Search PubMed⌕ Search

Biomedical subjects

S H Lau

Publications and source records attributed to S H Lau.

At least 19 recordsLinked to original sources
PubMed1986

Ionization and surface properties of verapamil and several verapamil analogues.

We have investigated the ionization and surface properties of verapamil (5-[(3,4-dimethoxyphenethyl)methylamino]-2-(3, 4-dimethoxyphenyl)-2-isopropylvaleronitrile, 1) and several verapamil analogues since these properties appear to be involved in the biologic activities of these compounds. Our results show that verapamil and its analogues are surface-active and bind to amphiphilic surfaces. The affinity toward, as well as the capacity of, an amphiphilic surface for verapamil and its ionizable analogues is pH dependent, with the surface having both higher affinity and capacity for the neutral form of the molecules. Thus, verapamil exists as protonated and neutral forms, both of which are free in solution and adsorbed to the interface, and the ionization of verapamil at an interface changes with respect to its ionization in solution. From analyses of the pH dependency of surface binding and of solution and interfacial ionizations, we determined the values of the four equilibrium constants. These equilibrium constants permit correlative studies between the pH-dependent abundance of each species and biologic activity. We discuss preliminary studies which indicate that the negative inotropic effect of verapamil is mediated by the membrane-bound neutral form of the drug.

Absorption↗
PubMed1985

A method for probing the affinity of peptides for amphiphilic surfaces.

We have developed a rapid method for probing the affinity of peptides toward an amphiphilic surface. Hydrophobic polystyrene-divinylbenzene beads of 5.7 +/- 1.5 micron diameter are coated with a monomolecular film of egg lecithin to achieve the equilibrium spreading density of the phospholipid, 6 X 10(-3) molecule/A2. The coated beads are ideally suited for assessing the affinity of peptides for phospholipid surfaces: Large quantities of lipid-coated beads of known surface area can be prepared easily and rapidly. Within the pH range 2.0 to 9.0, the adsorbed phospholipids are relatively resistant to hydrolysis and remain bound indefinitely. Following incubation with peptide ligands, beads can be separated from the reaction mixture by centrifugation. Peptides, such as melittin, which destroy or cause fusion of single bilayer phospholipid vesicles, cannot disrupt lecithin-coated beads in a comparable way, and do not displace lecithin from the surface of beads. After incubating these beads in solutions of peptides and proteins, we have determined the parameters for the binding of several ligands to the phospholipid surface. The binding of many amphiphilic peptides obeys a Langmuir adsorption isotherm, i.e., saturable reversible binding to independent and equivalent sites on the bead. That the binding is a true reversible equilibrium is shown by desorption of the ligand upon dilution. From the isotherm, the surface areas occupied by the ligand molecules were calculated, and were observed to be similar to those observed in monolayers at the air-water interface. In comparing the binding of amphiphilic peptides to that of completely hydrophilic peptides, we observed that only the former bind at levels measurable by our techniques. Thus, this method can serve as a rapid assay for detecting amphiphilicity in peptides of putative amphiphilic character.

Adsorption↗
PubMed1984

Coronary atherosclerosis among Hong Kong Chinese--a histological and morphometric study using electronic digitizer.

In order to document the prevalence of atherosclerosis of the major coronary arteries among Hong Kong Chinese, a study on material from autopsies done during the year 1981 in Queen Mary Hospital was carried out. The narrowest part of the proximal coronary arteries was studied by light microscopy and morphometrically by electronic digitizer. We found an onset of atherosclerosis in young adult males and a linear progression with age. Females had a delayed onset with a sharp rise after menopause. We were surprised to find an incidence of atherosclerosis among Hong Kong Chinese comparable with that in western populations, as distinct from Chinese in Mainland China. However, mortality due to ischemic heart disease remained relatively low. Racial factors may contribute to this partial dissociation between coronary atherosclerosis and ischemic heart disease.

Adolescent↗
PubMed1983

Surface properties of an amphiphilic peptide hormone and of its analog: corticotropin-releasing factor and sauvagine.

Synthetic corticotropin (adrenocorticotropic hormone)-releasing factor [CRF; for the sequence, see Vale, W., Spiess, J., Rivier, C. & Rivier, J. (1981) Science 213, 1394-1397] in aqueous solution exists predominantly as a random coil. At concentrations greater than 1 microM, the peptide shows a tendency to self-aggregate with a concurrent slight increase in the apparent alpha-helical content as measured by the CD spectrum. The alpha-helix formed by this molecule is highly amphiphilic--i.e., the hydrophilic and hydrophobic regions are segregated on opposite faces of the helix. As predicted from the potential amphiphilic structure, CRF binds avidly to the surface of single bilayer egg phosphatidylcholine vesicles. This binding appears to obey a simple Langmuir isotherm with the following parameters: Kd = 1.3 +/- 0.6 X 10(-7) M and capacity at saturation (N) = 11.0 +/- 1.0 mmol of peptide per mol of phospholipid. CRF also readily forms an insoluble monolayer at the air-water interface. The monolayer is composed of monomers of the hormone with molecular areas, A'0 = 22 A2 per amino acid, suggesting a compact secondary structure. Judged from the collapse pressure (19.0 +/- 0.1 dyne/cm; 1 dyne = 10 microN) of the monolayer, the amphiphilicity of CRF approximates that of plasma apolipoproteins, a class of proteins of the most pronounced amphiphilic character. These results suggest that the binding of CRF to the cell membrane is accompanied by the induction of an alpha-helical secondary structure and it is this predominantly helical form that is the biologically active form of the peptide.

Amino Acid Sequence↗
PubMed1979

Multiple mechanisms of tachycardias in a patient with the Wolff-Parkinson-White syndrome.

In a patient with the Wolff-Parkinson-White Syndrome we observed atrial fibrillation and three distinct paroxysmal re-entrant tachycardias. Intracardiac electrograms obtained during the tachycardias showed the mechanisms to be A-V nodal, accessory pathway and sinus node re-entry. When P wave morphology, R-P relationship and QRS configuration are considered, it is illustrated how these four tachyarrhythmias may be successfully diagnosed on the surface electrocardiogram. The therapeutic implications of multiple arrhythmias with different mechanisms in the Wolff-Parkinson-White Syndrome are discussed.

Anti-Arrhythmia Agents↗
PubMed1979

Congenital pulmonary artery branch stenosis: association with renal artery stenosis.

A patient had multiple bilateral stenoses of the pulmonary artery and its branches with systemic hypertension associated with mild stenoses of the renal arteries. Cardiac catheterization and angiocardiography are important in the evaluation of the degree of stenoses and pulmonary hypertension. This case suggests that in a child or young person with hypertension and a loud precordial murmur, lesions other than coarctation of the aorta may be present. Unexplained systemic hypertension requires further investigative workup which is essential for proper treatment and long-term management of these patients.

Adolescent↗
PubMed1978

The effect of digitalis on refractoriness of the intact canine His-Purkinje system.

The effect of therapeutic doses of digitalis on functional (F), relative (R) and effective (E) refractory periods (RP) of the His-Purkinje system (HPS) was studied in 12 open-chested, innervated adult mongrel dogs (10-20 kg) during control and 15, 30 and 45-60 min after 0.016 mg/kg of intravenous ouabain. To determine the stability of the preparation and to assess time-dependent changes in His-Purkinje refractoriness, another six dogs (Group II) had similar studies, but without drug administration. In all dogs, the His bundle was paced by using the plunge wire technique at a predetermined cycle length (CL) and a premature stimulus (S2) to the His bundle was introduced at decreasing S1 S2 intervals. Following ouabain, in Group I dogs, at the longest Cls tested (458 +/- 125 msec; +/- SD) there was significant increase in the FRP (+4.34%; P less than 0.05), RRP (S2 V2 (+6.57%, P less than 0.05), RRP (Ab) (+6%, P less than 0.05) and ERP (52%, P less than 0.05) of the HPS. These significant changes were generally observed 30 minutes after drug administration. Changes in RPs were of greater magnitude at longer CLs (greater than 400 msec), but insignificant at shorter CLs (less than 400 msec). The H-V interval during sinus rhythm and the S1 V1 interval during His bundle pacing at all CLs did not change after ouabain. In Group II dogs there were no significant change in His-Purkinje refractoriness over 60 minutes. These findings suggest that therapeutic doses of digitalis 1) tend to increase refractoriness within the HPS to a very small degree, 2) have no appreciable effect on His-Purkinje conduction, and 3) affect CL-dependent changes in refractoriness. The His bundle extrastimulus method is useful in studying the HPS in the intact heart.

Animals↗
PubMed1977

P loops during common and uncommon atrial flutter in man.

Atrial flutter has never been satisfactorily defined. The 'common' pattern of flutter was originally described by Lewis in 1913. Less frequently observed forms of flutter are termed 'uncommon'. Sixteen cases of the 'common' and 6 of the 'uncommon' type have been studied using isolated P loop vectorcardiography. All patients had some degree of atrioventricular block but none had evidence of digitalis excess. The atrial rates were regular and were in a range between 250 and 330/minute. Vagal manoeuvres increased AV block in each instance. All those with the 'common' type of flutter had P loops with a caudad-cephalad orientation and fifteen of the sixteen had forces which descended over the right atrium and ascended over the left atrium. The 6 cases of the uncommon type of flutter had rates which ranged between 250 and 300/minute and did not fulfil both of the criteria for 'common' flutter; namely continuous baselineu ndulation and prominent negative P deflections in the inferior leads. The cases with the 'uncommon' type of flutter had a variety of loop patterns. The most frequent type was oriented inferior slightly to the right and anterior. One patient satisfied criteria for left atrial flutter. In another the loop was oriented inferior leftward and anterior. The vectorcardiogram provides a rich source of descriptive data but does not identify the underlying mechanism(s) of flutter.

Aged↗
PubMed1977

Modification and abolition of re-entry within the His-Purkinje system in man by diphenylhydantoin.

The phenomenon of macrore-entry (Re) within the His-Purkinje system (HPS) was consistently observed in 10 of 19 patients during retrograde refractory period studies. Effects of intravenous infusion of diphenylhydantoin (DPH) on Re were studied in these 10 patients 10 minutes after completion of infusion (mean plasma level equal to 17.0 microgram/ml). Diphenylhydantoin modified determinants of Re in seven patients (group I) and abolished Re in the remaining three patients (group II). In group I, DPH shortened the critical V1 V2 from 310.0 +/- 30.5 to 292.9 +/- 25.6 msec (P less than 0.025) and critical V2 H2 intervals for Re from 201.4 +/- 18.4 to 185.0 +/- 13.8 msec (P greater than 0.05). In group II, DPH abolished Re in two of three patients by precluding attainment of critical V2 H2 intervals whereas Re was abolished in the remaining one patient despite attainment of critical V2 H2 intervals (vs control). For both groups, DPH significantly shortened functional and effective refractory periods of the HPS (P less than 0.001 and less than 0.01, respectively) without significantly affecting the effective refractory period of the ventricular muscle. Diphenylhydantoin either completely abolished or significantly shortened the retrograde gap zones in the HPS. It is concluded that diphenylhydantoin significantly shortens His-Purkinje system refractoriness, abolishing Re in the patients with higher degree of improvement in refractoriness.

Adult↗
PubMed1976

Abnormal Q waves in Wolff-Parkinson-White syndrome. Incidence and clinical significance.

Between January 1970 and January 1975 the diagnosis of Wolff-Parkinson-White syndrome was entertained in 44 patients. Thirty-one (70%) of these patients had negative sigma-deflections (Q waves) on one or more electrocardiographic leads, thereby simulating a pattern of myocardial infarction (Mi). Fifteen patients (34%) were initially referred with an erroneous diagnosis of Mi based on the presence of Q waves. In nine of these 15 patients, the referring diagnosis was Mi plus ventricular preexcitation; in six, the diagnosis of ventricular preexcitation was overlooked entirely. The incidence of misdiagnosis (34%) was exactly the same as that reportly by Wolff and White approximately 30 years ago. Erroneous diagnosis of Mi can be virtually eliminated by normalizing the QRS complex by premature stimulation of the atrium during the effective refractory period of the accessory pathway.

Adult↗
PubMed1976

Interventricular septal motion during preexcitation and normal conduction in Wolff-Parkinson-White syndrome: echocardiographic and electrophysiologic correlation.

Interventricular septal motion was studied by echocardiogram in 20 consecutive patients with documented Wolff-Parkinson-White (WPW) syndrome before and during electrophysiologic evaluation using His bundle recordings and pacing techniques. Characteristic abnormal interventricular septal motion was seen in 8 of 11 patients with type B WPW syndrome (groups I and II). All eight patients had electrocardiographic patterns consistent with an anomalous pathway located in the anterior right ventricular wall (group I). In five of these eight patients normalization of the QRS complex for one or more beats was accomplished and produced normalization of the septal motion in four; whereas in the fifth patient, who had an underlying atrial septal defect, the abnormal septal motion remained abnormal. All nine patients with type A WPW syndrome (groups III to V) had normal septal motion both during total preexcitation and during normalization of the QRS complex. The normalization of the abnormal interventricular septal motion with normalization of the QRS complex in type B WPW syndrome strongly suggests that the abnormal motion is related to an abnormal sequence of ventricular depolarization during preexcitation. Furthermore, persistent abnormal septal motion after normalization of the QRS complex suggests that other factors such as right ventricular volume overload may be responsible. Likewise, when abnormal septal motion occurs in the presence of type A WPW syndrome, an explanation other than preexcitation must be sought.

Adolescent↗
PubMed1976

Electrophysiologic effects of procainamide in subtherapeutic to therapeutic doses on human atrioventricular conduction system.

The effects of single intravenous infusions of 50 to 400 mg of procainamide on the functional properties of the atrioventricular (A-V) conduction system were studied in 36 patients and correlated with plasma concentrations. A 50 mg dose of procainamide resulted in a plasma concentration of less than 1.0 mug/ml and produced no electrophysiologic changes. Doses of 100, 200, 300 and 400 mg resulted in progresively increasing plasma concentrations (1.2, 1.8, 3.5 and 4.2 mug/ml, respectively). The effects of procainamide on the sinus rate were variable and not dose-related. The effects of doses of up to 300 mg on A-V nodal conduction were variable and not dose-related. Only in a dose of 400 mg did procainamide prolong A-V nodal conduction in six of seven patients. Whereas 100 mg had no effect on His-Purkinje system conduction, doses of 200, 300 and 400 mg prolonged His-Purkinje system conduction time by 6, 8 and 9 msec, respectively. Dose-related increases in atrial refractoriness started with a dose of 200 mg and became statistically significant with doses of 300 and 400 mg. The effects of procainamide on A-V nodal functional refractoriness were variable and not dose-related, but in doses of 100 to 400 mg, procainamide produced significant and progressively dose-related increases in His-Purkinje system refractoriness. Suppression of some types of ventricular arrhythmia by small doses of this drug may be explained by changes in refractoriness of the His-Purkinje system produced by doses of procainamide as small as 100 mg.

Atrioventricular Node↗
PubMed1976

The 1,2,3,4 phenomenon. Atrioventricular nodal gap in the dog.

This study confirms the facility with which the so-called 1,2,3,4 phenomenon can be reproduced in intact dog hearts. When a series of three atrial premature beats (A2, A3, A4) were delivered following a constant A1-A1 drive, we demonstrated a narrow zone of A1-A3 and A1-A4 intervals in which A4 conducted to the ventricles in the presence of A3 but not in its absence. We used His bundle and multiple atrial electrograms to produce the phenomenon in nine of 16 dogs. Facilitation of conduction of A4 (1) occurred above the His bundle, (2) occurred within narrow ranges of A1-A3 and A1-A4 intervals, (3) required penetration of A3 into the atrioventricular (AV) node, (4) required critically long A2-H2 intervals, (5) always was associated with prolonged A4-H4 intervals, and (6) was limited by atrial refractoriness. An apparent or pseudo-1,2,3,4 phenomenon demostrated in five of 16 dogs occurred with (1) latency between S4 and A4, (2) a sinus nodal or atrial reentry beat, or (3) an atrial escape beat. In the absence of A3, A4 could be made to conduct by preexciting the ventricle in advance of V2. We found no evidence for dual AV nodal pathways. Our results suggest that the underlying mechanism for the 1,2,3,4 phenomenon is analogous to the phenomenon of the gap in AV conduction.

Animals↗
PubMed1975

Induction of atrioventricular nodal reentrant tachycardia after atropine. Report of five cases.

After intravenous administration of 0.5 mg of atropine sustained atrioventricular (A-V) nodal reentrant tachycardia could be produced in five patients who had no prior historical or electrocardiographic evidence of supraventricular tachycardia. During the control period single atrial echo beats could be demonstrated in four of the five patients, but no instance of sustained tachycardia occurred. Atropine, known to enhance A-V nodal conduction, allowed achievement of longer A-H intervals (Case 1) and provided the necessary balance of conduction and refractoriness within the A-V nodal reentrant pathways (Cases 1 to 5) to sustain A-V nodal reentry in these patients.

Adolescent↗
PubMed1975

Time dependent changes in the functional properties of the atrioventricular conduction system in man.

Time dependent changes in the electrophysiological properties of the atrioventricular conducting system (AVCS) were determined at two or more cycle lengths (CL) in 22 patients using bundle of His (H) electrograms, incremental atrial pacing and atrial extrastimulus method. The atrioventricular (A-H interval) and intraventricular (H-V interval) conduction times and refractory periods (RP) of the atrium, the A-V node (AVN) and His-Purkinje system (HPS) were measured during the control period, and repeat measurements were made after a 30 minute interval in eight patients (group A), after a 60 minute interval in nine (group B) and after 30 and 60 minute intervals in five (group C). No statistically significant changes from control values were seen after 30 and 60 minute intervals in any group in sinus rate, A-V nodal conduction time and the onset of A-V nodal Wenckebach block. H-V intervals were identical to the control values in all groups. Insignificant changes from control values occurred in RP of the atrium and HPS. Only the functional refractory period (FRP) of the AVN showed a statistically significant decrease from control values in groups B and C. This decrease could be explained by changes in autonomic tone. These observations in general confirm the reproducibility of electrophysiological properties of AVCS within one hour, and further support the validity of the techniques utilized in this and previously reported studies in the evaluation of cardioactive drugs.

Adult↗