bluuebunny/crossref_metadata_2025 huggingface dataset:
Altering Expression Levels of Human Immunodeficiency Virus Type 1 gp120-gp41 Affects Efficiency but Not Kinetics of Cell-Cell Fusion
Authors: Lineberger Janet E. , Danzeisen Renee , Hazuda Daria J. , Simon Adam J. , Miller Michael D.
Published: July 2002

Human immunodeficiency virus (HIV) entry into a host cell requires the fusion of virus and cellular membranes that is driven by interaction of the viral envelope glycoproteins gp120 and gp41 (gp120/gp41) with CD4 and a coreceptor, typically either CXCR4 or CCR5. The stoichiometry of gp120/gp41:CD4:CCR5 necessary to initiate membrane fusion is not known. To allow an examination of early events in gp120/gp41-driven membrane fusion, we developed a novel real-time cell-cell fusion assay. Using this assay to study fusion kinetics, we found that altering the cell surface density of gp120/gp41 affected the maximal extent of fusion without dramatically altering fusion kinetics. Collectively, these observations are consistent with the view that gp120/gp41-driven membrane fusion requires the formation of a threshold number of fusion-active intercellular gp120/gp41:CD4:CCR5 complexes. Furthermore, the probability of reaching this threshold is governed, in part, by the surface density of gp120/gp41.
African Swine Fever Virus IAP-Like Protein Induces the Activation of Nuclear Factor Kappa B
Authors: Rodríguez Clara I. , Nogal María L. , Carrascosa Angel L. , Salas María L. , Fresno Manuel , Revilla Yolanda
Published: July 2002

African swine fever virus (ASFV) encodes a homologue of the inhibitor of apoptosis (IAP) that promotes cell survival by controlling the activity of caspase-3. Here we show that ASFV IAP is also able to activate the transcription factor NF-κB. Thus, transient transfection of the viral IAP increases the activity of an NF-κB reporter gene in a dose-responsive manner in Jurkat cells. Similarly, stably transfected cells expressing ASFV IAP have elevated basal levels of c-rel, an NF-κB-dependent gene. NF-κB complexes in the nucleus were increased in A224L-expressing cells compared with control cells upon stimulation with phorbol myristate acetate (PMA) plus ionomycin. This resulted in greater NF-κB-dependent promoter activity in ASFV IAP-expressing than in control cells, both in basal conditions and after PMA plus ionophore stimulation. The elevated NF-κB activity seems to be the consequence of higher IκB kinase (IKK) basal activity in these cells. The NF-κB-inducing activity of ASFV IAP was abrogated by an IKK-2 dominant negative mutant and enhanced by expression of tumor necrosis factor receptor-associated factor 2.
Synthesis, Reactions and Spectral Properties of Ethyl Esters of 2-Cyano-3-(5-X-2-furyl)acrylic Acid
Authors: Kada Rudolf , Ilavský Dušan , Štetinová Jarmila , Zalibera Lubomír , Paďour Jiří
Published: July 2002

The reaction of 5-X-2-furaldehydes (X = C6H5, COOCH3, COOC2H5, C6H5O, C6H5S, CH3S, 4-Cl-C6H4S, CH3SO2, C6H5SO2, 4-Cl-C6H4SO2) with ethyl cyanoacetate in dry ethanol catalyzed by sodium ethoxide yielded the corresponding ethyl 2-cyano-3-(5-X-2-furyl)acrylates. It was found that the reactions of these esters with cyanoacetophenone or ethyl acetoacetate do not afford the corresponding 4H-pyran derivatives but that there proceeds the exchange of ethyl acetoacetate or of ethyl cyanoacetate for the cyanoacetophenone carbanion. The same course has been observed also for the reactions of these substrates with malononitrile.
Crystallization of Pentaerythritol I. Solubility, Density and Metastable Zone Width
Authors: Karel Miloslav , Nývlt Jaroslav , Chianese Angelo
Published: July 2002

Solubility of pentaerythritol in water has been determined using literature data, the polythermal method and the dry residue method. Densities of its aqueous solutions have been measured using a pycnometer. Kinetics of crystallization of the pentaerythritol has been determined in laboratory experiments. In this paper, metastable zone width measurements have been employed for the assessment of the primary nucleation rate.
Study of Relationship Between Surface Anaesthesia and Chromatographic Properties of Alkoxy Esters of Phenylcarbamic Acid by Neural Network Method. Part I.
Authors: Hatrík Štefan , Lehotay Jozef , Čižmárik Jozef
Published: July 2002

The advanced mathematical method of neural network was employed for studying of surface anaesthetical activity of three homologous series of 2-, 3- and 4-alkoxy substituted morpholinoethyl, piperidinoethyl and azepanylethyl esters of phenylcarbamic acids. RP-HPLC capacity factors were used for the characterization of the lipophility of tested drugs and they were included to the neural network. The three-layer perceptron, that is trained by the back propagation of errors was successfully used for the supplementing of the incomplete original data matrix and also for the smoothing of the noisy biological data. The dependencies between the surface anaesthesia and the number of C atoms in the side alkoxy chain presented the peak character which is in agreement with the theoretical assumptions. Surface anaesthesia grew up in order from para to ortho position of alkoxy chain (para < meta < ortho) in individual homologous series. The azepanyl derivatives presented in average the highest surface anaesthesia. This fact is in agreement with the lowest polarity of azepanyl substituent.
Dehydrogenation, Deamination and Disproportionation of Diethylamine over Heteropoly Compounds
Authors: Ali Abdel-Ghaffar A. , Ali Laila I.
Published: July 2002

In a continuous flow system, transformation of diethylamine over heteropoly compounds was studied at 250 to 350 °C. It was found that ammonium molybdophosphate and tungstophosphate are the most active catalysts while copper molybdophosphate is the most stable one. 12-Molybdophosphoric acid and its salts were highly selective catalysts for dehydrogenation of diethylamine to ethyliden- ethylamine whereas 12-tungstophosphoric acid and its salts directed the reaction selectively to deamination. The role of Lewis acidity of metal cations, Bronsted acidity and basic sites in the reaction mechanism is discussed.
Size Exclusion Chromatography of Substituted Acetylene Polymers: Effect of Autooxidative Degradation of the Polymer During the Analysis
Authors: Vohlídal Jiří , Kabátek Zdeněk , Pacovská Marta , Sedláček Jan , Grubišic-Gallot Zlatka
Published: July 2002

The degradation of poly(phenylacetylene), a typical autoxidatively degradable polymer of substituted acetylene, is shown to take place inside the SEC (size exclusion chromatography) columns during the polymer analysis carried out with eluent (THF) not protected from air. Three types of experimental evidence are given based on the comparison of results of SEC analyses carried out: (i) with the eluent kept under air or argon atmosphere; (ii) with different flow rates of the eluent; and (iii) with and without the interruption of the analysis for a few hours. Other degradable polymers of substituted acetylene are mentioned and recommendations for their SEC analyses are given.
Steric Effects in Acid-Catalyzed Decomposition and Base-Catalyzed Cyclization of 1-(2-Alkoxycarbonylphenyl)-3-phenyltriazenes
Authors: Pytela Oldřich , Halama Aleš
Published: July 2002

Eight derivatives of 1-(2-alkoxycarbonylphenyl)-3-phenyltriazene (R = methyl, ethyl, propyl, isopropyl, butyl, isobutyl, hexyl, and allyl) have been synthesized and their UV-VIS, IR, 1H and 13C NMR spectra measured. The NMR spectra have been interpreted in detail. The kinetics of acid-catalyzed decomposition and base-catalyzed cyclization of the title compounds have been measured in 52.1% w/w methanol at 25.0 °C. The unit reaction order has been verified and the cyclization product has been identified. The pH-profiles obtained have been used to calculate the catalytic rate constants kA (acid-catalyzed decomposition) and kB (base-catalyzed cyclization) of all the derivatives; the constants have been interpreted with regard to inductive and steric effects. The catalytic rate constant kA has been found to be independent of the substituents. The catalytic rate constant kB depends statistically significantly upon both inductive and steric effects, the sensitivity to the former being more significant. The experimental results and their interpretation confirm the base-catalyzed cyclization mechanism with formation of tetrahedral intermediate as the rate-limiting step.
Synthesis and Spectral Properties of 1-(6-Methoxy-2-benzothiazolyl)-2-pyridones
Authors: Štetinová Jarmila , Kada Rudolf , Leško Ján , Dandárová Miloslava , Krublová Marcela
Published: July 2002

Substituted 1-(6-methoxy-2-benzothiazolyl)-2-pyridones 5a-5f have been prepared from N-(6-methoxy-2-benzothiazolyl)cyanoacetamide (2) which on reactions with 4-substituted benzaldehydes gives 3-aryl-2-cyano-N-(6-methoxy-2-benzothiazolyl)-2-propenamides 4a-4g. Derivatives 4a-4f were cyclized with malonodinitrile in the presence of piperidine to give the corresponding 2-pyridones 5a-5f. The IR, UV, 1H NMR and mass spectra of the substances synthesized are discussed.
Intramolecular Reductive Carbonylation of o-Nitroaniline by Carbon Monoxide to 2(3H)-Benzimidazolone
Authors: Macho Vendelín , Králik Milan , Bojsová Eva
Published: July 2002

o-Nitroaniline reacts with carbon monoxide under pressure in the presence of solvents (e.g. dioxane, tetrahydrofuran, N,N-dimethylformamide) and a catalytic system (sulfur or a low molecular sulfur compound - a basic medium - and optionally a vanadium(V) compound) at 370-445 K to give 2(3H)-benzimidazolone by intramolecular reductive carbonylation. Similarly to intermolecular carbonylation of nitroaromatic compounds also in the title reaction the efficiency of the sulfur component decreases in the order: COS > H2S >> CS2 > S. The promotor action of NH4VO3 and V2O5 is, however, less pronounced. The rate of the carbonylation increases with temperature, with optimal selectivity to the 2(3H)-benzimidazolone (>82%) at 390-425 K. The basicity of o-nitroaniline was found to be insufficient, and inorganic or organic bases had to be added to effect the reaction. The above two- (or three-) component systems catalyze also the intramolecular oxidative carbonylation of o-phenylenediamine to 2(3H)-benzimidazolone.
Synthesis of Triferrocenylbenzenes by Tantalum(V)-Catalyzed Cyclotrimerization of Ethynylferrocene. The Crystal Structure of 1,3,5-Triferrocenylbenzene
Authors: Štěpnička Petr , Císařová Ivana , Sedláček Jan , Vohlídal Jiří , Polášek Miroslav
Published: July 2002

Exclusive, high-yield formation of the cyclotrimers of ethynylferrocene (1) was observed when TaCl5 in benzene was employed as catalyst. Analysis of the resulting isomer mixture by means of HPLC and 1H NMR revealed the presence of 1,3,5-triferrocenylbenzene (sym-2) and 1,2,4-triferrocenylbenzene (asym-2) in the ratio of 4 : 6. A small amount of pure sym-2 isomer was isolated, and its solid-state structure was established by single-crystal X-ray diffraction. The molecules of sym-2 possess a distorted up-up-down arrangement of the ferrocenyl groups attached to the benzene ring.
Crystal and Molecular Structure of Di-μ-phenoxido-bis-[N-{(2-hydroxybenzyl)-(S)-alaninato-κ3-O,O',N}copper(II)]. A Simple Homodimetallic Model for N-terminal Tyrosine Coordination with (S)-Alanine as a Second Amino Acid Residue
Authors: Pakhomova Svetlana , Ondráček Jan , Jursík František
Published: July 2002

Single-crystal X-ray diffraction study established the dimeric [Cu2(ohb-(S)-Ala)2] structure (ohb-(S)-Ala = N-(2-hydroxybenzyl-(S)-alaninate). The complex crystallizes in the tetragonal space group P43212 with a = b = 8.849(1) Å, c = 24.913(2) Å, V = 1950.8(3) Å3, Z = 8. The Cu(II) ion has distorted square-pyramidal geometry with the equatorial positions occupied by three oxygen and one nitrogen atom. Each copper atom is weakly coordinated at the apical position by carbonyl oxygen atom of the neighbouring molecule at the distance 2.329(2) Å. The Cu-Cu separation 3.0204(7) Å and the Cu-O3-Cu angle 100.8(1)° lead to antiferromagnetic coupling (at room temperature μeff = 1.35 μB). The O1-Cu-O3 angle (154.9(1)°) indicates distortion of the square pyramid toward a trigonal bipyramid (t = 0.23).
Nonproteolyzed Form of DNA-Polymerase ε from T-Cell Spontaneous Lymphoma of Sprague-Dawley Inbred Rat: Isolation and Characterization
Authors: Birkuš Gabriel , Kramata Pavel , Votruba Ivan , Otová Berta , Otmar Miroslav , Holý Antonín
Published: July 2002

Using a simple isolation procedure and selective assay for the determination of enzyme activity the nonproteolyzed and proteolyzed form of DNA-polymerase ε (pol ε and pol ε*) from the lymphoma of Sprague-Dawley inbred rats were purified. Nonproteolyzed pol ε is composed of two subunits (240 000 and 50 000) with sedimentation coefficient 10.5 S, while the subunit composition of pol ε* was 145 000 and 73 000. Estimated Km values for dATP and dGTP as well as Ki values for acyclic nucleotide analogs (PMEApp, HPMPApp and PMEDAPpp) in pol ε and pol ε* catalyzed reactions have shown that a proteolysis probably does not affect pol ε binding site for dNTPs. Both enzymes (pol ε and pol ε*) possess 3'-5'-exonuclease activity with different Km for 3'-OH end of template poly dA-oligo dT18 (1.6 μmol/l and 0.36 μmol/l, respectively).
Stereospecific Synthesis of (+)-Muscarine from D-Glucose, Suitable for Preparation of 5-Substituted Analogues
Authors: Popsavin Velimir , Beric Ostoja , Radic Ljubica , Popsavin Mirjana , Cirin-Novta Vera , Miljković Dušan
Published: July 2002

A stereospecific synthesis of (+)-muscarine iodide (1) has been achieved starting from D-glucose as a chiral precursor. The key steps of the synthesis involved a stereospecific cyclization of 3,5-di-O-mesyl derivative 3 into the 2,5-anhydride 4, the stereospecific catalytic hydrogenation of unsaturated derivative 6, and the C-4 epimerization of alcohol 12 by Mitsunobu reaction.
Connections Between 11B NMR Chemical Shifts and Electronic Structure in Metallaboranes. A Précis
Authors: Fehlner Thomas P.
Published: July 2002

An analysis of selected sets of metallaboranes in terms of a molecular orbital (MO) model of 11B chemical shift change is used to demonstrate the origin of transition metal effects on boron shifts for: (i) M-B edge protonation; (ii) replacement of direct B-B by M-B interactions; (iii) encapsulation of B in a metal cluster; (iv) change in metal identity; and (v) change in vertex coordination number. Metal effects on both filled and unfilled MO's are important but changes in the latter appear to dominate. Consequently, models based solely on filled orbital properties, e.g., electronic charge, are inadequate. A short review with 56 references.
Application of the NT Solvent Nucleophilicity Scale to Attack at Sulfur: Solvolyses of Benzenesulfonyl Chlorides
Authors: Kevill Dennis N. , D'Souza Malcolm J.
Published: July 2002

The specific rates of solvolysis of benzenesulfonyl chloride and three 4-substituted derivatives can be very well correlated using the extended Grunwald-Winstein equation, with incorporation of NT solvent nucleophilicity and YCl solvent ionizing power values. In two instances, it was shown that almost identical correlations were obtained after the incorporation of methyl groups into the 2- and 6-positions of the benzene ring. No evidence was found for a dissociative (SN1) mechanism or for a duality of mechanism. All of the results can be rationalized in terms of a concerted bimolecular displacement (SN2) mechanism, involving attack by solvent at sulfur.
Fast Evaluation of Differential Capacity and Surface Charge in Electrical Double Layers with A.C. Oscillopolarography
Authors: Bi Shuping , Gao Hong , Tang Wei , Yang Zhiguo , Du Sidan , You Xiang , Wang Jiehui , Zhang Mingquan
Published: July 2002

The application of a.c. oscillopolarography for a fast evaluation of differential capacity and surface charge in electrical double layers on the mercury electrode is described. The Cd = f(E), Q = f(E) and γ = f(E) functions are displayed. The obtained values of differential capacity and surface charge densities are in agreement with those from the a.c. bridge method. The new method has the distinct advantages of a rapid analytical procedure, visual detection, very simple manipulation and low-cost instrumentation. It is very useful in practical analysis where accurate values of differential capacity and surface charge are not required.
Minor Ecdysteroid Components of Leuzea carthamoides
Authors: Vokáč Karel , Buděšínský Miloš , Harmatha Juraj
Published: July 2002

Fourteen minor ecdysteroid components were isolated and identified from the roots of Leuzea carthamoides (Willd.) DC. Two of them are new phytoecdysteroids: leuzeasterone (1) a six-member side-chain lactone, and (24Z)-29-hydroxy-24(28)-dehydromakisterone C (4) a structurally related sitostane type analogue and assumed biogenetic precursor of 1. The next one, 5α-20-hydroxyecdysone (6), is a rare A/B-ring trans-annelated epimer of the most common phytoecdysteroid 20-hydroxyecdysone. Further compounds: makisterone C (3), 3-epi-20-hydroxyecdysone (5), integristerone A (7), integristerone B (8), 22-oxo-20-hydroxyecdysone (10), taxisterone (11), rubrosterone (12), dihydrorubrosterone (13) and poststerone (14), are new constituents of L. carthamoides, though already reported as compounds isolated from other natural sources. Two earlier reported minor Leuzea ecdysteroids: the five-membered side-chain lactone carthamosterone (2) and the 11-hydroxy-substituted analogue isovitexirone (9), are also included because they are now better characterised. Certain previously described Leuzea ecdysteroids were not found in our material, which may indicate geographic, seasonal or cultivar variations.
The quality of research in sports journals: Table 1
Authors: Bleakley C , MacAuley D
Published: July 2002

Objective: To examine the evidence base of sports medicine research.

Methods: A sample of four major journals that present core research in sport and exercise medicine (British Journal of Sports Medicine,Medicine and Science in Sports and Exercise,Journal of Sports Medicine and Physical Fitness, andPhysical Therapy) was examined using assessment criteria taken from the READER method.

Results: Randomised controlled trials comprised 10% or less of all original research articles. Observational/descriptive studies were the most commonly published study design. There was a highly significant difference (p<0.0001) in the contents of the four journals but when they were compared by categorising the better quality methods together (randomised control trial, case-control, and cohort studies), the difference was not significant (p = 0.09).

Conclusions: The overall pattern of publication type seems remarkably stable over medical journals, indicating that the quality of sports medicine research is comparable to that in other specialities.
Immunohistochemical demonstration of oestrogen and progesterone receptors: correlation of standards achieved on in house tumours with that achieved on external quality assessment material in over 150 laboratories from 26 countries
Authors: Rhodes A , Jasani B , Balaton A J , Miller K D
Published: July 2002

Aims—To investigate the sensitivity of immunohistochemical (IHC) assays for oestrogen receptors (ER) and progesterone receptors (PR) achieved by laboratories on breast tumours fixed and processed in their own department, and to compare this with the degree of sensitivity they achieve on tumours circulated as part of an external quality assessment (EQA) programme.

Methods—On 10 occasions between April 1994 and June 1998, histological sections from breast cancers showing various degrees of expression of ER and PR were circulated for IHC staining to laboratories participating in the UK national external quality assessment scheme for immunocytochemistry (UK NEQAS-ICC). The staining of these tumours, in addition to that of tumours fixed and processed in the participants own laboratories (in house tumours), was assessed by a panel of four assessors, using the established UK NEQAS-ICC scoring system. For a selected assessment run, the degree of expression of participants in house tumours was evaluated by means of the semiquantitative quick score method.

Results—Although the scores awarded for the staining of in house tumours were generally higher than those awarded for the staining of UK NEQAS tumours, there was also a significant positive correlation between the two sets of scores. Using the quick score method of evaluation for one of the assessment runs, 47% of in house tumours were classified as having a high degree of ER expression. Of the remaining cases, a significant proportion initially classified as having only low or medium expression of ER were found to have higher expression when stained by the organising laboratory. The UK NEQAS-ICC centre's routine assay for hormonal receptors was found to be 90–100% efficient in achieving optimal demonstration of breast tumours from over 150 different laboratories.

Conclusions—The significant positive correlation between the results obtained on the UK NEQAS tumours and the in house tumours provides evidence for the view that results achieved on EQA material are accurate indicators of in house laboratory performance. Although most laboratories adequately detected tumours with high receptor expression, a large proportion of in house tumours classified initially by participants' staining as being of low or medium ER expression had a higher degree of expression when stained by the UK NEQAS-ICC centre. The efficiency of the organising centre's routine IHC method for ER and PR in optimally demonstrating participants in house breast tumours shows that variations in fixation and tissue preparation are not limiting factors preventing a different laboratory achieving optimal demonstration.
The ethics of anonymised HIV testing of pregnant women: a reappraisal
Authors: de Zulueta Paquita
Published: July 2002

Seroprevalence monitoring of HIV in pregnant women by anonymised unlinked testing has been widely adopted in the UK and other countries. The scientific rationale is to eliminate participation and selection bias. The ethical justification is that the public good outweighs any harm to individuals. The assumption has been that individuals have had their autonomy respected by the offer of informed consent. In the light of new scientific evidence, it is doubtful that the public good is best served by the continuation of anonymously testing women receiving antenatal care. It is submitted that it is no longer ethical for health professionals to refrain from informing pregnant women of the benefits of voluntary named testing, or to request their consent to anonymised testing. The legal and moral concept of duty of care is examined, and the abrogation of this duty through anonymisation is explained.
Frontiers in care: a case of compulsory treatment in AIDS dementia. Case study and commentaries
Authors: Higgs Roger , Pinching Anthony J
Published: July 2002

A patient with AIDS dementia was confronted and compulsorily prevented from flying out of the country before being admitted against his will to hospital. While finding this on balance justified in the circumstances the commentators raise moral questions about the levels of care in general practice and within the couple's own relationships.
Causal authorship and the equality principle: a defence of the acts/omissions distinction in euthanasia
Authors: Stauch Marc
Published: July 2002

This paper defends the acts/omissions distinction which underpins the present law on euthanasia, from various criticisms (including from within the judiciary itself), and aims to show that it is supported by fundamental principles. After rejecting arguments that deny the coherence and/or legal relevance of the distinction, the discussion proceeds to focus on the causal relationship between the doctor and the patient's death in each case. Although previous analyses, challenging the causal efficacy of omissions generally, are shown to be deficient, it is argued that in certain cases of causing death by omission the causal authorship of the doctor lapses. The final part of the paper examines why this should be morally significant and proposes an answer in terms of the principle of equality. Assuming all other factors are equal, the infringement of this principle provides an additional reason against actively killing a patient, which is not present in cases of passively letting die.
Neither consenting nor protesting: an ethical analysis of a man with autism
Authors: Diesfeld Kate
Published: July 2002

This article critically examines the 25 June 1998 decision by the House of Lords regarding the psychiatric admission of a man with autism.1Mr L was able neither to consent to, nor refuse, that admission and the disposition of his case illuminates the current debate regarding best interests of vulnerable adults by the judiciary and the psychiatric profession. This article begins with the assumption that hospitalisation was not the optimum response to Mr L's condition, provides alternative approaches to the interpretation of best interest and examines principles of liberty, anti-discrimination, and equal protection.
Mental incapacity and restraint for treatment: present law and proposals for reform
Authors: Bridgman Andrew M
Published: July 2002

The House of Lords in F v West Berkshire Health Authority [1989] considered the lawfulness of providing care and treatment for a mentally incapacitated adult. They did not, however, directly consider the use of restraint to enable the provision of care in the face of resistance from the patient. The law has since had good cause to give consideration to this important issue. This paper establishes the present law in the context of using restraint to deliver care. Although the legal principles established have derived from what might be considered to be “hard cases”, life-and-death cases, they apply to all aspects of routine medical, dental and nursing care. Further, the paper considers the recent government proposals and the effect those proposals may have on the routine care of such patients.
Dealing with prejudice
Authors: O'Rourke Alan
Published: July 2002

Few of us are free of all prejudices, however subtle and subconscious, and they may affect both patient care and teaching. Here I use reflection about a patient with HIV infection, from the points of view of two doctors caring for him and the patient himself, to explore prejudice against lifestyles that are considered “dangerous”. The paper then goes on to discuss research about physicians' attitudes to such cases, the teaching of ethics in a clinical environment and the need to support junior medical staff.
‘What is (mental) disease?’: an open letter to Christopher Boorse
Authors: Fulford K W M
Published: July 2002

This “open letter” to Christopher Boorse is a response to his influential naturalist (value-excluding) analysis of disease from the perspective of linguistic-analytic value theory. The key linguistic-analytic point against Boorse (and other naturalists) is that, although defining disease value free, he (and they) continue to use the term with clear evaluative connotations. A descriptivist (value-entailing) analysis of disease would allow value-free definition consistently with value-laden use: but descriptivism fails when applied to mental disorder because it depends on shared values whereas the values relevant to mental disorders are highly diverse. A part-function analysis, similarly, although initially persuasive for physical disorders, fails with the psychotic mental disorders because these, characteristically, involve disturbances of the rationality of the person as a whole. The difficulties encountered in applying naturalism to mental disorders point, linguistic-analytically, to the possibility that there is, after all, an evaluative element of meaning, deeply hidden but still logically operative, in the concept of disease.
Analysing health outcomes
Authors: Dowie Jack
Published: July 2002

If we cross-classify the absolutist-consequentialist distinction with an intuitive-analytical one we can see that economists probably attract the hostility of those in the other three cells as a result of being analytical consequentialists, as much as because of their concern with “costs”. Suggesting that some sources of utility (either “outcome” or “process” in origin) are to be regarded as rights cannot, says the analytical consequentialist, overcome the fact that fulfilling and respecting rights is a resource-consuming activity, one that will inevitably have consequences, in resource-constrained situations, for the fulfilment of the rights of others. Within the analytical consequentialist framework QALY-type measures of health outcome have the unique advantage of allowing technical and allocative efficiency to be addressed simultaneously, while differential weighting of QALYs accruing to different groups means that efficiency and equity can be merged into the necessary single maximand. But what if such key concepts of the analytical consequentialist are not part of the discursive equipment of others? Are they to be disqualified from using them on this ground? Is it ethical for intuition to be privileged in ethical discourse, or is the analyst entitled to “equal opportunities” in the face of “analysisism”, the cognitive equivalent of “racism” and “sexism”?
Impairment, disability and handicap—old fashioned concepts?
Authors: Jones R B
Published: July 2002

The drawbacks of using the concepts of models in discussing the problems of disabled people are discussed. It is suggested that the terms “impairment”, “disability”, and “handicap” can unify the different models and enhance the position of people with disabilities in society.
Let the consumer decide? The regulation of commercial genetic testing
Authors: Levitt Dr Mairi
Published: July 2002

Objectives—The development of predictive genetic tests provides a new area where consumers can gain knowledge of their health status and commercial opportunities. “Over-the-counter” or mail order genetic tests are most likely to provide information on carrier status or the risk of developing a multifactorial disease. The paper considers the social and ethical implications of individuals purchasing genetic tests and whether genetic information is different from other types of health information which individuals can obtain for themselves.

Design—The discussion is illustrated by findings from a questionnaire survey of university students as potential consumers. Topics covered included what health tests they had already used, expectations of genetic tests, willingness to pay, who should have access to the results and whether there need to be restrictions on such tests.

Sample—Six hundred and fifteen first-year students in the universities of Leuven, Cardiff, Central Lancashire, Vienna and Nijmegen studying either medicine or a non-science subject.

Results—Students were enthusiastic about genetic tests and had high expectations of their accuracy and usefulness but most thought they should be available through the health service and a minority thought that some tests, for example for sex selection, should not be available at all. There were few differences in responses by sex or subject of study but some by country. The paper also considers ethical and social issues outside the scope of a questionnaire survey of this type.

Conclusion—To address some of these issues the sale of genetic tests to individuals can be made subject to ethical guidelines or codes of practice, for example to protect vulnerable groups, but there are fundamental social and ethical questions which such guidelines cannot address.
Ethical considerations for services offering one-to-one guidance for primary care practitioners interested in research
Authors: Bateman H
Published: July 2002

Initiatives which offer support to primary care practitioners interested in research have become widespread in the UK. There has been little debate, however, about the ethical issues involved in such interactions with practitioners. Established codes of practice and analyses of the institutional and strategic contexts have been used to inform this discussion. The paper concludes with a recommendation that more explicit quasi-contractual relationships should be negotiated between those offering and those seeking help.
Patients' perceptions of information provided in clinical trials
Authors: Ferguson P R
Published: July 2002

Background: According to the Declaration of Helsinki, patients who take part in a clinical trial must be adequately informed about the trial's aims, methods, expected benefits, and potential risks. The declaration does not, however, elaborate on what “adequately informed” might amount to, in practice. Medical researchers and Local Research Ethics Committees attempt to ensure that the information which potential participants are given is pitched at an appropriate level, but few studies have considered whether the patients who take part in such trials feel they have been given adequate information, or whether they feel able to understand that information.

Objectives: To explore trial participants' views (i) on the amount of information provided, and (ii) of their own understanding of that information.

Design: Structured interviews of patients participating in clinical trials for the treatment of chronic medical condition.

Findings: Patients generally felt they were given an appropriate amount of information, and that they were able to understand all or most of it. They felt they were given adequate time to ask questions before agreeing to take part. In comparison with treatment given outwith the research setting, patients generally felt they received more information when participating in a clinical trial.

Conclusions: Researchers sometimes complain that patients are given too much information during clinical trials, and have limited understanding of that information. The present study shows that this perception is not necessarily shared by patients. More research is needed in this area, particularly to gauge whether patient understanding is indeed accurate.
Commentary on Glannon and Ross, and McKay
Authors: McLean S A M
Published: July 2002

The patient-doctor relationship has recently come under intense scrutiny, resulting in a re-evaluation of the basis of that relationship. The papers by Glannon and Ross, and McKay seek to identify the sources of authority in the patient-doctor relationship by evaluating it in terms of the concept of altruism. In this paper I argue that the analysis of Glannon and Ross, and of McKay is unnecessary and that the analysis offered by the latter is also flawed. I do acknowledge, however, that Glannon and Ross's description of doctors' responsibilities and patients' roles has much to commend it.
Thomson, the right to life, and partial birth abortion or two MULES for Sister Sarah
Authors: Alward P
Published: July 2002

In this paper, I argue that Thomson's famous attempt to reconcile the fetus's putative right to life with robust abortion rights is not tenable. Given her view, whether or not an abortion violates the fetus's right to life depends on the abortion procedure utilised. And I argue that Thomson's view implies that any late term abortion that involves feticide is impermissible. In particular, this would rule out the partial birth abortion technique which has been so controversial of late.
The criminalisation of HIV transmission
Authors: Chalmers J
Published: July 2002

Since Bennett, Draper, and Frith published a paper in this journal in 2000 considering the possible criminalisation of HIV transmission, an important legal development has taken place. February 2001 saw the first successful United Kingdom prosecution for the sexual transmission of disease for over a century, when Stephen Kelly was convicted in Glasgow of recklessly injuring his former girlfriend by infecting her with HIV. Whether English criminal law (as opposed to Scots law) can apply criminal penalties in such a case, however, still remains uncertain.

This paper, in addition to providing some background to the Kelly case, briefly explores the current possibilities for prosecution under English law. It then proceeds to outline and comment on the issues relevant to criminalisation, responding in part to points made by Bennett, Draper, and Frith and also by Bird and Leigh Brown in a recent article in theBritish Medical Journal.
Premature stopping and informed consent in AMI trials
Authors: Hilden J , Gammelgaard A
Published: July 2002

Clinical trials give rise to ethical dilemmas, especially in the acutely ill, but we take issue with two points raised in a recent comment on a specific acute myocardial infarction (AMI) trial. The commentators judged that the trial most likely could, and therefore should, have been terminated much earlier. By analysing the problem statistically we arrive at results that go against their intuitive judgment—they also see it as mandatory to update the patient Information sheet as trial results accrue and trends begin to emerge. In our view, interpreting subtle trends and borderlinep-values must rest with data monitoring boards, not patients. Moreover, patients with AMI or in other medical emergencies need very simple instructions. Empirical studies of the consent process confirm that the idea of a genuinely informed consent is problematic in such cases.
A comparison of professionals' and patients' understanding of asthma: evidence of emerging dualities?: Table 1
Authors: Sweeney K G , Edwards Karen , Stead Jonathan , Halpin David
Published: July 2002

Despite an increase in the provision of services to patients with asthma, morbidity from the disease remains high. Recent research (outside asthma) has raised the possibility that patients may develop a conceptualisation of illnesses which is not entirely compatible with the prevailing biomedical view. This paper compares the way in which health care professionals and patients with asthma described various aspects of the illness, using an approach which considered the type of knowledge which might be used to construct the respective conceptualisations of asthma. A qualitative method is empliyed, using focus groups. Eight focus groups were convened, four of professionals and four of patients with asthma. Following the initial data analysis, the results were reviewed linguistically, with particular attention to the use of metaphor.

The health care professionals and patients participating in this study agreed broadly in their explanations of the aetiology and drug treatment of asthma. The data suggest lack of congruence in the development of treatment strategies and locus of control. Health care professionals and patients in this study used linguistically different metaphors to represent the disease: the former more frequently used metaphors evoking on-going processes, the latter visualising the chest (in their use of metaphor) as a static container, emptying and filling throughout the course of the disease. Two commentaries from philosophical and anthropological literature are considered in order to offer theoretical accounts relevant to this interpretation. The data suggest an emerging duality in the approach to treatment plans, in the roles played by professionals and patients with asthma, and in the different types of knowledge used by professionals and patients to construct their respective working models of asthma.
Poetry, interpretation and unpredictability: a reply to Neil Pickering
Authors: Ahlzén Rolf , Stolt Carl-Magnus
Published: July 2002

In his article on poetry in health care education, Neil Pickering puts forward an argument of radical unpredictability: as we can never know in advance how a poem will be interpreted, it can be of no external use.1It is, however, exactly this potential to give rise to multiple interpretations that makes the poem valuable. We hold that the poem should be read and discussed with no other intention than to discover and reflect on its possible meanings. Exactly this process, preferably in dialogue with other readers, may very well serve as one of the ends of the poem, and the results of it hence constitute its external use.
Increased inflammation and intracellular calcium caused by ultrafine carbon black is independent of transition metals or other soluble components
Authors: Brown D M , Stone V , Findlay P , MacNee W , Donaldson K
Published: July 2002

OBJECTIVES

Particulate air pollution has been shown to cause adverse health effects, and the ultrafine particle component has been implicated. The aim of the present study was to investigate whether an ultrafine particle exerted its effects through transition metals or other soluble factors released from the surface of the particles.

METHODS

Both in vitro and in vivo models were used to test the imflammogenicity of carbon black (CB) and ultrafine carbon black (UfCB) and the role of transition metals was investigated by treating the particles with desferrioxamine mesylate (desferal), a transition metal chelator. Rats were instilled with particles and the cell population assessed by bronchoalveolar lavage (BAL). Calcium homeostasis in macrophages was assessed with a fluorimetric technique.

RESULTS

UfCB was inflammogenic compared with CB when instilled into Wistar rat lungs, an effect which could not be ameliorated by desferal treatment of the particles. Particle leachates produced no significant inflammation in vivo. In vitro experiments showed that the cytosolic calcium ion concentration in Mono Mac 6 cells was increased significantly after UfCB treatment and treatment of particles with desferal did not alter these effects. Particle leachates had no effect on cytosolic calcium ion concentration. Iron was not detected in leachates of the particles with the desferal assay, however, ng/mg of particles were detectable in citrate leachates with inductively coupled plasma-mass spectrometry (ICP-MS).

CONCLUSIONS

The increased inflammogenicity of UfCB compared with CB cannot be explained by soluble transition metals released from or by accumulation of iron at the particle surface. Differences may be accounted for by increased surface area or particle number.
Reactivity and recovery from different types of work measured by catecholamines and cortisol: a systematic literature overview
Authors: Sluiter Judith K , Frings-Dresen Monique H W , Meijman Theo F , van der Beek Allard J
Published: July 2002

OBJECTIVES

To review occupational health, laboratory, and sports literature on neuroendocrine reactivity and recovery from mental, combined mental and physical, or physical tasks.

METHODS

A systematic literature search was performed in eight databases. Studies with catecholamines or cortisol as effect variables measured in blood, urine, or saliva were included.

RESULTS

After application of inclusion and exclusion criteria, 77 studies from the initial 559 identified were taken into account. In occupational settings it was found that relatively few studies were conclusive about recovery, which formed a contrast with sports research. For reactivity and recovery up to 1 hour after performing the task, half of the studies considered physical tasks and more than two thirds showed incomplete recovery compared with baseline excretion of catecholamines and cortisol. Recovery extending to 3 days after the task was performed was often incomplete for cortisol after combined mentally and physically demanding tasks, and less often after solely mental or physical tasks. This type of recovery was more often incomplete for adrenaline (epinephrine) than for noradrenaline (norepinephrine), which was the case after mental as well as combined mental and physical tasks.

CONCLUSIONS

The results from laboratory and sports research may be transferable to some occupations, but more research is needed on the course of recovery relative to health effects in occupational settings.
Prevalence of Raynaud's phenomenon in Great Britain and its relation to hand transmitted vibration: a national postal survey
Authors: Palmer Keith T , Griffin Michael J , Syddall Holly , Pannett Brian , Cooper Cyrus , Coggon David
Published: July 2002

OBJECTIVES

To assess the prevalence of Raynaud's phenomenon in the general population of Great Britain and to estimate the proportion and number of cases attributable to hand transmitted vibration (HTV).

METHODS

A questionnaire was posted to a random sample of 22 194 adults of working age. Information was collected on the lifetime prevalence of finger blanching, smoking habits, and occupational and leisure time exposures to HTV. Associations with risk factors were explored by logistic regression, with odds ratios converted into prevalence ratios (PRs).

RESULTS

Among the 12 907 respondents, 1835 (14.2%) reported finger blanching at some time, including 1529 (11.8%) in whom symptoms were induced by cold, and 597 (4.6%) in whom the blanched area was also clearly demarcated. Prevalences were higher in women than men. Around one fifth of cases (2% of respondents) had consulted a doctor about their symptoms. By comparison with men who had never been exposed to HTV, the PR for cold induced blanching in those exposed only at work was 2.0 (95% CI 1.7 to 2.3), and in men exposed both at work and in leisure it was 2.5 (95% CI 2.1 to 3.1). Higher risks were found in men who consulted a doctor about cold induced blanching, among whom 37.6% of cases were estimated to arise from exposure to HTV. The estimated number of cases attributable to HTV nationally was 222 000 in men who reported extensive blanching (blanching affecting at least eight of the digits or 15 phalanges). Similar patterns of risk were found in women, but the attributable proportion was much lower (5.3% in cases consulting a doctor).

CONCLUSIONS

Raynaud's phenomenon is common in the general population. Many cases are attributable to HTV, especially in men, emphasising the public health importance of this common occupational hazard.
Is it feasible to construct a community profile of exposure to industrial air pollution?
Authors: Pless-Mulloli Tanja , Dunn Christine E , Bhopal Raj , Phillimore Peter , Moffatt Suzanne , Edwards John
Published: July 2002

OBJECTIVE

An epidemiological investigation to assess the validity of residential proximity to industry as a measure of community exposure.

METHODS

19 Housing estates in Teesside (population 1991: 77 330) in north east England were grouped into zones: A=near; B=intermediate; C=further from industry. With residential proximity of socioeconomically matched populations as a starting point a historical land use survey, historical air quality reports, air quality monitoring, dispersion modelling data, and questionnaire data, were examined.

RESULTS

The populations in zones A, B, and C were similar for socioeconomic indicators and smoking history.Areas currently closest to industry had also been closest for most of the 20th century. Historical reports highlighted the influence of industrial emissions to local air quality, but it was difficult to follow spatial pollution patterns over time. Whereas contemporary NOxand benzene concentrations showed no geographical variation, dispersion modelling of emissions (116 industrial stacks, traffic, and domestic sources) showed a gradient associated with industry. The presumed exposure gradient of areas by proximity to industry (A>B>C) was evident for all of zone A and most of zones B and C.

CONCLUSIONS

It was feasible to assemble a picture of community exposure by integration of measurements from different sources. Proximity of residence was a reasonable surrogate for complex community exposure.