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Biomedical subjects

S Lam

Publications and source records attributed to S Lam.

At least 37 records · Page 2Linked to original sources

A unitary patient record improves admission documentation in a medical assessment unit in a major teaching hospital.

OBJECTIVE: To ascertain the impact of the introduction of a unitary patient record (UPR) on clerking documentation of emergency medical admissions. DESIGN: Retrospective casenote audit. SUBJECTS AND SETTING: Random sample of 100 unselected admissions to the medical assessment unit of a major teaching hospital, comprising two groups pre- and post-introduction of the UPR. RESULTS: Statistically significant improvements in the documentation of several items were achieved; function before episode, ethnic origin, chest pain, breathlessness, ankle oedema, cough, bowel habit and locomotor symptoms and recording of blood pressure and peripheral pulses. There were trends towards improvement in other areas and there were no areas in which the UPR performed less well than standard documentation. CONCLUSIONS: Introduction of the UPR represents the successful application of multidisciplinary principles to over 10,000 acute general medical admissions. It has improved some, but not all, aspects of documentation. Revision of the design of the UPR should lead to further progress, as part of an ongoing process of development and re-audit.

Acute Disease↗

Detection and localization of early lung cancer by fluorescence bronchoscopy.

BACKGROUND: Curative therapy is available for patients with Stage 0 lung carcinoma, with a >90% 5-year survival rate. Promising chemopreventive agents also are under investigation currently to reduce the risk of lung carcinoma in high risk populations. However, preinvasive bronchial lesions (moderate to severe dysplasia and carcinoma in situ) are very small and thin. They are difficult to localize by conventional white-light bronchoscopy. Fluorescence bronchoscopy is a new diagnostic tool for the detection of these preinvasive lesions. METHODS: The data on the use of fluorescence bronchoscopy to detect and localize preinvasive lesions in current heavy smokers and in former smokers at the British Columbia Cancer Agency as well as the worldwide experience cited in MEDLINE, Index Medicus, and Deutsches Institut fur Medizinische Dokumentation und Information (Cologne, Germany) comparing white-light and fluorescence bronchoscopy using the lung imaging fluorescence endoscope (LIFE)-Lung device (Xillix Technologies Corp., Richmond, British Columbia, Canada) were reviewed. RESULTS: Among current heavy smokers and former smokers with sputum atypia, the prevalence of carcinoma in situ was 1.6%. Moderate or severe dysplasia was found in another 19%. The preinvasive lesions were found to be small: 55% measured < or = 1.5 mm in greatest dimension. Over 1000 cases have been reported in the literature between 1994 and 1999. Overall, 40% of the preinvasive lesions were detected by white-light bronchoscopy alone. The addition of fluorescence bronchoscopy increased the detection rate to an average of 80%. CONCLUSIONS: Preinvasive lesions, especially dysplastic lesions, are small. They are difficult to detect and localize by white-light bronchoscopy. Fluorescence bronchoscopy improves the detection rate. It is an important part of the armamentarium in the overall management of early lung cancer.

Bronchoscopy↗

Intranuclear huntingtin increases the expression of caspase-1 and induces apoptosis.

Expansion of a polyglutamine repeat in huntingtin causes Huntington's disease (HD). Although full-length huntingtin is predominantly distributed in the cytoplasm, N-terminal fragments of huntingtin with expanded polyglutamine tracts are able to accumulate in the nucleus and kill neurons through apoptotic pathways. Transgenic mice expressing N-terminal mutant huntingtin show intranuclear huntingtin accumulation and develop progressive neurological symptoms. Inhibiting caspase-1 can prolong the survival of these HD mice. How intranuclear huntingtin is associated with caspase activation and apoptosis is unclear. Here we report that intranuclear huntingtin induces the activation of caspase-3 and the release of cytochrome c from mitochondria in cultured cells. As a result, cells expressing intranuclear huntingtin undergo apoptosis. We show that intranuclear huntingtin increases the expression of caspase-1, which may in turn activate caspase-3 and trigger apoptosis. We propose that the increased level of caspase-1 induced by intranuclear huntingtin contributes to HD-associated cell death.

Animals↗

High resolution chromosome 3p allelotyping of human lung cancer and preneoplastic/preinvasive bronchial epithelium reveals multiple, discontinuous sites of 3p allele loss and three regions of frequent breakpoints.

Allele loss involving chromosome arm 3p is one of the most frequent and earliest known genetic events in lung cancer pathogenesis and may affect several potential tumor suppressor gene regions. To further study the role of chromosome 3p allele loss in the pathogenesis of lung cancer, we performed high resolution loss of heterozygosity (LOH) studies on 97 lung cancer and 54 preneoplastic/preinvasive microdissected respiratory epithelial samples using a panel of 28 3p markers. Allelic losses of 3p were detected in 96% of the lung cancers and in 78% of the preneoplastic/preinvasive lesions. The allele losses were often multiple and discontinuous, with areas of LOH interspersed with areas of retention of heterozygosity. Most small cell lung carcinomas (91%) and squamous cell carcinomas (95%) demonstrated larger 3p segments of allele loss, whereas most (71%) of the adenocarcinomas and preneoplastic/preinvasive lesions had smaller chromosome areas of 3p allele loss. There was a progressive increase in the frequency and size of 3p allele loss regions with increasing severity of histopathological preneoplastic/preinvasive changes. In analyses of the specific parental allele lost comparing 42 preneoplastic/preinvasive foci with those lost in the lung cancer in the same patient (n = 10), the same parental allele was lost in 88% of 244 comparisons for 28 3p markers (P = 1.2 x 10(-36) for this occurring by chance). This indicates the occurrence of allele-specific loss in these foci similar to that seen in the tumor by a currently unknown mechanism. Analysis of all of the data indicated multiple regions of localized 3p allele loss including telomere-D3S1597, D3S1111-D3S2432, D3S2432-D3S1537, D3S1537, D3S1537-D3S1612, D3S4604/Luca19.1-D3S4622/Luca4.1, D3S4624/Luca2.1, D3S4624/Luca2.1-D3S1582, D3S1766, D3S1234-D3S1300 (FHIT/FRA3B region centered on D3S1300), D3S1284-D3S1577 (U2020/DUTT1 region centered on D3S1274), and D3S1511-centromere. A panel of six markers in the 600-kb 3p21.3 deletion region showed loss in 77% of the lung cancers, 70% of normal or preneoplastic/preinvasive lesions associated with lung cancer, and 49% of 47 normal, mildly abnormal, or preneoplastic/preinvasive lesions found in smokers without lung cancer; however, loss was seen in 0% of 18 epithelial samples from seven never smokers. The 600-kb 3p21.3 region and the 3p14.2 (FHIT/FRA3B) and 3p12 (U2020/DUTT1) regions were common, independent sites of breakpoints (retention of heterozygosity by some markers and LOH by other markers in the immediate region). We conclude that 3p allele loss is nearly universal in lung cancer pathogenesis; involves multiple, discrete, 3p LOH sites that often show a "discontinuous LOH" pattern in individual tumors; occurs in preneoplastic/preinvasive lesions in smokers with and without lung cancer (multiple lesions often lose the same parental allele); frequently involves breakpoints in at least three very small defined genomic regions; and appears to have allele loss and breakpoints first occurring in the 600-kb 3p21.3 region. These findings are consistent with previously reported LOH studies in a variety of tumors showing allele loss occurring by mitotic recombination and induced by oxidative damage.

Adult↗

Perceptual style and behavioral pattern of individuals with functional gastrointestinal disorders.

The present research examined the perceptual style and coping pattern characterizing individuals with functional gastrointestinal disorders. A matched case-control design was adopted to compare differences among the target group of individuals with functional gastrointestinal disorders (n = 40), a pain control group of individuals with rheumatism (n = 40), and the community control group of healthy individuals (n = 40). Perceptual style was measured by both monitoring and blunting responses to hypothetical stressful situations, and coping pattern was measured by the use of coping strategies in real-life stressful events. Results revealed that participants with functional gastrointestinal disorders differed from their healthy and rheumatic counterparts in having higher monitoring and lower blunting scores and using action-oriented coping strategies regardless of the controllability of stressful situations.

Adaptation, Psychological↗

An evaluation of whole blood testing for Helicobacter pylori infection in the Chinese population.

BACKGROUND: Near patient tests for Helicobacter pylori were developed to assist in the management of dyspepsia patients in general practice. Most studies were performed in western populations. AIM: To evaluate the rapid whole blood test (Flexpack HP) for H. pylori in the Chinese population. METHODS: Consecutive dyspeptic patients referred for upper endoscopy were recruited. During upper endoscopy, biopsies were taken from the antrum and corpus for rapid urease test (CLO test) and histological examination. After endoscopy, the whole blood test (FlexPack HP) was performed according to the manufacturer's instruction. Patients then received a 13C-urea breath test. Results of the whole blood test were compared with the gold standard (CLO test, histology and 13C-urea breath test). RESULTS: A total of 294 consecutive patients gave a valid Flexpack HP result for interpretation. The mean age of patients was 47.7 (range 15-85) years. Analysis showed a sensitivity, specificity, positive predictive value, negative predictive value and accuracy of 58%, 92%, 91%, 63% and 73% respectively. CONCLUSION: The FlexPack HP whole blood test showed good specificity but lacked sensitivity. It is not sensitive enough to be used in a general practice setting for the test-and-treat approach in the Chinese population.

Adult↗

Combination therapy with lamivudine and famciclovir for chronic hepatitis B-infected Chinese patients: a viral dynamics study.

In vitro studies have shown that lamivudine and penciclovir (the active metabolite of famciclovir) act synergistically to inhibit hepatitis B virus (HBV) replication. We compared the effectiveness of HBV viral suppression by lamivudine monotherapy versus lamivudine plus famciclovir combination therapy in Chinese patients with chronic HBV infection. Twenty-one Chinese hepatitis B e antigen (HBeAg)-positive patients, with detectable HBV DNA (Digene Hybrid Capture II), were randomized to receive either lamivudine 150 mg/d orally (group 1, 9 patients) or lamivudine 150 mg/d plus famciclovir 500 mg 3 times a day orally (group 2, 12 patients) for 12 weeks, with a follow-up period of at least 16 weeks. Serial serum HBV-DNA levels were determined and a mathematical model with provision for incomplete inhibition of virus production during therapy was applied to analyze the dynamics of viral clearance. The mean antiviral efficacy was significantly greater in group 2 than in group 1 (0.988 +/- 0.012 vs. 0.94 +/- 0.03, P =.0012). HBV DNA returned to pretreatment level within 16 weeks after the end of initial treatment in 4 patients (66.7%) in group 1 and none in group 2 (P =.08), who remained HBeAg positive and received no further treatment after week 12. Hence, in Chinese chronic HBeAg-positive patients, combination therapy using lamivudine and famciclovir was superior to lamivudine monotherapy in inhibiting HBV replication. Further studies of longer duration are needed to define whether combination therapy will increase the HBeAg seroconversion rate and decrease the rate of emergence of lamivudine-resistant variants.

2-Aminopurine↗

The BMP1 gene is essential for pathogenicity in the gray mold fungus Botrytis cinerea.

In Magnaporthe grisea, a well-conserved mitogen-activated protein (MAP) kinase gene, PMK1, is essential for fungal pathogenesis. In this study, we tested whether the same MAP kinase is essential for plant infection in the gray mold fungus Botrytis cinerea, a necrotrophic pathogen that employs infection mechanisms different from those of M. grisea. We used a polymerase chain reaction-based approach to isolate MAP kinase homologues from B. cinerea. The Botrytis MAP kinase required for pathogenesis (BMP) MAP kinase gene is highly homologous to the M. grisea PMK1. BMP1 is a single-copy gene. bmp1 gene replacement mutants produced normal conidia and mycelia but were reduced in growth rate on nutrient-rich medium. bmp1 mutants were nonpathogenic on carnation flowers and tomato leaves. Re-introduction of the wild-type BMP1 allele into the bmp1 mutant restored both normal growth rate and pathogenicity. Further studies indicated that conidia from bmp1 mutants germinated on plant surfaces but failed to penetrate and macerate plant tissues. bmp1 mutants also appeared to be defective in infecting through wounds. These results indicated that BMP1 is essential for plant infection in B. cinerea, and this MAP kinase pathway may be widely conserved in pathogenic fungi for regulating infection processes.

Amino Acid Sequence↗

Sex-related differences in bronchial epithelial changes associated with tobacco smoking.

BACKGROUND: Lung cancer is the most common cause of cancer death in North American women. Because smoking-related changes in the bronchial epithelium and in lung function have not been studied in detail in women, we used fluorescence bronchoscopy-directed biopsy to determine the prevalence of high-grade preinvasive lesions in former and current smokers of both sexes. METHODS: Spirometry, white-light bronchoscopy, and fluorescence bronchoscopy were performed in 189 women and 212 men older than 40 years of age who had smoked 20 pack-years or more (pack-years = number of packs of cigarettes smoked per day x number of years of smoking). RESULTS: Carcinoma in situ was found in 1.8% of the subjects, severe dysplasia was found in 6.5%, and moderate dysplasia was found in 14% (all preinvasive lesions). Compared with men, women had a lower prevalence of high-grade preinvasive lesions in the observed airways (14% versus 31%; odds ratio = 0.18; 95% confidence interval = 0.04-0.88), and women with preinvasive lesions had fewer such lesions (two-sided P = .048). The prevalence of preinvasive lesions did not change substantially for more than 10 years after cessation of smoking. Lung function was associated with the prevalence of preinvasive lesions, but the association was weaker in women than in men. If the presence of airflow obstruction was defined by an FEV1/FVC (forced expiratory volume in 1 second/forced vital capacity) value of 70% or less, only 56% of the men and 44% of the women with preinvasive lesions had abnormal lung function. CONCLUSION: In developing strategies for chemoprevention or early detection of lung cancer in high-risk populations, it is important to consider the effect of sex and arbitrarily chosen lung function values on the prevalence of preinvasive airway lesions.

Adult↗

Allelic losses at chromosome 8p21-23 are early and frequent events in the pathogenesis of lung cancer.

Allelic losses on the short arm of chromosome 8 (8p) have been reported as frequent events in several cancers, including lung. However, no comprehensive mapping analysis of chromosome 8p in lung cancer tumors has been performed, and no data are available about the stage at which these abnormalities occur during the multistage development of lung cancer. Using 26 microsatellite markers, we mapped the chromosome 8 regions frequently deleted in lung cancer in 13 small cell carcinoma and 17 non-small cell lung carcinoma cell lines and in 68 microdissected archival primary lung tumors (22 small cell lung carcinomas, 25 squamous cell carcinomas, and 21 adenocarcinomas). We also studied the role of 8p deletions in lung cancer pathogenesis by examining 95 microdissected normal epithelium and preneoplastic samples from 11 surgically resected squamous cell lung carcinomas and from 58 bronchoscopy biopsy samples obtained from 31 current and former smokers. High frequencies of deletions at 8p21-23 regions were detected in lung cancer cell lines and in primary lung tumors. Deletions commenced early during the multistage development of lung cancer at the hyperplasia/metaplasia stage in cancer patients and in smokers without cancer. Allelic deletions persisted for up to 48 years after smoking cessation. There was a progressive increase of the overall 8p21-23 loss of heterozygosity frequency and in the size of the deleted region with increasing severity of histopathological preneoplastic changes. In epithelial samples from resected squamous cell lung carcinomas, we compared the presence of loss of heterozygosity at 8p21-23 with deletions at chromosomes 3p and 9p. Of interest, the pattern of deletions was not random, and 8p21-23 allelic losses always followed 3p deletions and usually followed 9p deletions. We conclude that 8p21-23 deletions are frequent and early events in the pathogenesis of lung carcinomas.

Adult↗

Early diagnosis of lung cancer.

Recent advances in computer-assisted image analysis, tumor biology, PCR-based assays, fluorescence bronchoscopy, spiral CT, endobronchial treatment modalities, and chemoprevention make it possible to re-examine the strategy of early detection in the comprehensive management of lung cancer.

Humans↗

Critically ill medical patients, their demographics and outcome.

There are few reports describing the demographic details and outcome of noncoronary medical patients on adult general intensive care units. It is not known how medical patients differ from other critically ill patients and how this may influence their outcome. Consequently, we recorded the demographic details of 374 critically ill medical patients and followed their survival for up to 3 years. Patients referred from medical specialties are younger, more severely ill and suffer a higher severity-of-illness-adjusted intensive care unit mortality than other patients. The short-term survival of medical patients is poor with a median survival of 40 days. Twenty per cent of medical patients die after discharge from intensive care but before 40 days. However, the long-term survival of medical patients is better than other patients and almost as good as the general population. Further research is required to identify those patients who are likely to survive beyond 40 days.

APACHE↗

Validation of an enzymatic method for the determination of trace levels of ethanol.

The validation of an enzymatic method for the determination of trace levels of ethanol is described. The method, which involves the use of alcohol dehydrogenase (ADH) and nicotinamide adenine dinucleotide (NAD+), was validated according to USP 23 requirements. The validation parameters, including linearity and range, accuracy (recovery), precision, ruggedness, limit of detection (LOD), and limit of quantitation (LOQ), were established satisfactorily. The method is specific and selective for ethanol except in the presence of propyl, isopropyl, or butyl alcohol.

Alcohol Dehydrogenase↗