Six cases of travel-associated legionnaires' disease in Ischia involving four countries

Summary The detection of travel-associated legionellosis can be extremely difficult; hence, an extensive case investigation is recommended in pneumonia-striken travellers and tourists, who are particularly at risk of acquiring the disease. On the Island of Ischia (Isola d'Ischia, Naples, Italy) a total of six cases of Legionnaires' disease occurred from 1986 to 1990. All patients (one man and two women from Germany, one Austrian woman, one Swiss man, and one Italian woman) had taken thermal baths and stayed in local hotels; they all experienced severe pneumonia, and three of them died. These cases were associated with hotels, and the hot-water supply was presumed to have transmitted the infection. Remedial procedures were applied to the hot-water plumbing of the hotels according to the WHO recommendations and were proved to be effective. The occurrences described in this paper stress the importance of rapid and accurate reporting of diagnosed cases to the country where the infection was probably acquired, in order to ensure early detection of endemic foci and emerging clusters of legionellosis.

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Sechs Fälle von reiseassoziierter Legionärskrankheit in Ischia unter Beteiligung von vier Ländern

Zusammenfassung Der Nachweis reiseassoziierter Legionärskrankheit gestaltet sich häufig schwierig. Eine Überwachung von Touristen und Reisenden, die ein erhöhtes Legionellose-Risiko haben, ist daher zu empfehlen. Zwischen 1986 und 1990 traten auf der Insel Ischia (Neapel, Italien) insgesamt sechs Fälle von Legionärskrankheit auf. Alle Patienten (ein Mann und zwei Frauen aus Deutschland, eine Österreicherin, ein Schweizer und eine Italienerin), die in Hotels auf der Insel wohnten, hatten Thermalbäder besucht. Sie erkrankten an schweren Pneumonien, wobei drei Todesfälle auftraten. Die Ansteckungsquelle konnte mit Hotels in Verbindung gebracht werden, wobei die Übertragung der Infektion über die Warmwasserleitungsnetze als gesichert anzunehmen war. Desinfektionsmaßnahmen in den betreffenden Hotels, die nach den Empfehlungen der WHO ausgeführt wurden, erwiesen sich als wirksam. Das genannte Infektionsgeschehen weist auf die Notwendigkeit hin, Fälle von Legionärskrankheit so rasch wie möglich dem Ursprungsland unter Angabe der vermuteten Infektionsquelle zu melden, um sicherzustellen, daß eine Früherkennung endemischer Herde bzw. assoziierter Legionellosen bekannt gemacht wird.

     

The role of resistance characteristics of viral strains in the prediction of the response to antiretroviral therapy in HIV infection

OBJECTIVE: To study the role of resistance characteristics of viral mutants in the prediction of virologic and immunologic response to antiretroviral therapy in HIV-infection. METHODS: This study is based on a mathematical model that generates viral and immunologic dynamics of HIV infection, taking into account drug-resistant mutants and therapy. We analyzed predictive factors of the increase in CD4 cell count and of the decrease in viral load from baseline after 6 months of HAART on a sample of 300 simulated individuals. The set of potential predictors was constituted by patients' state at initiation of therapy and by resistance characteristics of viral strains at that time. Predictive models, obtained by stepwise regression, were selected and compared using Mallows' Cp criterion. RESULTS: In addition to baseline viral load and CD4 cell count, known to influence response to therapy, baseline CD8 cell count and resistance characteristics of detectable strains are shown to improve the accuracy of the prediction. On the contrary, resistance parameters of low frequency viral mutants have no predictive value. CONCLUSIONS: Characteristics of preexisting detectable resistant mutants as determinants of virologic and immunologic response to antiretroviral therapy increase the capacity to predict the outcome of the treatment. Therefore, the use of phenotypic and genotypic testing could be crucial and should be considered for the choice of therapy.     

Expression profiling of 21 biomolecules in locally advanced nasopharyngeal carcinomas of Caucasian patients

Background

Since scarce data exist on the pathogenesis of nasopharyngeal carcinoma in Caucasian patients, we attempted to elucidate the responsible molecular pathways in this patient population.

Methods

Formalin-fixed paraffin-embedded tumor tissue samples from 107 patients, diagnosed with locally-advanced nasopharyngeal carcinoma and treated with chemotherapy or chemo-radiotherapy, were analyzed by immunohistochemistry for the expression of the following proteins: E-cadherin, P-cadherin, Fascin-1, Cyclin D1, COX-2, EGFR, VEGF-A, VEGF-C, VEGFR-2, VEGFR-3, ERCC1, p53, p63, Ki67, MAPT, phospho-p44/42MAPK, PTEN, phospho-AKT, phospho-mTOR, and phospho-GSK-3β. EBER status was assessed by in situ hybridization. The majority of the cases were included in tissue microarray. All stains were performed and assessed centrally by two pathologists. The median follow-up time was 76.8 (42.3 – 99.2) months.

Results

Biomolecules expressed in >90% of cases were: p53, COX-2, P-cadherin, EBER, phospho-GSK-3β, and Fascin-1. WHO II+III tumors were more frequently EBER & PTEN positive and VEGF-A negative. Advanced age was significantly associated with positive phospho-GSK-3β and ERCC1 expression; male gender with positive phospho-AKT and phospho-p44/42MAPK; and worse performance status (1 or 2) with negative Ki67, ERCC1, PTEN, and phospho-mTOR expression. Earlier disease stage was closely associated with p63, MAPT, PTEN, and Cyclin D1 positivity. Univariate Cox regression analysis highlighted Cyclin D1 as a negative prognostic factor for disease-free survival (p=0.034) and EBER as a positive one for overall survival (p=0.048). In multivariate analysis, advanced age and stage, poor performance status, and positive ERCC1 emerged as predictors of worse disease-free and overall survival, as opposed to positive phospho-mTOR. Clustering analysis defined two protein-expression groups being predictive of better overall survival (p=0.043).

Conclusions

Our study is the first to examine the activation and interaction of established biomolecules and signaling pathways in Caucasian NPC patients in an effort to reveal new therapeutic targets.     

Mutational profiling of the RAS,PI3K,MET and b-catenin pathways in cancer of unknown primary: a retrospective study of the Hellenic Cooperative Oncology Group

Cancer of unknown primary origin (CUP) had a poor prognosis, determined by clinico-histological characteristics, partly due to the lack of insights on its biology. We screened tumour DNA from 87 patients with CUP for CTNNB1 (coding exons 2,3,4,5), MET (coding exon 18), PIK3CA (coding exons 9,20), KRAS (coding exons 1,2), BRAF (coding exon 15) gene mutations by using dd-sequencing and evaluated their impact on prognosis. Mutated gene incidences in the 87 CUP cases were: KRAS 11 (12.6 %), BRAF 5 (5.7 %), PIK3CA 8 (9 %), MET 6 (6.7 %) and CTNNB1 18 (20.7 %). Several mutations in the KRAS gene were not the commonly encountered mutations in other solid tumours. Activating mutations were observed in 10.2 % in KRAS, 4.5 % in BRAF, 6.6 % in PIK3CA, 4.5 % in MET, and 19.5 % in CTNNB1. Activating mutations in PIK3CA coding exon 9 were inversely correlated with MET coding exon 18 activating mutations (p = 0.036). MET activating mutations were prognostic for poor Progression-Free Survival (median PFS 5 vs 9 months, p = 0.009) and Overall Survival (median OS 7 vs 20 months, p = 0.005). The complex profile of either CTNNB1 or MET mutations also had an adverse prognostic significance (median OS 11 vs 21 months, p = 0.015). No other gene mutation exhibited prognostic significance. In multivariate analysis, poor performance status, male gender, visceral disease and adenocarcinoma histology, but not gene mutations, were independently associated with poor patient outcome. CTNNB1 gene mutations are frequent, and along with MET mutations have an adverse prognostic effect in patients with CUP.     

Cetuximab plus FOLFOX6 or FOLFIRI in metastatic colorectal cancer: CECOG trial

AIM: To investigate efficacy and safety of cetuximab combined with two chemotherapy regimens in patients with unresectable metastatic colorectal cancer (mCRC). METHODS: Randomized patients received cetuximab with 5-fluorouracil (5-FU), folinic acid (FA) and oxaliplatin (FOLFOX) 6 (arm A, n = 74) or 5-FU, FA and irinotecan (FOLFIRI) (arm B, n = 77). KRAS mutation status was determined retrospectively in a subset of tumors (n = 117). RESULTS: No significant difference was found between treatment arms A and B ...     

Hierarchical model-based tracking of cervical vertebrae from dynamic biplane radiographs

We present a novel approach for automatically, accurately and reliably determining the 3D motion of the cervical spine from a series of stereo or biplane radiographic images. These images could be acquired through a variety of different imaging hardware configurations. We follow a hierarchical, anatomically-aware, multi-bone approach that takes into account the complex structure of cervical vertebrae and inter-vertebrae overlapping, as well as the temporal coherence in the imaging series. These significant innovations improve the speed, accuracy, reliability and flexibility of the tracking process. Evaluation on cervical data shows that the approach is as accurate (average precision 0.3 mm and 1°) as the expert human-operator driven method that was previously state of the art. However, unlike the previously used method, the hierarchical approach is automatic and robust; even in the presence of implanted hardware. Therefore, the method has solid potential for clinical use to evaluate the effectiveness of surgical interventions.     

Oral modifications during menopause

The menopause, a physiological process specific to elderly women (>50 years) is defined by various involutive phenomena occurred at general level and particularly in the stomatognatic system elements. The authors followed the influence of the oral contraceptives in changes of oral tissues during menopause. The study was carried on 148 elderly women during menopause split in two groups: group I (study group) who have used oral contraceptives in earlier years, group II (control group) without contraceptive therapy. The evaluation of the results was made using clinical exams and complementary investigations (X-ray, cytological, histopathological, mycological, salivary rate exams) and index quantification. The results showed the importance of the apparition of changes in to the oral tissues during menopause increased in comparison to the control group. Corresponding prevention strategies are the basis of oral health management in women at menopause.     

Available clinical markers of treatment outcome integrated in mathematical models to guide therapy in HIV infection

Because treatment failure in many HIV-infected persons may be due to multiple causes, including resistance to antiretroviral agents, it is important to better tailor drug therapy to individual patients. This improvement requires the prediction of treatment outcome from baseline immunological or virological factors, and from results of resistance tests. Here, we review briefly the available clinical factors that have an impact on therapy outcome, and discuss the role of a predictive modelling approach integrating these factors proposed in a previous work. Mathematical and statistical models could become essential tools to address questions that are difficult to study clinically and experimentally, thereby guiding decisions in the choice of individualized drug regimens.     

Principal intestinal parasites of dogs in Tirana,Albania

From 2004 to 2009, the digestive tracts of 111 dogs from suburban areas around Tirana, Albania, were examined for intestinal helminths. In addition, rectal faecal samples of all dogs were examined for protozoan infections and 48 faecal samples from dogs >6 months of age were processed with the Baermann technique to test for the excretion of lungworm larvae. The heart and pulmonary arteries of 30 dogs >6 months of age also were examined for nematode parasites. The intestinal parasite fauna of the dogs included three protozoan species (Cystoisospora canis, Cystoisospora ohioensis/burrowsi, Sarcocystis spp.), three cestode species (Dipylidium caninum, Taenia hydatigena, Echinococcus granulosus), five nematode species (Ancylostoma caninum, Uncinaria stenocephala, Toxocara canis, Toxascaris leonina, Trichuris vulpis) and one acanthocephalan (Centrorhynchus buteonis). Rates of infection were: 15.3% for C. canis, 31.5% for C. ohioensis/burrowsi, 1.8% for Sarcocystis spp., 65.8% for D. caninum, 16.2% for T. hydatigena, 2.7% for E. granulosus (genotype G1), 13.5% for A. caninum, 64.9% for U. stenocephala, 75.7% for T. canis, 0.9% for T. leonina, 21.6% for T. vulpis and 0.9% for C. buteonis. Up to six species of gastrointestinal parasites were found per dog. The 63 ≤6-month-old dogs harboured significantly (p < 0.001) fewer gastrointestinal parasite species concurrently (mean 2.65 ± 1.25 species per animal) than the 48 older animals (mean 3.77 ± 1.45 species per animal). Dogs >6 months of age harboured significantly (p < 0.05) more D. caninum, T. hydatigena, A. caninum, U. stenocephala and T. vulpis compared to younger dogs. Conversely, the younger dogs harboured significantly (p < 0.001) more T. canis than the older ones. There was no difference in the male and female dogs’ counts of individual intestinal helminth species apart from T. hydatigena in dogs >6 months of age: Male dogs harboured significantly (p < 0.05) more tapeworms than female dogs. Based on faecal examination, there was no indication for lungworm infection; however, two adult heartworms (Dirofilaria immitis) were found in the right ventricle of one dog.     

Malignant primary pulmonary tumor with hemangiopericytoma-like features: conventional hemangiopericytoma versus solitary fibrous tumor

Although extremely rare, the primitive lung hemangiopericytoma in adults is similar to hemangiopericytomas with other soft tissue localizations. Although generally benign and curable after radical surgery, it might also have a malignant clinical course with dissemination in both lungs, infiltration of vital organs (heart, pulmonary artery), extension to the adjacent tissues, and even pulmonary metastases. The treatment of choice is the complete tumor resection with negative surgical margins after excision. Certain histologic features might indicate a malignant potential. The clinical outcome of patients is variable: some are cured after radical surgery and others might present relapse and recurrences that necessitate a second intervention, radiation therapy, and/or chemotherapy. Over the years, the conventionally-defined hemangiopericytoma concept has evolved because of the nonspecific histologic growth pattern (characteristic monotonous appearance, moderate or high cellularity, and a well-developed branching vascular pattern) shared by numerous, unrelated benign or malignant lesions. Hemangiopericytoma is no longer considered a specific entity but rather as a characteristic growth pattern; in the heterogeneous group of hemangiopericytoma-like neoplasms, many lesion categories have been individualized and defined. We report an uncommon case of primitive lung tumor exhibiting hemangiopericytoma-like features, with an aggressive, fatal clinical course. Because of the major histologic overlap between solitary fibrous tumor and hemangiopericytoma and lack of clear classification criteria, we encountered difficulty in including this case in a known clinical entity; primitive solitary fibrous tumor of the lung, which mimics lung hemangiopericytoma, seemed to be the most plausible diagnosis. We discuss the case particularities and the radiologic and pathologic correlations.