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Robert Smith

Publications and source records attributed to Robert Smith.

At least 19 recordsLinked to original sources
PubMed2007

Asthma phenotypes.

PURPOSE OF REVIEW: Asthma is a heterogeneous disorder presenting with many phenotypes. Precise phenotypic definition has eluded the medical research community for years, despite recognition of different disease subtypes. Improved phenotypic characterization and knowledge of underlying pathobiology is necessary for linkage of specific genotypes with clinical disease manifestations. RECENT FINDINGS: Phenotyping has been difficult because asthma is likely to be comprised of overlapping syndromes with varying origins and heterogeneous pathobiology. Currently, the field is too reliant on classification by trigger or symptoms. Since genotypic and phenotypic heterogeneity are inherent in asthma, patients presenting with different asthma phenotypes may need tailored therapies. Studies have begun to link genetics with disease mechanism and therapeutic response. As disease etiology, onset, progression and severity vary greatly among patients, however, the relative contribution of genetic factors may be difficult to ascertain. Definition of the full array of complex biological consequences of molecular target modulation is a prerequisite for therapies based on this concept. SUMMARY: The advent of targeted therapies for asthma and clinical trials based on phenotype and genotype have raised interest in more accurate description of asthma phenotypes. Therapies based on phenotypic and genotypic characteristics may be useful in asthma management. A variety of factors, however, must be addressed before such approaches become standard.

Aspirin↗
PubMed2006

Environmental load of Cryptosporidium parvum oocysts from cattle manure in feedlots from the central and western United States.

The first step in assessing the risk of water contamination by Cryptosporidium parvum oocysts from feedlot cattle (Bos taurus) production systems is to quantify the number of C. parvum oocysts present in the fecal material deposited by feedlot cattle. Our primary objective for this project was to estimate the daily environmental load of C. parvum oocysts in fecal material deposited by feedlot cattle from across the central and western USA. Our secondary goal was to genotype isolates of C. parvum from feedlot cattle to help facilitate proper identification of mammalian sources of waterborne C. parvum. Based on 5274 fecal samples from 22 feedlots in seven states (California, Washington, Colorado, Oklahoma, Texas, Nebraska, and South Dakota), we estimated a point prevalence of C. parvum of 0.99 to 1.08% in fecal material from feedlot pens from a wide range of climates and a diverse range of feedlot management systems. On average, fresh fecal material from throughout feedlot systems (recent arrivals to nearing slaughter) contained about 1.3 to 3.6 oocysts/g feces, which roughly translates to about 2.8 x 10(4) to 1.4 x 10(5) oocysts/animal per day.

Animal Feed↗
PubMed2006

Are the headache guidelines useful in therapeutic decisions for primary care physicians, general neurologists, and headache specialists?

The International Headache Society Classification of Headache Disorders has been widely accepted as the gold standard for classification of headache. Initially a research tool, this classification is now increasingly used in the daily practice of headache medicine. Accurate diagnosis is a prerequisite to planning a therapeutic approach. The three commentaries here discuss the use of this tool in the setting of primary care, general neurology, and subspecialty headache medicine. As the Section Editor, I hope these perspectives are helpful to the reader.

Journal Article↗
PubMed2006

Automating arm movement training following severe stroke: functional exercises with quantitative feedback in a gravity-reduced environment.

An important goal in rehabilitation engineering is to develop technology that allows individuals with severe motor impairment to practice arm movement without continuous supervision from a rehabilitation therapist. This paper describes the development of such a system, called Therapy WREX or ("T-WREX"). The system consists of an orthosis that assists in arm movement across a large workspace, a grip sensor that detects hand grip pressure, and software that simulates functional activities. The arm orthosis is an instrumented, adult-sized version of the Wilmington Robotic Exoskeleton (WREX), which is a five degrees-of-freedom mechanism that passively counterbalances the weight of the arm using elastic bands. After providing a detailed design description of T-WREX, this paper describes two pilot studies of the system's capabilities. The first study demonstrated that individuals with chronic stroke whose arm function is compromised in a normal gravity environment can perform reaching and drawing movements while using T-WREX. The second study demonstrated that exercising the affected arm of five people with chronic stroke with T-WREX over an eight week period improved unassisted movement ability (mean change in Fugl-Meyer score was 5 points +/- 2 SD; mean change in range of motion of reaching was 10%, p < 0.001). These results demonstrate the feasibility of automating upper-extremity rehabilitation therapy for people with severe stroke using passive gravity assistance, a grip sensor, and simple virtual reality software.

Adult↗
PubMed2006

Cost effectiveness of extended adjuvant letrozole in postmenopausal women after adjuvant tamoxifen therapy: the UK perspective.

BACKGROUND: MA17 was a randomised placebo-controlled trial of letrozole 2.5 mg/day in 5187 estrogen receptor-positive, 50% node-negative, postmenopausal women (median age 62 years at enrollment) with early breast cancer, post-5 years' adjuvant tamoxifen therapy. The objective of this evaluation was to extrapolate the findings from the MA17 trial to estimate the lifetime cost effectiveness of letrozole in this setting. METHODS: A Markov model was used to estimate the incremental cost per QALY gained with extended adjuvant letrozole versus no therapy. Probabilities of disease progression and death were estimated using data from the MA17 study and other secondary sources. Costs of breast cancer care (letrozole therapy, surveillance, recurrences, terminal care) and treatment of osteoporosis and utilities were derived from literature. A full probabilistic sensitivity analysis was undertaken. The analysis was conducted from the perspective of the UK National Health Service (NHS) and cost estimates reflect 2004 values. All costs and outcomes were discounted at 3.5%. RESULTS: Extended adjuvant letrozole resulted in a gain of 0.36 QALYs per patient (13.66 vs 13.30 with no therapy). These benefits were obtained at an additional expected lifetime cost of 3732 pounds per patient (10,833 pounds letrozole vs 7101 pounds with no therapy). Cost effectiveness was estimated at 10,338 pounds per QALY gained (95% CI 5276, 43,828). The results were robust to sensitivity analyses. CONCLUSION: Five years of letrozole therapy appears to be cost effective from the NHS perspective and should be considered in women with early breast cancer, following tamoxifen adjuvant therapy.

Aged↗
PubMed2006

Vibration of micromachined circular piezoelectric diaphragms.

Electrically and mechanically excited resonances in micromachined circular piezoelectric diaphragms have been investigated. The diaphragm structures were piezoelectric unimorphs consisting of Pb(Zr0.52,Ti0.48)O3 (PZT) films and thermally grown silicon oxide (SiO2) layers. For electrical excitation, ring-shaped interdigitated (IDT) electrodes formed on the top of the PZT layer were used to induce strain in the diaphragms. The diaphragm structures behaved much like circular membranes in which the membrane tension was approximately 206 N/m, at the fundamental modes. For higher modes, the resonance frequencies deviated from the theoretical values due to the finite stiffness of the diaphragms. Under mechanical drive, both symmetric and asymmetric modes were excited. However, for electrical excitation, the symmetric modes were dominant due to the symmetry of the driving IDT electrodes. At a pressure of 727 Torr, the quality factor was approximately 250, and this rose to 2000 at pressures below 1 Torr. When a forward bias was applied to the diaphragm, the membrane tension decreased, but under reverse biases the tension increased. However, because of repoling under reverse biases greater than the coercive field of the PZT film, the achievable increase in the membrane tension was limited. In the diaphragm structure, the nonlinear vibration was governed by geometric nonlinearity rather than material nonlinearity. In addition, evidence of non-180 degrees domain wall motion of the PZT layer in released diaphragms was observed.

Journal Article↗
PubMed2005

Role of fibrinogen-like protein 2 prothrombinase/fibroleukin in experimental and human allograft rejection.

Immune coagulation is a major contributor to the pathogenesis of xenograft rejection, viral-induced hepatocellular injury and cytokine-induced fetal loss syndrome. In this study, we investigated the contribution of the novel gene product, fibrinogen-like protein 2 (fgl2) prothrombinase, in mediating immune injury in experimental and human acute allograft rejection. Using a mouse heterotopic cardiac transplant model, mouse fgl2(mfgl2)/fibroleukin mRNA transcripts and protein were highly expressed in macrophages, CD4- and CD8-positive T lymphocytes, and endothelial cells in rejecting cardiac allografts in association with deposits of fibrin. Although mfgl2-deficient mice rejected allografts at similar rates to littermate controls, survival of grafts from mfgl2-deficient mice were prolonged and deposition of intravascular fibrin was diminished. Treatment of wild-type mice with a neutralizing anti-fgl2 Ab ameliorated histological evidence for allorejection and intravascular fibrin deposition, and resulted in an increase in graft survival. To address further the relevance of fgl2 in acute allograft rejection, we examined kidney biopsies from patients who had undergone renal transplantation. Human fgl2 mRNA transcripts and protein were markedly expressed mainly in renal tubule cells, infiltrating lymphoid cells including macrophages, CD8(+) T cells, mature B cells (plasma cells), and endothelial cells. Dual staining showed fibrin deposition was localized mainly to blood vessels, in the glomerulus and interstitium and the lumen of tubules, and occurred in association with human fgl2 expression. These data collectively suggest that fgl2 accounts for the fibrin deposition seen in both experimental and human allograft rejection and provide a rationale for targeting fgl2 as adjunctive therapy to treat allograft rejection.

Adult↗
PubMed2005

The structural basis of blebbistatin inhibition and specificity for myosin II.

Molecular motors play a central role in cytoskeletal-mediated cellular processes and thus present an excellent target for cellular control by pharmacological agents. Yet very few such compounds have been found. We report here the structure of blebbistatin, which inhibits specific myosin isoforms, bound to the motor domain of Dictyostelium discoideum myosin II. This reveals the structural basis for its specificity and provides insight into the development of new agents.

Animals↗
PubMed2005

Detection and localization of occult lesions using breast magnetic resonance imaging: initial experience in a community hospital.

RATIONALE AND OBJECTIVES: To evaluate the outcome of diagnostic breast MR imaging followed by MR guided needle localization for mammographically and sonographically occult breast lesions in a community-based hospital. MATERIALS AND METHODS: Records of the initial 50 consecutive patients who underwent MR guided needle localizations at our institution from November 2001 to January 2003 were reviewed. Sixty-two lesions were localized by MR and were mammographically and sonographically occult. Pathology following excision was reviewed and correlated with the MR findings. RESULTS: Cancer was present in 15 % (9/62) of lesions or 18 % (9/50) of the women localized. Five of the lesions (56%) were invasive carcinoma and four (44%) were ductal carcinoma in situ (DCIS). High-risk lesions, including atypical ductal hyperplasia (ADH) and atypical lobular hyperplasia (ALH), were found in 6.5 % (4/62) of the lesions, while 3 % (2/62) of the lesions contained lobular carcinoma in situ (LCIS). Cancer plus high risk lesions were found in 15/62 (24%) lesions or 14/50 (28%) of women who underwent biopsy. CONCLUSION: The data in this study supports findings from other studies conducted by large research institutions. In this regard, it is important that community-based hospitals, such as the one operating this breast MR program, can achieve the same positive predictive values as those found in data emanating from academic institutions.

Adult↗
PubMed2005

The utilisation of intraosseous infusion in the resuscitation of paediatric major trauma patients.

Intraosseous lines are a reliable and rapid tool for obtaining vascular access in emergency situations, particularly in children. Their use is recommended when intravenous access cannot be easily secured and there is a need for fluid or pharmacological resuscitation. Training in this technique is included in the Advanced Trauma Life Support (ATLS) and Advanced Paediatric Life Support course (APLS) provider courses. The objective of this study is to analyse the national use of intraosseous lines in paediatric trauma in England and Wales. Data has been collected from the Trauma Audit and Research Network (TARN) group longitudinally over 14 years from 1988 to 2002. From 23,489 paediatric trauma cases, intraosseous lines were used in only 129 patients. Compared with the remainder of the paediatric data, we found that these were the younger (1-6 years), more severely injured patients (higher ISS, lower GCS, higher head, thorax, and abdominal AIS). The mortality of these patients was high at 64% compared with 4% overall. IO line use was greater in general than in Paediatric hospitals, perhaps due to good intravenous access skills in paediatric centres. We recommend that intraosseous line use should be a skill available to everybody involved in paediatric trauma resuscitation, particularly those who may not have refined paediatric intravenous cannulation skills.

Age Distribution↗
PubMed2005

Analysis and outcomes of right lobe hepatectomy in 101 consecutive living donors.

The shortage of deceased organ donors has created a need for right lobe living donor liver transplantation (RLDLT) in adults. Concerns regarding donor safety, however, necessitate continuous assessment of donor acceptance criteria and documentation of donor morbidity. We report the outcomes of our first 101 donors who underwent right lobectomy between April 2000 and November 2004. The cohort comprised 58 men and 43 women with a median age of 37.8 years (range: 18.6-55 years); median follow-up is 24 months. The middle hepatic vein (MHV) was taken with the graft in 55 donors. All complications were recorded prospectively and stratified by grade according to Clavien's classification. Overall morbidity rate was 37%; all complications were either grade 1 or 2, and the majority occurred during the first 30 days after surgery. Removal of the MHV did not affect morbidity rate. There were significantly fewer complications in the later half of our experience. All donors are well and have returned to full activities. With careful donor selection and specialized patient care, low morbidity rates can be achieved after right hepatectomy for living donor liver transplantation.

Adult↗
PubMed2004

Quantifying headache symptoms and other headache features from chart notes.

OBJECTIVES: To describe a method for quantifying headache symptoms/features in family practice charts for patients diagnosed with headache NOS (not otherwise specified, ICD-9: 784) and to determine the share of NOS headache diagnoses with clinical data strongly suggestive of migraine or probable migraine headache. BACKGROUND: Headache is one of the most common pain symptoms that brings patients to a family physician. However, the majority of headache sufferers do not receive a specific headache diagnosis when they visit physicians. METHODS: We examined the chart notes of 454 patients exclusively diagnosed with one or more ICD-9 coded headache NOS diagnoses from July 1, 1995 through December 31, 1999 at a large suburban, university-affiliated practice. We developed a template containing 20 headache items combining International Headache Society diagnostic criteria and additional headache symptoms/features, and decision rules for coding symptoms/features and collected data from patient charts. We then developed decision rules and reclassified NOS headaches into categories strongly suggestive of migraine, probable migraine headache, or other diagnosis. Our main outcome measure is the consistency in the application of decision rules and diagnostic criteria. RESULTS: With this method we estimate 3 in 10 (29%) headache NOS patients may have had migraine (8%) or probable migraine headache (21%). Reclassified migraine visits averaged 6.5 migraine symptoms and reclassified probable migraine headache visits 4.7 migraine symptoms. Logistic regression analysis supports the consistency of diagnostic criteria for classifying headache based on coded symptoms/features--our model correctly predicted 96% of visits. Evidence of physical examination was recorded at 75% of visits suggesting that physician attention is focused on elimination of secondary headache. CONCLUSIONS: We think the use of our rigorous procedures reveals that a substantial amount of migraine and probable migraine headache may be missed in everyday practice. We hope our findings will provide a basis for the development of diagnostic methods more closely suited to the needs of nonspecialists, and contribute to a better standard of care for headache patients seen in primary care practice. Finally, we are hopeful that other researchers will consider using our template and guideline procedures in their efforts to identify diagnostic patterns and study headache and other health problems.

Adult↗
PubMed2004

Q fever outbreak in industrial setting.

An outbreak of Q fever occurred in South Wales, United Kingdom, from July 15 through September 30, 2002. To investigate the outbreak a cohort and nested case-control study of persons who had worked at a cardboard manufacturing plant was conducted. The cohort included 282 employees and subcontractors, of whom 253 (90%) provided blood samples and 214 (76%) completed questionnaires. Ninety-five cases of acute Q fever were identified. The epidemic curve and other data suggested an outbreak source likely occurred August 5-9, 2002. Employees in the factory's offices were at greatest risk for infection (odds ratio 3.46; 95% confidence interval 1.38-9.06). The offices were undergoing renovation work around the time of likely exposure and contained straw board that had repeatedly been drilled. The outbreak may have been caused by aerosolization of Coxiella burnetii spore-like forms during drilling into contaminated straw board.

Case-Control Studies↗
PubMed2004

The ultrasound screen for penetrating truncal trauma.

A prospective blinded pilot study was performed at an urban level 1 trauma center to evaluate the efficacy of ultrasound in ruling out penetrating visceral truncal injury. For 8 months, 49 nonconsecutive patients who presented with truncal gunshot and stab wounds were evaluated by a 10-MHz ultrasound tranducer probe. The deepest muscle bundle and the fascia enveloping it was examined by ultrasound. These images were compared to the equivalent contralateral unaffected side of the patient. All the patients then underwent standard testing to evaluate for potential intracavitary injury. Forty-nine patients with a mean age of 28 years (SD, 8.8) were evaluated by ultrasound. A total of 58 injuries were evaluated of which 37 were stab wounds and 21 were gunshot wounds. Thoracoabdominal and back and flank injuries were the most commonly evaluated injuries. There were 20 true positives, 20 false positives, and 18 true negatives, each with approximately twice as many stab as gunshot wounds. There were no false negatives. The sensitivity and negative predictive value of ultrasound in determining clinically significant truncal visceral injury in penetrating truncal trauma is 100 per cent. The specificity and positive predictive value are both approximately 50 per cent. Ultrasonic examination of the injured abdominal wall layers in truncal penetrating trauma is an excellent screening tool. Simple comparative assessment with the unaffected contralateral side allows a highly sensitive method of decreasing the number of potentially morbid, time consuming, and expensive tests that are currently employed to rule out visceral injury.

Adult↗
PubMed2003

Clinical benefits of neoral C2 monitoring in the long-term management of renal transplant recipients.

BACKGROUND: Cyclosporine monitoring using the 2-hr postdose sample, C2, has been shown to have advantages in monitoring de novo renal transplant recipients. The purpose of this study was to assess cyclosporine exposure, using C2, in stable renal transplant patients previously monitored by C0 to determine the effect of dose reduction on patients with C2 more than 10% above target and the course of those with C2 at and more than 10% below target, whose dose was not modified. METHODS: One hundred and seventy-five patients, three or more months after transplantation, had C2 assessed. The relationship of C2 to C0 and of both to renal function was analyzed by linear regression. Blood pressure, serum creatinine level, and lipids were followed for a mean of 15+/-2.6 months. RESULTS: Eighty-five patients had values more than 10% above target, 42 were within 10% of target, and 48 were more than 10% below target. Cyclosporine dose was reduced in all patients above target. In this group, serum creatinine level was stable overall, but fell significantly in 46 (54%) of 85 from 153+/-55 to 132+/-49 microM. Blood pressure also fell in that group from 135/82 to 131/77. Serum creatinine level was stable in the remaining two groups of patients. CONCLUSIONS: These data suggest that dose reduction in many overexposed patients leads to improvements in renal function and blood pressure. Further study is required to confirm the long-term benefits of this strategy.

Adult↗