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Biomedical subjects

Bing Lam

Publications and source records attributed to Bing Lam.

17 recordsLinked to original sources

Randomised study of three non-surgical treatments in mild to moderate obstructive sleep apnoea.

BACKGROUND: Patients with mild to moderate obstructive sleep apnoea (OSA) may be managed with different treatment options. This study compared the effectiveness of three commonly used non-surgical treatment modalities. METHODS: Subjects with mild to moderate OSA were randomised to one of three treatment groups for 10 weeks: conservative measures (sleep hygiene) only, continuous positive airways pressure (CPAP) in addition to conservative measures or an oral appliance in addition to conservative measures. All overweight subjects were referred to a weight-reduction class. OSA was assessed by polysomnography. Blood pressure was recorded in the morning and evening in the sleep laboratory. Daytime sleepiness was assessed with the Epworth Sleepiness Scale. Health-related quality of life (HRQOL) was assessed with the 36-Item Short-Form Health Survey (SF-36) and Sleep Apnoea Quality of Life Index (SAQLI). RESULTS: 101 subjects with a mean (SEM) apnoea-hypopnoea index (AHI) of 21.4 (1.1) were randomised to one of the three groups. The severity of sleep-disordered breathing was decreased in the CPAP and oral appliance groups compared with the conservative measures group, and the CPAP group was significantly better than the oral appliance group. Relief from sleepiness was significantly better in the CPAP group. CPAP was also better than the oral appliance or conservative measures in improving the "bodily pain" domain, and better than conservative measures in improving the "physical function" domain of SF-36. Both CPAP and the oral appliance were more effective than conservative measures in improving the SAQLI, although no difference was detected between the CPAP and oral appliance groups. CPAP and the oral appliance significantly lowered the morning diastolic blood pressure compared with baseline values, but there was no difference in the changes in blood pressure between the groups. There was also a linear relationship between the changes in AHI and body weight. CONCLUSION: CPAP produced the best improvement in terms of physiological, symptomatic and HRQOL measures, while the oral appliance was slightly less effective. Weight loss, if achieved, resulted in an improvement in sleep parameters, but weight control alone was not uniformly effective.

Blood Pressure↗

Alleviation of sleep apnea in patients with chronic renal failure by nocturnal cycler-assisted peritoneal dialysis compared with conventional continuous ambulatory peritoneal dialysis.

Nocturnal hemodialysis has been shown to improve sleep apnea in patients who receive conventional hemodialysis. It was hypothesized that nocturnal peritoneal dialysis (NPD) also is effective in correcting sleep apnea in patients who receive continuous ambulatory PD (CAPD). Overnight polysomnography (PSG) was performed in 46 stable NPD and CAPD patients who were matched for demographic and clinical attributes. The prevalence of sleep apnea, defined as an apnea-hypopnea index (AHI; or frequency of apnea and hypopnea per hour of sleep) > or =15, was 52% for NPD patients and 91% for CAPD patients (P = 0.007). The mean (+/-SD) AHI in NPD and CAPD patients was 31.6 +/- 25.6 and 50.9 +/- 26.4 (P = 0.025), respectively. For validation of the efficacy of NPD in alleviating sleep apnea, a fixed sequence intervention study was performed in which 24 incident PD patients underwent one PSG study during mandatory cycler-assisted NPD while awaiting their turn for CAPD training and a second PSG recording shortly after they were established on stable CAPD. The prevalence of sleep apnea was 4.2% during NPD and 33.3% during CAPD (P = 0.016). AHI increased from 3.4 +/- 1.34 during NPD to 14.0 +/- 3.46 during CAPD (P < 0.001). With the use of bioelectrical impedance analysis, total body water content was significantly lower during stable NPD than CAPD (32.8 +/- 7.37 versus 35.1 +/- 7.35 L; P = 0.004). NPD delivered greater reductions in total body water (-2.81 +/- 0.45 versus -1.34 +/- 0.3 L; P = 0.015) and hydration fraction (-3.63 +/- 0.64 versus -0.71 +/- 0.52%; P = 0.005) during sleep. Pulmonary function tests remained unchanged before and after conversion from NPD to CAPD. These findings suggest that NPD may have a therapeutic edge over CAPD in sleep apnea that is associated with renal failure as a result of better fluid clearance during sleep.

Adult↗

Advanced glycation endproducts in nondiabetic patients with obstructive sleep apnea.

SUBJECT OBJECTIVE: The formation and accumulation of advanced glycation endproducts (AGEs) has been implicated in the progression of age-related diseases such as diabetes mellitus and atherosclerosis. We hypothesize that AGE concentrations may be increased in subjects with obstructive sleep apnea (OSA), a condition associated with increased oxidative stress. METHODS: One hundred nineteen nondiabetic patients with OSA and 234 age-matched healthy controls and 134 patients with type 2 diabetes were recruited for participation in the study. Serum AGEs were assayed by competitive enzyme-linked immunosorbent assay using a polyclonal rabbit antisera raised against AGE-RNase. RESULTS: Serum AGEs were increased in OSA subjects, as compared with controls, but were less increased than the AGEs of patients with type 2 diabetes (control: 3.22 +/- 0.54 unit per mL; OSA: 3.68 +/- 0.39; diabetes mellitus: 4.11 +/- 0.99; analysis of variance p < .01). In the subjects with OSA, serum AGEs correlated with the duration of nocturnal desaturation (r = 0.21, p = .025) and plasma total 8-isoprostane concentration, a biochemical marker of oxidative stress (r = 0.22, p = .015), but not with fasting glucose level. On general linear model univariate analysis, the association between serum AGEs and 8-isoprostane was independent of age, sex, body mass index, smoking status, and glucose. CONCLUSION: Serum levels of AGEs were increased in nondiabetic subjects with OSA and were associated with the severity of OSA. Whether increased AGE formation contributes significantly to the high cardiovascular risk associated with OSA remains to be determined.

Diabetes Mellitus, Type 2↗

Obstructive sleep apnea and the metabolic syndrome in community-based Chinese adults in Hong Kong.

OBJECTIVE: To investigate the relationship between obstructive sleep apnea (OSA) and the metabolic syndrome, an established cardiovascular risk factor, in middle-aged Chinese subjects. DESIGN: A prospective cross-sectional study from community-dwelling volunteers. SUBJECTS: Subjects of either sex between 30 and 60 years old were recruited from the staff in public institutions or visitors to community centers in Hong Kong. METHODS: Demographic and anthropomentric indices, blood pressure and metabolic profile (fasting blood glucose, total cholesterol, low-density lipoprotein-cholesterol, high-density lipoprotein-cholesterol and triglycerides) were measured. Overnight polysomnographic studies were conducted. Presence of obstructive sleep apnea (OSA) was defined as apnea-hypopnea index (AHI)5. Metabolic syndrome was defined by the criteria of the National Cholesterol Education Panel, but using Asian cut-off values for abdominal obesity. RESULTS: A total of 255 subjects (150 men, 105 women) were studied. Subjects with OSA had five-fold risk of having metabolic syndrome. OSA was associated with the metabolic syndrome or its components, including waist circumference, diastolic blood pressure and fasting glucose, after adjusting for confounding variables. The independent determinants of OSA were age, gender, body mass index (BMI) and the metabolic syndrome. CONCLUSION: Among community-based middle-aged Chinese subjects, the metabolic syndrome was independent predictor of OSA.

Adult↗

HDL dysfunction in obstructive sleep apnea.

OBJECTIVE: HDL is anti-atherogenic and has antioxidant property. HDL dysfunction has been reported in patients with coronary heart disease and we hypothesize that HDL may also be dysfunctional in obstructive sleep apnea (OSA), a condition associated with increased oxidative stress. METHODS: 128 OSA patients and 82 controls were recruited. HDL dysfunction was determined by evaluating the ability of HDL to inhibit LDL oxidation ex vivo. Plasma HDL was incubated with native LDL in the presence of dichlorofluorescein which fluoresced upon interaction with lipid oxidation products. Plasma levels of oxidized LDL and 8-isoprostane were measured by ELISA and a specific enzyme immunoassay, respectively. RESULTS: Plasma total 8-isoprostane levels were elevated in OSA subjects (p<0.01). Despite having similar concentrations of plasma lipids and apolipoproteins as controls, OSA subjects had greater degree of HDL dysfunction (p<0.01) and increased oxidized LDL levels (p<0.05). The apnea-hypopnea index was the main determinant of HDL dysfunction in OSA, accounting for 30% of its variance, with oxidized LDL and apolipoprotein AI contributing to 8% and 5% of its variance respectively (p<0.001). CONCLUSION: HDL is dysfunctional in preventing the formation and inactivation of oxidized lipids in OSA subjects and may partly contribute to their increased cardiovascular risk.

Adult↗

An indolent case of severe acute respiratory syndrome.

Severe acute respiratory syndrome (SARS) is a highly contagious and typically rapidly progressive form of atypical pneumonia, which spread from Asia to many parts of the world in early 2003. Clinical diagnosis of SARS requires the presence of unremitting fever and progressive pneumonia despite antibiotic therapy, particularly in the presence of lymphopenia and raised transaminase levels. We report the case of a woman who had undergone a successful allogeneic bone marrow transplant for acute myeloid leukemia. She presented initially with fever and a normal chest radiograph. Her indolent clinical course of SARS was punctuated by resolution of fever, but there was progressive radiologic deterioration and increasing serum antibody titer against SARS coronavirus. Treatment with oral prednisolone and ribavirin normalized her lymphopenia, altered transaminases, chest radiograph and high-resolution computed tomography appearances rapidly. Our experience should alert other clinicians in recognizing this atypical indolent presentation of SARS, to protect health care workers and the community at large and to ensure that these patients are properly treated.

Anti-Bacterial Agents↗

Computed tomographic evaluation of the role of craniofacial and upper airway morphology in obstructive sleep apnea in Chinese.

OBJECTIVES: To evaluate the relationship between cephalometric parameters, upper airway morphological factors and obstructive sleep apnea (OSA) in Chinese subjects. DESIGN: Polysomnogram (PSG) were performed and scored using standard criteria. Supine lateral cephalometric parameters and pharyngeal cross-sectional areas at the level of velopharynx (VA) and hypopharynx (HA) were measured from computed tomographic scans. The roles of these parameters and other anthropometric/demographic characteristics in OSA (apnea hypopnea index, AHI > or = 5) and their relationship with severity of OSA were explored by multiple logistic and multinominal regression analysis. RESULTS: Ninety-two subjects, ranging from normal (n = 36), mild/moderate OSA (n = 34) to severe OSA (n = 22), were evaluated. Compared with normal subjects, OSA subjects were heavier (body mass index 27 vs. 24 kg/m2) and older (47 vs. 42 years of age); had smaller VA size and VA to HA ratio, lower positioned hyoid bone, longer and thicker soft palate, and more retropositioned mandible relative to maxilla. After controlling for body mass index and age, subjects with severe OSA (AHI > 30) had more retropositioned mandible relative to maxilla (odds ratio, OR 1.31, P = 0.044) and longer soft palate (OR 1.16, P = 0.01), while those with mild/moderate OSA had larger VA to HA ratio (OR 0.17, P = 0.018). CONCLUSIONS: Craniofacial factors and upper airway morphology contributed to severity of OSA in Chinese subjects. Having controlled for obesity, more retropositioned mandible was associated with more severe OSA.

Cephalometry↗

Severe acute respiratory syndrome: temporal lung changes at thin-section CT in 30 patients.

PURPOSE: To evaluate lung abnormalities on serial thin-section computed tomographic (CT) scans in patients with severe acute respiratory syndrome (SARS) during acute and convalescent periods. MATERIALS AND METHODS: Serial thin-section CT scans in 30 patients (17 men, aged 42.5 years +/- 12.2 [SD]) with SARS were reviewed by two radiologists together for predominant patterns of lung abnormalities: ground-glass opacities, ground-glass opacities with superimposed linear opacities, consolidation, reticular pattern, and mixed pattern (consolidation, ground-glass opacities, and reticular pattern). Scans were classified according to duration in weeks after symptom onset. Longitudinal changes of specific abnormalities were documented in 17 patients with serial scans obtained during 3 weeks. Each lung was divided into three zones; each zone was evaluated for percentage of lung involvement. Summation of scores from all six lung zones provided overall CT score (maximal CT score, 24). RESULTS: Median CT scores increased from 1 in the 1st week to 12.5 in the 2nd week. Ground-glass opacities with or without smooth interlobular septal thickening and consolidation were predominant patterns found during the 1st week. Ground-glass opacities with superimposed irregular reticular opacities, mixed pattern, and reticular opacities were noted from the 2nd week and peaked at or after the 4th week. After the 4th week, 12 (55%) of 22 patients had irregular linear opacities with or without associated ground-glass opacities and CT scores greater than 5; five of these patients had bronchial dilatation. When specific opacities were analyzed in 17 patients, consolidation generally resolved completely (n = 4) or to minimal residual opacities; six (55%) of 11 patients with ground-glass opacities had substantial residual disease (CT scores > 5) on final scans. CONCLUSION: There is a temporal pattern of lung abnormalities at thin-section CT in SARS. Predominant findings at presentation are ground-glass opacities and consolidation. Reticulation is evident after the 2nd week and persists in half of all patients evaluated after 4 weeks. Long-term follow-up is required to determine whether the reticulation represents irreversible fibrosis.

Adult↗

A community study of sleep-disordered breathing in middle-aged Chinese women in Hong Kong: prevalence and gender differences.

STUDY OBJECTIVES: To investigate the prevalence of sleep-disordered breathing (SDB) and obstructive sleep apnea syndrome (OSAS) in community-based, middle-aged Chinese women, and to compare the differences between gender with a similar study in men. DESIGN: A cross-sectional study conducted in Hong Kong from 1998 to 2000. SETTING: Sleep questionnaires were distributed to women (30 to 60 years old) in three offices and two community centers. All were invited to undergo full polysomnography in a sleep laboratory. PARTICIPANTS: Questionnaires were distributed to 1,532 women, and 854 questionnaires were returned. Polysomnography was conducted in 106 respondents. MEASUREMENTS AND RESULTS: Conservative estimated prevalence of SDB (apnea-hypopnea index [AHI] > = 5) and OSAS (AHI > or = 5 plus excessive daytime sleepiness [EDS]) were 3.7% and 2.1%, respectively. Age-specific prevalence of OSAS was 0.5%, 2.2%, and 6.1% in the 30- to 39-year-old, 40- to 49-year-old, and 50- to 60-year-old age groups, respectively. Stepwise multiple logistic regression analysis identified body mass index (BMI) and age as predictors of SDB. Compared to Chinese men, the prevalence of SDB and OSAS in women was lower, but the gender difference decreased with age. The AHI of affected women was also significantly lower despite comparable BMI. Compared to men, women with SDB had same degree of self-reported snoring and a similar degree of EDS despite the lower AHI. CONCLUSIONS: This study demonstrated an estimated prevalence of OSAS at 2.1% among middle-aged Chinese women in Hong Kong, with a 12-fold rise from the fourth to the sixth decade of life. BMI and age were significant independent predictors of SDB. Compared to men, women with SDB had lower AHIs, despite similar BMIs.

Adult↗

Endothelial function in obstructive sleep apnea and response to treatment.

Impaired endothelium-dependent vascular relaxation is a prognostic marker of atherosclerosis and cardiovascular disease. We evaluated endothelium-dependent flow-mediated dilation (FMD) and endothelium-independent nitroglycerin (NTG)-induced dilation of the brachial artery with Doppler ultrasound in 28 men with obstructive sleep apnea (OSA) and 12 men without OSA. Subjects with OSA (apnea-hypopnea index; mean +/- SD, 46.0 +/- 14.5) had lower FMD compared with subjects without OSA (5.3 +/- 1.7% vs. 8.3 +/- 1.0%, p < 0.001), and major determinants of FMD were the apnea-hypopnea index and age. There was no significant difference in NTG-induced dilation. Subjects with OSA were randomized to nasal continuous positive airway pressure (nCPAP) or observation for 4 weeks. Subjects on nCPAP had significant increase in FMD, whereas those on observation had no change (4.4% vs. -0.8%, difference of 5.2%, p < 0.001). Neither group showed significant change in NTG-induced vasodilation. Eight subjects who used nCPAP for over 3 months were reassessed on withdrawing treatment for 1 week. On nCPAP withdrawal, FMD became lower than during treatment (p = 0.02) and were similar to baseline values. Our findings demonstrated that men with moderate/severe OSA have endothelial dysfunction and treatment with nCPAP could reverse the dysfunction; the effect, however, was dependent on ongoing use.

Adult↗

Severe acute respiratory syndrome: relationship between radiologic and clinical parameters.

PURPOSE: To quantify severity of severe acute respiratory syndrome (SARS) on chest radiographs and to determine its relationship with clinical parameters. MATERIALS AND METHODS: Forty patients (mean age, 42.90 years +/- 14.01 [SD]; median age, 41.5 years; age range, 25-82 years) with clinically diagnosed SARS were evaluated. Heart rate, oxygen saturation, temperature, and alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were recorded daily. Severity of lung changes on chest radiographs was scored according to percentage of involved lung. Radiographic scores at days of admission, treatment, and maximal radiographic score were extracted for statistical analysis with clinical parameters. Time to maximal radiographic score from admission and days between onset and beginning of treatment were determined. Correlations between radiographic and clinical parameters were evaluated with Spearman rank correlation. Sex differences with respect to clinical and radiographic parameters were evaluated with Mann-Whitney test. RESULTS: Median chest radiographic scores peaked 5 days after beginning of treatment before they declined. Maximal and treatment radiographic scores were inversely related to oxygen saturation (r = -0.67, P <.001; r = -0.35, P =.03). Admission radiographic score was correlated with admission AST level (r = 0.53, P =.003); treatment radiographic score, with treatment ALT and AST levels (r = 0.43, P =.007; r = 0.42, P =.019); and time to maximal radiographic score, with AST level at maximal radiographic score (r = -0.45, P =.006), admission radiographic score (r = -0.55, P <.001), treatment radiographic score (r = -0.58, P <.001), and admission ALT and AST levels (r = -0.44, P =.007; r = -0.58, P =.001). Treatment delay was associated with AST level at maximal radiographic score (r = 0.53, P =.001), treatment radiographic score (r = 0.60, P <.001), and time to maximal radiographic score (r = -0.36, P =.02). No sex differences occurred with respect to radiographic and clinical parameters (P >.05). CONCLUSION: Severity of lung abnormalities quantified on chest radiographs correlates with clinical and laboratory parameters.

Adult↗

High-dose pulse versus nonpulse corticosteroid regimens in severe acute respiratory syndrome.

The treatment of atypical pneumonia, subsequently termed severe acute respiratory syndrome (SARS), is controversial, and the efficacy of corticosteroid therapy is unknown. We have evaluated the clinical and radiographic outcomes of 72 patients with probable SARS (median age 37 years, 30 M), who received ribavirin and different steroid regimens in two regional hospitals. Chest radiographs were scored according to the percentage of lung field involved. Seventeen patients initially received pulse steroid (PS) (methylprednisolone > or =500 mg/day) and 55 patients initially received nonpulse steroid (NPS) (methylprednisolone <500 mg/day) therapy. The cumulative steroid dosage; intensive care unit admission, mechanical ventilation, and mortality rates; and hematologic and biochemical parameters were similar in both groups after 21 days. However, patients in the PS group had less oxygen requirement, better radiographic outcome, and less likelihood of requiring rescue PS therapy than their counterparts. There was no significant difference between the two groups in hemolytic anemia, severe secondary infections, or hematemesis, but patients in the PS group had less hyperglycaemia. Initial use of pulse methylprednisolone therapy appears to be a more efficacious and an equally safe steroid regimen when compared with regimens with lower dosage and should be considered as the preferred steroid regimen in the treatment of SARS, pending data from future randomized controlled trials.

Adult↗

A cluster of cases of severe acute respiratory syndrome in Hong Kong.

BACKGROUND: Information on the clinical features of the severe acute respiratory syndrome (SARS) will be of value to physicians caring for patients suspected of having this disorder. METHODS: We abstracted data on the clinical presentation and course of disease in 10 epidemiologically linked Chinese patients (5 men and 5 women 38 to 72 years old) in whom SARS was diagnosed between February 22, 2003, and March 22, 2003, at our hospitals in Hong Kong, China. RESULTS: Exposure between the source patient and subsequent patients ranged from minimal to that between patient and health care provider. The incubation period ranged from 2 to 11 days. All patients presented with fever (temperature, >38 degrees C for over 24 hours), and most presented with rigor, dry cough, dyspnea, malaise, headache, and hypoxemia. Physical examination of the chest revealed crackles and percussion dullness. Lymphopenia was observed in nine patients, and most patients had mildly elevated aminotransferase levels but normal serum creatinine levels. Serial chest radiographs showed progressive air-space disease. Two patients died of progressive respiratory failure; histologic analysis of their lungs showed diffuse alveolar damage. There was no evidence of infection by Mycoplasma pneumoniae, Chlamydia pneumoniae, or Legionella pneumophila. All patients received corticosteroid and ribavirin therapy a mean (+/-SD) of 9.6+/-5.42 days after the onset of symptoms, and eight were treated earlier with a combination of beta-lactams and macrolide for 4+/-1.9 days, with no clinical or radiologic efficacy. CONCLUSIONS: SARS appears to be infectious in origin. Fever followed by rapidly progressive respiratory compromise is the key complex of signs and symptoms from which the syndrome derives its name. The microbiologic origins of SARS remain unclear.

Adrenal Cortex Hormones↗

Extrapulmonary presentation of asymptomatic pulmonary lymphangioleiomyomatosis.

Lymphangioleiomyomatosis (LAM) is a rare parenchymal lung disease, which affects young women of childbearing age and is characterized pathologically by proliferation of interstitial smooth muscle and formation of cysts in the lung. While LAM is usually predominantly a respiratory disorder, it can also initially involve other extrapulmonary organs. We report the case of a 35-year-old Chinese woman, who presented with a 4-week history of left thigh swelling which was found to be secondary to compression of pelvic veins by a mass lesion. The latter was found histologically to show LAM. Despite the patient being asymptomatic and displaying normal lung function, a thoracic high resolution CT scan showed typical features of early LAM. This case further illustrates that LAM can have multisystem involvement, and demonstrates the importance of being aware of the diagnosis in cases presenting with extrapulmonary manifestation, in order that patients are diagnosed and managed appropriately.

Adnexal Diseases↗

Severe acute respiratory syndrome: radiographic evaluation and clinical outcome measures.

PURPOSE: To evaluate the relationship among chest radiographs, oxygen supplementation requirement, and treatment response in severe acute respiratory syndrome (SARS). MATERIALS AND METHODS: Forty patients (20 women, 20 men; mean age, 42.90 years +/- 14.01 [SD]; median age, 41.5 years; age range, 25-82 years) with SARS were evaluated. Daily chest radiographs were graded according to percentage of lung involvement during 20.15 days +/- 5.56 (median, 20 days; range, 14-38 days). Times between symptoms and treatment and time to reach maximal radiographic score from admission and treatment day were determined. Daily oxygen saturation (Sao2) and oxygen supplementation including mechanically assisted ventilation were recorded. Treatment response was defined as good, fair, and poor. Patterns of radiographic opacity at admission and at maximal radiographic score were noted. Differences in radiographic and clinical parameters with respect to oxygen supplementation and treatment response were respectively evaluated with Mann-Whitney and Kruskal-Wallis tests. RESULTS: Larger maximal radiographic scores, lower Sao2 at maximal radiographic change, longer time from treatment to maximal radiographic score (P <.01), and diffuse consolidation at maximal radiographic score were associated with oxygen supplementation. Parameters that influenced treatment response were time from symptom onset to treatment day (P =.003), time from admission to treatment day (P <.001), time to maximal radiographic score from treatment day (P =.001), maximal radiographic score (P =.009), Sao2 at maximal radiographic score (P =.13), and treatment radiographic score (P =.03). Fair responders had shorter time between admission and treatment than did either good (P <.001) or poor responders (P =.002) and shorter time between symptoms and treatment (P <.001) and lower treatment radiographic score (P =.012) than did good responders. Good (82%), poor (36%), and fair (33%) responders developed maximal chest radiographic scores within 4 days of treatment (P =.008). Radiographic patterns at both admission and maximal radiographic score did not influence treatment response. CONCLUSION: There are significant relationships among radiographic parameters, oxygen supplementation, and treatment response, and these relationships appear to be clinically useful in the treatment of SARS.

Adult↗

Obstructive sleep apnea is independently associated with insulin resistance.

Epidemiological studies have implicated obstructive sleep apnea (OSA) as an independent comorbid factor in cardiovascular and cerebrovascular diseases. It is postulated that recurrent episodes of occlusion of upper airways during sleep result in pathophysiological changes that may predispose to vascular diseases. Insulin resistance is a known risk factor for atherosclerosis, and we postulate that OSA represents a stress that promotes insulin resistance, hence atherogenesis. This study investigated the relationship between sleep-disordered breathing and insulin resistance, indicated by fasting serum insulin level and insulin resistance index based on the homeostasis model assessment method (HOMA-IR). A total of 270 consecutive subjects (197 male) who were referred for polysomnography and who did not have known diabetes mellitus were included, and 185 were documented to have OSA defined as an apnea-hypopnea index (AHI) > or =5. OSA subjects were more insulin resistant, as indicated by higher levels of fasting serum insulin (p = 0.001) and HOMA-IR (p < 0.001); they were also older and more obese. Stepwise multiple linear regression analysis showed that obesity was the major determinant of insulin resistance but sleep-disordered breathing parameters (AHI and minimum oxygen saturation) were also independent determinants of insulin resistance (fasting insulin: AHI, p = 0.02, minimum O(2), p = 0.041; HOMA-IR: AHI, p = 0.044, minimum O(2), p = 0.022); this association between OSA and insulin resistance was seen in both obese and nonobese subjects. Each additional apnea or hypopnea per sleep hour increased the fasting insulin level and HOMA-IR by about 0.5%. Further analysis of the relationship of insulin resistance and hypertension confirmed that insulin resistance was a significant factor for hypertension in this cohort. Our findings suggest that OSA is independently associated with insulin resistance, and its role in the atherogenic potential of sleep disordered breathing is worthy of further exploration.

Adult↗

Aberrant promoter methylation in Chinese patients with non-small cell lung cancer: patterns in primary tumors and potential diagnostic application in bronchoalevolar lavage.

This study was aimed at defining patterns of aberrant gene methylation in non-small cell lung cancer (NSCLC) in Chinese patients and its use in detecting cancer cells in bronchoalveolar lavage (BAL). The methylation-specific PCR (MSP) was used to study methylation of the p16, retinoic acid receptor-beta (RARbeta), death-associated protein (DAP) kinase, and O(6)-methylguanine-DNA-methyltransferase (MGMT) genes in 75 NSCLCs [44 adenocarcinomas and 31 squamous cell carcinomas (SCCs)] and 68 BALs from suspected lung cancers. More females had adenocarcinoma than SCC (11 of 44 versus 2 of 31, P = 0.04). Aberrant methylation in at least one gene was found in 63 of 75 (84%) NSCLCs. p16, RARbeta, DAP kinase, and MGMT methylation was similar in adenocarcinoma and SCC. However, females with NSCLC showed more frequent p16 methylation than males (12 of 13 versus 36 of 62, P = 0.02), because of more frequent p16 methylation in female adenocarcinomas (10 of 11 versus 17 of 33, P = 0.02). This sexual difference was not observed in RARbeta, DAP kinase, and MGMT. At 92%, the frequency of p16 methylation in Chinese female NSCLC is one of the highest known. For BAL, MSP and cytological analysis showed concordant and discordant results in 25 of 68 and 43 of 68 samples. Of 41 MSP+/cytology- cases, 35 were eventually shown to have malignant lung lesions, 4 were at high risk but had no evidence of lung cancer, and 2 were lost to follow-up. There were two MSP-/cytology+ cases. Frequent gene methylations were seen in Chinese NSCLC patients. More frequent p16 methylation was seen in female patients. MSP is a useful molecular adjunct for cancer cell detection in BAL samples.

Adenocarcinoma↗