Chronic Leg Ulceration Associated with Polycythemia Vera Responding to Ruxolitinib (Jakafi®)

We present the case of a 63-year-old white male with bilateral chronic leg ulcers due to polycythemia vera and hydroxyurea therapy who demonstrated dramatic healing of his wounds in response to ruxolitinib (Jakafi^®, Novartis), a novel Janus kinase-1 and -2 inhibitor. This patient's wound had previously been refractory to multiple surgical interventions and immunosuppression. After the initiation of ruxolitinib, the patient underwent successful split-thickness skin grafting, with resultant healing of his wounds. He was stable without prednisone and other immunosuppressant therapy and had healed at 6 months. Ruxolitinib therapy could represent a novel option for patients who develop persistent inflammatory wounds in the setting of polycythemia vera and hydroxyurea therapy.     

Mutants of type II heat-labile enterotoxin LT-IIa with altered ganglioside-binding activities and diminished toxicity are potent mucosal adjuvants

The structure and function LT-IIa, a type II heat-labile enterotoxin of Escherichia coli, are closely related to the structures and functions of cholera toxin and LT-I, the type I heat-labile enterotoxins of Vibrio cholerae and enterotoxigenic Escherichia coli, respectively. While LT-IIa is a potent systemic and mucosal adjuvant, recent studies demonstrated that mutant LT-IIa(T34I), which exhibits no detectable binding activity as determined by an enzyme-linked immunosorbent assay, with gangliosides GD1b, GD1a, and GM1 is a very poor adjuvant. To evaluate whether other mutant LT-IIa enterotoxins that also exhibit diminished ganglioside-binding activities have greater adjuvant activities, BALB/c mice were immunized by the intranasal route with the surface adhesin protein AgI/II of Streptococcus mutans alone or in combination with LT-IIa, LT-IIa(T14S), LT-IIa(T14I), or LT-IIa(T14D). All three mutant enterotoxins potentiated strong mucosal immune responses that were equivalent to the response promulgated by wt LT-IIa. All three mutant enterotoxins augmented the systemic immune responses that correlated with their ganglioside-binding activities. Only LT-IIa and LT-IIa(T14S), however, enhanced expression of major histocompatibility complex class II and the costimulatory molecules CD40, CD80, and CD86 on splenic dendritic cells. LT-IIa(T14I) and LT-IIa(T14D) had extremely diminished toxicities in a mouse Y1 adrenal cell bioassay and reduced abilities to induce the accumulation of intracellular cyclic AMP in a macrophage cell line.     

A Randomized Controlled Trial Evaluating Efficacy of Promoting a Home-Based HIV Self-Testing with Online Counseling on Increasing HIV Testing Among Men Who Have Sex with Men

We developed an innovative home-based HIV self-testing (HIVST) service that included mailing of a free HIVST kit, and providing online real-time instructions and pre-test/post-test counseling (HIVST-OIC). The present parallel-group and non-blinded randomized controlled trial was conducted to evaluate the efficacy of promoting HIVST-OIC in increasing HIV testing rate among 430 men who have sex with men (MSM), with access to online live-chat applications in Hong Kong. At month 6, as compared to the control group, the intervention group reported significantly higher prevalence of HIV testing of any type (89.8 vs. 50.7%; relative risk (RR): 1.77; p < 0.001). Among those who have taken up any HIV testing in the last six months, significant between-group difference was found in multiple male sex partnerships (34.2 vs. 47.7%, RR: 0.72; p = 0.021). HIVST-OIC has a strong potential in increasing prevalence of HIV testing and reducing sexual risk behaviors. Implementation research is warranted.     

p‐Synephrine,ephedrine, p‐octopamine and m‐synephrine: Comparative mechanistic,physiological and pharmacological properties

Confusion and misunderstanding exist regarding the lack of cardiovascular and other adverse health effects of p‐synephrine and p‐octopamine relative to ephedrine and m‐synephrine (phenylephrine) which are known for their effects on the cardiovascular system. These four molecules have some structural similarities. However, the structural and stereochemical differences of p‐synephrine and p‐octopamine as related to ephedrine and m‐synephrine result in markedly different adrenergic receptor binding characteristics as well as other mechanistic differences which are reviewed. p‐Synephrine and p‐octopamine exhibit little binding to α‐1, α‐2, β‐1 and β‐2 adrenergic receptors, nor are they known to exhibit indirect actions leading to an increase in available levels of endogenous norepinephrine and epinephrine at commonly used doses. The relative absence of these mechanistic actions provides an explanation for their lack of production of cardiovascular effects at commonly used oral doses as compared to ephedrine and m‐synephrine. As a consequence, the effects of ephedrine and m‐synephrine cannot be directly extrapolated to p‐synephrine and p‐octopamine which exhibit significantly different pharmacokinetic, and physiological/pharmacological properties. These conclusions are supported by human, animal and in vitro studies that are discussed.     

Higher Annual Operator Volume Is Associated With Better Reperfusion Rates in Stroke Patients Treated by Mechanical Thrombectomy: The ETIS Registry

Objectives

The aim of this study was to determine whether individual operator characteristics have an impact on reperfusion and procedural complication rates.

Women''s perceptions of abortion in Egypt

A rapidly implemented qualitative study was conducted to investigate the perceptions of women about abortion in Egypt using in-depth interviews with hospitalised patients and focus group discussions with family planning clients and non-contracepting women. The most salient issue confronting the patients (whether the abortion had been spontaneous or induced) was their physical survival. The necessity to return immediately to their daily routines was most troubling to the patients who felt a need to rest and recuperate. The provision of post-abortion contraception was found to be problematic as women believed their bodily balance needed restoring first and that their fertility would not return immediately. The provision of counselling to reduce anxiety and fears, accurate and easily comprehensible information about miscarriage, induced abortion and future fertility and support for the women's need to rest are important aspects of post-abortion care.     

Practical considerations for the use of nonsteroidal anti-inflammatory drugs and cyclo-oxygenase-2 inhibitors in hypertension and kidney disease

BACKGROUND: Selective cyclo-oxygenase (COX)-2 inhibitors (coxibs) produce the beneficial effects of nonsteroidal anti-inflammatory drugs (NSAIDs) while sparing the COX-1-mediated adverse effects on platelets and the gastrointestinal system. However, due to the presence of constitutive COX-2 in the human kidney, coxibs have the same potential for adverse renal effects as traditional NSAIDs. OBJECTIVE: To provide evidence-based guidelines for the use of traditional NSAIDs and coxibs in patients potentially at risk for renal and associated hemodynamic blood pressure effects. METHODS: All pertinent peer-reviewed papers were retrieved with the usual electronic search tools. RESULTS: Both traditional NSAIDs and coxibs compromise the glomerular filtration rate in patients at increased risk. If there are differences in the blood pressure-raising potential of these drugs, these differences do not appear to be clinically significant. CONCLUSIONS: The blood pressure should be monitored for all patients taking chronic NSAID or coxib therapy. If a clinically significant (4 to 5 mmHg or more) increase in blood pressure is detected, the NSAID or the coxib should be discontinued and replaced with acetaminophen, to which codeine might be added. If the NSAID or the coxib is considered necessary, the increase in blood pressure should be treated. In addition, if the glomerular filtration rate reserve is compromised, all patients (including those taking short term therapy) should be closely monitored for the early detection of signs and symptoms of renal failure.