AIMTo determine the deletion junctions of infertile men in Taiwan with azoospermia factor region c (AZFc) deletions and to evaluate the genotype/phenotype correlation.

METHODSGenomic DNAs from 460 infertile men were examined. Bacterial artificial chromosome clones were used to verify the accuracy of polymerase chain reaction. Deletion junctions of the AZFc region were determined by analysis of sequence-tagged sites and gene-specific markers.

RESULTSComplete AZFc deletions, including BPY2, CDY1 and DAZ genes, were identified in 24 men. The proximal breakpoints were clustered between sY1197 and sY1192, and the distal breakpoints were clustered between sY1054 and sY1125 in all but one of the 24 men. The testicular phenotypes of men with complete AZFc deletion varied from oligozoospermia, to hypospermatogenesis, to maturation arrest.

CONCLUSIONWe identified a group of infertile men with uniform deletion junctions of AZFc in the Taiwan population. Despite this homogeneous genetic defect in the AZFc region, no clear genotype/phenotype correlation could be demonstrated.

Asian Continental Ancestry Group ; genetics ; Base Sequence ; Chromosomes, Human, Y ; genetics ; DNA Primers ; Deleted in Azoospermia 1 Protein ; Gene Deletion ; Genetic Loci ; Humans ; Infertility, Male ; genetics ; Male ; Nuclear Proteins ; genetics ; Oligospermia ; genetics ; Phenotype ; Polymerase Chain Reaction ; Proteins ; genetics ; RNA-Binding Proteins ; genetics ; Seminal Plasma Proteins ; genetics ; Taiwan ; Testis ; anatomy & histology

Phaeochromocytomas are rare neuroendocrine tumours with variable clinical signs and symptoms. Hypertension, tachycardia, sweating and headaches are cardinal manifestations. Although nausea and abdominal pain are the more common gastrointestinal features, rare gastrointestinal spectrums have been reported that can mimic abdominal emergencies. Metabolic effects of hypercatecholaminaemia are vast and one such rare presentation is lactic acidosis. We describe a case of phaeochromocytoma presenting with both intestinal pseudo-obstruction as well as lactic acidosis. This case report highlights the importance of having a high index of suspicion for and early recognition of the gastrointestinal and metabolic manifestations of phaeochromocytomas.
Abdominal Pain ; Acidosis, Lactic ; complications ; Adrenal Gland Neoplasms ; complications ; diagnosis ; Diabetes Mellitus, Type 2 ; complications ; Dyslipidemias ; complications ; Female ; Humans ; Hypertension ; complications ; Intestinal Pseudo-Obstruction ; complications ; Middle Aged ; Neuroendocrine Tumors ; complications ; diagnosis ; Pheochromocytoma ; complications ; diagnosis ; Radiography, Abdominal

Hypoglycemia is a common finding in both daily clinical practice and acute care settings. The causes of severe hypoglycemia (SH) are multi-factorial and the major etiologies are iatrogenic, infectious diseases with sepsis and tumor or autoimmune diseases. With the advent of aggressive lowering of HbA1c values to achieve optimal glycemic control, patients are at increased risk of hypoglycemic episodes. Iatrogenic hypoglycemia can cause recurrent morbidity, sometime irreversible neurologic complications and even death, and further preclude maintenance of euglycemia over a lifetime of diabetes. Recent studies have shown that hypoglycemia is associated with adverse outcomes in many acute illnesses. In addition, hypoglycemia is associated with increased mortality among elderly and non-diabetic hospitalized patients. Clinicians should have high clinical suspicion of subtle symptoms of hypoglycemia and provide prompt treatment. Clinicians should know that hypoglycemia is associated with considerable adverse outcomes in many acute critical illnesses. In order to reduce hypoglycemia-associated morbidity and mortality, timely health education programs and close monitoring should be applied to those diabetic patients presenting to the Emergency Department with SH. ED disposition strategies should be further validated and justified to achieve balance between the benefits of euglycemia and the risks of SH. We discuss relevant issues regarding hypoglycemia in emergency and critical care settings.
Diabetes Mellitus/drug therapy ; Humans ; Hypoglycemia/blood/*chemically induced/*complications/epidemiology ; Hypoglycemic Agents/adverse effects/therapeutic use ; Insulin/adverse effects/therapeutic use

Background: and Purpose Migraine is a condition that is often observed to run in families, but its complex genetic background remains unclear. This study aimed to identify the genetic factors influencing migraines and their potential association with the family medical history. Methods: We performed a comprehensive genome-wide association study of a cohort of 1,561 outpatients with migraine and 473 individuals without migraine in Taiwan, including Han Chinese individuals with or without a family history of migraine. By analyzing the detailed headache history of the patients and their relatives we aimed to isolate potential genetic markers associated with migraine while considering factors such as sex, episodic vs. chronic migraine, and the presence of aura. Results: We revealed novel genetic risk loci, including rs2287637 in DEAD-Box helicase 1 and long intergenic non-protein coding RNA 1804 and rs12055943 in engulfment and cell motility 1, that were correlated with the family history of migraine. We also found a genetic location downstream of mesoderm posterior BHLH transcription factor 2 associated with episodic migraine, whereas loci within the ubiquitin-specific peptidase 26 exonic region, dual specificity phosphatase 9 and pregnancy-upregulated non-ubiquitous CaM kinase intergenic regions, and poly (ADP-ribose) polymerase 1 and STUM were linked to chronic migraine. We additionally identified genetic regionsassociated with the presence or absence of aura. A locus between LINC02561 and urocortin 3 was predominantly observed in female patients. Moreover, three different single-nucleotide polymorphisms were associated with the family history of migraine in the control group. Conclusions This study has identified new genetic locations associated with migraine and its family history in a Han Chinese population, reinforcing the genetic background of migraine. The findings point to potential candidate genes that should be investigated further.

Cardiotoxin III (CTX III), a basic polypeptide with 60 amino acid residues isolated from Naja naja atra venom, has been reported to have anticancer activity. CTX III-induced K562 cell apoptosis was confirmed by DNA fragmentation (DNA ladder, sub-G1 formation) and phosphatidylserine (PS) externalization with an IC50 value of 1.7 mug/ml at 48 h. A mechanistic analysis demonstrated that CTX III-induced apoptotic cell death was accompanied by up-regulation of both Bax and endonuclease G (Endo G), and downregulation of Bcl-X(L). CTX III had no effect on the levels of Bcl-2, Bid, XIAP survivin, and AIF proteins. CTX III treatment caused loss of the mitochondrial membrane potential (delta psi m), release of mitochondrial cytochrome c to the cytosol, and activation of both caspase-9 and -3. CTX III-induced apoptosis was significantly blocked by the broad-spectrum caspase inhibitor Z-VAD-FMK. However, CTX III did not generate reactive oxygen species (ROS) and antioxidants, including N-acetylcysteine and catalase, did not block CTX III-induced apoptosis in K562 cells. Modulation of Bax, Bcl-X(L), and the Endo G proteins, release of mitochondrial cytochome c, and activation of caspase-3 and -9 all are involved in the CTX III-triggered apoptotic process in human leukemia K562 cells.
bcl-X Protein/*metabolism ; bcl-2-Associated X Protein/*metabolism ; Up-Regulation/drug effects ; Reactive Oxygen Species/metabolism ; Mitochondrial Proteins/metabolism ; Mitochondrial Membranes/drug effects ; Membrane Potentials/drug effects ; K562 Cells ; Inhibitor of Apoptosis Proteins/metabolism ; Humans ; Endodeoxyribonucleases/*metabolism ; Down-Regulation/drug effects ; Direct Lytic Factors/*pharmacology ; Cytochromes c/metabolism ; Cell Proliferation/drug effects ; Caspases/metabolism ; Apoptosis/*drug effects

PURPOSE: Whether tamoxifen affects the risk of neurodegenerative disease is controversial. This nationwide population-based study investigated the risk of Parkinson's disease (PD) associated with tamoxifen treatment in female patients with breast cancer using Taiwan's National Health Insurance Research Database. METHODS: A total of 5,185 and 5,592 female patients with breast cancer who did and did not, respectively, receive tamoxifen treatment between 2000 and 2009 were included in the study. Patients who subsequently developed PD were identified. A Cox proportional hazards model was used to compare the risk of PD between the aforementioned groups. RESULTS: Tamoxifen did not significantly increase the crude rate of developing PD in female patients with breast cancer (tamoxifen group, 16/5,169; non-tamoxifen group, 11/5,581; p=0.246). Tamoxifen did not significantly increase the adjusted hazard ratio (aHR) for subsequently developing PD (aHR, 1.310; 95% confidence interval [CI], 0.605–2.837; p=0.494). However, tamoxifen significantly increased the risk of PD among patients followed up for more than 6 years (aHR, 2.435; 95% CI, 1.008–5.882; p=0.048). CONCLUSION: Tamoxifen treatment may increase the risk of PD in Taiwanese female patients with breast cancer more than 6 years after the initiation of treatment.
Asian Continental Ancestry Group* ; Breast Neoplasms* ; Breast* ; Female* ; Humans ; National Health Programs ; Neurodegenerative Diseases ; Parkinson Disease* ; Proportional Hazards Models ; Tamoxifen*

INTRODUCTIONThis study evaluates determinants, expectations, association with quality of life (QOL) and doctor's awareness of Complementary and Alternative Medicine (CAM) use in Singapore cancer patients.

MATERIAL AND METHODSWe interviewed 316 patients visiting the Cancer Centre of the National University Hospital on behaviour, attitudes and expectations towards CAM and assessed QOL via Euroqol Questionnaire (EQ-5D). Medical information was obtained from oncologists.

RESULTSOne hundred and seventy-three patients (55%) reported CAM use after cancer diagnosis. Chinese ethnicity, tertiary education, age <65 years and previous CAM use were independent predictors of CAM use. Fifty-one per cent of CAM users informed their doctors about their use and 15% of doctors reported to be aware of CAM use in these patients. Thirty-seven per cent believed CAM to be equally or more effective than conventional cancer therapies and 78% expected at least basic knowledge about CAM from their oncologists. Twenty-fi ve per cent of patients reported concurrent use of oral CAM and chemotherapy, of which oncologists were unaware in 86% of cases. CAM users had higher EuroQol utility scores than non-CAM users (0.79 versus 0.73, respectively, P = 0.03), in particularly those aged >or=65 years and those with stage IV disease.

CONCLUSIONSingapore cancer patients show high prevalence of CAM use, high expectations regarding its effectiveness and doctors' knowledge on CAM and many use it concurrently with chemotherapy or radiotherapy. Since oncologists are generally unaware of CAM use in their patients, doctor-patient communication on CAM use needs to be improved. The association of CAM use and higher QOL scores in some subgroups deserves further exploration.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Complementary Therapies ; utilization ; Female ; Humans ; Interviews as Topic ; Male ; Middle Aged ; Neoplasms ; therapy ; Quality of Life ; Singapore ; Surveys and Questionnaires ; Young Adult

BACKGROUNDAt present, the most effective treatment for pulmonary alveolar proteinosis (PAP) remains whole-lung lavage in spite of the usually accompanying severe hypoxemia, which is expected to be prevented by hyperoxygenated solution improving oxygen supply during lavage. In this study, the efficacy and safety of the effect of hyperoxygenated solution were evaluated.

METHODSFive patients underwent whole-lung lavage over a 28-month period. Each lung was lavaged with hyperoxygenated (HO) and normal saline solution (plain lactated Ringer's solution, NO) randomly and alternatively until the reclaimed fluid was clear. Random number was generated by computer before every cycle of lavage. If the number was odd, the patient was assigned to receive a lavage cycle with hyperoxygenated solution (HO group, n = 109); if the number was even, normal saline solution was used (NO group, n = 115). Data of saturation of peripheral oxygen (SPO(2)), mean arterial pressure (MAP), central venous pressure (CVP), heart rate (HR) and end-tidal carbon dioxide tension (P(ET)CO(2)) were taken down at 0, 30, 60, 90, 120, 150, 180, 210 and 240 seconds from the beginning of the instillation of solution, and frequency and volume of unilateral lung lavage were also recorded. Time interval between the left and the right lung lavage was 1 week.

RESULTSNo patient was withdrawn from the study due to low SPO(2) or leakage. Oxygen pressure was (730.21 +/- 7.43) mmHg in the hyperoxygenated solution against (175.73 +/- 5.92) mmHg in the normal saline solution (P < 0.01). Compared with baseline, SPO(2) increased significantly as the instillation of solution began (P < 0.01), leveled for about 30 seconds (P > 0.05), and then decreased significantly to the lowest at the time of drainage (compared with 120 seconds or peak, P < 0.01). SPO2 was higher in HO group than in NO group (P < 0.01). There were no significant differences in MAP, HR, CVP and P(ET)CO(2) between HO group and NO group (P > 0.05) and also among different time points (P > 0.05).

CONCLUSIONDuring the lung lavage for pulmonary alveolar proteinosis, hyperoxygenated solution could significantly improve oxygen supply in comparison with normal saline solution without obvious side effects.

Bronchoalveolar Lavage ; methods ; Female ; Humans ; Male ; Middle Aged ; Oxygen ; therapeutic use ; Pulmonary Alveolar Proteinosis ; therapy ; Sodium Chloride ; therapeutic use ; Treatment Outcome

INTRODUCTIONThe use of robotics in total knee arthroplasty (TKA) has been shown to minimise human error, as well as improve the accuracy and precision of component implantation and mechanical axis alignment. The present study aimed to demonstrate that robot-assisted TKA using ROBODOC® is safe and capable of producing a consistent and accurate postoperative mechanical axis.

METHODSWe prospectively recruited 27 consecutive patients who underwent robot-assisted TKA between May and December 2012. Two patients were excluded from the study due to intraoperative technical problems with the robot. Long-leg radiography and computed tomography were performed prior to surgery, and used for mechanical axis measurements and component sizing. DigiMatch™ ROBODOC® Surgical System software version 4.3.6 (Curexo Technology Corp, Fremont, CA, USA) was used in all cases to perform bone cuts in accordance with the preoperative plan.

RESULTSThe postoperative coronal mechanical alignment was within 3 degrees, with a mean alignment of -0.4 ± 1.7 degrees, confirming the accuracy of the preoperative surgical plan and bone cuts. The mean operating time was 96 ± 15 min, and preoperative planning yielded 100% implant sizing accuracy.

CONCLUSIONRobotics has the potential to enable surgeons to consistently attain ideal postoperative alignment. The use of bone movement monitors and an integrated navigation system enhances the safety profile of ROBODOC® by minimising errors. However, the role of the surgeon in TKA is still vital, as the surgeon is ultimately in charge of planning the surgery, its execution and ensuring soft tissue balance during TKA.

Aged ; Arthroplasty, Replacement, Knee ; instrumentation ; Female ; Humans ; Knee Joint ; diagnostic imaging ; Male ; Middle Aged ; Prospective Studies ; Robotic Surgical Procedures ; instrumentation ; Tibia ; surgery ; Tomography, X-Ray Computed

OBJECTIVE: Postoperative delirium (POD) is a highly prevalent complex neuropsychiatric syndrome in elderly patients. However, its pathophysiology is currently unknown. Early detection and prevention of POD is important; therefore, the aim of this study was to investigate the link between preoperative insulin growth factor 1 (IGF-1) levels in the serum and POD in the Chinese elderly patients. METHODS: One hundred and three patients who were undergoing an orthopedic operation took part in the study. Preoperative serum IGF-1 levels were measured. POD was determined daily using the Confusion Assessment Method (CAM) and DSM-IV TR. Baseline serum IGF-1 levels were compared between patients who did and did not develop POD. Correlation coefficients were calculated to evaluate relationship between baseline characteristics and serum IGF-1 levels. The relationship between baseline biomarkers and delirium status was investigated using logistic regression analysis, adjusting for potential confounding variables. RESULTS: Twenty-three patients developed POD. The POD group had lower MMSE scores and higher CCI scores and proportions of acute admission. Preoperative serum IGF-1 levels were correlated with MMSE scores and age (MMSE: r=0.230, p<0.05; age: r=-0.419, p<0.001). Baseline serum IGF-1 levels did not differ between patients who did and did not develop POD, even after adjusting for potential confounding factors, MMSE score, and age. CONCLUSION: No association was found between preoperative IGF-1 levels and POD, suggesting that they are not direct biomarkers of the incidence of POD among the Chinese elderly population. Further research with larger sample sizes is warranted to clarify the relationship.
Aged* ; Asian Continental Ancestry Group* ; Biomarkers ; Confounding Factors (Epidemiology) ; Delirium* ; Diagnostic and Statistical Manual of Mental Disorders ; Humans ; Incidence ; Insulin ; Insulin-Like Growth Factor I ; Logistic Models ; Orthopedics ; Sample Size