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A 15 Year old female patient with Sturge Weber Syndrome is presented. This neurocutaneous syndrome consists of angiomatosis of the skin and mucosa as well as the leptomeninges. This case report describes the classic presentation of the syndrome, emphasizing the oral manifestations. The radiographic and CT scan show the typical "tram line" intracranial calcifications. This case report presents a typical case of Sturge Weber Syndrome. It gives the radiological and CT scan findings and the important role played by them in the diagnosis of this syndrome. Emphasis is given to the differentiation of diphenylhydantoin induced gingival hyperplasia from the angiomatous enlargement of the gingiva before any treatment is planned.

Painful peripheral neuropathy belongs to major side-effects limiting cancer chemotherapy. Paclitaxel, widely used to treat several cancers, induces neurological symptoms including burning pain, allodynia, hyperalgesia and numbness. Therefore, identification of drugs that may effectively counteract paclitaxel-induced neuropathic symptoms is crucial. Here, we combined histopathological, neurochemical, behavioral and electrophysiological methods to investigate the natural neurosteroid 3α-androstanediol (3α-DIOL) ability to counteract paclitaxel-evoked peripheral nerve tissue damages and neurological symptoms. Prophylactic or corrective 3α-DIOL treatment (4 mg/kg/2 days) prevented or suppressed PAC-evoked heat-thermal hyperalgesia, cold-allodynia and mechanical allodynia/hyperalgesia, by reversing to normal, decreased thermal and mechanical pain thresholds of PAC-treated rats. Electrophysiological studies demonstrated that 3α-DIOL restored control values of nerve conduction velocity and action potential peak amplitude significantly altered by PAC-treatment. 3α-DIOL also repaired PAC-induced nerve damages by restoring normal neurofilament-200 level in peripheral axons and control amount of 2',3'-cyclic-nucleotide-3'-phosphodiesterase in myelin sheaths. Decreased density of intraepidermal nerve fibers evoked by PAC-therapy was also counteracted by 3α-DIOL treatment. More importantly, 3α-DIOL beneficial effects were not sedation-dependent but resulted from its neuroprotective ability, nerve tissue repairing capacity and long-term analgesic action. Altogether, our results showing that 3α-DIOL efficiently counteracted PAC-evoked painful symptoms, also offer interesting possibilities to develop neurosteroid-based strategies against chemotherapy-induced peripheral neuropathy. This article shows that the prophylactic or corrective treatment with 3α-androstanediol prevents or suppresses PAC-evoked painful symptoms and peripheral nerve dysfunctions in rats. The data suggest that 3α-androstanediol-based therapy may constitute an efficient strategy to explore in humans for the eradication of chemotherapy-induced peripheral neuropathy. journal article research support, non-u.s. gov't 2013 2013 11 15 imported

Vasospasm that develops in association with ergotamine use is a rarely seen but well-understood complication.A case is presented here of multiple fractures in which arteriospasm affecting all the arteries of the lower limb on the same side occurred 10 days posttrauma. In this case, the arteriospasm resulting from ergotamine addiction and high doses of ergotamine, which may be confused with post-traumatic angiospasm, was treated with a marcaine infusion by epidural catheter and heparin, iliomedin and nitronal infusion intravenously.This clinical condition should be borne in mind for all trauma cases determined to have arterial vasospasm, and the use of ergotamine must be queried when taking the anamnesis from the patient. Ergotamin kullanımına bağlı gelişen vazospazm nadir görülen ve iyi bilinen bir komplikasyondur. Bu yazıda çoklu kırığı olan ve travma sonrası 10. günde görülen ve aynı taraf alt ekstremitede tüm arterlerin etkilendiği arteriyospazm olgusu sunuldu. Bu olguda travma sonrası anjiyospazm ile karışabilecek olan ergotamin bağımlılığı ve aşırı doz egotamin kullanımı sonucu ortaya çıkan arteriyospazm; epidural kateter aracılığı ile marcain infüzyonu, intravenöz yolla heparin, iliomedin ve nitronal infüzyonu ile tedavi edildi. Tüm arteryel vazospazm saptanan travma olgularında bu klinik durum akılda tutulmalı ve hastadan anamnez alınırken ergotamin kullanımı mutlaka sorgulanmalıdır.

Mouse strain background can influence vulnerability to excitotoxic neuronal cell death and potentially modulate phenotypes in transgenic mouse models of human disease. Evidence supports a contribution of excitotoxicity to the selective death of medium spiny neurons in Huntington's disease (HD). Here, we assess whether strain differences in excitotoxic vulnerability influence striatal cell death in a knock-in mouse model of HD. Previous studies that evaluated resistance to excitotoxic lesions in several mouse models of HD had variable outcomes. In the present study, we directly compare one model on two different background strains to test the contribution of strain to excitotoxicity-mediated neurodegeneration. Mice of the FVB/N strain, which are highly vulnerable to excitotoxicity, become extremely resistant to quinolinic acid-induced striatal neurodegeneration with age, when carrying a huntingtin (Htt) allele expressing a HD transgene (CAG140). The resistance is much greater than the age-dependent resistance that has been previously reported in YAC128 mice. By 12 months of age, both heterozygous and homozygous FVB.CAG140 mice displayed virtually complete resistance to quinolinic acid-induced striatal neurodegeneration. A similar resistance develops in CAG140 mice on a C57BL/6N background although the effect size is smaller because C57BL/6N mice are already resistant due to genetic background. In a direct comparison with the YAC128 mice, FVB.CAG140 mice have greater resistance. FVB.CAG140 mice are also resistant to neurodegeneration following kainic acid-induced status epilepticus suggesting the existence of a common cellular mechanism that provides protection against multiple types of excitotoxic insult. These findings establish FVB.CAG140 mice as a useful model to investigate the cellular and molecular mechanisms that confer neuroprotection against excitotoxicity.

Apelin is a hypotensive peptide. Red blood cell (RBC) deformability and aggregation were previously demonstrated to be altered in various hypertension (HT) models. In the present study, we investigated possible alterations in RBC deformability and aggregation in response to apelin in DOCA-salt hypertensive rats. Rats were randomly divided into 4 groups: Control (C), Hypertension (HT), Apelin, and Apelin + Hypertension (Apelin + HT). HT was induced by injection of DOCA-salt (25 mg/kg, s.c.) twice weekly for 4 weeks, whereas apelin was administered (200 μg/kg i.p.) for 17 days. RBC deformability and aggregation were determined using an ektacytometer. Blood pressure was monitored using a tail cuff system. Systolic blood pressure was decreased in the Apelin and Apelin + HT groups and increased in the HT group. RBC deformability was not significantly altered in the HT group. Apelin administration induced a statistically significant increase in RBC deformability in control animals, whereas erythrocytic deformability in the Apelin + HT group was decreased compared to the Apelin group. RBC aggregation of hypertensive animals was reduced compared to controls. Apelin administration induced increased RBC aggregation in hypertensive rats. Our results showed favorable effects of apelin on RBC deformability in control animals, but not in hypertensive rats. © 2014 - IOS Press.

The potential use of functionalized carbon nanotubes (f-CNTs) for drug and gene delivery to the central nervous system (CNS) and as neural substrates makes the understanding of their in vivo interactions with the neural tissue essential. The aim of this study was to investigate the interactions between chemically functionalized multi-walled carbon nanotubes (f-MWNTs) and the neural tissue following cortical stereotactic administration. Two different f-MWNT constructs were used in these studies: shortened (by oxidation) amino-functionalized MWNT (oxMWNT-NH3(+)) and amino-functionalized MWNT (MWNT-NH3(+)). Parenchymal distribution of the stereotactically injected f-MWNTs was assessed by histological examination. Both f-MWNT were uptaken by different types of neural tissue cells (microglia, astrocytes and neurons), however different patterns of cellular internalization were observed between the nanotubes. Furthermore, immunohistochemical staining for specific markers of glial cell activation (GFAP and CD11b) was performed and secretion of inflammatory cytokines was investigated using real-time PCR (qRT-PCR). Injections of both f-MWNT constructs led to a local and transient induction of inflammatory cytokines at early time points. Oxidation of nanotubes seemed to induce significant levels of GFAP and CD11b over-expression in areas peripheral to the f-MWNT injection site. These results highlight the importance of nanotube functionalization on their interaction with brain tissue that is deemed critical for the development nanotube-based vector systems for CNS applications. The potential use of functionalized carbon nanotubes (f-CNTs) for drug and gene delivery to the central nervous system (CNS) and as neural substrates makes the understanding of their in vivo interactions with the neural tissue essential. The aim of this study was to investigate the interactions between chemically functionalized multi-walled carbon nanotubes (f-MWNTs) and the neural tissue following cortical stereotactic administration. Two different f-MWNT constructs were used in these studies: shortened (by oxidation) amino-functionalized MWNT (oxMWNT-NH3+) and amino-functionalized MWNT (MWNT-NH3+). Parenchymal distribution of the stereotactically injected f-MWNTs was assessed by histological examination. Both f-MWNT were uptaken by different types of neural tissue cells (microglia, astrocytes and neurons), however different patterns of cellular internalization were observed between the nanotubes. Furthermore, immunohistochemical staining for specific markers of glial cell activation (GFAP and CD11b) was performed and secretion of inflammatory cytokines was investigated using real-time PCR (qRT-PCR). Injections of both f-MWNT constructs led to a local and transient induction of inflammatory cytokines at early time points. Oxidation of nanotubes seemed to induce significant levels of GFAP and CD11b over-expression in areas peripheral to the f-MWNT injection site. These results highlight the importance of nanotube functionalization on their interaction with brain tissue that is deemed critical for the development nanotube-based vector systems for CNS applications. © 2013 Bardi et al.

Background: Infection of burn wounds is a serious problem because it can delay healing, increase scarring and invasive infection may result in the death of the patient. Antibiotic prophylaxis is one of several interventions that may prevent burn wound infection and protect the burned patient from invasive infections. Objectives: To assess the effects of antibiotic prophylaxis on rates of burn wound infection. Search methods: In January 2013 we searched the Wounds Group Specialised Register; The Cochrane Central Register of Controlled Trials (CENTRAL); Ovid MEDLINE; Ovid MEDLINE - In-Process & Other Non-Indexed Citations (2013); Ovid EMBASE; EBSCO CINAHL and reference lists of relevant articles. There were no restrictions with respect to language, date of publication or study setting. Selection criteria: All randomised controlled trials (RCTs) that evaluated the efficacy and safety of antibiotic prophylaxis for the prevention of BWI. Quasi-randomised studies were excluded. Data collection and analysis: Two review authors independently selected studies, assessed the risk of bias, and extracted relevant data. Risk ratio (RR) and mean difference (MD) were estimated for dichotomous data and continuous data, respectively. When sufficient numbers of comparable RCTs were available, trials were pooled in a meta-analysis to estimate the combined effect. Main results: This review includes 36 RCTs (2117 participants); twenty six (72%) evaluated topical antibiotics, seven evaluated systemic antibiotics (four of these administered the antibiotic perioperatively and three administered upon hospital admission or during routine treatment), two evaluated prophylaxis with non absorbable antibiotics, and one evaluated local antibiotics administered via the airway. The 11 trials (645 participants) that evaluated topical prophylaxis with silver sulfadiazine were pooled in a meta analysis. There was a statistically significant increase in burn wound infection associated with silver sulfadiazine compared with dressings/skin substitute (OR = 1.87; 95% CI: 1.09 to 3.19, I2 = 0%). These trials were at high, or unclear, risk of bias. Silver sulfadiazine was also associated with significantly longer length of hospital stay compared with dressings/skin substitute (MD = 2.11 days; 95% CI: 1.93 to 2.28). Systemic antibiotic prophylaxis in non-surgical patients was evaluated in three trials (119 participants) and there was no evidence of an effect on rates of burn wound infection. Systemic antibiotics (trimethoprim-sulfamethoxazole) were associated with a significant reduction in pneumonia (only one trial, 40 participants) (RR = 0.18; 95% CI: 0.05 to 0.72) but not sepsis (two trials 59 participants) (RR = 0.43; 95% CI: 0.12 to 1.61). Perioperative systemic antibiotic prophylaxis had no effect on any of the outcomes of this review. Selective decontamination of the digestive tract with non-absorbable antibiotics had no significant effect on rates of all types of infection (2 trials, 140 participants). Moreover, there was a statistically significant increase in rates of MRSA associated with use of non-absorbable antibiotics plus cefotaxime compared with placebo (RR = 2.22; 95% CI: 1.21 to 4.07). There was no evidence of a difference in mortality or rates of sepsis with local airway antibiotic prophylaxis compared with placebo (only one trial, 30 participants). Authors' conclusions: The conclusions we are able to draw regarding the effects of prophylactic antibiotics in people with burns are limited by the volume and quality of the existing research (largely small numbers of small studies at unclear or high risk of bias for each comparison). The largest volume of evidence suggests that topical silver sulfadiazine is associated with a significant increase in rates of burn wound infection and increased length of hospital stay compared with dressings or skin substitutes; this evidence is at unclear or high risk of bias. Currently the effects of other forms of antibiotic prophylaxis on burn wound infection are unclear. One small study reported a reduction in incidence of pneumonia associated with a specific systematic antibiotic regimen. © 2013 The Cochrane Collaboration.

BACKGROUND: Diabetes is a major threat to public health in the United States and worldwide. Understanding the role of environmental chemicals in the development or progression of diabetes is an emerging issue in environmental health. OBJECTIVE: We assessed the epidemiologic literature for evidence of associations between persistent organic pollutants (POPs) and type 2 diabetes. METHODS: Using a PubMed search and reference lists from relevant studies or review articles, we identified 72 epidemiological studies that investigated associations of persistent organic pollutants (POPs) with diabetes. We evaluated these studies for consistency, strengths and weaknesses of study design (including power and statistical methods), clinical diagnosis, exposure assessment, study population characteristics, and identification of data gaps and areas for future research. CONCLUSIONS: Heterogeneity of the studies precluded conducting a meta-analysis, but the overall evidence is sufficient for a positive association of some organochlorine POPs with type 2 diabetes. Collectively, these data are not sufficient to establish causality. Initial data mining revealed that the strongest positive correlation of diabetes with POPs occurred with organochlorine compounds, such as trans-nonachlor, dichlorodiphenyldichloroethylene (DDE), polychlorinated biphenyls (PCBs), and dioxins and dioxin-like chemicals. There is less indication of an association between other nonorganochlorine POPs, such as perfluoroalkyl acids and brominated compounds, and type 2 diabetes. Experimental data are needed to confirm the causality of these POPs, which will shed new light on the pathogenesis of diabetes. This new information should be considered by governmental bodies involved in the regulation of environmental contaminants.

An increasing number of women are diagnosed with cancer during pregnancy and lactation. Women are usually advised to interrupt breastfeeding during systemic anticancer treatment for fear of serious adverse effects to the nursed infant. However, the issue is poorly addressed in the literature and very few studies have evaluated the safety of breastfeeding during or after cytotoxic drugs or target agents administration. In this review we will analyze the available evidence that addresses the issue of anticancer drugs, targeted agents, antiemetics and growth-factors excretion in human milk. This could serve as a unique resource that may aid physicians in the management of breastfeeding cancer patients interested in maintaining lactation during treatment.

Background: Catenins are adhesion molecules that link cadherin molecules to cytoskeleton. The association of catenins to cadherins is a key step in the function of intact adhesion complexes, and alterations in catenin molecules can lead to the disruption of cell-cell adhesion, resulting in tumour aggressiveness and invasiveness in neoplastic disease. Material and methods: Urothelial lesions were chemically induced by BBN in ICR mice, and evaluated by immunohistochemistry to determine the staining pattern of β-cathenin. Results: In normal urothelium, 70% of β-catenin expression was at the cellular membrane level. In simple hyperplasia, the same pattern was observed in 66.67% of lesions. Nodular hyperplasia was observed only once with a membrane pattern. In dysplasia a 100% cytoplasmic pattern was seen. Invasive carcinoma showed an heterogeneous pattern with areas where the membrane, cytoplasm or nucleus were stained. On squamous metaplasia, the staining pattern was confined to the membrane, however, with heterogeneous immunoreactivity. Conclusions: β-cathenin is a good marker of the progression of bladder tumours chemically induced in mice by BBN. This work was supported by Portuguese Foundation for Science and Technology, Center for Studies in Education, Technologies and by Health and by strategic project PEst-OE/CED/UI4016/2011

Elvitegravir is a once daily inhibitor of HIV-1 integrase boosted by ritonavir. We aimed to compare the efficacy and safety of elvitegravir with raltegravir, another HIV-1 integrase inhibitor, in patients in whom previous antiretroviral treatment failed.We conducted a randomised, double-blind, double-dummy, phase 3 study at 234 sites in 13 countries. Eligible patients had plasma HIV RNA of 1000 copies per mL or greater, any CD4 cell count, and resistance to or 6 months' experience with at least two classes of antiretroviral drugs. They received an open-label background regimen of a fully active, ritonavir-boosted protease inhibitor and a second agent. We randomly allocated patients (1:1) by computer with a block size of four to receive either elvitegravir 150 mg once daily (n=361; 85 mg dose if given with atazanavir, or lopinavir with ritonavir) or raltegravir 400 mg twice daily (n=363). Placebo tablets were given to mask the difference in daily dosing. The primary endpoint was achievement and maintenance of virological response (HIV RNA50 copies per mL) through week 48. Non-inferiority was prespecified with a margin of 10%. We did a modified intention-to-treat analysis. This study is registered with ClinicalTrials.gov, number NCT00708162.Ten patients allocated elvitegravir and 12 assigned raltegravir were excluded from the analysis (either for protocol violations or because they did not receive treatment). 207 (59%) of 351 patients allocated elvitegravir achieved virological response compared with 203 (58%) of 351 assigned raltegravir (treatment difference 1·1%, 95% CI -6·0 to 8·2), meeting the criterion for non-inferiority (p=0·001). Three patients allocated elvitegravir had serious adverse events related to study drugs compared with seven assigned raltegravir; two and eight patients died, respectively. More individuals assigned elvitegravir reported diarrhoea up to week 48 (p=0·023), and more patients assigned raltegravir had grade 3 or 4 rises in alanine aminotransferase (p=0·020) or aspartate aminotransferase (p=0·009).Elvitegravir used in combination with a ritonavir-boosted protease inhibitor in treatment-experienced patients has similar efficacy and safety to raltegravir. Since elvitegravir can be given once a day compared with twice a day for raltegravir, elvitegravir might improve patients' adherence.Gilead Sciences.

Background Endotoxin exposure has been associated with asthma exacerbations and increased asthma prevalence. However, there is little data regarding personal exposure to endotoxin in children at risk, or the relation of personal endotoxin exposure to residential or ambient airborne endotoxin. The relation between personal endotoxin and personal air pollution exposures is also unknown. Methods We characterized personal endotoxin exposures in 45 school children with asthma ages 9-18 years using 376 repeated measurements from a PM2.5 active personal exposure monitor. We also assayed endotoxin in PM2.5 samples collected from ambient regional sites (N = 97 days) and from a subset of 12 indoor and outdoor subject home sites (N = 109 and 111 days, respectively) in Riverside and Whittier, California. Endotoxin was measured using the Limulus Amoebocyte Lysate kinetic chromogenic assay. At the same time, we measured personal, home and ambient exposure to PM2.5 mass, elemental carbon (EC), and organic carbon (OC). To assess exposure relations we used both rank correlations and mixed linear regression models, adjusted for personal temperature and relative humidity. Results We found small positive correlations of personal endotoxin with personal PM2.5 EC and OC, but not personal PM2.5 mass or stationary site air pollutant measurements. Outdoor home, indoor home and ambient endotoxin were moderately to strongly correlated with each other. However, in mixed models, personal endotoxin was not associated with indoor home or outdoor home endotoxin, but was associated with ambient endotoxin. Dog and cat ownership were significantly associated with increased personal but not indoor endotoxin. Conclusions Daily fixed site measurements of endotoxin in the home environment may not predict daily personal exposure, although a larger sample size may be needed to assess this. This conclusion is relevant to short-term exposures involved in the acute exacerbation of asthma.

Objectives Several case reports of lupus-like syndrome suggest that statins could have triggered the development of this rare autoimmune disease. However, data on the association between statin use and lupus-like syndrome are scarce. We assessed whether there was an association between statin use and the occurrence of lupus-like syndrome. Methods A case/noncase study based on individual case safety reports listed in the World Health Organization global individual case safety reports database (VigiBase) was conducted. According to World Health Organization adverse reaction terminology, cases were defined as reports of lupus-like syndrome. Each case was matched with 5 noncases by age, gender, and time of reporting. Use of statins was classified according to the Anatomical Therapeutic Chemical classification code system. Covariates, ie, use of corticosteroids, immunosuppressive drugs, nonsteroidal anti-inflammatory drugs, antidepressants, antiepileptics, proton pump inhibitors, and cardiovascular drugs, were determined. Multivariate logistic regression was used to calculate the reporting odds ratios with 95% confidence intervals. Results We identified 3362 reports of lupus-like syndrome as cases and 27,092 reports of other adverse drug reactions as noncases. Statins were more frequently reported as suspected drug in cases (3.2%) than in noncases (1.5%). After adjustment for several covariates, statins were associated with the reporting of lupus-like syndrome (reporting odds ratios 2.01; 95% confidence intervals 1.61-2.51). Conclusions We found an association between reporting of statins and lupus-like syndrome. Further studies are needed to confirm this finding in more detail and establish causality.

Three years after the introduction of natalizumab (NA) therapy for the second line treatment of relapsing-remitting multiple sclerosis (MS), Italian MS centers critically reviewed the scientific literature and their own clinical experience. Natalizumab was shown to be highly efficacious in the treatment of MS. However, the risk of progressive multifocal leukoencephalopathy was confirmed and defined better. This article summarizes the MS-SIN Study Group recommendations on the use of NA in MS, with particular reference to the appropriate selection and monitoring of patients as well as to the management of adverse events.

The primary objective of this open-label, two chemotherapy arm, phase 4 study was to evaluate the safety and efficacy of new developed recombinant granulocyte colony-stimulating factor (rG-CSF) used to prevent neutropenia-related complications in patients with metastatic breast cancer treated with docetaxel (75 mg/m2) and doxorubicin (50 mg/m2) or docetaxel (100 mg/m2) alone. Material and Methods. A total of 50 patients who were treated with a maximum of 6 cycles of either docetaxel-doxorubicin (36 patients) or docetaxel alone (14 patients) every 21 days were recruited from 3 centers in Lithuania. All the patients received study medication rG-CSF at a dosage of 5 μg/kg per day (Sicor Biotech UAB, Teva Group) from day 2 of each cycle and continued for minimum 5 days or until absolute neutrophil count reached ≥1.5×109/L. Results. A total of 611 adverse events were reported. Most of them were related to myelotoxic chemotherapy. Two patients withdrew due to adverse events (neuropathy and bone pain). One patient died possibly because of pulmonary thromboembolism. The most frequently reported adverse events related to study drug in the docetaxel-doxorubicin group and docetaxel groups were leukocytosis (22% and 21%, respectively), bone pain (19% and 21%, respectively), and headache (8% and 14%, respectively). The incidence of grade 4 neutropenia in both the groups was 47% and 29%, respectively, in all cycles and 42% and 21%, respectively, in cycle 1. The incidence of febrile neutropenia was 8% in cycle 1 and 14% across all cycles. The mean duration of febrile neutropenia was 2.1 days (SD, 1.9) in cycle 1 and 2.14 days (SD 2.0) across all cycles in both the treatment groups. Conclusion. [...].

Red meat intake is associated with an increased risk of colorectal cancer. We have previously shown that haemin, Hb and red meat promote carcinogen-induced preneoplastic lesions, aberrant crypt foci (ACF), in the colon of rats. We have also shown that dietary calcium phosphate inhibits haemin-induced promotion and normalises faecal lipoperoxides and cytotoxicity. Unexpectedly, high-calcium phosphate control diet-fed rats had more preneoplastic lesions in the colon than low-Ca control diet-fed rats. The present study was designed to find a Ca supplementation with no adverse effect, by testing several doses and types of Ca salts. Onein vitrostudy and two short-term studies in rats identified calcium carbonate as the most effective Ca salt to bind haemin vitroand to decrease faecal biomarkers previously associated with increased carcinogenesis: faecal water cytotoxicity and thiobarbituric acid-reactive substances. A long-term carcinogenesis study in dimethylhydrazine-injected rats demonstrated that a diet containing 100 μmol/g calcium carbonate did not promote ACF, in contrast with a previously tested calcium phosphate diet. The results suggest that calcium carbonate, and not calcium phosphate, should be used to reduce haem-associated colorectal cancer risk in meat eaters. They support the concept that the nature of the associated anion to a protective metal ion is important for chemoprevention.

High-risk human papillomaviruses (HPVs) contribute to cervical and other anogenital cancers, and they are also linked etiologically to a subset of head and neck squamous cell carcinomas (HNSCC). We previously established a model for HPV-associated HNSCC in which we treated transgenic mice expressing the papillomaviral oncoproteins with the chemical carcinogen 4-nitroquinoline-1-oxide (4-NQO). We found that the HPV-16 E7 oncoprotein was highly potent in causing HNSCC, and its dominance masked any potential oncogenic contribution of E6, a second papillomaviral oncoprotein commonly expressed in human cancers. In the current study, we shortened the duration of treatment with 4-NQO to reduce the incidence of cancers and discovered a striking synergy between E6 and E7 in causing HNSCC. Comparing the oncogenic properties of wild-type versus mutant E6 genes in this model for HNSCC uncovered a role for some but not other cellular targets of E6 previously shown to contribute to cervical cancer. © 2010 Elsevier Inc. 407 60 67 Cited By :28

Background: Obestatin plays a key role in the process of energy balance maintenance with an anorectic effect. The main aim of the study was to evaluate obestatin in uremic patients to determine whether it is correlated with nutritional and inflammatory status. Methods: We studied plasma obestatin in uremic patients (n = 50) undergoing hemodialysis therapy and in healthy subjects. Plasma obestatin was measured using an ELISA kit. Results: Obestatin levels in uremic patients were lower than in healthy subjects (p < 0.0001). Patients with a body mass index (BMI) >23 had lower obestatin levels than those with a BMI Conclusions: Based on the present observational data, obestatin might be implicated in the inflammatory state and the disturbances of calcium/phosphate metabolism of hemodialysis patients. However, further studies are warranted to determine whether this hormone plays a key role in contributing to malnutrition and to the chronic inflammatory process.

Epileptic seizures associated with intrathecal baclofen (ITB) application have been observed in patients with traumatic brain injury. A higher incidence of seizures has also been reported in patients with multiple sclerosis (MS) receiving ITB. To our knowledge, no case of a first epileptic seizure has been reported in the context of ITB bolus testing in MS. We report a 41-year-old female patient with primary progressive MS receiving olanzapine and oxcarbazepine for psychotic disorder. Five years prior she began to develop severe spastic quadriparesis, rendering her a candidate for ITB treatment. After ITB test bolus application, however, she experienced a first epileptic seizure. Our observation indicates that ITB may trigger seizures in patients with MS. The observed seizure occurred during ITB bolus testing despite antiepileptic co-medication, which concurs with previous reports suggesting that rapid changes in the dose of ITB may carry a higher risk of seizure induction.

A 40‐year‐old white woman with a history of venlafaxine abuse was admitted to our emergency department within 3 days after attempting suicide. On admission, blood pressure was 140/85 mm Hg with 70 beats per minute. The resting 12‐lead ECG showed a significant ST‐segment elevation in the anterolateral leads consistent with acute anterolateral myocardial infarction (anterolateral AMI). Noninvasive monitoring of blood oxygen saturation showed 97% while she was breathing room air. Laboratory findings showed the increase of troponin I up to 16 µg/L (normal range, 0–0.05 µg/L) and creatine kinase MB subunit levels up to 166 U/L (normal range, 0–25 U/L). An emergency coronary angiogram was normal. Venlafaxine is generally prescribed for the treatment of major depression, as well as, generalized and social anxiety. This is the first time in the literature that we describe an association between myocardial infarction and an overdose with venlafaxine. Copyright © 2010 Wiley Periodicals, Inc.

With longevity, postoperative cognitive decline in the elderly has emerged as a major health concern for which several factors have been implicated, one of the most recent being the role of anaesthetics. Interactions of anaesthetic agents and different targets have been studied at the molecular, cellular and structural anatomical levels. Recent in vitro nuclear magnetic resonance spectroscopy studies have shown that several anaesthetics act on the oligomerisation of amyloid beta peptide. Uncontrolled production, oligomerisation and deposition of amyloid beta peptide, with subsequent development of amyloid plaques, are fundamental steps in the generation of Alzheimer's disease. Amyloid beta peptide is naturally present in the central nervous system, and is found at higher tissue concentrations in the elderly. We argue that administering certain general anaesthetics to elderly patients may worsen amyloid beta peptide oligomerisation and deposition and thus increase the risk of developing postoperative cognitive dysfunction. The aim of this review is to highlight the clinical aspects of postoperative cognitive dysfunction and to find plausible links between possible anaesthetic effects and the molecular pathological mechanism of Alzheimer's disease. It is hoped that our hypothesis will stimulate further enquiry, especially triggering research into elucidating those anaesthetics that may be more suitable when cognitive dysfunction is a particular concern.

1533-4406 (Electronic) 0028-4793 (Linking) Comparative Study Journal Article Multicenter Study Randomized Controlled Trial Research Support, Non-U.S. Gov't; BACKGROUND: Fingolimod (FTY720), a sphingosine-1-phosphate-receptor modulator that prevents lymphocyte egress from lymph nodes, showed clinical efficacy and improvement on imaging in a phase 2 study involving patients with multiple sclerosis. METHODS: In this 12-month, double-blind, double-dummy study, we randomly assigned 1292 patients with relapsing-remitting multiple sclerosis who had a recent history of at least one relapse to receive either oral fingolimod at a daily dose of either 1.25 or 0.5 mg or intramuscular interferon beta-1a (an established therapy for multiple sclerosis) at a weekly dose of 30 microg. The primary end point was the annualized relapse rate. Key secondary end points were the number of new or enlarged lesions on T(2)-weighted magnetic resonance imaging (MRI) scans at 12 months and progression of disability that was sustained for at least 3 months. RESULTS: A total of 1153 patients (89%) completed the study. The annualized relapse rate was significantly lower in both groups receiving fingolimod--0.20 (95% confidence interval [CI], 0.16 to 0.26) in the 1.25-mg group and 0.16 (95% CI, 0.12 to 0.21) in the 0.5-mg group--than in the interferon group (0.33; 95% CI, 0.26 to 0.42; P

Recent data reported an association between VEGF-A genotype of tumors and median overall survival as well as grade 3 or 4 hypertension when using bevacizumab in metastatic breast cancer. In the present case we report a discordant VEGF-A genotype between tumor and normal tissue in a patient with a responsive hepatic lesion of chemoresistant breast cancer treated with bevacizumab and paclitaxel. Moreover, we show that, despite the very low VEGF-A protein expression, the neoplastic lesion was well vascularized and responded to bevacizumab therapy. The discordance of VEGF-A polymorphisms in tumor and germline DNA may suggest the importance of obtaining both information in order to predict a superior overall survival or a lower risk of hypertension in patients treated with taxanes and bevacizumab.

Hepatic angiosarcoma is a rare primary tumor of the liver with a mesenchymal origin. Diagnosis is difficult because clinical manifestations and imaging studies are inconclusive. In many cases a diagnosis is obtained during necropsy, not being apparent during the course of disease. It is associated with several risk factors, but these contribute to explaining only a few of all reported cases. When clinical manifestations begin progression is often fast, and possibilities for curative treatment are limited. We report two cases of hepatic angiosarcoma. In the first one, our patient had an insidious initial course, and then suddenly presented with hepatic failure followed by acute respiratory distress. A diagnosis was reached during necropsy. In the second case, we initiated the study of a chronic liver disease using fine-needle aspiration biopsy, which showed findings suggestive of hepatic angiosarcoma. In the following weeks the patient started on a torpid clinic course, and died from multiple organ failure. El angiosarcoma hepático es una neoplasia de estirpe mesenquimal de baja frecuencia y difícil diagnóstico por su forma inespecífica de manifestarse clínica y radiológicamente. Tanto es así que muchos diagnósticos se obtienen mediante necropsia, no siendo posible poner de manifiesto la enfermedad durante su curso. Se asocia a diferentes agentes etiológicos, pero en la mayoría de los casos no es posible establecer una exposición concreta a ninguno de ellos. Cuando comienza a manifestarse, la evolución suele ser rápida y las opciones de tratamiento curativo son escasas. Presentamos en nuestro trabajo dos casos de angiosarcoma hepático. En el primero, el paciente sufre en principio una evolución insidiosa, presentando al fin, y de forma abrupta, un cuadro de insuficiencia hepática seguido de distrés respiratorio, falleciendo por este motivo. El diagnóstico se alcanza en la necropsia. En el segundo caso se inicia un estudio de hepatopatía en el cual se indica una PAAF. Esta es informada como hallazgos compatibles con angiosarcoma hepático. El paciente presenta en las semanas ulteriores una evolución tórpida, falleciendo en fracaso multiorgánico.

Tyrimo tikslas. Ištirti rekombinacinio granuliocitų kolonijas stimuliuojamojo faktoriaus (rGKSF), skiriamo neutropenijos ir jos sukeltų komplikacijų profilaktikai, sergančiosioms metastazavusiu krūties vėžiu ir gydomoms citotoksiniais chemoterapiniais preparatais (docetakseliu ir doksorubicinu), saugumą ir veiksmingumą. Tyrimo medžiaga ir metodai. Trijuose Lietuvos centruose į tyrimą įtrauktos 36 pacientės, sergančios metastazavusiu krūties vėžiu, kurioms buvo skirta pirmos eilės chemoterapija docetakseliu (75 mg/m2) ir doksorubicinu (50 mg/m2) (AT). Chemoterapinių preparatų skirta iki šešių chemoterapijos kursų, kas 21 dieną, arba iki ligos progresavimo. Pacientėms buvo skirta rGKSF 5 mikrogramų kilogramui kūno svorio per dieną dozė pradedant nuo antrosios dienos pirmojo chemoterapijos kurso. Rezultatai. Dažniausiai pasireiškę nepageidaujami reiškiniai, susiję su rGKSF, buvo leukocitozė, kaulų skausmas ir galvos skausmas, pasireiškimo dažnis 22, 19, 8 proc., atitinkamai. Tyrimo metu pasireiškę nepageidaujami reiškiniai būdingi šios grupės preparatams šioje pacienčių populiacijoje. Febrilinės neutropenijos dažnis visų chemoterapijos kursų metu buvo 14 proc. Vidutinė febrilinės neutropenijos trukmė visų kursų metu buvo 2,14 dienos. Chemoterapijos kursų atidėjimo dažnis buvo 2 proc. Chemopreparatų dozės mažinimo atvejų nebuvo. Antibiotikų, skiriamų į veną febrilinei neutropenijai gydyti, poreikio dažnis buvo 19 proc. Gyvenimo kokybės tyrimas parodė statistiškai reikšmingą pacienčių emocinės būsenos pagerėjimą ir skausmo sumažėjimą. Lyginant su anksčiau paskelbtais duomenimis, rGKSF saugumo ir veiksmingumo savybės šio tyrimo metu atitiko kitų rinkoje esančių rGKSF preparatų savybes. Išvada. Pirminė neutropenijos ir jos sukeltų komplikacijų profilaktika rGKSF buvo saugi ir veiksminga sergančiosioms metastazavusiu krūties vėžiu ir gydomoms docetakselio ir doksorubicino deriniu.

We report a case of spontaneous hyphaema with no apparent predisposing cause except the assumption of an excessive warfarin dosage leading to over-anticoagulation; a literature search performed in Medline revealed only one case of spontaneous hyphaema resulting from warfarin therapy and no other ocular cause [1]. In case of overdosing, the incidence of warfarin-related hyphaemas could be higher, and it should be taken into account in clinical practice. A 72-year-old woman presented complaining of blurred vision and discomfort in her right eye of 1 day's duration. She had been taking 5 mg of warfarin sodium daily for atrial fibrillation for 2 years; she denied any other systemic disorder except hypertension and the history was negative for eye disease or treatment. The International Normalized Ratio (INR)/dosing was stable and the INR was regularly monitored every 3–4 weeks. The patient's compliance with the regimen was good; two episodes of self-limiting subconjunctival haemorrhage during the previous 12 months were reported. There was no recent illness and no new concurrent medications. Slit-lamp examination of the right eye revealed diffuse heame within the anterior chamber and a 2-mm layered hyphaema. No iris abnormalities were present. Gonioscopy was unremarkable and dilated fundus examination was within normal limits for age. The left eye was normal. Haematological evaluation disclosed prolonged activated partial thromboplastic time of 73.4 s (normal range 26–36 s) and INR of 5.56 (normal range 0.80–1.20). By the consent of the patient's haematologist, warfarin was discontinued until a subsequent haematological evaluation 3 days later. At that time she was asymptomatic and visual acuity was normal (best corrected visual acuity 1.0 decimels, or 20/20 snellen). The anterior chamber had cleared completely; minimum blood was visible on the iris surface and within the anterior iris stroma at 6 o'clock position. Gonioscopy and fundus examination were still negative for ocular abnormalities. Warfarin was reintroduced at a dose of 2.5 mg/day and the INR monitored 3 days later; the ocular bleeding has not recurred up to now. The use of the Naranjo probability scale revealed that the adverse event was possibly due to warfarin therapy (final score 4). Most spontaneous hyphaemas are associated with iris abnormalities, but this condition has been reported to occur from a variety of ocular causes (Table 1). Nunziata has reported a case of bilateral hyphaema in which no predisposing condition could be identified [2]. Table 1 Possible causes of hyphaema Various systemic conditions have been associated with spontaneous hyphaemas: haematological alterations such as sickle cell disease, acute lymphoblastic and myelocytic leukaemia, lymphomas, juvenile xanthogranuloma, histiocytosis X and many rheumatological disorders causing uveitis, such as Reiter's syndrome or ankylosing spondylitis (Table 1). Warfarin is the most commonly used drug for outpatient anticoagulation therapy and its main side-effect is bleeding; theoretically, this can occur in all organs, including the eye. Ocular bleeding can occur as subconjunctival, vitreal, retinal or choroidal haemorrhages; bloody tears have been also reported [3]. Cases of bleeding within the anterior chamber in non-operated eyes and linked to warfarin therapy in eyes with predisposing abnormalities have been previously reported by Greenfield and coworkers [4]. Aspirin and Ginkgo biloba also have been linked with spontaneous hyphaema [5, 6]. Ocular haemorrhages in warfarinized patients can be sight-threatening events, but often they are clinically benign and resolve without any sequelae. However, they may be the only indication that the patient is at risk for major bleeding episodes linked to over-anticoagulation. A number of studies have shown what amounts to an exponential increase in haemorrhagic complications as the INR increases to >5.0 [7]. Patients on warfarin therapy should be instructed to notice any change in their quality of vision; should any intraocular bleeding be diagnosed by the ophthalmologist, patients require immediate blood work and consultation with their primary care provider.

O colesteatoma de orelha média atingia mais de 5 milhões de pessoas até a década de 80. Vários modelos animais já foram utilizados para alternativas de tratamento do colesteatoma sem sucesso. OBJETIVO: Estudar os efeitos do ácido trans-retinóico, uso tópico na orelha externa em cobaias, na inibição da formação do colesteatoma de orelha média induzido pelo propilenoglicol. Estudo experimental prospectivo. MATERIAL E MÉTODOS: 25 cobaias foram submetidas à aplicação de propilenoglicol a 100% na bula timpânica bilateralmente e uma solução de ácido trans-retinóico foi aplicada topicamente (total de 5 aplicações) na orelha externa, região justa-timpânica, na orelha direita, enquanto na orelha esquerda aplicou-se solução fisiológica (orelha controle). As cobaias foram sacrificadas após 6 semanas do procedimento inicial e os ossos temporais foram separados, fixados e descalcificados, para análise macroscópica e histológica. RESULTADOS: Os achados macroscópicos evidenciaram a presença e suspeita de colesteatoma em 25% das orelhas direitas e 85% das orelhas esquerdas (P=0,0003*). Os achados histológicos dos 40 ossos temporais evidenciaram a presença de colesteatoma em 30% das orelhas direitas e 75% das orelhas esquerdas (P=0,0104*). CONCLUSÃO: O uso tópico do ácido trans-retinóico é efetivo na inibição da formação de colesteatoma induzido pelo propilenoglicol em cobaias. Middle ear cholesteatoma affected more than 5 million people until the 80`s. Many animal models were used, unsuccessfully, to study an alternative therapy to cholesteatoma. AIM: observe the effect of the trans-retinoic acid in the inhibition of middle ear cholesteatomas induced by propylene glycol. STUDY DESIGN: Clinical and Experimental. METHODS: 25 guinea pigs were submitted to the application of a 100% propylene glycol solution in their bulla bilaterally and a solution of trans-retinoic acid was applied locally in the external right ear, while in the left ear saline solution was applied (control ear). The guinea pigs were slaughtered and their temporal bones were prepared for macroscopic and histological analysis. RESULTS: The macroscopic findings had evidenced the presence of cholesteatoma in 25% of the right ears and 85% of the left ears (P=0.0003 *). The histological study had evidenced the presence of cholesteatoma in 30% of right ears and 75% of the left ears (P=0.0104*). CONCLUSION: The local use of the trans-retinoic acid is effective in inhibiting the induced formation of cholesteatomas in guinea pigs.

Propofol (2, 6-diisopropylphenol) is a potent intravenous hypnotic agent that is widely used in adults and children for sedation and the induction and maintenance of anaesthesia. Propofol has gained popularity for its rapid onset and rapid recovery even after prolonged use, and for the neuroprotection conferred. However, a review of the literature reveals multiple instances in which prolonged propofol administration (>48 hours) at high doses (>4 mg/kg/h) may cause a rare, but frequently fatal complication known as propofol infusion syndrome (PRIS). PRIS is characterized by metabolic acidosis, rhabdomyolysis of both skeletal and cardiac muscle, arrhythmias (bradycardia, atrial fibrillation, ventricular and supraventricular tachycardia, bundle branch block and asystole), myocardial failure, renal failure, hepatomegaly and death. PRIS has been described as an 'all or none' syndrome with sudden onset and probable death. The literature does not provide evidence of degrees of symptoms, nor of mildness or severity of signs in the clinical course of the syndrome. Recently, a fatal case of PRIS at a low infusion rate (1.9-2.6 mg/kg/h) has been reported. Common laboratory and instrumental findings in PRIS are myoglobinuria, downsloping ST-segment elevation, an increase in plasma creatine kinase, troponin I, potassium, creatinine, azotaemia, malonylcarnitine and C5-acylcarnitine, whereas in the mitochondrial respiratory electron transport chain, the activity of complex IV and cytochrome oxidase ratio is reduced. Propofol should be used with caution for sedation in critically ill children and adults, as well as for long-term anesthesia in otherwise healthy patients, and doses exceeding 4-5 mg/kg/h for long periods (>48 h) should be avoided. If PRIS is suspected, propofol must be stopped immediately and cardiocirculatory stabilization and correction of metabolic acidosis initiated. So, PRIS must be kept in mind as a rare, but highly lethal, complication of propofol use, not necessarily confined to its prolonged use. Furthermore, the safe dosage of propofol may need re-evaluation, and new studies are needed.

Emily Banks1†, Karen Canfell2 & Gillian Reeves3 †Author for correspondence 1The Australian National University, National Centre for Epidemiology & Population Health, ACT, 0200, Australia Tel.: +61 261 250 328; Fax: +61 261 250 740; E-mail: emily.banks@ anu.edu.au 2The Cancer Council New South Wales, Cancer Epidemiology Research Unit, Sydney, Woolloomooloo, NSW 2011, Australia 3University of Oxford, Cancer Research UK Epidemiology Unit, Oxford OX3 7LF, UK ‘A common misperception is that HRT has been shown to have significantly different effects in younger compared with older women.’

Background The authors studied the effects of the beach chair (BC) position, 10 cm H2O positive end-expiratory pressure (PEEP), and pneumoperitoneum on respiratory function in morbidly obese patients undergoing laparoscopic gastric banding. Methods The authors studied 20 patients (body mass index 42 +/- 5 kg/m2) during the supine and BC positions, before and after pneumoperitoneum was instituted (13.6 +/- 1.2 mmHg). PEEP was applied during each combination of position and pneumoperitoneum. The authors measured elastance (E,rs) of the respiratory system, end-expiratory lung volume (helium technique), and arterial oxygen tension. Pressure-volume curves were also taken (occlusion technique). Patients were paralyzed during total intravenous anesthesia. Tidal volume (10.5 +/- 1 ml/kg ideal body weight) and respiratory rate (11 +/- 1 breaths/min) were kept constant throughout. Results In the supine position, respiratory function was abnormal: E,rs was 21.71 +/- 5.26 cm H2O/l, and end-expiratory lung volume was 0.46 +/- 0.1 l. Both the BC position and PEEP improved E,rs (P < 0.01). End-expiratory lung volume almost doubled (0.83 +/- 0.3 and 0.85 +/- 0.3 l, BC and PEEP, respectively; P < 0.01 vs. supine zero end-expiratory pressure), with no evidence of lung recruitment (0.04 +/- 0.1 l in the supine and 0.07 +/- 0.2 in the BC position). PEEP was associated with higher airway pressures than the BC position (22.1 +/- 2.01 vs. 13.8 +/- 1.8 cm H2O; P < 0.01). Pneumoperitoneum further worsened E,rs (31.59 +/- 6.73; P < 0.01) and end-expiratory lung volume (0.35 +/- 0.1 l; P < 0.01). Changes of lung volume correlated with changes of oxygenation (linear regression, R2 = 0.524, P < 0.001) so that during pneumoperitoneum, only the combination of the BC position and PEEP improved oxygenation. Conclusions The BC position and PEEP counteracted the major derangements of respiratory function produced by anesthesia and paralysis. During pneumoperitoneum, only the combination of the two maneuvers improved oxygenation.

We determined the minimum local anaesthetic dose (MLAD) of spinal levobupivacaine and ropivacaine for Caesarean section. Ninety women were randomly allocated to two groups and received 3 ml of study solution by a combined spinal/epidural technique. The initial dose was 12 mg for levobupivacaine and 17 mg for ropivacaine groups. To be considered effective, a test solution had to achieve a visual analogue pain score (VAPS) of 30 mm or less at skin incision, uterine incision, birth, peritoneal closure, and at the end of surgery. Effective or ineffective responses determined, respectively, a 0.3 mg decrease or increase of the same drug for the next patient in the same group, using up-down sequential allocation. The MLAD of levobupivacaine was 10.58 mg (CI 95\%: 10.08-11.09) and the MLAD of ropivacaine 14.22 mg (CI 95\%: 13.67-14.77), using the Dixon and Massey formula. The potency ratio between spinal levobupivacaine and spinal ropivacaine was 1.34.

This experiment tested the effect of an injection of orexin A into the diagonal band of Broca on the sympathetic activity and body temperature. Concentration of glycerol into white fat of lumbar region, firing rates of sympathetic nerves to interscapular brown adipose tissue (IBAT), MAT and colonic temperatures, and heart rate were monitored in urethane-anesthetized male Sprague-Dawley rats for 30 min before and 150 min after injections of orexin A (0.4 and 0.7 nmol) into the diagonal band of Broca. The same variables were monitored in control rats with an injection of saline. The results show that orexin A increases glycerol concentration, sympathetic firing rate, IBAT and colonic temperatures, and heart rate. The saline injection did not induce any modification. These findings suggest that the diagonal band of Broca is a cerebral structure involved in the induction of the hyperthemia due to orexin A. (C) 2004 Elsevier B.V. All rights reserved.

Second malignancy after treatment of adult acute myeloid leukemia: cohort study on adult patients enrolled in the GIMEMA trials

Background: Certain medications may contribute to the etiology of depressive symptoms and disorders. Research in this area, however, has been hampered by methodological and conceptual problems. This review had two objectives: to identify evidence linking medical drugs to depressive symptoms and disorders, and to summarize this evidence in a clinically meaningful way. Methods: Electronic literature searches were performed and studies were reviewed with reference to critical methodological features. Results: No medications causing the typical major depressive syndrome were identified. Evidence was found linking corticosteroids, interferon-α, interleukin-2, gonadotropin-releasing hormone agonists, mefloquine, progestin-releasing implanted contraceptives and propranolol to the etiology of atypical depressive syndromes. Conclusions: A small number of drugs have been shown capable of inducing depressive symptoms. Drug-induced depression appears to differ symptomatically from classical major depression.

A 40-yr-old male was admitted to the intensive care unit following blunt chest trauma. He had multiple rib fractures, bilateral pneumothoraces, and acute respiratory failure requiring mechanical ventilation. Sedation was achieved with midazolam and morphine, and later with propofol. The patient was paralysed with a continuous infusion of cisatracurium 1.42-5.75 micro g kg(-1) min(-1). Methylprednisolone 125 mg i.v. every 12 h was also started. After discontinuation of the cisatracurium infusion 7 days later, the patient manifested a flaccid quadriplegia with absence of deep-tendon reflexes. No sensory deficits were observed. Electromyography (EMG), repetitive nerve stimulation testing, and single fibre EMG (SFEMG) were performed at regular intervals after stopping cisatracurium. Clinical symptoms and electrophysiological examinations supported the diagnosis of acute motor axonal polyneuropathy related to concomitant administration of cisatracurium and corticosteroid therapy.

We report a singular clinical condition observed following a short duration treatment with sulphasalazine (SSZ) in a 64-year-old woman affected by psoriatic arthritis. Two weeks after starting treatment, a high degree, subcontinuous fever occurred, together with systemic discomfort, fatigue, headache, and ultimately a moderate wakefulness impairment. Upon admission to the hospital, a malar rash became evident. Modest notes of hepatotoxicity were also evident. All of the symptoms suddenly resolved after SSZ withdrawal. The markers of hepatitis become negative just 2 months later. It is interesting to note that after dismissal, in order to counteract the severe arthritic conditions and the presence of a type 2 diabetes, a combined therapy with methotrexate and cyclosporin had to be used, with no renal or hepatic side effects and remarkable therapeutic effects. No markers of autoimmunity were found in this patient. The chronology and the clinical events here described may confirm the hypothesis of a idiosyncratic reaction to SSZ, closely resembling a rare, sometimes irreversible, condition known as "the 3 week sulphasalazine syndrome".

OBJECTIVE: The aim of the present study was to examine the relationship between serious arrhythmias in patients with psychotropic drug overdose and electrocardiography (ECG) findings that have been suggested previously to predict this complication. METHODS: Thirty-nine patients with serious arrhythmias (ventricular tachycardia, supraventricular tachycardia or cardiac arrest) after tricyclic antidepressant overdose or thioridazine overdose were compared with 117 controls with clinically significant overdose matched to each case for the drug ingested. These patients with psychotropic drug overdose had presented for treatment to the Department of Clinical Toxicology, Newcastle and to the Princess Alexandra Hospital, Brisbane. The heart rate, the QRS width, the QTc and QT intervals, the QT dispersion, and the R wave and R/S ratios in aVR on the initial ECGs were compared in cases and controls. RESULTS: The cases had taken dothiepin (16 patients), doxepin (six patients), thioridazine (five patients), amitriptyline (five patients), nortriptyline (three patients), imipramine (one patient) and a combination of dothiepin and thioridazine (three patients). In 20 of the 39 patients with arrhythmias, the arrhythmia had been a presumed ventricular tachycardia. Of the other 19 patients, 15 patients had a supraventricular tachycardia, two patients had cardiac arrests (one asystole, one without ECG monitoring) and two patients had insufficient data recorded to make classification of the arrhythmias possible. The QRS was >/= 100 ms in 82% of cases but also in 76% of controls. QRS >/= 160 ms had a sensitivity of only 13% and occurred in 2% of controls. QRS > 120 ms, QTc > 500 and the R/S ratio in aVR appeared to have a stronger association with the occurrence of arrhythmia: QRS > 120 ms (odds ratio [OR], 3.56; 95% confidence interval [CI], 1.46-8.68), QTc > 500 (OR, 3.07; 95% CI, 1.33-7.07), and R/S ratio in aVR > 0.7 (OR, 16; 95% CI, 3.47-74). Excluding thioridazine overdoses and performing the analysis for tricyclic antidepressant overdoses alone gave increased odds ratios for QRS > 120 ms (OR, 4.83; 95% CI, 1.73-13.5) and QTc > 500 (OR, 4.5; 95% CI, 1.56-13) but had little effect on that for the R/S ratio in aVR > 0.7 (OR, 14.5; 95% CI, 3.10-68). CONCLUSION: ECG measurements were generally weakly related to the occurrence of arrhythmia and should not be used as the sole criteria for risk assessment in tricyclic antidepressant overdose. The frequently recommended practice of using either QRS >/= 100 ms or QRS >/= 160 ms to predict arrhythmias is not supported by our study. R/S ratio in aVR > 0.7 was most strongly related to arrhythmia but had estimated positive and negative predictive values of only 41% and 95%, respectively. The use of these specific predictors in other drug overdoses is not recommended without specific studies