Milgram and Tuskegee—Paradigm Research Projects in Bioethics

This paper discusses the use of the Milgram obedience experiments and the Tuskegee syphilis study in the bioethical literature. The two studies are presented and a variety of uses of them identified and discussed. It is argued that the use of these studies as paradigms of problematic research relies on a reduction of their complexity. What is discussed is thus often constructions of these studies that are closer to hypothetical examples than to the real studies.     

Pelvic floor neuropathy in relation to the outcome of burch colposuspension

The aim of the study was to determine the role of neurogenic damage to pelvic floor muscles on the outcome of Burch colposuspension. Thirty women objectively continent after Burch colposuspension and 18 women with recurrent stress urinary incontinence (RSUI) were investigated with concentric needle electrode electromyography (EMG) in both pubococcygeus muscles and the external anal sphincter muscle. Neurogenic EMG patterns were significantly more often seen in the pubococcygeus muscles in women with RSUI than in women continent after the colposuspension (P<0.05). The distribution of neurogenic EMG patterns in the investigated muscles was significantly more pronounced in women with RSUI than in continent women: at least one pubococcygeus muscle with neurogenic EMG pattern, 72% vs. 34% (P<0.05); both pubococcygeus muscles, 50% vs. 13% (P<0.05); and all three investigated muscles 41% vs. 10% (P<0.05). In conclusion, the results imply an association between the outcome of the Burch colposuspension and the occurrence of neuropathy in the pelvic floor muscles. Occurrence of neurogenic damage in the pubococcygeus muscles seems to impair the outcome of Burch colposuspension.     

Intra-observer and inter-observer agreement of the manual examination of the lumbar spine in chronic low-back pain

Examination is a cornerstone in the manual procedures leading to mobilisation/manipulation of the low back. The observer variation of the more specific segmental tests remains to be investigated. Two skilled specialists in manual medicine examined the segmental changes in the lumbar spine. The patients were unknown to the examiners and no information of the case history was given. All test results were recorded by an observer present in the room who ensured that no conversation was allowed during the examination. The primary outcome measures were the kappa values for each test. The matching was defined as acceptable (acc) within two neighbouring levels and perfect (per) on the same level. Intra-observer variation (tested in 33 patients and 10 subjects without low-back pain): The agreement between first and second segmental diagnosis examination was 70% (per) and 82% (per + acc). Kappa values were: segmental diagnosis 0.60 (per) and 0.70 (per + acc), multifidus test 0.51 (per) and 0.60 (per + acc), sideflexion 0.57 (per) and 0.69 (per + acc), and ventral flexion 0.31 (per) and 0.45 (per + acc). Inter-observer variation (tested in 60 patients): The agreement for segmental diagnosis between the examiner A and B was 42% (per) and 75% (per + acc). Kappa values were: segmental diagnosis 0.21 (per) and 0.57 (acc), multifidus test 0.12 (per) and 0.48 (acc), sideflexion 0.22 (per) and 0.45 (acc), and ventralflexion 0.22 (per) and 0.44 (acc). By manual tests, skilled examiners seem to be able to diagnose segmental dysfunctions in the low back. The clinical implication of these dysfunctions remains to be clarified.     

Strong decline in female sterilization rates in Norway after the introduction of a new copayment system: a registry based study

Background  

January 1, 2002, copayment for outpatient female sterilization in Norwegian public hospitals increased from 33 euros to 750 euros after a revision of the health care system. The aim of the present study was to investigate the effect of the new copayment system on female sterilization epidemiology.     

Left ventricle haemodynamics and vaso-active hormones during graded supine exercise in healthy male subjects

Left ventricle systolic and diastolic functional parameters were measured by gated equilibrium radionuclide cardiography in 12 healthy men (age 33–51 years) at rest and during graded supine exercise. The leftventricle end-diastolic volume showed an initial small (11%) increase during low submaximal exercise [from mean 163 (SD 40) at rest to mean 181 (SD 48) ml], while left ventricle end-systolic volume decreased successively [from mean 59 (SD 19) to mean 39 (SD 21) ml] with increasing exercise. Stroke volume was therefore elevated at all exercise levels compared with rest [mean 104 (SD 23) ml], and the peak value [mean 128 (SD 33) ml] was found at the lowest exercise level, contributing 40% to the initial increase in cardiac output. Cardiac output increased from mean 6.2 (SD 1.4) at rest to mean 20.2 (SD 5.0) 1 · min^–1 at maximum. Left ventricle peak ejection and peak filling rates increased from mean 449 (SD 89) and mean 442 (SD 85) ml · s^–1 at rest to mean 996 (SD 227) and mean 1255 (SD 333) ml · s^–1, respectively, at maximum. The myocardium oxygen consumption, assumed to be proportional to the sum of the stroke work and the potential energy, increased fourfold, but absolute values were twice as high as expected, indicating that extrapolation from data obtained in dog hearts (as we have done) cannot be directly applied to humans. Selected vaso-active hormones were measured at all exercise intensities. Noradrenaline (NA), adrenaline (A) and angiotensin II (AII) concentrations showed a very pronounced increase at maximal exercise compared with the preceding lower intensites, while atrial natriuretic factor (ANF) and cyclic guanosinemonophosphate (cGMP) concentrations showed a more continuous increase, and dopamine (DA) remained almost unchanged. This speaks in favour of a crucial role for NA, A and AII in preserving blood pressure at maximum exercise, while DA probably has no importance for the cardiovascular homeostasis during exercise. Increases in concentrations of ANF and cGMP were highly correlated (r = 0.86). Our data supported the opinion that there is a cardiac limitation to maximal performance connected to the cardiac pumping capacity.     

Concordance between symptom screening and diagnostic procedure: the Hopkins Symptom Checklist-25 and the Composite International Diagnostic Interview I

The definition of case is a core issue in psychiatric epidemiology. Psychiatric symptom screening scales have been extensively used in population studies for many decades. Structured diagnostic interviews have become available during recent years to give exact diagnoses through carefully undertaken procedures. The aim of this article was to assess how well the Hopkins Symptom Checklist-25 (HSCL-25) predicted cases by the Composite International Diagnostic Interview (CIDI), and find the optimal cut-offs on the HSCL-25 for each diagnosis and gender. Characteristics of concordant and discordant cases were explored. In a Norwegian two-stage survey mental health problems were measured by the HSCL-25 and the CIDI. Only 46% of the present CIDI diagnoses were predicted by the HSCL-25. Comorbidity between CIDI diagnoses was found more than four times as often in the concordant cases (cases agreed upon by both instruments) than in the discordant CIDI cases. Concordant cases had more depression and panic/generalized anxiety disorders. Neither the anxiety nor the depression subscales improved the prediction of anxiety or depression. The receiver operating characteristic (ROC) curves confirmed that the HSCL-25 gave best information about depression. Except for phobia it predicted best for men. Optimal HSCL-25 cut-off was 1.67 for men and 1.75 for women. Of the discordant HSCL-25 cases, one -third reported no symptoms in the CIDI, one-third reported symptoms in the CIDI anxiety module, and the rest had symptoms spread across the modules. With the exception of depression, the HSCL-25 was insufficient to select individuals for further investigation of diagnosis. The two instruments to a large extent identified different cases. Either the HSCL-25 is a very imperfect indicator of the chosen CIDI diagnoses, or the dimensions of mental illness measured by each of the instruments are different and clearly only partly overlapping. Accepted: 11 November 1997     

Do concentrations of neurotransmitters measured in lumbar cerebrospinal fluid reflect the concentrations at brain level?

Summary CSF concentrations of vasoactive intestinal polypeptide (VIP), cholecystokinin (CCK), noradrenaline (NA) and dopamine (DA) were measured in the lateral ventricles and at the lumbar level in patients with normal pressure hydrocephalus (NPH). The concentrations of VIP (n=15), NA (n=10) and DA (n=10) were significantly higher at the lumbar level than at the ventricular level, whereas the concentrations of CCK (n=9) were similar at the two sites. A signifikant positive correlation between the concentrations measured at the two levels was found for VIP (r_s=0.65; p0.01) and DA (r_s=0.94; p0.001). The results indicate that the concentrations of transmitter substances measured in CSF at the lumbar level not necessarily are indicative for concentrations measured more centrally. The negative correlations between Evans ratio and L-CSF VIP (r_s=-0.76; p 0.001), and between resistance to outflow and V-CSF as well as L-CSF CCK (r_s=-0.75); p 0.05) might be explained by a reduction in number of cortical neurons or by disturbances in CSF dynamics in patients with NPH.     

Infectious salmon anemia virus (ISAV) genomic segment 3 encodes the viral nucleoprotein (NP), an RNA-binding protein with two monopartite nuclear localization signals (NLS)

Infectious salmon anemia virus (ISAV) is the type species of the genus Isavirus belonging to the Orthomyxoviridae, and causes serious disease in Atlantic salmon (Salmo salar). This study presents the expression and functional analysis of the ISAV genome segment 3, and provides further evidence that it encodes the viral nucleoprotein (NP). The encoded protein was expressed in a baculovirus system, and Western blot analysis showed that it corresponds to the 66-71 kDa structural protein previously found in purified ISAV preparations. RNA-binding activity was established by the interaction of viral and recombinant NP with single-stranded RNA transcribed in vitro. Immunofluorescence studies of infected cells showed the ISAV NP to be an early protein. It locates to the nucleus of infected cells before it is transported to the cytoplasm prior to virus assembly. A similar localization pattern was observed in cells transfected with the NP gene, confirming that the encoded protein has an intrinsic ability to be imported into the nucleus. Two monopartite nuclear localization signals (NLS) at amino acids (230)RPKR(233) and (473)KPKK(476) were identified by computer analysis, and validated by site-directed mutagenesis. In contrast to other orthomyxovirus-NPs, that have several NLSs that function independent of each other, both NLSs had to be present for the ISAV NP protein to be transported into the nucleus, indicating that these motifs cooperate to target the protein to the nucleus.