Culture-Expanded Autologous Adipose-Derived Mesenchymal Stem Cell Treatment for Osteonecrosis of the Femoral Head

BackgroudOutcomes of traditional treatment for osteonecrosis of the femoral head (ONFH) are not always satisfactory. Hence, cell-supplementation therapy has been attempted to facilitate necrotic-tissue regeneration. Adipose-derived mesenchymal stem cell (ADMSC) transplantation is potentially advantageous over bone marrow-derived MSC implantation, but its outcomes for ONFH remain unclear. The aim of this study was to determine 2-year radiological and clinical outcomes of culture-expanded autologous ADMSC implantation for ONFH.MethodsEighteen hips with necrotic lesions involving ≥ 30% of the femoral head were included. ADMSCs were harvested by liposuction and culture expanded for 3 passages over 3 weeks. With a 6-mm single drilling, ADMSCs were implanted into the necrotic zone. All patients underwent magnetic resonance imaging (MRI), single-photon emission computed tomography/computed tomography (SPECT/CT) at screening and 6 months, 12 months, and 24 months postoperatively. The primary outcome was the change in the size of necrotic area on MRI. Secondary outcomes were changes in clinical scores and radioisotope uptake on SPECT/CT. Conversion total hip arthroplasty (THA) was defined as the endpoint.ResultsPreoperatively, the necrotic lesion extent was 63.0% (38.4%–96.7%) of the femoral head. The mean Harris hip score was 89.2, the University of California at Los Angeles (UCLA) score was 5.6, and Western Ontario and McMaster Universities Arthritis index (WOMAC) was 79.4. Three patients underwent THA and 1 patient died in an accident. Finally, 11 patients (14 hips) were available for ≥ 2-year follow-up. At the last follow-up, no surgery-related complications occurred, and 14 of 17 hips (82%) were able to perform daily activities without THA requirement. There was no significant decrease in lesion size between any 2 intervals on MRI. However, widening of high signal intensity bands on T2-weighted images inside the necrotic lesion was observed in 9 of 14 hips (64%); 11 of 14 hips (79%) showed increased vascularity on SPECT/CT at 2 years postoperatively. No significant differences were observed between preoperative and 24-month mean Harris hip score (89.2 vs. 88.6), WOMAC (79.4 vs. 75.7), and UCLA score (5.6 vs. 6.2).ConclusionsOur outcomes suggest that culture-expanded ADMSC implantation is a viable option for ONFH treatment without adverse events.     

Immunogenicity,safety and reactogenicity of ROTAVAC® in healthy infants aged 6–8 weeks in Vietnam

BackgroundROTAVAC® is derived from human 116E rotavirus (RV) neonatal strain. In this study, we evaluated the immunogenicity, safety and reactogenicity of ROTAVAC® in Vietnam.MethodWe conducted a phase IV clinical trial in healthy infants aged 6–8 weeks using the complete regimen of ROTAVAC® with three doses. Serum anti-RV IgA was measured by enzyme-linked immunosorbent assay to assess the geometric mean concentration in infants who received the complete regimen of the vaccine.ResultsA total of 360 participants were enrolled in this clinical trial. The mean age ± standard deviation at enrollment was 6.9 ± 0.6 weeks. The anti-RV IgA titer was 4.01 ± 3.74 mg/ml pre-vaccination and substantially increased to 29.27 ± 80.64 mg/ml post-vaccination. The value of logIgA significantly increased (p = 0.003) from 0.28 ± 0.79 to 1.03 ± 0.54. The proportion of participants with equal to and greater than 3-fold and 4-fold shifts in pre- to post-vaccination antibody titer (IgA) were 55.4% and 48.3%, respectively. No adverse events or serious adverse events were recorded immediately within 30 min after the administration of each dose. The most common adverse events within 14 days after each visit were fever, unusual crying and irritability. Other adverse events occurred at a low rate, and no case of intussusception was noted.ConclusionsThe complete regimen of ROTAVAC® demonstrated an immunological response with clinically acceptable safety profile. Post-completion of this study, ROTAVAC® is now a WHO-prequalified vaccine and available in Vietnam.     

Biomechanical assessment with electromyography of post-stroke ankle plantar flexor spasticity

Spasticity has been defined as a motor disorder characterized by a velocity-dependent increase in tonic stretch reflex (muscle tone). Muscle tone consists of mechanical-elastic characteristics, reflex muscle contraction and other elements. The aims of this study were to determine whether to assess spasticity quantitatively, and to characterize biomechanical and electromyographic spasticity assessment parameters. These assessment parameters were described by investigating the correlation between clinical measures and the response to passive sinusoidal movement with consecutive velocity increments. Twenty post-stroke hemiplegic patients and twenty normal healthy volunteers were included in the study. Five consecutive sinusoidal passive movements of the ankle were performed at specific velocities (60, 120, 180, and 240 degrees/ sec). We recorded the peak torque, work, and threshold angle using a computerized isokinetic dynamometer, and simultaneously measured the rectified integrated electromyographic activity. We compared these parameters both between groups and between different velocities. The peak torque, threshold angle, work, and rectified integrated electromyographic activity were significantly higher in the post-stroke spastic group at all angular velocities than in the normal control group. The threshold angle and integrated electromyographic activity increased significantly and linearly as angular velocity increased, but the peak torque and work were not increased in the post-stroke spastic group. Peak torque, work, and threshold angle were significantly correlated to the Modified Ashworth scale, but the integrated electromyographic activity was not. The biomechanical and electromyographic approach may be useful to quantitatively assess spasticity. However, it may also be very important to consider the different characteristics of each biomechanical parameter.     

Inhibitory effects of plant extracts on adjuvant-induced arthritis

Twenty seven plant extracts were selected on the basis of ancient literature search for rheumatoid arthritis or similar syndrome. Methanol extract of each plant was prepared and administered orally to rats everyday at a dose of 200 mg/kg/day. Experimental arthritis was induced by subplantar injection of heat-killedMycobacterium butyricum to right hind paw of rats. This treatment provoked swelling of the treated paw in two phases, acute primary swelling and secondary arthritic swelling. An inhibition of secondary swelling was considered to be antiarthritic activity. Several plant methanol extracts such asAkebia quinata (caulis),Ephedra sinica (herba) andSophorae subprostrata (radix) were found to show significant inhibitory activity against secondary swelling at the dose tested. Our results strongly suggested an antiarthritic potential of these plant extracts.     

An improved synthesis of methyl p-hydroxyphenylalkanoates

Friedel-Crafts reaction of isopropoxybenzene with methyl α-chloro-α-(methylthio)acetate1 afforded methyl α-methylthio-p-isopropoxyphenylacetate2d, which was readily converted into methyl p-isopropoxyphenylacetate3 by reductive desulfurization with zinc dust in acetic acid. Methylation of3 with sodium hydride and methyl iodide gave methyl α-(p-isopropoxyphenyl)propionate5. Methyl p-hydroxyphenylalkanoates (4, 6), useful intermediates for some medicines, were easily prepared by treatment of3 and5 with titanium tetrachloride, respectively.     

Operative treatment of hypertrophic obstructive cardiomyopathy and aortic valve disease in infants

BACKGROUND: The indications for operative intervention for symptomatic hypertrophic obstructive cardiomyopathy (HOCM) in infancy and childhood are not well defined because of the rarity of the lesion. The traditional surgical procedure consists of septal myectomy. In an attempt to further improve the outcome of HOCM associated with concentric left ventricular hypertrophy and aortic valve disease in infancy, we have combined resection of the left ventricular septum and free wall with a Ross-Konno procedure. METHODS: Three infants (aged 3, 4, and 10 months) with HOCM (left ventricular aortic gradients of 75, 95, and 110 mmHg), associated concentric left ventricular hypertrophy, and valvar aortic stenosis (n = 1) or combined valvar aortic stenosis and regurgitation (n = 2) underwent extensive resection of fibroelastosis and subendocardial myocardium of the left ventricular septum and free wall in combination with a Ross-Konno operation. All three patients had marked systolic anterior motion of the mitral valve. The length of the incision into the ventricular septum was 1.8, 2.0, and 2.3 cm. RESULTS: In all three patients this procedure resulted in a marked reduction of width of the left ventricular septum (median 9 mm vs 14 mm preoperatively) and the left ventricular posterior free wall (median 8 mm vs 12 mm preoperatively) and an almost twofold increase of the left ventricular end-diastolic volume (median 13.5 cm3 vs 7.0 cm3 preoperatively). The neo-aortic valve functioned normally. Systolic anterior motion of the anterior leaflet of the mitral valve had completely resolved in two patients and had markedly regressed in the remaining patient. At follow-up of 15, 17, and 26 months, two patients had absence of a left ventricular outflow tract gradient and the third patient had a residual sub-valvar gradient of 15 mmHg. CONCLUSIONS: The reported procedure may be a valuable technique in severe forms of hypertrophic cardiomyopathy associated with aortic valve disease. The operation results in enlargement of the left ventricular stroke volume and improvement of the left ventricular diastolic function, restores aortic valve anatomy and function, and abolishes or decreases systolic anterior motion of the mitral valve.     

Synthesis of hexaprofen [2-(4-cyclohexylphenyl) propionic acid]

A novel preparative method for hexaprofen, which is a potent antiinflammatory agent, is described. Friedel-Crafts reaction of cyclohexylbenzene with ethyl α-chloro-α-(methylthio) acetate1 and α-chloro-α-(methylthio) acetonitrile2 afforded ethyl 2-(methylthio)-2-(4-cyclohexylphenyl) acetate7 and 2-methylthio-2-(4-cyclohexylphenyl) acetonitrile8, respectively. Compounds7 and8 were converted into the corresponding ethyl 2-methylthio-2-(4-cyclohexylphenyl) propionate9 and 2-methylthio-2-(4-cyclohexylphenyl) propionitrile10 by methylation with sodium hydride and methyl iodide. Hexaprofen13 was prepared by hydrolysis of ethyl 2-(4-cyclohexylphenyl) propionate11 and of 2-(4-cyclohexylphenyl) propionitrile12 followed by desulfurization of compounds9 and10.