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Biomedical subjects

R L White

Publications and source records attributed to R L White.

At least 127 records · Page 7Linked to original sources
PubMed1988

Stereoisomers of allenic amines as inactivators of monoamine oxidase type B. Stereochemical probes of the active site.

The kinetics of inactivation of mitochondrial monoamine oxidase type B (MAO-B) by a series of 18 stereoisomers of tertiary alpha-allenic amines have been investigated in detail. The chirality of the allene group in N-methyl-N-aralkylpenta-2,3-dienamines was found to have a profound effect on the inactivation rate, with the (R)-allenes being up to 200-fold more potent than their (S)-allenic counterparts. The ability of (S)-allenes to inactivate MAO was severely compromised by the presence of N-phenethyl or N-alpha-substituted-aralkyl substituents. The opposing chiralities in both the allene and aralkyl groups of (R,R)- and (S,S)-N-methyl-N-(1,2,3,4-tetrahydro-1-naphthyl)-penta-2,3-dienamine+ ++ resulted in a difference of more than 3 orders of magnitude in inactivation rates. The stereoselectivity of MAO-B was examined further with a series of reversible aralkylamine inhibitors; thus (R)-1,2,3,4-tetrahydro-1-naphthylamine was determined to be 150-fold more potent than its enantiomer.

Alkenes↗
PubMed1988

Malignant transformation in craniopharyngioma.

Malignant transformation in a craniopharyngioma has not been described previously. A 49-year-old woman presented with recurrence of a suprasellar craniopharyngioma diagnosed 35 years previously. The patient had been treated surgically for recurrence on five occasions. Radiation therapy had been administered 7 years before the final presentation. Tissue obtained from the fifth operation revealed malignant degeneration in a typical craniopharyngioma.

Craniopharyngioma↗
PubMed1988

Serum and tissue concentrations of cefoxitin and cefotaxime in women undergoing hysterectomy.

In a comparative study of serum and uterine tissue concentrations of cefoxitin and cefotaxime in patients undergoing hysterectomy, 40 patients were randomised to receive either cefoxitin 2g or cefotaxime 2g by intravenous administration. Serum samples were obtained before drug administration, at the ligation of the uterine arteries and at the end of surgery. Cefoxitin, cefotaxime and desacetylcefotaxime concentrations were determined by high performance liquid chromatography. The composite serum half-lives (determined by linear regression) for cefoxitin, cefotaxime and desacetylcefotaxime were 0.8, 0.7 and 2.1 hours, respectively. Although serum concentrations were higher for cefotaxime than for cefoxitin after a 2g dose, the uterine concentrations (at 40 mins) of cefoxitin were higher (51 micrograms/g vs 16 micrograms/g) than those of cefotaxime. After a 2g dose of cefotaxime the desacetylcefotaxime peak uterine concentration was 8 micrograms/g. Both drugs achieved adequate concentrations in serum and uterine tissue to prevent and treat infections caused by common Enterobacteriaceae such as Escherichia coli, with cefotaxime having a longer apparent duration of activity. However, cefoxitin provided serum and uterine concentrations above the minimum inhibitory concentration of Bacteroides fragilis for a longer period than did cefotaxime.

Adult↗
PubMed1988

Cytogenetic study of Kaposi's sarcoma associated with acquired immunodeficiency syndrome.

We performed cytogenetic studies on direct preparations and short-term cultures from Kaposi's sarcoma cells obtained from malignant pericardial effusion. The patient, a 46-year-old man with human immunodeficiency virus infection, initially presented with metastatic Kaposi's sarcoma. Despite therapy, his tumor proved aggressive, and the patient died of widespread pulmonary involvement nine months after diagnosis. Cytogenetic analysis revealed a predominant karyotype of 48,X,-Y, t(2;7)(q32;q36), +der(5)t(5;15)(q?15;q?15), -7, +del(7)(p15), +del(7)(p15), +der(8)t(8;D or G)(q24;p11.2), del(10)(p13), dup(12)(q24), t(18;20)(q21;q13). This case is described in relation to other published cytogenetic studies of this tumor.

Acquired Immunodeficiency Syndrome↗
PubMed1987

Characterization of a highly polymorphic region 5' to JH in the human immunoglobulin heavy chain.

A cloned DNA segment 1.25 kilobases (kb) upstream from the joining segments of the human heavy chain immunoglobulin gene revealed extensive polymorphic variation at this locus, and the polymorphic pattern was stably transmitted to the next generation. Genomic restriction analysis showed that the polymorphism was caused by insertions/deletions within an MspI/BamHI fragment. Sequencing of one allele, 848 base pairs (bp) long, revealed eleven 50-base-pair tandem repeats. A second allele, 648 bp long, was cloned from a human genomic cosmid library, sequenced, and found to contain four fewer repeats than the first allele. A survey of 186 chromosomes from unrelated individuals of primarily northern European descent revealed at least six alleles.

Alleles↗
PubMed1987

Phenytoin removal during plasma exchange.

Plasma exchange is currently being used to treat a variety of disorders including immune complex and hematologic disorders. It has been shown that the removal of plasma removes drugs bound to plasma proteins. This case documents the removal of phenytoin during plasma exchange therapy. Total and free phenytoin serum concentrations were obtained before and after each exchange. Aliquots were obtained from each pass, and total phenytoin concentrations were determined. The total phenytoin serum concentration increased during the first exchange, while the total concentration decreased as a result of the second exchange. It was determined that approximately 27.7 mg and 30.4 mg of phenytoin were removed by the first and second plasma exchanges, respectively.

Adolescent↗
PubMed1987

1-[[[5-(substituted phenyl)-2-oxazolyl]methylene]amino]-2,4- imidazolidinediones, a new class of skeletal muscle relaxants.

A series of 1-[[[5-(substituted phenyl)-2-oxazolyl]methylene]amino]- 2,4-imidazolidinediones (6a-t) was synthesized, and the compounds were evaluated for direct skeletal muscle inhibition in the pithed rat gastrocnemius muscle preparation. The correctness of structural assignment of the new series was verified by alternate, unequivocal synthesis of one representative structure (6f). The phenyloxazoles 6d, 6g, 6j, 6k, and 6l exhibited significant skeletal muscle relaxant activity when administered intravenously and orally. The skeletal muscle relaxant effect of these five compounds is similar to that of other direct-acting skeletal muscle relaxants. The oxazole moiety proved to be an acceptable isosteric replacement for furan, as the biological activity in the oxazole series was retained. The synthesis of this new class of compounds is described, and pharmacologic evaluation data are presented. A discussion of structure-activity relationships is also presented.

Animals↗
PubMed1987

Speech perception by four single-channel cochlear implant users.

Four profoundly deaf adults, each a recent recipient of a scala tympani implant, underwent auditory and auditory-visual speech comprehension evaluations. Two subjects had multiple-electrode auditory prostheses, and 2 had single-electrode implants. All subjects were tested preoperatively with a high-power hearing aid, and postoperatively with a single-channel wearable sound processor. Reported here are the results of the first formal speech recognition tests which were conducted during the 8 months after the sound processor fitting. Three subjects had used the single-channel processor on a daily basis for up to 8 months at the time of postoperative testing. The 4th subject was a nonuser. On listening tests, a comparison between pre- and post-implant scores revealed little difference for any subject. On postoperative speechreading tasks, all subjects identified medial consonant phonemes and 2-digit numerals better with stimulation than without. The 3 frequent users of the device experienced significant improvement on connected-discourse tracking, and their speechreading of videotaped and live voice CID Everyday Sentences (Davis & Silverman, 1978) was enhanced with the addition of stimulation. The nonuser was a very proficient speechreader at the outset and exhibited no significant difference on connected-discourse tracking with and without stimulation. Moreover her ability to speechread Everyday Sentences was hampered slightly by the addition of stimulation. This single-channel sound processor functioned as a sensory supplement for the 3 frequent users, but no subject was able to use the processor as a sensory substitute.

Adult↗
PubMed1987

Cochlear or nerve stimulation.

To stimulate through electrical stimulation the auditory nerve excitation patterns produced by a normal ear, it is necessary to control both the spatial and the timing aspects of the neural firing pattern. While the spatial localization, the "place" aspect of stimulation can probably be achieved adequately with either scala tympani or direct eighth nerve electrodes, only the eighth nerve electrodes have the potential to reproduce the detailed timing patterns of the normal nerve. While such complete control of the stimulation pattern is probably necessary to produce "natural" auditory percepts, it may well not be necessary for the conveying of the information in speech because of the plasticity and pattern recognition capabilities of the brain. Present encouraging results as open speech comprehension with scala tympani electrode arrays suggest that, in many cases at least, the cruder stimulation pattern control will suffice.

Cochlear Implants↗
PubMed1987

Ear-muscle.

Explore the source record for details and available documents.

Cochlear Implants↗
PubMed1987

Pitch perception by cochlear implant subjects.

Direct electrical stimulation of the auditory nerve can be used to restore some degree of hearing to the profoundly deaf. Percepts due to electrical stimulation have characteristics corresponding approximately to the acoustic percepts of loudness, pitch, and timbre. To encode speech as a pattern of electrical stimulation, it is necessary to determine the effects of the stimulus parameters on these percepts. The effects of the three basic stimulus parameters of level, repetition rate, and stimulation location on subjects' percepts were examined. Pitch difference limens arising from changes in rate of stimulation increase as the stimulating rate increases, up to a saturation point of between 200 and 1000 pulses per second. Changes in pitch due to electrode selection depend upon the subject, but generally agree with a tonotopic organization of the human cochlea. Further, the discriminability of such place-pitch percepts seems to be dependent on the degree of current spread in the cochlea. The effect of stimulus level on perceived pitch is significant but is highly dependent on the individual tested. The results of these experiments are discussed in terms of their impact on speech-processing strategies and their relevance to acoustic pitch perception.

Acoustic Stimulation↗
PubMed1987

Cefotaxime stability during in vitro microbiological testing.

Cefotaxime is a broad-spectrum cephalosporin which is metabolized or degraded to less active or inactive metabolites by serum esterases, elevated temperatures, or a pH outside of its stability range. Cefotaxime instability during in vitro microbiological susceptibility tests may lead to an underestimation of the antibacterial activity of the compound. Cefotaxime and desacetylcefotaxime solutions were studied under MIC and serum inhibitory titer testing conditions. Cefotaxime concentrations, as measured by high-performance liquid chromatography, decreased 20 to 30% over the incubation period in various systems tested; the greatest decline occurred in systems containing serum in the media. Changes in the results of microbiological susceptibility tests interpreted after 6 and 18 h of incubation were consistent with changes observed in the high-performance liquid chromatography analysis. This study demonstrates cefotaxime instability under conditions of in vitro microbiological testing.

Cefotaxime↗
PubMed1987

Mapping approaches to gene identification in humans.

Although a number of human genes that cause disease have been traced through the defective product, most genetic defects are recognized only by phenotype. When the biochemical defect is unknown, a gene can be located only through molecular approaches based on coinheritance (genetic linkage) of the disease phenotype with a particular allele of a polymorphic DNA marker that has already been mapped to a specific chromosomal region. Linkage studies in affected families have already localized genes for several important diseases, including cystic fibrosis. Finding a genetic linkage in families in which a disease segregates requires that the human genetic map have a large number of polymorphic markers; when the map is dense enough, any disease gene can be located by linkage to a known marker. Many DNA segments with a high degree of polymorphism are being found and mapped as markers in normal reference pedigrees. Genetic linkage mapping has implications even broader than its application to prenatal diagnosis or therapeutic strategy; analyzing mutations in important genes will illuminate basic mechanisms in molecular biology and the early events that lead to cancer and other disorders.

Chromosome Mapping↗