What does the future hold for high-level magnification in dentistry?
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Catalogs, Commercial as Topic↗
Biomedical subjects
David J Clark
Publications and source records attributed to David J Clark.
Reliability of elbow stretch reflex assessment in chronic post-stroke hemiparesis.
OBJECTIVE: To establish reliability of quantitative measures of elbow joint spastic hypertonia in post-stroke hemiparesis. METHODS: Nine subjects with post-stroke hemiparesis (mn duration: 42 months) were tested on three separate days. Biceps brachii and brachioradialis EMG were recorded during passive ramp-and-hold extensions applied at seven speeds between 30 and 210 degrees /s. EMG burst duration, onset position threshold, and burst intensity were used to evaluate reflex activity. Torque at 40 degrees of elbow flexion was used as a mechanical indicator of spastic hypertonia. RESULTS: Across speeds ICCs were consistent, means ranged between 0.63 and 0.85. Thus, relative reliability was fair to excellent for all parameters. Absolute reliability, determined using standard error of measurement expressed as a percentage of the mean score (%SEM), improved at higher speeds (> or = 120 degrees/s). CONCLUSIONS: These results establish reliability of reflex and mechanical measures of elbow spastic hypertonia post-stroke. The data demonstrate greater reflex detection at high speeds, indicating greater potential to document meaningful changes in these distinct aspects of spastic hypertonia following intervention. SIGNIFICANCE: Based on findings of this study, reliability was demonstrated using four parameters of reflex EMG and torque indicating measurement consistency across sessions. These observations motivate determination of requisite effect sizes for clinical trials that evaluate treatment outcome.
Aged↗
Global regulation by the yeast Spt10 protein is mediated through chromatin structure and the histone upstream activating sequence elements.
The yeast SPT10 gene encodes a putative histone acetyltransferase (HAT) implicated as a global transcription regulator acting through basal promoters. Here we address the mechanism of this global regulation. Although microarray analysis confirmed that Spt10p is a global regulator, Spt10p was not detected at any of the most strongly affected genes in vivo. In contrast, the presence of Spt10p at the core histone gene promoters in vivo was confirmed. Since Spt10p activates the core histone genes, a shortage of histones could occur in spt10Delta cells, resulting in defective chromatin structure and a consequent activation of basal promoters. Consistent with this hypothesis, the spt10Delta phenotype can be rescued by extra copies of the histone genes and chromatin is poorly assembled in spt10Delta cells, as shown by irregular nucleosome spacing and reduced negative supercoiling of the endogenous 2mum plasmid. Furthermore, Spt10p binds specifically and highly cooperatively to pairs of upstream activating sequence elements in the core histone promoters [consensus sequence, (G/A)TTCCN(6)TTCNC], consistent with a direct role in histone gene regulation. No other high-affinity sites are predicted in the yeast genome. Thus, Spt10p is a sequence-specific activator of the histone genes, possessing a DNA-binding domain fused to a likely HAT domain.
Base Sequence↗
Oral antiplatelet therapy and percutaneous coronary intervention.
The benefit of oral antiplatelet therapy following percutaneous coronary intervention (PCI) with intracoronary stent implantation is well established. Combined aspirin with clopidogrel or ticlopidine therapy is superior to aspirin alone in reducing thrombotic events after stent placement. Clopidogrel is the drug of choice, given that its efficacy is comparable to ticlopidine and it has a superior safety profile. Despite dual antiplatelet therapy, patients remain at risk of recurrent vascular events. Optimal timing, duration and dosage of antiplatelet therapy remain controversial. Recent evidence suggests additional benefit with clopidogrel pretreatment, high clopidogrel loading dose and long-term dual antiplatelet therapy post-PCI in high-risk patients.
Administration, Oral↗
A glance at what to look for when purchasing a new microscope.
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Dental Equipment↗
Safety and utility of intravascular ultrasound-guided carotid artery stenting.
Intravascular ultrasound (IVUS) is useful in evaluating coronary stent deployment. The aim of this study was to assess the safety and utility of IVUS in carotid artery stenting (CAS). Ninety-eight consecutive high-risk patients (107 arteries) underwent CAS. IVUS was performed prior to predilatation in 87 of the 107 vessels and in all 107 following stent deployment when an optimal angiographic appearance was obtained. Quantitative carotid angiography (QCA) and IVUS analysis were performed offline. Procedural success was 97%. Combined stroke or death at 30 days was 5.6%. IVUS measurements of the minimum lumen diameter (MLD) of the distal internal carotid artery (ICA) reference segment were similar to QCA (4.60 +/- 0.74 vs. 4.74 +/- 0.71 mm; P = 0.21). The ICA stent MLD was significantly smaller by IVUS compared to QCA (3.65 +/- 0.68 vs. 4.31 +/- 0.76 mm; P < 0.001). IVUS detected stent malapposition in 11%. IVUS findings, after an optimal angiographic result, necessitated additional treatment in 9% of procedures. Calcium was detected in more arteries with IVUS than angiography (61% vs. 46%; P < 0.05). Arteries with superficial lesion calcification subtending three or four quadrants by IVUS had a 31% incidence of stroke compared with a 1% incidence in arteries without severe superficial calcium (P < 0.001). We found IVUS imaging in CAS to be safe even prior to plaque dilatation. IVUS provides a more accurate assessment of stent dimensions, expansion, and apposition than angiography. Severe calcification by IVUS was associated with a higher risk of stroke.
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Purification and nucleosome mapping analysis of native yeast plasmid chromatin.
There is much evidence indicating the importance in gene regulation of the positions of nucleosomes with respect to DNA sequence. Low resolution chromatin structures have been described for many genes, but there is a dearth of detailed high resolution chromatin structures. In the cases where they are available, high resolution maps have revealed much more complex chromatin structures, with multiple alternative nucleosome positions. The discovery that ATP-dependent chromatin remodelling machines are recruited to genes, with their ability to mobilise nucleosomes on DNA and to alter nucleosomal conformation, emphasises the necessity for obtaining high resolution nucleosome maps, so that the details of these remodelling reactions can be defined in vivo. Here, we describe protocols for purifying plasmid chromatin from cells of the yeast Saccharomyces cerevisiae and for mapping nucleosome positions on the plasmid using the monomer extension mapping method. This method requires purified chromatin, but is capable of mapping relatively long stretches of chromatin in great detail. Typically, it reveals very complex chromatin structures.
Chromatin↗
Short-term infusion of the mu-opioid agonist remifentanil in humans causes hyperalgesia during withdrawal.
Numerous animal studies suggest that acute and chronic exposure to opioids can be associated with the development of hyperalgesia, i.e. an increased sensitivity to noxious stimuli. Hyperalgesia has been documented during withdrawal and on occasion while animals were still exposed to opioids. A pivotal role in the genesis of opioid-associated hyperalgesia has been attributed to a pain facilitating system involving the N-methyl-D-aspartate (NMDA)-receptor. In humans little direct evidence documents opioid-associated hyperalgesia, albeit observational data suggest that such hyperalgesia may be relevant in a clinical context. This study used a double blind, randomized, crossover and placebo-controlled design to test in opioid-naïve, healthy human volunteers whether hyperalgesia would develop within 30 min of stopping a 90-min infusion with the mu-opioid agonist remifentanil, and whether co-administration of the NMDA-receptor antagonist S-ketamine would prevent such hyperalgesia. We found that a skin area with pre-existing mechanical hyperalgesia was significantly enlarged after stopping the remifentanil infusion. However, the pain response to heat assessed in regular skin was not different before and after the infusion of remifentanil. Co-administration of the NMDA-receptor antagonist S-ketamine abolished observed enlargement of the hyperalgesic skin area. This study provides direct evidence in humans that short-term administration of an opioid can enhance hyperalgesia as observed during withdrawal and points to a potential role of the NMDA-receptor system in mediating such a hyperalgesic response. This study also points to a differential susceptibility of different pain modalities for the expression of hyperalgesia associated with opioid administration.
Adult↗
Definitive diagnosis of early enamel and dentin cracks based on microscopic evaluation.
UNLABELLED: The diagnoses of cracked teeth and incomplete coronal fracture have historically been symptom based. The dental operating microscope at 16x magnification can fundamentally change a clinician's ability to diagnose such conditions. Clinicians have been observing cracks under extreme magnification for nearly a decade. Patterns have become clear that can lead to appropriate treatment prior to symptoms or to devastation to tooth structure. Conversely, many cracks are not structural and can lead to misdiagnosis and overtreatment. Methodic microscopic examination, an understanding of crack progression, and an appreciation of the types of cracks will guide a doctor to make appropriate decisions. Teeth can have structural cracks in various stages. To date, diagnosis and treatment are very often at end stage of crack development. CLINICAL SIGNIFICANCE: This article gives new guidelines for recognition, visualization, classification, and treatment of cracked teeth based on the routine use of 16x magnification. The significance of enamel cracks as they relate to dentinal cracks is detailed.
Coloring Agents↗
SWI/SNF-dependent long-range remodeling of yeast HIS3 chromatin.
Current models for the role of the SWISNF chromatin remodeling complex in gene regulation are focused on promoters, where the most obvious changes in chromatin structure occur. Here we present evidence that the SWISNF complex is involved in the remodeling of the chromatin structure of an entire gene in vivo. We compared the native chromatin structures of a small yeast plasmid containing the HIS3 gene purified from uninduced and induced cells. Relative to uninduced chromatin, induced chromatin displayed a large reduction in negative supercoiling, a large reduction in sedimentation rate, and increased accessibility to restriction enzymes with sites located both near and far from the HIS3 promoter. These observations indicate that the entire plasmid was remodeled as a result of induction. Loss of supercoiling required the presence of the SWISNF remodeling complex and the activator Gcn4p in vivo. The TATA boxes were not required, suggesting that remodeling was not the result of transcription. The induction-dependent loss of negative supercoiling was not apparent in cells, indicating that the supercoils were lost preferentially from induced chromatin during purification. Thus, induced HIS3 chromatin has a highly labile structure that is revealed as a result of purification. It is concluded that induction of HIS3 creates a domain of labile chromatin structure that extends far beyond the promoter to include the entire gene. We propose that the SWISNF complex is recruited to the HIS3 promoter by Gcn4p and then directs remodeling of a chromatin domain, with important implications for transcription.
Chromatin↗
Comment on: Doverty et al, Hyperalgesic responses in methadone maintenance patients (Pain 2001;90;91-6).
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Animals↗
Screening for depression in a hepatitis C population: the reliability and validity of the Center for Epidemiologic Studies Depression Scale (CES-D).
RATIONALE: Depression is reported as a serious adverse event of antiviral therapy used to treat patients with hepatitis C (HCV); therefore, there is a need to identify a reliable and valid measure of depressive symptoms for this population. AIMS: To determine reliability, construct validity and predictive validity of the Center for Epidemiological Studies Depression Scale (CES-D) in a hepatitis C (HCV) population. ETHICAL ISSUES: Study reviewed/approved by the University Institutional Review Board and informed consent obtained. METHODS: Longitudinal design testing psychometric properties of the CES-D prior to treatment and 4 and 24 weeks postinitiation of treatment. Reliability was tested using Cronbach's coefficient alpha. Construct validity was tested, prior to therapy, using principal components factoring with varimax rotation. Predictive validity was tested using repeated measures analysis of variance (anova) of CES-D scores at 4 and 24 weeks postinitiation of treatment. RESULTS: Non-probability sample, 116 adult HCV patients [62 (53%) males and 54 (47%) females]. Reliability (Cronbach's alpha) = 0.88 pretreatment, 0.89 week 4 and 0.90 week 24. Construct validity testing revealed four factors: negative affect; positive affect; somatic; and depressed affect/somatic. Exception for two items, 'felt sad' and 'couldn't get going', all items loaded distinctly with correlation coefficients in the range of 0.51-0.84. Predictive validity testing revealed a statistically significant effect over time (P < 0.001) in the direction predicted (pretreatment x = 13.97; post 4 weeks x = 19.54 and 24 weeks x = 19.97). CONCLUSIONS: The CES-D is a reliable and valid instrument to screen for depressive symptoms in HCV patients. The instrument detected the predicted increase in depression associated with HCV. Examination of the sensitivity and specificity is needed to determine the most accurate cut-off score.
Adult↗
Meperidine exerts agonist activity at the alpha(2B)-adrenoceptor subtype.
BACKGROUND: The opioid agonist meperidine has actions, such as antishivering, that are more pronounced than those of other opioid agonists and that are not blocked with nonselective opioid antagonists. Agonists at the alpha(2) adrenoceptors, such as clonidine, are very effective antishivering drugs. Preliminary evidence also indicates that meperidine interacts with alpha(2) adrenoceptors. The authors therefore studied the ability of meperidine to bind and activate each of the alpha(2)-adrenoceptor subtypes in a transfected cell system. METHODS: The ability of meperidine to bind to and inhibit forskolin-stimulated cyclic adenosine monophosphate formation as mediated by the three alpha(2)-adrenoceptor subtypes transiently transfected into COS-7 cells has been tested. The ability of the opioid antagonist naloxone and the alpha(2)-adrenoceptor antagonists yohimbine and RX821002 to block the analgesic action of meperidine in the hot-plate test was also assessed. The ability of meperidine to fit into the alpha(2B) adrenoceptor was assessed using molecular modeling techniques. RESULTS: Meperidine bound to all alpha2-adrenoceptor subtypes, with alpha(2B) having the highest affinity (alpha(2B), 8.6 +/- 0.3 microm; alpha(2C), 13.6 +/- 1.5 microm, P < 0.05; alpha(2A), 38.6 +/- 0.7 microm). Morphine was ineffective at binding to any of the receptor subtypes. Meperidine inhibited the production of forskolin-stimulated cyclic adenosine monophosphate mediated by all receptor subtypes but was most effective at the alpha(2B) adrenoceptor (alpha(2B), 0.6 microm; alpha(2A), 1.3 mm; alpha(2C), 0.3 mm), reaching the same level of inhibition (approximately 70%) as achieved with the alpha2-adrenoceptor agonist dexmedetomidine. The analgesic action of meperidine was blocked by naloxone but not by the alpha 2-adrenoceptor antagonists yohimbine and RX821002. The modeling studies demonstrated that meperidine can fit into the alpha(2B)-adrenoceptor subtype. CONCLUSION: Meperidine is a potent agonist at the alpha2 adrenoceptors at its clinically relevant concentrations, especially at the alpha(2B)-adrenoceptor subtype. Activation of the alpha(2B) receptor does not contribute significantly to the analgesic action of meperidine. This raises the possibility that some of its actions, such as antishivering, are transduced by this mechanism.
Adenylyl Cyclase Inhibitors↗
Targeted histone acetylation at the yeast CUP1 promoter requires the transcriptional activator, the TATA boxes, and the putative histone acetylase encoded by SPT10.
The relationship between chromatin remodeling and histone acetylation at the yeast CUP1 gene was addressed. CUP1 encodes a metallothionein required for cell growth at high copper concentrations. Induction of CUP1 with copper resulted in targeted acetylation of both H3 and H4 at the CUP1 promoter. Nucleosomes containing upstream activating sequences and sequences farther upstream were the targets for H3 acetylation. Targeted acetylation of H3 and H4 required the transcriptional activator (Ace1p) and the TATA boxes, suggesting that targeted acetylation occurs when TATA-binding protein binds to the TATA box or at a later stage in initiation. We have shown previously that induction results in nucleosome repositioning over the entire CUP1 gene, which requires Ace1p but not the TATA boxes. Therefore, the movement of nucleosomes occurring on CUP1 induction is independent of targeted acetylation. Targeted acetylation of both H3 and H4 also required the product of the SPT10 gene, which encodes a putative histone acetylase implicated in regulation at core promoters. Disruption of SPT10 was lethal at high copper concentrations and correlated with slower induction and reduced maximum levels of CUP1 mRNA. These observations constitute evidence for a novel mechanism of chromatin activation at CUP1, with a major role for the TATA box.
Acetylation↗
What is the best contemporary treatment for in-stent restenosis?
In-stent restenosis (ISR) remains a challenging problem in percutaneous coronary intervention and the optimal treatment strategy remains unclear. The aim of this study was to compare the 18 month clinical outcomes in patients receiving sirolimus-eluting stents (SES) with vascular brachytherapy (VBT) for the treatment of ISR. Twenty-five consecutive patients treated with VBT were compared with 29 patients who had SES deployment for ISR. Major adverse cardiac events (MACE) were defined as a combination of death from cardiac causes, nonfatal myocardial infarction, or repeat TVR. At 18 month follow-up, the MACE rate was significantly lower in the SES compared with the VBT group (14% vs 40%, P=.03). One patient in the VBT group developed late stent thrombosis (at 10 months) and died; there was no stent thrombosis in the SES group. This observational study, taken with other recent reports, offers further credence to the use of SES for ISR. The results of randomized comparisons with VBT are awaited with interest.
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