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Biomedical subjects

S Chan

Publications and source records attributed to S Chan.

At least 91 records · Page 5Linked to original sources
PubMed1999

Altered calcium homeostasis and mitochondrial dysfunction in cortical synaptic compartments of presenilin-1 mutant mice.

Alzheimer's disease is characterized by amyloid beta-peptide deposition, synapse loss, and neuronal death, which are correlated with cognitive impairments. Mutations in the presenilin-1 gene on chromosome 14 are causally linked to many cases of early-onset inherited Alzheimer's disease. We report that synaptosomes prepared from transgenic mice harboring presenilin-1 mutations exhibit enhanced elevations of cytoplasmic calcium levels following exposure to depolarizing agents, amyloid beta-peptide, and a mitochondrial toxin compared with synaptosomes from nontransgenic mice and mice overexpressing wild-type presenilin-1. Mitochondrial dysfunction and caspase activation following exposures to amyloid beta-peptide and metabolic insults were exacerbated in synaptosomes from presenilin-1 mutant mice. Agents that buffer cytoplasmic calcium or that prevent calcium release from the endoplasmic reticulum protected synaptosomes against the adverse effect of presenilin-1 mutations on mitochondrial function. Abnormal synaptic calcium homeostasis and mitochondrial dysfunction may contribute to the pathogenic mechanism of presenilin-1 mutations.

Alzheimer Disease↗
PubMed1999

Incidence, prognosis, and etiology of end-stage liver disease in patients receiving home total parenteral nutrition.

BACKGROUND: Elevations in liver function tests have been reported in patients receiving total parenteral nutrition (TPN). The clinical aspects of end-stage liver disease (ESLD) associated with the prolonged use of home TPN have not been fully clarified. In previous series patients with duodenocolostomies appeared to be at higher risk than persons with some jejunum or ileum remaining in situ. METHODS: The records of 42 patients treated with home TPN for more than 1 year were examined. This constituted 283 person-years of home TPN. Patients with duodenocolostomies were examined as a separate group on the basis of the literature experience. RESULTS: Six of 42 patients who received chronic home TPN had ESLD with 100% subsequent mortality, at an average of 10.8 +/- 7.1 months after the initial bilirubin elevation. Thirteen of 42 patients had superior mesenteric artery or vein thrombosis (SMT) leading to duodenocolostomy. In 8 of these 13 patients with SMT and underlying inflammatory or malignant disorder, 2 had ESLD. The remaining 5 SMT patients who had only minimal liver enzyme elevation over 13.6 +/- 6.7 (range 3 to 19) years of home TPN were significantly younger (36 +/- 7 years vs 64 +/- 13 years) and did not have underlying inflammation either by clinical diagnosis or as reflected in the high normal serum albumin level (> or = 4.0 g/dL). Despite their extreme short bowel syndrome and long exposure to home TPN, ESLD did not develop. CONCLUSIONS: Approximately 15% of patients who receive prolonged TPN have ESLD with a high rate of morbidity and mortality. The combination of chronic inflammation and the short bowel syndrome appears to be necessary for the development of ESLD with prolonged home TPN.

Adult↗
PubMed1999

Patient-related barriers to cancer pain management in a palliative care setting in Hong Kong.

This article reviews a study of pain management and its barriers in Hong Kong. Using an interview technique, several measures were used to understand the level of concern in patients about pain, the patients' hesitancy in reporting pain, use of analgesics, and adequacy of medication for pain. A total of nine barriers were identified, which include "addiction," "tolerance," "side effects," "physician distraction," "good patient," "fear of injection," "time interval," "fatalism," and "disease progression." Thirty-nine interviews were carried out. The interviewees were all cancer patients with pain in a palliative setting in Hong Kong. When the findings in Taiwan and the United States were compared, it was found that the cancer patients in Hong Kong had a higher level of concern toward the patient-related barriers. It was also found that the level of concern was generally higher in the group with hesitancy in reporting pain and using analgesics. Last of all, this project also identified the educational needs of patients and health care workers in Hong Kong.

Adult↗
PubMed1999

Detection of circulating uroplakin-positive cells in patients with transitional cell carcinoma of the bladder.

PURPOSE: Although transitional cell carcinoma of the bladder (TCC) metastasizes frequently with devastating consequences, no marker has been available to monitor this process. Uroplakins are a group of specific markers for normal urothelium and are continuously expressed by the majority of TCCs. Detection of uroplakin-positive cells in the circulation would be a strong indication of hematogenous dissemination of tumor cells in patients with TCC. MATERIALS AND METHODS: Total RNAs were extracted from peripheral blood of 60 patients with TCC (50 non-metastatic and 10 metastatic) and 10 healthy controls, reverse-transcribed and subjected to polymerase chain reaction amplification (RT-PCR) using oligonucleotide primers of human uroplakin II gene. A uroplakin-expressing human bladder cancer cell line (RT4) was used as a positive control to establish the sensitivity of the RT-PCR assay. RESULTS: We showed that the PCR-amplification of the mRNA encoding uroplakin II (UPII), a 15-kDa urothelium-specific marker, constitutes a highly sensitive and specific assay for detecting 100% of transitional cell carcinoma tissue, and that this assay can detect a single bladder cancer cell in a 5-ml. blood sample. UPII mRNA was detected in the blood samples of 2 patients with metastatic bladder cancer without chemotherapy and 1 out of 8 such patients with chemotherapy, but not in those of 50 non-metastatic patients or normal controls. CONCLUSIONS: Uroplakin II is a highly specific marker for human TCC and the detection of uroplakin II in the peripheral blood is associated with metastatic spread of bladder cancer cells. The specific and sensitive detection of uroplakin II provides a useful adjunct for detecting bladder cancer metastasis, staging, and monitoring chemotherapeutic response.

Biomarkers, Tumor↗
PubMed1999

Tubal ectopic pregnancy: an evaluation of laparoscopic surgery versus laparotomy in 614 patients.

We performed a prospective nonrandomized multicentre study to compare laparoscopic surgery and laparotomy in the immediate surgical outcome of tubal ectopic pregnancy (TEP), at 9 teaching hospitals in Hong Kong with a laparoscopic surgical service, on all patients with the operative diagnosis of tubal ectopic pregnancy between July 1, 1996 and June 30, 1997. In the period studied, 630 patients were recruited of which 614 were suitable for analysis. In them, 382 (62.2%) had laparoscopic surgery while the rest had laparotomy with or without diagnostic laparoscopy. Significantly more cases of shock ended in laparotomy (86.1% versus 13.9%). After exclusion of patients with shock, laparoscopic surgery offered a significantly shorter postoperative hospital stay (mean 2.7 days versus 5.3 days), a slightly lower perioperative complication rate (8.1% versus 13.9%) and more conservative surgery (90.1% of all salpingotomies) than laparotomy. A longer operating time was needed for laparoscopic surgery (1.2 hours versus 1.01 hours).

Blood Loss, Surgical↗
PubMed1999

Motor neuron diseases: comparison of single-voxel proton MR spectroscopy of the motor cortex with MR imaging of the brain.

PURPOSE: To evaluate single-voxel proton magnetic resonance (MR) spectroscopy in detection of abnormality of the upper motor neuron in patients with motor neuron diseases. MATERIALS AND METHODS: In 43 of 50 patients with motor neuron disease and 14 of 14 control subjects, matching sets of MR spectra were obtained in the left and right motor cortex. The ratio of N-acetylaspartate (NAA) to creatine (Cr) was derived from peak area measurements. Mean ratios were calculated for control subjects and several patient groups, including patients with amyotrophic lateral sclerosis (ALS) or primary lateral sclerosis (PLS). MR images were evaluated for corticospinal tract hyperintensity and central sulcus dilatation. RESULTS: Mean NAA/Cr values were significantly different between control subjects and the ALS or PLS groups (P < .05). With an optimal cutoff of 2.5, NAA/Cr values were abnormal in 15 (79%) of 19 patients with ALS, 12 (67%) of 18 patients with PLS, and one (7%) of 14 control subjects. Corticospinal tract hyperintensity, central sulcus enlargement, or both were found in 43% of the ALS group, 24% of the PLS group, and 7% of the control group. CONCLUSION: NAA/Cr values determined at single-voxel proton MR spectroscopy are more sensitive than are standard findings at MR imaging in the detection of upper motor neuron disease.

Aged↗
PubMed1999

The natural history of CADASIL: a pooled analysis of previously published cases.

BACKGROUND AND PURPOSE: Although numerous families with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) have been reported, our understanding of the disease remains incomplete. Thus, we performed this study to investigate the phenotypic range and natural history of CADASIL. METHODS: We performed a pooled analysis of previously published cases. RESULTS: We identified 105 symptomatic patients in 33 families. Vascular risk factors were uncommon, with hypertension reported in only 8 patients. The mean age of symptom onset was 36. 7+/-12.9 years. Stroke or transient ischemic attack was an initial symptom in 45 patients, with a mean age of onset of 41.2+/-9.2 years. Migraine was also a common initial symptom, reported by 42 patients at a younger mean age of 28.3+/-11.7 years. Other initial symptoms included depression in 9 patients, cognitive impairment in 6 patients, and seizures in 3 patients. Regarding clinical course, 71 patients experienced a stroke or transient ischemic attack, and 52 of those patients had 1 or more recurrent ischemic events. Dementia was reported in 44 patients. Only 3 additional patients experienced migraine at a later time, while 13 additional patients developed depression. Six patients had seizures. Twenty-two of the 105 patients had died, with a mean age of death of 54.8+/-10.6 years. Nineteen of those 22 patients had experienced a stroke or transient ischemic attack and 19 patients were demented. CONCLUSIONS: CADASIL typically becomes evident in early or middle adulthood with migraine or an ischemic event, later manifests itself through recurrent subcortical ischemic strokes leading to a stepwise decline and dementia, and results in reduced survival.

Adolescent↗
PubMed1999

Prospective randomized trial of docetaxel versus doxorubicin in patients with metastatic breast cancer.

PURPOSE: This phase III study compared docetaxel and doxorubicin in patients with metastatic breast cancer who had received previous alkylating agent-containing chemotherapy. PATIENTS AND METHODS: Patients were randomized to receive an intravenous infusion of docetaxel 100 mg/m(2) or doxorubicin 75 mg/m(2) every 3 weeks for a maximum of seven treatment cycles. RESULTS: A total of 326 patients were randomized, 165 to receive doxorubicin and 161 to receive docetaxel. Overall, docetaxel produced a significantly higher rate of objective response than did doxorubicin (47.8% v 33.3%; P =.008). Docetaxel was also significantly more active than doxorubicin in patients with negative prognostic factors, such as visceral metastases (objective response, 46% v 29%) and resistance to prior chemotherapy (47% v 25%). Median time to progression was longer in the docetaxel group (26 weeks v 21 weeks; difference not significant). Median overall survival was similar in the two groups (docetaxel, 15 months; doxorubicin, 14 months). There was one death due to infection in each group, and an additional four deaths due to cardiotoxicity in the doxorubicin group. Although neutropenia was similar in both groups, febrile neutropenia and severe infection occurred more frequently in the doxorubicin group. For severe nonhematologic toxicity, the incidences of cardiac toxicity, nausea, vomiting, and stomatitis were higher among patients receiving doxorubicin, whereas diarrhea, neuropathy, fluid retention, and skin and nail changes were higher among patients receiving docetaxel. CONCLUSION: The observed differences in activity and toxicity profiles provide a basis for therapy choice and confirms the rationale for combination studies in early breast cancer.

Adult↗
PubMed1999

Nutrition management in the ICU.

Nutrition support plays an important role in the management of nutritional deficiencies in properly selected critically ill patients. A full nutritional assessment allows the calculation of appropriate feeding goals. The route of feeding, enteral or parenteral, is determined by the presence or absence of a functioning intestine and hemodynamic status of the patient. The specific roles of carbohydrates, fats, and protein need to be considered in order to prevent overfeeding and other complications. The efficacy of certain disease-specific enteral formulas has been demonstrated in clinical trials, however, careful cost-benefit analyses are required.

Critical Care↗
PubMed1999

Nonpharmacologic and pharmacologic management of weight gain.

Obesity increases the risk of several serious health problems, including heart disease, type II diabetes mellitus, hypertension, and osteoarthritis. Patients taking certain psychotropic medications may gain a significant amount of weight (as much as a 5% increase in body weight within 1 to 2 months), placing them at risk for obesity. Body weight monitoring and prudent drug selection are the best approaches to preventing weight gain in patients taking psychotropic drugs. When weight gain (> 5% of initial body weight) is unavoidable, intervention counseling should begin. Nonpharmacologic measures for managing weight gain include a balanced deficit diet of 1000 calories and higher, depending on the patient's weight; 30 to 60 minutes of physical activity daily; and behavioral training to restrain excess caloric intake. Each of these measures requires a considerable commitment on the part of the patient and works best with support from the physician and weight-loss support groups. Drug therapy for weight loss is available (at present, sibutramine is the only approved appetite suppressant in the United States); however, for most patients already being treated with a psychotropic agent, the risks (such as drug interactions, adverse events, compliance problems) of adding an antiobesity agent probably outweigh the benefits. Surgical intervention for obesity should be reserved for morbidly obese patients whose disease is intractable to medical therapy.

Anti-Obesity Agents↗
PubMed1999

Effect of beta-blockade on baroreceptor and autonomic function in heart failure.

Although beta-adrenoreceptor antagonists appear to be beneficial in chronic heart failure there is little information on their effects on autonomic and baroreceptor function which may have important prognostic implications. We sought to determine first whether beta-adrenoreceptor blockade will improve baroreceptor function and vagal tone in chronic heart failure, and second whether there were any differences between standard therapy with metoprolol and the second-generation vasodilating beta-blocker celiprolol. In this double-blind randomized placebo-controlled study 50 patients with stable chronic heart failure received either celiprolol 200 mg daily, metoprolol 50 mg twice daily or placebo for 12 weeks after a 4-week dose titration period. Thirty-five healthy normal subjects were also studied. Baroreceptor gain was assessed non-invasively by cross-spectral analysis of R-R and systolic blood pressure low- and high-frequency components (the alpha angle) during controlled respiration. High-frequency power was used as a measure of vagal modulation. Satisfactory recordings for analysis were obtained in 31 patients with heart failure. The results showed that at baseline baroreceptor gain (alphaHF) was significantly depressed in patients with heart failure compared with the normal control group (4.95+/-0. 55 versus 11.73+/-1.32 ms/mmHg, P<0.0001). After 12 weeks of treatment with metoprolol baroreceptor gain improved significantly whether measured while supine (P=0.03) or standing (P=0.009), and this was associated with a significant increase in R-R HF power (P=0. 008). There were no significant changes after treatment with celiprolol or placebo. We conclude that metoprolol but not celiprolol therapy restores baroreceptor gain towards normal and increases vagal tone in chronic heart failure. The ancillary properties of celiprolol do not appear to provide any advantages over metoprolol for the restoration of autonomic and baroreceptor function in heart failure.

Adrenergic beta-Antagonists↗
PubMed1998

Visualization of CD4/CD8 T cell commitment.

A system to innocuously visualize T cell lineage commitment is described. Using a "knock-in" approach, we have generated mice expressing a beta-galactosidase reporter in place of CD4; expression of beta-galactosidase in these animals appears to be an accurate and early indicator of CD4 gene transcription. We have exploited this knock-in line to trace CD4/CD8 lineage commitment in the thymus, avoiding important pitfalls of past experimental approaches. Our results argue in favor of a selective model of thymocyte commitment, demonstrating a fundamentally symmetrical process: engagement of either class of major histocompatibility complex (MHC) molecule by a differentiating CD4(+)CD8(+) cell can give rise to T cell antigen receptor (TCR)hi thymocytes of either lineage. Key findings include (a) direct demonstration of a substantial number of CD4-committed, receptor/coreceptor-mismatched cells in MHC class II- deficient mice, a critical prediction of the selective model; (b) highly efficient rescue of such "mismatched" intermediates by forced expression of CD8 in a TCR transgenic line, and an explanation of why previous experiments of this nature were less successful-a major past criticism of the selective model; (c) direct demonstration of an analogous, though smaller, population of CD8-committed mismatched intermediates in class I-deficient animals. Finally, we found no evidence of a CD4 default pathway.

Animals↗
PubMed1998

Prospective magnetic resonance imaging identification of focal cortical dysplasia, including the non-balloon cell subtype.

The purpose of this study was to determine the role of high-resolution T2-weighted fast multiplanar inversion-recovery (FMPIR) magnetic resonance (MR) imaging in detecting and delineating microscopic focal cortical dysplasia (FCD). We performed MR scans with FMPIR on 42 patients with suspected neocortical epilepsy. Ten MR studies were read prospectively as showing FCD; these case histories, electroencephalographic studies, and neuroimaging data were reviewed. Eight of these patients subsequently underwent focal cortical resection guided by intraoperative electrocorticography. The MR findings were correlated with pathological findings in these 8 patients. For purposes of radiological-pathological correlation, the FCD lesions were divided into two classes. Radiological classification was based on the absence (type A) or presence (type B) of T2 prolongation of the subcortical white matter. Pathological grading as type I or type II was based on a previously described pathological grading system. Specific MR findings associated with FCD included focal blurring of the gray-white matter interface (n = 9), thickening of the cortical ribbon (n = 7), and T2 prolongation of the subcortical white matter (n = 4). In 3 patients, the only MR finding that suggested FCD was localized blurring of the gray-white matter junction. In 2 of these 3 patients, the MR diagnosis of FCD could be made only by FMPIR. FCD was confirmed histologically in 7 of 8 patients, with insufficient tissue for complete histopathological evaluation in 1 case. Radiological classification of FCD agreed with pathological classification in 5 of 7 cases. Correlation of MR findings with intraoperative electrocorticography results indicated that the MR study localized the epileptogenic lesion correctly in 8 of 8 cases. Scalp ictal electroencephalographic studies localized the epileptogenic lesion in 5 of 8 cases; positron emission tomographic scans were focally abnormal in 3 of 3 cases. FMPIR MR imaging permitted accurate diagnosis and localization of FCD in all patients with pathologically proved FCD. MR identification of FCD aided presurgical planning and intraoperative management of these patients.

Adolescent↗
PubMed1998

Incident reporting in acute pain management.

Incident reporting is an effective tool for continuous quality improvement in clinical practice. A prospective study on voluntary incident reporting in pain management was conducted at a major teaching hospital in Hong Kong. Over a 12-month period, 53 incidents were reported in 1275 patients who received pain relief treatments which were supervised by the acute pain service. The majority of the incidents were first detected by the pain team. The most common incidents involved delivery circuits, delivery pump and drug administration. A large proportion (81.4%) of the incidents were thought to be preventable. Human factors were involved in 41.9% of the patients reported, most commonly associated with unfamiliar technique/inexperience, inattention and inadequate communication. Four patients developed major morbidity of which two were attributed to inadequate analgesia, while three others had major physiological changes without morbidity. Strategies have been formulated to prevent further occurrence of these incidents. We propose that incident reporting is a potentially useful tool in identifying and preventing adverse events in postoperative pain management.

Acute Disease↗