Acute perchloroethylene intoxication in an elderly woman: a case report.

BACKGROUND: Perchloroethylene is a colorless, strong-smelling substance commonly used for dry cleaning. Liver and kidney toxicities and carcinogenicity are well-known occupational hazards caused by chronic perchloroethylene exposure. Acute intoxication by ingestion of nondiluted perchloroethylene is rare in the adult population owing to its strong smell and taste. Very few data are available to physicians managing patients in this situation. CASE PRESENTATION: An 89-year-old Caucasian woman accidentally drank perchloroethylene while visiting her laundry, leading to a coma within a few minutes. The poison control center provided little information about perchloroethylene toxicity after ingestion, including an estimated long biological half-life (144 hour) and detrimental effects to liver and kidneys. A long intensive care unit stay was thus expected, potentially leading to several complications. After intubation, transitory hypoxemia appeared and rapidly resolved, while mild hemodynamic instability was managed with fluid resuscitation and anti-arrhythmic drugs. Twelve hours after perchloroethylene ingestion, the patient suddenly woke up and self-extubated. Less than 24 hours after ingestion, she was discharged from the intensive care unit, and 4 days later she was discharged home. CONCLUSION: The patient drank perchloroethylene from a bottle, which prevented her from smelling it, and owing to its taste, only a small sip was likely drunk. However, a much larger intake was presumed, given her rapid and profound central nervous system depression. This case was challenging owing to the paucity of information available regarding acute perchloroethylene ingestion and the duration and magnitude of its effect. The present report will hopefully be of support for clinicians managing patients with this rare acute intoxication.

Determination of cannabinoids in hair: Indicators for illegal vs CBD-rich cannabis use.

Cannabis products rich in cannabidiol (CBD) and low in Δ9-tetrahydrocannabinol (THC) (e.g., light cannabis in Italy) are becoming widely popular and available on the market as replacements for THC preparations and tobacco for their recreational and/or therapeutic benefits. In this paper, which aims to establish alternative discrimination parameters between hair samples from CBD-rich and THC-prevalent cannabis users, cannabinoid concentrations, such as THC, CBD, 11-nor-9-carboxy-Δ9-tetrahydrocannabinol (THC-COOH) and 11-hydroxy-Δ9-tetrahydrocannabinol (11-OH-THC) were quantified in 127 hair samples by a GC-MS/MS technique. Initially, this analysis was able to discriminate two cohorts: cohort 1 (individuals with THC values ≥ 0.05 ng/mg and THC-COOH ≥ 0.2 pg/mg or THC-positive users, n = 60) and cohort 2 (individuals with THC values ranging between 0.01 and 0.05 ng/mg and THC-COOH or 11-OH-THC ≥ LOQs, n = 67). The evaluation of CBD/THC ratio in cohort 2 identified two further sub-cohorts 2a (CBD/THC<<1 or ~ 1, THC-prevalent cannabis users) and 2b (CBD/THC>>1, suspected CBD-rich and THC-low cannabis users). The latter showed unusual profiles for THC metabolites, in particular for 11-OH-THC. Statistical evaluation of the data of cohort 1, cohort 2a and cohort 2b yielded significant differences in CBD/THC and THC/11-OH-THC. Based on the analysis of 337 seized cannabis samples and 630 CBD-rich/light cannabis samples by GC-FID and GC-MS, respectively, we also evaluated statistical differences in the CBD/THC ratio between biological (hair) and plant-derived samples. Considering the legal implications of a positive result, the obtained findings could be relevant for the interpretation of cannabinoid concentrations in hair. Further studies are necessary to elucidate the reason behind the unusual metabolic ratios.

Quantitative Lipidomic Analysis of Osteosarcoma Cell-Derived Products by UHPLC-MS/MS.

Changes in lipid metabolism are involved in several pathological conditions, such as cancer. Among lipids, eicosanoids are potent inflammatory mediators, synthesized from polyunsaturated fatty acids (PUFAs), which coexist with other lipid-derived ones, including endocannabinoids (ECs) and N-acylethanolamides (NAEs). In this work, a bioanalytical assay for 12 PUFAs/eicosanoids and 20 ECs/NAEs in cell culture medium and human biofluids was validated over a linear range of 0.1-2.5 ng/mL. A fast pretreatment method consisting of protein precipitation with acetonitrile followed by a double step liquid-liquid extraction was developed. The final extracts were injected onto a Kinetex ultra-high-performance liquid chromatography (UHPLC) XB-C18 column with a gradient elution of 0.1% formic acid in water and methanol/acetonitrile (5:1; v/v) mobile phase. Chromatographic separation was followed by detection with a triple-quadrupole mass spectrometer operating both in positive and negative ion-mode. A full validation was carried out in a small amount of cell culture medium and then applied to osteosarcoma cell-derived products. To the best of our knowledge, this is the first lipid profiling of bone tumor cell lines (SaOS-2 and MG-63) and their secretome. Our method was also partially validated in other biological matrices, such as serum and urine, ensuring its broad applicability as a powerful tool for lipidomic translational research.

Comparison of clinical and angiographic prognostic risk scores in elderly patients presenting with acute coronary syndrome and referred for percutaneous coronary intervention.

BACKGROUND: Multiple risk prediction models have been validated in all-age patients presenting with acute coronary syndrome (ACS) and treated with percutaneous coronary intervention (PCI); however, they have not been validated specifically in the elderly. METHODS: We calculated the GRACE (Global Registry of Acute Coronary Events) score, the logistic EuroSCORE, the AMIS (Acute Myocardial Infarction Swiss registry) score, and the SYNTAX (Synergy between Percutaneous Coronary Intervention with TAXUS and Cardiac Surgery) score in a consecutive series of 114 patients ≥75 years presenting with ACS and treated with PCI within 24 hours of hospital admission. Patients were stratified according to score tertiles and analysed retrospectively by comparing the lower/mid tertiles as an aggregate group with the higher tertile group. The primary endpoint was 30-day mortality. Secondary endpoints were the composite of death and major adverse cardiovascular events (MACE) at 30 days, and 1-year MACE-free survival. Model discrimination ability was assessed using the area under receiver operating characteristic curve (AUC). RESULTS: Thirty-day mortality was higher in the upper tertile compared with the aggregate lower/mid tertiles according to the logistic EuroSCORE (42% vs 5%; odds ratio [OR] = 14, 95% confidence interval [CI] = 4-48; p <0.001; AUC = 0.79), the GRACE score (40% vs 4%; OR = 17, 95% CI = 4-64; p <0.001; AUC = 0.80), the AMIS score (40% vs 4%; OR = 16, 95% CI = 4-63; p <0.001; AUC = 0.80), and the SYNTAX score (37% vs 5%; OR = 11, 95% CI = 3-37; p <0.001; AUC = 0.77). CONCLUSIONS: In elderly patients presenting with ACS and referred to PCI within 24 hours of admission, the GRACE score, the EuroSCORE, the AMIS score, and the SYNTAX score predicted 30 day mortality. The predictive value of clinical scores was improved by using them in combination.

Horizontal glottectomy: is it an out-of-date procedure?

PURPOSE: The aim of the study is to illustrate our experience with horizontal glottectomy (HG), reviewing the indications and results of this uncommon partial laryngectomy. MATERIALS AND METHODS: It is a retrospective study. We completed a chart review of patients who underwent partial laryngectomy between May 2003 and June 2010. Patients who underwent HG were included in the study. Data obtained were collected and analyzed. RESULTS: Seven male patients were included in the study (mean age was 78 years; range, 69-88 years). In all cases, the TNM classification was pT1bN0M0 apart from one patient who had pT1N1M0. Three patients had a moderately differentiated neoplasm (G2), whereas 4 patients had a well-differentiated tumor (G1). Tracheotomy tube removal, oral feeding, and voice analysis have been evaluated and reported in the study. Mean follow-up was 16 months. CONCLUSIONS: Horizontal glottectomy might be a worthwhile treatment option in selected patients nowadays. In older patients with anterior commissure involvement, this procedure guarantees adequate functional and good oncological results. This study may possibly help surgeons dealing with glottic cancer involving the anterior commissure because we believe that some patients could benefit from HG, even in this radiotherapy and transoral laser surgery "era."

Optimizing pemetrexed-gemcitabine combination in patients with advanced non-small cell lung cancer: a pharmacogenetic approach.

INTRODUCTION: The pemetrexed-gemcitabine combination is effective in patients with non-small cell lung cancer (NSCLC). Preclinical data suggest that pemetrexed may synergistically interact with gemcitabine by enhancing the expression of human equilibrative nucleoside transporter 1 (hENT1) and deoxycytidine kinase (dCK), increasing the uptake and intracellular activation of gemcitabine. A pharmacogenetic approach was adopted to evaluate hENT1 and dCK expressions in humans and to identify the potential best time interval to administer gemcitabine after pemetrexed in patients with advanced NSCLC. METHODS: The dCK and hENT1 expressions, examined by quantitative real-time polymerase chain reaction, were analyzed during each cycle before and at 1, 2, 4, 6, 24, and 48 hours after pemetrexed administration. The relative differences from baseline to each planned time, for peak values and for the relative difference at peak, were measured. RESULTS: Nineteen patients were treated with pemetrexed single agent (500 mg/m every 15 or 21 days). Quantitative real-time polymerase chain reaction analysis revealed a statistically significant (p < 0.001) biphasic increase in both hENT1 and dCK genes at 1 to 2 and 24 to 48 hours after pemetrexed administration. CONCLUSIONS: This is the first evidence of dCK and hENT1 induction by pemetrexed in humans, suggesting that the pemetrexed→gemcitabine combination should be optimized by the administration of gemcitabine 1 to 2 or 24 to 48 hours after pemetrexed. These results support further studies to validate the role of dCK/hENT1 in vivo modulation for the optimization of gemcitabine-pemetrexed combination in patients with NSCLC.

Diagnosis of anal human papillomavirus infection: polymerase chain reaction or cytology?

OBJECTIVES: To investigate the relationship between human immunodeficiency virus (HIV)-positive and HIV-negative patients engaging in promiscuous behaviors and anal human papillomavirus (HPV) infection diagnosed by polymerase chain reaction (PCR) and cytology. METHODS: Fifty-six HIV-positive patients and 49 HIV-negative patients who engaged in sexually promiscuous behavior were enrolled in the study. We performed cytological exams using the Pap smear and PCR for HPV-DNA detection, with identification of oncogenic strains. The 2001 Bethesda System terminology was used for the cytological exams. We also evaluated the immunologic status of the HIV-infected patients. RESULTS: PCR positivity for HPV-DNA was higher in the group of HIV-positive patients than in the group of HIV-negative patients with a statistically significant difference. In contrast we did not find any statistically significant difference by cytological exam. Oncogenic strains were equally distributed in the two groups. CONCLUSIONS: Our results indicate the importance of the cytological exam for anal HPV screening in the population at high risk of sexually transmitted disease and that HPV-DNA PCR can be used only as adjunct test.

CT and MR findings in synovial chondromatosis of the temporo-mandibular joint: our experience and review of literature.

OBJECTIVE: To compare Computed Tomography (CT) and Magnetic Resonance (MR) features and their diagnostic potential in the assessment of Synovial Chondromatosis (SC) of the Temporo-Mandibular Joint (TMJ). MATERIALS AND METHODS: Eight patients with symptoms and signs compatible with dysfunctional disorders of the TMJ underwent CT and MR scan. We considered the following parameters: soft tissue involvement (disk included), osteostructural alterations of the joints, loose bodies and intra-articular fluid. These parameters were evaluated separately by two radiologists with a "double blinded method" and then, after agreement, definitive assessment of the parameters was given. CT and MR findings were compared. RESULTS: Histopathological results showed metaplastic synovia in all patients and therefore confirmed diagnosis of SC. MR resulted better than CT in the evaluation of all parameters except the osteostructural alterations of the joints, estimated with more accuracy by CT scan. CONCLUSIONS: CT scan is excellent to define bony surfaces of the articular joints and flogistic tissue but it fails in the detection of loose bodies when these are not yet calcified. MR scan therefore is the gold standard when SC is suspected since it can visualize loose bodies at early stage and also evaluate disk condition and eventual extra-articular tissues involvement. The use of T2-weighted images and contrast medium allows identifying intra-articular fluid, estimating its entity and discriminating from sinovial tissue.

Diffusion-weighted MRI in cervical lymph nodes: differentiation between benign and malignant lesions.

OBJECTIVE: Purpose of our study was to assess the potential role of diffusion-weighted imaging (DWI) in the differential diagnosis between benign and malignant nodes. SUBJECT AND METHODS: We enrolled 32 subjects: 14 with benign lymphadenopathy, 17 patients with histologically proved malignant disease before beginning treatment and 1 patient with lymphoma after chemotherapeutic treatment. In all patients we used fast spin echo T2-weighted images in axial and coronal planes, fast spin echo T1-weighted images before and after contrast medium of administration in axial and coronal planes. Before contrast administration diffusion sequences were acquired on the axial and coronal plane (b factor of 0.500 and 1000 s/mm(2)) and then apparent diffusion coefficient (ADC) maps were reconstructed. RESULTS: On diffusion images, 13/14 patients with benign nodes showed low signal intensity and had high signal on ADC maps, whereas all patients with malignant diseases appeared hyperintense on diffusion images and with low signal intensity on ADC maps. Only a patient with tuberculosis showed a low ADC value. The mean ADC value of malignant nodes was about 0.85 × 10(-3)mm(2)/s, the mean value of benign nodes was 1.448 × 10(-3)mm(2)/s; this difference was statistically significant (p < 0.01). The mean ADC value of treated nodes was 1.75 × 10(-3)mm(2)/s. The best threshold value was 1.03 × 10(-3)mm(2)/s, obtaining a sensitivity of 100% and a specificity of 92.9%. CONCLUSIONS: Diffusion imaging could be considered an important supportive tool for the diagnosis of enlarged cervical lymphadenopathies.

Carotid stenting and transcranial Doppler monitoring: indications for carotid stenosis treatment.

BACKGROUND: Recently, angioplasty and stenting of carotid arteries (CAS) have taken the place of surgery. The aim of our study is to assess the role of transcranial Doppler (TCD) monitoring during CAS to address the embolic complications during the stages of the procedure, with or without embolic cerebral protection devices. METHODS: A total of 152 patients were submitted to carotid stenting. All patients were submitted to carotid arteries Duplex scanning. RESULTS: Neurological complications are related to TCD detection of corpuscolate signals in rapid succession. Even if no reduction of the overall incidence rate of microembolic signals (MES) was observed, a decrease in the number of corpuscolate emboli were recorded when a cerebral protection was working. CONCLUSIONS: According to our study, even in selected patients on the basis of preoperative diagnostic criteria, CAS is burdened by a nonnegligible risk of subclinical embolic ischemic events detected at TCD and confirmed by diffusion-weighted magnetic resonance imaging (DW-MRI).

Interstitial high-dose-rate brachytherapy after breast conserving surgery.

We evaluated local recurrence, toxicity rate and cosmetic outcome in 72 patients treated with high-dose-rate (HDR) brachytherapy after breast conserving surgery. HDR brachytherapy was administered: i) as partial breast irradiation (PBI) in 64 patients with low-risk early stage breast cancer, enrolled in a phase II prospective study; ii) as PBI after a second conservative surgery as treatment of local relapse in 3 patients; iii) for delivering a boost after whole breast external beam radiotherapy in 5 patients. Implantation was done during surgery (breast conserving or re-excision to achieve adequate surgical margins), with the wound open, or postoperatively. The implant was well tolerated in all patients, so no premature catheter removal was required. At a median follow-up of 32 months (range 5-52) no local recurrence has been observed. Toxicity was very low. Cosmetic outcome was excellent/good in a high percentage of patients. Our results suggest that PBI administered with HDR brachytherapy is feasible in selected patients with low risk early stage breast carcinoma. PBI seems feasible to repeat radiotherapy after a salvage breast conserving surgery for local relapse in a second attempt to preserve the breast.

Strain rate dobutamine echocardiography for prediction of recovery after revascularization in patients with ischemic left ventricular dysfunction.

BACKGROUND: The purpose of the present study was to assess the accuracy of quantitative segmental analysis by strain rate imaging (SRI) technique during dobutamine test for detecting myocardial recovery after revascularization in patients with chronic ischemic regional left ventricular (LV) dysfunction and compare results with those of 2-dimensional echocardiography (2D) and tissue Doppler imaging (TDI) as well as rest-4 hours-24 hours redistribution thallium SPECT (Tl SPECT). METHODS AND RESULTS: Forty-one patients with chronic ischemic regional LV dysfunction (EF 29 +/- 8%) underwent dobutamine 2D/TDI/SRI and Tl SPECT before and after myocardial revascularization. The sensitivity, specificity, and accuracy for the recovery of regional LV function were 73%, 81%, and 77% for dobutamine 2D; 77%, 82%, and 80% for dobutamine TDI; 86%, 88%, and 85% for dobutamine SRI; and 94%, 76%, and 84% for Tl tomography. The area under the ROC curve (AUC), which reflects the overall performance for the prediction of recovery, was 0.79 for systolic-SR, 0.81 for Tl SPECT, 0.83 for postsystolic strain, and 0.87 for isovolumic-SR. If both systolic and postsystolic SRI indexes were combined with Tl SPECT, the AUC was improved to 0.94. CONCLUSIONS: Dobutamine SRI is more accurate than TDI in identifying hibernating myocardium. Systo-diastolic values obtained using dobutamine SRI echocardiography and values derived from nuclear perfusion techniques may be complementary in assessing myocardial viability.

Kynurenic acid inhibits the release of the neurotrophic fibroblast growth factor (FGF)-1 and enhances proliferation of glia cells, in vitro.

1. Kynurenic (KYNA) and quinolinic (QUIN) acids are neuroactive tryptophan metabolites formed along the kynurenine pathway: the first is considered a non-competitive antagonist and the second an agonist of glutamate receptors of NMDA type. The affinity of these compounds for glutamate receptors is, however, relatively low and does not explain KYNA neuroprotective actions in models of post-ischemic brain damage. 2. We evaluated KYNA effects on the release of fibroblast growth factor (FGF)-1, a potent neurotrophic cytokine. Because KYNA exhibits a neuroprotective profile in vitro and in vivo, we anticipated that it could function as an autocrine/paracrine inducer of FGF-1 release. Studies were performed in several models of FGF-1 secretion (FGF-1 transfected NIH 3T3 cells exposed to heat shock, A375 melanoma cells exposed to serum starvation, growth factor deprived human endothelial cells). To our surprise, KYNA, at low concentration, inhibited FGF-1 release in all cellular models. QUIN, a compound having opposite effects on glutamate receptors, also reduced this release, but its potency was significantly lower than that of KYNA. 3. KYNA and QUIN also displayed a major stimulatory effect on the proliferation rate of mouse microglia and human glioblastoma cells, in vitro. 4. Our data suggest that minor changes of local KYNA concentration may modulate FGF-1 release, cell proliferation, and ultimately tissue damage in different pathological conditions.