis initially enrolled, 4-year outcomes were available on 119 patients (80.4%): 67 of 81 (83%) treated surgically and 52 of 67 (78%) treated nonsurgically. The surgically treated patients had more severe symptoms and worse functional status at baseline and better outcomes at 4-year evaluation than the nonsurgically treated patients. After 4 years, 70% of the surgically treated and 52% of the nonsurgically treated patients reported that their predominant symptom, either leg or back pain, was better (P = 0.05). Satisfaction of patients with their current state at 4 years was reported by 63% of the surgically treated and 42% of the nonsurgically treated patients (P = 0.04). Surgical treatment remained a significant determinant of 4-year satisfaction, even after adjustment for other independent predictors (P = 0.001). For the nonsurgically treated patients, there was no significant change in outcomes over 4 years, whereas the initial improvement seen in the surgically treated patients modestly decreased over the subsequent 4 years. CONCLUSIONS: For the patients with severe lumbar spinal stenosis, surgical treatment was associated with greater improvement in patient-reported outcomes than nonsurgical treatment at 4-year evaluation, even after adjustment for differences in baseline characteristics among treatment groups. The relative benefit of surgery declined over time but remained superior to nonsurgical treatment. Outcomes for the nonsurgically treated patients improved modestly and remained stable over 4 years. Determining whether outcomes continue to converge will require longer-term evaluation.

Activities of Daily Living↗

High-pressure suction drainage via a polyurethane foam in the management of poststernotomy mediastinitis.

BACKGROUND: This study was performed to evaluate the effectiveness of suction drainage in the management of early poststernotomy mediastinitis. METHODS: From September 1998 to August 1999, we encountered nine cases of poststernotomy mediastinitis out of 1,209 adult median sternotomies performed in this time period. All these cases were treated with suction drainage, which was recently introduced to our management protocol. From September 1997 to August 1998, we encountered 11 cases of poststernotomy mediastinitis of 1,343 adult median sternotomies. All these cases were initially treated by closed drainage and irrigation, which was our previous first-line management. We used the latter group as historical controls for the evaluation of suction drainage. Lengths of hospitalization were compared using the Mann-Whitney U test, and success versus failure of the primary treatment was compared using the chi2 test. RESULTS: Treatment with the suction dressing resulted in a decreased length of hospitalization after treatment starts (p = 0.02) and a lower rate of treatment failure (p = 0.03). CONCLUSIONS: The use of high-pressure suction drainage is a valuable adjunct in the early management of poststernotomy mediastinitis.

Aged↗

Transoesophageal echocardiography: its role in the management of patients in a district general hospital.

The aim of this study was to assess the value of a transoesophageal echocardiography (TOE) service in a district general hospital (DGH). A series of 151 consecutive cases was analysed retrospectively to determine the relative additional benefit of TOE over transthoracic echocardiography (TTE) in establishing diagnoses and making therapeutic decisions. Of the 151 cases, 140 were suitable for the two procedures to be compared. In 56%, TOE provided useful information for patient management. This consisted of the detection of new major findings (33%) and the exclusion of significant abnormalities (23%), suspected either clinically or by TTE. TOE made a minor clinical contribution in 8% of cases, while in 30% there was concordance between the two studies. Finally, in 6% both examinations were inconclusive. We conclude that TOE has a significant complementary role to TTE in terms of clinical diagnosis and patient management in the DGH setting.

Adolescent↗

Power-frequency electric and magnetic fields and risk of childhood leukemia in Canada.

In a case-control study of childhood leukemia in relation to exposure to power-frequency electric and magnetic fields (EMF), 399 children resident in five Canadian provinces who were diagnosed at ages 0-14 years between 1990 and 1994 (June 1995 in British Columbia and Quebec) were enrolled, along with 399 controls. Exposure assessment included 48-hour personal EMF measurement, wire coding and magnetic field measurements for subjects' residences from conception to diagnosis/reference date, and a 24-hour magnetic field bedroom measurement. Personal magnetic fields were not related to risk of leukemia (adjusted odds ratio (OR) = 0.95, p for trend = 0.73) or acute lymphatic leukemia (OR = 0.93, p for trend = 0.64). There were no clear associations with predicted magnetic field exposure 2 years before the diagnosis/reference date or over the subject's lifetime or with personal electric field exposure. A statistically nonsignificant elevated risk of acute lymphatic leukemia was observed with very high wiring configurations among residences of subjects 2 years before the diagnosis/reference date (OR = 1.72 compared with underground wiring, 95% confidence interval 0.54-5.45). These results provide little support for a relation between power-frequency EMF exposure and risk of childhood leukemia.

Adolescent↗