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Biomedical subjects

C Lai

Publications and source records attributed to C Lai.

At least 19 recordsLinked to original sources
PubMed1992

Haemodialysis as a model for studying endogenous plasma DNA: oligonucleosome-like structure and clearance.

The rate of clearance of extracellular plasma DNA in man has important implications for pathogenetic mechanisms in systemic lupus erythematosus (SLE), as well as for certain other clinical states. Present knowledge of this parameter is derived exclusively from studies of injected, naked DNA in animals. Recent information indicates that the physiologic form of plasma DNA in SLE is that of oligonucleosome-like molecules rather than of naked DNA and consists of multimeric complexes of DNA bound to histone, probably arising from an apoptotic process. In order to study the rate at which these oligonucleosome-like complexes are removed from plasma and to do so in man rather than experimental animals, we exploited the observation that during haemodialysis large amounts of DNA are released, apparently within the dialysis coil, into the patient's plasma. Since this release appears to cease promptly with termination of the procedure, it offered the potential for estimating the rate of removal of such DNA from human plasma. Moreover, if that DNA, as postulated, were shown to possess an oligonucleosome-like structure resembling that found endogenously in human SLE, the relevance of such information to the human disease state would be further enhanced. The present results support the conclusion that DNA released into plasma during haemodialysis possesses such an oligonucleosome-like structure. The plasma half-life of that DNA in man was found not to exceed 4 min. The highly dynamic state thus implied for extracellular endogenous plasma DNA in man has important implications for pathogenetic mechanisms dependent on dsDNA in SLE. Moreover, individuals undergoing chronic haemodialysis, who are thereby exposed to a very large cumulative amount of such DNA, might serve as models for studying its long-term sequelae.

DNA↗
PubMed1992

The role of the pericardium in conditioning the effects of physical training.

More work needs to be done on the extent to which the pericardium can modulate the cardiovascular response to exercise and the mechanisms whereby this modulation is brought about. Studies are needed to differentiate the effects of the pericardium on the cardiovascular exercise response, comparing trained with untrained subjects. Evidence is accumulating that exercise training in patients with heart failure improves not only the performance of exercising muscles, but also has some beneficial effects on central hemodynamics. The extent to which these beneficial effects can be attributed to conditioning the pericardium remains speculative.

Adaptation, Physiological↗
PubMed1992

Effect of calcium antagonists on exercise tests.

The aim of this study was to investigate the anti-ischemic and antianginal activity and the duration of the new dihydropyridine calcium blocker nisoldipine (NIS) in patients with stable angina pectoris. The research was carried out on 16 patients, all male, 41-68 (mean of 58) years of age, with stable angina pectoris and fixed ischemic threshold (variations < 15%). After a 10-day washout period, patients were randomized to treatment with either 10 mg of nisoldipine or placebo (PL), twice daily for 21 days, according to a double-blind, crossover design. Patients underwent maximal symptom-limited exercise testing at 10 W/min on a bicycle ergometer, twice during the washout period, and once at the end of each treatment period, 3 and 12 h after oral administration of the drugs. In comparison with placebo, nisoldipine increased the ischemic threshold (N, 704 +/- 45 s; PL, 548 +/- 35 s; p < 0.01) and anginal threshold (N, 766 +/- 44 s; PL, 699 +/- 42 s; p < 0.01) for at least 12 h, and the ST-segment depression significantly decreased at maximal work (PL, 2.4 +/- 0.1 mm; N, 1.8 +/- 0.2 mm; p < 0.01) and at maximal common work (PL, 2.4 +/- 0.1 mm; N, 1.15 +/- 0.2 mm; p < 0.01). Similar to placebo the rate-pressure product was not significantly changed at higher submaximal effort after N, but it was significantly increased at the level of ischemic threshold, suggesting an increase in coronary blood flow to ischemic zones. Nisoldipine possesses anti-ischemic and antianginal activity lasting at least 12 h. This activity seems to be due to an increase in coronary blood flow to ischemic zones.

Adult↗
PubMed1992

Slow-release gallopamil in patients with stable effort angina.

Gallopamil (GSR) is a new calcium-channel blocker. The anti-ischemic activity of GSR was investigated in 12 patients with stable angina of effort, with fixed ischemic threshold (variations < 15%). After a 7-day washout period, patients were randomized to receive treatment with either GSR 100 mg or placebo twice daily for 7 days. Patients underwent maximal symptom-limited exercise test, 10 W/min on a bicycle, during washout (twice) and after the end of each treatment period. Patients were studied by electrocardiogram and the cuff method for determining systolic blood pressure. After treatment with GSR, ischemic and anginal thresholds were increased for at least 12 h in comparison with placebo (ischemic threshold: GSR 663 +/- 37, placebo 571 +/- 36, p < 0.01; anginal threshold: GSR 708 +/- 32, placebo 646 +/- 38, p < 0.05). Rate-pressure product was not changed at the same levels of exercise, but it was significantly increased during exercise at ischemic threshold. In conclusion, GSR possesses an anti-ischemic and antianginal activity lasting at least 12 h. This activity seems due to an increase of coronary blood flow to ischemic areas.

Aged↗
PubMed1992

[The effect of nifedipine on arterial pressure and exercise tolerance in hypertensive patients].

The aim of this research was to assess whether the antihypertensive therapy with nifedipine, a dihydropyridine calcium-antagonist, is able to control hypertension not only at rest but also during exercise. So, 20 male hypertensive patients, mean age 48 years, were evaluated by symptom limited bicycle exercise (10 W/min) before and after 6 and 12 months of therapy with nifedipine in a slow releasing form (40-60 mg/day). Exercise tolerance significantly increased after 12 months of antihypertensive therapy with nifedipine (from 146 +/- 5 to 153 +/- 4 W, p < 0.05). Systolic and diastolic blood pressure decreased after 6 and 12 months both at rest (from 160 +/- 6/109 +/- 9 mmHg to 132 +/- 3/91 +/- 3 and 135 +/- 4/93 +/- 1 mmHg, respectively, both p < 0.001) and during exercise (at end exercise: from 238 +/- 7/121 +/- 5 mmHg to 216 +/- 6/106 +/- 3 and 213 +/- 6/107 +/- 3 mmHg, respectively, both p < 0.001). No significant changes in heart rate were observed during antihypertensive therapy both at rest and during exercise test. In conclusion, long-term antihypertensive therapy with nifedipine was effective in the control of hypertension both at rest and during physical stress. Moreover, an improvement in effort tolerance was observed in hypertensive patients.

Adult↗
PubMed1991

An extended family of protein-tyrosine kinase genes differentially expressed in the vertebrate nervous system.

We have used PCR to identify 13 novel protein-tyrosine kinase genes (tyro-1 to -13), six of which (tyro-1 to -6) are preferentially expressed in the developing vertebrate nervous system. The tyro-2 and tyro-9 genes encode kinase domains that exhibit strong amino acid sequence similarity to the equivalent regions of the receptors for EGF and FGF, respectively, and may encode novel receptors for these or related polypeptide ligands. The tyro-1 to -6 genes are all expressed during central nervous system neurogenesis and exhibit distinct and highly regionalized patterns of expression in the adult brain. Together with recent studies in invertebrates, these data are consistent with the hypothesis that protein-tyrosine kinases play a central role in neural development.

Amino Acid Sequence↗
PubMed1991

Bone-inducing activity of mature BMP-2b produced from a hybrid BMP-2a/2b precursor.

The human osteoinductive proteins BMP-2a and BMP-2b have been cloned and expressed in mammalian cells. In order to improve expression levels we examined the role of the proregion in assembly and export. Use of the BMP-2a proregion combined with the mature region of BMP-2b leads to dramatically improved expression of mature BMP-2b. Mature BMP-2b has been purified to near homogeneity from the BMP-2a/2b hybrid, and its structural properties and biological activity determined. Recombinant mature BMP-2b homodimer elicits bone formation in vivo.

Amino Acid Sequence↗
PubMed1991

[Effects of benazepril, a new ACE inhibitor, in effort angina pectoris].

The aim of this study was to evaluate the anti-ischemic efficacy of 2 different doses of benazepril (B), a new ACE-inhibitor, 10 and 20 mg, given per os. Fifteen male patients gave informed, written consent; they were aged 40-67 years, with stable effort angina pectoris and were randomly given, in double-blind condition, a tablet containing B 10 mg, B 20 mg or placebo (PL), once a day, according to a 3 x 3 latin square design. Bicycle exercise tests were performed on the same day, 2 and 10 hours after the last drug intake. B 10 mg and B 20 mg, in patients with stable effort angina, compared to placebo, increased ischemic threshold and decreased ischemic ST depression at maximal work, after 2 hours but not after 10 hours. In conclusion B 10 mg and B 20 mg showed anti-ischemic activity 2 hours after drug intake.

Adult↗
PubMed1991

[Transdermal nitroglycerin in stable effort angina. I. Therapeutic effect and duration of the action of a single dose. Comparison with placebo and isosorbide dinitrate].

To assess the efficacy of 2 doses of a transdermal system for nitroglycerin, 10 and 20 mg (NTTS 10 and NTTS 20) and isosorbide dinitrate 40 mg (ISD 40) on exercise tolerance test, a double-blind within patients placebo (PL) controlled study was performed: 12 male patients, aged 47-71 years, with stable effort angina, with fixed ischemic threshold, received, according to a 4 x 4 latin square design, NTTS 10, NTTS 20, ISD 40 and PL, at 7.00 am on 4 consecutive days. Bicycle exercise tests were performed 4 and 12 hours post-dosing, after which the systems were removed. NTTS 10 and 20 and ISD 40 increased significantly ischemic threshold, anginal threshold and decreased maximal ST depression at the fourth hour. Only NTTS 10 and NTTS 20 showed antiischemic activity after 12 hours. During exercise, at the fourth and twelfth hour, there was no significant difference in rate-pressure product between placebo and NTTS 10 and 20 and ISD 40. Therefore the antiischemic activity of these drugs was not related to a decrease of myocardial oxygen consumption. In conclusion, in comparison with PL, NTTS 10, 20 and ISD 40 had antiischemic and antianginal activity at the fourth hour, while at the twelfth hour this activity was observed only after NTTS 10 and 20, without differences between the 2 doses.

Administration, Cutaneous↗
PubMed1991

[Transdermal nitroglycerin in stable effort angina. II. Administration of continuous high doses and alternate high-low doses. Absence of tolerance].

Aim of this study was to evaluate the efficacy of 2 different schedules of nitroglycerin (N), given by means of transdermal therapeutic system (TTS): continuous (20 mg patch at 8.00 am and at 8.00 pm NTTS/c) and high/low doses therapy (20 mg patch at 8.00 am and 10 mg at 8.00 pm NTTS/a), respectively. Eighteen volunteers, gave informed, written consent; male patients, aged 57 +/- 2 years, with stable effort angina pectoris, were randomly given, in double-blind condition, NTTS/c, NTTS/a or placebo (PL), each for 1 week period, according to a 3 x 3 latin square design. Bicycle exercise tests were performed on the first and on the last day of each period of the study, 12 hours after the last patch. NTTS/c and NTTS/a increased ischemic threshold and decreased the ischemic depression ST at maximal common work, compared to placebo, without differences between tests performed at 1 and 7 day. In conclusion, NTTS/a showed antiischemic activity after 7 days, so no tolerance was observed in those patients.

Administration, Cutaneous↗
PubMed1991

Late-onset acid maltase deficiency in a Chinese girl.

Late-onset acid maltase deficiency is a rare disorder. We describe a nineteen year old Chinese girl who presented with diarrhoea, limb-girdle weakness and respiratory failure requiring mechanical ventilation. Electromyography showed polyphasic potentials and myotonic discharges. Muscle biopsy revealed features characteristic of acid maltase deficiency. Assay of acid alpha-glucosidase in cultured skin fibroblasts confirmed the diagnosis. Supportive treatment with nocturnal intermittent positive pressure ventilation via a nasal mask and dietary supplementation with branched-chain aminoacids proved effective in this patient. The cause of diarrhoea remained uncertain. This is the first documented case of acid maltase deficiency in Chinese adult.

Adolescent↗
PubMed1991

[A new anti-ischemic drug for the treatment of stable effort angina pectoris: nicorandil. Comparison with placebo and isosorbide-5-mononitrate].

The aim of this study was to investigate antianginal and antiischemic activity and tolerance of a new nitrate derivative, nicorandil (N). This research has been carried out in 18 patients, aged 47-70 years, suffering from stable effort angina with fixed ischemic threshold. The study started with 10 days of washout, during which the patients exercised twice on bicycle to verify the reproducibility of the test. Then, they took N or isosorbide-5-mononitrate (ISM) for 14 days according to a double blinded cross-over balanced study. Between the 2 periods patients took placebo (PL) for 14 days. In the first day and in the last day of each period, 2 hours after the last drug intake, patients performed a stress test on bicycle. Like ISM, N significantly increased, versus PL, 1 mm of ST depression time (ischemic threshold) in the first and in the last day, without differences between the 2 drugs and between the days. Moreover, ST depression was significantly lower at maximal common work (MCW) versus PL. The rate-pressure product was not different from PL after N and ISM at maximal common work, but is was increased at the ischemic threshold. In conclusion, like ISM, N has shown antiischemic activity in patients suffering from stable angina pectoris on effort with fixed ischemic threshold. After 14 days of treatment there was no evidence of tolerance. The activity of N seems essentially due to an increase of coronary blood flow to ischemic zones.

Aged↗
PubMed1991

[What have we learned from large trials?].

Clinical trials, during myocardial infarction, showed the importance of thrombolytic therapy on coronary patency, to improve left ventricular function, to reduce early and late mortality. Since the efficacy of thrombolytic therapy is now well established, most clinical trials were made to compare the efficacy of SK, rt-PA and APSAC and to evaluate concomitant drugs. Recanalization and coronary patency, reocclusion and incidence of side effects, left ventricle function's improvement and lowered mortality have been used to assess drugs' activity. At the moment the efficacy of three thrombolytic drugs seems to be the same. So the drug's choice is related not to drug's efficacy but to side effects of the drugs. Concomitant intravenous heparin therapy is now under study; utility of this therapy is shown by its theoretical assumptions and by clinical trials results. Large clinical trials are working to extend our knowledge, improving the patients' management in our every day clinical practice. Furthermore, large trials do not replace but go together with studies performed on few patients, whose results often give advance notice of those of large ones.

Clinical Trials as Topic↗
PubMed1990

Propionyl carnitine in stable effort angina.

The aim of this study was to investigate the anti-ischemic activity of propionyl carnitine (PC) in 18 informed, volunteer male patients, aged 37-70, suffering from a typical stable effort angina. The study design was randomized, balanced, crossover, and double blinded. The study lasted 75 days. In the first 15 days of washout the patients performed two maximal symptom-limited bicycle tests to verify the repeatability of the parameters examined. Then one group received PC for 30 days 500 mg three times a day, and the other group received placebo (PL) three times a day. At the end of 30 days the groups exchanged treatments. At the end of each period, 2 hours after the last oral administration, the patients performed a maximal symptom-limited bicycle exercise test with increased loads of 10 watts/min. No significant differences were observed between the two tests performed during the wash-out period, for a 1 mm ST-segment depression time, for the time to the end of exercise, and for the rate x pressure product at the same experimental time. The oral administration of PC in coronary patients increased both the 1 mm ST-segment depression time and the time to the end of exercise. Furthermore, the drug reduced the ischemic depression of ST at maximal common work and at maximal work. After PC, the rate x pressure product was not significantly different in relation to placebo at submaximal and maximal exercise. Thus PC seems to have an antiischemiclike effect, probably related to its metabolic activity.

Administration, Oral↗
PubMed1990

Effects of enalapril in normotensive patients with stable effort angina: a double blind, placebo controlled study.

To assess the anti-anginal and anti-ischaemic efficacy of the ACE-inhibitor enalapril in normotensive coronary patients, a double-blind, cross-over, placebo-controlled study was performed. Eight male patients, aged 45-68 years, with stable effort angina were given enalapril (10 mg) once a day or placebo for 7 days. Maximal exercise stress tests 10w/min in the upright position were performed at the end of each period. In comparison to placebo, enalapril increased significantly 1 mm of ST depression time and decreased significantly ST depression at maximal common work. Moreover, enalapril increased significantly the angina threshold and exercise duration. Three of the eight patients ended the exercise without pain. The rate-pressure product was not significantly modified at any time. Thus, the anti-ischaemic and anti-anginal activity may be due to an increase of coronary blood flow, rather than a reduction of MVO2 consumption.

Aged↗
PubMed1990

[Effects of indenolol on left ventricular mass in patients with essential arterial hypertension].

This study evaluated the effect of long-term antihypertensive therapy with indenolol, a beta blocking agent with beta 2 stimulating activity, its antihypertensive hemodynamic mechanism and its effect on hypertensive left ventricular (LV) hypertrophy. Fourteen hypertensive patients, mean age of 48 years, were serially studied during 12- month therapy with indenolol (60-120 mg daily), by recording blood pressure, electrocardiogram and echocardiogram. Blood pressure, heart rate and cardiac output significantly decreased after 1 months of therapy, LV posterior wall thickness decreased after 6 months, interventricular septum thickness and LV mass decreased after 12 months. LV fractional shortening did not change throughout the study. Blood pressure normalized (less than or equal to 140/90 mmHg) in 50% of the patients; LV mass normalized in 40% of the patients. In conclusion, indenolol was an effective antihypertensive agent, also in the long-term treatment. Its antihypertensive hemodynamic effect seems to be due mainly to a reduction in cardiac output. Indenolol caused a regression of LV hypertensive hypertrophy without impairment of LV systolic function.

Adult↗