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Biomedical subjects

K Chin

Publications and source records attributed to K Chin.

At least 19 recordsLinked to original sources
PubMed2006

Effect of nCPAP therapy on heart rate in patients with obstructive sleep apnoea-hypopnoea.

BACKGROUND: Elevated heart rate (HR) is a risk factor for cardiovascular disease. The effects of obstructive sleep apnoea-hypopnoea syndrome (OSAHS) on HR are controversial. AIM: To investigate the effect of nasal continuous positive airway pressure (nCPAP) therapy on HR in OSAHS patients. METHODS: Sixty-two OSAHS patients underwent 24-h electrocardiographic recording, both before and 3 or 4 days after instigation of nCPAP. RESULTS: After nCPAP was started, HR significantly decreased (mean +/- SD 71.8 +/- 10.6 vs. 67.5 +/- 9.4 bpm, p < 0.0001), both in the daytime (0600-2200 h, 76.3 +/- 12.2 vs. 72.2 +/- 10.2 bpm, p < 0.0001) and at night-time (2200-0600 h, 64.5 +/- 9.1 vs. 60.0 +/- 8.9 bpm, p < 0.0001). HR was significantly reduced in both periods in the 44 patients with hypertension and/or diabetes mellitus, but only during the night-time in the 18 with neither condition. Before nCPAP treatment, HR was positively correlated with percentage time of arterial O2 saturation <90% during sleep (p = 0.008) and with the apnoea-hypopnoea index during sleep (p = 0.003). In 15 patients undergoing HR for 2 days before starting nCPAP, the mean HRs for the two periods were similar (p = 0.95). DISCUSSION: nCPAP therapy appears to decrease HR in OSAHS patients, and may thereby reduce their risk of cardiovascular disease.

Adiponectin↗
PubMed2006

18-Fluorine-labelled 2-deoxy-2-fluoro-D-glucose positron emission tomography/computed tomography standardised uptake values: a non-invasive biomarker for the risk of metastasis from choroidal melanoma.

AIMS: To correlate the clinical, ultrasound and pathological features of the eyes first evaluated by 18-fluorine-labelled 2-deoxy-2-fluoro-d-glucose (FDG) positron emission tomography (PET)/computed tomography and then enucleated for choroidal melanoma. METHODS: 14 consecutive patients enucleated for choroidal melanoma were examined. At presentation, clinical, ultrasound and PET/computed tomography imaging were carried out. Ultrasound was used to measure the tumour size and evaluate the tumour shape and intrinsic vascularity (blood flow). Histopathological and immunohistochemical evaluations included tumour cell type, necrosis, glycogen content, vascularity and extrascleral extension. RESULTS: 13 tumours were T3 and one T2 (American Joint Committee on Cancer - International Union against Cancer). The mean tumour height was 10.6 (range 3.5-17.7) mm with a largest basal dimension of 19.3 (range 14.5-30) mm. Patients having melanoma with the highest six standardised uptake values ((SUV) > or =4.0) were (on average) >10 years older, their melanomas had larger basal dimensions and were epithelioid-cell type; three melanomas were centred anterior to the equator; three contained enlarged blood vessels (>150 mum in diameter); and three formed extrascleral extension. Patients with the two highest SUV tumours died due to metastatic melanoma. CONCLUSION: PET/computed tomography imaging offers a physiological assessment of glucose metabolism in primary choroidal melanomas. Increased FDG PET/computed tomography SUV was positively correlated with known clinical, pathological and ultrasound features linked to metastatic potential of choroidal melanoma.

Adult↗
PubMed2006

High sensitivity C-reactive protein in asthma.

Asthma is characterised by chronic inflammation of the airways, but the relevance of high-sensitivity assays for C-reactive protein (hs-CRP), which are known to be a sensitive marker of low-grade systemic inflammation, has not been fully studied in asthma. The objective was to examine serum hs-CRP levels in patients with asthma and their relationship to clinical characteristics and degree of airway inflammation. Serum hs-CRP levels were cross-sectionally examined in steroid-naive (n = 22) and steroid-inhaling (n = 23) adult patients with asthma and healthy controls (n = 14). All were nonsmokers. Serum hs-CRP levels were significantly increased in steroid-naive patients (mean+/-sd 1.33+/-1.48 mg.L(-1)) compared with controls (0.21+/-0.30 mg.L(-1)), but not in patients on inhaled corticosteroid. Among steroid-naive patients, serum hs-CRP levels significantly negatively correlated with indices of pulmonary function (forced expiratory volume in one second/forced vital capacity and forced mid-expiratory flow) and positively with sputum eosinophil count. Among patients on inhaled corticosteroid, hs-CRP levels did not correlate with any indices. In conclusion, an increase in serum C-reactive protein levels measured by high-sensitivity assays may be associated with airflow obstruction and airway inflammation, and may serve as a surrogate marker of airway inflammation in asthma.

Adult↗
PubMed2005

Design considerations for array CGH to oligonucleotide arrays.

BACKGROUND: Representational oligonucleotide microarray analysis has been developed for detection of single nucleotide polymorphisms and/or for genome copy number changes. In this process, the intensity of hybridization to oligonucleotides arrays is increased by hybridizing a polymerase chain reaction (PCR)-amplified representation of reduced genomic complexity. However, hybridization to some oligonucleotides is not sufficiently high to allow precise analysis of that portion of the genome. METHODS: In an effort to identify aspects of oligonucleotide hybridization affecting signal intensity, we explored the importance of the PCR product strand to which each oligonucleotide is homologous and the sequence of the array oligonucleotides. We accomplished this by hybridizing multiple PCR-amplified products to oligonucleotide arrays carrying two sense and two antisense 50-mer oligonucleotides for each PCR amplicon. RESULTS: In some cases, hybridization intensity depended more strongly on the PCR amplicon strand (i.e., sense vs. antisense) than on the detection oligonucleotide sequence. In other cases, the oligonucleotide sequence seemed to dominate. CONCLUSION: Oligonucleotide arrays for analysis of DNA copy number or for single nucleotide polymorphism content should be designed to carry probes to sense and antisense strands of each PCR amplicon to ensure sufficient hybridization and signal intensity.

Aneuploidy↗
PubMed2005

Prospective study of extracorporeal photopheresis in steroid-refractory or steroid-resistant extensive chronic graft-versus-host disease: analysis of response and survival incorporating prognostic factors.

We enrolled 25 patients with extensive, steroid-refractory chronic graft-versus-host disease (cGVHD) in a prospective trial evaluating the efficacy of extracorporeal photophoresis (ECP) in both skin and visceral cGVHD. The median time from transplant to initiation of ECP was 790 days. ECP was administered for 2 consecutive days every 2 weeks in 17 patients and once a week in eight patients until best response or stable disease. The median duration of therapy was 9 months (range 3-24 months). In all, 20 patients had improvement in cutaneous GVHD and six had healing of oral ulcerations. Steroid sparing or discontinuation of immunosuppressive medications was possible in 80% of patients. Response rates were similar between patients receiving treatment weekly vs every 2 weeks and in patients commencing ECP less than vs greater than 18 months from transplant (70 vs 66%). When patients were stratified based on the Akpek prognostic score, there was no difference in overall response between the favorable (Akpek score<2.5) and unfavorable risk groups, but patients with progressive onset cGVHD tended to have a higher response than those with de novo onset. In summary, we report improvement in skin and/or visceral cGVHD in 71% overall and 61% of high-risk patients.

Adolescent↗
PubMed2005

Relationship of airway wall thickening to an imbalance between matrix metalloproteinase-9 and its inhibitor in asthma.

BACKGROUND: The balance between matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) may be critical in extracellular matrix remodelling, a characteristic of asthmatic airways. An excess of TIMP-1 over MMP-9 has been associated with chronic airflow obstruction but the mechanisms underlying this association remain unknown. Recent computed tomographic (CT) studies indicate that airway wall thickening is associated with chronic airflow obstruction. METHODS: Sputum levels of MMP-9, TIMP-1, and their molar ratio were examined in 26 patients with stable asthma and their relationship with pulmonary function and airway wall thickness, assessed by a validated CT technique which measured wall area corrected by body surface area (WA/BSA), the ratio of WA to outer wall area (WA%), and the absolute wall thickness corrected by radicalBSA of a segmental bronchus (T/ radicalBSA), was examined. RESULTS: Sputum MMP-9 levels were inversely correlated with WA% and TIMP-1 levels were positively correlated with WA/BSA and T/ radicalBSA. The MMP-9/TIMP-1 molar ratio was inversely correlated with WA% and T/ radicalBSA and positively correlated with post-bronchodilator values of mid-forced expiratory flow and maximum expiratory flow at the quartile of lung volume. CONCLUSION: Excess TIMP-1 may have a pathogenetic role in airway wall thickening in asthmatic patients which may result in chronic airflow obstruction.

Asthma↗
PubMed2004

Phase I and pharmacokinetic study of MCC-465, a doxorubicin (DXR) encapsulated in PEG immunoliposome, in patients with metastatic stomach cancer.

BACKGROUND: MCC-465 is an immunoliposome-encapsulated doxorubicin (DXR). The liposome is tagged with polyethylene glycol (PEG) and the F(ab')2 fragment of human monoclonal antibody GAH, which positively reacts to >90% of cancerous stomach tissues, but negatively to all normal tissues. In preclinical studies, MCC-465 showed superior cytotoxic activity against several human stomach cancer cells compared with DXR or DXR-incorporated PEG liposomes. The main purpose of this trial was to define the maximum tolerated dose (MTD), dose limiting toxicity (DLT), recommended phase II dose and pharmacokinetics (PK) of MCC-465. PATIENTS AND METHODS: Patients with metastatic or recurrent stomach cancer were eligible for entry. The initial dose was 6.5 mg/m2. MCC-465 was administered as a 1-h infusion every 3 weeks and the treatment continued for up to six cycles. RESULTS: Twenty-three patients received a total of 62 cycles at the 6.5-45.5 mg/m2 dose level. DLTs were myelosuppression and appetite loss at the 45.5 mg/m2 dose level. Other toxicities were mild. Neither palmar-plantar erythrodysesthesia nor cardiotoxicity was observed. Acute reactions related to infusion were observed commonly in 16 patients over the entire dose range. While no antitumor response was observed, stable disease (SD) was observed in 10 out of 18 evaluable patients. The pharmacokinetic study showed a similar AUC and Cmax to Doxil. CONCLUSION: MCC-465 was well tolerated. The recommended dose for a phase II study of MCC-465, for a 3-week schedule, is considered to be 32.5 mg/m2 in an equivalent amount of DXR.

Adult↗
PubMed2004

A phase II study of single-agent docetaxel in patients with metastatic esophageal cancer.

BACKGROUND: To evaluate the activity and toxicity of docetaxel in patients with metastatic esophageal cancer. PATIENTS AND METHODS: Eligible patients had histologically confirmed carcinoma of the esophagus with measurable metastatic sites according to Response Evaluation Criteria in Solid Tumors (RECIST). Patients were either chemotherapy-naïve or previously treated with one regimen of chemotherapy. Docetaxel 70 mg/m(2) was administered intravenously over 1-2 h, every 21 days. RESULTS: Of 52 patients enrolled in this study, three were excluded because they did not receive docetaxel due to worsening condition after enrollment. Thirty-six patients had received prior platinum-based chemotherapy. The majority of patients (94%) had squamous cell carcinoma. Ten of 49 evaluable patients [20%; 95% confidence interval (CI) 10-34%] showed a partial response. Of the 10 partial responses, six patients had received prior platinum-based chemotherapy. Grade 3 or 4 neutropenia was noted in 43 of 49 patients (88%), and nine of 49 patients (18%) developed febrile neutropenia. Twenty-eight of 49 patients (57%) required lenograstim. Grade 3 anorexia and fatigue occurred in nine (18%) and six (12%) patients, respectively. Median survival time was 8.1 months (95% CI 6.6-11.3) and the 1-year survival rate was 35% (95% CI 21-48%). CONCLUSIONS: Docetaxel as a single agent is effective in esophageal cancer, but careful management of neutropenia is needed.

Adenocarcinoma↗
PubMed2003

Hyperbaric oxygen in the treatment of fecal incontinence secondary to pudendal neuropathy.

PURPOSE: Hyperbaric oxygen therapy has several physiologic effects on damaged nerves in animal models, which lead to an improvement in neurologic function. Idiopathic fecal incontinence secondary to pudendal neuropathy is usually treated with biofeedback, which shows improvement in only 50 percent of patients. METHODS: Thirteen patients (12 females, age range, 40-75 years) with chronic pudendal neuropathy and fecal incontinence were identified. They received 30 treatments of hyperbaric oxygen during a period of 6 weeks. Each treatment was at 2.4 atmospheres breathing pure oxygen for 90 minutes. Pudendal latencies were performed sequentially throughout the treatment and one and six months after it had finished. Questionnaires were used to assess improvements in symptoms and quality of life (Wexner fecal incontinence quality of life score). RESULTS: All patients completed the treatment without major complications. There was a consistent improvement of the latencies (on the left 2.36 msec initially, reduced to 2.08 msec at 6-month follow-up and on the right 2.23 msec, on the left reduced to 2.07 msec at 6 months). These improvements were significant (Wilcoxon's two-tailed, asymptomatic significance, comparing pretreatment to 6-month follow-up, left 0.005, right 0.003). Incontinence sores also improved (12.08 initially to 11.64 at the end of treatment, 10.55 at 1-month follow-up, and 10.45 at 6-month follow-up). Using the same test, the improvement in incontinence scores also was significant when comparing pre-end (0.05) and pre-one month (0.011) but not pre-six month (0.054). CONCLUSIONS: Hyperbaric oxygen therapy has improved pudendal nerve function and continence in this group of patients. The cause for this improvement in latencies is unclear at present but may be because of a direct effect on the nerve or an improvement in blood flow to the nerve through angiogenesis. However, these results are good enough to schedule further trials.

Adult↗
PubMed2003

Impaired cough reflex in patients with recurrent pneumonia.

BACKGROUND: A substantial proportion of patients with recurrent pneumonia do not have an apparent underlying condition, but they may have unknown defects in host defence mechanisms such as cough reflex. METHODS: Capsaicin cough sensitivity was measured in seven patients with recurrent pneumonia but no underlying condition. Recurrent pneumonia was defined as at least two episodes of pneumonia in 1 year, or three or more episodes at any time. After remission of pneumonia, 10 doubling concentrations of capsaicin (1.22-625 microM) were inhaled until five or more coughs were induced (cough threshold). Mucociliary clearance was assessed on the basis of nasal ciliary beat frequency and nasal clearance time. Twenty one age and sex matched healthy subjects were studied as controls. RESULTS: Each patient had 2-6 episodes of pneumonia. Most episodes developed in dependent lung segments, suggesting the involvement of silent aspiration. Log transformed cough threshold was significantly higher in patients than in controls (mean 2.37 M (95% CI 1.84 to 2.90) v 1.29 microM (95% CI 1.11 to 1.47); p<0.0001). The effect of pneumonia per se on cough reflex seemed unlikely since the cough threshold showed little change when re-examined after 3 months. The patients and controls did not differ with respect to the indices of mucociliary clearance. CONCLUSIONS: Impaired cough reflex may be involved in the pathogenesis of recurrent pneumonia.

Adult↗
PubMed2002

Multiple risk factors in neonatal sinovenous thrombosis.

The etiology of neonatal sinovenous thrombosis is poorly understood. The authors report the risk factors and radiologic features of neonatal sinovenous thrombosis seen over an 11-year period. Of 30 patients, 29% received extracorporeal membrane oxygenation treatment, and 23% had congenital heart disease. Genetic thrombophilias were present in four of the seven infants tested. Eighteen neonates had multiple maternal, neonatal, perinatal, or prothrombotic complications. Sinovenous thrombosis was often accompanied by infarction (50%) or intraventricular hemorrhage (33%).

Chorioamnionitis↗
PubMed2002

Plasma leptin levels and cardiac sympathetic function in patients with obstructive sleep apnoea-hypopnoea syndrome.

BACKGROUND: The control of body weight and cardiac sympathetic function in patients with obstructive sleep apnoea-hypopnoea syndrome (OSAHS) are important because both factors have significant effects on the mortality of these patients. It has recently been reported that OSAHS has a significant effect on the secretion of leptin, a hormone involved in the control of body weight and sympathetic nerve activity. In addition to the circadian rhythm of leptin secretion, the effects of one night of treatment with nasal continuous positive airway pressure (nCPAP) and the mechanism of the effects of nCPAP on nocturnal leptin secretion in patients with OSAHS has not yet been elucidated. METHODS: Blood samples were obtained at 21.00 hours, 00.00 hours, 03.00 hours, and 06.30 hours from 21 subjects with OSAHS (mean apnoea and hypopnoea index 52.4/h), with and without nCPAP treatment. Iodine-123 (I(123))-meta-iodobenzylguanidine (MIBG) imaging was used to evaluate myocardial sympathetic function before nCPAP treatment. RESULTS: Plasma leptin reached a peak level at 00:00 hours (p<0.01) in patients with OSAHS, both with and without nCPAP treatment. The first night of nCPAP treatment significantly decreased the plasma leptin levels at 03.00 hours (without nCPAP: mean (SE) 21.6 (4.7) ng/ml; with nCPAP: 19.3 (4.1) ng/ml, p<0.02) and at 06.30 hours (without nCPAP: 17.6 (3.8) ng/ml; with nCPAP: 15.2 (3.2) ng/ml, p<0.01). The magnitude of the decrease in leptin levels after nCPAP treatment was significantly correlated with cardiac sympathetic function measured before nCPAP treatment (p<0.03). CONCLUSIONS: Patients with OSAHS undergo nocturnal increases in leptin levels in spite of interruption of sleep due to apnoea and hypopnoea, a trend seen in normal subjects. Plasma leptin levels in patients with OSAHS decreased significantly after the first night of nCPAP treatment. Enhanced cardiac sympathetic function in these patients may contribute to the leptin levels before nCPAP treatment and vice versa.

3-Iodobenzylguanidine↗
PubMed2001

Aberrations in the fragile histidine triad (FHIT) gene in idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) seems to be closely associated with lung carcinogenesis. To identify the genetic characteristics of precancerous IPF lesions in the peripheral lung, we performed PCR-based microsatellite analysis with DNA extracted from microdissected tissues; fluorescent in situ hybridization (FISH) analysis of the fragile histidine triad (FHIT) gene and immunohistochemical analysis of Fhit protein expression in samples of metaplasias and bronchiolar epithelia obtained from patients with IPF. We used four microsatellite markers of the FHIT gene within or flanking the FHIT gene on chromosome 3p for loss of heterozygosity (LOH) analysis. LOH of the FHIT locus was frequently found among the lesions of metaplasias and bronchiolar epithelia in the patients with IPF [62 (52%) of 119 informative lesions]. Fifty-four (73%) of the 74 lesions of metaplasias and bronchiolar epithelia obtained from the IPF patients with lung carcinoma and 8 (17%) of the 46 samples obtained from the IPF patients without lung carcinoma showed LOH at the FHIT gene (P < 0.0001). We confirmed allelic loss in the metaplasias and bronchiolar epithelia of IPF by FISH analysis of the FHIT gene. Additionally, the level of Fhit protein expression in the metaplastic cells of IPF was frequently reduced. Our findings suggest that allelic loss of the FHIT gene may be involved in carcinogenesis in the peripheral lung of patients with IPF.

Acid Anhydride Hydrolases↗
PubMed2001

Acute effect of nasal continuous positive airway pressure therapy on the systemic immunity of patients with obstructive sleep apnea syndrome.

OBJECTIVES: To investigate whether in patients with obstructive sleep apnea syndrome (OSAS) the systemic immunity is disturbed and whether it changes with nasal continuous positive airway pressure (NCPAP) therapy. DESIGN: Polysomnography was performed on 18 OSAS patients (Group A) before NCPAP was started and again on the first night of NCPAP. Blood samples were collected at 8:00PM, 1:00AM and 6:00AM during each polysomnography. Lymphocyte subsets, lymphocyte blastformation, and natural killer (NK) cell activity were determined. Six normal subjects were also studied. A different six OSAS patients were studied over 6 days of NCPAP. SETTING: N/A. PATIENTS OR PARTICIPANTS: N/A. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: The only immunological parameter that significantly differed between the Group A OSAS patients either before or on the first night of NCPAP, and the normal subjects was the epinephrine level. Among the Group A OSAS patients, the following immunological parameters were significantly lower at 6:00AM on the first night of NCPAP than before NCPAP was started: percentage (49.4+/-1.9% before NCPAP vs 45.7+/-2.0% with NCPAP, mean+/-SEM, p<0.005) and absolute count of CD4+ cells (944.1+/-63.8 vs 829.6+/-71.3/mm3, p<0.05); absolute count of CD4+HLA-DR+ cells (91.9+/-13.3 vs 75.1+/-8.9/mm3, p<0.05); CD4+/CD8+ ratio (2.13+/-0.21 vs 1.91+/-0.18, p<0.05). The reduction in the percentage of CD4+ cells at 6:00AM was significantly correlated with the change in apnea-hypopnea index (AHI) (r=0.729, p<0.01). The CD4+ cell count recovered after 6 days of NCPAP. The lymphocyte blasfformation and NK cell activity levels did not change with NCPAP. CONCLUSIONS: First-night NCPAP therapy reduced the CD4+ cell count after sleep, which recovered after one week of NCPAP. OSAS patients do not have immunological abnormalities.

Adult↗
PubMed2001

Quantitative analysis of chromosomal CGH in human breast tumors associates copy number abnormalities with p53 status and patient survival.

We present a general method for rigorously identifying correlations between variations in large-scale molecular profiles and outcomes and apply it to chromosomal comparative genomic hybridization data from a set of 52 breast tumors. We identify two loci where copy number abnormalities are correlated with poor survival outcome (gain at 8q24 and loss at 9q13). We also identify a relationship between abnormalities at two loci and the mutational status of p53. Gain at 8q24 and loss at 5q15-5q21 are linked with mutant p53. The 9q and 5q losses suggest the possibility of gene products involved in breast cancer progression. The analytical techniques are general and also are applicable to the analysis of array-based expression data.

Breast Neoplasms↗
PubMed2001

Increase in bilirubin levels of patients with obstructive sleep apnea in the morning--a possible explanation of induced heme oxygenase-1.

STUDY OBJECTIVES: In the absence of heme oxygenase-1 (HO-1), which catalyzes the oxidation of heme to generate carbon monoxide and indirect bilirubin, hypoxia induces severe right ventricular dilation and infarction. Despite severe hypoxemia during sleep, patients with obstructive sleep apnea-hypopnea syndrome (OSAHS) rarely die during sleep. We hypothesized that apnea-related hypoxemia would induce HO-1 and increase bilirubin levels in the morning in OSAHS patients. Therefore, bilirubin levels in OSAHS patients were analyzed before and after nasal continuous positive airway pressure (nCPAP) therapy. DESIGN: Bilirubin levels in the afternoon before sleep and in the morning immediately after sleep were determined before and after nCPAP treatment. SETTING: University Hospital in Kyoto, Japan. PATIENTS: The subjects were 22 patients with OSAHS (mean (SEM) apnea and hypopnea index of 60 (5)) who were treated with nCPAP and 13 controls. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: Before nCPAP treatment, total after-sleep bilirubin level was significantly higher than the pre-sleep level (p<0.0001). The difference between the serum indirect bilirubin levels in the morning versus in the previous afternoon [D-(M-A)-IB] decreased significantly with nCPAP treatment (p<0.01). The magnitude of decrease in D-(M-A)-IB after nCPAP treatment correlated significantly with changes in the percent time spent with arterial O2 saturation below 90% (r=0.44; p=0.04) and 85% (r=0.49; p=0.02), respectively, during sleep after nCPAP treatment. CONCLUSIONS: The increase in bilirubin level by HO-1 might protect OSAHS patients from disorders related to hypoxemia.

Bilirubin↗