Autologous haematopoeitic stem cell rescue (AHSCR) for severe rheumatic disease in children: guidance for BSPAR members--executive summary.
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Arthritis, Juvenile↗
Biomedical subjects
J Davidson
Publications and source records attributed to J Davidson.
The effect of a hyposmotic shock and purinergic agonists on K+(Rb+) efflux from cultured human breast cancer cells.
The effect of a hyposmotic shock and extracellular ATP on the efflux of K(+)(Rb(+)) from human breast cancer cell lines (MDA-MB-231 and MCF-7) has been examined. A hyposmotic shock increased the fractional efflux of K(+)(Rb(+)) from MDA-MB-231 cells via a pathway which was unaffected by Cl(-) replacement. Apamin, charybdotoxin or removing extracellular Ca(2+) had no effect on volume-activated K(+)(Rb(+)) efflux MDA-MB-231 cells. An osmotic shock also stimulated K(+)(Rb(+)) efflux from MCF-7 cells but to a much lesser extent than found with MDA-MB-231 cells. ATP-stimulated K(+)(Rb(+)) efflux from MDA-MB-231 cells in a dose-dependent fashion but had little effect on K(+)(Rb(+)) release from MCF-7 cells. ATP-stimulated K(+)(Rb(+)) efflux was only inhibited slightly by replacing Cl(-) with NO(3)(-). Removal of external Ca(2+) during treatment with ATP reduced the fractional efflux of K(+)(Rb(+)) in a manner suggesting a role for cellular Ca(2+) stores. Charybdotoxin, but neither apamin nor iberiotoxin, inhibited ATP-stimulated K(+)(Rb(+)) release from MDA-MB-231 cells. Suramin inhibited the ATP-activated efflux of K(+)(Rb(+)). UTP also stimulated K(+)(Rb(+)) efflux from MDA-MB-231 cells whereas ADP, AMP and adenosine were without effect. A combination of an osmotic shock and ATP increased the fractional efflux of K(+)(Rb(+)) to a level greater than the sum of the individual treatments. It appears that the hyposmotically-activated and ATP-stimulated K(+) efflux pathways are separate entities. However, there may be a degree of 'crosstalk' between the two pathways.
Adenosine Triphosphate↗
The feasibility of a randomised, placebo-controlled clinical trial of homeopathic treatment of depression in general practice.
UNLABELLED: Depression is common in general practice and lack of concordance is an important problem in its treatment. Homeopathy has few side effects and is generally associated with good compliance. We report a study investigating the feasibility of a trial to compare the effectiveness of homeopathy with a conventional antidepressant and placebo. OBJECTIVES: To assess the feasibility of a general practice-based clinical trial comparing the effectiveness of individualised homeopathic treatment vs Fluoxetine (Prozac) vs placebo in the treatment of major depressive episodes of moderate severity. DESIGN: Randomised, double-dummy, double-blind parallel group clinical trial. SETTING: Lower Clapton Group Practice, East London. METHOD: Patients were recruited through their general practitioners as they presented during a 9 month period. Recruitment target was 30 patients. Eligibility was confirmed by a consultant psychiatrist using standard criteria (DSM-IV) and instruments Hamilton Depression Scale (HAMD). Suicidal and psychotic patients were excluded, additional precautions against suicide were incorporated. There was a 1 week run-in period and patients showing spontaneous improvement were excluded. Homeopathic treatment was prescribed by a GP qualified in homeopathy, from a 'limited list' of 30 homeopathic medicines, with the help of decision support software. Patients were randomised to receive verum Fluoxetine and placebo homeopathy, or verum homeopathy and placebo Fluoxetine, or placebo homeopathy and placebo Fluoxetine. Treatment duration was 12 weeks. The outcomes were: adverse drug reactions, clinical global impression (CGI); HAMD; mini international psychiatric Interview; Pittsburgh sleep quality index; Side-effects checklist; Short Form 12; treatment credibility questionnaire; work and social disability scale. The primary outcome measures were HAMD and CGI. RESULTS: A recruitment calculation indicated that over 230 suitable patients would be expected to attend the practice during the recruitment phase. Thirty one patients were referred for possible inclusion in the trial by their GPs. Twenty three met the entry criteria, 11 were randomised and 6 completed the study. Of the completers, one received homeopathy, 2 placebo and 3 Fluoxetine. CONCLUSIONS: A trial of this design in general practice is not feasible, because of recruitment difficulties, many of them linked to patient preference. Different approaches are required to recruit adequate patient numbers to trials of this sort.
Adult↗
Urban diffuse sources of faecal indicators.
Increasing concern about bathing water quality in Scotland has led to renewed interest in diffuse sources, as well as the already closely monitored municipal sewage effluents and combined sewer overflows (CSOs) that have been the subject of multi-million pound capital expenditure schemes for several years. Early investigations of diffuse sources focused on rural land uses. This paper is an initial effort to consider the possible significance of urban diffuse sources. A review of the potential for diffuse urban sources includes consideration of sewage pollution in surface water sewers, as well as non-human sources such as pigeon and other bird roosts, and faecal material from pets such as dogs and cats. Portobello beach in Edinburgh is the case study selected, because of earlier work done by Scottish Water and SEPA. The Figgate Burn crosses Edinburgh to discharge onto the beach at Portabello, and pollution sources in its catchment are described. Additional information is reported from Dunfermline, where the sewer network has provided examples of three ways in which sewage pollution can occur in urban streams, and also Scottish examples of measures to control some non-human sources (e.g. SUDS).
Animals↗
Microdistributions of prospective BNCT-compound CuTCPH in tissue sections with a heavy ion microbeam.
Microdistributions of the prospective BNCT-compound CuTCPH, a carborane-containing tetraphenylporphyrin with one Cu atom in its molecular structure, have been obtained in tissue sections of different organs of tumor-bearing and normal Syrian hamsters injected with the boron compound by employing a heavy ion microbeam. High resolution X-ray spectroscopy following micro-PIXE (Particle Induced X-ray Emission with micrometer-sized beams) with a focused (16)O ion beam was used. Focusing was performed with a heavy-ion scanning high-precision magnetic quadrupole triplet microprobe. Squamous Cell Carcinomas were induced on the right Cheek Pouch of Syrian Hamsters (HCP), sampled, cryo-sectioned and freeze-dried. Two-dimensional maps of elemental concentration were obtained by scanning the beam over the samples. Very non-uniform Cu concentrations were found in all sections.
Animals↗
The effect of atorvastatin on markers of bone turnover in patients with type 2 diabetes.
Retrospective and uncontrolled studies suggest that the lipid-lowering statin class of drugs has either no or beneficial effects on bone density and may reduce fracture risk. We have examined the effects of atorvastatin on serum and plasma markers of bone turnover in 25 patients (age 56 +/- 8 years) with type 2 diabetes (duration: 4.7 +/- 5.0 years, 16 female, 2 insulin-treated, 4 diet alone, and 19 on oral hypoglycemic agents) and baseline hypercholesterolemia (cholesterol 6.6 +/- 0.8 mmol/l) in a double-blind, placebo-controlled, crossover study of 12 weeks of placebo/40 mg of atorvastatin with an 8-week wash-out period. Atorvastatin resulted in a fall in total cholesterol of 2.3 +/- 0.9 mmol/l. There were no effects of active or placebo therapy on total alkaline phosphatase, bone-specific alkaline phosphatase, osteocalcin, or beta C-telopeptide of type 1 collagen (beta-CTX). We conclude that atorvastatin (40 mg/day) has no significant effect on bone turnover in man.
Atorvastatin↗
Process water treatment at the Ranger uranium mine, Northern Australia.
The conceptual development and piloting of an innovative water treatment system for process water produced by a uranium mine mill is described. The process incorporates lime/CO2 softening (Stage 1), reverse osmosis (Stage 2) and biopolishing (Stage 3) to produce water of quality suitable for release to the receiving environment. Comprehensive performance data are presented for each stage. The unique features of the proposed process are: recycling of the lime/CO2 softening sludge to the uranium mill as a neutralant, the use of power station off-gas for carbonation, the use of residual ammonia as the pH buffer in carbonation; and the recovery and recycling of ammonia from the RO reject stream.
Australia↗
Low energy proton irradiation effects on alveolar macrophages from young and aged rats.
A prospective study was undertaken to assess the radiotoxicity of accelerated particles in pulmonary alveolar macrophages (AM). We evaluated the effects of a single dose (10-75 Gy) of an external low-energy (20 MeV) proton beam on cultured AM oxidative metabolism and phagocytic function. Macrophages are the first line of defense against invading pathogens and are known to generate superoxide anion (O2), nitric oxide (NO), and mediators of antimicrobial and antitumoral defense mechanisms. We obtained AM by bronchoalveolar lavage from young (1-2 month old) and aged (9-12 month old) male Wistar rats. Cell viability, phagocytosis, O2 and NO production in control and proton-irradiated cultured AM were evaluated The effect of proton irradiation on cell viability was dose-dependent The higher doses induced a dramatic decrease in viability in the aged population. Phagocytosis increased 1.3-1.4 fold inboth populations irrespective of the dose delivered. Generation of O2 was always higher in the aged population for all the doses assayed and showed no significant variation from the control values. In the young population a clear increase was observed with doses of 25 and 50 Gy. NO production in AM from young animals rose in a dose-dependent manner. Conversely, proton irradiation did not affect NO production in macrophages from aged animals. The results of this study demonstrate that AM isolated from young and aged rats are functionally different and show a distinct behavior when exposed to proton irradiation. These findings suggest that age may condition response and must be taken into account when accelerated particle-radiotherapy protocols are considered as a valid therapeutic option for the treatment of cancer. To the best of our knowledge, this is the first report comparing sham-irradiated and proton-irradiated young and aged AM.
Aging↗
Juvenile dermatomyositis and Sjögren's syndrome occurring concurrently in an adolescent male.
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Adolescent↗
Cerebrovascular events in patients with significant stenosis of the carotid artery are associated with hyperhomocysteinemia and platelet antigen-1 (Leu33Pro) polymorphism.
BACKGROUND AND PURPOSE: Although risk factors for carotid artery stenosis caused by atherosclerosis are known, it is unclear what triggers "activation" of the atherosclerotic plaques and the ensuing thromboembolic cerebral events. The aim of this study was to evaluate whether thrombophilic factors, platelet glycoprotein (GP) polymorphisms, and homocysteine are associated with a risk of ischemic events in patients with significant carotid stenosis. METHODS: Consecutive patients with >/=50% carotid stenosis, whether symptomatic (with ipsilateral ischemic events) or asymptomatic, who were evaluated and followed in a neurovascular clinic were tested for plasma levels of homocysteine, C677T mutation in methylenetetrahydrofolate reductase, G20210A mutation of factor II, factor V Leiden, antiphospholipid antibodies, and polymorphisms of platelet membrane GP: human platelet antigen (HPA)-1, GP Ia (C807T), and GP Ib (variable number of tandem repeats, Kozak, and HPA-2). RESULTS: Eighty-six asymptomatic and 67 symptomatic patients were evaluated. The former group was older (73.7+/-6.9 versus 69.5+/-9.1 years, P=0.02). Major risk factors for stroke were similar in both groups. In symptomatic patients versus asymptomatic patients, hyperhomocysteinemia was 3-fold more frequent (34.3% versus 12.8%, respectively; P=0.002) and HPA-1a/b was almost 2-fold more common (38.8% versus 20.9%, respectively; P=0.01). All other thrombophilic factors and platelet polymorphisms studied did not differ significantly between the 2 groups. Multivariate analysis revealed that hyperhomocysteinemia and the HPA-1a/b genotype conferred a significant risk of cerebral ischemic events, with odds ratios (95% CI) of 4.07 (1.7 to 9.7) and 3.4 (1.5 to 7.8), respectively. CONCLUSIONS: Hyperhomocysteinemia and HPA-1a/b are independent risk factors for ischemic events in patients with significant carotid stenosis.
Aged↗
Rehabilitation of a quadruple amputee subsequent to electrical burns sustained whilst hang gliding.
PURPOSE: The purpose of this article is to describe the management, difficulties encountered and level of independence achieved during the initial stage of a quadruple amputee's rehabilitation. METHOD: This is a case study of the rehabilitation of the first known person losing all four limbs due to electrocution whilst hang gliding. RESULTS: The patient became a successful upper limb prosthetic user and returned to work six hours a day. Full independence in activities of daily living was not achieved nor considered practical. Independent walking was accomplished in physiotherapy. however an electric wheelchair remains the only functional means of mobility. CONCLUSION: The rehabilitation is described in detail to assist those managing such a rare and complex case.
Activities of Daily Living↗
Metabolic alterations without metal accumulation in the ovary of adult Bufo arenarum females, observed after long-term exposure to Zn(2+), followed by toxicity to embryos.
Long-term exposure of aquatic organisms to metals, even those considered micronutrients, may affect their metabolism and produce sublethal effects. We evaluated the effects of long-term exposure of adult amphibian (Bufo arenarum) females to 4 microg/L of Zn(2+) (ZnSO(4) x H(2)O) in Ringer solution on the concentration of Zn and Fe, the activity of the key enzyme of the pentose phosphate pathway glucose 6-phosphate dehydrogenase, and glutathione content, both in the liver and ovary of these animals. We also performed early embryonic development studies by in vitro insemination from control and treated females. Zn exposure rendered lower Zn concentrations in the ovaries than did exposure of animals to Ringer solution without metal addition (97 +/- 50 versus 149 +/- 46 Zn microg/wet tissue g). Zn and Fe concentration correlation was positive and linear in the ovary, but was negative and nonlinear in the liver of the studied females. The activity of the enzyme glucose 6-phosphate dehydrogenase decreased (0.0599 +/- 0.0109 versus 0.0776 +/- 0.0263 micromol of NADPH/min x mg of proteins) and the endogenous glutathione content increased (0.027 +/- 0.005 versus 0.018 +/- 0.007 mg/10 mg of proteins) in the ovary but remained unaltered in the liver as a consequence of Zn treatment. Our results suggest the existence of different mechanisms of regulation of Zn and Fe concentrations in the ovary and in the liver of adult B. arenarum females. Binding of Zn to low-molecular-weight proteins, as metallothioneins, may occur in the liver, thus protecting this organ from toxic effects. In the ovary high-molecular-weight proteins, like glucose-6-phosphate dehydrogenase, should be able to bind Zn, leading to oxidative stress responsible for the observed increase in endogenous glutathione content. Inhibition of the pentose phosphate pathway in the ovary by Zn can be responsible for the reproductive failure that we detected through embryos survival studies during early life stages: 81.3 +/- 6.3% of embryos from control females survived versus 63.1 +/- 13.8% of embryos from Zn-treated females at the branchial circulation stage of development.
Animals↗
Cytokines and cytokine inducers stimulate prostaglandin E2 entry into the brain.
Cytokine inducers and cytokines increase the circulating level of prostaglandin E2 (PGE2) during the acute-phase immune response. This occurs simultaneously with the onset of fever, indicating that brain levels of PGE2 also increase. This raises the possibility that PGE2 produced in the peripheral circulation, not necessarily at distant sites from the brain, may penetrate the brain and be present in the cerebrospinal fluid (CSF). Blood and CSF levels of PGE2 in rabbits were measured by radioimmunoassay during fever stimulated in response to lipopolysaccharide (LPS), polyinosinic:polycytidylic acid (poly I:C) and interleukin-1 (IL-1) given i.v. The effect of the prostaglandin synthesis inhibitor ketoprofen on these parameters was also studied. In addition, the level of radioactivity in the CSF was measured following the administration of [125I]-labelled PGE2 i.v. during fever induced by LPS, poly I:C, IL-1 or tumor necrosis factor alpha (TNFalpha). Both LPS and poly I:C stimulated an increase in plasma and CSF levels of PGE2 over a 5-h period with a peak at 60 min and 90 min, respectively, which occurred in parallel with the changes in body temperature. Ketoprofen abolished the rise in plasma and CSF PGE2 levels and the rise in body temperature in response to LPS, poly I:C and IL-1. In experiments where animals were given [125I]-labelled PGE2 i.v., radioactivity well above the background level was measured in samples of CSF collected from LPS-, poly I:C-, IL-1- or TNFalpha-pretreated animals. In contrast the radioactivity present in samples of CSF perfusate collected from control (saline-treated) animals was indistinguishable from the background level. These data indicate that cytokine inducers and cytokines increase the mass level of PGE2 in blood and CSF and also increases the entry, from the peripheral circulation, of radiolabelled PGE2 into the third cerebral ventricle.
Acute-Phase Reaction↗
Thrombophilia as a cause for central and branch retinal artery occlusion in patients without an apparent embolic source.
PURPOSE: To assess the prevalence of vascular risk factors and thrombophilias in central and branch retinal artery occlusion in patients in whom an embolic source is not apparent. METHODS: The study group consisted of 21 consecutive patients with retinal artery occlusion (RAO) in whom Doppler ultrasonography of the carotid arteries and transthoracic or transoesophageal echocardiography were normal. Laboratory methods included polymerase chain reaction for detection of factor V G1691A, factor II G20210A and methylentetrahydrofolate reductase C677T mutations, assays of plasma levels of protein C, free protein S, antithrombin, fibrinogen and homocysteine; and tests for the presence of lupus anticoagulant and anticardiolipin antibodies. Controls for the laboratory tests were 243 healthy subjects. RESULTS: Nine of the 21 (43%) patients had at least one thrombophilic marker: 4 were homozygous for MTHFR C677T, 1 was heterozygous for factor V G1691A, 1 had a high titre of IgM anticardiolipin, 2 were heterozygous for factor V G1691A and homozygous for MTHFR C677T, and 1 had lupus anticoagulant, a high titre of IgM anticardiolipin, homozygosity for MTHFR C677T and hyperhomocysteinaemia. An interaction between vascular risk factors and thrombophilias seemed important since out of 14 patients with hypertension, diabetes and/or hypercholesterolaemia 7 (50%) had a thrombophilia. Homozygous MTHFR C677T was a significant risk factor with odds ratio of 3.18 (95% CI 1.20-8.47). The prevalence of factor V G1691A was also higher in the RAO patients versus controls with an odds ratio of 2.36 (95% CI 0.63-8.88), but this value did not reach significance, probably due to the small sample size. CONCLUSION: A search for thrombophilia in RAO is advisable in patients without evident source of emboli even when vascular risk factors are identified.
Acute Disease↗
Engraftment-associated hypophosphatemia--the role of cytokine release and steep leukocyte rise post stem cell transplantation.
Hypophosphatemia associated with bone marrow transplantation has been infrequently reported. The suggested mechanism is phosphate uptake by the replicating cells. Various cytokines are associated with the development of hypophosphatemia. The present study evaluated the interrelationship between cytokine release, the rise in WBC and the development of hypophosphatemia during the engraftment period. Blood samples were obtained from 60 patients undergoing peripheral blood stem cell transplant, on the day of admission and then daily from the day of transplant until discharge. Hypophosphatemia developed in 62% of the patients. The median day of minimal phosphorus level was +8 and it antedated engraftment by 2 days. There was a significant correlation between the day of minimal phosphorus level and the day of maximal WBC and a significant correlation between the fall in phosphorus level and WBC rise. IL-6 and IL-8 showed similar kinetics. Higher IL-6 and IL-8 levels were directly associated with lower phosphorus levels. In conclusion, hypophosphatemia commonly occurs in the post-transplant period. We assume that both a direct effect of cytokine release and an increased consumption by the dividing WBCs contribute to its appearance. As its occurrence usually antedates engraftment it can be used as a forerunner for WBC recovery.
Adult↗
Do constitutional types really exist? A further study using grade of membership analysis.
'Constitutional types' are a feature of homeopathy. Constitutions are constellations of mental, physical and general features. We present results of a 152-item 'Constitutional Type Questionnaire' (CTQ), relating to 19 major constitutional remedies. Patients referred to the Royal London Homoeopathic Hospital (RLHH) were recruited from outpatient clinics. Each remedy was assigned eight associated features. Each item is rated as it applies to the subject most of the time on a five-point scale. Grade of Membership analysis (GOM) was used for evaluation of remedy profiles. Four hundred and forty-seven individuals provided usable data. Demographic data were collected. A nine pure type solution provided the best fit to the data. Few subjects had exclusive 'membership' of one pure type. There are some difficulties in interpretation; for instance some groups were characterised by the absence of 'constitutional' features. Some pure types are coherent, recognisable types. The results give some support to the homeopathic concept of constitution. CTQ results correlate quite well with the actual prescribing of homeopaths. Further validation with other cohorts is required and with refinement it might become a useful screening method. It cannot simulate complex information processing performed by homeopathic practitioners.
Female↗
The Constitutional Type Questionnaire: validation in the patient population of the Royal London Homoeopathic Hospital.
In homeopathy the choice of a medicine is based on the total 'picture' presented by the patient. This picture includes 'constitutional type' which comprises personality, and general physical features. The Constitutional Type Questionnaire (CTQ) is designed to systematically assess constitutional types. This study examines the reliability and validity of the CTQ. Four hundred and seventy-two outpatients attending clinics at the Royal London Homoeopathic Hospital completed the CTQ, a 152-item scale rating features traditionally considered typical of 19 constitutional homeopathic medicine 'pictures' on 5-point frequency or severity scales. A subsample was retested after 1 week to measure the test-retest reliability. Another subsample was prescribed a medicine by a homeopathic doctor. Prescriptions were compared with the CTQ, to assess the content validity of the scale. The construct validity was measured by Grade of Membership (GOM) analysis. The scale demonstrated good test-retest reliability (r=0.73), internal consistency (r=0.95). The correlation between CTQ results and the medicine prescribed by the homeopathic doctor was 75.8%. The GOM analyses are reported by Davidson et al elsewhere in this issue of the journal. Although the CTQ could be improved, the scale displays good reliability and validity.
Homeopathy↗