Risk factors for atherosclerosis - can they be used to identify the patient with multisystem atherosclerosis?

Risk factors are often used in preventive care programmes to identify the patient at particular risk for developing atherosclerosis. Risk factors for atherosclerosis have also been shown to be linked to the presence of the disease at a given time, a fact that may be helpful when screening for additional atherosclerotic disease in the known arteriopath. Risk factors .were recorded in 471 patients admi"ed to hospital with symptoms of atherosclerosis. In patients admi"ed primarily with peripheral vascular disease, risk factors linked to the presence of additional coronary artery disease were a family history of ischaemic heart disease (odds ratio = 2,6), the presence of carotid artery disease (odds ratio = 1,9) and high fasting serum triglyceride levels (P < 0,04). Grouping these factors together usin.g logistic regression, ischaemic heart disease could be predicted with a sensitivity of 72% and a specificity of 43%. Patients admitted with carotid artery disease were more likely to have ischaemic heart disease in the presence of peripheral vascular disease (odds ratio = 1,9) and a raised serum cholesterol level (P < 0,02), while female gender (odds ratio = 2,9) and an increase in age (P< 0,001) were linked to an increased prevalence of concomitant atherosclerosis in patients admmed with acute myocardial infarction or for elective coronary artery bypass surgery. Using an age cut-off point, additional atherosclerosis could be predicted with a sensitivity of 32% and a specificity of 88% in these patients

Detecting asymptomatic coronary artery disease using routine exercise testing and exercise thallium scintigraphy in patients with atherosclerotic vascular disease

ECG-monitored exercise testing has been proposed as a relatively inexpensive and effective means of screening for asymptomatic coronary artery disease in patients presenting for peripheral vascular surgery. Despite the fact that exercise thallium scintigraphy is also dependent on the patient's ability to exercise, using this test in conjunction with ECG-monitored exercise testing may enhance sensitivity and specificity of non-invasive evaluation. Thirty-two patients were subjected to ECG-monitored exercise testing, exercise thallium scintigraphy and coronary angiography. The sensitivity of ECGmonitored exercise testing for detecting coronary artery disease was calculated at 81,8% and the specificity at 87,5%, while the figures for exercise thallium scintigraphy were 73,1% and 33,3% respectively. Using these two methods in combination yielded a predictive accuracy of 90,6%. The only advantage of exercise thallium scintigraphy over exercise ECG appears to be in patients in whom the latter test could not be interpreted or was non-diagnostic

The Globular Cluster Systems in the Coma Ellipticals. II: Metallicity Distribution and Radial Structure in NGC 4874, and Implications for Galaxy Formation

Deep HST/WFPC2 (V,I) photometry is used to investigate the globular cluster system (GCS) in NGC 4874, the central cD galaxy of the Coma cluster. The luminosity function of the clusters displays its normal Gaussian-like shape and turnover level. Other features of the system are surprising: the GCS is (a) spatially extended, with core radius r_c = 22 kpc, (b) entirely metal-poor (a narrow, unimodal metallicity distribution with mean [Fe/H] = -1.5), and (c) modestly populated, with specific frequency S_N = 3.7 +- 0.5. We suggest on the basis of some simple models that as much as half of this galaxy might have accreted from low-mass satellites, but no single one of the three classic modes of galaxy formation (accretion, disk mergers, in situ formation) can supply a fully satisfactory formation picture. Even when they are used in combination, strong challenges to these models remain. The principal anomaly in this GCS is essentially the complete lack of metal-rich clusters. If these were present in normal (M87-like) numbers in addition to the metal-poor ones that are already there, then the GCS in total would more closely resemble what we see in many other giant E galaxies.Comment: 27 pp. with 9 Figures. Astrophys.J. 533, in press (April 10, 2000

Clinical, biochemical, and genetic spectrum of MADD in a South African cohort: an ICGNMD study

\ua9 2024, The Author(s).Background: Multiple acyl-CoA dehydrogenase deficiency (MADD) is an autosomal recessive disorder resulting from pathogenic variants in three distinct genes, with most of the variants occurring in the electron transfer flavoprotein-ubiquinone oxidoreductase gene (ETFDH). Recent evidence of potential founder variants for MADD in the South African (SA) population, initiated this extensive investigation. As part of the International Centre for Genomic Medicine in Neuromuscular Diseases study, we recruited a cohort of patients diagnosed with MADD from academic medical centres across SA over a three-year period. The aim was to extensively profile the clinical, biochemical, and genomic characteristics of MADD in this understudied population. Methods: Clinical evaluations and whole exome sequencing were conducted on each patient. Metabolic profiling was performed before and after treatment, where possible. The recessive inheritance and phase of the variants were established via segregation analyses using Sanger sequencing. Lastly, the haplotype and allele frequencies were determined for the two main variants in the four largest SA populations. Results: Twelve unrelated families (ten of White SA and two of mixed ethnicity) with clinically heterogeneous presentations in 14 affected individuals were observed, and five pathogenic ETFDH variants were identified. Based on disease severity and treatment response, three distinct groups emerged. The most severe and fatal presentations were associated with the homozygous c.[1067G > A];c.[1067G > A] and compound heterozygous c.[976G > C];c.[1067G > A] genotypes, causing MADD types I and I/II, respectively. These, along with three less severe compound heterozygous genotypes (c.[1067G > A];c.[1448C > T], c.[740G > T];c.[1448C > T], and c.[287dupA*];c.[1448C > T]), resulting in MADD types II/III, presented before the age of five years, depending on the time and maintenance of intervention. By contrast, the homozygous c.[1448C > T];c.[1448C > T] genotype, which causes MADD type III, presented later in life. Except for the type I, I/II and II cases, urinary metabolic markers for MADD improved/normalised following treatment with riboflavin and L-carnitine. Furthermore, genetic analyses of the most frequent variants (c.[1067G > A] and c.[1448C > T]) revealed a shared haplotype in the region of ETFDH, with SA population-specific allele frequencies of < 0.00067–0.00084%. Conclusions: This study reveals the first extensive genotype–phenotype profile of a MADD patient cohort from the diverse and understudied SA population. The pathogenic variants and associated variable phenotypes were characterised, which will enable early screening, genetic counselling, and patient-specific treatment of MADD in this population

KPNB1 (karyopherin (importin) beta 1)

Review on KPNB1 (karyopherin (importin) beta 1), with data on DNA, on the protein encoded, and where the gene is implicated

Residual allergenicity of amino acid-based and extensively hydrolysed cow’s milk formulas

Background. Criteria for labelling infant feeds as suitable for the dietary management of cow’s milk protein allergy (CMPA) rely on proving the hypoallergenicity of such feeds or clinical studies showing that the feeds are tolerated by 90% of children with proven CMPA. South African (SA) labelling legislation does not indicate what testing is necessary to prove hypoallergenicity.Objectives. To evaluate all extensively hydrolysed cow’s milk formulas and amino acid-based formulas available in SA for residual allergen content, protein size and amino-acid content.Results. All amino-acid and extensively hydrolysed formulas were found to be similar in composition, with no residual cow’s milk allergens detectable by enzyme-linked immunosorbent assay. Furthermore, proteins were absent and only small molecules in the size range of amino acids and possibly of very small oligopeptides were detected.Conclusions. These findings indicate that the formulas are extremely likely to be compliant with the definition of hypoallergenicity as tolerance in 90% of proven sufferers from cow’s milk allergy. The formulas may therefore be labelled as suitable for the dietary management of infants with CMPA

Plasma sarcosine does not distinguish early and advanced stages of prostate cancer

Introduction. Diagnosis of prostate cancer by prostate specific antigen (PSA) is error-prone and cannot distinguish benign prostatic hyperplasia (BPH) from malignant disease, nor identify aggressive and indolent types. Methods. We determined serum sarcosine (N-methylglycine) in 328 cancer patients by gas chromatography (GC)/mass spectroscopy (MS) and searched for correlations with early (stage T1/T2) and advanced (stage T3/T4) disease. Results. Serum sarcosine of male control patients ranged from 1.7 µmol/l to 4.8 µmol/l. In prostate cancer patients, sarcosine ranged from 2.8 µmol/l to 20.1 µmol/l. Expressed as the sarcosine/alanine ratio, serum control values were 9.4±5.5x10-3 (mean±SD) compared with 21.6±9.0; 28.5±16.6; 22.7±7.7 and 22.2±11.0 for patients diagnosed with T1, T2, T3 and T4 prostate tumours, respectively. The small differences between T1, T2, T3 and T4 patients were not statistically significant (p=0.51). However, the conventional PSA marker significantly correlated with T stage in these patients (r=0.63;