[Argentinean consensus guidelines on the identification and clinical care of secondary progressive multiple sclerosis]. / Consenso sobre la identificación y seguimiento de la esclerosis múltiple secundaria progresiva en Argentina.

INTRODUCTION: The identification, diagnosis, follow-up, and treatment of patients with secondary progressive multiple sclerosis (SPMS) show significant differences between health care professionals in Argentina. AIM: To provide consensus recommendations on the management of patients with SPMS in Argentina to optimize patient care. DEVELOPMENT: A panel of expert neurologists from Argentina dedicated to the diagnosis and care of multiple sclerosis patients gathered during 2019 and 2020 to carry out a consensus recommendation on the diagnosis and treatment of SPMS patients in Argentina. To achieve consensus, the methodology of 'formal consensus-RAND/UCLA method' was used. Recommendations were established based on published evidence and the expert opinion. Recommendations focused on how to define SPMS and how to follow SPMS patients. CONCLUSION: The recommendations of this consensus guidelines attempt to optimize the care of SPMS patients in Argentina.

TITLE: Consenso sobre la identificación y seguimiento de la esclerosis múltiple secundaria progresiva en Argentina.Introducción. Existen diferencias significativas en el diagnóstico, la identificación y el seguimiento de pacientes con esclerosis múltiple secundaria progresiva (EMSP) entre los profesionales de la salud a cargo de su tratamiento. Objetivo. Proveer recomendaciones sobre el tratamiento de los pacientes con EMSP en Argentina con el fin de optimizar su cuidado. Desarrollo. Un grupo de neurólogos expertos en esclerosis múltiple de Argentina elaboró un consenso para el tratamiento de pacientes con EMSP en la región mediante metodología de ronda de encuestas a distancia y reuniones presenciales. Se establecieron 33 recomendaciones basadas en la evidencia publicada y en el criterio de los expertos que participaron. Las recomendaciones se enfocaron en el diagnóstico y el seguimiento de los pacientes con EMSP. Conclusión. Las recomendaciones establecidas en el presente consenso permitirían optimizar el cuidado y el seguimiento de los pacientes con EMSP en Argentina.

Wadi el-Sheikh: A new archaeological investigation of ancient Egyptian chert mines.

This article provides an overview of the first results from archaeological investigations at Wadi el-Sheikh in Egypt by the University of Vienna Middle Egypt Project. Chert was an important raw material used to produce tools, implements and jewelry in ancient times. Wadi el-Sheikh was exploited over thousands of years as it was probably the most important source of chert in Pharaonic civilization. The results of our new investigations that involved surveys and test excavations indicate the presence of large scale mining activities in the first half of the 3rd Millennium B.C.E. which allow for detailed insights into the amount of raw material extracted, the mining methods used and the lithic products manufactured in this area. These aspects are contextualized on the background of ancient Egyptian state-organized resource acquisition strategies and economy.

Impaired DNase1-mediated degradation of neutrophil extracellular traps is associated with acute thrombotic microangiopathies.

BACKGROUND: Acute thrombotic microangiopathies (TMAs) are characterized by excessive microvascular thrombosis and are associated with markers of neutrophil extracellular traps (NETs) in plasma. NETs are composed of DNA fibers and promote thrombus formation through the activation of platelets and clotting factors. OBJECTIVE: The efficient removal of NETs may be required to prevent excessive thrombosis such as in TMAs. To test this hypothesis, we investigated whether TMAs are associated with a defect in the degradation of NETs. METHODS AND RESULTS: We show that NETs generated in vitro were efficiently degraded by plasma from healthy donors. However, NETs remained stable after exposure to plasma from TMA patients. The inability to degrade NETs was linked to a reduced DNase activity in TMA plasma. Plasma DNase1 was required for efficient NET degradation and TMA plasma showed decreased levels of this enzyme. Supplementation of TMA plasma with recombinant human DNase1 restored NET-degradation activity. CONCLUSIONS: Our data indicate that DNase1-mediated degradation of NETs is impaired in patients with TMAs. The role of plasma DNases in thrombosis is, as of yet, poorly understood. Reduced plasma DNase1 activity may cause the persistence of pro-thrombotic NETs and thus promote microvascular thrombosis in TMA patients.

Determination of hydrogen cluster velocities and comparison with numerical calculations.

The use of powerful hydrogen cluster jet targets in storage ring experiments led to the need of precise data on the mean cluster velocity as function of the stagnation temperature and pressure for the determination of the volume density of the target beams. For this purpose a large data set of hydrogen cluster velocity distributions and mean velocities was measured at a high density hydrogen cluster jet target using a trumpet shaped nozzle. The measurements have been performed at pressures above and below the critical pressure and for a broad range of temperatures relevant for target operation, e.g., at storage ring experiments. The used experimental method is described which allows for the velocity measurement of single clusters using a time-of-flight technique. Since this method is rather time-consuming and these measurements are typically interfering negatively with storage ring experiments, a method for a precise calculation of these mean velocities was needed. For this, the determined mean cluster velocities are compared with model calculations based on an isentropic one-dimensional van der Waals gas. Based on the obtained data and the presented numerical calculations, a new method has been developed which allows to predict the mean cluster velocities with an accuracy of about 5%. For this two cut-off parameters defining positions inside the nozzle are introduced, which can be determined for a given nozzle by only two velocity measurements.

Genetic dissection of fruit quality traits in the octoploid cultivated strawberry highlights the role of homoeo-QTL in their control.

Fruit quality traits are major breeding targets in the Rosaceae. Several of the major Rosaceae species are current or ancient polyploids. To dissect the inheritance of fruit quality traits in polyploid fleshy fruit species, we used a cultivated strawberry segregating population comprising a 213 full-sibling F1 progeny from a cross between the variety 'Capitola' and the genotype 'CF1116'. We previously developed the most comprehensive strawberry linkage map, which displays seven homoeology groups (HG), including each four homoeology linkage groups (Genetics 179:2045-2060, 2008). The map was used to identify quantitative trait loci (QTL) for 19 fruit traits related to fruit development, texture, colour, anthocyanin, sugar and organic acid contents. Analyses were carried out over two or three successive years on field-grown plants. QTL were detected for all the analysed traits. Because strawberry is an octopolyploid species, QTL controlling a given trait and located at orthologous positions on different homoeologous linkage groups within one HG are considered as homoeo-QTL. We found that, for various traits, about one-fourth of QTL were putative homoeo-QTL and were localised on two linkage groups. Several homoeo-QTL could be detected the same year, suggesting that several copies of the gene underlying the QTL are functional. The detection of some other homoeo-QTL was year-dependent. Therefore, changes in allelic expression could take place in response to environmental changes. We believe that, in strawberry as in other polyploid fruit species, the mechanisms unravelled in the present study may play a crucial role in the variations of fruit quality.

A novel algorithm for the determination of bacterial cell volumes that is unbiased by cell morphology.

The determination of cell volumes and biomass offers a means of comparing the standing stocks of auto- and heterotrophic microbes of vastly different sizes for applications including the assessment of the flux of organic carbon within aquatic ecosystems. Conclusions about the importance of particular genotypes within microbial communities (e.g., of filamentous bacteria) may strongly depend on whether their contribution to total abundance or to biomass is regarded. Fluorescence microscopy and image analysis are suitable tools for determining bacterial biomass that moreover hold the potential to replace labor-intensive manual measurements by fully automated approaches. However, the current approaches to calculate bacterial cell volumes from digital images are intrinsically biased by the models that are used to approximate the morphology of the cells. Therefore, we developed a generic contour based algorithm to reconstruct the volumes of prokaryotic cells from two-dimensional representations (i.e., microscopic images) irrespective of their shape. Geometric models of commonly encountered bacterial morphotypes were used to verify the algorithm and to compare its performance with previously described approaches. The algorithm is embedded in a freely available computer program that is able to process both raw (8-bit grayscale) and thresholded (binary) images in a fully automated manner.

Color Doppler ultrasound imaging in varicoceles: is the venous diameter sufficient for predicting clinical and subclinical varicocele?

PURPOSE: Investigating the diagnostic value of color Doppler ultrasound for defining the varicocele grade according to WHO criteria. METHODS: A total of 217 men (129 with clinical varicocele and 88 without clinical varicocele) were investigated by physical examination and color Doppler ultrasound and categorized according to WHO varicocele criteria (0, subclinical, I, II, and III). Diameter and reflux of the largest vein in the pampiniform plexus were measured bilaterally with the patient in the supine position in rest and during the Valsalva maneuver. To assess the possibility of differentiating varicocele grade by venous diameter, optimal cut-point values were determined by receiver-operator characteristic (ROC) analysis. RESULTS: With increased varicocele grade, a larger vein diameter was more significant in rest and during Valsalva (in all cases P < 0.05), except between grade I and grade II. Retrograde peak flow velocities were similar in every group (in all cases P > 0.1). Only grade III varicoceles demonstrated significantly increased peak flow values compared with all other grades (P < 0.001). There were no side-related differences when comparing identical varicocele grades (in all cases P > 0.1). Venous diameters above 2.45 mm in rest (sensitivity 84%, specificity 81%) or 2.95 mm during Valsalva (sensitivity 84%, specificity 84%) predicted the presence of a clinical varicocele. CONCLUSIONS: Our findings support the hypothesis that clinical varicoceles can be predicted with high accuracy based only on the diameter of testicular veins using cut-point values of >2.45 mm in rest or >2.95 mm during Valsalva maneuver in the supine position.

Epoetin theta: efficacy and safety of IV administration in anaemic haemodialysis patients in the maintenance phase in comparison to epoetin beta.

OBJECTIVE: To compare the efficacy and safety of epoetin theta and epoetin beta in anaemic patients with chronic kidney disease, undergoing haemodialysis and previously on stable maintenance therapy with epoetin beta. METHODS: In this multicentre, randomised, controlled, double-blind study 270 haemodialysis patients were treated intravenously (i.v.) for 24 weeks with either epoetin theta (n = 180) or epoetin beta (n = 90). The primary efficacy endpoint was the change in haemoglobin (Hb) from baseline to end of treatment (efficacy evaluation period, EEP, weeks 15-26). Hb levels, weekly doses of epoetin theta or epoetin beta required to maintain Hb levels, dose changes, safety, tolerability and immunogenicity were evaluated. CLINICAL TRIAL REGISTRATION: EudraCT No. 2005-000143-28. RESULTS: Mean Hb values were similar in both treatment groups at baseline and during the 24-weeks treatment period. The estimated treatment difference between epoetin theta and epoetin beta from baseline to EEP was -0.01 g/dL (95% confidence interval: -0.24, 0.21), p = 0.9021, indicating that the difference between both groups was not statistically significant. The weekly doses of epoetin theta or epoetin beta required to maintain Hb levels were nearly the same. The changes from baseline to EEP in patients who switched to treatment with epoetin theta (95.5-99.7 IU/kg(BW)) were smaller than in patients staying on their epoetin beta therapy (89.0-98.0 IU/kg(BW)). The profile and the frequency of adverse drug reactions (ADRs) were similar in both treatment groups (21.7% epoetin theta; 22.2% epoetin beta). The most common ADRs were hypertension, headache and arteriovenous fistula thrombosis. None of the patients developed anti-erythropoietin antibodies. CONCLUSIONS: Epoetin theta (i.v.) has a similar efficacy compared to epoetin beta (i.v.) in haemodialysis patients based on Hb changes from baseline to end of treatment (non-inferiority). The safety profile was similar in both groups. Patients could be switched from maintenance treatment with epoetin beta to epoetin theta without relevant dose changes.

Pseudomeningocele induced transient loss of consciousness in Marfan syndrome.

Anterior and posterior meningoceles are the severest clinical expression of dural ectasia in patients with Marfan syndrome. Meningoceles and pseudomeningoceles have been reported from either asymptomatic, to causing headache, back pain, leg pain, radiculopathy, constipation and/or urinary symptoms. This article includes a case report of a 31-year-old woman, who presented with recurrent transient loss of consciousness thought to be secondary to acute changes in intracranial pressure transmitted from a pseudomeningocele.

Nicotine and its metabolites in amniotic fluid at birth--assessment of prenatal tobacco smoke exposure.

Amniotic fluid was collected from 78 pregnant women at birth additionally with their urine prior to delivery as well as neonatal urine and meconium. The smoking markers, nicotine and its metabolites cotinine and trans-3'-hydroxycotinine (OH-cotinine), were determined using high-performance liquid chromatography (HPLC). The self-reported smoking status during pregnancy determined by means of a questionnaire was verified by measurement of maternal urine. In all smokers, nicotine metabolites were detected in amniotic fluid and in 80% of them nicotine as well. However, the sum of the nicotine metabolites (Sum(met)) was significantly lower (p < .001) in amniotic fluid (704 +/- 464 nmol/L) than in meconium (921 +/- 588 nmol/L), neonatal urine (1139 +/- 813 nmol/L) and maternal urine (4496 +/- 3535 nmol/L). Concentrations of nicotine metabolites in amniotic fluid correlated well (p < .001) with that in the other specimen types. After environmental tobacco smoke (ETS) exposure, no nicotine or nicotine metabolites were detectable in amniotic fluid but only in maternal and neonatal urine. Analysis of amniotic fluid at birth lends itself to verifying smoking habits during pregnancy and clearly discriminating from ETS exposure, but it is not a suitable approach to differentiating between ETS exposure and non-exposure.

Automated quality assessment of autonomously acquired microscopic images of fluorescently stained bacteria.

Quality assessment of autonomously acquired microscopic images is an important issue in high-throughput imaging systems. For example, the presence of low quality images (>or=10%) in a dataset significantly influences the counting precision of fluorescently stained bacterial cells. We present an approach based on an artificial neural network (ANN) to assess the quality of such images. Spatially invariant estimators were extracted as ANN input data from subdivided images by low level image processing. Different ANN designs were compared and >400 ANNs were trained and tested on a set of 25,000 manually classified images. The optimal ANN featured a correct identification rate of 94% (3% false positives, 3% false negatives) and could process about 10 images per second. We compared its performance with the image quality assessment by different humans and discuss the difficulties in assigning images to the correct quality class. The computer program and the documented source code (VB.NET) are provided under General Public Licence.

Contribution of the 15 amino acid repeats of truncated APC to beta-catenin degradation and selection of APC mutations in colorectal tumours from FAP patients.

The adenomatous polyposis coli (APC) protein is a negative regulator of the mitogenic transcription factor beta-catenin by stimulating its proteasomal degradation. This involves several APC domains, including the binding sites for axin/conductin, the recently described beta-Catenin Inhibitory Domain (CID) and the third 20 amino acid repeat (20R3) that is a beta-catenin-binding site. The four 15 amino acid repeats (15R) and the 20R1 are also beta-catenin-binding sites, but their role in beta-catenin degradation has remained unclear. We show here that binding of beta-catenin to the 15R of APC is necessary and sufficient to target beta-catenin for degradation whereas binding to the 20R1 is neither necessary nor sufficient. The first 15R displays the highest affinity for beta-catenin in the 15R-20R1 module. Biallelic mutations of the APC gene lead tocolon cancer in familial adenomatous polyposis coli (FAP) and result in the synthesis of truncated products lacking domains involved in beta-catenin degradation but still having a minimal length. The analysis of the distribution of truncating mutations along the APC sequence in colorectal tumours from FAP patients revealed that the first 15R is one target of the positive selection of mutations that lead to tumour development.

Lung deposition after inhalation with various nebulisers in preterm infants.

AIM: To compare pulmonary deposition after inhalation with three different nebulisers in preterm infants under conditions relevant to practice. METHODS: The relative lung deposition (bioavailability) was estimated by inhalation of the marker substance, sodium cromoglycate (SCG), and measurement of urinary excretion of SCG. Seventeen spontaneously breathing preterm infants received 20 mg of SCG as nebuliser solution by means of (a) an LC Star jet nebuliser; (b) an LS 290 ultrasonic nebuliser; and (c) a Projet ultrasonic nebuliser in a randomised three-period, crossover design. Serial urine samples were collected until about 12 hours after inhalations, and the excreted SCG was determined by high-performance liquid chromatography. RESULTS: The mean (SD) total amounts of SCG excreted in urine measured after inhalation with the LC Star nebuliser (0.089 (0.036) mg) were significantly higher than those obtained with the LS 290 (0.055 (0.019) mg) or the Projet nebuliser (0.046 (0.025) mg). The average pulmonary deposition after inhalation using the LC Star, LS 290 and Projet devices was estimated as 0.89%, 0.55% and 0.46% of the nominal dose, respectively. CONCLUSION: Inhalation with the LC Star jet nebuliser producing the greatest proportion of droplets <2 mum yielded a higher lung deposition in preterm infants than the LS 290 and Projet ultrasonic nebulisers.

Assessment of prenatal tobacco smoke exposure by determining nicotine and its metabolites in meconium.

Meconium samples collected from 115 neonates were analysed for nicotine, cotinine and trans -3-hydroxycotinine (OH-cotinine) by means of high-performance liquid chromatography (HPLC) to identify prenatal smoke exposure. The self-reported maternal smoking status during pregnancy was determined by means of a questionnaire and verified by measurements in urine prior to childbirth. The total sum of nicotine and its metabolites (Sum(tot)) of the first passed meconium samples was 1560 +/- 1024 pmol/g in newborns of smoking mothers. Smoking of less than five cigarettes was clearly detected. Sum(tot) remained constant in all meconium samples passed by a neonate in succession. However, the proportion of nicotine decreased with the time of passage after birth and the OH-cotinine proportion increased, whereas cotinine hardly changed. Nicotine or its metabolites were not detectable in meconium (detection limit < 20 pmol/g), when the mothers were only exposed to environmental tobacco smoke (ETS) using the HPLC method. The hypothesis that the content of nicotine metabolites in meconium reflects long-term smoke exposure could not be confirmed in newborns whose mothers had quit smoking during the latter half of pregnancy. Determining Sum(tot) enables the intensity of continuous smoking during pregnancy to be estimated in all meconium samples passed by a newborn.

Identification of SCAR markers linked to Rca 2 anthracnose resistance gene and their assessment in strawberry germ plasm.

Bulked segregant analysis combined with AFLPs was used to identify molecular markers linked to the Rca 2 gene conferring resistance to Colletotrichum acutatum pathogenicity group 2 which causes anthracnose in the octoploid strawberry Fragaria x ananassa. DNA bulks originating from a cross between the resistant cultivar 'Capitola' and the susceptible cultivar 'Pajaro' were screened with 110 EcoRI/M se IAFLP combinations. Four AFLP markers were found linked in coupling phase to Rca 2 with recombination percentages between 0% and 17.7%. Among the four markers linked to the resistance gene, two were converted into SCAR markers (STS-Rca 2417 and STS-Rca 2240) and screened in a large segregating population including 179 genotypes. The Rca 2 resistance gene was estimated to be 0.6 cM from STS-Rca 2417 and 2.8 cM from STS-Rca 2240. The presence/absence of the two SCAR markers was further studied in 43 cultivars of F. x ananassa, including 14 susceptible, 28 resistant, and one intermediate genotype. Results showed that 81.4% and 62.8% of the resistant/susceptible genotypes were correctly predicted by using STS-Rca 2417 and STS-Rca 2240, respectively. The 14 susceptible genotypes showed no amplification for either SCARs. These developed SCARs constitute new tools for indirect selection criteria of anthracnose resistance genotypes in strawberry breeding programs.

Audiovisual mirror neurons and action recognition.

Many object-related actions can be recognized both by their sound and by their vision. Here we describe a population of neurons in the ventral premotor cortex of the monkey that discharge both when the animal performs a specific action and when it hears or sees the same action performed by another individual. These 'audiovisual mirror neurons' therefore represent actions independently of whether these actions are performed, heard or seen. The magnitude of auditory and visual responses did not differ significantly in half the neurons. A neurometric analysis revealed that based on the response of these neurons, two actions could be discriminated with 97% accuracy.

Characterization of mixed disomic and polysomic inheritance in the octoploid strawberry (Fragaria x ananassa) using AFLP mapping.

A two-way pseudo-testcross strategy, combined with Single Dose Restriction Fragment (SDRF) marker analysis, was used for genetic mapping in the octoploid cultivated strawberry Fragaria x ananassa (2n = 8 x = 56). Based on a 113 full-sib progeny from a cross between the variety Capitola and the clone CF1116, we generated two parental maps using Amplified Fragment Length Polymorphism (AFLP) markers. Ninety two percent of the markers (727 out of 789) showed ratios corresponding to simplex markers (the majority being SDRF markers), and 8% (62 out of 789) fitted a multiplex ratio. Linkage maps were first established using SDRF markers in coupling phase. The female map comprised 235 markers distributed among 43 co-segregation groups, giving a map size of 1,604 cM. On the male map, 280 markers were assigned to 43 co-segregation groups, yielding a map size of 1,496 cM. Once the co-segregation groups were established, their association was tested using repulsion-phase markers. In total, taking into account associations representing the same linkage groups, 30 linkage groups were detected on the female side and 28 on the male side. On the female map, 68.3% of the pairwise marker linkages were in coupling versus 31.7% in repulsion phase, and the corresponding figures on the male map were 72.2% and 27.8%, respectively. In addition, both groups linked only in the coupling phase and groups linked in the repulsion phase were characterized. The observations suggest that the meiotic behavior of the F. x ananassa genome is neither fully disomic nor fully polysomic, but rather mixed. The genome may not be as completely diploidized as previously assumed.

Nearly complete genetic maps of Pinus sylvestris L. (Scots pine) constructed by AFLP marker analysis in a full-sib family.

We have constructed nearly complete linkage maps of Pinus sylvestris (L.) using AFLP markers based on a two-way pseudo-testcross strategy in a full-sib family founded in an advanced breeding program. With 39 primer combinations, a total of 737 markers (320 from the mother and 417 from the father) segregated in a 1:1 ratio, corresponding to DNA polymorphism: heterozygous in one parent and null in the other. In the maternal parent, 188 framework markers were mapped in 12 linkage groups, equivalent to the Pinus haploid chromosome number, with a total coverage of 1,695.5 cM. In the paternal parent, 245 framework markers established a map with 15 linkage groups, spanning a genome length of 1,718.5 cM. The estimated total map length was L(F) = 1,681 cM for the female and L(M) = 1,645 cM for the male using a modified method-of-moment estimator. Combining these values with those estimated from the observed map lengths in both parents, we estimated the genome length in Scots pine to be between 1,600 and 2,100 cM. Our genome coverage was estimated to be more than 98% with a framework marker interval of 20 cM for both parents. Most of the female and male linkage groups were associated through the analysis of the intercross markers.

Association of the GPIa C807T and GPIIIa PlA1/A2 polymorphisms with premature myocardial infarction in men.

Aims Recent studies have reported an association between the platelet glycoprotein (GP) Ia C807T polymorphism and myocardial infarction, whereas other studies have reported contradictory results concerning the platelet GPIIIa PlA1/A2 polymorphism. In most of these studies the patients were older than 45 years. Thus we decided to examine both genotypes in 287 men who had their first myocardial infarction before age 45, and a group of 138 healthy controls. Methods and Results The frequency of T807 allele carriers was similar among myocardial infarction patients and among controls (54.6% vs 62.3%; odds ratio (OR) 0.73; 95% confidence interval (CI), 0.47-1.12). The frequency of PlA2 carriers was higher in cases than in controls (26.5% vs 15.2%; OR 1.65; CI, 1.09-2.54). After performing a logistic regression analysis, taking into account other cardiovascular risk factors, this difference did not remain significant. The combination of the risk alleles of both genotypes had no major effect on the myocardial infarction risk. Conclusions The GPIIIa PlA2 allele is not independently associated with the risk of premature myocardial infarction. The T807 allele of the GPIa gene alone or in combination with the PlA2 allele had no major effect on premature myocardial infarction risk.

Association of serum apolipoprotein A-I (but not high-density lipoprotein cholesterol) with healed myocardial infarction in men independent of serum insulin and C-peptide.

Low serum levels of high-density lipoprotein (HDL) cholesterol or apolipoprotein A-I and high serum levels of insulin increase the risk of coronary heart disease (CHD) and can indicate insulin resistance. We tested the strength, independence, and interactions of associations between HDL cholesterol (or apolipoprotein A-I), insulin (or C-peptide), glucose, and CHD in 95 male nondiabetic patients with CHD who were <60 years old, in 92 probands from the PROCAM study, and in 61 non-cardiologic patients; all subjects were matched by age, body mass index, and smoking habits. Systemic hypertension (odds radio [OR] 2.8, 95% confidence intervals [CI] 1.6 to 4.8), high serum levels of glucose (OR 2.3, 95% CI 1.6 to 4.8), insulin (OR 2.1, 95% CI 1.3 to 3.6), and C-peptide (OR 4.1, 95% CI 2.2 to 7.5) as well as low serum levels of HDL cholesterol (OR 2.0, 95% CI 1.1 to 3.5) or apolipoprotein A-I (OR 3.9, 95% CI 2.1 to 7.1) had significant associations with CHD. At multivariate analysis, systolic blood pressure, glucose, apolipoprotein A-I, and C-peptide, but not HDL cholesterol and insulin, had consistent independent associations with CHD. Thus, the combined measurement of apolipoprotein A-I and C-peptide may improve the identification of nondiabetic patients at increased risk for CHD.