Coronary artery fistula presenting as bacterial endocarditis

Coronary artery fistula is often considered to be a benign and rare congenital anomaly. It is usually an incidental finding encountered during routine cardiac catheterization. We report a case of a patient presenting with endocarditis involving a large coronary artery fistula connecting an aneurysmal circumflex coronary artery to the coronary sinus. The diagnosis was initially made by echocardiography and confirmed by cardiac catheterization. In addition, we briefly discuss the literature on management of this coronary anomaly.     

Feasibility of near real-time image-guided sinus surgery using intraoperative fluoroscopic computed axial tomography.

OBJECTIVE: One of the main limitations of image-guided surgery is that navigation relies on the use of a CT scan obtained before surgery and is unable to be updated during the procedure. A software addition has been developed to allow reconstruction of CT-like images from a series of fluoroscopic scans and integrate these into an image-guided system (GE Healthcare Surgical Navigation, Lawrence, MA). We report our initial experience with a series of patients undergoing intraoperative fluoroscopic navigation in sinus surgery. STUDY DESIGN AND SETTINGS: After institutional review board clearance, we prospectively studied 14 consecutive patients undergoing image-guided sinus surgery with the use of intraoperative fluoroscopy. RESULTS: All patients had preoperative and postoperative fluoroscopic images reconstructed into CT-like images. By the conclusion of the study, images were adequate in quality and accurate navigation was achieved. CONCLUSION: Real-time image-guided sinus surgery using fluoroscopy is feasible. Future studies will need to focus on defining the procedures that could benefit, such as tumor resection, to enhance patient safety during these operations.     

Rotigotine transdermal patch in early Parkinson's disease: a randomized, double-blind, controlled study versus placebo and ropinirole.

Rotigotine is a new, non-ergot dopamine agonist formulated in a transdermal delivery system. The present study was to investigate the efficacy and safety of the rotigotine transdermal patch in the treatment of early Parkinson's disease. Patients (n = 561) were randomized to rotigotine, ropinirole, or placebo. The titration period was up to 13 weeks, and there was a minimum dose-maintenance period of 24 weeks for ropinirole and 33 weeks for rotigotine. The primary endpoint was the proportion of patients with a minimum of 20% decrease in the combined Unified Parkinson's Disease Rating Scale Part II and Part III scores. The responder rate in the rotigotine group was significantly higher than in the placebo group (52% vs. 30%, P < 0.0001). Transdermal rotigotine at doses < or =8 mg/24 h did not show noninferiority to ropinirole at doses < or =24 mg/day. In a post-hoc subgroup analysis, rotigotine < or =8 mg/24 hours had a similar efficacy to ropinirole at doses < or =12 mg/day. The rotigotine transdermal patch was well tolerated. The most common adverse events were application-site reactions, nausea, and somnolence. Application-site reactions were predominantly mild or moderate in intensity. In conclusion, the rotigotine transdermal patch represents an effective and safe option for the treatment of patients with early Parkinson's disease.     

Prostate cancer after heart transplantation: unicenter case-control study.

BACKGROUND: We have noted an unexpectedly high incidence of prostate cancer in our heart transplant recipients (HTR). METHODS: We conducted a retrospective review of patients after heart transplantation to investigate the prevalence, treatment, and outcome of prostate cancer diagnosed after systematic screening (study group). We compared them with case-matched HTR (control). RESULTS: Among 702 recipients, 15 patients had elevated prostate-specific antigen (PSA) levels. Fourteen cases of prostate cancer were diagnosed and treated. The median time between transplantation and prostate cancer diagnosis was 73 months. No patient was diagnosed in a locally advanced (>T2) or metastatic stage. Eleven patients (78.6%) received curative treatment. During follow-up (median, 44 months), 1 patient died from prostate cancer. The survival rate between the study and control groups did not differ. CONCLUSION: Routine PSA testing is recommended as a screening test for prostate cancer in patients after heart transplantation. We believe this could also result in detection of early stages of prostate cancer, thus allowing curative treatment, and achieving similar survival to other case-matched HTR with no prostate cancer.     

Lipid transfer protein: a pan-allergen in plant-derived foods that is highly resistant to pepsin digestion

BACKGROUND: Lipid transfer proteins (LTPs) are small molecules of approximately 10 kD that demonstrate high stability. They have recently been identified as allergens in the Rosaceae subfamilies of the Prunoideae (peach, apricot, plum) and of the Pomoideae (apple). They belong to a family of structurally highly conserved proteins that are also present in non-Rosaceae vegetable foods. OBJECTIVE: The aim of this study was to investigate the cross-reactivity to non-Rosaceae LTPs, and to study the role of protein stability in allergenicity. METHODS: Thirty-eight patients with a positive SPT to Rosaceae fruit extracts enriched for LTP were characterized by interview and SPT. To investigate IgE cross-reactivity between Rosaceae and non-Rosaceae LTPs, RAST and RAST inhibition as well as ELISA and ELISA inhibition were performed, using whole food extracts and purified LTPs. Both purified natural LTPs (peach, carrot and broccoli) and Pichia pastoris recombinant LTPs (carrot and wheat) were included. Pepsin digestion was used to address the role of stability in the allergenicity of LTPs. RESULTS: IgE antibodies to Rosaceae LTPs reacted to a broad range of vegetable foods, including Gramineae (cereals), Leguminosae (peanut), Juglandaceae (walnut), Anacardiaceae (pistachio), Brassicaceae (broccoli), Umbelliferae (carrot, celery), Solanaceae (tomato), Cucurbitaceae (melon), and Actinidiaceae (kiwi). Binding and inhibition studies with purified natural and recombinant LTPs confirmed their role in this cross-reactivity. Many of these cross-reactivities were accompanied by clinical food allergy, frequently including systemic reactions. Antibody binding to LTP was shown to be resistant to pepsin treatment of whole extract or purified LTP. CONCLUSION: LTP is a pan-allergen with a degree of cross-reactivity comparable to profilin. Due to its extreme resistance to pepsin digestion, LTP is a potentially severe food allergen.     

Synergistic interaction of topographic features in the production of bone-like nodules on Ti surfaces by rat osteoblasts

The objective of this study was to study the responses of osteoblast-like cells to rough Titanium (Ti)-coated epoxy surfaces of differing topographic complexity. Four topographies were studied: polished (PO), coarse-blasted (CB), acid-etched (AE) and coarse-blasted+acid-etched (SLA). Rat osteoblasts were cultured on these surfaces and their morphology, thickness as well as the number and size of bone-like nodules measured. To determine cell shape and cell thickness, fluorescein-5-thiosemicarbazide was used to stain the cell components including the cell membrane, the stained cells were optically sectioned using epifluorescent microscopy and the optical sections were computationally reconstructed to obtain three-dimensional images in which cell volume and cell thickness could be determined. Similarly optical sections of bone-like nodules labeled with tetracycline were also reconstructed to determine their size. The different surface topographies were found to alter the thickness and morphology of osteoblasts cultured on these surfaces. Osteoblasts produced significantly more and larger nodules on SLA compared to other surfaces. Nevertheless and perhaps surprisingly, given the evidence in various cell populations that cell shape can affect cell differentiation, cell thickness was not directly correlated with an increase in bone-like nodule formation. Data were analyzed by factorial analysis of variance. In this way the primary effect of each surface treatment ( i.e. blasting and acid etching) could be assessed as well as their interaction. Both the acid etching and blasting processes significantly affected the number and size of bone-like nodules cultured on Ti surfaces. Moreover there were significant interaction effects indicating that surface topographic features can act synergistically to enhance bone formation. This result suggests that a useful approach to the optimization of surfaces for bone production could involve systematic investigation of combinations of processes each of which produces distinct surface topographical features.     

Mechanisms of cold sensitivity of paramyotonia congenita mutation R1448H and overlap syndrome mutation M1360V

Missense mutations of the human skeletal muscle voltage-gated Na⁺ channel (hSkM1) cause a variety of neuromuscular disorders. The mutation R1448H results in paramyotonia congenita and causes cold-induced myotonia with subsequent paralysis. The mutation M1360V causes an overlapping syndrome with both K⁺-induced muscle weakness and cold-induced myotonia. The molecular mechanisms of the temperature dependence of these disorders are not well understood. Therefore we investigated physiological parameters of these Na⁺ channel mutations at different temperatures. Channel proteins were recombinantly expressed in human embryonic kidney cells and studied electrophysiologically, using the whole-cell patch-clamp technique. We compared the wild-type (WT) channel with both mutants at different temperatures. Both mutations had slower inactivation and faster recovery from inactivation compared to WT channels. This effect was more pronounced at the R1448H mutation, leading to a larger depolarization of the cell membrane causing myotonia and paralysis. The voltage dependence of activation of R1448H was shifted to more negative membrane potentials at lower temperature but not at the M1360V mutation or in the WT. The window current by mutation R1448H was increased at lower temperatures. The results of this study may explain the stronger cold-induced clinical symptoms resulting from the R1448H mutation in contrast to the M1360V mutation.     

Congenital clubfoot in Europe: A population‐based study

We aimed to assess prevalence, birth outcome, associated anomalies and prenatal diagnosis of congenital clubfoot in Europe using data from the EUROCAT network, and to validate the recording of congenital clubfoot as a major congenital anomaly by EUROCAT registries. Cases of congenital clubfoot were included from 18 EUROCAT registries covering more than 4.8 million births in 1995–2011. Cases without chromosomal anomalies born during 2005–2009, were randomly selected for validation using a questionnaire on diagnostic details and treatment. There was 5,458 congenital clubfoot cases of which 5,056 (93%) were liveborn infants. Total prevalence of congenital clubfoot was 1.13 per 1,000 births (95% CI 1.10–1.16). Prevalence of congenital clubfoot without chromosomal anomaly was 1.08 per 1,000 births (95% CI 1.05–1.11) and prevalence of isolated congenital clubfoot was 0.92 per 1,000 births (95% CI 0.90–0.95), both with decreasing trends over time and large variations in prevalence by registry. The majority of cases were isolated congenital clubfoot (82%) and 11% had associated major congenital anomalies. Prenatal detection rate of isolated congenital clubfoot was 22% and increased over time. Among 301 validated congenital clubfoot cases, diagnosis was confirmed for 286 (95%). In conclusion, this large population‐based study found a decreasing trend of congenital clubfoot in Europe after 1999–2002, an increasing prenatal detection rate, and a high standard of coding of congenital clubfoot in EUROCAT.     

Temporal profile of potassium channel dysfunction in cerebrovascular smooth muscle after experimental subarachnoid haemorrhage

The pathogenesis of cerebral vasospasm after subarachnoid haemorrhage (SAH) involves sustained contraction of arterial smooth muscle cells that is maximal 6–8 days after SAH. We reported that function of voltage-gated K⁺ (K_V) channels was significantly decreased during vasospasm 7 days after SAH in dogs. Since arterial constriction is regulated by membrane potential that in turn is determined predominately by K⁺ conductance, the compromised K⁺ channel dysfunction may cause vasospasm. Additional support for this hypothesis would be demonstration that K⁺ channel dysfunction is temporally coincident with vasospasm. To test this hypothesis, SAH was created using the double haemorrhage model in dogs and smooth muscle cells from the basilar artery, which develops vasospasm, were isolated 4 days (early vasospasm), 7 days (during vasospasm) and 21 days (after vasospasm) after SAH and studied using patch-clamp electrophysiology. We investigated the two main K⁺ channels (K_V and large-conductance voltage/Ca²⁺-activated (K_Ca) channels). Electrophysiologic function of K_Ca channels was preserved at all times after SAH. In contrast, function of K_V channels was significantly decreased at all times after SAH. The decrease in cell size and degree of K_V channel dysfunction was maximal 7 days after SAH. The results suggest that K_V channel dysfunction either only partially contributes to vasospasm after SAH or that compensatory mechanisms develop that lead to resolution of vasospasm before K_V channels recover their function.