Chloramphenicol Induces Autophagy and Inhibits the Hypoxia Inducible Factor-1 Alpha Pathway in Non-Small Cell Lung Cancer Cells.

Chloramphenicol is an inexpensive and excellent bactericidal antibiotic. It is used to combat anaerobic infections in the Third World countries, whereas its systemic application has been abandoned in developed countries. However, in recent years, clinicians have reintroduced chloramphenicol in clinical practice. In this study, chloramphenicol was found to repress the oxygen-labile transcription factor, hypoxia inducible factor-1 alpha (HIF-1α), in hypoxic A549 and H1299 cells. Furthermore, it suppressed the mRNA levels of vascular endothelial growth factor (VEGF) and glucose transporter 1, eventually decreasing VEGF release. Chloramphenicol initiated the autophagy pathway in treated cells, as observed by the increase in formation of Atg12-Atg5 conjugates, and in beclin-1 and LC3-II levels. The chloramphenicol-mediated HIF-1α degradation was completely reverted by autophagic flux blockage. In HIF-1α-overexpressing cells, the formation of HIF-1α/SENP-1 (Sentrin/SUMO-specific protease 1) protein complex seemed to facilitate the escape of HIF-1α from degradation. Chloramphenicol inhibited HIF-1α/SENP-1 protein interaction, thereby destabilizing HIF-1α protein. The enhancement in HIF-1α degradation due to chloramphenicol was evident during the incubation of the antibiotic before hypoxia and after HIF-1α accumulation. Since HIF-1α plays multiple roles in infections, inflammation, and cancer cell stemness, our findings suggest a potential clinical value of chloramphenicol in the treatment of these conditions.

Sample Size Re-Estimation without Breaking the Blind in Clinical Trial.

From a regulatory perspective, it is important that the sample size recalculation is performed such that all persons involved in the study remain blinded. The proposed method is an extension of the work by Shih and Zhao (1997) to continuous endpoints. The treatment means are constructed by the convex combinations of the stratum means and then estimated by using the linear model of the stratum responses. In this article, the properties of the proposed estimators are studied. Simulation experiments are conducted to evaluate the difference between two estimators. The unblind estimators for the population mean and the population variance perform better than those of the blind estimators in terms of bias and mean square errors in the most of cases. Given a particular sample size, the accuracies of the blind means and the blind variances depend on the treatment proportions in each stratum. An example of interim analysis is given in this article to illustrate the use of sample size determination. The proposed sample size calculations are recommended in the interim analyses to meet Committee for Proprietary Medical Products requirement, retaining the blinding.

The probability of spontaneous regression of lumbar herniated disc: a systematic review.

OBJECTIVE: To determine the probability of spontaneous disc regression among each type of lumbar herniated disc, using a systematic review. DATA SOURCES: Medline, Cochrane Library, CINAHL, and Web of Science were searched using key words for relevant original articles published before March 2014. Articles were limited to those published in English and human studies. REVIEW METHODS: Articles had to: (1) include patients with lumbar disc herniation treated conservatively; (2) have at least two imaging evaluations of the lumbar spine; and (3) exclude patients with prior lumbar surgery, spinal infections, tumors, spondylolisthesis, or spinal stenosis. Two reviewers independently extracted study details and findings. Thirty-one studies met the inclusion criteria. Furthermore, if the classification of herniation matched the recommended classification of the combined Task Forces, the data were used for combined analysis of the probability of disc regression of each type. Nine studies were applicable for probability calculation. RESULTS: The rate of spontaneous regression was found to be 96% for disc sequestration, 70% for disc extrusion, 41% for disc protrusion, and 13% for disc bulging. The rate of complete resolution of disc herniation was 43% for sequestrated discs and 15% for extruded discs. CONCLUSIONS: Spontaneous regression of herniated disc tissue can occur, and can completely resolve after conservative treatment. Patients with disc extrusion and sequestration had a significantly higher possibility of having spontaneous regression than did those with bulging or protruding discs. Disc sequestration had a significantly higher rate of complete regression than did disc extrusion.

Stroke risk in poliomyelitis survivors: a nationwide population-based study.

OBJECTIVES: To assess the prevalence and risk of stroke among adults with polio and controls. DESIGN: A prospective, probability-sampling, 6-year population-based cohort study. SETTING: A National Health Insurance Research Database consisting of 316,355 randomly selected enrollees. The database is related to a National Health Insurance program with more than 22 million participants. PARTICIPANTS: After excluding patients under 40 years of age, polio patients (N=212) (mean age ± SD, 54.0±10.2 y; 57.1% men) were identified from the database from January 1, 2003 to December 31, 2008. For each polio patient, 2 age- and sex-matched patients were recruited as controls. Control patients did not have any neuromuscular diseases commonly found in childhood. The frequencies of patients with potential risk factors for stroke were assessed. INTERVENTION: None. MAIN OUTCOME MEASURE: The prevalence and the adjusted odds ratio of ischemic stroke among polio patients and the controls were estimated. RESULTS: Polio patients had a higher prevalence of stroke (10.8% vs 2.4%, P<.001) than the controls. Polio patients with hypertension had a much higher prevalence of stroke (23.0%). The risk of stroke was higher for polio patients compared with the controls, yielding an adjusted odds ratio of 4.17 (95% confidence interval, 1.84-9.45, P<.001). Polio was a significant risk factor for stroke independent from hypertension, diabetes mellitus, hyperlipidemia, and cardiac diseases. CONCLUSIONS: Adults with polio had a high prevalence of ischemic stroke. Polio was an additional risk factor for stroke. Polio patients with hypertension might potentiate the risk of stroke. Developing a health promotion program, suitable for polio patients, to increase participation in activities and exercises may be essential, especially for polio patients with hypertension.

Clustering of functioning and disability profile based on the WHO disability assessment schedule 2.0 - a nationwide databank study.

OBJECTIVE: To compare and cluster the health status and disability restrictions associated with eight major physiological functions of body systems, using functioning domains of WHO Disability Assessment Schedule 2.0. DESIGN: Retrospective analyses of a nation-wide disability database. SETTING: Population-based study. PARTICIPANTS: Records from patients >18 years of age with disability were obtained from the Taiwan Data Bank of Persons with Disability (July 2012-November 2017). Disability functioning profile of the following diagnosis were analyzed: stroke, schizophrenia, hearing loss, liver cirrhosis, chronic kidney disease, congestive heart failure, burn, head and neck cancer. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Demographic data, severity of impairment, and Disability Assessment Scale scores were obtained and analyzed. Radar charts were constructed using the WHO Disability Assessment Schedule 2.0. functioning domain score. Degree of similarity between any two given diagnosis was assessed by cluster analysis, comparing the Euclidean distances between radar chart data points among the six domains. RESULTS: Based on cluster analysis of similarities between functioning domain profiles, the eight diagnoses were grouped into different disability clusters. Four clusters of disability were named according to the type restriction patterns: global-impact cluster (stroke); interaction-restriction cluster (schizophrenia, hearing loss); physical-limitation cluster, (liver cirrhosis, CKD, and congestive heart failure); and specific-impact cluster (burn, head and neck cancer). The rates of institutionalization and unemployment differed between the four clusters. CONCLUSION: We converted WHO Disability Assessment Schedule 2.0. functioning domain scores into six-dimensioned radar chart, and demonstrate disability restrictions can be further categorized into clusters according to similarity of functioning impairment. Understanding of disease-related disabilities provides an important basis for designing rehabilitation programs and policies on social welfare and health that reflect the daily-living needs of people according to diagnosis.Implication for RehabilitationThe use of radar charts provided a direct visualization of the scope and severity of disabilities associated with specific diagnoses.Diagnosis-related disabilities can be organized into clusters based on similarities in WHODAS 2.0 disability domain profiles.Knowledge of the characteristics of disability clusters is important to understand disease-related disabilities and provide a basis for designing rehabilitation.

Oncological and functional outcomes of intersphincteric resection for low rectal cancer.

BACKGROUND: The intersphincteric resection technique has been used to extend the opportunity for sphincter preservation in patients with very low rectal cancer. The aim of this study is to assess the long-term oncological and functional outcomes of intersphincteric resection. METHODS: Patients with extraperitoneal rectal cancer were treated and retrospectively chart reviewed. The oncological and functional outcomes were evaluated. Comparisons of the overall disease-free survival and recurrence were analyzed for the different surgical procedures. RESULTS: From July 2002 to August 2009, 162 patients with extraperitoneal rectal cancer were retrospectively chart reviewed. One-hundred one patients (62.3%) underwent low anterior resection, 26 patients (16%) received radical proctectomy and intersphincteric resection with coloanal anastomosis, and 23 (14.2%) had abdominoperineal resection. The sphincter preservation rate was 80%. In the intersphincteric resection group, overall survival rates at 3 and 5 y were 83% and 83%, and disease-free survival at 3 and 5 y were 82% and 76%, respectively. The mean stool frequency was 4.7 per 24 h. There were 38.1% of patients suffering from stool fragmentation, and 23.8% had nocturnal defecation. About one-third of the patients required antidiarrheal medications. Overall, 90.8% of patients were satisfied with the functional results of surgery. CONCLUSIONS: Our data show intersphincteric resection for low rectal cancer is feasible and safe. Preoperative radiotherapy may negatively affect symptom-specific quality of life.

Contribution of ischemic stroke to hip fracture risk and the influence of gender difference.

OBJECTIVES: To clarify the contribution of stroke to the risk of hip fracture (HF) and the influence of gender difference on HF, and to estimate the incidence rate of poststroke HF. DESIGN: A prospective, probability-sampling, 10-year, population-based cohort study. SETTING: A National Health Insurance Research Database consisting of 200,432 randomly selected enrollees. PARTICIPANTS: Subjects with acute ischemic stroke (N=1951; mean age ± SD, 65.6 ± 9.8y; 56.5% men) were identified. For each stroke subject, 2 age- and gender-matched controls were recruited. Control subjects did not have any brain disease. Those subjects younger than 45 years were excluded. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: The incidence rate and the adjusted hazard ratio of sustaining an HF were estimated. The cumulative HF-free probability was plotted. RESULTS: Stroke subjects had a higher incidence rate of HF than their controls (women: 11.3 vs 4.4/1000 person-years, P<.001; men: 5.6 vs 2.9/1000 person-years, P<.001). The risk of HF was higher among stroke subjects, yielding an adjusted hazard ratio (95% confidence interval) of 2.33 (1.62-3.34) for women and 1.73 (1.12-2.68) for men. Compared with men with stroke, women with stroke had an adjusted hazard ratio of 1.83 (1.18-2.85). Stroke subjects had a lower cumulative HF-free probability throughout the 10-year duration than did the control subjects (women, P<.001; men, P=.005). Half of the poststroke HFs occurred within 2.5 years of the onset of stroke. CONCLUSIONS: Ischemic stroke is a risk factor for HF, which is at work over and beyond age and gender. Being a woman with stroke increases this fracture risk. An active program for fracture prevention might prove effective for stroke subjects, and this may be especially true for women.

Adults with polio are at risk of hip fracture from middle age: A nationwide population-based cohort study.

BACKGROUND: Having motor impairment since childhood and being at risk of osteoporosis and falls, adults with polio would be more likely to suffer a hip fracture (HF) and may experience different epidemiological characteristics from the general population. OBJECTIVE: To estimate the risk and incidence of HF in adults with polio. DESIGN: Using a national database, we conducted a population-based cohort study. We identified patients with polio using the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) code of 138. For each patient with polio, we randomly selected five age- and sex-matched control subjects. Those subjects aged <40 years were excluded. We analyzed participants aged 40˜64 years (middle-aged) and subjects aged ≥65 years (elderly) separately and recognized subjects who had an HF (ICD-9-CM code, 820) only when they received hospitalization to care for the illness from January 1, 2003 to December 31, 2008. RESULTS: We identified 403 adults with polio (mean age ± standard deviation, 47.2 ± 8.6 years). Compared to the controls, patients with polio had a higher incidence of HF (all, 4.1 vs. 1.1/1000 person-years, p = 0.002; middle-aged, 2.3 vs. 0.3/1000 person-years, p < 0.001; male, 6.2 vs. 0.9/1000 person-years, p < 0.001); had a younger mean age (±standard deviation) of fracturing a hip (61.0±14.9 vs. 74.4±9.3 years, p = 0.015); had a lower cumulative HF-free probability (±standard error) before the age of 65 years (0.970±0.017 vs. 0.988±0.007, p<0.001) and throughout the study duration (0.415 ± 0.296 vs. 0.682 ± 0.158, p<0.001); and had a higher risk of HF, yielding an adjusted hazard ratio (95% confidence interval) of 3.58 (1.45˜8.79, p = 0.006). Patients with polio aged >48.2 years were likely to experience an HF. CONCLUSIONS: Adults with polio are at risk of HF. A customized HF prevention program is important for people with polio. The program should be started early in middle-age and should include men.

Incidence and risk of major heart diseases in middle-aged adults with moderate to severe vision impairment: a population-based cohort study.

BACKGROUND/AIM: To estimate the incidence and risk of major adverse cardiovascular events (MACEs), including heart failure and ischaemic heart disease, among middle-aged people with a visual disability (VD). METHODS: We used a national health insurance research database to conduct a population-based cohort study from 1 January 2000 to 31 December 2013. Patients with VD aged 35~65 years were recruited. For each VD patient, five age-matched, sex-matched and comorbidity-matched patients were randomly selected and recruited as controls. Control patients had no documented disability. RESULTS: This study recruited 978 patients with VD (mean age±SD, 55.1±7.8 years; 48.9% male) and 4677 controls. Compared with the same sex of the controls, women with VD had higher incidence of MACE 1 (7.9 vs 2.8/1000 person-years, p<0.001), MACE 2 (27.5 vs 16.9/1000 person-years, p<0.001), MACE 3 (3.7 vs 1.4/1000 person-years, p<0.005) and MACE 4 (4.5 vs 2.5/1000 person-years, p<0.05), and men with VD had higher incidence of MACE 1 (4.6 vs 2.0/1000 person-years, p<0.005). Compared with the controls, patients with VD had lower cumulative MACE 1~MACE 4-free probabilities and had an independently higher risk of MACE 1~MACE 4 during the 13-year study, yielding an adjusted hazard ratio range of 1.31~2.75. Those persons with VD who had diabetes and hypertension had greater risks of MACE 1~MACE 4. CONCLUSIONS: Middle-aged adults with VD were at risk of MACEs. A programme for MACE prevention is important for middle-aged people with VD. This is especially true for women and for those who also have diabetes and hypertension.

Incidence and risk of major adverse cardiovascular events in middle-aged patients with chronic kidney disease: a population-based cohort study.

PURPOSE: For early prevention, information regarding the incidence of major adverse cardiovascular events (MACEs) in middle-aged patients with chronic kidney disease (CKD) may be more beneficial than that regarding MACE prevalence. But, literature comparing the incidence and risk of MACEs in middle-aged patients with CKD with the controls using a population-based cohort study is scant. Our aim was to estimate the incidence and risk of MACEs, such as congestive heart failure (CHF) and ischemic heart disease (IHD), in middle-aged patients with advanced (stages 3-5) CKD. METHODS: From the National Health Insurance Research Database, 261 patients aged 35-65 years who had received advanced CKD diagnoses in 2000 and 1305 age-, sex-, and comorbidity-matched controls were recruited. Patients with CHF alone (MACE 1), IHD alone (MACE 2), or CHF and IHD (MACE 3) diagnoses between January 1, 2001, and December 31, 2008, were identified in the CKD and control groups. RESULTS: Patients (mean age ± standard deviation, 50.0 ± 8.3 years; female, 56%) exhibited a higher incidence of MACE 1, MACE 2, and MACE 3 (11.9 vs. 1.4/1000, 30.7 vs. 13.4/1000, and 13.4 vs. 1.7/1000 person-years, respectively, all p < 0.001) and were at a higher risk of experiencing MACEs than the controls (adjusted hazard ratios: MACE 1, MACE 2, and MACE 3: 8.57, 2.26, and 3.80, respectively, all p < 0.001). CONCLUSIONS: CKD is an independent risk factor for CHF and IHD among patients aged 35-65 years. Early intervention for preventing CHF and IHD in middle-aged patients with CKD is crucial.

Implementation of a cloud-based electronic medical record exchange system in compliance with the integrating healthcare enterprise's cross-enterprise document sharing integration profile.

In 2011, the Ministry of Health and Welfare of Taiwan established the National Electronic Medical Record Exchange Center (EEC) to permit the sharing of medical resources among hospitals. This system can presently exchange electronic medical records (EMRs) among hospitals, in the form of medical imaging reports, laboratory test reports, discharge summaries, outpatient records, and outpatient medication records. Hospitals can send or retrieve EMRs over the virtual private network by connecting to the EEC through a gateway. International standards should be adopted in the EEC to allow users with those standards to take advantage of this exchange service. In this study, a cloud-based EMR-exchange prototyping system was implemented on the basis of the Integrating the Healthcare Enterprise's Cross-Enterprise Document Sharing integration profile and the existing EMR exchange system. RESTful services were used to implement the proposed prototyping system on the Microsoft Azure cloud-computing platform. Four scenarios were created in Microsoft Azure to determine the feasibility and effectiveness of the proposed system. The experimental results demonstrated that the proposed system successfully completed EMR exchange under the four scenarios created in Microsoft Azure. Additional experiments were conducted to compare the efficiency of the EMR-exchanging mechanisms of the proposed system with those of the existing EEC system. The experimental results suggest that the proposed RESTful service approach is superior to the Simple Object Access Protocol method currently implemented in the EEC system, according to the irrespective response times under the four experimental scenarios.

(±)3,4-methylenedioxyamphetamine inhibits the TEA-sensitive K⁺ current in the hippocampal neuron and the Kv2.1 current expressed in H1355 cells.

The whole-cell patch clamp method was used to study the effects of (±)3,4-methylenedioxyamphetamine (MDA) in hippocampal CA1 neurons from neonatal rats and in lung epithelial H1355 cells expressing Kv2.1. Extracellular application of MDA (30 µM) induced bursts of action potentials in hippocampal CA1 neurons exhibiting single spike action potentials without a bursting firing pattern, and promoted action potential bursts in hippocampal CA1 neurons exhibiting bursting firing of action potentials. Whereas MDA (30 and 100 µM) markedly decreased the delayed outward current in hippocampal CA1 neurons, MDA (100 µM) only slightly decreased the fast-inactivating K(+) current (I(A)) current. Furthermore, MDA (100 µM) substantially decreased the delayed outward current in the presence of 4-aminopyridine (4-AP; 3 mM), but did not significantly decrease the delayed outward current in the presence of tetraethylammonium (TEA; 30 mM). MDA (100 µM) also inhibited the current in H1355 cells expressing Kv2.1. Our results have shown that MDA inhibits the TEA-sensitive K(+) current in the hippocampus and the Kv2.1 current expressed in H1355 cells. These effects may contribute to the pharmacological and toxicological effects of MDA.

Reappraisal of the anticancer efficacy of quercetin in oral cancer cells.

BACKGROUND: Despite increased experience in therapy, the overall outcome of oral squamous cell carcinoma (OSCC) has not improved because of the relative resistance to chemotherapeutic drugs in addition to local invasion and frequent regional lymph node metastases. Quercetin (Qu) is a principal flavonoid compound and an excellent free-radical-scavenging antioxidant that promotes apoptosis. Limited reports regarding the molecular or cellular role of Qu in anticancer properties on OSCC have been presented. This study was conducted to clarify the efficacy of Qu on OSCC in vitro and further to evaluate the possible mechanism(s). METHODS: Cultured OSCC cells (SCC-25) and human gingival fibroblasts (HGFs) were treated with different concentrations of Qu. Cell viability and cell colony-forming potential were detected with the MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) and colony growth assays. Cell-cycle analysis and apoptosis were measured by flow cytometry. Cell migration and invasion were tested using the micropore chamber assay. RESULTS: Cell viability and colony-forming potential were decreased in a dose-dependent manner following Qu treatment. Qu also dose-dependently inhibited the proliferation of SCC-25 cells via both G1 phase cell cycle arrest and mitochondria-mediated apoptosis. In addition, Qu also decreased the abilities of migration and invasion of SCC-25 cells in a dose-dependent manner. CONCLUSION: Qu effectively inhibits cell growth and invasion/migration of SCC-25 cells in vitro. The cellular and molecular mechanisms are via cell cycle arrest accompanied by mitochondria-mediated apoptosis. Our findings suggest that Qu may have potential as a new chemopreventive agent or serve as a therapeutic adjuvant for OSCC.

Pathogen colonization in patients with acute cerebral stroke.

PURPOSE: To identify the pathogens that frequently cause infection and to explore their clinical features in acute stroke patients. METHODS: From June 1, 1999 to December 31, 2008, we reviewed medical records of 263 patients with acute stroke and 351 controls. Within 30 days from admission, 109 and 107 patients had one or more bacterial cultures, respectively. The cumulative bacteria-free probability of all patients and the incidence of each isolated pathogen were assessed. We searched for the factors associated with isolation of different Gram-negative bacilli (GNB). RESULTS: Patients with recent stroke were prone to healthcare-associated colonization within 2 weeks from admission. One-fourth of stroke patients had positive bacterial culture. Stroke patients had a high incidence of Staphylococcus aureus and various GNB in their sputum. When urinary tract infections (UTIs) began 9 days or more after admission, the contributory pathogens were most often glucose-nonfermenting bacilli. However, if UTIs occurred within 9 days after admission, the pathogens were likely to be Enterobacteriaceae bacilli. CONCLUSIONS: Stroke patients had high incidence of pathogenic bacteria in their sputum which might be prone to pneumonia. The time after admission of the onset of UTI is useful information for predicting contributory pathogens and planning for appropriate treatment.

Quercetin suppresses drug-resistant spheres via the p38 MAPK-Hsp27 apoptotic pathway in oral cancer cells.

BACKGROUND: Treatment failure in oral squamous cell carcinoma (OSCC) leading to local recurrence(s) and metastases is mainly due to drug resistance. Cancer stem cells (CSCs) are thought be responsible for the development of drug resistance. However, the correlations between CSCs, drug resistance, and new strategy against drug resistance in OSCC remain elusive. METHODS: A drug-resistant sphere (DRSP) model was generated by using a nonadhesive culture system to induce drug-resistant cells from SCC25 oral cancer cells. A comparative analysis was performed between the parent control cells and DRSPs with a related treatment strategy focusing on the expression of epithelial-mesenchymal transition (EMT)-associated markers, drug-resistance-related genes, and CSC properties in vitro, as well as tumorigenicity and the regimen for tumor regression in vivo. RESULTS: Our data show the presence of a phenomenon of EMT with gradual cellular transition from an epithelioid to mesenchymal-like spheroid morphology during induction of drug resistance. The characterization of DRSPs revealed the upregulation of the drug-resistance-related genes ABCG2 and MDR-1 and of CSC-representative markers, suggesting that DRSPs have greater resistance to cisplatin (Cis) and stronger CSC properties compared with the control. Moreover, overexpression of phosphorylated heat-shock protein 27 (p-Hsp27) via the activation of p38 MAPK signaling was observed in DRSPs. Knockdown of Hsp27 decreased Cis resistance and induced apoptosis in DRSPs. Furthermore, an inhibitor of Hsp27, quercetin (Qu), suppressed p-Hsp27 expression, with alterations of the EMT signature, leading to the promotion of apoptosis in DRSPs. A xenographic study also confirmed the increase of tumorigenicity in DRSPs. The combination of Qu and Cis can reduce tumor growth and decrease drug resistance in OSCC. CONCLUSIONS: The p38 MAPK-Hsp27 axis plays an important role in CSCs-mediated drug resistance in OSCC. Targeting this axis using Qu combined with Cis may be a treatment strategy to improve prognosis in patients with OSCC.

Antimüllerian hormone and polycystic ovary syndrome.

OBJECTIVE: To assess the relationship between antimüllerian hormone (AMH) and parameters related to polycystic ovary syndrome (PCOS). DESIGN: Prospective study. SETTING: Academic tertiary care center. PATIENT(S): A total of 290 women. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Parameters related to insulin resistance and metabolic syndrome. RESULT(S): Women with polycystic ovary morphology had significantly higher AMH levels than women in the control group. The prevalence of PCOS increased from 21% in the low-AMH (<4 ng/mL) group to 37% in the moderate-AMH (4-11 ng/mL) group and 80% in the high-AMH (>11 ng/mL) group. However, significant differences in insulin resistance parameters were not observed among groups. The results of the correlation analysis revealed that AMH levels were positively correlated with LH, total T, A, and total cholesterol content; however, AMH levels were negatively correlated with age, body mass index, and the number of menstrual cycles per year. AMH levels were not correlated with insulin resistance parameters. CONCLUSION(S): Elevated serum AMH levels increase the risk of PCOS but do not affect the risk of insulin resistance or metabolic syndrome.

Inappropriate gonadotropin secretion in polycystic ovary syndrome.

OBJECTIVE: To evaluate inappropriate gonadotropin secretion in women with polycystic ovary syndrome (PCOS). DESIGN: Retrospective study. SETTING: Academic tertiary center. PATIENT(S): A total of 373 women were classified into three groups: [1] healthy control women (n = 48); [2] women who were positive for PCOS risk factor; and [3] women with PCOS (n = 251). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Gonadotropin levels, LH-FSH ratio, body mass index, and clinical and/or biochemical presentations of PCOS. RESULT(S): The area under the receiver operating characteristic curve, used to predict PCOS for the LH-FSH ratio, showed similar diagnostic performance to total T and average ovarian volume. The LH-FSH ratio exhibits greater observed accuracy than total T and average ovarian volume for evaluation of women with oligomenorrhea or anovulation. An LH-FSH ratio of >1 presented the best combination of sensitivity and specificity. Body mass index was positively correlated with total T in non-PCOS and PCOS groups; however, body mass index was negatively correlated with LH in PCOS but showed no correlation in non-PCOS subjects. CONCLUSION(S): The LH-FSH ratio is a valuable diagnostic tool in evaluating women with PCOS and oligomenorrhea or anovulation, and an LH-FSH ratio of >1 may be used as a decision threshold. The link between body mass index and LH may provide clues for further understanding the pathological milieu of PCOS.