Is there a definition of remission in late-life depression that predicts later relapse?

Remission of depressive symptoms is the goal of all antidepressant therapy. Rating scales define remission in clinical trials, but it is unclear how well these definitions predict risk of later relapse. We measured the sensitivity and specificity of a range of Montgomery-Asberg Depression Rating Scale (MADRS) cutoff scores at 3- and 6-months, wherein scores above a given cutoff would predict relapse over an 18-month period. We examined 153 elderly depressed subjects exhibiting a MADRS < or = 15 after 3 or 6 months of antidepressant therapy. Subjects who subsequently exhibited a MADRS > 15 during the 18-month study period were defined as relapsed. Receiver operating characteristic (ROC) curves were developed and area under the curve (AUC) values calculated for the sensitivity and specificity of 3- and 6-month MADRS scores to predict future relapse. The 3-month ROC had an AUC value of 0.63; the 6-month ROC had an AUC value of 0.66. There was no MADRS cutoff found that could predict likelihood of relapse with good sensitivity and specificity. A post hoc analysis where relapse rate was adjusted by controlling for medical comorbidity, disability, and social support showed no change in the ROCs or AUC values. The higher the MADRS score at 3 and 6 months, the greater the likelihood of relapse. With no clean MADRS cutoff score, the goal of antidepressant therapy should be the lowest possible degree of depressive symptomatology to minimize risk of later relapse. Definitions of remission that are better associated with longer-term outcomes are needed.     

Formulation Development,Process Optimization,and In Vitro Characterization of Spray-Dried Lansoprazole Enteric Microparticles

This research focuses on the development of enteric microparticles of lansoprazole in a single step by employing the spray drying technique and studies the effects of variegated formulation/process variables on entrapment efficiency and in vitro gastric resistance. Preliminary trials were undertaken to optimize the type of Eudragit and its various levels. Further trials included the incorporation of plasticizer triethyl citrate and combinations of other polymers with Eudragit S 100. Finally, various process parameters were varied to investigate their effects on microparticle properties. The results revealed Eudragit S 100 as the paramount polymer giving the highest gastric resistance in comparison to Eudragit L 100-55 and L 100 due to its higher pH threshold and its polymeric backbone. Incorporation of plasticizer not only influenced entrapment efficiency, but diminished gastric resistance severely. On the contrary, polymeric combinations reduced entrapment efficiency for both sodium alginate and glyceryl behenate, but significantly influenced gastric resistance for only sodium alginate and not for glyceryl behenate. The optimized process parameters were comprised of an inlet temperature of 150°C, atomizing air pressure of 2 kg/cm², feed solution concentration of 6% w/w, feed solution spray rate of 3 ml/min, and aspirator volume of 90%. The SEM analysis revealed smooth and spherical shape morphologies. The DSC and PXRD study divulged the amorphous nature of the drug. Regarding stability, the product was found to be stable under 3 months of accelerated and long-term stability conditions as per ICH Q1A(R2) guidelines. Thus, the technique offers a simple means to generate polymeric enteric microparticles that are ready to formulate and can be directly filled into hard gelatin capsules.     

Isolation and characterization of degradation impurities in docetaxel drug substance and its formulation

The degradation of docetaxel drug substance and its injection formulation has been investigated. The majority of impurities were observed in a base degradation study and all five degradation products were characterized. These impurities were isolated, enriched and were subjected to mass and NMR spectral studies. Based on the spectral data, these were characterized as 10-deacetyl baccatin III, 7-epi-10-deacetyl baccatin III, 7-epi-10-oxo-10-deacetyl baccatin III, 7-epi docetaxel and 7-epi-10-oxo-docetaxel, respectively. The last two impurities were also detected in the stability study of docetaxel formulation. Out of these degradation impurities two substances have been previously identified while the other three previously unreported.     

A case of colouterine fistula managed laparoscopically

Fistulas between the uterus and bowel are rarely reported. We report successful laparoscopic management of a colouterine fistula caused by a foreign body in the uterus. Fistulas between the gastrointestinal tract and the female genital tract are usually found between the vagina and rectum as a result of complications of childbirth or iatrogenic trauma. Communication between the uterus and bowel is rarely reported. We report successful laparoscopic management of an unusual case of colouterine fistula caused by a foreign body in the uterus.     

Protective effects of Terminalia arjuna against Doxorubicin-induced cardiotoxicity

Terminalia arjuna has been marked as a potential cardioprotective agent since vedic period. The present study was aimed to investigate the effects of butanolic fraction of Terminalia arjuna bark (TA-05) on Doxorubicin (Dox)-induced cardiotoxicity. Male wistar rats were used as in vivo model for the study. TA-05 was administered orally to Wistar rats at different doses (0.42 mg/kg, 0.85 mg/kg, 1.7 mg/kg, 3.4 mg/kg and 6.8 mg/kg) for 6 days/week for 4 weeks. Thereafter, all the animals except saline and TA-05-treated controls were administered 20 mg/kg Dox intraperitonially. There was a significant decrease in myocardial superoxide dismutase (38.94%) and reduced glutathione (23.84%) in animals treated with Dox. Concurrently marked increase in serum creatine kinase-MB (CKMB) activity (48.11%) as well as increase in extent of lipid peroxidation (2.55-fold) was reported. Co-treatment of TA-05 and Dox resulted in an increase in the cardiac antioxidant enzymes, decrease in serum CKMB levels and reduction in lipid peroxidation as compared to Dox-treated animals. Electron microscopic studies in Dox-treated animals revealed mitochondrial swelling, Z-band disarray, focal dilatation of smooth endoplasmic reticulum (SER) and lipid inclusions, whereas the concurrent administration of TA-05 led to a lesser degree of Dox-induced histological alterations. These findings suggest that butanolic fraction of Terminalia arjuna bark has protective effects against Dox-induced cardiotoxicity and may have potential as a cardioprotective agent.     

Laparoscopic management of a large recurrent benign mucinous cystadenoma of the ovary

Introduction Benign mucinous cystadenomas account for 15% of all ovarian neoplasms and up to 80% of all mucinous tumors. Laparoscopy has become an accepted method of management for ovarian cysts and its role is expanding as large benign adnexal masses more than 10 cm can be managed safely and effectively. Case report We report a 25-year-old nulliparous lady with a huge benign mucinous cystadenoma managed by laparoscopic cystectomy, followed by an early recurrence within 2 months. Left salpingo-oophorectomy was performed on a repeat laparoscopy due to suspicion of malignancy on ultrasound. Pathology revealed a benign cyst. Conclusion Since mucinous tumors are usually benign and multilocular, management of young patients is challenging, especially in the case of recurrence which is very rare.     

Genital tuberculosis: an important cause of Asherman’s syndrome in India

Objective To demonstrate the association between genital endometrial tuberculosis and Asherman's syndrome. Materials and methods A total of 28 women who underwent hysteroscopy with or without laparoscopy for suspected Asherman’s syndrome from symptoms (amenorrhoea or oligomenorrhoea, and or primary or secondary infertility) and who were found to have genital tuberculosis on endometrial biopsy (histopathology or culture) or positive polymerase chain reaction (PCR) on endometrial aspirate or positive findings of tuberculosis on laparoscopy or hysteroscopy were enrolled in this retrospective study. Results The mean age and parity were 26.5 years and 0.3, respectively. There was past history of TB in 67.8% women. All women had menstrual dysfunction, with oligomenorrhoea and hypomenorrhoea in 16 (57%) women and amenorrhoea in 12 (42.8%). All women had primary (n = 19, 67.8%) or secondary (n = 9, 32%) infertility. On hysteroscopy, there were various grades of adhesions in all women, with grade I in 17.8%, grade II in 28.5%, grade III in 28.5% and grade IV in 17.5% women. Only four women (14.3%) had open ostia, while others had bilateral (28.5%) or unilateral (21.3%) blocked ostia or inability to see ostia (28.5%). On laparoscopy performed on 18 women, there were varying grades of adhesions in 16 (88.8%) women, with beading (33.3%), tubercles (33.3%), caseation (11.1%) and tubo-ovarian masses (11.1%). The diagnosis of genital TB was made by histopathology (tuberculous granuloma) on endometrial biopsy in 28.6%, positive culture in 3.6%, positive polymerase chain reaction (PCR) in 46.4% and observation of tubercles, beading or caseation on laparoscopy in 17.8% or shaggy cavity with caseation on hysteroscopy in 3.6% women. Conclusion Genital tuberculosis appears to be an important and common cause of Asherman's syndrome in India, causing oligomenorrhoea or amenorrhoea with infertility.     

Laparoscopic findings in female genital tuberculosis

OBJECTIVES: To evaluate the laparoscopic findings in genital tuberculosis (TB). METHODS: A total of 85 women of genital TB, who underwent diagnostic laparoscopy for infertility or chronic pelvic pain were enrolled in this retrospective study conducted in our unit at All India Institute of Medical Sciences, New Delhi, India from September 2004 to 2007. RESULTS: The mean age was 28.2 years and the mean parity was 0.24. Most women were from poor socioeconomic status (68.1%). Past history of TB was seen in 29 (34.1%) women with pulmonary TB in 19 (22.35%) women and extrpulmonary in 10 (11.7%) women. Most women presented with infertility (90.6% primary 72.9%; secondary 17.6%) while the rest had chronic pelvic pain (9.4%). The mean duration of infertility was 6.2 years. A total of 49 (57.6%) women had normal menses, while hypomenorrhea, oligomenorrhea, secondary amenorrhea and menorrhagia were seen in 25 (30.1%), 3 (3.5%), 5 (5.9%), and 2 (2.4%) women respectively. Diagnosis of genital TB was made by histopathological evidence of TB granuloma in 16 (18.8%) (Endometrial biopsy in 12.9%, laparoscopy biopsy in 5.9%) women, demonstration of acid fast bacilli (AFB) on microscopy in 2(2.3%), positive AFB culture in 2 (2.3%), positive polymerase chain reaction (PCR) in 55 (64.7%) and laparoscopic findings of genital TB in 40 (47.1%). The various findings on laparoscopy were tubercles on peritoneum (12.9%) or ovary (1.2%), tubovarian masses (7.1%), caseous nodules (5.8%), encysted ascitis in 7.1% women. Various grades of pelvic adhesions were seen in 56(65.8%) women. The various findings on fallopian tubes were normal looking tubes in (7.1%), inability to visualize in 12(14.1%), presence of tubercles on tubes in 3 (3.52%), caseous granuloma in 3 (3.52%), hydrosalpinx in 15 (17.6%) (Right tube 11.7%, left tube 5.9%), pyosalphinx in 3 (3.5%) on right tube and 2 (2.35%) in left tube, beaded tube in 3 (3.5%) on right tube, 4 (4.7%) in left tube with tobacco pouch appearance in 2 (2.35%) women. The right tube was patent in 9 (10.6%) while left tube was patent in 10(11.7%) cases only, while they were either not seen (absent in one case due to previous salphingectomy, inability to see due to adhesion in 14.12%) or blocked at various sites with cornual end being most common in 3 (3.5%) showing multiple block in right tube and 4.7% in left tube. CONCLUSION: There is a significant pelvic morbidity and tubal damage in genital tuberculosis.     

Fetal cardiac rhabdomyoma with maternal tuberous sclerosis complicating pregnancy

INTRODUCTION: Tuberous sclerosis is an autosomal dominant disorder of hamartoma formation that can manifest as cardiac or central nervous system lesions and adversely affect maternal and fetal outcome. CASE REPORT: We report a case of maternal tuberous sclerosis with fetal cardiac rhabdomyoma detected in utero at 26 weeks gestation. CONCLUSION: To conclude, a pregnancy complicated by maternal or fetal tuberous sclerosis deserves careful vigilance and the fetus should undergo prenatal fetal Doppler echocardiography and if possible an MRI, so that parents can be counseled regarding its future prognostic implications.