Intracellular neutralization of Sendai and influenza viruses by IgA monoclonal antibodies.
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Animals↗
Biomedical subjects
D Fletcher
Publications and source records attributed to D Fletcher.
Rate of oxygen consumption by parotid atrophic acinar cells from rats fed liquid diet.
Adult male rats were maintained on a nutritionally adequate liquid-diet or laboratory chow and water (control), for 9 days. They were then killed and the parotid glands removed. Enzymatically dispersed acinar-cell preparations were used to study rates of oxygen consumption (QO2) using a Clark oxygen electrode. For both CON and LD cell preparations the basal QO2 was 0.132 (+/- 0.03-0.05) nmol O2 per microgram DNA per min and in each case this was increased approx. 2.4-fold under stimulation by carbachol (10 microM) and approx. 3.1-fold by adrenaline (10 microM). Isoprenaline (10 microM) elicited no significant increase in QO2. Addition of ouabain (2.5 mM) or removal of Ca2+ from the extracellular medium prevented the action of carbachol to increase QO2 over a sustained period. There were no significant differences in the basal, agonist-stimulated, or ouabain-sensitive QO2 by dispersed acinar cells from liquid-diet rats compared to control. The results are consistent with the notion that liquid diet-induced atrophy represents a physiological adaptation rather than a pathological change. Nevertheless, they also indicate that in the acinar cells from liquid-diet rats the Na+/K+ ATPase is required to operate at normal levels of energy consumption despite the reduced acinar-cell volume and consequently lower levels of agonist-elicited transepithelial ion movements known to occur in these cells.
Animal Feed↗
Influence of timing on the analgesic effect of intravenous ketorolac after orthopedic surgery.
This study evaluated the pre-emptive analgesic effect of intravenous (i.v.) ketorolac (KET) for total hip replacement (THR). Sixty patients who underwent surgery for THR under general anesthesia were randomly allocated to 3 groups. Two i.v. injections were administered: one before induction and one after surgery. The patients were studied prospectively in a double-blind manner. The control group (CONT; n = 20) received 2 ml of normal saline (NS) for both injections. The pre-operative KET group (PRE; n = 20) received 60 mg of KET and then 2 ml of NS. The postoperative KET group (POST; n = 20) received 2 ml of NS and then 60 mg of KET. General anesthesia was standardized with a intra-operative cumulated dose of fentanyl limited to 4 micrograms/kg. In the recovery room (RR), pain was controlled with an i.v. tritration of morphine; thereafter, on the surgical ward, patients used a patient-controlled analgesia (PCA) pump (Abbott). Pain was evaluated with a visual analogue scale (VAS) at rest and movement in the RR, then every hour for 6 h and every 6 h for 5 days. The side effects monitored were: sedation, respiratory depression, nausea, perioperative bleeding. The patients and surgery were similar for the 3 groups. Upon arrival in the RR, VAS scores taken at rest and at movement were lower for the PRE group than for the CONT and POST groups. Otherwise, VAS scores were similar in all 3 groups. The cumulative dose of morphine in the PRE group was lower than that for the CONT and POST groups from 0 to 6 h.(ABSTRACT TRUNCATED AT 250 WORDS)
Aged↗
Resistance to fever induction and impaired acute-phase response in interleukin-1 beta-deficient mice.
We used gene targeting in embryonic stem cells to introduce an IL-1 beta null allele in mice. The IL-1 beta-deficient mice develop normally and are apparently healthy and fertile. The IL-1 beta null mice responded normally in models of contact and delayed-type hypersensitivity or following bacterial endotoxin LPS-induced inflammation. The IL-1 beta-deficient mice showed equivalent resistance to Listeria monocytogenes compared with wild-type controls. In contrast, when challenged with turpentine, which causes localized inflammation and tissue injury, the IL-1 beta mutant mice exhibited an impaired acute-phase inflammatory response and were completely resistant to fever development and anorexia. These results highlight a central role for IL-1 beta as a pyrogen and a mediator of the acute-phase response in a subset of inflammatory disease models, and support the notion that blocking the action of a single key cytokine can alter the course of specific immune and inflammatory responses.
Acute-Phase Reaction↗
Predictive value of acid-fast smears of sputum obtained by expectoration versus induction or bronchoalveolar lavage in patients with tuberculosis.
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Bronchoalveolar Lavage↗
[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↗
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↗
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↗
[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↗
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↗
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↗
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↗
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↗
[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↗
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↗
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↗
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↗
[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↗