Transcatheter closure of patent foramen ovale with radiofrequency: acute and intermediate term results in 144 patients

AIMS: Currently available devices for transcatheter closure of patent foramen ovale (PFO) which rely on a permanent implant have limitations, including late complications. The study objective was to evaluate the safety, feasibility, and effectiveness of the PFx Closure System, the first transcatheter technique for PFO closure without an implantable device. METHODS AND RESULTS: A prospective study of 144 patients was conducted at nine clinical sites from October 2005 through August 2007. All patients had a history of cryptogenic stroke, transient ischemic attack, migraines, or decompression illness. The mean balloon stretched diameter of the PFO was 7.9 +/- 2.5 mm. Technical success (successful application of radiofrequency energy) was achieved in 130 patients. One patient required a transfusion as a result of blood loss during the procedure. There were no other major procedural complications. There were no recurrent strokes, deaths, conduction abnormalities, or perforations following the procedure. At a mean follow-up of 6 months, successful closure was achieved in 79 patients (55%). In PFOs with balloon sized or stretched diameters less than 8 mm, the closure rate was 72% (53/74). CONCLUSION: This study demonstrates that transcatheter closure of a PFO without a permanent implant is technically feasible and safe. Further technique and device modifications are required to achieve higher closure rates.

Acetaldehyde as an underestimated risk factor for cancer development: role of genetics in ethanol metabolism

Chronic ethanol consumption is a strong risk factor for the development of certain types of cancer including those of the upper aerodigestive tract, the liver, the large intestine and the female breast. Multiple mechanisms are involved in alcohol-mediated carcinogenesis. Among those the action of acetaldehyde (AA), the first metabolite of ethanol oxidation is of particular interest. AA is toxic, mutagenic and carcinogenic in animal experiments. AA binds to DNA and forms carcinogenic adducts. Direct evidence of the role of AA in alcohol-associated carcinogenesis derived from genetic linkage studies in alcoholics. Polymorphisms or mutations of genes coding for AA generation or detoxifying enzymes resulting in elevated AA concentrations are associated with increased cancer risk. Approximately 40% of Japanese, Koreans or Chinese carry the AA dehydrogenase 2*2 (ALDH2*2) allele in its heterozygous form. This allele codes for an ALDH2 enzyme with little activity leading to high AA concentrations after the consumption of even small amounts of alcohol. When individuals with this allele consume ethanol chronically, a significant increased risk for upper alimentary tract and colorectal cancer is noted. In Caucasians, alcohol dehydrogenase 1C*1 (ADH1C*1) allele encodes for an ADH isoenzyme which produces 2.5 times more AA than the corresponding allele ADH1C*2. In studies with moderate to high alcohol intake, ADH1C*1 allele frequency and rate of homozygosity was found to be significantly associated with an increased risk for cancer of the upper aerodigestive tract, the liver, the colon and the female breast. These studies underline the important role of acetaldehyde in ethanol-mediated carcinogenesis.

Ethanol-induced cytochrome P4502E1 causes carcinogenic etheno-DNA lesions in alcoholic liver disease

Oxidative stress is thought to play a major role in the pathogenesis of hepatocellular cancer (HCC), a frequent complication of alcoholic liver disease (ALD). However, the underlying mechanisms are poorly understood. In hepatocytes of ALD patients, we recently detected by immunohistochemistry significantly increased levels of carcinogenic etheno-DNA adducts that are formed by the reaction of the major lipid peroxidation product, 4-hydroxynonenal (4-HNE) with nucleobases. In the current study, we show that protein-bound 4-HNE and etheno-DNA adducts both strongly correlate with cytochrome P450 2E1 (CYP2E1) expression in patients with ALD (r = 0.9, P < 0.01). Increased levels of etheno-DNA adducts were also detected in the liver of alcohol-fed lean (Fa/?) and obese (fa/fa) Zucker rats. The number of nuclei in hepatocytes stained positively for etheno-DNA adducts correlated significantly with CYP2E1 expression (r = 0.6, P = 0.03). To further assess the role of CYP2E1 in the formation of etheno-DNA adducts, HepG2 cells stably transfected with human CYP2E1 were exposed to ethanol with or without chlormethiazole (CMZ), a specific CYP2E1 inhibitor. Ethanol increased etheno-DNA adducts in the nuclei of CYP2E1-transfected HepG2 cells in a concentration-dependent and time-dependent manner, but not in vector mock-transfected control cells. CMZ blocked the generation of etheno-DNA adducts by 70%-90% (P < 0.01). CONCLUSION: Our data support the assumption that ethanol-mediated induction of hepatic CYP2E1 leading inter alia to highly miscoding lipid peroxidation-derived DNA lesions may play a central role in hepatocarcinogenesis in patients with ALD.

Aufbruch in der Hochschullehre. Kompetenzen und Lernende im Zentrum

Durch die Bologna-Reform an den Hochschulen soll die Beschäftigungsfähigkeit der Studierenden verbessert werden. Damit geht ein verändertes Selbstverständnis von Hochschulunterricht einher. Im Fokus steht der Aufbau von überprüfbaren Kompetenzen. Lehrpersonen aus verschiedenen fachlichen Disziplinen zeigen an konkreten Beispielen ein derart gestaltetes Lehren und Lernen.

Melan-a-positive "pseudomelanocytic nests": a pitfall in the histopathologic and immunohistochemical diagnosis of pigmented lesions on sun-damaged skin

We encountered recently 3 cases with a histopathologic diagnosis of melanoma in situ on sun-damaged skin (male = 2, female = 1; median age: 59 years; range: 52-60 years). The diagnosis was based mainly on the finding of actinic elastosis in the dermis and increased number of melanocytes in the epidermis and was confirmed by strong positivity for Melan-A in single cells and in small nests ("pseudomelanocytic nests"), located at the dermoepidermal junction. Indeed, examination of slides stained with hematoxylin and eosin revealed the presence of marked hyperpigmentation and small nests of partially pigmented cells at the dermoepidermal junction, positive for Melan-A. The histologic and especially the immunohistochemical features were indistinguishable from those of melanoma in situ on chronic sun-damaged skin. In addition, a variably dense lichenoid inflammation was present. Clinicopathologic correlation, however, showed, in all patients, the presence of a lichenoid dermatitis (phototoxic reaction, 1 case; lichen planus pigmentosus, 1 case; and pigmented lichenoid keratosis, 1 case). Our cases clearly show the histopathologic pitfalls represented by lichenoid reactions on chronic sun-damaged skin. Immunohistochemical investigations, especially if performed with Melan-A alone, may lead to confusing and potentially disastrous results. The unexpected staining pattern of Melan-A in cases like ours raises concern about the utility of this antibody in the setting of a lichenoid tissue reaction on chronic sun-damaged skin. It should be underlined that pigmented lesions represent a paradigmatic example of how immunohistochemical results should be interpreted carefully and always in conjunction with histologic and clinical features.

Scabies outbreak in an intensive care unit with 1,659 exposed individuals--key factors for controlling the outbreak

OBJECTIVE: To investigate a large outbreak of scabies in an intensive care unit of a university hospital and an affiliated rehabilitation center, and to establish effective control measures to prevent further transmission. DESIGN: Outbreak investigation. SETTING: The intensive care unit of a 750-bed university hospital and an affiliated 92-bed rehabilitation center. METHODS: All exposed individuals were screened by a senior staff dermatologist. Scabies was diagnosed on the basis of (1) identification of mites by skin scraping, (2) identification of mites by dermoscopy, or (3) clinical examination of patients without history of prior treatment for typical burrows. During a follow-up period of 6 months, the attack rate was calculated as the number of symptomatic individuals divided by the total number of exposed individuals. INTERVENTIONS: All exposed healthcare workers (HCWs) and their household members underwent preemptive treatment. Initially, the most effective registered drug in Switzerland (ie, topical lindane) was prescribed, but this prescription was switched to topical permethrin or systemic ivermectin as a result of the progression of the outbreak. Individuals with any signs or symptoms of scabies underwent dermatological examination. RESULTS: Within 7 months, 19 cases of scabies were diagnosed, 6 in children with a mean age of 3.1 years after exposure to the index patient with HIV and crusted scabies. A total of 1,640 exposed individuals underwent preemptive treatment. The highest attack rate of 26%-32% was observed among HCWs involved in the care of the index patient. A too-restricted definition of individuals at risk, noncompliance with treatment, and the limited effectiveness of lindane likely led to treatment failure, relapse, and reinfestation within families. CONCLUSIONS: Crusted scabies resulted in high attack rates among HCWs and household contacts. Timely institution of hygienic precautions with close monitoring and widespread, simultaneous scabicide treatment of all exposed individuals are essential for control of an outbreak.