A case report of catheter-related bloodstream infection due to Trichosporon coremiiforme in a patient with secondary neutropenia to HIV.

Here, we describe an invasive infection due to Trichosporon coremiiforme in an HIV positive patient with neutropenia. The strain was first erroneously identified as Trichosporon asahii by conventional methods, but correctly identified by mass spectrometry using matrix-assisted laser desorption/ionization time-of-flight technology (MALDI-TOF MS) and ribosomal DNA sequencing. The infection was successfully resolved after antifungal treatment with amphotericin B and fluconazole. This case report is a contribution to the study of T. coremiiforme infections and reinforces its relevance as a species capable of causing invasive human infection in immunocompromised patients and also contributes to the study of its susceptibility profile against antifungal drugs.

Management of atrial fibrillation in the Emergency Department: current approach and future expectations.

Atrial fibrillation (AF) is the most common cardiac dysrhythmia and occurs in 3.3%-10% of emergency admissions. It is frequently quoted for people over the age of 75, but the cases of AF in young subjects without structural heart disease are also increasing, therefore, leading to the evaluation of "lonely atrial fibrillation" as a new challenge for the clinician. The first diagnosis and treatment often occur in the emergency room and the emergency physician has therefore to evaluate the initial step towards the therapeutic decisions. Although international standard guidelines are available, AF treatment in the Emergency Department (ED) is still heterogeneous in terms of the management strategy chosen. There are two main strategies for the management of AF: rate and rhythm control. Moreover, antithrombotic treatment is pivotal in AF to prevent cardioembolic stroke and it is considered a primary objective after an accurate assessment of antithrombotic treatment risks and benefits. The introduction of innovative echocardiographic approach, directly in ED, seems to improve the management and risk stratification of patients with AF. This review aims to provide an overview about the current approach and the future expectations in the management of AF in ED. This manuscript represents a synopsis of the lectures on AF management in the ED of the Third Italian GREAT Network Congress, that was hold in Rome, 15-19 October 2012. We decided to use only the most relevant references for each contribution as suggested by each participant at this review.

Safety and efficacy of low-dose fondaparinux (1.5 mg) for the prevention of venous thromboembolism in acutely ill medical patients with renal impairment: the FONDAIR study.

BACKGROUND: Renal impairment is common, affecting around 40% of acutely ill medical patients, and is associated with an increased risk of both venous thromboembolism (VTE) and bleeding. The clinical benefit of effective thromboprophylactic strategies may be outweighed in these patients by an excessive rate of hemorrhage. OBJECTIVE: To assess the safety and efficacy of lower prophylactic doses of fondaparinux in acutely ill medical patients with renal impairment. PATIENTS/METHODS: We carried out a multicenter, investigator-initiated, prospective cohort study. Patients at risk of VTE with a creatinine clearance between 20 and 50 mL min(-1) were treated with fondaparinux 1.5 mg qd for a minimum of 6 to a maximum of 15 days. The primary outcome was the incidence of major bleeding; secondary outcomes were clinically relevant non-major bleeding (CRNMB) and symptomatic VTE. RESULTS: We enrolled 206 patients with a mean age of 82 years, mean creatinine clearance of 33 mL min(-1) , and a mean Charlson co-morbidity index of 8.2. One patient had major bleeding (0.49%, 95% confidence interval [CI] 0.03-3.10), eight had CRNMB (3.88%, 95% CI 1.81-7.78) and three developed symptomatic VTE (1.46%, 0.38-4.55). Twenty-three patients (11.17%, 7.36-16.48) died. No independent predictors of bleeding were found at univariate analysis. CONCLUSIONS: The addition of moderate to severe renal impairment to patients with traditional risk factors for VTE identified a population of very elderly acutely ill medical patients potentially at high risk of both VTE and bleeding complications. The recently approved lower prophylactic dose of fondaparinux appears to be a safe and relatively effective strategy in these patients.

A spontaneous decrease of blood pressure occurs in acute ischemic stroke with favourable neurological course.

BACKGROUND: In the acute phase of ischemic stroke the relationship between blood pressure (BP) and clinical outcome remains not clear. The aim of our study was to evaluate the association of stroke severity and BP measurements in the acute phase of stroke, and whether early variation of neurological status affects BP profiles. METHODS: BP on admission was obtained with mercurial sphygmomanometer and 24h-ambulatory BP monitoring (ABPM) was performed on days 1(st) and 6(th). Enrolled patient were grouped according to the neurological deficit at onset (graded by the NIHSS) in group A, (NIHSS score ≤ 10, mild/moderate) and group B (NIHSS score > 10, moderate/severe) and according to the occurrence of early neurological improvement, defined as a NIHSS score reduction of at least 4 points at the 6(th) day in group C (improved) and in group D (not improved). RESULTS: A total of 57 patients were enrolled. On admission sphygmomanometric systolic BP values were higher in group A with respect to group B (158,5 mmHg ± 26,9 vs 147,7 mmHg ± 15,5 respectively; p = 0.6) whereas no difference was found in ABPM. On admission sphygmomanometric BP and ABPM were similar in group C and group D. At the 6(th) day ABPM, both systolic BP and diastolic BP values were significantly reduced in clinically improved patients (Δ systolic BP 1(st) to 6(th) day = 9,9±13,3 in group C vs 0,5±17,6 in group D, p < 0,05; Δ diastolic BP 1(st) to 6(th) day = 5,1± 8,4 mmHg in group C vs 1,3 ± 9,7 mmHg in group D, p = ns) whereas no change in the 24-h BP profile was observed in patients without early improvement. CONCLUSION: BP on admission in not related to the stroke severity and does not predict early neurological outcome and patients that show an early neurological improvement show also a reduction of the BP profile.

Effect of intravenous tirofiban and aspirin in reducing short-term and long-term neurologic deficit in patients with ischemic stroke: a double-blind randomized trial.

BACKGROUND: Thrombolysis with rt-PA is the only approved pharmacological therapy for acute ischemic stroke presently administrable in a 3-hour window (very recently extended to 4.5 h). After this time, the choice is limited to endovascular treatment and antiplatelet drugs, mainly aspirin (ASA), the efficacy of which in the acute phase of stroke has poorly been evaluated. We compared the efficacy of tirofiban, a GP-IIb/IIIa inhibitor, and ASA, with both drugs being administered within 6 h. METHODS: 150 patients were randomly assigned to treatment with tirofiban or ASA, both given for 3 days in a double-blind regimen. Major inclusion criteria were stroke onset within 6 h and a baseline National Institute of Health Stroke Scale (NIHSS) score of 5-25. Outcome variables were the proportion of patients with a NIHSS score reduction of > or =4 points after 72 h, and the proportion of patients with an mRS score of 0-1 at 3 months. RESULTS: The trial, originally planned to enroll 300 patients, was halted after enrollment of 150 patients at interim analysis due to the lack of a trend difference between the 2 treatment groups. Neurological improvement at 72 h was observed in 56% of the patients in each group. At the 3-month follow-up, minimal or absent disability was seen in 45% of the patients in the tirofiban group and 53% in the ASA group; these differences were not statistically significant. Three-month mortality was the same in both groups (10.6%); the rates of symptomatic intracranial hemorrhage were 1% (tirofiban) and 4% (ASA). CONCLUSION: In spite of the fact that the null hypothesis was not supported by our data, we found results supporting the safety (and potential efficacy) of ASA and tirofiban when used in the first hours of acute ischemic stroke. However, this needs to be confirmed by further studies.

Factors influencing delay in presentation for acute stroke in an emergency department in Milan, Italy.

BACKGROUND AND AIMS: Early treatment is critical for successful intervention in acute stroke. The aim of this study was to describe delays in presentation to hospital and in the emergency department (ED) management of patients with acute stroke and to identify factors influencing these delays in an Italian urban hospital. METHODS: The present series includes all patients presenting with acute stroke, in whom arrival delay was ascertainable. To describe delays into the ED, the triage-visit delay, visit-computed tomography (CT) delay and visit-CT report delay were registered. Type of stroke, severity of stroke assessed using the modified National Institute of Health Stroke Scale (mNIHSS) scale, level of consciousness, history of previous stroke or previous hospital admission, use of the emergency medical service (EMS), onset of stroke during day or night and admission during working or non-working day were registered for every patient. Univariate and multivariate analysis were performed to evaluate factors influencing early arrival. RESULTS: Over a one-year period 537 patients with acute stroke were evaluated; 375 patients in whom arrival delay was ascertainable were included in the study. Median arrival delay was 5.4 h (interquartile range (IQR) 2.7-11.6); 104 patients (28%) arrived within 3 h and 198 (53%) within 6 h. Triage-visit delay was 0.3 h (IQR 0.2-0.7), visit-CT scan delay was 1.2 h (IQR 0.8-1.9), visit-CT report delay was 2.7 h (IQR 1.7-4.5). Triage-visit delay and visit-CT delay were shorter for patients presenting within 3 h. The type of stroke was ischaemic in 240 (64%), haemorrhagic in 61 (16%) and transient ischaemic attack in 74 (20%). The median basal mNIHSS score was 5 (IQR 3-10); 64 patients (17%) had an altered level of consciousness, 103 (27%) had had a previous stroke, 223 (59%) had had a previous hospital admittance. In this series 214 patients (57%) arrived with the EMS, 323 (86%) presented with symptoms during the day, 261 (70%) were admitted during working days. Univariate analysis showed a significantly shorter arrival delay in patients calling the EMS (median 4.2 vs 7.2 h; p<0.001) and in patients with a higher basal mNIHSS score (Spearman rho = -0.204; p<0.001) or altered level of consciousness (normal 5.8 h, not alert but arousable 3.8, not alert but arousable with strong stimulation 2.5, totally unresponsive 6.0; p = 0.005). Multivariate analysis showed that use of the EMS and higher basal mNIHSS score were independent variables associated with a shorter arrival delay. CONCLUSION: A substantial proportion of patients does not arrive at the ED in a suitable time for reperfusion therapy. Patients using the EMS have a shorter arrival delay. Approximately half of the patients with stroke are sufficiently aware of the urgency of this clinical condition to activate the emergency telephone system.

Azithromycin in the treatment of Plasmodium falciparum gametocytes. Preliminary observation.

BACKGROUND: Treatment of malaria represents a problem as antimalarial drugs are relatively few, and because of the increasing widespread resistance of Plasmodium falciparum to most of these drugs. A partial efficacy of azithromycin against Pl. falciparum hepatic stage and against trophozoytes in the erythrocytic stages of the disease has been demonstrated. No data concerning the activity against gametocytes are available, and primaquine stands as the only therapy against Pl. falciparum gametocytes. Primaquine causes haemolysis in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency, so primaquine therapy is usually avoided. A better tolerated therapy against gametocytes would be useful to reduce malaria transmission. We present the results of a study concerning the efficacy of azithromycin in the treatment of P. falciparum gametocytes. METHODS: A prospective study was performed: 4 patients with Pl. falciparum gametocytes (3 children, 1 adult) were treated with azithromycin for concomitant bacterial infections; in the meantime two children with gametocytes were taken as control. Azithromycin was administered as recommended. RESULTS: Gametocytes were detectable in children thick blood smears after 8, 5 and 6 days respectively after the beginning of azithromycin therapy, while they were undetectable in the adult thick blood smear 5 days after the beginning of the therapy. The gametocytes spontaneously disappeared in the two controls 4 to 6 days after the beginning of observation. CONCLUSIONS: These data suggest that azithromycin seems ineffective against Pl. falciparum gametocytes. Further studies are needed in order to determine whether azithromycin treated gametocytes are infective to mosquitoes or not, and to confirm this first observation.

Transient global amnesia or subarachnoid haemorrhage? Clinical and laboratory findings in a particular type of acute global amnesia.

Acute global amnesia may be due to several causes, such as transient global amnesia (TGA), acute drug-related confusional state, toxic substances, metabolic abnormalities, infective diseases, cerebral tumours, cerebrovascular accidents, subarachnoid haemorrhage and epilepsy. In particular both TGA and subarachnoid haemorrhage may be precipitated by sexual activity; by contrast the two diseases are quite different in prognosis and treatment. Ten subjects were admitted in the period 1997-99 to our emergency department for acute global amnesia related to sexual activity. They represented 18% of total acute global amnesias observed in the same period. All patients were males, aged between 41 and 64 years. TGA was found in nine cases, while one patient had subarachnoid haemorrhage, due to rupture of an aneurysm of the right middle cerebral artery. The patient with subarachnoid haemorrhage showed neurologic defects (second-degree nystagmus and retropulsion), while no major neurologic abnormalities were found in TGA. Likewise computerized tomography (CT) scan was positive only in the case of subarachnoid haemorrhage. Patients and relatives in most cases left out sexual activity as a trigger factor. This experience indicates that acute global amnesia related to sexual activity is mostly due to TGA. Major neurologic signs are suggestive of subarachnoid haemorrhage and an immediate CT scan is recommended. Targeted questions are needed to identify the cause of the event.

Metastatic oligodendroglioma. Case report.

We report a case of remote metastasis of oligodendroglioma. Similar cases are reported in the literature for malignant cerebral tumors. Our case seems rather different because of low grade histology. Potential malignancy was evidenced only by further investigations with labeling indexes.

Safety and pharmacologic activity of a new nitrate ester, ITF 296, after intravenous administration in healthy volunteers.

To evaluate the safety and pharmacologic activity of ITF 296 in humans, three groups of healthy male normotensive subjects were studied. The first two groups (six subjects each) received, in ascending order, three dose levels of ITF 296 by 30-min intravenous infusion (group I, 0.1, 0.5, 1.0 microgram/kg/min; group II, 2.0, 4.0, 6.0 micrograms/kg/min). The third group of eight subjects received, in ascending order, four dose levels of ITF 296 (10, 20, 40, 80 micrograms/kg) by 1-min i.v. injection. The study was double-blind, and placebo-controlled according to a within-patient, incomplete, unbalanced block design, such that each subject received the placebo once. Hemodynamics were assessed by means of Dynamap and BOMED. The following parameters were evaluated at different times before and after ITF 296 administration: systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), stroke volume index (SVI), cardiac index (CI), and systemic vascular resistance index (SVRI). Blood samples for kinetic assessment of ITF 296 were taken before and at different times after ITF 296 administration. The drug was well tolerated. Only a few mild (except for one, moderate) side effects (mainly headache and dizziness) were reported, usually at the higher dose levels. All safety clinical chemistry and hematologic parameters were unaffected. After i.v. infusion of ITF 296, blood pressure started to fall at the dose of 2 micrograms/kg/min, DBP being significantly reduced at doses above 1 microgram/kg/min. The effect lasted for up to 60 min after the end of the infusion. The increase in heart rate was only modest, although apparently dose-dependent. SVI was only slightly reduced, and the other hemodynamic parameters did not change. After bolus administration of ITF 296, SBP was significantly reduced starting at a dose of 20 micrograms/kg with higher doses producing a more marked effect (up to -15 mm Hg). DBP was significantly reduced only at the higher dose level of 80 micrograms/kg. The effect lasted for up to 60 min after bolus administration. HR was slightly increased after doses of 40 and 80 micrograms/kg. SVI was slightly reduced and a small transient decrease in CI was observed, whereas SVRI did not change. Satisfactory, linear kinetic correlation was found between total doses administered and AUCs measured. ITF 296 in healthy male normotensive volunteers was effective and well tolerated. The results of this study justify the planning of further studies in patients in order to test the anti-ischemic activity of the compound.

Influence of glutathione administration on the disposition of free and total platinum in patients after administration of cisplatin.

The kinetics of platinum (Pt) was studied in 12 patients suffering from non-small-cell lung cancer or pleural mesothelioma. Each subject received an infusion of cisplatin (CDDP, 80 mg/m2), and six patients were pretreated with glutathione (GSH, 2.5 g given i.v.) at 15 min prior to the cisplatin infusion. After a 3- to 4-week interval, all patients were given a second course of treatment on the same schedule. A biexponential model was fitted to plasma concentrations of total and ultrafilterable Pt. The excretion of Pt in urine was evaluated during the first 48 h after the CDDP infusion. Following the administration of CDDP alone or with GSH pretreatment, the pharmacokinetic parameters of Pt did not significantly differ between the treatments. Also, the unbound fraction determined at each sampling time did not vary significantly between the treatments. However, it is noteworthy that the mean values obtained for the terminal half-life, the volume of distribution, the renal clearance, the percentage of the dose excreted in the urine, and the mean residence time of total Pt were higher in patients who had been pretreated with GSH, suggesting that GSH might increase both the rate of Pt elimination and the extent of Pt distribution and, as a consequence of the latter, might prolong the residence time of Pt in the body. In addition, the unbound fraction of Pt from the 4th to the 48th was higher following the first dose of CDDP+GSH than after treatment with CDDP alone. Because of the rather high variability in the values of the parameters obtained, further work is planned using a larger number of patients.

First dose and steady state pharmacokinetics of nimesulide and its 4-hydroxy metabolite in healthy volunteers.

The pharmacokinetics of nimesulide (4-nitro-2-phenoxymethane-sulfonanilide, NMS), a non-steroidal antiinflammatory drug, and of its 4-hydroxy metabolite (4-nitro-2-(4'-hydroxy-phenoxy)-methane sulfonanilide, OH-NMS) was studied after a single oral dose (200 mg) and after repeated treatments (100 mg every 12 hours for 7 days) of NMS to two groups of 12 healthy volunteers. Plasma concentrations of NMS and OH-NMS were followed for 48 hours after the single dose and up to the 12th hour on the 1st day and on the 7th day during repeated treatment. After the single dose of 200 mg peak plasma concentrations of the drug (9.85 micrograms/ml) were reached at 3.17 hours and the half-life during the elimination phase was 4.95 hours. The metabolite reached highest plasma levels (3.03 micrograms/ml) at 5.33 hours and its apparent half-life was similar to that of the parent drug (4.78 hours). NMS plasma levels on the 7th day, predicted from the results of the 1st day, were similar to the measured values. The pharmacokinetics of NMS or OH-NMS after single or repeated dose was not time or dose dependent.

A polygraphic study of systolic time intervals and their correlations with heart rate and workload during supine ergometry in one hundred normal subjects.

The present study was designed to investigate systolic time intervals (STI) in 100 normal subjects undergoing continuous-maximal supine cycle ergometry and to search for possible linear correlations between STI (dependent variables) and heart rate, diastolic blood pressure, systolic blood pressure, age, sex, weight, and height (independent variables), by stepwise regression analysis. The only significant correlation discovered in the study was between the contractility index (isometric contraction time-ICT) and the total work produced by each participant. Exercise tolerance was limited primarily by shortening of the ICT interval, all subjects discontinuing the test when ICT reached 13.7 +/- 7 ms.

Influence of the heart rate on mean circumferential shortening velocity: echocardiographic study of 183 normal subjects.

Echocardiography was used to explore the influence of independent variables (age, body surface area and heart rate) on the mean circumferential shortening velocity (MVCF) in 183 healthy subjects. Multiple stepwise regression analysis shows that heart rate is the only variable of the three just mentioned that influences MVCF. A regression equation is evolved and proposed as an index of MVCF correction for varying heart rates.

Determination of bezafibrate in human plasma and urine by high-performance liquid chromatography.

A selective and time-saving high-performance liquid chromatographic method to assess bezafibrate plasma and urine levels is described. Bezafibrate is extracted from plasma matrix using diethyl ether, after acidification with hydrochloric acid. The urine samples are directly analysed, after dilution with the mobile phase. The method is used to assess bezafibrate plasma and urine levels in man, after administration of therapeutic doses of bezafibrate. The results obtained are in agreement with previously published data.