Jin-Ying Lu

Adiponectin: a biomarker of obesity-induced insulin resistance in adipose tissue and beyond

Adiponectin is one of the most thoroughly studied adipocytokines. Low plasma levels of adiponectin are found to associate with obesity, metabolic syndrome, diabetes and many other human diseases. From animal experiments and human studies, adiponectin has been shown to be a key regulator of insulin sensitivity. In this article, we review the evidence and propose that hypo-adiponectinemia is not a major cause of obesity. Instead, it is the result of obesity-induced insulin resistance in the adipose tissue. Hypo-adiponectinemia then mediates the metabolic effects of obesity on the other peripheral tissues, such as liver and skeletal muscle and may also exert some direct effects on end-organ damage. We propose that deciphering the molecular details governing the adiponectin gene expression and protein secretion will lead us to more comprehensive understanding of the mechanisms of insulin resistance in the adipose tissue and provide us new avenues for the therapeutic intervention of obesity and insulin resistance-related human disorders.

Incidence and species distribution of candidaemia in Asia: a laboratory-based surveillance study

The epidemiology of candidaemia varies between hospitals and geographic regions. Although there are many studies from Asia, a large-scale cross-sectional study across Asia has not been performed. We conducted a 12-month, laboratory-based surveillance of candidaemia at 25 hospitals from China, Hong Kong, India, Singapore, Taiwan and Thailand. The incidence and species distribution of candidaemia were determined. There were 1601 episodes of candidaemia among 1.2 million discharges. The overall incidence was 1.22 episodes per 1000 discharges and varied among the hospitals (range 0.16-4.53 per 1000 discharges) and countries (range 0.25-2.93 per 1000 discharges). The number of Candida blood isolates and the total number of fungal isolates were highly correlated among the six countries (R² = 0.87) and 25 hospitals (R² = 0.77). There was a moderate correlation between incidence of candidaemia and the intensive care unit (ICU)/total bed ratio (R² = 0.47), although ICUs contributed to only 23% of candidaemia cases. Of 1910 blood isolates evaluated, Candida albicans was most frequently isolated (41.3%), followed by Candida tropicalis (25.4%), Candida glabrata (13.9%) and Candida parapsilosis (12.1%). The proportion of C. tropicalis among blood isolates was higher in haemato-oncology wards than others wards (33.7% versus 24.5%, p 0.0058) and was more likely to be isolated from tropical countries than other Asian countries (46.2% versus 18.9%, p 0.04). In conclusion, the ICU settings contribute, at least in part, to the incidence variation among hospitals. The species distribution is different from Western countries. Both geographic and healthcare factors contribute to the variation of species distribution.

Adiponectin levels among patients with chronic hepatitis B and C infections and in response to IFN-alpha therapy.

Abstract: Aims: The study was designed to survey the change of adiponectin levels before and after interferon‐α (IFN‐α) therapy in patients with chronic hepatitis B and C infections.

Effects of air bubbles and tube transportation on blood oxygen tension in arterial blood gas analysis.

BACKGROUND AND PURPOSE Pneumatic tube transport has been reported to aggravate the error in partial pressure of oxygen (PO(2)) measurements caused by air bubbles. The aim of this study was to clarify the effect of manual and pneumatic tube methods of sample transportation and different amounts of air bubbles on arterial blood gas analysis. METHODS Blood gas samples from 15 patients and a pooled wasted blood mixture with 3 different levels of PO(2) were analyzed to determine the effects of air bubbles and manual versus pneumatic tube transportation on PO(2) levels. RESULTS PO(2) increased significantly in samples containing 10% air bubbles and was exaggerated by pneumatic tube transport (from 115.63 +/- 9.31 mm Hg to 180.51 +/- 11.29 mm Hg, p < 0.001). In samples with low PO(2) ( approximately 30 mm Hg), the measurement was not aberrant regardless of the method of transportation or the amount of air bubbles contained in the specimen. However, in samples with medium and high PO(2) (> 70 mm Hg), aberrances in measurements were noted even with only 0.5% air bubbles and regardless of whether the sample was transported by manual methods or pressurized tube. The increments of PO(2) correlated positively with the amount of air introduced into the specimens. Thus, the measured PO(2) increased 8.13 and 31.77 mm Hg when 0.5% and 10% air bubbles were introduced, respectively, to samples with medium PO(2) (p < 0.05). The interaction between the amount of air bubbles and the method of transportation was significant (p < 0.001). CONCLUSIONS Trapped air in the syringe should be expelled as thoroughly as possible, since the presence of only 1% air bubbles can result in aberrance in PO(2) measurement. Samples for blood gas analysis should be carried in ambient pressure to the laboratory because pneumatic tube delivery systems significantly aggravate the air bubble-related aberrance in PO(2) measurement.

Interference caused by the contents of serum separator tubes in the Vitros CRP assay

Background: We have observed discrepancies between C-reactive protein (CRP) measured in serum prepared from a serum separator tube (SST) and that obtained from a plain tube, when using the Vitros CRP assay. Our study aimed at elucidating the cause of these discrepancies. Methods: Eighty-seven specimens from hospitalized patients with various types of inflammatory disease were analysed using a fixed-point immuno-rate method on a Vitros CRP slide. The serum was prepared simultaneously in both vacuum and SSTs. We also performed mixing tests by adding 47 samples of serum prepared from plain tubes to SSTs and incubating for 15 min before CRP analysis. Results: Lower values of CRP were found in serum prepared from plain tubes than in serum from SSTs. Addition of serum prepared from plain tubes to SSTs and incubating for 15 min increased the CRP values significantly. The ratio of CRP measured in serum prepared from plain tubes and from SSTs did not differ significantly from the ratio obtained when serum was prepared in a plain tube then added to an SST. Discussion: We propose that SSTs can adsorb some macromolocules that form complexes with CRP. The addition of SST gel to serum results in the release of CRP molecules from these complexes, which enhances the antigen-antibody reaction on the Vitros CRP slide and increases the measured CRP concentrations.

Lower plasma adiponectin is correlated to higher alanine aminotransferase independent of metabolic factors and hepatitis B virus carrier status.

Background: Adiponectin has been linked to the metabolic syndrome and coronary artery disease in recent years. The animal and human data also suggest that adiponectin may be beneficial for liver functions. The aim of this study was to investigate the correlation between plasma adiponectin level and liver function tests in adults with or without chronic hepatitis B virus (HBV) infection.

Evaluation and Improvement Strategy of Analytical Turnaround Time in the Stat Laboratory

BACKGROUND/PURPOSE Laboratory analytical turnaround time represents laboratory effectiveness. Our study aimed to evaluate laboratory analytical turnaround time to optimize workflow and shorten analytical turnaround time. METHODS We used the laboratory information system in a 2000-bed teaching hospital to compute and analyze the 90th percentile turnaround time of the Stat Laboratory from 2001 to 2003. RESULTS The overall 90th percentile turnaround time in the Stat Laboratory was 40-49 minutes and positively correlated with test volume. The daily test volume in the Stat Laboratory has grown significantly in the latter 2 half-years of the study as compared with the previous 2 half-years (p < 0.05 and p < 0.001, respectively). The daily longest turnaround time occurred in the early morning, and troponin-I testing contributed to the majority of incidences of prolongation of analytical turnaround time. We prioritized the performance of troponin-I testing, which resulted in a reduction of the analytical turnaround time by about 18 minutes (from 66 to 48 minutes) and no increment of overall turnaround time (42 to 44 minutes) despite continuously increasing test volume. CONCLUSION These findings demonstrated that a dedicated means of process control was able to significantly improve laboratory efficiency.

Heparin interference in the cerebrospinal fluid protein assay measured with a pyrogallol red-molybdate complex.

BACKGROUND Increased cerebrospinal fluid (CSF) total protein is a useful indicator of meningeal or central nervous system disease. Occasionally the primary care physicians added heparin to CSF samples to avoid clotting. The aim of this study is to investigate the interference of heparin on CSF total protein measurement. METHODS CSF specimens were collected from 230 in-patients with various diseases and analyzed by the Vitros 950 PROT slide and the Toshiba TBA-120FR assay. After adding 0, 0.0625, 0.25, 0.5, 0.75, 1, 2 and 4 IU/ml of heparin that was diluted in 20 microl of normal saline to 180 microl of CSF aliquots, CSF total protein concentrations were determined again by the 2 assay systems in the absence or presence of protamine. RESULTS At low (<40 mg/dl) and mildly increased (40-or<100 mg/dl) CSF total protein, the measured protein concentrations significantly decreased up to 91% when 4 IU/ml of heparin was added to the samples before being analyzed by the Toshiba TBA-120FR assay. At moderately increased (100-or<200 mg/dl) and high (>or=200 mg/dl) CSF total protein, 62% and 27% decreases were found, respectively. Only 1-8% decline was found when 4 IU/ml of heparin was added to the samples before being analyzed by the Vitros 950 PROT assay. Addition of protamine partially reversed the interference of heparin. CONCLUSIONS The interference of heparin in the CSF total protein assay is dependent on the reaction principle, especially when the CSF total protein level is normal to mildly elevated.

Immune checkpoint inhibitor therapy-induced hypophysitis ∼ a case series of Taiwanese patients

Immune checkpoint blockade-based immunotherapy is a new modality of cancer treatment with a unique mechanism that has gained increased numbers of indication and is now used in several cancer types. However, immune-related adverse events (irAEs) emerge as a new entity of diseases involving one or multiple organ systems. irAEs could result in interruption of immunotherapy, morbidities or even death. Among various manifestations of irAEs, immune-mediated hypophysitis is rare but important, requiring prompt diagnosis and treatment to avoid life-threatening conditions. We report seven cases of immune-mediated hypophysitis in Taiwan. They suffered from various types of advanced cancer and received different regimens of immune checkpoint inhibitors. The time of onset after initiation of immunotherapy ranged from 5 to 36 weeks. All seven subjects were diagnosed of central adrenal insufficiency, while four of them had primary hypothyroidism. There was no typical finding of infiltrative hypophysitis on the pituitary MRI. There was no documented hormone recovery after diagnosis of hypophysitis, and the tumor responses to immunotherapy were variable in these seven patients. In conclusion, immune-mediated hypophysitis is often irreversible. Fortunately, it can be managed adequately with hormone replacements. Further investigations are warranted to unveil underlying mechanisms and ethnic differences to guide the solutions.

Using Ion Torrent sequencing to study genetic mutation profiles of fatal thyroid cancers

BACKGROUND/PURPOSE Surgery followed by radioiodine is a mainstay of treatment for thyroid cancers of follicular origins. However, about 5% of the thyroid cancers are non-operable and/or radioiodine-refractory diseases, which are either locally advanced or metastatic and result in a survival of less than 5 years. How to treat this population of thyroid cancer patients becomes a critical issue requiring further understanding of the tumors genetic information. METHODS We used formalin-fixed paraffin-embedded specimens of 22 fatal thyroid cancers and their corresponding non-tumor parts, if available, to yield genomic DNA, and applied the Ion Torrent™ Personal Genome Machine (IT-PGM) System (Life Technologies), a next generation sequencing technology, to interrogate 740 mutational hotspots in 46 oncogenes. We further validated the results by conventional direct sequencing. RESULTS We confirmed 21 mutations of 11 oncogenes in the 22 fatal thyroid cancer samples. Among them, the MET p.N375S and MLH1 p.V384D mutations, each was detected in two cases, and has rarely been found to be involved in thyroid cancer pathogenesis before. We also identified homozygous PDGFRA p.V824V mutation in eight out of the 22 cases, while the non-tumor counterparts carried heterozygous PDGFRA p.V824V mutation. We noted that the Ion Torrent technique unfortunately showed high false positive rates for detecting EGFR mutations in thyroid cancers. CONCLUSION The extensive genetic studies provide new insights to future targeted therapy in these patients. IT-PGM proved to be valuable for comprehensively searching genetic mutations in potentially fatal thyroid cancers.