[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.
Ethylene oxide (EtO) is an alkylating agent and a model direct-acting mutagen and carcinogen. This study has evaluated a panel of biologic markers including EtO-hemoglobin adducts (EtO-Hb), sister-chromatid exchanges (SCEs), micronuclei, chromosomal aberrations (CAs), DNA single-strand breaks (SSB) and an index of DNA repair (ratio of UDS to NA-AAF-DNA binding) in the peripheral blood cells of 34 workers at a sterilization unit of a large university hospital and 23 controls working in the university library. Comprehensive environmental histories were obtained on each subject including detailed occupational and smoking histories. Industrial hygiene data obtained prior to the study and personal monitoring during the 8 years preceding the study showed that workers were subject to low-level exposure near or below the current Occupational Safety and Health Administration (OSHA) standard of 1 ppm (TWA). Personal monitoring data obtained during 2 weeks prior to blood sampling were uniformly less than 0.3 ppm (TWA). After adjusting for smoking, EtO workplace exposure was significantly (p less than 0.001) associated with EtO-Hb (a carcinogen-protein adduct) and 2 measures of SCEs [the average number of SCEs/cell (SCE50) and the number of high frequency cells (SCEHFC)]. There was an apparent suppression of DNA repair capacity in EtO-exposed individuals as measured by the DNA repair index; i.e., the ratio of unscheduled DNA synthesis (UDS) and NA-AAF-DNA binding (p less than 0.01). No association of DNA repair index with smoking was found. Another important finding of this study is the highly significant correlation between EtO-Hb adduct levels and SCEHFC (p less than 0.01) and SCEs (p less than 0.02) which provides evidence of a direct link between a marker of biologically effective dose and markers of genotoxic response. In contrast, micronuclei, CAs and SSBs were not significantly elevated in the workers. The activity of the u-isoenzyme of glutathione-S-transferase (GT) was measured as a possible genetic marker of susceptibility and a modulator of biomarker formation. However, possibly because of confounding by age, no significant relationships were found between GT and any of the exposure-related markers by ANOVA or among other independent variables by regression. This study demonstrates significant effects of low-level EtO exposure, independent of smoking history, near or below 1 ppm on multiple biomarkers and suggests that the current OSHA standard may not be adequately protective. Previously described effects of smoking on EtO-Hb adducts, SCEs and SCEHFC were also seen in this study.(ABSTRACT TRUNCATED AT 400 WORDS)
METHODS. Latino (n = 358) and Anglo (n = 113) adults living in the San Diego area were surveyed on nutrition, smoking, and cancer screening behaviors. The Latino respondents were dichotomized into a low (L-Latino) or high (H-Latino) acculturation group according to a median split of an acculturation index. RESULTS. After controlling for age, years of education, gender, marital status, and income, significant cross-cultural differences were found in saturated fat/cholesterol avoidance, and fiber and high calorie food consumption. L-Latino respondents had the lowest degree of saturated fat/cholesterol avoidance, followed by H-Latinos and Anglos. A pattern of decreasing consumption with increasing acculturation was observed for fiber and high calorie foods. Significant differences were found among women in the prevalence of Pap smear exams, with L-Latinas having the lowest prevalence of ever and in the past year having had a Pap smear, followed by H-Latinas and Anglos. A similar significant pattern was observed among women 50 years of age or older with respect to the prevalence of ever having had a mammogram.
Fluconazole is a recently licensed antifungal agent that has gained widespread use in the medical community. Despite a lack of controlled trials in invasive fungal infections, this agent is often prescribed because of ease of administration and concern over amphotericin B toxicity. Three cases of systemic fungal infections in which fluconazole use resulted in unambiguous microbiologic and clinical failure are reported.
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Sleep apnea, which affects 10% of men in the mean age group, is a common illness, and arterial hypertension one of its early symptoms. For the large group of, mainly young, patients with mild to moderate sleep apnea and arterial hypertension it is important to have a drug treatment available which will effectively control blood pressure without exacerbating symptoms of sleep apnea. We studied the effects of antihypertensive agents on blood pressure, sleep and sleep apnea in a randomized double-blind study of 24 patients with a sleep apnea activity of more than 10 apnea phases per hour of sleep and arterial hypertension with diastolic blood pressure values in the sitting position greater than or equal to 95 mm Hg. Mean age was 51 (range: 33-69) years, mean body mass index 31.4 (24.9-40.6) kg/m2. The study protocol envisaged two baseline measurements in the sleep laboratory, after which the medication was administered for 8 days. On the last 2 days of the treatment, polysomnographic leads were once again recorded in the sleep laboratory. The patients received either the beta-blocker metoprolol (1 x 100 mg/day) or the angiotensin-converting enzyme inhibitor cilazapril (1 x 2.5 mg/day). Systolic and diastolic blood pressure were decreased by both substances as expected. Total sleep time was 358 (233-425) min vs. 332 (255-383) min in the metoprolol group and 368 (295-424) min vs. 341 (265-434) min in the cilazapril group which is statistically not different between the two groups nor between the proportions of non-REM and REM sleep.(ABSTRACT TRUNCATED AT 250 WORDS)
Arterial blood pressure patterns in 12 men with sleep apnea and arterial hypertension were studied at baseline and after 6 months' therapy with nasal continuous positive airway pressure (nCPAP). Preexisting antihypertensive medication was discontinued 1 week before baseline measurements. Weight did not change during the study period; body mass index was 29.3 (range, 25.4-38.5) vs. 29.3 (25.0-38.5). During therapy the apnea index decreased from 58 (range 30-73) to 2 (range 0-7) apneic episodes per hour (p less than 0.01). Intra-arterial systolic (BP sys.) and diastolic (BP dias.) blood pressure and heart rate decreased during therapy (p less than 0.001). Mean values +/- 95% confidence intervals were as follows: BP sys., 147.1 (+/- 1.6) mm Hg vs. 126.4 (+/- 1.5) mm Hg; BP dias., 81.6 (+/- 0.8) mm Hg vs. 69.4 (+/- 0.6) mm Hg; heart rate, 68.8 (+/- 0.7) beats/min vs. 65.4 (+/- 0.7) beats/min. Furthermore, the variability of these parameters decreased during therapy: variability BP sys., 53.8 (+/- 1.1) mm Hg vs. 25.6 (+/- 1.1) mm Hg; variability BP dias., 35.6 (+/- 0.7) mm Hg vs. 17.9 (+/- 0.7) mm Hg; variability of heart rate, 28.1 (+/- 0.7) beats/min vs. 14.9 (+/- 0.7) beats/min (p less than 0.001). During treatment we found that blood pressure scores already dropped during the awake phase, with a further decrease during non-REM and REM sleep (p less than 0.001). Our results, which demonstrate the reversibility of high blood pressure upon treatment of sleep apnea, indicate that sleep apnea can be an etiological factor in hypertension. Sleep apnea should therefore be considered in the differential diagnosis of arterial hypertension.
The potential of biologic markers to provide more timely and precise risk assessments for environmental carcinogens is viewed against the current state-of-the-art in biological monitoring/molecular epidemiology. Biologic markers such as carcinogen-DNA adducts and oncogene activation are currently considered valid qualitative indicators of potential risk, but for most chemical exposures research is needed to establish their validity as quantitative predictors of cancer risk. Biologic markers have, however, already provided valuable insights into the magnitude of interindividual variation in response to carcinogenic exposures, with major implications for risk assessment.
Sleep-related breathing disorders are associated with considerably impaired vitality and reduced life expectancy. In this respect, a particularly important role is played by obstructive snoring and obstructive or mixed sleep apnoea. Because of the often underestimated prevalence of sleep-related breathing disorders and their association with hypertension in greater than 50% of patients, it is important to introduce antihypertensive drug therapy that does not exacerbate the effects and the degree of these disorders, and that above all produces an adequate lowering of blood pressure by night. In the present study in 12 patients, it has been shown that the new ACE inhibitor, cilazapril, achieves a good reduction in blood pressure over 24 hours and during all stages of sleep, without any negative influence on the ratio of REM: nonREM sleep. The apnoea index was reduced from 40 (range 12 to 84) to 27 (range 0 to 72) apnoeas per hour of sleep (p less than 0.01). It will be increasingly important to take into account the effects of antihypertensive therapy on other clinical parameters, especially the nocturnal blood pressure profile and its association with sleep-related breathing disorders.