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Biomedical subjects

P Liu

Publications and source records attributed to P Liu.

At least 361 records · Page 20Linked to original sources

Quantitative evaluation of aqueous isopropanol enhancement of skin flux of terbutaline (sulfate). I. Ion associations and species equilibria in the formulation.

It has been reported previously that saturated terbutaline sulfate in aqueous isopropanol significantly enhances the terbutaline flux through human skin in vitro. This paper demonstrates that the effect of isopropanol on the permeant species in the formulation contributes to the flux enhancement. This demonstration is based on studies involving measurements of conductivity and pKa as well as NMR spectroscopy in isopropanol-water mixtures. Increasing isopropanol concentration inhibits the proton dissociation of terbutaline and results in the ion associations between the protonated terbutaline and its counterion, sulfate anion. The species present in the formulation include protonated terbutaline, the negatively charged terbutaline-sulfate (1:1) ion pair, and the neutral terbutaline-sulfate (2:1) ion triplet. The results of the studies provide the basis for a quantitative evaluation of the species equilibria in solutions of terbutaline sulfate. The saturated terbutaline sulfate in 60% isopropanol produces the maximum concentration of the neutral ion triplet. This result is almost parallel to the terbutaline skin flux, which maximized at 60-80% isopropanol.

1-Propanol↗

Measurement of pharyngeal transit time by electrical impedance tomography.

The feasibility of using electrical impedance tomography (EIT) for measuring pharyngeal transit time has been investigated. Imaging sequences were obtained on the neck in a group of eight healthy subjects when swallowing solutions of different electrical conductivities. The solutions used were aqueous Dioralyte (1.5 S m-1) and tap water (0.04 S m-1). The effects of movement upon the images were large compared with the changes due to the solutions, but these were cancelled by a subtraction technique. The mean value of the EIT pharyngeal transit time parameter was 370 +/- 120 ms. EIT has the advantage that repeated measurements could be performed without fear of hazard in contrast to the established technique of video fluoroscopy which involves ionising

Adult↗

Persistence of viral genome into late stages of murine myocarditis detected by polymerase chain reaction.

BACKGROUND: Enteroviruses have been considered as the most common etiologic agents in clinical myocarditis and dilated cardiomyopathy; however, their pathogenetic role remains unknown. Hence, the relation of viral replication and development of cardiomyopathy has been determined in a murine model of myocarditis by evaluating the persistence of viral genome during acute and chronic stages of myocarditis by means of Northern blot hybridization and polymerase chain reaction (PCR). METHODS AND RESULTS: DBA/2 mice (n = 146) were injected peritoneally with 10 plaque-forming units of encephalomyocarditis (EMC) virus, and the control mice (n = 33) were injected with normal saline. Animals were randomly killed at 4, 7, 10, 14, 21, 28, 35, and 42 days after infection. Histology revealed acute myocardial necrosis with massive inflammatory cell infiltrate peaking on day 14 followed by increasing fibrosis and declining chronic inflammation features compatible with dilated cardiomyopathy between days 21 and 42. Northern blot analysis of control and infected hearts showed detectable viral RNA in the infected hearts initially at day 4, peaking by day 7, diminishing between day 7 and day 14, and absent at day 21 and day 28. However, potential viral remnants present in low quantities and undetectable by Northern blot were further detected by PCR followed by confirmation with an internal oligonucleotide probe after day 14 up to day 42. CONCLUSIONS: Viral RNA signals on Northern blot showed a strong correlation with massive myocyte necrosis on day 14, but the viral RNA fragment was consistently detectable into late stages of cardiomyopathy on days 21, 28, 35, and 42 by PCR. This indicated that the mature virions are fully developed early in infection and are capable of persisting in the myocardium after virus-mediated myocytolysis stage. Therefore, PCR is an extremely sensitive method for detecting residual viral genome and viral persistence in the myocardium and may offer insights into the pathogenesis of chronic myocarditis leading to dilated cardiomyopathy.

Animals↗

Verapamil ameliorates the clinical and pathological course of murine myocarditis.

The effects of the calcium channel blocking agent, verapamil, were studied in a murine model of viral myocarditis. Three groups of 8-wk-old DBA/2 mice (n = 25 each) were inoculated with 10 plaque-forming units of encephalomyocarditis virus and randomized to three treatment regimens. Group 1 mice received verapamil intraperitoneally (5 mg/kg per d) for 7 d before infection, followed by verapamil orally (mean dose of 3.5 mg/mouse per d) in drinking water during infection. Group 2 mice received only verapamil orally starting on day 4 after infection, coincident with peak viremia. Group 3 (infected control) received no verapamil in regular drinking water after viral inoculation. Additional control animals were studied in group 4 (n = 21), consisting of uninfected control animals receiving intraperitoneal and oral verapamil at doses identical to group 1, and in group 5 (n = 21), consisting of uninfected and untreated controls. Animals were randomly killed from each group (n = 7) at 7, 14, and 28 d after infection. Routine histology was performed blindly on an apical slice of each heart and semi-quantitatively graded for inflammation, necrosis, calcification, and fibrosis on a scale of 0-4. Digital planimetry was performed to measure the absolute and relative areas of inflammation and necrosis. The pretreated animals in group 1 showed marked reduction in inflammation and necrosis (score of 3.7 +/- 1.4 vs. 8.7 +/- 2.0 in group 3 on day 14, P < 0.05) and were indistinguishable from the posttreated group 2 mice (score of 4.0 +/- 1.5 vs. 8.7 +/- 2.0 in group 3 on day 14, P < 0.05). All the uninfected control animals (groups 4 and 5) showed no myocardial lesions whether treated with verapamil or not. Quantitative planimetry confirmed decreased inflammation and necrosis (2.0 +/- 3.3% in group 1 and 3.5 +/- 3.1% in group 2 vs. 21.9 +/- 22.6% in group 3 on day 14). Untreated infected hearts injected with liquid silicone rubber exhibited extensive areas of focal microvascular constriction and microaneurysm formation; verapamil treatment in either group 1 or 2 completely abolished these abnormalities, resembling uninfected controls in groups 4 or 5. We conclude that verapamil, whether given before infection or after peak viremia in an encephalomyocarditis model of murine myocarditis, significantly reduces the microvascular changes and myocardial necrosis, fibrosis, and calcification leading to cardiomyopathy. This suggests the potentially important role of calcium and microvascular spasm in the pathogenesis of viral myocarditis leading to dilated cardiomyopathy, and may have future therapeutic implications.

Animals↗

Reverse redistribution on exercise thallium scintigraphy: relationship to coronary patency and ventricular function after myocardial infarction.

OBJECTIVE: To define prevalence, pathophysiology and relation to thrombolytic therapy of reverse redistribution (appearance of a new, or worsening of an existing, scintigraphic defect on 4 h delayed images compared with the stress thallium image). DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: Referral centre. PATIENTS: Sixty-three patients with acute myocardial infarction. INTERVENTIONS: Tomographic exercise thallium scintigraphy, radionuclide angiography, and quantitative coronary angiography. MAIN RESULTS: Tomographic exercise thallium scintigraphy performed at day 10 revealed fixed defects in 15 patients, reversible defects in 22 patients and reverse redistribution in 26 patients; no difference in treatment assignment (tissue plasminogen activator versus placebo) was found among the three groups. Left ventricular function was similar in patients with fixed or reversible defects and reverse redistribution; global ejection fraction was 48 +/- 14, 51 +/- 10 and 48 +/- 5%, respectively, and regional infarct ejection fraction was 36 +/- 15, 40 +/- 13 and 37 +/- 18%, respectively. However, nitroglycerin administration resulted in a significantly greater improvement in regional ejection fraction in reverse redistribution patients (5 +/- 4%) than that in patients with fixed defect (2 +/- 5%, P < 0.05) or reversible defects (3 +/- 5%, P < 0.05). The infarct-related artery had a greater cross-sectional area in reverse redistribution patients (1.5 +/- 1.42 mm2) compared with those with reversible defects (0.50 +/- 0.26 mm2, P < 0.05), but was similar to fixed defect patients (1.04 +/- 0.88). CONCLUSIONS: Reverse redistribution on tomographic thallium scintigraphy is a frequent phenomenon (occurring in 40% of patients following acute myocardial infarction) and is independent of thrombolytic therapy. Patients with reverse redistribution have a more widely patent infarct-related artery and similar ventricular function, but significantly greater functional improvement following nitroglycerin administration compared with those with reversible or fixed defects. These data suggest myocardial salvage within the infarct zone in some patients with reverse redistribution.

Animals↗

Fatal esophageal-arterial fistula 17 years following tetralogy of Fallot repair.

Blalock-Taussig shunts (subclavian to pulmonary anastomoses) have remained the most effective palliation in cyanotic heart disease. Late complications are rare but can be devastating. The case of a 26-year-old female with tetralogy and an original Blalock shunt constructed at age four years is reported. Despite subsequent primary repair of the tetralogy and presumed ligation of the Blalock shunt, the patient succumbed to a fatal hemorrhage due to esophageal-arterial fistula involving the Blalock shunt. The circumstances leading to this dramatic outcome are outlined and discussed. It is important for cardiologists caring for congenital heart disease patients to be aware of the late complications of congenital heart surgery, and carry out the proper follow-up investigations.

Adult↗

Coronary haemodynamics and myocardial metabolism during weaning from mechanical ventilation in cardiac surgical patients.

The present clinical study was undertaken to assess the alterations in myocardial metabolism and coronary haemodynamics during weaning from mechanical ventilation in postoperative cardiac surgical patients. Global and regional myocardial blood flow and metabolism were assessed using a dual port coronary sinus-great cardiac vein thermodilution catheter in 17 patients who had undergone coronary revascularization and who were being weaned from mechanical ventilation. Anaerobic myocardial metabolism, as demonstrated by the production of myocardial lactate, manifested in 8 of 17 patients during at least one of the weaning phases. There were no differences in coronary blood flow between patients who produced myocardial lactate and those who maintained aerobic cardiac metabolism. However, lactate producers exhibited larger changes in systemic vascular resistance and mean arterial pressure than the non-lactate producers. This metabolic manifestation of myocardial ischaemia was not accompanied by electrocardiographic changes of ischaemia, nor presence of chest pain, and may represent another form of silent ischaemia. We conclude that despite coronary revascularization, the myocardium may remain vulnerable to ischaemic anaerobic metabolism in the immediate postoperative period.

Adult↗

Serial magnetic resonance imaging in patients following acute myocardial infarction.

The detection of serial changes in magnetic resonance (MR) signal intensity of the heart following acute myocardial infarction may provide a useful method of characterizing tissue healing. Fourteen patients with acute Q-wave infarction underwent T2-weighted, spin-echo cardiac imaging during hospitalization, followed by one or more additional MR studies (total 31) over a 6- to 27-wk period (mean: 3 mo). Visual assessment of the images demonstrated a gradual reduction in signal intensity and localization of the bright signal to the subendocardium of the infarction region over the three-mo study period. A quantitative measurement of signal intensity (infarction/normal myocardium) fell from 1.81 +/- 0.42 on the initial study to 1.34 +/- 0.37 (p less than 0.05) at a mean of 14 wk. Two patients had an increase in signal intensity on the follow-up study and both patients had been readmitted with acute coronary syndromes. In summary, characterization of changes in signal intensity may provide a useful method of assessing myocardial healing following acute myocardial infarction. Further studies are indicated to determine the prognostic significance of these parameters.

Female↗

Quantitative evaluation of ethanol effects on diffusion and metabolism of beta-estradiol in hairless mouse skin.

The influence of low levels of ethanol on the simultaneous diffusion and metabolism of beta-estradiol (E2 beta) in hairless mouse skin was quantitatively evaluated. A wide range of diffusion/metabolism experiments was conducted with full-thickness skin, stripped skin, and dermis at the various ethanol levels. The experiments were carried out in a two-chamber diffusion-cell system where ethanol was present in both the donor and the receiver chambers at equal concentrations. Analysis of the experimental data with several enzyme distribution models further showed that the best model was that for which the enzyme activity resided totally in the epidermis and near the basal layer of the epidermis. The ethanol effects were separated and quantified in terms of the diffusion and metabolism parameters. Aqueous ethanol, even at low concentrations (greater than or equal to 25%), was found to have two important effects on E2 beta transport: ethanol functions as an inhibitor of the enzymatic conversion of E2 beta to estrone (E1) in the viable epidermis, and ethanol is able to enhance the transport of permeants across the lipoidal pathway of the stratum corneum.

Animals↗

Cotransport of estradiol and ethanol through human skin in vitro: understanding the permeant/enhancer flux relationship.

The thermodynamic and kinetic limits of ethanol-enhanced estradiol skin transport have been investigated by studying the relationship between estradiol and ethanol steady-state flux in the cotransport of permeant and enhancer in situations in which there exists an enhancer solvent gradient across the skin ("asymmetric" configuration). For aqueous ethanol solution saturated with estradiol, the flux of estradiol across the human epidermal membrane is empirically observed to be linear with the ethanol flux. A physical model approach has been used to determine the basis of this empirical linearity and to predict permeant/enhancer transport across the skin for the asymmetric configuration. Enhancement factors, determined with a balanced ethanol concentration across the skin ("symmetric" configurations), are used to predict fluxes in the asymmetric configurations. The model demonstrates that ethanol enhances the stratum corneum transport of estradiol and of itself by increasing the respective diffusion coefficients at lower concentrations (less than 50%) and by both increasing the diffusion coefficients and decreasing the membrane activity coefficients at moderate concentrations (50 to 75%). The model also demonstrates that the permeant flux, in general, is not linear with the cotransported enhancer flux.

Biological Transport, Active↗

The study of serum apoprotein levels as indicators for the severity of angiographically assessed coronary artery disease.

Serum apoprotein A-I (Apo A-I) and B (Apo-B) concentrations were determined in 40 subjects undergoing coronary angiography for past myocardial infarction and angina pectoris, and the authors studied the relationship between the apoprotein concentrations and the severity of coronary artery disease (CAD). During this study, serum total cholesterol, triglyceride, and high-density lipoprotein, low-density lipoprotein, and very low density lipoprotein cholesterol concentrations were determined to control analysis. The results showed that the decrease in serum Apo A-I levels was the best indicator distinguishing CAD from non-coronary artery disease; the Apo B/Apo A-I ratio had the most consistent association with the severity of CAD as assessed by angiography; Apo B/Apo A-I values ranging from 0.98 to 1.00 might be considered critical values for early CAD.

Adult↗

[Study on comparison of the determination of lead concentrations in saliva and blood].

The correlation between lead level in whole-saliva and whole-blood was investigated. The samples for Pb-determination were taken from 473 school-age children chosen from eight elementary schools located in urban and suburban districts where no industrial lead pollution was found. The coefficient of correlation between salivary and blood lead levels was low (r = 0.155 2). When the Pb-S concentrations were adjusted according to salivary protein and expressed by micrograms Pb per gram of salivary protein, the coefficient r calculated again became slightly higher. The means of Pb-S of children in different schools were about a quarter of that of Pb-B. It may be concluded that the salivary lead concentration is not suitable for use as an indicator to measure the individual body burden of lead instead of blood lead in the case of investigation on low-exposed population. The Pb-S value can, however, be used to investigate the Pb-B level of a population, by four times the mean value of Pb-S of the population. Both the Pb-B and Pb-S were related to Pb in air significantly.

Air Pollutants↗

Prospective assessment of cardiac function in patients with Kaposi's sarcoma and the acquired immune deficiency syndrome.

Prospective evaluation of cardiac function was undertaken in 21 patients with Kaposi's sarcoma (KS) and the acquired immune deficiency syndrome (AIDS) as part of a phase II clinical trial of 4'epirubicin. All patients were homosexual or bisexual males of median age 34 years (range 23-65). All patients had disseminated cutaneous involvement by KS and seven had systemic organ involvement. No patient had a history of cardiac symptoms, and physical examination of the cardiovascular system was within normal limits for all patients. The baseline ECG was normal in only nine patients (45%). Five had non-specific S-T segment and T-wave changes. Two had poor R-wave progression, and one patient each had incomplete right bundle branch block, left axis deviation, and voltage criteria suggestive of left ventricular hypertrophy. Radionuclide angiography was performed on all patients and compared to 12 age-matched, low-likelihood male controls. The mean ejection fraction (EF) at rest was 61.0 +/- 8.4%, and was not significantly different from the normal control value of 62.4 +/- 7.0%. Similarly the EF during exercise was 66.7 +/- 5.0%, again not significantly different from the control value of 67.8 +/- 5.8%. A drop in EF during exercise was seen in five of 15 KS patients compared to three of 12 controls. Chamber size was normal for both ventricles in only 14 patients (67%) with right ventricular dilatation seen in seven patients (33%). Wall motion abnormalities were also seen in nine patients (42.9%), with the right ventricle affected in eight patients (38.1%), chiefly involving the apex. No chamber size or wall motion abnormalities were seen in the control patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Acquired Immunodeficiency Syndrome↗