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Biomedical subjects

D Edwards

Publications and source records attributed to D Edwards.

At least 19 recordsLinked to original sources

Clinical phenotype and molecular analysis of a three-generation family with an interstitial deletion of the short arm of chromosome 5.

We report on a 3-generation family with an interstitial deletion of the short arm of chromosome 5. Varied manifestations were found among the affected individuals including microcephaly, hypertonia, and micrognathia; mental retardation was common to all affected individuals. High resolution chromosome analysis was interpreted as del(5) (pter- > p14.3::p13.3- > qter). Molecular comparison of the deletion in this family with individuals with other 5p deletions suggests that the clinical findings are due specifically to the chromosomal material deleted from 5p13.

Abnormalities, Multiple

Construction and characterisation of a yeast artificial chromosome library containing three haploid maize genome equivalents.

We have constructed a yeast artificial chromosome (YAC) library using high-molecular-weight DNA prepared from agarose-embedded leaf protoplasts of the maize inbred line UE95. This library contains 79,000 clones with an average insert size of 145 kb and should therefore represent approximately three haploid genome equivalents. The library is organised as an ordered array in duplicate microtitre plates. Forty-one pools of DNA from 1920 individual clones have been prepared for rapid screening of the library by the polymerase chain reaction (PCR). Using this approach, together with conventional colony hybridisation, we have been able to identify between one and eight positive clones for every probe used.

Chloroplasts

The role of computed tomography (CT) in the investigation of unexplained haemoptysis.

Forty patients with a history of haemoptysis, normal chest radiographs apart from evidence of chronic airflow limitation, and normal fibreoptic bronchoscopy (or blood alone in the bronchial tree) were investigated by computed tomography (CT). Abnormalities were seen in 20 (50%) of the CT scans. Seven of the patients had evidence of bronchiectasis (18%), one of whom also had a mass. In four (10%) cases a mass alone was detected (two tuberculous, two malignant). In a further four (10%) scans alveolar consolidation was present and in three cases abnormal vessels were detected (7.5%). One patient had cystic changes shown in their scan and multiple nodules were shown in the final patient. The contralateral lungs of 93 patients undergoing CT for pre-operative assessment of bronchogenic carcinoma were used as controls. In six (6%) of these patients abnormalities were detected by CT. Pleural nodules were observed in two patients, fat in the transverse fissure in another, atelectasis in two patients and an apical bulla in the other abnormal scan. The relative risk for patients with unexplained haemoptysis having abnormal CT scans compared to the control group of patients was 7.75. We conclude that computed tomography is of value in the investigation of patients with unexplained haemoptysis.

Adult

Effect of physiotherapy on the auditory evoked response of paralysed, sedated patients in the intensive care unit.

Auditory evoked response (AER) was recorded before, during and after physiotherapy in 11 paralysed (atracurium 0.56 (SD) 0.13 mg kg-1 h-1), sedated (propofol 2.2 (1.0) mg kg-1 h-1; fentanyl 4.4 (2.3) micrograms kg-1 h-1) and critically ill patients undergoing ventilation in the intensive care unit (ICU). The latency of the negative wave, NB, was reduced by physiotherapy (mean 44.8 (SD) 7.9 ms before, 41.0 (6.8) ms during (P less than 0.01, non-parametric Friedman test) and 45.6 (6.3) ms after physiotherapy); NB amplitude showed no consistent change (-0.81 (1.4) microV, -0.81 (1.5) microV and -0.71 (1.3) microV, respectively). NB latency responded to patient arousal at constant levels of sedation and this requires further evaluation as a means of monitoring sedation in paralysed patients in the ICU.

Adult

Upper extremity impairment in workers performing repetitive tasks.

A series of subjective and objective measures were chosen to determine impairment of upper extremity function in 157 workers performing repetitive tasks. Workers were asked to respond to questions regarding their perception of the presence or absence of numbness, pain, weakness, or swelling in their upper extremities. Objective tests consisted of the measurement of grip strength, pinch strength, Semmes-Weinstein monofilament sensory responses, vibrometer responses, neurometer measurement, and the presence or absence of Tinel's or Phalen's signs. These measures were considered collectively to estimate the overall levels of impairment of each individual. Overall findings show that 55 percent of workers examined had impairment scores of 2 or more and 75 percent had scores of 1 or more. Significant differences were found in impairment ratings between job types. Those jobs requiring the highest repetition with the least rest per cycle had the highest impairment ratings. Workers that rotated jobs had impairment scores significantly less (p less than 0.005) than the average of workers performing single-task jobs. We conclude that cumulative trauma disorders are more prevalent than originally believed and that the disorder is best examined from an overall functional impairment perspective.

Adult

Gestational changes in Ca2+ transport across rat placenta and mRNA for calbindin9K and Ca(2+)-ATPase.

The unidirectional maternofetal clearance (Kmf) of 45Ca was measured across the rat placenta over the last one-third of gestation. Kmf for 45Ca normalized to its diffusion coefficient in water (Kmf/Dw) increased 72-fold between days 15 and 22 of gestation from 3.5 +/- 0.3 to 253.1 +/- 22.0 cm/g placenta, respectively. At 15 and 18 days of gestation, Kmf/Dw for 45Ca was similar to Kmf/Dw for the paracellular marker [14C]mannitol, but at 21 and 22 days of gestation, Kmf/Dw for 45Ca was significantly higher than Kmf/Dw for [14C]mannitol, indicating that an additional route of transfer, other than diffusion, becomes available to calcium during this period. Northern hybridization analysis demonstrated that rat placental calbindin9K-to-beta-actin mRNA ratio increased 135-fold between 15 and 22 days of gestation and was temporally associated with the gestational increase in Kmf/Dw for 45Ca. In contrast, rat placental Ca(2+)-ATPase-to-beta-actin mRNA ratio increased only two- to threefold over the same gestational period and did not mirror the gestational changes in calcium clearance. These trends suggest that the expression of placental calbindin9K, but not Ca(2+)-ATPase, may be rate limiting to placental calcium transport in the rat.

Actins

A consumer-operated case management project.

The idea that patients and former patients might themselves be involved in service delivery has become increasingly popular in recent years. Once viewed as an expression of patient protest without clinical merit, self-help services are now, at least in some places, accepted and endorsed by mental health planning authorities. This month's guest columnists describe the philosophical underpinnings of a state-funded consumer-operated case management program in Oregon and discuss both the hope and some of the potential difficulties that such an experimental effort may generate.

Activities of Daily Living

Umbilical artery velocimetry in predicting perinatal outcome with intrapartum fetal distress.

The aim of this study was to see whether umbilical artery Doppler velocimetry predicts intrapartum fetal distress evidenced by poor perinatal outcome. Umbilical velocimetry was performed on 102 parturients with a presumptive diagnosis of fetal distress based on fetal heart rate (FHR) patterns. A mean systolic-diastolic ratio (S/D) of 3 or more after 30 weeks' gestation was considered abnormal. Poor perinatal outcome was defined by any of the following: small for gestational age, low Apgar score, acidosis, meconium below the vocal cords, prolonged neonatal hospital stay, neonatal intensive care unit admission, and neonatal morbidity. Eighty-two patients had normal S/Ds and 20 had abnormal ratios. Eighteen neonates (90%) in the abnormal-SD group had at least one adverse outcome, compared with only 13 (15.8%) of those with a normal S/D, a statistically significant difference (P less than .001). Umbilical artery S/D used as a screening tool to detect poor perinatal outcome had a sensitivity of 65-100%, specificity of 83-92%, positive predictive value of 20-81%, negative predictive value of 91-100%, and a kappa index of 0.24-0.63. These findings suggest that umbilical artery Doppler velocimetry may be useful as an adjunct in the assessment of intrapartum FHR patterns suggesting fetal distress.

Adult

Factors affecting the normal and branched-chain acyl moieties of teicoplanin components produced by Actinoplanes teichomyceticus.

Teicoplanin, a glycopeptide antibiotic produced by Actinoplanes teichomyceticus, comprises five main components, denoted T-A2-1 to T-A2-5, differing in the structure of their acyl side chain, which is linear in T-A2-1 and T-A2-3 and branched in the other components. Production of T-A2-1, characterized by a linear C10:1 acyl moiety, is entirely dependent on the presence of linoleate in the fermentation medium. Addition to the medium of oleic acid esters at 2 g l-1 increases the yields of T-A2-3, characterized by a linear C10:0 acyl chain, about threefold. The antibiotic linear side chains thus appear to originate from C18 unsaturated acid by beta-oxidation degradation. The percentage of T-A2-2, T-A2-4 and T-A2-5, bearing the iso-C10:0, anteiso-C11:0 and iso-C11:0 acyl moieties, respectively, is strongly influenced by the presence in the medium of the amino acids known to be precursors of branched-chain fatty acids. Thus, valine increases the production of T-A2-2 whereas isoleucine or leucine increase the relative yields of T-A2-4 or T-A2-5, respectively. Analysis of the total cell lipids upon addition of the same amino acid shows corresponding increases in the proportion of the iso-C16:0, iso-C15:0 or anteiso-C17:0. A mutant A. teichomyceticus strain, which produces a novel teicoplanin with a linear C9:0 chain, differs from the wild strain in the presence of the linear C17:1 acid in its lipids.(ABSTRACT TRUNCATED AT 250 WORDS)

Acylation

In vitro modulation of the eosinophil-dependent enhancement of the permeability of the bronchial mucosa.

1. Basolateral to apical albumin flux has been measured in sheets of bovine bronchial and tracheal mucosa mounted in vitro. 2. Addition of guinea-pig peritoneal eosinophils or neutrophils to the basolateral side of such tissues had no significant influence on the transmucosal flux of albumin in either the bronchial or tracheal mucosa. 3. Stimulation of eosinophils or neutrophils by the calcium ionophore A23187, or by their presentation to an opsonized airways mucosa, resulted in a significant increase in the transbronchial flux of albumin. This effect was seen after only 60 min incubation of the leucocytes with the bronchial mucosa, and was no greater when the contact time was extended to 180 min. Incubation of bronchial mucosal tissues with 1 mg ml-1 polyarginine for 3 h produced a significant increase in albumin flux, but was ineffective at 0.5 mg ml-1. 4. In contrast to the bronchial mucosa, the tracheal mucosa appeared resistant to the effects of stimulated eosinophils and neutrophils. 5. The lipoxygenase inhibitor AA-861 failed to influence the ability of eosinophils to augment the transmembrane flux of albumin. However, insertion of a Millipore filter mask between the eosinophils and the bronchial mucosa significantly inhibited the eosinophil-dependent enhancement of mucosal permeability. 6. The broad spectrum antiproteinase alpha 2-macroglobulin achieved almost total ablation of the action of stimulated eosinophils in the bronchial mucosa. These results suggest that proteinases may make a significant contribution to the genesis of epithelial injury, whereas leukotrienes do not.

Animals

Concentrations of atracurium and laudanosine in cerebrospinal fluid and plasma in three intensive care patients.

We have measured concentrations of atracurium and laudanosine in cerebrospinal fluid (CSF) and plasma in three intensive care patients receiving atracurium infusions of 22.5-106 h duration to maintain neuromuscular block. Two patients had suffered severe closed head injuries and the third patient had developed respiratory failure following the clipping of two intracranial aneurysms. The total dose of atracurium given was 14.3-136.6 mg kg-1; rate of infusion was 0.6-1.38 mg kg-1 h-1. Plasma concentrations of atracurium and laudanosine were 0.73-3.11 micrograms ml-1 and 0.48-8.65 micrograms ml-1, respectively; CSF concentration of laudanosine was 70-440 ng ml-1. No adverse effects attributable to these concentrations of laudanosine were observed.

Adult

Bronchography in the assessment of patients with lung collapse for endoscopic laser therapy.

In an attempt to improve selection of patients and the efficacy of endoscopic laser treatment, a bronchographic technique has been developed for patients with tumours causing complete endobronchial obstruction. This technique has shown patent distal airways in 16 out of 17 patients with a collapsed lung or lobe. These airways were abnormally dilated in each case, suggesting bronchiectasis. In one patient the appearances of bronchiectasis were sufficiently severe to decide against attempting treatment. Treatment was not attempted in another patient as a large cavity was seen within the collapsed lung and this was thought to carry a risk of postoperative infection and haemorrhage. Treatment with a neodymium YAG laser under general anaesthesia successfully recanalised the airway in 12 of the 15 remaining patients and was associated with a substantial reduction in breathlessness. The procedure was abandoned prematurely in one patient because of life threatening haemorrhage. In the remaining two patients in whom treatment was unsuccessful bronchography had suggested very extensive endobronchial obstruction. Spirometry and radionuclide lung scans were performed before and after treatment in eight patients treated successfully and showed significant improvements. Four patients were investigated within two weeks of lung re-expansion by repeat bronchography (three patients) or computed tomography (one patient); in each case the calibre of the airways had returned almost to normal. Thus the radiological demonstration of bronchial dilation in a collapsed lung does not necessarily imply a diagnosis of irreversible bronchiectasis and should not be regarded as a contraindication to treatment. It is concluded that preoperative bronchography provides reliable data on the extent of tumour, the patency of the distal airways, and presence of extensive cavitation. This information should facilitate successful laser treatment.

Adult

Antibiotic SB22484: a novel complex of the aurodox group. II. Structure elucidation of the four factors.

SB22484, active against Neisseriae gonorrhoeae and Neisseriae meningitidis, is a complex of four factors, designed 1 through 4, which from two pairs of isomers, 1 and 3, and 2 and 4. Factors 1 and 3 account for 65% of the complex, factor 3 being the predominant one. On the basis of the existing and implemented correlations between structure and physico-chemical characteristics (UV and IR spectroscopies, ionization properties, MS as FAB and as negative and positive CI, 1H NMR spectroscopy as 2D COSY and NOESY) in the aurodox field, the complete structures were assigned. Factor 3 can be described as N-[7-[5(R)-[7-[1,2-dihydro-4-hydroxy-1H-2-oxo-3-pyridinyl]-6-methyl- 7-oxo-1(E),3(E),5(E)-heptatrienyl]tetrahydro-3(S),4(R)-dihydrox yfuran-2 (S)-yl]-6(S)-methoxy-5,7(R)-dimethyl-2(E),4(E)-heptadienyl]-alpha (S)-methyl-5(S)-methyltetrahydro-2(S),4(S or R)-dihydroxy-6(S)-[1(E), 3(Z)-pentadienyl]-2H-pyran-2-acetamide. Factor 1 is an epimer of factor 3 with the opposite configuration at the anomeric center. Factors 2 and 4 have an ethyl group instead of the methyl group alpha to the acetamide moiety and are in the same stereochemical relationship as the pair 1 and 3.

Acid-Base Equilibrium

Method for evaluating performance of clinical pharmacists.

A performance-evaluation process that satisfies Joint Commission on Accreditation of Healthcare Organizations criteria and state policies is described. A three-part, criteria-based, weighted performance-evaluation tool specific for clinical pharmacists was designed for use in two institutions affiliated with the University of Washington. The three parts are self-appraisal and goal setting, peer evaluation, and supervisory evaluation. Objective criteria within each section were weighted to reflect the relative importance of that characteristic to the job that the clinical pharmacist performs. The performance score for each criterion is multiplied by the weighted value to produce an outcome score. The peer evaluation and self-appraisal/goal-setting parts of the evaluation are completed before the formal performance-evaluation interview. The supervisory evaluation is completed during the interview. For this evaluation, supervisors use both the standard university employee performance evaluation form and a set of specific criteria applicable to the clinical pharmacists in these institutions. The first performance evaluations done under this new system were conducted in May 1989. Pharmacists believed that the new system was more objective and allowed more interchange between the manager and the pharmacist. The peer-evaluation part of the system was seen as extremely constructive. This three-part, criteria-based system for evaluation of the job performance of clinical pharmacists could easily be adopted by other pharmacy departments.

Employee Performance Appraisal

Liquid chromatography-mass spectrometry coupling and its application in pharmaceutical research.

The advantages and technical problems related to the on-line connection of liquid chromatography and mass spectrometry are described, with special emphasis on applications in pharmaceutical chemistry. The most important characteristics of various interfaces, such as direct liquid introduction, Magic, continuous flow fast atom bombardment and thermospray, are discussed. Special applications to the study of thermally very labile compounds are considered.

Chromatography, Liquid