Prevalence of Nontraumatic Osteonecrosis of the Femoral Head and its Associated Risk Factors in the Chinese Population: Results from a Nationally Representative Survey / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Nontraumatic osteonecrosis of the femoral head (NONFH) is a debilitating disease that represents a significant financial burden for both individuals and healthcare systems. Despite its significance, however, its prevalence in the Chinese general population remains unknown. This study aimed to investigate the prevalence of NONFH and its associated risk factors in the Chinese population.</p><p><b>METHODS</b>A nationally representative survey of 30,030 respondents was undertaken from June 2012 to August 2013. All participants underwent a questionnaire investigation, physical examination of hip, and bilateral hip joint X-ray and/or magnetic resonance imaging examination. Blood samples were taken after overnight fasting to test serum total cholesterol, triglyceride, and high-density lipoprotein (HDL) and low-density lipoprotein (LDL) levels. We then used multivariate logistic regression analysis to investigate the associations between various metabolic, demographic, and lifestyle-related variables and NONFH.</p><p><b>RESULTS</b>NONFH was diagnosed in 218 subjects (0.725%) and the estimated NONFH cases were 8.12 million among Chinese people aged 15 years and over. The prevalence of NONFH was significantly higher in males than in females (1.02% vs. 0.51%, χ2 = 24.997, P < 0.001). Among NONFH patients, North residents were subjected to higher prevalence of NONFH than that of South residents (0.85% vs. 0.61%, χ 2 = 5.847, P = 0.016). Our multivariate regression analysis showed that high blood levels of triglycerides, total cholesterol, LDL-cholesterol, and non-HDL-cholesterol, male, urban residence, family history of osteonecrosis of the femoral head, heavy smoking, alcohol abuse and glucocorticoid intake, overweight, and obesity were all significantly associated with an increased risk of NONFH.</p><p><b>CONCLUSIONS</b>Our findings highlight that NONFH is a significant public health challenge in China and underscore the need for policy measures on the national level. Furthermore, NONFH shares a number of risk factors with atherosclerosis.</p>

Effect of superior retinacular artery damage on osteonecrosis of the femoral head / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Osteonecrosis of the femoral head (ONFH) is the result of dysfunctional blood supply, but associations between specific damaged arteries, imaging changes and clinical sign require more understanding. We investigated characteristics of ONFH that pertain to blood supply, imaging appearance, and clinical feature to judge the prognosis of ONFH.</p><p><b>METHODS</b>Clinical data were collected for 92 patients (118 hips) with ONFH, including gender, age, duration of pain (from initial clinical presentation to arthroplasty), cause, stage, and classification. Magmatic resonance imaging and X-rays were obtained of all patients to diagnose ONFH. The sizes of lesions were classified by necrotic index. The location of necrosis was classified as Type A, B, or C using the grading system by magmatic resonance imaging and X-rays. All hips were imaged with digital subtraction angiography to visualize their blood-supply characteristics. Hips were divided into groups based on the source artery for femoral head damage: superior retinacular artery (S), inferior retinacular artery (I), and combined superior and inferior retinacular arteries (S+I). Via digital subtraction angiography, imaging appearances and clinical data in three groups were compared.</p><p><b>RESULTS</b>ONFH was caused by damage in either the superior or inferior retinacular artery, or both, in all of 118 hips. The group with only inferior retinacular artery damage reported longer hip pain duration than the other groups. The probability of the lesion extending laterally to the acetabular edge in group S was much more than it in group I. Necrosis indices of the patients in S and S+I were higher than those in group I.</p><p><b>CONCLUSIONS</b>ONFH associated with interruption of the superior and inferior retinacular arteries in this study. When the former alone was damaged, the necrosis of the volume was larger, the risk of femoral head collapse was higher and the time from initial clinical presentation to arthroplasty was shorter.</p>

Determinations of mifepristone and its metabolites and their pharmacokinetics in healthy female Chinese subjects / 药学学报

The aim of this study is to establish an HPLC method for simultaneous determinations of mifepristone and its metabolites, mono-demethylated mifepristone, di-demethylated mifepristone and C-hydroxylated mifepristone in plasma and to evaluate the pharmacokinetic characteristics of mifepristone tablet. Twenty healthy female Chinese subjects were recruited and a series of blood samples were collected before and after 0.25, 0.5, 1.0, 1.5, 2.0, 4.0, 8.0, 12.0, 24.0, 48.0, 72.0 and 96.0 hours administration by a single oral dose of 75 mg mifepristone tablet. Mifepristone and its three metabolites were extracted from plasma using ethyl acetate and determined by high performance liquid chromatography. The main pharmacokinetic parameters of mifepristone and its metabolites, including Cmax, tmax, MRT, t(1/2), V, CL, AUC(0-96 h) and AUC(0-infinity), were calculated by Drug and Statistical Software Version 2.0. The simple, accurate and stable method allows the sensitive determinations of mifepristone and its metabolites in human plasma up to 4 days after oral administration of 75 mg mifepristone tablet and the clinical applications of their pharmacokinetic studies.

Comparison of different pharmacodynamic models for pharmacokinetic-pharmacodynamic (PK-PD) modeling of carvedilol / 药学学报

The paper is aimed to investigate the pharmacokinetic (PK) and the pharmacodynamic (PD) properties of carvedilol using indirect response and effect-compartment link models, and compare the fitness of PK-PD models. Twenty male healthy Chinese volunteers received a single oral dose of 20 mg of carvedilol. The plasma concentrations of carvedilol were determined by reversed-phase HPLC method with fluorescence detection, and the pharmacokinetic parameters were calculated by DAS2.0. The mean arterial blood pressure was measured and the pharmacodynamics of carvedilol was characterized by tail-cuff manometry. The main pharmacokinetic parameters of carvedilol were as follows, t1/2 (4.56 +/- 2.56) h, Cmax (46.29 +/- 21.07) ng x mL(-1), AUC(0-infinity) (173.76 +/- 87.36) ng x mL(-1) x h. The estimated Kin was (0.41 +/- 0.31)% h(-1), Kout was (0.40 +/- 0.26) h(-1), the IC50 value was (24.40 +/- 21.10) ng x mL(-1) and the area under the effect curve (AUE) was (3.82 +/- 1.46)% h for the indirect response PD model. The Ke0 was (0.35 +/- 0.27) h(-1), the EC50 was (24.30 +/- 24.30) ng x mL(-1), and the AUE was (5.65 +/- 2.54)% h for the effect-compartment model. The HPLC method can be used for the pharmacokinetic study of carvedilol. The proposed effect-compartment link model provided more appropriate and better-fitting PK/PD characteristics than the indirect response model in Chinese healthy volunteers according to Akaike's information criterion values.

HPLC-MS/MS method for determination of sodium cromoglycate concentration in human plasma and its pharmacokinetics / 药学学报

The study established an HPLC-MS/MS method for determining the concentrations of sodium cromoglycate in human plasma and evaluated the pharmacokinetics of nasal drops and nasal spray. A C18 column was used to separate sodium cromoglycate in plasma with a mobile phase of a mixture of ammonium-methanol (involves 50% acetonitrile) (15:85) at a flow rate of 0.4 mL x min(-1). Electronic spray ionization (ESI) and multiple-reaction monitoring (MRM) were used for the determination of sodium cromoglycate in human plasma. The linear range of the standard curve of sodium cromoglycate was from 0.3 to 20 ng x mL(-1), and the minimum concentration of detection was 0.3 ng x mL(-1). The extraction recovery was more than 94.1%, intra-day and inter-day RSD were less than 14.3%. After a single dose of sodium cromoglycate, the main pharmacokinetic parameters of nasal spray and nasal drops were as follows, T(1/2)(1.82 +/- 0.54) h, (1.59 +/- 0.52) h; Tmax (0.47 +/- 0.12) h, (0.44 +/- 0.15) h; Cmax, (9.79 +/- 4.66) ng x mL(-1), (10.88 +/- 4.05) ng x mL(-1); AUC(0-5 h)(11.52 +/- 3.46) ng x mL(-1) x h x h, (12.63 +/- 4.23) ng x mL(-1) x h, Fr(93.6 +/- 13.8)%. The method is sensitive, rapid and accurate. It is suitable for therapeutic drug monitoring and human pharmacokinetic study of sodium cromoglycate.

Determination of betamethasone in human plasma by liquid chromatography with tandem mass / 药学学报

A sensitive and selective liquid chromatography-tandem mass spectrometric (LC-MS/MS) method was developed and validated for the determination of betamethasone in human plasma. The analyte was isocratically eluted on a Venusil XBP C8 column (200 mm x 3.9 mm ID, 5 microm) with methanol-water mol x L(-1) ammonium formate) (80:20) at a flow rate of 0.4 mL x min(-1), and detected (containing 5 mmol x L(-1) ammonium formate) (80:20) at a flow rate of 0.4 mL x min(-1), and detected with a triple quad LC-MS/MS using ESI with positive ionization. Ions monitored in the multiple reaction monitoring (MRM) mode were m/z 393.3-->355.2 for betamethasone and m/z 361.3-->343.2 for prednisolone (IS). Betamethasone was extracted from 0.5 mL human plasma with ethyl acetate. The average recovery is 88.24% and the low limit of quantitation (LLOQ) was 0.5 ng x mL(-1). The 3-day validation study demonstrated excellent precision and accuracy across the calibration range of 0.5-80.0 ng x mL(-1). The method was successfully applied to the pharmacokinetic study of compound betamethason injection in healthy Chinese volunteers.

Pharmacokinetics and biodistribution of 3H-norcantharidin in mice / 药学学报

A single dose of 3H-norcantharidin solution was intragastrically given, blood, tissues, urine and feces were collected as scheduled, and radioactivity in these samples was determined by tritium tracing method to investigate the pharmacokinetics, tissue distribution and excretion of norcantharidin in Kunming mice. The pharmacokinetic characteristics of norcantharidin were evaluated by DAS version 2.0. The blood concentration reached to maximum 0. 5 h after intragastric administration. The radioactivity in tissues was high in small intestine, gallbladder, stomach, adrenal gland, kidney, heart and uterus 15 minutes after administration, descending with time, and high in gallbladder, adrenal gland and uterus 3 hours post dosing. The 24 h accumulative excretion ratio of urine and feces were 65.40% and 1.33% respectively. 3H-norcantharidin was easily absorbed after orally given to mice, the radioactivity was high and existed for a long-time in gallbladder, adrenal gland and uterus, and low but also existed for a long-time in large intestine, thymus and fat tissue. 3H-norcantharidin was declined quickly in small intestine, stomach, kidney and heart, and occurred rarely in brain. Norcantharidin was excreted mainly by urinary route and seldom in feces, which may be the cause of the urinary stimulation side effects observed. Because the radioactivity measured were the sum of 3H labeled norcantharidin and its metabolites, further studies on the disposition of norcantharidin in mammal animals, on the separation or identification of metabolites and, if any, on their activities, are fairly needed.

Determination of curcumol in plasma by HPLC-MS/MS method and its pharmacokinetics in Beagle dogs / 药学学报

To establish a high performance liquid chromatography (HPLC) coupled with tandem mass spectrometry quantitative detection method for the determination of curcumol, the main ingredient of zedoary turmeric oil fat emulsion, and investigate its pharmacokinetics in Beagle dogs, nine healthy Beagle dogs were divided into three groups, and blood samples were collected at scheduled time points after intravenous injection of 7.5, 10 and 12.5 mg x kg(-1) zedoary turmeric oil fat emulsion. The concentrations of curcumol were determined and pharmacokinetics was calculated. A good linearity was obtained from 0.25 to 100 ng x mL(-1) in plasma. The relative recoveries were from 91.33% to 103.17%, and the absolute recoveries were from 31.61% to 37.20%. The intra-day and inter-day variances (RSD) were < 15%. The main pharmacokinetic parameters of curcumol after intravenous injection of 7.5, 10 and 12.5 mg x kg(-1) zedoary turmeric oil fat emulsion were as follows, T1/2 : (2.0 +/- 0.4), (1.7 +/- 0.2) and (2.3 +/- 0.8) h, AUC(0-infinity): (15.1 +/- 2.7), (18.3 +/- 2.0) and (29.5 +/- 4.0) ng x mL(-1) x h; MRT: (0.9 +/- 0.1), (0.8 +/- 0.2) and (0.8 +/- 0.1) h, CL: (21.9 +/- 4.0), (24.9 +/- 6.0) and (18.4 +/- 1.2) L x h(-1) x kg; Vd : (65.4 +/- 26.5), (62.0 +/- 13.4) and (61.2 +/- 19.8) L x kg(-1), respectively. The developed method was rapid, highly sensitive and specific and could be used in curcumol pharmacokinetic studies in vivo. A three-compartment model was best fit to the plasma concentration--time curves obtained in Beagle dogs and the plasma AUC was increased proportionally with doses.

Free iliac crest grafts with periosteum for treatment of old acetabular defects / 中华创伤杂志(英文版)

<p><b>OBJECTIVE</b>To inquire into the therapeutic effectiveness of free iliac crest grafts with periosteum on old acetabular defects.</p><p><b>METHODS</b>From February 1996 to June 2005, 9 patients were treated with free iliac crest grafts with periosteum to reconstruct old acetabular defects. There were 7 males and 2 females and the average age was 41.3 years. The acetabular defects were caused by traffic accidents in 6 cases and fall injury in 3 cases. The time from injury to treatment was 4-13 months and averaged 8 months. Intraoperatively we firstly removed the acetabular fracture fragments of the posterior wall. The femoral head was then reduced. Bone graft was harvested from the iliac crest with periosteum, which was sculpted with a rongeur to conform to the defect. The concave (iliac fossa) side of the graft was placed toward the femoral head. The graft was securely fixed by two to three leg screws.</p><p><b>RESULTS</b>Postoperative syndrome was not found in any of the cases. Harris' score system showed that the score raised from 32.3 points preoperatively to 81 points postoperatively. The hip function was evaluated as excellent in 3 cases, good in 4 cases and fair in 2 cases.</p><p><b>CONCLUSIONS</b>Although this procedure could not exactly reproduce the anatomy of the hip joint, it enables to restore the posterior stability, provide bone-stock for the hip joints and prevent dislocation of the femoral head.</p>

Safety and tolerance study of single oral dose of adefovir dipivoxil tablets in healthy volunteers / 中华实验和临床病毒学杂志

<p><b>BACKGROUND</b>To assess the safety and tolerance of adefovir dipivoxil tablet in Chinese healthy volunteers.</p><p><b>METHODS</b>Totally 42 healthy volunteers were enrolled in the study, 21 were female and 21 were male and their age ranged from 19 to 26 years. The subjects were randomly divided into 5, 10, 20, 40 and 60 mg dose-groups (6-10 subjects in each group) based on sex and weight, beginning with the 5 mg dose-group. Clinical symptoms, vital signs, electrocardiogram, routine blood test, routine urine test, prothrombin time and blood biochemical tests were recorded and evaluated.</p><p><b>RESULTS</b>No significant changes were found in clinical symptoms, vital signs and laboratory tests after dosing, except slight elevations of alanine aminotransferase in 2 subjects and bilirubin in 6 subjects observed and some gastrointestinal symptoms such as nausea and diarrhea found in 3 subjects, but the frequency and severity of all the adverse reactions were not found to be related to the dosages.</p><p><b>CONCLUSION</b>The results showed that single oral dose of adefovir dipivoxil 60 mg or less was safe and tolerable.</p>

Conservative methods for osteonecrosis of the femoral head: the review of 1005 cases / 中华外科杂志

<p><b>OBJECTIVE</b>To research on the conservative methods used to preserve the femoral head of patients with osteonecrosis of the femoral head.</p><p><b>METHODS</b>In these series surgical procedures the osteonecrotic lesion was removed and various vascularized bone blocks or periosteal flaps with its nutrient vessels were transferred to regain sphericity of the femoral head and reinforce the sequestrum. The current study assessed 1005 patients (1226 hips) operated on from 1989 to 2002 with an average follow-up of 5.1 years (range, 1.5-15 years). The mean age of the patients was 37.4 years (range, 17-65 years).</p><p><b>RESULTS</b>Sixty-one hips (57 patients) had conversion surgery to a total hip arthroplasty because of progressive collapse or severe pain, or both. In the patients without failure, postoperative Harris hip score improved significantly. Of the 1174 reconstructions that were in situ, 1041 (89.4%) were clinically successful, and 878 (75.4%) were radiologically successful. In relation to the stage of necrosis according to the classification system of Ficat and Alert, good results were achieved in 95.3% of the patients with stages II disease, 87.9% with stages III and 60.8% with stages IV.</p><p><b>CONCLUSIONS</b>Conservative methods of vascularized bone block or periosteal flap transfer should be considered in active symptomatic patients to preserve the femoral head. In addition, the earlier the stages of the disease the better outcome could be obtained.</p>

Relative bioavalability of hydrochloride eperisone granule in healthy volunteers / 中国临床药理学与治疗学

Aim The relative bioavalability of hydrochloride eperisone granule in 10 healthy volunteers was studied. Methods The time-plasma concentrations of hydrochloride eperisone granule, as test drug, and myonal, as reference drug, were determined by GC-MS, with tolperisone senuing as internal standard.The pharmacokinetic parameters of both reference and test drug were calculated and analyzed with two-one side test and confidential interval test. Results The results showed that the AUC0-8, AUC0-∞, Cmax, Tpeak, t1/2(?) and t1/2(?) were (17.9?1.3)ng?h?ml-1 and(18.6?1.6)ng?h?ml-1, (19.1?1.2)ng?h?ml-1 and (20.2?1.6)ng?h?ml-1, (5.2?0.5)ng?ml-1 and (5.4?0.5) ng?ml-1, (1.05?0.18)h and (1.08?0.23)h, (0.78? 0.13)h and ( 0.82?0.14)h,( 1.8?0.3)h and (1.8?0.3)h, respectively. The relative bioavalability of test drug was (105? 5)%. Conclusion It can be concluded that the test and reference are bioequivalented between individuals, preparations and periods.