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Biomedical subjects

W W Yew

Publications and source records attributed to W W Yew.

At least 55 records · Page 3Linked to original sources

Fibreoptic bronchoscopy in the diagnosis of lung cancer.

A total of 562 patients with lung cancer was evaluated by fibreoptic bronchoscopy (FOB) by three bronchoscopic diagnostic procedures: biopsy, bronchial brushing and bronchial washing. Endoscopically visible tumours (EV) were detected in 264, while 257 had endoscopically nonvisible tumours > or = 2 cm in diameter and FOB was done without fluoroscopy because of limited availability (ENV). Forty-one had small (< 2 cm), endoscopically nonvisible tumours with FOB performed under uniplanar fluoroscopy (ENV + F). The overall diagnostic yield rates of FOB were 98.1%, 61.5% and 58.5% for the EV, ENV and ENV + F cases, respectively. Reviewing the differential yield rates of the three diagnostic techniques and comparing them with the results of previous studies led to the following conclusions. (1) Combinations of biopsy with brushing and biopsy with washing can diagnose more than 95% of all fibreoptic bronchoscopy positive cases with endoscopically visible tumours. Performing either of these combinations may be more cost-effective than doing all three techniques routinely. (2) For cases with endoscopically nonvisible tumours, performance of all three diagnostic techniques is recommended, especially when fibreoptic bronchoscopy is performed without fluoroscopic guidance, as washing and brushing seem to compensate for a lower yield of the biopsy. (3) For tumours < 2 cm in diameter, knowledge on the diagnostic efficacy of fibreoptic bronchoscopy was limited owing to the small size of previous studies. The yield of 58.5% for fibreoptic bronchoscopy in these patients with performance of all three diagnostic procedures was comparatively high. It could be further increased to 75.6% if supplemented by percutaneous needle biopsy when fibreoptic bronchoscopy turned out to be nondiagnostic. If available, the use of transbronchial needle aspiration may also increase the overall diagnostic yield of fibreoptic bronchoscopy in these cases.

Biopsy↗

Serum pharmacokinetics of antimycobacterial drugs in patients with multidrug-resistant tuberculosis during therapy.

Serum samples of 13 patients with multidrug-resistant tuberculosis were taken 0, 1, 2, 4, 8 h after administration of antimycobacterial drugs for assay of levels in order to gain further insight into their basic pharmacokinetics. The drugs assessed were amikacin, kanamycin, ofloxacin, levofloxacin, para-aminosalicylic acid, prothionamide, cycloserine, pyrazinamide and ethambutol. Techniques used for assay were reversephase high-performance liquid chromatography, gas liquid chromatography and fluorescent polarization immunoassay. The results from 12 patients were evaluated. These provided new pharmacokinetic data on high-dose levofloxacin, cycloserine and prothionamide given once daily, and could be useful in guiding the scheduling of drugs. The data obtained might also lead to insights into the development of therapeutic drug monitoring in multidrug-resistant tuberculosis.

Adult↗

Rapid diagnosis of smear-negative pulmonary tuberculosis via fibreoptic bronchoscopy: utility of polymerase chain reaction in bronchial aspirates as an adjunct to transbronchial biopsies.

Fibreoptic bronchoscopy was performed on 190 patients with chest radiographic lesions and negative sputum smears for acid-fast bacilli. Aside from obtaining transbronchial biopsies for histological examination, bronchial aspirate specimens were also tested for Mycobacterium tuberculosis complex DNA by a conventional polymerase chain reaction (PCR) technique. Of 177 transbronchial biopsies performed, a diagnosis was found in 64 cases [43 cases of tuberculosis (TB), 17 cases of lung carcinoma and four cases of other infective/inflammatory diseases] giving a diagnostic yield of 36.2%. PCR was positive in 105 of 108 finally diagnosed cases of TB and 22 of 82 non-TB cases. The sensitivity, specificity, positive predictive value and negative predictive value of PCR when applied to bronchial aspirate specimens for diagnosing smear-negative pulmonary TB were 97.2%, 73.2%, 82.7% and 95.2% respectively. Therefore, detection of M. tuberculosis complex DNA in bronchial aspirates by PCR might have an adjunctive place to transbronchial biopsies in the rapid diagnosis of smear-negative pulmonary tuberculosis.

Adolescent↗

Therapeutic drug monitoring in antituberculosis chemotherapy.

Therapeutic drug monitoring in antituberculosis chemotherapy may play a strategic role in improving outcomes in selected patients. The most important use is in assisting clinicians to optimize therapy to achieve success and minimize toxicity. The other principal indication lies in the management of interaction of antituberculosis drugs with other drugs.

Antitubercular Agents↗

High seroprevalence of Helicobacter pylori in active bronchiectasis.

Helicobacter pylori causes chronic inflammation of the gastric mucosa and has been identified in tracheobronchial secretions. Serum IgG against H. pylori was therefore measured prospectively in consecutive subjects with bronchiectasis (n = 100; mean age +/- SD 55.1 +/- 16.7 yr), active pulmonary tuberculosis (n = 87; age, 57.3 +/- 19.1 yr), and healthy volunteers (n = 94; age, 54.6 +/- 7.6 yr). Seropositivity was found in 76.0% of bronchiectatic subjects, which was significantly higher than that of the control (54.3%, p = 0.001) and tuberculous (52.9%, p = 0.0001) groups. Multiple logistic regression, adjusted for age, sex, occupational social class, and number of persons living in the household, showed that H. pylori IgG levels of the bronchiectatic group were still significantly higher than that of the control (p = 0.0014) and tuberculous (p = 0.0154) groups. Multiple regression analysis revealed associations between H. pylori serology and sputum volume (p = 0.03) and age (p = 0.001) in the bronchiectatic patients, but not lung function indices or causes of bronchiectasis. The H. pylori seroprevalence in bronchiectasis was significantly (p = 0.0002) higher in patients who produced more (83.1%) than those who produced less than 5 ml sputum/24 h (58.6%). This is the first report of a high H. pylori seroprevalence in bronchiectasis which appears to be specific. Further studies are indicated to evaluate the possible pathogenic role of H. pylori in bronchiectasis.

Age Factors↗

A case of concomitant tuberculosis and sarcoidosis with mycobacterial DNA present in the sarcoid lesion.

A 35-year-old Chinese woman initially presented with histologically and bacteriologically confirmed tuberculous lymphadenitis. She was also found to have thrombocytopenia, elevated serum alkaline phosphatase, and bilateral lung infiltrates. After 15 months of antituberculosis treatment, despite resolution of the cervical lymphadenopathy, she started to experience dyspnea. Chest radiograph appearance, thrombocyte count, and liver biochemistry had all deteriorated as well. Histologic findings from tissues obtained via transbronchial biopsy and open lung biopsy were consistent with sarcoidosis but also showed the presence of mycobacterial DNA by the polymerase chain reaction. She subsequently achieved a very good response clinically, radiographically, hematologically, and biochemically with 1-year of corticosteroid treatment for her sarcoidosis, and she remained relapse-free afterwards. The concomitant presence of tuberculosis and sarcoidosis in this patient together with the presence of mycobacterial DNA in the sarcoid lesion reiterate the possibility that mycobacteria or some of its components may be capable of inducing the immune response and the pathologic changes of sarcoidosis.

Adult↗

Future directions in the development of new antitubercular drugs. Where do we go from here?

The global resurgence of tuberculosis and rampant drug resistance have rekindled the need for and interest in the development of new antitubercular drugs. Delineation of the possible drug targets furnished by the various mycobacterial cell components might result in rational approaches to the development of such agents. In the future, molecular genetics might help both in the bioengineering and rapid screening of the activity of new compound. Collaboration is anticipated between the pharmaceutical industry and academic institutions in these areas.

Antitubercular Agents↗

Mediastinal irradiation for graft-versus-host disease in a heart-lung transplant recipient.

Graft-versus-host disease in solid organ transplantation is very rare, but the prognosis is poor when the condition causes pancytopenia. We report a case of graft-versus-host disease in a heart-lung transplant recipient who at 2 weeks after transplantation had development of features of graft-versus-host disease, including bone marrow aplasia, that could not be attributed to drugs or viral infections. The diagnosis was confirmed by skin biopsy and demonstration of chimerism of peripheral lymphocytes. Augmentation of immunosuppression with intravenous methylprednisolone resulted in improvement in liver function but had no effect on the pancytopenia. Mediastinal irradiation was given with increase in both white blood cell and platelet counts. Unfortunately the patient eventually died of gastrointestinal bleeding and fungemia.

Adult↗

Refractory seizures in a young army cohort.

This survey covered male Singapore citizens born in 1974 who were medically screened at the age of 18 years before enlistment for compulsory military service. Suspected epileptics were referred to government hospitals for further management. Out of 20,542 men, there were 121 epileptics, giving a cumulative incidence of 5 per 1000 by age 18 years. We had information on 106 (87%) of these individuals and were able to interview them and review their hospital records. Seventy-three of the 106 (69%) epileptics had generalised seizures while 14 (13%) had refractory seizures. There was no statistically significant racial bias amongst these epileptics. Unprovoked afebrile seizures occurred early in these patients, half of whom had seizures onset before 7 years of age. Nine refractory epileptics had a history of febrile seizures, 4 of which were complex febrile seizures. Magnetic resonance imaging identified mesial temporal sclerosis in 2 patients and a hypothalamic lesion in 1 patient. Computed tomographic scans revealed focal cortical atrophy in 2 patients. Nine other patients had normal imaging studies. Nine out of 14 (64%) patients with refractory epilepsy had partial seizures; 4 (29%) had generalised seizures and 1 (7%) was unclassified. This is in contrast to the distribution of the entire cohort of epileptics studied. Two out of 9 patients with refractory partial seizures (gelastic epilepsy and mesial temporal sclerosis) had undergone surgery while 6 of the other 7 patients refused to consider surgery.

Adolescent↗

Detection and evaluation of p53 intron 2 polymorphism in lung carcinomas in Hong Kong.

A polymorphism in intron 2 of the p53 gene, which gives rise to 2 alleles, A1 and A2, was analyzed by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) and direct DNA-sequencing techniques. The distribution of this allele in the peripheral blood in the Chinese population comprising 27 healthy individuals, 30 bronchiectasis patients, 34 non-small-cell lung cancer (NSCLC) patients and 27 SCLC patients was analyzed. The genotypic distributions for this marker were significantly different between the blood of healthy individuals and SCLC patients. There was no significant difference between genotypes of Caucasians and Chinese. Tumors, normal lungs and peripheral blood of 83 adenocarcinoma and 10 squamous cell carcinoma patients were also studied. There was a significant difference in the distribution of the genotypes detected in tumor tissues vs. blood of adenocarcinoma patients. The frequency of detection of the A1/A1 genotype in the tumor tissues was increased in adenocarcinoma patients as compared with the blood of adenocarcinoma patients and was decreased in the blood of SCLC patients as compared with the blood of healthy individuals. Survival rates in Hong Kong adenocarcinoma patients with the A1/A1 genotype were lower than those in patients with A1/A2 and A2/A2 genotypes up to 30 months post-operation. Point mutations were detected at the p53 intron 2 polymorphic locus in NSCLC specimens, with a mutation rate of 15.4% (8/52). All mutations were GC transversions. The significance of this instability in p53 intron 2 remains to be elucidated.

Adenocarcinoma↗

Analysis of L-myc and GSTM1 genotypes in Chinese non-small cell lung carcinoma patients.

The genotypes of L-myc and GSTM1 genes were studied in normal lung tissues of 98 non-small cell lung carcinoma (NSCLC) patients from Hong Kong using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) techniques. Results showed a statistical difference in L-myc genotypes between Chinese and African Americans (P = 0.02). A significant deficit in heterozygotes resulting in the departure from Hardy-Weinberg equilibrium in lung cancer female patients was detected (0.01 < P < 0.02). There were significant differences in survival times in patients having L-L and S-S genotypes, with shorter survival times in the patients with L-L genotypes (0.01 < P < 0.05). Data on age, size of tumor, histological types, and lymph node metastasis showed no significant association with L-myc genotype. The survival time in the GSTM1-negative (null gene) group was significantly different from the GSTM1 positive group between 16 and 24 months after operation (0.01 < P < 0.05). There was no significant difference in the distribution of GSTM1 genotypes between Chinese and Caucasian Americans.

Biomarkers, Tumor↗

Chromosomal 11 alterations in non-small-cell lung carcinomas in Hong Kong.

We examined 60 non-small-cell lung cancer (NSCLC) patients for evidence of genetic alterations on chromosome 11 with nine polymorphic markers by Southern blot and microsatellite marker analysis. These analyses detected genetic alterations at both the 11p and 11q arms. At the 11p15 Ha-ras locus, the loss of heterozygosity (LOH) occurred in three out of 11 (27.3%) of the informative cases; at the 11p11-q12 D11S149 locus, the LOH occurred in two out of nine (22.2%) of the informative cases; and at the 11q13 INT-2 locus, the LOH occurred in four out of 18 (22.2%) of the informative cases. Microsatellite markers in the 11q12-q13 region revealed genetic alterations for PYGM in eight out of 54 (14.8%) of the specimens studied and 10 out of 55 (18.2%) of the specimens for the INT-2 marker. The data suggest genetic alterations occur in some of the lung cancer patients in both the 11p and 11q regions.

Adult↗

p53 mutations in non-small cell lung carcinomas in Hong Kong.

Lung resections from 50 Chinese patients in Hong Kong diagnosed as having non-small cell lung carcinoma were examined for the presence of mutations in the p53 gene by polymerase chain reaction single-stranded conformation polymorphism methods and for aberrant protein expression by immunostaining techniques. Eight-point mutations in the evolutionarily conserved exon 5 through 8 regions were detected. Abnormal expression of p53 detectable by immunostaining techniques was seen in 23 specimens tested. There was no statistically significant correlation between the detection of p53 aberrations and age, sex, smoking history, histologic type, and tumor stage. Aberrant p53 protein levels detectable by immunostaining were significantly associated with the clinical and nodal staging of the tumors.

Adenocarcinoma↗