Gene therapy restores the transcriptional program of hematopoietic stem cells in Fanconi anemia.

Clinical trials have shown that lentiviral-mediated gene therapy can ameliorate bone marrow failure (BMF) in nonconditioned Fanconi anemia (FA) patients resulting from the proliferative advantage of corrected FA hematopoietic stem and progenitor cells (HSPC). However, it is not yet known if gene therapy can revert affected molecular pathways in diseased HSPC. Single-cell RNA sequencing was performed in chimeric populations of corrected and uncorrected HSPC co-existing in the BM of gene therapy-treated FA patients. Our study demonstrates that gene therapy reverts the transcriptional signature of FA HSPC, which then resemble the transcriptional program of healthy donor HSPC. This includes a down-regulated expression of TGF-ß and p21, typically up-regulated in FA HSPC, and upregulation of DNA damage response and telomere maintenance pathways. Our results show for the first time the potential of gene therapy to rescue defects in the HSPC transcriptional program from patients with inherited diseases; in this case, in FA characterized by BMF and cancer predisposition.

Improved collection of hematopoietic stem cells and progenitors from Fanconi anemia patients for gene therapy purposes.

Difficulties in the collection of hematopoietic stem and progenitor cells (HSPCs) from Fanconi anemia (FA) patients have limited the gene therapy in this disease. We have investigated (ClinicalTrials.gov, NCT02931071) the safety and efficacy of filgrastim and plerixafor for mobilization of HSPCs and collection by leukapheresis in FA patients. Nine of eleven enrolled patients mobilized beyond the threshold level of 5 CD34+ cells/µL required to initiate apheresis. A median of 21.8 CD34+ cells/µL was reached at the peak of mobilization. Significantly, the oldest patients (15 and 16 years old) were the only ones who did not reach that threshold. A median of 4.27 million CD34+ cells/kg was collected in 2 or 3 aphereses. These numbers were markedly decreased to 1.1 million CD34+ cells/kg after immunoselection, probably because of weak expression of the CD34 antigen. However, these numbers were sufficient to facilitate the engraftment of corrected HSPCs in non-conditioned patients. No procedure-associated serious adverse events were observed. Mobilization of CD34+ cells correlated with younger age, higher leukocyte counts and hemoglobin values, lower mean corpuscular volume, and higher proportion of CD34+ cells in bone marrow (BM). All these values offer crucial information for the enrollment of FA patients for gene therapy protocols.

[Informations on psychotropics and their adaptations for patients suffering from mental disorders in France during the SARS-CoV-2 epidemic]. / Informations relatives aux psychotropes et à leurs adaptations éventuelles pour les patients souffrant de troubles psychiques en France pendant l'épidémie à SARS-CoV-2.

The 2019-20 coronavirus pandemic (SARS-CoV-2; severe acute respiratory syndrome coronavirus 2) has dramatic consequences on populations in terms of morbidity and mortality and in social terms, the general confinement of almost half of the world's population being a situation unprecedented in history, which is difficult today to measure the impact at the individual and collective levels. More specifically, it affects people with various risk factors, which are more frequent in patients suffering from psychiatric disorders. Psychiatrists need to know: (i) how to identify, the risks associated with the prescription of psychotropic drugs and which can prove to be counterproductive in their association with COVID-19 (coronavirus disease 2019), (ii) how to assess in terms of benefit/risk ratio, the implication of any hasty and brutal modification on psychotropic drugs that can induce confusion for a differential diagnosis with the evolution of COVID-19. We carried out a review of the literature aimed at assessing the specific benefit/risk ratio of psychotropic treatments in patients suffering from COVID-19. Clinically, symptoms suggestive of COVID-19 (fever, cough, dyspnea, digestive signs) can be caused by various psychotropic drugs and require vigilance to avoid false negatives and false positives. In infected patients, psychotropic drugs should be used with caution, especially in the elderly, considering the pulmonary risk. Lithium and Clozapine, which are the reference drugs in bipolar disorder and resistant schizophrenia, warrant specific attention. For these two treatments the possibility of a reduction in the dosage - in case of minimal infectious signs and in a situation, which does not allow rapid control - should ideally be considered taking into account the clinical response (even biological; plasma concentrations) observed in the face of previous dose reductions. Tobacco is well identified for its effects as an inducer of CYP1A2 enzyme. In a COVID+ patient, the consequences of an abrupt cessation of smoking, particularly related with the appearance of respiratory symptoms (cough, dyspnea), must therefore be anticipated for patients receiving psychotropics metabolized by CYP1A2. Plasma concentrations of these drugs are expected to decrease and can be related to an increase risk of relapse. The symptomatic treatments used in COVID-19 have frequent interactions with the most used psychotropics. If there is no curative treatment for infection to SARS-CoV-2, the interactions of the various molecules currently tested with several classes of psychotropic drugs (antidepressants, antipsychotics) are important to consider because of the risk of changes in cardiac conduction. Specific knowledge on COVID-19 remains poor today, but we must recommend rigor in this context in the use of psychotropic drugs, to avoid adding, in patients suffering from psychiatric disorders, potentially vulnerable in the epidemic context, an iatrogenic risk or loss of efficiency.

Successful engraftment of gene-corrected hematopoietic stem cells in non-conditioned patients with Fanconi anemia.

Fanconi anemia (FA) is a DNA repair syndrome generated by mutations in any of the 22 FA genes discovered to date1,2. Mutations in FANCA account for more than 60% of FA cases worldwide3,4. Clinically, FA is associated with congenital abnormalities and cancer predisposition. However, bone marrow failure is the primary pathological feature of FA that becomes evident in 70-80% of patients with FA during the first decade of life5,6. In this clinical study (ClinicalTrials.gov, NCT03157804 ; European Clinical Trials Database, 2011-006100-12), we demonstrate that lentiviral-mediated hematopoietic gene therapy reproducibly confers engraftment and proliferation advantages of gene-corrected hematopoietic stem cells (HSCs) in non-conditioned patients with FA subtype A. Insertion-site analyses revealed the multipotent nature of corrected HSCs and showed that the repopulation advantage of these cells was not due to genotoxic integrations of the therapeutic provirus. Phenotypic correction of blood and bone marrow cells was shown by the acquired resistance of hematopoietic progenitors and T lymphocytes to DNA cross-linking agents. Additionally, an arrest of bone marrow failure progression was observed in patients with the highest levels of gene marking. The progressive engraftment of corrected HSCs in non-conditioned patients with FA supports that gene therapy should constitute an innovative low-toxicity therapeutic option for this life-threatening disorder.

Evaluation of endothelial function and diastolic function in patients with primary hyperparathyroidism before and after parathyroidectomy.

INTRODUCTION: Primary hyperparathyroidism (PHPT) is the leading cause of outpatient hypercalcemia associated with increased cardiovascular risk. The flow-mediated vasodilation (FMV) has been proposed as a non-invasive method for assessing endothelial function. OBJECTIVE: To compare the endothelial dysfunction measured by FMV and diastolic dysfunction in patients with PHPT before and after parathyroidectomy. METHOD: We performed a quasi-experimental (before-after) study to evaluate diastolic function and FMV in patients with PHPT before and six months after parathyroidectomy. RESULTS: Fifteen patients completed study: 12 women and 3 men; 73% presented lithiasis, 27% osteoporosis and 53% metabolic syndrome; 73% presented diastolic dysfunction before the surgery and 60% after the surgery (p = 0.09). Post-isquemia brachial diameter improved from 41 mm (before surgery) to 46 mm (after surgery; p = 0.020). After surgery, we also observed an increase in the brachial diameter pre vs. post-ischemia from 41 to 46 mm (p = 0.005). Before surgery, the change in the delta of brachial diameter pre and post-ischemia was 1 mm and up to 4 mm after surgery (p = 0.03). CONCLUSIONS: There is a minor endothelial dysfunction measured by FMV in patients who underwent surgery for PHPT at 6 months after surgery, as well as a trend towards improvement in diastolic dysfunction. Echocardiography can be useful in the preoperative evaluation in patients with asymptomatic PHPT.

INTRODUCCIÓN: El hiperparatiroidismo primario (HPTP) es la principal causa de hipercalcemia ambulatoria y se ha asociado con un riesgo cardiovascular elevado. La vasodilatación mediada por flujo (VMF) es un método no invasivo que evalúa la función endotelial. OBJETIVO: Comparar la disfunción endotelial mediante VMF y la disfunción diastólica en pacientes con HPTP antes y después de la paratiroidectomía. MÉTODO: Mediante un estudio cuasiexperimental (antes-después) se evaluaron la función diastólica y la VMF antes y 6 meses después de realizar una paratiroidectomía. RESULTADOS: Se incluyeron 15 pacientes con HPTP: 12 mujeres (80%) y 3 hombres (20%); el 73% presentaron litiasis, el 27% osteoporosis y el 53% síndrome metabólico; el 73% tenían disfunción diastólica antes de la cirugía y el 60% después de la cirugía (p = 0.09). Los diámetros braquiales post-isquemia mejoraron de 41 mm antes de la cirugía a 46 mm tras la cirugía (p = 0.020). Así mismo, los diámetros braquiales preisquemia vs. post-isquemia después de la cirugía mejoraron de 41 a 46 mm (p = 0.005). Antes de la cirugía, el cambio en la delta del diámetro braquial preisquemia y post-isquemia fue de 1 mm, y subió a 4 mm después de la cirugía (p = 0.03). CONCLUSIONES: Existe una menor disfunción endotelial medida por VMF en pacientes posoperados por HPTP a los 6 meses de la cirugía. El estudio ecocardiográfico puede ser de utilidad en la evaluación preoperatoria de los pacientes con HPTP asintomáticos.

Incidence of MRI-detected brain lesions and neurocognitive function after electrical cardioversion in anticoagulated patients with persistent atrial fibrillation.

BACKGROUND: After electrical cardioversion (eCV) in patients with atrial fibrillation (AF), the risk for clinically apparent cerebral thromboembolism is increased in the subsequent weeks. To date, there is little evidence on the incidence of acute brain lesions (ABL) detected with cerebral magnetic resonance imaging (MRI) after eCV, in particular in patients treated with the Non-Vitamin K Antagonist oral anticoagulants (NOAC). AIMS: The aim of this pilot study was to evaluate the incidence of MRI-detected ABL, as well as the neuro-cognitive function after eCV in patients with persistent AF using NOACs as compared to phenprocoumon. METHODS AND RESULTS: 50 consecutive patients with persistent AF (mean age 69.6±3.5years, 26 male) were evaluated in this prospective study. Cerebral 3Tesla MRI and neuro-cognitive assessment using the National Institutes of Health Stroke Scale (NIHSS) score and the Montreal Cognitive Assessment Test (MoCA) were performed in all patients within 24h before eCV and after a median follow-up duration of 14days (Q1: 13, Q3: 19days). Patients were treated with an OAC for at least 4weeks after eCV and according to the CHA2DS2-Vasc-score thereafter. Thirty-nine patients were treated with NOACs (Dabigatran 10/50 [20%], Apixaban 21/50 [42%] and Rivaroxaban 8/50 [16]) and 11/50 patients with Phenprocoumon (22%). No patient developed ABL on cerebral MRI at the 2-week follow-up. Neurological as well as cognitive function were similar before and 2weeks after eCV (NIHSS-score: p=0.35; MoCa score: p=0.21). CONCLUSION: Electrical CV in patients with persistent AF, in particular when treated with NOACs, carries a low risk for the development of MRI-detected ABL or neurocognitive decline. CLINICAL TRIALS REGISTRATION: GermanClinicalTrialsRegister number: DRKS00010460.

[Right ventricular outflow tract tachycardia 30 years after surgical correction of tetralogy of Fallot]. / Rechtsventrikuläre Ausflusstrakt-Tachykardie 30 Jahre nach chirurgischer Fallot-Teratologie-Korrektur.

This case report describes a 31-year-old man with a sustained wide complex tachycardia with left bundle brunch block morphology after surgical repair of a tetralogy of Fallot. The tachycardia was inducible after orciprenaline administration after ventricular stimulation with one extra beat. In combination with the three-dimensional electroanatomic mapping system and pace mapping technique the origin of the tachycardia was identified at the lateral free wall of the right ventricular outflow tract tachycardia (RVOT) inferior of the pulmonary valve. Successful radiofrequency ablation was performed and the patient is still free from ventricular tachycardia.

[Cardiac resynchronisation with atrial sensing: Is it feasible?]. / Kardiale Resynchronisation mit VDD-Elektrode : Geht das?

In this article the cases of two female patients with heart failure (functional class III) and an intrinsic complete left bundle branch block are reported. Both patients have had an implanted cardioverter defibrillator (ICD) connected to a VDD lead for primary prevention of sudden cardiac death. Atrial sensing was good/acceptable with a physiological frequency histogram and normal PQ time. A system upgrade to cardiac resynchronization therapy device (CRT) was planned. The VDD lead was directly connected to the Bivent ICD. The follow up showed stable measurements and a high biventricular pacing rate. Thus, usage of VDD leads for atrial sensing in CRT seems to be possible in a selected patient population.

Polyploidy and hybridization as main factors of speciation: complex reticulate evolution within the grass genus Helictochloa.

To study the origin and evolution of naturally occurring polyploids, we performed phylogenetic analyses of nuclear ribosomal DNA spacers combined with molecular cytogenetics in 55 accessions of 27 taxa of the oat genus Helictochloa. A complex pattern of reticulate evolution was revealed with many diploid species and extensive polyploidy up to 20x. Altogether 11 groups of internal transcribed spacer (ITS) sequences can be distinguished. Sequences from 1-3 different ITS lineages were detected in polyploids. Cytogenetic data allow reconstruction of 8 basic monoploid chromosome sets. Six of these genomes occur in different combinations in the polyploid species. Two genomes are only found in diploids. Our sequence and karyological data highlight the occurrence of autopolyploidy and allopolyploidy, provide new information about the evolutionary history of taxa, and allow a more accurate systematic treatment of the concerned species. The geographical distribution of the 11 ITS lineages distinguished is highly structured and points to an origin of the genus in western Asia, presumably in grasslands like steppes or mountain steppes and meadows. The evolutionary basal lineages are of Asian, Minor Asian and east Mediterranean distribution and are present also in North America. The western and central parts of the Mediterranean and northern Europe harbor the modern lineages.

[Radiation therapy in patients with cardiac pacemakers or implantable cardioverter defibrillators. Interdisciplinary safety recommendations]. / Strahlentherapie bei Patienten mit Herzschrittmachern oder implantierbaren Kardioverter-Defibrillatoren. Interdisziplinäre Sicherheitsempfehlungen.

BACKGROUND: With increasing numbers of implanted pacemakers and implantable cardioverter defibrillators (ICD) and a rising incidence of malignant tumors, there is a growing probability of radiation-mediated device dysfunction. The only guidelines for the management of patients with cardiac pacemakers in the case of radiation therapy were published in 1994 and have not been updated since then. Based on the current evidence and modern device technology, the present paper aims to develop contemporary and interdisciplinary safety recommendations for the minimization of patient risk. METHODS AND RESULTS: A systematic literature research was carried out including the most relevant medical electronic databases. The search yielded 147 articles published between 1994 and 2012 of which 45 met the selection criteria and of these studies 34 presented primary data (9 in vitro and 25 in vivo studies). The impact of ionizing radiation varied significantly between implanted devices and ranged from no functional changes to complete loss of function. Important device dysfunctions included changes in sensing capability, altered pacing pulses or rate, changed or disabled tachyarrhythmia ICD therapies, early battery depletion and loss of telemetry. Modern pacemakers and ICDs are more sensitive to radiation than older models. Potentially life-threatening complications were observed after exposure of the pulse generator to comparatively low radiation doses (0.11 Gy). CONCLUSIONS: Practical recommendations for patient management and safety are presented that can be readily adopted by any institution carrying out radiation therapy.

[Magnetic resonance imaging and implantable cardiac devices. Current status and future perspectives of MR-compatible systems]. / Magnetresonanztomographie und implantierbare kardiale Devices. Stellenwert und Ausblick von MR-kompatiblen Systemen.

Conventional pacemakers and implantable cardioverter-defibrillators (ICD) have always been regarded as a contraindication to magnetic resonance imaging (MRI). MR-compatible systems represent a recent and particularly important innovation, since they will provide device patients with significantly improved access to MR examinations. However, the safe application of MR-compatible technology requires a detailed understanding of the strictly defined cardiologic and radiologic requirements and conditions that are to be adhered to before and during an MR examination. The present article gives an overview of problematic MR interactions with implanted devices, illustrates the most important aspects of MR-compatible pacemaker and ICD systems, analyzes their current clinical status, and offers a critical perspective.

Unmasking of myopotential oversensing by an integrated bipolar defibrillator lead following AV node ablation.

A 73-year-old man with nonischemic cardiomyopathy underwent catheter ablation of ventricular tachycardia that had resulted in frequent shocks from his implanted cardiac resynchronization therapy defibrillator (CRT-D). Coexisting atrial fibrillation required AV node ablation which rendered the patient pacemaker dependent. During follow-up, recurrent episodes of dizziness occurred caused by inhibition of pacing due to oversensing of pectoral muscle myopotentials. Surgical revision was performed and the intraoperative examination revealed an intact integrated bipolar defibrillator lead with appropriate connections to the CRT-D header. The placement of an additional pace/sense lead completely resolved the patient's symptoms and no further myopotential oversensing was recorded.

Iceman Survived due to Cooling Device.

Although mild hypothermia treatment is part of the standard postresuscitation care today, no standard method for treatment of accidental severe hypothermia has been yet established. Different strategies including invasive and noninvasive methods have been described in the literature. We present the case of a 75-year-old man with accidental severe hypothermia (23°C) and demonstrate that using a surface cooling device with automatic controlled temperature feedback mechanism (ArcticSun2000 Medivance, Louisville, Colorado, USA) is an effective and safe method for controlled rewarming in this life-threatening setting.

Extensive clonality of the endemic Calamagrostis pseudopurpurea Gerstl. ex O.R. Heine in central Germany revealed by RAPD markers.

Calamagrostis pseudopurpurea is one of only a few endemic species in Germany and is confined to the catchment area of the River Mulde in the states of Saxony and Saxony-Anhalt. We studied the genetic structure and seed viability across its entire distribution area. Patterns of random amplified polymorphic DNA (RAPD) variation were analysed using 183 individuals from 43 stands in order to assess the overall genetic structure and the extent of clonality. In addition, four related Calamagrostis species (C. canescens, C. epigejos, C. phragmitoides and C. villosa) were included in our study to consider the probable phylogenetic origin of C. pseudopurpurea. We detected two clearly different RAPD phenotypes of C. pseudopurpurea, each distributed along the river banks of two spatially isolated stream courses. Both phenotypes are present downstream of the confluence. Our results indicate that C. pseudopurpurea originates from two distinct periods of hybridisation between the same parental taxa, and that clonal propagation is most likely the main reproduction method. In line with its hybrid origin, embryos of sampled C. pseudopurpurea caryopses were found to be mostly degraded or unviable over several years. Calamagrostis pseudopurpurea is genetically closer to C. canescens and C. phragmitoides than it is to other studied species, but C. canescens and C. phragmitoides have not been proven to be direct parental taxa of C. pseudopurpurea. Calamagrostis pseudopurpurea should therefore still be treated as a separate species that needs special attention from a conservation point of view.

Neutrophils in cerebrospinal fluid without pleocytosis.

Neutrophils in cerebrospinal fluid (CSF) samples are commonly considered a pathological feature; however, there is little information on the frequency and significance of these cells in CSF samples without pleocytosis. Therefore, the frequency and possible clinical significance of neutrophils in CSF was investigated. In a retrospective study comprising 1556 consecutive CSF samples, cytologies and patient records were reviewed. Five hundred thirty-eight CSF samples without pleocytosis were identified. Neutrophils were detected in 35.5% of these samples. The presence of neutrophils was associated with sepsis (P < 0.01), recent epileptic seizure (P < 0.0001), and blood contamination (P < 0.01). Amongst patients without CSF pleocytosis, CNS infections were not more frequent if neutrophils were present. Neutrophils are frequently observed in CSF with normal leukocyte counts. As sepsis but not CNS infection occurred more frequently in these patients, we conclude that in the absence of CSF pleocytosis, neutrophils are not indicative of CNS infections.

Metformin-associated lactic acidosis in patients with renal impairment solely due to drug accumulation?

AIM: We suspect that the life-threatening complication of metformin-associated lactic acidosis, solely due to drug accumulation following renal impairment, occurs more frequently than that previously reported and is not necessarily associated with other predisposing factors for lactic acidosis. METHODS: During a period of 13 months, at a tertiary referral centre, the incidence of lactic acidosis of any aetiology was 12.8% [67 of 524 total intensive care unit (ICU) admissions]. Metformin-associated lactic acidosis solely as the result of drug accumulation was diagnosed in 6% of all the patients suffering from lactic acidosis (4 of 67 patients). RESULTS: These patients presented with severe circulatory shock due to lactic acidosis. We could not identify any predisposing factor for lactic acidosis other than renal impairment. Intercurrent deterioration of diabetic nephropathy was suspected to be responsible for the accumulation of metformin followed by lactic acidosis, finally resulting in multiorgan failure. The diagnosis was supported by extensively elevated serum levels of metformin. Two patients died during ICU treatment. CONCLUSIONS: Our data indicate that the incidence of metformin-associated lactic acidosis solely due to metformin accumulation is possible and underestimated. Symptoms of metformin-associated lactic acidosis are unspecific and physicians should be aware that metformin, if prescribed in patients with renal impairment, can cause fatal lactic acidosis due to drug accumulation.

[Transparotidean approach to surgical management of condylar neck fractures. A prospective study]. / Der transparotideale Zugang zur operativen Versorgung von Collumfrakturen. Eine prospektive Studie.

AIM: Different surgical approaches for the open treatment of mandibular condylar fractures are described in the literature. We evaluated the morbidity of the transparotidean approach in a prospective study over 5 1/2 years. PATIENTS AND METHODS: A total of 48 patients with 52 condylar neck fractures class II and IV according to the Spiessl and Schroll classification were treated by a transparotidean approach. Rigid internal fixation was performed by means of miniplate fixation. After surgery, no mandibulomaxillary fixation was performed. The occurrence of surgical and functional complications was documented both during hospitalization and 1, 3, 6 and >9 months after surgery. RESULTS: In none of our patients were major problems in wound healing such as infection of the fracture site observed. At the beginning of the study, in four cases a fistula of the parotid gland was seen within the initial days after surgery; after careful wound closure of the parotid capsula in the following operations, no further complications involving fistulas were observed. Signs of temporary palsy of the facial nerve caused by the hooks occurred in ten (19.6%) of all patients but was completely reversible within the first 6 months after the procedure. One patient suffered temporarily from a minimal malocclusion and two patients from symptoms of the temporomandibular joint 6 months postoperatively. In three patients we observed miniplate fractures without consecutive dysfunction of the TMJ or malocclusion. CONCLUSION: Open reduction and rigid internal fixation of condylar neck fractures by transparotidean approach is a recommendable procedure in class II and IV fractures. With the advantages of minimal tissue alteration and rare complications on the one hand and sufficient exposure of the fracture site on the other hand, this technique has been established as a standard procedure in treating condylar neck fractures by open reduction.

[On the indications for and morbidity of segmental resection of the mandible for squamous cell carcinoma in the lower oral cavity]. / Zur Indikation und Morbidität der Kontinuitätsresektion des Unterkiefers beim Plattenepithelkarzinom der unteren Mundhöhlenetage.

BACKGROUND: Segmental resection of the mandibula in oral cancer surgery leads to both functional and aesthetic problems. The decision to preserve or resect the mandible depends on the vicinity of the lesion to the bone. Consequently, based on the rules of safety margins to all planes that are recommended for soft tissues, each lesion that is closer than 10 mm to the mandible needs resection of the bone. PATIENTS AND METHODS: To establish data-based treatment modalities, a retrospective study was initiated and the results from all preoperative staging investigations of 152 patients with intraoral squamous cell carcinoma who underwent continuity or marginal resection of the mandible were evaluated. The histological outcome of the resected bone was compared to the staging results. Functional rehabilitation and long-term follow-up including survival rates were evaluated. The study reports on typical complications following segmental resection such as fracture of the reconstruction plate and demonstrates experiences with secondary microsurgical reconstructive surgery. RESULTS: Mainly in cases of stage T1 and T2 carcinomas which are closer than 10 mm to the bone and clinically do not show any infiltration to the mandible, a marginal resection seems to be adequate. The decision about the extension of mandibular resection can be based on intraoperative cross sectional investigation of the periosteum. The survival rate of patients with intraoral carcinomas close to the mandible who underwent marginal mandibulectomy seems to be the same as in cases of continuity resection. A more conservative management of mandibular resection seems to be adequate and a data-based concept to standardize therapy of mandibular resection is presented.

Calculation of individual cardiovascular risk in a primary prevention setting shows a high number of patients with a high risk score.

On occasion of the annual convention of the European Society of Cardiology, general awareness was used to stage an event to inform the public about cardiovascular risk and cardiovascular disease. After the measurement of blood pressure, HDL and total cholesterol and after answering questions on smoking and medication visitors received a printout showing their individual calculated cardiovascular event rate over the next ten years. For the calculation of the expected event rate, the algorithm of the Adult Treatment Panel III was used. Of the 43,500 visitors 1513 were screened, 651 male, 862 female. Of those screened in this primary prevention setting 143 male (22.07%) and 9 female (1.02%) had an expected cardiovascular event rate of 20% or more over the next ten years requiring immediate action according to the current guidelines. The calculated risk scores are considerably lower than would be expected in a representative sample from the population. This indicates that patients with a high cardiovascular risk possibly do not take part in unstructured primary screening events.

Molecular diversity and physical mapping of 5S rDNA in wild and cultivated oat grasses (Poaceae: Aveneae).

5S rDNA repeats studied in five genera of Aveneae have lengths between 285 and 329 bp (Avena sativa, Avena macrostachya, 26 species of Helictotrichon, Pseudarrhenatherum longifolium, Lagurus ovatus, and Trisetum spicatum). In only a single species (Helictotrichon aetolicum) an additional repeat of 456 bp occurs infrequently. Variation is largely due to insertions or deletions in the nontranscribed spacer as determined from sequences of 163 independent clones. The 5S gene of the Aveneae studied is conserved in length and sequence except for Helictotrichon bromoides and Helictotrichon marginatum in which duplications occur at two different sites. This new type of duplication and all duplications reported to date in 5S genes of angiosperms are shown to center on defined palindromic sequences. The "uncommon" 5S gene sequences detected in some Aveneae are not necessarily nonfunctional as pseudogenes because the essential features of the internal control region are maintained even after such duplication events. In each instance such gene sequences have spacers with unmodified structure, indicating that change in gene sequence is not necessarily coupled with change in adjacent spacers. The value of 5S spacer sequences for genomic identifications in Aveneae is exemplified in A. macrostachya (perennial), A. sativa (annual), and several diploid taxa of the genus Helictotrichon.