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Biomedical subjects

C Klein

Publications and source records attributed to C Klein.

At least 73 records · Page 4Linked to original sources

Noninvasive detection of myocardial ischemia from perfusion reserve based on cardiovascular magnetic resonance.

BACKGROUND: Myocardial perfusion reserve can be noninvasively assessed with cardiovascular MR. In this study, the diagnostic accuracy of this technique for the detection of significant coronary artery stenosis was evaluated. METHODS AND RESULTS: In 15 patients with single-vessel coronary artery disease and 5 patients without significant coronary artery disease, the signal intensity-time curves of the first pass of a gadolinium-DTPA bolus injected through a central vein catheter were evaluated before and after dipyridamole infusion to validate the technique. A linear fit was used to determine the upslope, and a cutoff value for the differentiation between the myocardium supplied by stenotic and nonstenotic coronary arteries was defined. The diagnostic accuracy was then examined prospectively in 34 patients with coronary artery disease and was compared with coronary angiography. A significant difference in myocardial perfusion reserve between ischemic and normal myocardial segments (1.08+/-0.23 and 2.33+/-0.41; P<0.001) was found that resulted in a cutoff value of 1.5 (mean minus 2 SD of normal segments). In the prospective analysis, sensitivity, specificity, and diagnostic accuracy for the detection of coronary artery stenosis (> or =75%) were 90%, 83%, and 87%, respectively. Interobserver and intraobserver variabilities for the linear fit were low (r=0.96 and 0.99). CONCLUSIONS: MR first-pass perfusion measurements yielded a high diagnostic accuracy for the detection of coronary artery disease. Myocardial perfusion reserve can be easily and reproducibly determined by a linear fit of the upslope of the signal intensity-time curves.

Coronary Angiography↗

Isolation and characterization of glycosylphosphatidylinositol-anchored, mucin-like surface glycoproteins from bloodstream forms of the freshwater-fish parasite Trypanosoma carassii.

Wild and farmed freshwater fishes are widely and heavily parasitized by the haemoflagellate Trypanosoma carassii. In contrast, common carp, a natural host, can effectively control experimental infections by the production of specific anti-parasite antibodies. In this study we have identified and partially characterized mucin-like glycoproteins which are expressed in high abundance [(6. 0+/-1.7)x10(6) molecules.cell(-1)] at the surface of the bloodstream trypomastigote stage of the parasite. The polypeptide backbone of these glycoproteins is dominated by threonine, glycine, serine, alanine, valine and proline residues, and is modified at its C-terminus by a glycosylphosphatidylinositol membrane anchor. On average, each polypeptide carries carbohydrate chains composed of about 200 monosaccharide units (galactose, N-acetylglucosamine, xylose, sialic acid, fucose, mannose and arabinose), which are most probably O-linked to hydroxy amino acids. The mucin-like molecules are the target of the fish's humoral immune response, but do not undergo antigenic variation akin to that observed for the variant surface glycoprotein in salivarian trypanosomes. The results are discussed with reference to the differences between natural and experimental infections, and in relation to the recently delineated molecular phylogeny of trypanosomes.

Amino Acids↗

[CT-assisted volumetry and densitometry of distraction osteogenesis lengthened mandibular areas].

Gradual callus distraction in the correction of hypoplastic areas in the viscerocranial skeleton is an established method due to its efficacy. Whereas functional and esthetical improvements can be seen easily, it is impossible to get the increase of the bony mass right using the distractor scale or by clinical investigation. Only in animal studies can volumetric and densitometric measurements be done directly. By permission of the local ethics commission, in a clinical study, CT data of 24 children (12 unilateral and bilateral hypoplasias each) taken before and after mandibular distraction osteogenesis were used to get information on the amount of created bone and the grade of ossification of the callus at the time of the distractor removal. The CT data were prepared for computer evaluation using software which had been especially developed for this investigation. The quality of the investigation was influenced by disturbed data acquisition (insufficient sedation, Gantry deviation, different axial cuts). Therefore, the estimation of the real increase of bone was not possible, but all in all an increase of the volume could be seen. Using a grey scale analysis, the grade of new bone ossification was over 90% at the time of distractor removal. In our opinion, these results argue against the use of CT scans for the validation of a mandibular distraction. The estimation of the volume is very imprecise, the grade of ossification of the new bone very constant.

Absorptiometry, Photon↗

[Genetics of dystonia].

To date, at least 12 types of primary dystonia can be distinguished on a genetic basis. A 3-bp deletion in the DYT1 gene causes early onset, generalized torsion dystonia (TD), and mutations in the GTP cyclohydrolase I and the tyrosine hydroxylase genes result in dopa-responsive dystonia (DYT5). A missense change in the D2 dopamine receptor in one large family (DYT11) has recently been implicated in myoclonus-dystonia. Furthermore, seven other loci for dystonia genes have been mapped to chromosomal regions, including a locus for a mixed dystonia phenotype (DYT6), one form of focal dystonia (DYT7), three types of paroxysmal dystonia (DYT8-10), X-linked dystonia-parkinsonism (DYT3), and rapid-onset dystonia-parkinsonism (DYT12). No positive linkage results have yet been obtained for autosomal recessive TD (DYT2) and several other families of different types of dominantly inherited TD (DYT4). In addition, hereditary secondary dystonia may occur as part of familial diseases of the basal ganglia, metabolic and storage disorders, and various X-linked and other familial neurodegenerative syndromes affecting the basal ganglia. It may be anticipated that the traditional clinical and etiological classifications of dystonia will increasingly be replaced by a genetic one and that the identification of more dystonia genes may lead to a better understanding of these largely nondegenerative disorders.

Dystonia↗

Optomotor and neuropsychological performance in old age.

While a delayed initiation of visually guided saccades with increasing age has been documented in a number of studies, little research has been done on the control of antisaccades. The present study investigates aging effects on the control of visually guided saccades (prosaccades) and antisaccades as well as a selection of neuropsychological functions by the cross-sectional comparison of 14, 22, and 16 participants aged 20-35 years, 59-73 years, and 74-88 years, respectively. The geriatric and neurological status of the elder participants (including evidence from computed tomography, electroencephalography, and neurological soft signs) was assessed. In four task blocks of 200 trials each, pro- and antisaccades were elicited under the 200-ms-gap and overlap conditions. Left- and right-sided stimuli were presented in random order at 4 degrees, and the order of the task blocks was varied within each age group. In addition, the Wisconsin card-sorting test (WCST) and working memory, go-nogo discrimination, alertness, and stimulus-response incompatibility tests were administered. Participants aged 59-73 years exhibited widespread reductions of optomotor and neuropsychological performance, with greatest effect sizes of age differences in the optomotor parameters and the WCST measures. A further decay after the age of 73 years was discernible in those optomotor functions reflecting saccade disinhibition (in particular, directional errors during the antisaccade task and premature responses) and the performance in some neuropsychological tests. In line with previously published reports, variance in optomotor performance could be explained by two factors, accounting for a total of 76% of the age variance. Our results suggest that the investigation of saccade control may be a highly sensitive tool for neurodevelopmental aging research.

Adult↗

Abnormally phosphorylated protein tau in the cortex of aged individuals of various mammalian orders.

Aged individuals of mammalian species displaying hyperphosphorylated tau protein may be suitable natural models for investigating neurodegenerative alterations occurring, for example, in Alzheimer's disease. Therefore, autoptic tissue from the entorhinal, motor and prefrontal cortices of 14 mammalian species was screened using the monoclonal antibody AT8, which is directed against a phosphorylated epitope of human tau and applicable to the tissues of aged domestic animals, as shown in previous studies. AT8-immunoreactive neuronal processes and perikarya were revealed in Campbell's guenon, rhesus monkey, baboon, rabbit, spectacled bear, guanaco, reindeer and bison. Signs for considerable neuropathological alterations in aged bisons also included neuropil threads, whereas AT8 immunoreactivity in the other species was only sparsely scattered. Hyperphosphorylated tau in the brain of an 28-year-old rhesus monkey was also detected by AT100, PHF-1 and TG-3 antibodies, but only in the hippocampal formation and entorhinal cortex, which are known as starting point for tangle spreading in the cortex of Alzheimer patients.

Aging↗

Transumbilical breast augmentation.

Surgical augmentation has been performed since 1899, with varying results. Recent developments in endoscopic instrumentation have enabled surgeons to perform many types of procedures through small incisions located at a distance from the surgical site. The transumbilical breast augmentation (TUBA) has advantages over other methods, including a quicker recovery, less pain, and lower chances of complications. This article familiarizes perioperative personnel with TUBA and how to care for the patients who undergo this procedure.

Breast Implantation↗

Nitric oxide selectively inhibits adenylyl cyclase isoforms 5 and 6.

We have previously shown that N18TG2 neuroblastoma cells express the type 6 adenylyl cyclase and that preincubation with nitric oxide (NO) attenuates Gs- and forskolin-stimulated activity. Here we show that this inhibition reflects a direct action of NO on the adenylyl cyclase. Preincubation of N18TG2 cell membranes and insect cell membranes expressing recombinant type 5 and type 6 isoforms with NO donors leads to an inhibition of forskolin-stimulated adenylyl cyclase activity. NO donors do not alter the type 1 (representative of the type 1,3,8 family) or type 2 (representative of the type 2,4, 7 family) isoforms expressed in insect cells, even under conditions of compromised assay conditions or a range of temperatures. Thus, the ability of NO to inhibit adenylyl cyclase stimulation is dependent upon the nature of the isoform present, and appears to represent a unique regulation of the type 5,6 isoform family.

Adenylyl Cyclase Inhibitors↗

Body packer: cocaine intoxication, causing death, masked by concomitant administration of major tranquilizers.

Cocaine, derived from the leaves of the shrub Erythroxylon coca, which grows on the slopes of the Andes, remains one of the most widely abused illicit drugs (Johnson et al., 1993). Its abuse appears to be increasing and as a result, so is its trafficking across borders, with ever-increasing sophistication of concealment (Rouse, 1992). Over the past few years, cases of cocaine intoxication have been reported, resulting from ruptured packets of cocaine that have been swallowed, or inserted into the vagina or rectum by couriers (drug smugglers), so called 'body packers' or 'mules' (Westli and Mittleman, 1981; Ricaurte and Langston, 1995). Cocaine is a powerful sympathomimetic and central nervous system stimulant, an overdose of which causes primarily cardiac, neurological and psychiatric effects (Ricaurte and Langston, 1995). Acute toxicity is dose-related and is characterized in the first place by its sympathomimetic effects, which include tachycardia, hypertension and hyperthermia arrythmias, followed by seizures. Brainstem depression and cardio-respiratory collapse, stroke, coma, intracranial vasculitis, myocardial infarction and sudden death have all been reported in cocaine abuse (Ricaurte and Langston, 1995). We present a fatal case with neurological and psychiatric symptoms, but without the usual cardiac and systemic signs.

Adult↗

Sonography of the temporomandibular joint from 60 examinations and comparison with MRI and axiography.

BACKGROUND AND OBJECTIVE: Establishing a diagnosis of temporomandibular joint disorder is mainly based on clinical assessment, functional examination, nuclear magnetic resonance imaging (MRI) and axiography. Sonographic examination was compared with MRI and axiography in assessing temporomandibular joint (TMJ) function in 55 patients. PATIENTS AND METHODS: Fifty-five patients with different TMJ problems were examined clinically, by means of axiography, sonography and some also by MRI. The range of motion was measured by sonography and axiography and the results compared using Student's t-test. Anatomical details diagnostic for disc-displacement were tested by sonography and MRI. RESULTS: The average time required for sonography was 2 min and for axiography 20 min. The mean measurement differences for condylar movement in maximal mouth opening was 1.7 mm, for protrusion 1.6 mm and for mediotrusion 2.5 mm. The range of condylar movement as measured by sonography and axiography coincided for opening and for protrusion (statistically significant). No significance was found for lateral excursions. The concordance in diagnosis of disc dislocation, hypermobility and impaired range of motion when comparing ultrasound with MRI was 83%. All sonographic examinations were performed by one person only. Sixty repeat examinations in patients produced no complaints and showed an absolute range of difference of 0.6 mm, with a relative range of 7%. Student's t-test was significant (p<0.05) (two repetitive measurements). CONCLUSION: Sonography proved to be a fast and reliable method for evaluating the range of movement of the TMJ. The lateral joint capsule, lateral disc, and upper condyle could be demonstrated. Pathological processes such as anterior or lateral disc displacement, disc perforation, seroma following contusion, capsular fibrosis, crystalline structures in the synovia and fracture dislocation of the condyle could be diagnosed with considerable reliability when compared with MRI. However, the medial aspect of the joint, medial disc dislocation and the angulation of the condylar slope could not be seen.

Adult↗

Temporal lobe epilepsy associated up-regulation of metabotropic glutamate receptors: correlated changes in mGluR1 mRNA and protein expression in experimental animals and human patients.

Aberrant axonal reorganization and altered distribution of neurotransmitter receptor subtypes have been proposed as major pathogenic mechanisms for hippocampal hyperexcitability in chronic temporal lobe epilepsies (TLE). Recent data point to excitatory class I metabotropic glutamate receptors (mGluR1 and mGluR5) as interesting candidates. Here, we have analyzed the hippocampal distribution and mRNA expression of mGluR1 and mGluR5 in two rat models of limbic seizures, i.e. electrical kindling and intraperitoneal kainate injections, as well as in human TLE. Quantitative RT-PCR analysis detected a significant increase of hippocampal mGluR1 gene transcript levels in kainate treated and kindled rats. In addition, microdissected hippocampal tissue samples localized this increase to the dentate gyrus. Using immunohistochemistry with mGluR1alpha subtype specific antibodies, increased labeling was observed within the dentate gyrus molecular layer (DG-ML). A similar pattern of increased mGluR1alpha neuropil staining was found within the DG-ML of epilepsy patients (n = 42) compared with peritumoral hippocampus specimens obtained from nonepileptic patients (biopsy controls, n = 3). This increase was detected in TLE patients with segmental hippocampal cell loss, as well as in TLE patients with focal lesions but no histopathological alterations of the hippocampus. In contrast, mGluR5 immunoreactivity and mRNA expression were not significantly altered in the DG-ML. Our data demonstrate a striking regional induction of mGluR1alpha in the hippocampal dentate gyrus of experimental animals with limbic seizures as well as in human patients with chronic, intractable TLE. This increase corresponds to functional alterations of class I mGluRs observed in seizure models and may significantly contribute to hippocampal hyperexcitability in focal human epilepsies.

Adult↗

Growth differentiation factor-9 stimulates proliferation but suppresses the follicle-stimulating hormone-induced differentiation of cultured granulosa cells from small antral and preovulatory rat follicles.

In addition to pituitary gonadotropins and paracrine factors, ovarian follicle development is also modulated by oocyte factors capable of stimulating granulosa cell proliferation but suppressing their differentiation. The nature of these oocyte factors is unclear. Because growth differentiation factor-9 (GDF-9) enhanced preantral follicle growth and was detected in the oocytes of early antral and preovulatory follicles, we hypothesized that this oocyte hormone could regulate the proliferation and differentiation of granulosa cells from these advanced follicles. Treatment with recombinant GDF-9, but not FSH, stimulated thymidine incorporation into cultured granulosa cells from both early antral and preovulatory follicles, accompanied by increases in granulosa cell number. Although GDF-9 treatment alone stimulated basal steroidogenesis in granulosa cells, cotreatment with GDF-9 suppressed FSH-stimulated progesterone and estradiol production. In addition, GDF-9 cotreatment attentuated FSH-induced LH receptor formation. The inhibitory effects of GDF-9 on FSH-induced granulosa cell differentiation were accompanied by decreases in the FSH-induced cAMP production. These data suggested that GDF-9 is a proliferation factor for granulosa cells from early antral and preovulatory follicles but suppresses FSH-induced differentiation of the same cells. Thus, oocyte-derived GDF-9 could account, at least partially, for the oocyte factor(s) previously reported to control cumulus and granulosa cell differentiation.

Animals↗

Growth differentiation factor-9 stimulates rat theca-interstitial cell androgen biosynthesis.

Growth differentiation factor-9 (GDF-9) was shown recently to be essential for early follicular development, including the appearance of the theca layer. Theca cells provide the androgen substrate for aromatization and estrogen production by granulosa cells. Using biologically active recombinant GDF-9 (rGDF-9) and an androgen-producing immortalized theca-interstitial cell (TIC) line or primary TIC, we have examined the action of this paracrine hormone on theca cell steroidogenesis. The effect of GDF-9 on TIC progesterone synthesis was marginal and inconsistent in the primary cultures. In immortalized theca cells, GDF-9 attenuated the forskolin-stimulated progesterone accumulation. More significantly, this oocyte-derived growth factor enhanced both basal and stimulated androstenedione accumulation in the primary and transformed TIC cultures. The effects of GDF-9 on steroidogenesis by preovulatory follicles were relatively modest. Likewise, it did not affect the maturation of follicle-enclosed oocytes. The effect of GDF-9, an oocyte product, on TIC androgen production suggests a regulatory role of the oocyte on theca cell function and hence on follicle development and differentiation. This direct effect of GDF-9 on thecal steroidogenesis is consistent with its recently demonstrated actions on thecal cell recruitment and differentiation.

Androgens↗

Nonrandom distribution of metaphase AgNOR staining patterns on human acrocentric chromosomes.

The metaphase nucleolar organizer regions (NORs) contain ribosomal genes associated with proteins such as upstream binding factor (UBF) and RNA polymerase I (RPI). These genes are clustered in 10 loci of the human acrocentric chromosomes (13, 14, 15, 21, and 22). Some NOR-associated proteins, termed AgNOR proteins, can be specifically stained by silver. In this study we took advantage of technical advances in digital imaging, image restoration techniques, and factorial correspondence analysis (FCA) to study the different AgNOR staining patterns of metaphase chromosomes in human lymphocytes. Three predominant patterns could be distinguished: pair (47%), stick-like (28%), and unstained (18%) structures. By studying the frequency of occurrence of each pattern on different chromosomes, two groups could be defined. Chromosomes 13, 14, and 21 carried predominantly pair or stick-like AgNOR structures, whereas chromosomes 15 and 22 mainly carried pair AgNOR structures or remained unstained. We suggest that the different AgNOR shapes reflect both the number of ribosomal genes carried by each chromosome and the differential recruitment of active ribosomal genes in each NOR cluster. This is the first study showing a nonrandom distribution of AgNOR shape among acrocentric chromosomes.

Chromosomes, Human↗

Magnetic resonance real-time imaging for the evaluation of left ventricular function.

New ultrafast gradient systems and hybrid imaging sequences make it possible to acquire a complete image in real time, without the need for breathholding or electrocardiogram (ECG) triggering. In 21 patients, left ventricular function was assessed by the use of a turbo-gradient echo technique, an echo-planar imaging (EPI) technique, and a new real-time imaging technique. End-diastolic and end-systolic volumes, left ventricular muscle mass, and ejection fraction of the ultrafast techniques were compared with the turbo-gradient echo technique. Inter- and intraobserver variability was determined for each technique. Image quality was sufficient for automated contour detection in all but two patients in whom foldover occurred in the real-time images. Results of the ultrafast imaging techniques were comparable with conventional turbo-gradient echo techniques. There was a tendency to overestimate the end-diastolic volume by 3.9 and 1.3 ml with EPI real-time imaging, the end-systolic volume by 0.9 and 5.0 ml, and the left ventricular mass by 2.6 and 23.8 g. Ejection fraction showed a tendency to be overestimated by 1.1% with EPI and underestimated by 4.5% with real-time imaging. Correlation between EPI real-time imaging and turbo-gradient echo were 0.94 and O.95, respectively, for end-diastolic volumes, 0.98 and 0.96, respectively, for end-systolic volumes, and 0.96 and 0.89, respectively, for left ventricular mass. Inter- and intraobserver variability was low with all three techniques. Real-time imaging allows an accurate determination of left ventricular function without ECG triggering. Scan times can be reduced significantly with this new technique. Further studies will have to assess the value of real-time imaging for the detection of wall motion abnornmalities and the imaging of patients with atrial fibrillation.

Analysis of Variance↗

[Experiences with an arterialized venous flap for intraoral defect reconstruction].

This clinical investigation should try out the suitability of arterialized venous forearm flaps for immediate reconstruction of intraoral defects after excision of an oral squamous cell carcinoma. In contrast to the free radial forearm flap there is no need for either sacrificing a peripheral artery or jeopardizing motor nerves. As the exact function of arterialized venous flaps is still unknown we had to take into account the possible loss of the flap. Therefore we used this flap in patients with small or medium sized defects only. All skin fat flaps were raised out of the right forearm using two different flap types. In 34 patient we used a flap with a superficial vein passing through (type I), in 5 patients we took a flap with two parallel proximal veins (type II). After the flap had been sutured into the intraoral defect, in flap type I the original distal end of the vein was anastomosed to an artery and the original proximal end to a vein. In flap type II there was no specific differentiation between the veins both. 18 (46.2%) of the flaps survived completely, 9 (23%) had superficial epithelial loss or some marginal necrosis and 12 (30.8%) became completely necrotic. Areas of partial loss developed slowly and formed stable granulation tissue. The flap donor sites were either closed primarily (n = 19) or were covered with split thickness skin graft (n = 20). There were no functional problems of the donor forearms. These results contrast with the high success rates achieved with orthodox free forearm flaps. Further research into venous flaps is essential.

Adult↗