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Biomedical subjects

J Farrell

Publications and source records attributed to J Farrell.

At least 19 recordsLinked to original sources

Formation of a nematic fluid at high fields in Sr3Ru2O7.

In principle, a complex assembly of strongly interacting electrons can self-organize into a wide variety of collective states, but relatively few such states have been identified in practice. We report that, in the close vicinity of a metamagnetic quantum critical point, high-purity strontium ruthenate Sr3Ru2O7 possesses a large magnetoresistive anisotropy, consistent with the existence of an electronic nematic fluid. We discuss a striking phenomenological similarity between our observations and those made in high-purity two-dimensional electron fluids in gallium arsenide devices.

Journal Article↗

Endoscopic retrograde cholangiopancreatography after pancreaticoduodenectomy for benign and malignant disease: indications and technical outcomes.

BACKGROUND AND STUDY AIMS: Patients undergoing pancreaticoduodenectomy develop postoperative complications related to surgery and their disease. Very little data are available on the role or success of endoscopic retrograde cholangiopancreatography (ERCP) in such patients. The aim of this study was to evaluate the indications and role of diagnostic and therapeutic ERCP after pancreaticoduodenectomy for both benign and malignant disease. PATIENTS AND METHODS: This study was a 10-year (1990 - 2000) single institution retrospective review of all ERCPs performed on patients who had undergone pancreaticoduodenectomy surgery. Indications for the ERCP and technical procedural success were studied. RESULTS: 29 patients with a pancreaticoduodenectomy underwent 56 ERCPs. Reasons for surgery were neoplasia and chronic pancreatitis. Indications for ERCP included evaluation of jaundice and pain. Technical success related to the clinical indication (jaundice 69 %, pain 54 %). CONCLUSION: ERCP plays an important role in the management of postpancreatic surgery problems including biliary and anastomotic strictures, and should be the modality of choice. However, surgical technique may make the afferent limb inaccessible, and the ductal anastomosis difficult to identify in patients with some types of pancreaticoduodenectomy. Closer collaboration between surgeon and endoscopist may allow alterations in surgical technique to improve postoperative ERCP success.

Balloon Occlusion↗

Measurement of the electric form factor of the neutron at Q2=0.5 and 1.0 GeV2/c2.

The electric form factor of the neutron was determined from measurements of the d-->(e-->,e'n)p reaction for quasielastic kinematics. Polarized electrons were scattered off a polarized deuterated ammonia (15ND3) target in which the deuteron polarization was perpendicular to the momentum transfer. The scattered electrons were detected in a magnetic spectrometer in coincidence with neutrons in a large solid angle detector. We find G(n)(E)=0.0526+/-0.0033(stat)+/-0.0026(sys) and 0.0454+/-0.0054+/-0.0037 at Q(2)=0.5 and 1.0 (GeV/c)(2), respectively.

Journal Article↗

A clinical procedure to predict the value of temporary occlusion therapy in keratoconjunctivitis sicca.

PURPOSE: To evaluate the effects of dissolvable collagen punctal plugs on the symptoms, tear stability and volume in aqueous deficient dry eyes. METHODS: Sixty-two aqueous deficient dry eye patients of mixed aetiology underwent lacrimal punctal occlusion with dissolvable collagen plugs. The subjects were randomly allocated to one of two treatment groups: group I (n = 36) had their lower puncta occluded and group II (n = 26) had both their upper and lower puncta occluded. The effectiveness of this treatment was clinically assessed by (1). scoring subject symptoms and (2). measuring the tear parameters of tear thinning time (TTT) and tear meniscus height (TMH) as indicators of tear stability and volume, respectively. Following baseline measurements, patients were reviewed at time intervals of 5 and 12 days post-occlusion. A group of age- and gender-matched normals (n = 45) was recruited for comparison (group III). RESULTS: Tear volume and stability were significantly higher in group III compared with I and II at baseline. In the treated groups on both days 5 and 12: (1). symptom score reduced significantly from a median value of 7 to 3 (p = <0.001); (2). tear stability increased significantly from a median value of 3 to 5 s by day 5 (p <or= 0.001); reduced between days 5 and 12 (p < 0.05) and remained below the stability in group III at all times; (c). tear volume increased significantly by day 5 in both treatment groups from a median value of 0.13 to 0.20 mm (p<or=0.001), remained stable by day 12 in group II but reduced in group I (p < 0.05); (d). the increase in tear volume was negatively correlated with pre-treatment tear volume; (e). symptom score correlated with both baseline tear volume and stability. CONCLUSION: Collagen plugs improved tear status in the aqueous deficient dry eyes. Occluding both upper and lower puncta with temporary collagen plugs offers no practical beneficial gain compared with occluding just the lower punctum.

Adult↗

Hypersensitivity reactions to carbamazepine: characterization of the specificity, phenotype, and cytokine profile of drug-specific T cell clones.

Administration of carbamazepine (CBZ) causes hypersensitivity reactions clinically characterized by skin involvement, eosinophilia, and systemic symptoms. These reactions have an immune etiology; however, the role of T cells is not well defined. The aim of this study was to characterize the specificity, phenotype, and cytokine profile of CBZ-specific T cells derived from hypersensitive individuals. Proliferation of blood lymphocytes was measured using the lymphocyte transformation test. CBZ-specific T cell clones were generated by serial dilution and characterized in terms of their cluster of differentiation and T cell receptor V beta phenotype. Proliferation, cytotoxicity, and cytokine secretion were measured by [(3)H]thymidine incorporation, (51)Cr release, and enzyme-linked immunosorbent assay, respectively. HLA blocking antibodies were used to study the involvement of antigen-presenting cells. The specificity of the drug T cell receptor interaction was studied using CBZ metabolites and other structurally related compounds. Lymphocytes from hypersensitive patients (stimulation index: 32.1 +/- 24.2 [10 microg ml(-1)]) but not control patients (stimulation index: 1.2 +/- 0.4 [10 microg ml(-1)]) proliferated upon stimulation with CBZ. Of 44 CBZ-specific T cell clones generated, 10 were selected for further analysis. All 10 clones were either CD4+ or CD4+/CD8+, expressed the alpha beta T cell receptor, secreted IFN-gamma, and were cytotoxic. T-cell recognition of CBZ was dependent on the presence of HLA class II (DR/DQ)-matched antigen-presenting cells. The T cell receptor of certain clones could accommodate some CBZ metabolites, but no cross-reactivity was seen with other anticonvulsants or structural analogs. These studies characterize drug-specific T cells in CBZ-hypersensitive patients that are phenotypically different from T cells involved in other serious cutaneous adverse drug reactions.

Adult↗

Kinetics of soluble chromium removal from contaminated water by zerovalent iron media: corrosion inhibition and passive oxide effects.

Permeable reactive barriers containing zerovalent iron are being increasingly employed for in situ remediation of groundwater contaminated with redox active metals and chlorinated organic compounds. This research investigated the effect of chromate concentration on its removal from solution by zerovalent iron. Removal rates of aqueous Cr(VI) by iron wires were measured in batch experiments for initial chromium concentrations ranging from 100 to 10 000 microg/L. Chromate removal was also measured in columns packed with zerovalent iron filings over this same concentration range. Electrochemical measurements were made to determine the free corrosion potential and corrosion rate of the iron reactants. In both the batch and column reactors, absolute rates of chromium removal declined with increasing chromate concentration. Corrosion current measurements indicated that the rate of iron corrosion decreased with increasing Cr(VI) concentrations between 0 and 5000 microg/L. At a Cr(VI) concentration of 10 000 microg/L, Tafel polarization diagrams showed that chromium removal was affected by its diffusion rate through a passivating oxide film and by the ability of iron to release Fe2+ at anodic sites. In contrast, water reduction was not mass transfer limited, but chromium did decrease the exchange current for the hydrogen evolution reaction. Even at the most passivating concentration of 10 000 microng/L, effluent Cr(VI) concentrations in the column reactors reached a steady state, indicating that passivation had also reached a steady state. Although chromate contributes to iron surface passivation, the removal rates are still sufficiently fast for in situ iron barriers to be effective for Cr(VI) removal at most environmentally relevant concentrations.

Carcinogens↗

Electrochemical investigation of the rate-limiting mechanisms for trichloroethylene and carbon tetrachloride reduction at iron surfaces.

The mechanisms involved in reductive dechlorination of carbon tetrachloride (CT) and trichloroethylene (TCE) at iron surfaces were studied to determine if their reaction rates were limited by rates of electron transfer. Chronoamperometry and chronopotentiometry analyses were used to determine the kinetics of CT and TCE reduction by a rotating disk electrode in solutions of constant halocarbon concentration. Rate constants for CT and TCE dechlorination were measured as a function of the electrode potential over a temperature range from 2 to 42 degrees C. Changes in dechlorination rate constants with electrode potential were used to determine the apparent electron-transfer coefficients at each temperature. The transfer coefficient for CT dechlorination was 0.22 +/- 0.02 and was independent of temperature. The temperature independence of the CT transfer coefficient is consistent with a rate-limiting mechanism involving an outer-sphere electron-transfer step. Conversely, the transfer coefficient for TCE was temperature dependent and ranged from 0.06 +/- 0.01 at 2 degrees C to 0.21 +/- 0.02 at 42 degrees C. The temperature-dependent TCE transfer coefficient indicated that its reduction rate was limited by chemical dependent factors and not exclusively by the rate of electron transfer. In accord with a rate-limiting mechanism involving an electron-transfer step, the apparent activation energy (Ea) for CT reduction decreased with decreasing electrode potential and ranged from 33.0 +/- 1.6 to 47.8 +/- 2.0 kJ/mol. In contrast, the Ea for TCE reduction did not decline with decreasing electrode potential and ranged from 29.4 +/- 3.4 to 40.3 +/- 3.9. The absence of a potential dependence for the TCE Ea supports the conclusion that its reaction rate was not limited by an electron-transfer step. The small potential dependence of TCE reaction rates can be explained by a reaction mechanism in which TCE reacts with atomic hydrogen produced from reduction of water.

Carbon Tetrachloride↗

Electrochemical and spectroscopic study of arsenate removal from water using zero-valent iron media.

This study investigated the mechanisms involved in removing arsenate from drinking water supplies using zero-valent iron media. Batch experiments utilizing iron wires suspended in anaerobic arsenate solutions were performed to determine arsenate removal rates as a function of the arsenate solution concentration. Corrosion rates of the iron wires were determined as a function of elapsed time using Tafel analysis. The removal kinetics in the batch reactors were best described by a dual-rate model in which arsenate removal was pseudo-first-order at low concentrations and approached zero-order in the limit of high arsenate concentrations. The presence of arsenate decreased iron corrosion rates as compared to those in blank 3 mM CaSO4 background electrolyte solutions. However, constant corrosion rates were attained after approximately 10 days elapsed, indicating that the passivation processes had reached steady state. The cathodic Tafel slopes were the same in the arsenate and the blank electrolyte solutions. This indicates that water was the primary oxidant for iron corrosion and that arsenate did not directly oxidize the iron wires. The anodic Tafel slopes were greater in the arsenate solutions, indicating that arsenate formed complexes with iron corrosion products released at anodic sites on the iron surfaces. Ion chromatography analyses indicated that there was no measurable reduction of As(V) to As(III). X-ray absorption spectroscopy analyses indicated that all arsenic associated with the zero-valent iron surfaces was in the oxidation state. Interatomic arsenic-iron distances determined from EXAFS analyses were consistent with bidentate corner-sharing among arsenate tetrahedra and iron octahedra. Results from this study show that under conditions applicable to drinking water treatment, arsenate removal by zero-valent iron media involves surface complexation only and does not involve reduction to metallic arsenic.

Arsenates↗

Transplantation of a fetus with paternal Thy-1(+)CD34(+)cells for chronic granulomatous disease.

A fetus diagnosed with X-linked chronic granulomatous disease was transplanted with Thy-1(+)CD34(+) cells of paternal origin. The transplant was performed at 14 weeks gestation by ultrasound guided injection into the peritoneal cavity. The fetus was delivered at 38 weeks gestation after an otherwise uneventful pregnancy. Umbilical cord blood was collected and used to determine the level of peripheral blood chimerism as well as levels of functional engrafted cells. Flow cytometry was used to detect donor leukocytes identified as HLA-A2(-)B7(+) cells, whereas recipient cells were identified as HLA-A2(+)B7(-) cells. No evidence of donor cell engraftment above a level of 0.01% was found. PCR was used to detect HLA-DRB1*15(+) donor cells among the recipient's HLA-DRB1*15(-) cells, but no engraftment was seen with a sensitivity of 1:1000. The presence of functional, donor-derived neutrophils was assessed by flow cytometry using two different fluorescent dyes that measure reactive oxygen species generated by the phagocyte NADPH oxidase. No evidence of paternal-derived functional neutrophils above a level of 0.15% was observed. Peripheral blood and bone marrow samples were collected at 6 months of age. Neither sample showed engraftment by HLA typing using both flow cytometry and PCR. Functional phagocytes were also not observed. Furthermore, no indication of immunological tolerance specific for the donor cells was indicated by a mixed lymphocyte reaction assay performed at 6 months of age. While there appears to be no engraftment of the donor stem cells, the transplant caused no harm to the fetus and the child was healthy at 6 months of age. Analyses of fetal tissues, obtained from elective abortions, revealed that CD3(+) T cells and CD56(+)CD3(-) NK cells are present in the liver at 8 weeks gestation and in the blood by 9 weeks gestation. The presence of these lymphocytes may contribute to the lack of donor cell engraftment in the human fetus.

Adult↗

The HELLP syndrome, a prospective study.

OBJECTIVE: We undertook this study to evaluate the incidence and outcome of HELLP in Irish patients. In addition, duration and trends of the abnormal laboratory results were studied. STUDY DESIGN: This prospective observational study screened 12068 pregnant women between January 1995 and March 1997. Any pregnant woman with hypertension, proteinuria, thrombocytopenia or anemia was monitored for hemolysis and elevated liver transaminases, from the time of recruitment till six weeks postpartum or resolution. RESULTS: Thirteen of 12068 pregnant women (0.11%) developed HELLP. All had hypertension and 84.6% had proteinuria. Delivery was the only factor found to terminate the syndrome. Acute renal dysfunction was noted in 53.8% but none required dialysis. Laboratory parameters stabilized by the sixth postpartum day. Fetal mortality was 1 out of 14. There were no maternal deaths. CONCLUSIONS: HELLP syndrome is a rare but potentially serious complication of pregnancy. Correlation with laboratory data and early intervention are vital in achieving a favorable outcome for both mother and fetus.

Adult↗

Determination of threshold energy dose for ultrasound-induced transdermal drug transport.

Low-frequency (20 kHz) ultrasound has been shown to enhance transdermal transport of drugs, a phenomenon referred to as sonophoresis. In this paper, we report the threshold energy dose for ultrasound-induced transdermal drug transport. The threshold was determined by in vitro measurements of the dependence of sonophoretic enhancement on ultrasound parameters, including intensity, duty cycle, and exposure time. While the enhancement varies linearly with ultrasound intensity and exposure times, it is independent of the duty cycle in the range of parameters studied. The enhancement is also directly proportional to the ultrasound energy density once the threshold value is crossed. For full thickness pig skin, the threshold value is about 222 J/cm(2). The overall dependence of transport enhancement on ultrasound parameters is similar to that of cavitation measured in a model system, pitting of aluminum foil. Specifically, the extent of pitting is proportional to ultrasound intensity and exposure time and is independent of duty cycle. Furthermore, the extent of pitting is also proportional to the ultrasound energy density. The similarity between the parametric dependence of transport enhancement and cavitation is consistent with previous findings that cavitation plays the dominant role in sonophoresis.

Administration, Cutaneous↗

Synergistic effect of low-frequency ultrasound and sodium lauryl sulfate on transdermal transport.

Application of low-frequency ultrasound has been shown to enhance transdermal transport of drugs (low-frequency sonophoresis). In this paper, we show that the efficacy of low-frequency ultrasound in enhancing transdermal transport can be further increased by its combination with sodium lauryl sulfate (SLS), a well-known surfactant. The dependence of the ultrasound-SLS-mediated transport on ultrasound parameters, including intensity, net exposure time, and duty cycle, is discussed. The transdermal transport enhancement is proportional to ultrasound intensity as well as to exposure time, and is independent of duty cycle as long as the net exposure time is the same. The synergistic effect of SLS and ultrasound on transdermal transport increases linearly with SLS concentration. The enhancement is also proportional to the ultrasound energy density beyond a threshold value, which suggests that a certain minimum amount of energy density is required before noticeable changes in skin permeability occur. A similar dependence of the transdermal transport enhancement on energy density is observed in the case of the enhancement induced by ultrasound alone. Although the threshold energy density value in the presence of SLS is about 10 times lower than that in the case of ultrasound alone, the relationship between enhancement and energy density in the presence and in the absence of SLS is otherwise similar. Possible mechanisms for the synergistic effect of ultrasound and SLS are also discussed.

Aluminum↗

Renal thrombotic microangiopathy associated with interferon-alpha treatment of chronic myeloid leukemia.

Recent reports have documented the development of renal thrombotic microangiopathy in patients with chronic myeloid leukemia (CML) who have undergone treatment with interferon-alpha. The pathogenesis of the renal lesion in such cases remains unclear. We report the case of a patient with chronic myeloid leukemia who developed renal failure and nephrotic syndrome while being treated with hydroxyurea and interferon-alpha. The renal biopsy showed features of chronic thrombotic microangiopathy. The patient had serologic and functional evidence of anti-phospholipid antibody. Interferon-alpha is known to cause induction of multiple autoantibodies. We propose that in the context of CML, interferon-alpha treatment can induce pathogenic anti-phospholipid antibodies that result in renal thrombotic microangiopathy. This has important implications for patients with CML receiving immune-stimulating therapy because it suggests that prospective monitoring of such patients for anti-phospholipid antibody might identify those at risk of developing thrombotic microangiopathy. Furthermore, patients with established anti-phospholipid antibody syndrome in this context might benefit from intervention such as early anticoagulation.

Antiphospholipid Syndrome↗

Enhancing perioperative nursing practice: developing a course for the surgeon's assistant.

This article describes the development of a new English National Board (ENB) course for nurses wishing to adopt the role of the surgeon's assistant. The original request for a course of this nature came from the clinicians working in hospitals in the Manchester area, including not only theatre nurses and managers but also surgeons and individuals already practising as surgeon's assistants. This course has been designed with the support of the nursing and medical staff in local trusts, who have been widely consulted. It was developed collaboratively with nurse educationalists, in order to standardise training and education for nurses in practice who wished to adopt this expanding role.

Curriculum↗

Serum beta 2-microglobulin levels in patients chronically dialyzed with CA-210 versus CT-190 dialysis membranes.

beta 2-Microglobulin (B2M) amyloidosis (dialysis-related amyloidosis), manifested primarily by carpal tunnel syndrome and destructive osteoarthropathy, is a major sequel of long-term dialysis. Previous investigators have shown that high-flux biocompatible synthetic membranes (e.g., polyacrylonitrile) lower beta 2M levels when compared to cellulosic membranes (e.g., cuprophane). To date, however, no study has compared beta 2M levels of patients dialyzed with the two more biocompatible cellulosic membranes CA-210 (cellulose acetate) and CT-190 (cellulose triacetate; high flux, more biocompatible). We retrospectively compared the serum beta 2M levels in two chronic hemodialysis populations: 22 patients on CT-190 and 21 patients on CA-210. There was no difference between the two groups with regard to age, sex, or duration of dialysis. The patients on the CA-210 membrane had significantly higher serum beta 2M levels (mean +/- SE; 53.6 +/- 4.7 vs. 36.8 +/- 2.6 mg/l, CA-210 vs. CT-190, respectively, p = 0.003). Subsequently we switched 13 patients dialyzed with a CA-210 membrane to a CT-190 membrane and followed serum beta 2M levels for 14 months. We found a significant decrease in serum beta 2M levels within 1 month which was maintained over 14 months of follow-up (47.4 +/- 4.4 vs. 62.8 +/- 6.7 mg/l, CT-190 at 14 months vs. CA-210 at baseline, respectively, p < 0.01).

Biocompatible Materials↗

The value of a phenol red impregnated thread for differentiating between the aqueous and non-aqueous deficient dry eye.

To determine the clinical viability of a phenol red impregnated cotton thread in differentiating between normal, aqueous deficient and non-aqueous deficient dry eyes. Subjects were recruited on the basis of subjective symptoms, tear stability, rose bengal staining, Schirmer test, conjunctival hyperaemia, patency and number of meibomian glands, presence of mucin strands, appearance of lower tear meniscus. Based on the outcome of the tests, subjects were categorised as either aqueous deficient dry eyes, non-aqueous dry eyes or normals. Subjects were randomised and a thread was applied by inserting into the lower fornix of the right eye and leaving the thread in place for 120 sec. All data was collected under similar ambient conditions. After gathering all the data, the codes were broken. Mean (+/- S.D.) thread wetting values were, all dry eyes (n = 59) 18.4 mm (5.9). Aqueous deficient dry eyes (n = 35), 15.5 mm (4.6). Non-aqueous deficient dry eyes [n = 24], 22.7 mm (5.0). For the normals (n = 38), 19.4 mm (5.0). Differences between (i) normals and aqueous deficient dry eyes and (ii) aqueous deficient and non-aqueous deficient dry eyes were significant (p = 0.01). Difference between all dry eyes and normals was not significant. For the aqueous deficient and non-aqueous deficient dry eyes only, using a cut-off value of 20 mm the calculated sensitivity and specificity values were 86% and 83% respectively. This cotton thread test can effectively differentiate between aqueous deficient and non-aqueous deficient dry eye.

Adult↗