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Biomedical subjects

M S Chang

Publications and source records attributed to M S Chang.

At least 343 records · Page 19Linked to original sources

Systemic delivery of insulin through eyes to lower the glucose concentration.

An attempt has been made in this study to develop a simple, economical and painless method for the delivery of insulin systemically without using parenteral routes. Insulin was shown to be absorbed effectively into systemic circulation through the eyes. With 0.125% (0.031 mg/25 microliters), 1% (0.25 mg/25 mg/25 microliters) insulin instilled topically into the eyes, systemic blood concentrations of 1.3 ng/ml, 9 ng/ml, and 24 ng/ml, respectively, could be attained. When 25 microliters of 1%, 2% and 5% insulin plus 1% saponin solution were instilled into eyes they reached 63 ng/ml, 89 ng/ml and 195 ng/ml, respectively in the systemic circulation. These results indicate that the systemic absorption of 1% insulin through the eyes can be enhanced at least 7-fold when 1% of the surfactant, saponin, was added to the solution. However, the insulin absorption was not affected by aminopeptidase inhibition nor by the change of pH in the range of 5 to 8. Most importantly, the blood glucose was reduced concomitantly with the increase of blood insulin when 50 microliters of 1% insulin in 1% saponin solution was instilled in the eyes. The blood glucose of alloxan-treated diabetic animals reduced drastically from 370 mg % to 185 mg % in 90 min and further to 75 mg % in another 150 min. In normal animals, 25 microliters of 1% insulin in 1% saponin reduced blood glucose from 102 mg % to 50 mg % in an hour and blood glucose remained low for at least 3 hrs. These results indicate that insulin can be delivered systemically through the eyes, particularly with the surfactant enhancers, such as saponin. This new method is economical and simple as compared with parenteral administration and/or minipump implantation. It is hoped that this new method would improve patients' compliancy in using insulin for diabetes treatment.

Animals↗

The efficacy and safety of recombinant tissue plasminogen activator infusion in acute myocardial infarction.

UNLABELLED: Recombinant tissue plasminogen activator (rt-PA) is the most promising agent use for salvaging ischemic myocardium in acute infarction. To assess the safety and efficacy of rt-PA thrombolytic therapy, an open label clinical trial was conducted. Patients of acute myocardial infarction with angina, occurring within the five previous hours, was treated with rt-PA 100 mg infusion within three hours; followed with coronary arteriography to assess the patency rate of infarct vessels. Twenty-five cases of acute myocardial infarction were studied over a 10-month period. The patients, 24 male and one female, were aged 58.1 +/- 7.7 years. Rt-PA was given at 3.17 +/- 1.0 hour. Infarct-related vessels had opened in 21/24 cases when examined with coronary arteriogram three hours after infusion. Good antegrade flow of grade 2 to 3 was gained in 20/24 cases, representing an 83% success rate. One patient expired from cardiogenic shock during the infusion; another was expired from noncardiac accident after coronary bypass graft. The total inhospital mortality rate was about 8%. There was no major bleeding complication except in one case with gastrointestinal bleeding requiring transfusion. IN CONCLUSION: rt-PA is safe and effective in the treatment of acute myocardial infarction in the early stage. Coronary arteriography can be safely delayed until three hours postinfusion, and the achieved reperfusion rate is up to 83%.

Adult↗

Minimal requirement of effective dilation diameter of balloon(s) in percutaneous transluminal mitral valvotomy.

40 patients are included to study the minimal requirement of effective dilation diameter of balloon(s) in performing percutaneous transluminal mitral valvotomy (PTMV) to obtain good hemodynamic and long-term follow-up consequences. The patients are divided into 2 groups depending on the ratio of effective dilation diameter of balloon(s) (determined by calculating the cross-sectional area of the oval enveloping the one or two balloons and then taking the diameter of the circle with the same area) to mitral annular diameter (determined by 2-dimensional echocardiography) (Balloon-Mitral Anular Ratio, BMAR). BMAR in group 1 may be equal to or greater than 0.80 or 0.90, BMAR in group 2 may be less than 0.80 or 0.90. From the careful analysis, the statistically significant immediate hemodynamic improvement, e.g. the reduction of trans-valvular pressure gradient, left atrial pressure, pulmonary artery systolic pressure, the increase of mitral valve area, can be obtained even BMAR is less than 0.80. However, the increase of stroke volume index after PTMV can only be obtained with the BMAR equal to or greater than 0.80. The long-term improvement, determined by greater increment of exercise duration, is also only obtained if the BMAR equal to or greater than 0.80 at PTMV. Therefore, we conclude that to obtain the adequate and satisfactory immediate hemodynamic and long-term follow-up results of PTMV, the BMAR must exceed 0.80.

Adult↗

Prospective evaluation of a discriminant function for prediction of recurrent symptomatic ventricular tachycardia or ventricular fibrillation in coronary artery disease patients receiving amiodarone and having inducible ventricular tachycardia at electrophysiologic study.

Induction of ventricular tachycardia (VT) at electrophysiologic study in patients taking amiodarone poorly predicts recurrence of VT. Consequently, a discriminant function was developed (using parameters based on retrospective data) that appeared to identify high-risk patients. These parameters included ventricular effective refractory period, corrected QT interval, initiation of a repetitive ventricular response and the mode of VT induction. In the present study these parameters were prospectively evaluated in 60 patients with coronary artery disease and sustained VT or ventricular fibrillation (VF), in whom VT was still induced at electrophysiologic study during amiodarone therapy. Thirteen patients had recurrent events (sudden death in 8 and sustained VT in 5) and 47 patients had no symptomatic arrhythmia recurrence (follow-up for 16 +/- 2 months, mean +/- standard error of the mean). The ventricular effective refractory period, corrected QT interval and presence of a repetitive ventricular response did not discriminate between patients with and without symptomatic arrhythmia recurrence. However, an easier mode of VT induction during amiodarone therapy versus control was highly predictive of arrhythmia recurrence: 9 of 13 (69%) recurrences were in this group. In contrast, only 4 of 44 (9%) patients who had either the same or harder mode of VT induction had a recurrent event. Overall, 9 of 16 (56%) patients with an easier mode of VT induction had a recurrence, including 6 of the 8 patients with subsequent sudden cardiac death. It is concluded that electrophysiologic testing during amiodarone therapy is useful to identify high-risk patients.

Administration, Oral↗

Differential sensitivity of sinus node, atrioventricular node, atrium, and ventricle to propranolol.

The purpose of this study was to test the hypothesis that less propranolol was required to block stellate-induced shortening of atrial and ventricular effective refractory periods (ERPs) than was required to prevent stellate-induced shortening of the spontaneous sinus nodal cycle length and atrioventricular (AV) nodal conduction time. Studies were performed in open-chest, neurally decentralized dogs anesthetized with secobarbital. We determined the dose of propranolol (propranolol dose-response curves) required to block the effects of 1 Hz, 2 Hz, and 4 Hz bilateral ansae subclaviae stimulation on sinus nodal automaticity, AV nodal conduction, and atrial and ventricular ERPs. We found that propranolol at a dose of 0.5 mg/kg eliminated ansae subclaviae-induced shortening of atrial and ventricular ERPs, whereas sinus nodal cycle length and AV nodal conduction time still shortened. These data indicate a differential sensitivity of the sinus and AV nodes compared with atrial and ventricular myocardium to the beta-adrenergic receptor-blocking effects of propranolol in response to efferent sympathetic neural stimulation. Clinical implications are that it might be possible to treat sympathetically mediated ventricular arrhythmias with doses of propranolol that still preserve sinus and AV nodal responses.

Animals↗

Systemic delivery of enkephalin peptide through eyes.

Leu-enkephalin is one of the important peptides which could become useful drugs in the clinics because of its analgesic action and its availability in mass quantity through biotechnology production. It is found in this study that enkephalin can be effectively absorbed systemically through eyes without using a surfactant as absorption enhancer. Enkephalin at 0.125% (31.25 micrograms/25 microliter) reached a plateau of blood concentration at 11.5 ng/ml in 3-4 hrs and stayed high for 8-9 hrs. In contrast, the blood concentration of enkephalin declined rapidly after i.v. administration with a T1/2 of less than 30 min and reached the lowest point at 22 ng/ml in 5 hrs. With higher concentrations at 1% (.25 mg/25 microliter) and 5% (1.25 mg/25 microliter) similar absorption kinetics was observed except that they reached higher plateau of blood concentration at 72 ng/ml and 233 ng/ml, respectively.

Absorption↗

Breeding-site productivity of the swamp forest mosquitoes Mansonia bonneae and Ma. dives in Sarawak, east Malaysia.

Studies on larval population densities and adult emergence rates of the Brugian filariasis vectors Mansonia bonneae Edwards and Ma. dives Schiner were conducted in freshwater swamp forest bordering the Sadong River, Serian District, Sarawak, East Malaysia, during 1984-85. Three species of aquatic host-plants in the Family Araceae were identified as supporting immature stages of the Ma. bonneae/dives complex. Proportions of positive plants were 4.7%, 6.5% and 3.4% with 6.4 +/- 2.6, 7.3 +/- 2.8 and 10.1 +/- 1.1 larvae per positive plant, respectively, for the plant species Homalomena cordata Schott, H. rostrata Griffiths and Hydrostemma motleyi (Hook. f.) Mabberley. These data indicate no significant preferences between the three types of host-plant. Detailed monitoring of the host-plant H. cordata revealed no significant monthly fluctuations in larval density per plant nor the proportion of positive plants. 11.6% of larvae were Ma. dives and 88.4% were Ma. bonneae. Mean daily yields of Ma. bonneae/dives adults per square metre of H. cordata vegetated water surface were 0.45 males plus 0.57 females during the wet season (December-February) compared with 0.2 males plus 0.31 females during the dry season (June-August). Thus output of adults per plant was approximately halved, and suitable breeding areas were further reduced, during the dry season. By extrapolation from these rates, a crude mean estimate for productivity of Ma. bonneae/dives females is 1.6 million per hectare per annum in swamp forest habitats vegetated with any of the host-plants studied.

Animals↗

Coronary spasm complicating sclerotherapy of esophageal varices.

There are rare serious cardiac complications associated with endoscopic examination. An episode of coronary artery spasm developed in a 68-year-old man during endoscopic sclerotherapy for esophageal varices. The coronary artery spasm may have been triggered by a reflex increase in sympathetic discharge under stressful circumstances, and may occur most often in patients with preexisting heart disease. In patients with severe cardiac disease, ECG monitoring during the procedure seems justified.

Aged↗

Enzyme polymorphism of the malaria vector, An. balabacensis (Diptera: Culicidae) revisited--why sample natural populations?

Two separate observations from recent electrophoretic studies of the systematics and population genetics of laboratory-reared populations which had a long history of colonization in various laboratories, were found to be inconsistent with the present study which used wild-caught populations from East Malaysia. Reanalysis of the two data sets generally indicated a low amount of genetic variation in laboratory colonies. The latter is characterized by higher frequency of monomorphic loci, low average heterozygosity values and, in one extreme case, no variability at two loci. However, natural populations of An. balabacensis and An. leucosphyrus showed more protein variability by the use of polyacrylamide gel electrophoresis. Since laboratory-maintained mosquitoes are genetically and phenotypically different from those in the field, results of laboratory studies on the systematics and population genetics of Anopheles species complexes may be biased.

Animals↗

Supernormal conduction in accessory atrioventricular connections.

Prospective electrophysiologic evaluation of 74 patients with ventricular preexcitation revealed 4 patients who had supernormal anterograde conduction over an accessory atrioventricular pathway. In each patient, anterograde conduction over the accessory pathway was present at relatively slow sinus rates, but the accessory pathway anterograde effective refractory period was substantially prolonged. During premature atrial stimulation, a "window" of supernormal conduction was identified at which closely coupled atrial extrastimuli conducted over the accessory pathway, whereas longer premature intervals resulted in accessory pathway block. Causes other than supernormal conduction to explain this phenomenon, for example, phase 4 block, were unlikely in each case. Although the mechanism of supernormal conduction in humans is unknown, the electrophysiologic findings in our patients are similar to those reported in patients with supernormal conduction in the His-Purkinje system.

Adult↗

Electrophysiologic and antiarrhythmic effects of oral encainide in patients with atrioventricular nodal reentry or nodoventricular reentry.

Three patients with drug-resistant atrioventricular (AV) nodal reentrant tachycardia and two patients with reciprocating tachycardia associated with nodoventricular pathways received oral encainide after a control drug-free electrophysiologic study. In one patient with AV nodal reentry, encainide prolonged anterograde AV nodal conduction, produced complete ventriculoatrial (VA) block, and prevented tachycardia induction. Encainide had no effect on AV or VA conduction in the second patient with AV nodal reentry, and tachycardia with similar cycle length was still induced. The third patient was not studied while receiving encainide, but spontaneous AV nodal reentrant tachycardia occurring multiple times daily was abolished. In both patients with nodoventricular pathways, anterograde AV nodal and VA conduction were prolonged by encainide and tachycardia was no longer inducible. Two patients with AV nodal reentry were given long-term encainide therapy and have been free of recurrent arrhythmias for 16 and 30 months. One patient with a nodoventricular pathway has been without arrhythmia recurrence after 73 months of encainide therapy; the other patient required addition of propranolol to encainide because of recurrent tachycardia. We conclude that encainide can prolong anterograde AV nodal and VA conduction and prevent induced and spontaneous tachycardia in some patients with drug-resistant and highly symptomatic AV nodal or nodoventricular reentry.

Administration, Oral↗

Cloning and expression of recombinant, functional ricin B chain.

The cDNA encoding the B chain of the plant toxin ricin has been cloned and expressed in monkey kidney COS-M6 cells. The recombinant B chain was detected by labeling the transfected cells with [35S]methionine and [35S]-cysteine and demonstrating the secretion of a protein with a Mr of 30,000-32,000 that was not present in the medium of mock-transfected COS-M6 cells. This protein was specifically immunoprecipitated by an anti-ricin or anti-B-chain antibody and the amount of recombinant B chain secreted by the COS-M6 cells was determined by a radioimmunoassay. Virtually all of the recombinant B chain formed active ricin when mixed with native A chain; it could also bind to the galactose-containing glycoprotein asialofetuin as effectively as native B chain. These results indicate that the vast majority of recombinant B chains secreted into the medium of the COS-M6 cells retain biological function.

Animals↗

Double and triple sequential shocks reduce ventricular defibrillation threshold in dogs with and without myocardial infarction.

The role of optimal placement of electrodes and mode of shock delivery from a defibrillator was examined in dogs with and without myocardial infarction. Single, double and triple truncated exponential shocks separated by 1 ms were delivered through various electrode combinations and cardiac vectors after electrical induction of ventricular fibrillation. A single shock through a pathway not incorporating the interventricular septum (catheter electrodes or epicardial patches between anterior and posterior left ventricle) required the highest total energy (22.6 and greater than 26.4 J, respectively) and peak voltage (1,004 and greater than 1,094 V, respectively) to terminate ventricular fibrillation. A single shock through a pathway including the interventricular septum required lower total energy and peak voltage to defibrillate. Combinations of two sequential shocks between an intracardiac catheter electrode and anterior left ventricular epicardial patch, between the catheter electrode and subcutaneous extrathoracic plate and between three ventricular epicardial patches all significantly reduced total energy (7.7, 8.7 and 7.8 J, respectively) and peak voltage (424, 436 and 424 V, respectively) needed to defibrillate. Three sequential shocks exerted no significant additional reduction in total energy of the defibrillation threshold than did two sequential shocks. Infarcted canine heart required less peak voltage but not total energy to terminate ventricular fibrillation than did noninfarcted heart. Therefore, two sequential shocks over different pathways reduce both total energy and peak voltage required to terminate ventricular fibrillation.

Animals↗