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Biomedical subjects

S Chandler

Publications and source records attributed to S Chandler.

At least 19 recordsLinked to original sources
PubMed2005

Silver absorption and antibacterial efficacy of silver dressings.

OBJECTIVE: To evaluate the patterns of silver release from selected sustained silver-release dressings and the protective role of proteins in wound exudate and wound scale. The bactericidal action of silver in chronic wound therapy is also examined. METHOD: Sequential microbiological examination of wound swabs from seven patients with chronic wounds and sampling of wound exudate and wound scale. Silver content was measured using atomic absorption spectrometry. The ability of Contreet Foam to absorb exudate and release silver was studied in punch biopsy wounds in a rodent model. RESULTS: Silver accumulation in wound exudate correlated well with its viscosity and protein content. Silver bound to wound scale and debris was approximately proportional to the silver ion release from dressings. Bacterial burden was controlled, but not eliminated, following chronic silver therapy. CONCLUSION: Silver dressings (Acticoat-7, Actisorb Silver, Contreet Foam, Aquacel Ag and Flamazine) were found to be safe for use in chronic wound therapy. Excess silver ion is bound by wound exudate and wound scale as a protective mechanism. Silver-release dressings are not likely to result in germ-free wounds. Further studies are needed to examine potential silver resistance.

Aged↗
PubMed2003

Back injuries in young fast bowlers--a radiological investigation of the healing of spondylolysis and pedicle sclerosis.

OBJECTIVE: To demonstrate the efficacy of various radiological diagnostic modalities in assessing lower back pain in young fast bowlers. METHODS: Ten cricketers who presented to either a physiotherapist or a doctor with suspected spondylolysis underwent an X-ray, a single photon emission computed tomography (SPECT) bone scan and a computed tomography (CT) scan to assess the severity of the injury. Three and 12 months after the initial CT scan, second and third CT scans were performed in order to assess whether healing had taken place. After the initial radiological investigation the subjects diagnosed with spondylolysis or pedicle sclerosis underwent prescribed intervention and rehabilitation which included physiotherapy modalities, postural correction, and specific individually graded flexibility, stabilisation, strengthening and cardiovascular programmes. RESULTS: Radiographs were normal in 8 subjects, while 2 had evidence of sclerosis. The isotope scan showed increased uptake in all of the subjects. The CT scans showed no fracture (N = 3), partial fractures (N = 3), complete fractures (N = 2) and old fractures bilaterally (N = 2). When the follow-up CT scan was carried out at 3 months, 1 of the subjects had developed a partial fracture of the left pars interarticularis on the inferior border, which showed complete union when CT scanned at 12 months. At 3 months the partial and complete fractures showed progressive healing in 2 subjects, with complete healing in all the other cases. Complete healing was achieved in all subjects at 12 months, with the exception of 1 subject who showed near-complete union, with a small area of fibrous union on the inferior border and 2 old bilateral fractures that remained un-united. RESULTS: From the results it is evident that when a young fast bowler presents with backache after bowling, it would be appropriate to do an X-ray, a bone scan and a CT scan to make the diagnosis. Discontinuing the fast bowling and following an active rehabilitation programme should result in spontaneous resolution and healing of the fractures. If it is not detected early a fibrous or non-union fracture could result.

Adolescent↗
PubMed2000

Outcome of cancer pain consultations.

BACKGROUND: All major cancer centers in the United States are equipped with pain management consultation services. We report on the outcome of such consultations within 24 hours from the intervention. METHODS: All consecutive patients referred to the pain management service of a tertiary care cancer center were assessed before and 14-24 hours after the intervention. RESULTS: A total of 45 patients completed the study. The mean current pain intensity score was 5.2 on the Visual Analogue Scale before the consultation and 2.7 after the consultation (P < 0.05). The pain was described as excruciating on the Categorical Scale by three patients before the consultation and by no patients after the consultation. CONCLUSIONS: In hospitalized cancer patients with difficult to control pain, cancer pain consultations result in a measurable effect within 24 hours of the pharmacologic intervention. To avoid unnecessary suffering, timeliness is of the utmost importance when requesting and delivering cancer pain consultations.

Adult↗
PubMed2000

An alternative algorithm for dosing transdermal fentanyl for cancer-related pain.

Many cancer patients are undermedicated and inappropriately managed for pain, leading to a diminished quality of life. Patients with moderate to severe pain often require opioid analgesics. Recently published guidelines emphasize individualization of opioid treatment to provide the drug and route of administration that meet the needs of the particular patient. Intolerable side effects, ineffective pain relief, or a change in the patient's clinical status can dictate the need for a new pain management regimen. Physicians must be able to readily quantify relative analgesic potency when converting from one opioid to another or from one route of administration to another. Transdermal fentanyl (Duragesic) is an opioid agonist that has been shown to be safe and effective for the treatment of cancer pain. However, clinicians should realize that the manufacturer's recommendations for equianalgesic dosing of transdermal fentanyl may result in initial doses that are too low in some patients, and in a titration period that is too long. Under these circumstances, the patient is likely to experience unrelieved pain. An alternative dosing algorithm that considers both a review of the literature and our combined clinical experience with transdermal fentanyl should help clinicians individualize the treatment of pain.

Administration, Cutaneous↗
PubMed1999

Nucleosome structure completely inhibits in vitro cleavage by the V(D)J recombinase.

Lineage specificity and temporal ordering of immunoglobulin (Ig) and T-cell receptor (TCR) gene rearrangement are reflected in the accessibility of recombination signal sequences (RSSs) within chromatin to in vitro cleavage by the V(D)J recombinase. In this report, we investigated the basis of this regulation by testing the ability of purified RAG1 and RAG2 proteins to initiate cleavage on positioned nucleosomes containing RSS substrates. We found that nicking and double-strand DNA cleavage of RSSs positioned on the face of an unmodified nucleosome are entirely inhibited. This inhibition was independent of translational position or rotational phase and could not be overcome either by addition of the DNA-bending protein HMG-1 or by the use of hyperacetylated histones. We suggest that the nucleosome could act as the stable unit of chromatin which limits recombinase accessibility to potential RSS targets, and that actively rearranging gene segments might be packaged in a modified or disrupted nucleosome structure.

Acetylation↗
PubMed1998

Matrix metalloproteinase expression in an experimentally-induced DTH model of multiple sclerosis in the rat CNS.

In an experimentally-induced DTH model of MS, we examined mRNA and protein expression of a range of MMPs and of TNFalpha to establish the contribution that individual MMPs might make to the pathogenesis. In control rat brain, mRNA for all of the MMPs examined was detectable. However, by immunohistochemistry, only MMP-2 could be detected. In the DTH lesions, significant increases in the level of mRNA expression were observed for MMP-7, MMP-8, MMP-12, and TNFalpha. Where expression of MMP mRNA was increased, there was a corresponding increase in protein expression detected by immunohistochemistry. To determine whether the upregulated MMPs could invoke destructive events in the CNS, highly purified activated MMP-7, MMP-8, and MMP-9 were stereotaxically injected into the brain parenchyma. All provoked recruitment of leukocytes and BBB breakdown. In addition, MMPs 7 and 9 induced loss of myelin staining. In conclusion, specific MMPs are upregulated in DTH lesions; for the most part, measurement of mRNA was a predictor of increased protein expression. From our injections of MMPs, it is clear that the upregulated MMPs in the DTH lesions could participate in the disruption of the BBB, leukocyte recruitment, and tissue damage.

Animals↗
PubMed1998

Asymmetric linker histone association directs the asymmetric rearrangement of core histone interactions in a positioned nucleosome containing a thyroid hormone response element.

We describe histone-DNA cross-linking in a positioned nucleosome containing a thyroid hormone response element (TRE) from the Xenopus laevis thyroid hormone receptor betaA gene (TRbetaA). Histones H3 and H4 are cross-linked to DNA in the nucleosome core within 30 base pairs to either side of the dyad axis. Histone H2A cross-links to DNA in the core at the dyad axis, and histones H2A and H2B have extensive interactions with DNA 40-80 bp away from the dyad axis. Linker histone H5 and the globular domain of Xenopus H1(0) associate asymmetrically with DNA at one edge of the TRbetaA nucleosome. Nevertheless, the asymmetric association of H5 leads to a significant rearrangement of core histone-DNA contacts at the dyad axis of the nucleosome. In the presence of linker histone, cross-linkings of H4 within 15 bp to one side of the dyad axis, of histone H2A at the dyad axis, and of H2A and H2B 40-80 bp to one side of the dyad axis are all reduced. This reduction in cross-linking occurs preferentially on the side of the nucleosome to which H5 is bound. Our results indicate that core histone contacts within mononucleosomes are conformationally dynamic and that linker histone incorporation at the edge of the nucleosome can influence core histone-DNA interactions in an asymmetric way including contacts at the dyad axis.

Animals↗
PubMed1997

Matrix metalloproteinases, tumor necrosis factor and multiple sclerosis: an overview.

The matrix metalloproteinases (MMPs) are a family of at least 14 zinc-dependent enzymes which are known to degrade the protein components of extracellular matrix. In addition, MMPs and related enzymes can also process a number of cell surface cytokines, receptors, and other soluble proteins. In particular we have shown that the release of the pro-inflammatory cytokine, tumor necrosis factor-alpha, from its membrane-bound precursor is an MMP-dependent process. MMPs are expressed by the inflammatory cells which are associated with CNS lesions in animal models of multiple sclerosis (MS) and in tissue from patients with the disease. MMP expression will contribute to the tissue destruction and inflammation in MS. Drugs which inhibit MMP activity are effective in animal models of MS and may prove to be useful therapies in the clinic.

Animals↗
PubMed1997

A continuous patient activity monitor: validation and relation to disability.

The measurement of patient activity over prolonged periods has been attempted with accelerometer-based devices, but these summate total acceleration and deceleration over time periods, are difficult to relate to recognizable activities and are influenced by passive movement. We describe the development of a portable monitor of ambulation. This logs posture (sitting, standing and lying) and number and vigour of steps in real time over prolonged periods, usually 24 h. This is based on a system of position sensors and an accelerometer which is sampled when the subject is standing. Data are processed through an interface and stored on a Psion Series 3 'palm top' computer. The system has been validated against observation, and the relationship of activity to disability in rheumatoid arthritis explored.

Adult↗
PubMed1997

Patients' perceptions of outcomes of a Canadian hospitalization.

Notes that with health care reform moving at tremendous speed throughout Canada, a great deal of interest in outcomes research has been generated. States that the research team consisted of 17 professional practice leaders from eight disciplines. Proposes, through the research, to identify from the perspective of former patients what results they hoped to achieve prior to discharge from hospital and what facilitated and hindered them in achieving these results. Reports that a representative sample was selected for the study. Forty-one former patients each participated in up to two focus groups, with a total of 16 focus groups conducted. Hierarchical analysis revealed themes that fell within the framework of structure, process and outcomes. The findings will assist in ensuring that more appropriate and effective care is offered to patients by a variety of disciplines.

Adult↗
PubMed1996

Macrophage metalloelastase degrades matrix and myelin proteins and processes a tumour necrosis factor-alpha fusion protein.

The matrix metalloproteinases (MMPs) are a group of enzymes which have the ability to degrade extracellular matrix. They also cleave non-matrix proteins such as myelin basic protein and alpha 1-antitrypsin and they are able to process tumour necrosis factor-alpha (TNF) to its mature form. We have cloned, expressed and purified human macrophage metalloelastase (EC 3.4.24.65), an MMP recognised for its ability to degrade elastin, but whose substrate specificity has not yet been defined. With the exception of type I collagen this enzyme degraded all matrix proteins tested, namely: type IV collagen, type I gelatin, fibronectin, laminin, vitronectin and proteoglycan. It also degraded myelin basic protein, cleaved alpha 1-antitrypsin and released TNF from a pro-TNF fusion protein. Thus, in common with several other MMPs, macrophage metalloelastase has a broad substrate range which extends beyond that of elastin alone.

Animals↗
PubMed1995

Matrix metalloproteinases degrade myelin basic protein.

Matrix metalloproteinases (MMPs) are a group of enzymes responsible for the degradation of interstitial connective tissue and basement membrane. The coding sequences for five of the human MMPs, viz. interstitial collagenase, 72 kDa gelatinase, stromelysin-1, matrilysin and 92 kDa gelatinase, were cloned and expressed in Chinese hamster ovary cells, and the proteins purified. The enzymes were compared for their ability to digest myelin basic protein, the major extrinsic membrane protein of central nervous system myelin. The most active on this substrate was 72 kDa gelatinase, followed by stromelysin-1; interstitial collagenase, matrilysin and 92 kDa gelatinase were of comparable but lesser activity. Production of these enzymes by glia or infiltrating inflammatory cells could therefore contribute to demyelination in neuroinflammatory disease.

Animals↗
PubMed1995

Guidelines for the clinical use of transdermal fentanyl.

Transdermal (TTS) fentanyl therapy has emerged as an effective alternative to the use of oral opioids for the control of pain in certain cancer patients. These patients are those with moderate to severe chronic pain, with a stable baseline pain pattern. Patients receiving this treatment should first be titrated to stable pain relief with oral opioids and should have recourse during therapy to fast-acting, short-duration analgesics for the control of incident pain. TTS fentanyl dosing schedules should be based upon the patient's requirement for rescue dosing and duration of effective pain control. The average requirement to change fentanyl patches is every 72 h, although 48-h dosing is necessary in a few patients. This novel route of fentanyl administration allows convenient outpatient treatment, the possibility of a lower incidence of side effects, and may thus aid compliance.

Administration, Cutaneous↗
PubMed1994

Characterization of the effect of cholecystokinin (CCK) on neurons in the periaqueductal gray of the rat: immunocytochemical and in vivo and in vitro electrophysiological studies.

The periaqueductal gray (PAG) is an important integration site for pain, autonomic functions, vocalization, fear and anxiety. Cholecystokinin (CCK) is a major neurotransmitter in the PAG and CCK receptors are heterogeneously distributed within the PAG. Since CCK antagonists are anxiolytic and potentiate morphine analgesia, it is possible that these effects of CCK are mediated through alteration of neuronal activities in the PAG. The goals of this study were to examine the anatomical and physiological properties of the PAG CCK containing systems. The distribution of CCK-containing axons and boutons in PAG was examined using immunohistochemical procedures. These studies show that CCK-like immunoreactive (CCK-LIR) fibers and terminals are present throughout PAG, but are particularly heavily concentrated in a focal column that runs longitudinally throughout the rostrocaudal axis of dorsolateral PAG and in nucleus cuneiformis which represents a caudolateral extension of PAG. The physiological effects of CCK on PAG neurons were examined in both in vivo and in vitro preparations. In the in vivo experiments multibarreled electrodes were used to record from PAG neurons and to apply CCK and the CCK antagonists, CR1409 and proglumide. Of 37 neurons recorded in vivo, CCK caused excitation in 25 cells, inhibited 7 cells and had no effect on 5 cells. The excitatory effect was blocked by CR1409 in 11/11 cells tested. Proglumide blocked the excitatory response of CCK in 12/14 cells. Proglumide blocked the inhibitory effect in 2 of 7 cells, but CR1409 had no effect on CCK-evoked inhibition in 7 cells tested. Extracellular, conventional intracellular and whole cell patch clamping procedures were used to study CCK actions in the in vitro slice preparation. In the extracellular recording experiments, responses of PAG cells to CCK were measured in slices that were maintained at 22 degrees C (room temperature) and at 32 degrees C. CCK excited 40/56, inhibited 7/56 and had no effect on 9/56 cells; excitatory responses were blocked by CR1409 in 32/36 cells and by proglumide in 25/27 cells tested. Inhibitory responses to CCK were unaffected by CR1409, but were blocked in 3/7 cells by proglumide. Conventional intracellular recordings were made from 13 cells.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1993

Distribution of calcium binding protein mRNAs in rat cerebellar cortex.

The distribution of three calcium binding protein mRNAs in the rat cerebellar cortex was investigated using alkaline phosphatase labelled specific antisense oligodeoxynucleotide probes. Calbindin D28k mRNA was detected in the Purkinje cells, parvalbumin mRNA was located in the Purkinje cells and also in basket/stellate cells of the molecular layer. Calretinin in contrast was found only in the granule cell layer. Use of multiple alkaline phosphatase (AP)-labelled oligodeoxynucleotides resulted in an increase in signal strength and reduced detection time with no increase in background staining indicating the utility of these enzyme labelled probes for non-isotopic in situ.

Animals↗
PubMed1992

Inducers of leukemic cell differentiation cause down-regulation of RB gene expression.

Expression of the retinoblastoma (RB) tumor suppressor gene during cell differentiation induced by dimethyl sulfoxide or sodium butyrate was studied in HL-60 human promyelocytic leukemia cells. As cells progressed through the cell cycle, the amount of RB protein per cell increased with homeostasis maintained, so that the amount of RB protein relative to the total cell mass remained almost constant. Dimethyl sulfoxide was used to induce these promyelocytic leukemia cells to undergo terminal differentiation into mature myeloid cells. There was an early reduction in the RB protein expressed per cell. The reduction in expression was similar for cells in all cell cycle phases. There was also progressively reduced expression at later times as cells terminally differentiated. This was compared to the case in which sodium butyrate was used to induce the differentiation of HL-60 cells into mature monocytic cells. An early reduction in RB protein expression per cell also occurred. It occurred for cells in all cell cycle phases as well. Thus, the induced differentiation of HL-60 cells along either the myeloid or the monocytic differentiation lineage involves an early reduction in RB expression, which is common to both pathways. The reduction anteceded proliferative arrest or differentiation. In both cases, the final, resulting G0-differentiated cells had less RB protein per cell than the proliferating, immature, leukemic precursor cells.

Butyrates↗