Regulating the gene: From genetic consumption to regulatory trust

In this article, we examine the changing terms on which genetics-based technologies in two areas agriculture (Genetically Modified Organism, GMOs) and health (genetic diagnostics) have been regulated. These are used to illustrate and examine the proposition that shifts in the politics of governance and regulation (associated in part with the advent of the negotiation state) have meant that the responsibility for the social management of new technology is increasingly shared between the state and the consumer. However, this redistribution of the social management of risk, we argue, fails to establish a sufficient basis for a legitimate regulatory trust. We suggest that trust will depend on embedding broad social values and a self-critical agenda within the regulatory regime itself.     

Different pattern of risk factors for atopic and nonatopic asthma among children – report from the Obstructive Lung Disease in Northern Sweden Study

BACKGROUND: A cross-sectional study was performed among 78-year-old schoolchildren during the winter of 1996 in three municipalities in the most northern province of Sweden, Norrbotten. The study was the starting point of a longitudinal study of asthma, rhinitis, eczema, and type-1 allergy, and provided data on prevalence and risk factors for these conditions. The aim of the present study was to validate the classification of asthma based on a parental questionnaire, and to examine risk factors for atopic and nonatopic asthma. METHODS: The ISAAC questionnaire with additional questions was distributed by the schools to the parents. The response rate was 97%, and 3431 completed questionnaires were returned. The children in Kiruna and Lule? were also invited to be skin tested, and 2149 (88%) were tested with 10 common airborne allergens. A structured interview was administered by pediatricians in stratified samples of the children to test the validity of the diagnosis of asthma based on the questionnaire. RESULTS: After the validation study, the prevalence of "ever asthma" was estimated to be 8.0%. The specificity of the question, "Has your child been diagnosed as having asthma by a physician?", was high, >99%, while the sensitivity was around 70%. The strongest risk factor for "ever asthma" was a positive skin test (OR 3.9). Risk factors for asthma in the asthmatics who were not sensitized were family history of asthma, OR 3.6; breast-feeding less than 3 months, OR 1.8; past or present dampness at home, OR 1.8; smoking mother, OR 1.7; and male sex, OR 1.6. Among the sensitized asthmatics, only a family history of asthma was a significant risk factor (OR 3.0), while breast-feeding less than 3 months was not associated with an increased risk (OR 1.0). A synergistic effect between genetic and environmental factors was found especially in the nonatopic asthmatics; the children with a family history of asthma who had a smoking mother and past or present dampness at home had an OR for "ever asthma" of 13. CONCLUSIONS: Different risk-factor patterns were found for asthma and type-1 allergy. In addition, the risk factors for atopic or allergic asthma diverged from those for nonatopic asthma.     

Reflex testing I: algorithm for lipid and lipoprotein measurement in coronary heart disease risk assessment

We reviewed the current literature in order to construct a reflex testing algorithm that maximizes clinical utility and cost-effectiveness of lipid and lipoprotein testing. The algorithm was based on the 2nd Report of the National Cholesterol Education Program Adult Treatment Panel guidelines for use of total cholesterol (TC), triglycerides (TG), HDL-C, and LDL-C, and published reports describing the clinical use of apolipoprotein B and lipoprotein (a). The success of this algorithm was tested in a low-risk general and a high-risk hyperlipidemic patient population. Lipid data and non-lipid risk factors were obtained from a national database and from patients seen at two lipid clinics. A total of 16 968 individuals from the National Health and Nutrition Examination Survey III database comprised the low-risk group, and 239 patients examined in the Hartford Hospital and Washington University Lipid Clinics comprised the high-risk group. We found a solid scientific base to support the NCEP guidelines and reasonable support for limited testing of apoB and Lp(a). According to the algorithm, the direct LDL-C assay was deemed unnecessary in 98% and 91% of low- and high-risk subjects, respectively, if one assumes that the Friedewald equation is adequate with TG≤4.00 g/l. With a more conservative cutoff of TG≤2.50 g/l, the algorithm canceled 92% and 81% of direct LDL tests, respectively. The algorithm also limited TG to 20 and 64%, apoB to 6 and 20%, and Lp(a) to 15 and 56%, of low- and high-risk groups, respectively. Use of a comprehensive, reflex algorithm for coronary heart disease risk assessment will substantially reduce the utilization of laboratory services without diminishing the clinical value of these tests. The algorithm will prevent the overuse of certain expensive tests (direct LDL) while promoting the limited use of underutilized tests [apoB and Lp(a)].     

Estimation of physiologic ability and surgical stress (E-PASS) as a new prediction scoring system for postoperative morbidity and mortality following elective gastrointestinal surgery

(Received for publication on Oct. 25, 1997; accepted on July 7, 1998)     

Hypothesis: is low prenatal vitamin D a risk-modifying factor for schizophrenia?

The central nervous system is increasingly being recognised as a target organ for vitamin D via its wide-ranging steroid hormonal effects and via the induction of various proteins such as nerve growth factor. This paper proposes that low maternal vitamin D may impact adversely on the developing foetal brain, leaving the affected offspring at increased risk of adult-onset schizophrenia. The hypothesis can parsimoniously explain diverse epidemiological features of schizophrenia, such as the excess of winter births, increased rates of schizophrenia in dark-skinned migrants to cold climates, the increased rate of schizophrenia births in urban versus rural setting, and the association between prenatal famine and schizophrenia. Studies that will allow rejection of the hypothesis are proposed.     

Neuronal correlates of real and illusory contour perception: functional anatomy with PET

Illusory contours provide a striking example of the visual system's ability to extract a meaningful representation of the surroundings from fragmented visual stimuli. Psychophysical and neurophysiological data suggest that illusory contours are processed in early visual cortical areas, and neuroimaging studies in humans have shown that Kanizsa-type illusory contours activate early retinotopic visual areas that are also activated by real contours. It is not known whether other types of illusory contours are processed by the same mechanisms, nor is it clear to what extent attentional effects may have influenced these results, as no attempt was made to match the salience of real and illusory stimuli in previous imaging studies. It therefore remains an open question whether there are any brain regions specifically involved in the perception of illusory contours. To address these questions, we have used 15O-butanol positron emission tomography (PET) and a novel kind of illusory contour stimulus that is induced only by aligned line ends. By employing a form discrimination task that was matched for attention and stimulus salience across conditions we were able to directly contrast perception of real and illusory contours. We found that the regions activated by illusory contour perception were the same as those activated by real contours. Only one region, located in the right fusiform gyrus, was significantly more strongly activated by perception of illusory contours than by real contours. In addition, a principal component analysis suggested that illusory contour perception is associated with a change in the correlation between V1 and V2. We conclude that different kinds of illusory contours are processed by the same cortical regions and that these regions overlap extensively with those involved in processing of real contours. At the regional level, perception of illusory contours thus appears to differ from perception of real contours by the degree of involvement of higher visual areas as well as by the nature of interaction between early visual areas.     

Evidence for curvilinear interpolation from dot alignment judgements

Visual interpolation between dots responsible for rectilinear versus curvilinear contour interpretation was examined with the psychophysical forced directional response (FDR) paradigm. Regular four-dot polygon segments, together with a target dot, were presented to the subjects for 150 ms. Subjects were required to indicate the direction of deviation of the target dot from the midpoint of the intermediate line segment. Crucial variables were the outer angle of the line segments and symmetry axis orientation of the polygon segment. Logistic regression analyses showed that curvilinear interpolation occurred for angles up to 30 degrees, but emerged more pervasively under the vertical symmetry axis orientation for angles up to 60 degrees.     

Perinatal mortality trends in a referral hospital

A comparative study of perinatal mortality patterns over a period was conducted at a teaching hospital of South India. Among the 6,048 babies born from January 1984 to December 1985 (Group A), there were 265 (43.8/1000) still births and 127 (22.0/1000) early neonatal deaths. Three hundred and thirty seven (41/1000) babies were still born and 235 (29.8/1000) early neonatal deaths out of 8,215 deliveries during 1992–93 (Group B). The perinatal mortality rate (PMR) in Group A and B were 57.9/1000 and 57.7/1000 respectively. Unbooked cases accounted for the majority (> 75%) of perinatal deaths during both the periods. The overall mortality rates in unbooked cases were three to four times higher than booked cases. Among the various causes of still births, antepartum haemorrhage and uterine rupture had increased. Septicaemia was the major cause of early neonatal deaths in Group A, but in Group B birth asphyxia and prematurity were the leading causes. Effective interventions like creating awareness among the target population to utilise maternal and child health services and early referral of high risk cases with improved intranatal and perinatal care can decrease the perinatal mortality.     

Long-term lowering of blood pressure after carotid and vertebrobasilar ischemic stroke

We followed up 107 patients experiencing a first-ever ischemic stroke after having been affected by essential hypertension for at least one year, in order to analyze the phenomenon of post-stroke blood pressure lowering. Of the 82 patients still surviving after three months of follow-up, 44 (54%) had normal arterial blood pressure values. There were no significant differences between these normotensive patients and the 38 with high blood pressure in terms of cerebrovascular risk factors or disability, but blood pressure normalized in 34 of the 54 patients experiencing a carotid stroke (63%) and in only 10 of the 28 experiencing vertebrobasilar stroke (36%) (p=0.035). These data may offer a starting point for further studies of the neurogenesis of arterial hypertension.

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Sommario Al fine di analizzare il fenomeno della normalizzazione della pressione arteriosa dopo ictus cerebrale in pazienti prima ipertesi, abbiamo osservato 107 soggetti con primo ictus ischemico, che erano già precedentemente affetti da ipertensione arteriosa da almeno un anno. Degli 82 (77%) sopravvissuti a tre mesi di follow-up, 44 (54%) hanno mostrato una normalizzazione della pressione arteriosa. L'incidenza di fattori di rischio per malattia cerebrovascolare e disabilità grave non è risultata significativamente diversa nel gruppo degli ipertesi rispetto ai normotesi. Tuttavia la normalizzazione della pressione arteriosa è stata osservata in 34 dei 54 pazienti con ictus carotideo (63%) e solo in 10 dei 28 con ictus vertebrobasilare (36%) (p=0.035). Riteniamo che tali dati offrano uno spunto per ulteriori ricerche sulla genesi neurogena dell'ipertensione arteriosa essenziale.

     

Appendicitis: Higher risk in Mexican Americans?

Objectives. Mexican Americans (MAs), compared to white non‐Hispanics (WNHs), have higher rates of biliary disease, noninsulin dependent diabetes, and endstage renal disease but lower rates of lung cancer, hip fractures, and mortality from coronary heart disease. Relatively little research has been done to identify other ethnic differences in disease incidence. We used surgical procedure rates to confirm known ethnic differences and to explore our clinical suspicion that MAs have higher rates of appendectomy than WNHs.

Methods. We used a registry of surgical procedures at two teaching hospitals in South Texas to calculate proportional operation ratios (PORs) for MAs versus WNHs. These two hospitals are the primary source of acute hospital care for the indigent in the area. The POR is arithmetically identical to proportional incidence and mortality ratios.

Results. MAs underwent appendectomy proportionally more often than WNHs at both hospitals (POR = 1.41 and 1.75, p < 0.0001). Other significant PORs were consistent with known ethnic disease differences in biliary tract operations, vascular access for chronic hemodialysis, lung cancer, and coronary artery bypass.

Conclusions. These findings support the hypothesis that MAs may undergo appendectomy more often than WNHs and so may be at higher risk of appendicitis.