Search PubMed⌕ Search

Biomedical subjects

D Fletcher

Publications and source records attributed to D Fletcher.

At least 73 records · Page 4Linked to original sources
PubMed1995

Cultural differences in attitudes, values, and beliefs about osteoporosis in first and second generation Japanese-American women.

This study examines attitudinal differences related to osteoporosis between first and second generation Japanese-American women. In an interview, the women completed a battery of tests assessing their attitudes, values, and beliefs about the diagnosis, treatment, and follow-up care of osteoporosis. The groups differed in their general knowledge of osteoporosis, perceptions of the disease, attributions of its causes, anticipated and preferred support mechanisms for care, and anticipated areas of concern for self-or other-care. There were also considerable differences in treatment compliance and feelings toward physicians. The findings were discussed in relation to the effects of culture on health-care attitudes and behaviors.

Acculturation↗
PubMed1995

[Optimal use of non opioid analgesics].

This review describes the mechanisms of analgesic effect, advantages and risks related to the perioperative use of non steroidal antiinflammatory drugs (NSAID's). The NSAID's should be used as the first analgesic, around the clock, with a rapid onset of the therapy. Their combination with other NSAID's (acetaminophen) or opioids can have an additive analgesic effect and may limit frequent secondary effects as nausea and vomiting. Their potential toxicity must be remembered and the contra indications, maximum doses and duration of treatment have to be respected.

Acetaminophen↗
PubMed1995

Frequency domain estimation of covariate effects in multichannel brain evoked potential data.

An evoked potential is the recorded brain electrical response to a stimulus such as an auditory click. In most evoked potential experiments, the response is studied as a function of covariates such as stimulus characteristics and drug states. We propose a frequency domain model of multichannel evoked potential data that includes parameters representing the effects of covariates on the amplitude and latency (time from stimulus presentation) of the response. The variability of the response among scalp electrodes is modeled by the activity of one or more equivalent electrical dipoles. The frequency domain representation allows considerable data reduction, facilitates modeling of the noise, and leads to a simple approximate expression for the latency effects. We describe maximum likelihood estimation of the model parameters and construction of approximate confidence intervals for the covariate effects. We report the results of a simulation study in which we evaluated the bias of the estimators and the coverage rate of the confidence intervals. We also report the results of an application to auditory evoked potentials recorded from five subjects.

Algorithms↗
PubMed1995

Phorbol ester treatment of U937 cells with altered protein kinase C content and distribution induces cell death rather than differentiation.

Overexpression of protein kinase C (PKC)-zeta, an atypical PKC isoform, in U937 cells stimulates certain parameters of phenotypic maturation and increases expression of endogenous alpha and beta PKC isoforms. In response to 12-O-tetradecanoylphorbol-13-acetate (TPA), parental U937 cells displayed growth arrest and differentiated into a monocyte/macrophage-like cell line, while PKC-zeta cells underwent death. The ability of GF109203X to inhibit TPA-induced death of PKC-zeta cells suggested that activation of a conventional isoform was necessary to induce apoptosis. While exhibiting unique morphological changes, parameters indicative of a further degree of differentiation were not observed in TPA-treated PKC-zeta cells. TPA-induced down-regulation of PKC activity was similar in both cells. While modest quantitative differences in individual isoform down-regulation existed, intracellular localization of isoforms prior to activation differed significantly between U937 and PKC-zeta cells. Expression of gadd45 was induced by TPA in PKC-zeta but not parental cells and occurred as a primary response to TPA and prior to the onset of cell death. These data suggest that the decision of a cell to undergo death or differentiation in response to phorbol esters may, in part, be modulated by alterations within the PKC signal transduction pathway.

Antigens, CD↗
PubMed1995

[Midazolam versus placebo before spinal anesthesia].

The goal of this randomized, double blind and multicentric study was to compare the effects of midazolam (M) and placebo (P) administered by titration before puncture for spinal anaesthesia on the comfort of 211 patients scheduled for elective surgery after oral premedication with hydroxyzine. The administered dose of midazolam was 3.4 +/- 1.3 mg (mean +/- SD). Anxiety was nil in 92% of the patients of the M group and in 64% of the patients of the P group (p < 0.001) and memorization of the pain of the puncture was reported in 34% of the patients of the M group and in 66% of the patients of the P group (p < 0.001). However cooperation of the patient and easiness of the puncture were similar in both groups. In conclusion titrated sedation with midazolam before puncture for spinal anaesthesia increases the comfort of the patient.

Adjuvants, Anesthesia↗
PubMed1994

Atlanto-occipital and lateral atlanto-axial joint pain patterns.

STUDY DESIGN: Five asymptomatic subjects underwent provocative injections of the lateral atlanto-axial and atlanto-occipital joints. OBJECTIVES: This study isolated and stimulated the lateral atlanto-axial and atlanto-occipital joints via fluoroscopically guided intra-articular injections to determine if they are potential pain generators. If they are pain generators, preliminary pain pattern maps will be constructed. SUMMARY OF BACKGROUND DATA: The cervical zygapophyseal joints (C2-3 to C6-7) are potential pain generators as demonstrated by referred pain induced via isolated intra-articular joint injections in normal subjects. Tentative referral patterns based on direct mechanical stimulation of the lateral atlanto-axial and atlanto-occipital joints have not been reported. METHODS: Five volunteers without histories of upper cervical pain underwent two joint injections each. In all five subjects, the left atlanto-occipital and right lateral atlanto-axial joints were stimulated via injection of contrast medium causing distension of the joint capsule. RESULTS: Referred pain was produced with all ten injections. The lateral atlanto-axial injections resulted in consistent referral patterns, whereas the atlanto-occipital referral patterns varied significantly. A tentative composite diagram of the experimentally induced pain was created for each joint. CONCLUSION: This study confirms the nociceptive ability of these cervical synovial joints. This study may assist the clinician in the differential diagnosis of head and neck pain.

Adult↗
PubMed1994

Characterisation of cDNA and genomic clones encoding homologues of the 65 kDa regulatory subunit of protein phosphatase 2A in Arabidopsis thaliana.

Two cDNA species encoding sequences homologous to the 65 kDa regulatory subunit (PR 65) of protein phosphatase 2A (PP2A) have been isolated from an Arabidopsis thaliana cDNA library. These were designated pDF1 and pDF2. pDF1 is 1795 bp long and by comparison with the human and porcine PP2A regulatory subunit sequences represents a full-length clone. It encodes a predicted polypeptide of 587 amino acid residues. pDF2 is truncated at the 5' end by 237 bp. The complete nucleotide sequences have been determined for both cDNA species. Comparison of the nucleotide and the deduced amino acid sequences showed that the two sequences were homologous but not identical and therefore must be derived from two different genes. Northern blot analysis was performed on total RNA and poly(A)+ RNA isolated from seed at various stages of development and from young leaf material of Brassica napus L. (oilseed rape). Both cDNA probes hybridised to a single major mRNA species of ca. 2.2 kb. The highest level of expression was observed in the total RNA from developing rape seed at about 33 days after flowering, and the transcript level in the poly(A)+ RNA of the seed was higher than in young leaf of oilseed rape. Southern blot analysis was performed on two varieties of A. thaliana and B. napus genomic DNA; this identified a small family of genes in A. thaliana consisting of at least 2 or 3 members and a larger multigene family in B. napus of at least 5 or 6 members. Two independent genomic clones were isolated from an A. thaliana genomic library. Sequencing of a fragment common to both revealed that the sequence was identical in both clones and, therefore, they were assumed to contain the same genomic sequence. The genomic sequence selected, designated regA, is 3639 bp long and the coding sequence contains eleven introns. The gene encodes a predicted polypeptide of 590 amino acid residues. The sequence comparison with both cDNA sequences showed that it is homologous but not identical to the two, confirming that at least three different genes exist in A. thaliana which encode PR65 of PP2A.

Amino Acid Sequence↗
PubMed1994

Enhanced physical therapy for arm function after stroke: a one year follow up study.

Ninety seven patients with stroke who had participated in a randomised trial of conventional physical therapy nu an enhanced therapy for arm function were followed up at one year. Despite the emphasis of the enhanced therapy approach on continued use of the arm in everyday life, the advantage seen for some patients with enhanced therapy at six months after stroke had diminished to a non-significant trend by one year. This was due to some late improvement in the conventional therapy group whereas the enhanced therapy group remained static or fell back slightly. It is recommended that trials should be conducted comparing very intensive therapy for the arm with controls without treatment. This would provide a model of the effects of therapy on intrinsic neural recovery that would be relevant to all areas of neurological rehabilitation.

Aged↗
PubMed1994

Interpleural infusion of 2% lidocaine with 1:200,000 epinephrine for postthoracotomy analgesia.

The value of intrapleural analgesia after thoracotomy is still controversial. We investigated the pharmacokinetics of interpleural analgesia in 14 patients with and without thoracic drainage (Groups TD+ and TD-, respectively) to determine the safety of the technique. The infusion led to a high steady-state concentration (Css) of 5.91 +/- 2.46 mg/mL in Group TD-. We then performed a placebo-controlled double-blind study on 16 patients to evaluate the analgesic effects of an interpleural infusion of 2% lidocaine using intravenous patient-controlled analgesia (PCA) with morphine and a visual analog scale score (VAS). In both studies an initial bolus of 3 mg/kg of 2% lidocaine was followed by an infusion of 1 mg.kg-1.h-1 for 48 h. The VAS score was slightly reduced after the bolus (6.6 +/- 1.0 vs 8.7 +/- 0.3; P < 0.05 vs the placebo group) but the cumulative doses of morphine were similar in both groups. There was a slight, but not sustained, improvement in pulmonary function test. In conclusion, interpleural analgesia by continuous infusion of lidocaine is poor after thoracotomy and may lead to blood levels in the toxic range.

Aged↗
PubMed1994

[Can facilitation of nociceptive transmission be prevented?].

The sensitization of the central nervous system secondary to nociceptive stimuli is a recent concept. This report reviews the available data about sensitization in animals and man, its mechanisms, and possible techniques of prevention which have been described as preemptive analgesia. The multiple studies have shown that sensitization occurs but is a continuous phenomenon. This continuous phenomenon, partially dependent of the peripheral inputs, can be prevented by some drugs but the modalities and the efficacy of these techniques are still debated.

Analgesia↗
PubMed1994

Overexpression of protein kinase C-zeta stimulates leukemic cell differentiation.

A function for protein kinase C-zeta (PKC-zeta), a member of the phorbol ester nonresponsive atypical protein kinase C subfamily, in modulating differentiation was examined in the leukemic U937 cell. Transfected U937 cells stably overexpressing PKC-zeta displayed a longer doubling time, lower saturation density at confluency, and an increase in adherence to plastic as compared to control cells. PKC-zeta cells expressed a more differentiated phenotype as assessed by changes in morphology, surface antigen expression, and lysosomal enzyme activities and were distinct from parental U937 cells stimulated to differentiate by exposure to phorbol esters. In contrast to parental U937 cells, PKC-zeta cells constitutively expressed mRNA transcripts for c-jun and a low mobility AP-1 binding activity. Thus, PKC-zeta overexpression stimulates a type of phenotypic differentiation that differs significantly from maturation occurring upon activation of other PKC subfamilies induced by phorbol ester treatment. Increased expression of the c-jun protooncogene and an increase in AP-1 binding activity in PKC-zeta cells provides a potential mechanism for explaining the altered differentiation status of this cell.

Antigens, CD↗
PubMed1993

Pharmacokinetics and biological activity of kinetensin in conscious sheep.

Kinetensin is a nonapeptide, originally isolated from pepsin-treated plasma, that shares some sequence homology with the C-terminal end of neurotensin. The present study was designed to determine, by infusing kinetensin to conscious sheep, the pharmacokinetics and a neurotensin-like biological activity (pancreatic polypeptide response) of kinetensin. Kinetensin was rapidly metabolized, approximately 200-fold more rapidly than neurotensin. The majority of the metabolism occurred in the circulation as demonstrated both in vivo and in vitro. The lung and gut cleared kinetensin also. Inhibition of converting enzyme, present in highest concentration in the lung, abolished lung clearance but was without effect on kinetensin metabolism by the gut or in the general circulation. Arterial infusion of kinetensin which achieved high blood kinetensin levels at the pancreas did not increase plasma pancreatic polypeptide. We conclude that the extremely rapid degradation of exogenous kinetensin, together with the lack of biological activity, makes it unlikely that kinetensin plays a role as a circulating regulatory peptide. Nevertheless, since the putative kinetensin substrate circulates at microM concentrations, it is feasible that kinetensin is generated and metabolized at the target organ.

Animals↗
PubMed1993

Abnormal chest x-rays in intravenous drug users: implications for tuberculosis screening programs.

OBJECTIVES: The purpose of the study was to (1) determine the prevalence of significant abnormalities in routine chest x-rays used to screen for pulmonary tuberculosis in intravenous drug users and (2) evaluate the ability of the purified protein derivative skin test to identify persons with such abnormalities. METHODS: We conducted a cross-sectional screening study on 1314 persons admitted to an opiate detoxification unit in an urban jail. Purified protein derivative tuberculin reactivity and the prevalence of abnormalities consistent with tuberculosis on screening chest x-rays were evaluated. The chest x-ray was obtained independent of the skin test. RESULTS: The chest x-rays of 73 of the inmates (5.6%) showed abnormalities consistent with tuberculosis. Tuberculin skin testing missed 17 of 26 chest x-rays (65%) with significant infiltrates. CONCLUSIONS: Purified protein derivative screening is insensitive to chest x-ray abnormalities that require additional diagnostic evaluation for tuberculosis. Routine chest studies should be performed on all intravenous drug users admitted to congregate housing settings.

Adult↗
PubMed1993

[The clinical reality of preventive analgesia].

Preemptive analgesia is based on neurophysiological studies suggesting that a nociceptive input may induce a prolonged hyperexcitability of the central nervous system. This plasticity of the nervous system seems to be more easily prevented than treated. The clinical application of preemptive analgesia is not yet possible. Further clinical and fundamental studies using a good methodology are necessary. This article reviews available clinical data with a special interest for anti-inflammatory drugs that the author has personally evaluated.

Humans↗
PubMed1992

Intracellular neutralization of virus by immunoglobulin A antibodies.

IgA is thought to neutralize viruses at the epithelial surface of mucous membranes by preventing their attachment. Since IgA, a polymeric immunoglobulin, is transported through the lining of epithelial cells by the polymeric-immunoglobulin receptor and since viruses are obligate intracellular parasites, we hypothesized that IgA antibodies may also interfere with viral replication by binding to newly synthesized viral proteins within infected cells. Polarized monolayers of Madin-Darby canine kidney epithelial cells expressing the polymeric-immunoglobulin receptor were infected on the apical surface with Sendai virus. Anti-Sendai virus IgA monoclonal antibody delivered from the basolateral surface colocalized with viral protein within the cell, as documented by immunofluorescence. More importantly, anti-viral IgA reduced virus titers greater than 1000-fold (P less than 0.0001) in apical supernatants and greater than 10-fold (P less than 0.0001) in cell lysates from monolayers treated with anti-viral IgA compared with those treated with either anti-viral IgG or an irrelevant IgA monoclonal antibody. We believe that the differences in viral titers between cell layers treated with specific IgA, which enters the epithelial cell by binding to the polymeric-immunoglobulin receptor, and those treated with specific IgG, which does not enter the cells, or irrelevant IgA indicate that specific intracellular IgA antibodies can inhibit viral replication. Thus, in addition to the classical role of humoral antibodies in extracellular defense, IgA antibody may be able to neutralize microbial pathogens intracellularly, giving IgA a role in host defense that has traditionally been reserved for cell-mediated immunity.

Animals↗
PubMed1992

Induction of emphysema and bronchial mucus cell hyperplasia by intratracheal instillation of lipopolysaccharide in the hamster.

The aim of this study was to determine whether lipopolysaccharide-induced elastase release from recruited neutrophils in the hamster lung would induce emphysema, measured by mean linear intercept (Lm) and bronchial mucus cell hyperplasia (BMCH), scored in tissue sections stained with periodic acid-Schiff. Lipopolysaccharide (LPS) was instilled transorally twice a week for up to 5 weeks in hamsters. At 4 weeks after seven LPS instillations, Lm amounted to 87.6 +/- 1.2 microns, while it was 68.3 +/- 1.5 microns after seven saline instillations (P less than 0.01). At 6 months after the sixth LPS instillation, the Lm of these lungs was 83.3 +/- 1.6 microns, indicating irreversible tissue destruction. LPS-treated hamsters showed marked to severe BMCH, which was most evident in large intrapulmonary airways. Instillations of highly selective inhibitor of hamster PMN elastase resulted in 50 per cent inhibition of LPS-induced emphysema. The development of BMCH was inhibited by approximately 35 per cent by this agent. To study the response in time of cellular infiltration after a single LPS instillation, the lungs of groups of four hamsters were lavaged at different time points. PMN recruitment showed peak values at 4 and 48 h after LPS instillation and returned to baseline values at 96 h. Simultaneous intratracheal instillation of LPS and anti-TNF alpha antiserum resulted in a considerable reduction of neutrophil influx into bronchoalveolar spaces in the first 6 h after instillation.

Animals↗
PubMed1992

Enhanced physical therapy improves recovery of arm function after stroke. A randomised controlled trial.

Previous research on stroke rehabilitation has not established whether increase in physical therapy lead to better intrinsic recovery from hemiplegia. A detailed study was carried out of recovery of arm function after acute stroke, and compares orthodox physiotherapy with an enhanced therapy regime which increased the amount of treatment as well as using behavioural methods to encourage motor learning. In a single-blind randomised trial, 132 consecutive stroke patients were assigned to orthodox or enhanced therapy groups. At six months after stroke the enhanced therapy group showed a small but statistically significant advantage in recovery of strength, range and speed of movement. This effect seemed concentrated amongst those who had a milder initial impairment. More work is needed to discover the reasons for this improved recovery, and whether further development of this therapeutic approach might offer clinically significant gains for some patients.

Activities of Daily Living↗