Short- and long-term risk of cardiovascular events in white-coat hypertension.

The prognostic impact of white-coat hypertension is not yet completely clear. In this study, we investigated cardiovascular outcome in sustained hypertension, white-coat hypertension and normotension in the short and long term. The occurrence of fatal and nonfatal cardiovascular events was evaluated in 1732 subjects with clinical hypertension (1333 with sustained and 399 with white-coat hypertension) and 305 with normotension. White-coat hypertension was defined as clinical hypertension and daytime blood pressure <135/85 mm Hg. During the period of observation (mean 6.4 years, range 0.7-13.1), 152 cardiovascular events occurred. The event rate per 100 patient-years in subjects with normotension, white-coat and sustained hypertension was 0.38, 0.44 and 1.58, respectively. Event-free survival was significantly different among the groups (P<0.0001). After adjustment for several covariates, Cox regression analysis showed that cardiovascular risk was significantly higher in patients with sustained than in those with white-coat hypertension (relative risk (RR) 3.32, 95% confidence interval (CI) 1.81-6.12, P=0.0001), whereas there was no significant difference between normotension and white-coat hypertension. When events were analysed separately, cardiac and cerebrovascular risk were significantly higher in sustained than in white-coat hypertension (RR 4.16, 95% CI 1.48-11.6, P=0.007, and RR 4.12, 95% CI 1.62-10.5, P=0.003, respectively) and not significantly different between white-coat hypertension and normotension. Event-free survival had the same trend for the whole period of observation both when cardiovascular events were examined together and when cardiac and cerebrovascular events were analysed separately. In this study, cardiovascular risk in white-coat hypertension was significantly lower than that in sustained hypertension and not significantly different from normotension both in the short and long term.

Reflux oesophagitis in children; the role of endoscopy. A multicentric Italian survey.

BACKGROUND: The decision whether to perform endoscopy in children with suspected reflux oesophagitis is not a straightforward one. Few symptoms are specific for oesophagitis and the diagnosis is not always correlated even to visual findings on endoscopy. AIM: The aim of this study was to define the role of endoscopy and especially of histology in the diagnosis of reflux oesophagitis and to examine the correlations between symptoms, endoscopic findings and histology in children with suspected gastroesophageal reflux disease. PATIENTS AND METHODS: One hundred and thirty-six patients with a clinical diagnosis of reflux oesophagitis, aged 1-18 years (mean 8.43; standard deviation +/-4.4), were enrolled from 12 Italian Paediatrics Gastroenterology Centres; symptom score, endoscopic and histologic oesophagitis scores were observed before and after therapy with proton pump inhibitors. RESULTS: Before therapy, a high correlation between the prevailing symptom score and endoscopic score was demonstrated, but not with histologic score: there was a significant tendency for histologic grade to exceed visual findings. After therapy, endoscopic score and histologic score were significantly improved. CONCLUSIONS: Oesophageal biopsies increase the diagnostic accuracy of upper endoscopy. Histologic grading is often much more important than the endoscopic appearance, so that endoscopic oesophageal biopsies are very important aids in the diagnosis of oesophagitis. Appropriate clinical evaluation of symptoms must occur before endoscopic examination.

Effectiveness of montelukast versus budesonide on quality of life and bronchial reactivity in subjects with mild-persistent asthma.

Insufficient data exist to evaluate the comparative effects of inhaled corticosteroids (ICS) versus leukotriene receptor antagonist (LTRA) on airway inflammation and quality of life (QoL). The aim of the study was to compare the effectiveness of montelukast compared to budesonide at different doses on QoL and bronchial reactivity in mild-asthmatic adult patients. 45 subjects with bronchial asthma were randomly assigned to a different treatment and divided in 3 treatment groups: A: 400 mg of budesonide twice a day; B: 10 mg of montelukast daily; C: 10 mg of montelukast daily plus 400 mg of budesonide twice a day. At the beginning of the study and at the end of the treatment period (16 weeks) all patients underwent complete clinical evaluation, pulmonary function testing and methacholine challenge test (MCHt). In group A the increase from baseline was 153.4&#x0025;, in group C was 133.2&#x0025;, and in group B 247.7&#x0025;, the latter increase being statistically significant compared to that in the other 2 groups (p&#x003C; 0.005 Wilcoxon test). In all domains the improvement in quality of life in the group treated with montelukast (group B) was significantly greater than that in the group treated with both medications (group C): in particular, the improvement was consistent in the symptoms (p&#x003C; 0.01) and emotions (p&#x003C; 0.01) domains, and weaker in the physical activity (p&#x003C; 0.05). A similar difference was observed between group B and A, but only in the symptoms (p&#x003C;0.01), emotions (p&#x003C;0.01), and environmental stimuli domains (p&#x003C;0.05). The personal perception of their own disease is important for a correct therapeutic management of asthma. In order to optimize the treatment, a complete adherence of the patient to the treatment itself is required, to be achieved through simplification of therapeutic schedule and easy administration of medications. Montelukast may be considered a valid alternative in the treatment of mild-persistent asthma, both for the clinical and functional benefits and for the great advantage of the once-daily dosage, which consistently improves the compliance with the chronic treatment of the disease.

Incidence of RBD and hallucination in patients affected by Parkinson's disease: 8-year follow-up.

We describe the 8-years follow-up of 80 patients affected by idiopathic, L-dopa-responsive Parkinson's disease. All patients were evaluated at baseline and during the follow-up with visual evoked potential, P300 event related potentials and polysomnography. The patients and their relatives compiled sleep and hallucination questionnaires. Statistical analysis was performed to evaluate if visual abnormalities, abnormal P300 recordings or sleep disturbances were linked to the development and hallucinations. Our results show that abnormal vision and abnormal P300 did not correlate with the incidence of hallucinations. However, the presence of REM sleep behavioral disorder (RBD) was significantly related to the development of hallucinations,independently of age, gender or duration of disease but dependent on the amount of dopaminoagonist treatment.

Cholesterol reduction and stroke occurrence: an overview of randomized clinical trials.

We performed a meta-analysis of randomized clinical trials of more than 6 months duration to describe how fatal and nonfatal strokes are related to cholesterol lowering and to the type of intervention. A total of 41 individual trials including approximately 80,000 subjects and followed for an average of about 4 years were included in the overview. There was a 16% (95% CI, 7-25%) reduction in risk of stroke among treated patients compared to control patients (test for heterogeneity, p = 0.76). When trials that used different interventions were separately examined, a significant reduction in stroke occurrence was observed only for those using statins as active treatment (risk reduction 23%; 95% CI 13-33%). A variance-weighted regression analysis of the logarithmic odds ratios for stroke incidence against the percentage of cholesterol reduction indicated that a reduction of fatal and nonfatal stroke can be obtained for a cholesterol reduction of 9% (95% CI 6.8-13.6%). The combined data of primary and secondary prevention trials indicate that a large reduction of blood cholesterol, achievable with statin drugs, can reduce the incidence of stroke.

Leukocyte adhesion molecules and leukocyte-platelet interactions during hemodialysis: effects of different synthetic membranes.

Membranes made from synthetic polymers, in general, are considered as being biocompatible membranes and tend to be treated as a homogeneous group. However, all of these membranes have multiple and different characteristics that may contribute to interactions with blood components. As a consequence, the biocompatibility profile of synthetic membranes may vary. In the present cross-over study, we examined by flow cytometry the effects (expressed as % change from predialysis values) of three different synthetic polymers (polysulfone, PSF; polyacrylonitrile-co-sodium methallyl sulfonate, AN69; ethylenevinylalcohol, EVAL) on the expression of leukocyte adhesion molecules (CD11b/CD18, CD15s) and the interactions between leukocytes and platelets under conditions of routine clinical use. For neutrophils, a statistically significant difference was found in CD15s expression for EVAL as compared to AN69 (p<0.05) and in CD11b/CD18 expression for PSF as compared to both EVAL (p<0.01) and AN69 (p<0.05). No difference between membranes was found on the expression of such adhesive molecules on monocytes. Significant differences in platelet-neutrophil (but not in platelet-monocyte) coaggregate formation were observed between PSF and both EVAL (p<0.001) and AN69 (p<0.01). Reactive oxygen species production by neutrophil population during hemodialysis was significantly different between each pair of synthetic polymers (PSF vs EVAL, p<0.001; PSF vs AN69, p<0.001; AN69 vs EVAL, p<0.05). Our data demonstrate that in terms of leukocyte adhesion receptors and platelet-leukocyte interactions, the biocompatibility profile of the synthetic membranes polysulphone, AN69 and EVAL shows many similarities but also several significant differences. Our results support the concept that biocompatibility evaluation of each membrane should be based exclusively on data generated by that membrane in order to avoid errors based on assumptions about group characteristics.

[Hospital management of the acute cerebrovascular patient. Results of a study carried out in the region of Abruzzo]. / La gestione ospedaliera del paziente cerebrovascolare acuto. Risultati di uno studio condotto nella Regione Abruzzo.

Acute cerebrovascular disease is a major cause of morbility, disability and mortality. Despite its enormous importance in term of public health, considerable uncertainty still exists regarding the efficacy and cost-effectiveness of many routine clinical practices currently used in the management of stroke. A multicenter study was conducted on 204 patients (100 males and 104 females; mean age 71.5 years; range 21-94) consecutively admitted in 12 hospitals in Abruzzo (Southern Italy) from September 1, 1990 to December 31, 1990, because of sudden onset of neurological deficit which was presumed to be of a vascular origin. One hundred and ninety-six patients were hospitalized less than 24 hours after stroke onset. Cerebral computerized tomography was performed in 135 patients, but only 43 had the examination within 24 hours of symptoms onset. Other instrumental investigations (carotid doppler, transcranial doppler, echocardiography, etc.) were rarely performed. Ischemic stroke was diagnosed in 69 patients, intraparenchimal hemorrhagic stroke in 33, sub-arachnoid hemorrhage in 10, undefined stroke in 40 and transient ischemic attack in 49. Antioedema were largely used in the first 48 hours after admission, and osmotic diuretics (glycerol and mannitol) were preferred to steroid treatment. Antiplatelet drugs (25.8%), calcium antagonists (20.1%) and barbiturates (19.1%) were also frequently prescribed. In conclusion, our study had shown an absolute lackness of standard criteria for management of patients with acute cerebrovascular disease.

Family history and socioeconomic factors as predictors of myocardial infarction, unstable angina and stroke in an Italian population. PROGETTO 3A Investigators.

A comprehensive case-control study was conducted in an Italian region in order to compare the influence of family history of cardiovascular events, socioeconomic factors, social networks, and their joint associations with major risk factors, on the risk, of myocardial infarction (MI), unstable angina (UA) and ischemic stroke (IS). A total of 513 patients with MI, 178 with UA, 237 with IS, and 928 hospitalised controls were recruited. The odds ratio (OR) of MI for two or more relatives with a positive history of MI was 3.6 (95% CI: 1.8-7.3). Family history of MI was predictive for UA (OR = 5.8; 95% CI: 1.2-28.7), but not for IS. A family history of stroke was more associated with the risk of MI than of IS. After adjustment for known risk factors, the OR of MI for more educated people was 2.1 (1.3-3.6) compared with less-educated people. Large family size seemed to be protective for MI. The effect of major risk factors on MI ranged from additive (diabetes) to multiplicative jointly with high education and family history of MI. A family history of stroke increased IS risk threefold jointly with smoking and hyperlipidemia, and eightfold with diabetes. Besides a family history of MI and IS, in this community a higher educational status seems to better identify groups at increased risk of MI. The joint associations have important preventive implications since by identifying high-risk individuals (for MI and IS) a more careful assessment and control of risk factors amenable to intervention may be performed.

A positive relation between high hemoglobin values and the risk of ischemic stroke. Progetto 3A Investigators.

We examined the relationship between the hemoglobin concentration and the risk of ischemic stroke using data from a hospital-based case-control study. A total of 143 patients (age 30-69 years) with a diagnosis of cerebral infarction confirmed by computerized tomography scan and 143 age- and sex-matched controls entered the study. Hemoglobin was higher in the patients with stroke (14.2 +/- 1.6 g/l, mean +/- SD) than in controls (13.7 +/- 1.6 g/l; p < 0.05). Compared with subjects with hemoglobin levels of less than 13 g/l (reference category), the relative risk of ischemic stroke, after allowance for potential risk factors, was 2.0 (95% CI 0.8-4.9) for the 13-13.9 g/l quartile, 2.8 (95% CI 1.2-6.5) for the 14-14.9 g/l quartile, and 3.2 (95% CI 1.4-7.4) for the 14 + g/l quartile (chi 2 for linear trend 7.27, p < 0.01). We conclude that the hemoglobin concentration may be an indicator of risk for ischemic stroke.

Serum cholesterol and risk of ischemic stroke: results of a case-control study. On behalf of PROGETTO 3A Investigators.

BACKGROUND: While a positive relation between serum cholesterol and the risk of myocardial infarction has been consistently reported, the association between serum cholesterol and the risk of ischemic stroke lacks consistency. To further investigate the strength of cholesterol as a risk factor for myocardial infarction and stroke we conducted a comparative study. METHODS: A case-control study was conducted from 1990 to 1992. A network of 21 hospitals in Abruzzo, southern Italy, was created. First, computerized tomography scans confirmed ischemic stroke patients (230 with median age: 64; range: 31-69 years) and 230 sex- and age-matched controls with acute disorders unrelated to known cardiovascular risk factors. Acute myocardial infarction patients (513) and 513 matched controls were simultaneously recruited for a parallel study comparison. Total serum cholesterol concentration was measured within the first 48 hr following admission and the response to a structured questionnaire was evaluated. RESULTS: The mean (standard deviation) serum cholesterol level was 220.7 mg/dl (50.9) among stroke patients and 201.5 mg/dl (41.6) among controls (P < 0.0001). Compared with the lowest quintile (< 160 mg/dl), the odds ratio of ischemic stroke for patients in the highest quintile (> 240 mg/dl), after simultaneous adjustment for other potentially confounding covariates, was 2.6 (95% confidence interval: 1.4-4.8). A significant linear trend in risk was found (chi 2 1 df = 7.27, P < 0.01). Within each total serum cholesterol quintile, adjusted odds ratios for myocardial infarction were higher than that for ischemic stroke, and a stronger linear trend in risk was found (chi 2 1 df = 21.3, P < 0.0001). CONCLUSIONS: Our data confirm the strong linear relationship between total serum cholesterol and the risk of myocardial infarction and suggest that, at least in our population, cholesterol seems to be an indicator of ischemic stroke risk.

From pharmacological promises to controlled clinical trials to meta-analysis and back: the case of nimodipine in cerebrovascular disorders.

On the basis of their promising experimental evidence, calcium channel blockers are today largely used in clinical practice for treatment of patients with cerebrovascular disorders. We propose a meta-analytical evaluation of published clinical trials on nimodipine, a dihydropiridin calcium antagonist, in subarachnoid hemorrhage and in ischemic stroke. In seven trials of subarachnoid hemorrhage, 112 deaths occurred among 682 patients randomized to active treatment compared with 154 deaths among 689 control patients (odds ratio of 0.68, 95% confidence interval of 0.52 to 0.90). Poor outcome due to delayed cerebral ischemia following subarachnoid hemorrhage was also lower in the group allocated to receive nimodipine (odds ratio of 0.47, 95% confidence interval of 0.36 to 0.62). In 12 trials of ischemic stroke, 382 deaths occurred among 2056 patients allocated to receive nimodipine compared to 288 deaths among 1462 control patients (odds ratio of 0.98, 95% confidence interval of 0.82 to 1.18). Pooled results strongly suggest a protective effect of nimodipine in delayed cerebral ischemia following subarachnoid hemorrhage and no effect in ischemic stroke, but the direction and the significance of these results are due to the contribution of a single large trial on subarachnoid hemorrhage and of two trials on ischemic stroke, which account respectively for 40% and 65% of randomized patients. The dissociated effect of nimodipine on these similar conditions could be related to its preventive role in ischemic damage, resembling animal models of ischemic stroke where a beneficial effect of calcium antagonists was clearly shown only when treatment was started before experimental cerebral artery occlusion. In this view, the negative results obtained from the clinical setting of ischemic stroke seem to indicate nimodipine as an aspecific neuroprotective agent without a curative effect.

[Can the changes in dietary fat intake reduce the risk of onset and development of atherosclerosis and of ischemic cardiopathy in particular?]. / Può la modificazione dei grassi alimentari ridurre il rischio di insorgenza e sviluppo dell'aterosclerosi ed in particolare della cardiopatia ischemica?

In this review we have collected data from epidemiologic studies and clinical trials published from 1968 to 1989 on the relationship between dietary fat and risk of coronary heart disease. Although the reported observational studies of diet and coronary heart disease provide general support for the classic diet-heart hypothesis, evidence of specific dietary lipids is weak. A positive association with saturated fat intake was seen in two prospective studies. A positive association with cholesterol intake was found in only two cohort studies, and an inverse relationship with polyunsaturated fat intake in only one. Clear evidence from dietary trials in the prevention of coronary heart disease has not been found. The analysis of trends in coronary heart disease and stroke mortality of developed countries has shown a discrepancy between fat intakes, cholesterol levels and mortality. The reduction in intake of certain foods "at high risk" such as meat, eggs, milk and cheese, as a preventive intervention, is based on weak scientific evidence. A strategy program has to emphasize the maintenance of ideal body weight by caloric control, an adequate level of physical activity, and the control of other risk factors such as hypertension, hypercholesterolemia, and diabetes.

Diagnosis of diabetic polyneuropathy. Correlation between clinical and instrumental findings and assessment of simple diagnostic criteria.

In the present study minimal clinical and electrophysiological criteria for the diagnosis of diabetic polyneuropathy (DP) have been tested in 48 unselected subjects attending an outpatient service for diabetics at the University Hospital of Chieti. A standard electrophysiological examination was performed in all patients on the median nerve (sensory and motor), peroneal nerve and sural nerve. Depending on the importance of the laboratory values for each nerve, nerve conduction velocity, distal latency and potential amplitude were given separate scores ranging from 0.5 to 2. A diagnosis of probable DP was made when abnormal findings were present in more than one nerve with a total score of 2.5 or more. As a whole, 28 cases (58%) had abnormal laboratory findings supporting the diagnosis of probable DP. There was a relatively high correlation between probable DP and a positive clinical examination although the validity coefficients of the neurological exam were not high enough to allow its use as a screening test for DP.

Effects of rationalizing drug treatment of patients with epilepsy and mental retardation.

Eighty patients with epilepsy and mental retardation were observed for a mean period of 12.5 months to assess the effects of 'rationalisation' of their drug treatment on both epilepsy and behaviour. Anticonvulsant drugs were modified to provide the best seizure control with the lowest toxicity, and psychotropic drugs also were monitored and modified if necessary to obtain the best results. At the end of the follow-up period the number of anti-epileptic drugs had fallen from 1.84 to 1.05 per patient. On admission to the study 47 patients were being treated with 85 psychotropic drugs: at the end of the follow-up 44 patients were taking 63 drugs. Seizures were significantly reduced in 16 of 39 patients with unsatisfactory control on admission to the study. Among 41 patients with initial satisfactory control, only 16 had relapse of seizures. Behavior did not change significantly.

Early prognosis of epilepsy. Effects of treatment in the first follow-up year.

A multicenter prospective investigation was conducted in 17 teaching and general hospitals in Italy to assess the efficacy of the care delivered to previously untreated patients with epilepsy. 175 cases were included and allocated to monotherapy. Only 112 cases completed the first year of follow-up. Of these, 59 (52.7%) were completely controlled and 53 (47.3%) had one or more seizure relapses. Controlled and uncontrolled patients were compared with respect to the main variables believed to influence non-responsiveness to standard therapy. The proportion of cases with relapses was significantly associated with the number of seizures reported before treatment was started. Selected seizure patterns (absences, myoclonic seizures) and prolonged disease duration were also reported more frequently among patients with recurrences. The implications of these findings are discussed with respect to drug response and prognosis of epilepsy.

Antiepileptic drug toxicity: definition and mechanism of action.

A detailed review of the adverse reactions of anticonvulsants is given, focusing on the definitions of drug toxicity, sources of information, patterns of drug utilization, pharmacokinetic variables and different mechanisms of action. The information available in the literature provides a wide spectrum of drug toxicity with no attempt at a practical definition of the reported events. This favors uncertainty among practising physicians, who are led to use the individual items with different attitudes. Suggestions are given for the evaluation, prevention and treatment of anticonvulsant drug toxicity.

Drug treatment of epilepsy. Outlines, criticism and perspectives.

This article focuses on important aspects relevant to the assessment of antiepileptic treatment and critically reviews the existing knowledge in this area. The principal variables considered are the commencement of treatment, choice of appropriate drug, efficacy of monotherapy, and cessation of treatment. When seizure recurrences after the first unprovoked seizure are considered, contradictory data have been provided on the role of early (i.e. after the first seizure) therapy in preventing relapses. The choice of the appropriate drug seems to be dictated more by clinical toxicity than by truly greater efficacy since there is no evidence of significant differences in efficacy among the 'major' anticonvulsants such as phenytoin, phenobarbitone, carbamazepine and primidone. Monotherapy is the preferred treatment, at least in previously untreated patients, since up to 90% of cases are completely controlled after variable periods of observation. Cessation of therapy after prolonged seizure control is followed by relapses in a varying percentage of cases depending on several factors, among which is the duration of the period of control. As yet, a definitive comparison of the available information has been prevented by major methodological differences and by partial investigation of the various aspects of the care of the patient with epilepsy. To provide a tentative answer to some of the open questions concerning the impact of anticonvulsant therapy on the prognosis of the disease, an alternative approach has been proposed, based on the active surveillance of a cohort of newly referred patients started on monotherapy in routine care conditions over a period of more than 5 years. The feasibility of this approach is being tested in a multicentre prospective study currently in progress in Italy.