Biomedical subjects

K K Tan

Publications and source records attributed to K K Tan.

At least 55 records · Page 3Linked to original sources

PubMed1996

Unusual ritual burns of the hand.

Six hands from five patients were seen with full-thickness burns following a ritual practice between June 1993 and June 1994. Three hands were treated with excision and medium-thickness split-skin grafts, one patient was treated with a medium-thickness split skin graft taken from the instep of the foot. The first patient with bilateral burns of the palms refused surgery and returned 3 months later with contractures of the palms. The results of the treated hands are presented.

Adolescent↗

PubMed1996

In vivo PO2 imaging in the porcine model with perfluorocarbon F-19 NMR at low field.

Quantitative pO2 imaging in vivo has been evaluated utilizing F-19 NMR in the porcine model at 0.14 T for the lungs, liver, and spleen following i.p. administration of the commercial perfluorotributylamine (FC-43)-based perfluorocarbon (PFC) emulsion, Oxypherol-ET. Calculated T1 maps obtained from a two spin-echo saturation recovery/inversion recovery (SR/IR) pulse protocol are converted into quantitative pO2 images through a temperature-dependent calibration curve relating longitudinal relaxation rate (1/T1) to pO2. The uncertainty in pO2 for a T1 measurement error of +/- 5% as encountered in establishing the calibration curves ranges from +/- 10 torr (+/- 40%) at 25 torr to +/- 16 torr (+/- 11%) at 150 torr for FC-43 (37 degrees C). However, additional uncertainties in T1 dependent upon the signal-to-noise ratio may be introduced through the SR/IR calculated T1 pulse protocol, which might severely degrade the pO2 accuracy. Correlation of the organ image calculated pO2 with directly measured pO2 in airway or blood pools in six pigs indicate that the PFC resident in lung is in near equilibrium with arterialized blood and not with airway pO2, suggesting a location distal to the alveolar epithelium. For the liver, the strongest correlation implying equilibrium was evident for venous blood (hepatic vein). For the spleen, arterial blood pO2 (aorta) was an unreliable predictor of pO2 for PFC resident in splenic tissue. The results have demonstrated the utility and defined the limiting aspects quantitative pO2 imaging in vivo using F-19 MRI of sequestered PFC materials.

Animals↗

PubMed1996

An unusual cause of dysphagia.

A case of dysphagia caused by anterior cervical osteophytes is presented. Although dysphagia and cervical spondylosis are common presenting problems, they are often unrelated to each other. The association between the two should, therefore, be accepted with caution; adequate investigation is necessary to avoid misdiagnosis. Review of the literature showed that this condition is relatively rare. The most likely mechanism of dysphagia is interference with swallowing at the pharyngo-oesophageal junction, although osteophytes in the lower cervical spine may also interfere with oesophageal peristalsis. Apart from the osteophytes of cervical spondylosis, those resulting from Forestier's disease, or Diffuse Idiopathic Skeletal Hyperostosis (DISH) have also been described to cause dysphagia.

Cervical Vertebrae↗

PubMed1996

Unilateral pulmonary agenesis: an unusual cause of respiratory distress in the newborn.

Unilateral pulmonary agenesis is a rare disorder and is an unusual cause of respiratory distress in the newborn. It is often associated with other congenital abnormalities, as documented in about 200 cases of unilateral pulmonary agenesis in the current literature. The onset and mode of presentation are highly variable, from asymptomatic cases discovered incidentally to symptomatic cases diagnosed in early infancy. We report a newborn infant with right pulmonary agenesis associated with facial and skeletal abnormalities who presented with respiratory distress. Unilateral pulmonary agenesis should be considered in the differential diagnosis of respiratory distress in the newborn, particularly when there are other associated congenital abnormalities.

Female↗

PubMed1995

Blood cyclosporine concentrations and cytomegalovirus infection following heart transplantation.

We have attempted to identify major risk factors for cytomegalovirus (CMV) infection and disease following heart transplantation, with emphasis on the degree and type of immunosuppression used. One hundred and eleven consecutive heart transplant recipients were studied for the first 4 months. Data from the 95 who survived at least 1 month were analyzed using multiple Cox regression. Blood cyclosporine concentrations (CsAbc) > 550 micrograms L-1 were associated with a 4.4-fold increase in risk of CMV infection during the next week (95% confidence interval = 1.2-16.2). Other significant risk factors for CMV infection included antirejection treatment in the past 14 days, a drop in white blood cell count, receiving a CMV antibody-positive donor organ, and primary diagnosis other than cardiomyopathy. We found that patients experiencing a CMV infection were at 3 times the risk of subsequently developing symptomatic CMV disease (95% confidence interval = 1.1-9.7). In addition, the proportion of patients developing symptomatic CMV disease was significantly higher amongst those with a median CsAbc > 550 micrograms L-1 for at least 1 week (29% vs. 10%; P = 0.02) or who had been treated for rejection more frequently than once every 6 weeks (31% vs. 12%; P = 0.04) during the first 4 months. CMV antibody-negative recipients of antibody-positive donor organs had a higher rate of symptomatic CMV disease than did other serological combinations (67% vs. 10%; P = 0.0001). We conclude that the risk of CMV infection and symptomatic disease following heart transplantation may be critically influenced by early management of immunosuppression as well as by donor serology.

Cyclosporine↗

PubMed1995

Relative bioavailability of cyclosporin from conventional and microemulsion formulations in heart-lung transplant candidates with cystic fibrosis.

Patients with cystic fibrosis absorb cyclosporin poorly and erratically. We have compared the relative bioavailability of cyclosporin from conventional and microemulsion formulations in 5 adult heart-lung transplant candidates with cystic fibrosis. Relative bioavailability was compared at two dose levels (200 mg and 800 mg). A randomized 4-period cross-over study was performed with at least a 7 day washout period between each single dose pharmacokinetic study. Blood cyclosporin concentrations were measured by a selective monoclonal antibody-based radioimmunoassay. The bioavailability of cyclosporin from the microemulsion formulation was 1.84 (95% C.I. 1.05 to 3.22; P = 0.04) and 2.09 (95% C.I. 0.95 to 4.61; P = 0.06) times higher compared with the conventional formulation at 200 mg and 800 mg respectively. Cmax following the microemulsion formulation was 3.38 (C.I. 1.14 to 10.59; P = 0.04) and 2.77 (C.I. 1.48 to 5.19; P = 0.01) times higher compared with the conventional formulation at 200 mg and 800 mg respectively. The higher Cmax following the microemulsion formulation was accompanied by shorter tmax. An enhancement of cyclosporin absorption with the microemulsion formulation was demonstrated in each patient for at least one dose level. We conclude that rate and extent of cyclosporin absorption from the microemulsion formulation is greater compared with the conventional formulation in patients with cystic fibrosis. The potential therapeutic and economic benefits of the microemulsion formulation should be evaluated in cystic fibrosis patients following heart-lung transplantation.

Adult↗

PubMed1995

Estimation of population pharmacokinetics using the Gibbs sampler.

Quantification of the average and interindividual variation in pharmacokinetic behavior within the patient population is an important aspect of drug development. Population pharmacokinetic models typically involve large numbers of parameters related nonlinearly to sparse, observational data, which creates difficulties for conventional methods of analysis. The nonlinear mixed-effects method implemented in the computer program NONMEM is a widely used approach to the estimation of population parameters. However, the method relies on somewhat restrictive modeling assumptions to enable efficient parameter estimation. In this paper we describe a Bayesian approach to population pharmacokinetic analysis which used a technique known as Gibbs sampling to simulate values for each model parameter. We provide details of how to implement the method in the context of population pharmacokinetic analysis, and illustrate this via an application to gentamicin population pharmacokinetics in neonates.

Anti-Bacterial Agents↗

PubMed1995

Effect of dietary fat on the pharmacokinetics and pharmacodynamics of cyclosporine in kidney transplant recipients.

OBJECTIVE: To investigate the effect of dietary fat on the pharmacokinetics and pharmacodynamics of cyclosporine. METHODS: Sixteen stable kidney transplants recipients (mean age, 50.4 years; age range, 19 to 63 years; six women) who were maintained on oral cyclosporine therapy were randomized to receive a high- or low-fat diet for periods of 7 days in a balanced crossover study. The crossover was separated by a 7-day washout period, when the usual diet was followed. Oral cyclosporine was taken once daily with breakfast. Twenty-four-hour pharmacokinetic studies were conducted during each dietary period on day 6 after oral cyclosporine and on day 7 after a 3-hour intravenous cyclosporine infusion (30% of oral dose). Sequential blood samples were also taken after the oral dose on day 6 for lymphocyte transformation studies. RESULTS: The mean breakfast fat intake and total daily fat intake were 6.5 and 5.5 times higher, respectively, during the high-fat diet than during the low-fat diet. The bioavailability and clearance of cyclosporine were found to be significantly higher during the high-fat diet (p = 0.02 and p = 0.01, respectively). As a consequence, the area under the blood concentration-time curve (AUC) after the oral dose was not significantly different between the two diets. There were no significant differences in concanavalin A-stimulated proliferation of peripheral blood lymphocytes between the high- and low-fat diets. CONCLUSIONS: An increased fat content of food significantly increases cyclosporine bioavailability and clearance. However, this is unlikely to be of clinical importance during oral administration because the AUC and pharmacodynamics of cyclosporine are not affected significantly.

Adult↗

PubMed1995

Calcitonin gene-related peptide as an endogenous vasodilator: immunoblockade studies in vivo with an anti-calcitonin gene-related peptide monoclonal antibody and its Fab' fragment.

1. Calcitonin gene-related peptide (CGRP) is localized in perivascular sensory neurons and is a potent vasodilator. We investigated the utility of immunoblockade as an in vivo technique for probing the role of CGRP as an endogenous vasodilator. 2. The effects of an anti-CGRP monoclonal antibody (MAb; coded C4.19) and its Fab' fragment on CGRP-induced changes in blood pressure and skin blood flow were studied in pentobarbitone-anaesthetized rats. Antidromic skin vasodilatation in the rat hind paw was measured by laser Doppler fluxmetry. 3. The dose-response relationship for the hypotensive effect of intravenous rat alpha CGRP (r alpha CGRP) was similarly shifted rightward by MAb C4.19 IgG (1 mg/rat; intravenously) and Fab' fragment (2 mg/rat; intravenously). The C-terminal fragment of human alpha CGRP (h alpha CGRP8-37) also blocked the hypotensive effect of r alpha CGRP. 4. MAb C4.19 Fab' fragment (2 mg/rat; intravenously) and h alpha CGRP8-37 (100 nmol/kg; intravenously), but not MAb C4.19 IgG (up to 3 mg/rat; intravenously) or normal mouse Fab' fragment (2 mg/rat; intravenously), blocked the increased skin blood flow response to antidromic stimulation of the saphenous nerve. 5. The mean percentage changes in skin blood flow parameters due to MAb C4.19 Fab' fragment were significantly different from those due to normal mouse Fab' fragment (unpaired t-test; P < 0.05) but not from those due to h alpha CGRP8-37. 6. The results demonstrate the pharmacokinetic advantage of Fab' fragment over IgG for immunoblockade studies in vivo and support the role of CGRP in mediating skin vasodilatation.

Animals↗

PubMed1995

Absorption of cyclosporin from conventional and new microemulsion oral formulations in liver transplant recipients with external biliary diversion.

1. Less than 5% of a dose of the conventional oral formulation of cyclosporin, Sandimmun, is absorbed in liver transplant recipients with external biliary drainage, necessitating intravenous administration of the drug and exposing the patient to increased risk of severe side-effects. 2. We compared the pharmacokinetics of the conventional oral formulation of cyclosporin with that of the new microemulsion formulation, Neoral, in eight liver transplant recipients with external biliary diversion. Patients were maintained on a continuous infusion of cyclosporin until steady-state conditions had been achieved. They were then given a test dose (10 mg kg-1) of either the conventional or microemulsion formulation (randomised order) followed by the same dose of the other formulation. Parent cyclosporin concentrations were measured in whole blood samples collected at timed intervals over the 24 h after the oral doses and pharmacokinetic parameters calculated. 3. The bioavailability of cyclosporin from the microemulsion formulation was, on average, 6.5-fold (95% C.I. 1.9 to 11.1-fold) greater than that of the conventional formulation, indicating the improved absorption characteristics of the new oral microemulsion formulation during external bile drainage. 4. A significant negative correlation was found between the external bile drainage volume and bioavailability of cyclosporin from the microemulsion formulation (r = -0.8; P = 0.016), suggesting that variability in cyclosporin absorption from the microemulsion formulation may still be at least partly attributable to bile- dependence.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorption↗

PubMed1995

Baby walker associated scalding injuries seen at University Hospital Kuala Lumpur.

Baby walker associated injuries are occurring in Malaysia. Most are not noticed as paediatricians are more concerned with the treatment of the injury and forget the preventive measures required to overcome this problem. We believe that baby walkers should be banned in Malaysia as the risks of injury far outweighs any benefits. We present 4 cases of baby walker associated scalding injuries.

Burns↗

PubMed1995

Multidrug-resistant tuberculosis.

In 1993, the World Health Organization declared tuberculosis a global emergency. Tuberculosis is the leading cause of death attributable to a single infectious pathogen. One-third of the world's population are at risk of developing the disease. In countries confronted with the human immunodeficiency virus (HIV) epidemic, the overlap of these two populations leads to a rapid acceleration of active tuberculosis and of the emergence of multidrug-resistant tuberculosis. Multidrug-resistant tuberculosis is defined as isolates resistant to both isoniazid and rifampicin with or without resistance to other antituberculosis drugs. In the United States, outbreaks of multidrug-resistant tuberculosis have been reported in patients with HIV infection and acquired immunodeficiency syndrome (AIDS) as well as HIV sero-negative patients. These reports have caused great concern owing to the very high case-fatality rate. The treatment outcome of multidrug-resistant tuberculosis is poor. The use of second-line drugs is frequently associated with toxicity and intolerance. Patients require admission to hospitals at the beginning of treatment and adjunctive resectional surgery should be considered when the sputum does not convert after 4 months of therapy. The incidence of multidrug-resistant tuberculosis among Singapore residents remains low. Organisms resistant to one drug occurred in 3.8% of newly diagnosed tuberculosis cases with positive culture and 8.7% of relapsed tuberculosis cases with positive cultures. Organisms resistant to two or more drugs occurred in 1.6% of newly diagnosed culture positive tuberculosis cases and 4.6% of relapsed cases where cultures were positive. This is the result of vigilant surveillance, effective treatment including supervised chemotherapy and close monitoring for non-compliance.

Humans↗

PubMed1995

Congenital absence of incus--a rare abnormality.

A case is described of a nine-year-old girl with a bilateral and symmetrical congenital absence of incus. This very rare abnormality has been described only once previously in the literature. Although the pathology may be rare, treatment is straightforward and prognosis good. A discussion of middle ear embryology and a review of the literature is presented.

Child↗

PubMed1995

Tuberculosis--fighting a losing battle?

Tuberculosis has resurfaced as a "global emergency" in recent years not only in terms of increase in number of cases world-wide but also the emergence of the deadly multidrug-resistant tuberculosis. World Health Organisation (WHO) has issued a call for the global community to step up its vigilance against the disease. Chemotherapy is the most powerful tool in the fight against tuberculosis and should be used with utmost care and under stringent conditions. It is not enough just to prescribe the correct medication, but more importantly, the patient must be closely monitored for compliance and progress. Any facility which provides for the treatment of tuberculosis must have a good working mechanism to detect treatment defaulter and take immediate remedial action. Only then can we maintain a high standard of control of the disease and prevent the emergence of drug-resistant organisms.

Adult↗

PubMed1995

Dopa-responsive dystonia of childhood: a case report.

A 5-year-old Chinese boy presented with difficulty in walking and weakness of his lower limbs for one year, especially towards the evening. Bilateral equinovarus posturing of the feet and tremors of the upper limbs were noted on physical examination. Dopa-responsive dystonia was diagnosed after a remarkable symptomatic response to levodopa. This disorder is reported here to highlight an often misdiagnosed condition is children which is important because it is treatable. Dopa-responsive dystonia should be considered in the differential diagnosis of gait disturbance in children.

Child, Preschool↗

PubMed1995

A light and electron microscopic study of HLA-DR positive cells in the human cerebral cortex and subcortical white matter.

Specimens of histologically normal human cerebral cortex and subcortical white matter were obtained during neurosurgical operations and studied by electron microscopy and immunocytochemistry using an antibody against HLA-DR. Greater numbers of labelled cells were present in the white matter than in the overlying cortex. The labelled cells consisted of ramified microglia and perivascular cells. Microglia were often found just outside the walls of small blood vessels, but perivascular cells were actually enclosed by two leaflets of basement membrane in the walls of capillaries, arterioles and venules up to 100 microns in luminal diameter. Labelled microglial processes were often seen enclosing neuronal processes in the cortex and myelinated and unmyelinated axons in the white matter. The enclosed processes appeared healthy, and without features of degenerating neurons. These observations are consistent with a previous suggestion that microglia continually modify the processes of central nervous system neurons by a process of phagocytosis. An intact blood-brain barrier is likely to be of great importance in preventing antigen presentation of the processed neuronal, and perhaps even oligodendrocytic, antigenic peptide fragments to circulating lymphocytes.

Adolescent↗

PubMed1995

Prolonged treatment with omeprazole does not improve the eradication rate of Helicobacter pylori infection--a short report [corrected].

Omeprazole has been shown to have a suppressive effect on Helicobacter pylori. The aim of this study was to determine if prolonged treatment with omeprazole would result in a higher eradication rate than short course treatment. Twenty patients with endoscopy proven duodenal ulcers and unequivocal evidence of Helicobacter pylori (HP) infection based on culture, histology, urease test and Gram's stain of a fresh tissue smear were treated with omeprazole 40 mg om for 2-4 weeks. Following ulcer healing, patients received either maintenance omeprazole 20 mg om or placebo for up to one year. All 20 patients had healed ulcers following a 2-4 week course of omeprazole 40 mg om.. All were negative for HP at the end of treatment. Thirteen patients received short course therapy with omeprazole only, followed by placebo. On follow-up endoscopy at 3 months, only one of 13 (7.7%) had eradicated the bacteria. Seven patients received maintenance treatment with omeprazole 20mg om for one year. Following completion of treatment, patients were followed up at 1, 3 and 6 months. Only one of 7 (14.3%) patients had eradicated the infection on long term follow-up. The eradication rates of HP with both short and long course omeprazole monotherapy were low.

Adult↗

PubMed1995

Mesial temporal lobe epilepsy in Singapore.

Mesial temporal lobe epilepsy due to mesial temporal sclerosis is a distinctive syndrome and a surgically remediable form of epilepsy. We present 26 Singaporean cases of mesial temporal lobe epilepsy defined by clinical, electroencephalographic and MR features and validated by good surgical outcome (12 seizure free, 5 with two or fewer seizures) in all 17 patients who have so far undergone surgery and who have been followed up for at least 6 months. Sixty-five percent of patients experienced their first seizure in the setting of a febrile illness. Seventy-three percent of patients had seizure onset before the age of 10 years and the median interval between seizure onset and intractability of seizures was 3.75 years. 80.7% of patients had an aura and an equal number had at least one lateralizing sign during their seizures. Sixty-four percent of patients had predominantly unilateral anterior temporal interictal spikes. Eighty-eight percent of patients had seizures which were lateralised on scalp ictal EEG. MRI abnormalities were most frequently seen in the head and body of the hippocampal formation. Asymmetric hippocampal atrophy was more common than hippocampal T2 or T2* signal changes. There is much similarity in characteristics of mesial temporal lobe epilepsy in our population compared to what has been published regarding Caucasian subjects.

Adolescent↗