Spectrum of digoxin-induced ocular toxicity: a case report and literature review.

BACKGROUND: Digoxin intoxication results in predominantly digestive, cardiac and neurological symptoms. This case is outstanding in that the intoxication occurred in a nonagenarian and induced severe, extensively documented visual symptoms as well as dysphagia and proprioceptive illusions. Moreover, it went undiagnosed for a whole month despite close medical follow-up, illustrating the difficulty in recognizing drug-induced effects in a polymorbid patient. CASE PRESENTATION: Digoxin 0.25 mg qd for atrial fibrillation was prescribed to a 91-year-old woman with an estimated creatinine clearance of 18 ml/min. Over the following 2-3 weeks she developed nausea, vomiting and dysphagia, snowy and blurry vision, photopsia, dyschromatopsia, aggravated pre-existing formed visual hallucinations and proprioceptive illusions. She saw her family doctor twice and visited the eye clinic once until, 1 month after starting digoxin, she was admitted to the emergency room. Intoxication was confirmed by a serum digoxin level of 5.7 ng/ml (reference range 0.8-2 ng/ml). After stopping digoxin, general symptoms resolved in a few days, but visual complaints persisted. Examination by the ophthalmologist revealed decreased visual acuity in both eyes, 4/10 in the right eye (OD) and 5/10 in the left eye (OS), decreased color vision as demonstrated by a score of 1/13 in both eyes (OU) on Ishihara pseudoisochromatic plates, OS cataract, and dry age-related macular degeneration (ARMD). Computerized static perimetry showed non-specific diffuse alterations suggestive of either bilateral retinopathy or optic neuropathy. Full-field electroretinography (ERG) disclosed moderate diffuse rod and cone dysfunction and multifocal ERG revealed central loss of function OU. Visual symptoms progressively improved over the next 2 months, but multifocal ERG did not. The patient was finally discharged home after a 5 week hospital stay. CONCLUSION: This case is a reminder of a complication of digoxin treatment to be considered by any treating physician. If digoxin is prescribed in a vulnerable patient, close monitoring is mandatory. In general, when facing a new health problem in a polymorbid patient, it is crucial to elicit a complete history, with all recent drug changes and detailed complaints, and to include a drug adverse reaction in the differential diagnosis.

Arvostus- ja jaksotussäännökset – FAS vs. IAS - suomalaiset pörssiyritykset 1997-2000

Tämän pro gradu –tutkielman teoriaosan tavoitteena on tutkia vertai-lemalla IAS-tilinpäätöstä (International Accounting Standards) ja IAS-standardeja, sekä vuosina 1993 ja 1997 voimaan tulleita kirjanpitolakeja, ja selvittää millaisia eroja näiden välillä on arvostus- ja jaksotus-säännöksien osalta. Empiirisessä osuudessa tavoitteena on tutkia, ovatko suomalaiset pörssiyhtiöt valinneet Suomen kirjanpitolaista sellaisia vaihtoehtoja, jotka ovat lähempänä IAS-standardeja (arvostus- ja jaksotussäännösten osalta). Tutkimuksen metodologia on lähinnä nomoteettista tutkimusotetta. Tutkimus on komparatiivista analyysiä kirjanpitolain ja IAS-tilinpäätöksen välillä. Tutkimuksessa käsitellään kaikki IAS-standardit, mutta tarkempi tarkastelu käydään arvostus- ja jaksotussäännösten osalta. Näitä eriä verrataan Suomen kirjanpitolain vastaaviin kohtiin. Empiirisessä osassa tutkitaan yritysten vuosikertomuksien avulla onko ns. IAS-yritysten ja FAS-yritysten (Finnish Accounting Standards) välillä eroja. Kuusi tarkastelussa mukana olevaa erää ovat arvostusmenetelmät, hankintameno, alimman arvon periaate, tutkimus- ja kehittämismenot, leasing ja eläkemenot. Eroja löytyy, joten monilla yrityksillä saattaa tulla vielä tulla kiire, sillä tilinpäätökset pitää tehdä IAS:n mukaisesti vuoteen 2005 mennessä

Osakeyhtiön sivuuttaminen, kohdistamisongelmana tulonsaaja - OY vs. osakas

Tutkielman tavoitteena on tutkia veronkiertosäännöksen eli VML 28 §:n soveltamista sivuutettaessa osakeyhtiö verotuksessa. Tutkielma on rajattu tapauksiin, joissa osakeyhtiön tuloa on sivuutettu ja verotettu osakkaan palkkatulona. Tutkielma muodostuu lähinnä kirjallisuuteen ja lainsäädäntöön perustuvista teoriaosista sekä oikeuskäytäntöön pohjautuvasta tutkimusosasta. Tutkimus on oikeusdogmaattinen, eli tarkoituksena on selvittää voimassa olevan lainsäädännön sisältö. Tutkimuksessa on käyty läpi korkeimman hallinto-oikeuden ja hallinto-oikeuksien päätöksiä ja selvitetty näiden avulla kriteerejä, joita voidaan pitää tunnusmerkkeinä vallitsevasta palkkasuhteesta. Tämä saattaa johtaa verotuksessa osakeyhtiön tulon sivuuttamiseen. Päätös osakeyhtiön sivuuttamisesta tehdään kuitenkin aina kokonaisarvioinnin perusteella. Päätöksen lopputulokseen vaikuttaa kuitenkin merkittävästi mm. osakeyhtiön toimeksiantajien lukumäärä. Mikäli toimeksisaaja työskentelee hyvin samankaltaisissa olosuhteissa kuin toimeksiantajan työntekijät, voidaan osakeyhtiö verotuksessa sivuuttaa, mikäli tilanne tulee esille esim. verotarkastuksen yhteydessä.

Anàlisi dels estats financers de l’IBEX 35 vs. CAC 40 en el període 2007-2012

Aquest treball final de grau consisteix en una comparativa, en el període 2007-2012, entre dos grans índexs. L’IBEX 35 per les empreses espanyoles, i el CAC 40 per les empreses franceses. En el treball es presenten els índexs borsaris juntament amb les empreses que els formen. Seguidament es realitzen tot un seguit d’estudis per determinar quin índex borsari presenta una millor situació financera. Els estudis consisteixen en una anàlisi a curt termini, una anàlisi a llarg termini, l’anàlisi econòmic, l’anàlisi de l’ECPN i, com a últim, l’anàlisi de l’EFE. Finalment s’arriben a unes conclusions globals que determinaran quines empreses estan millor, les franceses o les espanyoles.

Prooxidant/Antioxidant Balance in Hypoxia: A Cross-Over Study on Normobaric vs. Hypobaric "Live High-Train Low".

"Live High-Train Low" (LHTL) training can alter oxidative status of athletes. This study compared prooxidant/antioxidant balance responses following two LHTL protocols of the same duration and at the same living altitude of 2250 m in either normobaric (NH) or hypobaric (HH) hypoxia. Twenty-four well-trained triathletes underwent the following two 18-day LHTL protocols in a cross-over and randomized manner: Living altitude (PIO2 = 111.9 ± 0.6 vs. 111.6 ± 0.6 mmHg in NH and HH, respectively); training "natural" altitude (~1000-1100 m) and training loads were precisely matched between both LHTL protocols. Plasma levels of oxidative stress [advanced oxidation protein products (AOPP) and nitrotyrosine] and antioxidant markers [ferric-reducing antioxidant power (FRAP), superoxide dismutase (SOD) and catalase], NO metabolism end-products (NOx) and uric acid (UA) were determined before (Pre) and after (Post) the LHTL. Cumulative hypoxic exposure was lower during the NH (229 ± 6 hrs.) compared to the HH (310 ± 4 hrs.; P<0.01) protocol. Following the LHTL, the concentration of AOPP decreased (-27%; P<0.01) and nitrotyrosine increased (+67%; P<0.05) in HH only. FRAP was decreased (-27%; P<0.05) after the NH while was SOD and UA were only increased following the HH (SOD: +54%; P<0.01 and UA: +15%; P<0.01). Catalase activity was increased in the NH only (+20%; P<0.05). These data suggest that 18-days of LHTL performed in either NH or HH differentially affect oxidative status of athletes. Higher oxidative stress levels following the HH LHTL might be explained by the higher overall hypoxic dose and different physiological responses between the NH and HH.

An outcome and cost analysis of anal fistula plug insertion vs endorectal advancement flap for complex anal fistulae.

AIM: The study aimed to compare the rate of success and cost of anal fistula plug (AFP) insertion and endorectal advancement flap (ERAF) for anal fistula. METHOD: Patients receiving an AFP or ERAF for a complex single fistula tract, defined as involving more than a third of the longitudinal length of of the anal sphincter, were registered in a prospective database. A regression analysis was performed of factors predicting recurrence and contributing to cost. RESULTS: Seventy-one patients (AFP 31, ERAF 40) were analysed. Twelve (39%) recurrences occurred in the AFP and 17 (43%) in the ERAF group (P = 1.00). The median length of stay was 1.23 and 2.0 days (P < 0.001), respectively, and the mean cost of treatment was euro5439 ± euro2629 and euro7957 ± euro5905 (P = 0.021), respectively. On multivariable analysis, postoperative complications, underlying inflammatory bowel disease and fistula recurring after previous treatment were independent predictors of de novo recurrence. It also showed that length of hospital stay ≤ 1 day to be the most significant independent contributor to lower cost (P = 0.023). CONCLUSION: Anal fistula plug and ERAF were equally effective in treating fistula-in-ano, but AFP has a mean cost saving of euro2518 per procedure compared with ERAF. The higher cost for ERAF is due to a longer median length of stay.

New cationic nanovesicular systems containing lysine-based surfactants for topical administration: Toxicity assessment using representative skin cell lines

Many strategies for treating diseases require the delivery of drugs into the cell cytoplasm following internalization within endosomal vesicles. Thus, compounds triggered by low pH to disrupt membranes and release endosomal contents into the cytosol are of particular interest. Cationic nanovesicles have attracted considerable interest as effective carriers to improve the delivery of biologically active molecules into and through the skin. In this study, lipid-based nanovesicles containing three different cationic lysine-based surfactants were designed for topical administration. We used representative skin cell lines and in vitro assays to assess whether the cationic compounds modulate the toxic responses of these nanocarriers. The nanovesicles were characterized in both water and cell culture medium. In general, significant agglomeration occurred after 24 h incubation under cell culture conditions. We found different cytotoxic responses among the formulations, which depended on the surfactant,cell line (3T3, HaCaT, and THP-1) and endpoint assayed (MTT, NRU, and LDH). Moreover, no potential phototoxicity was detected in fibroblast or keratinocyte cells, whereas only a slight inflammatory response was induced, as detected by IL-1a and IL-8 production in HaCaT and THP-1 cell lines, respectively. A key finding of our research was that the cationic charge position and the alkyl chain length of the surfactants determine the nanovesicles resulting toxicity. The charge on the a-amino group of lysine increased the depletion of cell metabolic activity, as determined by the MTT assay, while a higher hydrophobicity tends to enhance the toxic responses of the nanovesicles. The insights provided here using different cell lines and assays offer a comprehensive toxicological evaluation of this group of new nanomaterials.