Biomedical subjects

S Peters

Publications and source records attributed to S Peters.

At least 55 records · Page 3Linked to original sources

PubMed2001

Valsartan for prevention of restenosis after stenting of type B2/C lesions: the VAL-PREST trial.

The following study was performed to evaluate the effects of chronic 6-month administration of the angiotensin I receptor antagonist valsartan on restenosis rate after stenting of type B2/C lesions in comparison to placebo. Despite encouraging results of the BENESTENT and STRESS trials, stenting of complex coronary lesions leads to an in-stent restenosis rate of up to 40%. Several attempts at systematic medical therapy (e.g., ACE inhibitors) have not improved these results. Because of the important role of angiotensin in endothelial function, the hypothesis that angiotensin I receptor antagonists after stent implantation lead to a reduction of the in-stent restenosis rate should be tested in a single-center trial. Two hundred and fifty patients with type B2/C coronary lesions were randomized in an open-label study with respect to age, gender, lesion type and indication of percutaneous coronary intervention to a chronic administration of 80 mg valsartan or placebo (beta-blocking agents and/or ACE inhibitors). In-stent restenosis rate according to quantitative coronary angiography (QCA) and need for reintervention as primary and secondary endpoints were analyzed after a repeat angiogram at 6 months in 99 patients with 80 mg valsartan and 101 patients with placebo. Chronic administration of 80 mg valsartan reduced the in-stent restenosis rate to 19.2% (n = 19/99) in comparison to placebo with an in-stent restenosis rate of 38.6% (n = 39/101) (p < 0.005). Reintervention rate was 28.7% (n = 29/101) in the placebo group and only 12.1% (n = 12) in the valsartan group (p < 0.005). QCA analysis of stented coronary segments disclosed no differences in reference vessel diameter (2.68 +/- 0.26 mm in the valsartan group versus 2.71 +/- 0.24 mm in the placebo group) but significant differences in stented vessel diameter (2.17 +/- 0.27 mm in the valsartan group and 1.60 +/- 0.20 mm in the placebo group) (p < 0.000001).

Aged↗

PubMed2001

Fibrin sealant coated stents compared with non-coated stents in a porcine carotid artery model. Preliminary study report.

BACKGROUND: Balloon expandable metal stents (BEMS) are used to treat restenosis following percutaneous transluminal angioplasty (PTA) and as primary treatment. Intimal proliferation (IP) and resultant restenosis occurs in 25-50% of patients despite all preventive measures. OBJECTIVE: to test the intra-arterial response to the insertion of a fibrin sealant (FS) coated BEMS vs an uncoated BEMS by measuring endothelization and IP. HYPOTHESIS: that a BEMS coated with FS will lead to rapid endothelization and prevent or reduce IP. RATIONALE: FS consists of fibrinogen and thrombin. Thrombin affects endothelial cell proliferation and reduces smooth muscle proliferation, the forerunner of IP and restenosis. Normal endothelium also releases substances that promote vascular relaxation and normal smooth muscle tone regulation. METHODS: Thirty-40 kg pigs (EA), Palmaz-Shatz BEMS (Cordis), FS Tissucol (Baxter Immuno). Stents were uniformly coated with FS in a special mold. Both coated and uncoated stents were mounted on balloon catheters and deployed caudad in the carotid arteries via an arteriotomy. Angiograms were obtained postdeployment. All specimens were examined grossly, photographed then fixed for histology and in some cases, scanning electron microscopy (SEM). RESULTS: Fifteen animals form this preliminary report. Sacrifice at five days as per original protocol showed insufficient stent incorporation. Thereafter 1/2 of the animals were sacrificed at 15 days and 1/2 at 30 days. PATENCY: coated stents: 6 patent, 9 thrombosed. UNCOATED: 7 patent, 8 thrombosed. Of five EA given postoperatively low molecular weight heparin (LMWH) 4 animals had patent stents 80%. HISTOLOGY: varying degrees of IP were seen in all specimens. In general the coated stents showed a greater degree than the uncoated. STENOSIS: presacrifice angiography revealed that where the stents were patent no stenosis was present, in fact, some demonstrated mild dilatation. This was particularly the case with the coated stents. CONCLUSIONS: Coating stents with FS is not detrimental. IP in these EA at 30 days did not produce stenosis. Postoperative LMWH appears helpful in maintaining patency in a thrombogenic experimental animal. Further study maintaining EA for 6-12 months should resolve whether the IP seen had achieved its maximum expression or would progress and produce stenosis.

Angioplasty, Balloon↗

PubMed2000

Nestling growth and song repertoire size in great reed warblers: evidence for song learning as an indicator mechanism in mate choice.

Females of many songbird species show a preference for mating with males that have larger song repertoires, but the advantages associated with this preference are uncertain. We tested the hypothesis that song complexity can serve as an indicator of male quality because the development of the brain regions underlying song learning and production occurs when young birds typically face nutritional and other stresses, so that song reflects how well a male fared during post-hatch development. A key prediction of this hypothesis is that variation in nestling condition should correspond to variation in the adult song repertoires of individuals. We used data from a long-term study of the great reed warbler (Acrocephalus arundinaceus) to test this prediction, correlating two measures of nestling development with subsequent repertoire size of males. We found that the length of the innermost primary feather, a standard measure of development, significantly predicted first-year repertoire size. The relationship between repertoire size and body mass was nearly significant, in spite of the large variance inherent in this measure. These data support the idea that song may provide females with information about a male's response to developmental stress, which in turn is expected to correlate with indirect or direct benefits she might receive.

Animals↗

PubMed2000

Randomised comparison of the effectiveness and costs of community and hospital based mental health services for children with behavioural disorders.

OBJECTIVE: To test the hypothesis that a community based intervention by secondary child and adolescent mental health services would be significantly more effective and less costly than a hospital based intervention. DESIGN: Open study with two randomised parallel groups. SETTING: Two health districts in the north of England. PARTICIPANTS: Parents of 3 to 10 year old children with behavioural disorder who had been referred to child and adolescent mental health services. INTERVENTION: Parental education groups. MAIN OUTCOME MEASURES: Parents' and teachers' reports of the child's behaviour, parental depression, parental criticism of the child, impact of the child's behaviour on the family. RESULTS: 141 subjects were randomised to community (n=72) or hospital (n=69) treatment. Primary outcome data were obtained on 115 (82%) cases a year later. Intention to treat analyses showed no significant differences between the community and hospital based groups on any of the outcome measures, or on costs. Parental depression was common and predicted the child's outcome. CONCLUSIONS: Location of child mental health services may be less important than the range of services that they provide, which should include effective treatment for parents' mental health problems.

Child↗

PubMed2000

Polymorphism of HIV type 1 gag p7/p1 and p1/p6 cleavage sites: clinical significance and implications for resistance to protease inhibitors.

Amino acid substitutions at HIV-1 Gag p7/p1 and p1/p6 cleavage sites may be selected under antiretroviral pressure or represent natural polymorphisms. Whether changes are associated with specific protease (PR) mutation patterns and different clinical evolution has not been investigated. p7/p1 and p1/p6 cleavage site sequences from sera from 110 patients infected with HIV-1 were compared by regression analysis, using clinical, laboratory, and sequence variables, and the evolution of CD4(+) cell counts and viral load over time. Sixteen of 35 (46%) individuals naive to PR inhibitors (PIs), and 49 of 75 (65%) receiving PI-containing regimens had a p7/p1 and/or p1/p6 cleavage site polymorphism (p = 0.06). A431V and/or L449F were present exclusively among individuals failing PI treatment (17 of 75 [23%] and 3 of 75 [3%], respectively). There was a significant association between A431V and PR M46I,L (OR 13.7; 95% CI 4.2-44.3) and V82A,F,T (OR 8.8; 95% CI 2.7-27.8). Natural polymorphism P453L was strongly associated with the selection of PR I84V (OR 49.5; 95% CI 12-212) and selected against V82 mutation (OR 0.15; 95% CI 0.02-1. 2). After a median followup of 15 months, no polymorphism was associated with parameters of disease progression among individuals failing treatment. Only a limited set of amino acid substitutions can be tolerated at p7/p1 and p1/p6 cleavage sites. A431V is selected in association with specific PR inhibitor mutations. Natural polymorphism P453L might direct the PR resistance pathway through I84V instead of V82 mutation. No short-term clinical impact of cleavage site substitutions was documented.

Capsid↗

PubMed2000

Tourette's syndrome improvement with pergolide in a randomized, double-blind, crossover trial.

OBJECTIVE: To determine whether pergolide, a mixed D1-D2-D3 dopamine agonist, is efficacious and safe in the treatment of children with Tourette's syndrome. BACKGROUND: Neuroleptics, which block dopamine transmission, are currently used for treatment of children with severe tics, but major side effects and limited efficacy reduce clinical utility. Prior open-label reports of pergolide suggest potential benefit. METHODS: The authors enrolled 24 children age 7 to 17 years with Tourette's disorder, chronic motor tic disorder, or chronic vocal tic disorder by Diagnostic and Statistical Manual of Mental Disorders (4th ed.) criteria, plus severity criteria on the Yale Global Tic Severity Scale (YGTSS) of > or =20, in a double-blind, placebo-controlled, crossover study. Children were randomized to receive either placebo or up to 300 microg/day pergolide for the first 6-week treatment period, with a 2-week placebo washout, followed by crossover to the alternate treatment. The primary outcome measure was tic severity assessed by YGTSS. RESULTS: Compared with placebo treatment, pergolide treatment was associated with significantly lower YGTSS scores (42.0 +/- 20.4 versus 23.5 +/- 18.7; F = 12.0, df = 1, 17, p = 0.0011). No patient had a serious adverse event and pergolide was well tolerated. CONCLUSIONS: In this randomized, placebo-controlled, crossover trial, pergolide appeared to be a safe and efficacious treatment for Tourette's syndrome in children.

Adolescent↗

PubMed2000

Extrapyramidal motor signs in degenerative ataxias.

BACKGROUND: Extrapyramidal motor signs (EPS) are well-known symptoms of degenerative ataxia. However, little is known about frequency and appearance of EPS in subtypes of ataxia. METHODS: We characterized 311 patients with ataxia clinically and genetically. Course of the disease and EPS were investigated according to a standardized protocol. Diagnostic and prognostic impact of EPS in subtypes of ataxia was analyzed by Kaplan-Meier plots. RESULTS: Extrapyramidal motor signs occurred in all forms of ataxia, but frequency and type of EPS varied between genetically and clinically defined subtypes. Postural tremor in hereditary ataxias was typical for spinocerebellar ataxia type 2 (SCA2). Dystonia was generally rare in ataxias, but, if present, suggested SCA3. We observed a parkinsonian variant of SCA3 in which parkinsonism was present in the beginning of the disease and responded well to levodopa therapy, leading to diagnostic confusion. Parkinsonism in SCA3 was independent of CAG repeat length but ran in families, suggesting modifying genes. In idiopathic sporadic cerebellar ataxia (ISCA), EPS are more frequent in late-onset than in early-onset forms. In 50% of ISCA patients with parkinsonism, the diagnosis of multiple system atrophy remained questionable because of normal autonomic function. CONCLUSIONS: Extrapyramidal motor signs can help to predict the genetic subtype of ataxia. Extrapyramidal motor signs were more frequent in genetic subtypes in which basal ganglia affection has been demonstrated by postmortem studies. However, no type of EPS was specific for an underlying mutation. In ISCA, EPS are an adverse prognostic factor. Parkinsonism is especially associated with a more rapid course of the disease. Arch Neurol. 2000;57:1495-1500

Aged↗

PubMed2000

Neurotransplantation in neurodegenerative disease: a survey of relevant issues in developmental neurobiology.

Neural development and transplantation therapies in neurodegenerative disease share a particular feature. In both cases, undifferentiated neural precursor cells are required to differentiate into a range of neural cell types in a tissue-specific fashion. This similarity opens the possibility that the mechanisms that drive neural development play a similar role in CNS repair. In this chapter, two aspects of neural development are considered in terms of their relevance to CNS repair: the diversity of neural precursor cells and positional specification. We present evidence to suggest that neural stem cells have a degree of diversity that is beyond what might have been expected a priori. We also show that neural stem cells express genes that might encode a positional specification for these cells, and consider a number of hypotheses about the role of positional specification in CNS repair.

Animals↗

PubMed2000

[Detection of nitric oxide synthases in physiological and pathophysiological processes of the nasal mucosa].

Nitric oxide (NO) can play an important role in the regulation of vascular tone and neurotransmission, as well as in non-specific immunoreactions and inflammation in a variety of tissues. Increased quantities of nitric oxide in respired air can be measured during inflammatory processes. However, the exact role and precise sources of NO under physiological and pathophysiological conditions within the airways remain to be defined. Three isoforms of NO-synthases can be distinguished: two constitutive (neuronal and endothelial) Ca(2+)-dependent cNOS and one inducible Ca(2+)-independent iNOS (NOS II). Constitutive NOS (NOS I and III) release a basal amount of NO under physiological conditions. The inducible form once expressed can catalyse the generation of large quantities of NO. Many kinds of cells, such as macrophages, neutrophils, endothelium and smooth muscle cells, are capable of expressing NOS II. Since all isoforms of NO-synthase seem to be present in nasal tissues and the expression of iNOS under inflammatory conditions seems to be responsible for excessive production of NO, the distribution of NOS-isoforms (especially NOS II) in normal and inflammatory nasal tissue, as well as the exact requirements for expression of iNOS remain to be proven. Non-inflamed fresh human nasal mucosa from the middle turbinate was compared immuno-histologically with nasal mucosa having the typical findings of chronic polypoid rhinosinusitis (i.e., polypoid middle turbinates and polyps of the middle nasal duct). In order to gain more information about the mechanisms of acute inflammation, non-inflamed vital turbinates were incubated in vitro with the proinflammatory substances bacterial lipopolysaccharides (LPS) and tumor necrosis-factor (TNF) for 30, 60, 90, 120, 180 and 240 min. Subsequent to exposure to NADPH-diaphorase and immunostaining with specific antibodies to each NOS-isoform, clearly increased or initiated expressions of inducible NOS (iNOS) in blood vessels, glands, macrophages and epithelium of chronically inflamed and LPS-incubated nasal tissue became apparent in comparison to the non-inflamed controls. In contrast, NOS III/NOS I seemed to be not affected. The onset of immunohistochemically recognizable NOS II expression was observed after 90 min incubation with of LPS/TNF-alpha. Polypoid tissue showed a strong increase in submucosal thickness and a high infiltration of iNOS-positive leukocytes (granulocytes and macrophages) compared to the LPS-incubated non-inflamed specimens. These findings implicate NOS II generated nitric oxide as a key agent for causing swelling, secretion and obstruction in patients with acute and chronic polypoid or allergic rhinitis. These findings also suggest that molecular NO has to be considered in the pathophysiology of chronic polypoid rhinosinusitis.

Chronic Disease↗

PubMed2000

Familial hypertrophic cardiomyopathy associated with prolongation of the QT interval.

In a 61 year old female patient who suffered from atypical chest pain we diagnosed long QT syndrome by QTc duration of 467 ms, macroscopic T wave alternans and notched T waves in three leads and hypertrophic cardiomyopathy with asymmetric thickening of basal parts of the septum (2.0 cm) without relevant outflow tract obstruction by echocardiography. Coronary angiography could exclude coronary artery disease. In a systematic family screening two sons of the patient could also be diagnosed as having long QT syndrome with QTc durations of 472 and 496 ms and asymmetric septal thickening (1.8 and 2.1 cm, respectively). One of these two sons suffered from pre-syncope, the other was asymptomatic despite maximum sports activity. In the third son, LQTS and hypertrophic cardiomyopathy could be excluded.

Adult↗

PubMed2000

Genetic background of apparently idiopathic sporadic cerebellar ataxia.

Disease-causing mutations have been identified in various entities of autosomal dominant ataxia and in Friedreich's ataxia. However, no molecular pathogenic factor is known to cause idiopathic cerebellar ataxias. We investigated the CAG/CTG trinucleotide repeats causing spinocerebellar ataxia types 1, 2, 3, 6, 7, 8 and 12, and the GAA repeat of the frataxin gene in 124 patients apparently suffering from idiopathic sporadic ataxia, including 20 patients with the clinical diagnosis of multiple system atrophy. Patients with a positive family history, a typical Friedreich phenotype, or symptomatic ataxia were excluded. Genetic analyses uncovered the most common Friedreich mutation in 10 patients with an age at onset between 13 and 36 years. The SCA6 mutation was present in nine patients with disease onset between 47 and 68 years of age. The CTG repeat associated with SCA8 was expanded in three patients. One patient had SCA2 attributable to a de novo mutation from a paternally transmitted, intermediate allele. We did not identify the SCA1, SCA3, SCA7 or SCA12 mutation in idiopathic sporadic ataxia patients. No trinucleotide repeat expansion was detected in the MSA subgroup. This study has revealed the genetic basis in 19% of apparently idiopathic ataxia patients. SCA6 is the most frequent mutation in late onset cerebellar ataxia. The frataxin trinucleotide expansion should be investigated in all sporadic ataxia patients with onset before age 40, even when the phenotype is atypical for Friedreich's ataxia.

Age of Onset↗

PubMed2000

Tolcapone increases maximum concentration of levodopa.

No significant increase of the maximum concentration (Cmax) of levodopa after addition of catechol-O-methyltransferase inhibitor tolcapone occurred in previous pharmacokinetic studies predominantly on healthy volunteers. We compared pharmacokinetics of levodopa in plasma before and after addition of tolcapone in 13 treated parkinsonian subjects under standardized conditions. We found a significant increase of Cmax of levodopa after the addition of tolcapone. This may represent one cause for the occurrence of dyskinesia previously early in the course of treatment with tolcapone.

Aged↗

PubMed2000

Xanthone 6-hydroxylase from cell cultures of Centaurium erythraea RAFN and Hypericum androsaemium L.

Xanthone 6-hydroxylase activity was detected in the microsomal fractions from two plant cell cultures. The enzyme from cultured cells of Centaurium erythraea (Gentianaceae) exhibited absolute specificity for 1,3,5-trihydroxyxanthone as substrate, whereas xanthone 6-hydroxylase from cell cultures of Hypericum androsaemum (Hypericacaea) preferred the isomeric 1,3,7-trihydroxyxanthone but used 1,3,5-trihydroxyxanthone also to a small extent. Both xanthones were regioselectively hydroxylated in position 6. The xanthone 6-hydoxylases are cytochrome P450 monooxygenases, as shown by their dependence on NADPH and molecular oxygen and their inhibition by carbon monoxide and typical P450 inhibitors. In both cell cultures, xanthone accumulation was preceded by an increase in xanthone 6-hydroxylase activity.

Cells, Cultured↗

PubMed2000

Lateralisation of perceptual processing of pro- and anti-social emotions displayed in chimeric faces.

Previous studies using a restricted range of split field chimeric faces suggest that the processing of facial emotional expressions is a highly lateralised phenomenon. Two theories have emerged with regard to the role the two cerebral hemispheres play in this processing. The "right hemisphere" hypothesis (e.g. Borod, Koff, Lorch, & Nicholas, 1988) suggests that the right hemisphere plays a prominent role in the processing of both positive and negative facial expressions. In contrast, the "valence hypothesis" (e.g. Reuter-Lorenz & Davidson, 1981) proposes that, while the right hemisphere plays the major role in processing negative emotions, the left hemisphere has a special role for positive emotions. Using all six of the human "universal facial expressions" (Ekman &Friesen, 1971) we present evidence that, superimposed onto a left visual field advantage (right hemisphere specialisation) for emotional processing, there is a "left shift" (right visual field advantage) for pro- as opposed to anti-social expression. We propose that facial expressions that are likely to be related to approach for communicative purposes initiate a greater degree of left hemisphere involvement. As a consequence, we suggest that for future laterality studies, the six universal emotional expressions should be reconsidered using a pro- to anti-social dimension rather than positive and negative groupings.

Journal Article↗

PubMed2000

Applied behavior management and acquired brain injury: approaches and assessment.

Individuals who have acquired brain injury (ABI) may express themselves through the use of challenging behaviors, such as aggression, withdrawal, disinhibition, and self-destructive behaviors. This article describes the effectiveness of behavior interventions derived from the assessment of behavior in a community-based setting. The premise is that behavior, no matter how difficult, has function, purpose, and meaning for the individual. A therapeutic model of behavior assessment is presented that bases its strength on behavior assessment and well-trained staff. A well-formulated behavior management plan is developed, reinforcing alternative behaviors teaching skills, and reducing unwanted behaviors. Through the use of data collection methods, the treatment team identifies variables related to unwanted behavior and outcomes of consequences as they relate to the behavior. Illustrated through a case study, the behavioral treatment model is defined through behavior identification, initial assessments, treatment approaches, and tracking outcomes.

Aggression↗

PubMed2000

Succession of microbial communities during hot composting as detected by PCR-single-strand-conformation polymorphism-based genetic profiles of small-subunit rRNA genes.

A cultivation-independent technique for genetic profiling of PCR-amplified small-subunit rRNA genes (SSU rDNA) was chosen to characterize the diversity and succession of microbial communities during composting of an organic agricultural substrate. PCR amplifications were performed with DNA directly extracted from compost samples and with primers targeting either (i) the V4-V5 region of eubacterial 16S rRNA genes, (ii) the V3 region in the 16S rRNA genes of actinomycetes, or (iii) the V8-V9 region of fungal 18S rRNA genes. Homologous PCR products were converted to single-stranded DNA molecules by exonuclease digestion and were subsequently electrophoretically separated by their single-strand-conformation polymorphism (SSCP). Genetic profiles obtained by this technique showed a succession and increasing diversity of microbial populations with all primers. A total of 19 single products were isolated from the profiles by PCR reamplification and cloning. DNA sequencing of these molecular isolates showed similarities in the range of 92.3 to 100% to known gram-positive bacteria with a low or high G+C DNA content and to the SSU rDNA of gamma-Proteobacteria. The amplified 18S rRNA gene sequences were related to the respective gene regions of Candida krusei and Candida tropicalis. Specific molecular isolates could be attributed to different composting stages. The diversity of cultivated bacteria isolated from samples taken at the end of the composting process was low. A total of 290 isolates were related to only 6 different species. Two or three of these species were also detectable in the SSCP community profiles. Our study indicates that community SSCP profiles can be highly useful for the monitoring of bacterial diversity and community successions in a biotechnologically relevant process.

Bacteria↗

PubMed2000

Luteal progesterone relates to histological endometrial maturation in fertile women.

To examine the relationship between endometrial histological maturation and reproductive hormones, we studied 11 fertile women, aged 18-37 yr. All participants had had at least 1 previous pregnancy and cycled regularly, every 25-35 days. Women collected daily, first morning voided urine for measurement of estradiol and progesterone metabolite excretion, estrone conjugates (E1c), and pregnanediol glucuronide (Pdg), respectively, throughout the cycle of study. Hormones were normalized for creatinine. Between 7-9 days after home detection of a LH surge (Sure Step), participants underwent an endometrial biopsy using a small bore (Pipelle) catheter. Tissue was prepared for histological and biochemical analyses. The histological analysis is reported herein. Endometrium was dated by 3 authors (N.S., D.H., and S.P.), all of whom were blinded to the participant's identity or timing of biopsy within her cycle. Final dating was agreed upon based upon the method of Noyes et al. E1c and Pdg were integrated throughout the cycle using the trapezoidal rule, and correlations were sought between deviation from expected histology (based upon urinary hormones and LH surge) and integrated hormone values. E1c varied over a 2-fold range in these normal women, from 1196-2040 ng/cycle. Pdg excretion was much more variable, ranging from 22-119 microg/cycle. No relationship could be found between histological lagging of endometrial maturation and lower excretion of E1c. A moderate correlation was observed (Spearman's r = 0.6; P < 0.05) between degree of histological maturation and integrated Pdg. Of two women with evidence of a disparity between gland and stromal development (glands lagging behind stroma by >2 days), one excreted 24 microg Pdg/cycle, the next to lowest value. We conclude that normal fertile women experience a wide range of hormone concentrations in the face of normal endometrial maturation. Progesterone appears to exert a dose-related effect on endometrial maturation, and the techniques we used, although relatively crude clinical measures, appeared to be sufficient to detect this relationship.

Adolescent↗

PubMed2000

Object recognition may distort size perception.

Size estimation may be influenced by characteristics recalled about the object viewed. This study evaluated the influence of object familiarity on estimation of size. We compared size estimates of several familiar objects with size estimates of undefined objects matched for dimensions of pattern and color. Those estimating the size of the familiar objects made significantly larger errors than those estimating the size of the undefined objects. In a second study size estimation errors from memory were larger than when objects were directly viewed. Experience with the objects appears to decrease accuracy of estimates of size but errors may be reduced by directly observing the object.

Color Perception↗