In vitro generated extracellular matrix and fluid shear stress synergistically enhance 3D osteoblastic differentiation

This study instituted a unique approach to bone tissue engineering by combining effects of mechanical stimulation in the form of fluid shear stresses and the presence of bone-like extracellular matrix (ECM) on osteodifferentiation. Rat marrow stromal cells (MSCs) harvested from bone marrow were cultured on titanium (Ti) fiber mesh discs for 12 days in a flow perfusion system to generate constructs containing bone-like ECM. To observe osteodifferentiation and bone-like matrix deposition, these decellularized constructs and plain Ti fiber meshes were seeded with MSCs (Ti/ECM and Ti, respectively) and cultured in the presence of fluid shear stresses either with or without the osteogenic culture supplement dexamethasone. The calcium content, alkaline phosphatase activity, and osteopontin secretion were monitored as indicators of MSC differentiation. Ti/ECM constructs demonstrated a 75-fold increase in calcium content compared with their Ti counterparts after 16 days of culture. After 16 days, the presence of dexamethasone enhanced the effects of fluid shear stress and the bone-like ECM by increasing mineralization 50-fold for Ti/ECM constructs; even in the absence of dexamethasone, the Ti/ECM constructs exhibited approximately a 40-fold increase in mineralization compared with their Ti counterparts. Additionally, denatured Ti/ECM* constructs demonstrated a 60-fold decrease in calcium content compared with Ti/ECM constructs after 4 days of culture. These results indicate that the inherent osteoinductive potential of bone-like ECM along with fluid shear stresses synergistically enhance the osteodifferentiation of MSCs with profound implications on bone-tissue-engineering applications.     

Role of misoprostol in overcoming an unsatisfactory colposcopy: a randomized double-blind placebo-controlled clinical trial

OBJECTIVE: To assess the effectiveness of vaginal misoprostol in overcoming an unsatisfactory colposcopy and to analyse the factors that might influence the response to misoprostol, i.e. age, menopausal status, duration of menopause and cervical characteristics. STUDY DESIGN: A randomized double-blind placebo-controlled clinical trial. METHODS: Forty patients with unsatisfactory colposcopy were recruited from the colposcopy clinic and were randomly allocated to receive either 400 microg misoprostol or similar-looking placebo tablets vaginally. Repeat colposcopy was performed after 6 h noting the side effects, if any. RESULTS: One patient was excluded from the misoprostol group because postdrug colposcopic examination could not be done due to a technical fault. Of the 19 patients in the misoprostol group, 15 (78.9%) had satisfactory examination compared to only 6 of the 20 (30%) patients in the placebo group. This effect of misoprostol was statistically significant (p = 0.004). Misoprostol in the present study averted 3 cone biopsies and 12 endocervical curettages. The side effects of misoprostol were comparable in both groups. The slit-like external os and the posterior cervical lip as the site of unsatisfactory colposcopy had better conversion rates compared to pinhole os (66.6 vs.81.2%) and anterior lip involvement (85.7 vs.100%). CONCLUSION: Four hundred micrograms of intravaginal misoprostol is an effective and safe method to convert an unsatisfactory colposcopy into a satisfactory one.     

Comparison of Mifepristone Followed by Misoprostol with Misoprostol Alone for Treatment of Early Pregnancy Failure: A Randomized Double-Blind Placebo-Controlled Trial

Objective

To compare the efficacy and safety of mifepristone followed by misoprostol with misoprostol alone in the management of early pregnancy failure (EPF).

Study Design

A randomized double-blind placebo-controlled clinical trial.

Methods

Ninety-two women with EPF ≤12 weeks were recruited and randomly allocated to receive either mifepristone 200 mg (n = 46) or placebo (n = 46). Forty-eight hours later, patients in both the groups were given 800 µg misoprostol per-vaginum. If no expulsion occurred within 4 h, repeat doses of 400 µg misoprostol were given orally at 3-hourly interval to a maximum of 2 doses in women ≤9 weeks by scan and 4 doses in women >9 weeks by scan.

Results

Pre-treatment of misoprostol with mifepristone significantly increased the complete abortion rate (86.7 vs. 57.8%, p = 0.009) and, hence, reduced the need for surgical evacuation (13.3 vs. 42.2%, p = 0.002), induction to expulsion interval (4.74 ± 2.24 vs. 8.03 ± 2.77 h, p = 0.000), mean number of additional doses of misoprostol required (0.68 vs. 1.91, p = 0.000), and side effects.

Conclusion

Use of mifepristone prior to misoprostol in EPF significantly improves the efficacy and reduces the side effects of misoprostol alone.

     

Uterine Avulsion: A Rare Cause of Cryptomenorrhea

BackgroundCryptomenorrhea at menarche is commonly due to mullerian duct anomalies. Uterine avulsion due to blunt pelvic trauma is a very rare cause of cryptomenorrhea. But so far no case of uterine avulsion has been reported due to a childhood trauma without pelvic fracture.CaseA 15-year-old young girl was evaluated for delayed menarche and the diagnosis of hematometra with obstruction at the level of internal cervical os was made on radiological examination. Detailed history revealed significant childhood blunt pelvic trauma when at the age of 3 years she was run over by a tractor. But the presence or absence of pelvic fracture was never documented as no radiographs were obtained. On abdominopelvic exploration cervix was well formed. Uterine body was found to be separated from the supravaginal cervix and there was a peritoneal window in between. During surgery hematometra was drained and the continuity of the uterine outflow tract was restored. Post surgery patient started having normal periods.Summary and ConclusionsThough very rare, uterine avulsion during pelvic trauma may cause cryptomenorrhea. Therefore such history should be sought in all cases of obstruction of the cervical canal because cryptomenorrhea has a much better prognosis than cervical congenital dysgenesis.     

Identification and characterization of novel and rare susceptible variants in Indian amyotrophic lateral sclerosis patients

neurogenetics - Rare missense variants play a crucial role in amyotrophic lateral sclerosis (ALS) pathophysiology. We report rare/novel missense variants from 154 Indian ALS patients, identified...     

Fetotoxicity of warfarin anticoagulation

Introduction  

Fetal warfarin syndrome (warfarin embryopathy) is a consequence of maternal ingestion of warfarin during pregnancy. Warfarin fetotoxicity comprises wide range of manifestations including dysmorphology in neonate with characteristic classical features of nasal hypoplasia and stippling of epiphyses.     

Scintigraphy in evaluation of the hypoplastic right hepatic lobe: a rare variant

A rare variant of right hepatic lobe hypoplasia associated with high gallbladder position in the right upper abdomen is described. Pain is frequent and may be due to cholelithiasis. It is important to recognize this variant because an associated hypertrophic left hepatic lobe can clinically masquerade as an abdominal mass. Radionuclide studies and abdominal computerized tomography are useful in defining the hypertrophied left hepatic lobe and ectopic gallbladder. The duodenum and hepatic flexure are positioned high due to space left by the hypoplastic right lobe.     

Paradoxical embolic strokes in a liver transplant recipient with atrial septal defect undergoing therapeutic plasma exchange

Therapeutic plasma exchange (TPE) is a technique used to separate blood components into layers based on their density difference, thus removing plasma and exchanging it with replacement fluids. A variety of adverse reactions has been described during TPE. Thrombotic events, especially strokes, are extremely rare complications of TPE. Our patient was a 55‐year‐old female with history of decompensated nonalcoholic steatohepatitis (NASH) liver cirrhosis. She underwent an orthotopic liver transplant (OLT) that was complicated with asystole during reperfusion. Cardiac workup revealed a new atrial septal defect (ASD) with left to right flow. Within the first 5 days after surgery, she developed refractory and persistent hyperbilirubinemia, with total bilirubin levels as high as 42 mg/dL. Our plasmapheresis service was consulted to initiate TPE. Towards the end of the first and only session of TPE, the patient developed hypoxia and left‐sided hemiplegia. Stroke response was initiated, and the patient was intubated. MRI done 24 hours after the incident showed multiple acute small embolic infarcts scattered within the bilateral cerebral and cerebellar hemispheres. Bilateral lower and upper extremities venous duplex studies were positive for acute left internal jugular (IJ) vein thrombosis. Patient was treated with anticoagulation and the IJ catheter was removed. Patient also had closure of her ASD. On last follow up, she was doing well with complete reversal of neurologic deficits and stable liver function. Our patient had an uncommon complication of TPE. Her thrombosis manifested with multiple embolic strokes that would not have happened without an ASD with left to right flow.