Relationship between flame retardants and respiratory health- A systematic review and meta-analysis of observational studies.

Chronic respiratory diseases are a dealing cause of death and disability worldwide. Their prevalence is steadily increasing and the exposure to environmental contaminants, including Flame Retardants (FRs), is being considered as a possible risk factor. Despite the widespread and continuous exposure to FRs, the role of these contaminants in chronic respiratory diseases is yet not clear. This study aims to systematically review the association between the exposure to FRs and chronic respiratory diseases. Searches were performed using the Cochrane Library, MEDLINE, EMBASE, PUBMED, SCOPUS, ISI Web of Science (Science and Social Science Index), WHO Global Health Library and CINAHL EBSCO. Among the initial 353 articles found, only 9 fulfilled the inclusion criteria and were included. No statistically significant increase in the risk for chronic respiratory diseases with exposure to FRs was found and therefore there is not enough evidence to support that FRs pose a significantly higher risk for the development or worsening of respiratory diseases. However, a non-significant trend for potential hazard was found for asthma and rhinitis/rhinoconjunctivitis, particularly considering urinary organophosphate esters (OPEs) including TNBP, TPHP, TCEP and TCIPP congeners/compounds. Most studies showed a predominance of moderate risk of bias, therefore the global strength of the evidence is low. The limitations of the studies here reviewed, and the potential hazardous effects herein identified highlights the need for good quality large-scale cohort studies in which biomarkers of exposure should be quantified in biological samples.

Combined use of Nassarius reticulatus imposex and statolith age determination for tracking temporal evolution of TBT pollution in the NW Portuguese continental shelf.

Spatial and temporal trends of tributyltin (TBT) pollution on the northern continental shelf of Portugal (5-34 m depth) were assessed using Nassarius reticulatus as a bioindicator. Imposex levels were determined in 2006 and 2010, and integrated with age readings from statoliths for a better chronological analysis of the data. Females affected with imposex were detected in 84% of the sites surveyed in 2006, with levels higher than the Ecological Quality Objective (EcoQO) set by the OSPAR Commission for N. reticulatus (VDSI < 0.3) in approximately half of those sites. In 2010, imposex was only detected in 20% of the surveyed sites and, when detected, the VDSI were lower than the EcoQO, except for one location. The comparison between the current results and the levels previously reported for 2004 and 2005 in the same offshore area evidences a clear decline of imposex in 2010 that confirms the efficacy of Regulation (EC) No. 782/2003 and the IMO AFS-Convention (entered into force in 2003 and 2008, respectively). Moreover, the age of the whelks used in the monitoring is estimated in 3-5 years, indicating that actual TBT water contamination in 2010 may in fact be lower than that extrapolated from the imposex levels. We conclude that the legislation was indeed very effective in reducing TBT pollution in the NW Portuguese continental shelf, not only in terms of the magnitude but also in terms of fast field repercussion.

Responses of benthic macroinvertebrate communities to a Bti-based insecticide in artificial microcosm streams.

Bioinsecticides based on the bacterium Bacillus thuringiensis subsp. israelensis (Bti) are increasingly being applied directly into aquatic compartments to control nuisance mosquitoes and blackflies and are generally considered environmentally friendly alternatives to synthetic insecticides. Bti-based insecticides are considered highly selective, being Diptera-specific, and supposedly decompose rapidly in the environment. Nevertheless, their safety to non-target species and freshwater ecosystems has been questioned by recent studies, which in fact document possible indirect effects in aquatic food webs such as the decrease of prey availability to predators. This work aimed to evaluate the potential effects of a Bti-based insecticide (VectoBac® 12AS) on a freshwater macroinvertebrate community and on stream ecological functions by using artificial microcosm streams. Artificial microcosm streams were colonized with a macroinvertebrate community plus periphyton collected in a stream together with Alnus glutinosa leaf packs. They were exposed for 7 days to different Bti treatments (0, 12, 120, 1200 µg/L), which are within the recommended concentrations of application in aquatic compartments for blackfly and mosquito control. Besides invertebrate community structure and abundance, effects were evaluated regarding leaf decomposition and primary production as measures of ecosystem functioning. Community structure was significantly altered in all Bti treatments after 7 days of exposure, mostly due to a decline in chironomids, followed by oligochaetes, which both belong to the deposit-feeders' functional group. Direct effects on oligochaetes are surprising and require further research. Also, reductions of leaf decomposition due to Bti-induced sublethal effects on shredders (reduced feeding) or mortality of chironomids (that can also feed on coarse organic matter) observed in our study, represent potential indirect effects of Bti in aquatic ecosystems. Our short-exposure experiment evidenced some negative effects on stream benthic invertebrate communities and on ecosystem functioning that must be considered whenever Bti is used in water bodies for blackfly or mosquito control programs.

Epicutaneous patch testing in drug hypersensitivity syndrome (DRESS).

BACKGROUND: In some patterns of cutaneous adverse drug reactions, and depending on the culprit drug, patch testing has been helpful in confirming its cause. Its value in Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) has not been established in a large cohort of patients. OBJECTIVE: The aim of the present study is to evaluate the safety and usefulness of patch testing in DRESS. PATIENTS/METHODS: Between January 1998 and December 2008, we studied 56 patients with DRESS induced by antiepileptic agents in 33 patients (59%), allopurinol in 19 (34%) and sulfasalazine, cotrimoxazole, tenoxicam, and amoxicillin in 1 patient each (7%). RESULTS: A positive patch test reaction was observed in 18 patients (32.1%), of which 17 were with antiepileptics and 1 with tenoxicam. In the antiepileptic group, carbamazepine alone was responsible for 13 of 17 positive reactions (76.5%). Patch tests with allopurinol and its metabolite were negative in all cases attributed to this drug. CONCLUSIONS: In this study, patch testing was a safe and useful method in confirming the culprit drug in DRESS induced by antiepileptic drugs, whereas it had no value in DRESS induced by allopurinol. The pathogenesis of DRESS is not yet entirely clarified, but positive patch tests suggest a drug-dependent delayed hypersensitivity mechanism.

Neurofibromatosis-associated pulmonary hypertension: an ominous duo.

The authors report a rare clinical case of a patient with neurofibromatosis type 1 (NF1) complicated by pulmonary hypertension (PH), which presents with rapid progression. An exhaustive investigation was performed to identify the main aetiology of the PH. It was concluded that the PH could be associated with NF1, and so belonged in group 5 of the clinical classification of PH. In general, such patients have a poor long-term prognosis due to the inexistence of proven, effective treatment. Further studies are needed to better understand the mechanisms of NF1-associated PH.

Marfan syndrome revisited: From genetics to the clinic. / Síndrome de Marfan revisitada ­ da genética à clínica.

Marfan syndrome is an autosomal dominant connective tissue disease with an estimated incidence of 1 in 5000 individuals. In 90% of cases it is caused by mutations in the gene for fibrillin-1, the main constituent of extracellular microfibrils. Studies on animal models of Marfan syndrome have revealed that fibrillin-1 mutations interfere with local TGF-ß signaling, in addition to impairing tissue integrity. The cardinal features involve the cardiovascular, ocular and skeletal systems. The diagnosis of Marfan syndrome is made according to the revised Ghent nosology. Early identification and appropriate management are critical for patients with Marfan syndrome, who are prone to the life-threatening cardiovascular complications of aortic aneurysms and aortic dissection. The standard treatment includes prophylactic beta-blockers in order to slow down dilation of the ascending aorta, and prophylactic aortic surgery. The success of current medical and surgical treatment of aortic disease in Marfan syndrome has substantially improved mean life expectancy, extending it above 72 years. This review aims to provide an overview of this hereditary disorder.

Levels of TBT and other selected organotin compounds in duplicate diet samples.

Organotin compounds (OTs) are ubiquitous contaminants with a broad range of applications ranging from biocides and pesticides to catalysts for the production of polyurethane foams and silicones. The deleterious effects of some OTs (particularly tributyltin - TBT) upon wildlife and experimental animals are well documented and include endocrine disruption, immunotoxicity, neurotoxicity, genotoxicity and metabolic dysfunction in which obesity is included. However, virtually no data on the current human exposure levels is available. In order to bridge this gap, we quantified for the first time the levels of OTs in duplicate diet samples from members of the University of Aveiro in Portugal. OTs were detected in 32% of the 28 diet samples analyzed, at relatively low levels. TBT and monobutyltin were detected only in two samples and dibutyltin was detectable in three samples. Dioctyltin was quantified in four samples and monooctyltin in three samples. Phenyltins were below the detection limit in all the diet samples analyzed. Overall, for the vast majority of the samples (89%), the estimated daily intakes (EDI) of organotins through food were much lower than the established tolerable daily intakes (TDI). Hence, for the majority of the participants the risk associated with food ingestion is low.

Transient zinc deficiency in a breast fed, premature infant.

A 5-month-old-male was observed for an acrodermatitis enteropathica-like skin eruption evolving since the second month. He was born prematurely at 27 weeks and his neonatal course was complicated by respiratory distress syndrome, sepsis and subependimary haemorrhage. He was fed with breast milk from the second day of life, fortified initially by a protein mineral supplement containing zinc. Serum zinc concentration was low and the mother's serum and milk had normal zinc values. Oral zinc supplementation was introduced with total clearing after three weeks. Treatment lasted 22 months and no relapse was observed after discontinuation. Premature infants have a negative zinc balance mainly secondary to inadequate stores and high requirements. The relevance of these factors is illustrated by the present case where symptomatic zinc deficiency developed despite maternal milk with normal zinc content and a milk fortifier containing zinc.

Brominated flame retardants and organochlorine compounds in duplicate diet samples from a Portuguese academic community.

Concentrations of persistent organic pollutants (POPs), including polybrominated diphenyl ethers (PBDEs), hexabromocyclododecanes (HBCDDs), polychlorinated biphenyls (PCBs), hexachlorocyclohexane isomers (HCHs), hexachlorobenzene (HCB), chlordane compounds (CHLs) and dichlorodiphenyltrichloroethane and its metabolites (DDTs), were measured in duplicate diet samples from 21 volunteers at a Portuguese academic community (University of Aveiro). Overall, the levels of the target compounds were low, with detection frequencies varying widely depending on the compounds and with brominated flame retardants (BFRs) registering the lowest detection frequencies. Among PCB congeners, nondioxin-like PCBs were predominant and detected in the majority of the samples. Organochlorine pesticides were also detected in the majority of the samples, with 100% detection for DDTs and HCHs. Estimated daily intakes (EDIs) were calculated using lower and upper bound estimations, and in both cases values were far below the currently established tolerable daily intakes for PCBs and OCs and the reference doses for PBDEs and HBCDDs.

Lead in duplicate diet samples from an academic community.

Lead is a naturally occurring element that with the advent of the industrial era became a serious environmental and public health issue. Leaded gasoline, lead based paints, use of lead in plumbing and water pipes, ceramics with lead-containing glazes and tobacco smoke are potential sources of lead exposure for humans. Despite these multiple sources, food is still considered the most important one for the general non-smoking population. Hence, in the present study, the dietary intake of lead was determined in duplicate diet samples provided by 30 participants working or studying at University of Aveiro, Portugal. Pb was detected in all the analysed samples with values ranging between 0.009 and 0.10mgkg-1 ww which correspond to estimated daily intakes between 0.22 and 3.5µgkg-bw-1day-1. Risk estimations disclose that at least 3.3% and 26.7% of the participants might suffer cardiovascular and nephrotoxic effects, respectively.

Brominated, chlorinated and phosphate organic contaminants in house dust from Portugal.

House dust is an important matrix to evaluate the human exposure to a large number of contaminants including organochlorine compounds and flame retardants. In this study, we measured the levels of polybrominated diphenyl ethers (PBDEs), hexabromocyclododecanes (HBCDDs), 1,2-bis(2,4,6-tribromophenoxy) ethane (BTBPE), decabromodiphenyl ethane (DBDPE), polychlorinated biphenyls (PCBs) and several organophosphorus flames retardants (PFRs) in 28 house dust samples collected between 2010 and 2011 in two Portuguese cities, Aveiro and Coimbra. Among the measured compounds, PFRs, particularly tris(2-ethylhexyl) phosphate (TEHP), triphenyl phosphate (TPHP), 2-ethylhexyl diphenyl phosphate (EHDPP) and tris(methylphenyl) phosphate (TMPP), were the dominant group (median: 3200ngg(-1)). PBDE levels were the second highest (median: 340ngg(-1)) with great predominance of BDE 209 (median 270ngg(-1)), followed by HBCDDs (median: 150ngg(-1)), DBDPE (54ngg(-1)), PCBs (median: 6.3ngg(-1)) and BTBPE (median: 1.2ngg(-1)). Estimated daily intakes (EDIs) via dust ingestion showed a higher intake of PFRs (median: 4.6ngkg-bw(-1)day); however for all contaminants the EDIs were much lower than the established reference dose (RfD) values. Therefore, the studied population is exposed to non-hazardous levels of the target compounds when considering the exposure through house dust ingestion.

Epidemiological profile and postoperative complications of women undergoing gynecological surgery in a reference center in the northern Brazilian legal Amazon.

OBJECTIVE: To evaluate the epidemiological profile and the operative complications of patients undergoing gynecological operations for benign diseases in a tertiary public hospital in the state of Roraima, Brazil. METHODS: We conducted a retrospective survey through the analysis of 518 records of patients submitted to gynecological operations between January and June 2012. We included the three major operations during this period (n = 175): hysterectomy, colpoperineoplasty and suburethral sling placement. We excluded 236 cases of tubal ligation and 25 cases where it was not possible to access to medical records. RESULTS: The mean age was 47.6 years; the education level of most patients was completed junior high (36.6%); 77% were from the State capital, 47.4% were in stable relationships and 26.3% were housewives. The majority of patients had given birth three or more times (86.6%), with previous vaginal delivery in 50.2%, and cesarean delivery, 21%. The main diagnostic indications for surgical treatment were uterine myoma (46.3%), urinary incontinence (27.4%) and genital dystopias (17.7%). We found three cases (1.7%) of high-grade intraepithelial lesions on Pap smear. The most common procedure was total hysterectomy (19.8%), 15.5% vaginally. The most common complication was wound infection (2.2%). CONCLUSION: Women undergoing gynecological operations due to benign disease had a mean age of 47 years, most had levels of basic education, came from the capital, were in stable relationships, predominantly housewives, multiparous and showed low operative complication rates.

From sub cellular to community level: toxicity of glutaraldehyde to several aquatic organisms.

The biocide glutaraldehyde (GA) is widely used as a disinfectant and sterilizing agent against bacteria and virus in hospital and veterinary facilities. GA or its metabolites may reach aquatic ecosystems due to incomplete or inadequate treatment of wastewaters. Data about GA effects at lethal and a sub lethal level to non-target organisms is needed so that a risk assessment to aquatic ecosystems can be done. Thus, in this work a battery of toxicity tests with primary producers, primary consumers and secondary consumers were performed and a species sensitive distribution (SSD) for GA was built. Moreover, effects on biomarkers (catalase, lactate dehydrogenase, glutathione-S-transferase, and cholinesterase) were measured in Danio rerio embryos and adults. Primary consumers (Thamnocephalus platyurus 24h - EC50=3.6 mg/l; Daphnia magna 48 h - EC50=6.6 mg/l) and D. rerio adults (96 h - LC50=5.5mg/l) were slightly more sensitive to GA than D. rerio embryos (96 h - LC50=22.2mg/l) and primary producers (Lemna minor 168 h - EC50=73.8 mg/l; Pseudokirchneriella subcapitata 72h - EC50=12.3mg/l; Chlamydomonas reinhardtii 72 h - EC50=14.6 mg/l; Chlorella vulgaris 72 h - EC50=31.3mg/l). However, no significant differences between the trophic levels were found and general HC5 and HC50 values of 0.6 and 11.4 mg/l were respectively estimated. Despite the low GA toxicity to D. rerio embryos, hatching delay and malformations were found (96 h - EC50=11.9 mg/l). For biomarkers, an inhibition of lactate dehydrogenase activity was observed in embryos whereas an inhibition in catalase, lactate dehydrogenase and glutathione-S-transferase activities was observed in adults. Thus, GA is moderately toxic (doses>1mg/l) to aquatic organisms, independently of the trophic level. However, considering the varied range of effects depending on the life stage and organism tested and relatively low HC5 value of 0.6 mg/l, mesocosm and chronic toxicity tests seem to be the next step in direction of more realistic scenarios of GA risk assessment in aquatic ecosystems.

[Adverse drug events in hospital: pilot study with trigger tool]. / Eventos adversos a medicamentos em hospital terciário: estudo piloto com rastreadores.

OBJECTIVE: To estimate the frequency of and to characterize the adverse drug events at a terciary care hospital. METHODS: A retrospective review was carried out of 128 medical records from a hospital in Rio de Janeiro in 2007, representing 2,092 patients. The instrument used was a list of triggers, such as antidotes, abnormal laboratory analysis results and sudden suspension of treatment, among others. A simple random sample of patients aged 15 and over was extracted. Oncologic and obstetric patients were excluded as were those hospitalized for less than 48 hours or in the emergency room. Social and demographic characteristics and those of the disease of patients who underwent adverse events were compared with those of patients who did not in order to test for differences between the groups. RESULTS: Around 70.0% of the medical records assessed showed at least one trigger. Adverse drug events triggers had an overall positive predictive value of 14.4%. The incidence of adverse drug events was 26.6 per 100 patients and 15.6% patients suffered one or more event. The median length of stay for patients suffering an adverse drug event was 35.2 days as against 10.7 days for those who did not (p < 0.01). The pharmacological classes most commonly associated with an adverse drug event were related to the cardiovascular system, nervous system and alimentary tract and metabolism. The most common active substances associated with an adverse drug event were tramadol, dypirone, glibenclamide and furosemide. Over 80.0% of events provoked or contributed to temporary harm to the patient and required intervention and 6.0% may have contributed to the death of the patient. It was estimated that in the hospital, 131 events involving drowsiness or fainting 33 involving falls, and 33 episodes of hemorrhage related to adverse drug effects occur annually. CONCLUSIONS: Almost one-sixth of in-patients (16.0%) suffered an adverse drug event. The instrument used may prove useful as a technique for monitoring and evaluating patient care results. Psycothropic therapy should be critically appraised given the frequency of associated events, such as excessive sedation, lethargy, and hypotension.

Pachyonychia congenita type 2 (Jackson-Lawler syndrome) or PC-17: case report.

Pachyonychia congenita (PC) is a rare genodermatosis caused by mutations in any of the four genes KRT6A, KRT6B, KRT16, or KRT17, which can lead to dystrophic, thickened nails and focal palmoplantar keratoderma, among other manifestations. Although classically subdivided into two major variants, PC-1 (Jadassohn-Lewandowski syndrome) and PC-2 (Jackson-Lawler syndrome), according to the localization of the mutations in the KRT6A/KRT16 or KRT6B/KRT17 genes, respectively, a classification system based on the mutant gene (PC-6a, PC-6b, PC-16 and PC-17) has been recently proposed. We report a 2-year-old female patient with a history of thickened and discolored nails, small cystic papulonodules on the central face, dry, unruly and curly hair, slight palmoplantar hyperkeratosis, and natal teeth. Both her father and paternal grandfather presented onychodystrophy, palmoplantar keratoderma, and previous excision of "sebaceous" cysts. Molecular genetic analysis of the patient revealed a missense mutation (c.1163T>C) in heterozygosity in exon 6 of the KRT17 gene, confirming the diagnosis of PC-2 (Jackson-Lawler type), or PC-17. We conclude that PC is a relatively easy and consistent clinical diagnosis, but a high index of suspicion is required if the diagnosis is to be made correctly. With this case, the authors intend to draw attention to this condition and the role of the dermatologist in the diagnosis.