OBJECTIVETo explore mid-term follow up results of distal fixation prosthesis in treating unstable intertrochanteric fractures in elderly patients.

METHODSFrom May 2008 to March 2014,58 elderly patients with unstable intertrochanteric were treated with distal fixation prosthesis, among them, there were 15 males and 43 females aged from 75 to 87 years old with an average of 83.2 years old. Fracture were classified according to Evans classification, 39 cases were type I c and 19 cases were type I d. Surgical risk was evaluated before operation, 9 patients were performed total hip arthroplasty and 49 patients were performed prosthetic replacement hip joint function of patients with different age period, Evans classificaton, prothesis type, fixation method were evaluated respectively by using Harris score.

RESULTSFifty-six patients were followed up from 13 to 36 months with an average of 21.6 months. Harris score was 83.51 ± 6.40, 5 cases got excellent results, 38 cases good and 13 cases moderate. Harris score of patients aged from 75 to 80 years old was 88.64 ± 2.35, 81.64 ± 6.40 in patients aged more than 80 years old, and had significant differences between two groups; Harris score in patients with type Evans I c was 83.64 ± 6.53, and 83.11 ± 6.08 in type Evans I d, while there was no significant differences between two groups. There was no obvious meaning in Harris score between patients with tension band (83.63 ± 6.15) and without tension band (82.41 ± 6.57). There was no significant meaning in Harris score between patients with normal distal fixation prosthesis (83.34 ± 6.43) and femoral moment reconstruction distal fixation prosthesis (83.92 ± 6.51). There was 1 patient occurred hip joint dislocation on the operative side and re-dislocation after manual reduction, then received open reduction. Two patients occurred femoral osteolysis without clinical symptoms, and treated conservative treatment.

CONCLUSIONArtificial joint replacement for unstable intertrochanteric fractures in elderly patients, hip joint function in patients aged more than 80 years old is worse, while there was no obvious market effect in fracture classification, whether to use tension band and type of distal fixation prosthesis, moreover, proximal femoral osteolysis should be focused on.

Aged ; Aged, 80 and over ; Arthroplasty, Replacement, Hip ; Female ; Femur ; surgery ; Follow-Up Studies ; Fracture Fixation, Intramedullary ; Hip Fractures ; surgery ; Hip Joint ; surgery ; Hip Prosthesis ; Humans ; Male ; Treatment Outcome

AIMTo prepare self-microemulsifying drug delivery system (SMEDDS) containing atorvastatin,and decrease its size to improve the solubility in the stomach. And to study the effect of the resultant microemulsion in reducing the presystemic clearance in the gastrointestinal mucosa and hepatic first-pass metabolism, improving the oral bioavailability, and reducing side effect and expenditure.

METHODSPseudoternary phase diagrams were used to evaluate the self-microemulsification existence area. The HPLC analyses in vitro and in vivo were set up. Solubility in various vehicles was determined. The self-microemulsification efficiency was assessed, such as self-microemulsification time, stability, particle size and zeta potential. SMEDDS containing atorvastatin, non-ionic surfactant and lipid were prepared. Droplet size/distributions and zeta potential of the resultant microemulsion were determined. Photos were taken with transmission electron microscope. Oral bioavailability was studied on prepared SMEDDS hard capsules and compared with that of the conventional tablet in Beagle dogs in vivo.

RESULTSThe optimal formulations had wide microemulsion existent field and had good self-microemulsifying efficiency. Droplet size was within 100 nm and showed Gaussian distribution. After oral administration of SMEDDS capsules and the conventional tablet to fasted Beagle dogs, the Cmax from SMEDDS was greater than that of the conventional tablet. AUC from zero to 24 h of SMEDDS was about 1.5-fold higher than that of the conventional tablet. Oral bioavailability of atorvastatin SMEDDS was greater than that of the conventional tablet.

CONCLUSIONThe results indicated the potential use of SMEDDS for the delivery of atorvastatin to increase its oral bioavailability.

Administration, Oral ; Animals ; Area Under Curve ; Atorvastatin Calcium ; Biological Availability ; Dogs ; Drug Delivery Systems ; Emulsions ; Glycerol ; analogs & derivatives ; chemistry ; Heptanoic Acids ; administration & dosage ; blood ; pharmacokinetics ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; administration & dosage ; blood ; pharmacokinetics ; Male ; Particle Size ; Polyethylene Glycols ; chemistry ; Pyrroles ; administration & dosage ; blood ; pharmacokinetics ; Solubility

AIMTo develop a pharmacokinetic model for the enterohepatic circulation of mycophenolic acid (MPA).

METHODSTwenty healthy volunteers were orally given a single dose of 500 mg mycophenolate mofetil. Plasma samples were collected during 48 hours and MPA concentration was measured by HPLC method. Pharmacokinetic (PK) model was established based on physiological and biopharmaceutical consideration and PK parameters were obtained using nonlinear mixed effect model.

RESULTSThe proposed model included an intestinal compartment and gall bladder compartment in addition to the central compartment. The predicted time-concentration curve and AUC0-t, Cmax, Tmax estimated by the established model were in agreement with the observations.

CONCLUSIONThe established model was well defined for the MPA disposition and could afford a useful approach for the further clinical investigation.

Adult ; Area Under Curve ; Enterohepatic Circulation ; physiology ; Glucuronides ; pharmacokinetics ; Humans ; Immunosuppressive Agents ; pharmacokinetics ; Male ; Models, Biological ; Mycophenolic Acid ; administration & dosage ; analogs & derivatives ; blood ; pharmacokinetics

AIMTo determine the relationship between C3435T mutation in exon 26 of the human multidrug resistant 1 gene and cyclosporine (CsA) pharmacokinetic (PK) parameters among healthy Chinese volunteers by nonlinear mixed effect model (NONMEM).

METHODSTwenty healthy subjects were given orally a single dose of 500 mg CsA in microemulsion solution. Blood CsA concentrations were measured with HPLC and the genotype for the C3435T polymorphism of MDR1 gene was determined with the PCR and restriction fragment length polymorphism. The results were further confirmed by sequencing. NONMEM was performed to assess the effect of genotype on CsA PK profile.

RESULTSMDR1 C3435T genotype was identified as the best predictor of CsA systemic exposure. The relative bioavailability of CsA was 40% higher in subjects who carried at least one 3435C allele compared to that of TT type individuals in the study population.

CONCLUSIONThe MDR1 C3435T genotype offers a potential basis of mechanism to explain inter-subject differences in CsA oral bioavailability.

Administration, Oral ; Adult ; Biological Availability ; Cyclosporine ; administration & dosage ; pharmacokinetics ; Exons ; Genes, MDR ; genetics ; Genetics, Population ; Genotype ; Humans ; Male ; Mouth ; metabolism ; Polymorphism, Genetic

BACKGROUNDThe result would be disastrous if the superior pulmonary sulcus tumor (Pancoast tumor) was misdiagnosed as degenerative cervical spine diseases. The aim of this study was to investigate the differential diagnosis methods of cervical radiculopathy and superior pulmonary sulcus tumor.

METHODSClinical manifestations, physical, and radiological findings of 10 patients, whose main complaints were radiating shoulder and arm pain and later were diagnosed with superior pulmonary sulcus tumor, were reviewed and compared with those of cervical radiculopathy.

RESULTSSuperior pulmonary sulcus tumor patients have shorter mean history and fewer complaints of neck pain or limitation of neck movement. Physical examination showed almost normal cervical spine range of motion. Spurling's neck compression test was negative in all patients. Anteroposterior cervical radiographs showed the lack of pulmonary air at the top of the affected lung in all cases and first rib encroachment in one case. The diagnosis of superior pulmonary sulcus tumor can be further confirmed by CT and MRI.

CONCLUSIONSBy the method of combination of history, physical examination, and radiological findings, superior pulmonary sulcus tumor can be efficiently differentiated from cervical radiculopathy. Normal motion range of the cervical spine, negative Spurling's neck compression test, and the lack of pulmonary air at the top of the affected lung in anteroposterior cervical radiographs should be considered as indications for further chest radiograph examinations.

Adult ; Aged ; Diagnosis, Differential ; Female ; Humans ; Male ; Middle Aged ; Pancoast Syndrome ; diagnosis ; Radiculopathy ; diagnosis

OBJECTIVETo explore the pharmacologic mechanism of gardenin in treating cerebral ischemia, by studying its effect on gene expression profile in brain of rats with focal cerebral ischemia (FCI).

METHODSTotal RNAs were isolated from rats with FCI and those treated with gardenin. The mRNAs were reversely transcribed to cDNA with incorporation of fluorescent Cy5- or Cy3-dUTP to prepare hybridization probes. The PCR products of 4096 genes were spotted on the chip after a serial treatment. The mixed probes were hybridized to the cDNA microarray. Axon Genepix 4000B and GenePixPro 3.0 software were used to scan and analyze the fluorescent signals.

RESULTSIn the group treated with gardenin, there were 70 genes had expression profiles different to that in the model group in the focal cerebral ischemic brain tissue, in which 68 were up-regulated and 2 down-regulated.

CONCLUSIONGardenin has regulatory effect on the gene expression in rats with focal cerebral ischemia, which elucidates part of the pharmacologic mechanism of Qingkailing in molecular level.

Animals ; Brain Ischemia ; genetics ; metabolism ; Gene Expression Profiling ; Gene Expression Regulation ; drug effects ; Male ; Pyridines ; pharmacology ; Rats ; Rats, Sprague-Dawley

This study developed a method for simultaneously assessing the inhibitory potency of compounds on five major cytochrome P-450 ( CYP450) enzymes using a cocktail of probe substrates. A cocktail selective substrates consisting of the phenacetin (PN, CYP1A2), dextromethorphan (DM, CYP2D6), tolbutamide (TB, CYP2C9), omeprazole (OPZ, CYP2C19) and midazolam (MPZ, CYP3A4) was incubated with human liver microsomes. The concentrations of the substrate metabolites paracetamol, dextrorphan, 4-hydroxytolbutamide, 5-hydroxyomeprazole and 1'-hydroxymidazolam were determined by LC/MS/MS in a single assay sample. The method was validated by incubating known CYP inhibitors--alpha-naphthoflavone (ANF, CYP1A2), quinidine (QND, CYP2D6), sulfaphenazole (SUL, CYP2C9), fluconazole (FLU, CYP2C19) and ketoconazole (KET, CYP3A4) with the individual substrates and with the substrate cocktail. The IC50 values were then determined. The IC50s (micromol x L(-1)) were in good agreement with those obtained with individual substrates (alpha-naphthoflavone, 0.18 vs 0.26; quinidine, 0.058 5 vs 0.058 4; sulfaphenazole, 0.48 vs 0.45; fluconazol, 17.5 vs 11.4; ketoconazole, 0.22 vs 0.24) and with previously reported values in the literature. This cocktail probe substrate method can be utilized for the rapid simultaneous determination of the inhibition potential of compounds on the five CYP450 enzymes.
Chromatography, Liquid ; Cytochrome P-450 Enzyme Inhibitors ; Enzyme Inhibitors ; pharmacology ; Humans ; Inhibitory Concentration 50 ; Tandem Mass Spectrometry

OBJECTIVETo study the clinicopathologic features of different variants of primary focal segmental glomerulosclerosis (FSGS).

METHODSOne hundred and two cases of FSGS were retrieved from the archival files of Peking University First Hospital during the past 6-year period. The pathologic findings were reviewed and the degrees of active and chronic changes were assessed by morphometric analysis. The histopathologic patterns were then correlated with clinical manifestations.

RESULTSAmongst the 102 cases of primary FSGS studied, 55.9% belonged to the NOS (not other specified) variant, while the perihilar, cellular, tip and collapsing variants accounted for 6.9%, 25.5%, 4.8% and 6.9% respectively. The level of proteinuria in the cellular and tip variants were much higher than that in the NOS variant; and the incidence of nephrotic syndrome in the tip and collapsing variants was higher than that in the other three variants (chi(2) = 12.23, P < 0.05). The activity score of the cellular and collapsing variants was also higher than that of the other three variants (P < 0.05). The interval between disease onset and renal biopsy diagnosis in the perihilar variant was longer than that in the other variants. The chronicity score of this variant was higher than that of the tip and NOS variants (P < 0.05). On the other hand, the total scores of active and chronic changes of the tip variant was lower than that of the cellular and collapsing variants (P < 0.05); and its chronic score was lower than that of the NOS and perihilar variants (P < 0.05).

CONCLUSIONSThe NOS variant is the commonest morphologic pattern seen in primary FSGS. The cellular and collapsing variants are the patterns associated with active lesions, while perihilar variant is the pattern associated with chronic lesions. The tip variant shows mild pathological changes compared with the other patterns.

Adolescent ; Adult ; Creatinine ; blood ; Female ; Glomerulosclerosis, Focal Segmental ; blood ; classification ; pathology ; Humans ; Kidney Glomerulus ; pathology ; Male ; Serum Albumin ; metabolism ; Young Adult

Objective To detect the positive rates of antibodies against avian influenza virus (AIV) subtypes H5, H6, H7 and H9 among people in poultry occupations in Guangdong province and to analyze the transmission of various subtypes of AIV from poultry to human contacts for the prevention and control of novel AIV infection in human beings.Methods Serum specimens were collected from 1066 peo-ple in poultry occupations ( occupational group) and 205 people not in poultry occupations ( non-occupational group) in 10 cities of Guangdong province.The inactivated AIV strains, isolated from poultry or environment of Guangdong province, were used as antigens to detect antibodies against AIV subtypes H5, H6, H7 and H9 by using the hemagglutination inhibition ( HI) assay.Results The positive rates of antibodies against AIV subtypes H5, H6, H7 and H9 carried by people from the occupational group were respectively 0.44%, 0%, 0.30%and 0.30%in 2013 and 1.08%, 0.0%, 0.0%and 0.27%in 2014.Only the anti-H9 anti-bodies were detected in serum samples collected form people in the non-occupational group in 2013 with a positive rate of 0.95%.No significant differences with the positive rates of anti-AIV antibodies were found between the occupational group and the non-occupational group.However, the geometric mean titer ( GMT) of anti-AVI antibodies in people from the occupational group was higher than that of the non-occupational group.Conclusion Although a grand spread of AIV from avian to human is not likely to happen yet, con-tacting with poultry is the risk factor for AIV infection in Guangdong population.A long-term surveillance of anti-AIV antibodies in serum should be strengthened among people in poultry occupations for the timely pre-vention and control of novel AIV outbreak.

OBJECTIVETo investigate the cause of failure after autogenous bone graft with limb fracture nonunion,to explore the major influencing factor of the treatment, and to research the evidence for improving the treatment of nonunion.

METHODSA retrospective analysis was done with 367 cases suffering from autogenous bone graft surgery after limb fracture nonunion between January 1995 to December 2011. Among them,there were 198 males and 169 females aged 12 to 89 years (means 53.5 years) with duration of 23 to 49 months. The treatment effect assessed with X-ray and CT after grafting in the treatment, and 32 cases were detected nonunion again, and others' fixations were dismantled by operation after fracture healing. The following correlation including factorsages,gender,smoking, nutritional status during therapy,classification of primary fracture,location of fracture, type of nonunion, changing the type of fixation,type of fixation and complicating disease were evaluated by Logistic stepwise regression to discover the influencing factors of the failure of union.

RESULTSThe treatment failure rate was 8.72% in the patients with surgery and graft included in the statistics for the late re-admitted in 6 to 12 months followed-up. Smoking, classification of primary fracture, type of nonunion, changing the type of fixation, complicating disease had influence to incidence rate of union after autogenous bone graft.

CONCLUSIONAutogenous bone graft is the utility method for limb fracture nonunion. Smoking, classification of primary fracture, classification of nonunion,changing the type of fixation, complicating disease are the risk factors of nonunion after graft. Patients should be advised to stop smoking in the nonunion bone graft. And at the same time, the treatment of related diseases, analysis of the original fracture and nonunion,aggressive treatment of infection, and developing better surgical solutions before surgery, as well as changing the fixation methods can reduce the risk of failure of the graft.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Bone Transplantation ; Child ; Extremities ; injuries ; Female ; Fracture Fixation ; Fracture Healing ; Fractures, Ununited ; surgery ; Humans ; Male ; Middle Aged ; Transplantation, Autologous ; Treatment Failure