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Biomedical subjects

John Butler

Publications and source records attributed to John Butler.

At least 37 records · Page 2Linked to original sources
PubMed2004

Best evidence topic reports. Metoclopramide versus placebo with opioid.

A short cut review was carried out to establish whether metoclopramide reduced nausea and vomiting after the administration of morphine. Altogether 405 papers were found using the reported search, of which one presented the best evidence to answer the clinical question. The author, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of this best paper are tabulated. A clinical bottom line is stated.

Analgesics, Opioid↗
PubMed2003

Sarco/endoplasmic-reticulum calcium ATPase SERCA1 is maintained in the endoplasmic reticulum by a retrieval signal located between residues 1 and 211.

The location of sarco/endoplasmic-reticulum calcium ATPase (SERCA) retention/retrieval motifs in the sequence of the SERCA1 has been investigated by examining the subcellular location in COS-7 cells of enhanced-green-fluorescent-protein-tagged calcium-pump chimaeras. These chimaeras have been constructed from the fast-twitch SERCA1 and the plasma-membrane calcium ATPase PMCA3. The N-terminal, central and C-terminal segments of these calcium pumps were exchanged between SERCA1 and PMCA3. The segments exchanged correspond to residues 1-211, 212-711 and 712-994 of SERCA1, and residues 1-264, 265-788 and 789-1159 of PMCA3 respectively. Only chimaeras containing the N-terminal segment of SERCA1 were located in the endoplasmic reticulum (ER), whereas chimaeras containing the N-terminal segment from PMCA3 were able to escape from the ER and enter the endomembrane pathway en route for the plasma membrane. Co-localization of SERCA1 in COS-7 cells with the ER/Golgi-intermediate compartment marker ERGIC53 indicates that SERCA1 is maintained in the ER by a process of retrieval. These results indicate that the N-terminal region of SERCA1, containing transmembrane helices M1 and M2, contains an ER-retrieval signal.

Animals↗
PubMed2003

Place of residence and risk of fracture in older people: a population-based study of over 65-year-olds in Cardiff.

Fracture prevention strategies will be most cost-effective if targeted on groups of frail elderly people who are at particularly high risk of falls and fractures. Elderly people living in care homes are one potential target population, but fracture incidence in this setting remains poorly defined in many countries. We used the All Wales Injury Surveillance System (AWISS) in a population-based study of people aged over 65 years living in the city of Cardiff. We linked a postcode-based register of all sheltered accommodation and all residential and nursing homes in the city with injury data from Cardiff's single Accident and Emergency Department. Cardiff has 47,700 residents aged over 65 years with 1918 (4.0%) living in residential or nursing homes and 1868 (3.9%) in sheltered accommodation. In 1999 we identified a total of 1305 fractures including 366 hip fractures, giving a crude fracture incidence of 27.4/1000 per year and 7.7/1000 per year, respectively. Care home residents suffered 213 fractures, 95 of which were of the hip, giving a crude fracture incidence of 111.1/1000 per year and 49.5/1000 per year, respectively. People living in sheltered accommodation suffered 94 fractures, including 28 at the hip, giving a crude fracture incidence of 51.4/1000 per year and 15.3/1000 per year, respectively. People in care homes and sheltered accommodation tend to be older than those living in the community, and we adjusted for this by calculating age- and gender-standardized relative ratios for each setting. Compared with the community dwelling population, care home residents had an overall fracture risk of 2.9 (95% CI 2.5-3.3) and a hip fracture risk of 3.3 (95% CI 2.6-4.2). People in sheltered accommodation had a total fracture risk of 1.7 (95% CI 1.4-2.1), and a hip fracture risk of 1.6 (95% CI 1.1-2.4). Such figures support the potential cost-effectiveness of strategies that seek to prevent fractures in care homes and sheltered accommodation, and are of special interest to those planning intervention studies in these settings.

Accidental Falls↗
PubMed2003

A feasibility study of a Salix viminalis gravel hydroponic system to renovate primary settled wastewater.

A Salix viminalis/gravel system based on hydroponics was developed for wastewater renovation in order to avoid the problems of soil damage and pollution associated with long-term application of wastewater to soil. For such a system to work the mineral elements applied must match closely the requirements of the tree species. To examine this the growth and nutrient uptake of S. viminalis in wastewater was compared with that in Long Ashton nutrient solution (1/4 strength). S. viminalis grew more slowly in wastewater than in Long Ashton solution, but exhibited no obvious deficiency or toxicity symptoms. Since industrial wastewaters often contain metals, the extent to which copper might inhibit wastewater treatment in this system was also examined. S. viminalis was grown in wastewater amended with 10 and 100 ppm copper. Trees were unaffected by wastewater with 10 ppm copper when compared to trees grown in wastewater alone. Wastewater containing with 100 ppm copper was too toxic for the trees to thrive and wastewater treatment was reduced. Treatment efficiencies for unamended wastewater were 57.7% for nitrogen, 90.6% for phosphorus and 24.9% for potassium. These efficiencies are much greater than those quoted for a Salix/soil system, and thus Salix/gravel systems may have potential for wastewater treatment in environmentally sensitive areas or situations.

Biodegradation, Environmental↗
PubMed2003

Synthesis and biological evaluation of novel diaziridinylquinone-acridine conjugates.

The synthesis and biological evaluation of a homologous series of conjugates (9-13) of 2,5-diaziridinylbenzoquinone (DZQ) and 9-carbonylacridine, a DNA intercalating moiety, via a polymethylene unit (n=2-6) are described. In addition, the non-acridine compound 14, analogous to compound 12, and the 5-methyl-DZQ derivatized conjugate 15, an analog of compound 10, were also prepared. Through a Comet assay, compounds 9-13 were shown to produce DNA interstrand cross-links at submicromolar concentrations, consistent with K562 leukemia cells accumulating in the G2/M stage in the cell cycle. The cytotoxicity of compounds 9-15 was examined using a MTT assay on several human cancer cell lines, including chronic myeloid leukemia K562, the non-small cell lung cancers H596 and H460, and colon carcinoma cells BE and HT29. H460 and HT29 are rich in DT-diaphorase (DTD), and H596 and BE cells have negligible amounts of functional DTD. Under continuous exposure of drugs, except to the non-aziridine compound 19b, the IC50 values of all other compounds were determined to be in the range of 0.3-11.3 nM. Compound 10, which has a propyl linker group, was subjected to in vivo studies. When BDF1 mice with established mouse mammary carcinoma were treated with compound 10 (2 mg/kg at day 1 and 5 mg/kg at day 7), a significant delay (9-10 days) in cancer growth was recorded when compared to untreated controls. Furthermore, administration of compound 10 to nu/nu BDF1 mice bearing human lung cancer H460 xenograft (1.5 mg/kg for 10 for five consecutive days from day 13 and 17) also showed a significant reduction in tumor growth compared to untreated controls. The half-life of compound 10 in the presence of five different peptidases (porcine esterase, carboxypeptidase A, B and Y, and pepsin) was determined to be between 30 and 60 h.

Acridines↗
PubMed2003

Serum amylase and acute pancreatitis.

A short cut review was carried out to establish whether a normal serum amylase value rules out the diagnosis of acute pancreatitis. Altogether 191 papers were found using the reported search, of which four presented the best evidence to answer the clinical question. The author, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of these best papers are tabulated. A clinical bottom line is stated.

Acute Disease↗
PubMed2003

NAD(P)H: quinone oxidoreductase 1 expression in kidney podocytes.

NAD(P)H:quinone oxidoreductase 1 (NQO1; DT-diaphorase; DTD) is a cytosolic two-electron reductase, and compounds of the quinone family such as mitomycin C are efficiently bioactivated by this enzyme. The observation that DT-diaphorase is highly expressed in many cancerous tissues compared to normal tissues has provided us with a potentially selective target that can be exploited in the design of novel anticancer agents. Because of the relative lack of information about the cell-specific expression of DT-diaphorase, the purpose of this study was to map the distribution of this enzyme in normal human tissues. Fifteen tissue samples from normal human kidney were analyzed for expression of DT-diaphorase by immunohistochemistry (two-step indirect method). We found a specific high expression of DT-diaphorase in glomerular visceral epithelial cells (podocytes). These results suggest that a high expression of DT-diaphorase in podocytes could play a major role in the pathogenesis of renal toxicity and mitomycin C-induced hemolytic uremic syndrome, in which injury to the glomerular filtration mechanism is the primary damage, leading to a cascade of deleterious events including microangiopathic hemolytic anemia and thrombocytopenia. This observation has potential therapeutic implications because the DT-diaphorase metabolic pathway is influenced by many agents, including drugs, diet, and environmental cell factors such as pH and oxygen tension.

Humans↗
PubMed2002

Duroflo II heparin bonding does not attenuate cytokine release or improve pulmonary function.

BACKGROUND: Comparison of the cytokine generation and leukocyte activation properties of Duroflo II heparin bonded bypass circuit (Baxter Healthcare Corp, Compton, UK) and the conventional cardiopulmonary bypass circuit. Attempt to correlate these to pulmonary dysfunction postoperatively. METHODS: Forty patients undergoing elective, isolated coronary artery bypass grafting were randomly allocated to have either plain extracorporeal circuits (group C) or heparin bonded extracorporeal circuits (group H). Full systemic heparinization was used in all patients. The inflammatory response was assessed by measuring plasma levels of interleukin-6, interleukin-8, interleukin-10, and polymorphonuclear elastase. Gas exchange was assessed by measuring the PaO2/FIO2 ratio. RESULTS: Significant impairment of oxygenation was seen in both groups with the lowest values at the end of the operation before a gradual return to normal during the next 6 hours. There were no differences between the groups in gas exchange or times to extubation. There were significant elevations in all the cytokines, with interleukin-6 levels peaking at 4 hours in group H and 24 hours in group C, before starting to return to normal at 48 hours. The patterns of interleukin-8 and interleukin-10 rise were identical in the two groups. Polymorphonuclear elastase reached a peak at the end of the operation in group H and remained elevated up to 24 hours, whereas levels continued to rise in group C up to 4 hours. There were no significant differences in levels between groups at any time. There were no differences between the groups in blood loss or blood product usage. CONCLUSIONS: Cardiopulmonary bypass induces a systemic inflammatory response with release of cytokines and activation of leukocytes. This correlates with the severe deterioration in pulmonary gas exchange from preoperative levels up to 6 hours postoperatively (p < 0.05). In the presence of systemic heparinization, Duroflo II heparin bondingtf the circuits has minor effects on the pattern of evolution of this inflammatory response.

Adult↗
PubMed2002

Towards evidence based emergency medicine: best BETs from the Manchester Royal Infirmary. Detection of pneumoperitoneum on erect chest radiograph.

A short cut review was carried out to establish whether a normal erect chest radiograph excludes the diagnosis of perforated abdominal viscus. Altogether 37 papers were found using the reported search, of which two presented the best evidence to answer the clinical question. The author, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of these best papers are shown in table 1. A clinical bottom line is stated.

Abdominal Injuries↗
PubMed2002

Towards evidence based emergency medicine: best BETs from the Manchester Royal Infirmary. Cervical spine radiography in alert asymptomatic blunt trauma patients.

A short cut review was carried out to establish whether a normal cervical spine radiograph excludes bony cervical spine injury in alert, asymptomatic trauma patients. Altogether 232 papers were found using the reported search, of which six presented the best evidence to answer the clinical question. The author, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of these best papers are shown in table 2. A clinical bottom line is stated.

Cervical Vertebrae↗
PubMed2002

Towards evidence based emergency medicine: best BETs from the Manchester Royal Infirmary. Serum amylase or lipase to diagnose pancreatitis in patients presenting with abdominal pain.

A short cut review was carried out to establish whether serum amylase was better than serum lipase in the diagnosis of pancreatitis in patients presenting with abdominal pain. Altogether 320 papers were found using the reported search, of which seven presented the best evidence to answer the clinical question. The author, date, and country of publication, patient group studied, study type, relevant outcomes, results, and study weaknesses of these best papers are tabulated. A clinical bottom line is stated.

Abdominal Pain↗
PubMed2002

Towards evidence based emergency medicine: best BETs from Manchester Royal Infirmary. Antibiotics in patients with isolated chest trauma requiring chest drains.

A short cut review was carried out to establish whether the administration of antibiotics reduces the incidence of intrathoracic infection in patients who have had a chest drain inserted after trauma. Altogether 321 papers were found using the reported search, of which two presented the best evidence to answer the clinical question. The author, date and country of publication, patient group studied, study type, relevant outcomes, results, and study weaknesses of these best papers are tabulated. A clinical bottom line is stated.

Antibiotic Prophylaxis↗
PubMed2002

Towards evidence based emergency medicine: best BETs from Manchester Royal Infirmary. Lignocaine premedication before rapid sequence induction in head injuries.

A short cut review was carried out to establish whether pretreatment with lignocaine (lidocaine) reduces the rise in intracranial pressure associated with intubation of head injured patients. Altogether 85 papers were found using the reported search, of which three presented the best evidence to answer the clinical question. The author, date and country of publication, patient group studied, study type, relevant outcomes, results, and study weaknesses of these best papers are tabulated. A clinical bottom line is stated.

Anesthetics, Local↗
PubMed2002

Imaging findings of cochlear nerve deficiency.

BACKGROUND AND PURPOSE: High-resolution T2-weighted fast spin-echo MR imaging provides excellent depiction of the cisternal and intracanalicular segments of the vestibulocochlear and facial nerves. Absence or reduction in caliber of the cochlear nerve (deficiency) has been described in association with congenital sensorineural hearing loss (SNHL). Depiction of cochlear nerve integrity may be important for diagnosis and management of SNHL. METHODS: We retrospectively reviewed high-resolution T2-weighted fast spin-echo MR images of 22 patients examined for SNHL who had deficiency of the cochlear nerve. Images were evaluated for the presence and comparative size of the component nerves (facial, cochlear, superior vestibular, and inferior vestibular nerves), relative size of the internal auditory canal (IAC), and any associated inner ear abnormalities. The clinical history, results of the clinical examination, and audiometric findings were reviewed for each patient. RESULTS: Deficiency of the cochlear nerve was observed in 12 patients with congenital SNHL and in 10 patients with acquired SNHL. Hypoplasia of the IAC was observed in association with congenital deficiency of the cochlear nerve in 11 of 12 patients. Deficiency of the cochlear nerve was observed in association with acoustic schwannoma in two cases and with acquired labyrinthine abnormalities in seven cases. Hypoplasia of the IAC was not observed in association with acquired SNHL. CONCLUSION: Deficiency of the cochlear nerve can be shown by high-resolution T2-weighted fast spin-echo MR imaging. Deficiency may be observed in association with congenital or acquired SNHL and may be important in the assessment of patients for cochlear implantation. Hypoplasia of the IAC is an indicator of congenital cochlear nerve deficiency.

Adult↗
PubMedDate not supplied

Monitoring neoadjuvant chemotherapy in breast cancer using quantitative diffuse optical spectroscopy: a case study.

Presurgical chemotherapy is widely used in the treatment of locally advanced breast cancer. Monitoring the response to therapy can improve survival and reduce morbidity. We employ a noninvasive, near-infrared method based on diffuse optical spectroscopy (DOS) to quantitatively monitor tumor response to neoadjuvant chemotherapy. DOS was used to monitor tumor response in one patient with locally advanced breast cancer throughout the course of her therapy. Measurements were performed prior to doxorubicin-cyclophosphamide therapy and at several time points over the course of three treatment cycles (68 days). Our results show strong tumor to normal (T/N) tissue contrast in total hemoglobin concentration (T/N=2.4), water fraction (T/N=6.9), tissue hemoglobin oxygen saturation, S(t)O(2) (T/N=0.9), and lipid fraction (T/N=0.7) prior to treatment. Over a 10-week period, the peak total hemoglobin and water dropped 56 and 67%, respectively. Lipid content nearly returned to baseline (T/N =0.9) while S(t)O(2) exceeded pretreatment levels (T/N =1.5). Approximately half of the hemoglobin and water changes occurred within 5 days of treatment (26 and 37%, respectively). These data suggest that noninvasive, quantitative optical methods that characterize tumor physiology may be useful in assessing and optimizing individual response to neoadjuvant chemotherapy.

Adenocarcinoma↗
PubMedDate not supplied

Spatial variations in optical and physiological properties of healthy breast tissue.

Near-infrared (NIR) diffuse optical spectroscopy (DOS) and diffuse optical imaging (DOI) show promise as noninvasive clinical techniques for breast cancer screening and diagnosis. Since NIR methods are based on optical contrast between healthy and diseased tissue, it is essential to characterize the sources of endogenous contrast in normal subjects. We report intra- and inter-subject variation and bilateral asymmetry of the optical and physiological parameters of 31 women using a seven-wavelength NIR frequency-domain photon migration (FDPM) instrument. Wavelength-dependent absorption and reduced scattering parameters (micro(a) and micro(s'), respectively) were measured in four major quadrants and the areolar regions of left and right breasts. These values were used to determine tissue concentrations of oxy-(HbO(2)) and deoxy-(Hb-R) hemoglobin, lipid content, water concentration, and tissue "scatter power." Mean total hemoglobin for premenopausal (PRE) women (20 to 30 microM) is approximately two-fold higher than for postmenopausal (POST) subjects at all positions. POST women have approximately 50% higher lipid content (50 to 60%) than PRE at all positions. Water concentration on average is 1.8-fold higher for PRE subjects (30 to 40%) than POST. These differences are most pronounced when comparing the areolar complex to the other regions of the breast. In premenopausal women, the areolar regions have 40 to 45% increased total hemoglobin concentration (THC), 20 to 25% lower lipid content, and 30 to 60% higher scatter power versus the quadrants. Small-scale (3 cm) changes in optical properties are negligible compared to large-scale variations over all quadrants, where the intrinsic spatial heterogeneity of healthy breast tissue is 20 to 40% for micro(a) and 5 to 12% for micro(s'). Although no consistent right-left differences are observed in the study population, relative differences between symmetric positions ranged from 18 to 30% for THC, 10 to 40% for adipose, 10 to 25% for water, and 4 to 9% for scattering (674 nm) within an individual.

Adolescent↗