Intraplatelet cyclic guanosine-3',5'-monophosphate levels during pregnancy and preeclampsia.

OBJECTIVE: To investigate the intraplatelet cyclic guanosine-3',5'-monophosphate (cGMP) levels during normal pregnancy and preeclampsia. STUDY DESIGN: Pregnant women (n = 15), women with preeclampsia (n = 15), and nonpregnant, normotensive women (n = 15) were included. Intraplatelet cyclic guanosine-3',5'-monophosphate levels were measured by an enzyme-linked immunosorbent assay. RESULTS: Intraplatelet cGMP levels were significantly different among all groups (p < 0.02). The values were higher in normal pregnant women (mean 19.8 SD 2.6 fmol/10(5) platelets) in comparison to nonpregnant women (mean 7.6 SD 0.3 fmol/10(5)platelets; p = 0.001) and women with preeclampsia (mean 11.3 SD 1.8 fmol/10(5) platelets; p = 0.05). Plasma nitric oxide levels did not reveal differences between all groups. CONCLUSIONS: The results of this study in a high-risk Andean population demonstrated that intraplatelet cyclic guanosine-3',5'-monophosphate levels are decreased during preeclampsia compared to normal pregnancy, suggesting a lack in action of nitric oxide.     

Neoadjuvant therapy of renal cell carcinoma: A novel treatment option in the era of targeted therapy?

The study was carried out to evaluate the effectiveness, toxicity and optimal duration of neoadjuvant therapy for patients with organ‐confined or locally advanced renal cell carcinoma in the era of targeted agents. A literature review was carried out using Medline/Pubmed articles, as well as congress reports from the last five American Society of Clinical Oncology, American Urological Association and European Association of Urology Annual Meetings. Neoadjuvant targeted therapy is feasible and shows toxicity similar to that seen in a palliative setting. Most studies recommend an application for 2–4 months. The current data situation is best for sunitinib. Surgery can apparently be carried out the day right after discontinuing the drug. However, even sunitinib leads to only a mean 10% decrease in primary tumor size, and one‐quarter to one‐fifth of all patients show local tumor progression during treatment. Few patients (approximately 12%) with a vena cava tumor thrombus achieve a significant decrease in its level under neoadjuvant therapy; here too, progression is observed in a significant number of cases. Even the new targeted agents show limited effectiveness in achieving relevant remissions of the primary tumor. Furthermore, tumor progression is seen in a significant percentage of patients during neoadjuvant therapy. Thus, even today in the era of targeted agents, a neoadjuvant approach should only be made in patients with localized or locally advanced renal cell carcinoma, which primarily seem to be absolutely inaccessible by (partial) nephrectomy.     

Current surgical treatments for Parkinson's disease and potential therapeutic targets

Currently, the most common surgical treatment for Parkinson's disease is deep brain stimulation(DBS). This treatment strategy is typically reserved for bradykinesia, rigidity and tremor in patients who no longer respond to medication in a predictable manner or who suffer medication-induced dyskinesias. In addition to DBS, ablative procedures like radiofrequency, radiosurgery and focused ultrasound are also utilized for select tremor symptoms. In this review, we discuss evolving surgical techniques, targets, and emerging technology. In addition, we evaluate potential paradigm shifts in treatment, including gene therapy, immunotherapy and cell transplantation. While these new techniques and treatment options are still in their infancy, advances in Parkinson's disease treatment are rapidly expanding.     

The role of accountable care organizations in delivering value

The goal of Accountable Care Organizations is to improve patient outcomes while maximizing the value of the services provided. This will be achieved through the use of performance and quality measures that facilitate efficient, cost-effective, evidence-based care. By creating a network connecting primary care physicians, specialists, rehabilitation facilities and hospitals, patient care should be maximized while at the same time delivering appropriate value for those services provided. The Medicare Shared Savings Program will financially reward ACOs that meet performance standards while at the same time lowering costs. The orthopaedic surgeon can only benefit by understanding how to participate in and negotiate the complexities of these organizations.     

The physiology and toxicology of acute inhalation phosphine poisoning in conscious male rats

Phosphine (PH₃) is a toxidrome-spanning chemical that is widely used as an insecticide and rodenticide. Exposure to PH₃ causes a host of target organ and systemic effects, including oxidative stress, cardiopulmonary toxicity, seizure-like activity and overall metabolic disturbance. A custom dynamic inhalation gas exposure system was designed for the whole-body exposure of conscious male Sprague-Dawley rats (250–350?g) to PH₃. An integrated plethysmography system was used to collect respiratory parameters in real-time before, during and after PH₃ exposure. At several time points post-exposure, rats were euthanized, and various organs were removed and analyzed to assess organ and systemic effects. The 24?h post-exposure LCt₅₀, determined by probit analysis, was 23,270?ppm?×?min (32,345?mg?×?min/m³). PH₃ exposure affects both pulmonary and cardiac function. Unlike typical pulmonary toxicants, PH₃ induced net increases in respiration during exposure. Gross observations of the heart and lungs of exposed rats suggested pulmonary and cardiac tissue damage, but histopathological examination showed little to no observable pathologic changes in those organs. Gene expression studies indicated alterations in inflammatory processes, metabolic function and cell signaling, with particular focus in cardiac tissue. Transmission electron microscopy examination of cardiac tissue revealed ultrastructural damage to both tissue and mitochondria. Altogether, these data reveal that in untreated, un-anesthetized rats, PH₃ inhalation induces acute cardiorespiratory toxicity and injury, leading to death and that it is characterized by a steep dose-response curve. Continued use of our interdisciplinary approach will permit more effective identification of therapeutic windows and development of rational medical countermeasures and countermeasure strategies.     

Characterization of 10 polymorphic microsatellite loci for White-breasted mesites (Mesitornis variegata)

We characterized 10 specific microsatellite loci for White-breasted mesites (Mesitornis variegata), an endemic bird species from western Madagascar. Nine loci were in Hardy–Weinberg equilibrium, and we detected 4–10 alleles per locus (mean = 6.1). These primers will be used to study the mating system and social organization of White-breasted mesites and may have applications for the conservation of the few remaining populations of this vulnerable and still poorly studied species.