bluuebunny/crossref_metadata_2025 huggingface dataset:
Towards an Effective Chemotherapy of Virus Infections: Therapeutic Potential of Cidofovir [(S)-1-[3-Hydroxy-2-(phosphonomethoxy)propyl]cytosine, HPMPC] for the Treatment of DNA Virus Infections
Authors: De Clercq Erik
Published: July 2002

The acyclic nucleoside phosphonate HPMPC [(S)-1-[3-hydroxy-2-(phosphonomethoxy)propyl]cytosine, cidofovir, Vistide®] has a unique profile among the antiviral agents in that it is active against a much broader spectrum of DNA viruses than any other antiviral agent, and, furthermore, shows a long-lasting antiviral activity, thus enabling infrequent dosing (for intravenous administration, as infrequent as once a week or every other week). HPMPC owes its antiviral activity to a selective inhibitory effect on viral DNA synthesis: as has been demonstrated for human cytomegalovirus (CMV), HPMPC leads to DNA chain termination following the incorporation of two consecutive HPMPC residues. The activity spectrum of HPMPC encompasses herpes-, adeno-, polyoma-, papilloma-, and poxviruses. It has been approved for the treatment of CMV retinitis in AIDS patients and has proved effective in the treatment of herpes simplex virus (HSV) infections (particularly those that are resistant to acyclovir), human papilloma virus (HPV) infections (e.g. anogenital warts and recurrent laryngeal papillomatosis) and poxvirus infections (e.g. molluscum contagiosum). It is now further explored for its therapeutic potential in the treatment of HSV, CMV and HPV infections, and various other DNA virus infections, including adenovirus infections (e.g. keratoconjunctivitis), polyomavirus infections such as PML (progressive multifocal leukoencephalopathy), poxvirus infections (e.g. molluscum contagiosum), Epstein-Barr virus (EBV)-associated infections, and human herpesvirus type 8 (HHV-8)-associated infections (e.g. Kaposi's sarcoma).
Comparing the Acidities of Microporous Aluminosilicate and Silico-Aluminophosphate Catalysts: A Combined Quantum Mechanics-Interatomic Potential Function Study
Authors: Sauer Joachim , Schröder Klaus-Peter , Termath Volker
Published: July 2002

DFT-B3LYP calculations are performed on 4-ring models of aluminophosphates (AlPOs) and silico-aluminophosphates (SAPOs). The results are used to fit the parameters of ion pair shell model potential functions. The potentials obtained are tested in lattice energy minimizations for berlinite and the microporous materials AlPO-18, AlPO-40, AlPO-52, and VPI-5. Not only does the potential reproduce the observed structures (average error of the cell constants 1.3%), it also predicts vibrational frequencies over the whole frequency range equally well (maximum deviation 50 cm-1). The potential is used to predict the structures and properties of Bronsted acid sites in an aluminosilicate and a SAPO with the chabazite framework structure (HSSZ-13 and HSAPO-34). A new combined quantum mechanics-intermolecular potential function approach (QM-Pot) is used at the DFT level. Comparison is made with full periodic DFT calculations using plane wave basis sets. The deprotonation energies corrected for systematic errors of the methods used are 1 231-1 235 and 1 261-1 280 kJ/mol for HSSZ-13 and HSAPO-34, respectively. The same acid site has a lower acidity in a SAPO than in an aluminosilicate zeolite of the same structure.
Apple-Tree Shoots and Transformed Carrot and Apple Roots Used as Biocatalysts in Enantioselective Acetate Hydrolysis, Alcohol Oxidation and Ketone Reduction
Authors: Mironowicz Agnieszka , Kromer Krystyna
Published: July 2002

(±)-1-Phenylethyl (1), (±)-1-(1-naphthyl)ethyl (2), (±)-1-(2-naphthyl)ethyl (3) and (±)-menthyl (4) acetates were hydrolyzed using apple-tree shoots and hairy roots of carrot and apple-tree to afford alcohols, which, subsequntly, in the same environment, were oxygenated to ketones. Pure (S)-1-(2-naphthyl)ethanol ((S)-(-)-7), (R)-1-phenylethyl acetate ((R)-(+)-1), (R)-1-(1-naphthyl)ethyl acetate ((R)-(+)-2), (S)-1-phenylethanol ((S)-(-)-5) and (-)-menthol (1R,2S,5R)-(-)-8) have been produced.
Extraction of Alkaline and Alkaline-Earth Metal Cations at Synergistic Action of Bis[undecahydro-7,8-dicarbaundecaborato(2-)]cobaltate(1-) and Substituted Calix[n]arenes in Nitrobenzene
Authors: Vaňura Petr , Stibor Ivan
Published: July 2002

The extraction of alkaline and alkaline-earth metal cations at synergistic action of bis[undecahydro-7,8-dicarbaundecaborato(2-)]cobaltate(1-) and substituted calix[n]arenes (n = 4 and 6) in nitrobenzene was investigated. It was found that the lower-rim-substituted calix[4]arene with four (diethylcarbamoyl)methyl groups extracts calcium, strontium and barium in the systems under study much better than calixarenes which do not contain amide groups. Synergistic factor values log S(Ca) = 7, log S(Sr) = 5.5 and log S(Ba) = 5.4 were found. The competition of K+ and Na+ in the extraction of strontium is much lower than in analogous systems containing crown ethers. The addition of calixarene causes a synergistic effect in the extraction of sodium and an antagonistic effect in the extraction of cesium.
Isolation and Structure of [(PPh3)3(PPh2)2Pd4B20H16]. A Possible Prognostic for New Globular Borane-Based Cluster Architectures
Authors: Yao Hai-Jun , hu Chun-Hua , Sun Jie , Jin Ruo-Shui , Zheng Pei-Ju , Bould Jonathan , Greatrex Robert , Kennedy John D. , Ormsby Daniel L. , Thornton-Pett Mark
Published: July 2002

A novel metallaborane compound, [(PPh3)3(PPh2)2Pd4B20H16], prepared from [PdCl2(PPh3)2] and [B10H10]2- in EtOH, exhibits a globular cluster architecture consisting of two twelve-vertex closo {PdB11} cluster units fused to generate a condensed globular {PdB20} assembly that has a tetrahedral {B4} borons-only core. There is dynamic bonding between this borane-based assembly and an unusual exopolyhedral palladium-based domain consisting of a {(PPh3)Pd(PPh2)Pd(PPh2)Pd(PPh3)} string. The central tetrahedral borons-only core suggests a new type of globular "megaloborane" architectural principle for higher condensed boron hydrides, which is assessed by ab initio studies at the STO-3G level on protonated [B28H18]2- and related structures: results suggest energetic minimisation at neutral [B27H21].
Relationships Between the Chemical Structure of Substances and Their Antimycobacterial Activity Against Atypical Strains. Part 18. 3-Phenyl-2H-1,3-benzoxazine-2,4(3H)-diones and Isosteric 3-Phenylquinazoline-2,4(1H,3H)-diones
Authors: Waisser Karel , Macháček Miloš , Dostál Hynek , Gregor Jiří , Kubicová Lenka , Klimešová Věra , Kuneš Jiří , Palát Karel , Hladůvková Jana , Kaustová Jarmila , Möllmann Ute
Published: July 2002

A series of 3-phenyl-2H-1,3-benzoxazine-2,4(3H)-diones 2 and 3-phenylquinazoline-2,4(1H,3H)-diones 5 substituted on the phenyl rings were synthesized. The target compounds as well as the intermediates were tested against Mycobacterium tuberculosis, M. kansasii, and M. avium. The replacement of the oxygen atom by nitrogen resulted in a decrease or loss of antimycobacterial activity. 2-[(Ethoxycarbonyl)amino]benzanilides 4 appeared to be inactive. Salicylanilides 1 and 3-phenyl-2H-1,3-benzoxazine-2,4(3H)-diones 2 exhibit significant activity against both M. tuberculosis and nontuberculous mycobacteria (the MICs within the range of 4-250 μmol/l for all compounds). The antimycobacterial activity of the compounds increases with increasing both electron-withdrawing properties and hydrophobicity of the substituent(s) on the phenyl moiety. The antimycobacterial profile of the compounds was analyzed according to the criteria based on vector algebra, such as cosine coefficients. Moreover, salicylanilides 1 exhibit activity against other microorganisms tested by the agar diffusion method.
Investigation of Catechin and Acridine Derivatives Using Voltammetric and Fluorimetric DNA-Based Sensors
Authors: Vaníčková Mária , Labuda Ján , Bučková Miriam , Surugiu Ioana , Mecklenburg Michael , Danielsson Bengt
Published: July 2002

The preconcentration-differential pulse voltammetric detection scheme with a carbon paste electrode bulk phase modified with DNA was used for the investigation of behaviour and the determination of trace levels of catechin and acridine derivatives. The effect of electrochemical activation of the electrode and the DNA-type was examined. The results are compared with those obtained by fluorimetric measurement of the TO-PRO-3 dye : DNA complex in the presence of analytes. With voltammetric biosensors, the detection limits are in the nmol l-1 concentration region. Using competitive reagents, the intercalation of analytes to DNA is indicated.
Synthesis and Analgesic Activity of Some Substituted 1-Benzofurans and 1-Benzothiophenes
Authors: Rádl Stanislav , Hezký Petr , Konvička Petr , Krejčí Ivan
Published: July 2002

2-Benzoyl- and 2-(pyridylcarbonyl)-1-benzofuran-3-amines were prepared from 2-hydroxybenzonitrile and corresponding bromoethanone derivatives. 2-Benzoyl- and 2-(pyridylcarbonyl)-1-benzothiophene-3-amines were prepared analogously from 2-sulfanylbenzonitrile. 2-Benzoyl-1-benzofuran-3-amine treated with acetic anhydride or ethyl chloroformate provided the corresponding N-acetyl or N-ethoxycarbonyl derivatives. These N-activated compounds were alkylated with ethyl bromoacetate to provide ethyl N-acetyl-N-(2-benzoyl-1-benzofuran-3-yl)glycinate and ethyl N-(2-benzoyl-1-benzofuran-3-yl)-N-ethoxycarbonylglycinate, respectively. Their mild hydrolysis gave the corresponding glycine derivatives. Methylation of ethyl N-(2-benzoyl-1-benzofuran-3-yl)carbamate gave the corresponding N-methyl carbamate, which was hydrolyzed to N-methyl-(2-benzoyl-1-benzofuran-3-yl)amine. 2-Benzoyl-7-methoxy-1-benzofuran-3-amine and 2-(4-methoxybenzoyl)-1-benzofuran-3-amine were demethylated with boron tribromide to the corresponding hydroxy derivatives; their O-alkylation with ethyl bromoacetate than gave ethyl [(3-amino-2-benzoyl-1-benzofuran-7-yl)oxy]acetate and ethyl {4-[(3-amino-1-benzofuran-2-yl)carbonyl]phenoxy}acetate, respectively. The mild hydrolysis of these esters provided corresponding acids. Similarly, alkylation of the hydroxy derivatives with (dimethylamino)propyl chloride gave corresponding (dimethylamino)propoxy derivatives. 2-Hydroxybenzonitrile treated with 2-bromo-1-(2-, 3-, or 4-pyridyl)ethan-1-one provided the respective 2-(pyridylcarbonyl)-1-benzofuran-3-amine. Similar 2-(pyridylcarbonyl)-1-benzothiophene-3-amines were prepared analogously from 2-sulfanylbenzonitrile. 2-Benzoyl-3-(bromomethyl)-1-benzofuran treated with dimethylamine, 1-methylpiperazine, and sodium 1-methylpiperidine-4-thiolate gave the corresponding alkylation products. Several compounds were found to exhibit considerable analgesic activity.
Cyclization of Substituted Phenyl N-(2-Hydroxybenzyl)carbamates in Aprotic Solvents. Synthesis of 4H-1,3-Benzoxazin-2(3H)-ones
Authors: Mindl Jaromír , Hrabík Oldřich , Štěrba Vojeslav , Kaválek Jaromír
Published: July 2002

The kinetics of cyclization of substituted phenyl N-(2-hydroxybenzyl)carbamates and their N-methyl analogs, prepared by the reaction of 2-(aminomethyl)phenols with substituted phenyl chloroformates, was studied in dioxane or toluene at the temperatures 110-180 °C. Electron-withdrawing substituents in the leaving phenoxy group strongly accelerate the rate of cyclization (ρ = 2.45 ± 0.15) while the substituents in the other ring have virtually no effect. The cyclization was catalyzed with triethylamine in toluene but not in dioxane. On the basis of these results, the most convenient method for preparation of substituted 4H-1,3-benzoxazin-2(3H)-ones was a one-hour reflux of substituted 4-nitrophenyl N-(2-hydroxybenzyl)carbamates in dioxane. Based on the influence of substituents, solvents (dioxane and toluene) and triethylamine, the reaction mechanism and structure of the transition state were proposed.
Electrochemical Reductions of Ni2+, Cu2+ and Zn2+ Complexes of Azinyl Methyl Ketoximes on Mercury
Authors: Cibulka Radek , Císařová Ivana , Ondráček Jan , Liška František , Ludvík Jiří
Published: July 2002

Electroreductions of Ni2+, Cu2+ and Zn2+ complexes of azinyl (pyridin-2-yl, pyridazin-3-yl, pyrimidin-2-yl, pyrimidin-4-yl, pyrazinyl) methyl ketoximes on mercury electrode were studied using dc polarography. Three different types of complex behavior on the mercury electrode were observed: In the Ni2+ complexes, the hydroxyimino group of the ligand is reduced, whereas in the Cu2+ complexes, the reduction proceeds on the metal ion. With Zn2+ complex of methyl pyridin-2-yl ketoxime, only reduction waves of the uncoordinated ligand and metal were observed due to a rapid decomplexation pre-equilibrium. The structure of [Zn(methyl pyridin-2-yl ketoxime)2(NO3)2], isolated from water-ethanolic solution, was determined by X-ray diffraction. The distorted octahedral coordination sphere around the zinc atom, made up of two pyridine and two oxime nitrogen atoms and two nitrate oxygen atoms, was verified.
Isolation of DT-Diaphorase [NAD(P)H Dehydrogenase (Quinone)] from Rat Liver Cytosol: Identification of New Enzyme Substrates, Carcinogenic Aristolochic Acids
Authors: Stiborová Marie , Hájek Miroslav , Vošmiková Hana , Frei Eva , Schmeiser Heinz H.
Published: July 2002

Cytosolic fractions isolated from liver and kidney of rats treated with β-naphthoflavone, Sudan I, ellipticine, phenobarbital, ethanol, acetone and natural carcinogenic and nephrotoxic nitroaromatics, aristolochic acids, were tested for the activity of DT-diaphorase [NAD(P)H dehydrogenase (quinone), EC 1.6.99.2]. While the most efficient inducers of DT-diaphorase in liver were Sudan I, ellipticine and aristolochic acids, the highest increase in the DT-diaphorase activity in kidney was produced by aristolochic acids. No increase in the enzyme activity was determined after treatment of rats with acetone. DT-Diaphorase was isolated from liver cytosol of Sudan I-treated rats by the procedure consisting of fractionation with ammonium sulfate, gel permeation chromatography on a Sephadex G-150 column, affinity chromatography on an Affi-Gel Blue (Cibracron Blue Agarose) column and re-chromatography on Sephadex G-150. Rat DT-diaphorase catalyzed NAD(P)H-dependent reduction of menadione (vitamin K3), vitamin K1and 4-nitrosophenol as substrates. Moreover, we newly identified two carcinogenic nitroaromatic compounds, aristolochic acids, as other substrates of DT-diaphorase. A selective inhibitor of the human DT-diaphorase, dicoumarol, inhibited the catalytic activity of the rat purified enzyme.
Simple NMR Determination of 5α/5β Configuration of 3-Oxosteroids
Authors: Chodounská Hana , Buděšínský Miloš , Šídová Romana , Šíša Miroslav , Kasal Alexander , Kohout Ladislav
Published: July 2002

A simple method to distinguish the 5α- from the 5β-isomers of 3-oxosteroids based on low-frequency 1H NMR spectra was proposed. Additional 1H and 13C NMR characteristics were derived from the comparison of completely assigned spectra of the 5α- and 5β-isomers. The effect of substitution at different positions of steroid skeleton was evaluated on a series of isomeric 3-oxosteroids, prepared for this purpose.
A pilot study examining injuries in elite gaelic footballers
Authors: Cromwell F , Walsh J , Gormley J
Published: July 2002

Objectives—To quantify injuries in elite gaelic footballers and to determine the nature, sites, and outcome of injuries and the possible risk factors involved.

Methods—Information on injuries was collected from six elite gaelic football teams by a questionnaire. The footballers were asked to recall injuries over the preceding six month period.

Results—A total of 88 out of 107 subjects sustained injuries over the study period. Ninety five injuries were recorded, giving an incidence rate of 1.78 injuries per subject per year, of which 35% were recurring. It was found that 35% of injuries were sustained during training sessions. Lower body injuries predominated (77%), the ankle being the most commonly injured anatomic site. Most injuries were soft tissue in nature: muscle, 33%; ligament, 32%; tendon, 16%. The most common situations giving rise to injuries were collision (22%) and twist/turn (19%). Foul play only accounted for about 6% of injuries. Mean time off play as a result of injury was 17.3 days, and hospital admission was necessary for 15% of the injuries.

Conclusion—Despite the limitations of a retrospective of this nature, the study provides useful and important information on injuries in gaelic footballers.
Stress reactivity to and recovery from a standardised exercise bout: a study of 31 runners practising relaxation techniques
Authors: Solberg E E , Ingjer F , Holen A , Sundgot-Borgen J , Nilsson S , Holme I
Published: July 2002

Objective—To compare the efficacy in runners of two relaxation techniques with regard to exercise reactivity and recovery after exercise.

Methods—Thirty one adult male runners were studied prospectively for six months in three groups practising either meditation (n = 11) or autogenic training (n = 11) or serving as controls (n = 10). Before and after the six months relaxation intervention, indicators of reactivity to exercise and metabolism after exercise (blood lactate concentration, heart rate (HR), and oxygen consumption (Vo2)), were tested immediately after and 10 minutes after exercise. Resting HR was also assessed weekly at home during the trial. State anxiety was measured before and after the intervention.

Results—After the relaxation training, blood lactate concentration after exercise was significantly (p<0.01) decreased in the meditation group compared with the control group. No difference was observed in lactate responses between the autogenic training group and the control group. There were no significant differences among the groups with regard to HR, Vo2, or levels of anxiety.

Conclusion—Meditation training may reduce the lactate response to a standardised exercise bout.
Echocardiographic characteristics of male athletes of different age
Authors: Pavlik G , Olexó Z , Osváth P , Sidó Z , Frenkl R
Published: July 2002

Two dimensionally guided M mode and Doppler echocardiographic data for 578 male subjects (106 non-athletic and 472 athletes) were analysed from two aspects: (a) in the young adult category (19–30 years of age), competitors in different groups of sports were studied; (b) in the different age groups (children, 10–14 years; adolescent juniors, 15–18 years; young adults, 19–30 years; adults, 31–44 years; older adults 45–60 years), data for athletes and non-athletes were compared. Morphological variables were related to body size by indices in which the exponents of the numerator and denominator were matched. Morphological signs of athletic heart were most consistently evident in the left ventricular muscle mass: in the young adult group, the highest values were seen in the endurance athletes, followed by the ball game players, sprinters/jumpers, and power athletes. A thicker muscular wall was the main reason for this hypertrophy. Internal diameter was only increased in the endurance athletes, and this increase was more evident in the younger groups. The E/A quotient (ratio of peak velocity during early and late diastole) indicated more effective diastolic function in the endurance athletes. The values for E/A quotient also suggested that regular physical activity at an older age may protect against age dependent impairment of diastolic function.
Sepsis and mechanisms of inflammatory response: is exercise a good model?
Authors: Shephard R J
Published: July 2002

Objectives—The immune changes induced by a bout of prolonged and vigorous exercise have been suggested to be a useful experimental model of sepsis and the inflammatory response. Available literature was reviewed to evaluate this hypothesis.

Methods—Literature describing the immune response to various patterns of exercise was compared with data on the immune changes observed during sepsis and inflammation.

Results—Although there are qualitative similarities between the immune responses to exercise and sepsis, the magnitude of the changes induced by most forms of exercise remains much smaller than in a typical inflammatory response. Indeed, the exercise induced changes in some key elements such as plasma cytokine concentrations are too small to be detected reliably by current technology.

Conclusions—If exercise is to provide a valid model of sepsis and the inflammatory response, it will be necessary to focus on subjects who are willing to exercise extremely hard, to use the pattern of exercise that has the greatest effect on the immune system, and to combine this stimulus with other psychological, environmental, or nutritional stressors.
Skateboarding injuries of today
Authors: Forsman L , Eriksson A
Published: July 2002

Background—Skateboarding injuries have increased with the rise in popularity of the sport, and the injury pattern can be expected to have changed with the development of both skateboard tricks and the materials used for skateboard construction.

Objective—To describe the injury pattern of today.

Methods—The pattern of injuries, circumstances, and severity were investigated in a study of all 139 people injured in skateboarding accidents during the period 1995–1998 inclusive and admitted to the University Hospital of Umeå. This is the only hospital in the area, serving a population of 135 000.

Results—Three of the 139 injured were pedestrians hit by a skateboard rider; the rest were riders. The age range was 7–47 years (mean 16). The severity of the injuries was minor (AIS 1) to moderate (AIS 2); fractures were classified as moderate. The annual number of injuries increased during the study period. Fractures were found in 29% of the casualties, and four children had concussion. The most common fractures were of the ankle and wrist. Older patients had less severe injuries, mainly sprains and soft tissue injuries. Most children were injured while skateboarding on ramps and at arenas; only 12 (9%) were injured while skateboarding on roads. Some 37% of the injuries occurred because of a loss of balance, and 26% because of a failed trick attempt. Falls caused by surface irregularities resulted in the highest proportion of the moderate injuries.

Conclusions—Skateboarding should be restricted to supervised skateboard parks, and skateboarders should be required to wear protective gear. These measures would reduce the number of skateboarders injured in motor vehicle collisions, reduce the personal injuries among skateboarders, and reduce the number of pedestrians injured in collisions with skateboarders.
Histiocytic lymphoma presenting as a testicular tumour and terminating in acute monoblastic leukaemia
Authors: Hull D R , Alexander H D , Markey G M , Lyness R W , Morris T C M
Published: July 2002

A 58 year old man presented in 1995 with a swollen testicle. After orchidectomy, a diagnosis of poorly differentiated lymphoma was made. Lymphoid, epithelial, and seminoma markers were all negative. Six months later he developed a buccal lesion, which was biopsied and reported as a high grade non-Hodgkin's lymphoma. It responded completely to chemotherapy but within a year he developed a forearm swelling, which was biopsied and imprints made before fixation of the material. Immunocytochemistry on the imprints showed positivity with antibodies to CD4, CD68, and muramidase, and the non-specific esterase cytochemical stain was strongly positive, leading to a diagnosis of true histiocytic lymphoma. Despite further treatment, the patient entered a terminal acute leukaemic phase, the blasts marking as monoblasts. Review of all the biopsies, including molecular investigations and further immunohistochemistry studies performed retrospectively on the original biopsy, demonstrated that this was the same malignant cell line throughout, and we conclude that this is a case of histiocytic lymphoma, initially presenting as a testicular tumour and terminating in acute monoblastic leukaemia. A diagnosis of histiocytic lymphoma should be considered when lymphoid markers are negative in an apparent lymphoma, but should not be made without recourse to appropriate immunophenotypic and molecular studies.
An investigation of the Peutz-Jeghers gene (LKB1) in sporadic breast and colon cancers
Authors: Forster L F , Defres S , Goudie D R , Baty D U , Carey F A
Published: July 2002

Aims—To explore the role of the Peutz-Jeghers gene (LKB1) in sporadic breast and colon cancers.

Methods—Thirty consecutive sporadic carcinomas of the breast and 23 of the colon were selected. DNA was extracted from paraffin wax embedded tissue and analysed for loss of heterozygosity (LOH) at microsatellite markers D19S886 and D19S565 close to the LKB1 gene. Tumours showing LOH were screened for LKB1 mutations by single strand conformational polymorphism (SSCP).

Results—Five breast carcinomas showed LOH (21% and 7% of those informative for D19S886 and D19S565, respectively). Five of the colorectal carcinomas showed LOH (15% and 36% of those informative for D19S886 and D19S565, respectively), with one sample showing allele loss with both markers. Screening of these 10 carcinomas by SSCP identified one migrational shift but sequencing revealed an intronic polymorphism only. Therefore, no coding mutations were found in these carcinomas.

Conclusions—These findings suggest that although allele loss at the LKB1 locus occurs relatively frequently in sporadic breast and colon cancers, mutations do not seem to be a feature.
Abnormal haemoglobins, Hb Takamatsu and Hb G-Szuhu, detected during the analysis of glycated haemoglobin (HbA1C) by high performance liquid chromatography
Authors: Moriwaki Y , Yamamoto T , Shibutani Y , Harano T , Takahashi S , Hada T
Published: July 2002

Background—During medical checkups of two unrelated female outpatients during their annual health examination and one male inpatient suffering from cardiac failure the glycated haemoglobin (HbA1C) concentrations measured by high performance liquid chromatography (HPLC) were low, in spite of normal fasting plasma glucose concentrations. However, HbA1Cconcentrations measured by latex immunoagglutination and fructosamine concentrations were within the normal range.Method—Investigations were performed to elucidate the reasons for these discrepancies.

Results—Abnormal haemoglobins, Hb Takamatsu and Hb G-Szuhu, were found. The HPLC chromatogram showed an additional peak near HbA1a+b, which resulted in falsely low HbA1Cconcentrations. Isoelectric focusing analysis of the patients' haemoglobin disclosed abnormal haemoglobins, which migrated faster than normal HbA1in the two female patients and slower in the male patient. The cDNA sequence and amino acid analyses of the haemoglobin α-chains and β-chains indicated the presence of the haemoglobin variant β 120 Lys→Gln in the two female patients and β 80 Asn→Lys in the male patient; that is, Hb Takamatsu and Hb G-Szuhu.

Conclusions—These cases show how these silent haemoglobin variants can result in falsely low HbA1Cconcentration readings when using HPLC.
Interaction of insulin withBurkholderia pseudomalleimay be caused by a preservative
Authors: Simpson Andrew J H , Wuthiekanun Vanaporn
Published: July 2002

Aim—To re-examine the previously reported in vitro interaction of insulin withBurkholderia pseudomallei, in the light of a suggestion that the interaction may have resulted from the presence of the preservative m-cresol in commercial preparations.

Methods—Broth culture studies ofB pseudomalleiwere performed with and without the addition of m-cresol and various preparations of insulin.

Results—Growth ofB pseudomalleiwas inhibited by m-cresol at the concentrations found in pharmaceutical insulin preparations, and by the insulin preparation Humulin R, but not by pure insulin.

Conclusions—The results of previous experiments may have been confounded by the presence of the preservativem-cresol.
Type 1 diabetes mellitus masking primary antibody deficiency: Figure 1
Authors: Johnston S L , Virgo P F , Unsworth D J
Published: July 2002

A patient with a history of recurrent cutaneous and pulmonary infections, nephrotic syndrome, and an established diagnosis of type 1 diabetes was found to have unsuspected and unrecognised primary immunodeficiency. On review of the case, previous investigations pointed to the correct diagnosis over 10 years earlier. This combination of diagnoses has not previously been reported. The patient is now well on replacement intravenous immunoglobulin therapy, urinary loss of IgG having been specifically excluded before treatment. This case highlights how antibody deficiency can easily be missed despite an obvious infection history unless results are interpreted carefully and in context.
Application of microsatellite PCR techniques in the identification of mixed up tissue specimens in surgical pathology
Authors: Gras Esther , Matias-Guiu Xavier , Catasus Lluis , Arguelles Rosmary , Cardona Dolors , Prat Jaime
Published: July 2002

A fragment of tumour was erroneously mixed up with an endometrial biopsy. Microsatellite polymerase chain reaction (PCR) clearly demonstrated the extraneous nature of the fragment. Microsatellite PCR may be useful for the identification of mislabelled or mismatched tissue fragments in surgical pathology specimens.
Pregnancy associated endometriosis with pronounced stromal myxoid change
Authors: McCluggage W G , Kirk S J
Published: July 2002

A case of endometriosis presenting as a mass in the groin of a pregnant woman is described. The mass increased in size during the pregnancy and the radiological features were suspicious of malignancy. Histological examination showed atrophic glands set in an abundant stroma. This was not typical of normal endometrial stroma but had a pronounced myxoid appearance with areas of decidualisation. The atypical site of the endometriosis together with the unusual stromal changes resulted in diagnostic confusion. Although stromal decidualisation is well recognised in endometriosis in pregnancy, pronounced myxoid change appears unusual. The myxoid change in this case may be a degenerative phenomenon related to pregnancy.
A technique for the evaluation of failed fallopian tube ligation with metal clips: Figure 1
Authors: Leonard N , Mawhinney W H B , Malcolm A J
Published: July 2002

The evaluation of fallopian tubes after failed tubal ligation can be difficult because conventional histopathological techniques are unable to section the metal clips when in situ. Once the clips have been removed, any evidence of tube patency is lost. This report describes a technique of embedding and sectioning that enables sections to be made while the metal clips are still in situ. This is a modification of a method first described to embed mineralised bone and involves the use of plastic embedding and a diamond saw. Using this technique, a permanent record is made of the tube location and patency.
Issues of consent and the primary-school medical
Authors: Bradley P
Published: July 2002

This article discusses what level of consent is needed from a child or parent before a primary-school medical can take place (ie where children are aged under 12). It also considers whether there are occasions when a doctor can see a child if the parents have failed to give consent or have explicitly refused consent.

Primary-school children are considered incompetent to make decisions about their own medical treatment and so their consent does not need to be gained before a medical takes place, although it is highly desirable to obtain it. However, a doctor cannot justify a decision to see a child purely in terms of the benefit conferred on the child. Parents can be wronged if their wishes are ignored and usually those wishes should be considered overriding. Normally, general consent, which need not be fully informed, is needed before a school medical. However, if a child is considered to be in danger of being harmed significantly or suspected to have a major medical condition, a medical should go ahead regardless of the level of consent obtained from the parent, so that a reasonable standard of health is maintained for the child.
Intuitions, principles and consequences
Authors: Shaw A B
Published: July 2002

Some approaches to the assessment of moral intuitions are discussed. The controlled ethical trial isolates a moral issue from confounding factors and thereby clarifies what a person's intuition actually is. Casuistic reasoning from situations, where intuitions are clear, suggests or modifies principles, which can then help to make decisions in situations where intuitions are unclear. When intuitions are defended by a supporting principle, that principle can be tested by finding extreme cases, in which it is counterintuitive to follow the principle. An approach to the resolution of conflict between valid moral principles, specifically the utilitarian and justice principles, is considered. It is argued that even those who justify intuitions by a priori principles are often obliged to modify or support their principles by resort to the consideration of consequences.
Is it in a neonate's best interest to enter a randomised controlled trial?
Authors: Allmark Peter , Mason Su , Gill A Bryan , Megone Christopher
Published: July 2002

Clinicians are required to act in the best interest of neonates. However, it is not obvious that entry into a randomised controlled trial (RCT) is in a neonate's best interest because such trials often involve additional onerous procedures (such as intramuscular injections) in return for which the neonate receives unproven treatment or a placebo. On the other hand, neonatology needs to develop its evidence base, and RCTs are central to this task. The solution posited here is based on two points. First, “best interest” is not equivalent to “the best possible interest” only to “best interest within a certain realm”. The realm of deliberation when asking the title question is the neonate's health. Deliberating in this realm may involve the exclusion from consideration of some factors that might be thought relevant (such as parental wealth). Furthermore, circumstances may dictate the need to deliberate on other factors that might be thought irrelevant (such as health care resources). Second, deciding on a neonate's best interest does not involve “putting oneself in its shoes”. Rather, it involves asking in what it has an interest, or stake. These will include some things in which we all, as human beings, have a stake, such as medical progress. Putting these two points together, in the realm of health the answer to whether RCT entry is in a neonate's best interest is usually very finely balanced. Where this is the case, it is reasonable to invoke a broader notion of best interest and include a broader range of elements in which the neonate has a stake, including medical progress. In this way RCT entry can, usually, be said to be in a neonate's best interest.
The process of informed consent for urgent abdominal surgery
Authors: Kay R , Siriwardena A K
Published: July 2002

Objectives—To assess perceptions of the informed consent process in patients undergoing urgent abdominal surgery.

Design—A prospective observational study was carried out using structured questionnaire-based interviews. Patients who had undergone urgent abdominal surgery were interviewed in the postoperative period to ascertain their perceptions of the informed consent process. Replies were compared to responses obtained from a control group undergoing elective surgery, to identify factors common to the surgical process and those specific to urgent surgery. Patients' perceptions of received information were also compared to the information perceived to have been provided by the consent obtainers.

Setting—Gastrointestinal surgical service of a university teaching hospital.

Patients—Seventy-four consecutive patients undergoing urgent abdominal surgery and 80 control patients undergoing elective surgery.

Main measurements—Principal outcome measures were patients' perceptions of factors interfering with the ability to give informed consent, assessment of the quality of informed consent and the degree of discussion of the expected outcomes.

Results—Forty-nine of the seventy-four (66%) patients undergoing urgent surgery perceived that pain did not affect their ability to give informed consent. Twenty-seven reported an adverse effect of analgesia on the ability to give informed consent. Only 22% of patients undergoing urgent surgery perceived that there had been any discussion of potential side effects and complications of surgery.

Conclusion–The majority of patients in this series with acute intra-abdominal surgical conditions perceive that they retain the ability to give informed consent for surgery. There is a need for improved discussion of therapeutic options and likely outcomes.
How economics could extend the scope of ethical discourse
Authors: Williams Alan
Published: July 2002

Ethical discourse is typically inconclusive, and with good reason. But this inconclusiveness is a distinct disadvantage when it comes to helping publicly accountable policy-makers in the health care system provide an ethical justification for their decisions. It is suggested that instead of ending with platitudinous statements such as that a balance has to be struck between the rival ethical considerations, empirical research should be undertaken to elicit the quantitative trade-offs that the affected general public would be prepared to accept when striking this balance. In the expected absence of any consensus, it is further suggested that the views of the median person be taken as the best approximation to the group view. Finally it is argued that, far from this quantitative approach lacking humanity by treating individuals as “mere statistics”, it shows greater compassion than the proponents of those approaches whose fellow feeling can only be stirred by information pertaining to identified individuals.
Disability matters in medical law
Authors: Diesfeld Kate
Published: July 2002

The British Parliament stated that health services would be covered by the Disability Discrimination Act 1995 (the act). However, when people with disabilities are at their most vulnerable, for example when in hospital or subject to medical procedures, the antidiscrimination law fails them. A review of cases indicates that when people with disabilities are subject to medical treatment, the legislative protections are allowed to vanish. Instead, medical decisions are justified on obscure notions such as “best interests”, often with irreversible or even terminal results. This article examines the relevant provisions and limitations of the act, the features of notable non-treatment decisions, and the act's potential to guide future decision making. It argues that antidiscrimination legislation should be assertively applied to protect vulnerable people.
What is the role of clinical ethics support in the era of e-medicine?
Authors: Parker Michael , Gray J A Muir
Published: July 2002

The internet is becoming increasingly important in health care practice. The number of health-related web sites is rising exponentially as people seek health-related information and services to supplement traditional sources, such as their local doctor, friends, or family. The development of e-medicine poses important ethical challenges, both for health professionals and for those who provide clinical ethics support for them. This paper describes some of these challenges and explores some of the ways in which those who provide clinical ethics support might respond creatively to them. By offering ways of responding to such challenges, both electronically and face-to-face, the providers of clinical ethics support can show themselves to be an indispensable part of good quality health care provision
Rationing, randomising, and researching in health care provision
Authors: Edwards S J L , Kirchin S
Published: July 2002

In this paper the need for valid evidence of the cost-effectiveness of treatments that have not been properly evaluated, yet are already available, albeit in short supply, are examined. Such treatments cannot be withdrawn, pending proper evaluation, nor can they be made more widely available until they have been shown to be cost-effective. As a solution to this impasse the argument put forward recently by Toroyanet alis discussed. They say that randomised controlled trials of such resources could be done but only if resources are randomly allocated independently of a research context. Relevant outcome data could then be collected for research, given this opportunity. (There are already a few investigators who have turned limited resources, mostly health service provision, to their advantage in this way.) We agree. We disagree with Toroyanet alon a number of points. First, they claim that no ethical issue relating to equipoise arises. We disagree and this disagreement depends on our showing that equipoise should be maintained in a relationship that they do not consider. Secondly, they say that consent to data collection is always needed. Again we disagree. Thirdly, they claim that the previous two issues are the only possible ethical issues that could arise. We argue, instead, that there is a further conflict of interests that has ethical import.
Arguments at cross-purposes: moral epistemology and medical ethics
Authors: Loughlin M
Published: July 2002

Different beliefs about the nature and justification of bioethics may reflect different assumptions in moral epistemology. Two alternative views (put forward by David Seedhouse and Michael H Kottow) are analysed and some speculative conclusions formed. The foundational questions raised here are by no means settled and deserve further attention.
Reply to Brassington
Authors: Szasz T
Published: July 2002

I thank Brassington for his reply, especially for stating “that there is rather a lot going for Szasz's argument, and I agree broadly with the conclusion”. In further support of my thesis regarding the fictitious nature of mental illness as a disease similar to diseases of bodily organs, I add the reminder that, prior to the sixteenth century, the word “mind” meant only minding. The birth of the concept of mind as an entity and of the term “mind” as a noun is the symptom of the metamorphosis of the mediaeval, religious view of the world into the modern, scientific view of it.
Supererogation and the profession of medicine
Authors: McKay A C
Published: July 2002

In the light of increasing public mistrust, there is an urgent need to clarify the moral status of the medical profession and of the relationship of the clinician to his/her patients. In addressing this question, I first establish the coherence, within moral philosophy generally, of the concept of supererogation (the doing of more than one's duty). I adopt the notion of an act of “unqualified” supererogation as one that is non-derivatively good, praiseworthy, and freely undertaken for others' benefit at the risk of some cost to the agent. I then argue that committing oneself to the profession of clinical medicine is an act of this kind. This is the case, not because the aim of medicine is to help patients, but because of the open ended commitment of time and the vulnerability to the consequences of failure that the clinician must accept.
Neuromuscular blockers—a means of palliation?
Authors: Hawryluck L
Published: July 2002

As we die, our respiratory pattern is altered and we seem to gasp and struggle for each breath. Such gasping is commonly seen as a clear sign of dyspnoea and suffering by families and loved ones, however, it is unclear whether it is perceived at all by the dying person. Narcotics and sedatives do not seem to affect these gasping respirations. In this issue of theJournal of Medical Ethics,we are asked to consider whether the last gasp of a dying patient could be or, perhaps, evenshouldbe avoided by administering neuromuscular blockers to palliate dying patients. For many reasons, such as our current failure to alleviate pain and distress, stories of inadequate analgesia and sedation in critically ill paralysed patients and the inability to know the intent—whether to palliate or to euthanise—it would seem that administering neuromuscular blockers should not be ethically permissible.
The technological invention of disease
Authors: Hofmann Bjørn
Published: July 2002

Technology has come to play a profound role in medicine since the middle of the 19th century, and many scholars have analysed the role of technology in medicine. Parallel to this development there has been a comprehensive debate on the concept of disease. This article combines these fields and investigates the influence of technology on the concept of disease. With reference to the literature it tries to elaborate an explicit account of the constitutive role of technology in relation to the concept of disease. It will be argued that technology constitutes the concept of disease in three profound ways. Firstly, technology provides the physiological, biochemical, and biomolecular entities that are applied in defining diseases. Secondly, it establishes the way we try to gain knowledge of disease and the way we recognise disease in practice. Technology constitutes the signs, markers and end points that define disease entities and it strongly influences the explanatory models of disease as well as medical taxonomy. Thirdly, technology establishes how we act towards disease: thorough diagnosis and treatment technology establishes the actions that constitute the concept of disease. Altogether, this constitutive technological influence on the concept of disease is considered as a technological invention of disease.
Job strain, social support in the workplace, and haemoglobin A1c in Japanese men
Authors: Kawakami N , Akachi K , Shimizu H , Haratani T , Kobayashi F , Ishizaki M , Hayashi T , Fujita O , Aizawa Y , Miyazaki S , Hiro H , Hashimoto S , Araki S
Published: July 2002

OBJECTIVES

To examine the association between job strain (defined in the model of job demands and job control) and social support at the workplace with levels of glycosylated haemoglobin A1c (HbA1c)

METHODS

All male employees aged 40–60 in a manufacturing firm, Japan, were invited to take part in the study. A blood sample was taken from the participants and HbA1c (%) was measured. Job strain and social support at the workplace were assessed with the job content questionnaire (JCQ). After excluding those who had a history of diabetes mellitus or other chronic diseases, data from 268 male day workers were analyzed.

RESULTS

Age adjusted average concentrations of HbA1c were significantly higher in the highest quartile group of job strain or the lowest quartile group of social support at the workplace (p<0.05). Multiple linear regression analysis indicated that job strain was significantly and positively related to HbA1c (p<0.05), whereas social support at the workplace was significantly and negatively related to HbA1c (p<0.05), both after controlling for other covariates.

CONCLUSIONS

Greater job strain and lower social support at the workplace may be associated with increased concentrations of HbA1c. Increased blood glucose may be a physiological mediator between job strain or social support at the workplace and coronary heart disease.