Generating anatomical models of the heart and the aorta from medical images for personalized physiological simulations.

The anatomy and motion of the heart and the aorta are essential for patient-specific simulations of cardiac electrophysiology, wall mechanics and hemodynamics. Within the European integrated project euHeart, algorithms have been developed that allow to efficiently generate patient-specific anatomical models from medical images from multiple imaging modalities. These models, for instance, account for myocardial deformation, cardiac wall motion, and patient-specific tissue information like myocardial scar location. Furthermore, integration of algorithms for anatomy extraction and physiological simulations has been brought forward. Physiological simulations are linked closer to anatomical models by encoding tissue properties, like the muscle fibers, into segmentation meshes. Biophysical constraints are also utilized in combination with image analysis to assess tissue properties. Both examples show directions of how physiological simulations could provide new challenges and stimuli for image analysis research in the future.

Slow and continuous application of human recombinant bone morphogenetic protein via biodegradable poly(lactide-co-glycolide) foamspheres.

Bone morphogenetic proteins (BMPs) are multifunctional cytokines that were originally identified as molecules that induce bone and cartilage formation in vivo. In order to increase the efficacy of this potent protein for application in medicine, a carrier system is needed to retain the BMP at the preferred site. Here we present and characterize a slow-release carrier system for pure human recombinant (rh)BMP. The large porous microspheres, called 'foamspheres', are biodegradable, because they consist of poly(lactide-co-glycolide) acids and release loaded rhBMP slowly and continuously. In vivo studies in rodents revealed that rhBMP-loaded foamspheres increased the thickness of the calvarial bone of rats by 222%. When the same amount of rhBMP was applied via a gelatine-based hydrogel, the increase in bone height was only 66%. Thus, the carrier system for rhBMP is an important factor for the efficacy of BMPs.

The latency of evoked otoacoustic emissions: its relation to hearing loss and auditory evoked potentials.

The latencies of transient evoked otoacoustic emissions (TEOAE), distortion product otoacoustic emissions (DPOAE) and auditory brainstem responses (ABR) have been studied in 173 patients with cochlear hearing impairment. No systematic or significant correlation between the OAE latency and the hearing loss at the corresponding frequency could be found, whereas the ABR latencies increase by a small but significant amount with increasing hearing loss. This can be explained by a broadening of the excited area and its shifting towards a more apical position if the hair cell population in the basal turn is depleted. Because of the considerable intersubject variability of OAE latencies the data do not allow to decide whether they are not influenced by cochlear hearing loss or whether an effect is merely not observable. The large variability is attributed to the interindividual differences of OAE generation time and return delay whereas the travel time of the primary wave is less variable as can be seen from the low variability of ABR latencies.

High prevalence of a variety of epidermodysplasia verruciformis-associated human papillomaviruses in psoriatic skin of patients treated or not treated with PUVA.

Epidermodysplasia verruciformis-associated human papillomaviruses and in particular human papillomavirus type 5 were recently shown to be highly prevalent in psoriatic skin. We have analyzed lesional skin from 54 psoriasis patients for infections with genital-specific and epidermodysplasia verruciformis-specific human papillomaviruses to define the spectrum of involved human papillomavirus types and to test if it is influenced by psoralen ultraviolet A therapy. Using polymerase chain reaction analysis we could detect human papillomavirus sequences in skin lesions of 83% of the tested patients. In contrast, human papillomavirus-DNA was only demonstrated in 19% of skin samples from 42 dermatologically healthy, immunocompetent individuals. Sequence analysis of the polymerase chain reaction amplimers revealed 14 human papillomavirus types, all belonging to the epidermodysplasia verruciformis or epidermodysplasia verruciformis-related papillomaviruses. Only in one case we identified sequences related to those of genital viruses, which, however, represented a putatively new human papillomavirus type. The most prevalent human papillomavirus type in our patient series was human papillomavirus type 36, found in 62% of the patients positive for human papillomavirus-DNA, followed by human papillomavirus type 5 (38%) and human papillomavirus type 38 (24%). Multiple infections with two to five different human papillomavirus types could be detected in skin samples of 63% of the analyzed patients. The overall human papillomavirus detection rate did not differ significantly between patients which have been subjected to psoralen ultraviolet A photochemotherapy or solely treated with topical preparations (77 vs 89%). Human papillomavirus type 5, however, could be detected significantly more frequent in lesions of psoralen ultraviolet A-treated patients (p < 0.001). Our data strongly argue for infections with epidermodysplasia verruciformis-specific papillomaviruses being an almost consistent feature of the lesional psoriatic skin and substantiate the importance of further studies to elucidate a possible involvement of human papillomaviruses in psoriasis pathology.

Heart rate variability and ischaemia in patients with coronary heart disease and stable angina pectoris; influence of drug therapy and prognostic value. TIBBS Investigators Group. Total Ischemic Burden Bisoprolol Study.

AIMS: Determination of the influence of therapy with bisoprolol and nifedipine on the heart rate variability of patients from the Total Ischemic Burden Bisoprolol Study and examination of the prognostic value. METHODS AND RESULTS: Four hundred and twenty-two patients with stable angina were included. The heart rate variability was determined over a period of 24 h. Parameters determined: standard deviation of the mean of all corrected RR intervals, standard deviation of all 5 min mean cycle lengths, square root of the mean of the squared differences of successive corrected RR intervals. Nifedipine reduced the mean values of all heart rate variability parameters tested. Square root of the mean of the square differences of successive corrected RR intervals increased under bisoprolol. Standard deviation of the mean of all corrected RR intervals and standard deviation of all 5 min mean cycle lengths increased from low baseline values and declined from higher baseline values. The increase in heart rate variability under therapy was accompanied by a tendency towards a better prognosis. Patients with an increase in heart rate variability and simultaneous complete suppression of ischaemia under therapy displayed no serious events in the course of one year. CONCLUSIONS: The increase in the heart rate variability, which can be regarded as prognostically favourable, was predominantly observed under bisoprolol. The parameter constellation of an increase in heart rate variability and complete ischaemia suppression on the 48-h Holter ECG was associated with the greatest benefit.

Dietary tocotrienols reduce concentrations of plasma cholesterol, apolipoprotein B, thromboxane B2, and platelet factor 4 in pigs with inherited hyperlipidemias.

Normolipemic and genetically hypercholesterolemic pigs of defined lipoprotein genotype were fed a standard diet supplemented with 50 micrograms/g tocotrienol-rich fraction (TRF) isolated from palm oil. Hypercholesterolemic pigs fed the TRF supplement showed a 44% decrease in total serum cholesterol, a 60% decrease in low-density-lipoprotein (LDL)-cholesterol, and significant decreases in levels of apolipoprotein B (26%), thromboxane-B2 (41%), and platelet factor 4 (PF4; 29%). The declines in thromboxane B2 and PF4 suggest that TRF has a marked protective effect on the endothelium and platelet aggregation. The effect of the lipid-lowering diet persisted only in the hypercholesterolemic swine after 8 wk feeding of the control diet. These results support observations from previous studies on lowering plasma cholesterol in animals by tocotrienols, which are naturally occurring compounds in grain and palm oils and may have some effect on lowering plasma cholesterol in humans.

Antihypertensive monotherapy with nitrendipine in general practice.

Efficacy and tolerability of antihypertensive monotherapy with the calcium antagonist nitrendipine were investigated in a 6-month open trial in 495 patients with mild to moderate essential hypertension from 101 practicing internists and general practitioners. Previous antihypertensive therapy (57.4%) was stopped for 1 week and therapy then started with nitrendipine, 20 mg once daily. Sixty-one patients discontinued therapy prematurely because of unwanted effects, mostly characteristic with dihydropyridines (headaches, flushing, and ankle edema), and 23 patients because of insufficient efficacy. In 75% of the remaining 411 patients, the goal blood pressure was achieved by nitrendipine monotherapy (10 mg in 17.6%, 20 mg in 73.3%, and 20 mg b.i.d. in 8%) and diastolic blood pressure was between 90 and 95 mm Hg in another 6%. The reduction in blood pressure did not result in changes of heart rate or weight. Nitrendipine was effective in patients of all age groups but patients older than 60 years of age showed a significantly greater fall in systolic pressure than middle-aged or young patients. At the end of the study, 15 patients still reported side effects. Nitrendipine appears to be well suited for first-line therapy of mild to moderate essential hypertension.

A potato mitochondrial isoleucine tRNA is coded for by a mitochondrial gene possessing a methionine anticodon.

The nucleotide sequence of a potato mitochondrial tRNA(Ile) has been determined. This tRNA has a lysidine-like minor nucleotide in the first position of the anticodon (position 34). The corresponding mitochondrial gene has been cloned and sequenced. This gene has a CAT anticodon which corresponds to methionine. The C residue in the anticodon must therefore be post-transcriptionally modified. The mature tRNA has isoleucine-accepting activity but no methionine-accepting activity. This is the first report showing that in plant mitochondria a post-transcriptional modification could change the amino-acid specificity of a tRNA, as compared to that of the corresponding gene.

Transfer RNAs of potato (Solanum tuberosum) mitochondria have different genetic origins.

Total transfer RNAs were extracted from highly purified potato mitochondria. From quantitative measurements, the in vivo tRNA concentration in mitochondria was estimated to be in the range of 60 microM. Total potato mitochondrial tRNAs were fractionated by two-dimensional polyacrylamide gel electrophoresis. Thirty one individual tRNAs, which could read all sense codons, were identified by aminoacylation, sequencing or hybridization to specific oligonucleotides. The tRNA population that we have characterized comprises 15 typically mitochondrial, 5 'chloroplast-like' and 11 nuclear-encoded species. One tRNA(Ala), 2 tRNAs(Arg), 1 tRNA(Ile), 5 tRNAs(Leu) and 2 tRNAs(Thr) were shown to be coded for by nuclear DNA. A second, mitochondrial-encoded, tRNA(Ile) was also found. Five 'chloroplast-like' tRNAs, tRNA(Trp), tRNA(Asn), tRNA(His), tRNA(Ser)(GGA) and tRNA(Met)m, presumably transcribed from promiscuous chloroplast DNA sequences inserted in the mitochondrial genome, were identified, but, in contrast to wheat (1), potato mitochondria do not seem to contain 'chloroplast-like' tRNA(Cys) and tRNA(Phe). The two identified tRNAs(Val), as well as the tRNA(Gly), were found to be coded for by the mitochondrial genome, which again contrasts with the situation in wheat, where the mitochondrial genome apparently contains no tRNA(Val) or tRNA(Gly) gene (2).

[Value of a new simple mechanical large intestine preparation in comparison with PEG lavage]. / Wertigkeit einer neuen einfachen mechanischen Dickdarmvorbereitung im Vergleich zur PEG-Lavage.

UNLABELLED: The subjective incommodation of the patient by the well established methods of colonic cleansing for operation or endoscopic examination gave a reason to evaluate the efficacy of a new mechanical method in a prospective randomized study. 60 patients were divided in two groups: Colonic preparation was performed by YAL-irrigation in group 1, by oral lavage with PEG (polyethylene glycol electrolyte) in group 2. We found no fecal residue in 29.6% of the YAL group compared to 22.2% in the PEG group, a small amount of liquid stool in 29.6% (YAL) compared to 48.1% (PEG), a large amount of liquid stool in 25.9% of both groups and a solid stool in 14.8% (YAL) compared to 3.7% (PEG). The examination of the mucosal surface was hindered by solid or large amounts of liquid stool in 14.8% of group 1 and in 11.1% in the PEG group, particularly localized in the right hemicolon. In group 1, a significantly better valuation in subjective patient tolerance was found: 18.9% (YAL) compared to 77.8% (PEG) (p less than 0,0001) showed symptoms of patient discomfort. IN CONCLUSION: The simple mechanical preparation with YAL has been shown not to be as safe as with the PEG lavage. However, the YAL method seems to be a useful alternative in patients with suspected stenosis, tendency for vomiting as well as for examination or operation of the left hemicolon.