Biomedical subjects

R L White

Publications and source records attributed to R L White.

At least 109 records · Page 6Linked to original sources

PubMed1991

A method for evaluating the selectivity of electrodes implanted for nerve simulation.

The scale of stimulating electrodes possible for use in functional electrical stimulation to restore motor and sensory function is rapidly approaching that of individual neurons. Although the electrodes may approach the dimensions of single nerve cells, it is unclear if the region of excitation elicited by each electrode will be correspondingly small. Previous techniques for evaluating this have either been tedious or have lacked the resolution necessary. This paper describes a method that uses the refractory interaction of the compound action potentials elicited by a stimulus pulse pair, along with high-resolution recording of those potentials, to achieve measurements of the selectivity of stimulation down to the scale of a few axon diameters. The feasibility of this technique is demonstrated in sciatic nerves of frogs (Rana Catesbiana) acutely implanted with a sapphire electrode array.

Action Potentials↗

PubMed1991

Aztreonam pharmacokinetics in burn patients.

The pharmacokinetics of aztreonam in eight adult patients with severe burn injuries (total body surface area burn, 49% +/- 21% [mean +/- standard deviation]) were studied. The time of initiation of study following burn injury was 7.0 +/- 1.4 days. Four patients at first dose and at steady state were studied. Aztreonam concentrations were measured by high-performance liquid chromatography, and a two-compartment model was used to fit the data. No significant differences in any pharmacokinetic parameters between first dose and steady state were observed. Volume of distribution of the central compartment after first dose (0.14 liters/kg) and volume of distribution at steady state (0.31 liters/kg) were approximately 30% higher than those reported for other patient populations. Total drug clearance and renal drug clearance when normalized to creatinine clearance (CLCR) were similar to those previously reported for other critically ill patients. CLCR was strongly correlated with renal drug clearance (r = 0.94) and total drug clearance (r = 0.95). The extent and degree of burn (percent second or third degree burn) were poorly correlated with all pharmacokinetic parameters with the exception of the volume of distribution at steady state, which was correlated with both total body surface area burn (r = 0.95) and percent second degree burn (r = 0.83). Aztreonam pharmacokinetics are altered as a result of thermal injury; however, CLCR can be used to assess the clearance of aztreonam in burn patients.

Adolescent↗

PubMed1991

Pseudoresistance of Pseudomonas aeruginosa resulting from degradation of imipenem in an automated susceptibility testing system with predried panels.

During the use of a single lot of custom breakpoint panels (Sensititre; Radiometer America Inc., Westlake, Ohio), imipenem susceptibility declined from 70 to 44% for clinical isolates of Pseudomonas aeruginosa. With a new lot, susceptibility increased to 73%. Subsequent evaluations with P. aeruginosa ATCC 27853 revealed a similar susceptibility pattern and an increase in the MIC of imipenem when determined in panels with increasing ages. Imipenem concentrations were determined by high-performance liquid chromatography by using 11 different lots of MIC and breakpoint panels (139 to 893 days of age). The amount of imipenem remaining declined from 94.4 to 13.8% (r = 0.9225) over the age range of the panels. These data suggest that imipenem in Sensititre MIC and breakpoint panels degrades over time and that the decrease in imipenem may be largely responsible for the decline in P. aeruginosa susceptibility.

Drug Resistance, Microbial↗

PubMed1991

Excitation of neurons in the medullary raphe increases gastric acid and pepsin production in cats.

The nucleus raphe obscurus (NRO) has recently emerged as an important nucleus for excitation of gastric motor activity through projections to the dorsal motor nucleus of the vagus (DMV) [P. J. Hornby, C. D. Rossiter, R. L. White, W. P. Norman, D. H. Kuhn, and R. A. Gillis. Am. J. Physiol. 258 (Gastrointest. Liver Physiol. 21): G91-G96, 1990; and M. J. McCann, G. E. Herman, and R. C. Rogers. Brain Res. 486: 181-184, 1989]. A neurotransmitter thought to be involved in this NRO-DMV pathway is thyrotropin-releasing hormone (TRH), a peptide that excites gastric activity when microinjected into the DMV. The purpose of the present study was to determine whether gastric acid and pepsin secretion were altered by 1) activation of neurons in the NRO by microinjection of kainic cid and 2) microinjection of TRH into the DMV in chloralose-anesthetized cats. Microinjection of kainic acid into the NRO increased gastric acid secretion [baseline was 6 +/- 2 (mu eq) H+/15 min (n = 7) and increased to 8 +/- 2, 26 +/- 11 (P less than 0.05), and 21 +/- 7 mu eq/15 min (P less than 0.05) during the first, second, and third 15-min periods after microinjection, respectively]. Pepsin output also increased from a baseline of 287 +/- 67 pepsin units (PU) (n = 4) to 507 +/- 126 PU 15 min postinjection, 541 +/- 118 PU 30 min after injection (P less than 0.05), 608 +/- 92 PU 45 min after injection (P less than 0.05), and 700 +/- 156 PU 60 min postinjection (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1991

In vivo inactivation of tobramycin by piperacillin.

In vivo inactivation of aminoglycosides by antipseudomonal penicillins in patients with renal failure can be a significant problem when these drugs are used together in certain gram-negative infections. Our article illustrates the possible magnitude of this interaction and the resultant effect on aminoglycoside pharmacokinetic parameters. Penicillin concentrations remain relatively unaffected by this interaction. This article stresses the need for close monitoring of aminoglycoside concentrations when combined with antipseudomonal penicillins in this patient population.

Drug Interactions↗

PubMed1990

The CEPH consortium primary linkage map of human chromosome 10.

The first CEPH consortium map, that of chromosome 10, is presented. This primary linkage map contains 28 continuously linked loci defined by genotypes generated from CEPH family DNAs with 37 probe and enzyme combinations. Cytogenetic localization of some of the genetic markers indicates that the consortium map extends, at least, from 10p13 to 10q26. The order of loci on the consortium map agrees with the physical localization data. The female map spans 309 cM (206 cM if an approximation of interference is included in the mapping function used to construct the map), and the mean genetic distance of intervals is 11 cM (7 cM). Also presented are maps of chromosome 10 from each of five CEPH collaborating laboratories, based on genotypes for all relevant markers in the CEPH database. The CEPH consortium map of chromosome 10 should be useful for localization of any gene of interest falling within the span covered. The genotypes in the chromosome 10 consortium map database are now available to the scientific community.

Chromosome Mapping↗

PubMed1990

Gap junctional conductance between pairs of ventricular myocytes is modulated synergistically by H+ and Ca++.

Gap junctional conductance (gj) between cardiac ventricular myocyte pairs is rapidly, substantially, and reversibly reduced by sarcoplasmic acidification with CO2 when extracellular calcium activity is near physiological levels (1.0 mM CaCl2 added; 470 microM Ca++). Intracellular calcium concentration (Cai), measured by fura-2 fluorescence in cell suspensions, was 148 +/- 39 nM (+/- SEM, n = 6) and intracellular pH (pHi), measured with intracellular ion-selective microelectrodes, was 7.05 +/- 0.02 (n = 5) in cell pair preparations bathed in medium equilibrated with air. Cai increased to 515 +/- 12 nM (n = 6) and pHi decreased to 5.9-6.0 in medium equilibrated with 100% CO2. In air-equilibrated low-calcium medium (no added CaCl2; 2-5 microM Ca++), Cai was 61 +/- 9 nM (n = 13) at pHi 7.1. Cai increased to only 243 +/- 42 nM (n = 9) at pHi 6.0 in CO2-equilibrated low-calcium medium. Junctional conductance, in most cell pairs, was not substantially reduced by acidification to pHi 5.9-6.0 in low-calcium medium. Cell pairs could still be electrically uncoupled reversibly by the addition of 100 microM octanol, an agent which does not significantly affect Cai. In low-calcium low-sodium medium (choline substitution for all but 13 mM sodium), acidification with CO2 increased Cai to 425 +/- 35 nM (n = 11) at pHi 5.9-6.0 and gj was reduced to near zero. Junctional conductance could also be reduced to near zero at pHi 6.0 in low-calcium medium containing the calcium ionophore, A23187. The addition of the calcium ionophore did not uncouple cell pairs in the absence of acidification. In contrast, acidification did not substantially reduce gj when intracellular calcium was low. Increasing intracellular calcium did not appreciably reduce gj at pHi 7.0. These results suggest that, although other factors may play a role, H+ and Ca++ act synergistically to decrease gj.

Acid-Base Equilibrium↗

PubMed1990

Effects of supraphysiologic temperature and broth dilution on serum protein binding.

Pooled human serum, unheated (UU) and heated at 56 degrees C for 30 (HU-30) and 60 (HU-60) min, and these media diluted 1:1 with broth (UD, HD-30, and HD-60) were used to assess the effects of supraphysiologic temperature and broth dilution on the serum protein binding of ceftriaxone. Protein binding was determined by ultrafiltration and subsequent high-performance liquid chromatography analysis. Significant differences in protein binding between UU and HU-60 (P less than 0.05), UD and HD-60 (P less than 0.01), HD-30 and HD-60 (P less than 0.01), and all undiluted and diluted media (P less than 0.01) were found. These alterations in protein binding may influence the in vitro microbiologic testing of highly protein-bound antibiotics.

Adult↗

PubMed1990

Medullary raphe: a new site for vagally mediated stimulation of gastric motility in cats.

Thyrotropin-releasing hormone (TRH) is clearly implicated in the control of gastric function via interactions in the dorsal motor nucleus of the vagus (DMV) of the cat. The source of the TRH innervation of the DMV is important to determine because this region could be of importance in control of gastric function. TRH-immunoreactive (ir) neurons are located in the raphe obscurus (Ro), raphe pallidus (Rp), and raphe magnus (Rm). Retrograde tracer applied to the DMV resulted in the most numerous labeled neurons in the caudal Ro and Rp in the same region where TRH-ir neurons are located. To address the question whether DMV-projecting neurons in the raphe subnuclei play a role in control of gastric motility, the following experiments were performed in alpha-chloralose-anesthetized cats while recording pyloric motility and blood pressure. Microinjection of a cell body excitant L-glutamate (44-200 nl, 0.5 M) into the caudal Ro and Rp in 15 experiments produced significant increases in pyloric minute motility index (MMI) of 4.9 +/- 1.5 (from 1.6 +/- 0.7 preinjection to 6.5 +/- 1.8 postinjection, P less than 0.05). Mean blood pressure (MBP) decreased significantly in these animals by 12 +/- 7 mmHg (from 100 +/- 6 to 88 +/- 8 mmHg, P less than 0.05). Saline microinjection in the same sites in seven cases resulted in no significant change in pyloric MMI (-1.0 +/- 0.8) or MBP (-4 +/- 11 mmHg). In five of these experiments, a second microinjection of L-glutamate (132-240 nl) was performed into the caudal Ro and Rp after spinal cord transection. This resulted in a significant increase in pyloric MMI of 3.3 +/- 0.9 (from 1.0 +/- 0.5 preinjection to 4.3 +/- 1.1 postinjection, P less than 0.05) but no change in MBP (+1 +/- 1 mmHg). Bilateral vagotomy resulted in the abrupt cessation of the pyloric response to caudal Ro and Rp stimulation. Microinjection of L-glutamate into the rostral Rp and caudal Rm in nine experiments resulted in no significant changes in pyloric MMI (-0.4 +/- 0.8) or MBP (-10 +/- 11 mmHg). These data indicate that a population of neurons in the caudal raphe nuclei, which may contain TRH, project to the DMV. In addition, excitation of these neurons causes an increase in gastric motility that is not caused by inhibition of sympathetic outflow to the gut but rather by excitation of vagal neurons in the DMV.

Animals↗

PubMed1990

Genetic linkage map of six polymorphic DNA markers around the gene for familial adenomatous polyposis on chromosome 5.

A genetic linkage map of six polymorphic DNA markers close to the gene (APC) for familial adenomatous polyposis (FAP) on chromosome 5q is reported. One hundred fifty-five typed members of nine FAP kindred provided more than 90 meioses for linkage analysis. A number of crucial recombination events have been identified which are informative at three or more loci, allowing confident ordering of parts of the map. There was no evidence of genetic heterogeneity, with all families showing linkage of at least one chromosome 5 marker to the gene. Recombination data and two-point linkage analysis support a locus order of centromere-pi 227-C11P11-ECB27-L5.62-APC-EF5.44-YN5.48-telomer e, although EF5.44 could lie in the interval L5.62-APC or ECB27-L5.62. No recombinants were identified between APC and either EF5.44 or YN5.48, but published deletion mapping in colorectal carcinomas and linkage analysis in FAP suggest that YN5.48 is 1-3 cM from APC. The present study suggests that YN5.48 and L5.62 delineate a small region of chromosome 5 within which the EF5.44 locus lies very close to the APC gene. These data not only allow use of flanking markers for presymptomatic diagnosis of FAP but also provide a high-density map of the region for isolation of the APC gene itself and for further assessment of the role of chromosome 5 deletions in the biology of sporadic colorectal cancer.

Adenomatous Polyposis Coli↗

PubMed1990

Pharmacodynamics of trimethoprim-sulfamethoxazole in Listeria meningitis: a case report.

Infections in the cerebrospinal fluid (CSF) occur in an area of impaired host defenses; therefore, bactericidal antibiotics that reach adequate concentrations in the CSF are necessary for treatment. Measurements of antibiotic penetration into the CSF include CSF inhibitory and bactericidal titers, the absolute antibiotic concentration in the CSF, and the CSF: serum concentration ratio. We present the case of a patient with Listeria monocytogenes meningitis who failed to respond clinically to standard therapy, and whose organism demonstrated tolerance to Ampicillin (MBC: MIC = 258:1) that successfully responded to trimethoprim-sulfamethoxazole (TMP-SMX). The CSF peak bactericidal titer to TMP-SMX was 1:8, corresponding to that reported as necessary for successful outcome in patients with meningitis. The CSF peak: MBC ratios for TMP and SMX were less than 3:1 and equal to 3:1, respectively. These individual ratios are lower than those suggested for successful treatment of meningitis; however, the recommended ratios were established using single agents and did not account for synergistic activity with a drug combination such as TMP-SMX. The failure of standard therapy in this patient underscores the importance of MIC/MBC testing when tolerance is suspected or when CSF penetration of antibiotics is relatively poor. In addition, measurements of CSF inhibitory and bactericidal titers, which incorporate the antibiotic concentration in the CSF, susceptibility of the infecting microorganism, and host defense factors, may be useful in monitoring patients with meningitis.

Adult↗

PubMed1990

Antibiotic prophylaxis and tourniquet inflation in total knee arthroplasty.

Twenty-four patients receiving total knee arthroplasty (TKA) were randomized into one of three groups based on tourniquet inflation one, two, or five minutes after administration 1 g cefazolin. Simultaneous serum, soft-tissue, and bone samples were obtained at regular intervals during surgery. All soft-tissue and bone samples were corrected for cefazolin content. The percentage of cefazolin penetration into soft tissue and bone was calculated using the area under the concentration time curve. Adequate cefazolin concentrations for soft tissue and bone were defined as greater than or equal to 4 x minimum inhibitory concentration90 (MIC90 = 1 microgram/ml) of cefazolin to Staphylococcus aureus and coagulase-negative staphylococci. Patients were similar in age, actual body weight, creatinine clearance, and length of tourniquet inflation. The median percentage of cefazolin penetration into soft tissue and bone for the five-, two-, and one-minute groups was 14.5% and 4.6%, 6.7% and 3.0%, and 5.9% and 4.6%, respectively; the percentage of penetration into soft tissue between the five- and one-minute groups was statistically significant. A higher percentage of patients achieved the desired cefazolin concentration (greater than or equal to 4 micrograms/g) if a five-minute interval was selected. The five-minute group achieved the highest mean ratios of concentration to MIC compared with the two- and one-minute groups, although the differences were not statistically significant. The standard 1 g of cefazolin with a five-minute interval between administration and tourniquet inflation resulted in adequate mean soft-tissue and bone concentrations for prophylaxis during TKA with a tourniquet time less than two hours. Additional doses are not warranted after tourniquet release.

Aged↗

PubMed1990

The effect of tourniquet inflation on cefazolin tissue penetration during total knee arthroplasty.

Patients undergoing total knee arthroplasty were randomized to tourniquet inflation 1, 2, or 5 minutes after a 1-g dose of cefazolin. Serum, soft tissue, and bone samples were obtained at 10, 30, and 60 minutes after inflation, immediately prior to tourniquet release (PTR), and 5 minutes after release. Areas under the concentration-time curve (AUC10-PTR) were calculated using the linear trapezoidal method and normalized to actual body weight, creatinine clearance, and length of tourniquet inflation. The percentage of penetration was calculated using the normalized values for the respective AUCs. Differences among the groups were analyzed using analysis of variance or the Kruskal-Wallis test where appropriate. Groups were similar for age, actual body weight, duration of tourniquet inflation, and creatinine clearance (p greater than 0.05). The median percentages of penetration for soft tissue and bone at 5, 2, and 1 minute were 14.5% and 4.6%, 6.7% and 3.0%, and 5.9% and 4.6%, respectively. Only the percentage of soft tissue penetration between 5 and 1 minute was significantly different (p = 0.015). Gender and type of anesthesia (general, epidural) had no effect on cefazolin penetration into soft tissue or bone. Although increasing the time interval between cefazolin administration and tourniquet inflation resulted in higher soft tissue drug concentrations, a 1-minute interval resulted in soft tissue and bone cefazolin concentrations at or above the minimum inhibitory concentration for microorganisms likely to be encountered in this surgical procedure.

Adolescent↗

PubMed1989

Measurement of delta-(L-alpha-aminoadipyl)-L-cysteinyl-D-valine synthetase activity in Streptomyces clavuligerus by high-performance liquid chromatography after precolumn derivatization with o-phthaldialdehyde.

A procedure for rapid, sensitive measurement of delta-(L-alpha-aminoadipyl)-L-cysteinyl-D-valine (ACV) in complex cell extracts has been developed by adapting a widely used method for high-performance liquid chromatography analysis of amino acids. Samples were oxidized with performic acid and derivatized with o-phthaldialdehyde-mercaptoethanol to give the fluorescent isoindole derivative of the peptide sulfonate. The procedure was used to assay Streptomyces clavuligerus cell extracts and partially purified fractions for ACV synthetase activity and to determine some characteristics of the enzyme reaction. The presence of a second enzyme with cysteine as a substrate was also indicated.

Chromatography, High Pressure Liquid↗

PubMed1989

Physical mapping of the von Recklinghausen neurofibromatosis region on chromosome 17.

The von Recklinghausen neurofibromatosis (NF1) locus has been linked to chromosome 17, and recent linkage analyses place the gene on the proximal long arm. NF1 probably resides in 17q11.2, since two unrelated NF1 patients have been identified who possess constitutional reciprocal translocations involving 17q11.2 with chromosomes 1 and 22. We have used a somatic-cell hybrid from the t(17;22) individual, along with other hybrid cell lines, to order probes around the NF1 locus. An additional probe, 17L1, has been isolated from a NotI linking library made from flow-sorted chromosome 17 material and has been mapped to a region immediately proximal to the translocation breakpoint. While neither NF1 translocation breakpoint has yet been identified by pulse-field gel analysis, an overlap between two probes, EW206 and EW207, has been detected. Furthermore, we have identified the breakpoint in a non-NF1 translocation, SP-3, on the proximal side of the NF1 locus. This breakpoint has been helpful in creating a 1,000-kb pulsed-field map, which includes the closely linked NF1 probes HHH202 and TH17.19. The combined somatic-cell hybrid and pulsed-field gel analysis we report here favors the probe order D17Z1-HHH202-TH17.19-CRYB1-17L1-NF1- (EW206, EW207, EW203, L581, L946)-(ERBB2, ERBA1). The agreement in probe ordering between linkage analysis and physical mapping is excellent, and the availability of translocation breakpoints in NF1 should now greatly assist the cloning of this locus.

Animals↗

PubMed1989

Small central cervical disc syndrome: evaluation and treatment of chronic disabling neck pain.

In this retrospective study of 22 patients with severe disabling neck, interscapular, and shoulder pain we evaluated the effectiveness of magnetic resonance imaging (MRI) for the diagnosis of small central cervical disc ruptures, and anterior cervical discectomy for the treatment of this condition. Conservative therapy had failed for all patients. All had been disabled for their normal activities for at least 6 months. MRI demonstrated two patterns of mid- or parasagittal disc disease. Anterior cervical discectomy produced nine excellent, six good, five fair, and two poor results. All but one patient returned to his/her former occupation. MRI is essential in the evaluation of patients with chronic neck pain who have failed conservative therapy and present with axial rather than appendicular complaints. Anterior cervical discectomy can be useful in well-selected patients with this syndrome.

Adult↗

PubMed1988

The elasmobranch spiracular organ. II. Physiological studies.

The spiracular sense organs of the little skate, Raja erinacea, and the smooth dogfish, Mustelus canis, respond to movements of the hyomandibula-cranial joint. Afferent activity was recorded from the spiracular organ nerve in isolated preparations consisting of at least part of the cranium, the hyomandibula, and the spiracular organ and nerve. Afferents are excited by hyomandibular flexion at its joint with the cranium. Single unit recordings in the little skate revealed a single class of units that were slowly adapting, and had a regular firing pattern. Single unit firing rate increased up to about 70 spikes/s during hyomandibular flexion from a spontaneous rate at rest of 15-20 spikes/s, and could often be silenced by hyomandibular extension. The direction of excitation is consistent with the orientation of the hair cell ciliary bundles observed in morphological studies (Barry et al. 1988). Local deformations of the cupula are sufficient to excite or inhibit primary afferent firing, and volume changes in the spiracular organ as a whole are not necessary. The spiracular organs are relatively insensitive to electrical stimuli, vibration, or water movement. In conclusion, the spiracular organ functions as a sensitive joint receptor.

Animals↗

PubMed1988

Genetic linkage between lipoprotein(a) phenotype and a DNA polymorphism in the plasminogen gene.

Coronary heart disease risk correlates directly with plasma concentrations of lipoprotein(a) (Lp(a)), a low-density lipoprotein-like particle distinguished by the presence of the glycoprotein apolipoprotein(a) (apo(a)), which is bound to apolipoprotein B-100 (apoB-100) by disulfide bridges. Size isoforms of apo(a) are inherited as Mendelian codominant traits and are associated with variations in the plasma concentration of lipoprotein(a). Plasminogen and apo(a) show striking protein sequence homology, and their genes both map to chromosome 6q26-27. In a large family with early coronary heart disease and high plasma concentrations of Lp(a), we found tight linkage between apo(a) size isoforms and a DNA polymorphism in the plasminogen gene; plasma concentrations of Lp(a) also appeared to be related to genetic variation at the apo(a) locus. We found free recombination between the same phenotype and alleles of the apoB DNA polymorphism. This suggests that apo(a) size isoforms and plasma lipoprotein(a) concentrations are each determined by genetic variation at the apo(a) locus.

Adult↗