Midazolam infusion in a pediatric intensive care unit.
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Child↗
Biomedical subjects
J Hughes
Publications and source records attributed to J Hughes.
[3H]PD 140376: a novel and highly selective antagonist radioligand for the cholecystokininB/gastrin receptor in guinea pig cerebral cortex and gastric mucosa.
The specific binding characteristics of the novel cholecystokinin (CCK)B/gastrin receptor-selective peptoid antagonist radioligand [3H]PD 140376 were investigated using membrane homogenates prepared from guinea pig cerebral cerebral cortex and gastric fundic mucosa. [3H]PD 140376 (0.01-10 nM) bound to both cerebral cortex and gastric gland homogenates with comparable high affinity (Kd, 0.1-0.2 nM) and to an apparent single population of sites with Bmax values of 119 and 296 fmol/mg of protein, respectively. The level of specific binding, defined as that displaced by unlabeled CCK sulfated octapeptide, was routinely between 60 and 70% in the cortex and between 50 and 60% in the fundic mucosa. Pharmacological characterization of the [3H]PD 140376-labeled binding sites with a series of agonist and antagonist ligands selective for each of the CCK receptor subtypes demonstrated, in both preparations, an affinity profile consistent with that of the CCKB/gastrin receptor. However, Hill slopes for the competition curves for the unlabeled agonist ligands against specific [3H]PD 140376 binding were significantly less than unity, whereas those for the antagonist ligands, including unlabeled PD 140376, were close to unity. The affinity and Hill slope for PD 140376 and the related CCKB/gastrin antagonist CI-988 were unaffected by the presence of the nonhydrolyzable GTP analogue guanylyl-5'-imidodiphosphate. In contrast, guanylyl-5'-imidodiphosphate caused a characteristic decrease in affinity and an increase in the Hill slopes towards unity for the agonist ligands CCK sulfated octapeptide and pentagastrin. The binding characteristics of unlabeled PD 140376 were also unaffected by the presence of the monovalent cation sodium. In conclusion, the present study has demonstrated that [3H]PD 140376 is the most potent and selective antagonist radioligand yet described for the characterization of CCKB/gastrin receptors in the central and peripheral nervous systems.
Animals↗
The clinical use of pedobarography.
Several years' experience with different pedobarograph systems has demonstrated that foot pressure measurements can be used as a clinical tool. This tool can aid a surgeon's decision making, but it cannot be used diagnostically in isolation from clinical data. The clinical uses are both direct and indirect. The direct uses can be summarized as follows: to assess the effect of treatment by examination before and after a surgical procedure; to monitor progress by means of sequential measurements and to design and assess the effectiveness of orthoses. These uses are demonstrated with reference to a number of studies of normal subjects compared to patient groups using the dynamic pedobarograph. Indirect uses come from the growing body of knowledge emerging from laboratories using this equipment for research. This is helping us to understand weightbearing foot function both in health and disease. Clinicians intending to invest in the equipment can also obtain useful guidelines on the reliability of the different systems and measurements and best ways to standardize methodology. Some examples of these indirect uses are illustrated with results from studies using the dynamic pedobarograph and the EMED F system.
Foot↗
Soluble forms of vascular adhesion molecules, E-selectin, ICAM-1, and VCAM-1: pathological significance.
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Animals↗
[Treatment of depressed patients: current trends. Combination cognitive group therapy with cognitive adjustment for depressed inpatients].
Depressed patients represent a major part of the inpatient population. The following treatment program was developed in order to respond to this problem in a symptom- and cost-effective way. Cognitive therapy was chosen for it's learning aspect and combined with pharmacotherapy. The four-week treatment program is implemented in an open-ended group setting, where daily therapy sessions are associated with various group activities. The pre- and posttreatment and six months follow-up results of the first 80 patients are presented.
Adult↗
Skyrmion recoil in pion-nucleon scattering.
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Journal Article↗
Diet and calcium stones.
OBJECTIVE: To review the current literature on the dietary modification of urinary risk factors as a means of reducing the likelihood of recurrent stone formation and to develop practical dietary recommendations that might be useful to this end. DATA SOURCES: MEDLINE was searched for English-language articles published from 1983 to 1990. Additional references were selected from the bibliographies of identified articles. STUDY SELECTION: Nonrandomized trials and retrospective reviews were included because of a paucity of randomized controlled trials. DATA SYNTHESIS: Information on the dietary intake of calcium, oxalate, protein, sodium and fibre and on alcohol and fluid intake was used to develop practical guidelines on dietary modification. CONCLUSION: Dietary modification plays an important role in the reduction of urinary risk factors in patients with calcium stone disease of the urinary tract. As an initial form of prevention attention should be directed toward moderating the intake of calcium, oxalate, protein, sodium and alcohol and increasing the intake of fibre and water. Future research should include an assessment of the long-term reduction of dietary and urinary risk factors and the rates of recurrence of calcium stones.
Alcohol Drinking↗
A molecular and biochemical analysis of the structure of the cyanogenic beta-glucosidase (linamarase) from cassava (Manihot esculenta Cranz).
The cyanogenic beta-glucosidase (linamarase) of cassava is responsible for the first step in the sequential break-down of two related cyanoglucosides. Hydrolysis of these cyanoglucosides occurs following tissue damage and leads to the production of hydrocyanic acid. This mechanism is widely regarded as a defense mechanism against predation. A linamarase cDNA clone (pCAS5) was isolated from a cotyledon cDNA library using a white clover beta-glucosidase heterologous probe. The nucleotide and derived amino acid sequence is reported and five putative N-asparagine glycosylation sites are identified. Concanavalin A affinity chromatography and endoglycosidase H digestion demonstrate that linamarase from cassava is glycosylated, having high-mannose-type N-asparagine-linked oligosaccharides. Consistent with this structure and the extracellular location of the active enzyme is the identification of an N-terminal signal peptide on the deduced amino acid sequence of pCAS5.
Amino Acid Sequence↗
Retinal speed gradients and the perception of surface slant.
Previous work has demonstrated a difference in human sensitivity to compressive and shearing speed gradients. This raises the possibility that the ability to estimate the slant of a surface may vary with its direction of tilt. No such variance was found here, which may indicate that slant estimation depends upon deformation rather than upon compression or shear.
Humans↗
Lateral band translocation for swan-neck deformity.
Lateral band translocation involves transfer of the dorsally subluxed radial lateral band to the palmar aspect of the joint where it is maintained by a sling created between the flexor superficialis tendon and the palmar plate. Thirty fingers with swan-neck deformity of differing causes and a preoperative hyperextension deformity averaging 16 degrees were treated. After operation all swan-neck deformities were corrected and the average flexion contracture was 11 degrees. The range of preoperative flexion was either regained or improved. There were no recurrences and no complications. This relatively simple procedure is an effective treatment of swan-neck deformity and an attractive alternative to previously described procedures.
Female↗
Melphalan concentration and distribution in the tissues of tumour-bearing limbs treated by isolated limb perfusion.
Levels of melphalan (L-phenylalanine mustard) were measured in the tissues of tumour-bearing limbs treated by isolated limb perfusion (ILP). 41 samples of melanoma tissue, normal fat and skin were excised from 15 patients during ILP. A high performance liquid chromatography assay was used to measure melphalan concentrations. Levels of melphalan were higher in tumour than in fat (P < 0.01, Wilcoxon signed-ranks test), and not significantly different from levels in adjacent skin. In 2 cases there was significant regional toxicity in the treated limb, but this was not related to the levels of melphalan measured in the tissues of the limb. It is encouraging that the concentrations of melphalan which were achieved in large necrotic nodules by ILP were similar to those in well-perfused normal skin.
Adipose Tissue↗
A method for screening the quality of hospital care using administrative data: preliminary validation results.
Applying a computerized algorithm to administrative data to help assess the quality of hospital care is intriguing. As Iezzoni and colleagues point out, there are major differences of opinion as to the worth of such efforts. This article significantly advances the state of the art in using administrative data to screen for potential quality-of-care problems. In addition, this work on identifying complications of care goes well beyond the emphasis of many government organizations on hospital mortality rates. One question, however, not raised in the paper is: What is a practical upper limit to the sensitivity and specificity in comparing computerized screen results with the consensus judgments of a group of independent physicians? Advanced statistical techniques (such as bootstrapping) might be used to estimate the stability of consensus judgments by physician groups. When the judgments of two groups of physicians are compared with each other, the resulting sensitivity and specificity will not be .99! In addition, more training of members of the physician panels would probably have increased interrater reliability. While acknowledging this problem, the researchers' detailed analysis of the panel results is intriguing and represents a model for such studies. It is hoped that the authors will follow up on the avenues opened here. Furthermore, what degree of accuracy is necessary to identify facilities with higher-than-expected rates of complications? The authors discuss problems involved in using administrative data to target hospitals and departments for more costly in-depth reviews of quality. It is hoped that the promising findings that are reported here will be validated in other studies. Certainly their algorithms should find a ready audience in insurers and hospitals willing to try them out. Finally, should we expect additional research to lead to improvement in the authors' algorithms? I believe the algorithms will prove difficult to improve upon; but perhaps we should not worry about this. At some point, however, the cost of trying to identify and correct quality problems in "minimally outlier" hospitals will exceed the benefits, particularly given alternative uses for the funds. Might we now be close the the "flat of the curve" in the development of such systems for identification of quality problems? This issue should be discussed much further in future studies.
Abstracting and Indexing↗
The pharmacokinetic advantages of isolated limb perfusion with melphalan for malignant melanoma.
We describe melphalan pharmacokinetics in 26 patients treated by isolated limb perfusion (ILP). Group A (n = 11) were treated with a bolus of melphalan (1.5 mg kg-1), and in a phase I study the dose was increased to 1.75 mg kg-1. The higher dose was given as a bolus to Group B (n = 9), and by divided dose to Group C (n = 6). Using high performance liquid chromatography (HPLC) the concentrations of melphalan in the arterial and venous perfusate (during ILP) and in the systemic circulation (during and after ILP) were measured. Areas under the concentration time curves for perfusate (AUCa, AUCv) and systemic (AUCs) data were calculated. In all three groups the peak concentrations of melphalan were much higher in the perfusate than in the systemic circulation. The pharmacokinetic advantages of ILP can be quantified by the ratio of AUCa/AUCs, median value 37.8 (2.1-131). AUCa and AUCv were both significantly greater in Group B than in Group A (P values less than 0.01, Mann-Whitney). In Groups B and C acceptable 'toxic' reactions occurred but were not simply related to melphalan levels. Our phase I study has allowed us to increase the dose of melphalan to 1.75 mg kg-1, but we found no pharmacokinetic advantage from divided dose administration.
Arteries↗
Reliability of labial closure force measurements in normal subjects and patients with CNS disorders.
This study determined the reliability of maximal upper and lower lip closing forces measured using a strain-gauged cantilever beam assembly. An intraclass correlation approach was used to explicitly partition the "error free" between-subject variance and measurement error variance across repeated days (2) and across repeated trials (5). Ten healthy adults served as controls and 30 patients with diagnoses of multiple sclerosis, cerebrovascular accident, or Parkinson's disease served as subjects. The intraclass correlation analyses revealed generally high reliability (R greater than .90) for upper and lower lip force measurements, for various combinations of control and/or patient groups, and within each individual patient group. There was moderate correspondence between the quantitative measures of lip force and the clinical assessment of combined upper (r = .67) and lower lip closure force (r = .62) but low correspondence between the quantitative measures of lip force and the presence of motor speech deficit. The lower lip force of patients with Parkinson's disease (M = 3.1 N) on Day 1 was markedly reduced from that of all other patient groups and controls (M = 10.1 N). These results yield helpful information for the design of investigations of oral-motor weakness and for the quantitative assessment of an individual's clinical status.
Aged↗
Temporal integration of spatially filtered visual images.
Factors which govern the temporal integration of spatial information were examined in a group of five experiments. A series of high-pass and low-pass spatially filtered versions of a visual scene were generated. Observers' ratings of these filtered versions of the scene for perceived image quality indicated that quality was determined both by the bandwidth of spatial information and the presence of high-spatial-frequency edge information. When sequences of three different versions of the scene were presented over an interval of 120 ms the perceived quality of the resulting composite image was determined both from the ratings of the individual components of that sequence and from the order in which these components were presented. When the order of spatial information in a sequence moved from coarse to fine detail the perceived quality of the composite image was significantly better than when the order moved from fine to coarse. This evidence of a coarse-to-fine bias in pattern integration was further investigated with a detection paradigm. The pattern of errors once again indicated that temporal integration of spatial information was superior when a coarse-to-fine mode of information delivery was employed. Taken together the data indicate that the pattern-integration mechanism has an inherent order bias and does not accumulate spatial information so efficiently when the 'natural' coarse-to-fine order is violated.
Attention↗
Percutaneous laser disc decompression. A new therapeutic modality.
The authors present a new advance in the treatment of herniated disc disease using percutaneous Nd:YAG laser to vaporize a small portion of nucleus pulposus, thereby decompressing the disc. In vitro and in vivo animal data are presented. Three hundred seventy-seven magnetic resonance imaging or computed tomography scan-documented, herniated, nonsequestered lumbar intervertebral discs with corresponding clinical findings in 333 patients were so treated in an outpatient setting. The longest follow-up was 62 months, with a mean of 26 months. According to the Macnab criteria, there was a good to fair response in 261 patients (78.4%), and a poor response in 72 (21.6%); 166 patients experienced relief of pain during the procedure. One-third of repeat magnetic resonance imaging scans at 4-6 months postlaser treatment showed modest to moderate decrease of disc herniation.
Adult↗
CI988, a selective antagonist of cholecystokininB receptors, prevents morphine tolerance in the rat.
1. The effect of chronic treatment with CI988, a recently developed selective antagonist of cholecystokinin type-B receptors (CCKB receptors) on the tolerance to morphine analgesia was studied in rats with the hot plate test. 2. Morphine tolerance was induced with the use of two paradigms. Morphine was injected i.p. either in a schedule of increasing doses (1-32 mg kg-1) twice daily for 6 days or at a fixed dose (3 mg kg-1) daily for 29 days. 3. In both series of experiments, tolerance to the analgesic effect of morphine was prevented by simultaneous treatment with i.p. CI988. Chronic treatment with only CI988 daily for up to 29 days did not reduce the analgesic effect of a weekly injection of morphine. 4. CI988 did not diminish the physical dependence to morphine, as examined with naloxone precipitated withdrawal. 5. The present results provide evidence that chronic treatment with a selective CCKB receptor antagonist could prevent tolerance to the analgesic effect of morphine without affecting morphine-induced physical dependence. Application of CCK antagonists may be clinically important in treating chronic pain patients by preventing morphine tolerance and by eliminating the need to increase morphine doses to unacceptable levels.
Animals↗
The antagonism of benzodiazepine withdrawal effects by the selective cholecystokininB receptor antagonist CI-988.
The ability of a selective cholecystokininB (CCKB) receptor antagonist, CI-988, to block benzodiazepine withdrawal effects was examined in mice. The discontinuation of twice daily administration of diazepam (1 mg kg-1, i.p.) induced withdrawal anxiogenesis and a proconvulsant effect. In contrast, no such effects were seen following withdrawal from similar administration of CI-988. However, CI-988 dose-dependently (0.001-1.0 mg kg-1, s.c.) antagonized both the anxiogenesis and the proconvulsant effect following diazepam-withdrawal.
Animals↗