[The diagnostic significance of lipoprotein(a)].
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Biomedical subjects
Publications and source records attributed to J Mayer.
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The von Willebrand factor (vWF) is found in plasma and in platelets. The concentration and multimeric composition of the vWF in platelets of 160 patients with bleeding tendency were examined since very little is known about the platelet vWF. For quantitative analysis of the platelet vWF, a modified ELISA was established. A reference range from 70%-130% of platelet vWF concentration considered normal was established by examining 80 healthy blood donors. 16.9% of the 160 patients showed a decreased vWF concentration in platelets only, while all the other coagulation parameters were normal. 3 of our patients belong to the same family and suggesting an autosomal dominant genetic transmission for the von Willebrand disease type 1-3. The data also suggests, that a quantitative and qualitative analysis of the vWF in plasma and platelets is required for an exact diagnosis of the von Willebrand disease.
In a study of 20 patients with hypercholesterolemia (type IIa) the effects of lovastatin (20-80 mg/day) on various clotting and thrombosis parameters were monitored for 12 months. On 11 occasions various cholesterol fractions and clotting parameters were determined in each patient. In addition, the clotting inhibitors AT III, protein C, protein S, and C1-esterase inhibitor and the fibrinolysis parameters plasminogen and alpha 2-antiplasmin were examined. Platelet function was monitored on the basis of spontaneous and induced (collagen, ADP, epinephrine, ristocetin) aggregation. Lovastatin in the above dosage brought about a 66 mg/dl (from 320 +/- 12.6 to 254 +/- 12.0 mg/dl) reduction in the total cholesterol level and a 56 mg/dl (from 244 +/- 11.4 to 188 +/- 12.1 mg/dl) reduction in LDL cholesterol at the end of the study. Fibrinogen showed a significance decrease during the study period, whereas PT and aPTT remained unaffected. The initial slopes of the ADP-induced platelet aggregation revealed a significant decrease. C-reactive protein and platelet count remained within the normal range, indicating no significant change. Thrombin clotting time, AT III, C1-esterase inhibitor, plasminogen, and alpha 2-antiplasmin were not modified. Protein C and S behaved in a contradictory way, but remained within the normal range. Long-term treatment with lovastatin was associated with a significant reduction of fibrinogen levels and platelet aggregation induced by ADP in type-IIa hypercholesterolemic patients. These alterations, as well as their role in cardiovascular disease, should be the subject of further investigations.
Rates of spine surgery (discectomy, laminectomy, fusion) vary several-fold among "small areas" such as counties or hospital market areas. To ascertain why this is so, an analysis was conducted of variability in rates among counties in the State of Washington (N = 39). Since, unlike previous published reports, this study excluded patients with cancer, major trauma, and infection, as well as those with cervical and thoracic procedures, rates in this study pertain specifically to the problem of low-back pain. Six classes of variables to explain variability among county rates were defined: I) percentage of the labor force in heavy labor and transportation occupations; II) socioeconomic conditions; III) neurologic and orthopedic surgeon density; IV) occupancy rate of back surgery hospitals; V) primary payer and VI) health care availability. In all, the effect of 28 explanatory variables was tested. In doing so, the authors took into account the possibility of spurious correlation. The rate of surgery for low-back pain varied nearly 15-fold among counties. The explanatory variables that were tested, however, accounted for only a minor part of the variability. The hypothesis that "physician practice style factor" accounts for the major part is explored; potential properties of practice style factor are specified for further testing.
Prevention of environmentally related cancer will be enhanced by the availability of sensitive early warning systems and by improvements in quantitative assessment of human risks. Accordingly, we have carried out a series of molecular epidemiologic studies aimed at validating a panel of biologic markers, including carcinogen-DNA and -protein adducts, sister chromatid exchange, micronucleus formation, DNA strand breaks, and DNA repair capacity. Results from three such studies illustrate the usefulness of these biomarkers in elucidating low-dose-response relationships, correlations between biomarkers, and the range of variation in biomarkers between individuals exposed to similar concentrations of carcinogens. Low-level workplace or ambient exposures to styrene, ethylene oxide, and polycyclic aromatic hydrocarbons (PAH) were associated with significant increases in both molecular dose of carcinogens (adducts) and various markers of preclinical effects. Correlations between biomarkers varied by exposure. For example, in the styrene study, sister chromatid exchange frequency was not correlated with any of the markers, in contrast to the studies of ethylene oxide and PAH. Significant molecular effects were observed not only in occupationally exposed people but also in residents of an area in Poland characterized by high levels of air pollution. For example, the mean PAH-DNA level in exposed residents (winter sample) was 30.4 adducts per 10(8) nucleotides. This level was significantly higher than that of adducts seen in summer samples from the same area (4.2/10(8), or in winter samples from residents of a rural area (11.01/10(8). Significant seasonal variation in PAH-DNA adduct formation in this group was consistent with recorded fluctuations in air pollution levels. Striking interindividual variation was observed in all three exposed populations.
The von Willebrand disease (vWD) is the most severe coagulopathy. Because of the complex biochemical structure of the von Willebrand factor (vWF), a great number of types and subtypes of the vWD were found. A screening of vWD can only be done by examining the bleeding time, the ristocetin cofactor activity (risto) and by an immunological determination of the vWF concentration. Examinations of 200 patients with a bleeding tendency showed that the ratio vWF/risto < 0.7 indicates a high probability for an abnormal multimeric structure of vWF. The exact determination of the vWD subtype then has to be done by a SDS-agarose gel electrophoresis. In 16.8% of our patients we found a decreased vWF concentration in the platelets. These patients showed normal plasmatic coagulation factors, but a bleeding tendency and a prolonged bleeding time. For diagnosis of vWD the bleeding time, immunological determination of the vWF and the risto should be done first. If a ratio vWF/risto < 0.7 or a prolonged bleeding time with a bleeding tendency is found, the separation of the vWF multimers into plasma and platelets and the determination of the vWF concentration in platelets should be carried out for an exact diagnosis of vWD.
Fifty patients with sleep-related breathing disorders and arterial hypertension underwent diagnostic polysomnography for two nights; EEG, EOG, EMG, and respiratory signals were recorded in parallel with invasive blood pressure. Computerized evaluation was performed to calculate systolic and diastolic blood pressure values, as well as heart rate beat-to-beat. All signals were stored once per second for further evaluation. These time series were analyzed in respect of underlying periodicities by means of spectral analysis. It was possible to distinguish four different groups of patients according to the compressed spectral arrays. Pronounced peaks of different extents were found that reflected both periodicities of respiration (3-5 s) and periodicities of sleep apnea (30-60 s). A comparison of spectral analysis of blood pressure and heart rate showed that systolic blood pressure is suited best to recognize periodicities related to respiration and apneas.
Sleep related breathing disorders are of high prevalence and are often associated with essential hypertension. It is therefore necessary to study blood pressure continuously in all patients with sleep related breathing disorders and arterial hypertension as well as in all patients with essential hypertension and suspected sleep apnoea. To investigate the usefulness of a non-invasive continuous volume-clamp method during sleep we used this technique in parallel with 130 sleep recordings and performed a validation study of the Finapres instrument on a subgroup where continuous invasive blood pressure recordings were available. Absolute pressure values of Finapres are valid when the position and the movement of the sensor were carefully observed and only appropriate segments of the recordings were taken for further evaluation. The high beat to beat resolution of the systolic and diastolic pressure is the main advantage of this non-invasive technique because it reflects rapid blood pressure variations as they occur in sleep related breathing disorders. This could be investigated only invasively until now.
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The authors assessed the plasma viscosity by means of a capillary viscosimeter of their own design and assessed at the same time the concentration of 22 plasma proteins or lipids. Based on the results of these examinations it proved possible to elaborate an original equation which describes the plasma viscosity as a function of the concentration of fibrinogen, alpha-2-globulins (and among them most probably haptoglobin), gammaglobulins, IgA and IgM. The authors discuss in detail the importance of this finding for clinical haemorheology.
Twelve male outpatients participating in a methadone maintenance treatment program were evaluated for the effects of acute administration of methadone on brain functioning (contingent negative variation or CNV), attention performance (reaction time and continuous performance test), and psychophysiological activity (heart rate and eye blink rate). Individual differences in response to methadone were assessed by classifying patients into two groups on the basis of basal CNV shapes: Type A (quick rise time) and type B (slow rise time). Methadone produced a pattern of increased electrical brain activity (CNV) and enhanced attention performance in type B patients and elevated heart rate and lowered eye blink rate in type A subjects. Results are interpreted in terms of the distraction-arousal and the eye blink-hedonia hypotheses.
Caloric regulation and the development of obesity were examined in rats which had received parenteral injections of monosodium glutamate (MSG) as neonates. Rats were injected with either 2 mg/g or 4 mg/g MSG on alternate days for the first 20 days of life. Lee Indices of obesity were calculated at 22, 70, and 130 days of age. Animals in the 4 mg/g group were significantly more obese than controls at all three ages. However, both food intake and body weight of this group were significantly lower than those of controls. In adulthood, the ability to regulate caloric intake was tested by allowing animals access to diets of varying caloric densities. While control animals maintained relatively constant caloric intakes across dietary conditions, MSG-treated animals demonstrated an inability to respond to caloric challenges. Treated animals decreased caloric intake on a diluted diet and consumed more calories than controls when presented with a calorically dense diet. This inability to regulate caloric intake is compared with regulatory deficits observed in animals sustaining lesions of the ventromedial hypothalamus. The value of an animal model of juvenile-onset obesity is also discussed.
The reliability of the scale was measured by the test-retest scores of adolescent alcoholics and adolescents who drink infrequently; its validity was assessed by psychiatrists' and others' ratings of the items, the scores of adolescents reporting alcohol misuse and the factor-analyzed scores of a large population of high-school studnets.
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