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Biomedical subjects

R D White

Publications and source records attributed to R D White.

At least 163 records · Page 9Linked to original sources
PubMed1987

Regional left ventricular wall thickening by magnetic resonance imaging: evaluation in normal persons and patients with global and regional dysfunction.

Gated magnetic resonance imaging (MRI) provides excellent anatomic evaluation of the heart, but its capability for assessing cardiac physiology is less clear. Accordingly, regional left ventricular (LV) wall thickening was evaluated by multiphasic transverse images in 37 patients with a variety of myocardial diseases and in 9 normal subjects. Angiography and 2-dimensional echocardiography (2-D echo) were used for comparison. End-diastolic and end-systolic wall thickness, absolute systolic wall thickening and percent systolic wall thickening were determined in 7 regions. Mean systolic wall thickening in normal subjects was not significantly different among the regions. However, there was considerable individual variation in wall thickening, ranging from 18 to 100%. Patients with LV hypertrophy (n = 4), amyloid cardiomyopathy (n = 1), constrictive pericarditis (n = 5), and hypertrophic cardiomyopathy (n = 3) had absolute and percent systolic wall thickening within normal limits. Infarcted segments in patients with ischemic heart disease (n = 17) had reduced absolute and percent systolic wall thickening, often combined with diastolic wall thinning, whereas mean percent systolic wall thickening in adjacent normal myocardial regions was higher than in normal volunteers (p less than 0.001). In patients with coronary artery disease, MRI had a sensitivity and specificity of 93% in detecting regional wall motion abnormalities. Because sagittal images were not acquired, inferior wall motion abnormalities were not assessed by MRI due to parallel wall sectioning in transverse images.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiomegaly↗
PubMed1987

Coronary artery bypass graft patency: noninvasive evaluation with MR imaging.

A noninvasive means of determining coronary artery bypass graft (CABG) patency in symptomatic patients would be an important clinical asset. The accuracy of magnetic resonance (MR) imaging was evaluated for this purpose. Multiphasic electrocardiographically gated MR imaging examinations were performed in 25 patients with a total of 72 grafts. Transverse images of the heart at ten anatomic levels were obtained at five or six phases of the cardiac cycle. The MR images were read blindly to determine CABG patency versus occlusion, and these results were compared with those of coronary angiography performed within 2 months before the MR imaging. MR imaging correctly disclosed 43 patent grafts and 13 occluded grafts (predictive accuracy, 78%). Patency and occlusion were incorrectly diagnosed from MR imaging findings in five and four CABGs, respectively. CABG status could not be determined in seven (10%) grafts because the grafts were visualized at only one anatomic level. Thus, the accuracy of a definitive MR imaging evaluation was 91% (43 of 47 grafts) for patency determination and 72% (13 of 18 grafts) for occlusion determination. MR imaging appears to be a useful method for the noninvasive evaluation of CABGs.

Adult↗
PubMed1987

Cine MR imaging: potential for the evaluation of cardiovascular function.

MR imaging is valuable in defining cardiac anatomy in a variety of cardiac abnormalities. However, evaluation of cardiac function by this technique has been limited by long imaging times and low temporal resolution. New, recently described pulse sequences shorten imaging time considerably and improve temporal resolution. This paper reports our early experience with cine MR imaging of the heart, a technique of gradient-recalled acquisition in the steady state (GRASS) that uses low flip angles and gradient-recalled echoes. Images were obtained in 36 subjects (14 normal volunteers and 22 patients with coronary artery or valvular heart disease) and displayed in a cinegraphic mode for assessment of cardiac function. The acquisition of 10 to 12 levels, covering the whole heart with up to 24 time frames per level, required a maximum imaging time of only 30 min. Because systole and diastole were readily identified, and the contrast between blood and surrounding structures was excellent, systolic wall thickening, wall motion, and motion of the cardiac valves were visualized easily. Regions of myocardial infarcts were clearly visible and characterized by lack of systolic wall thickening and/or diastolic wall thinning. Turbulence caused signal loss within the flowing blood, which usually had higher signal intensity than myocardium. Therefore, turbulent blood flow in valvular regurgitation and in valvular and subvalvular stenosis could be detected. Cine MR imaging is a promising new technique for the evaluation of myocardial and valvular function.

Adult↗
PubMed1987

MR imaging of pulmonary arterial hypertension and pulmonary emboli.

Intraluminal signal in the pulmonary arteries on spin-echo, ECG-gated MR images is limited to the diastolic phase of the cardiac cycle in normal subjects. Initial experience has indicated that signal persisting during systole may be characteristic of slow blood flow associated with pulmonary arterial hypertension (PAH) or of thrombotic material secondary to pulmonary embolism. This study analyzes our cumulative experience (31 patients) with multiphasic, double spin-echo MR for assessing PAH and/or suspected pulmonary embolism. In PAH, the abnormal systolic signal showed an intensity increase from first to second echo. This pattern was observed in 92% of PAH patients, including 100% of patients with pulmonary systolic pressures greater than or equal to 80 mm Hg and 60% of patients with pressures less than 80 mm Hg. At any focus in the pulmonary arteries, such signal disappeared at some phase of the cardiac cycle. In patients with pulmonary embolism, signal from thrombus was fixed throughout the cardiac cycle and showed little or no increase in relative intensity change from first- to second-echo image. Using this guideline, MR made six confirmed positive and four confirmed negative diagnoses of proximal pulmonary embolism, while it failed to identify thrombus in the one patient with a peripheral pulmonary embolism. Intraluminal signal in the pulmonary arteries caused by PAH or pulmonary embolism can be differentiated in most instances using multiphasic, double spin-echo, ECG-gated MR. However, at its current stage of development, the procedure does not appear to be useful for the evaluation of peripheral pulmonary embolism.

Humans↗
PubMed1987

Effect of orally administered pilocarpine on serum enzymes, organ weights and histopathology in meadow voles.

Fifteen mature meadow voles (Microtus pennsylvanicus) were assigned to each of four diets: 1) basal; 2) basal + .001% pilocarpine (PLCN); 3) basal + .01% PLCN; 4) basal + .10% PLCN in a completely randomized design to measure the effect of PLCN on liver, kidney and parotid gland histopathology and feed intake. Meadow voles were fed each treatment for 14 d prior to euthanasia. Serum glutamic oxaloacetate transaminase, glutamic pyruvate transaminase and alkaline phosphatase levels were unaffected by dietary PLCN. Liver fresh weight tended to decrease with PLCN treatment, but kidney weight was not consistently affected. Parotid gland fresh weight decreased by 31% as the dietary level of PLCN increased from 0 to .10%. One of 15 voles on the control treatment died. Twelve of the remaining 14 voles showed no histopathological changes in the organs studied, but one showed segmental cystic dilation of some convoluted tubules and one showed chronic cortical interstitial nephritis. One vole of the 15 on the .001% PLCN treatment died. Eleven of the 14 remaining voles showed no histopathological changes in the organs studied, while two voles showed segmental cystic dilation of some convoluted tubules and one showed slight hydropic degeneration of hepatocytes. There was no mortality among voles fed .01% PLCN. Nine of the 15 voles showed no histopathological changes in the organs, while four showed slight hydropic degeneration of hepatocytes and one showed segmental cystic dilation of some convoluted tubules. Three of 15 voles died while fed .10% PLCN. The remaining 12 voles showed no histopathological changes in the above-mentioned organs, although three voles showed slight hydropic degeneration of hepatocytes.

Alanine Transaminase↗
PubMed1986

Reduction in potency and reversal of left-shifting activity of BW12C with the major and minor components of chicken hemoglobin.

The effects of the left-shifting, anti-sickling compound BW12C (5-(2-formyl-3-hydroxyphenoxy)pentanoic acid) on the oxygen saturation curve of whole chicken blood and the isolated major (AII) and minor (AI) components of chicken hemoglobin have been studied. The results support the postulated major binding mode for BW12C to human hemoglobin of bridging between the alpha-chain terminal amino groups in the oxy conformation with an important hydrophobic component contributed mainly by Pro 77 alpha residues. In chicken AII (Pro 77 alpha----Ser) BW12C still left-shifts at high concentrations but its potency is greatly reduced (at least 10-fold). In chicken AI (Pro 77 alpha----Ser and Val 1 alpha----Met) BW12C is a right-shifter with a potency comparable to that of 2,3-diphosphoglycerate suggesting that binding at the beta-chain termini in the deoxy conformation is now dominant with alpha-chain binding no longer significant.

Aldehydes↗
PubMed1986

Characterization of the binding of the anti-sickling compound, BW12C, to haemoglobin.

The anti-sickling agent BW12C [Beddell, Goodford, Kneen, White, Wilkinson & Wootton (1984) Br. J. Pharmacol. 82, 397-407] was designed to left-shift the oxygen saturation curve of haemoglobin (HbA) by preferential binding to the oxy conformation at a single site between the terminal amino groups of the alpha-chains through Schiff's base formation, ionic and hydrophobic interactions. In the present work, Schiff's base linkages formed with [14C]BW12C were reduced with NaBH4 and the alpha- and beta-globin chains separated. Under oxy conditions at a molar ratio of 2:1, the covalently bound BW12C is localized almost exclusively on a single alpha-chain; tryptic digestion confirms the terminal amino group (alpha 1-valine) as the reaction site, in accord with the design hypothesis. However, about half the labelled BW12C is released on tetramer disruption, suggesting the presence of additional non-covalent binding. Under deoxy conditions, alpha- and beta-chains are labelled approximately equally, and at higher molar ratios additional binding in both oxy and deoxy conditions is seen. Isoelectric-focusing studies under oxy conditions show a complex pattern of modified bands for both HbA and HbA1c (blocked beta-terminal amino groups) but no modification for HbA carbamylated at both alpha- and beta-terminal amino groups or at the alpha-chains only, again confirming the alpha-terminal amino region as the main interaction site. Equilibrium dialysis measurements under oxy conditions indicate two strong binding sites with a binding constant of less than 10(-6) M and a number of weaker binding sites. The present data thus confirm that BW12C binds at the intended locus but reveal additional non-covalent binding at an undefined site, and weaker binding through Schiff's base formation with other amino groups.

Aldehydes↗
PubMed1986

Effect of BW12C on oxygen affinity of haemoglobin in sickle-cell disease.

Eight subjects with sickle-cell disease in the symptom-free steady-state received a single one-hour infusion of the new anti-sickling agent BW12C on a total of eleven occasions. A dose-dependent increase in wholeblood oxygen affinity was observed, resulting from the action of BW12C in stabilising the oxy-conformation of haemoglobin and causing a left shift of the oxygen saturation curve. At the highest dose given (20 mg/kg bodyweight), up to 23% of haemoglobin was modified to a BW12C-reacted high-affinity form without evidence of tissue hypoxia. There was biochemical and rheological evidence for a transient decrease in haemolytic rate.

Adult↗
PubMed1986

Noninvasive evaluation of suspected thoracic aortic disease by contrast-enhanced computed tomography.

Traditionally, suspected thoracic aortic disease has been evaluated by aortography, which has associated risks because it is invasive. With the introduction of computed tomography (CT), a noninvasive alternative has become available. In the present retrospective study, the potential clinical value of CT in providing correct diagnoses and pertinent information required for current therapies is evaluated. For this purpose, results of CT in 200 patients examined for suspected thoracic aortic disease were compared with "hard" (surgical and autopsy findings) or "soft" (follow-up clinical information) evidence of the true diagnoses. Aortographic results, available in 51 patients (26%), were also compared with available clinical evidence. Excluding inadequate examinations, the diagnostic accuracy of the independently and blindly interpreted results of CT and aortography were similar (86% and 87%, respectively) in patients with true diagnoses confirmed by hard evidence. When patients evaluated for aortic damage from acute blunt chest trauma were also excluded, the accuracy was 90% for CT and 86% for aortography. Specifically, CT was 83% and 67% accurate in proved (i.e., confirmed by hard evidence) type A and type B dissections, respectively (75% for both type A and B by aortography). In the 183 patients suspected of having thoracic aortic disease not attributable to acute blunt chest trauma and with follow-up information, 91% would have been managed appropriately based on their CT evaluation alone. In the subset of patients who underwent aortographic evaluation as well, 91% would have been managed appropriately based on aortography alone. The accuracy for combined CT and aortography was 94%.(ABSTRACT TRUNCATED AT 250 WORDS)

Aortic Dissection↗
PubMed1986

Unscheduled DNA synthesis in rat tracheal epithelial cells, hepatocytes and spermatocytes following exposure to methyl chloride in vitro and in vivo.

Measurement of DNA repair as unscheduled DNA synthesis (UDS) in vitro following exposure in vivo in multiple tissues from the same treated animal can provide valuable information relating to the tissue- and organ-specificity of chemically induced DNA damage. UDS was evaluated in primary cultures of rat tracheal epithelial cells, hepatocytes and pachytene spermatocytes after exposure in vitro to methyl chloride (MeCl), and after isolation from the same treated animal following inhalation exposure in vivo. Concentrations of 1-10% MeCl in vitro induced UDS in hepatocytes and spermatocytes, but not in tracheal epithelial cells. Inhalation exposure to MeCl in vivo (3000-3500 ppm 6 h/day for 5 successive days) failed to induce DNA repair in any cell type. In vivo exposure to 15 000 ppm MeCl for 3 h also failed to induce UDS in tracheal epithelial cells and spermatocytes, but did cause a marginal increase in UDS in hepatocytes. Thus, MeCl appears to be a weak, direct-acting genotoxicant. While activity could be measured in hepatocytes and spermatocytes directly in vitro, only extremely high concentrations of MeCl elicited a response in the whole animal, and then only in hepatocytes.

Animals↗
PubMed1986

Inhibition of the acute toxicity of methyl chloride in male B6C3F1 mice by glutathione depletion.

Previous data have demonstrated that methyl chloride (MeCl) is toxic to B6C3F1 mice under both acute and chronic exposure conditions, and that conjugation of MeCl with glutathione (GSH) is a key step in the metabolism of MeCl. This study examined the role of GSH in mediating the acute toxicity of MeCl to liver, kidney, and brain of male B6C3F1 mice. The lethal effects of a single 6-hr inhalation exposure of B6C3F1 males to 2500 ppm MeCl were completely prevented by pretreatment with the GSH synthesis inhibitor, L-buthionine-S,R-sulfoximine (4 mmol L-BSO/kg, ip 1.5 hr prior to MeCl exposure). GSH levels (measured as nonprotein sulfhydryl) in liver and kidney were depleted to 19 and 25% of control values, respectively, at the start of the exposure; the ratio of dead/exposed mice during the 18-hr postexposure declined from 14/15 mice to 0/10. Also, the LC50 for MeCl increased from 2200 to 3200 ppm in male mice pretreated with BSO. The hepatic toxicity of MeCl was detected by increased alanine aminotransferase (ALT) activities in serum 18 hr after a 6-hr exposure to 1500 ppm MeCl (2147 +/- 1327 IU/liter vs 46 +/- 6 in controls). Liver toxicity was inhibited when B6C3F1 males were depleted of GSH prior to MeCl exposure by BSO pretreatment (43 +/- 2), fasting (100 +/- 47), or injection of diethyl maleate (42 +/- 16). The effects of GSH depletion on MeCl toxicity to brain and kidney were determined in B6C3F1 males exposed to 1500 ppm MeCl 6 hr/day, 5 days/week for 2 weeks, with and without daily pretreatment with 2 mmol L-BSO/kg. This dose of BSO depleted hepatic and renal GSH by 28 and 60%, respectively, at the start of MeCl exposure. BSO-pretreated mice were protected from the central nervous system toxicity of MeCl, as assessed by microscopic examination of the granule cell layer of the cerebellum. BSO pretreatment also inhibited the renal toxicity of MeCl as measured by incorporation of [3H]thymidine ([3H]TdR) into renal DNA, an indicator of cell regeneration after cortical necrosis. [3H]TdR incorporation was 105 +/- 10,337 +/- 40, and 60 +/- 15 dpm/microgram DNA in nonexposed controls, MeCl, and MeCl + BSO treatment groups, respectively. These results indicate that GSH is an important component in the toxicity of MeCl to multiple organ systems in B6C3F1 mice. Reaction of MeCl with GSH appears to constitute a mechanism of toxication, contrary to the role usually proposed for GSH in detoxifying xenobiotics.

Animals↗
PubMed1986

Induction of hypoxia in normal and malignant tissues by changing the oxygen affinity of hemoglobin--implications for therapy.

The drug BW12C, which increases the oxygen affinity of hemoglobin, reduces oxygen availability to tissues. This results in protection against radiation damage to the hemopoietic system and epidermal Langerhans cells in CBA mice. The drug also protects against beta-irradiation damage in pig epidermis. BW12C increases the hypoxic cell fraction in tumors and histological examination of an experimental T cell lymphoma shows that the induced hypoxia leads to tumor necrosis.

Aldehydes↗
PubMed1986

Xanthofibroma of the mandible.

A review of the literature reveals very few lesions within bone which appear to be xanthofibromas (fibrous histiocytomas) similar to those found in the soft tissues without other associated lesions. These are even more rare within the jaw bones. This case is presented to document such a lesion.

Adult↗
PubMed1986

meso-Tetra(hydroxyphenyl)porphyrins, a new class of potent tumour photosensitisers with favourable selectivity.

We compared para-, meta- and ortho-isomers of meso-tetra(hydroxyphenyl)porphyrin (p-, m- and o-THPP) and the potassium salt of the para compound (K-p-THPP) with haematoporphyrin derivative (HpD) and Photofrin II in their ability to sensitise tumours, skin and brain to light. HpD and Photofrin II induced modest tumour photosensitisation at the cost of substantial skin and brain sensitisation. At doses low enough to keep sensitisation of these normal tissues within acceptable limits, tumour sensitisation was sufficient to give necrosis only approximately 2 mm deep after exposure to 10 J cm-2 light. In contrast, doses of p-THPP, K-p-THPP and m-THPP that produced skin and brain sensitivity within acceptable limits sensitised tumours enough to give 4-9 mm necrosis after 10 J cm-2 light. m-THPP was, on a molar basis, about 25-30 times as potent as HpD and Photofrin II in sensitising tumours. o-THPP was also a potent tumour photosensitiser, but induced a prohibitive degree of skin photosensitivity even at low doses. It is unlikely that these differences in relative selectivity are due to differences in such photophysical parameters as optimum activating wavelength (which would affect tissue penetration by light), or light absorption, and physicochemical factors that determine tissue localisation may be involved. The high tumour sensitising potency and favourable tissue selectivity of m-THPP, p-THPP and K-p-THPP make them promising candidates for clinical tumour phototherapy.

Animals↗
PubMed1986

Induction of DNA repair in rat spermatocytes and hepatocytes by 1,2-dibromoethane: the role of glutathione conjugation.

1,2-Dibromoethane (EDB) is a widely used industrial chemical, and a well-known mutagen and carcinogen. EDB is biotransformed either by cytochrome P450-dependent oxidation, leading to the formation of bromoacetaldehyde, or by enzyme-catalyzed conjugation with glutathione, giving rise to reactive half-sulfur mustard compounds and their derivatives. In vitro mutagenicity and DNA binding studies suggest that the latter pathway is the primary source of genotoxic metabolites from EDB. In this study we have examined EDB-induced unscheduled DNA synthesis (UDS) in F-344 rat pachytene spermatocytes and hepatocytes. EDB (10-100 microM) induced UDS in both hepatocytes and spermatocytes in vitro. In contrast, only hepatocytes exhibited UDS when isolated from rats given EDB (100 mg/kg) 2 h earlier, and only then if the compound was given i.p. rather than orally. Preincubation of hepatocytes or spermatocytes with inhibitors of cytochrome P450-mediated oxidation had no effect on EDB induction of UDS in vitro. In contrast, depletion of cellular glutathione strongly inhibited EDB-induced UDS in both cell types in vitro. Treatment of rats with 175 mg metyrapone/kg (an inhibitor of hepatic mixed-function oxidases) 1 h prior to administration of EDB in vivo had no effect on EDB-induced UDS in hepatocytes, but led to a positive UDS response to EDB in spermatocytes in vivo. This suggests that the mixed-function oxidase pathway of metabolism is the primary route of clearance of EDB and that inhibition of cytochrome P450-mediated oxidation led to a more extensive tissue distribution of the parent compound. These data also suggest that the pathway which produces genotoxic metabolites from EDB in hepatocytes and spermatocytes, in vitro and in vivo, involves the conjugation of EDB to glutathione and its subsequent metabolism.

Animals↗