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Biomedical subjects

L McLaughlin

Publications and source records attributed to L McLaughlin.

At least 19 recordsLinked to original sources
PubMed2002

A survey to examine attitudes and patterns of practice of physiotherapists who perform cervical spine manipulation.

As part of the process of developing a Clinical Practice Guideline (CPG) on cervical spine manipulation (CSM), a working group sent out an 82-item postal survey to 150 randomly selected Ontario physiotherapists (PTs) who perform spinal manipulation, to collect information on the socio-demographics, practices, opinions of risk, and attitudes towards CPGs of these PTs (n = 118; response rate = 79%). Of the 118 respondents who performed spinal manipulation, 41 performed CSM. Respondents strongly agreed with three out of six indications listed in the survey for applying CSM: segmental fixation, stiff but stable joint, internal derangement (over 70%). Respondents also strongly agreed (over 88%) that all screening tests listed in the survey should be performed prior to applying CSM: tests for irritability, stability, vascular and neurological systems. Respondents rated patient education, other manual therapy, and exercise as the most common adjuncts to CSM (over 88%). Respondents reported seeing mild complications or side effects only rarely following the application of CSM. Fourteen percent of respondents reported having a written CSM policy or CPG on CSM in their work setting. Feedback from this survey will be used in developing a CSM CPG. A future survey will evaluate changes in clinical practice and in attitudes toward CPGs some time after the dissemination of the CSM CPG.

Adult↗
PubMed2002

Clinical practice guideline on the use of manipulation or mobilization in the treatment of adults with mechanical neck disorders.

PURPOSE: An evidence-based clinical practice guideline was developed to ascertain the risks and benefits for manipulation or mobilization in treating mechanical neck disorders with or without radicular findings or cerviogenic headache. Pain, function, patient satisfaction and adverse events were appraised. METHODS: The practice guideline development cycle/model and Cochrane reviewing process, critiquing past reviews, randomized trials and surveys were used. RESULTS: Manipulation and mobilization alone showed similar effects as placebo, wait period, or control group, and appeared similar in benefit for pain relief. While high-technology exercises were superior to manipulation alone for improving long-term pain scores, manipulation plus low-technology exercise had the same effect. Patient satisfaction scores favoured manipulation plus low-technology exercise over manipulation alone, and high-technology exercise alone. Multi-modal care including some combination of manipulation or mobilizations and exercise was superior to control, other physical medicine methods, and rest. Based on weak evidence, estimates for serious complication for manipulation ranged from one in 20,000 to five in 10,000,000. RECOMMENDATIONS: Stronger evidence suggests a multi-modal management strategy using mobilization or manipulation plus exercise is beneficial for relief of mechanical neck pain. Weaker evidence suggest less benefit to either manipulation/mobilization done alone than when used with exercise. The risk rate is uncertain.

Evidence-Based Medicine↗
PubMed2001

Solar ultraviolet-induced erythema in human skin and nuclear factor-kappa-B-dependent gene expression in keratinocytes are modulated by a French maritime pine bark extract.

The procyanidin-rich French maritime pine bark extract Pycnogenol (PBE) has been investigated for its effect in protecting human skin against solar UV-simulated light-induced erythema. Twenty-one volunteers were given an oral supplementation of Pycnogenol: 1.10 mg/kg body weight (b. wt.)/d for the first 4 weeks and 1.66 mg/kg b. wt./d for the next 4 weeks. The minimal erythema dose (MED) was measured twice before supplementation (baseline MED), once after the first 4 weeks of supplementation, and a last time at the end of the study. The UVR dose necessary to achieve 1 MED was significantly increased during PBE supplementation. Since the activation of the pro-inflammatory and redox-regulated transcription factor NF-kappaB is thought to play a major role in UVR-induced erythema, the effect of PBE was also investigated in the human keratinocyte cell line HaCaT. PBE, added to the cell culture medium, inhibited UVR-induced NF-kappaB-dependent gene expression in a concentration-dependent manner. However, NF-kappaB-DNA-binding activity was not prevented, suggesting that PBE affects the transactivation capacity of NF-kappaB. These data indicate that oral supplementation of PBE reduces erythema in the skin. Inhibition of NF-kappaB-dependent gene expression by PBE possibly contributes to the observed increase in MED.

Administration, Oral↗
PubMed2001

On the characteristics of migration of oligomeric DNA in polyacrylamide gels and in free solution.

We review a model for the free-solution electrophoretic mobility of oligomeric double-stranded (ds) DNA. We have found that the free-solution mobility of ds DNA increases as the molecular weight of the fragment increases, up to a few hundred base pairs. This insight is combined with recent advances in the nature of counterion condensation theory of very short DNA fragments to describe quantitatively the electrophoretic mobility of oligomeric single-stranded DNA in polyacrylamide gels. The model predicts, in agreement with recent experiments, that significant anomalous migration exists with short DNA sequences, the onset of which is dependent on the size of polyacrylamide gel pores. For terminal phosphate-labeled DNA fragments, the free-solution mobility is no longer proportional to the ratio of the total effective charge and the friction coefficient. These changes in properties affect the characteristics of migration of end-labeled DNA fragments in polyacrylamide gels.

DNA↗
PubMed2000

Apolipoprotein J/clusterin limits the severity of murine autoimmune myocarditis.

Apolipoprotein J/clusterin (apoJ/clusterin), an intriguing protein with unknown function, is induced in myocarditis and numerous other inflammatory injuries. To test its ability to modify myosin-induced autoimmune myocarditis, we generated apoJ-deficient mice. ApoJ-deficient and wild-type mice exhibited similar initial onset of myocarditis, as evidenced by the induction of two early markers of the T cell-mediated immune response, MHC-II and TNF receptor p55. Furthermore, autoantibodies against the primary antigen cardiac myosin were induced to the same extent. Although the same proportion of challenged animals exhibited some degree of inflammatory infiltrate, inflammation was more severe in apoJ-deficient animals. Inflammatory lesions were more diffuse and extensive in apoJ-deficient mice, particularly in females. In marked contrast to wild-type animals, the development of a strong generalized secondary response against cardiac antigens in apoJ-deficient mice was predictive of severe myocarditis. Wild-type mice with a strong Ab response to secondary antigens appeared to be protected from severe inflammation. After resolution of inflammation, apoJ-deficient, but not wild-type, mice exhibited cardiac function impairment and severe myocardial scarring. These results suggest that apoJ limits progression of autoimmune myocarditis and protects the heart from postinflammatory tissue destruction.

Animals↗
PubMed1999

Antioxidants modulate acute solar ultraviolet radiation-induced NF-kappa-B activation in a human keratinocyte cell line.

Exposure of the human skin to ultraviolet radiation (UVR) leads to depletion of cutaneous antioxidants, regulation of gene expression and ultimately to the development of skin diseases. Although exogenous supplementation of antioxidants prevents UVR-induced photooxidative damage, their effects on components of cell signalling pathways leading to gene expression has not been clearly established. In the present study, the effects of the antioxidants alpha-lipoic acid, N-acetyl-L-cysteine (NAC) and the flavonoid extract silymarin were investigated for their ability to modulate the activation of the transcription factors nuclear factor kappa B (NF-kappaB) and activator protein-1 (AP-1) in HaCaT keratinocytes after exposure to a solar UV simulator. The activation of NF-kappaB and AP-1 showed a similar temporal pattern: activation was detected 2 h after UV exposure and maintained for up to 8 h. To determine the capacity of activated NF-kappaB to stimulate transcription, NF-kappaB-dependent gene expression was measured using a reporter gene assay. The effects of the antioxidants on NF-kappaB and AP-1 activation were evaluated 3 h after exposure. While a high concentration of NAC could achieve a complete inhibition, low concentrations of alpha-lipoic acid and silymarin were shown to significantly inhibit NF-kappaB activation. In contrast, AP-1 activation was only partially inhibited by NAC, and not at all by alpha-lipoic acid or silymarin. These results indicate that antioxidants such as alpha-lipoic acid and silymarin can efficiently modulate the cellular response to UVR through their selective action on NF-kappaB activation.

Acetylcysteine↗
PubMed1999

Transient monocyte release of interleukin-10 in response to traumatic brain injury.

A significant component of the immune response to trauma results in the systemic presence of cytokines which have the potential to suppress the patient's immune response to infection and contribute to post-injury complications. We assayed peripheral blood leukocytes obtained from 10 patients with head trauma to determine their production of interleukin (IL). Serum was assayed for the presence of IL-10, TGFbeta1, and IFNgamma by ELISA. Peripheral blood leukocytes were screened for intracellular IL-10 and IFNgamma by fluorescence-activated flow cytometry, and cytokine-specific mRNA was detected by the polymerase chain reaction. We detected an immediate, but transient, presence of IL-10 in the sera of all 10 patients who suffered head trauma. IL-10-specific intracytoplasmic immunofluorescence was also detected immediately after injury in peripheral blood monocytes, but not in lymphocytes or granulocytes. IL-10-specific mRNA was detected in peripheral blood leukocytes in only 50% of patients immediately after injury, when the highest serum levels of IL-10 were observed. Our data indicates that release of pre-formed IL-10 by monocytes contributes to the presence of IL-10 found in patient peripheral blood immediately after head injury.

Adolescent↗
PubMed1999

Treadmill exercise-induced tendon hypertrophy: assessment of tendons with different mechanical functions.

The equine superficial digital flexor tendon (SDFT) functions as an energy store during high-speed gaits reducing the energetic cost of locomotion. To enable the SDFT to function effectively, the appropriate mechanical properties are essential. We tested the hypothesis that the SDFT does not undergo gross hypertrophy in response to high-intensity exercise whereas tendons not involved in energy storage undergo adaptive hypertrophy. Two groups (n = 6) of Thoroughbred fillies were trained at high-intensity on a high-speed equine treadmill for 5 months (short-term study) or 18 months (long-term study). Age-matched groups (n = 6) of horses undertook low-intensity exercise only for the same time period. Throughout the short-term study the SDFT and deep digital flexor tendon (DDFT) were ultrasonograpically scanned at mid-metacarpal level and cross-sectional area (CSA) calculated. At the end of the short-term study (horse age = 2 years) and long-term study (horse age = 3 years) the left SDFT, DDFT, suspensory ligament (SL) and common digital extensor tendon (CDET) were harvested and CSA calculated. Comparison of the DDFT from 2- and 3-year-old horses revealed an age-related increase in CSA which was confirmed by ultrasonographs. Post mortem analysis showed a significant hypertrophy of the CDET with high-intensity training in the short-term study (younger horses). CSA did not differ significantly between training groups for any of the structures following long-term training. These results suggest a structure specific hypertrophic response to the imposed training regime.

Animals↗
PubMed1999

Treatment of mammalian cells with the endoplasmic reticulum-proliferator compactin strongly induces recombinant and endogenous xenobiotic metabolizing enzymes and 3-hydroxy-3-methylglutaryl-CoA reductase in vitro.

Some xenobiotics induce membrane-bound drug metabolizing enzymes (Xme) and a profound proliferation of the endoplasmic reticulum (ER) in vivo. However these effects are much weaker in vitro, possibly due to absence of certain transcription factors. We tested the possibility that ER proliferation can affect the level of ER-resident enzymes even in the absence of transcriptional activation. For this purpose we analysed the effects of compactin, which has been shown to induce ER proliferation in vitro, on recombinant Xme, which were expressed from a constitutive viral promoter. High levels of recombinant UDP-glucuronosyltransferase UGT1A6 were achieved by amplification of the UGT1A6 cDNA using the dihydrofolate reductase cDNA as selectable marker in DHFR- CHO cells. Treatment of the resulting cell lines with lipoprotein-deficient serum in the absence and presence of compactin for 5 days resulted in a 1.3- and 2.3-fold, respectively, increase of the UGT enzyme activity towards 4-methylumbelliferone, paralleled by an induction of immunoreactive UGT1A6 protein. Similarly, treatment with this 3-hydroxy-3-methylglutaryl-CoA reductase inhibitor increased the endogenous P450 reductase activity 2.6-fold, concomitant with an increase of immunodetectable protein. As expected compactin induced the level of 3-hydroxy-3-methylglutaryl-CoA reductase. Increased levels of this protein have been associated with a proliferation of the ER. Compactin treatment of a separate cell line that expressed recombinant human P450 reductase increased this enzyme activity fivefold. Pulse-chase experiments revealed that the induction of the recombinant Xme by compactin was most likely due to decreased protein degradation. Our results show that enzyme systems unrelated to those involved in cholesterol biosynthesis are affected by compounds known to affect membrane biogenesis. Since this effect extends to heterologously expressed enzymes, it also provides an efficient means by which to increase the levels of recombinant ER proteins.

Animals↗
PubMed1998

Web-based resources for clinical protocol management.

The data monitoring regulatory procedures, and administrative tasks associated with protocol management have become increasingly complex. Relational database technology and Internet-based connectivity offer resources to improve the quality and efficiency of protocol operations. At Fox Chase Cancer Center, we have developed a suite of database applications for protocol management and tracking of patient accrual. All data transactions and reporting occur through a graphical web browser interface using standard Internet technology. Security and confidentiality have been addressed through encryption, user authentication, address restriction, and database authority. Database management has been tightly integrated with protocol operations to avoid duplication of resources and effort. Data query functions also extend to other institutional resources, such as tumor registry and the hospital clinical laboratory, to further reduce the need for redundant data storage. Newer components, such as chemotherapy orders and toxicity reporting, have been incorporated in a modular fashion. Although custom software development can be expensive and time-consuming, it offers the best opportunity for successful integration with existing resources, staff, and procedures, as well as collaboration with other institutions.

Clinical Protocols↗
PubMed1998

Women and coronary disease: relationship between descriptors of signs and symptoms and diagnostic and treatment course.

BACKGROUND: Heart disease is the No. 1 killer among women in the United States. Differences in the clinical features of coronary heart disease among men and women have been reported, along with various approaches to the diagnostic workup and therapeutic interventions. PURPOSE: To explore the relationship between descriptors of signs and symptoms of coronary heart disease and follow-up care and to investigate any differences between male and female patients. METHODS: Structured interviews with patients and chart audits were used to assess initial signs and symptoms, associated cardiac-related signs and symptoms, and the diagnostic tests and interventions used for treatment. The sample consisted of 98 patients (51 women and 47 men) who were admitted with a medical diagnosis of myocardial infarction. RESULTS: Chest pain was the most common sign or symptom reported by both men and women. The 4 most common associated signs and symptoms were identical in men and women: fatigue, rest pain, shortness of breath, and weakness. However, significantly more women than men reported loss of appetite, paroxysmal nocturnal dyspnea, and back pain. Women were also less likely than men to have angiography and to receive i.v. nitroglycerin, heparin, and thrombolytic agents as part of acute management of myocardial infarction. CONCLUSION: Chest pain remains the initial symptom of acute myocardial infarction in both men and women. However, women may experience some different associated signs and symptoms than do men. Despite these similarities, men still are more likely than women to have angiography and to receive a number of therapies.

Adult↗
PubMed1997

Identification of microtubule-associated protein tau isoforms in Alzheimer's paired helical filaments.

AD66 proteins derived from sodium dodecylsulfate (SDS) insoluble paired helical filaments (PHF) were isolated from Alzheimer's brain using a purification procedure developed previously in this laboratory, and characterized by immunologic and chemical cleavage methods. AD66 proteins were immunoreactive with antibodies that recognize the amino terminal, tubulin-binding, and carboxy terminal domains of microtubule-associated protein tau indicating the presence of the entire tau sequence in AD66 proteins. These proteins were reactive with antibody 423 that binds to PHF but not human adult tau. Immunologic and chemical cleavage studies indicated that only two of the six tau isoforms were present in these proteins. AD66 proteins were comprised of tau proteins containing only three tubulin binding domains with either a 29 amino acid insert or no amino terminal insert. For comparative purposes, SDS soluble PHF-tau (A68 proteins) was purified from Alzheimer's brains and normal adult tau purified from control brains. Antibody Alz-50 was immunoreactive with PHF-tau or normal tau regardless of alkaline phosphatase treatment while immunoreactivity was only observed with dephosphorylated AD66 proteins. A second phosphorylated epitope on AD66 proteins but not PHF-tau or normal tau proteins was demonstrated with antibody PHF9. These data suggest that AD66 proteins represent a more phosphorylated form of tau than PHF-tau or normal tau proteins. Two-dimensional gel electrophoresis demonstrated that AD66 proteins have higher apparent molecular weights and lower pI values than normal tau, differences possibly due to the greater phosphorylation observed in these proteins.

Adult↗
PubMed1995

Characterization of human T cell clones specific for coronavirus 229E.

Coronaviruses (CV) are pleomorphic enveloped RNA viruses that are ubiquitous in nature, causing a variety of diseases in both man and domestic animals. In man, CV are generally associated with upper respiratory tract infections. The two prototype strains that are the best studied human CV isolates and which are thought to be responsible for most of the respiratory infections caused by CV are called 229E and OC43. Humoral responses consisting of neutralizing antibodies to CV are present in most individuals by six years of age. Although the cellular immune response to CV in man has not been characterized at all, it is known that the spike (S) and nucleocapsid (N) proteins elicit the major cell mediated immune responses in the mouse. This report describes the production and characterization of eleven independently isolated T cell clones that are specific for the human CV(HCV) 229E. The T cell clones are CD4+ and presumably recognize a processed viral peptide presented by class II molecules on the surface of antigen presenting cells. Of six 229E-specific T cell clones tested against purified viral proteins, three recognize the 180 kD spike glycoprotein while the other three recognize the 55 kD nucleocapsid phosphoprotein. Analysis of the human T cell mediated response to HCV will provide information regarding which viral proteins elicit the immunodominant response, what the fine specificity of these T cell clones are (immuno-dominant peptides), and what the T cell receptor (TCR) and cytokine usage is of these virus specific clones.

Capsid↗
PubMed1995

Evaluation of a point-of-care testing product for drugs of abuse; testing site is a key variable.

We evaluated the EZ-SCREEN Test Kit (Editek, Inc., Burlington, NC), a point-of-care screening test for the presence of cocaine metabolite (benzoylecgonine; BE), cannabinoids (tetrahydrocannabinol; THC) and opiates in urine. Patient specimens (n = 34) were tested in the laboratory using both Abbott Laboratories ADx (ADx) and EZ-SCREEN (EZS-LAB), and by the nursing staff of an inpatient substance abuse treatment program using the EZ-SCREEN (EZS-RN). We found comparable analytical efficiency between methods used in the laboratory (> 95% for all three analytes with EZS-LAB and ADx) but lower efficiency for THC and BE with point-of-care testing (approximately 82% for EZS-RN). Efficiency for EZS-RN opiates was 100%. We conclude that the EZ-SCREEN Test Kit may not be suitable for use in a busy clinical setting, unless specific measures are taken to insure the accuracy of point-of-care testing (e.g., minimal interruption or distraction, careful training). We recommend that prior to routine use of point-of-care testing products they be evaluated under normal working conditions with personnel who will eventually be required to perform routine testing.

Cocaine↗
PubMed1995

In vivo models of thrombogenic potential: usefulness and limitations.

The thrombogenicity of prothrombin complex concentrates (PCCs) has been known as a risk factor since their first clinical use about 30 years ago. The development of in vivo models to define the thrombogenic components in PCCs was instrumental in providing a logical basis for selecting in vitro assays to screen for the distribution of such components during the manufacture of PCCs, and to minimize their appearance in the final product. Even so, these thrombogenic components are not completely removed, as shown in our canine nonstasis model of thrombogenicity: PCCs were still found to elicit a thrombogenic response, shown by increased fibrinopeptide A, fibrin(ogen) degradation products, activated partial thromboplastin time, and decreased fibrinogen and platelet counts when clinically relevant doses were used. The new generation of high-purity factor IX (HP-FIX) concentrates differs from PCCs because these products contain only negligible amounts of clotting factors other than factor IX, lower amounts of activated clotting factors, and, in products we have assayed, no coagulant-active phospholipids. When we infused a number of HP-FIX products in the canine nonstasis model, no thrombogenic response was observed at doses considerably greater than PCC doses that did elicit a response. Likewise, HP-FIX products were much less thrombogenic than PCCs when tested in small-animal stasis and nonstasis thrombogenicity models. Small-animal models are also useful for evaluating the role of factor IXa as a potential thrombogenic contaminant of concentrates and ensuring minimal amounts in the final product. The limitations associated with extrapolating in vivo model data will be shown to be minimal if ongoing clinical studies continue to demonstrate the low thrombogenic potential of HP-FIX concentrates in humans.

Animals↗
PubMed1994

Alzheimer's paired helical filaments: amyloid precursor protein epitope mapping.

Paired helical filaments (PHF) were electrophoretically purified and solubilized from Alzheimer's neurofibrillary tangles and consisted of a primary 66 kDa protein on SDS-PAGE analysis. A panel of antibodies raised against restricted regions of the beta-amyloid precursor protein (APP) were employed for epitope mapping studies of this 66 kDa PHF protein. Western blot studies revealed that C-terminal APP antibodies were immunoreactive with the 66 kDa PHF protein. Further analysis revealed that only antisera raised against peptides that include the beta/A4-amyloid region within the C-terminal portion of APP were immunoreactive with PHF proteins. These data complement previous immunocytochemical studies which indicated that C-terminal APP antibodies preferentially label PHF-containing neurofibrillary tangles in Alzheimer's brain. The present data suggest a similarity of secondary or tertiary structure between beta/A4-amyloid and PHF which accounts for the cross-reactivity of beta/A4-amyloid antibodies with PHF proteins.

Alzheimer Disease↗
PubMed1994

Knowledge and beliefs of dentists regarding temporomandibular disorders and chronic pain.

To assess the knowledge and beliefs of practicing dentists regarding temporomandibular disorders and chronic pain, a random sample of dentists in the Kansas City metropolitan area was surveyed. A survey instrument examining knowledge and beliefs in four domains (psychophysiological, psychiatric disorders, chronic pain, and pathophysiology) was used. The responses of the practicing dentists were compared to the responses of panels of experts. Results indicated that dentists generally agreed with experts in the psychophysiological and psychiatric disorders domains but disagreed with the experts in the chronic pain and pathophysiology domains. Specialists and general dentists did not differ from one another in their responses. The findings partially replicate an earlier, similar survey of dentists in the Seattle, Washington, area. The findings suggest that the role of psychiatric disorders and psychophysiologic factors in the etiology of temporomandibular disorders is widely acknowledged by practicing dentists. However, there is considerable discrepancy between practicing dentists and temporomandibular disorder experts on the pathophysiology of temporomandibular disorders and how best to diagnose and treat these chronic conditions.

Adult↗