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Biomedical subjects

P Eng

Publications and source records attributed to P Eng.

At least 37 records · Page 2Linked to original sources
PubMed2001

Cytochrome P4501A2 (CYP1A2) activity and lung cancer risk: a preliminary study among Chinese women in Singapore.

There is increasing evidence for the role of heterocyclic and other arylamines in carcinogenesis, including lung carcinogenesis. Chinese women have a high rate of lung cancer despite a low smoking prevalence, and studies in this population may provide useful information on risk factors other than smoking. Hepatic CYP1A2 and NAT2 are involved in the metabolism of carcinogenic arylamines, and NAT2 also catalyzes the detoxification pathway for these compounds. In this study, we examined the effect of CYP1A2 activity using a urinary caffeine metabolic ratio assay for 54 Chinese women with newly diagnosed lung cancer (including 28 adenocarcinomas) and 174 hospital controls. Among them, NAT2 genotype was available for 47 cases and 98 controls. There was no effect of CYP1A2 activity on overall risk of lung cancer in the study population [odds ratio (OR) 0.8, 95% confidence interval (CI) 0.4-1.6, adjusted for age at diagnosis, smoking and cruciferous vegetable intake]. For adenocarcinomas, the OR was 1.5, 95% CI 0.6-3.4. After further adjustment for NAT2 acetylator genotype, the OR for adenocarcinoma was 1.8 (95% CI 0.7-4.8). When the combined NAT2/CYP1A2 status was examined, women with slow NAT2 and rapid CYP1A2 activity were at highest risk (adjusted OR 6.9, 95% CI 1.3-37.6) relative to women with rapid NAT2 and slow CYP1A2 activity, for lung adenocarcinoma. While larger studies are needed to confirm or refute these results, they are consistent with a role for heterocyclic arylamines in lung carcinogenesis in this primarily non-smoking population.

Adenocarcinoma↗
PubMed2001

Primary intrathoracic malignant effusion: a descriptive study.

BACKGROUND: Patients who present with malignant pleural/malignant effusion without a definite primary site are not well described in the medical literature. In the course of our clinical practice, we have observed certain traits that are peculiar to patients with such a presentation. We have applied the term primary intrathoracic malignant effusion (PIME) to describe this condition. STUDY OBJECTIVES: Patients must fulfill the following criteria before a diagnosis of PIME can be made: clinical presentation dominated by pleural/pericardial effusion; histologic proof of malignancy obtained from the pleura and/or pericardium; no definite primary site in the lungs or elsewhere from CT scan of the chest, chest radiograph, or physical and endoscopic examination; no history of malignancy; and no history of asbestos exposure. Exposure to environmental tobacco smoke (ETS) among the nonsmokers was examined in a case-control setting. METHODS: We conducted a retrospective search of our database of patients who were referred to the Department of Medical Oncology with a diagnosis of pleural/pericardial effusion from January 1993 to January 2000. RESULTS: Seventy-one of 200 patients from our database met the criteria. A significant majority of the patients were women (65%) and nonsmokers (72%). All patients had adenocarcinoma shown on biopsy. The majority of patients (63%) had disease localized to the intrathoracic serosal surfaces; the rest had distant metastases involving the lung (50%), bone (27%), liver (19%), brain (8%), and skin (4%). Six patients had two or more sites of distant metastases. There was a significant association with ETS exposure when compared to a control group comprised of patients with colonic cancer, matched for sex and age. The median survival was 10 months for patients with disease localized to the pleura/pericardium and 7 months for those with distant metastases. Thirty-eight patients (54%) received chemotherapy. All had platinum-based chemotherapy, except for three patients. The median survival for patients treated or not treated with chemotherapy was 12 months and 5 months, respectively. This difference in survival was statistically significant (p = 0.003). CONCLUSIONS: PIME should be viewed as a distinct entity. Its etiology remains largely unknown, although exposure to environmental tobacco smoke may play a part. Platinum-based chemotherapy may have a positive biological effect on this disease. More studies are required to elucidate the epidemiology, possible etiologic factors, and treatment options for this group of patients.

Adult↗
PubMed2001

Dietary isothiocyanates, glutathione S-transferase -M1, -T1 polymorphisms and lung cancer risk among Chinese women in Singapore.

Chinese populations consume a diet relatively high in isothiocyanates (ITCs), a derivative of cruciferous vegetables known to have cancer-protective effects. This class of compounds is metabolized by the glutathione S-transferase family of enzymes, which are also involved in the detoxification of tobacco-related carcinogens such as polycyclic aromatic hydrocarbons and alkyl halides. We evaluated the association between dietary isothiocyanate intake, GSTM1 and GSTT1 polymorphisms, and lung cancer risk in 420 Chinese women: 233 histologically confirmed lung cancer patients and 187 hospital controls. Among these, 58.8% of cases and 90.3% of controls were lifetime nonsmokers. An allele-specific PCR method was used to detect the presence or absence of the GSTM1 and GSTT1 genes in DNA isolated from peripheral blood. Higher weekly intake of ITCs (above the control median value of 53.0 micromol) reduced the risk of lung cancer to a greater extent in smokers [adjusted odds ratio (OR), 0.31; 95% confidence interval (CI), 0.10-0.98] than nonsmokers (OR, 0.70; 95% CI, 0.45-1.11). The inverse association was stronger among subjects with homozygous deletion of GSTM1 and/or GSTT1. Among nonsmokers with GSTM1-null genotype, higher intake of ITCs significantly reduced the risk of lung cancer (OR, 0.54; 95% CI, 0.30-0.95), an effect not seen among those with detectable GSTM1 (OR, 1.07; 95% CI, 0.50-2.29). Our results, in a Chinese female population, are consistent with the hypothesis that ITC is inversely related to the risk of lung cancer, and we show that among nonsmokers this effect may be primarily confined to GST-null individuals. Conjugation and elimination of ITCs is enhanced in GST-non-null relative to -null individuals, such that the GST metabolic genotype modifies the protective effect of ITCs on lung cancer development.

Adult↗
PubMed2000

Pressure-time curve predicts minimally injurious ventilatory strategy in an isolated rat lung model.

BACKGROUND: We tested the hypothesis that the pressure-time (P-t) curve during constant flow ventilation can be used to set a noninjurious ventilatory strategy. METHODS: In an isolated, nonperfused, lavaged model of acute lung injury, tidal volume and positive end-expiratory pressure were set to obtain: (1) a straight P-t curve (constant compliance, minimal stress); (2) a downward concavity in the P-t curve (increasing compliance, low volume stress); and (3) an upward concavity in the P-t curve (decreasing compliance, high volume stress). The P-t curve was fitted to: P = a. tb +c, where b describes the shape of the curve, b = 1 describes a straight P-t curve, b < 1 describes a downward concavity, and b > 1 describes an upward concavity. After 3 h, lungs were analyzed for histologic evidence of pulmonary damage and lavage concentration of inflammatory mediators. Ventilator-induced lung injury occurred when injury score and cytokine concentrations in the ventilated lungs were higher than those in 10 isolated lavaged rats kept statically inflated for 3 h with an airway pressure of 4 cm H2O. RESULTS: The threshold value for coefficient b that discriminated best between lungs with and without histologic and inflammatory evidence of ventilator-induced lung injury (receiver-operating characteristic curve) ranged between 0.90-1.10. For such threshold values, the sensitivity of coefficient b to identify noninjurious ventilatory strategy was 1.00. A significant relation (P < 0.001) between values of coefficient b and injury score, interleukin-6, and macrophage inflammatory protein-2 was found. CONCLUSIONS: The predictive power of coefficient b to predict noninjurious ventilatory strategy in a model of acute lung injury is high.

Animals↗
PubMed2000

Endobronchial stenting in patients requiring mechanical ventilation for major airway obstruction.

OBJECTIVE: To examine the value of therapeutic rigid bronchoscopy on subsequent ventilator weaning in ventilated patients with major airway obstruction. MATERIALS AND METHODS: Retrospective review of the medical records of patients who were receiving mechanical ventilation up to the time of rigid bronchoscopy over the period from September 1994 to January 1999. The setting is in an acute tertiary hospital. All patients underwent rigid bronchoscopy with endoscopic techniques (forceps removal, balloon dilation Nd:YAG laser resection and stent insertion) aimed at restoration of major airway patency. RESULTS: Seven patients were identified; 2 with benign stenosis and 5 with malignant stenosis. Six out of the 7 patients had presented with acute respiratory distress requiring emergent intubation, whilst 1 patient had extubation difficulties following general anaesthesia with endotracheal intubation. Three out of the 7 patients had previously failed extubation attempts. All 7 patients were successfully extubated within 48 hours following the procedure. CONCLUSIONS: Therapeutic rigid bronchoscopy is effective in the acute management of respiratory distress from central airway obstruction. Dramatic improvements in ventilatory status following therapeutic rigid bronchoscopy allow ventilator liberation in a select group of patients with an otherwise good performance status.

Adult↗
PubMed2000

Hard metal lung disease--the first case in Singapore.

INTRODUCTION: We report the first case of hard metal lung disease in Singapore and the occupational investigative work and control measures that were undertaken. CLINICAL PICTURE: A 38-year-old machinist in the tool manufacturing industry presented with exertional dyspnoea and cough. Chest X-ray revealed bilateral reticulonodular infiltrates with honeycombing. High resolution computed tomography scan of the thorax confirmed the presence of interstitial fibrosis. Open biopsy of the lung showed features of pneumoconiosis. Particle induced X-ray emission (PIXE) analysis, a relatively new elemental analysis technique, performed on the lung biopsy specimen confirmed the presence of tungsten and titanium; and he was diagnosed to have hard metal lung disease. Microbiologic, serologic and histologic investigations excluded an infective cause. Serial pulmonary function tests on follow-up showed no progression. He presented with haemoptysis 10 months later and was diagnosed to have tuberculosis on the basis of positive sputum and bronchoalveolar lavage cultures for Mycobacterium tuberculosis complex. TREATMENT: Preventive measures and permanent transfer to non-cobalt work were instituted. OUTCOME: The interstitial fibrosis appears to have stabilised. CONCLUSION: The diagnosis of hard metal lung disease must be considered in a worker exposed to cobalt presenting with interstitial fibrosis.

Adult↗
PubMed2000

A man with osteoblastic metastasis and hypocalcaemia.

We report a case of an 80-year-old man with osteoblastic metastases from advanced carcinoma of the prostate presenting with a grand mal seizure resulting from severe hypocalcaemia. He had low serum phosphate and ionised calcium levels, elevated serum skeletal alkaline phosphatase and intact parathormone levels. 99mTc radioisotope bone scan revealed a "super bone scan" suggestive of osteomalacia. The serum 1, 25-dihydroxycholecalciferol level was unexpectedly elevated. The biochemical abnormalities persisted despite high dose calcium replacement, but improved with supraphysiological doses of 1,25 (OH)2 vitamin D3 (Rocaltrol) therapy. We hypothesise that the hypocalcaemia in this patient was due to vitamin D resistance secondary to a humoral factor secreted by the tumour.

Aged↗
PubMed2000

Fumes from meat cooking and lung cancer risk in Chinese women.

Chinese women are recognized to have a high incidence of lung cancer despite a low smoking prevalence. Several studies have implicated domestic exposure to cooking fumes as a possible risk factor, although the exact carcinogens have yet to be identified. Heterocyclic amines are known carcinogens, which have been identified in cooked meat, and also in fumes generated during frying or grilling of meats. We conducted a case-control study of 303 Chinese women with pathologically confirmed, primary carcinomas of the lung and 765 controls to examine the association between exposure to meat cooking and lung cancer risk. Data on demographic background, smoking status, and domestic cooking exposure, including stir-frying of meat, were obtained by in-person interview while in hospital. The response rates among eligible cases and controls were 95.0 and 96.9%, respectively. The proportion of smokers (current or ex-smokers) among cases and controls was 41.7 and 13.1%, respectively. Adenocarcinomas comprised 31.5% of cancers among smokers and 71.6% among nonsmokers. When cases were compared with controls, the odds ratio (OR) for lung cancer (all subtypes) among ex-smokers was 4.3 [95% confidence interval (CI) 2.7-6.8] and that among current smokers was 5.0 (95% CI, 3.4-7.3). Among smokers, women who reported that they stir-fried daily in the past had a significantly increased risk of lung cancer (adjusted OR, 2.0; 95% CI, 1.0-3.8) and among these women, risk was enhanced for those who stir-fried meat daily (OR, 2.7; 95% CI, 1.3-5.5). Women who stir-fried daily but cooked meat less often than daily did not show an elevated risk (OR, 1.0. 95% CI, 0.5-2.4). Risk was further increased among women stir-frying meat daily who reported that their kitchen was filled with oily fumes during cooking (OR, 3.7; 95% CI, 1.8-7.5). These cooking practices on their own did not increase risk among nonsmokers in our study population. Our results suggest that inhalation of carcinogens, such as heterocyclic amines generated during frying of meat, may increase the risk of lung cancer among smokers. Further studies in different settings are warranted to examine this possibility, which may also help to explain the higher risk observed among women smokers compared with men.

Adenocarcinoma↗
PubMed1999

Induction chemotherapy followed by concurrent chemoradiotherapy in stage III unresectable non-small cell lung cancer.

The favourable experience with the combination regimen of vinorelbine, ifosfamide and cisplatin (NIP) in patients with metastatic non-small cell lung cancer (NSCLC) has led to a protocol assessing this regimen as an induction treatment in patients with stage III unresectable NSCLC, followed by thoracic radiotherapy with concurrent daily cisplatin as a radiosensitizer. Two cycles of NIP were administered 21 days apart; each cycle comprised i.v. vinorelbine 25 mg/m2 on days 1 and 8, i.v. ifosfamide 3 g/m2 on day 1 with MESNA as uroprotection, and i.v. cisplatin 50 mg/m2 on day 1. Radical thoracic radiotherapy commenced on day 43 to a total dose of 64 Gy and i.v. cisplatin 6 mg/m2 was given concurrently prior to each fraction of radiation as a sensitiser. Two more cycles of NIP were given to patients who responded favourably to the induction treatment about 2 weeks after completion of radiation. Between July 1995 and July 1997, 44 patients were treated with this protocol. This treatment schedule was generally well tolerated. Grade 3-4 neutropenia occurred in 50% of the patients and neutropenic sepsis was seen in 8. Grade 3-4 oesophagitis was uncommon. Most of the patients were able to complete the induction and concurrent chemoradiotherapy phase. Major response occurred in 75% of the patients with 2 (4.5%) complete responses (CR). A total of 6 patients achieved CR after chemoradiotherapy. At a median follow-up of 35 months, the median overall survival for all patients was 15 months with a 3-year survival rate of 24%. The median overall survival for stage IIIA patients was 19 months with a 3-year survival rate of 39% in contrast to 13 months' median overall survival and only 15% 3-year survival rate for stage IIIB. The NIP regimen results in a high response rate in NSCLC and this treatment programme seems to benefit selected patients with stage III disease.

Adult↗
PubMed1999

NAT2 slow acetylator genotype is associated with increased risk of lung cancer among non-smoking Chinese women in Singapore.

Among non-smokers, the factors resulting in lung carcinogenesis are poorly understood. We conducted a hospital-based case-control analysis of 294 Chinese women, of whom 217 were non-smokers, to evaluate the role of polymorphic N-acetyltransferase (NAT2) as a susceptibility factor for the disease. The proportion of slow acetylator genotypes among non-smoking cases (n = 92) and controls (n = 125) was 38.0 and 24.0%, respectively [odds ratio (OR) 2.0, 95% confidence interval (CI) 1.1-3.7]. No effect of NAT2 genotype was seen among smokers. Among non-smokers, the effect was marked for adenocarcinomas (OR 2.1, 95% CI 1.1-4.0). As NAT2 activity is known to modify risk of arylamine-induced carcinogenesis, our results suggest that exposure to arylamines in the environment may play a role in risk of lung cancer among non-smokers.

Acetylation↗
PubMed1999

Neural network prediction of obstructive sleep apnea from clinical criteria.

STUDY OBJECTIVES: Clinical prediction models for the diagnosis of obstructive sleep apnea (OSA) have lacked the accuracy necessary to confidently replace polysomnography (PSG). Artificial neural networks are computer programs that can be trained to predict outcomes based on experience. This study was conducted to test the hypothesis that a generalized regression neural network (GRNN) could accurately classify patients with OSA from clinical data. STUDY DESIGN: Retrospective review. SETTING: Regional sleep referral center. PATIENTS: Randomly selected records of patients referred for possible OSA. MEASUREMENTS: The neural network was trained using 23 clinical variables from 255 patients, and the predictive performance was evaluated using 150 other patients. RESULTS: The prevalence of OSA in this series of 405 patients (293 men and 112 women) was 69%. The trained GRNN had an accuracy of 91.3% (95% confidence interval [CI], 86.8 to 95.8). The sensitivity was 98.9% for having OSA (95% CI, 96.7 to 100), and the specificity was 80% (95% CI, 70 to 90). The positive predictive value that the patient would have OSA was 88.1% (95% CI, 81.8 to 94.4), whereas the negative predictive value that the patient would not have OSA (if so classified) was 98% (95% CI, 94 to 100). CONCLUSIONS: Appropriately trained GRNN has the ability to accurately rule in OSA from clinical data, and GRNN did not misclassify patients with moderate to severe OSA. In this study, use of the neural network could have reduced the number of PSG studies performed. Prospective validation of the neural network for the diagnosis of OSA is now required.

Adolescent↗
PubMed1998

Transudative malignant pleural effusions: prevalence and mechanisms.

BACKGROUND: Malignant pleural effusions are classically exudative, though occasionally they can be transudative. We attempted to determine the prevalence of transudative malignant pleural effusions and to describe their clinical and radiographic characteristics. METHODS: We studied the medical records of 215 patients with malignant pleural effusion, which contained complete data on pleural fluid analysis for 171 of them. RESULTS: Eight cases of transudative malignant effusion were found. Seven of these eight patients had a concomitant disorder known to cause transudative pleural effusion. One patient had fluid overload due to renal failure, and another had been admitted earlier with congestive heart failure. Two patients had definite evidence of deep venous thrombosis, allowing us to postulate pulmonary embolism as a factor contributing to transudation. Three patients had CT evidence of superior vena cava obstruction. Only one patient had no known associations with causes of transudative effusion. CONCLUSION: Malignant pleural effusions were transudative in 5% of our patients. In all except one patient, some evidence suggested the concomitant presence of a transudative state.

Aged↗
PubMed1998

Albuterol delivered by metered-dose inhaler (MDI), MDI with spacer, and Rotahaler device--a comparison of efficacy and safety.

A randomized double-blind, triple crossover study was conducted on 20 asthmatic patients (7 males and 13 females; age 40.9 +/- 14.2 Caucasians, 11 blacks, and 1 oriental. Criteria for admission included FEV1 < or = 80% of predicted when inhaled beta-agonists were witheld for at least 6 hrs and oral beta-agonists for 12 hr, in addition to at least 15% increase in FEV1, 15 min after treatment with albuterol with spacer delivery. Each of the study patients were tested on each of 3 separate days (within the same week) at baseline, 15, 30, 60, 120, 180, 240, 300, and 360 min post treatment. On each day albuterol was delivered by one of the 3 delivery devices and the other two methods delivered placebo. Albuterol was administered at the maximum recommended dosages of two puffs for MDI. Two puffs for MDI with spacer, and two capsules for Rotahaler. Spirometry, blood pressure and heart rate were measured at each testing interval. The mean percentage in FEV1 was higher in Rotahaler group compared to MDI with spacer (p < 0.001) and no significant difference in FEV1 was found between Rotahaler and MDI alone (p = 0.31). No significant changes in heart rate or blood pressure were associated with albuterol delivery by any of the three methods. Albuterol inhaled as a microfine powder was more effective than the same drug delivered as an aerosol by either MDI or MDI with spacer.

Adult↗
PubMed1998

Case series of bronchoscopic removal of tracheobronchial foreign body in six adults.

Tracheobronchial foreign body is rare in adults. Diagnosis is difficult and requires a high index of suspicion. We report 6 cases of tracheobronchial foreign bodies in adults and their removal, as well as a literature review of this topic. Case records, chest radiographs and computed tomographies (CT) of the thorax were reviewed. There were 5 males and 1 female with a median age of 63.5 years. One patient could not protect his airway (tracheostomy). Foreign bodies were sutures (2), vegetable matter like peanuts, vegetables and popcorn (3), and a voice prosthesis. Main symptoms were cough, haemoptysis and breathlessness. There were few signs on physical examination and chest X-rays were not helpful in diagnosis. All patients had fibreoptic bronchoscopy although 3 subsequently required rigid bronchoscopy for foreign body removal. All foreign bodies were successfully removed without any complications.

Aged↗
PubMed1998

Malaria requiring intensive care.

We studied 24 consecutive adult patients with malaria who required intensive care between 1 January 1994 and 31 December 1997. This was out of a total of 256 patients hospitalised at the Singapore General Hospital with malaria during these 4 years. Our aim was to characterise the type and severity, clinical features, complications, treatment and outcome of adult patients with malaria who required intensive care. In addition, we compared the actual and predicted mortality based on the Acute Physiology and Chronic Health Evaluation II (APACHE II) score. The travel history, prophylaxis, duration of fever before receiving treatment, type of malaria and severity, clinical data, complications, APACHE II score, treatment and outcome were analysed. Most cases were imported by locals travelling overseas or foreigners infected with the parasite elsewhere. Four patients had vivax malaria and 20 patients had severe falciparum malaria. All but 1 patient received transfusion with blood products and 6 patients with severe falciparum malaria had exchange transfusions. Complications were restricted to infection with P. falciparum: 9 patients required acute dialysis and 8 required mechanical ventilation. Three patients died giving a mortality of 15% for severe falciparum malaria. The overall mortality of patients with malaria was 1.2%. The mortality of patients with malaria requiring intensive care was 12.5% as compared with a predicted mortality of 18.7% based on the APACHE II prognostication system.

APACHE↗