First trimester bleeding evaluation

First trimester bleeding is a common presentation in the emergency room. Ultrasound evaluation of patients with first trimester bleeding is the mainstay of the examination. The important causes of first trimester bleeding include spontaneous abortion, ectopic pregnancy, and gestational trophoblastic disease; 50% to 70% of spontaneous abortions are due to genetic abnormalities. In normal pregnancy, the serum beta hCG doubles or increases by at least 66% in 48 hours. The intrauterine GS should be visualized by TVUS with beta hCG levels between 1000 to 2000 mIU/mL IRP. Visualization of the yolk sac within the gestational sac is definitive evidence of intrauterine pregnancy. Embryonic cardiac activity can be identified with CRL of >5 mm. A GS with a mean sac diameter (MSD) of 8 mm or more without a yolk sac and a GS with an MSD of 16 mm or more without an embryo, are important predictors of a nonviable gestation. A GS with a mean sac diameter of 16 mm or more (TVUS) without an embryo is a sonographic sign of anembryonic gestation. A difference of <5 mm between the mean sac diameter and the CRL carries an 80% risk of spontaneous abortion. Approximately 20% of women with first trimester bleeding have a subchorionic hematoma. The presence of an extra ovarian adnexal mass is the most common sonographic finding in ectopic pregnancy. Other findings include the tubal ring sign and hemorrhage. About 26% of ectopic pregnancies have normal pelvic sonograms on TVUS. Complete hydatidiform mole presents with a complex intrauterine mass with multiple anechoic areas of varying sizes (Snowstorm appearance). Twenty-five percent to 65% of molar pregnancies have associated theca-leutin cysts. Arteriovenous malformation of the uterus is a rare but life-threatening cause of vaginal bleeding in the first trimester. The sonographic findings in a patient with first trimester bleeding should be correlated with serum beta hCG levels to arrive at an appropriate clinical diagnosis.     

An innovative medical school curriculum to enhance exposure to genetics and genomics: Updates and outcomes

PurposeIn 2011, we introduced an innovative parallel curriculum at Baylor College of Medicine, formerly called the Genetics Track Curriculum and now called the Genetics and Genomics Pathway, aimed at providing an opportunity for an enriched educational experience throughout medical school. In this report, we describe our 10-year experience with the program and highlight growth in enrollment as well as academic achievements of graduating students.MethodsWe reviewed the data of students enrolled in this pathway, including retention, satisfaction, student-driven curriculum changes, scholarly outcomes, and career outcomes.ResultsFrom September 2011 to June 2021, 121 students were enrolled in the Genetics and Genomics Pathway program. In total, 64 students (64/121 = 53%) left the program before graduating (the majority, after their first year). Of the 57 remaining students, 29 graduated (29/57, approximately 51%), and 4 of the 29 students (4/29 = 14%) matched into a genetics training program.ConclusionThis novel program serves as a mechanism for garnering increased interest and competence in medical genetics. The longitudinal nature of the program fosters enthusiasm for genetics and provides ample opportunity to develop valuable research skills. Given the ongoing shortage of providers in this field, such programs are vital to increase the size of the workforce and broaden the knowledge of providers in diverse fields.     

Characterization of LY2775240, a selective phosphodiesterase‐4 inhibitor,in nonclinical models and in healthy subjects

AbstractLY2775240 is a highly selective, potent and orally‐administered inhibitor of phosphodiesterase 4 (PDE4), and is being investigated as a treatment option for inflammatory disorders, such as psoriasis. LY2775240 was investigated in rodent and rhesus monkey nonclinical models. Treatment with LY2775240 led to significant reductions in TNFα production, a marker of PDE4 engagement upon immune activation, in both nonclinical models. In the first part of a 2‐part first‐in‐human randomized study, a wide dose range of LY2775240 was safely evaluated and found to be well‐tolerated with common adverse events (AEs) of nausea, diarrhea, and headache. No serious AEs were reported. The pharmacokinetic profile of LY2775240 was well‐characterized, with a half‐life that can support once‐a‐day dosing. An ex vivo pharmacodynamic (PD) assay demonstrated dose‐dependent PDE4 target engagement as assessed by reduction in TNFα production. A 20 mg dose of LY2775240 led to near‐maximal TNFα inhibition in this PD assay in the first part of the study and was selected for comparison with the clinical dose of apremilast (30 mg) in the crossover, second part of this study. The 20 mg dose of LY2775240 demonstrated sustained maximal (50%–80%) inhibition of TNFα over all timepoints over the 24‐h duration. The comparator apremilast achieved peak inhibition of ~ 50% at only 4 h postdose with a return to about 10% inhibition within 12 h of dosing. In summary, the nonclinical data and safety, tolerability, and PK/PD data in healthy subjects supports further investigation of LY2775240 in inflammatory indications. Study Highlights

• WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC?

Phosphodiesterase 4 (PDE4) inhibitors, such as apremilast, are currently approved to treat autoimmune disorders, such as psoriasis. LY2775240 is an oral PDE4 inhibitor being developed for treatment of a variety of inflammatory disorders. The degree of enzymatic inhibition achieved by PDE4 inhibitors clinically is poorly understood.

• WHAT QUESTION DID THIS STUDY ADDRESS?

This study investigated single ascending doses of LY2775240, a highly selective oral PDE4 inhibitor, in healthy subjects. LY2775240 was well‐tolerated over the dose range evaluated, and pharmacokinetic/pharmacodynamic (PD) profiles were well‐characterized.

• WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE?

This study evaluated different doses of LY2775240 and subsequently compared a selected LY2775240 dose with the clinical dose of apremilast with an ex vivo assay. This information builds a connection between target engagement and clinical efficacy.

• HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE?

This is the first report of an ex vivo PD assay that has been systematically implemented in a PDE4 inhibitor Phase 1 study. Early investigation of exposure‐response relationships versus a comparator can support evaluation of clinically meaningful doses of investigational agents.     

Successful switch (tOPV to bOPV) in India: Tribute to a resilient health system

In accordance with the end game strategies for polio eradication a synchronized switch plan from tOPV to bOPV was implemented globally in 2016. The National Committee for Polio Eradication (NCCPE) validated the switch activities in India. An expert group of 104 academics conducted field visits in 25 states and 2 Union territories for independent verification (after an initial round of verification by the National Polio Surveillance Project [NPSP]). The objectives were to validate withdrawal and disposal of tOPV by screening cold chain points in public and private sector health facilities in both rural and urban areas; additionally, availability of bOPV and IPV was also documented. 34 filled tOPV and 5 empty vials were detected inside cold chain equipment and 17 outside. The disposal mechanism was found to be reasonably adequate. The key strategies -- ‘throttling’ of vaccine supplies well ahead of the switch date while preventing stock outs at various immunization points, simultaneously working with the regulators to delicense the tOPV on the switch date and helping manufacturers to calibrate vaccine production according to national timelines, and strong and persistent advocacy with professional associations to align with national bOPV and IPV policy facilitated successful accomplishment of the switch process. Effective implementation of the switch strategy in India also bears testimony to the resilience of the health system operating under diverse and heterogeneous governance.     

Transverse Colon Volvulus with Chilaiditis Syndrome

Volvulus of transverse colon is a rare cause of large bowel obstruction. To our knowledge only 75 cases have been reported in the world literature and additionally only three cases of transverse colon volvulus with Chilaiditis syndrome have been reported to date. Because of its rarity here we report a case of transverse colon volvulus which was indeed associated with Chilaiditis syndrome. This is probably the fourth case of Chilaiditis syndrome caused by transverse colon volvulus.     

Novel dithranol phospholipid microemulsion for topical application: development, characterization and percutaneous absorption studies

The objective of this study was to develop and characterize a novel dithranol-containing phospholipid microemulsion systems for enhanced skin permeation and retention. Based on the solubility of dithranol, the selected oils were isopropyl myristate (IPM) and tocopherol acetate (TA), and the surfactants were Tween 80 (T80) and Tween 20 (T20). The ratios of cosurfactants comprising of phospholipids and ethanol (1?:?10) and surfactant to co-surfactant (1?:?1 and 2.75?:?1) were fixed for the phase diagram construction. Selected microemulsions were evaluated for globule size, zeta potential, viscosity, refractive index, per cent transmittance, stability (freeze thaw and centrifugation), ex vivo skin permeation and retention. The microemulsion systems composed of IPM and T80 with mean particle diameter of 72.8?nm showed maximum skin permeation (82.23%), skin permeation flux (0.281?mg/cm2/h) along with skin retention (8.31%) vis-à-vis systems containing TA and T20. The results suggest that the developed novel lecithinized microemulsion systems have a promising potential for the improved topical delivery of dithranol.     

A case of successfully treated acute respiratory distress syndrome complicating Plasmodium falciparum malaria

While endemic malaria has been eliminated in the United States, approximately 1200 mostly imported cases are reported annually in the country, with fewer than 20 recorded deaths. Because of the rarity of this disease in the United States, clinicians are often unfamiliar with its diagnosis and presentation. In a review of all malaria deaths in the United States from 1963 to 2001, failure to diagnose malaria on initial presentation, promptly initiate treatment, and/or prescribe appropriate antimalarial drugs were identified as contributing factors to death. Plasmodium falciparum can lead to a particularly severe type of malaria complicated by acute respiratory distress syndrome (ARDS), and physicians must be alert to the possibility of this diagnosis in immigrants and returning travelers. We report a case of successfully treated acute respiratory distress syndrome complicating imported P falciparum malaria at a large teaching hospital in Washington, DC.     

Simultaneous spectrophotometric estimation of Hydrochlorothiazide, Atenolol and Losartan potassium in tablet dosage form

Two simple, accurate and reproducible spectrophotometric methods have been developed for the simultaneous estimation of Hydrochlorothiazide (Hctz), Atenolol (Atn) and Losartan potassium (Los) in combined tablet dosage forms. The first method involves determination using the simultaneous equation method, the sampling wavelengths selected are, 272.5 nm, 224 nm and 250 nm over the concentration ranges of 0.5-30 microg/ml, 1-50 microg/ ml and 1-60 microg/ml for Hctz, Atn and Los respectively. The second method is the First order derivative method, the sampling wavelengths selected for estimation of Hctz, Atn and Los are 280.5 nm, 233 nm and 244 nm with linearity in the concentration ranges of 0.5-30 microg/ ml, 1-50 microg/ml and 1-60 microg/ml respectively. The results of the analysis were validated statistically and recovery studies were carried out as per ICH guidelines.     

Sonographic evaluation of ectopic pregnancy

Ectopic pregnancy is a high-risk condition that occurs in 1.9% of reported pregnancies. Although the clinical triad of pain, bleeding, and amenorrhea is considered very specific for an ectopic pregnancy, ultrasound plays important role in detecting the exact location of the ectopic pregnancy and also in providing guidance for minimally invasive treatment. This article discusses the main sonographic features of ectopic pregnancy at various common and unusual locations. In addition, it provides insight into the role of hormonal markers in the diagnosis and management of ectopic pregnancy.