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Biomedical subjects

C Stewart

Publications and source records attributed to C Stewart.

At least 19 recordsLinked to original sources
PubMed2006

Muromonab-CD3 (Orthoclone OKT3), methylprednisolone and cyclosporine for acute graft-versus-host disease prophylaxis in allogeneic bone marrow transplantation.

We report the results of a prospective non-randomized phase II study of Muromonab-CD3 (Orthoclone OKT3), an anti-CD3 monoclonal antibody, with methylprednisolone (MP) and cyclosporine (CSA) for acute GVHD (aGVHD) prophylaxis in 22 hematologic malignancy patients. OKT3 was given at 0.1 mg/kg/day with a maximum dose of 5 mg/day. Initial MP dose was 1000 mg before OKT3, with subsequent doses at 1 mg/kg/day before each OKT3 infusion with a planned taper beginning at day +28. CSA (3 mg/kg/day) was given as a continuous infusion at day -1 and adjusted to maintain serum levels between 250 and 399 ng/ml. Allogeneic BMT donors were HLA-matched siblings (n = 17), single HLA-mismatched-related (n = 1) and HLA-matched unrelated (n = 4). All patients achieved neutrophil engraftment at a median 11 days (range, 8-25 days). By intent-to-treat, the cumulative incidence of grade II-IV aGVHD was 33% (95% CI 13-53%) at a median 26 days post-BMT (range, 14-84 days). Chronic GVHD developed in 11/12 evaluable patients. Eight patients (36%) developed OKT3 first dose reactions; no cases of post-transplant lymphoproliferative disorder were observed. OKT3 depleted peripheral CD3+ cells in vivo as measured by flow cytometry. OKT3+MP+CSA combination is moderately effective aGVHD prophylaxis, however, it is unlikely to be superior to CSA+MTX.

Adolescent↗
PubMed2005

Rituximab in combination with fludarabine chemotherapy in low-grade or follicular lymphoma.

PURPOSE: To evaluate the safety and efficacy of fludarabine plus rituximab in treatment-naive or relapsed patients with low-grade and/or follicular non-Hodgkin's lymphoma. PATIENTS AND METHODS: This was an open-label, single-arm, single-center phase II study enrolling 40 patients. During the first week of the study, patients received two infusions of rituximab 375 mg/m2 administered 4 days apart. Seventy-two hours after the second infusion of rituximab, patients received the first of six cycles of fludarabine chemotherapy (25 mg/m2/d for 5 days on a 28-day cycle). Single infusions of rituximab were administered 72 hours before the second, fourth, and sixth cycles of fludarabine, and two infusions of rituximab were given 4 weeks after the last cycle of fludarabine. Treatment duration was 26 weeks. RESULTS: An overall response rate of 90% (80% complete response rate) was achieved in the intent-to-treat population. Similar response rates were seen in treatment-naive and previously treated patients. The median duration of response has not been reached at 40+ months. The median follow-up time in this study is 44 months (range, 15 to 66 months). In patients positive for the 14;18 translocation in blood and/or marrow at enrollment, molecular remission was achieved in 88% of cases, with patients remaining negative for up to 4 years to date. Hematologic toxicity was manageable, and except for a 15% incidence of herpes simplex/zoster infections, infectious complications were rare. Nonhematologic toxicities were minimal. CONCLUSION: Rituximab plus fludarabine was well tolerated and associated with an excellent complete response rate, including molecular remissions, in patients with low-grade or follicular lymphoma.

Adult↗
PubMed2005

Skeletal and cardiac muscle defects in a murine model of Emery-Dreifuss muscular dystrophy.

Previous histological findings, physiological data, and behavioral observations on the A-type lamin knockout mouse (Lmna(-/-)) suggest that important aspects of this model resemble the human Emery-Dreifuss muscular dystrophy (EDMD) phenotype. The main goal of our experiments was to study skeletal and cardiac muscle function in this murine model to obtain the semiquantitative data needed for more detailed comparisons with human EDMD defects. Measurements of the mechanical properties of preparations from two different skeletal muscle groups, the soleus and the diaphragm, were made in vitro. In addition, records of the electrocardiogram, and measurements of heart rate variability were obtained; and phasic contractions (unloaded shortening) of enzymatically isolated ventricular myocytes were monitored. Soleus muscles from Lmna(-/-) mice produced less force and work than control preparations. In contrast, force and work production in strips of diaphragm were not changed significantly. Lead II electrocardiograms from conscious, restrained Lmna(-/-) mice revealed slightly decreased heart rates, with significant prolongations of PQ, QRS, and 'QT' intervals compared with those from control recordings. These ECG changes resemble some aspects of the ECG records from humans with EDMD; however, the cardiac phenotype in this Lmna(-/-) mouse model appears to be less well-defined/developed. Ventricular myocytes isolated from Lmna(-/-) mice exhibited impaired contractile responses, particularly when superfused with the beta-adrenergic agonist, isoproterenol (1 microM). This deficit was more pronounced in myocytes isolated from the left ventricle(s) than in myocytes from the right ventricle(s). In summary, tissues from the Lmna(-/-) mouse exhibit a number of skeletal and cardiac muscle deficiencies, some of which are similar to those which have been reported in studies of human EDMD.

Animals↗
PubMed2004

Receptor of advanced glycation end product (RAGE) expression in the minor salivary glands of patients with Sjögren's syndrome: a preliminary study.

OBJECTIVE: Receptor for advanced glycation end product (RAGE) is a cell-surface receptor with ligands capable of inducing proinflammatory responses in autoimmunity. We investigated the immunohistochemical expression and immunoblotting of RAGE in labial salivary glands from Sjögren's syndrome (SS) patients. MATERIAL AND METHODS: Ten minor salivary glands from SS and 15 from normal salivary tissue adjacent to mucocele were stained immunohistochemically using an antibody to RAGE. Immunoblotting was performed on four SS biopsies and four controls from normal gland. RESULTS: Immunohistochemistry showed all sections positive for RAGE. The SS sections did not statistically differ from controls. In immunoblotting, SS samples expressed approximately 100% more RAGE than controls [probability (p)<0.03, Student's t-test]. CONCLUSIONS: RAGE is present in the labial salivary glands of both normal and SS patients, with preliminary data suggesting over-expression in SS tissues. The role of RAGE in the pathogenesis of SS has yet to be determined.

Aged↗
PubMed2004

A laser speckle imaging technique for measuring tissue perfusion.

Laser Doppler imaging (LDI) has become a standard method for optical measurement of tissue perfusion, but is limited by low resolution and long measurement times. We have developed an analysis technique based on a laser speckle imaging method that generates rapid, high-resolution perfusion images. We have called it laser speckle perfusion imaging (LSPI). This paper investigates LSPI output and compares it to LDI using blood flow models designed to simulate human skin at various levels of pigmentation. Results show that LSPI parameters can be chosen such that the instrumentation exhibits a similar response to changes in red blood cell concentration (0.1%-5%, 200 microL/min) and velocity (0-800 microL/min, 1% concentration) and, given its higher resolution and quicker response time, could provide a significant advantage over LDI for some applications. Differences were observed in the LDI and LSPI response to tissue optical properties. LDI perfusion values increased with increasing tissue absorption, while LSPI perfusion values showed a slight decrease. This dependence is predictable, owing to the perfusion algorithms specific to each instrument, and, if properly compensated for, should not influence each instrument's ability to measure relative changes in tissue perfusion.

Algorithms↗
PubMed2004

Long uvula: an unusual cause of chronic cough.

Chronic cough is a distressing symptom for patients and parents in paediatric practice. Investigations of the child with persistent cough can be simple or complex depending on the underlying cause. There are some unusual reasons for chronic cough, which need to be kept in mind when investigating the cause. A case of a long, floppy uvula causing chronic cough through mechanical irritation of upper airway is reported.

Chronic Disease↗
PubMed2003

Effect of PSC 833, a potent inhibitor of P-glycoprotein, on the growth of astrocytoma cells in vitro.

Malignant astrocytomas have been found to express P-glycoprotein (Pgp, mdr1 gene product). It was hypothesized that in addition to conferring multidrug resistance, Pgp is intimately associated with the development of astrocytomas. Accordingly, we studied the effect of PSC 833 (PSC, Novartis), a potent inhibitor of Pgp, on the growth of Pgp-expressing astrocytoma cells. The results showed that in all the cell lines tested, PSC (10-60 microM) inhibited the growth as well as induced cell death. Cells exposed to PSC exhibited DNA ladder characteristic of apoptosis. PSC-induced cell death could be reversed by Z-VAD-fmk, a general caspase inhibitor, indicating that PSC-induced cell death was characteristic of caspase-mediated apoptosis. These results suggest a novel therapeutic strategy in the treatment of malignant astrocytomas by inhibitors of Pgp.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2003

Endoscopic laser imaging of tissue perfusion: new instrumentation and technique.

BACKGROUND AND OBJECTIVES: New instrumentation, based on a previously established laser speckle perfusion imaging (LSI) technique is evaluated for its ability to capture and generate blood flow images during endoscopic surgery. STUDY DESIGN/MATERIALS AND METHODS: Investigations are detailed in an in-vitro blood flow model simulating physiological properties of vascularized tissue, and in-vivo in rabbit joint capsule tissue. RESULTS: In-vitro measurements showed a linear response of the instrument to blood flow in the range of 0-800 microl/minute, where data points were significantly correlated with an r(2) value of 0.96. In-vivo measurements showed a 58.7% decrease to the medial collateral ligament during occlusion of the femoral artery. CONCLUSIONS: Blood flow images demonstrate that the endoscopic LSI technique is capable of measuring relative tissue blood flow changes at high resolutions and rapid response times and incorporates well with endoscopic surgeries.

Animals↗
PubMed2003

IGF-1 and insulin receptor expression in the minor salivary gland tissues of Sjögren's syndrome and mucoceles--immunohistochemical study.

OBJECTIVE: To investigate the expression of IGF-1 receptors and insulin receptors on the minor salivary gland (MSG) tissues of patients diagnosed with Sjögren's syndrome (SS) and normal salivary gland tissue surrounding mucoceles. SUBJECTS AND METHODS: Five MSG tissue sections from SS and seven from mucocele patients were stained immunohistochemically using antibody to IGF-1 receptor and insulin receptor in a horse radish peroxidase and DAB system. RESULTS: The expression of the insulin receptor was increased in the SS sections compared with controls, while the insulin-like growth factor-1 receptor was more intensely expressed in the controls. CONCLUSION: The presence of differential expression of receptors for IGF and insulin might suggest a possible role of these growth factors in the pathogenesis of SS.

Aged↗
PubMed2002

Comparison of laser speckle and laser Doppler perfusion imaging: measurement in human skin and rabbit articular tissue.

Laser Doppler perfusion imaging (LDI) is currently used in a variety of clinical applications, however, LDI instruments produce images of low resolution and have long scan times. A new optical perfusion imager using a laser speckle measurement technique and its use for in vivo blood flow measurements are described. Measurements of human skin and surgically exposed rabbit tissue made using this instrument were compared with a commercial laser Doppler perfusion imaging instrument. Results from blood flow measurements showed that the laser speckle imager measured an 11-67% decrease in blood flow under arterial occlusion. Under similar conditions, the laser Doppler imager measured blood flow decreases of 21-63%. In comparison with LDI, it was observed that the higher temporal resolution of the laser speckle imager was more sensitive to measuring the hyperaemic response immediately following occlusion. This in vivo study demonstrated some of the several advantages laser speckle imaging has over conventional LDI, making the new instrument more versatile in a clinical environment.

Animals↗
PubMed2002

An EMG-based, muscle driven forward simulation of single support phase of gait.

This paper describes the process used to generate lower limb kinematics during single limb stance phase of gait, using musculoskeletal modelling, muscle driven forward simulation and gradient based optimisation techniques (including design of experiment techniques). Initial inputs to the forward simulation process were the normalised quantified muscle activation patterns of 22 muscles, and the initial segmental configuration (both angles and angular velocity) derived from Winter (The biomechanics and motor control of human gait, 1987, University of Waterloo Press, pp. 1-72). Two distinct musculoskeletal models (one including 6 DOF, the other 7 DOF) were defined and a muscle driven forward simulation was implemented.A series of optimisation sequences then were executed to modify the muscle activation patterns and initial segmental configuration, until the system output of the forward simulation approximated the angle data reported by. The accuracy and effectiveness of the analysis sequence proposed and the model response obtained using two distinct musculoskeletal models were verified and analysed with respect to the kinesiology of normal walking.

Biomechanical Phenomena↗
PubMed2002

The assessment and management of strabismus and amblyopia: a national audit.

AIMS: To determine what systems are in place within ophthalmic services for the assessment and management of children suspected of having amblyopia and strabismus. To find out what methods are used for the assessment of these children. METHODS: A questionnaire-based study auditing 288 orthoptic departments in the UK. RESULTS: Responses were received from 75% orthoptic departments. Most hospitals employ more than one system for the assessment of strabismus and amblyopia, which is generally dependent on route of referral. These include 'orthoptic assessment without refraction' (66%), 'combined orthoptist and ophthalmologist assessment' (66%), while 22% have an entirely orthoptist/optometric system. Ophthalmologists are involved in the initial assessment in 145 units (67%), whereas some units involve an ophthalmologist only if response to treatment is poor (15%), or if surgery is required (6%). Fourteen per cent of units reviewed all children, with discharge criteria being based on normal visual acuity (52%), accurate visual acuity (39%) and a normal orthoptic assessment (42%). Seventy-six per cent of units review some children, commonly as a result of family history (55%), parental concern (43%), poor co-operation (30%) and young age (72%). In the absence of squint or amblyopia children are discharged at the first visit, in only 8% of units. There is considerable variation in the tests used to assess visual acuity. LogMAR-based tests (eg EDTRS) are not routinely used in 75% of units. CONCLUSION: Different systems exist for the assessment and management of squint and amblyopia across the country. While much of this variation is to be expected given their possible aetiologies, some could be reduced to produce a more cohesive service. There is also considerable scope for rationalising the tests used to screen infants and children for amblyopia and strabismus.

Amblyopia↗
PubMed2002

Elastin distribution in the myometrial and vascular smooth muscle of the human uterus.

Magnetic resonance imaging and transvaginal ultrasonography in women of reproductive age suggest that the myometrium consists of inner and outer layers. It was hypothesized that these structural and functional differences in the myometrium might be associated with a variation in elastin distribution. Fifty-one hysterectomy specimens representing all phases of the normal menstrual cycle were studied by immunocytochemistry, orcein staining and image analysis. Elastin was present within the outer myometrial smooth muscle, but was less widely distributed in the inner smooth muscle. Immunoreactivity and staining were observed in the myometrial arteries and arterioles and within the basal portions of endometrial arterioles. Elastin was also present in perivascular tissue, particularly near the large vessels. More extravascular (i.e. perivascular and smooth muscle) elastin was present in the outer myometrium in all cases, although no distinct layering was observed. Semi-quantitative analysis of the elastin distribution in 11 full thickness specimens demonstrated a decreasing gradient from outer to inner myometrium rather than distinct layering. Contrary to previous reports, these data suggest that the external region of the myometrium is more elastic than the inner region and that elastin is found throughout the arteriolar tree of the human uterus.

Elastin↗
PubMed2001

Assessing competence to refuse medical treatment.

Doctors have a duty to ensure that patients in their care who refuse medical treatment are competent to do so. Doctors who comply with an incompetent patient's refusal of treatment risk harm to the patient and are breaching their duty of care. On the other hand, doctors who treat a competent patient against the patient's will violate his or her autonomy and commit a battery. The test of competence is a legal one, with the courts being the final arbiters in cases of doubt. Assessment of competence involves a three-step process of determining whether the patient (a) can comprehend and retain relevant information, (b) believes the information, and (c) can weigh the information in the balance and arrive at a choice. Asking patients a few simple questions can help doctors assess their competence.

Adult↗
PubMed2001

Cholinergic modulation of covert attention in the rat.

RATIONALE: Nicotine is known to facilitate attentional processing, but its role in processing spatial and non-spatial cues is not well established in rodents. OBJECTIVE: These experiments tested the hypothesis that nicotine facilitates the orienting of attention in space but has no effect on non-spatial cues and that the benefits are blocked by the nicotinic antagonist mecamylamine. METHODS: Eight male rats were trained to insert their noses in an opening, which triggered the presentation of cue and target lights in a modified covert orienting task. Four types of trials were presented: valid cues (cue and target lights on the same side of the nose hole), invalid cues (cue and targets on opposite sides), double cues (both cue lights illuminated, target on either side), and no cue (cue lights omitted, targets on either side). The reaction time required to withdraw the nose from the fixation hole (RT) and the time for the rat to move to the feeder (MT) were measured. RESULTS: Nicotine decreased all RTs in a dose-dependent manner but significantly lowered the invalid cue RTs and the validity effect (invalid-valid cue RT). Mecamylamine slowed RTs in a dose-dependent fashion and reduced the validity effect by significantly slowing the valid cue RTs. With mixtures of a fixed strength of nicotine and an increasing dose of mecamylamine, RTs showed nicotine-like effects at low doses and mecamylamine-like effects at high doses. Neither of these drugs had a major effect on non-orienting trials (double and no cue RTs), and the alerting effect (no cue RTs-double cue RTs). CONCLUSIONS: Taken together with recent work in humans and non-human primates, these results suggest that the nicotinic cholinergic modulation of visual covert orienting is conserved across species despite different ecological niches.

Animals↗
PubMed2001

Disseminated intravascular coagulation (DIC).

Disseminated intravascular coagulation (DIC) is a condition that is seen in critical care areas in association with a number of precipitating conditions. DIC is often described as a paradoxical disease process of concurrent haemorrhage and thrombus formation, resulting in a range of clinical manifestations related to end organ ischaemia. This article will discuss the coagulation cascade as a basis for understanding the aetiology and pathophysiology of DIC. The discourse surrounding medical treatment will be highlighted to enable bedside nurses to understand the divergent orders they may receive from physicians for different patients. Management of the patient experiencing DIC will be approached from a multidisciplinary focus, as well as highlighting the specific nursing considerations and alternatives from an independent focus.

Disseminated Intravascular Coagulation↗