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Biomedical subjects

C E Wright

Publications and source records attributed to C E Wright.

At least 109 records · Page 6Linked to original sources

Visual evoked potentials in elderly patients with primary or multi-infarct dementia.

Flash and pattern-reversal visual evoked potentials (VEP) were recorded in 35 elderly patients with dementia, and 19 controls of equivalent age. Dementia produced a slowing of the major positive (P2) component of the flash VEP but did not affect the latency of the flash P1 component or the P100 pattern-reversal component. This unusual type of abnormality was found in both primary and multi-infarct types of dementia, and has previously been found in primary presenile dementia. The results show that the VEP can be used for the diagnosis of multi-infarct, and primary presenile and senile dementias.

Aged↗

Taurine conjugation of bile acids protects human cells in culture.

The primary trihydroxy bile acid, cholate, both free and conjugated, is nontoxic in cultured human lymphoblastoid cells incubated in vitro. The primary dihydroxy bile acid, chenodeoxycholate, was more toxic at high concentrations than at low concentrations, but conjugation with taurine reversed it. The free secondary bile acids, deoxycholate and lithocholate, corresponding respectively to cholate and chenodeoxycholate, are extremely toxic, the latter more than the former. Conjugation with taurine reversed the toxicity, as did glycine. Neither free taurine nor free glycine added to unconjugated bile acids decreased toxicity.

Bile Acids and Salts↗

Pathology of the optic nerve and visual association areas. Information given by the flash and pattern visual evoked potential, and the temporal and spatial contrast sensitivity function.

Spatial and temporal contrast sensitivity functions (CSF) were compared with visual evoked potentials (VEP) in two groups of patients with pathology selectively affecting different parts of the visual pathway. These consisted of 10 patients with a selective delay of the pattern VEP due to demyelination of one optic nerve (unilateral optic neuritis) and 11 patients with a selective delay of the flash VEP due to pathology of the visual association areas (primary presenile dementia, or Alzheimer's disease). The results led to the following conclusions. Comparison of the VEP and CSF results indicated that VEP latency was more closely associated with the temporal CSF than the spatial CSF. Pathology of the visual association areas which selectively increased the latency of the flash P2 component also reduced sensitivity at low and medium temporal frequencies. In demyelination of the optic nerve, a highly significant correlation was found between the delay of the pattern reversal VEP and sensitivity at high temporal frequencies. Comparison of the results in these two types of pathology suggests that the pattern VEP and flash P1 component, the spatial CSF, and temporal CSF at high temporal frequencies are all processed in the geniculostriate pathway. The flash P2 component and temporal CSF at low and medium frequencies were affected differently from the other measures. The possibility that these processes are transmitted by nongeniculate pathways is discussed.

Adult↗

Diverse vascular responses to serotonin in the conscious rabbit: effects of serotonin antagonists on renal artery spasm.

Vascular conductance in the mesenteric, hindquarter, and renal beds of the conscious rabbit was derived from regional blood flow (pulsed Doppler flowmeter) and ear artery pressure. After autonomic ganglion blockade (mecamylamine), serotonin (5-HT, 5-hydroxytryptamine) infusion, 3-60 micrograms/kg/min i.v., dilated the mesenteric and hindquarter beds but caused renal blood flow to fall to zero. Angiography confirmed that serotonin had caused the conduit renal arteries to spasm. This response was unaltered by 1 mg/kg prazosin but was antagonised by 0.5 mg/kg ketanserin and 0.5 mg/kg methysergide. Only the latter drug shifted the dilator-response curves in the other two beds. Methiothepin, 1 mg/kg, flattened both the dilator and constrictor response curves, perhaps by binding to an allosteric site on the serotonin receptor. 5-Carboxamidotryptamine (5-CT) caused about half the renal arteries to spasm at less than 30 ng/kg/min and dilated the other beds. From the antagonist data, we suggest that 5-HT2 receptors mediate the contraction of the renal artery, but that "5-HT1-like" receptors mediate the dilatation in the renal, mesenteric, and hindquarter beds in the conscious rabbit. 5-CT is not helpful in defining the receptors in the renal artery. The rather special spasmogenic response to serotonin in the renal artery is worthy of further research to reveal what factors may lead to large artery spasm.

Animals↗

Vascular amplifier properties in renovascular hypertension in conscious rabbits. Hindquarter responses to constrictor and dilator stimuli.

The local responses of the resistance vessels of the hindquarters of conscious, renal hypertensive (cellophane wrap) and sham-operated normotensive rabbits were studied during infusions of constrictor (norepinephrine, methoxamine, angiotensin II) and dilator (acetylcholine, adenosine, serotonin) drugs. The rabbits had implanted Doppler ultrasonic flow probes on the lower aorta and an indwelling catheter for intra-arterial infusion of drugs. Autonomic blockade with mecamylamine and propranolol was used to determine local vascular effects of each drug uncomplicated by reflex changes. Logistic dose-vascular response curves were characterized by their range from resting to maximum response, their 50% effective dose (i.e., sensitivity or dose at middle of the response range), and the average slope about the 50% effective dose. At maximum dilatation the vascular resistance was about 70% greater in hypertensive rabbits than in normotensive rabbits. There were no significant differences in 50% effective dose values between curves for hypertensive and normotensive rabbits for constrictor or dilator drugs. However, with all drugs the hypertensive rabbits showed about twice the change in vascular resistance per unit dose compared with the normotensive rabbits. These results suggest that hypertrophy of the muscles of the precapillary vessels makes them a nonspecific amplifier of vascular resistance changes evoked by constrictor and dilator stimuli. They do not support previous claims of specific changes in "sensitivity" or claims that local amplifier action is unimportant in hypertension.

Animals↗

Salutary effects of prostaglandin E1 in perfused rat lungs injured with hydrogen peroxide.

Studies were conducted in isolated, buffer-perfused rat lungs to determine if prostaglandin (PG) E1 attenuated pulmonary edema provoked by hydrogen peroxide (H2O2). When lungs were challenged by 60 min of perfusion with H2O2 (generated by the reaction between glucose and glucose oxidase) the wet weight-to-dry weight ratio increased from control by 54%, indicating development of pulmonary edema. In contrast, lungs treated simultaneously with H2O2 plus PGE1 (1 microgram/min) failed to exhibit an elevated wet-to-dry weight ratio. H2O2-injured lungs demonstrated a modest 2 torr increase in pulmonary arterial perfusion pressure that was not influenced by simultaneous treatment with PGE1. Both radioimmunoassay (RIA) and high-performance liquid chromatographic (HPLC) analysis detected increased amounts of (5S)-5-hydroxy-6,8,11,14 eicosatetraenoic acid in the perfusion medium of H2O2-injured lungs (RIA, 48.0 +/- 14.7; HPLC, 54.8 +/- 13.5) relative to controls (RIA, 6.6 +/- 1.6; HPLC, 6.8 +/- 1.9), and simultaneous treatment with PGE1 tended to blunt this increase (RIA, 29.2 +/- 8.3; HPLC, 29.8 +/- 7.6). PGE1 abolished the increase in wet weight-to-dry weight ratio induced by exogenous leukotriene C4. Production of H2O2 by the glucose-glucose oxidase reaction was not influenced by PGE1. Taken together, these observations indicate that PGE1 attenuates H2O2-induced pulmonary edema formation in buffer-perfused rat lungs by mechanisms that may relate to inhibition of lung 5'-lipoxygenase activation and/or to inhibition of the injurious effects of endogenously produced lipoxygenase products.

Alprostadil↗

Minoxidil analysis in human plasma using high-performance liquid chromatography with electrochemical detection. Application to pharmacokinetic studies.

A method is described for determination of minoxidil in human plasma using high-performance liquid chromatography with electrochemical detection. The method is specific and sensitive (500 pg/ml), however, minoxidil and minoxidil sulfate cannot be differentiated due to rapid autohydrolysis of minoxidil sulfate to minoxidil. The extraction procedure employs a C18 preparatory column to remove endogenous plasma constituents which would interfere with the assays. The calibration curves are linear for concentrations from 500 pg to 10 ng/ml. Within-day and between-day reproducibility are satisfactory with coefficient of variation less than 5.7% for all concentrations. Sample recovery from extraction is consistent at 45 to 55% at low and high concentrations, respectively. A pharmacokinetic study in a hypertensive volunteer receiving two different oral doses of minoxidil (1.25 and 2.5 mg) on different occasions demonstrates the utility of the method.

Chemical Phenomena↗

Serial visual evoked potential recordings in Alzheimer's disease.

Primary presenile dementia slows the major positive component of the visual evoked potential to flash stimulation but does not affect the visual evoked potential to patterned stimulation. The progressive effect of Alzheimer's disease was followed in a 58 year old woman over three and a half years from the development of the earliest symptoms to complete mental incapacity. The pattern reversal visual evoked potential remained normal, but the flash visual evoked potential gradually slowed from 129 ms in 1981 to 153 ms in 1984. The severity of the abnormality of the flash visual evoked potential thus reflected the severity of the dementia. Electroencephalography, computed tomography, and psychometric tests indicated generalised cortical disease, but the results were not specific to dementia. The combination of a slowed flash and normal pattern visual evoked potential seems to be specific to Alzheimer's disease and supports the use of flash and pattern visual evoked potentials in routine diagnostic testing for this condition.

Alzheimer Disease↗

The flash and pattern VEP as a diagnostic indicator of dementia.

Ninety-one patients with forgetfulness, confusion and depression were referred for visual evoked potential and electroencephalographic investigation. The patients were subdivided, on clinical symptoms alone, into a group of 41 with evidence of dementia and a patient control group of 50 with effective disorders. A second control group of 30 normal volunteers of equivalent age was used. In dementia the P2 component of the flash visual evoked potential is delayed, while the pattern reversal P100 component is of normal latency. This unusual combination of results from the two different visual stimuli is shown to be more specific than either the electroencephalogram or computerised tomography in the diagnosis of dementia.

Aged↗

The influence of hemodialysis on the pharmacokinetics of ibuprofen and its major metabolites.

The pharmacokinetics of ibuprofen and its two major metabolites, the hydroxy and carboxy derivatives, were studied in seven functionally anephric subjects undergoing hemodialysis therapy. Subjects received ibuprofen 800 mg tid for 14 days. Hemodialysis was performed three times weekly during this period. Arterial and venous blood samples were collected before dialysis and along with dialysate, and during the final dosing interval and dialysis session. No accumulation of ibuprofen plasma concentrations and an absence of intact ibuprofen in dialysate indicated clearance through metabolic pathways. The metabolites did accumulate significantly (mean plasma levels, carboxy 249 micrograms/mL and hydroxy 57 mu/mL); however, both were detected in dialysate. Mean extraction efficiencies were 0.16 (hydroxy) and 0.15 (carboxy). Dialysis clearance calculated by arterial-venous difference was found to agree with actual recovery in dialysate for both metabolites. Side effects were not observed in any subject.

Adult↗

Endothelium-dependent relaxation is unaltered by hypertension, cholesterol or intimal thickening.

The effect of cellophane wrap hypertension (WRAP) and hypercholesterolemia (1% cholesterol diet, CHOL) for 4 weeks was assessed on the endothelium-dependent vasodilator response to acetylcholine in conscious rabbits after pharmacological autonomic blockade. Dose-response curves for the hindlimb vascular resistance (ear artery pressure/lower aortic blood flow; Doppler flowmeter) and acetylcholine infusion (i.v.) doses were unaltered in sensitivity (ED50) for any of the treatment groups. The range and slope of the curves were significantly altered by WRAP, CHOL or WRAP plus CHOL for acetylcholine and adenosine infusions consistent with medial hypertrophy in resistance vessels and raised serum viscosity. The effect of intimal thickening on the response to endothelium derived relaxing factor (EDRF) was tested in dog carotid artery ring segments in vitro 4 weeks after endothelium removal. The relaxation responses to acetylcholine (EDRF-dependent) and adenosine or nitroglycerin were not significantly altered by the neo-intima. Therefore the response to EDRF released by acetylcholine in resistance vessels was unaltered by hypertension, hypercholesterolemia or both together. Neo-intimal thickening in response to initial endothelium loss does not appear to alter EDRF responses in the carotid artery.

Animals↗

Hypertension alters slope and range but not sensitivity to vasoconstrictor and vasodilator agents in the rabbit hindquarter.

The vascular reactivity (slope and range) and location parameter (ED50) of dose-response curves in the hindquarter vascular bed in conscious rabbits previously subjected to renal cellophane wrapping or sham operation were examined. The animals were instrumented with pulsed Doppler flow transducers and chronic indwelling aortic catheters for intra-arterial drug infusion. The rabbits were ganglion-blocked with mecamylamine before constructing full dose-response curves to intra-arterial infusions of methoxamine, noradrenaline, angiotensin II, acetylcholine, adenosine and serotonin. Curves relating dose to conductance were fitted to the experiments involving constrictors and curves relating dose to vascular resistance fitted to those involving dilator drugs. With both classes of drugs the reactivity was significantly higher in the hypertensive animals than in sham-operated rabbits. There was no difference in sensitivity (ED50 value) between the hypertensive and control animals for any agonist tested. The increased reactivity, but not sensitivity, could be entirely accounted for by the vascular amplifier action of medial hypertrophy in hypertension.

Animals↗

Changes in the human visual evoked potential caused by the anticholinergic agent hyoscine hydrobromide: comparison with results in Alzheimer's disease.

The anticholinergic drug hyoscine hydrobromide produced a slowing of the P2 and N3 components of the flash visual evoked potential (VEP) in young normals but did not affect the pattern reversal VEP. These results, which are similar to those found in Alzheimer's disease, could be explained by an underlying defect of the cholinergic system.

Adult↗

Effects of hypertension and hypercholesterolemia on vasodilatation in the rabbit.

Vasodilator substances act either directly on vascular smooth muscle (e.g., adenosine) or indirectly (e.g., acetylcholine) on endothelial cells that respond by releasing an unknown powerful, short-lived relaxing factor. To determine whether chronic hypertension or hypercholesterolemia or both would alter the release of the endothelium-derived relaxing factor, experiments were performed in hypertensive rabbits (5-week cellophane wrap perinephritis; mean blood pressure, 134.7 mm Hg) and normotensive rabbits (mean blood pressure, 80 mm Hg) with a Doppler flow transducer and perivascular balloon implanted on the lower abdominal aorta. Rabbits were fed either 1% cholesterol or control diet for 4 weeks before the experiment. On the day of the experiment, resting hindlimb vascular resistance was greatest in hypertensive rabbits fed 1% cholesterol diet, followed (in descending order) by hypertensive rabbits, normotensive rabbits fed 1% cholesterol diet, and normotensive rabbits. Pharmacological autonomic reflex blockade was induced, and steady state intravenous infusion curves to acetylcholine, serotonin, and adenosine were constructed. Sensitivity (location of effective dose, 50%) to the three vasodilator agents was altered less than twofold from the values in normotensive rabbits for any treatment group. The maximum vasodilator response to acetylcholine, but not to adenosine or serotonin, infusion was reduced significantly in the treated rabbits compared with that in normal rabbits. Reactive hyperemic responses to 5 to 80 seconds of ischemia were not significantly different among the treatment groups. These results indicate that hypertension with or without hypercholesterolemia does not greatly alter the responsiveness of the hindlimb resistance vasculature to these three vasodilator agents or to ischemia.

Acetylcholine↗

The incidence of diarrheal disease in a defined population of rural Egypt.

A prospective study of diarrheal illness was conducted for 2 years in 309 families who were part of an epidemiologic research center population in rural Egypt. The rates of illness peaked in the first year of life with between 5 and 6 episodes per person year at risk. Although no seasonal variation in reported diarrhea was demonstrated for the total population, age-specific differences in seasonal occurrence were noted. The incidence did not consistently vary by village size, nor did rates vary by sex.

Adolescent↗

The influence of age on the electroretinogram and visual evoked potential.

Changes in the ERG and VEP across the life span were investigated. The dark adapted and scotopic ERGs both showed a progressive increase in the implicit times of the A and B waves and a reduction in the amplitude of the AB configuration. There was also an increase in the implicit times of the oscillatory potentials of the photopic ERG. The flash and pattern onset-offset VEP both showed changes in waveform with age whilst the waveform of the pattern reversal VEP was constant. The amplitudes of the components of the flash and pattern reversal VEP were very high in the teenage group, but once reduced, were constant from the twenties onwards, showing no further consistent age changes. The latencies of the components of the pattern VEPs showed an increase with age which could be accounted for by the reduction in retinal illuminance due to the decrease in pupil diameter with age. However, the increase in the latency of the flash major positive (P2) component was greater than that expected from the decrease in retinal illuminance alone, suggesting that this is due to neural factors.

Adolescent↗