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Biomedical subjects

C McArthur

Publications and source records attributed to C McArthur.

18 recordsLinked to original sources
PubMed2001

Il-13 and IFN-gamma: interactions in lung inflammation.

Chronic inflammatory diseases of the lungs, such as asthma, are frequently associated with mixed (Th2 and Th1) T cell responses. We examined the impact of critical Th1 and Th2 cytokines, IFN-gamma and IL-13, on the responses in the lungs. In a mouse model of airway inflammation induced by mixed T cell responses, the number of Th1 (IFN-gamma-positive) cells was found to be negatively correlated with airway hyperreactivity. In these mice, blockade of IL-13 partially inhibited airway hyperreactivity and goblet cell hyperplasia but not inflammation. In contrast, in mice that responded with a polarized Th2 response to the same Ag, blockade of IL-13 inhibited airway hyperreactivity, goblet cell hyperplasia, and airway inflammation. These results indicated that the presence of IFN-gamma would modulate the effects of IL-13 in the lungs. To test this hypothesis, wild-type mice were given recombinant cytokines intranasally. IFN-gamma inhibited IL-13-induced goblet cell hyperplasia and airway eosinophilia. At the same time, IFN-gamma and IL-13 potentiated each other's effects. In the airways of mice given IL-13 and IFN-gamma, levels of IL-6 were increased as well as numbers of NK cells and of CD11c-positive cells expressing MHC class II and high levels of CD86. In conclusion, IFN-gamma has double-sided effects (inhibiting some, potentiating others) on IL-13-induced changes in the lungs. This may be the reason for the ambiguous role of Th1 responses on Th2 response-induced lung injury.

Allergens↗
PubMed2001

Histopathologic analysis of endovascular stent grafts from patients with aortic aneurysms: Does healing occur?

BACKGROUND: Research with animal models has demonstrated tissue healing of endovascular grafts in both native arterial segments and in experimentally created arterial aneurysms. Fundamental to the successful clinical use of endovascular grafts for the treatment of aneurysmal disease is the creation of a permanent hemostatic seal between the graft ends and the arterial wall. Characteristics of this healing process in patients with aneurysmal disease have not been fully studied. In this study, we analyzed the macroscopic and histopathologic changes of the arterial wall after endovascular repair of aortic aneurysms. METHODS: Over a 7-year period, 313 patients were treated with endovascular grafts to exclude arterial aneurysms of the thoracic and abdominal aorta. Of these patients, 11 had their endovascular grafts recovered for analysis. Five graft specimens were recovered during subsequent open aortic surgery. Six grafts were recovered at autopsy after the death of the patient of causes unrelated to the patient's endovascular graft. All specimens were fixed in formalin. Histologic analysis included light microscopy with hematoxylin and eosin and trichrome stains. Well-preserved specimens were selected after light microscopic examination and postfixed in 3% buffered glutaraldehyde for electron microscopy. The aortas from autopsy specimens were removed en bloc and fixed in formalin; representative regions of each graft were sectioned for analysis. Adherence of the graft to the vessel wall was categorized as densely adherent or easily separated after graft explantation. Traction applied to the graft-aortic anastomosis was equal to traction generated by suspending a standardized 2-kg weight. Infrarenal graft specimens were obtained with supraceliac aortic clamping, longitudinal aortotomy, and graft sampling before endograft revision. RESULTS: In eight patients, endograft fixation was found to be firmly adherent to the arterial wall. A translucent film of fibrinous material was consistently seen across the entire luminal surface of the endograft. Light and electron microscopy failed to demonstrate an endothelial layer or organized pseudointima at the graft-artery interface. CONCLUSION: Despite suggestive experimental data regarding endograft healing in animals, minimal graft incorporation was apparent in the stent grafts recovered in this study. A greater emphasis on the construction and mechanism of fixation of endograft attachment systems will be important for long-term device function.

Aged↗
PubMed2001

Endovascular repair of para-anastomotic aneurysms of the aorta and iliac arteries: preferred treatment for a complex problem.

PURPOSE: Standard surgical repair of para-anastamotic aneurysms (PAAs) of the abdominal and thoracic aorta and the iliac arteries has been associated with high morbidity and mortality rates. We reviewed our continuing experience with endovascular repair of these lesions to determine whether this approach is favorable and durable. METHODS: All patients with PAAs of the aorta or iliac arteries who underwent endovascular treatment of their lesions between August 1993 and July 1999 were prospectively followed up, and data on age, previous aortic pathology and surgery, size of PAA, time to diagnosis, and symptoms at presentation were recorded. Preoperative, intraoperative, and postoperative imaging studies were analyzed. All patients had endovascular stent-grafts placed under digital fluoroscopic guidance in the operating room. Data on intraoperative and postoperative complications, mortality, and endoleaks were reviewed. RESULTS: From August 1993 to July 1999, 28 patients (20 men, 8 women) had 35 PAAs of the aorta or iliac arteries. There were 5 thoracic aortic, 12 abdominal aortic, and 18 iliac artery PAAs. Three patients had a contained rupture of their PAA. All patients who had originally undergone reconstruction for occlusive disease had lesions consistent with false aneurysms, whereas 73% of the aortic or iliac PAAs in patients originally treated for aneurysm disease appeared to be true aneurysms. Thirty-four of 35 PAAs were successfully excluded with stent-grafts (97%). There was one death at 30 days (3.6%) in a patient who was successfully treated endovascularly for a contained rupture of a thoracic PAA. There were four major postoperative complications (14.2%) in the 28 patients who were treated. One patient had continued perfusion of a thoracic aortic PAA (type I endoleak). The in-hospital length of stay after endovascular repair of PAA was 4 days (range, 1-18 days). The mean follow-up period was 21 months (range, 1-68 months). CONCLUSION: Endovascular repair of aortic and iliac artery PAAs is technically feasible and provides a high rate of lesion exclusion. Morbidity and mortality rates appear lower than those reported for open surgical repair. These patients can typically be discharged by the second postoperative day. Endovascular therapy for stable ruptured PAAs can be successfully performed and should be considered as an option only when appropriate devices and expertise are available. For uncomplicated PAAs of the aorta and iliac arteries, endovascular therapy may be more favorable than surgical repair.

Adult↗
PubMed1999

Cost comparison of antibacterial therapies for serious infections. A New Zealand 3-hospital study.

OBJECTIVE: The first aim was to identify and determine the economic costs of the regimens currently used in 3 New Zealand hospitals in the treatment of bacterial infections in haematology patients with febrile neutropenia and in intensive care patients with severe infections. The second was to develop a spreadsheet-based decision analytic model for use by hospital decision-makers as an aid in evaluating the comparative cost of drug regimens. DESIGN AND SETTING: The research utilised time and motion and microcosting techniques. The analytical perspective adopted for the study was that of a hospital administrator or clinical manager. PATIENTS AND INTERVENTIONS: Patients were eligible for inclusion in the study if either they were treated with the imipenem/cilastatin monotherapy, or could have been treated with this regimen. The final analysis considered 360 patient-treatment days and 8 antibacterials. MAIN OUTCOME MEASURES AND RESULTS: Drug acquisition cost ranged from 4.52 New Zealand dollars ($NZ; 1997 values) per patient-treatment day for gentamicin to $NZ104.81 for imipenem. The cost per patient-treatment day (when other cost components such as fluid additives, giving sets and needles were added) ranged from $NZ8.75 for gentamicin to $NZ129.12 for tazobactam. Drug acquisition cost, as a percentage of total drug preparation and administration cost, ranged from 52% for gentamicin to 93% for piperacillin. Giving sets and intravenous (i.v.) fluids were found to be important cost items when they were required specifically for the treatment regimen. There was a mean monitoring rate of 0.40 at a cost of $NZ6.41 per patient-treatment day for gentamicin. It was estimated that nephrotoxicity could add between $NZ23 and $NZ43 per day to the cost of aminoglycoside treatment. CONCLUSIONS: Although the small sample sizes of the study mean that results should be regarded as indicative rather than conclusive, there were sufficient information to construct a working model and show how the total cost of an antibacterial regimen could be evaluated in practical terms. The important cost drivers were found to be drug cost, the use of fluids and giving sets, and monitoring.

Anti-Infective Agents↗
PubMed1997

Indirect calorimetry.

Indirect calorimetry can be a useful tool to define nutritional status, determine nutritional requirements, and assess response to nutritional interventions. Measurements of oxygen consumption and carbon dioxide production may be used to determine cardiac output and work of breathing, and estimate the components of minute ventilation. An understanding of the potential technical and physiological pitfalls is necessary to obtain meaningful and useful information.

Acid-Base Equilibrium↗
PubMed1994

Role of endothelium-derived nitric oxide in stimulation of Na(+)-K(+)-ATPase activity by endothelin in rabbit aorta.

An endothelium-derived factor with the properties of nitric oxide (NO) has recently been implicated in the regulation of basal Na(+)-K(+)-adenosinetriphosphatase (ATPase) activity in vascular smooth muscle. To determine whether this factor also plays a role in the stimulation of ouabain-sensitive (OS) 86Rb uptake by specific agonists, studies were carried out using rabbit aortic rings. In endothelium-intact rings incubated for 3 h with Krebs-Henseleit solution containing 5.5 mM glucose, endothelin (ET) caused a concentration-dependent increase in OS 86Rb uptake (maximal increase = 205%, with 100 nM ET). Incubation with phenylephrine (Phe; 0.1 and 1 microM) or phorbol 12,13-dibutyrate (PDBu; 0.1 microM), under the same conditions, increased OS 86Rb uptake by 128, 144, and 140%, respectively. Removal of endothelium before incubation decreased the ability of ET to stimulate OS 86Rb uptake by 38-45%, but it did not diminish the stimulation of OS 86Rb uptake by Phe or PDBu. An increase in the concentration of glucose from 5.5 to 44 mM diminished ET-stimulated OS 86Rb uptake by 50% in endothelium-intact rings but had no effect on Phe- or PDBu-induced increases in OS 86Rb uptake. Addition of the NO synthase inhibitor NG-monomethyl-L-arginine (L-NMMA; 0.3 mM) to the medium decreased ET-stimulated OS 86Rb uptake by 40%. Guanosine 3',5'-cyclic monophophate (cGMP) formation in endothelium-intact rings was also increased (65%) by ET but not by Phe or PDBu. The increase in cGMP by ET was totally inhibited by L-NMMA or endothelium denudation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Stimulation of vascular Na(+)-K(+)-ATPase activity by nitric oxide: a cGMP-independent effect.

An endothelium-derived factor with the properties of nitric oxide (NO) has been implicated in the regulation of Na(+)-K(+)-adenosinetriphosphatase (ATPase) activity in vascular smooth muscle. To examine this phenomenon further and to explore its modulation by guanosine 3',5'-cyclic monophosphate (cGMP), studies were carried out in the isolated rabbit aorta. Incubation of endothelium-denuded rings with NO (1 microM) or sodium nitroprusside (SNP, 10 microM) caused a time-dependent increase in ouabain-sensitive (OS) 86Rb uptake with the maximal stimulation (approximately 170%) seen after 20 min. In contrast, increases in cGMP concentration caused by NO and SNP (40- and 20-fold increases, respectively) were transient, with peak values observed after 2 min and significantly lower values by 10 min. The ability of NO or SNP to increase OS Rb uptake in endothelium-denuded rings was not mimicked by incubation with 8-bromo- or dibutyryl-cGMP or increases in cGMP caused by treatment with the phosphodiesterase inhibitor isobutylmethylxanthine. Depletion of intracellular cGMP levels by the guanylate cyclase inhibitor LY83583 also did not alter OS Rb uptake. SNP-stimulated OS Rb uptake was not inhibited by LY83583 in endothelium-denuded rings; however, it was completely prevented by the Na(+)-H+ exchange inhibitors amiloride and ethylisopropylamiloride. The results suggest that NO stimulates Na(+)-K(+)-ATPase activity in rabbit aorta by a mechanism independent of its ability to increase the intracellular cGMP concentration. They also suggest that NO may stimulate Na(+)-K(+)-ATPase activity secondary to increases in Na(+)-H+ exchange.

Amiloride↗
PubMed1994

The medial tibial syndrome. The role of surgery.

Among authors over the past 35 years, medial tibial syndrome, or "shin splints," has been interpreted to mean many different things. We present a review of the literature to attempt to ascribe one definition to this clinical entity, and to clearly define its symptoms, signs, pathophysiology, biomechanics, and treatment. In addition, we describe our results with five patients whose seven affected limbs eventually required surgery for this condition, and we compare them to the results in the literature.

Adolescent↗
PubMed1991

Validation of a clinical antisaccadic eye movement test in the assessment of dementia.

The ability to generate antisaccades (eye movements deliberately made in the direction opposite to that of a visual stimulus) may be used to assess central nervous system function in a variety of neurologic and psychiatric disorders. However, the usefulness of this paradigm in clinical practice is limited by the need for an oculographic laboratory. We describe a clinical version of such an antisaccadic task and present normative data from 332 subjects. We also examined clinical antisaccades and cognitive performance in 30 patients with Alzheimer's disease, five patients with Huntington's disease, and 12 patients with pseudodementia. In Alzheimer's disease, error rates in the clinical antisaccadic test correlated well with those from a laboratory-based antisaccadic task measured on the same day by infrared oculography, confirming that the clinical antisaccadic test is a valid analog of the more sophisticated laboratory paradigms. Clinical antisaccadic error rates correlated strongly with the severity of dementia in Alzheimer's disease, and correlations with cognitive performance suggested that the clinical antisaccadic test may have some specificity for frontal lobe dysfunction. Patients with pseudodementia had normal clinical antisaccadic error rates, and the test may therefore be of use in differentiating dementia from pseudodementia. This clinical antisaccadic test provides a simple, reliable, and inexpensive quantitative clinical tool that is of value in the assessment of disturbances of higher cortical function.

Adolescent↗
PubMed1989

Awake inspiratory airway occlusion in normal humans is followed by hyperpnea and hypocapnia.

The ventilatory response following 15 seconds of inspiratory airway occlusion at functional residual capacity (FRC) was studied in nine normal supine awake subjects. Expired minute ventilation (VE), CO2 output (VCO2), tidal volume (VT), and end-tidal PCO2 (PETCO2) were measured on a breath-by-breath basis. Alveolar PCO2 rose 5.6 mm Hg during the apnea (P less than 0.001). Ventilation rose 10.8 L/min on the first breath following apnea and remained elevated above control measurements for five breaths (P less than 0.05). The persistent hyperpnea was due to an increase in tidal volume and was associated with alveolar hypocapnia for 6 breaths or 30 sec (P less than 0.05) and an increase in CO2 output for 4 breaths (P less than 0.05). Changes in end-tidal PCO2 correlated with excess CO2 output relative to control measurements immediately prior to airway occlusion (P less than 0.03). After 15 sec airway occlusion at FRC, there is alveolar hypercapnia with a 2.6-fold first breath rise in ventilation. Persistent alveolar hyperventilation lasting 30 sec following airway occlusion may be due to delays in central chemoreceptor response or an afterdischarge phenomenon. This overshoot hypercapnia following airway occlusion may have some relevance to the development of central apneas following obstructive apnea episodes.

Adolescent↗
PubMed1989

[High-resolution eye movement recording in the assessment of neurologic complications in HIV-1 infection].

HIV-1 related brain disease gives rise to widespread eye movement abnormalities that include impairment of fixation, saccadic speed and accuracy, antisaccadic generation and smooth pursuit function. Quantitative high resolution recording of eye movements is a valuable, non-invasive technique both for measuring the severity and progression of the AIDS dementia complex and the early detection of neurologic dysfunction in asymptomatic HIV-seropositive subjects or in patients with AIDS. In particular, it may be of use in neurologically at-risk patients requiring antiviral therapy and in monitoring the neurologic responses to such treatment.

AIDS Dementia Complex↗