Biomedical subjects
Publications and source records attributed to D Graham.
1. Neuropathological changes in experimental animals have been observed with vigabatrin treatment in mice, rats and dogs. 2. These changes have comprised intramyelinic oedema which is reversible on cessation of treatment. 3. In human studies so far, no intramyelinic oedema has been noted. It is not clear whether humans will show the neurotoxicity observed in animals; close monitoring of patients is indicated.
The inhibition of atherosclerosis by estrogen has been shown clinically and experimentally, but the mechanism by which this occurs is unknown. Previous studies have shown that estrogen enhances the uptake of low-density lipoprotein (LDL) by bovine aortic endothelial cells (BAEC) while not altering membrane binding at saturating levels of LDL. In this study the effect of estrogen on LDL binding kinetics has been investigated. Computer-assisted Scatchard analysis of binding data suggests a single-site binding model. Estrogen-treated BAEC showed a lower binding affinity (Ka = 2.47 +/- 0.74 E7 M-1) than control cells (1.95 +/- 0.21 E7 M-1) (p = 0.0012). Estrogen-treated cells, however, had a greater binding capacity (Bmax = 1.26 +/- 0.07 E-10M) than control cells (Bmax = 8.49 +/- 0.44 E-11M) (p = 0.0004). The latter was due primarily to a difference in LDL binding at higher concentrations of LDL (greater than 40 micrograms/ml). These findings are consistent with an estrogen-stimulated increase in low-affinity binding of LDL to BAEC, which may not be directly receptor mediated and which appears to enhance the uptake of LDL at higher lipoprotein concentrations. Such alterations in LDL uptake by endothelial cells could influence the formation of atherosclerotic plaque.
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A simple modification (patent pending) of existing systems of closed suction drainage is described herein. This system maintains patency in a closed sterile manner and facilitates sampling of drainage for laboratory analysis.
Forty-three women with neurological complications secondary to eclampsia or severe pre-eclampsia were studied by CT scanning and in six intracranial pressure (ICP) monitoring was carried out. In seven women who died, neuropathological findings were correlated with clinical features. Cerebral oedema was present in 27 of the patients studied and the severity of oedema correlated to the duration of intermittent seizures. In five of the six women who had ICP measured, this was found to be transiently high. Intracranial haemorrhage was demonstrated in four of the 43 women, all of whom died. Hypoxic-ischaemic cerebral damage and fibrinoid necrosis were the most important neuropathological lesions identified. The management of neurological complications of eclampsia may be placed upon a more rational basis by an understanding of the mechanisms responsible for these lesions.
We studied 24 young adult male volunteers experimentally inoculated with type 39 rhinovirus to determine whether the course of viral infection was modified by exposure to moderate levels of ozone (0.3 ppm for 6 h per day) over the 5 days after virus inoculation. No differences in rhinovirus titers in nasal secretions, recruitment of neutrophils into nasal secretions, levels of interferon in nasal lavage fluid, in vitro lymphocyte proliferative responses to rhinovirus antigen, or levels of convalescent serum neutralizing antibody to type 39 rhinovirus were demonstrated in relation to ozone exposure. The level and pattern of ozone exposure used in this experiment had no demonstrable adverse effects on the immune responses necessary to limit and terminate rhinovirus infection of the upper respiratory tract.
From July 1980 to January 1986, 170 patients who had unilateral heel pain were examined, x-ray filmed, and treated in a similar fashion. Radiographs of painful and nonpainful heels were measured. There was a statistically significant increased thickness of the heel fat pad and subfascial area compared with that of the control subject (the nonpainful side). A tightness of the Achilles tendon and a new sign, which the authors are designating as the "saddle" sign, were other prominent features. A treatment program of stretching exercises and walking seemed to be effective in relief of symptoms.
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Aortic dissections limited to the abdominal aorta occur infrequently. We have identified four cases of abdominal aortic dissection and have reviewed these in combination with 43 previously reported cases to identify factors that influence the prognosis and management of this disease. Abdominal aortic dissections are similar to thoracic dissections in their presentation, with acute shearing pain and systolic hypertension occurring commonly. Although the diagnosis may be made by ultrasonography or CT scanning, angiography is the definitive diagnostic study. Factors found to be associated with high mortality include presentation with acute pain (p less than 0.0003), involvement of visceral vessels (p less than 0.02), and rupture (p less than 0.000002). Chronicity appears to be protective (p less than 0.04), although chronic dissections may present acutely. Although prosthetic replacement of the involved aorta is the treatment of choice in most cases, nonoperative management with regular follow-up can be considered in asymptomatic chronic dissections.
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Information about health concerns of adolescents can assist in assessment and treatment of their particular medical problems. Because teachers are important figures in the lives of young people, their beliefs about student health concerns are often solicited. A survey to assess adolescent health concerns and teachers' beliefs about student health concerns was conducted in two urban high schools on a sample of 831 students and 146 teachers. An assessment of 22 health concerns among the students revealed that a moderate level of concern existed on virtually every issue (the mean percentage "very concerned" was 55%), with black students and girls reporting more concern about many topics. In contrast, teachers significantly underestimated the level of concern of the students by an average of 13%, consistently having inaccurate beliefs about the types and level of student concerns. Students are concerned about health issues and are in need of health education and counseling in these areas. Teachers are not always aware of the level and types of student health concerns and may not be good sources of information about adolescent health.
Two hundred and thirty-four paediatric medical records from August 1985 and 257 from August 1986, were evaluated and compared by criteria audit in order to assess the effects of the introduction of a structured admission form. The presence or absence of predetermined items of clinical relevance were recorded. A statistically significant improvement in the recording of 12 of 23 key items occurred following the introduction of a structured format. However, two of these items were recorded less frequently in the new notes. Changing working hours for house officers and an increase in overseas graduates had no significant influence on the results. Structured case records can improve information gathering, but careful design and reevaluation are important.
The messages for two small but abundant apolipoproteins found in lamprey blood plasma were cloned with the aid of oligonucleotide probes based on amino-terminal sequences. In both cases, numerous clones were identified in a lamprey liver cDNA library, consistent with the great abundance of these proteins in lamprey blood. One of the cDNAs (LAL1) has a coding region of 105 amino acids that corresponds to a 21-residue signal peptide, a putative 8-residue propeptide, and the 76-residue mature protein found in blood. The other cDNA (LAL2) codes for a total of 191 residues, the first 23 of which constitute a signal peptide. The two proteins, which occur in the "high-density lipoprotein fraction" of ultracentrifuged plasma, have amino acid compositions similar to those of apolipoproteins found in mammalian blood; computer analysis indicates that the sequences are largely helix-permissive. When the sequences were searched against an amino acid sequence data base, rat apolipoprotein IV was the best matching candidate in both cases. Although a reasonable alignment can be made with that sequence and LAL1, definitive assignment of the two lamprey proteins to typical mammalian classes cannot be made at this point.
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[3H]Paroxetine is a highly selective ligand for the 5-hydroxytryptamine transporter complex and the specific binding of this ligand to membrane fractions from cerebral cortex or hippocampus was studied in rats treated with specific inhibitors of the uptake of 5-hydroxytryptamine and monoamine oxidase inhibitors. The Kd and Bmax of the binding of [3H]paroxetine to cerebral cortical membranes of the rat was unaffected, compared to sham controls, by either acute or chronic administration with citalopram or chlorimipramine. Also, chronic treatment with chlorimipramine did not alter the parameters of the binding of [3H]paroxetine to hippocampal membranes from the rat compared to sham controls. Furthermore, chronic and acute treatments with clorgyline or deprenyl did not produce any significant changes in the Kd and Bmax of the binding of [3H]paroxetine to cerebral cortical membranes in the rat. These findings on the binding of [3H]paroxetine are discussed in light of previous equivocal results on the plasticity of neuronal binding sites for [3H]imipramine after various pharmacological treatments.
Equilibrium saturation analysis of the binding of [3H]tryptamine to membranes from the cerebral cortex of the rat at 0 degrees C indicated that [3H]tryptamine bound to a single class of high affinity binding sites (Kd = 1.29 +/- 0.13 nM). The binding of [3H]tryptamine was potently inhibited by tryptamine itself, beta-carboline, tetrahydro-beta-carboline and several beta-phenylethylamine derivatives. Structure-activity relationships of the beta-phenylethylamines tested showed that substitutions in para-position were the most potent with the following rank order of potency H less than OH less than Cl less than OCH3. Although chronic treatment with parachlorophenylalanine did not affect the parameters of the binding of [3H]tryptamine to cerebral cortical membranes of the rat, chronic treatment with clorgyline and deprenyl resulted in a 49% decrease in the density of binding sites for [3H]tryptamine, with no change in Kd. This modulation of the binding of [3H]tryptamine lends support to the proposal that binding sites for [3H]tryptamine could represent a specific class of receptors in the CNS. As such, the structure-activity relationships revealed within and between the various families of compounds tested provides useful information for the development of new chemical tools as potential agonists and/or antagonists at these sites.
Ninety-six fetuses of uncomplicated concordant twin pregnancies were monitored by ultrasonic cephalometry from 13 to 38 weeks gestation. The biparietal diameter (BPD) growth of 96 twin fetuses was then compared to a sample of 299 uncomplicated, appropriate-for-gestational-age singleton pregnancies. Regression analysis applied to these measurements of BPD on twin and singleton pregnancies showed no significant difference in biparietal diameter between uncomplicated singleton and twin pregnancies. It is concluded that charts derived from singleton pregnancies may be reliably used for estimation of gestational age of twins.