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1.
Semin Musculoskelet Radiol ; 28(2): 180-192, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38484770

ABSTRACT

Increase in youth sports participation, longer duration of play, and earlier starting points have increased the prevalence of acute and repetitive overuse musculoskeletal injuries. This rise in injury rates has led to increased efforts to better understand the susceptible sites of injury that are unique to the growing immature skeleton. Upper extremity injuries are currently the best studied, particularly those that occur among pediatric baseball players and gymnasts. The weak link in skeletally immature athletes is the growth plate complex that includes those injuries located at the epiphyseal and apophyseal primary physes and the peripherally located secondary physes. This article reviews the anatomy and function of these growth plate complexes, followed by a discussion of the pathophysiologic mechanisms, spectrum of imaging findings, and existing evidence-based guidelines for injury prevention and return to play.


Subject(s)
Athletic Injuries , Baseball , Humans , Adolescent , Child , Athletic Injuries/diagnostic imaging , Return to Sport , Upper Extremity/diagnostic imaging , Upper Extremity/injuries , Athletes , Radiologists , Baseball/injuries
2.
Int J Mol Sci ; 24(24)2023 Dec 05.
Article in English | MEDLINE | ID: mdl-38138972

ABSTRACT

Despite the recent progress in the diagnosis of tuberculosis (TB), the chemotherapeutic management of TB continues to be challenging. Mycobacterium tuberculosis (Mtb), the etiological agent of TB, is classified as the 13th leading cause of death globally. In addition, 450,000 people were reported to develop multi-drug-resistant TB globally. The current project focuses on targeting methionine aminopeptidase (MetAP), an essential protein for the viability of Mtb. MetAP is a metalloprotease that catalyzes the excision of the N-terminal methionine (NME) during protein synthesis, allowing the enzyme to be an auspicious target for the development of novel therapeutic agents for the treatment of TB. Mtb possesses two MetAP1 isoforms, MtMetAP1a and MtMetAP1c, which are vital for Mtb viability and, hence, a promising chemotherapeutic target for Mtb therapy. In this study, we cloned and overexpressed recombinant MtMetAP1c. We investigated the in vitro inhibitory effect of the novel MetAP inhibitor, OJT008, on the cobalt ion- and nickel ion-activated MtMetAP1c, and the mechanism of action was elucidated through an in silico approach. The compound's potency against replicating and multi-drug-resistant (MDR) Mtb strains was also investigated. The induction of the overexpressed recombinant MtMetAP1c was optimized at 8 h with a final concentration of 1 mM Isopropyl ß-D-1-thiogalactopyranoside. The average yield from 1 L of Escherichia coli culture for MtMetAP1c was 4.65 mg. A preliminary MtMetAP1c metal dependency screen showed optimum activation with nickel and cobalt ions occurred at 100 µM. The half-maximal inhibitory concentration (IC50) values of OJT008 against MtMetAP1c activated with CoCl2 and NiCl2 were 11 µM and 40 µM, respectively. The in silico study showed OJT008 strongly binds to both metal-activated MtMetAP1c, as evidenced by strong molecular interactions and a higher binding score, thereby corroborating our result. This in silico study validated the pharmacophore's metal specificity. The potency of OJT008 against both active and MDR Mtb was <0.063 µg/mL. Our study reports OJT008 as an inhibitor of MtMetAP1c, which is potent at low micromolar concentrations against both active susceptible and MDR Mtb. These results suggest OJT008 is a potential lead compound for the development of novel small molecules for the therapeutic management of TB.


Subject(s)
Mycobacterium tuberculosis , Tuberculosis, Multidrug-Resistant , Tuberculosis , Humans , Nickel/pharmacology , Aminopeptidases/genetics , Aminopeptidases/chemistry , Tuberculosis/microbiology , Methionyl Aminopeptidases , Tuberculosis, Multidrug-Resistant/drug therapy , Metals/pharmacology , Cobalt/pharmacology , Antitubercular Agents/chemistry
3.
Lancet Reg Health Am ; 27: 100613, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37860751

ABSTRACT

Background: Local area immigrant fraction is strongly and positively correlated with local life expectancy in the United States. The aim of the study was to determine the relationship between local area immigrant fraction and local prevalence of coronary heart disease (CHD) and stroke. Methods: Cross-sectional study design, with ZIP code as the unit of observation. Demographic data was obtained from the American Community Survey, and linked to indicators of health access (e.g., insurance, annual check-ups, cholesterol screening), obesity, behavior (smoking, exercise), and cardiovascular outcomes data from the 2020 Population Level Analysis and Community Estimates. Multivariable regression and path analyses were used to assess both direct and indirect relationships among variables. Findings: CHD prevalence was lower in the second (3.9% relative difference, 95% CI: 3.1-4.5%), third (6.5%, 95% CI: 5.8-7.1%), and fourth (14.8%, 95% CI: 14.1-15.8%) quartiles of immigrant fraction compared to the lowest (p-trend <0.001). These effects remained robust in multivariable analysis following adjustment for indicators of access, obesity, and behavioral variables (p-trend <0.0001). For stroke, only the highest quartile demonstrated a significant difference in prevalence (2.1%, 95% CI: 1.2-3.0% with full adjustment). In CHD path analysis, ∼45% of the association of immigrant fraction was direct, and ∼55% was mediated through lower prevalence of deleterious behaviors (e.g., smoking). In stroke path analysis, the effect was entirely mediated through indirect effects. Interpretation: In the United States, ZIP codes with higher immigrant fractions have lower prevalence of cardiovascular diseases. These associations are partially mediated through differences in health behaviors at the community level. Funding: NIH (K08CA252635, P30AG0059304, K24HL150476), Stanford University, Rutgers University.

4.
J Control Release ; 266: 238-247, 2017 Nov 28.
Article in English | MEDLINE | ID: mdl-28987879

ABSTRACT

Worldwide, tuberculosis (TB) remains one of the most prevalent infectious diseases causing morbidity and death in >1.5 million patients annually. Mycobacterium tuberculosis (Mtb), the etiologic agent of TB, usually resides in the alveolar macrophages. Current tuberculosis treatment methods require more than six months, and low compliance often leads to therapeutic failure and multidrug resistant strain development. Critical to improving TB-therapy is shortening treatment duration and increasing therapeutic efficacy. In this study, we sought to determine if lung hemodynamics and pathological changes in Mtb infected cells can be used for the selective targeting of microparticles to infected tissue(s). Thioaptamers (TA) with CD44 (CD44TA) targeting moiety were conjugated to discoidal silicon mesoporous microparticles (SMP) to enhance accumulation of these agents/carriers in the infected macrophages in the lungs. In vitro, CD44TA-SMP accumulated in macrophages infected with mycobacteria efficiently killing the infected cells and decreasing survival of mycobacteria. In vivo, increased accumulations of CD44TA-SMP were recorded in the lung of M. tuberculosis infected mice as compared to controls. TA-targeted carriers significantly diminished bacterial load in the lungs and caused recruitment of T lymphocytes. Proposed mechanism of action of the designed vector accounts for a combination of increased uptake of particles that leads to infected macrophage death, as well as, activation of cellular immunity by the TA, causing increased T-cell accumulation in the treated lungs. Based on our data with CD44TA-SMP, we anticipate that this drug carrier can open new avenues in TB management.


Subject(s)
Aptamers, Nucleotide/administration & dosage , Drug Carriers/administration & dosage , Hyaluronan Receptors/genetics , Mycobacterium tuberculosis , Tuberculosis/drug therapy , Animals , Cells, Cultured , Female , Humans , Hyaluronan Receptors/metabolism , Lung/immunology , Lung/metabolism , Macrophages/metabolism , Mice, Inbred BALB C , Silicon/administration & dosage , T-Lymphocytes/immunology , Tuberculosis/immunology , Tuberculosis/metabolism
5.
Tuberculosis (Edinb) ; 101S: S73-S77, 2016 12.
Article in English | MEDLINE | ID: mdl-27856197

ABSTRACT

Mycobacterium tuberculosis (Mtb) and the Human Immunodeficiency Virus (HIV) pose a major public health threat. The 2015 World Health Organization (WHO) report estimates that one in three HIV deaths is due to Mtb, the causative agent of Tuberculosis (TB). The lethal synergy between these two pathogens leads to a decline in the immune function of infected individuals as well as a rise in morbidity and mortality rates. The deadly interaction between TB and HIV, along with the heightened emergence of drug resistance, drug-drug interactions, reduced drug efficacy and increased drug toxicity, has made the therapeutic management of co-infected individuals a major challenge. Hence, the development of new drug targets and/or new drug leads are imperative for the effective therapeutic management of co-infected patients. Here, we report the characterization of 2-hydroxy-1-naphthaldehyde isonicotinoyl hydrazone (311), a known inhibitor of HIV-1 replication and transcription as a new inhibitor of methionine aminopeptidases (MetAPs) from Mycobacterium tuberculosis: MtMetAP1a and MtMetAP1c. MetAP is a metalloprotease that removes the N-terminal methionine during protein synthesis. The essential role of MetAP in microbes makes it a promising chemotherapeutic target. We demonstrated that 311 is a potent and selective inhibitor of MtMetAP1a and MtMetAP1c. Furthermore, we found that 311 is active against replicating and aged non-growing Mtb at low micromolar concentrations. These results suggest that 311 is a promising lead for the development of novel class of therapeutic agents with dual inhibition of TB and HIV for the treatment of TB-HIV co-infection.


Subject(s)
Aminopeptidases/antagonists & inhibitors , Antitubercular Agents/pharmacology , Bacterial Proteins/antagonists & inhibitors , Enzyme Inhibitors/pharmacology , Mycobacterium tuberculosis/drug effects , Tuberculosis/drug therapy , Aminopeptidases/metabolism , Anti-HIV Agents/pharmacology , Bacterial Proteins/metabolism , Coinfection , Dose-Response Relationship, Drug , HIV Infections/drug therapy , HIV Infections/virology , High-Throughput Screening Assays , Humans , Isoniazid/pharmacology , Mycobacterium tuberculosis/enzymology , Mycobacterium tuberculosis/growth & development , Tuberculosis/microbiology
6.
Tuberculosis (Edinb) ; 101S: S119-S123, 2016 12.
Article in English | MEDLINE | ID: mdl-27742463

ABSTRACT

While there have been research efforts to find faster and more efficient diagnostic techniques for tuberculosis (TB), it is equally important to monitor a patient's response to treatment over time, especially with the increasing prevalence of multi-drug resistant (MDR) and extensively-drug resistant (XDR) TB. Between sputum smear microscopy, culture, and GeneXpert, only culture can verify viability of mycobacteria. However, it may take up to six weeks to grow Mycobacterium tuberculosis (Mtb), during which time the patient may have responded to treatment or the mycobacteria are still viable because the patient has MDR or XDR TB. In both situations, treatment incurs increased patient costs and makes them more susceptible to host-drug effects such as liver damage. Coenzyme Factor 420 (F420) is a fluorescent coenzyme found naturally in mycobacteria, with an excitation peak around 420 nm and an emission peak around 470 nm. Using Mycobacterium smegmatis, we show that live and dead mycobacteria undergo different rates of photobleaching over a period of 2 min. These preliminary experiments suggest that the different photobleaching rates could be used to help monitor a patient's response to TB treatment. In future studies, we propose to describe these experiments with Mtb as both M. smegmatis and Mtb use F420.


Subject(s)
Microscopy, Fluorescence , Mycobacterium Infections, Nontuberculous/diagnosis , Mycobacterium smegmatis/enzymology , Optical Imaging/methods , Riboflavin/analogs & derivatives , Biomarkers/metabolism , Humans , Microbial Viability , Mycobacterium Infections, Nontuberculous/microbiology , Mycobacterium smegmatis/isolation & purification , Predictive Value of Tests , Riboflavin/metabolism , Time Factors
7.
Ann Am Thorac Soc ; 12(1): 12-20, 2015 Jan.
Article in English | MEDLINE | ID: mdl-25419914

ABSTRACT

RATIONALE: HIV-associated tuberculosis remains a major health problem among the gold-mining workforce in South Africa. We postulate that high levels of recent transmission, indicated by strain clustering, are fueling the tuberculosis epidemic among gold miners. OBJECTIVES: To combine molecular and epidemiologic data to describe Mycobacterium tuberculosis genetic diversity, estimate levels of transmission, and examine risk factors for clustering. METHODS: We conducted a cross-sectional study of culture-positive M. tuberculosis isolates in 15 gold mine shafts across three provinces in South Africa. All isolates were subject IS6110-based restriction fragment length polymorphisms, and we performed spoligotyping analysis and combined it with basic demographic and clinical information. MEASUREMENTS AND MAIN RESULTS: Of the 1,602 M. tuberculosis patient isolates, 1,240 (78%) had genotyping data available for analysis. A highly diverse bacillary population was identified, comprising a total of 730 discrete genotypes. Four genotypic families (Latin American Mediterranean spoligotype family; W-Beijing; AH or X; and T1-T4) accounted for over 50% of all strains. Overall, 45% (560/1,240) of strains were genotypically clustered. The minimum estimate for recent transmission (n - 1 method) was 32% (range, 27-34%). There were no individual-level risk factors for clustering, apart from borderline evidence for being non-South African and having self-reported HIV infection. CONCLUSIONS: The high M. tuberculosis genetic diversity and lack of risk factors for clustering are indicative of a universal risk for disease among gold miners and likely mixing with nonmining populations. Our results underscore the urgent need to intensify interventions to interrupt transmission across the entire gold-mining workforce in South Africa.


Subject(s)
DNA, Bacterial/genetics , Mining , Molecular Epidemiology/methods , Mycobacterium tuberculosis/genetics , Tuberculosis/epidemiology , Adult , Cross-Sectional Studies , Female , Genotype , Gold , Humans , Incidence , Male , Mycobacterium tuberculosis/isolation & purification , Polymorphism, Restriction Fragment Length , South Africa/epidemiology , Tuberculosis/microbiology
8.
Poult Sci ; 93(1): 187-93, 2014 Jan.
Article in English | MEDLINE | ID: mdl-24570438

ABSTRACT

The physico-chemical quality attributes of meat from broilers with significant differences in growth rate were investigated in this study. Two chicken populations from a random mating broiler control population were established as a slow-growing subpopulation (SG) with an average growth rate of 229 g/wk and a fast-growing subpopulation (FG) with an average growth rate of 319 g/wk. The initial pH at 15 min and final pH after 24 h were higher (P < 0.05) in breast muscle from FG than muscle from the SG population. Muscle from the SG had higher (P < 0.05) L* and b* of 57.0 and 11.2, compared with L* and b* of 55.8 and 10.5 from the FG. Although no difference in a* was observed, hue angle was different (P < 0.05) at 52.7 and 50.4 in FG and SG populations, respectively. Water-holding capacity was 25 to 27% and not different between the populations, but 5-d drip loss at 8.48% was higher (P < 0.05) in the muscle from the SG compared with the FG at 6.44%. Cook yield was higher (P < 0.05) in the FG muscle at 86.92% compared with the SG muscle at 85.96%. There was a positive correlation of +0.20 between pH difference and drip loss only in the FG. Significantly higher (P < 0.05) cook yields were observed in muscle from FG than SG chickens. The lower weight, higher L* value, and lower initial and final pH values in the SG population, coupled with higher drip loss and lower cook yield, likely result from differences in growth rate.


Subject(s)
Chickens/growth & development , Chickens/genetics , Muscle, Skeletal/physiology , Animals , Female , Male
9.
PLoS One ; 8(12): e82727, 2013.
Article in English | MEDLINE | ID: mdl-24367546

ABSTRACT

RATIONALE: Each year 1 million persons acquire permanent U.S. residency visas after tuberculosis (TB) screening. Most applicants undergo a 2-stage screening with tuberculin skin test (TST) followed by CXR only if TST-positive at > 5 mm. Due to cross reaction with bacillus Calmette-Guérin (BCG), TST may yield false positive results in BCG-vaccinated persons. Interferon gamma release assays exclude antigens found in BCG. In Vietnam, like most high TB-prevalence countries, there is universal BCG vaccination at birth. OBJECTIVES: 1. Compare the sensitivity of QuantiFERON-TB Gold In-Tube Assay (QFT) and TST for culture-positive pulmonary TB. 2. Compare the age-specific and overall prevalence of positive TST and QFT among applicants with normal and abnormal CXR. METHODS: We obtained TST and QFT results on 996 applicants with abnormal CXR, of whom 132 had TB, and 479 with normal CXR. RESULTS: The sensitivity for tuberculosis was 86.4% for QFT; 89.4%, 81.1%, and 52.3% for TST at 5, 10, and 15 mm. The estimated prevalence of positive results at age 15-19 years was 22% and 42% for QFT and TST at 10 mm, respectively. The prevalence increased thereafter by 0.7% year of age for TST and 2.1% for QFT, the latter being more consistent with the increase in TB among applicants. CONCLUSIONS: During 2-stage screening, QFT is as sensitive as TST in detecting TB with fewer requiring CXR and being diagnosed with LTBI. These data support the use of QFT over TST in this population.


Subject(s)
BCG Vaccine/therapeutic use , Skin Tests/methods , Tuberculosis/diagnosis , Tuberculosis/epidemiology , Adolescent , Adult , Emigrants and Immigrants , Female , Humans , Male , Sensitivity and Specificity , Young Adult
10.
Am J Respir Crit Care Med ; 187(2): 206-11, 2013 Jan 15.
Article in English | MEDLINE | ID: mdl-23103734

ABSTRACT

RATIONALE: Although IFN-γ release assays (IGRAs) are widely used to screen for Mycobacterium tuberculosis infection in high-income countries, published data on repeatability are limited. OBJECTIVES: To determine IGRA repeatability. METHODS: The study population included consecutive patients referred to The Methodist Hospital (Houston, TX) between August 1, 2010 and July 31, 2011 for latent tuberculosis (TB) infection screening with an IGRA (QuantiFERON-TB Gold In-Tube; Cellestis, Carnegie, Australia). We performed multiple IGRA tests using leftover stimulated plasma according to a prospectively formulated quality control protocol. We analyzed agreement in interpretation of test results classified according to manufacturer-recommended criteria and repeatability of quantitative TB response. MEASUREMENTS AND MAIN RESULTS: During the study period, 1,086 test results were obtained from 543 subjects. Per the manufacturer's cut-point, the result of the second test was discordant from that of the first in 28 (8%) of 366 patients with valid test results, including 13 with an initial negative result and 15 with an initial positive result. Although agreement between repeat test results was high (κ = 0.84; 95% confidence interval, 0.79-0.90), the normal expected range of within-subject variability in TB response on retesting included differences of ± 0.60 IU/ml for all individuals (coefficient of variation, 14%), and ± 0.24 IU/ml (coefficient of variation, 27%) for individuals whose initial TB response was between 0.25 and 0.80 IU/ml. CONCLUSIONS: There is substantial variability in TB response when IGRAs are repeated using the same patient sample. IGRA results should be interpreted cautiously when TB response is near interpretation cut-points.


Subject(s)
Latent Tuberculosis/diagnosis , Adult , Female , Humans , Immunoassay/methods , Immunoassay/standards , Interferon-gamma/immunology , Male , Reagent Kits, Diagnostic , Reproducibility of Results
11.
Tuberculosis (Edinb) ; 93 Suppl: S38-46, 2013 Dec.
Article in English | MEDLINE | ID: mdl-24388648

ABSTRACT

Tuberculosis genotypic clustering is used as a proxy for recent transmission. The association between clustering and recent transmission becomes problematic when the genotyping method lacks specificity in defining a cluster, as well as for clusters with extensive jurisdictional histories and/or common genotypes. We investigated the four largest spoligotype/12 loci MIRU-VNTR-defined clusters in Harris County, Texas from 2006-2012 to determine their historical contribution to tuberculosis morbidity, estimate the contributions from recent and remote transmission, and determine the impact of secondary genotyping on cluster definition. The clusters contained 189, 64, 51 and 38 cases. Each cluster was linked to cluster(s) previously identified by Houston Tuberculosis Initiative; 3 since 1995 and the fourth in 2002. Among cases for which timing of Mycobacterium tuberculosis transmission relative to tuberculosis disease could be ascertained, nearly equal proportions were associated with recent and remote transmission. The extent to which genotyping with an additional 12 MIRU-VNTR loci modified the cluster definition varied from little or no impact for the two smaller clusters to moderate impact for the larger clusters. Tuberculosis control measures to reduce morbidity associated with large clusters must involve strategies to identify and treat individuals who recently acquired infection, as well as persons infected for years.


Subject(s)
Bacterial Typing Techniques/methods , Mycobacterium tuberculosis/isolation & purification , Tuberculosis/transmission , Age Factors , DNA, Bacterial , Evolution, Molecular , Female , Genotype , Humans , Male , Molecular Epidemiology , Social Class , Texas , Tuberculosis/epidemiology , Tuberculosis/prevention & control , United States
12.
PLoS One ; 6(1): e16317, 2011 Jan 21.
Article in English | MEDLINE | ID: mdl-21283700

ABSTRACT

An ancestral polymorphic allele of the human autophagy-related gene IRGM1 is associated with altered gene expression and a genetic risk for Crohn's Disease (CD). We used the single nucleotide polymorphism rs10065172C/T as a marker of this polymorphic allele and genotyped 370 African American and 177 Caucasian tuberculosis (TB) cases and 180 African American and 110 Caucasian controls. Among African Americans, the TB cases were more likely to carry the CD-related T allele of rs10065172 (odds ratio of 1.54; 95% confidence interval, 1.17-2.02; P<0.01) compared to controls. Our finding suggests that this CD-related IRGM1 polymorphic allele is also associated with human susceptibility to TB disease among African Americans.


Subject(s)
Black or African American/genetics , GTP-Binding Proteins/genetics , Genetic Predisposition to Disease/ethnology , Polymorphism, Single Nucleotide , Tuberculosis/ethnology , Tuberculosis/genetics , Alleles , Crohn Disease/genetics , GTP-Binding Proteins/physiology , Genetic Markers , Genetic Predisposition to Disease/genetics , Humans , White People/genetics
14.
J Mol Cell Cardiol ; 43(6): 744-53, 2007 Dec.
Article in English | MEDLINE | ID: mdl-17959196

ABSTRACT

The intracellular circadian clock consists of a series of transcriptional modulators that together allow the cell to perceive the time of day. Circadian clocks have been identified within various components of the cardiovascular system (e.g. cardiomyocytes, vascular smooth muscle cells) and possess the potential to regulate numerous aspects of cardiovascular physiology and pathophysiology. The present study tested the hypothesis that ischemia/reperfusion (I/R; 30 min occlusion of the rat left main coronary artery in vivo) alters the circadian clock within the ischemic, versus non-ischemic, region of the heart. Left ventricular anterior (ischemic) and posterior (non-ischemic) regions were isolated from I/R, sham-operated, and naïve rats over a 24-h period, after which mRNAs encoding for both circadian clock components and known clock-controlled genes were quantified. Circadian clock gene oscillations (i.e. peak-to-trough fold differences) were rapidly attenuated in the I/R, versus the non-ischemic, region. Consistent with decreased circadian clock output, we observe a rapid induction of E4BP4 in the ischemic region of the heart at both the mRNA and protein levels. In contrast with I/R, chronic (1 week) hypobaric chamber-induced hypoxia did not attenuate oscillations in circadian clock genes in either the left or right ventricle of the rat heart. In conclusion, these data show that in a rodent model of myocardial I/R, circadian clocks within the ischemic region become rapidly impaired, through a mechanism that appears to be independent of hypoxia.


Subject(s)
Biological Clocks/genetics , Circadian Rhythm/genetics , Myocardial Reperfusion Injury/genetics , Myocardium/metabolism , Myocardium/pathology , Animals , Basic Helix-Loop-Helix Transcription Factors/genetics , Basic Helix-Loop-Helix Transcription Factors/metabolism , CLOCK Proteins , Cell Hypoxia , Gene Expression Regulation , Male , Rats , Rats, Wistar , Trans-Activators/genetics , Trans-Activators/metabolism
15.
Am J Physiol Heart Circ Physiol ; 293(4): H2385-93, 2007 Oct.
Article in English | MEDLINE | ID: mdl-17616739

ABSTRACT

Multiple extracardiac stimuli, such as workload and circulating nutrients (e.g., fatty acids), known to influence myocardial metabolism and contractile function exhibit marked circadian rhythms. The aim of the present study was to investigate whether the rat heart exhibits circadian rhythms in its responsiveness to changes in workload and/or fatty acid (oleate) availability. Thus, hearts were isolated from male Wistar rats (housed during a 12:12-h light-dark cycle: lights on at 9 AM) at 9 AM, 3 PM, 9 PM, and 3 AM and perfused in the working mode ex vivo with 5 mM glucose plus either 0.4 or 0.8 mM oleate. Following 20-min perfusion at normal workload (i.e., 100 cm H(2)O afterload), hearts were challenged with increased workload (140 cm H(2)O afterload plus 1 microM epinephrine). In the presence of 0.4 mM oleate, myocardial metabolism exhibited a marked circadian rhythm, with decreased rates of glucose oxidation, increased rates of lactate release, decreased glycogenolysis capacity, and increased channeling of oleate into nonoxidative pathways during the light phase. Rat hearts also exhibited a modest circadian rhythm in responsiveness to the workload challenge when perfused in the presence of 0.4 mM oleate, with increased myocardial oxygen consumption at the dark-to-light phase transition. However, rat hearts perfused in the presence of 0.8 mM oleate exhibited a markedly blunted contractile function response to the workload challenge during the light phase. In conclusion, these studies expose marked circadian rhythmicities in myocardial oxidative and nonoxidative metabolism as well as responsiveness of the rat heart to changes in workload and fatty acid availability.


Subject(s)
Circadian Rhythm , Heart/physiology , Myocardial Contraction , Myocardium/metabolism , Oleic Acid/metabolism , Animals , Glucose/metabolism , Glycogenolysis , Heart/drug effects , Lactic Acid/metabolism , Male , Myocardial Contraction/drug effects , Myocardium/enzymology , Oleic Acid/pharmacology , Oxidation-Reduction , Oxygen Consumption , Perfusion , Rats , Rats, Wistar , Research Design , Time Factors
16.
Orthod Craniofac Res ; 6(1): 63-71, 2003 Feb.
Article in English | MEDLINE | ID: mdl-12627797

ABSTRACT

OBJECTIVES: To compare the judgments of facial esthetics, defects and treatment needs between laypersons and professionals (orthodontists and oral surgeons) as predictors of patient's motivation for orthognathic surgery. DESIGN: Two panels of expert and naïve raters were asked to evaluate photographs of orthognathic surgery patients for facial esthetics, defects and treatment needs. Results were correlated with patients' motivation for surgery. SETTING AND SAMPLE POPULATION: Fifty-seven patients (37 females and 20 males) with a mean age of 26.0 +/- 6.7 years were interviewed prior to orthognathic surgery treatment. Three color photographs of each patient were evaluated by a panel of 14 experts and panel of 18 laypersons. EXPERIMENTAL VARIABLES: Each panel of raters were asked to evaluate the facial morphology, facial attractiveness and recommend surgical treatment (independent variables). The dependent variable was the patient's motivation for orthognathic surgery. Outcome measure--Reliability of raters were analyzed using an unweighted Kappa coefficient and a Cronbach alpha coefficient. Correlations and regression analyses were used to quantify the relationship between variables. RESULTS: Expert raters provided reliable ratings of certain morphological features such as excessive gingival display and classification of mandibular facial form and position. Based on the facial photographs both expert and naïve raters agreed on facial attractiveness of patients. The best predictors of patients' motivation for surgery were the naïve profile attractiveness rating and the patients' expected change in self-consciousness. CONCLUSIONS: Expert raters provide more reliable ratings on certain morphologic features. However, the layperson's profile attractiveness rating and the patients' expected change in self-consciousness were the best predictors for patients' motivation for surgery. These data suggest that patients' motives for treatment are not necessarily related to objectively determined need. Patients' decision to seek treatment was more correlated to laypersons' rating of attractiveness because they see what other laypersons see, and are directly or indirectly affected by others reactions to their appearance. These findings may provide useful information for clinicians in counseling patients who seek orthognathic surgery.


Subject(s)
Attitude to Health , Esthetics , Face/anatomy & histology , Malocclusion/surgery , Motivation , Adolescent , Adult , Female , Gingiva/pathology , Humans , Logistic Models , Male , Malocclusion/pathology , Malocclusion/psychology , Mandible/pathology , Middle Aged , Needs Assessment , Orthodontics , Photography , Reproducibility of Results , Self Concept , Statistics as Topic , Students , Surgery, Oral
17.
Pediatr Dent ; 23(3): 265-9, 2001.
Article in English | MEDLINE | ID: mdl-11447962

ABSTRACT

PURPOSE: The purpose of this survey is to evaluate current usage of local and topical anesthesia by Pediatric Dentist to evaluate the current practices. METHODS: Surveys were sent to 3051 pediatric dentists asking about types of anesthetics, considerations in determining local anesthetic dosage, time used to inject a cartridge and shortcomings of topical preparations. Data were computed for percentage responses. RESULTS: The response rate was 55%. Only 49% used exact body weight to determine local anesthetic dosage. The mostly commonly used needles for infiltrations were 30-gauge short and blocks were 27-gauge short. Only 11% of the respondents were using > or = 60 seconds to inject a full cartridge. Topical anesthetics were used by most, with the most commonly used brand being Hurricaine [correction of Hurricane]. A third waited 60 seconds before injecting after the application of the topical anesthetic. Most patients (89%) disliked the taste of topical anesthetics and adverse drug reactions were rarely seen. CONCLUSIONS: The findings of this study demonstrate that Pediatric Dentists are most commonly using Lidocaine as the preferred type of local anesthetic using 30 gauge short needle for infiltrations and 27 gauge short needle for blocks. Most were taking anywhere from 11-> 60 seconds to inject a cartridge. Topical anesthetic was used by most and the preferred brand was Hurricaine, however their perception of the effectiveness of topical anesthetics varied. There also appears to be a need to develop newer and better mode of topical anesthetic delivery system in the pediatric dental population.


Subject(s)
Anesthesia, Dental , Anesthesia, Local , Anesthetics, Local/administration & dosage , Attitude of Health Personnel , Pediatric Dentistry , Practice Patterns, Dentists' , Administration, Topical , Benzocaine/administration & dosage , Body Weight , Child , Drug Delivery Systems , Drug Utilization , Equipment Design , Humans , Injections , Lidocaine/administration & dosage , Needles , Nerve Block , Patient Satisfaction , Surface Properties , Time Factors , United States
18.
Am J Orthod Dentofacial Orthop ; 119(1): 11-20, 2001 Jan.
Article in English | MEDLINE | ID: mdl-11174532

ABSTRACT

A tandem-loop nickel titanium temperature-activated palatal expansion appliance was developed that produces light, continuous pressure on the midpalatal suture and requires little patient cooperation or laboratory work. The purpose of this study was to compare the effectiveness of the nickel titanium palatal expansion appliance with that of a rapid palatal expansion appliance. The study sample comprised 25 patients who required palatal expansion as part of their orthodontic treatment. The sample was divided into 2 groups, with 13 patients in the nickel titanium group and 12 patients in the rapid palatal expansion group. Study models were taken before treatment and at the end of the retention period after expansion. Intermolar width, palatal width, palatal depth, alveolar tipping, molar tipping, and molar rotation were analyzed. In addition, occlusal radiographs were obtained before and 2 weeks after expansion to evaluate for sutural separation by the appliances. Results showed significant increases in midpalatal sutural separation, tipping of the alveolus, and tipping of the molars after expansion in both groups. However, greater midpalatal sutural separation was found in the rapid palatal expansion group and greater molar rotation was found in the nickel titanium group. Stepwise multiple regression analysis showed that alveolar tipping, palatal width change, and molar tipping are the best predictors of intermolar width change in the rapid palatal expansion group. Radiographic evidence of midpalatal sutural separation was less obvious in the nickel titanium group. These results suggest that both the nickel titanium and the rapid palatal expansion appliances are capable of expanding the maxillary dentition and alveolar process and are equally capable of correcting posterior crossbites. In the current study, the rapid palatal expander widened the palate more reliably, whereas the nickel titanium expander tipped the molars buccally to a greater extent and caused more distal molar rotation. The clinician's choice of expander will depend on his or her initial diagnosis and treatment goals.


Subject(s)
Dental Alloys , Nickel , Orthodontic Appliance Design , Orthodontic Appliances , Palatal Expansion Technique/instrumentation , Titanium , Alveolar Process/pathology , Child , Cranial Sutures/diagnostic imaging , Cranial Sutures/pathology , Dental Arch/pathology , Female , Forecasting , Humans , Male , Malocclusion/therapy , Maxilla/pathology , Models, Dental , Molar/pathology , Palate/diagnostic imaging , Palate/pathology , Radiography , Regression Analysis , Reproducibility of Results , Rotation
19.
Am J Orthod Dentofacial Orthop ; 118(4): 414-20, 2000 Oct.
Article in English | MEDLINE | ID: mdl-11029737

ABSTRACT

The purpose of this study was to use the Peer Assesment Rating (PAR) index score to evaluate the treatment and posttreatment changes of Class III patients treated by protraction facemask. The sample consisted of 20 Chinese children, 6 to 11 years old, with Class III skeletal malocclusion who had been treated with maxillary expansion and a protraction facemask. The average treatment time was 8.2 months, followed by 1 year of retention with a Class III functional appliance. Study casts were taken pretreatment (T1), posttreatment (T2), 1 year follow-up (T3), and 2 years follow-up (T4). After treatment, PAR scores were calculated for each time period. Differences among the 4 time periods were analyzed with the Wilcoxin matched-pairs test. Significant reductions in PAR scores were found at T2 (56%), T3 (70%), and T4 (63%) compared with T1. Immediately posttreatment (T2), 17 (85%) of 20 patients had improved PAR scores by a reduction of at least 30%. Reductions were caused primarily by correction of the anterior crossbite. One year after treatment (T3), further reductions in PAR score were noted (P <.01) as a result of better alignment of the anterior segment, improvement of the buccal occlusion, and overbite and midline corrections. Two years after treatment (T4), PAR scores were higher than at the previous time period. The increases were due to relapses in overjet (4 of 20 patients), overbite, and centerline corrections. These results indicate that significant reductions in the severity of Class III malocclusion can be achieved with early orthopedic facemask treatment. In most cases, further improvement in the PAR score can be expected 1 and 2 years after treatment. In a few patients, the benefits of early treatment are negated by relapses in overjet, overbite, and centerline corrections during the follow-up period.


Subject(s)
Extraoral Traction Appliances , Malocclusion, Angle Class III/therapy , Orthodontics, Corrective/instrumentation , Outcome Assessment, Health Care/methods , Peer Review, Health Care , Child , Female , Humans , Male , Orthodontic Appliance Design , Orthodontic Retainers , Recurrence , Reproducibility of Results , Statistics, Nonparametric
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