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Biomedical subjects

D E Roberts

Publications and source records attributed to D E Roberts.

At least 37 records · Page 2Linked to original sources

Antineutrophil cytoplasmic autoantibodies in the immunodiagnosis of systemic necrotizing vasculitis.

If testing of ethanol-fixed neutrophils remains the most commonly used method to screen for ANCA. C-ANCA is highly sensitive and specific for Wegener's granulomatosis if strict criteria in defining this IF pattern are followed. P-ANCA is not specific for MPO-ANCA, when used as a screening test. Because of the increasing recognition of atypical cytoplasmic staining patterns and the lack of specificity of nuclear staining of neutrophils for MPO-ANCA, confirmatory testing by ELISA is advisable in all cases of atypical neutrophil cytoplasmic staining and in all cases of neutrophil nuclear or perinuclear staining.

Antibodies, Antineutrophil Cytoplasmic↗

Pyridostigmine bromide does not alter thermoregulation during exercise in cold air.

This study examined the effects of acute and chronic pyridostigmine bromide (PB) administration on thermoregulatory and metabolic responses to exercise in cold air (5 degrees C). Seven healthy men completed two 7-day trials in a double-blind, crossover experimental design: during one trial they received PB (30 mg three times daily) and during the other trial they received placebo. For each trial, subjects attempted four (3 h) exercise tests: low-intensity exercise (approximately 25% VO2max) and moderate-intensity exercise (approximately 50% VO2max), on days 2 and 3 and again on days 6 and 7. Metabolic rate, body temperatures, and venous blood samples were obtained before and during exercise. Red blood cell acetylcholinesterase inhibition induced by PB increased (p < 0.05) from 34% on day 1 to 43% on days 3-7. Metabolic rate, body temperatures, and regional heat conductance responses were not different between trials. Plasma glucose, glycerol, free fatty acid, lactate, sodium, and potassium concentrations were not different between trials. In addition, differences were not found between acute and chronic experiments for any thermoregulatory or metabolic responses. These findings demonstrate that the PB dosage used by military personnel, as a pharmacological defense against nerve-agent poisoning, should not cause any adverse thermoregulatory or metabolic effects during moderate activity in cold climates.

Adult↗

Cold-weather field feeding: an overview.

Extremely cold environments are a challenge to military field feeding operations due to freezing and inadequate intakes of rations and water. The U.S. Army Research Institute of Environmental Medicine conducted a series of three cold-weather field feeding studies to test, modify, and contribute data for the development of Cold-Weather Feeding Doctrine. Conclusions from these studies show that command emphasis is essential for ration and water storage and distribution to prevent freezing, and adequate ration and water consumption to prevent weight loss and dehydration. Since any ration mix can be configured to meet cold-weather feeding requirements, the decision of which ration to use should be based on logistical support and constraints, mission requirements, and water availability.

Dehydration↗

Eliminating needless testing in intensive care--an information-based team management approach.

OBJECTIVE: To determine if the application of an information-based management system in adult intensive care units (ICU) can produce sustained decreases in the use of laboratory resources and costs. DESIGN: Interventional study with prospective data collection on consecutive patients admitted during three time periods. SETTING: A 10-bed adult surgical ICU and an eight-bed adult medical ICU in a tertiary care hospital. PATIENTS: All patients admitted to an ICU during a 7-month baseline period (n = 647), a 1-yr intervention period (n = 1236), and a 2-yr follow-up period (n = 2349). INTERVENTIONS: Using a management database to track the use of 123 laboratory investigations during the baseline period, nine frequently ordered investigations (determination of blood gases, glucose, potassium, electrocardiogram, chest radiograph, sodium, chloride, complete blood count with differential, and serum osmolality) were targeted for reduction. Specific policies were developed by a multidisciplinary committee within the ICU to reduce the utilization of these laboratory, radiology, and cardiology tests. The policies were applied to all patients admitted during the 1-yr intervention period and during the 2-yr follow-up period. MEASUREMENTS AND MAIN RESULTS: A 25% reduction was observed in the frequency of all 123 monitored tests during the intervention period. The most dramatic reductions occurred in the nine targeted tests (range 19% to 46%) (p < .001). There were significant reductions in only 13 of the untargeted 114 investigations during this period. Potential annual cost savings were > $150,000 Canadian. No increases in ICU mortality rate, length of stay, or cost of medication were observed, and the reductions in the frequency of targeted tests were maintained during the 2-yr follow-up period. CONCLUSIONS: Application of an information-based multidisciplinary management system in the ICU can produce marked and sustained reductions in unnecessary testing in a cost-effective manner. Although rationing of intensive care services may be necessary, reducing needless testing can be a safe and effective cost-containment strategy in the ICU.

Cost Control↗

Is there a need for improved pharmacy services to the operating theatre?

A study to assess the control and handling of drugs within an operating theatre complex (10 theatres) of an 850-bed hospital, has revealed the presence of unusable medication and thus highlighted the need for improved pharmacy services. The aims and objectives of the pharmacy department to enhance such services included improvement of drug control of stock medication and the introduction of clinical pharmacy services within the operating theatre. To undertake this, three systems were evaluated with reference to systems already in use in the U.S.A. Operating theatre visits by a clinical pharmacist, coupled with the expansion of the existing drug distribution service, were identified as the most cost-effective methods that would allow the objectives to be met. Consequently, this has now been implemented within the operating theatre complex.

Evaluation Studies as Topic↗

Inhibition of human neutrophil migration in vitro by low-molecular-mass products of nontypeable Haemophilus influenzae.

Nontypeable Haemophilus influenzae commonly causes infections in the lower and upper respiratory tract, although the mechanisms of its colonization and persistence in the airways are unclear. Culture filtrates from six clinical isolates of this bacterium were assessed for their abilities to influence neutrophil function in vitro. Each culture filtrate was assessed on six separate occasions with neutrophils obtained from six different donors. During the log and early stationary phases of growth (0 to 18 h), culture filtrates contained primarily neutrophil chemokinetic activity but no activity affecting neutrophil migration toward the chemotactic factors N-formyl-L-methionyl-L-leucyl-L-phenylalanine and leukotriene B4. In contrast, filtrates obtained after 24 h of culture contained factors which inhibited neutrophil migration toward both of these chemotactic factors. This chemotaxis-inhibitory activity persisted between 24 and 72 h of bacterial culture, and it was not associated with the presence of either chemotactic or chemokinetic activity as assessed by checkerboard analysis. Gel filtration of pooled 72-h filtrates yielded three major peaks of chemotaxis-inhibitory activity. Endotoxin was present together with two other low-molecular-mass hydrophobic factors of approximately 8 and 2 kDa. These low-molecular-mass factors are chloroform insoluble and heat stable, and they are inactivated by protease, periodate, and diborane reduction. Activity was completely retained on a wheat germ agglutinin column, and it could be eluted with N-acetyl-D-glucosamine. These data suggest that inhibitory activity is associated with N-acetyl-D-glucosamine-containing glycopeptides, possibly derived from the bacterial cell wall. The production of these compounds may contribute to the persistence of this bacterium in vivo by inhibiting neutrophil chemotaxis in the microenvironment of the respiratory mucosa.

Biological Factors↗

Haemophilus influenzae infection of human respiratory mucosa in low concentrations of antibiotics.

We examined the effects of 0.25 and 0.5 minimal inhibitory concentrations (MIC) of amoxicillin, loracarbef, and ciprofloxacin on the interaction of a clinical isolate of nontypable Haemophilus influenzae (NTHi) with human adenoid organ culture. Adenoid tissue was embedded in agar so that only the mucosal surface was exposed. Minimum essential medium containing NTHi with or without antibiotics was added to the organ culture and incubated with 5% CO2 at 37 degrees C for 24 h. The organ cultures (n = 6) were assessed for several parameters by light microscopy (LM) and transmission electron microscopy (TEM). Bacterial viable counts after 24 h were not significantly different in all organ cultures. Compared with uninfected controls at 24 h, infection with NTHi caused significant (p < 0.05) damage to epithelium as assessed by LM: reduced ciliary beat frequency (CBF), disruption of epithelium integrity, and reduced number of ciliated sites. TEM showed extrusion of cells from the epithelial surface, loss of cilia from ciliated cells, cytoplasmic blebbing, and mitochondrial damage. In the presence of 0.25 and 0.5 MIC of all three antibiotics, the mucosal damage was significantly less (p < 0.05). We conclude that in the presence of sub-MIC levels of amoxicillin, loracarbef, and ciprofloxacin, NTHi infection causes less functional (CBF) and structural damage.

Adenoids↗

Cold weather field evaluation of the 18-Man Arctic Tray Pack Ration Module, the meal, ready-to-eat, and the Long Life Ration Packet.

The Army Field Feeding System was evaluated for its ability to provide adequate nutrition and hydration during a 10-day cold weather field exercise. Soldiers consumed the 18-Man Arctic Tray Pack Ratio Module with either a wet-pack (Meal, Ready-to-Eat) or a dehydrated (Long Life Ration Packet) individual ration. Both feeding regimens were acceptable, meeting protein and micronutrients requirements. However, the soldiers consumed only 70% of their energy requirement, thus losing an average of 0.9% of body weight. This weight loss, although not excessive, underscores the importance of maintaining an adequate food intake during extended cold weather military field operations.

Adolescent↗

Policy for controlling pain after surgery: effect of sequential changes in management.

OBJECTIVE: To observe the effects of introducing an acute pain service to the general surgical wards of a large teaching hospital. DESIGN: A study in seven stages: (1) an audit of current hospital practice succeeded by the sequential introduction to the general surgical wards of (2) pain assessment charts; (3) an algorithm to allow more frequent use of intramuscular analgesia; (4) increased use of local anaesthetic techniques of wound infiltration and nerve blocks; (5) an information sheet for patients about postoperative pain; (6) the introduction of patient controlled analgesia; (7) a repeat audit of hospital practice. Data were collected on each patient 24 hours after operation. SETTING: University Hospital of Wales, which has both district general and tertiary referral functions. PATIENTS: 2035 patients over nine months from all surgical specialties (excluding cardiac) at the hospital. General surgical operations were studied in detail and separated into major, intermediate, and minor for data collection. MAIN OUTCOME MEASURES: A change in the median visual analogue pain scores 24 hours after surgery for pain during relaxation, pain on movement, and pain on deep inspiration at each stage of the study. RESULTS: There was a reduction in median visual analogue scores during the study. The median (95% confidence interval) scores for pain during relaxation decreased from 45 (34 to 53) in stage 1 to 16 (10 to 20) in stage 7 for major surgical procedures. Pain on movement decreased from 78 (66 to 80) to 46 (38 to 48), and pain on deep inspiration decreased from 64 (48 to 78) to 36 (31 to 38). The reductions in median scores for intermediate and minor operative procedures showed similar patterns. CONCLUSIONS: The introduction of an acute pain service to the general surgical wards led to considerable improvement in the level of postoperative pain as assessed by visual analogue scores. Simple techniques of regular pain assessment and the more frequent use of intramuscular analgesia as a result of using an algorithm were particularly effective.

Algorithms↗

Value of postprocedural chest radiographs in the adult intensive care unit.

OBJECTIVE: To evaluate the necessity for postprocedural chest radiographs after catheterization of central veins, insertion of pulmonary artery catheters, and placement of endotracheal tubes. DESIGN: Prospective, controlled study. SETTING: Two academic tertiary adult ICUs. PATIENTS: Consecutive patients (n = 316) requiring central vein cannulation or endotracheal intubation in the ICUs. INTERVENTION: After each invasive procedure, the physician was instructed to complete a detailed evaluation sheet. Criteria based on the details of the procedure and immediate postprocedural clinical evaluation of the patient were used to determine the likelihood of a radiologically detectable complication. Actual radiologic findings were subsequently compared against clinical predictions. MAIN OUTCOME MEASUREMENTS: Ability of housestaff to correctly predict the absence of radiologically detectable postprocedural complications (predictive negatives). RESULTS: Ability to predict the absence of complications after cordis catheter insertions via the subclavian vein or internal jugular vein was very high (151/152; p < .001). Unsuspected complications were more frequent with central vein multilumen catheter insertions (3/24; p < .001). Ability to predict uncomplicated pulmonary artery catheterization was also high (110/111; p < .001). Physicians were unable to predict the majority of complications associated with endotracheal intubations (28/32; p > .50). CONCLUSIONS: The use of a protocol that includes an evaluation of the characteristics of the procedure and postprocedural physical examination can greatly reduce the need for routine chest radiographs after subclavian and internal jugular vein cordis catheterizations and pulmonary artery catheter placement. Chest radiographs should be performed after endotracheal intubation and multilumen catheter insertion.

Catheterization, Central Venous↗

Antineutrophil cytoplasmic autoantibodies.

The identification of ANCA and their association with systemic vascular inflammation has become quite useful in both the diagnosis and management of patients with necrotizing vasculitic conditions. Primary autoantibody specificities have been identified, and many more await further characterization. As with ANA, it is highly probable that ANCA will not only complement patient care, but will provide means helpful in exploring the molecular structures and biochemical pathways within granulocytic phagocytes.

Antibodies, Antineutrophil Cytoplasmic↗

Autoantibodies to native myeloperoxidase in patients with pulmonary hemorrhage and acute renal failure.

Sera from 245 patients were screened by indirect immunofluorescence for perinuclear/nuclear staining (P-ANCA) of ethanol-fixed neutrophils, a staining pattern which is associated with the presence of antibodies to myeloperoxidase. Using immunoblot and immunoprecipitation techniques on 15 P-ANCA-positive sera, 13 patients demonstrated antibody to purified or native myeloperoxidase but not to denatured myeloperoxidase. In patients with P-ANCA, the most frequent reason for medical attention was hemoptysis (8/13; 62%). Of the 15 sera with P-ANCA, acute renal failure was identified in 9 patients (60%). Five patients (33%) had both. All patients (eight of eight) with hemoptysis had antibodies which bound functional MPO as compared to three of seven P-ANCA-positive patients without hemoptysis (P less than 0.001), suggesting that antibodies which recognize conformational sites on native myeloperoxidase occur in a subgroup of patients with alveolar hemorrhage as their presenting clinical sign. These findings may provide insight into the disease process associated with P-ANCA. We further identify a subgroup of patients with a severe pulmonorenal syndrome and antibodies recognizing native myeloperoxidase.

Acute Kidney Injury↗

Intrinsic alteration of the reactive properties of arteries during hypothermia.

This study compares the reactive and contractile properties of helical strips of femoral arteries taken from normothermic rabbits and rabbits that were anesthetized with pentobarbital and cooled to 25 degrees C. The purpose of this comparison was to see if previous exposure to whole body hypothermia would alter vascular muscle responsiveness to norepinephrine. We found that, after 2 h of in vivo hypothermia, the hypothermic-derived vascular strips contracted more slowly, but required from 10 to 100 times less norepinephrine to have a detectable contractile response. This continued while the tissue was in vitro for at least 12 h. Although the maximal tension developed by the strips was equivalent, the ED50 values for the hypothermic-derived arteries were lower than those of the normothermic tissue. This study has identified prolonged alterations in in vitro vascular responsiveness attributable to previous exposure to whole body hypothermia, which may help to explain the disruptions of blood pressure during and following exposure of the whole body to cold.

Animals↗

IS10 promotes adjacent deletions at low frequency.

Some transposable elements move by a replicative mechanism involving cointegrate formation. Intramolecular cointegration can generate a product called an "adjacent deletion" in which a contiguous chromosomal segment adjacent to the transposon is deleted while the element responsible remains intact. Insertion sequence IS10 is thought to transpose by a nonreplicative mechanism. In the simplest models, nonreplicative transposition cannot give rise to an adjacent deletion because an intrinsic feature of such transposition is excision of the IS element from the donor location. We report here that IS10 can generate adjacent deletions, but at a frequency which is approximately 1/30th the frequency of transposition for the same element. We suggest that these deletions might arise either by nonreplicative transposition events that involve two IS10 elements located on sister chromosomes or by aberrant nonreplicative events involving cleavage and ligation at only one end of the element.

Blotting, Southern↗

Evaluation of drug information for cardiology patients.

1. Cardiologists and pharmacists at the University Hospital of Wales collaborated to write 20 individual leaflets incorporating guidelines for a range of drugs used in the treatment of cardiology patients. The Plain English Campaign advised on the intelligibility and presentation of the information. 2. One hundred and twenty-five patients from the Regional Cardiology Unit, University Hospital of Wales were randomly allocated to receive usual verbal counselling about their drug treatment with or without an individualised drug information wallet. Two weeks after discharge from hospital patients completed a postal questionnaire to determine their satisfaction with the information about their drug treatment and their understanding of it. Forty-nine questionnaires were returned from the leaflet group and 52 from the control group. 3. The provision of written guidelines resulted in significant improvements in patients' satisfaction with their drug treatment (chi 2 = 33.3, P less than 0.001) and their understanding of it (P less than 0.001, Mann-Whitney test). Overall, patients who received leaflets were more likely to be aware of the potential side effects of their drugs but less likely to be apprehensive about them. Succinct guidelines concerning drug therapy can be assimilated by cardiology patients and provide them with a permanent record for future reference.

Adult↗

Clinical pharmacokinetics of epoetin (recombinant human erythropoietin).

Epoetin (recombinant human erythropoietin, EPO) is of proven benefit in the treatment of renal anaemia, and preliminary reports suggest that it may have a role in the management of other anaemic conditions. Pharmacokinetic and therapeutic studies have examined the use of epoetin administered intravenously, intraperitoneally and subcutaneously, and there is accumulating evidence that the last route has several advantages. After intravenous administration, epoetin is distributed in a volume comparable to the plasma volume, and plasma concentrations decay monoexponentially with a half-life of between 4 and 12 hours. Administration of epoetin in peritoneal dialysis fluid results in detectable concentrations in the bloodstream after 1 to 2 hours, and peak concentrations of the order of 2 to 4% of those obtained with the same intravenous dose are found after approximately 12 hours. The bioavailability of epoetin administered intraperitoneally in dialysis fluid is about 3 to 8%, but this may be increased by injecting the drug into a dry peritoneal cavity. Subcutaneous administration results in peak concentrations at about 18 hours which are 5 to 10% of those found after the same intravenous dose. The bioavailability of subcutaneous epoetin is about 20 to 30% and detectable serum concentrations are still present 4 days after administration, in contrast to intravenous administration after which concentrations have returned to baseline within 2 to 3 days. Remarkably little is known about the metabolic fate of either erythropoietin or epoetin. In addition, there is much controversy surrounding the relative roles of the kidney and liver in the catabolism of epoetin. About 3 to 10% of epoetin is excreted unchanged in the urine. In common with other glycoproteins, the carbohydrate residues which constitute 40% of its molecular size are essential for maintaining the stability of epoetin in circulation. Desialated epoetin, although biologically active in vitro, is cleared very rapidly from plasma with resultant loss of activity. Further work is required, however, in identifying the pathways of metabolism and elimination of this glycoprotein hormone.

Animals↗