HPV testing in primary screening of older women.

Certain types of the human papilloma virus (HPV) are well established as the primary cause of cervical cancer. Several studies have shown that HPV testing can improve the detection rate of high-grade cervical intraepithelial neoplasia (CIN), but these have been carried out primarily in younger women. In this study we evaluated the role of HPV testing as an adjunct to cytology in women aged 35 or over. An additional aim was to evaluate commercially available kits for HPV testing. A total of 2988 eligible women aged 34 or more attending for a routine smear in 40 general practitioner practices received HPV testing in addition to routine cytology, after having given written informed consent. Samples were assayed by polymerase chain reaction (PCR) and two versions of the Hybrid Capture test for HPV, and women were invited for colposcopy if there was any cytological abnormality (including borderline smears) or the PCR test was positive. Any apparent abnormality was biopsied and loop-excision was performed as necessary. CIN was judged by histology; 42 women had high-grade CIN, of which six were cytology negative (86% sensitivity for borderline or worse) and three had a borderline smear (79% sensitivity for mild dyskaryosis or worse). The positive predictive value of a borderline smear was only 3.1%. Eleven high-grade lesions were negative by the PCR HPV test (sensitivity 74%). The first generation Hybrid Capture II test had a similar sensitivity but an unacceptably high false positive rate (18.3%), while the newer Hybrid Capture II microtitre kit had a 95% sensitivity and a 2.3% positivity rate in normal women when used at a 2 pg ml(-1) cut-off (positive predictive value 27%). Cytology performed very well in this older cohort of women. The newer Hybrid Capture II microtitre test may be a useful adjunct, especially if the results reported here are reproducible in other studies. A combined screening test offers the possibility of greater protection and/or longer screening intervals, which could reduce the overall cost of the screening programme.

Quality of life in treated hypertension: a case-control community based study.

The aim of this case-control community study was to determine whether there was a difference in quality of life between hypertensive subjects and matched normotensive controls. Cases aged 40-79 years were randomly selected from a hypertensive register and matched with controls for age, sex, ethnicity and health centre. Cases had phase V diastolic blood pressure (DBP) > or = 100 mm Hg or systolic blood pressure (SBP) > or = 180 mm Hg, or were on anti-hypertensive medication. Controls had DBP < or = 90 mm Hg and no record of raised BP or anti-hypertensive treatment within the past year. Quality of life was measured by self-administered questionnaire. Data from 90 matched pairs, average age 62 years, with 47% men, were analysed; 80 hypertensive subjects were on anti-hypertensive medication. Hypertensive subjects showed an impairment in well-being compared with controls. They had a lower Health Status Index, had more sickness absence from work, greater symptomatic complaint and impaired psychological well-being. Relatives also reported a poorer quality of life in the hypertensive subjects. This impairment could be a result of the disease, adverse effects of drug treatment or to the effects of labelling.

[Effectiveness of a patient-centered psychosomatic consultation service. Report of a catamnestic study]. / Zur Wirksamkeit des patientenzentrierten psychosomatischen Konsiliardienstes. Bericht über eine katamnestische Untersuchung.

After a short review of the latest scientific publications on psychosomatic consultation activity the results of an empirical study of the consultant service in the Department of Psychotherapy and Psychosomatic Medicine at the Frankfurt University Medical Center are presented. Patient documentations and data from a retrospective investigation were analysed in order to trace the effectivity of psychosomatic consultation activities. To document the various dimensions of the consultative process and their interdependence different groups of patients were derived by means of cluster analysis. The results are in many aspects encouraging for psychosomatic consultative practice, as they show that even few consultations can have an important influence on the patient's further development.

The diffusion of L(+)-ascorbic acid across DPPC vesicle membranes.

The transmembrane diffusion of L(+)-ascorbic acid has been studied by means of 1H-n.m.r. spectroscopy using small unilamellar DPPC vesicles as a model system. It is shown that the electro-neutral form of L(+)-ascorbic acid diffuses faster across the membranes than the anionic form by about two orders of magnitude. The diffusion is influenced by a molecular interaction between L(+)-ascorbate and the membrane surface and depends also on the fluidity of the membrane. The calculated permeation coefficients of neutral L(+)-ascorbic acid are between 6 x 10(-10) and 3 x 10(-8) cm s-1 (35-52 degrees C).

The influence of amino acid ligands and vitamin C on the reduction potential of Fe (III): polarographic and electron spin resonance investigations.

The pH dependence of Fe(III)-amino acid complexes has been studied polarographically and by means of ESR spectroscopy. It could be shown that, at least, two complexes exist: one with a low molecular weight, ESR detectable at acid pH, and one with a high molecular weight at alkaline pH, ESR non detectable. The half wave potential of Fe(III) is lowered by amino acid ligands. The redox interaction of the Fe(III)-amino acid complexes with vitamin C results in a decrease of the ascorbyl radical concentration. Ascorbic acid also forms a complex with Fe(III) as indicated by a polarographic half wave potential near -0.55 V vs. S.C.E. at pH 7.

The reversibility of the vitamin C redox system: electrochemical reasons and biological aspects.

The biological efficacy of vitamin C depends on its redox abilities as given by the relations between ascorbic acid, semidehydroascorbic acid, and dehydroascorbic acid. It is shown by means of proton magnetic resonance spectroscopy that the enzymatic (by ascorbate oxidase) as well as non-enzymatic (by iodine) oxidation of ascorbic acid is, in principle, reversible despite the hydration and structural changes during the formation of dehydroascorbic acid. The strong redox activity of semidehydroascorbic acid which results in a fast disproportionation to ascorbic acid and dehydroascorbic acid is inferred from an inversion of the electrochemical potentials of the vitamin C redox system. The capacity of this is maintained by a fast reduction of dehydroascorbic acid e.g. by reduced glutathione, preventing its delactonization and further degradation.

[31P- and 1H-NMR-investigations about the interaction of ATP with Mg2+, Ca2+, and monoamines (author's transl)]. / 31P- und 1H-NMR-Untersuchungen über die Wechselwirkung von ATP mit Mg2+, Ca2+ und Monoaminen.

The interaction between aromatic amines and ATP is based upon an electrostatic attraction of the protonated amino groups to the negatively charged phosphate groups of ATP combined with a stacking association between the ring systems. The complexes formed are relatively weak (association constants 4--48 M-1), shortlived (life time smaller than 0.02 s), and mainly 1:1 in stoichiometry preferring the terminal phosphate of ATP as the site of association. The divalent metal ions Mg2+ and Ca2+ bond stronger than the amines (association constants 1500 and 100 M-1, resp.) prefer the beta-phosphate group changing thereby the geometry of the ATP phosphate chain. Thus, they reduce the amine-ATP association in ternary mixtures.

Stacking interaction of nucleobases: NMR investigations. III. Molecular aspects of the solvent dependence.

The stacking interaction between nucleic acid bases has been investigated by the determination of the self-association of 6-methylpurine in various mixtures of water and nonaqueous solvents in order to elucidate the solvent effect. The parameters of stacking association as well as of local solvent-solute interactions have been measured by means of NMR technique. The influences of local hydration and of solvent-solvent interactions on the stacking ability are discussed.

1H-NMR investigations on the hydrogen bond formation between the tranquilizers diazepam and nitrazepam and some nucleobases.

The formation of hydrogen bonds between the minor tranquilizers diazepam and nitrazepam and a few nucleobases was studied in deuterochloroform solution by means of proton magnetic resonance spectroscopy. The thermodynamic and spectroscopic data of the associations were evaluated on the basis of a dimer model, using the concentration dependent shifts of the protons involved in hydrogen bonds. The interactions of nitrazepam (deltaH0=-10 to -21 kJ/mol; deltaG025 -0.2 to -7.4 kJ/mol) were found to be stronger than those of diazepam (deltaH0=-10 to -13 kJ/mol; deltaG025=6.0 to 6.4 kJ/mol). The various binding sites of the benzodiazepines for hydrogen bonds are discussed.

Stacking interactions of nucleobases: NMR-investigations. II. Self-association of purine-and pyrimidine-derivatives.

The self-association of various purine- and pyrimidine-derivatives in D2O has been studied by means of NMR technique. The thermodynamic quantities have been calculated using an isodesmic NMR model. Among the nucleobases investigated, the adenine-derivatives were found to be most suitable for quantitative determination. A comparison of methylated adenine-derivatives and the pH-dependence of the self-association lead to the conlcusion, that the stacking associates are stabilized by special van der Waals interactions based, essentially, on the polarizability of the pi-electron-system of the assciated molecules.

Stacking interactions of nucleobases: NMR-investigations. I. Self association of N6, N9-dimethyladenine and N6-dimethyl-N9-ethyladenine.

The selfassociation of N6,N9-dimethyladenine and N6-dimethyl-N9-ethyladenine has been studied by means of NMR technique. The thermodynamic quantities have been calculated using an isodesmic NMR model with three NMR parameters (the monomer shift deltaM and two complex shifts delta2 and delta3). The dependence of the thermodynamic quantities on the NMR parameters is discussed. Special attention is given to the determination of deltaM and its temperature dependence. Calculations with delta3 = 2 - delta2 and deltaM taken independently of temperature result in an average entropy deltaS = - 17.9 +/- 1.8 e.u. for N6,N9-dimethyladenine and deltaS = - 16.7 +/- 1.7 e.u. for N6-dimethyl-N9-ethyladenine and in an average enthalpy deltaH = - 7.2 +/- 0.6 kcal - mol-1 for both substances investigated.