Biomedical subjects
Publications and source records attributed to M S Chang.
We describe a patient whose electrocardiograms showed ventricular tachycardia and atrial flutter which could be reproduced by arm movements. Careful review of the initiation and termination of the arrhythmia, the relation of the arrhythmia to body motion, and the associated symptoms and signs may be helpful to differentiate artifact from true arrhythmia.
The acute efficacy of rapid loading of oral long-acting enalapril in congestive heart failure remains to be established. We evaluated the efficacy of this treatment modality in 22 patients with chronic congestive heart failure N.Y.H.A. functional class ranging from II-IV with Creatinine level less than 2 mg/dl. Following hemodynamic evaluation, there was significant favorable change in the left ventricular functional curve. Moreover, acute hemodynamic assessment showed a significant reduction in pulmonary capillary wedge pressure from 19.2 +/- 4.8 to 17.2 +/- 4.7 mmHg (p less than 0.005) and an increases in stroke volume index from 28.3 +/- 9.2 to 33.1 +/- 7.5 ml/m (p less than 0.005). After rapid enalaprilization, blood pressure fell from 127 +/- 21/78 +/- 15 to 108 +/- 21/68 +/- 15 mmHg (p less than 0.005), systemic vascular resistance from 1725 +/- 602 to 1370 +/- 376 dyne.sec.cm-5 (p less than 0.05) and pulmonary vascular resistance from 262 +/- 19 to 218 +/- 65 dyne.sec.cm-5 (p less than 0.05). Cardiac index rose significantly from 2.43 +/- 0.62 to 2.60 +/- 0.50 l/min/m2 (p less than 0.05). In terms of neurohumoral assessments, there was a significant inhibition of the renin-angiotensin-aldosterone system. Aldosterone fell from 21.3 +/- 13.4 to 9.4 +/- 8.0 ng/dl and plasma renin activity rose from 3.3 +/- 4.6 to 11.3 +/- 11.0 ng/nl/hr (p less than 0.005). Plasma norepinephrine and epinephrine levels were found to have significant reduction in addition to antidiuretic hormone concentration. During short-term trial, left ventricular ejection fraction was significantly elevated from 27.5 +/- 6% to 32.8 +/- 10.8% (p less than 0.005). Thus, this limited study clearly demonstrates the rapid administration of enalapril not only achieves inhibition of renin-angiotensin-aldosterone system but also reduces preload and afterload significantly in the failing heart. We conclude that rapid enalaprilization is an effective methodology which still needs meticulous attention, providing significant hemodynamic and symptomatic benefits in patients with chronic congestive heart failure.
A control programme against subperiodic brugian filariasis was implemented in three villages, (Kg. Ampungan, Kg. Sebangkoi and Kg. Sebamban) in Sarawak, Malaysia. In Kampong Ampungan, the mass administration of diethylcarbamazine (DEC-citrate) combined with residual house spraying of pirimiphos-methyl reduced microfilarial rate to 8% of the pre-treatment level and microfilarial density (MfD50) to 44% of the pre-treatment level over a period of four years. In Kampong Sebangkoi and Kampong Sebamban, where only mass DEC therapy was applied, the microfilarial rate and MfD50 declined distinctly in the second blood survey but increased gradually in two subsequent follow-up blood surveys. In Kg, Ampungan, we observed a significant reduction of infective biting rate (88.3%), infection rate (62.5%) and transmission potential (88.1%) of Mansonia bonneae at the fourth spray round. The corresponding reduction rates in Kg. Sebangkoi and Kg. Sebamban were 35.3%, 26.7%, 42.2% and 24%, 30.8% and 15.4% respectively. The biting density of the vector was reduced by 79.8% indoors and 31.8% outdoors at the sprayed village, while only a slight decrease in densities (17.9% indoors and 12.4% outdoors) was observed at the unsprayed village. Bioassay tests revealed that pirimiphos-methyl had a substantial fumigant effect on the vector. The integrated control measure in controlling subperiodic brugian filariasis is discussed.
Lens protein-induced ocular inflammation in rabbits was used to study the action mechanism of some anti-inflammatory agents. Indomethacin, a cyclooxygenase inhibitor, markedly reduced PGE2 and PGF2 alpha in the iris and ciliary body at 2 h but PGE2 only at 4 h. REV 5901, a lipoxygenase inhibitor, only significantly reduced PGE2 levels in the ciliary body at 4 h. PGF2 alpha levels were not affected by REV 5901. When indomethacin and REV 5901 were combined, both PGE2 and PGF2 alpha were suppressed at 2 and 4 h in both iris and ciliary body. Neither matrine nor prednisolone produced significant effects on the levels of PGE2 and PGF2 alpha. However, prednisolone exhibited the greatest reduction in chemotaxis of leukocytes followed by REV 5901. Indomethacin, on the contrary, produced a significant increase in chemotaxis of leukocytes. Matrine produced a decrease in leukocyte counts but was not statistically significant. These results indicate that indomethacin is effective in the early phase of inflammation to reduce PG's production whereas prednisolone and REV 5901 were more effective in the late phase of inflammation. Combined use of REV 5901 and indomethacin could become a drug of choice for the treatment of ocular inflammation without inducing corticosteroidal side effects.
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STUDY OBJECTIVE: The aim was to compare regional wave transmission and reflection properties along the aorta in age matched normotensive and hypertensive subjects. DESIGN: Simultaneous upstream and downstream micromanometer pressures were recorded at five regions from the ascending aorta to the iliac artery. Recordings were made in the baseline condition in both groups and during sustained isometric handgrip exercise in the normotensives to see if increasing the blood pressure to hypertensive levels would eliminate baseline differences between the two groups. SUBJECTS: Only subjects who had no coronary or valvular heart disease were studied. Normotensive subjects (n = 8) were selected from those undergoing electrophysiological testing whose blood pressures were consistently in the normal range (systolic less than 140, diastolic less than 90 mm Hg). Age matched hypertensive subjects (n = 17) were those in whom secondary causes of hypertension were excluded and who had repeated measurements of raised blood pressure. MEASUREMENTS AND RESULTS: In each region pulse wave velocity was estimated from the simultaneous upstream and downstream pressure records using the foot to foot method, and apparent phase velocity was obtained from Fourier analysis of the two pressures. The intensity of wave reflections was judged by the magnitude of fluctuations of the harmonics of apparent phase velocity about the mean of the higher frequency harmonics. In both groups in the baseline state there were regional variations in the pulse wave velocity with the lowest values occurring just proximal to the renal arteries and highest values occurring in the iliac artery. Likewise, in both groups the extent of wave reflections varied regionally--pronounced reflections were seen in the ascending aorta and from just proximal to the renal arteries to the aortic bifurcation but not in the mid-thoracic or iliac regions. The hypertensives had higher pulse wave velocity than normotensives only in the iliac artery (780 v 567 cm.s-1) and had more reflections in the three regions in which reflections were evident. Although handgrip in the normotensive group eliminated regional differences in pulse wave velocity between the groups, reflections were still greater in the hypertensives. CONCLUSIONS: Essential hypertension affects the regional properties of the aortic wall. These alterations are manifested by increased peripheral wave-speed and increased wave reflections along the aorta. The differences in wavespeed but not reflection properties are eliminated when the pressures are matched by handgrip, suggesting that factors other than the level of blood pressure per se are responsible for the alterations in reflection properties.
Catheter balloon mitral valvuloplasty (BMV) was performed in 50 patients and 32 of them undergoing BMV with double balloon technique were studied to evaluate the usefulness of echocardiography in the prediction of early results of BMV. Five echocardiographic variables including mitral valve motion, mitral valve thickness, subvalvular change, commissural calcification and left atrial dimension were evaluated. Each variable was divided into mild, moderate and severe subgroups. Before valvuloplasty there were no differences in mitral valve area among any subgroup for any variable. After valvuloplasty, variables associated with a greater increase in mitral valve area from mild and moderate subgroups than from severe subgroup included mitral valve motion, mitral valve thickness, and subvalvular change, but not commissural calcification or left atrial dimension. We scored the former 3 variables as 0, 1 and 2 points in the mild, moderate and severe subgroups, respectively. The sums of individual scores in these 3 variables were further divided into 3 groups: 12 patients had a lower score (less than 2), 10 patients had a score of 3-4 and 10 patients had a higher score (greater than 5). Patients with lower scores tended to have greater increases in mitral valve areas after valvuloplasty than those with higher scores. Thus, mitral valve motion, mitral valve thickness and subvalvular change may be useful to predict a greater increase in mitral valve area after valvuloplasty. A lower score of echocardiographic variables anticipates successful balloon mitral valvuloplasty, which may be helpful in patient selection.
A prospective study was undertaken of the high-frequency components of the terminal portion of the QRS complex in 38 Chinese patients with acute myocardial infarction (AMI) (mean age 62 +/- 5.6 years) within the first week after the acute event (5.5 +/- 1.2 days). Another 44 normals served as controls (mean age 57 +/- 9.6 years). The electrocardiogram was averaged at a filter band pass of 80-300 Hz. The low voltage span (LVS) of the signals less than 40 microV in the terminal portion of QRS, the root-mean-square (RMS) voltage (V) of terminal 40 msec of the QRS complex, and the total duration of signal-averaged QRS vector complex were measured in both the normal subjects and patients. The LVS was abnormally prolonged in 16 of 38 patients (42%), and in only 16% of normals (p less than 0.05). The RMS-V was abnormal (less than 25 microV) in 29 of 38 patients (76%), and in only 20% of normals (p less than 0.0005), and the signal-averaged QRS vector complex was abnormal (greater than 120 msec) in 26 of 38 patients (68%), and only 9% of normals (p less than 0.005). There was no significant correlation between any of the signal-averaged parameters, the site of AMI and total creatine kinase (CK) or CK-MB values. The signal-averaged parameters also showed no relationship to either the cardiothoracic (C/T) ratio or the left ventricular ejection fraction, determined by the Tc-99 m pertechnetate first pass blood pool technique. Holter ECG monitoring was performed twice in all AMI patients, at 7 to 18 days after the acute event (12 days average) and 3 weeks after the first recording. There were only four episodes of non-sustained ventricular tachycardia (VT), all during the second monitoring period. Three episodes (10%) occurred in patients with positive late potentials (LPs), defined by an RMS-V less than 25 microV in the terminal portion of QRS vector; one episode (11%) occurred in patients with negative LPs (9 patients). Although the incidence of LPs is significantly higher in patients with an AMI than in normal controls, the LPs detected by body surface signal-averaged ECG did not predict the occurrence of in- and out-of-hospital VTs. Thus, after AMI, Chinese patients may not be as prone to develop VTs as are Caucasians. Furthermore, the appearance of LPs is independent of cardiac size and left ventricular ejection fraction.
The measurement of the ultimate effects of the microbial insecticides on mosquito density is best obtained by assessment of adult populations. The main aims of this study are: (1) to assess the effect of Bacillus thuringiensis israelensis (Bti) FC Skeetal and Bactimos briquettes on the emergence rate of Mansonia bonneae developed from the introduced first-instar stage larvae and (2) to measure the effect of these two formulations of insecticides on Mansonia adult populations emerging from the natural breeding plots. Bti Skeetal and Bactimos briquettes at the lower applied dosages of 2.3 kg/ha and 1 briquette case/20 m2 respectively achieved 39-40% pupation rates and 31.5-34.2% adult emergence rates. At these low applied dosages, there was little or no direct effect on pupation from the surviving larvae and thereafter on the emergence of adults from the pupae. A two-fold increase in dosage, however, produced a drastic decline in the pupation rate and adult emergence rate. The rates dropped to 6.5% (pupation) and 4.3% (adult emergence) of the total larvae for Bactimos briquettes and to merely 1.5% (pupation) and 1.3% (adult emergence) of the total larvae for Skeetal. In studying the effect of Bti on the field populations of Mansonia mosquitos, two plots each were treated with Bactimos at 1 briquette case/10 m2 and Skeetal at 4.6 kg/ha. A wooden pyramid-shaped screened cage was placed on a cluster of host plants for a period of 2 weeks to trap the emerging adult mosquitoes. There were a total of 24 clusters of host plants in each plot.(ABSTRACT TRUNCATED AT 250 WORDS)
Effects of intravenous (IV) and intravertebral arterial (IA) administrations of alpha-2 adrenoceptor agonist, clonidine (CLO) and its antagonist, yohimbine (YOH, 0.05 mg/kg, IA), on the ventricular tachycardia (VT) induced with IV acetyl strophanthidin (AS) were studied in cats anesthetized with intraperitoneal chloralose. IVAS does-dependently produced cardiac arrhythmias including complete atrioventricular conduction block (118 +/- 14 micrograms/kg), junctional tachycardia (128 +/- 20 micrograms/kg), multiform ventricular premature beats (157 +/- 21 micrograms/kg) and sustained VT (220 +/- 23 micrograms/kg). IACLO dose for terminating VT induced with IVAS was about one fifth of IVCLO dose. IACLO dose for terminating VT induced with IVAS + IVYOH was significantly higher than that in VT induced with IVAS (14.8 +/- 3.7 vs 5.8 +/- 1.0 micrograms/kg, p less than 0.005). These experiments clearly demonstrated that IAYOH specifically antagonized the antiarrhythmic effect of IA CLO on the AS-induced VT. Since small dose of IA administration of the drugs acts mainly on the central nervous system, we suggest that the antiarrhythmic effect of CLO on AS-induced VT is likely through the central alpha-2 adrenoceptor.
To study the mechanism of symptomatic postural hypotension in the elderly, we collected 11 such patients to further divide them into group 1 with central nervous system (CNS) involvement and group 2 without CNS involvement. Group 1 was the so-called Shy-Drager syndrome, and group 2 was the elderly postural hypotension not secondary to the medications or other systemic diseases. All patients had various degree of autonomic dysfunction and heterogenous defects in the reflex arc of autonomic nervous system (ANS). Both groups also had normal plasma volume but reduced blood volume. Patients in group 1 had normal level of plasma norepinephrine in recumbent posture, but failed to increase normally after standing (p less than 0.05, as compared the percentage rising with that of the controls). Patients in group 2 had near normal level of plasma norepinephrine in recumbent posture and could rise normally after standing. They also had normal level of plasma epinephrine in recumbent posture, but failed to rise normally after standing (p less than 0.05 as compared with the controls). These findings suggested that impaired responsiveness of end organs as blood vessels and adrenal medulla is one of the major causes responsible for the symptomatic postural hypotension in the elderly without CNS involvement.
Alpha atrial natriuretic peptide (alpha-ANP) and brain natriuretic peptide are homologous polypeptide hormones involved in the regulation of fluid and electrolyte homeostasis. These two natriuretic peptides apparently share common receptors and stimulate the intracellular production of cyclic GMP as a second messenger. Molecular cloning has defined two types of natriuretic peptide receptors: the ANP-C receptor of relative molecular mass (Mr) 60-70,000 (60-70 K), which is not coupled to cGMP production and may function in the clearance of ANP and the ANP-A receptor of Mr 120-140 K, which is a membrane form of guanylate cyclase in which ligand binding to the extracellular domain activates the cytoplasmic domain of the enzyme. Here we report the cloning and expression of a second human natriuretic peptide-receptor guanylate cyclase, the ANP-B receptor. The ANP-B receptor is preferentially activated by porcine brain natriuretic peptide rather than human alpha-ANP, whereas the ANP-A receptor responds similarly to both natriuretic peptides. These observations may have important implications for our understanding of the central and peripheral control of cardiovascular homeostasis.
Atrial natriuretic peptide (ANP) is a polypeptide hormone whose effects include the induction of diuresis, natriuresis and vasorelaxation. One of the earliest events following binding of ANP to receptors on target cells is an increase in cyclic GMP concentration, indicating that this nucleotide might act as a mediator of the physiological effects of the hormone. Guanylate cyclase exists in at least two different molecular forms: a soluble haem-containing enzyme consisting of two subunits and a non-haem-containing transmembrane protein having a single subunit. It is the membrane form of guanylate cyclase that is activated following binding of ANP to target cells. We report here the isolation, sequence and expression of a complementary DNA clone encoding the membrane form of guanylate cyclase from rat brain. Transfection of this cDNA into cultured mammalian cells results in expression of guanylate cyclase activity and ANP-binding activity. The ANP receptor/guanylate cyclase represents a new class of mammalian cell-surface receptors which contain an extracellular ligand-binding domain and an intracellular guanylate cyclase catalytic domain.
We isolated cDNAs encoding a 115 kd human atrial natriuretic peptide (alpha ANP) receptor (ANP-A receptor) that possesses guanylate cyclase activity, by low-stringency hybridization with sea urchin Arbacia punctulata membrane guanylate cyclase probes. The human ANP-A receptor has a 32 residue signal sequence followed by a 441 residue extracellular domain homologous to the 60 kd ANP-C receptor. A 21 residue transmembrane domain precedes a 568 residue cytoplasmic domain with homology to the protein kinase family and to a subunit of the soluble guanylate cyclase. COS-7 cells transfected with an ANP-A receptor expression vector displayed specific [125I]alpha ANP binding, and exhibited alpha ANP stimulated cGMP production. These data demonstrate a new paradigm of cellular signal transduction where extracellular ligand binding allosterically regulates cyclic nucleotide second-messenger production by a receptor cytoplasmic catalytic domain.
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By the use of fluorophotometry, ocular inflammation induced by lens proteins can be objectively quantified. This method of measuring inflammation was applied to studying the effectiveness of a cyclooxygenase inhibitor, indomethacin, and a lipoxygenase inhibitor, REV 5901, in reducing ocular inflammation induced by lens proteins. Pretreatment with indomethacin prevented the leakage of fluorescein into the anterior chamber up to 2 hrs after intracameral injection of lens proteins. After the first 2 hrs, fluorescein concentration in the pretreated eye rapidly increased to equal the control eye by 4 hrs. When REV 5901 was used to pretreat the eye, there was an increase in fluorescein leakage up to 3 hrs after lens protein injection. However, when a combination of indomethacin and REV 5901 was used to pretreat the eye, there was a significant reduction in fluorescein leakage up to 5 hrs after the injection of lens proteins. The reduction of fluorescein leakage with a combination of indomethacin and REV 5901 was greater than that obtained with prednisolone alone. These results indicate that prostaglandins are the primary mediators of inflammation in the early phase (less than 3 hr) of lens protein induced ocular inflammation and leukotrienes are the primary mediators in the late phase (greater than 3 hr) of lens protein induced ocular inflammation. Also the use of a nonsteroidal antiinflammatory drug which blocks only one arm of the arachidonic acid cascade may potentiate the production of metabolites in the other arm of the cascade. By using a combination of a cyclooxygenase inhibitor and a lipoxygenase inhibitor, metabolites from both arms of arachidonic acid cascade are reduced, hence reducing inflammation in both the early phase and late phase of lens protein induced ocular inflammation.