Showing papers by "University of Münster published in 1998"

Genetic basis and molecular mechanism for idiopathic ventricular fibrillation

Abstract: Ventricular fibrillation causes more than 300,000 sudden deaths each year in the USA alone. In approximately 5-12% of these cases, there are no demonstrable cardiac or non-cardiac causes to account for the episode, which is therefore classified as idiopathic ventricular fibrillation (IVF). A distinct group of IVF patients has been found to present with a characteristic electrocardiographic pattern. Because of the small size of most pedigrees and the high incidence of sudden death, however, molecular genetic studies of IVF have not yet been done. Because IVF causes cardiac rhythm disturbance, we investigated whether malfunction of ion channels could cause the disorder by studying mutations in the cardiac sodium channel gene SCN5A. We have now identified a missense mutation, a splice-donor mutation, and a frameshift mutation in the coding region of SCN5A in three IVF families. We show that sodium channels with the missense mutation recover from inactivation more rapidly than normal and that the frameshift mutation causes the sodium channel to be non-functional. Our results indicate that mutations in cardiac ion-channel genes contribute to the risk of developing IVF.

The International Study of Asthma and Allergies in Childhood (ISAAC). ISAAC Steering Committee.

Abstract: Despite considerable research, the aetiology of asthma and allergic disease remains poorly understood. The International Study of Asthma and Allergies In Childhood (ISAAC), was founded to maximize the value of epidemiological research into asthma and allergic disease by establishing a standardized methodology and facilitating international collaboration. It has achieved its specific aims which are to describe the prevalence and severity of asthma, rhinitis and eczema in children living in different centres and to make comparisons within and between countries; to obtain baseline measures for assessment of future trends in the prevalence and severity of these diseases; and to provide a framework for further aetiological research into genetic, lifestyle, environmental and medical care factors affecting these diseases. The ISAAC design comprises three phases. Phase One used simple core written questionnaires for two age groups, and was completed in 156 collaborating centres in 56 countries and a total of 721 601 children participated. In the 13–14 years age group 155 centres from 56 countries participated, of which 99 centres completed a video questionnaire. For the 6–7 years age group there were 91 collaborating centres in 38 countries. ISAAC Phase One has demonstrated a large variation in the prevalence of asthma symptoms in children throughout the world including hitherto unstudied populations. It is likely that environmental factors were responsible for major differences between countries. The results provide a framework for studies between populations in contrasting environ-ments which are likely to yield new clues about the aetiology of asthma. ISAAC Phase Two will investigate possible aetiological factors, particularly those suggested by the findings of Phase One. ISAAC Phase Three will be a repetition of Phase One in the year 2000 to assess trends in prevalence.

Mutation rate in human microsatellites: influence of the structure and length of the tandem repeat.

Abstract: Summary In 10,844 parent/child allelic transfers at nine short-tandem-repeat (STR) loci, 23 isolated STR mismatches were observed. The parenthood in each of these cases was highly validated (probability >99.97%). The event was always repeat related, owing to either a single-step mutation ( n =22) or a double-step mutation ( n =1). The mutation rate was between 0 and 7×10 −3 per locus per gamete per generation. No mutations were observed in three of the nine loci. Mutation events in the male germ line were five to six times more frequent than in the female germ line. A positive exponential correlation between the geometric mean of the number of uninterrupted repeats and the mutation rate was observed. Our data demonstrate that mutation rates of different loci can differ by several orders of magnitude and that different alleles at one locus exhibit different mutation rates.

Crystal structure of a plant catechol oxidase containing a dicopper center.

Abstract: Catechol oxidases are ubiquitous plant enzymes containing a dinuclear copper center. In the wound-response mechanism of the plant they catalyze the oxidation of a broad range of ortho-diphenols to the corresponding o-quinones coupled with the reduction of oxygen to water. The crystal structures of the enzyme from sweet potato in the resting dicupric Cu(II)-Cu(II) state, the reduced dicuprous Cu(I)-Cu(I) form, and in complex with the inhibitor phenylthiourea were analyzed. The catalytic copper center is accommodated in a central four-helix-bundle located in a hydrophobic pocket close to the surface. Both metal binding sites are composed of three histidine ligands. His 109, ligated to the CuA site, is covalently linked to Cys 92 by an unusual thioether bond. Based on biochemical, spectroscopic and the presented structural data, a catalytical mechanism is proposed in which one of the oxygen atoms of the diphenolic substrate binds to CuB of the oxygenated enzyme.

Consensus on Microembolus Detection by TCD

Abstract: Transcranial Doppler ultrasound is capable of detecting microembolic material, both gaseous and solid, within the intracranial cerebral arteries. To avoid discrediting this promising and exciting new technique, experts in this field met in January 1997 in Frankfurt, Germany, to discuss the limitations and problems of embolus detection and to determine guidelines for its proper use in clinical practice, as well as in scientific investigations. In particular, the authors suggest that studies report the following parameters: (1) ultrasound device, (2) transducer type and size, (3) insonated artery, (4) insonation depth, (5) algorithms for signal intensity measurement, (6) scale settings, (7) detection threshold, (8) axial extension of sample volume, (9) fast Fourier transform (FFT) size (number of points used), (10) FFT length (time), (11) FFT overlap, (12) transmitted ultrasound frequency, (13) high-pass filter settings, and (14) recording time. There was agreement that no current system of automatic embolus detection has the required sensitivity and specificity for clinical use.

Ultraviolet Light Induces Apoptosis via Direct Activation of CD95 (Fas/APO-1) Independently of Its Ligand CD95L

Abstract: Induction of apoptosis in keratinocytes by UV light is a critical event in photocarcinogenesis. Although p53 is of importance in this process, evidence exists that other pathways play a role as well. Therefore, we studied whether the apoptosis-related surface molecule CD95 (Fas/APO-1) is involved. The human keratinocyte cell line HaCaT expresses CD95 and undergoes apoptosis after treatment with UV light or with the ligand of CD95 (CD95L). Incubation with a neutralizing CD95 antibody completely prevented CD95L-induced apoptosis but not UV-induced apoptosis, initially suggesting that the CD95 pathway may not be involved. However, the protease CPP32, a downstream molecule of the CD95 pathway, was activated in UV-exposed HaCaT cells, and UV-induced apoptosis was blocked by the ICE protease inhibitor zVAD, implying that at least similar downstream events are involved in CD95- and UV-induced apoptosis. Activation of CD95 results in recruitment of the Fas-associated protein with death domain (FADD) that activates ICE proteases. Immunoprecipitation of UV-exposed HaCaT cells revealed that UV light also induces recruitment of FADD to CD95. Since neutralizing anti-CD95 antibodies failed to prevent UV-induced apoptosis, this suggested that UV light directly activates CD95 independently of the ligand CD95L. Confocal laser scanning microscopy showed that UV light induced clustering of CD95 in the same fashion as CD95L. Prevention of UV-induced CD95 clustering by irradiating cells at 10°C was associated with a significantly reduced death rate. Together, these data indicate that UV light directly stimulates CD95 and thereby activates the CD95 pathway to induce apoptosis independently of the natural ligand CD95L. These findings further support the concept that UV light can affect targets at the plasma membrane, thereby even inducing apoptosis.

Use of L-asparaginase in childhood ALL.

Abstract: Owing to the high efficacy of L-asparaginase in the treatment of acute lymphatic leukaemia the enzyme was introduced into the chemotherapy schedules for remission induction of this disease shortly after results of large-scale clinical trials had become available. Since asparaginase monotherapy was associated with a high response rate but short remission duration, the enzyme is currently employed within the framework of combination chemotherapy schedules which achieve treatment response in about 90% and long-term remissions in the majority of patients. Recently initiated clinical trials have still confirmed the eminent value of asparaginase in the combination chemotherapy of acute lymphatic leukaemia and of some subtypes of non-Hodgkin lymphoma, and its important role as an essential component of multimodal treatment protocols. Despite the unique mechanism of action of this cytotoxic substance which shows relative selectivity with regard to the metabolism of malignant cells, some patients experience toxic effects during asparaginase therapy. Immunological reactions toward the foreign protein include enzyme inactivation without any clinical manifestations as well as anaphylactic shock. Severe functional disorders of organ systems result from the impaired homeostasis of the amino acids asparagine and glutamine. The changes affecting the proteins of the coagulation system have considerable clinical impact as they may induce bleeding as well as thromboembolic events and may be associated with life-threatening complications when the central nervous system is involved. Risk factors predisposing to thromboembolic complications are hereditary resistance against activated protein C and any other hereditary thrombophilia. Other organ systems potentially affected by relevant functional disorders are the central nervous system, the liver, and the pancreas, with patients who have a history of pancreatic disorders carrying an especially high risk of developing pancreatitis. Studies on the mechanisms of action and the occurrence of resistance phenomena have shown that a treatment response may only be expected if the malignant cells are unable to increase their asparagine synthetase activity to an extent providing enough asparagine to the cell; one may thus conclude that the enzyme-induced asparagine depletion of the serum constitutes the decisive cytotoxic mechanism. Independent of the asparagine depletion related cytotoxicity however, there are other mechanisms of clinical relevance like induction of apoptosis. Besides this, further influences on signal transduction cannot be excluded. Only few publications have dealt with the question of minimum trough activities to be ensured before each subsequent asparaginase dose in order to maintain uninterrupted asparagine depletion under treatment, and answers to this problem are not definitive. Clinical studies using enzymes from E. coli strains indicate that a trough activity of 100 U/l will suffice for complete asparagine depletion of the fluid body compartments with the preparations studied. These findings have been transferred to enzymes from other E. coli strains as well as those isolated from Erwinia chrysanthemi and to the PEG-conjugated E. coli asparaginases. It might be desirable to countercheck the results for confirmation or correction. The dosage and administration schedule of the various enzyme preparations required for complete asparagine depletion over a period of time have been insufficiently defined. While pharmacokinetic studies showed clinically relevant differences in biological activity and activity half-lives for enzymes from different biological sources, the findings of recently published clinical trials indicate that the therapeutic efficacy is affected when different asparaginase preparations are given by identical therapy schedules. (ABSTRACT TRUNCATED)

The Münster Heart Study (PROCAM). Results of follow-up at 8 years.

Abstract: The Munster Heart Study (PROCAM) was initiated in 1979 in order to examine cardiovascular risk factors, cardiovascular events including myocardial infarction and stroke, and mortality in people at work. Examination at entry comprised a standardized case history, measurement of blood pressure and anthropometric data, a resting electrocardiogram, and measurement of more than 20 laboratory parameters in a fasting blood sample. The prevalence data in this report are based upon a single examination of 17,437 men aged 40.4 +/- 11.3 years (mean +/- SD) and 8065 women aged 35.7 +/- 12.1 years, which took place between 1979 and 1991. Severe hypercholesterolaemia (> 300 mg.dl-1) was seen in 5% of men and 8% of women aged 45 to 64 years. In men, the prevalence of hypertriglyceridaemia (> 200 mg.dl-1) rose from 5% at age 20 to 20% at age 45 and remained constant thereafter; in women the prevalence of hypertriglyceridaemia increased linearly from 2% at age 20 to 7% at age 60. The LDL/HDL ratio was higher in men than in women at all age groups; in the age group 45 to 64 years, LDL/HDL ratios > 5 were approximately twice as common in men. Lipoprotein(a) levels were distributed in a highly skewed fashion. In men, a slight rise in the geometric mean lipoprotein(a) concentration occurred with age, whereas in women a dramatic increase was seen after age 40. Using multivariate analysis by the multiple logistic function method, total cholesterol, HDL cholesterol, LDL cholesterol and log-transformed triglycerides showed a significant (P < 0.001) age-adjusted correlation with the presence of major coronary events. A risk algorithm has been developed for men aged 40 to 65 years which takes into account the independent risk factors of HDL cholesterol, LDL cholesterol, triglycerides, fibrinogen, age, systolic blood pressure, cigarette smoking, presence of diabetes mellitus and family history of myocardial infarction and angina pectoris. This algorithm can be used in clinical practice to calculate the 8-year risk of an individual suffering a myocardial infarction.

Spontaneous Skin Ulceration and Defective T Cell Function in CD18 Null Mice

Abstract: A null mutation was prepared in the mouse for CD18, the β2 subunit of leukocyte integrins. Homozygous CD18 null mice develop chronic dermatitis with extensive facial and submandibular erosions. The phenotype includes elevated neutrophil counts, increased immunoglobulin levels, lymphadenopathy, splenomegaly, and abundant plasma cells in skin, lymph nodes, gut, and kidney. Very few neutrophils were found in spontaneously occurring skin lesions or with an induced toxic dermatitis. Intravital microscopy in CD18 null mice revealed a lack of firm neutrophil attachment to venules in the cremaster muscle in response to N -formyl- methionyl-leucyl-phenylalanine. A severe defect in T cell proliferation was found in the CD18 null mice when T cell receptors were stimulated either by staphylococcal enterotoxin A or by major histocompatibility complex alloantigens demonstrating a greater role of CD11/CD18 integrins in T cell responses than previously documented. The null mice are useful for delineating the functions of CD18 in vivo.

Neuropeptides in the skin: interactions between the neuroendocrine and the skin immune systems.

Abstract: The interaction between components of the nervous system and multiple target cells in the cutaneous immune system has been receiving increasing attention. It has been observed that certain skin diseases such as psoriasis and atopic dermatitis have a neurogenic component. Neuropeptides released by sensory nerves that innervate the skin and often contact epidermal and dermal cells can directly modulate functions of keratinocytes, Langerhans cells (LC), mast cells, dermal microvascular endothelial cells and infiltrating immune cells. Among these neuropeptides the tachykinins substance P (SP) and neurokinin A (NKA), calcitonin gene-related peptide (CGRP), vasoactive intestinal peptide (VIP) and somatostatin (SOM) have been reported to effectively modulate skin and immune cell functions such as cell proliferation, cytokine production or antigen presentation under physiological or pathophysiological conditions. Expression and regulation of their corresponding receptors that are expressed on a variety of skin cells as well as the presence of neuropeptide-specific peptidases such as neutral endopeptidase (NEP) or angiotensin-converting enzyme (ACE) determine the final biological response mediated by these peptides on the target cell or tissue. Likewise, skin cells like keratinocytes or fibroblasts are a source for neurotrophins such as nerve growth factor that are required not only for survival and regeneration of sensory neurons but also to control responsiveness of these neurons to external stimuli. Therefore, neuropeptides, neuropeptide receptors, neuropeptide-degrading enzymes and neurotrophins participate in a complex, interdependent network of mediators that modulate skin inflammation, wound healing and the skin immune system. This review will focus on recent studies demonstrating the role of tachykinins, CGRP, SOM and VIP and their receptors and neuropeptide-degrading enzymes in mediating neurogenic inflammation in the skin.

Development of the Multiple Metabolic Syndrome: An Epidemiologic Perspective

Abstract: It has been observed repeatedly that risk factors for cardiovascular diseases tend to co-occur within individuals (1, 2). Typically, disturbances of glucose metabolism, dyslipidemias, central obesity, and elevated blood pressure are among the metabolic and hemodynamic components considered. These observations have been made both on the individual level and at the population level as associations between these risk factors. Since each of these conditions is highly prevalent in adulthood, it is reasonable to expect clusters due to chance alone. However, it has been speculated for some time that co-occurrence of these conditions is due to a common underlying process. Several terms have been proposed to describe the clustering of metabolic disorders, among them syndrome X, the insulin resistance syndrome, and the multiple metabolic syndrome (table 1) (3-13). For the purposes of this review, the latter terminology, the multiple metabolic syndrome, will be adopted since it does not rely on assumptions about underlying etiologic mechanisms and retains a certain neutrality. The term "multiple metabolic" implies primarily more than one metabolic abnormality, but does not preclude the interpretation that several syndromes may, in fact, be subsumed under this heading. This review will focus on the multiple metabolic syndrome largely from an epidemiologic perspective. There are several excellent review papers that have concentrated on the physiologic or clinical perspectives (3, 12, 14).

Persistent Infection with Small Colony Variant Strains of Staphylococcus aureus in Patients with Cystic Fibrosis

Abstract: In a 34-month prospective study to determine the prevalence of Staphylococcus aureus small colony variants (SCVs) in cystic fibrosis (CF) patients, S. aureus SCVs or SCVs plus normal S. aureus were recovered from 26 of 78 patients; 27 patients harbored only normal S. aureus. By pulsed-field gel electrophoresis, clonal identity was demonstrated of SCV and normal strains isolated at the same time and of multiple S. aureus SCV and normal strains in consecutive specimens from individual patients. All S. aureus SCVs were resistant to antifolate antibiotics, while the corresponding parent strains were susceptible, and in 11 of 12 SCV/normal pairs, gentamicin was less active against S. aureus with the SCV phenotype than against the normal isolate. Analysis of the underlying auxotrophism of SCVs revealed hemin, thymidine, and/or menadione dependencies. Thus, S. aureus SCVs are highly prevalent in respiratory secretions of CF patients, persist over extended periods, and may contribute to S. aureus persistence in CF patients.

Comparison of the Ability of Partially N-acetylated Chitosans and Chitooligosaccharides to Elicit Resistance Reactions in Wheat Leaves

Abstract: Chitin, a linear polysaccharide composed of (1→4)-linked 2-acetamido-2-deoxy-β-d-glucopyranose (GlcNAc) residues, and chitosan, the fully or partially N- acetylated, water-soluble derivative of chitin composed of (1→4)-linked GlcNAc and 2-amino-2-deoxy-β-d-glucopyranose (GlcN), have been proposed as elicitors of defense reactions in higher plants. We tested and compared the ability of purified (1→4)-linked oligomers of GlcNAc (tetramer to decamer) and of GlcN (pentamer and heptamer) and partially N- acetylated chitosans with degrees of acetylation (DA) of 1%, 15%, 35%, 49%, and 60% and average degrees of polymerization between 540 and 1100 to elicit phenylalanine ammonia-lyase (PAL) and peroxidase (POD) activities, lignin deposition, and microscopically and macroscopically visible necroses when injected into the intercellular spaces of healthy, nonwounded wheat ( Triticum aestivum L.) leaves. Purified oligomers of (1→4)-linked GlcN were not active as elicitors, whereas purified oligomers of (1→4)-linked GlcNAc with a degree of polymerization ≥ 7 strongly elicited POD activities but not PAL activities. Partially N- acetylated, polymeric chitosans elicited both PAL and POD activities, and maximum elicitation was observed with chitosans of intermediate DAs. All chitosans but not the chitin oligomers induced the deposition of lignin, the appearance of necrotic cells exhibiting yellow autofluorescence under ultraviolet light, and macroscopically visible necroses; those with intermediate DAs were most active. These results suggest that different mechanisms are involved in the elicitation of POD activities by GlcNAc oligomers, and of PAL and POD activities by partially N- acetylated chitosan polymers and that both enzymes have to be activated for lignin biosynthesis and ensuing necrosis to occur.

Metal Clusters and Colloids

Abstract: The properties of solid matter are determined by the “infinite” three-dimensional arrangement of its building blocks. These can consist of single ions, covalently organized units such as “SiO2” in quartz, or individual molecules in a molecular lattice, e.g., I2 in iodine crystals. What does “infinite” mean? How small can a piece of a distinct material become and still be the same material? The optical properties of quartz, the brilliance of diamond, the conductivity of graphite, or the melting point of gold will all change at some point if the number of specific building blocks becomes small enough. In the last decade there has been important progress towards answering these questions and it has been shown that the nature of materials can dramatically change if the borderline of what we call the “solid state” is reached. Nanometer-sized “cutouts” of various solid materials have been made and their properties studied. In all cases the chemical and physical properties deviate considerably from those of the bulk: the rules of classical mechanics are replaced by those of quantum mechanics. A few examples are presented to elucidate this. Fullerenes as well as carbon nanotubes are considered as nature’s fascinating answer to what happens if the size of an element is reduced to the

Rapid and Specific Detection of Toxigenic Staphylococcus aureus: Use of Two Multiplex PCR Enzyme Immunoassays for Amplification and Hybridization of Staphylococcal Enterotoxin Genes, Exfoliative Toxin Genes, and Toxic Shock Syndrome Toxin 1 Gene

Abstract: Two multiplex PCR enzyme immunoassays (PCR-EIAs) were developed for Staphylococcus aureus exotoxin gene screening as an alternative to the conventional biological assays, which depend on detectable amounts of toxins produced. One set of oligonucleotide primers and probes was designed to search for enterotoxin A to E genes (entA, entB, entC, entD, and entE), and the other one was designed to detect the staphylococcal exfoliative toxin genes (eta and etb) and the toxic shock syndrome toxin 1 gene (tst). Oligonucleotide primers were used as published previously, modified or newly developed to meet the requirements of both good size-distinguishable amplification bands of multiplex PCR and the temperature limit of the uracil DNA glycosylase system for carryover protection. Amplification products were visualized by agarose gel electrophoresis, and specificity was controlled with the aid of a DNA EIA system using oligonucleotide probes derived from the sequences of the S. aureus toxin genes. PCR procedures were performed by using template nucleic acids extracted from a panel of S. aureus reference strains and from a collection of 50 clinical strains. The PCR results were compared with those of immunological toxin production assays. This multiplex PCR-EIA system offers an alternative method for the rapid, sensitive, specific, and simultaneous detection of the clinically important exotoxin potency of isolated S. aureus strains for diagnostic purposes as well as research studies.

Risk factors associated with alterations in carotid-intima-media thickness in hypertension: baseline data from the European lacidipine study on atherosclerosis

Abstract: Background The possibility that calcium antagonists exert an anti-atherosclerotic action at least partly independently of the blood-pressure-lowering effect is supported by results of a large number of experimental studies and can now be investigated by quantitative B-mode ultrasound imagining of the carotid artery walls. Design The European Lacidipine Study on Atherosclerosis (ELSA) is a prospective, randomized, double-blind, multinational trial comparing effects of 4-year treatment based on the long-acting, highly lipophilic calcium antagonist lacidipine with those of treatment based on the β-blocker atenolol on the development of carotid artery wall alterations in patients (aged 45-75 years) with mild-to-moderate hypertension (systolic blood pressure 150-210 mmHg and diastolic blood pressure 95-115 mmHg). While the intervention study is progressing, this article summarizes baseline data obtained from the whole cohort of 2259 patients randomly allocated to treatment Methods Baseline ultrasound data were obtained from two replicate examinations performed shortly before random allocation to treatment by certified sonographers at 23 referral centres and read at the ultrasound coordinating centre at the Wake Forest University School of Medicine. Intima-media thickness was measured at up to 12 different sites in the carotid artery tree and expressed as the mean of the maxima at these sites (M max ), the mean of the maxima at four sites in the distal common carotid artery and bifurcation (CBM max ) and the maximum intima-media thickness (T max ). Baseline demographic and clinical measurements were performed by investigators in 410 peripheral clinical units and 24 h ambulatory blood pressure monitorings read and validated by members of a centralized unit at the University of Milan. The statistical analysis centre at the Technische Universitat Munchen received and analysed all baseline data, by calculating means ± SD, medians and ranges and performing correlation (Spearman correlation coefficients) and multiple regression analyses. Results Prevalence of carotid artery wall alterations among the hypertensive patients randomly allocated to treatment in the ELSA was very high: 82% had T max ≥ 1.3 mm ('plaques' according to protocol) and 17% had T max ≥ 1.0 and <1.3 mm ('thickening'), with a median of two plaques per patient We found significant correlations between ultrasound measurements and the following demographic and clinical variables: age, sex, systolic blood pressure and pulse pressure (both clinic and ambulatory), concentrations of total, high-density lipoprotein and low-density lipoprotein cholesterol and triglycerides, smoking habit and duration of hypertension. We found no significant correlation to diastolic blood pressure and glucose concentration. A multiple regression analysis indicated significant variables in the following rank order: age, 24 h ambulatory pulse pressure, sex, low-density lipoprotein cholesterol concentration, triglyceride concentration, smoking and clinic systolic blood pressure. Conclusions Analysis of baseline data from the ELSA has shown that there is an extremely marked prevalence of carotid artery wall alterations among mild-to-moderate, middle-aged hypertensive patients.

The emergence of triglycerides as a significant independent risk factor in coronary artery disease

Abstract: The Prospective Cardiovascular Munster (PROCAM) study involved 4849 middle-aged men who were followed up for 8 years to record the incidence of coronary heart disease (CHD) events according to the risk factors present at study entry. The study showed that fasting levels of triglycerides were an independent risk factor for CHD events, irrespective of serum levels of high density lipoprotein cholesterol (HDL-C) or low density lipoprotein cholesterol (LDL-C). Other independent predictors of CHD included serum levels of LDL-C and HDL-C, age, systolic blood pressure, cigarette smoking, diabetes mellitus, a family history of myocardial infarction and angina pectoris, but did not include total serum cholesterol levels. Individuals with an LDL-C/HDL-C ratio > 5 had a 19.2% chance of experiencing a CHD event in the next 8 years. Furthermore, if an LDL-C/HDL-C ratio > 5 was combined with hypertriglyceridaemia (> or = 2.3 mmol. l-1), the risk of CHD increased to 26.9%. The association between hypertriglyceridaemia and CHD events may be related to the presence of atherogenic, triglyceride-rich particles in plasma, such as LDL and very low density lipoproteins. High triglyceride levels may also predispose to thrombosis. Individuals with potentially atherogenic lipid profiles should be managed initially through the introduction of lifestyle changes. However, if these fail to achieve recommended target values, lipid-lowering therapy should be considered.

Cortical reorganization and phantom phenomena in congenital and traumatic upper-extremity amputees.

Abstract: The relationship between phantom limb phenomena and cortical reorganization was examined in five subjects with congenital absence of an upper limb and nine traumatic amputees. Neuromagnetic source imaging revealed minimal reorganization of primary somatosensory cortex in the congenital amputees (M=0.69 cm, SD 0.24) and the traumatic amputees without phantom limb pain (M=0.27 cm, SD 0.25); the amputees with phantom limb pain showed massive cortical reorganization (M=2.22 cm, SD 0.78). Phantom limb pain and nonpainful phantom limb phenomena were absent in the congenital amputees. Whereas phantom limb pain was positively related to cortical reorganization (r=0.87), nonpainful phantom phenomena were not significantly correlated with cortical reorganization (r=0.34). Sensory discrimination was normal and mislocalization (referral of stimulation-induced sensation to a phantom limb) was absent in the congenital amputees. The role of peripheral and central factors in the understanding of phantom limb pain and phantom limb phenomena is discussed in view of these findings.

In Vivo High Resolution MRI of the Calcaneus: Differences in Trabecular Structure in Osteoporosis Patients

Abstract: The purpose of this study was to use high resolution (HR) magnetic resonance (MR) images of the calcaneus to investigate the trabecular structure of patients with and without osteoporotic hip fractures and to compare these techniques with bone mineral density (BMD) in differentiating fracture and nonfracture patients. Axial and sagittal HR MR images of the calcaneus were obtained in 50 female (23 postmenopausal patients with osteoporotic hip fractures and 27 postmenopausal controls). A three-dimensional gradient-echo sequence was used with a slice thickness of 500 micron and in plane resolution of 195 x 195 micron. Texture analysis was performed using morphological features, analogous to standard histomorphometry and fractal dimension. Additionally, BMd measurements of the hip (dual-energy X-ray absorptiometry) were obtained in all patients. Significant differences between both patient groups were obtained using morphological parameters and fractal dimension as well as hip BMD (p < 0.05). Odds ratios for the texture parameters apparent (app.) bone volume/total volume and app. trabecular separation were higher than for hip BMD. Receiver operator characteristic values of texture measures and hip BMD were comparable. In conclusion, trabecular structure measures derived from HR MR images of the calcaneus can differentiate between postmenopausal women with and without osteoporotic hip fractures.

High-precision neuromagnetic study of the functional organization of the human auditory cortex.

Abstract: Previous studies have proven that a dipole source analysis of the auditory evoked field is capable of providing evidence of the tonotopic organization of the human auditory cortex. To explore the natu