Implantable loop recorders for assessment of syncope: increased diagnostic yield and less adverse outcomes with the latest generation devices.

AIM: Aim of the study was to compare the diagnostic yield of implantable loop recorders (ILR) of two successive generations for the assessment of syncope. METHODS: Data on patients who had undergone ILR implantation for unexplained syncope in four Italian public hospitals were retrospectively acquired from the Medtronic Clinical Service database. After implantation, routine follow-up examinations were performed every 90 days, while urgent examinations were carried out in the event of syncope recurrence. RESULTS: The following findings were regarded as diagnostic: ECG documentation of a syncope recurrence; documentation of any of the arrhythmias listed by the current guidelines as diagnostic findings even if asymptomatic. Between November 2002 and March 2010, 107 patients received an ILR (40 Medtronic Reveal® Plus; 67 Medtronic Reveal® DX/XT) and underwent at least one follow-up examination. Diagnoses were made in 7 (17.5%) and 24 (35.8%) (P=0.043) patients, with a median time of 228 and 65 days, respectively. Three (42.9%) and 21 (87.5%) (P=0.029) diagnoses were based on automatically detected events, while adverse outcomes occurred in 6 and in 1 (P=0.01) patients, respectively. CONCLUSION: Our results show that the new-generation device offer a higher diagnostic yield, mainly as a result of its improved automatic detection function, and is associated with fewer adverse outcomes.

Liposomal amphotericin B eye drops to treat fungal keratitis: physico-chemical and formulation stability.

Local fungal infections with Candida, Fusarium, Curvularia and Aspergillus can lead to serious ulceration of the cornea and must be treated rapidly. The current treatment consists of 0.15% (w/v) amphotericin B eye drops prepared from Fungizone, containing deoxycholate, irritant for the cornea, which reduces patient compliance. Eye drops based on liposomal amphotericin B (AmBisome would be a convenient alternative; however, according to the manufacturer's instructions, AmBisome can only be kept refrigerated for 1 week after reconstitution. A longer shelf-life at ambient temperature would be preferable for a preparation made in a hospital pharmacy and delivered to patients. Thus, the possibility of storing an ophthalmic preparation of 0.5% (w/v) liposomal amphotericin B after reconstitution was investigated. After 6 months at room temperature or at +2-8 degrees C, the hydrodynamic diameter measured by quasi-elastic light scattering remained constant at 108 +/- 30 nm with a polydispersity index lower than 0.15. Amphotericin B content, checked by a validated HPLC method, was maintained between 94 and 107%. Amphotericin B and soy phosphatidylcholine proportions remained constant, indicating that the liposomes remained intact and retained the drug. These results show the feasibility of an ophthalmic preparation based on liposomal amphotericin B developed in hospital pharmacies.

Pulmonary excretion of carbon monoxide in the human newborn infant as an index of bilirubin production: III. Measurement of pulmonary excretion of carbon monoxide after the first postnatal week in premature infants.

Using a single pass, flow-through system, the excretion rate of endogenously produced carbon monoxide (VeCO) was measured as an index of bilirubin production in 41 Caucasian infants of various gestational ages after the first postnatal week. twenty-one were less than or equal to 32 weeks gestation. The mean slope for the 25 premature infants with multiple VeCO determinations was -0.21 +/- 0.11 (SE) microliters/kg/hour per day (P less than .025, one-tailed). Fifteen premature infants with at least three VeCO determinations during the first 30 days of life had an average decrease in total CO excreted of 1.33% per day compared to the extrapolated initial value of total CO excretion of 27.0 +/- 2.0 (SE) microliters/hour, giving a calculated maximum red cell life span of 75 days.

Pulmonary excretion of carbon monoxide in the human infant as an index of bilirubin production. IV. Effects of breast-feeding and caloric intake in the first postnatal week.

Measurements of the pulmonary excretion rate of carbon monoxide (VEco) as an index of bilirubin production in the first several days of life were taken from 64 breast-fed or bottle-fed infants. Twenty-one infants (greater than or equal to 37 weeks of gestation) were breast-fed; 43 infants (28 to 42 weeks of gestation) were bottle-fed a commercially prepared formula. Information pertaining to their caloric intake during the 24-hour period preceding VEco determination was taken from 38 of the 43 infants who were bottle-fed and they were placed into three groups based on their caloric intake: (1) less than or equal to 60 kcal/kg/day (19 infants); (2) 61 to 100 kcal/kg/day (7 infants); and (3) greater than 100 kcal/kg/day (12 infants). There was no significant difference in bilirubin production between bottle-fed and breast-fed infants. No effect of caloric deprivation on bilirubin production was demonstrated. The mean VEco values were 18.5 +/- 0.9 (SE) for group 1, 17.7 +/- 1.8 (SE) for group 2, and 16.2 +/- 1.1 (SE) microliter/kg/hr for group 3.

Revising diagnosis-related groups for neonates.

Groups of neonates who are usually treated at hospitals that provide specialized pediatric care are not adequately classified by the use of diagnosis-related groups (DRGs). Therefore, a set of revised DRGs, pediatric modified DRGs (PM-DRGs), have been developed. Use of PM-DRGs substantially improves the classification of neonates in the following ways: a single pediatric modified major diagnostic category has been defined to include only and all neonates (patients younger than 29 days of age when admitted to the hospital); deaths and transfers of newborns are no longer combined into a single group; birth weight (rather than diagnosis) is used as the primary variable to differentiate categories of neonates; and duration of mechanical ventilation, presence of major problems, and surgery are used to define specific PM-DRGs. A total of 46 PM-DRGs have been developed to replace the 7 DRGs for neonates. Based on a sample of discharged patients from 13 children's hospitals, the overall variance reduction in duration of stay for neonates using PM-DRGs was 38.7% compared with 20.4% for DRGs. Variance reduction for PM-DRGs was 45.9% compared with 16.3% for DRGs when operating cost per case was used instead of duration of stay. After removing outliers at 150 days, the duration of stay variance reduction was 53.3% vs 23.6%, respectively, and the operating cost variance reduction was 58.8% vs 17.8%, respectively.

Methodology of head-up tilt testing potentiated with sublingual nitroglycerin in unexplained syncope.

Shortened head-up tilt testing (HUT) potentiated with sublingual nitroglycerin (60 degrees passive standing for 20 minutes followed, if negative, by 400 microg of sublingual nitroglycerin spray with the test continuing for another 20 minutes) differs from conventional nitroglycerin HUT for a shorter drug-free phase (20 vs 45 minutes). To compare the positivity rate of the 2 protocols, both tests were performed in a randomized sequence in 10 patients with unexplained syncope (study 1), and another 42 patients were randomly assigned either to conventional or to shortened nitroglycerin HUT (study 2). To evaluate the reproducibility of the shortened nitroglycerin HUT, another 38 patients with unexplained syncope underwent 2 consecutive tests within a 7+/-8 day interval (study 3). Finally, to evaluate the specificity of the test, 47 control subjects underwent shortened nitroglycerin HUT (study 4). Seven positive responses were observed during shortened nitroglycerin HUT, and there were 8 positive responses during conventional nitroglycerin HUT (p = NS) in the study 1 group. Fifteen positive (71%) responses, 5 negative responses, and 1 exaggerated response were observed during shortened nitroglycerin HUT; 16 positive (76%, p = NS vs. shortened nitroglycerin HUT), 3 negative, and 2 exaggerated responses were observed during conventional nitroglycerin HUT in the study 2 group. During the first test, 21 patients (55%) had a positive, 15 patients had a negative, and 2 patients had an exaggerated response in study group 3. During the second test, 15 positive (39%), 19 negative, and 4 exaggerated responses were observed. Thus, the reproducibility was 67% for a positive and 94% for a negative test. In control subjects, 2 positive (4%) responses, 38 negative, and 7 exaggerated responses were observed with a specificity of 96% in study group 4. In patients with unexplained syncope, shortened nitroglycerin HUT allowed a positivity rate similar to that of the conventional test. Moreover, the shortened test provided a high specificity and adequate reproducibility for both the positive and the negative responses.

Hyperoxic reperfusion exacerbates postischemic renal dysfunction.

BACKGROUND: Hyperoxic reperfusion from global ischemia worsens functional outcome because of oxygen radical-mediated injury. This study tested the hypothesis that hyperoxic reperfusion would exacerbate postischemic renal dysfunction. METHODS: Twenty-nine healthy, uninephrectomized, male mongrel rabbits (Oryctolagus cuniculus) in 3 groups were subjected to 30 minutes of complete normothermic renal ischemia followed by reperfusion under hyperoxic or normoxic conditions. The groups were: hyperoxically reperfused (n = 8), normoxically reperfused (n = 8), hyperoxic sham (no ischemia, n = 5), and allopurinol-pretreated (50 mg/kg, intravenously), hyperoxically reperfused animals (n = 8). Plasma concentrations of creatinine, urea nitrogen and electrolytes were measured at 0, 24, 48, and 72 hours after ischemia and served as functional outcome markers. Histopathologic analysis of kidneys for injury was performed by an expert who was blinded to the procedures. RESULTS: Plasma creatinine in hyperoxically reperfused rabbits was significantly elevated above normoxic (P =.02) and sham (P =.003) animals by 48 hours and remained elevated to 72 hours. Plasma urea nitrogen in hyperoxically reperfused rabbits was significantly elevated above the normoxic group (P = .01), the sham group (P = .02), and the allopurinol group (P = .04) by 72 hours. These coincided with a significantly elevated histopathologic injury score in hyperoxically reperfused rabbits compared with sham (P = .019), normoxic (P = .035), and allopurinol-pretreated hyperoxically reperfused animals (P = .037). CONCLUSIONS: Hyperoxic reperfusion exacerbates renal dysfunction after 30 minutes of complete normothermic ischemia. This dysfunction may be mediated by oxygen radical-related injury.

Effects of ionic and zwitterionic surfactants on the stabilization of bovine catalase.

The activity and stability of beef liver catalase have been investigated in the presence of different ionic and zwitterionic surfactants. All cationic and zwitterionic surfactants used in this work have no effect on the initial activity of catalase, but several of them allow the enzyme to retain a high residual activity for longer periods of time than those observed in the absence of any additives. However, the interactions between surfactants and catalase appear to be very peculiar, and certain zwitterionic surfactants have been found to remarkably slow down enzyme degradation, with the enzyme completely preserving its activity after several weeks at temperatures of up to 30 degrees C. This effect is probably due to an interaction between the surfactant and the intersubunit region of the protein; this interaction could stabilize the quaternary structure of the enzyme.

Effect of a single Ditazole dose on platelet aggregation and prostaglandin formation.

The in vitro activity of the non-steroidal anti-inflammatory agent Ditazole was investigated in a group of 20 male patients at thrombotic risk in comparison with placebo in a completely randomized cross-over design. A single Ditazole administration was able to induce a significant decrease in the number of circulating platelet aggregates (CPA), platelet aggregability by ADP and in thromboxane production by platelets. No significant changes were found in platelet cAMP concentration and in plasma 6keto-PGF1 alpha levels. Present results indicate that Ditazole affects platelet aggregation in a double way, by decreasing both the reversible and the ADP-induced aggregation. The lack of effects on plasma 6keto-PGF1 alpha concentration suggests that Ditazole can reduce platelet aggregation without affecting prostacyclin production.

Outbreak of aseptic meningitis by echo 4: prevalence of clinical cases among adults.

Twenty five cases of meningitis occurred in urban areas surrounding a city (Modena) in Northern Italy, in the period May-July 1999. When the patients were admitted to the Infectious Diseases Division of the University of Modena and Reggio Emilia Hospital and studied by virological and serological methods, the meningitis proved to have an enteroviral origin and enterovirus ECHO 4 type was responsible for all cases of illness. An epidemiological characteristic of the enteroviral meninigitis outbreak was the adult age in 23 out of the 25 patients (mean age 24.50 +/- 7.84 years). The monthly distribution of the aseptic meningitis cases was the following: five cases occurred in May, 13 in June and seven in July. The origin of the spread of the virus infection and the reason for its sudden end remained unknown. The unusual drop in temperature which occurred in the geographic area involved in the aseptic meningitis outbreak at the beginning of August could have interfered with the slowdown in virus circulation.

Neuropsychological outcome of survivors of out-of-hospital cardiac arrest.

Thirty patients resuscitated from out-of-hospital cardiac arrest (15 with and 15 without postanoxic coma on admission) underwent a clinical examination and neuropsychological testing. In order to assess quality of life, they were compared to two matched control groups; 15 patients with previous myocardial infarction and 15 healthy subjects. None of the survivors showed severe neurologic impairment, and all had returned to self-sufficient physical activity. However, the behavior rating scale scores were significantly worse in patients with postanoxic coma. The processing ability linked to memory was significantly worse in the postanoxic coma group. Mood disorders were also observed in this group, but they did not have pathological significance. The remarkably low incidence of neurologic and psychological sequelae in these resuscitated patients, particularly in those with early clinical evidence of severe cerebral damage, is an encouraging result that supports the therapeutic systems development and efforts in the management of out-of-hospital cardiac arrest.

[After the 2001 European Society of Cardiology Guidelines: is it possible to reduce the number of patients with syncope to be hospitalized?]. / Dopo le Linee Guida 2001 della Società Europea di Cardiologia: è possibile ridurre il numero di pazienti con sincope da ospedalizzare?

AIM: The aim of this paper was to evaluate how many patients with syncope should be hospitalized according to the 2001 European Society of Cardiology (ESC) Guidelines on the management of syncope. METHODS: Starting from August 2002 we prompted a Syncope Unit (SU), as a multi-disciplinary functional structure including the Emergency Department. One of the main objectives of the SU was the implementation of the 2001 ESC Guidelines on Syncope and of the relevant criteria for hospitalization. All the clinical data concerning the patients presenting with syncope were prospectively collected and stored in a dedicated database. RESULTS: Between September 1, 2002 and April 30, 2003, 402 patients were observed for a syncope. Out of these, 19 had a cardiogenic syncope, 3 focal neurologic disorders, 25 a severe trauma, 4 severe orthostatic hypotension and 5 carotid syncope. Therefore, 56 patients out of 402 were found to have indication to therapeutical hospitalization. Among the remaining 346 patients, 83 patients were found to have a structural heart disease and/or an abnormal ECG, 1 had syncope during exercise, 3 presented a familial history of sudden death. Thirty-three were found to have severe comorbidities and further 14 had occasional indication to hospitalization. Thus, 190 out of the 402 patients with syncope (47.3%) presented at least 1 criterion for hospitalization according to the ESC Guidelines. CONCLUSION: The implementation of the ESC Guidelines on Syncope is technically feasible. Nevertheless, even when the Guidelines are strictly observed, a high percentage of patients with syncope has still to be hospitalized. Our data suggest that new criteria should be established for a safe Emergency Department discharge of the patients with syncope, particularly of those with structural heart disease or abnormal ECG.

Primary coronary angioplasty in acute myocardial infarction: is it possible to prevent postinfarction cardiac rupture?

BACKGROUND: Cardiac rupture is a leading cause of death among patients hospitalized for acute myocardial infarction (AMI). The aim of our retrospective study was to evaluate the impact of primary coronary angioplasty (PTCA) on this not common but usually fatal complication. METHODS: Since January 1998 PTCA has been the routine treatment for AMI patients in our Institution monitored during the first 12 hours from symptom onset. The AMI patients hospitalized between January 1998 and December 1999 (Group A) were retrospectively compared to those observed between January 1996 and December 1997 (Group B, historical control group), mainly treated with systemic thrombolysis. Patients hospitalized after 12 hours of symptom onset were excluded from the study. Data were analyzed on an intention-to-treat design. RESULTS: Group A consisted of 204 patients (148 males, 56 females, mean age 67 +/- 11 years), 165 (81%) of whom underwent coronary angiography. Group B consisted of 185 patients (123 males, 62 females, mean age 71 +/- 12 years), 78 (42%) of whom were treated with thrombolysis and 33 (18%) with PTCA. The groups did not differ as regards the time delay before hospital entry, Killip class at admission and site of AMI. Fourteen patients (6.8 %) of Group A and 20 (10.8%) of Group B died in the Cardiology Division. No deaths due to cardiac rupture were observed among the 165 Group A patients, nor among the 33 Group B patients treated with PTCA. Cardiac rupture was the cause of death for 1 out of 14 (7%) patients in Group A, and for 8 out of 20 (40%) patients in Group B (p < 0.02 Group A vs Group B). Nine Group A patients and 11 Group B patients died because of cardiogenic shock. CONCLUSION: A lower cardiac rupture incidence was observed among Group A patients in comparison to those of Group B. Thus our data, although not randomized, suggest the ability of primary PTCA in preventing post-AMI cardiac rupture.

The spectrum of pericardial effusion in acute myocardial infarction: an echocardiographic study.

BACKGROUND: The aim of this study was to assess the prevalence of pericardial effusion in acute myocardial infarction and the different prognosis associated with distinct patterns of pericardial effusion (anechoic/hypoechoic vs hyperechoic effusion). METHODS: Five hundred eighty-five consecutive patients admitted to the Coronary Care Unit for acute myocardial infarction were initially considered. Forty of them were excluded due to a technically poor acoustic window. The remaining 545 patients were studied by two-dimensional echocardiography at admission, before discharge (after an average of 9 days in the Coronary Care Unit) and whenever there was an important change in the clinical status (chest pain, lipothymia or syncope, hemodynamic deterioration with systolic blood pressure < 90 mmHg, cardiac arrest). RESULTS: Pericardial effusion was found in 51 patients (9%). Three distinct textural patterns of pericardial effusion were noted on the basis of the echogenic properties: 1) anechoic or hypoechoic pericardial effusion was frequent (30 patients), mild or moderate and generally benign; 2) hyperechoic type "A" effusion pattern was rare (2 patients) and associated with fever, leukocytosis and pericardial rubs; 3) hyperechoic type "B" was frequent (19 patients), large and always associated with major complications (all cases cardiac tamponade and/or death). CONCLUSIONS: Pericardial effusion is not an uncommon finding in serial echo evaluation of patients with acute myocardial infarction, especially when infarction is anterior, extensive and Q wave. Echocardiographically detected pericardial effusion shows different textural patterns with hypoanechoic effusion more frequent, limited and prognostically benign than hyperechoic effusion larger and often associated with adverse events.

[Dynamic electrocardiogram and syncope: a couple in real crisis?]. / Elettrocardiogramma dinamico e sincope: una coppia definitivamente in crisi?

Holter monitoring is still considered as a class I diagnostic tool for the assessment of syncope. This is due to poor yield of the diagnostic techniques available until the middle 1980s. However, considering the impressive progress made in the differential diagnosis of this clinical condition, such widespread use is no longer justified. The limitations of Holter monitoring are highlighted by its costs per diagnosis and, in particular, by comparison with other maneuvers, such as the head-up tilt test or the carotid sinus massage, which have a higher positive predictive value for patients with syncope of unknown origin. The diagnostic yield of Holter monitoring has to be considered particularly low among patients free from structural heart disease in whom the risk of arrhythmic syncope is extremely low.

[The tilt test enhanced with oral nitroglycerin in patients with unexplained syncope: the Italian Protocol. The Working Group on Syncope of the Associazione Italiana di Aritmologia e Cardiostimolazione--the Arrhythmia Area of the Associazione Nazionale Medici Cardiologi Ospedalieri]. / Tilt test potenziato con nitroglicerina orale nei pazienti con sincope inspiegata: "Il Protocollo Italiano". Gruppo di Lavoro sulla Sincope AIAC--Area Aritmie ANMCO.

The head-up tilt testing potentiated with oral nitroglycerin, devised by an Italian group, is a simple, safe and powerful, but still not a standardized, diagnostic tool. In fact, owing to its rapid diffusion, the original protocol received, often arbitrarily, subsequent modifications. Thus a task force of experienced cardiologists defined the best methodology for the test on strictly evidence-based criteria. Particular attention was reserved to some controversial topics, such as the tilting angle, the duration of the passive and pharmacological stages of the test, the type and dosage of the drug utilized. We hope that the enclosed protocol, named by us as "The Italian Protocol", will be accepted as the standard methodology of the head-up tilt testing potentiated with oral nitrates.

Electron microscope study on a transmissible cytotoxic factor isolated from cerebrospinal fluid of neurological patients: analysis of its structure and of its effects on various types of cell cultures.

AIMS: In previous studies, the present group showed that a factor, present in the cerebrospinal fluid of seven neuro-patients, was capable of inducing cell damages on cell cultures of epithelial cells (Vero), glial cells (DG54-MG) and human primary lymphocytes. The cytotoxicity, once induced, could be transmitted to fresh cell cultures using crude preparations obtained from the cytotoxic cell cultures. METHODS AND RESULTS: The present electron microscope study describes in detail the pathological changes occurring in the previously assayed cultured cell types, and for the first time in human fibroblasts, as a consequence of the treatment with crude cytotoxic preparation. It also demonstrates with reasonable certainty the absence of virus-like particles in both the treated cells and the partially purified cytotoxic fraction. Indeed high-resolution electron microscopy analysis shows that this fraction consists almost entirely of protein spheroids with a diameter of 8-12 nm. CONCLUSIONS: The possible significance of nanotubular aggregates, observed in particular in the glial and in the epithelial cells undergoing cytotoxic damage, is also discussed.

[Left ventricular free wall rupture during a myocardial infarct: its incidence, clinical presentation, evolution]. / Rottura della parete libera del ventricolo sinistro in corso di infarto miocardico: incidenza, presentazione clinica, evoluzione.

Of 554 patients hospitalized for acute myocardial infarction, 61 (11%) died in the Intensive Care Unit. Echocardiography (performed at admission, at discharge and in every case of modification of the clinical course) allowed the diagnosis of left ventricular free wall rupture (RPLVS) in 20. The clinical course was acute in 13 of the latter, presenting with electromechanical dissociation (DEM). Pericardiocentesis allowed survival of one patient of this group. In 6 patients RPLVS had a subacute pattern, with progressive hypotension (in 2 cases preceded by syncope): pericardiocentesis allowed temporary stabilization of 4 patients; 2 had surgical repair with 1 long-term survivor. In 1 patient RPLVS began with lipothymia, and then he stabilised spontaneously. Many physiopathological mechanisms are discussed which could explain the great clinical variability of RPLVS. Awareness that RPLVS can appear with patterns different from DEM is fundamental for the diagnosis of subacute RPLVS. Indeed, this form of RPLVS, when recognized, can be treated with an encouraging prognosis.

Determing the pulmonary excretion rate of carbon monoxide in newborn infants.

A simplified technique was devised for measurement carbon monoxide excretion rates in newborn infants. Determinations can be performed quickly and repetitively in a noninvasive manner, with a sensitivity sufficient for use even on small preterm infants. Resolution of the method is +/- 4.3 mul/h (SD); however, variations in infant respiration rate may cause much greater changes in actual excretion rate. Preliminary results with five full-term newborn agree to within 15% of previously reported data. The system will be used extensively in ongoing studies involving total bilirubin production as a function of gestational age.