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Biomedical subjects

T Y Chan

Publications and source records attributed to T Y Chan.

At least 19 recordsLinked to original sources

Is primidone the drug of choice for epileptic patients with QT-prolongation? A comprehensive analysis of literature.

Sudden unexplained/unexpected death (SUDEP) in epilepsy is a major cause of death accounting for 7-17% of the mortality among epileptic patients. Prolongation of QT-interval has been issued as a major mechanism in SUDEP since it is associated with fatal cardiac arrhythmias. This condition may be further precipitated by anti-epileptic treatment. Despite thorough literature research, we did not find any reports suggesting that primidone is responsible for QT-prolongation. On the contrary, all the retrieved reports addressed that the drug shortened QT-interval and corrected signs and symptoms of the underlying disease.

Anticonvulsants↗

Phylogenetic relationships and evolutionary history of the shrimp genus Penaeus s.l. derived from mitochondrial DNA.

Mitochondrial DNA sequences were used to reconstruct the phylogeny of the Penaeus s.l. genus of marine shrimp. This phylogeny was used to test the validity of hypotheses on the species groupings, in particular the subgenus/genus subdivision, and on the species' evolutionary history. Newly derived sequences of both 16S rRNA and COI genes from 19 species of Penaeus s.l. and one outgroup were combined with previous sequences from seven additional species to allow analysis of 26 of the 28 recognised (or nominated) species. Phylogenetic analyses do not support the validity of all the previously created six subgenera (or genera) but provide evidence for division of the genus into two previously unrecognised clades (Melicertus+Marsupenaeus and Penaeus s.s.+Fenneropenaeus+Farfantepenaeus+Litopenaeus). A key conclusion from a previous molecular study, that the subgenera Farfantepenaeus and Litopenaeus are paraphyletic, was rejected. The molecular data support an Indo-West Pacific origin of the genus, with a single relatively recent colonisation of the Western Hemisphere, and subsequent subdivision into two clades prior to the emergence of the Panamanian isthmus.

Animals↗

Pain and disability in a group of Chinese elderly out-patients in Hong Kong.

OBJECTIVE: To investigate the relationship between musculoskeletal pain and disability among a group of geriatric out-patients. DESIGN: Consecutive case series. SETTING: Regional hospital, Hong Kong. PARTICIPANTS: Attendees at a geriatric specialist out-patient clinic from October 2002 to February 2003. MAIN OUTCOME MEASURES: Pain duration, location, intensity, and frequency; use of analgesics; ability to identify the cause of pain; disability (Barthel index) and Lawton Instrumental Activities of Daily Living scale score; depressive symptoms (Geriatric Depression Scale score); and self-reported sleep quality. RESULTS: Of the 749 respondents, 461 (61.5%) had experienced pain in the previous 2 weeks. Among these patients, 51.3% had received a pain-relieving drug. Compared with men, women reported a higher pain intensity (5.87 versus 5.26; P=0.001), had a lower Barthel index (96.0 versus 97.9; P=0.005), and had a lower score on the Lawton Instrumental Activities of Daily Living scale (42.19 versus 44.52; P=0.008). Multivariate logistic regression showed that the presence of pain was associated with female sex (odds ratio=2.25), poor self-rated health (0.69), and depression (1.54). CONCLUSION: Pain is a common problem among the elderly population, but it is not associated with physical disability, and only half of the patients received analgesics. The study provides information for health care workers to develop strategies to better assess and manage pain problems among elderly people.

Activities of Daily Living↗

Role of monocyte L-selectin in the development of post-traumatic organ failure.

The vascular leucocyte adhesion molecule, L-selectin, plays an important early role in monocyte trafficking at sites of inflammation, a process which leads to the development of inflammatory organ failure. In this prospective observational study, we investigate whether early numerical and functional changes in circulating monocytes, expression of monocyte L-selectin (CD62L) and monocyte:neutrophil L-selectin ratios are related to the subsequent development of post-traumatic organ failure (OF) and multiple organ dysfunction syndrome (MODS). Monocyte counts and cell surface L-selectin were measured by an automated cell counter and flow cytometry, respectively. Of 164 trauma patients admitted to a university emergency department resuscitation room, 64 had multiple injuries, 51 developed OF, 20 developed MODS and 21 died. Early monocyte counts in patients with multiple injuries were lower in those who developed MODS (0.44 x 10(9)/l) compared with those who did not (0.60 x 10(9)/l; P=0.024). Monocyte L-selectin mean channel fluorescence increased with injury severity and was highest in those who developed MODS (P=0.033). In the sub-group of patients with multiple injuries, L-selectin mean channel fluorescence was also greater in those patients who developed MODS compared with patients who did not develop MODS (P=0.042). The monocyte to neutrophil count ratio also decreased with injury severity (P=0.006). Using optimal cut off values for L-selectin mean channel, fluorescence, the positive and negative predictive values for OF was 43.5 and 91.4%, respectively and for MODS it was 25.4 and 92.9%, respectively. Alterations in early circulating monocyte counts and L-selectin expression after injury are related to the development of post-traumatic organ failure and suggest an area in the inflammatory pathway that may be influenced by L-selectin blockade.

Adolescent↗

Urinary epinephrine and norepinephrine interrelations with obesity, insulin, and the metabolic syndrome in Hong Kong Chinese.

The metabolic syndrome is characterized by a clustering of cardiovascular risk factors including type 2 diabetes mellitus, hypertension, dyslipidemia, and obesity. Elevated plasma insulin and urinary norepinephrine (noradrenaline) and reduced urinary epinephrine (adrenaline) excretion are associated with obesity in Caucasian populations. We examined the interrelationships between obesity, plasma insulin, and urinary catecholamine excretion in Chinese subjects with various components of the metabolic syndrome. A total of 577 Chinese subjects (aged 38 +/- 10 years; 68% with type 2 diabetes mellitus, hypertension, dyslipidemia, obesity, and/or albuminuria and 32% healthy subjects) were studied, all of whom had a plasma creatinine less than 150 micromol/L. The blood pressure, height, weight, waist and hip circumference, and fasting plasma glucose, insulin, lipid, and creatinine levels were measured. A 24-hour urine sample was collected for measurement of albumin and catecholamine excretion. The body mass index (BMI) and waist circumference were used as measures of general and central obesity, respectively. The insulin resistance index was estimated by the calculated product of fasting plasma insulin and glucose concentrations. Patients with an increasing number of components of the metabolic syndrome (type 2 diabetes mellitus, hypertension, dyslipidemia, obesity, and/or albuminuria) were more obese, hyperglycemic, dyslipidemic, and albuminuric and had higher blood pressure, plasma insulin, insulin resistance indices, and 24-hour urinary norepinephrine excretion but lower urinary epinephrine output (all P < .005). Increasing quintiles of BMI in the whole population or waist circumference in both sexes were associated with increasing trends for adverse lipid profiles, plasma insulin, insulin resistance indices, and urinary norepinephrine excretion but a decreasing trend for urinary epinephrine output (all P < .001). There were close associations between age, obesity, blood pressure, fasting plasma glucose, lipid, insulin, insulin resistance indices, and urinary catecholamine excretion. Using stepwise multiple regression analysis (all P < .001), 34% of the variability of the BMI and 45% of that of the waist circumference were independently related to gender (waist higher in males and BMI higher in females), increased plasma insulin, triglyceride, and urinary norepinephrine excretion, and decreased high-density lipoprotein (HDL) cholesterol and urinary epinephrine output. In Chinese subjects with different manifestations of the metabolic syndrome, hyperinsulinemia, insulin resistance, elevated norepinephrine, and reduced epinephrine excretion were closely associated with general and central obesity. Based on these findings, we postulate that complex interactions between the insulin and sympathoadrenal systems may lead to the development of obesity and the metabolic syndrome.

Adult↗

Unsupervised classification of noisy chromosomes.

MOTIVATION: Almost all methods of chromosome recognition assume supervised training; i.e. we are given correctly classified chromosomes to start the training phase. Noise, if any, is confined only in the representation of the chromosomes and not in the classification of the chromosomes. During the recognition phase, the problem is simply to calculate the string edit distance of the unknowns to the representatives chosen from the training phase and classify the unknowns accordingly. RESULTS: In this paper, a general method to tackle the difficult unsupervised induction problem is described. The success of the method is demonstrated by showing how the inductive agent learns weights in a dynamic manner that allows it to distinguish between noisy median and telocentric chromosomes without knowing their proper labels. The process of learning is characterized as the process of finding the right distance function, i.e. the distance function that can nicely separate the classes.

Algorithms↗

In situ adenocarcinoma of the bladder.

In situ adenocarcinoma of the bladder has not been well studied. Only one other case not associated with infiltrating adenocarcinoma has been reported in the literature. We identified 19 biopsies of in situ adenocarcinoma of the bladder without concurrent infiltrating adenocarcinoma or villous adenoma from the surgical pathology files of the Johns Hopkins Hospital between May 1984 and July 2000. The majority of patients (89%) were seen in consultation. The mean age at diagnosis was 70.4 years (range 48-88 years) and 79% were male. None of the patients developed a pure infiltrating adenocarcinoma; however, two patients had invasive urothelial carcinoma with focal glandular differentiation on prior or subsequent specimens. Two cases were pure in situ adenocarcinoma and 10 were seen with carcinoma in situ and/or papillary transitional cell cancer without invasion. Most patients (74%) had invasive carcinoma on either concurrent or subsequent specimens (five small cell and nine transitional cell [four micropapillary]). The majority (84%) of in situ adenocarcinomas were papillary, often seen in combination with either cribriform or flat architecture. In most cases the in situ adenocarcinoma was the predominant component when it was present with another in situ urothelial carcinoma. Seventy-nine percent of in situ adenocarcinomas showed >5 mitoses/10 HPF and 42% showed >10 mitoses/10 HPF. Moderate to severe nuclear pleomorphism was seen in 84% of cases. All cases showed apoptosis, and only one case showed focal necrosis. Seven patients were treated with cystectomy within 2-12 months. Of the other 12 patients, 10 were followed for a mean of 19.3 months (range 1-62 months). Ten (52%) patients were treated with bacille Calmette-Guérin, of whom four had no residual tumor on subsequent biopsy or cystectomy specimens. Three patients developed metastatic disease. In situ adenocarcinoma is a rare lesion that has a high incidence of association with small cell and micropapillary transitional cell carcinomas. When identified, in situ adenocarcinoma may indicate subsequent development of specific types of prognostically poor invasive carcinomas.

Adenocarcinoma↗

Chronicity of neurological features in ciguatera fish poisoning.

A 43-year-old woman complained of colicky abdominal pain, followed by numbness, myalgias, and muscle weakness in the four limbs after eating a grouper (Epinepheius spp.). She presented to our hospital 36 hours later with increased myalgias, muscle weakness, and malaise. On examination, the muscle power and sensation in her four limbs appeared to be normal. She was given an intravenous infusion of mannitol 20% (200 ml over 1 hour) and an intramuscular injection of diclofenac (75 mg). Her myalgias then improved and she was discharged. She presented to our hospital again 1 week later with poor appetite, malaise, numbness of the four limbs, and increased muscle weakness. On examination, the muscle weakness was more marked in the lower limbs (4+/5) than in the upper limbs (5-/5) and proximally than distally. She also had some difficulty in getting up from a squatting position. She was given another intravenous infusion of mannitol 20% (200 ml over 1 hour), following which there was subjectively slight improvement in her muscle weakness. Herplasma creatine phosphokinase level was normal. Electromyography performed 4 weeks later revealed no abnormalities. When she was reviewed 45 days after the consumption of the grouper, her muscle weakness and malaise had improved considerably. She could then stand up from a squatting position. However, mild impairment of finger grip was still present. Chronicity of neurological features in other reported cases (e.g., chronic fatigue, relapse of symptoms after exposure to ciguateric fish or alcohol, and peripheral neuropathy) may also indicate a lengthy persistence of ciguatoxins in the body.

Adult↗

Interaction between warfarin and danshen (Salvia miltiorrhiza).

OBJECTIVE: To discuss the potential for an adverse interaction between the Chinese herb danshen, the dry root and rhizome of Salvia miltiorrhiza Bge, and warfarin. DATA SOURCES: A MEDLINE search was performed (from January 1966 through October 2000) using the key words danshen and Salvia miltiorrhiza. All articles written in English or with an English extract were considered for review. STUDY SELECTION AND DATA EXTRACTION: All studies of antithrombotic effects of danshen or interaction between danshen and warfarin were evaluated. Previous case reports of an adverse interaction between danshen and warfarin were reviewed. DATA SYNTHESIS: Danshen is commonly used in mainland China for the treatment of atherosclerosis-related disorders such as cardiovascular and cerebrovascular diseases. Danshen can affect hemostasis in several ways, including inhibition of platelet aggregation, interference with the extrinsic blood coagulation, antithrombin III-like activity, and promotion of fibrinolytic activity. Single-dose and steady-state studies in rats indicated that danshen increased the absorption rate constants, AUCs, maximum concentrations, and elimination half-lives, but decreased the clearances and apparent volume of distribution of both R- and S-warfarin. Consequently, the anticoagulant response to warfarin was exaggerated. Three cases have previously been published reporting gross overanticoagulation and bleeding complications when patients receiving chronic warfarin therapy also took danshen. CONCLUSIONS: Because of both pharmacokinetic and pharmacodynamic interactions, danshen should be avoided in patients taking warfarin.

Animals↗

Does increased needle biopsy sampling of the prostate detect a higher number of potentially insignificant tumors?

PURPOSE: Several studies have documented that increased biopsy sampling, that is 6 versus 12 biopsy cores, can detect more prostate cancer. It is unknown whether increased sampling of the prostate will detect a higher number of potentially insignificant tumors. MATERIALS AND METHODS: We searched the surgical pathology files at The Johns Hopkins Hospital for patients in whom prostate needle biopsy was performed by a single urologist between April 1993 and April 2000, and subsequently underwent radical prostatectomy. Patients who underwent radical prostatectomy and had 8 core biopsies or less between March 1994 and August 1999 were also studied. Clinically significant tumors were defined as those with volume greater than 0.5 cc, Gleason score 7 or greater or nonorgan confined disease. RESULTS: A total of 297 patients with a mean age of 60 years (range 36 to 75) were evaluated. Group 1 consisted of 107 men with 8 core biopsies or less, including 51 with 6, and group 2 comprised 190 men with 9 cores or greater, including 145 with 12. The 2 groups were equal in regard to prostate specific antigen, age, digital rectal examination and transrectal ultrasound gland volume at biopsy. The only difference between the groups was a higher number of cores with cancer in group 2 (mean 2.8 versus 2.1, p = 0.0006). Of the patients who underwent radical prostatectomy 59.6% had Gleason score 6 or less, 26.3% 3+4, 6.7% 4+3 and 7.4% 8 to 9. There were 12.4% of patients with positive margins, 36.4% extraprostatic extension, and 5.4% seminal vesicle invasion and/or lymph node metastasis. Tumor volumes averaged 1.1 cc (range 0.01 to 10.7) and 60.9% of tumors were greater than 0.5 cc. Clinically significant tumors were seen in 77.4% of patients in group 1 and 74.6% in group 2. There was no significant difference in Gleason score, margin status, tumor volume, seminal vesicle invasion, or lymph node metastasis between groups 1 and 2, or in a subset analysis of men with 6 versus 12 core biopsies. However, patients in whom cancer was diagnosed with 9 core biopsies or greater were more likely to have organ confined disease (p = 0.02). CONCLUSIONS: Although increased sampling of the prostate does not increase the detection of potentially insignificant tumors, it does appear to detect earlier stage cancer.

Adult↗

A neural network predicts progression for men with gleason score 3+4 versus 4+3 tumors after radical prostatectomy.

OBJECTIVES: To determine the significance of Gleason scores 3+4 (GS3+4) versus 4+3 (GS4+3) with respect to biochemical recurrence in a retrospective review of a series of men with clinically localized prostate cancer who underwent radical retropubic prostatectomy (RRP) and to develop and test an artificial neural network (ANN) to predict the biochemical recurrence after surgery for this group of men using the pathologic and clinical data. METHODS: From 1982 to 1998, 600 men had pathologic Gleason score 7 disease without lymph node or seminal vesicle involvement. We analyzed the freedom from biochemical (prostate-specific antigen) progression after RRP on 564 of these men on the basis of their GS3+4 versus GS4+3 (Gleason 7) status. The Cox proportional hazards model was used to determine the importance of Gleason 7 status as an independent predictor of progression. In addition, an ANN was developed using randomly selected training and validation sets for predicting biochemical recurrence at 3 or 5 years. Different input variable subsets, with or without Gleason 7 status, were compared for the ability of the ANN to maximize the prediction of progression. Standard logistic regression was used concurrently on the same random patient population sets to calculate progression risk. RESULTS: A significant recurrence-free survival advantage was found in men who underwent RRP for GS3+4 compared with those with GS4+3 disease (P <0.0001). The ANN, logistic regression, and proportion hazard models demonstrated the importance of Gleason 7 status in predicting patient outcome. The ANN was better than logistic regression in predicting patient outcome, in terms of prostate-specific antigen progression, at 3 and 5 years. CONCLUSIONS: A simple modification of the Gleason scoring system for men with Gleason 7 disease revealed a difference in the patient outcome after RRP. ANN models can be developed and used to better predict patient outcome when pathologic and clinical features are known.

Disease Progression↗

Prognostic significance of Gleason score 3+4 versus Gleason score 4+3 tumor at radical prostatectomy.

OBJECTIVES: To determine the clinical significance of Gleason score 3+4 versus 4+3 on radical prostatectomy. METHODS: Of 2390 men who underwent radical prostatectomy by a single surgeon, 570 had Gleason score 7 tumors without lymph node metastasis, seminal vesicle invasion, or tertiary Gleason pattern 5. Patients were evaluated for biochemical recurrence (prostate-specific antigen progression) and distant metastases. RESULTS: Eighty percent of patients had Gleason score 3+4, 20% had 4+3. The rate of established extraprostatic extension at radical prostatectomy for Gleason score 3+4 and 4+3 tumors was 38.2% and 52.7%, respectively (P = 0.008). With a mean follow-up of 4.6 years for men without progression, Gleason score 4+3 tumors had an increased risk of progression independent of stage and margin status (P <0.0001). The 5-year actuarial risk of progression was 15% and 40% for Gleason score 3+4 and 4+3 tumors, respectively. The mean time to progression was 4.4 years for Gleason score 3+4 tumors and 3.2 years for Gleason score 4+3 tumors. We stratified the patients into four prognostic groups on the basis of organ-confined status, margin status, and Gleason score (3+4 versus 4+3). The 5-year actuarial risk of progression was 10%, 35%, 45%, and 61%, with 10-year progression rates of 29%, 42%, 69%, and 84%, for the four groups. 3.9% of patients with Gleason score 3+4 and 10. 5% with Gleason score 4+3 tumors developed metastatic disease within a mean of 5.7 and 5.6 years, respectively. A Gleason score of 4+3 versus 3+4 was predictive of metastatic disease (P = 0.002) but not local recurrence. CONCLUSIONS: Gleason score 7 tumors are heterogeneous in their biologic behavior. The differences in prognosis for patients with Gleason scores 3+4 and 4+3 tumors at radical prostatectomy are significant. Although the assessment of the percentage of pattern 4 at radical prostatectomy is not likely to be reproducible, the distinction between Gleason score 3+4 and 4+3 should be easier for pathologists to perform.

Actuarial Analysis↗

Vitamin D deficiency and susceptibility to tuberculosis.

Vitamin D, a modulator of macrophage function, can activate human anti-mycobacterial activity. Vitamin D deficiency is therefore associated with a higher risk of tuberculosis (TB) infection, as indicated by several observations. First, TB tends to occur during the colder seasons when cutaneous synthesis of vitamin D from sun exposure is reduced and serum vitamin D levels are lower. Second, patients with untreated TB, particularly those from a temperate climate, have lower serum vitamin D levels than healthy subjects. Third, the incidence of TB is higher among subjects with relatively low serum vitamin D levels, such as the elderly, uremic patients, and Asian immigrants in the U.K.

Age Factors↗

Increased plasma free cyclic-AMP levels following major trauma and their relevance to the immune response.

BACKGROUND: Following injury, neutrophil mobilisation is an important element of the immune response. The ideal features of an agent responsible for this mobilisation would include the ability to mobilise neutrophils without activating them, and rapid reversibility. This study investigates the hypothesis that raised levels of plasma adrenaline following trauma act via cyclic adenosine monophosphate (cAMP) to mobilise neutrophils, and measures the amount of cAMP extruded from cells into the plasma following injury. METHODS: 20-ml samples of venous blood were drawn from 34 trauma patients within 3 h of injury and divided between three sample tubes: (1) ethylene diamine tetra-acetic acid anticoagulant (EDTA) for full blood count; (2) cooled EDTA for cAMP levels; and (3) cooled lithium heparin for catecholamines. The latter two tubes were immediately centrifuged at low temperature and the supernatant plasma deep frozen pending analysis. Adrenaline was measured using high pressure liquid chromatography (HPLC) and cAMP measured by an enzyme immunoassay technique. RESULTS: 34 patients, six of whom had sustained minor trauma (ISS 1-8), 12 moderate trauma (ISS 9-15) and 16, major trauma (ISS 16 and above) were studied. Median age was 39 years (range 16-77) and 30 patients were male. Plasma adrenaline levels were available for 28 of the patients. Plasma free cAMP levels were significantly raised in patients with major trauma (P < 0.006). There were positive correlations between the plasma levels of cAMP and adrenaline (rho 0.660, P = 0.011), adrenaline and neutrophil count (rho 0.654, P = 0.01) and cAMP and neutrophil count (rho 0.508, P = 0.013). CONCLUSIONS: Evidence is presented of the possible inter-relationships between neutrophil counts, adrenaline levels and cAMP levels following injury, supporting the proposition that neutrophil mobilisation pathways are activated early via beta-adrenergic stimulation.

Adolescent↗