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Biomedical subjects

R L White

Publications and source records attributed to R L White.

At least 19 recordsLinked to original sources
PubMed1992

The CEPH consortium linkage map of human chromosome 15q.

The CEPH consortium map of chromosome 15q is presented. The map contains 41 loci defined by genotypes generated from CEPH family DNAs with 45 different probe and restriction enzyme combinations contributed by 10 laboratories. A total of 29 loci have been placed on the map with likelihood support of at least 1000:1. The map extends from 15q13 to 15q25-qter. Multipoint linkage analyses provided estimates that the male, female, and sex-averaged maps extend for 127, 190, and 158 cM, respectively. The largest interval is 21 cM and is between D15S37 and D15S74. The on-average locus spacing is 5.6 cM and the mean genetic distance between the 21 uniquely placed loci is 8 cM.

Chromosome Mapping↗
PubMed1992

Growth morphology of Streptomyces akiyoshiensis in submerged culture: influence of pH, inoculum, and nutrients.

Most media in which the growth of shaken submerged cultures of Streptomyces akiyoshiensis was examined did not support the formation of well-dispersed mycelial suspensions. Investigation of the culture conditions promoting dispersed growth showed the pH of the culture medium to be of critical importance; an initial value of 5.5 minimized aggregation of the mycelium while supporting adequate biomass production. In cultures started at this pH, spore inocula gave better mycelial dispersal than did vegetative inocula; with spore inocula, growth morphology was also less affected by inoculum size. The composition of the nutrient solution influenced the extent of mycelial dispersal; slow growth was often associated with clumping but no clear correlation was observed between pellet formation and the ability of carbon or nitrogen sources to support rapid growth. Increasing the phosphate concentration from 0.5 to 15 mM caused a modest decrease in mycelial aggregation. Conditions promoting a well-dispersed mycelium suitable for studying the physiological control of secondary metabolism also supported the formation of 5-hydroxy-4-oxonorvaline by S. akiyoshiensis.

Aminolevulinic Acid↗
PubMed1992

Effects of a videotape feedback package on the peer interactions of children with serious behavioral and emotional challenges.

Peer interactions are among the greatest challenges experienced by children who have severe emotional and behavioral problems. This study evaluated an intervention package designed to increase the ratio of these children's desirable to undesirable interactions. The package included three principal components: (a) observation of videotapes following regularly scheduled peer activity sessions; (b) self-evaluation of the children's peer interactions observed on the videotapes; and (c) delayed feedback and reinforcement for desirable peer interactions. Five students from two elementary schools participated. Multiple baseline designs and one reversal were used to evaluate the effects of the intervention package. The results showed that the intervention produced lower levels of undesirable peer interactions and higher ratios of desirable to undesirable interactions for all participants. The results are discussed in regard to their conceptual and applied implications and in terms of specific directions for future research.

Affective Symptoms↗
PubMed1992

Ex vivo protein binding of clindamycin in sera with normal and elevated alpha 1-acid glycoprotein concentrations.

Clindamycin is a lincosamide antibiotic that binds primarily to alpha 1-acid glycoprotein (AAG), an acute-phase serum protein. Many studies have shown that AAG concentrations increase in response to stress, including infection, myocardial infarction, and trauma. The objectives of this study were to determine the serum protein binding of various clindamycin concentrations in sera with normal and elevated AAG concentrations. Serum was obtained from 4 healthy volunteers and 12 patients with pathophysiologic conditions known to elevate serum AAG concentrations. Timing for collection was determined from the literature, corresponding with the expected peak concentration for each disease state. Samples were assayed for AAG by radial immunodiffusion and were spiked with clindamycin to achieve total concentrations of 10 micrograms/ml (n = 18), 4 micrograms/ml (n = 10), and 2 micrograms/ml (n = 7). Protein binding was determined by ultrafiltration and subsequent high-performance liquid or gas chromatography. Protein binding was dependent on the serum concentrations of both AAG and clindamycin. When AAG concentrations increased from 101-150 mg/dl to 201 mg/dl or greater, mean protein binding increased from 81.2% to 92.4% (p = 0.1265) and from 61.3% to 88.6% (p less than 0.05) at clindamycin concentrations of 2 and 4 micrograms/ml, respectively. With AAG concentrations between 101 and 150 mg/dl, mean protein binding increased from 62.4% at 10 micrograms/ml to 81.2% at 2 micrograms/ml (p = 0.1514). Since AAG concentrations may increase in certain patients, the concentration of free (pharmacologically active) drug may fall below the minimum inhibitory concentration for several pathogens earlier in a dosing interval.

Chromatography, Gas↗
PubMed1992

Pharmacoeconomic evaluation of treatment of penetrating abdominal trauma.

The hospital, pharmacy, and antibiotic costs for patients with penetrating abdominal trauma were compared with reimbursement received; these costs were also analyzed to assess the potential impact of a total prospective pricing system (PPS). During a four-year period, 46 patients admitted solely for penetrating abdominal trauma were retrospectively evaluated: their discharge summaries indicated that, for 9 patients, reimbursement was based on diagnosis-related groups (DRGs) under the PPS; 9 patients had private insurance; and 28 were classified as "self-paying/no insurance." All costs, corrected for inflation, were reported in 1989 dollars. Antibiotics represented 22.5%, 1.7%, and 0.5% of pharmacy, hospital, and DRG reimbursement, respectively; pharmacy costs were 8.5% of hospital costs and 2.3% of DRG reimbursement. For all 46 patients, a net loss of $295 per patient was incurred. Four patients accounted for 43% of the hospital costs. If the hospital had been reimbursed for all of these patients by prospective pricing and DRGs, it would have had a median profit of $9730 in 42 of 46 patients. Costs exceeded DRG reimbursement in the remaining four patients by a median of $8210. Antibiotic costs and pharmacy costs represent a small portion of hospital costs and DRG reimbursement for patients with penetrating abdominal trauma; thus, cost containment efforts in these patients should be directed at other ancillary services and length of stay.

Abdominal Injuries↗
PubMed1991

The CEPH consortium linkage map of human chromosome 1.

This paper describes the Centre d'Etude du Polymorphisme Humain (CEPH) consortium linkage map of human chromosome 1. The map contains 101 loci defined by genotypes generated from CEPH family DNAs with 146 different contributions from 11 laboratories. A total of 58 loci are uniquely placed on the map with likelihood support of at least 1000:1. The map extends from loci in the terminal bands of both chromosome arms (locus D1Z2 in 1p36.3 and D1S68 in 1q44) and is anchored at the centromere by the D1Z5 alpha-satellite polymorphism. With the exception of a single locus, the remaining loci are arrayed on the fixed map in short intervals and their possible locations are indicated. Multipoint linkage analyses provided estimates that the male, female, and sex-averaged maps extend for 308, 478, and 390 cM, respectively. The sex-averaged map contains only four intervals greater than 15 cM, and the mean genetic distance between the 58 uniquely placed loci is 6.7 cM.

Chromosome Mapping↗
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↗