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Biomedical subjects

D A Scott

Publications and source records attributed to D A Scott.

At least 19 recordsLinked to original sources
PubMed1996

Detection of intravenous fluid extravasation using resistance measurements.

Resistance to fluid infusion can be derived from measurements of pressure at two or more flow rates. We measured resistance in 31 patients using a pressure-monitoring infusion pump (Model 560, IVAC) by recording pressure at five flow rates (0, 50, 100, 200, and 300 mL/hr), and computing resistance as the slope of the pressure versus flow curve. Resistance was measured subcutaneously (Rtissue) and intravenously (Rvein) immediately after unsuccessful or successful IV catheter placement. In all patients, Rtissue was always greater than Rvein. The difference ranged from 23 resistance units (RU) to 4166 RU, with a mean difference of 1147 RU (p < 0.0001, Student's t-test). Unpaired analysis of the data was performed to assess the ability of resistance to indicate extravasation in the absence of prior Rvein measurement. The median value for Rvein was 62 RU (range -13.6 to 420 RU), and for Rtissue, 544 RU (range 65.7 to 4170 RU). Receiver operating characteristic (ROC) analysis revealed that a 200-RU threshold detected infiltration with 0.90 sensitivity and 0.91 specificity. We conclude that elevated resistance during fluid infusion is an important early and easily measurable finding in fluid extravasation.

Extravasation of Diagnostic and Therapeutic Materi↗
PubMed1996

Resistance to fluid flow in veins.

We evaluated the resistance to fluid infusion in the veins of 118 adult patients after intravenous catheter insertion prior to elective surgery. Hydraulic resistance in veins was defined as the slope of the pressure-flow relationship obtained by measuring venous pressure at several fluid flow rates. A resistance unit (RU) was defined as 1 mmHg/L/hr. Resistance in veins ranged from -12.1 to 732 RU, with 50th and 95th percentiles being 22 and 198 RU, respectively. Venous resistance was not significantly affected by site of catheter insertion, tissue characteristics at the insertion site, age, sex, patient anxiety, American Society of Anesthesiologists physical status, or catheter size. This report provides a distribution of resistance to fluid infusion in arm veins of adult patients.

Adult↗
PubMed1996

Comparative effects of plain and epinephrine-containing bupivacaine on the hemodynamic response to cervical plexus anesthesia in patients undergoing carotid endarterectomy.

OBJECTIVES: This study was designed to investigate whether the addition of epinephrine as a vasoconstrictor additive to local anesthetic affects the hemodynamic profile after cervical plexus block in patients presenting for carotid endarterectomy. DESIGN: A prospective, double-blind, randomized trial. SETTING: A university hospital. PARTICIPANTS: Forty patients scheduled for carotid endarterectomy under regional anesthesia (cervical plexus block). INTERVENTIONS: Patients were randomized to one of two groups. Group P (20 patients) received plain bupivacaine; group E (20 patients) received bupivacaine with epinephrine, 5 micrograms/mL. All patients received 2 mg/kg of bupivacaine, and group E received 2 micrograms/kg of epinephrine. The electrocardiogram and intra-arterial blood pressure were monitored continuously, and recordings of heart rate and blood pressure were recorded at predetermined intervals from before the block until the skin incision. RESULTS: After the block, group E developed a sustained increase in heart rate of approximately 15% (p < 0.01), whereas group P showed no change. Systolic blood pressure increased significantly with time over the study period in both groups (p < 0.01). Diastolic blood pressure increased significantly in group P (p < 0.01) but not in group E. CONCLUSIONS: Concerning cervical plexus block with bupivacaine, the use of epinephrine is associated with an increase in heart rate consistent with a beta-adrenergic effect from systemic absorption of the epinephrine. An increase in systolic blood pressure independent of the use of epinephrine also occurs, but epinephrine appears to mitigate against an increase in diastolic blood pressure.

Adult↗
PubMed1996

Postoperative analgesia by continuous extradural infusion of ropivacaine after upper abdominal surgery.

Ropivacaine is a new local anaesthetic with advantages that suggest an important role in the provision of postoperative analgesia. The main aim of this study was to investigate the dose-response relationship of extradural infusion of ropivacaine. We studied 36 ASA I-III patients undergoing upper abdominal surgery during general anaesthesia and extradural block (catheter insertion at T6-9) using 0.5% ropivacaine in a randomized, double-blind study. After surgery nine patients each received an extradural infusion of either ropivacaine 0.1%, 0.2%, 0.3% or saline at a rate of 10 ml h-1 for 21 h. All patients had access to i.v. morphine via a PCA device. The ropivacaine groups consumed significantly less morphine over the 21-h infusion period than the saline group (medians: saline 75 mg; 0.1% ropivacaine 32 mg; 0.2% ropivacaine 39 mg; 0.3% ropivacaine 13 mg) (P < 0.05). Pain (VAS scores) at rest was significantly lower in all ropivacaine groups than in the saline group after 4 h of infusion (medians: saline 45 mm; 0.1% ropivacaine 15 mm; 0.2% ropivacaine 12 mm; 0.3% ropivacaine 0 mm). Pain on coughing was significantly less in all ropivacaine groups than in the saline group after 4 h infusion (medians: saline 67 mm; 0.1% ropivacaine 44 mm; 0.2% ropivacaine 33 mm; 0.3% ropivacaine 0 mm) and for 0.2% and 0.3% ropivacaine at later times. Motor block was negligible throughout the infusion. Patient satisfaction was higher in the 0.2% and 0.3% ropivacaine groups than in the two other groups.

Abdomen↗
PubMed1996

Localization of the Usher syndrome type ID gene (Ush1D) to chromosome 10.

The Usher syndromes (USH) are a group of autosomal recessive diseases characterized by progressive pigmentary retinopathy and sensorineural hearing loss. Five USH genes have been mapped and at least one additional gene is known to exist. By homozygosity mapping in a consanguineous family, a sixth USH gene has been localized. Clinical findings in the four affected children are consistent with established diagnostic criteria for Ush1. Linkage to known USH loci was excluded, and using two genomic DNA pools, one from the affected children and the other from the parents, 161 polymorphic markers evenly spaced across the autosomal human genome were screened. The location of the Ush1D gene was defined by the only region showing homozygosity by descent in the affected siblings, a 15 cM interval on chromosome 10q bounded by D10S529 and D10S573.

Chromosome Mapping↗
PubMed1996

Leukocyte rolling velocity and its relation to leukocyte-endothelium adhesion and cell deformability.

To explore the relationship between the rolling velocity of leukocytes (VWBC) and wall shear rates (gamma), measurements of VWBC were made along the length of rat mesenteric venules in which a gradient in gamma was induced by compressing the venule with a blunted microprobe to form a stenosis in which gamma varied from 300 to 1500 s-1. For individual WBCs that rolled through stenosis, VWBC was proportional to gamma for its entire range, in contrast to previous studies that have shown a plateau in VWBC vs. gamma for the ensemble population. Comparisons of the slope of VWBC/gamma for individual cells with ensemble values of VWBC obtained in the entrance region of the stenosis were made during suffusion of the tissue with the chemoattractant N-formylmethionyl-leucyl-phenylalanine (FMLP), to increase WBC-EC adhesion and WBC stiffness, or colchicine and cytochalasin B to increase WNC deformability. Under control conditions, the slope of individual cells was significantly 20% greater than VWBC/gamma, whereas it was significantly reduced by 48% during suffusion with FMLP. With exposure to colchicine, the slope was 78% lower than VWBC/gamma and compared with control was similar in magnitude to that obtained with FMLP. Cytochalasin also reduced the slope by 22% compared with control and 34% compared with VWBC/ gamma. The diminished slopes of VWBC vs. gamma were consistent with published theoretical models that suggest a reduced slope with increased strength of adhesion of WBC deformability. It is thus concluded that the apparent plateau in VWBC vs. gamma arises due to the heterogeneity of adhesive and/or deformability properties in the ensemble population of circulating WBCs.

Animals↗
PubMed1996

An autosomal recessive nonsyndromic-hearing-loss locus identified by DNA pooling using two inbred Bedouin kindreds.

Autosomal recessive nonsyndromic hearing loss (ARNSHL) is the most common form of severe inherited childhood deafness. We present the linkage analysis of two inbred Bedouin kindreds from Israel that are affected with ARNSHL. A rapid genomewide screen for markers linked to the disease was performed by using pooled DNA samples. This screen revealed evidence for linkage with markers D9S922 and D9S301 on chromosome 9q. Genotyping of individuals from both kindreds confirmed linkage to chromosome 9q and a maximum combined LOD score of 26.2 (recombination fraction [theta] .025) with marker D9S927. The disease locus was mapped to a 1.6-cM region of chromosome 9ql3-q2l, between markers D9S15 and D9S927. The disease segregates with a common haplotype in the two kindreds, at markers D9S927, D9S175, and D9S284 in the linked interval, supporting the hypothesis that both kindreds inherited the deafness gene from a common ancestor. Although this nonsyndromic-hearing-loss (NSHL) locus maps to the same cytogenetic interval as DFNB7, it does not overlap the currently defined DFNB7 interval and may represent (1) a novel form of NSHL in close proximity to DFNB7 or (2) a relocalization of the DFNB7 interval to a region telomeric to its reported location. This study further demonstrates that DNA pooling is an effective means of quickly identifying regions of linkage in inbred families with heterogeneous autosomal recessive disorders.

Arabs↗
PubMed1995

Ca2+ storage in Trypanosoma brucei: the influence of cytoplasmic pH and importance of vacuolar acidity.

The hypothesis that changes in cytosolic pH effect the release from intracellular compartments of stored calcium in Trypanosoma brucei was addressed by the use of procyclic and bloodstream trypomastigotes of T. brucei loaded with the fluorescent reagents 2',7'-bis-(2-carboxyethyl)-5(and 6)-carboxyfluorescein (BCECF) to measure intracellular pH (pHi), or fura 2 to measure intracellular free calcium ([Ca2+]i). Experiments were performed in EGTA-containing buffers, so increases in [Ca2+]i reflected release of stored calcium rather than Ca2+ entry. Nigericin reduced pHi and increased [Ca2+]i in loaded cells, whilst propionate reduced pHi, but did not affect [Ca2+]i, and NH4Cl increased both variables, so there appears to be no correlation between pHi and [Ca2+]i. Treatment of the cells with the calcium ionophore ionomycin under similar conditions (nominal absence of extracellular Ca2+) resulted in an increase of [Ca2+]i which was greatly increased by addition of either NH4Cl, nigericin or the vacuolar H(+)-ATPase inhibitor bafilomycin A1. Similar results were obtained when the order of additions was reversed or when digitonin-permeabilized cells were used with the Ca2+ indicator arsenazo III. The results suggest that more Ca2+ is stored in this acidic compartment in procyclic than in bloodstream forms. Taking into account the relative importance of the ionomycin-releasable and the ionomycin-plus-NH4Cl-releasable Ca2+ pools, it is apparent that a significant amount of the Ca2+ stored in T. brucei trypomastigotes is present in the acidic compartment thus identified.

Ammonium Chloride↗
PubMed1995

Intracellular Ca2+ storage in acidocalcisomes of Trypanosoma cruzi.

The use of digitonin to permeabilize the plasma membrane of Trypanosoma cruzi allowed the identification of a non-mitochondrial nigericin- or bafilomycin A1-sensitive Ca(2+)-uptake mechanism. Proton uptake, as detected by ATP-dependent Acridine Orange accumulation, was also demonstrated in these permeabilized cells. Under these conditions Acridine Orange was concentrated in abundant cytoplasmic round vacuoles. This latter process was inhibited (and reversed) by bafilomycin A1, nigericin and NH4Cl in different stages of T. cruzi. Ca2+ released Acridine Orange from permeabilized cells, suggesting that the dye and Ca2+ were being accumulated in the same acidic compartment and that Ca2+ was taken up in exchange for protons. Addition of bafilomycin A1 (5 microM), nigericin (1 microM) or carbonyl cyanide p-trifluoromethoxyphenylhydrazone (FCCP; 1 microM) to fura 2-loaded epimastigotes increased their intracellular Ca2+ concentration ([Ca2+]i). Although this effect was more noticeable in the presence of extracellular Ca2+, it was also observed in its absence. Addition of NH4Cl (10-40 mM) to different stages of T. cruzi, in the nominal absence of extracellular Ca2+ to preclude Ca2+ entry, increased both [Ca2+]i in fura 2-loaded cells, and intracellular pH (pHi) in 2',7'-bis-(2-carboxyethyl)-5-(and -6)-carboxyfluorescein acetoxymethyl ester (BCECF)-loaded cells. Treatment of the cells with the Ca2+ ionophore ionomycin under similar conditions (nominal absence of extracellular Ca2+) resulted in an increase in [Ca2+]i and a significantly higher increase in [Ca2+]i after addition of NH4Cl, nigericin or bafilomycin A1, all agents which increase the pH of acidic compartments and make ionomycin more effective as a Ca(2+)-releasing ionophore. Similar results were obtained when the order of additions was reversed. Taking into account the relative importance of the ionomycin-releasable and the ionomycin plus NH4Cl-releasable Ca2+ pools, it is apparent that most of the Ca2+ stored in different stages of T. cruzi is present in the acidic compartment thus identified. Taken together, these results are consistent with the presence of a Ca2+/H+ exchange system in an acidic vacuole, which we have named the 'acidocalcisome' and which appears to be a unique organelle present in trypanosomatids.

Acridine Orange↗
PubMed1995

The pathway of secretion of proteinases in Trichomonas vaginalis.

Trichomonads secrete large amounts of hydrolytic enzymes into liquid growth medium. Proteinase release by Trichomonas vaginalis has been quantified after resuspension of the parasite in a simple buffered maltose medium. After 6 h incubation, 70-90% of each of two cysteine proteinase activities, one towards benzyloxycarbonyl-arginyl-arginine 4-nitroanilide (Z-RR-Nan) and the other active towards N-benzoyl-prolyl-phenylalanyl-arginine 4-nitroanilide (Bz-PFR-Nan), was extracellular. This release was insensitive to changes in pH within the range from 5.5 to 8.6 but was partially inhibited by chloride ions. The secretion of activity towards Bz-PFR-Nan was temperature-sensitive but was still detectable down to 14 degrees C. Neither this nor other cysteine proteinase activities were detectable on the surface of parasites. Release was stimulated by various amines and monensin, suggesting that secretion was from or via acidic compartments. The intracellular activity towards Bz-PFR-Nan could be totally and irreversibly inhibited by treating the parasites with benzyloxycarbonyl-phenylalanyl-alanine diazomethylketone (Z-FA-DMK), without otherwise harming the cells. Regeneration and routing of the proteinases responsible for this activity was followed after removal of the inhibitor. There was a significant rise in the intracellular level of activity before it became detectable in the medium. The release of this activity was accelerated by amines and monensin, but the build-up of enzyme activity within cells was not prevented. Organelles containing cysteine proteinases banded as a single peak in Percoll density gradients. The density of these increased when cells were treated with dextran. The activity towards Bz-PFR-Nan which reappeared after Z-FA-DMK treatment has a similar distribution. The proteinase-containing fraction could be distinguished from an early (5 min) endosome fraction, suggesting that it was composed of late endosomes/lysosomes. Thus these results imply that the secretion pathway for proteinases necessarily involves lysosomes/late endosomes.

Amines↗
PubMed1995

Predictability of EEG interictal spikes.

To determine whether EEG spikes are predictable, time series of EEG spike intervals were generated from subdural and depth electrode recordings from four patients. The intervals between EEG spikes were hand edited to ensure high accuracy and eliminate false positive and negative spikes. Spike rates (per minute) were generated from longer time series, but for these data hand editing was usually not feasible. Linear and nonlinear models were fit to both types of data. One patient had no linear or nonlinear predictability, two had predictability that could be well accounted for with a linear stochastic model, and one had a degree of nonlinear predictability for both interval and rate data that no linear model could adequately account for.

Biophysical Phenomena↗
PubMed1995

Epidural ropivacaine infusion for postoperative analgesia after major lower abdominal surgery--a dose finding study.

Ropivacaine exhibits less cardiotoxicity and causes less motor block than bupivacaine when used in equianalgesic doses. This makes ropivacaine potentially well suited for epidural infusion for postoperative analgesia. The aim of this study was to determine which of three concentrations of epidurally administered ropivacaine infused for postoperative analgesia would attenuate intravenous opioid analgesia requirements while also minimizing motor block. Forty ASA I-III patients, having major lower abdominal surgery, completed the study. They were randomly assigned to one of four treatment groups: Group S, control, epidural saline (n = 10); Group 1, epidural 0.1% ropivacaine (n = 10); Group 2, epidural 0.2% ropivacaine (n = 10); and Group 3, epidural 0.3% ropivacaine (n = 10). The study was double-blind. Initial epidural analgesia was established with 0.5% ropivacaine, and then general anesthesia induced for surgery. Once in the recovery room, epidural infusions were commenced at 10 mL/h and maintained at that rate for 21 h. Intravenous patient controlled analgesia (PCA) morphine was used as required by the patients for supplemental analgesia. Total PCA morphine use was more over the 21-h period in Group S than all the ropivacaine groups, being significantly so for Group 2 (median values: Group S, 43.3 mg; Group 1, 18.7 mg; Group 2, 7.5 mg; Group 3, 19 mg; for Group 2, P = 0.03). Visual analog scale (VAS) scores on coughing were significantly lower (i.e., less pain) than control for all ropivacaine groups after 4 h of infusion and also for Groups 2 and 3 after 8 h of infusion. (Median VAS (mm) on coughing at 8 h: Group S = 70, Group 1 = 56, Group 2 = 32, Group 3 = 0; for Groups 2 and 3, P < 0.05 compared to Group S). There was a dose-related increase in the amount of motor block, with Group 3 having significantly more motor block than all other groups at 4 and 8 h.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Postoperative analgesia using epidural infusions of fentanyl with bupivacaine. A prospective analysis of 1,014 patients.

BACKGROUND: Epidural fentanyl/bupivacaine infusions often are limited to high dependency units or intensive care units. One thousand fourteen patients receiving epidural fentanyl/bupivacaine infusions for analgesia after major surgery who were managed in the general surgical ward were prospectively surveyed. METHODS: Patients leaving the recovery room with an epidural catheter in situ were assessed three times a day by acute pain service personnel for quality of pain relief, using a rating scale that accounted for pain on movement. The presence of side effects and complications was assessed. RESULTS: Data were collected from February 1990 to May 1993. The average duration of infusion was 3 days. A patient's pain relief was rated as good to excellent on 82.6% of visits. Side effects possibly attributable to fentanyl included sedation (7.4%), pruritus (10.2%), nausea and vomiting (3.1%), and respiratory depression (1.2%). Respiratory depression commonly was associated with sedation and was detected easily on the postsurgical ward, with only four patients requiring naloxone (0.4%). Side effects possibly related to bupivacaine included unpleasant sensory block (2.6%), significant lower limb motor block (3.0%), and hypotension (6.6%). There were two cases of epidural hematoma. Inflammation at the epidural catheter insertion site occurred in 3.8% (38), of which 42% (16) had some cutaneous purulence detected. There were no epidural space infections. Mechanical problems, including dislodgment of the catheter, accounted for 18.7% of infusion discontinuations within the first 72 h. CONCLUSIONS: Postoperative epidural fentanyl/bupivacaine infusions are effective and can be managed readily in general postsurgical wards with minimal complications provided that appropriate patient observations are performed.

Adolescent↗
PubMed1995

A comparison of albumin, polygeline and crystalloid priming solutions for cardiopulmonary bypass in patients having coronary artery bypass graft surgery.

This study was designed to assess the effect of different prime solution compositions on a patient's fluid balance, transfusion requirements, renal function and haemodynamic stability over the first 24 hours postbypass. Ninety-three patients presenting for first-time coronary artery bypass graft (CABG) surgery were randomly allocated to receive one of three prime solutions for the CPB pump: albumin (4.6%) + Plasmalyte (Group A, n = 32), polygeline (Hemaccel) + Plasmalyte (Group P, n = 29), or crystalloid (Plasmalyte) alone (Group C, n = 32). Patients, anaesthetists, surgeons and intensive care unit (ICU) staff were all blinded as to the solution type. The groups were demographically and haemodynamically similar. There were no differences between the groups with respect to white cell or platelet counts during the study. There was a significant difference in haemoglobin levels between the groups on weaning from CPB and on arrival in the ICU (Group C > Groups P and A, p < 0.001 for both times). There was no difference in blood transfusion requirements between any of the groups. During CPB, Group C required significantly more crystalloid than the other groups (p < 0.001). Urine output was significantly higher in Group C compared with Groups P and A at all time periods up to and including ICU 12 hours (p < 0.05). The use of frusemide was significantly higher in the ICU in Groups P and A (p < 0.01). There was a net gain of 3132 +/- 412 ml in Group C in 24 hour fluid balance, which was significantly higher than Group A (2166 +/- 223 ml, p = 0.04). Our results show that, in this patient population, there is no advantage in using a colloid-based prime solution over a purely crystalloid solution from a haemotologic or haemodynamic point of view for the first 24 hours after CPB. There appears to be an increase in extracellular fluid (ECF) retention in Group C, but this caused no related problems in the study period. On the other hand, diuretics (frusemide) needed to be given significantly less often in these patients to offset oliguria.

Albumins↗
PubMed1994

Infections in cancer patients: some controversial issues.

Despite more than two decades of clinical research into the management of infections in the neutropenic cancer patient, many patients still develop serious morbidity from infection and all too many still die. A number of controversies surround (a) the use of combination versus monotherapy for initial empiric administration; (b) the use of vancomycin as part of the initial regimen; (c) the origin of Staphylococcus epidermidis infections (i.e., mostly from vascular catheters or mostly from the alimentary canal); (d) the use of acyclovir for herpes simplex prophylaxis during remission induction for acute leukemia patients not undergoing bone marrow transplantation; (e) the use of alimentary canal microbial suppression or reverse isolation in a room with laminar air flow, or both, as infection prevention techniques. Current recommendations and observations include the following. (a) Monotherapy with ceftazidime or imipenem is effective and appropriate for patients with moderate granulocytopenia at limited risk for infection with a resistant organism. Combination therapy is recommended for patients with profound, persistent granulocytopenia who are at high risk for gram-negative bacteremia; such bacteremic patients have a better prognosis with combined-modality therapy. (b) Vancomycin need not be included in the initial regimen although some centers may choose to do so because of the high prevalence of gram-positive bacteremias. (c) Despite the ubiquitous presence of indwelling vascular catheters, most S. epidermidis infections among neutropenic patients originate from along the alimentary canal. (d) Herpes simplex infection is much more common following standard remission induction chemotherapy than previously recognized. Acyclovir will reduce these infections and concurrently probably reduce the likelihood of resultant bacterial/fungal co-infections and superinfections. (e) Selective microbial suppression is appropriate for patients expected to experience prolonged (more than 2 weeks) or profound (below 100 granulocytes/microliters) granulocytopenia. Agents chosen should suppress aerobic but not anaerobic flora (maintain colonization resistance) and need to have an effect on both the oral cavity and esophagus as well as the intestines.

Anti-Bacterial Agents↗
PubMed1994

Cloning and sequencing of the genes encoding Escherichia coli cytolethal distending toxin.

Escherichia coli strains expressing cytolethal distending toxin (CDT) cause elongation of CHO cells at 24 h, followed by progressive cellular distention and death for up to 120 h. Similar distention and cytotoxicity are seen in HeLa, HEp-2, and, to a lesser extent, Vero cells. The initial elongation in CHO cells is indistinguishable from that caused by E. coli heat-labile toxin (LT). In contrast to those from LT strains, supernatants from these strains have no effect on Y-1 adrenal cells. TnphoA was introduced into CDT-positive E. coli E6468/62 (O86:H34), isolated from a child with diarrhea, and 13 CDT-negative transconjugants were identified. DNA probes constructed from DNA flanking the TnphoA insertion sites of CDT-negative mutants were used to identify a CDT-positive clone from an E6468/62 genomic library with a 5.5-kb insert. Exonuclease deletions were created and assayed in CHO cells. In this manner, a 2.3-kb CDT-active region was defined, and the nucleotide sequence was determined. Sequence analysis identified three open reading frames (ORFs), designated cdtA, cdtB, and cdtC. These contain 711, 819, and 570 bp, respectively, and encode polypeptides with predicted molecular masses of 25.5, 29.8, and 20.3 kDa, respectively. Each ORF has a putative signal sequence, and there are 4-bp overlaps between cdtA and cdtB and between cdtB and cdtC. The nucleotide and predicted amino acid sequences have no significant homology with those of any previously reported genes or proteins. By in vitro transcription-translation and an anti-alkaline phosphatase immunoblot, native proteins and/or fusion proteins corresponding to each ORF were identified.

Amino Acid Sequence↗