Predictors of outcome for patients with severe respiratory failure requiring non invasive mechanical ventilation.

OBJECTIVE: Failure to identify patients in whom non-invasive ventilation (NIV) would be unsuccessful may cause inappropriate delay in intubation. Aim of this study was to determine predictors of NIV failure. PATIENTS AND METHODS: We retrospectively evaluated COPD patients, undergoing NIV for at least 12h because of hypercapnic acute respiratory failure. Univariable and multivariable analyses were performed on: age, gender, APACHE II and GCS, gas exchange at admission, during NIV and at discharge/death, length of stay. ROC analysis for pH START and APACHE II were performed. RESULTS: Among 201 individuals enrolled, NIV failed in 50. In the logistic regression model only APACHE II was found to have an independent effect on the outcome (p < 0.0001, OR 1.179, 95% CI 1.101-1.263 as quantitative variable; p < 0.0001, OR 3.753, 95% CI 1.798-7.835, as qualitative variable, > 20.5). CONCLUSIONS: APACHE II may be a crucial parameter in predicting NIV failure; further multicentric studies are needed to better define NIV indications.

Colchicine, cyclophosphamide and prednisone in the treatment of mild-moderate idiopathic pulmonary fibrosis: comparison of three currently available therapeutic regimens.

STUDY OBJECTIVES: In this study we evaluated the role of three currently available therapeutic regimens in the treatment of early stages of idiopathic pulmonary fibrosis (IPF). PATIENTS: The study population consisted of 57 consecutive suspected individuals with IPF. Patients with interstitial pneumonias other than IPF and subjects with advanced disease or contraindication to therapy were excluded. We evaluated 30 subjects with mild-moderate IPF, homogeneous baseline characteristics and prognostic parameters that were assigned to 3 treatment regimens: group 1 (n = 11): prednisone 1 mg/kg/ day; group 2 (n = 9): prednisone 0.5 mg/kg/day plus cyclophosphamide 100 mg/day; group 3 (n = 10): prednisone 0.5 mg/kg/day plus colchicine 1 mg/day. We analysed response to therapy by analysis of a clinical-radiographic-physiologic (CRP) score before treatment and at 6 months intervals for 18 months. Side effects and three years survival rate were also investigated. RESULTS: Although our study was performed in a subset of patients with early disease's stages, these data showed that none of the regimens was able to interfere with IPF's course. However treatment with colchicine plus prednisone resulted in fewer side effects and re-evaluation parameters showed a significant decrease of dyspnoea (p < 0.01). No significant differences were observed in survival rate among the three groups. CONCLUSIONS: None of the regimens analyzed was effective even in the treatment of the early stages of IPF. The association colchicine/corticosteroids could be considered a safe and not expensive regimen that may be used in the treatment of IPF, especially in patients who have experienced adverse effects from immunosuppressive agents, while waiting for newer therapeutic strategies.

[Therapeutic effect of the association between pulmonary ventilation and aerosol--inhalation with sulphureous mineral water in the chronic bronchopneumopathies]. / Effetto terapeutico dell'associazione ventilazione polmonare e aerosol-inalazione con acqua minerale solfurea nelle broncopneumopatie cronico-ostruttive (BPCO).

AIM: Our research evaluates the efficacy of the inalation therapy by mineral sulphureous water in patients suffering from cronic bronchopneumopathy. MATERIALS AND METHODS: From August to October 2002, two groups of patients, randomly selected, suffering from cronic bronchopneumonopathy, were studied at spa center "Pompeo" in Ferentino (FR). Every patient was treated daily during a cycle of twelve days. The first group was treated by pneumonic mechanical ventilation associated to sulphureous water aerosolinalation, the second by mechanical pulmonary ventilation associated to sulphureous water aerosol-inalation medicated with flunisolide. Every patient carried out spirometry, before and after treatment, and the measurement of FEV1 was considered a good parameter to evaluate the respiratory function. RESULTS: All patients reported an improvement in symptoms as dyspnea and cough. Results obtained show a significant functional improvement of respiratory function in both groups, evaluated by FEV1. Equal efficacy treating the patients by medicated and not medicated treatments stress the therapeutic role of mineral sulphureous waters in chronic bronchopneumopathies. Our research points out the usefullness of pneumonic ventilation associated with sulphureous water aerosol-inalation in patients suffering from chronic bronchopneumopathies.

[Efficacy-safety relationship of AT1 angiotensin II receptor antagonists: current data]. / Rapporto efficacia-sicurezza degli antagonisti recettoriali AT1 per l'angiotensina II: dati attuali.

In evolution of hypertension's treatment it may no be sufficient to lower blood pressure to achieve beneficial effects in long term outcomes. Several goals of antihypertensive treatment remain unrealized. There is so great interest for new drugs that may protect target organs and improve outcomes. The angiotensin II, the major effector of the renin-angiotensin-aldosterone system, causes a variety of potentially noxious cardiovascular effects which are specially mediated by AT1 subtype receptors. AT1 receptor blockers (losartan, candesartan, irbesartan, valsartan) are available drugs in the angiotensin-II-antagonist class. This paper examine the peculiar features of this new class of drugs.

A 23Na-NMR study on cation transport systems in a patient with hypokalemic periodic paralysis.

Erythrocytes from a patient with hypokalemic periodic paralysis (HPP) have been studied, in order to investigate the presence of alterations of membrane cation active transport systems. An original 23Na-NMR method has been used, capable of evaluating quantitatively the Na+ efflux due to the Na+/K+/Cl- cotransport. This method uses a loading system to increase internal cellular Na+ concentration: in the patient with HPP both the internal Na+ concentration after loading and the Na+/K+/Cl- cotransport activity were decreased in comparison to the controls. Our data seem to confirm that the fall of K+ serum levels during attacks in HPP must be ascribed to a shift of K+ from extra- to intracellular compartment (with consequent changes in the fibrocellular membrane polarity), due to an alteration of membrane cation transport system: which does not only consist in a hyperactivity of Na+/K+ ATPase (already described by other AA.), but also in a "secondary" decreased K+ efflux driven by the cotransport. The decrease of cotransport activity may be considered as "compensatory" (in fact, the intracellular Na+ content is normal), since this transport system can work as a kind of "emergency" system that can "help" the ATPase-dependent pump in extruding any excess of cell Na+ content, or can be depressed by any decrease of this value, caused by an hyperactivity of the Na+/K+ ATPase. The decreased cotransport activity results in a powerful contribution to the increase of intracellular potassium due to the hyperactivity of the Na+/K+ pump. This method could supply a useful diagnostic marker in all uncertain cases.

[Cardiac and renal sodium-modulating hormones in juvenile arterial hypertension. The physiopathological aspects and therapeutic results of a trial at the Policlinico Militare Celio in Rome]. / Ormoni sodiomodulanti cardiaci e renali nell'ipertensione arteriosa giovanile. Considerazioni fisiopatologiche e terapeutiche derivate da una esperienza condotta nel Policlinico Militare Celio di Roma.

Sodium balance plays a primary role in blood pressure regulation. Atrial natriuretic peptide, a recently discovered natriuretic substance, seems to participate in renal sodium handling, but its behavior in essential hypertension has not been fully defined. In our study, to avoid the "contamination" of factors other than hypertension, we evaluated the plasma levels of atrial natriuretic peptide in young men at military draft age. Our main results showed that plasma atrial natriuretic peptide levels are higher in young hypertensives with low plasma renin activity and low urinary excretion of active kallikrein. The influence of a positive genetic background for essential hypertension on plasma atrial natriuretic peptide levels was also investigated. Our data showed slightly elevated levels of the atrial hormone in young normotensives with a family history of hypertension.

Natriuretic hormones in young hypertensives and in young normotensives with or without a family history of hypertension.

The behavior of plasma atrial natriuretic factor (ANF) and digoxin-like substance (DLS), and the daily urinary excretion of kallikrein (uKK) were evaluated in young hypertensives and in young normotensives with or without a family history of essential hypertension. Each group was also evaluated, separating those with low plasma renin activity from the total sample. The sample group was made up of 75 young males; 31 hypertensives (mean age 22.7 +/- 2.5 years), 28 normotensives with hypertensive heredity (normotensives F+) (mean age 22.2 +/- 1.9 years) and 16 normotensives (mean age 22.0 +/- 2.1 years). An inverse correlation between ANF and PRA was shown in all groups. In hypertensives, ANF was inversely correlated with uKK (r = -0.664, P less than .0001). Plasma ANF (P less than .012) and DLS (P less than .0001) were higher in hypertensives than in normotensives, while uKK excretion was lower (P less than .0001). Plasma levels of DLS were higher in F+ normotensives than in normotensives (P less than .003). Low renin hypertensives showed the lowest uKK excretion (P less than .0001 v normal-high renin hypertensives). Furthermore, low renin hypertensives showed the highest plasma levels of ANF (P less than .0001 v normal high renin hypertensives) and DLS (P less than .012 v normal-high renin hypertensives). Plasma ANF (P less than .0001) was higher, while uKK was lower (P less than .045) in low renin F+ normotensives than in normal-high renin ones. In conclusion, our data indicate that plasma ANF and DLS are elevated since the early phase of hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)

[Irritable colon. Physiopathologic and therapeutic aspects]. / Il colon irritabile. Aspetti fisiopatologici e terapeutici.

The authors review the pathophysiologic mechanisms involved in bowel motility and in its alterations. Several symptoms are present in a form of bowel disease usually defined as "irritable bowel", in which a lot of polymorphic aspects appear to coincide. The first part of the paper is concerned with the symptoms and suggested pathophysiology and pathogenesis of the disorder while the latter part deals with the non-pharmacologic and pharmacologic treatment options.

[Correlations between circulation levels of natriuretic atrial peptide and urinary excretion of kallikrein in young normotensive and hypertensive subjects]. / Correlazioni tra livelli circolanti di peptide atriale natriuretico ed escrezione urinaria di callicreina nel giovane normoteso ed iperteso.

The relationships between atrial natriuretic peptide (ANP) and the renal sodium-modulating systems have not yet been completely examined. In particular, the relationships between ANP and the kinins system are almost unknown. We thus examined an extremely selected cohort of normotensive (n = 29, mean age 21 +/- 2 years) and hypertensive subjects (n = 51m mean age 21 +/- 2.9 years), both without hypertensive heredity. After 7 days under normal sodium intake (120 mEq of Na+/day), blood samples were taken in the morning on awaking, for radioimmunoassay of plasma levels of aldosterone, ANP and renin activity. Blood was again drawn after one active hour in orthostatism. We also evaluated urinary kallikrein excretion from urine collected over the previous 24 hours. Our results showed higher plasma levels of ANP in young hypertensives than in normotensives (statistical significance p less than 0.0025). Urinary excretion of kallikrein was markedly reduced (p less than 0.001) in the hypertensive group (0.46 +/- 0.3 U/24 h) compared to youths with normal blood pressure (0.79 +/- 0.24 U/24 h), in which a relationship between plasma ANP and urinary kallikrein was not evident; young hypertensives, on the other hand, showed an inverse correlation (r = -0.72; p less than 0.001). Finally, our investigation, aside from establishing the presence of high circulating ANP levels even at the initial phases of hypertension, points out a new possible means of feedback among sodium-modulating systems. The opposite relationship between ANP and urinary kallikrein excretion in young hypertensives could be attributed to reduced activity of the renal kinins system and a compensatory attempt on the part of ANP.

Plasma atrial natriuretic peptide in young normotensive subjects with a family history of hypertension and in young hypertensive patients.

Plasma atrial natriuretic peptide (ANP) behavior was evaluated in 26 untreated essential hypertensives, 21 normotensives, and 20 normotensives with hypertensive heredity under normal sodium intake (120 mEq of Na+/day). All subjects were men, mean age 22.1 +/- 1.9 years. Plasma ANP was evaluated by radioimmunoassay on samples collected in supine position upon waking and again after 1 h of orthostatism. Resulting data showed that ANP in hypertensives (supine = 44.5 +/- 19.4 pg/mL, orthostatism = 24.1 +/- 11.6 pg/mL) was at higher levels than in controls (supine = 38.3 +/- 19.4 pg/mL, orthostatism = 19.9 +/- 10.6 pg/mL) or in normotensives with hypertensive heredity (supine = 42.1 +/- 16.8 pg/mL, orthostatism = 23.2 +/- 10.8 pg/mL). Mean ANP level was higher in the latter group than in the control group (supine = +9%; orthostatism = +14.2%). In conclusion, plasma ANP is raised in young essential hypertensives, resulting in slightly elevated levels in normotensives with hypertensive heredity.

[Effects of active postural inhibition on circulating levels of atrial natriuretic peptide in young hypertensive and normotensive subjects in the presence or absence of positive family history of essential arterial hypertension]. / Effetti della inibizione posturale attiva sui livelli circolanti di peptide atriale natriuretico nel giovane iperteso e normoteso in presenza o meno di familiarità positiva per ipertensione arteriosa essenziale.

The effect of active changes in posture, from recumbency to up-right position (60 min) on the circulating levels of atrial natriuretic peptide (ANP) were studied in 52 hypertensive patients, in 30 healthy human subjects and in 24 normotensive subjects with hypertensive parents. At the end of the orthostatic challenge, plasma ANP levels were reduced by about 40% (p less than 0.01) in all subjects without significant differences between the three groups. This indicates that the active postural inhibition of ANP release is substantially similar in the different subjects here studied.

[Effects of active orthostatism on blood levels of atrial natriuretic peptide in the healthy subject]. / Effetti dell'ortostatismo attivo sui livelli plasmatici di peptide atriale natriuretico nel soggetto normale.

The effects of active changes in posture, from recumbency to upright position (60 minutes), on the circulating levels of atrial natriuretic peptide (ANP) in healthy human subjects were studied by using a radioimmunoassay method. In supine position, plasma ANP levels ranged from 12 pg/ml to 51.5 pg/ml, with an average level of 35.3 +/- 11.5 pg/ml. After 1 hour of orthostatic position, plasma ANP levels varied from 10 pg/ml to 35 pg/ml, with an average level of 21 +/- 11.5 pg/ml. These results suggest that ANP is involved in the hemodynamic modifications following postural stimuli. Thus, postural changes can be taken in to account for evaluating plasma ANP behaviour properly.

[Epidemiology of chronic obstructive bronchopneumopathies]. / Epidemiologia delle broncopneumopatie croniche ostruttive.

Mortality due to respiratory diseases has been stable in Italy during this century, but this stability seems to be artificial due to TBC and pneumonias mortality decrease and chronic obstructive pulmonary disease (COPD) and cancer mortalities increase. In 1977 COPD morbidity caused 3,000,000 off-days, but these old data probably underestimated the real situation: indeed the greatest mortality is registered, as it is well know, in the elderly subjects (greater than 75 years), and this age was not considered in these data. More recently, a finalized project has been established by the National Research Council (CNR) to obviate poorness of data on COPD epidemiology with particular regard to its morbidity. At the present time, data have not yet been published. COPD appears to affect males more than females, while race does not seem important in COPD distribution. Moreover, a marked increase in respiratory dysfunction is observed with age. Alpha-1-antitrypsin deficit plays a significant role in COPD pathogenesis, while the influence of surface cells antigens and secretory state is still unclear. COPD is more frequent in some families than in general population, as well as in monozygote twins than in dizygote ones. However, the influence of genetically determined predisposition could be overestimated, being COPD frequencies in these cases linked to other risk factors. According to the "Dutch hypothesis" bronchial hyperreactivity is an indispensable condition in COPD pathogenesis, while "British hypothesis" gives more importance to recurrent bronchial inflammation. Some contaminants play an important role in COPD pathogenesis, both in urban (NO2, NO3, SO3) and working environments (coke, etc.). Smoke is the last factor considered in the pathogenesis of COPD.(ABSTRACT TRUNCATED AT 250 WORDS)

[Atrial natriuretic factor: an epidemiological study. Preliminary results]. / Il fattore natriuretico atriale: studio epidemiologico. Risultati preliminari.

We performed an epidemiological study on the atrial natriuretic factor pattern in a young population. Subjects were recruited in the Ospedale Militare Principale of Rome among young men liable to conscription, whose hospitalization was due either to essential hypertension or to other pathologies (not influencing our study, such as headache etc.). The recruitment lead to the formation of three different groups: normotensives, normotensives with family history of hypertension (mother and/or father) and hypertensives. On the morning of the study (after 7 days of pharmacological wash-out, under a diet containing 120 mEq of Na+/die), blood samples were taken. Plasma atrial natriuretic factor, renin activity and aldosterone were assayed by RIA. Digoxin-like immunoreactive substance was assayed by a solid-phase radioimmunoassay, following the extraction of plasma. Serum creatinine, sodium, potassium and urinary sodium and potassium (24 h before the study) were assayed by standard methods. Urinary kallikrein was assayed by chromogenic substrate S-2266. So far, we have studied 60 subjects (26 hypertensives, 21 normotensives and 13 normotensives with family history) and we wish to discuss in this article the preliminary results concerning the atrial natriuretic factor and its relationship with renin activity, aldosterone and blood pressure. Our results show that the mean plasma levels of atrial natriuretic factor in the hypertensive group were higher, although not significantly, than those of the other two groups and that the normotensives with family history had slightly higher levels as compared to normotensives (Delta % = + 7.4).(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of captopril on blood pressure and renin-angiotensin-aldosterone system in hypertensive subjects after inhibition of renal vasodilative system.

The aim of this study is to contribute to the understanding of the probable role of the renin-angiotensin-aldosterone, the kallikrein-kinins and the prostaglandins systems on the various types of essential hypertension and also their contribution to the action of captopril. Nineteen patients, 7 with high and 12 with normal or low levels of plasma renin activity (PRA), have been studied. Captopril (100 mg) was administered in acute dosage, blood pressure was checked for two hours and PRA and plasma aldosterone were assayed. The same trial was repeated after inhibition of prostaglandin-synthetase with indomethacin and kallikrein with trasylol, alternatively, and then with indomethacin and trasylol, contemporaneously. Our results showed that the renal vasodilative system was probably also involved in the mechanism of action of captopril, but that this drug reduced blood pressure mainly through a block of angiotensin II production in both groups of patients. Thus the finding of a normal or low PRA does not justify the conclusion that angiotensin II is not one of the mechanisms responsible for an elevated arterial pressure.