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Biomedical subjects

J R Thompson

Publications and source records attributed to J R Thompson.

At least 127 records · Page 7Linked to original sources

Phenytoin hypersensitivity syndrome.

The purpose of the current manuscript is to familiarize the primary physician with the presentation of phenytoin hypersensitivity syndrome, and to discuss management options. A review of all admissions to the University of Mississippi Medical Center over a five year period revealed 4 cases of phenytoin hypersensitivity syndrome. These cases are presented and the phenytoin hypersensitivity syndrome, characterized most commonly by fever, cutaneous eruption and lymphadenopathy, is described. It is emphasized that the clinician must be aware of the syndrome and must recognize it on presentation. Theories regarding etiology and treatment options are discussed. It is recommended that all patients with symptoms of phenytoin hypersensitivity syndrome be hospitalized and that steroids be initiated.

Adolescent↗

Crystal structure of cellular retinoic acid binding protein I shows increased access to the binding cavity due to formation of an intermolecular beta-sheet.

A recombinant form of murine apo-cellular retinoic acid binding protein I (apo-CRABPI) has been purified and crystallized at pH 5.0, and the crystal structure has been refined to an R-factor of 19.6% at a resolution of 2.7 A. CRABPI binds all-trans retinoic acid and some retinoic acid metabolites with nanomolar affinities. Coordinates of the holo form of CRABP were not available during the early stages of the study, and in spite of numerous homologs of known structure, phases were not obtainable through molecular replacement. Instead, an interpretable electron density map was obtained by multiple isomorphous replacement methods after improvement of the heavy-atom parameters with density modified trial phases. Two molecules of apo-CRABPI occupy the P3121 asymmetric unit and are related by pseudo 2-fold rotational symmetry. Unique conformational differences are apparent between the two molecules. In all of the family members studied to date, there is a lack of hydrogen bonds between two of the component beta-strands resulting in a gap in the interstand hydrogen bonding pattern. In the crystallographic dimer described here, a continuous intermolecular beta-sheet is formed by using this gap region. This is possible because of an 8 A outward maximum displacement of the tight turn between the third and fourth beta-strands on one of the molecules. The result is a double beta-barrel containing two apo-CRABPI molecules with a more open, ligand-accessible binding cavity, which has not been observed in other structures of a family of proteins that bind hydrophobic ligands.

Amino Acid Sequence↗

High-performance liquid chromatographic analysis of beta-phenylethylamine for the estimation of in vivo protein synthesis.

A rapid, sensitive, and automated reversed-phase liquid chromatographic method was developed for the analysis of phenylalanine as beta-phenylethylamine, for the measurement of in vivo protein synthesis. beta-Phenylethylamine was derivatized with o-phthaldialdehyde (OPA) to form a fluorescent derivative that was successfully measured in tissue cell fluids and hydrolysates as the decarboxylation product of phenylalanine. The system was extremely sensitive enabling the accurate determination of 0.5 pmol in biological samples. Analysis time was less than 11 min, so that 130 samples can be analysed per day. The method eliminates the need for time-consuming column extraction procedures. This method offers substantial advantages over existing methods for the isolation and determination of beta-phenylethylamine.

Animals↗

Influence of stage of lactation on glucose and glutamine metabolism in isolated enterocytes from dairy cattle.

Pathways of glutamine and glucose metabolism in early-, mid-, and late-lactation dairy cows were evaluated by in vitro incubations of enterocytes for 2 hours with [U-14-C]glutamine and [U-14C]glucose. Enterocytes from early-lactation cows produced greater amounts of CO2 from glutamine in concentrations that ranged from 2 to 8 mmol/L than enterocytes from either mid- or late-lactation cows. Enterocytes from early-lactation cows also produced greater amounts of CO2 from 4 and 6 mmol/L glucose than enterocytes from either mid- or late-lactation cows. Glutamine was metabolized via glutaminolysis mainly to ammonia, alanine, aspartate, glutamate, and CO2, and more of these products were produced in enterocytes from early-lactation cows than from pooled mid- and late-lactation (PML) cows. Glucose was metabolized mainly to lactate, as compared with pyruvate and CO2. Lactate and CO2 production were both greater in enterocytes from early-lactation cows than from PML cows. Glutamine as the sole substrate accounted for all the energy requirements of enterocytes from early-lactation cows but contributed only 31% in the presence of glucose. Similarly, glucose accounted for all the energy requirements of enterocytes from early-lactation cows and contributed 69% in the presence of glutamine. In enterocytes from all cows, the rate of adenosine triphosphate (ATP) production was greater in the presence of both glucose and glutamine compared with that in the presence of either substrate alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗

Applications of epidemiological techniques.

Epidemiology is the study of disease occurrence in human populations. Its methodology could be used in health services research and medical audit. In fact, most ophthalmologists today should be using some form of epidemiological technique to evaluate their own practice and the service they are providing for their patients.

Epidemiologic Methods↗

Ultrasound assessment of liver and kidney brightness in infants. Use of the gray-level histogram.

RATIONALE AND OBJECTIVES: Ultrasonic image analysis aims to provide information related to tissue histology. Routine ultrasonography uses subjective criteria for analysis. Quantitation of the image is expected to aid diagnosis and may be helpful in follow-up of pathology. The authors describe normal findings in infant liver and kidney. METHODS: Texture parameters derived from the gray-level histogram and the first order statistics from the ultrasound images of the liver, right kidney, and a tissue-mimicking phantom in 50 newborn infants were studied. RESULTS: A set of normal values for mean and standard deviation of the histogram for infant liver and kidney was established. Results of a time-related study indicate that in infants the liver is not a good internal standard for tissue characteristic comparison. CONCLUSIONS: The method described and results obtained provide a basis of normality for further studies of pathology in infant renal and hepatic disease.

Humans↗

Circulatory effects of ventilator rate and end-expiratory pressure in unparalysed preterm infants.

Impairment of cerebrovascular autoregulation may be important in the pathogenesis of ischaemic brain injury in preterm infants. A previous study in ventilated preterm infants paralysed with pancuronium showed that changes in cerebral blood flow velocity (CBFV) were related to concomitant changes in arterial blood pressure. In a similar study in unparalysed infants, changes in CBFV in response to changes in ventilator rate or end-expiratory pressure were independent of associated changes in the arterial blood pressure. These results emphasize the importance of avoiding large swings in blood pressure in paralysed infants. Whether alternative paralysing agents have similar effects warrants further study.

Blood Pressure↗

Children's vision screening: impact on inequalities in central England.

STUDY OBJECTIVE: To investigate the relationship between age at presentation of amblyopia and social deprivation before and after the introduction of changes to a vision screening service. DESIGN: Two cohorts of children treated for amblyopia in 1983 and 1992. SETTING: THe orthoptic department of Leicester Royal Infirmary. PARTICIPANTS: The 209 patients treated for amblyopia who first attended the orthoptic department in 1983, and 203 who first attended in 1992. MEASUREMENTS: Age at presentation to the orthoptic department was the main outcome measure. Social deprivation was measured by Townsend deprivation score for the electoral ward in which the child lived, using 1981 and 1991 census data. MAIN RESULTS: After the introduction of changes in the screening programme, the mean at presentation of amblyopia associated with microtropia or no strabismus was reduced from 6.6 years to 5.0 years. In 1983 there was a significant relationship between deprivation and age at presentation (p = 0.0001), with those from more deprived areas presenting later. No similar association was found in children referred in 1992 (p = 0.17). There was no change in mean age of presentation of amblyopia associated with a large angle of strabismus (3.3 years in 1983 and 1992) and no relationship between deprivation and age at presentation 1983 or 1992 (p = 0.24 and p = 0.39 respectively). CONCLUSION: Since the introduction of changes to vision screening, the relationship between social deprivation and the age of presentation of asymptomatic amblyopia seems to have disappeared. Children are now referred earlier and those from deprived areas are not being overlooked.

Age Factors↗

Efficacy of ivermectin pour-on against Ostertagia ostertagi infection and residues in the American bison, Bison bison.

Sixteen American bison, Bison bison, were artificially infected with 10(5) infective stage larvae of Ostertagia ostertagi on 21 April 1993. At 42 days post-infection eight bison were treated with 0.5% ivermectin pour-on (500 micrograms/kg bodyweight) and eight treated with the carrier only. Bison were necropsied 17 and 18 days post-treatment (21 and 22 June 1993, respectively). Mean (+/- SE) of 5,413 (+/- 1,716) adults and 565 (+/- 305) immature O. ostertagi were recovered at necropsy from bison treated with the carrier. No O. ostertagi were detected in bison treated with ivermectin pour-on. Based on the levels of the ivermectin marker metabolite in liver and adipose tissue 18 days post-treatment, the established bovine withdrawal time of 48 days appears adequate to insure that violative residues do not occur.

Adipose Tissue↗

Aminoglycoside-induced Fanconi's syndrome.

Nephrotoxicity manifested by renal insufficiency is a well-known consequence of aminoglycoside administration in hospitalized patients. We report two cases of aminoglycoside-induced nephrotoxicity as manifested by proximal tubular dysfunction (Fanconi's syndrome). In the two patients reported, the tubular dysfunction occurred at the extremes of renal function. In both patients, tubular function returned to normal when the antibiotic was discontinued. Because of the widespread use of these antibiotics in the critically ill patient, it may be prudent to recognize this disorder when managing fluids, electrolytes, and nutrition.

Adult↗

The presentation of children with amblyopia.

This study reports the presentation of 961 children who underwent amblyopia treatment at seven orthoptic centres in the United Kingdom. We confirmed previous authors' findings of a small but significant increased incidence of left-sided compared with right-sided amblyopia overall. For pure anisometropic amblyopia this difference was very marked and a possible pathophysiological mechanism is proposed. The mean age of presentation for anismetropic, strabismic and mixed amblyopia was 5.6, 3.3 and 4.4 years, respectively. Neither sex nor race affected the age of presentation. Despite their older age, children with pure anisometropic amblyopia had the best initial visual acuity, with 25% of anisometropes having an initial visual acuity of less than 6/18 compared with 39% of strabismics and 50% of mixed amblyopes. The ages and initial acuities of the strabismic patients in this series are at least as favourable as those of patients reported from outside the UK. There were variations in the age and proportion of patients presenting with anisometropic amblyopia at the different centres, suggesting a failure in the referral of anisometropic amblyopia of importance in interpreting epidemiological studies.

Age Factors↗

Factors affecting the outcome of children treated for amblyopia.

The outcome of treatment for amblyopia and the factors that affect this are not well understood. A major reason for this has been the exclusion from previous large studies of a sometimes unknown number of patients because of failure to comply with treatment. This paper analyses the outcome of amblyopia treatment in a retrospective review of the orthoptic records of a cohort of 961 children treated for amblyopia at seven centres who first attended in 1983. The final visual acuity was recorded by Snellen or matching methods in 894 children (93%). Of these, 48% achieved 6/9 or better, 35% less than 6/9 but better than or equal to 6/18, and 17% achieved less than 6/18. The outcome was best for pure anisometropic amblyopia, intermediate for pure strabismic amblyopia and least good for mixed strabismic and anisometropic amblyopia with a final visual acuity of 6/10.2, 6/12.8 and 6/14.8 respectively. While the age at start of treatment did not correlate with final visual acuity both poor initial visual acuity and poor compliance were associated with poor outcome. The main factor affecting the outcome of amblyopia treatment is the initial visual acuity. Comparison with the literature suggests that the results of treatment in this country may be falling far short of what would be possible in ideal circumstances with unlimited resources.

Age Factors↗

Reliability of the Cambridge Low Contrast Gratings.

We examined the reliability of the Cambridge Low Contrast Gratings over four sessions at intervals of 1 hour, 1 day and 1 week. The 95% ranges of difference scores were found to be +/- 10.3 and +/- 10.5 test units for left and right eyes respectively. These reliability estimates span almost one-quarter of the test's dynamic range and one-third of the subjects' performance range. Practice effects were not found to be significant. Though previous reports have emphasized the usefulness of the Cambridge Gratings in screening for eye disease, caution is advised when interpreting changes that occur over time.

Adolescent↗

An ATF/CREB site is the major regulatory element in the human herpesvirus 6 DNA polymerase promoter.

Human herpesvirus 6 (HHV-6) is a recently described T-cell pathogen whose medical relevance and molecular biology are just beginning to be addressed. As a first look at the regulation of viral genes, control of the HHV-6 DNA polymerase promoter was examined. Polymerase gene transcription in HHV-6-infected cells was found to initiate from a single site located 115 bases upstream of the translation start codon. A polymerase promoter-chloramphenicol acetyltransferase reporter gene construct failed to be expressed in uninfected T cells but was highly active in HHV-6-infected cells. Mutational data indicated that the polymerase promoter is TATA-less. Mutational analysis also revealed that the major upstream promoter regulatory element required for transcriptional activity in HHV-6-infected cells is a palindromic ATF/CREB transcription factor binding site. The significance of this site for promoter induction was further demonstrated by the fact that the polymerase ATF/CREB element, when appended to a heterologous basal promoter, is highly responsive to HHV-6 infection. Two protein complexes were found to bind in a specific manner to the ATF/CREB motif in both uninfected and HHV-6-infected T-cell nuclear extracts. Site-specific mutation of the ATF/CREB site resulted in loss of protein binding as well as loss of promoter activity in HHV-6-infected cells.

Activating Transcription Factors↗