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Biomedical subjects

L H Ling

Publications and source records attributed to L H Ling.

At least 19 recordsLinked to original sources
PubMed2002

Molecular descriptors that influence the amount of drugs transfer into human breast milk.

Most drugs are excreted into breast milk to some extent and are bioavailable to the infant. The ability to predict the approximate amount of drug that might be present in milk from the drug structure would be very useful in the clinical setting. The aim of this research was to simplify and upgrade the previously developed model for prediction of the milk to plasma (M/P) concentration ratio, given only the molecular structure of the drug. The set of 123 drug compounds, with experimentally derived M/P values taken from the literature, was used to develop, test and validate a predictive model. Each compound was encoded with 71 calculated molecular structure descriptors, including constitutional descriptors, topological descriptors, molecular connectivity, geometrical descriptors, quantum chemical descriptors, physicochemical descriptors and liquid properties. Genetic algorithm was used to select a subset of the descriptors that best describe the drug transfer into breast milk and artificial neural network (ANN) to correlate selected descriptors with the M/P ratio and develop a QSAR. The averaged literature M/P values were used as the ANN's output and calculated molecular descriptors as the inputs. A nine-descriptor nonlinear computational neural network model has been developed for the estimation of M/P ratio values for a data set of 123 drugs. The model included the percent of oxygen, parachor, density, highest occupied molecular orbital energy (HOMO), topological indices (chiV2, chi2 and chi1) and shape indices (kappa3, kappa2), as the inputs had four hidden neurons and one output neuron. The QSPR that was developed indicates that molecular size (parachor, density) shape (topological shape indices, molecular connectivity indices) and electronic properties (HOMO) are the most important for drug transfer into breast milk. Unlike previously reported models, the QSPR model described here does not require experimentally derived parameters and could potentially provide a useful prediction of M/P ratio of new drugs only from a sketch of their structure and this approach might also be useful for drug information service. Regardless of the model or method used to estimate drug transfer into breast milk, these predictions should only be used to assist in the evaluation of risk, in conjunction with assessment of the infant's response.

Animals↗
PubMed2001

Annulus paradoxus: transmitral flow velocity to mitral annular velocity ratio is inversely proportional to pulmonary capillary wedge pressure in patients with constrictive pericarditis.

BACKGROUND: The early diastolic velocity of the mitral annulus (E') is reduced in patients with diastolic dysfunction and increased filling pressures. Because transmitral inflow early velocity (E) increases progressively with higher filling pressures, E/E' has been shown to have a strong positive relationship with pulmonary capillary wedge pressure (PCWP) and left ventricular end-diastolic pressure. However, previous studies have primarily involved patients without a pericardial abnormality. In constrictive pericarditis (CP), E' is not reduced, despite increased filling pressures. This study evaluated the relationship between E/E' and PCWP in patients with CP. METHODS AND RESULTS: We studied 10 patients (8 men; mean age, 64+/-7 years) with surgically confirmed CP. Doppler echocardiography was performed to measure early and late diastolic transmitral flow velocities. Tissue Doppler echocardiography was performed to measure E'. PCWP was measured with right heart catheterization. All patients were in sinus rhythm. Mean E and E' were 91+/-15 cm/s and 11+/-4 cm/s, respectively. Mean PCWP was 25+/-6 mm Hg. E' was positively correlated with PCWP (r=0.69, P=0.027). There was a significant inverse correlation between E/E' and PCWP (r=-0.74, P=0.014). Despite high left ventricular filling pressures, E/E' (mean, 9+/-4) was <15 in all but 1 patient. CONCLUSIONS: Paradoxical to the positive correlation between E/E' and PCWP in patients with myocardial disease, an inverse relationship was found in patients with CP.

Aged↗
PubMed2001

Poisoning with the recreational drug paramethoxyamphetamine ("death").

OBJECTIVE: To describe the clinical features of paramethoxyamphetamine (PMA; "death") poisoning and to compare these with those of people with self-reported "ecstasy" poisoning. DESIGN: Retrospective casenote review. PARTICIPANTS AND SETTING: 22 patients who presented to the Emergency Department of the Royal Adelaide Hospital (RAH), a major metropolitan teaching hospital, between 1 January 1996 and 31 December 1998 with PMA poisoning identified through urine drug screens; and 61 patients with self-reported ecstasy poisoning between 1 September 1997 and 31 December 1998 found through the hospital databases. RESULTS: Patients with PMA poisoning presented with tachycardia (64%), hyperthermia (temperature > 37.5 degrees C; 36%), coma (41%), seizures (32%), arrhythmias (23%), and QRS intervals > or = 100 ms (50%) with greater frequency and often greater severity than those with self-reported ecstasy poisoning. Two patients with PMA poisoning presented with severe hypoglycaemia (blood glucose level, < 1.5 mmol/L) accompanied by hyperkalaemia (K+ concentration, > 7.5 mmol/L). CONCLUSIONS: At our hospital, PMA poisonings accounted for most of the severe reactions among people who believed they had taken ecstasy. Hypoglycaemia and hyperkalaemia may be specific to PMA poisoning. PMA toxicity should be suspected with severe or atypical reactions to "ecstasy", and confirmed by chromatographic urine drug screens.

Adolescent↗
PubMed2001

Analysis of systolic and diastolic time intervals during dobutamine-atropine stress echocardiography: diagnostic potential of the Doppler myocardial performance index.

Systolic and especially diastolic Doppler time intervals may be early markers of myocardial ischemia inducible by dobutamine-atropine stress echocardiography (DASE). We postulated that the Doppler myocardial performance index (MPI) may help differentiate ischemic from nonischemic responses. Hemodynamic and Doppler echocardiography variables were measured prospectively at every stress level of DASE in 32 patients (mean age 67 +/- 13 years). Adequate recordings were obtained in 27 patients; 13 had an ischemic response (group I) and 14 a nonischemic response (group II). Heart rate differed between groups at baseline. At equivalent peak stress, left ventricular wall motion score index was significantly greater and ejection fraction lower in group I patients. Of the Doppler variables, only the MPI consistently differed between groups, irrespective of the number of stress levels compared. The Doppler MPI may be a useful adjunct to wall motion analysis in the detection of myocardial ischemia during DASE.

Adrenergic beta-Agonists↗
PubMed2000

Calcific constrictive pericarditis: is it still with us?

BACKGROUND: The presence of pericardial calcification on a plain radiograph strongly suggests constrictive pericarditis in patients with heart failure. However, calcific constrictive pericarditis is considered rare in the United States since tuberculosis incidence has decreased, and doubt has therefore been raised about the importance of this radiologic finding in modern cardiovascular practice. OBJECTIVE: To determine the clinical and prognostic significance of pericardial calcification on radiography in patients with constrictive pericarditis. DESIGN: Retrospective cohort study. SETTING: Tertiary referral center. PATIENTS: A consecutive series of 135 patients (mean age +/- SD, 56 +/- 16 years) who from 1985 through 1995 had constrictive pericarditis confirmed surgically (n = 133) or by autopsy (n = 2). Patients were divided into two groups: those with pericardial calcification on chest radiography (group I) and those without (group II). MEASUREMENTS: Clinical and diagnostic findings were compared in both groups, and outcome was compared in 132 patients who had pericardiectomy. RESULTS: Pericardial calcification was seen in 36 patients (27%). The cause of constrictive pericardial disease was indeterminate in 67% of patients in group I and in 21% of patients in group II (P < 0.001). Patients in group I had had symptoms for a longer period and were more likely to have pericardial knock, larger atrial size, and atrial arrhythmia. Significantly more perioperative deaths were seen in group I, but incidence of late survival and incidence of noncalcific disease were similar in both groups. CONCLUSIONS: Pericardial calcification is a common finding in patients with constrictive pericarditis. It is often associated with idiopathic disease and other markers of disease chronicity and is an independent predictor of increased perioperative mortality rates.

Adolescent↗
PubMed2000

Diagnosis of pacemaker lead infection using transoesophageal echocardiography: a case report.

INTRODUCTION: Vegetative lead infection is an uncommon complication of permanent pacemaker implantation. The diagnosis is difficult using conventional imaging methods. CLINICAL PICTURE: An elderly Indian woman with a history of diabetes mellitus developed Staphylococcus aureus infection after implementation of a permanent pacemaker. Following a non-diagnostic transthoracic echocardiogram, transoesophageal echocardiography was performed and showed a large vegetative mass attached to the pacemaker lead within the right atrium. TREATMENT: The pacemaker was removed and intravenous vancomycin administered for six weeks. OUTCOME: She was discharged well but demised two months later from a second episode of septicaemia. CONCLUSIONS: Pacemaker lead infection remains a challenging management problem. Transoesophageal echocardiography can facilitate its diagnosis.

Aged↗
PubMed1999

Constrictive pericarditis in the modern era: evolving clinical spectrum and impact on outcome after pericardiectomy.

BACKGROUND: The clinical spectrum of constrictive pericarditis (CP) has been affected by a change in incidence of etiological factors. We sought to determine the impact of these changes on the outcome of pericardiectomy. METHODS AND RESULTS: The contemporary spectrum of CP in 135 patients (76% male) evaluated at the Mayo Clinic from 1985 to 1995 was compared with that of a historic cohort. Notable trends were an increasing frequency of CP due to cardiac surgery and mediastinal radiation and presentation in older patients (median age, 61 versus 45 years). Perioperative mortality decreased (6% versus 14%, P = 0.011), but late survival was inferior to that of an age- and sex-matched US population (57+/-8% at 10 years). The long-term outcome was predicted independently by 3 variables in stepwise logistic regression analyses: (1) age, (2) NYHA class, and most powerfully, (3) a postradiation cause. Of 90 late survivors in whom functional class could be determined, functional status had improved markedly (2.6+/-0.7 at baseline versus 1.5+/-0.8 at latest follow-up [P<0.0001]), with 83% being free of clinical symptoms. CONCLUSIONS: The evolving profile of CP, with increasingly older patients and those with radiation-induced disease in the past decade, significantly affects postoperative prognosis. Long-term results of pericardiectomy are disappointing for some patient groups, especially those with radiation-induced CP. By contrast, surgery alleviates or improves symptoms in the majority of late survivors.

Adolescent↗
PubMed1999

Left ventricular systolic and diastolic function after pericardiectomy in patients with constrictive pericarditis: Doppler echocardiographic findings and correlation with clinical status.

OBJECTIVES: The study assessed changes in left ventricular systolic and diastolic function after pericardiectomy in patients with constrictive pericarditis and correlated postoperative Doppler echocardiographic findings with clinical status. BACKGROUND: Despite the efficacy of pericardiectomy, some patients with constrictive pericarditis fail to improve postoperatively. Data on serial evaluation of systolic and diastolic function after pericardiectomy and its relation to clinical status are not available. METHODS: From 1985 to 1995, a total of 58 patients with constrictive pericarditis underwent pericardiectomy and had at least one follow-up Doppler echocardiographic study with a respirometer: 23 patients had one examination within 3 months postoperatively, 19 had a study within 3 months and another one more than 3 months postoperatively, and 16 had one study more than 3 months postoperatively. RESULTS: In the early postoperative period, diastolic function was normal in 17 patients (40.5%), restrictive in 17 (40.5%), and constrictive in 8 (19%). Among 19 patients who had serial Doppler echocardiography, in 2 patients with restrictive physiology and 5 with constrictive physiology the results had become normal, and 1 patient who had had constrictive physiology had restrictive findings. In late follow-up, left ventricular end-diastolic diameter increased compared with preoperative measurement (p = 0.0009). Diastolic filling pattern at late follow-up was normal in 20 patients (57%), restrictive in 12 (34%) and constrictive in 3 (9%). There was a significant relationship between diastolic filling patterns and symptomatic status (chi2 = 20.9, p < 0.0001). Patients with persistent abnormal diastolic filling on Doppler echocardiography had had symptoms for a longer time preoperatively than did patients with normal diastolic physiology (p = 0.0471). CONCLUSIONS: Diastolic filling characteristics remain abnormal in a substantial number of patients with constrictive pericarditis after pericardiectomy. These abnormalities may resolve gradually but can persist. Diastolic filling abnormalities after pericardiectomy correlate well with clinical symptoms and tend to occur in patients who have had symptoms longer preoperatively. This finding supports the recommendation that pericardiectomy be performed promptly in symptomatic patients with constrictive pericarditis.

Adolescent↗
PubMed1999

Sudden death in mitral regurgitation due to flail leaflet.

OBJECTIVES: We sought to assess the incidence and determinants of sudden death (SUD) in mitral regurgitation due to flail leaflet (MR-FL). BACKGROUND: Sudden death is a catastrophic complication of MR-FL. Its incidence and predictability are undefined. METHODS: The occurrence of SUD was analyzed in 348 patients (age 67 +/- 12 years) with MR-FL diagnosed echocardiographically from 1980 through 1994. RESULTS: During a mean follow-up of 48 +/- 41 months, 99 deaths occurred under medical treatment. Sudden death occurred in 25 patients, three of whom were resuscitated. The sudden death rates at five and 10 years were 8.6 +/- 2% and 18.8 +/- 4%, respectively, and the linearized rate was 1.8% per year. By multivariate analysis, the independent baseline predictors of SUD were New York Heart Association (NYHA) functional class (p = 0.006), ejection fraction (p = 0.0001) and atrial fibrillation (p = 0.059). The yearly linearized rate of sudden death was 1% in patients in functional class I, 3.1% in class II and 7.8% in classes III and IV. However, of 25 patients who had SUD, at baseline, 10 (40%) were in functional class I, 9 (36%) were in class II and only 6 (24%) in class III or IV. In five patients (20%), no evidence of risk factors developed until SUD. In patients with an ejection fraction > or =60% and sinus rhythm, the linearized rate of SUD was not different in functional classes I and II (0.8% per year). Surgical correction of MR (n = 186) was independently associated with a reduced incidence of SUD (adjusted hazard ratio [95% confidence interval] 0.29 [0.11 to 0.72], p = 0.007). CONCLUSIONS: Sudden death is relatively common in patients with MR-FL who are conservatively managed. Patients with severe symptoms, atrial fibrillation and reduced systolic function are at higher risk, but notable rates of SUD have been observed without these risk factors. Correction of MR appears to be associated with a reduced incidence of SUD, warranting early consideration of surgical repair.

Aged↗
PubMed1999

Constrictive pericarditis and pleuropulmonary disease linked to ergot dopamine agonist therapy (cabergoline) for Parkinson's disease.

Cabergoline is one of several ergoline dopamine agonist medications used in the treatment of Parkinson's disease (PD). We diagnosed constrictive pericarditis (CP) in a patient with PD receiving cabergoline therapy (10 mg daily), who had symptoms and signs of congestive heart failure (CHF). In the absence of previous reported cases of this condition linked to ergoline drugs, cabergoline was not initially identified as the cause. Shortly thereafter, however, the patient developed of a severe pleuropulmonary inflammatory-fibrotic syndrome, a recognized complication of ergoline medications, thus suggesting a common pathogenesis due to cabergoline therapy. To our knowledge, this is the first case in the English literature, although we speculate that CP may be more common than reported among patients with PD who are treated with an ergoline drug (cabergoline, bromocriptine, pergolide, or lisuride). The diagnosis of CP is difficult and requires a high level of suspicion; symptoms may masquerade as CHF due to common mechanisms such as coronary artery disease. In patients with PD who are taking not only cabergoline but also one of the other ergoline drugs, CP should be suspected if symptoms of CHF develop.

Aged↗
PubMed1997

Early surgery in patients with mitral regurgitation due to flail leaflets: a long-term outcome study.

BACKGROUND: The optimal timing for surgery in patients with mitral regurgitation is disputed. Because of the frequency of left ventricular dysfunction, which is difficult to predict, early surgery has been recommended, but its potential benefits have not been demonstrated. METHODS AND RESULTS: The outcomes of 221 patients (mean age, 65 +/- 13 years; 71% males) with flail leaflets diagnosed with two-dimensional echocardiography between 1980 and 1989 who were eligible for operation were analyzed. Group I comprised 63 patients who had early mitral valve surgery (within 1 month after diagnosis). Group II comprised 158 patients initially treated conservatively (80 of whom were operated on later). Group I patients were younger (P=.009), had more symptoms (P<.0001), and were more frequently in atrial fibrillation (P=.023) than group II patients. There was no difference in ejection fraction between the groups. The early surgery strategy was followed by an improved overall survival rate (P=.028) and a lower incidence of cardiovascular deaths (P=.025), congestive heart failure (P=.046), and new chronic atrial fibrillation (P=.032), as confirmed by multivariate analysis (adjusted risk ratios of 0.31, 0.18, 0.38, and 0.05, respectively; all P<.02). CONCLUSIONS: In patients with mitral regurgitation due to flail leaflets, the strategy of early surgery versus conservative management is associated with an improved long-term survival rate, decreased cardiac mortality, and decreased morbidity after diagnosis. This outcome advantage suggests that early surgery is a reasonable treatment option to be considered in low-risk candidates with repairable valves and severe mitral regurgitation.

Aged↗
PubMed1997

Pericardial thickness measured with transesophageal echocardiography: feasibility and potential clinical usefulness.

OBJECTIVES: This study assessed the reliability of transesophageal echocardiographic measurements of pericardial thickness and the potential diagnostic usefulness of this technique. BACKGROUND: Transthoracic echocardiography cannot reliably detect thickened pericardium. The superior resolution achieved with transesophageal echocardiography should allow better pericardial definition. METHODS: Pericardial thickness measured at 26 locations in 11 patients with constrictive pericarditis who underwent intraoperative transesophageal echocardiography was compared with pericardial thickness measured with electron beam computed tomography. Intraobserver and interobserver variabilities were determined. Pericardial thickness was then measured in 21 normal subjects. With these values as a guide, two observers reviewed 37 transesophageal echocardiographic studies to determine whether echocardiographic measurement of pericardial thickness could be used to distinguish diseased from normal pericardium. RESULTS: The correlation between echocardiographic and computed tomographic measurements (r > or = 0.95, SE < or = 0.06 mm, p < 0.0001) was excellent. The +/-2 SD limits of agreement were +/-1.0 mm or less for pericardial thickness < 5.5 mm and +/-2.0 mm or less for the entire range of thicknesses. Intraobserver and interobserver agreements were good. Mean normal pericardial thickness was 1.2 +/- 0.8 mm (+/-2 SD) and did not exceed 2.5 mm. Pericardial thickness > or = 3 mm on transesophageal echocardiography was 95% sensitive and 86% specific for the detection of thickened pericardium. CONCLUSIONS: Measurement of pericardial thickness with transesophageal echocardiography is reproducible and should be a valuable adjunct in assessing constrictive pericarditis.

Case-Control Studies↗
PubMed1997

Dobutamine stress echocardiography in the elderly Asian patients.

Dobutamine stress echocardiography (DSE) is an established non-invasive technique for the evaluation of coronary artery disease (CAD). It has been shown to be both safe and accurate. However, its utility and safety in the elderly, in particular, elderly Asian patients has not been studied. Between September 1992 and December 1994, we performed a total of 75 consecutive DSE studies in patients over the age of 65. Of these, 50 (67%) were females. Forty-nine patients had hypertension, 26 had diabetes mellitus, 10 were smokers, 5 had a recent or previous myocardial infarction and another 4 had a history of heart failure. Indications for DSE were, inability to perform the standard treadmill exercise test (40 patients), an abnormal resting electrocardiogram (ECG) (14 patients), a prior false positive or inconclusive treadmill test, risk stratification post myocardial infarction (4 patients) or preoperative cardiac evaluation (23 patients). The test was terminated in the majority of patients following attainment of the target heart rate. Atropine stimulation was required in 61 (81%) patients. Chest pain was provoked in 11 patients. No death or myocardial infarction occurred. Minor non-cardiac symptoms occurred in another 6 patients but this did not necessitate termination of the procedure. Three patients had transient hypotension, none of which was symptomatic. Arrhythmia occurred in 23 patients but the majority were isolated atrial or ventricular premature beats (20); 1 patient had atrial fibrillation and another developed transient junctional rhythm. Only one patient developed ventricular tachycardia but this was not haemodynamically significant and terminated easily with an intravenous dose of lignocaine. A conclusive result could be obtained in 72 (96%) patients. We concluded that DSE could be performed and interpreted in the majority of elderly Asian patients studied. Despite supplemental atropine, an aggressive dosing protocol and the inclusion of patients with a myocardial scar or history of heart failure, adverse effects were rare and often did not require any specific therapy.

Aged↗