Adrenal insufficiency in thyroid cancer patients treated with tyrosine kinase inhibitors and detected by ACTH stimulation test.

PURPOSE: Advanced thyroid cancer patients treated with tyrosine kinase inhibitors (TKI) can develop several adverse events (AEs), including adrenal insufficiency (AI). METHODS: We studied 55 patients treated with TKI for radioiodine-refractory or medullary thyroid cancer. The adrenal function was evaluated during follow-up by performing serum basal ACTH, and basal and ACTH-stimulated cortisol. RESULTS: Twenty-nine/55 (52.7%) patients developed subclinical AI during TKI treatment as demonstrated by a blunted cortisol response to ACTH stimulation. All cases showed normal values of serum sodium, potassium and blood pressure. All patients were immediately treated, and none showed an overt AI. Cases with AI were all negative for adrenal antibodies and did not show any adrenal gland alteration. Other causes of AI were excluded. The onset time of the AI, as measured in the subgroup with a first negative ACTH test, was < 12 months in 5/9 (55.6%), between 12 and 36 months in 2/9 (22.2%) and > 36 months in 2/9 (22.2%) cases. In our series, the only prognostic factor of AI was the elevated, although moderate, basal level of ACTH when the basal and stimulated cortisol were still normal. The glucocorticoid therapy improved fatigue in most patients. CONCLUSIONS: Subclinical AI can be developed in > 50% of advanced thyroid cancer patients treated with TKI. This AE can develop in a wide period ranging from < 12 to > 36 months. For this reason, AI must be looked for throughout the follow-up to be early recognized and treated. A periodic ACTH stimulation test, every 6-8 months, can be helpful.

Radio-iodine refractory thyroid cancer patients: a tailored follow-up based on clinicopathological features.

OBJECTIVE: To report the experience of a single center for the selection of radioiodine-refractory (RAIR) thyroid cancer patients (RAIR-TC) who needed tyrosine kinase inhibitor (TKIs) treatment. PATIENTS AND METHODS: We evaluated all features of 279 RAIR-TC patients both at the time of diagnosis and at the RAIR diagnosis. RESULTS: Ninety-nine patients received indication to TKIs (Group A), while 180 remained under active surveillance (Group B). Group A had greater tumor size, more aggressive histotype, more frequent macroscopic extrathyroidal extension, distant metastases, advanced AJCC stage, and higher ATA risk of recurrence. After RAIR diagnosis, 93.9% of Group A had progression of disease (PD) after which TKIs' therapy was started. The remaining 6.1% of patients had a so severe disease at the time of RAIR diagnosis that TKIs' therapy was immediately started. Among Group B, 42.7% had up to 5 PD, but the majority underwent local treatments. The mean time from RAIR diagnosis to the first PD was shorter in Group A, and the evidence of PD within 25 months from RAIR diagnosis was associated with the decision to start TKIs. CONCLUSIONS: According to our results, a more tailored follow-up should be applied to RAIR-TC patients. A too strict monitoring and too many imaging evaluations might be avoided in those with less-aggressive features and low rate of progression. Conversely, RAIR-TC with an advanced stage at diagnosis and a first PD occurring within 25 months from RAIR diagnosis would require a more stringent follow-up to avoid a late start of TKIs.

Patients with Lemierre syndrome have a high risk of new thromboembolic complications, clinical sequelae and death: an analysis of 712 cases.

BACKGROUND: Lemierre syndrome is characterized by head/neck vein thrombosis and septic embolism usually complicating an acute oropharyngeal bacterial infection in adolescents and young adults. We described the course of Lemierre syndrome in the contemporary era. METHODS: In our individual-level analysis of 712 patients (2000-2017), we included cases described as Lemierre syndrome if these criteria were met: (i) primary site of bacterial infection in the head/neck; (ii) objectively confirmed local thrombotic complications or septic embolism. The study outcomes were new or recurrent venous thromboembolism or peripheral septic lesions, major bleeding, all-cause death and clinical sequelae. RESULTS: The median age was 21 (Q1-Q3: 17-33) years, and 295 (41%) were female. At diagnosis, acute thrombosis of head/neck veins was detected in 597 (84%) patients, septic embolism in 582 (82%) and both in 468 (80%). After diagnosis and during in-hospital follow-up, new venous thromboembolism occurred in 34 (5.2%, 95% CI 3.8-7.2%) patients, new peripheral septic lesions became evident in 76 (11.7%; 9.4-14.3%). The rate of either was lower in patients who received anticoagulation (OR: 0.59; 0.36-0.94), higher in those with initial intracranial involvement (OR: 2.35; 1.45-3.80). Major bleeding occurred in 19 patients (2.9%; 1.9-4.5%), and 26 died (4.0%; 2.7-5.8%). Clinical sequelae were reported in 65 (10.4%, 8.2-13.0%) individuals, often consisting of cranial nerve palsy (n = 24) and orthopaedic limitations (n = 19). CONCLUSIONS: Patients with Lemierre syndrome were characterized by a substantial risk of new thromboembolic complications and death. This risk was higher in the presence of initial intracranial involvement. One-tenth of survivors suffered major clinical sequelae.

Lenvatinib as a salvage therapy for advanced metastatic medullary thyroid cancer.

PURPOSE: Patients with advanced progressive metastatic medullary thyroid cancer (MTC), show poor prognosis and few available systemic therapeutic options. After the loss of clinical benefit with other tyrosine kinase inhibitors (TKI), we evaluated the use of lenvatinib as salvage therapy. METHODS: Ten patients who experienced the loss of clinical benefit after treatment with at least one previous TKI, were treated with lenvatinib. We assessed patient's response immediately before, at the first (first-EV) and last (last-EV) evaluation, after the beginning of treatment. RESULTS: At first-EV, one patient died, while all the remaining 9 showed a stable disease (SD) in the target lesions. At last-EV, SD was still observed in seven patients, while partial response (PR) and progressive disease (PD), in one patient each. Conversely, analyzing all target and non-target lesions, at first-EV, we observed PR in one patient and SD in eight patients. At last-EV, PR was shown in two patients and SD was shown in seven. Bone metastases showed stable disease control at both first-EV and last-EV in only approximately 60% of cases. Tumor markers (CTN and CEA) decreased at first-EV, while they increased at last-EV. Seven patients experienced at least one dose reduction during treatment with lenvatinib. CONCLUSIONS: In this real-life clinical experience, lenvatinib showed interesting results as salvage therapy in patients with advanced progressive metastatic MTC patients. Its usefulness could be effective in patients without any other available treatment, because previously used or unsuitable, especially with negative RET status with no access to the new highly selective targeted therapies.

SARS-CoV-2 contact tracing among disadvantaged populations during epidemic intervals should be a priority strategy: results from a pilot experiment in Barcelona.

OBJECTIVES: The aim of this study was to trace contacts of coronavirus disease 2019 (COVID-19) hospitalised patients and determine the risk factors of infection in urban areas. STUDY DESIGN: Longitudinal analysis of contacts identified from index cases. METHODS: A contact tracing study was carried out in the Northern Metropolitan area of Barcelona, Spain, during the inter-epidemic lapse of May to July 2020, a period of low SARS-CoV-2 incidence. Index cases were notified from the referral hospital. Contacts were traced and followed up for 14 days. Reverse transcription polymerase chain reaction was performed on day 0 and day 14 for contacts. RESULTS: In total, 368 contacts were identified from 81 index cases (median of seven contacts per index case), from which 308 were traced successfully. The median age of contacts was 28 years, 62% (223 of 368) were men. During the follow-up period, 100 contacts tested positive for COVID-19 (32.5% [95% confidence interval {CI} = 27.3-38.0]), with a secondary infection rate of 48.3% (95% CI = 40.8-55.9) among housemates. Clusters of index and respective contacts tended to aggregate within disadvantaged neighbourhoods (P < 0.001), and non-national index cases (N = 28, 34.1%) resulted in higher secondary infection rates compared with nationals (51.0% [95% CI = 41.0-60.9] vs 22.3% [95% CI = 16.8-28.8]; P < 0.001). CONCLUSIONS: Disadvantaged communities experience a disproportionate burden of COVID-19 and may act as infection reservoirs. Contact tracing with a cross-cutting approach among these communities is required, especially during inter-epidemic periods.

Design of an industrial solid waste processing line to produce refuse-derived fuel.

Municipal Solid Waste (MSW) from the city of Boa Esperança, Minas Gerais, Brazil, was used to produce refuse-derived fuel (RDF). The MSW contains residues from human society, including product packaging, bottles, batteries, organic waste, fines, textiles, health textiles, plastics, glass, and metals, among others. The following protocol was performed during the conversion of MSW to RDF: (i) the raw MSW was placed in a silo and sent to a primary crusher using a metal conveyor belt, which reduced the particle size to 80 mm; (ii) the biomass was transferred to a selective waste collection platform by a rubber conveyor belt, and the recyclable waste, metals, and glasses were separated manually; (iii) residual metals were removed by a magnetic separator; (iv) the waste was transferred to a secondary crusher which reduced the particle size to 60 mm; (v) the waste passed through an airborne separator to remove materials with high density, such as glass, stones, and organic materials, using a metallic conveyor belt; (vi) the particle size was reduced to 40 mm by a tertiary crusher; (vii) the aluminium was separated from the non-metallic materials (plastic, paper, rubber, etc.) using an eddy current separator; (viii) the particle size was reduced to 25 mm using a quaternary crusher; (ix) the MSW was introduced into a rotary dryer using a metal conveyor belt, where the moisture content was reduced to close to 15 wt%, which required thermal energy equivalent to 186 kWh; (x) the RDF was used in a thermochemical reactor and 4148 kWh of thermal energy was produced. In addition, the MSW and RDF were analysed, and the elemental composition and combustion characteristics were determined. Based on these results, the protocol evaluated was found to be effective in the conversion of MSW to RDF, which can be used as a source of renewable fuel.

Long-term clinical and echocardiographic outcomes of Mitraclip therapy in patients nonresponders to cardiac resynchronization.

OBJECTIVES: This study deals with clinical and echocardiographic outcomes in cardiac resynchronization therapy (CRT) nonresponders patients undergoing Mitraclip procedure. BACKGROUND: Functional mitral regurgitation (FMR) occurs in approximately one-third of heart failure (HF) patients. Resynchronization therapy may correct FMR in patients with HF; however, significant FMR persists in 20-25% of CRT patients. METHODS: All patients included were previously treated with CRT for at least 6 months and remained classified as New York Heart Association (NYHA) functional class III or IV despite optimal medical therapy; the echocardiographic assessment showed lack of decrease of the left ventricular end-systolic volume (LVESV) of at least 10% and residual moderate-to-severe or severe FMR. Clinical and echocardiographic follow-up was scheduled at 1, 3, 6, and 12 months after Mitraclip implantation, and every 6 months thereafter. RESULTS: Thirty patients fulfilled inclusion criteria. Before Mitraclip implantation NYHA class was III in 83% and IV in 17% of patients; after CRT no patient experienced an improvement in FMR. There was a significant improvement in NYHA class from baseline to 6 months, which remained sustained at 12 and 24 months. The degree of FMR significantly improved from baseline to 6 months and from 6 to 12 months. There was left ventricle remodeling with significant reduction of LVESV and an increase of left ventricle ejection fraction at 6 and 12 months, while the opposite trend was noted between 12 and 24 months CONCLUSION: Treatment of moderate to severe FMR in CRT nonresponder is feasible, safe, and reasonably effective in reducing cardiac symptoms.

External validation of AF-BLEED for predicting major bleeding and for tailoring NOAC dose in AF patients: A post hoc analysis in the ENGAGE AF-TIMI 48.

OBJECTIVE: AF-BLEED, a simple bleeding risk classifier, was found to predict major bleeding (MB) in patients with atrial fibrillation (AF) and identify AF patients at high risk of MB who might potentially benefit from a lower direct oral anticoagulant dose. This post hoc study aimed to externally validate these findings in the ENGAGE AF-TIMI 48 (Effective aNticoaGulation with factor Xa next Generation in Atrial Fibrillation-Thrombolysis in Myocardial Infarction study 48) trial. METHODS: The ENGAGE AF-TIMI 48 trial randomized AF patients to higher-dose edoxaban regimen (HDER 60/30 mg) versus lower-dose edoxaban regimen (LDER 30/15 mg), with prespecified dose reduction criteria. AF-BLEED was calculated in the modified intention-to-treat cohort (n = 21,026 patients) used for primary outcome analysis. Annualized event rates and hazard ratios (HRs) were obtained for the primary composite outcome (PCO) and its single components (MB, ischemic stroke/systemic embolism and death) to compare LDER 30 mg with HDER 60 mg in both AF-BLEED classes. RESULTS: AF-BLEED classified 2882 patients (13.7 %) as high-risk, characterized by a two- to three-fold higher MB risk than AF-BLEED classified low-risk patients. AF-BLEED classified high-risk patients randomized to LDER 30 mg demonstrated a 3.3 % reduction in MB at the cost of a 0.5 % increase in ischemic stroke/systemic embolism. LDER 30 mg resulted in a 3.1 % reduction of PCO compared to HDER 60 mg (HR of 0.81; 95%CI 0.65-1.01). Additional to existing dose reduction criteria, another 6 % of patients could potentially benefit of this dose adjustment strategy. CONCLUSION: AF-BLEED could identify AF patients to be at high risk of major bleeding. Our findings support the hypothesis that LDER 30 mg might provide a reasonable option in AF patients with legitimate bleeding concerns.

ADAMTS13 and Von Willebrand factor in patients undergoing hemodialysis.

Hemodialysis (HD) is associated with increasing thrombotic trend. Vascular access thrombosis (VAT) increases morbidity in HD patients. The aim of this study was to evaluate ADAMTS13 and VWF plasma levels from patients undergoing HD as putative biomarkers of the hypercoagulability state, as well the association between these markers and VAT occurrence. This study included 195 patients on HD for more than 6 months. HD patients were allocated into two groups according to the occurrence or not of previous episode of VAT; HD with VAT (N = 46) and HD without VAT (N = 149). ADAMTS13 and VWF were performed by ELISA. There was no significant difference between HD patients with and without VAT for ADAMTS13 and VWF levels. However, VWF levels were higher (P < 0.001) and ADAMTS13 were lower (P < 0.001) in HD patients, comparing to the control group composed by healthy subjects without kidney disease, age and sex-matched (N = 80). Taken together our data suggest a potential role of the kidneys function compromised on ADAMTS13 synthesis or metabolism, regardless other known sources of ADAMTS13. The imbalance between ADAMTS13 and VWF levels does not explain the development of VAT in HD patients by itself, although it should contribute for the hypercoagulability state. Therefore, additional studies to identify other risk factors are warranted and essential for better management of HD patients.

Clinical, electrocardiographic and echocardiographic abnormalities in Latin American migrants with newly diagnosed Chagas disease 2005-2009, Barcelona, Spain.

Following Latin American migration, Chagas disease has inevitably appeared in non-endemic countries in Europe and elsewhere. New policies are necessary to prevent transmission in those countries but the long, often undetected chronic period of the early stages of the disease also renders epidemiological studies important. The main objective of our study was to determine the presence of clinical, electrocardiogram (ECG) and echocardiographic abnormalities in a population of Latin American migrants infected with Trypanosoma cruzi at the moment of diagnosis. We performed a hospital-based observational study of 100 adult patients with newly diagnosed Chagas infection between January 2005 and December 2009. Thirty-seven patients were classified within the Brazilian Consensus on Chagas cardiomyopathy early cardiac stages (A or B1) and 49 presented pathological findings (stage B2) according to the Panamerican Health Organization Classification. Overall, 49 patients showed ECG and/or echocardiographic alterations. The presence of ECG and ecocardiographic alterations were significantly associated (p=0.038). The most frequent ECG and echocardiographic findings were right bundle branch block (12 cases) and impaired left ventricular wall relaxation (24 cases), respectively. In conclusion, ECG and echocardiographic alterations coherent with Chagas cardiomyopathy were found in a large proportion of newly diagnosed Latin American migrants infected with T. cruzi. In the mid-term, Chagas disease might become an important cause of chronic cadiomyopathy in our attendance area.

The current status of decision-making procedures and quality assurance in Europe: an overview.

The 2005 Report on Social Responsibility and Health of the UNESCO International Bioethics Committee (Ibc) proposes a new approach to implementing the right to healthcare and suggests a number of Courses of Action to be followed in various fields. Based on the latest available data, we intend to present an overview of the current state of European health systems in two of those fields-decision-making procedures and quality assurance in health care-and to attempt a comparison of the situation with the Report's provisions, in order to pave the way for the identification of what still has to be done to bridge international recommendations and the reality of policy and practice in Europe's health care.

Distribution of 'promoter' sandflies associated with incidence of classic Kaposi's sarcoma.

The patchy geographical distributions of classic Kaposi's sarcoma (KS) and human herpesvirus type 8 (HHV-8), better known as Kaposi's sarcoma-associated herpesvirus (KSHV) remain unexplained. It has been proposed that certain species of bloodsucking insects ('promoter arthropods') promote the reactivation of HHV-8/KSHV and facilitate both HHV-8/KSHV transmission and KS development. This hypothesis was tested by sampling the presence and density of human-biting Diptera with CDC light traps in two areas of Sardinia with contrasting incidence rates of classic KS. In total, 11,030 specimens (99.9% sandflies and 0.1% mosquitoes) belonging to 10 species were collected from 40 rural sites. Five of these species are considered to be possible promoter arthropods because of the irritation their bites cause: Phlebotomus perniciosus Newstead; Phlebotomus perfiliewi Parrot (Diptera: Psychodidae); Aedes berlandi Seguy; Culiseta annulata (Schrank) and Culex theileri Theobald (Diptera: Culicidae). Five species are probable 'non-promoters' because their bites are not particularly irritating: Culiseta longiareolata (Macquart); Culex pipiens s.l.; Anopheles algeriensis Theobald; Anopheles maculipennis s.l., and Anopheles plumbeus Stephens. A significant correlation was found between the geographical distribution of promoter arthropods and incidence rates of KS (Spearman's r = 0.59,P < 0.01). Promoter arthropods were more likely to be caught in areas with cutaneous leishmaniasis and a past high prevalence of malaria, and in areas of limestone, acid volcanic soil and cereal cultivation. The study supports the association between promoter arthropods and classic KS, which may explain the geographic variability of KS and HHV-8/KSHV, and highlights the links with a number of variables previously associated with the incidence of KS.

Biogeographical origin and varicella risk in the adult immigration population in Catalonia, Spain (2004-2006).

Immigrants to the European Union may have a higher susceptibility to varicella-zoster virus primo-infection than the indigenous population. There is no evidence as yet that this is caused by genetic or social factors. Therefore, susceptibility could be due to a lesser transmission of the virus in their ecosystems of origin. A multicentre observational study was performed from July 2004 to June 2006 in four primary healthcare centres in Catalonia, Spain, monitoring varicella incidences and comparing standardised incidence rates and standardised rate ratios among different populations classified according to their biogeographical origin (holarctic, Asian paleotropical, African paleotropical or neotropical). Overall, 516 varicella cases were recorded. The standardised incidence rates per 1,000 inhabitants per year were: holarctic: 2.17 (95% confidence interval (CI): 1.95-2.39); autochthonous 2.26 (95% CI: 2.03-2.49); immigrants 3.59 (95% CI: 2.92-4.26); neotropical 4.50 (95% CI: 3.28-5.71); non-holarctic 5.38 (95% CI: 4.27-6.14); Asian paleotropical 7.03 (95% CI: 4.77-9.28); and African paleotropical 7.05 (95% CI: 1.12-23.58). The difference to the autochthonous population was greatest in immigrants of neotropical origin (standardised rate ratio = 2.07 (95% CI: 1.61-2.64) or 4.5 excess cases per 1,000 inhabitants per year) and Asian paleotropical origin (standardised rate ratio = 3.24 (95% CI: 2.47-4.11) or 9.6 excess cases per 1,000 inhabitants per year). Biogeographical origin may therefore account for the vulnerability of certain immigrant populations to varicella, in particular those from Asian paleotropical (Indostan and Southeast Asia) and neotropical (South America and the Caribbean) ecosystems. Vaccination of immigrants at high risk (fertile women, healthcare workers) could be recommendable.

Blood-feeding preferences of Aedes albopictus (Diptera: Culicidae) in urban and rural settings within the province of Rome, Italy.

We here report the results of field trials carried out in Rome with the aim to obtain data on the feeding behaviour of Aedes albopictus, in relation to different availability and abundance of putative hosts. Human Blood Index values were found higher than 75% in urban areas, where humans represented the most abundant hosts, and lower than 60% in rural areas, where host alternative to humans were frequent. The overall results confirm the generalist feeding-behaviour shown by this species in its original range of distribution and highlighting its high potential as vector of human pathogens in urban areas of Italy.

Targeted Therapy in Thyroid Cancer: State of the Art.

Thyroid cancer typically has a good outcome following standard treatments, which include surgery, radioactive iodine ablation for differentiated tumours and treatment with thyrotropine hormone-suppressive levothyroxine. Thyroid cancers that persist or recur following these therapies have a poorer prognosis. Cytotoxic chemotherapy or external beam radiotherapy has a low efficacy in these patients. 'Target therapy' with tyrosine kinase inhibitors (TKIs) represent an important therapeutic option for the treatment of advanced cases of radioiodine refractory (RAI-R) differentiated thyroid cancer (DTC), medullary thyroid cancer (MTC) and possibly for cases of poorly differentiated (PDTC) and anaplastic thyroid cancer (ATC). In the last few years, several TKIs have been tested for the treatment of advanced, progressive and RAI-R thyroid cancers and some of them have been recently approved for use in clinical practice: sorafenib and lenvatinib for DTC and PDTC; vandetanib and cabozantinib for MTC. The objective of this overview is to present the current status of the treatment of advanced DTC, MTC, PDTC and ATC with the use of TKIs by describing the benefits and the limits of their use. A comprehensive analysis and description of the molecular basis of these drugs and the new therapeutic perspectives are also reported. Some practical suggestions are also given for the management to the potential side-effects of these drugs.

Predictors of failure after single faecal microbiota transplantation in patients with recurrent Clostridium difficile infection: results from a 3-year, single-centre cohort study.

OBJECTIVES: Faecal microbiota transplantation (FMT) is an effective treatment for recurrent Clostridium difficile infection (CDI). Although a single faecal infusion is usually sufficient to eradicate CDI, a considerable number of patients need multiple infusions to be cured. The aim of this study was to identify predictors of failure after single faecal infusion in patients with recurrent CDI. METHODS: We included patients with recurrent CDI prospectively treated with FMT by colonoscopy. By means of univariate and multivariate analysis, variables including female gender, age, number of CDI recurrences, severity of CDI, hospitalization, inadequate bowel preparation, unrelated donor, and use of frozen faeces, were assessed to predict failure after single faecal infusion. RESULTS: Sixty-four patients (39 women; mean age 74 years) were included. Of them, 44 (69%) were cured by a single faecal infusion, whereas 20 (31%) needed repeat infusions. Overall, FMT cured 62 of 64 (97%) patients. In the subgroup of patients with severe CDI, only eight of 26 (30%) were cured with a single infusion. At multivariate analysis, severe CDI (OR 24.66; 95% CI 4.44-242.08; p 0.001) and inadequate bowel preparation (OR 11.53; 95% CI 1.71-115.51; p 0.019) were found to be independent predictors of failure after single faecal infusion. CONCLUSIONS: Severe CDI and inadequate bowel preparation appear to be independent predictors of failure after single faecal infusion in patients treated with FMT by colonoscopy for recurrent CDI. Our results may help to optimize protocols and outcomes of FMT in patients with recurrent CDI.

[Tropical medicine consultation]. / La consulta de medicina tropical.

Tropical medicine consultations are fully justified in settings with the latest modern technology, where specific complementary tests are available and there are professionals with experience in tropical questions. That is to say, in tertiary hospitals. If such consultations took place in secondary hospitals or in primary care, they could be considered inefficient or unjustifiable from the point of view of the volume of patients attended to. However, there is a care deficit with respect to preventive activities concerning travellers or immigrants who have recently arrived from countries with a low income and where there is a high prevalence of imported diseases that are less recognised in our normal health milieu. Thus, international health units, which combine preventive and curative activities in a framework of public health provision and in a functional situation between the hospital level and that of primary care, offer a more efficient and suitable profile for the characteristics of the Spanish population. Their implementation depends on policy makers, the offer of a realistic portfolio of services, the existence of quality control monitoring and the possibility of managing information through a computer network.

[Haemorrhagic exanthema due to dengue virus induced by acetylsalicylic acid]. / Exantema hemorrágico por virus dengue inducido por ácido acetil-salicílico.

Dengue fever, a viral infectious disease characteristic of tropical climates, is considered to be a re-emergent pathology responsible for several serious outbreaks in the last decade. Some factors have been involved in the spread of the virus and its vectorial mosquito carrier: human alteration of the ecosystems, improvement and speed in the transit of goods and people and climate changes. As a reflection of this, an increase in imported cases is probable, especially in tourists coming from endemic areas, considering its short period of incubation (7-10 days). The recognition of personal antecedents of journeys, the main symptoms of the disease and the potential presence of complications (haemorrhagic dengue) should be included in the examination of fever of unknown origin or feverish exanthema. The case of a patient is presented whose clinical picture of classic dengue fever was worsened by self-treatment with acetylsalicylic acid.

Enrichment in Specific Soluble Sugars of Two Eucalyptus Cell-Suspension Cultures by Various Treatments Enhances Their Frost Tolerance via a Noncolligative Mechanism.

A cell-suspension culture obtained from the hybrid Eucalyptus gunnii/Eucalyptus globulus was hardened by exposure to lower temperatures, whereas in the same conditions cells from a hybrid with a more frost-sensitive genotype, Eucalyptus cypellocarpa/Eucalyptus globulus, were not able to acclimate. During the cold exposure the resistant cells accumulated soluble sugars, in particular fructose and sucrose, with a limited increase in cell osmolality. In contrast, the cell suspension that was unable to acclimate did not accumulate soluble sugars in response to the same cold treatment. To an extent similar to that induced after a cold acclimation, frost-hardiness of the cells increased after a 14-h incubation with specific soluble sugars such as sucrose, raffinose, fructose, and mannitol. Such hardening was also observed for long-term cultures in mannitol-enriched medium. This cryoprotective effect of sugars without exposure to lower temperatures was observed in both the resistant and the sensitive genotypes. Mannitol was one of the most efficient carbohydrates for the cryoprotection of eucalyptus. The best hardiness (a 2.7-fold increase in relative freezing tolerance) was obtained for the resistant cells by the cumulative effect of cold-induced acclimation and mannitol treatment. This positive effect of certain sugars on eucalyptus freezing tolerance was not colligative, since it was independent of osmolality and total sugar content.