PubMed Health⌕ Search

Biomedical subjects

R Hsu

Publications and source records attributed to R Hsu.

At least 19 recordsLinked to original sources
PubMed2006

Magnetic resonance spectroscopy for measuring the biodistribution and in situ in vivo pharmacokinetics of fluorinated compounds: validation using an investigation of liver and heart disposition of tecastemizole.

BACKGROUND AND OBJECTIVE: The study of biodistribution and in situ pharmacokinetics is a challenging, but sometimes very important, aspect of premarketing characterization of drugs. We aimed to develop a non-invasive fluorine magnetic resonance (MR) spectroscopic method for the absolute quantitation of a mono-fluorinated compound and of its metabolites in the heart and liver of healthy subjects for this purpose. METHOD: We used fluorine MR spectroscopy (MRS) at 4 T (Tesla) and external standardization in an open label multiple-dose study. Twenty-three healthy adult subjects were enrolled in the study. The surface coil localized fluorine MR spectrum was monitored in the heart and liver at baseline and after oral administration of multiple doses of tecastemizole. Steady-state measurements were made at set time points that depended upon dose, and washout measurements were made only on subjects in which in vivo fluorine signal was observed. RESULTS AND DISCUSSION: At 4 T, under the given experimental conditions, the method had a lower limit of quantitation (LLOQ) of about 2.6 microm and a limit of detection (LOD) of about 0.3 microm for solution state samples (linewidth approximately 15 Hz). The measurement reproducibility was 6.4% using a 50 microm phantom. The effect of MR operator and spectral analyst on the calculated calibration curve slope was small, with inter-rater correlation coefficients of 0.999 and 0.998 respectively. MR signal from fluorine-containing tecastemizole-related moieties was observed in situ only at day 8 in the liver of three of five subjects dosed at 270 mg/day. The average in situ concentration was estimated to be 58+/-22 microm, with an average test-retest reproducibility of 216%. Extrapolating the in vitro results to human measurements, with an approximate linewidth of 250 Hz, predicts in situ LOD and LLOQ values of approximately 6 and 44 microm respectively. However, the human study had a fluorine MRS LOD of approximately 20 microm. The decrease in sensitivity and the increase in variability of the in vivo, in situ measurements compared with the validation study most likely arose from coil placement and incomplete rephasing of the MR signal by the respiratory phase compensation method. CONCLUSION: The measured concentrations were the lowest ever recorded for a multi-dose exogenous mono-fluorinated compound in the human liver using a validated fluorine MR quantitation method. The proposed non-invasive MR method for studying the biodistribution and in situ pharmacokinetics of mono-fluorinated compounds in the liver and heart should have broader application to the development of non-invasive biomarkers.

Adult↗
PubMed2006

Establishing a rural Emergency Medical Retrieval Service.

In 2004 the Argyll and Clyde health board established the Emergency Medical Retrieval Service to support its rural community hospitals. This article describes both why the service was established and its aims. This service covers a geographically extensive area, with approximately 85,000 people living in remote locations. Rural general practitioners in six community hospitals provide initial patient assessment and resuscitation. Providing emergency care and safe transfer of seriously ill and injured patients presenting to these community hospitals is a significant challenge. All parties involved felt that there was a need to provide a service to transport critically ill and injured patients from these remote locations to definitive care. The idea of the team is to bring the resuscitation room to the patient in the rural setting. With this aim and in order to implement the Intensive Care Society guidelines for the transport of critically ill patients, it was decided that consultants in Emergency Medicine and Anaesthetics with an interest in critical care would staff the service medically. This service is unique within the UK and the authors aim to report our findings from ongoing research and audit in future papers.

Air Ambulances↗
PubMed2002

Blood flow and red blood cell deformation in nonuniform capillaries: effects of the endothelial surface layer.

OBJECTIVE: A theoretical model is used to examine the mechanics of red blood cell (RBC) motion in nonuniform capillaries. The model includes effects of the endothelial surface layer (ESL), which is a layer of macromolecules adjacent to the endothelium and which impedes plasma flow. METHODS: The motion of an RBC traversing a capillary with diameter varying sinusoidally between 5.4 microm and 7.4 microm is simulated numerically. The ESL is assumed to be 0.7-microm wide and deformable. Axisymmetric RBC shapes are assumed. Lubrication theory is used to analyze the motion of plasma around the RBC and through the ESL. RESULTS: In a nonuniform capillary with no ESL, moving RBCs undergo large transient deformations and predicted flow resistance is substantially higher than in a uniform capillary with the same mean diameter. The presence of a deformable ESL reduces the transient fluid shear stresses and deformations experienced by RBCs traversing a nonuniform capillary. With an ESL, the increase in flow resistance resulting from nonuniformity is less than twofold versus three- to fourfold with no ESL in vessel geometries with the same ESL-free luminal region. CONCLUSIONS: The presence of the ESL reduces the impact of capillary irregularity on flow resistance and may protect RBCs traversing irregular capillaries from damage due to large, rapidly fluctuating external stresses.

Capillaries↗
PubMed2001

Vastus medialis obliquus and vastus lateralis activity in open and closed kinetic chain exercises in patients with patellofemoral pain syndrome: an electromyographic study.

OBJECTIVES: To evaluate the electromyographic activities of vastus medialis obliquus (VMO) and vastus lateralis (VL) muscles in open and closed kinetic chain exercises in subjects with patellofemoral pain syndrome (PFPS). DESIGN: Case-controlled study. SETTING: Rehabilitation science center in a tertiary medical center. PARTICIPANTS: Ten patients with bilateral knee pain diagnosed with PFPS and 10 healthy volunteers. INTERVENTIONS: Subjects performed open kinetic chain exercise on an isokinetic dynamometer and closed kinetic chain exercise by squat-to-stand and stand-to-squat tasks. Surface electromyography was done for the VMO and VL muscles. MAIN OUTCOME MEASURES: VMO/VL ratios were calculated after normalization of muscle activities. RESULTS: The VMO/VL ratios of PFPS subjects were significantly lower than were those of unimpaired subjects during knee isokinetic closed kinetic chain exercises (p = .047). However, there was no statistical difference in VMO/VL ratio between subjects with and without PFPS during closed kinetic chain exercises (p = .623). Maximum VMO/VL ratio was obtained at 60 degrees knee flexion in closed kinetic chain exercise. CONCLUSION: In closed kinetic chain exercises, more selective VMO activation can be obtained at 60 degrees knee flexion. Maximal VMO/VL ratio was observed at this knee flexion angle, and muscle contraction intensity was also greatest.

Adult↗
PubMed2001

Quantitative and qualitative assessment of women's experience of a one-stop menstrual clinic in comparison with traditional gynaecology clinics.

OBJECTIVE: A quantitative and qualitative evaluation of the views of patients attending two types of clinics for menstrual disorders. METHODS: Semi-structured qualitative interview and quantitative questionnaire. SETTING: Five traditional general gynaecology clinics and a one-stop menstrual clinic, where investigations are performed and results given to patients on the same day. PARTICIPANTS: Two hundred and thirty-nine women (126 from the gynaecology clinic and 113 from the menstrual clinic) were recruited into the quantitative study; 18 and 26 patients from the gynaecology and the menstrual clinic, respectively, were interviewed for the qualitative study. MAIN OUTCOME MEASURES: Women's views about their care and progress towards resolution of their problem. RESULTS: Following the initial consultation, 106 (84%) of the gynaecology clinic, and 98 (87%) of the menstrual clinic patients completed the first part of the questionnaire. Of those, 75 (71%) and 79 (81%) patients from the two types of clinic, respectively, completed a follow up questionnaire one year later. There were statistically significant differences in all the components of the first part of the questionnaire (information, continuity, waiting, organisation, and limbo) in favour of the one-stop menstrual clinic. After one year, there was a statistically significant difference in one of the components, patient centeredness, but not in overall process co-ordination. The interviews showed that patients attending the menstrual clinic appreciated getting the results of their investigations on the same day. They also found the organisation of the one-stop menstrual clinic more closely suited to their needs and as a result were more likely to feel they were making progress. CONCLUSION: Women were consistently more positive about their experience in the one-stop clinic. One-stop clinics organised to meet the needs of patients might be appropriate for other clinical conditions. The combination of quantitative and qualitative methods is an effective method of assessing patients' views of health services.

Adult↗
PubMed2001

Motion of red blood cells in a capillary with an endothelial surface layer: effect of flow velocity.

Interior surfaces of capillaries are lined with macromolecules forming an endothelial surface layer (ESL). A theoretical model is used to investigate effects of flow velocity on motion and axisymmetric deformation of red blood cells in a capillary with an ESL. Cell deformation is analyzed, including effects of membrane shear and bending elasticity. Plasma flow around the cell and through the ESL is computed using lubrication theory. The ESL is represented as a porous layer that exerts compressive forces on red blood cells that penetrate it. According to the model, hydrodynamic pressures generated by plasma flow around the cell squeeze moving red blood cells into narrow elongated shapes. If the ESL is 0.7 microm wide, with hydraulic resistivity of 2 x 10(8) dyn x s x cm(-4), and exerts a force of 20 dyn/cm2, predicted variation with flow velocity of the gap width between red blood cell and capillary wall agrees well with observations. Predicted gap at a velocity of 0.1 mm/s is approximately 0.6 microm vs. approximately 0.2 microm with no ESL. Predicted flow resistance increases markedly at low velocities. The model shows that exclusion of red blood cells from the ESL in flowing capillaries can result from hydrodynamic forces generated by plasma flow through the ESL.

Animals↗
PubMed2001

Effect of the endothelial surface layer on transmission of fluid shear stress to endothelial cells.

Responses of vascular endothelial cells to mechanical shear stresses resulting from blood flow are involved in regulation of blood flow, in structural adaptation of vessels, and in vascular disease. Interior surfaces of blood vessels are lined with a layer of bound or adsorbed macromolecules, known as the endothelial surface layer (ESL). In vivo investigations have shown that this layer has a width of order 1 microm, that it substantially impedes plasma flow, and that it excludes flowing red blood cells. Here, the effect of the ESL on transmission of shear stress to endothelial cells is examined using a theoretical model. The layer is assumed to consist of a matrix of molecular chains extending from the surface, held in tension by a slight increase in colloid osmotic pressure relative to that in free-flowing plasma. It is shown that, under physiological conditions, shear stress is transmitted to the endothelial surface almost entirely by the matrix, and fluid shear stresses on endothelial cell membranes are very small. Rapid fluctuations in shear stress are strongly attenuated by the layer. The ESL may therefore play an important role in sensing of shear stress by endothelial cells.

Blood Flow Velocity↗
PubMed2000

Fab fragments directed against laminin 5 induce subepidermal blisters in neonatal mice.

Patients with one form of cicatricial pemphigoid have IgG autoantibodies directed against laminin 5 (alpha3beta3gamma2), an adhesion protein in epidermal basement membrane. Anti-laminin 5 autoantibodies are not found in patients with other skin or mucosal diseases and hence serve as a specific marker for this autoimmune blistering disorder. The demonstration that experimental and patient anti-laminin 5 IgG are pathogenic in animal models indicated that such autoantibodies are central to disease pathophysiology. To investigate further the role of antibody valence and complement in triggering lesion formation in vivo, rabbit anti-laminin 5 (or normal, control) Fab fragments were passively transferred to neonatal BALB/c mice. Mice receiving anti-laminin 5 Fab fragments developed, in a dose-related fashion, circulating anti-basement membrane antibodies, deposits of immunoreactive rabbit IgG (but not murine C3) in epidermal basement membranes, and subepithelial blisters of skin and mucous membranes. Such alterations were not observed in mice treated with equivalent concentrations of normal rabbit Fab fragments. These studies demonstrated that neither complement activation nor cross-linking of laminin 5 in epidermal basement membranes was required for induction of subepidermal blister formation in this animal model of a human autoimmune bullous disease.

Animals↗
PubMed2000

Quantitation of N-(3,5-dichloropyrid-4-yl)-3-cyclopentyloxy-4-methoxybenzamide and 4-amino-3,5-dichloropyridine in rat and mouse plasma by LC/MS/MS.

The metabolism of N-(3,5-dichloropyrid-4-yl)-3-cyclopentyloxy-4-methoxybenzamide (RP73401), a phosphodiesterase IV (PDE IV) inhibitor is extensive (unpublished); however, until recently, studies for this compound did not report 4-amino-3,5-dichloropyridine (ADCP) as a metabolite either in vitro or in vivo. This prompted a reinvestigation into the metabolism of RP73401 in rats and mice using mass spectrometry. The results of the reinvestigation confirmed that 4-amino-3,5-dichloropyridine was formed via the metabolism of RP73401 both in vitro and in vivo. In order to further investigate RP73401 hydrolysis in vivo, a liquid chromatography/mass spectrometry assay was developed and validated for the simultaneous determination of RP73401 and ADCP in rat and mouse plasma. The method used Waters Oasis HLB brand solid phase extraction cartridges to isolate the analytes (RP73401 and ADCP) and internal standard from the plasma. HPLC chromatographic separation was achieved using a Zorbax SB C18 HPLC column and detection was accomplished using positive ion atmospheric pressure chemical ionization tandem mass spectroscopy in multiple reaction monitoring (MRM) mode. The assay was developed and validated over the range of 0.5-100 ng ml(-1) for RP73401 and 5-500 ng ml(-1) for ADCP using 0.050 ml of plasma. The assay proved to be sensitive, accurate, precise and specific for RP73401 and ADCP. Intraday and interday quality control results routinely showed accuracy and precision to be within +/- 20%. This LC/MS/MS method was subsequently employed to investigate the hydrolysis of RP73401 in the rat and mouse, and determine the effects of tri-o-tolyl phosphate (TOTP, a carboxylesterase inhibitor) preadministration on the hydrolysis reaction in the rat.

Animals↗
PubMed2000

Human anti-laminin 5 autoantibodies induce subepidermal blisters in an experimental human skin graft model.

Patients with one form of cicatricial pemphigoid have IgG antibasement membrane autoantibodies against laminin 5 (alpha3beta3gamma2). Although passive transfer of rabbit anti-laminin 5 IgG to neonatal mice has been shown to induce subepidermal blisters that mimic those in patients, it has not been possible to directly assess the pathogenic activity of human autoantibodies in this animal model because the latter do not bind murine skin. To address this question, a disease model in adult mice as well as SCID mice bearing human skin grafts was developed. Adult BALB/C mice challenged with rabbit anti-laminin 5 IgG developed, in a concentration-related fashion, erythema, erosions, and crusts surrounding injection sites, histologic evidence of noninflammatory, subepidermal blisters, and deposits of rabbit IgG and murine C3 in epidermal basement membranes. Anti-laminin 5 IgG also induced subepidermal blisters in: adult complement-, mast cell-, and immuno-deficient mice; adult BALB/C mice pretreated with dexamethasone; and human skin grafts on SCID mice. Alterations did not develop in matching controls challenged with identical amounts of purified normal rabbit IgG or bovine serum albumin. Using this adult mouse model, human skin grafts on SCID mice were challenged with purified IgG from patients with alpha subunit-specific, anti-laminin 5 autoantibodies, or normal controls. Patient (but not control) IgG induced epidermal fragility as well as noninflammatory, subepidermal blisters in grafted human (but not adjacent murine) skin. Moreover, whereas all mice that received patient autoantibodies had anti-laminin 5 IgG in their circulation, deposits of human IgG were present only in the epidermal basement membranes of grafts. Interestingly, these in situ and circulating autoantibodies were predominately of the IgG4 subclass. These studies demonstrate that human anti-laminin 5 autoantibodies are pathogenic in vivo and describe an animal model that can be used to define disease pathomechanisms and biologically important domains within this autoantigen.

Animals↗
PubMed2000

Are self-expanding metal mesh stents useful in the treatment of benign esophageal stenoses and fistulas? An experience of four cases.

OBJECTIVE: The aim of this study was to review the long-term results of treating benign esophageal fistula and stenosis using self-expanding metal stents. METHODS: We treated four patients using covered mesh or coiled stents. We removed the stents electively in two patients (one endoscopically and one during planned partial esophagectomy) and unexpectedly in one patient who developed bleeding. One stent migrated and required laparotomy for removal. RESULTS: Placement of self-expanding metal stents successfully sealed the benign fistula in two patients and reestablished swallowing in two other patients with complicated achalasia. Two patients were swallowing normally on long-term follow-up, one died of the underlying disease, and one required gastrostomy. CONCLUSION: Temporary use of self-expanding metal stents as a feasible option for treating benign esophageal stenosis and fistula in patients who have failed other conventional treatments.

Aged↗
PubMed2000

Theoretical simulation of oxygen transport to brain by networks of microvessels: effects of oxygen supply and demand on tissue hypoxia.

OBJECTIVE: Simulations of oxygen delivery by a three-dimensional network of microvessels in rat cerebral cortex were used to examine how the distribution of partial pressure of oxygen (PO2) in tissue depends on blood flow and oxygen consumption rates. METHODS: Network geometry was deduced from previously published scanning electron micrographs of corrosion casts. A nonlinear least-squares method, using images obtained at three different angles, was used to estimate vessel locations. The network consisted of 50 segments in a region 140 microm x 150 microm x 160 microm. A Green's function method was used to predict the PO2 distribution. Effects of varying perfusion and consumption were examined, relative to a control state with consumption 10 cm3O2/100 g per min and perfusion 160 cm3/100 g per min. RESULTS: In the control state, minimum tissue PO2, was 7 mm Hg. A Krogh-type model with the same density of vessels, but with uniform spacing, predicted a minimum tissue PO2 of 23 mm Hg. For perfusion below 60% of control, tissue hypoxia (PO2 <1 mm Hg) was predicted. When perfusion was reduced by 75%, the resulting hypoxia could be eliminated by a 31% reduction in oxygen consumption rate. CONCLUSIONS: The simulations suggest that tissue hypoxia resulting from a severe decrease in brain perfusion, as can occur in stroke, may be avoided by a moderate decrease in oxygen consumption rate.

Animals↗
PubMed1999

Anti-epiligrin cicatricial pemphigoid with antibodies against the gamma2 subunit of laminin 5.

BACKGROUND: Cicatricial pemphigoid (CP) is a scarring subepithelial mucocutaneous blistering disease characterized by anti-basement membrane zone autoantibodies. Anti-epiligrin CP is an uncommon variant that has been recently characterized. Severe laryngeal involvement is infrequently observed in all forms of CP and has been documented in only 2 patients with anti-epiligrin CP. OBSERVATIONS: We report a case of CP exhibiting extensive laryngeal and ocular involvement. Histological, immunofluorescence, and immunoprecipitation studies confirmed the diagnosis of anti-epiligrin CP. Immunoblotting studies demonstrated the presence of antibodies against the alpha3 and the gamma2 subunit of laminin 5. CONCLUSION: This article expands the diversity of the clinical and immunopathologic features of this newly characterized variant of CP.

Aged↗
PubMed1999

Mucosal morbidity in patients with epidermolysis bullosa acquisita.

BACKGROUND: Epidermolysis bullosa acquisita is an acquired inflammatory and/or dermolytic subepidermal blistering disease characterized by IgG autoantibodies to type VII collagen. Four patients with documented epidermolysis bullosa acquisita were evaluated by a multidisciplinary team of care providers (4 dermatologists, an ophthalmologist, a radiologist, a voice and speech specialist, and an otolaryngologist) for 1 to 5 years to characterize mucosal involvement and its complications and response to treatment. Patients were evaluated clinically and by slitlamp examinations, endoscopies, computed tomographic scans, and videofluorographic swallowing studies. Spiral computed tomographic scans for virtual endoscopy were used for the nontraumatic evaluation of airways in 2 patients with respiratory tract compromise. OBSERVATIONS: Involvement of 5 or more mucosal sites--mouth, nose, conjunctiva, pharynx, and larynx--was documented in all patients. Complications included ankyloglossia, periodontal disease, scarring and crusting of nasal mucosa, symblepharon formation, obstruction of nasolacrimal ducts, deformation of the epiglottis, impaired phonation, dysphagia, esophageal strictures, and supraglottic stenosis requiring emergency tracheostomy. CONCLUSIONS: Epidermolysis bullosa acquisita may extensively (or predominantly) affect mucosal epithelia in a manner resembling cicatricial pemphigoid. Mucosal disease in these patients is often subclinical, can lead to serious complications, and is best managed using a multidisciplinary approach.

Adult↗
PubMed1999

Endoscopy-based triage significantly reduces hospitalization rates and costs of treating upper GI bleeding: a randomized controlled trial.

BACKGROUND: Many patients with upper gastrointestinal (GI) bleeding have a benign outcome and could receive less intensive and costly care if accurately identified. We sought to determine whether early endoscopy performed shortly after admission in the emergency department could significantly reduce the health care use and costs of caring for patients with nonvariceal upper GI bleeding without adversely affecting the clinical outcome. METHODS: All eligible patients with upper GI bleeding and stable vital signs were randomized after admission to undergo endoscopy in 1 to 2 days (control) or early endoscopy in the emergency department. Patients with low-risk findings on early endoscopy were discharged directly from the emergency department. Clinical outcomes and costs were prospectively assessed for 30 days. RESULTS: We randomized 110 consecutive stable patients with nonvariceal upper GI bleeding during the 12-month study period. The baseline demographic features, endoscopic findings, and the clinical outcomes were no different between the two groups. However the findings of the early endoscopy allowed us to immediately discharge 26 of 56 (46%) patients randomized to that group. No patient discharged from the emergency department suffered an adverse outcome. The hospital stay (median of 1 day [interquartile range of 0 to 3 days] vs. 2 days [interquartile range of 2 to 3 days], p = 0.0001) and the cost of care ($2068 [interquartile range of $928 to $3960] versus $3662 [interquartile range of $2473 to $7280], p = 0.00006) were significantly less for the early endoscopy group. CONCLUSIONS: Early endoscopy performed shortly after admission in the emergency department safely triaged 46% of patients with nonvariceal upper GI bleeding to outpatient care, which significantly reduced hospital stay and costs.

Adult↗