A Critical Review of Properties of Modafinil and Analytical, Bioanalytical Methods for its Determination.

Modafinil is a synthetic molecule used for the treatment of narcolepsy. Narcolepsy is a neurological disorder, due to which people experience frequent excessive daytime sleepiness (EDS). Nevertheless, there are some concerns about modafnil quality control. The modafinil enantiomers are both biologically active. However, it has been reported that the pharmacological properties of the both enantiomers are different and that the S-enantiomer is eliminated three times faster than the R-enantiomer. Therefore, most of the pharmaceutical companies have shifted to produce armodafinil (R-enantiomer) instead of the racemate. This article discusses about the critical review of the literature, the impact of the use of modafinil in the treatment of narcolepsy patients and other diseases, its physicochemical properties, toxicological properties, synthetic methods, analytical and bioanalytical methods and challenges that remain in order to ensure the quality. This article mainly focused on review of process related impurities, enantiomeric separation, metabolites of modafinil in various biofluids and pharmaceutical formulations using HPLC, LC-MS, GC-MS, CE, HPTLC and spectrophotometric methods.

LC-MS/MS structural characterization of stress degradation products including the development of a stability indicating assay of Darunavir: An anti-HIV drug.

Darunavir, an anti-HIV drug was subjected to forced degradation under acid, base, thermal and neutral hydrolysis, oxidation and photolysis as prescribed by ICH guidelines. Four major degradation products were formed under acid and base hydrolysis, while stable under neutral and thermal hydrolysis, oxidative and photolysis. The drug and its degradation products were separated on Hiber, LiChrospher® 60, RP-select B, C8 column (250mm×4.6mm i.d., 5µm) using 10mM ammonium acetate: acetonitrile (52:48, v/v) as mobile phase in an isocratic elution mode by LC. The degradation products were characterized by LC-MS/MS and fragmentation pathways were proposed. The proposed structures of degradation products were confirmed by HRMS and the LC method was validated with respect to specificity, linearity, accuracy, recovery, LOD and LOQ.

Delayed presentation of a bowel Bovie injury after laparoscopic ventral hernia repair.

INTRODUCTION: Bowel injury during laparoscopic surgery is a rare but serious complication. A Bovie injury to the bowel can cause delayed perforation of the viscus, thus increasing the possibility of a preventable morbidity. Patients presenting with perforation peritonitis within 24 hours and up to 2 to 3 weeks after laparoscopic Bovie injury to the bowel have been reported in the literature. CASE DESCRIPTION: A 74-year-old woman underwent a laparoscopic ventral hernia mesh repair. Intraoperatively, a small area of superficial Bovie injury to the small bowel was repaired with Lembert sutures and tissue glue. Postoperatively, the patient recovered well, but she presented with perforation peritonitis 3 months after surgery. An exploratory laparotomy showed a jejunal perforation in the same area that was injured with cautery and repaired during the previous surgery. The patient was only using inhaled steroids for asthma on and off but had a remote history of chemotherapy and radiation for colorectal cancer. CONCLUSION: Bovie injury to the bowel has a hidden depth, causing a slow transmural tissue necrosis, and it might also impair local healing and eventually lead to perforation. Thus, the patient may present later than the usual period for wound healing and remodeling as previously reported. Given the disastrous consequence, it is imperative to perform a good surgical repair of even a minor Bovie injury to the bowel. This is the first report of a delayed presentation (>1 month) of a Bovie injury of the bowel.

Receptor changes in metachronous breast tumors--our experience of 10 years.

INTRODUCTION: Patients with primary breast cancer (PBC) are at 2 to 6 times higher risk for developing synchronous and metachronous breast cancer (MBC). The pathology and behavior of MBC still remains unclear. METHODS: We reviewed the charts of 108 women with MBC at our hospital over the past 10 years. Profile patterns of the estrogen receptor (ER), the progesterone receptor (PR), and Her2/neu receptors were explored. RESULTS: Of 33 patients with ER(+)/PR(+) in the primary tumor, 23 (70%) retained the status in MBC. Forty-five (92%) of 49 patients with ER(-)/PR(-) in the primary tumor remained the same in MBC. Most Her2(-) tumors (22/31, 71%) remained negative, but 50% (8/16) of Her2(+) tumors became negative. CONCLUSIONS: Most MBC retained the ER/PR expression patterns irrespective of the treatment for the primary tumor, thus suggesting a common origin. Because MBCs tend to be triple negative and thus more aggressive, early detection and close surveillance techniques must be devised.

Mutations of TFAP2B in congenital heart disease patients in Mysore, South India.

BACKGROUND & OBJECTIVES: Cardiac malformations in the young constitute a major portion of clinically significant birth defects. Congenital heart disease (CHD) is a common congenital cardiac birth defect, affecting nearly 1 per cent of all live births. Patent ductus arteriosus (PDA) is clinically significant foetal circulation anomaly, second most common form of CHD which constitutes approximately 10 per cent of total CHDs. The study aimed to screen for TFAP2B mutations in CHD patients of Mysore. METHODS: With informed consent, 100 clinically diagnosed CHD patients and 50 healthy controls in Mysore, south India, were recruited for the analysis of screening of mutations. MassARRAY analysis of 5 prominent mutations of TFAP2B was performed. RESULTS: The analysis did not show any of the five mutations of TFAP2B screened by massARRAY in patients and controls, indicating that these mutations were not involved in the manifestation of CHD in the patients at Mysore, south India. INTERPRETATION & CONCLUSIONS: The findings suggest the lack of involvement of known mutations of TFAP2B with syndromic or nonsyndromic CHDs in Mysore patients.

Prolonged (longer than 3 hours) laparoscopic cholecystectomy: reasons and results.

For the experienced surgeon, the average operative time for a laparoscopic cholecystectomy is less than 1 hour. There has been no study documenting the causes and results of prolonged (longer than 3 hours) surgery. A retrospective study was done of patients who underwent cholecystectomy between January 2003 and December 2007. A total of 3126 cholecystectomies were done. After excluding patients who had a planned open cholecystectomy and patients who had additional laparoscopic surgeries, we identified 70 patients who had a planned laparoscopic cholecystectomy with operative time exceeding 3 hours. Multivariate stepwise logistic regression was performed analyzing the various factors leading to prolonged surgery. Of the 70 patients, ranging in age from 21 to 92 years (mean, 57 years), most (n = 53) were female. Operative time ranged from 3 hours to 6 hours 40 minutes (mean, 3 hours 37 minutes). Emergency:elective admission ratio was 9:5 and acute cholecystitis (n = 40) was the most common indication. Common characteristics were obesity (n = 44, P = 0.031), intra-abdominal adhesions (n = 43, P = 0.004), and previous abdominal surgeries (n = 40, P = 0.002). Intraoperative complications included spillage of stones (n = 6), bile duct injury (n = 3), and bleeding (n = 3). The possibility of prolonged laparoscopic cholecystectomy should be anticipated in patients with obesity and previous abdominal operations. Prolonged surgery increases the risk of complications (bile duct injury, bleeding) and prolongs the postoperative hospital stay.

Large fibroepithelial polyp of vulva.

A rare case of a large fibroepithelial polyp (FEP) of the vulva is described. The polypoidal growth was 10 cm in its largest diameter, having a long pedicle with features of inflammation secondary to infection, and was found arising from the left labia majora. The patient did not manifest any signs of recurrence following excision. A large and infected FEP of the vulva is a rare occurrence and hence reported.

LC-MS/MS studies of ritonavir and its forced degradation products.

Forced degradation of ritonavir (RTV), under the conditions of hydrolysis (acidic, basic and neutral), oxidation, photolysis and thermal stress as prescribed by ICH was studied using LC-MS/MS. Eight degradation products were formed and their separation was accomplished on Waters XTerra C(18) column (250 mm x 4.6 mm i.d., 5 microm) using water:methanol:acetonitrile as (40:20:40, v/v/v) mobile phase in an isocratic elution mode by LC. The method was extended to LC-MS/MS for characterization of the degradation products and the pathways of decomposition were proposed. No previous reports were found in the literature regarding the characterization of degradation products of ritonavir.

Aetiopathological and clinical study of erythroderma.

Erythoderma first described by Hebra in 1868 is a reaction pattern, characterised by generalised and confluent erythema with desquamation affecting more than 90% of body surface and is usually accompanied by systemic manifestation including some metabolic changes. Tile study was envisaged to assess their profile of aetiology, clinical features and to correlate with histopathological findings. Twenty-four patients (18 males and 6 females) with erythroderma were considered for the study. All patients were hospitalised, detailed history was taken and were subjected to relevant investigations--haemogram, serum proteins, liver and renal function tests, routine and microscopic urine tests, HIV screening, x-ray chest, ultrasound abdomen, FNAC of enlarged lymph nodes and skin biopsy. The age group affected ranged between 7 and 70 years, peak incidence between 50 and 60 years. The male to female ratio was 3:1. Scaling, erythema and pruritus were predominant clinical manifestations. In 12 clinically suspected psoriatic erythroderma, only in 6 cases the histopathological features were correlated to psoriasis and remaining showed non-specific chronic dermatitis. Two patients were found to be HIV-positive. There is good clinicopathological correlation in erythroderma caused by lichen planus, atopic dermatitis, seborroeic dermatitis, non-bullous congenital ichthyosiform erythroderma. Drugs were found to be aetiological factor in 3 cases. The study was conducted to assess variations in clinical, aetiological and histopathological profile of erythroderma. The present series had high percentage of erythroderma secondary to preexisting dermatoses. The onset of disease was insidious except in drug-induced erythroderma where it was acute.

Forehead plaque: a cutaneous marker of CNS involvement in tuberous sclerosis.

BACKGROUND: Tuberous sclerosis complex (TSC) is a neurocutaneous genodermatosis characterized by hamartoma formation in multiple organs. There are no definite cutaneous markers suggestive of central nervous system (CNS) involvement in TSC. AIMS: To study association of forehead plaque seen in tuberous sclerosis patients and CNS involvement in TSC. METHODS: This is a retrospective study of 15 cases of tuberous sclerosis in varying age groups - from 1.5 to 50 years. All the cases were thoroughly evaluated with detailed history; clinical examination; and relevant investigations like X-rays of chest, skull, hands and feet; ultrasound abdomen and computed tomography of brain. RESULTS: Out of the 15 cases, CNS involvement was seen in 8 cases. Seizures were present in 8 cases (53.33%) and mental retardation was seen in 6 cases (40%). Computerized tomography of brain revealed subependymal nodules (SENs) in eight cases (53.33%). In addition to SENs, subependymal giant cell astrocytomas and cortical tubers were seen in 2 cases each. Out of these 8 cases having CNS involvement, in 7 cases forehead plaque was observed. In 1 case, no forehead plaque was observed (X 2 = 1.07, P < 0.05). CONCLUSION: This study shows that there is a statistically significant relationship between the presence of a forehead plaque and CNS involvement in TSC. Therefore, forehead plaque may be considered as a novel cutaneous marker to know the CNS involvement in TSC at an early stage.

Neuropathological changes in vibration injury: an experimental study.

Vibration syndrome, a clinical condition arising from chronic use of vibrating tools, is associated with a spectrum of neurovascular symptoms. To date, only its vascular pathology has been extensively studied; we sought to determine what direct neurologic injury, if any, is caused by vibration. Hindlimbs of anesthetized rats were affixed to a vibrating platform 4 h a day for 7 days. Study animals were vibrated with set parameters for frequency, acceleration, velocity, and amplitude; control animals were not vibrated. On day 7, nerves were studied by light and electron microscopy. While light microscopy showed minimal histologic differences between vibrated (n=12) and control (n=12) nerves, electron microscopic changes were dramatic. Splitting of the myelin sheath and axonal damage (e.g., myelin balls and "finger ring") were consistently seen in both myelinated and nonmyelinated axons. Despite relatively short vibration, definite pathology was demonstrated, suggesting that vibration syndrome has a direct neurologic component.

Tuberous xanthomas in type IIA hyperlipoproteinemia.

A 4-year-old obese girl with multiple yellowish, plaques and nodular lesions showed features of tuberous xanthomato in Type IIa hyperlipoproteinemia.

Dyschromatosis Universalis.

Hyperpigmented macules all over the body intermignled with mottled depigmentation were observed in two brothers from Varanasi. Hyperpigmented macules were present since birth and increased ill number and size during childhood. Depigmentation developed at the age of eigh, years and increased during adolescence. This entity described as dyschromatosis universalis in the Japanese and the Europeans has not been described in the Indians so far.