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Biomedical subjects

S Rose

Publications and source records attributed to S Rose.

At least 55 records · Page 3Linked to original sources
PubMed2001

Components of clinical trials for vasovagal syncope.

The time is ripe for adequately powered, randomized, placebo-controlled clinical trials in vasovagal syncope. Vasovagal syncope is a common syndrome, the symptoms of which can be troublesomely frequent. It is usually diagnosed by tilt-table testing, although this has persistent problems with both sensitivity and specificity. Patients with syncope and positive tilt tests have been the subjects of numerous studies of natural history, risk stratification, and treatment. This paper discusses studies of treatments for vasovagal syncope in the context of a classification of the levels of evidence that can be gleaned from clinical studies. The reasons for placebo-controlled trials are reviewed, as is the evidence for various methods of risk stratification. Data for power calculations are presented for the primary outcome, the time to the first syncope recurrence. Strengths and weakness of the four main types of outcomes for clinical trials are compared.

Clinical Trials as Topic↗
PubMed2001

Utilization of the rpoB gene as a specific chromosomal marker for real-time PCR detection of Bacillus anthracis.

The potential use of Bacillus anthracis as a weapon of mass destruction poses a threat to humans, domesticated animals, and wildlife and necessitates the need for a rapid and highly specific detection assay. We have developed a real-time PCR-based assay for the specific detection of B. anthracis by taking advantage of the unique nucleotide sequence of the B. anthracis rpoB gene. Variable region 1 of the rpoB gene was sequenced from 36 Bacillus strains, including 16 B. anthracis strains and 20 other related bacilli, and four nucleotides specific for B. anthracis were identified. PCR primers were selected so that two B. anthracis-specific nucleotides were at their 3' ends, whereas the remaining bases were specific to the probe region. This format permitted the PCR reactions to be performed on a LightCycler via fluorescence resonance energy transfer (FRET). The assay was found to be specific for 144 B. anthracis strains from different geographical locations and did not cross-react with other related bacilli (175 strains), with the exception of one strain. The PCR assay can be performed on isolated DNA as well as crude vegetative cell lysates in less than 1 h. Therefore, the rpoB-FRET assay could be used as a new chromosomal marker for rapid detection of B. anthracis.

Animals↗
PubMed2001

Renal arterial stenosis in renal allografts: retrospective study of predisposing factors and outcome after percutaneous transluminal angioplasty.

PURPOSE: To determine the predisposing factors to transplant renal arterial stenosis (TRAS) and assess the outcome of percutaneous transluminal angioplasty (PTA) as the primary treatment. MATERIALS AND METHODS: Of 831 renal allograft recipients (584 cadaveric, 247 living related) between January 1991 and December 1998, 72 had hypertension and/or renal dysfunction. All 72 underwent arteriography, and their medical charts were retrospectively reviewed. RESULTS: Prevalence of TRAS was 3.1% (26 of 831). Technical success rate of PTA was 94% (16 of 17), and clinical success rate was 82% (14 of 17). Those with renal dysfunction had a mean pre-PTA creatinine value of 2.6 mg/dL (230 micromol/L) +/- 0.5 (SD) versus a 1-week post-PTA value of 1.7 mg/dL (150 micromol/L) +/- 0.3 (P <.001). Of those with hypertension, all but one had substantial improvement in mean diastolic blood pressure. At 26.9 months mean follow-up in 16 patients with successful PTA, two stenoses reoccurred, and two grafts were lost to chronic rejection. TRAS was present in 14 of 45 end-to-side anastomoses and 12 of 27 end-to-end anastomoses (P =.31), and TRAS was more prevalent in cadaveric grafts (24 of 584) than in living related grafts (two of 247). In cadaveric grafts, the mean cold ischemia time was 29.0 hours +/- 6.9 in those with TRAS (n = 24), as compared with 25.5 hours +/- 8.1 in those with no TRAS (n = 39; P = .35). Seven of 17 patients with acute rejection and six of 35 with chronic rejection had TRAS. CONCLUSION: Primary treatment of TRAS with PTA has good intermediate-term results. TRAS is more prevalent in cadaveric allografts with long cold ischemia time.

Adult↗
PubMed2001

Attachment disorganization and dissociative symptoms in clinically treated adolescents.

OBJECTIVE: To examine the association of unresolved and unclassifiable attachment with dissociative symptomatology in a sample of 133 adolescents in psychiatric treatment. METHOD: The study compared 69 adolescents who were unresolved and unclassifiable with 64 adolescents who were not unresolved and unclassifiable. Attachment organization was assessed using the Adult Attachment Interview (AAI). Dissociative symptomatology was assessed using a scale derived from the Youth Self Report (YSR) behaviour checklist. RESULTS: A continuing unresolved and unclassifiable response to attachment-related trauma was correlated with dissociative symptomatology for both male and female adolescents. CONCLUSIONS: Cognitive disorganization may be an important variable mediating between the effects of earlier traumatic caregiving experiences and later dissociative symptoms.

Adolescent↗
PubMed2001

Patterns of wheel running are related to Fos expression in neuropeptide-Y-containing neurons in the intergeniculate leaflet of Arvicanthis niloticus.

A variety of nonphotic influences on circadian rhythms have been documented in mammals. In hamsters, one such influence, running in a novel wheel, is mediated in part by the pathway extending from neuropeptide-Y (NPY)-containing cells within the intergeniculate leaflet (IGL) of the thalamus to the hypothalamic suprachiasmatic nucleus (SCN). Arvicanthis niloticus is a species in which all individuals are diurnal with respect to general activity and body temperature when they are housed without a running wheel, but access to a running wheel induces a subset of individuals to become nocturnal. In the first study, the authors evaluated the possibility that nocturnal and diurnal patterns of wheel running in Arvicanthis are correlated with differences in IGL function. Adult male Arvicanthis housed in a 12:12 light-dark (LD) cycle were monitored in wheels, classified as nocturnal or diurnal, and then perfused either 4 h after lights-on or 4 h after lights-off. Sections through the intergeniculate leaflet were processed for immunohistochemical labeling of Fos and NPY. The percentage of NPY cells that expressed Fos was significantly influenced by an interaction between time of day and phenotype such that it rose from night to day in diurnal animals, and from day to night in nocturnal animals. In the second experiment, the authors established that running in a wheel actually induces Fos in the IGL of Arvicanthis. Specifically, the proportion of NPY cells expressing Fos was increased by access to wheels in nocturnal animals at night and in diurnal animals during the day. In the third experiment, the authors established that lesions of the IGL eliminate NPY fibers within the SCN, suggesting that these IGL cells project to the SCN in this species as has been established in other rodents. Together, these data demonstrate a clear difference in NPY cell function in nocturnal and diurnal Arvicanthis that appears to be caused, at least in part, by the differences in their wheel-running patterns, and that NPY cells within the IGL project to the SCN in Arvicanthis.

Animals↗
PubMed2001

Moving on from old dichotomies: beyond nature-nurture towards a lifeline perspective.

BACKGROUND: Genetics is increasingly being used to explain human behaviours, with growing enthusiasm for what could be termed 'genetic determinism', which an ultra-Darwinist approach seeks to apply to all aspects of the human condition. AIMS: To consider the validity of the claims concerning the genetics of human behaviour and psychological distress. METHOD: A critical review of the current assumptions about the relative contributions of genetics and the environment. RESULTS AND CONCLUSIONS: Organisms are in constant interaction with their environment: that is, organisms select environments just as environments select organisms. Like organisms, environments evolve and are homeodynamic rather than homeostatic; both 'genome' and 'envirome' are abstractions from this continuous dialectic.

Attention Deficit Disorder with Hyperactivity↗
PubMed2001

An empirical analysis of stressors for gay men and lesbians.

This research describes the empirical classification of stressors for gay men and lesbians. Volunteer respondents were recruited through a free local gay and lesbian newspaper, through gay and lesbian student organizations nationwide, through gay and lesbian bookstores nationwide, and at a gay festival in St. Louis. Nine hundred seventy-nine (979) participants completed a 70-item measure with stressors that had been identified in previous qualitative research. Participants were asked to indicate the degree to which they had experienced stress associated with a variety of experiences. Participants also completed a measure of dysphoria (CES-D), responded about their degree of openness regarding sexual orientation, and provided information about their relationship status and involvement with gay groups and activities. Using confirmatory factor analysis, a six-factor model was predicted to account for the data. One-factor, six-factor, and ten-factor models were tested. The ten-factor model yielded the best fit with the data and accounted for 63.5% of the variance. The factor structure remained stable when gay men were compared to lesbians, when those endorsing a predominantly gay versus exclusively gay orientation were compared, and when those in a relationship were compared to those who were not in a relationship. Increased gay stress was associated with more dysphoria. Implications of these findings are discussed and directions for future research are considered.

Adult↗
PubMed2001

Alas, poor Darwin.

No, not a reflection on the environmental threat to the Galapagos. Rather, it is a reference to Darwin's own complaint, towards the end of his life, concerning those who misunderstood and misrepresented his theories.

Biological Evolution↗
PubMed2000

Expression and distribution of CYP2C enzymes in rat basal ganglia.

The function and integrity of the basal ganglia is modulated by sex steroids whose activity may be controlled by P450 enzymes, such as members of the CYP2C subfamily. The expression of CYP2C enzymes in rat basal ganglia was examined by immunohistochemistry along with some of the factors that might control their expression. Whereas no CYP2C11 or CYP2C12 immunoreactivity was detected in the basal ganglia of either male or female rats, marked CYP2C13 immunoreactivity was evident in neurones of the subthalamic nucleus, substantia nigra, and interpeduncular nucleus. Strong CYP2C13 immunoreactivity was also expressed in the cortex, olfactory tubercle, hippocampus, dentate gyrus, hypothalamic nuclei, medial habenular nucleus, red nucleus, and medial forebrain bundle. Similar results were found in male and female rats. Following 6-hydroxydopamine lesioning of the nigro-striatal tract, tyrosine hydroxylase immunoreactivity was absent and CYP2C13 immunoreactivity was decreased markedly in the substantia nigra pars compacta, implying its presence in dopaminergic neurones. Modulation of sex steroids, using castrated rats, had no effect on the number of CYP2C13 positive neurones in the substantia nigra pars compacta. These results indicate that CYP2C13 protein is constitutively and widely expressed in rat brain. However, its expression is not sex-specific and is unaffected by castration. The role of CYP2C13 in brain is unknown but it may be involved in the generation of neurosteroids and catecholoestrogens.

Animals↗
PubMed2000

Phosphoacetylation of histone H3 on c-fos- and c-jun-associated nucleosomes upon gene activation.

The induction of immediate-early (IE) genes, including proto-oncogenes c-fos and c-jun, correlates well with a nucleosomal response, the phosphorylation of histone H3 and HMG-14 mediated via extracellular signal regulated kinase or p38 MAP kinase cascades. Phosphorylation is targeted to a minute fraction of histone H3, which is also especially susceptible to hyperacetylation. Here, we provide direct evidence that phosphorylation and acetylation of histone H3 occur on the same histone H3 tail on nucleosomes associated with active IE gene chromatin. Chromatin immunoprecipitation (ChIP) assays were performed using antibodies that specifically recognize the doubly-modified phosphoacetylated form of histone H3. Analysis of the associated DNA shows that histone H3 on c-fos- and c-jun-associated nucleosomes becomes doubly-modified, the same H3 tails becoming both phosphorylated and acetylated, only upon gene activation. This study reveals potential complications of occlusion when using site-specific antibodies against modified histones, and shows also that phosphorylated H3 is more sensitive to trichostatin A (TSA)-induced hyperacetylation than non-phosphorylated H3. Because MAP kinase-mediated gene induction is implicated in controlling diverse biological processes, histone H3 phosphoacetylation is likely to be of widespread significance.

Acetylation↗
PubMed2000

Brief psychological interventions ("debriefing") for trauma-related symptoms and the prevention of post traumatic stress disorder.

OBJECTIVES: To assess the effectiveness of brief psychological debriefing for the management of psychological distress after trauma, and the prevention of post traumatic stress disorder. SEARCH STRATEGY: Electronic searching of MEDLINE, EMBASE, PsychLit, PILOTS, Biosis, Pascal, Occ.Safety and Health, CDSR and the Trials Register of the Depression, Anxiety and Neurosis group. Hand search of Journal of Traumatic Stress. Contact with leading researchers. SELECTION CRITERIA: The inclusion criteria for all randomized studies was that they should focus on persons recently (one month or less) exposed to a traumatic event, should consist of a single session only, and that the intervention involve some form of emotional processing/ventilation by encouraging recollection/reworking of the traumatic event accompanied by normalisation of emotional reaction to the event. DATA COLLECTION AND ANALYSIS: 8 trials fulfilled the inclusion criteria. Quality was generally poor. Data from two trials could not be synthesised. MAIN RESULTS: Single session individual debriefing did not reduce psychological distress nor prevent the onset of post traumatic stress disorder (PTSD). Those who received the intervention showed no significant short term (3-5 months) in the risk of PTSD (pooled odds ratio 1.0, 95% ci 0.6-1.8). At one year one trial reported that there was a significantly increased risk of PTSD in those receiving debriefing (odds ratio 2.9, 95% ci 1.1-7.5). The pooled odds ratio for the two trials with follow ups just included unity (odds ratio 2.0, 95% ci 0.9-4.5). There was also no evidence that debriefing reduced general psychological morbidity, depression or anxiety. REVIEWER'S CONCLUSIONS: There is no current evidence that psychological debriefing is a useful treatment for the prevention of post traumatic stress disorder after traumatic incidents. Compulsory debriefing of victims of trauma should cease.

Crisis Intervention↗
PubMed2000

[Severe craniocerebral trauma in multiple trauma. An assessment of the interaction of local and systemic mediator responses].

Isolated severe head trauma (SHT) or SHT in combination with multiple injuries are important factors for the prognosis of morbidity and mortality in patients suffering from the consequences of accidents. The prognosis mainly depends on the presence of primary mechanic brain injury and the development of secondary brain damage. Causes for the development of secondary brain damage are the intracranial space demand after traumatic injury and edema formation which may result in iscemia, as well as inflammatory processes. Both isolated SHT and polytrauma with or without brain damage may result in a systemic inflammatory response syndrome (SIRS) due to the synthesis of cytokines and other inflammatory mediators which may cause a single or multiple organ failure (MOF). Often the organism is able to survive isolated traumatic injuries and functional disturbances, but in combination or cumulation they may be lethal. The hypermetabolism after SHT is often regarded as an interaction between the central nervous system and the whole organism by the activation of the neuroendocrine axis. In contrast to the consequences of SHT for the whole organism, multiple injuries after polytrauma may affect brain functions, such as the shock dependent disturbance of the brain perfusion accompanied by brain hypoxia which may lead to an aggravated prognosis. Moreover, coagulation, metabolism and fracture healing are influenced by the onset of SIRS as well. Our knowledge about the bidirectional inflammatory interaction between brain and whole organism is still limited. In this context, the effects of secondary surgical interventions which may additionally, stress a traumatized body have to be considered and are the subject for actual clinical discussions and experimental studies. This article tries to summarize some important aspects on this topic.

Brain Injuries↗
PubMed2000

Anticancer efficacy of the irreversible EGFr tyrosine kinase inhibitor PD 0169414 against human tumor xenografts.

PURPOSE: The involvement of the EGF receptor (EGFr) family of receptors in cancers suggests that a selective inhibitor of the tyrosine kinase activity of the EGFr family could have a therapeutic effect. PD 0169414, an anilinoquinazoline, is a potent irreversible inhibitor of the EGFr family tyrosine kinase activity with IC(50) values of 0.42 nM against the isolated EGF receptor, and 4.7 nM and 22 nM against EGF- and heregulin-mediated receptor phosphorylation in A431 and MDA-MB-453 cells, respectively. METHODS AND RESULTS: Oral administration of 260 mg/kg per day PD 0169414 for 15 days to animals bearing advanced-stage A431 epidermoid carcinoma produced a 28.2-day delay in tumor growth and resulted in three complete and three partial tumor regressions in six animals. Toxicity at this dose level was limited to <6% loss of initial body weight. Doses of 160 and 100 mg/kg per day produced tumor growth delays of 29.5 and 20.9 days and two and one complete regressions in six animals, respectively. Subcutaneous, intraperitoneal, and oral routes of administration have also shown in vivo antitumor activity of PD 0169414 in a panel of human tumor xenografts. Responsive tumor lines include A431 (human epidermoid carcinoma), H125 (NSCL carcinoma), MCF-7 and UISO-BCA1 (human breast carcinoma), and SK-OV-03 (human ovarian carcinoma). The therapeutic effect ranged from delayed tumor growth (6.4 days delayed tumor growth for 14 days of treatment) to tumor regressions (32.2 days delayed tumor growth and five partial regressions in six animals) in these model systems. CONCLUSION: PD 0169414 is a specific, irreversible inhibitor of EGFr family tyrosine kinases with significant in vivo activity against a variety of relevant human tumor xenografts.

3T3 Cells↗