Exhaled breath condensate nitrite in premature infants with bronchopulmonary dysplasia.

BACKGROUND: Tracheal aspirate is the conventional method to measure biomarkers of inflammation and oxidation from premature infants on mechanical ventilation at risk for bronchopulmonary dysplasia (BPD), but this method is invasive. Exhaled breath condensate (EBC) is a novel, non-invasive method that has been used in older populations. Nitrite, a stable metabolite of nitric oxide (NO), is elevated in inflammatory conditions. We aim to investigate the feasibility of EBC nitrite collection from ventilated premature infants and to quantify EBC nitrite in infants with and without BPD. We hypothesize that EBC nitrite correlates with TA nitrite, and that EBC nitrite in the first week of life is higher in infants who will develop BPD than those without BPD. METHODS: In a pilot prospective cohort study, TA and EBC were collected in the first week of life from mechanically ventilated premature infants. Nitrite levels were measured using chemiluminescence. RESULTS: EBC nitrite significantly correlated with TA nitrite (r = 0.45, p = 0.025). Of 40 infants, 33 (82.5%) developed BPD. EBC and TA nitrite levels collected in the first week of life had a higher trend in infants with BPD than those without BPD (p = 0.23 and 0.38 respectively). CONCLUSIONS: Higher trend of EBC nitrite in the first week of life was associated with the development of BPD. Correlation of nitrite level in EBC with that in TA (conventional method) highlights the utility of EBC as an alternative, non-invasive method to measure inflammation. Further refinement of conditions and timing may optimize the predictive value of EBC nitrite.

A case of clear renal cell cancer associated to meningioma and verrucous carcinoma of frontal region in an old patient.

Here we report the concomitant development in an 82 year-old patient of three different neoplasms with different histology, degree of differentiation and clinical aggressiveness. In fact, the patient presented a verrucous carcinoma with unusual location at her head frontal region and a concomitant calcified meningioma of the frontal region of the brain. At the moment of the examination also a clear renal cell carcinoma, that was the cause of patient decease, was discovered. At our knowledge, this is the first case of concomitant presentation of these three tumours. Even if the present case was not correlated with any hereditary feature the presence of a genetic predisposition common to all the three tumours can not be excluded, but the casual co-existence of different both genetic and environmental factors can be also suggested.

Longitudinal study of vasopressin-cell antibodies and of hypothalamic-pituitary region on magnetic resonance imaging in patients with autoimmune and idiopathic complete central diabetes insipidus.

Diagnosis of autoimmune central diabetes insipidus (CDI) is based on the presence of autoantibodies to AVP-secreting cells (AVPcAb) or the coexistence of other autoimmune polyendocrine syndromes; moreover, it can be also suggested by the presence of lymphocytic infundibulo-neurohypophysitis, evidenced by biopsy of pituitary stalk and/or by pituitary stalk thickening on magnetic resonance imaging (MRI). However, so far, in clinical CDI patients with lymphocytic infundibulo-neurohypophysitis, AVPcAb have not been investigated and in those with or without autoimmune polyendocrine syndromes (APS), longitudinal studies on the behavior of AVPcAb alone, or of both AVPcAb and hypothalamic pituitary imaging on MRI are lacking. Aim of this work was to investigate in these patients the occurrence of AVPcAb (by indirect immunofluorescence) and of pituitary stalk thickening (by MRI) and their longitudinal changes during a follow-up period. We studied 22 patients, aged 29-53, with APS and complete CDI, grouped as follows: 10 with recent onset (< or =1.5 yr) of CDI (group 1a) and 12 with CDI of long-term duration (> or = 7 yr) (group 1b); moreover, a group of 13 patients with apparent idiopathic CDI of recent onset (<1.5 yr) were studied. They were divided, on the basis of the detection of AVPcAb as follows: 5 AVPcAb positive patients (aged 19-26) classified as isolated autoimmune CDI (group 2) and 8 AVPcAb negative patients (aged 21-26), classified as true idiopathic CDI (group 3). All patients were evaluated yearly, along 5 yr, for AVPcAb and for hypothalamic-pituitary region imaging. At study entry, 8/10 (80%) of patients in group 1a and 7/12 (58.3%) in group 1b were positive for AVPcAb and persisted positive subsequently, during all the follow-up period, even if at lower titers. All patients in group 2 were positive and all those in group 3 were negative for AVPcAb and persisted positive and negative, respectively, for all the follow-up study. Among the AVPcAb-positive patients, only 5 in group 1a and 2 in group 2 showed also pituitary stalk thickening at the first observations, which however spontaneously disappeared subsequently indicating a possible lymphocytic infundibulo-neurohypophysitis. All patients in the studied groups showed loss of the hyperintense signal of the neurohypophysis on MRI at entry and during all the follow-up period. Results of this longitudinal study suggest: 1) AVPcAb, frequently present at high titers in recent phases of CDI, persist subsequently, even if at lower titers, several years after the onset of disease. 2) The occurrence of a lymphocytic infundibulo-neurohypophysitis suggested by the pituitary stalk thickening on MRI only in patients positive for AVPcAb confirms a further autoimmune variant of CDI also in these cases. 3) The longitudinal behavior of patients in group 3 suggests that the absence of AVPcAb at the onset of clinical idiopathic CDI is able to exclude a subsequent appearance of these antibodies and consequently an autoimmune involvement in CDI of these patients. Instead the finding of AVPcAb in several patients with only CDI, thought at first clinical observation as idiopathic, indicates that the prevalence of autoimmune CDI must be considered much higher than that so far reported.

[Assessment of plasma lipid profile in acute coronary syndromes. The use of fibrinolytics and heparin do not affect it significantly]. / Andamento del profilo lipidico plasmatico nelle sindromi coronariche acute. L'uso di fibrinolitici ed eparina non lo modificano significativamente.

BACKGROUND: Neurohormonal and metabolic responses to acute ischemic events associated with thrombolysis and heparin induce substantial changes in the lipid profile (acute phase response). The aim of this study was to assess changes in total cholesterol and triglycerides in patients with acute coronary syndrome, admitted to our Intensive Coronary Care Unit (ICCU). METHODS: The study included 1051 consecutive patients, 316 with unstable angina, 583 with Q wave acute myocardial infarction (AMI) and 152 with non-Q wave AMI. Total cholesterol and triglycerides were measured in all patients at time 0 (admission), at time 1 (the morning following admission), at time 2 (the morning after discontinuation of heparin treatment). RESULTS: The mean value of total cholesterol at admission was 235, 210 and 197 mg% at admission, time 1 and time 2, respectively. Triglyceride levels were 234, 178 and 189 mg%, respectively. In the subgroup of thrombolized AMI the reduction in total cholesterol at time 1 and time 2 resulted similar in comparison with non-thrombolized AMI (p = NS). The decrease in triglycerides showed a similar pattern in the different subgroups. Comparison was also done according to sex, age, and complications. CONCLUSIONS: These data confirm that mean total cholesterol and triglycerides at admission are sharply higher than values considered normal in the literature. Within 24 hours of admission there is a 10.7% drop in total cholesterol which increases to 16.2% after a few days (mean 3.4 days). Total cholesterol determination upon admission in patients with acute coronary syndromes is necessary in order to know the true concomitant lipid profile during the precipitating ischemic events. The decision of initiating early therapy with statins would then appear more justified.

Comparison of verapamil versus felodipine on heart rate variability in hypertensive patients.

OBJECTIVE: We evaluated the effect of two calcium channel blockers, verapamil and felodipine, on heart rate variability in hypertensive patients. DESIGN: Time and frequency domain measures of heart rate variability were obtained from 24 h Holter recording in 25 previously untreated hypertensive patients without left ventricular hypertrophy, before and after 3 months of verapamil slow-release treatment (240 mg once daily) or felodipine extended-release treatment (10 mg once daily). RESULTS: Blood pressure values decreased with both drugs. Measures of heart rate variability, comparable at baseline in the two groups, were unchanged after felodipine. After verapamil, the average RR interval, the square root of the mean of the squared differences between all adjacent normal RR intervals (r-MSSD) and the percentage of differences between all adjacent normal RR intervals > 50 ms (pNN50), measures of vagal modulation of heart rate, increased (from 735 +/- 67 to 827 +/- 84 ms, P < 0.001; from 30 +/- 10 to 44 +/- 15 ms, P < 0.001; and from 3 +/- 2 to 7 +/- 6%, P < 0.01, respectively) and were higher than after felodipine. The coefficient of variation, a measure that compensates for heart rate effects, increased only after verapamil (from 5.8 +/- 1.3% to 6.6 +/- 1.0%; P < 0.05). High frequency power and its coefficient of component variance, both representing the vagal modulation of heart rate, increased after verapamil (from 5.33 +/- 0.29 to 5.80 +/- 0.27 In units, P < 0.001 and from 1.9 +/- 0.3 to 2.2 +/- 0.25%; P < 0.05). Finally, the low to high frequency power ratio, an indicator of sympathovagal balance, with a high value suggesting a sympathetic predominance, decreased after verapamil (from 2.16 +/- 0.41 to 1.36 +/- 0.35; P < 0.001), confirming the improvement in vagal modulation of heart rate. CONCLUSION: In hypertensive patients, despite a comparable anti-hypertensive effect, verapamil, but not felodipine, has favourable effect on cardiac autonomic control.

Effects of aspirin or picotamide, an antithromboxane agent, in combination with low-intensity oral anticoagulation in patients with acute myocardial infarction: a controlled randomized pilot trial.

BACKGROUND AND OBJECTIVE: Combined treatment with antiplatelet drugs and oral anticoagulants seems more effective than monotherapy in the reduction of thrombotic episodes in patients with ischemic heart diseases. We compared the safety and efficacy of two different antiplatelet drugs, aspirin (asa) and picotamide (pico)--a dual antithromboxane agent--in combination with low-intensity oral anticoagulation with warfarin or acenocoumarol in acute myocardial infarction (AMI). PATIENTS AND METHODS: Primary endpoint of the study was to compare the incidence of major events (death, reinfarction, postinfarction angina and heart failure) in AMI patients undergoing thrombolytic therapy. In a controlled randomized parallel group pilot study, 101 patients with AMI were enrolled and treated with asa 160 mg/die plus low-intensity oral anticoagulation (target INR: 1.5-2.5) (n = 51) or pico 300 mg/tid plus low-intensity oral anticoagulation (n = 50). Secondary endpoint of the study was to compare the cumulative incidence of major events plus major hemorrhagic episodes defined as macroscopic hematuria, nose bleeding and melena. RESULTS: The two groups were well matched regarding the main demographic and clinical variables. AMI location was anterior in 22 and 20 patients in the pico and asa group respectively, inferoposterior in 27 (pico) and 29 (asa) patients. At the end of the six-month period, major events were observed in 20 patients in the pico group and in 31 patients in the asa group (p < 0.05). The cumulative incidence of major clinical events plus major hemorrhagic episodes was significantly lower in the pico group in comparison with the asa group (28 vs 48; p < 0.001). CONCLUSION: The results of this pilot study suggest that combination therapy with picotamide and low-intensity oral anticoagulation could be a safe and effective alternative to aspirin in patient with AMI. This hypothesis should be confirmed by controlled randomized trial with an adequate sample size.

Influence of autonomic tone on QT interval duration.

The autonomic tone has been shown to influence the duration of the QT interval, however the independent contribution of sympathetic and parasympathetic tone is not fully elucidated. The influence of autonomic tone on QT duration was studied in 10 young healthy volunteers by evaluating the changes in QT and RR duration induced by i.v. isoproterenol infusion and by standing before and after i.v. administration of propranolol or atropine. Furthermore, the relationship between RR interval and QT duration was evaluated during nocturnal sinus arrhythmia and submaximal exercise test. Low doses of isoproterenol reduced RR (p < 0.01) but not QT interval duration, while higher doses influenced both RR (p < 0.0001) and QT (p < 0.001) duration. Propranolol did not influence standing-induced shortening of RR and QT intervals; on the contrary, atropine administration abolished standing-induced QT interval shortening, without influencing RR changes. QT duration resulted significantly related to preceding RR interval at peak exercise (r = 0.87, p < 0.001) and during nocturnal sinus arrhythmia (r = 0.73, p < 0.0005), however, the regression lines showing the correlation between QT and preceding RR interval were different. Both sympathetic and parasympathetic tone appear to contribute to heart rate-independent changes in QT duration. In the basal state parasympathetic more than sympathetic tone influences the relation QT-heart rate. Major increases of sympathetic nervous system activity may change the relation QT-heart rate. Thus, in case of abrupt autonomic changes, any proposed formula for heart rate correction of QT may result inappropriate, also in the normal range of heart rate.

[Safety of the dipyramidole echocardiography test in elderly coronary disease patients]. / Sicurezza del test eco-dipiridamolo in pazienti coronaropatici anziani.

We prospectively studied the feasibility and safety of high-dose dipyridamole echocardiography in 166 patients (77 younger and 89 elderly patients) referred for clinical evaluation of coronary artery disease. The feasibility of dipyridamole echocardiography test was 80.5% in the young and 82% in the elderly (p = n.s.). The incidence of side effects during dipyridamole echocardiography was similar in two groups, except for dyspnea which was observed in 20% in the older and 4% in the younger (p < 0.01). Our data demonstrate that the dypiridamole test combined with echocardiographic monitoring of regional myocardial contractility may be considered a valid non invasive method for evaluating coronary artery disease in the elderly.

[Treatment of ischemic heart disease in the elderly. Comparison of diltiazem, verapamil and gallopamil]. / La terapia della cardiopatia ischemica nell'anziano. Confronto diltiazem, verapamil e gallopamil.

The medical therapy of myocardial ischemia in elderly patients has not been well evaluated. We studied the age-related changes in 127 patients with proved coronary artery disease and stable effort angina the efficacy and the safety of diltiazem 120 mg tid, verapamil 120 mg tid and gallopamil 50 mg tid a medium term parallel, double blind cross-over placebo controlled study. All patients have been clinically and ergometrically evaluated. In middle-age patients diltiazem, verapamil and gallopamil induced a significant increasing of exercise duration and time to onset ST segment depression > or = 1 mm. In the elderly patients both verapamil and diltiazem as increased the exercise duration and ischemic threshold, while the diltiazem did not increased the exercise duration even if the time of onset ST segment depression > or = 1 mm is increased. At peak exercise the ST segment depression have been reduced both in middle-age and elderly patients after active drugs. Weekly angina and DNT consumption have been significantly reduced after diltiazem, verapamil and gallopamil in middle-age and elderly patients. Side effects have not been relevant even if gallopamil as a lower frequency of them in comparison to diltiazem and verapamil. No patients stopped the treatment because major side effects. Our experience suggests that diltiazem, verapamil and gallopamil have a similar efficacy and rare well tolerated. The choice of one instead of another must be suggested on the basis of side effects developing.

[Bronchiolitis. Our clinical experience in the 4 years from 1981 to 1984]. / La bronchiolite. La nostra esperienza clinica nel quadriennio 1981-1984.

The clinical experience of 661 children with bronchiolitis is reported in four-years period to gain a better understanding of diagnosis and pathogenesis of bronchiolitis. Upper airways infections, expiratory dyspnea, clear sound by chest percussion, vesicular rales and whistling by chest auscultation, air trapping on the chest radiography were considered as essential data of diagnosis. It was found in 595 patients: expiratory dyspnea, air trapping, vesicular r. and whistling in 85% and whistling only in 15%; hypoxemia in 20% combined with hypercapnic acidosis in 10%; normoxemia in 80% combined with hypocapnia in 54%; hyperlactemia in 64% combined with an increment in the serum of CPK in 50% and of GPT in 30%; virus were cultured in 27%, adenovirus and RSV were identified in 90%. Instead it was found in 66 patients: air trapping but no difficult breath, with normal chest auscultation; crisis of cyanosis or paleness-cyanosis chilly sweat in 80% were motive of admission. The clinical and/or radiological features of "air trapping" were considered as essential symptoms and signs of bronchiolitis. The insufficient systemic perfusion was considered as a frequent occurrence and as cause for sudden respiratory and circulatory emergency.

[Biochemical monitoring of the insufficient systemic perfusion in bronchiolitis]. / Monitoraggio biochimico di deficit di perfusione sistemica nella bronchiolite.

Biochemical monitoring was performed on 113 sucklings affected with bronchiolitis in order to evaluate early onset of insufficient systemic perfusion. Values of haematic lactate, GPT and CPK levels in the serum, partial tension of haematic gases were evaluated on first day of hospitalization. Haemogasanalytic monitoring made it possible to differentiate two groups of infants: 21 patients with hypoxemia and 92 patients with normoxemia. Monitoring of lactatemia, CPK and GPT activity evidenced following values: hyperlactemia (66.6%), increased CPK levels (47.6%), increased GPT levels (14.2%) in the group of infants with hypoxemia. Hyperlactemia (55.4%), increased CPK levels (62%), increased GPT levels (19.5%) in the group of patients with normoxemia. These findings show no significant difference between the two groups and frequent occurrence of tissular hypoxia attributable to insufficient systemic perfusion. Moreover the results of such biochemical monitoring permit precise indication about appropriate treatment.

Update on the Lannett and Pharmadyne decisions.

The implications of litigation concerning the authority of FDA in premarket approval of drugs are discussed. Since a recent paper on the Lannett and Pharmadyne decisions, several related court cases have been tried. The principal case discussed in Premo Pharmaceutical Laboratories, Inc. v. U.S., where the FDA's authority to require premarket approval of "me-too" drugs was temporarily thrown into jeopardy by a district court's decision involving Premo's Insulase brand of chlorpropamide tablets. However, an appeal, the decision was reversed and the case dismissed. The courts' opinions for these decisions are discussed, as well as related developments.

Implications of the Lannett and Pharmadyne decisions.

The Lannett (United States v. Articles of Drug) and Pharmadyne (Pharmadyne Laboratories, Inc. v. Kennedy) court decisions are explained and their implications regarding premarket approval of drugs are discussed. The Lannett decision has led to confusion over whether FDA premarketing approval is required for products containing drugs recognized as safe and effective. The Lannett decision has no binding legal effect. Premarketing clearance must be obtained by all drug manufacturers, including the producers of generics.