PubMed Health⌕ Search

Biomedical subjects

L Hurley

Publications and source records attributed to L Hurley.

16 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↗
PubMed2002

Automated colorimetric screen for apyrase inhibitors.

Apyrases are enzymes that efficiently hydrolyze ATP and ADP and may operate both inside and outside the cell. Although apyrases are important to a variety of cellular mechanisms and uses in industry, there are no available apyrase-specific inhibitors. Colorimetric assays based on the Fiske-Subbarow method for measuring inorganic phosphate are able to detect the release of inorganic phosphate from ATP and other nucleotides. We found that this type of assay could be automated and used to screen for apyrase-inhibiting compounds by assaying for a reduction in released phosphate in the presence of potential inhibitors. The automation of this assay allowed for the successful screening of a commercially available compound library. Several low molecular weight compounds were identified that, when used at micromolar concentrations, effectively inhibited apyrase activity.

Apyrase↗
PubMed2000

DNA G-quadruplexes, telomere-specific proteins and telomere-associated enzymes as potential targets for new anticancer drugs.

Telomeres and telomerase have been subjects to a tremendous attention from scientists and oncologists during the past 5 years. This interest has been motivated by the potential of telomerase as a tumor marker for the diagnosis and the prognosis of cancer. The possible use of telomerase or telomeres as new targets for anticancer drugs also triggered investigations. The expression of telomerase was found in overall 85% of cancers. Telomerase is early expressed during oncogenesis with a gradient indicating that a high level of telomerase expression could be associated with a bad prognosis. Therefore, drugs targeting telomerase and telomeres might be useful in many human tumors with little restrictions regarding the tumor type or on the stage of the disease. Moreover, since telomerase is not or slightly expressed in normal cells, it has been postulated that drugs targeting telomerase would induce low toxicity. The race for the discovery of telomerase inhibitors has started while the identification of the components controlling telomerase, telomeres, cell survival, senescence, and apoptosis was still in progress. The recent identification of components regulating telomere length and telomerase expression (TRF1, TRF2, and tankyrase) opened a variety of new opportunities to control telomerase/telomere interactions. Meanwhile, a proof of principle was provided that changing telomere interactions with telomere binding proteins by chemical or biological means can induce cancer cell death. Interestingly, recent data challenge the old paradigm which suggested that a long exposure to telomerase and telomere inhibitors is necessary to induce anticancer effects. In this paper, we review the most recent information concerning the regulation of telomere length and telomerase expression, with emphasis on mechanisms that might translate into new drug discovery.

Animals↗
PubMed2000

Effect of telomere and telomerase interactive agents on human tumor and normal cell lines.

Shortening of telomeres along with an up-regulation of telomerase is implicated in the immortality of tumor cells. Targeting either telomeres or telomerase with specific compounds has been proposed as an anticancer strategy. Because telomerase activity and telomeres are found in normal cells, telomere or telomerase targeting agents could induce side effects in normal tissues. We evaluated the effects of telomere and telomerase interactive agents in human tumor and normal cell lines to try to determine the potential side effects those agents might induce in patients. Toxicity of the G-quadruplex interactive porphyrins (TMPyP4, TMPyP2) and azidothymidine (AZT) were tested using a cell-counting technique against normal human cell lines (CRL-2115 and CRL-2120, fibroblasts; NHEK-Ad, adult keratinocytes; CCL-241, small intestinal cells; NCM 460, colonic mucosal epithelial cells) and human tumor cell lines (MDA-MB 231 and Hs 578T, breast cancer; SK-N-FI, neuroblastoma; HeLa, cervix cancer; MIA PaCa-2, pancreatic cancer; HT-29 and HCT-116, colon cancer; DU 145, prostatic cancer cell line). Telomerase activity of these cell lines was measured by a non-PCR-based conventional assay. The effects of TMPgammaP2, TMPyP4, and AZT were also evaluated against normal human bone marrow specimens, using a granulocyte-macrophage colony-forming assay (CFU-GM). AZT showed very low cytotoxic effects against normal and tumor cell lines, with the IC50 values above 200 microM. The IC50 values for TMPyP2 and TMPyP4 in normal human cell lines were in the range of 2.9-48.3 microM and 1.7-15.5 microM, respectively, whereas in tumor cell lines the IC50 values were 11.4-53 microM and 9.0-28.2 microM, respectively. Within the tissue types, keratinocytes were more sensitive to TMPyP4 than fibroblasts, and small intestinal cells were more sensitive than colonic mucosal epithelial cells. The IC50 for TMPyP2 and TMPyP4 in the normal marrow colony-forming assays were 19.3 +/- 5.1 microM and 47.9 +/-1.0 microM, respectively. In conclusion, the in vitro cytotoxicity of the telomere interactive agent TMPyP4 is comparable in human tumor and normal cell lines, which indicates that TMPyP4 could have effects on normal tissues.

Bone Marrow Cells↗
PubMed1999

Biodegradable implants from poly-(alpha-hydroxy acid) polymers for isoniazid delivery.

SETTING: In vitro and in vivo study of an isoniazid (INH) drug delivery system. OBJECTIVE: To develop a system for the treatment of tuberculosis using a subcutaneous polymer implant with a large drug load released slowly over a long period. INH delivery by biodegradable poly-(alpha-hydroxy acid) polymers was evaluated using ground polymer and compression molded implants. DESIGN: Rate of drug release and structural stability of the implant in an aqueous environment were measured, as were in vivo evaluations of the duration of measurable levels of INH in serum and urine. RESULTS: Factors that influenced the suitability of an implant in an in vitro system included polymer molecular weight and crystallinity, polymer and drug particle size, drug loading dose, and press temperature and pressure. The implant characteristics that most closely approached optimal conditions include a polymer of 100% L-lactide with low intrinsic viscosity, polymer particle size <75 micron, and INH particle = 126-180 micron, INH loading dose not to exceed 46%, and press conditions of 70 degrees C and 345000 kPa. Studies of subcutaneous implants in rabbits and baboons show that INH is released from the implant for 15 to 26 weeks. CONCLUSIONS: An INH-containing polymer was developed that was structurally stable in an aqueous environment and that released INH over a period of at least 15 weeks. Studies with infected animals will be necessary to determine the dose required for prophylaxis and treatment of active disease.

Animals↗
PubMed1995

Hedamycin intercalates the DNA helix and, through carbohydrate-mediated recognition in the minor groove, directs N7-alkylation of guanine in the major groove in a sequence-specific manner.

BACKGROUND: The pluramycins are a class of antitumor antibiotics that exert their biological activity through interaction with DNA. Recent studies with the analog altromycin B have determined that these agents intercalate into the DNA molecule, position carbohydrate substituents into both major and minor grooves, and alkylate the DNA molecule by epoxide-mediated electrophilic attack on N7 of guanine located to the 3' side of the drug molecule. Alkylation is sequence dependent and appears to be modulated by glycoside substituents attached at the corners of a planar chromophore. The altromycin B-like analogs preferentially alkylate 5'AG sequences; hedamycin-like analogs prefer 5'TG and 5'CG sequences. Although the mechanism of guanine modification by altromycin B has been extensively studied, the mechanism of action of hedamycin has not been previously determined. RESULTS: Using high-field NMR, we have shown that hedamycin stacks to the 5' side of the guanine nucleotide at the site of intercalation in a DNA decamer, positioning both aminosaccharides into the minor groove to direct alkylation by the epoxide moiety on N7 of guanine. The C10 linked N,N-dimethylvancosamine sugar moiety interacts to the 5' side of the intercalation site, while the C8 linked anglosamine moiety interacts to the 3' side. The binding interactions of the two aminosugars steer the C2 double epoxide located in the major groove into the proximity of N7 of guanine. Unexpectedly, it is not the first epoxide that undergoes electrophilic addition to N7 of guanine, which would correspond to altromycin B, but the second, terminal epoxide. CONCLUSIONS: We have used two-dimensional NMR to elucidate the sequence-selective recognition of DNA by hedamycin and the mechanism of covalent modification of guanine by this antibiotic. Characterization of the intermolecular interactions between both hedamycin and altromycin B and their targeted DNA sequences has yielded a better understanding of the reasons for variations in sequence selectivity and alkylation reactivity among the pluramycin compounds.

Alkylation↗
PubMed1994

Multiple retroperitoneal schwannomas: case report and review of the literature.

We report a rare case of multiple retroperitoneal schwannomas, initially believed to be an adrenal carcinoma with metastasis. These benign tumors were discovered in a patient presenting with vague back pain. Preoperative radiographic and endocrine evaluations suggested a nonfunctioning adrenal tumor. The final diagnosis and its juxta-adrenal origin were confirmed by histological and immunohistochemical studies. A review of the literature on retroperitoneal schwannoma is included.

Humans↗
PubMed1993

Interstrand cross-linking by bizelesin produces a Watson-Crick to Hoogsteen base-pairing transition region in d(CGTAATTACG)2.

1H NMR analysis of the bizelesin adduct of d(CGTAATTACG)2 indicates that adenines six base pairs apart on opposite DNA strands are cross-linked, yielding two major adduct conformations differing in the central duplex region (5'AATT-3'): one (major product) contains an AT step wherein both adenines are syn-oriented and Hoogsteen base paired to thymines (5HG model); the other contains anti-oriented AT-step adenines that show no evidence of hydrogen bonding with pairing thymines (5OP model). The 5OP model consists of three conformers undergoing exchange and differing in the orientation of the AT-step thymines. Bizelesin's size, rigidity, and cross-linking properties restrict the DNA adduct's range of motion and freeze out DNA conformation(s) adopted during the cross-linking process. This most reactive DNA sequence, 5'-TAATTA-3', yields an adduct conformation (5HG) containing a stable region of Watson-Crick (WC) to Hoogsteen (HG) to Watson-Crick base-pairing transitions. While bizelesin exercises a selective effect on DNA conformation, it intrudes into regions of base stacking less than other Hoogsteen pairing-inducing drugs (e.g., echinomycin). Because of this capacity to induce stable Hoogsteen base pairing with only minimal distortion of base-base stacking, bizelesin affords an opportunity to explore this unusual DNA conformation.

Base Sequence↗
PubMed1991

Mycotic aortic aneurysm infected by Clostridium septicum--a case history.

The authors describe a sixty-seven-year-old hypertensive, diabetic man with a mycotic abdominal aortic aneurysm infected with Clostridium septicum. The patient had colonic polyps but no malignant disease. They could find only one other report of a mycotic aneurysm infected with C. septicum. In that case, as in most other cases of C. septicum bacteremia, the patient had gastrointestinal cancer. Their case suggests that treatment for a clostridial infection should be considered in patients with known gastrointestinal disease, signs and symptoms of sepsis, and abdominal pain. Conversely, patients known to have a C. septicum infection should be evaluated for gastrointestinal lesions.

Aged↗
PubMed1983

Importance and accuracy of bone age ratings in a computerized growth evaluation system.

Bone age ratings according to Greulich and Pyle and to Tanner and co-workers (RUS) of 88 children from two pediatric endocrine centers were compared with ratings from 2 trained technicians and independent ratings from a consulting pediatric endocrinologist. Considering the mean of all ratings as 'true bone age', the mean errors of the individual estimations were small (0.15-0.38 years for the Greulich and Pyle method, 0.12-0.27 years for the method according to Tanner and co-workers). Only in 2 of 338 ratings were differences larger than 1 year observed. In these 2 cases, there was marked dissociation between the maturation of carpal and phalangeal bones. It is concluded that estimations of bone maturation can be carried out reliably by properly trained technicians.

Age Determination by Skeleton↗
PubMed1983

Toward a methodology of the short-term effects of neurodevelopmental treatment.

Neurodevelopmental treatment (NDT) is a technique widely used by physical and occupational therapists in the treatment of neuromuscular disorders; however, quantitative evidence supporting its use has yet to be provided. Several studies have attempted to examine the effects of NDT, but because of poor research methodology, conclusions drawn to support the use of NDT are not based on reliable or well-documented evidence. The purpose of this study was to develop a reliable method of measuring short-term, objective changes in children with cerebral palsy and to measure the immediate effects of NDT and play interventions. A single subject design was replicated with four subjects receiving NDT and nonspecific play over a 5-week time period. Pre- and post-test items were designed to reflect qualitative changes in movement, postural tone, and reflex activity, and were videotaped and coded using interval and time-sampling techniques. The results of this study are equivocal; they neither validate nor invalidate NDT. This study provides a methodology for the investigation of the short-term effects of NDT.

Cerebral Palsy↗