Eliciting renal failure in mosquitoes with a small-molecule inhibitor of inward-rectifying potassium channels.

Mosquito-borne diseases such as malaria and dengue fever take a large toll on global health. The primary chemical agents used for controlling mosquitoes are insecticides that target the nervous system. However, the emergence of resistance in mosquito populations is reducing the efficacy of available insecticides. The development of new insecticides is therefore urgent. Here we show that VU573, a small-molecule inhibitor of mammalian inward-rectifying potassium (Kir) channels, inhibits a Kir channel cloned from the renal (Malpighian) tubules of Aedes aegypti (AeKir1). Injection of VU573 into the hemolymph of adult female mosquitoes (Ae. aegypti) disrupts the production and excretion of urine in a manner consistent with channel block of AeKir1 and renders the mosquitoes incapacitated (flightless or dead) within 24 hours. Moreover, the toxicity of VU573 in mosquitoes (Ae. aegypti) is exacerbated when hemolymph potassium levels are elevated, suggesting that Kir channels are essential for maintenance of whole-animal potassium homeostasis. Our study demonstrates that renal failure is a promising mechanism of action for killing mosquitoes, and motivates the discovery of selective small-molecule inhibitors of mosquito Kir channels for use as insecticides.

Irreversible atorvastatin-associated hearing loss.

Drug-associated ototoxicity is a potentially irreversible adverse event. Among the several 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) available in the United States, only atorvastatin is associated with tinnitus, but none are associated with any forms of hearing loss. A search of the published literature (1950-August 2011) revealed no published case reports of ototoxicity associated with statins. To our knowledge, we describe the first case of progressive, irreversible hearing loss in a 32-year-old man 18 months after starting atorvastatin therapy. He began taking atorvastatin 20 mg every evening for treatment of hypercholesterolemia. Six months later, he complained of occasional episodes of tinnitus, which resolved spontaneously. An audiogram was obtained and was normal. By 18 months, the tinnitus became continuous. Another audiogram revealed bilateral "cookie-bite" middle-frequency hearing loss. Atorvastatin was immediately discontinued, and the patient was fitted with hearing aids. Four years after drug discontinuation, his hearing loss had neither progressed nor regressed. Use of the Naranjo adverse drug reaction probability scale indicated a possible (score of 2) temporal and causal relationship between the patient's hearing loss and atorvastatin. Causes of "cookie-bite" hearing loss include chronic exposure to loud noises, presbycusis, genetic predisposition, and drugs. The manufacturer of atorvastatin has received three unpublished cases of deafness, but claims that causal relationships were not established. Despite these claims by the manufacturer, based on this case report, we recommend that clinicians and patients be aware of the risk of atorvastatin-associated tinnitus and permanent hearing loss. Further research is needed to better understand the mechanism and frequency of this adverse event.

An indoor air quality assessment for vulnerable populations exposed to volcanic vog from Kilauea Volcano.

The Ka'u District of Hawaii is exposed to sulfurous air pollution called vog from the ongoing eruption of Kilauea Volcano. Increased volcanic activity in 2008 prompted an indoor air quality assessment of the district's hospital and schools. All indoor sulfur dioxide concentrations were above the World Health Organization's average 24-hour recommendation. Indoor penetration ratios were up to 94% of ambient levels and dependent upon building construction or the use of air-conditioning. Health-promotion efforts for vulnerable populations at the hospital and schools are under way to improve indoor air quality and respond to those affected by vog exposure.

The use of ultrasound to determine timing of Pavlik harness discontinuation in treatment of developmental dysplasia of the hip.

The timing of Pavlik harness removal in patients with developmental dysplasia of the hip is typically determined by clinical examination. Ultrasound is considered more sensitive than clinical examination in diagnosis of instability of the hip, but it is not routinely used in cases of developmental dysplasia of the hip, especially when determining the timing of Pavlik harness removal. The purpose of this study is to investigate if ultrasound examination is more effective than clinical examination alone in determining completion of Pavlik harness treatment. Fifty consecutive infants with developmental dysplasia of the hip were given both a clinical examination and dynamic ultrasound examination to determine if Pavlik harness treatment could be discontinued. A pediatric orthopedist conducted the physical examinations. Both a radiologist and a pediatric orthopedist interpreted the ultrasounds. Cost estimates for ultrasound and operative procedures were obtained at our institution and compared. The average age at the time of Pavlik harness placement was 5.3 days, and the average age at the time of ultrasound was 54.3 days. There were 35 females and 15 males and 31 left hips, 4 right hips, and 15 bilateral hips. All 50 patient hips were deemed clinically stable prior to obtaining an ultrasound. The ultrasound interpretations by a radiologist and pediatric orthopedist were in agreement in all cases. In one case, the ultrasound results did not correlate with results of the clinical examination. In that one case, the hip was clinically stable, but dynamic ultrasound revealed that the hip was located, but dislocatable. The Pavlik harness was reapplied to the patient for an additional 42 days. At 1-year follow-up the hip is stable and developing normally as determined by radiographs. The cost comparison revealed that the cost of 50 ultrasounds is less than the cost of a single operative procedure. The use of ultrasound to determine the timing of Pavlik harness cessation is justified from both a financial and a patient outcome perspective in this small study. Larger studies are needed before ultrasound examination used to help determine Pavlik cessation is considered standard of care.

Posterior sternoclavicular epiphyseal fracture-dislocation with delayed diagnosis.

Posterior sternoclavicular joint dislocations and epiphyseal fractures are relatively rare injuries. We present a case report of a 16-year-old male who presented with a 10-day delay in diagnosis. The medial clavicular fragment was widely displaced and rested against the cervical vertebral body. Despite the degree of displacement, the patient had very few symptoms, and the diagnosis was not appreciated in the emergency department and became apparent at 10-day clinic follow-up. Treatment consisted of attempts at closed reduction, which were not successful. Open reduction was performed and the repair done with strong sutures. At 1-year follow-up the patient is doing well without any symptoms. A literature review consisting of anatomy, ossification patterns, classification systems, diagnosis and associated symptoms, imaging recommendations, treatment recommendations, outcomes, and complications is included.