AIDS and heart disease: is cardiac surgery justified?

A compromised immune system, limited survival and increased risk to the anaesthetic and surgical team of acquiring HIV infection have been the major concerns in offering cardiac surgery to patients with AIDS. The current report presents a patient with AIDS who underwent successful, uncomplicated coronary artery surgery. He remains free of ischaemic and any infectioe symptoms 12 months postoperatively.     

Botulinum Toxin in the Treatment of Muscle Specific Oro-Facial Pain: A Literature Review

Facial pain associated with temporomandibular joint (TMJ) and surrounding structures has been a challenge to clinicians as far as diagnosis and management is concerned. Complexity of anatomical structures within a small area, function of teeth and surrounding periodontal ligament, action of muscles, pathologies, lack of diagnostic investigations, all these complicate specific diagnosis of TMJ disorders. Various classifications have been designed and studied to help diagnose and treat TMJ related disorders, of which the simplest one is pain from TMJ proper and surrounding muscles. Many treatment modalities to treat pain arising from muscles around TMJ like splints, mouth restriction exercises, injection of sclerosing agents etc. have been used with various degrees of success. Botulinum toxin has been shown to be effective in the treatment of oro-facial pain due to muscular disorders and the same is discussed in detail in this review literature.     

Revival of the abandoned therapeutic wortmannin by nanoparticle drug delivery

One of the promises of nanoparticle (NP) carriers is the reformulation of promising therapeutics that have failed clinical development due to pharmacologic challenges. However, current nanomedicine research has been focused on the delivery of established and novel therapeutics. Here we demonstrate proof of the principle of using NPs to revive the clinical potential of abandoned compounds using wortmannin (Wtmn) as a model drug. Wtmn is a potent inhibitor of phosphatidylinositol 3' kinase-related kinases but failed clinical translation due to drug-delivery challenges. We engineered a NP formulation of Wtmn and demonstrated that NP Wtmn has higher solubility and lower toxicity compared with Wtmn. To establish the clinical translation potential of NP Wtmn, we evaluated the therapeutic as a radiosensitizer in vitro and in vivo. NP Wtmn was found to be a potent radiosensitizer and was significantly more effective than the commonly used radiosensitizer cisplatin in vitro in three cancer cell lines. The mechanism of action of NP Wtmn radiosensitization was found to be through the inhibition of DNA-dependent protein kinase phosphorylation. Finally, NP Wtmn was shown to be an effective radiosensitizer in vivo using two murine xenograft models of cancer. Our results demonstrate that NP drug-delivery systems can promote the readoption of abandoned drugs such as Wtmn by overcoming drug-delivery challenges.     

Effect of early diagnosis and treatment with percutaneous lead extraction on survival in patients with cardiac device infections

Cardiac device infections (CDIs) represent a serious complication after the implantation of pacemakers and defibrillators. In addition to antimicrobials, complete hardware removal, mostly with percutaneous lead extraction (PLE), is necessary to limit recurrences. However, CDI diagnosis is often difficult and is sometimes delayed, and scarce data exist on how the timing of PLE may affect clinical outcomes. In this study, the in-hospital outcomes of 52 consecutive patients with CDIs who underwent PLE were retrospectively analyze. Co-morbidities such as diabetes mellitus, congestive heart failure, renal insufficiency, and end-stage renal disease were highly prevalent in the study cohort. Patients were divided into group A (bacteremia or device endocarditis) and group B (localized pocket infection). In-hospital mortality was 29% in group A and 5% in group B (p = 0.02) and was due mostly to sepsis. Hospital stays were shorter in group B patients (5.7 vs 21.7 days, p <0.001). Presentation with hypotension was more commonly observed in group A patients and was associated with higher in-hospital mortality, whereas pocket findings correlated with better survival. Postoperative courses after PLE were uneventful in most patients, and no fatal complications were observed. PLE was performed significantly earlier in group B patients (hospitalization day 1.3 vs 7.6, p <0.001). PLE performed within 3 hospitalization days was associated with lower in-hospital mortality (p = 0.01). In conclusion, PLE performed within 3 days from admission is associated with shorter hospitalization and better survival. A timely diagnosis is crucial, particularly in the absence of local findings, because early treatment with PLE is likely to prevent the catastrophic outcomes of unrelenting CDIs.     

Reconstruction of complex aplasia cutis congenita

Aplasia cutis congenita is a rare scalp defect with occasional absence of underlying bone and dura. Patients with small defects respond well to conservative management. However, larger defects often can pose management and technical challenge. Successful management of a large, composite aplasia cutis congenita defect using Integra dermal regeneration matrix is presented. At 16 months, the patient showed a stable and supple scalp with evidence of calvarial regeneration.     

Endothelial caveolar hub regulation of adenosine triphosphate-induced endothelial nitric oxide synthase subcellular partitioning and domain-specific phosphorylation

ATP leads to endothelial NO synthase (eNOS)/NO-mediated vasodilation, a process hypothesized to depend on the endothelial caveolar eNOS partitioning and subcellular domain-specific multisite phosphorylation state. We demonstrate herein that, in both the absence and presence of ATP, the uterine artery endothelial caveolae contain specific protein machinery related to subcellular partitioning and act as specific focal "hubs" for NO- and ATP-related proteins. ATP-induced eNOS regulation showed a complex set of multisite posttranslational phosphorylation events that were closely associated with the enzyme's partitioning between caveolar and noncaveolar endothelial subcellular domains. The comprehensive model that we present demonstrates that ATP repartitioned eNOS between the caveolar and noncaveolar subcellular domains; specifically, the stimulatory (PSer635)eNOS was substantially higher in the caveolar pool with subcellular domain-independent increased levels on ATP treatment. The stimulatory (PSer1179)eNOS was not altered by ATP treatment. However, the inhibitory (PThr495)eNOS was regulated predominantly in the caveolar domain with decreased levels on ATP action. In contrast, the agonist-specific (PSer114)eNOS was localized in the noncaveolar pool with increased levels on ATP stimulation. Thus, the endothelial caveolar membrane system plays a pivotal role(s) in ATP-associated subcellular partitioning and possesses the relevant protein machinery for ATP-induced NO regulation. Furthermore, these subcellular domain-specific phosphorylation/dephosphorylation events provide evidence relating to eNOS spatio-temporal dynamics.