Philip Morris USA v. Williams: A Confusing Distinction

In Philip Morris USA v. Williams, the United States Supreme Court held 5-4 that it is unconstitutional under the Due Process Clause of the Constitution for a jury to award punitive damages for harm caused to individuals other than the plaintiff. Thus, the Court concluded that, under the Constitution, a trial court could not levy punitive damages out of a desire to punish a company for injuries it inflicts upon others who are essentially, strangers to the litigation. However, the Court confusingly drew a narrow and arguably contradictory distinction to justify its holding. Under Philip Morris USA, a jury may not use punitive damages to punish a defendant directly on account of harms it is alleged to have visited on nonparties, but a jury is still permitted to consider the harm to third parties to determine the reprehensibility of the defendant\u27s conduct, one of the three factors in assessing the constitutionality of punitive damages. Justice Ginsburg in her dissent wrote that the distinction slips from my grasp

Epidemiology and seropositivity of dengue fever cases in a tertiary care hospital of NCR in 2013

Background: Dengue has been known to be endemic in India for over two centuries. Dengue fever is more commonly seen in adultsand older children. Clinical presentation varies from mild to severe fatal forms; therefore, laboratory diagnosis is very essential.Objective: The surveillance study was conducted to analyze dengue seropositivity and epidemiological profile among patients withdengue fever like illness who presented to the outpatient department or was admitted to a tertiary care private hospital in Ghaziabad,Uttar Pradesh from January 2013 to December 2013. Materials and Methods: Serum samples from 1186 clinically suspecteddengue fever cases (671 males and 515 females) were received in serology laboratory over the period of 1 year. The samples werescreened for non-structural protein 1 (NS1) antigen and IgM and IgG dengue specific antibodies by rapid immunochromatographictest. Results: Out of total 1186 blood samples tested, 574 were found to be positive for dengue infection. Of 574 blood samples, NS1Ag was positive in 498 (86.7%) cases while IgM with or without NS1 Ag was positive in 15 (2.6%) cases. Conclusion: A detailedand continuous epidemiological surveillance is required for monitoring the incursions and spread of dengue viruses. This will helpin undertaking and implementing effective control and management strategies

Validated HPLC Method for Concurrent Determination of Antipyrine, Carbamazepine, Furosemide and Phenytoin and its Application in Assessment of Drug Permeability through Caco-2 Cell Monolayers

The present work explains the development and validation of a simple, rapid and sensitive liquid chromatographic method for the simultaneous determination of antipyrine (ANT), carbamazepine (CBZ), furosemide (FSD) and phenytoin (PHTN). Chromatographic analysis was carried out by a reversed phase technique on a C18 column, using water pH 3.0 and 50:50 mixtures of methanol and acetonitrile (58:42 v/v) as the mobile phase, at a flow-rate of 1.0 ml/min and a column temperature of 40°C. Detection was carried out at 205 nm for CBZ and PHTN and at 230 nm for ANT and FSD. The proposed method was evaluated for validation parameters including linearity, range, accuracy, precision, limit of detection (LOD), limit of quantification (LOQ) and specificity. Elution of drugs ANT, FSD, PHTN, and CBZ was observed at 4.1, 5.1, 12.3 and 13.5 min, respectively. The method was found to be linear (R2 ≥ 0.999) in the concentration range of 5–100 μM, with an acceptable accuracy and relative standard deviation. Results of intra- and inter-day validation (n=3) showed the method to be efficient for routine determination of these permeability markers in Caco-2 cell monolayer permeability studies. The method was successfully utilized for determination of standard compounds in Caco-2 permeability experiments

Removal of a Three Piece Foreign Body from a Child's Lung

Foreign body aspiration can be a life-threatening event especially in young children because they have smaller diameters of airway lumen, moreover, the delay in the diagnosis and subsequent therapeutic intervention can further increase the risk of morbidity. A retained foreign body can result in inflammatory response and granulation tissue formation around the object which make the foreign body removal difficult. In such situations surgical intervention is usually needed but with interventional pulmonology modalities we can restrict the need for surgery. Rigid bronchoscopy under general anaesthesia is the gold standard of diagnosis and management of foreign body aspiration. However, nowadays flexible bronchoscopy is more widely available and most pulmonary physicians are trained in its use so it can be used to remove such foreign bodies. We hereby report a case of a neglected foreign body which remained in the bronchus of a child for 11 days, successfully removed by flexible bronchoscopy

Weight Loss Can Lead to Resolution of Gastroesophageal Reflux Disease Symptoms: A Prospective Intervention Trial

This is the peer reviewed version of the following article: Singh, M., Lee, J., Gupta, N., Gaddam, S., Smith, B. K., Wani, S. B., Sullivan, D. K., Rastogi, A., Bansal, A., Donnelly, J. E. and Sharma, P. (2013), Weight loss can lead to resolution of gastroesophageal reflux disease symptoms: A prospective intervention trial. Obesity, 21: 284–290. doi:10.1002/oby.20279, which has been published in final form at http://doi.org/10.1002/oby.20279. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.OBJECTIVE Weight gain is an important risk factor for gastroesophageal reflux disease (GERD); however, whether weight loss can lead to resolution of GERD symptoms is not clear. Our aim was to measure the impact of weight loss on GERD symptoms. DESIGN AND METHODS In a prospective cohort study at a tertiary referral center, overweight/obese subjects (BMI 25-39.9 kg/m2) were enrolled in a structured weight loss program. Weight loss strategies included dietary modifications, increased physical activity and behavioral changes. At baseline and at 6 months, BMI and waist circumference were measured and all participants completed a validated reflux disease questionnaire. RESULTS A total of 332 adult subjects, mean age 46 years and 66% women were prospectively enrolled. At baseline, the mean body weight, BMI, and waist circumference were 101 (±18) kg, 35 (±5) kg/m2 and 103 (±13) cm. At 6 months, majority of the subjects (97%) lost weight (average weight loss: 13 ± 7.7 kg) and as compared with baseline, there was a significant decrease in the overall prevalence of GERD (15 vs. 37%; P < 0.01) and the mean GERD symptom score (1.8 vs. 5.5; P < 0.01). Overall, 81% of the subjects had reduction in GERD symptom scores; 65% had complete resolution and 15% had partial resolution of reflux symptoms. There was a significant correlation between % body weight loss and reduction in GERD symptom scores (r = 0.17, P < 0.05). CONCLUSIONS In conclusion, the overall prevalence of GERD symptoms is high (37%) in overweight and obese subjects. A structured weight loss program can lead to complete resolution of GERD symptoms in the majority of these subjects

Topical therapy with clobetasol propionate 0.025% for various dermatological conditions

Topical corticosteroids (TC) are the most commonly prescribed medications for the treatment of several dermatoses. Owing to their potent effect of relieving symptoms, these drugs are indicated for the use of inflammatory and pruritic presentations of dermatologic conditions. Clobetasol propionate (CP) is the most common TC used to treat itching, redness, and swelling caused by some skin conditions. It possesses anti-inflammatory, antipruritic, and vasoconstrictive properties. To exert its effect, CP binds to cytoplasmic glucocorticoid receptors and subsequently activates glucocorticoid receptor-mediated gene expression, thus resulting in the synthesis of certain anti-inflammatory proteins, while inhibiting the synthesis of certain inflammatory mediators. This case series discusses the efficacy, safety, and clinical experience of using CP 0.025% cream for the treatment of different dermatologic conditions

Preclinical formulation for the pharmacokinetics and efficacy of GBO-006, a selective polo like kinase 2 (PLK2) inhibitor for the treatment of triple negative breast cancer

GBO-006 was shown to be a highly specific and selective PLK2 inhibitor that promoted mitotic arrest in various cancer cell lines, subsequently resulting in their apoptotic death. Intraperitoneal alternate day dosing of GBO-006 using 100 % DMSO as formulation showed significant tumor regression in xenograft models, demonstrating proof of concept of PLK2 inhibition in vivo. These studies necessitated the development of a suitable and GRAS (generally considered as safe) preformulation for pharmacokinetic and efficacy studies. GBO-006 possesses challenging physicochemical and biopharmaceutical properties like poor solubility in aqueous media, low permeability and a crystalline nature. Different methods like cosolvency, complexation and micellar solubilization were employed to improve the solubility of GBO-006. A strategy of co-solvency is used to solubilize the GBO-006 up to 10 mg/mL. A formulation with 20 % DMSO, 40 % PEG 400, 30 % of 100 mM citrate buffer (pH 3.0) and 10 % solutol displayed clear solution without any visual precipitation of the drug even after 2 weeks of storage. GBO-006 showed moderate clearance in rat and high systemic clearance in mouse and dog. It showed poor oral bioavailability across all species. Intraperitoneal dosing of GBO-006 demonstrated the linear exposure. GBO-006 showed significant inhibition of tumor progression

DESIGN AND PERFORMANCE VERIFICATION OF NEWLY DEVELOPED DISPOSABLE STATIC DIFFUSION CELL FOR DRUG DIFFUSION/PERMEABILITY STUDIES

Objectives: The present study describes a disposable static diffusion cell for in vitro diffusion studies to achieve better results as compared to well existing Franz diffusion cell (FDC) in terms of the absence of bubbles, variable receptor compartment, ease of handling, and faster results.Materials and Methods: The cell consists of a cup-shaped donor compartment made of semi permeable that could be either cellophane membrane or, animal skin fitted to a rigid frame, which is supported on a plastic plate that contains a hole for the sample withdrawal. The receptor compartment is a separate unit, and it could be any container up to 500ml volume capacity. The most preferred receptor compartment is glass beaker. In the present study, goatskin was used as semi-permeable membrane and verification of its performance was carried out through diffusion studies using gel formulations of one each of the four-selected biopharmaceutical classification system (BCS) class drugs. Metronidazole, diclofenac sodium, fluconazole, and sulfadiazine were used as model drugs for BCS Class I, II, III, and IV, respectively.Results: The newly developed diffusion cell (NDDC) was found to provide faster and more reproducible results as compared to FDC. At the time interval of 24 h, the cell was found to exhibit a higher diffusion of metronidazole, diclofenac sodium, fluconazole, and sulfadiazine by 0.65, 0.65, 0.32, and 0.81 folds, respectively. The faster release obtained with NDDC was attributed to a larger surface area of skin as compared to that in FDC.Conclusion: It was concluded that better reproducibility of results could be achieved with NDDC