The measuring of substantia nigra hyperechogenicity in an Italian cohort of Parkinson disease patients: a case/control study (NOBIS Study).

Transcranial sonography (TCS) shows an increased echogenic area of the substantia nigra (SN) in patients with Parkinson disease (PD). It has been increasingly used in the diagnosis of PD and its differentiation from atypical parkinsonian syndromes. Here, we studied the diagnostic accuracy of SN TCS in Italian patients. In this blinded cross-sectional study (NOBIS study), two expert neuro-sonologists performed TCS in 25 PD patients and 29 age- and sex-matched controls. The study participants were completely hidden to the TCS investigators using large drapery. One month later, the SN TCS recordings were re-read by the initial investigator, and cross-read by the second reader. Diagnostic accuracy was estimated on the first reading, intra-reader reliability on re-reading, and inter-reader reliability on cross-readings. The mean SN echogenic area was larger in the patients (0.24 cm2) than in the controls (0.15 cm2; Mann-Whitney test, p < 0.001). SN measures did not differ between right and left, or between ipsilateral and contralateral to the clinically more affected side. There was no correlation between SN echogenicity and PD severity or duration. High intra-reader (concordance correlation coefficient 0.93) and inter-reader (0.98) agreement of SN measurements was found. The diagnostic accuracy for the detection of PD was high (area under receiver-operating characteristic curve 0.91; 95% CI 0.83-1.00) with an optimum cut-off value for SN echogenic area of 0.18 cm2 with the device used here (specificity 0.83-0.90; sensitivity 0.72-0.92). This study supports the use of SN TCS in the diagnostic workup of PD if performed by trained readers.

Secreted Wnt antagonists during eradication of cytomegalovirus infection in solid organ transplant recipients.

We evaluated secreted wingless (Wnt) modulators during cytomegalovirus (CMV) infection in solid organ transplant recipients (SOTr). The major findings were: (i) Plasma levels of Dickkopf-1 (DKK-1) were significantly lower in patients with CMV DNAemia above lower level of quantification at baseline. (ii) Receiver operating characteristic analysis indicated that low DKK-1 and increased secreted frizzled related protein-3 levels were predictors of poor virological outcomes during follow-up. Our findings demonstrate an imbalanced pattern of circulating secreted Wnt modulators in SOTr with poor virological outcomes following treatment for CMV disease, and may suggest a role for dysregulated Wnt signaling on viral pathogenesis during CMV infection.

Carotid plaque morphology improves stroke risk prediction: usefulness of a new ultrasonographic score.

Carotid thickening and plaque detected by B-mode imaging ultrasound are useful to improve the ischemic risk evaluation in asymptomatic subjects over and beyond the traditional cardiovascular risk factors. Some plaque's echographic parameters help describing the vascular risk. We hypothesized that the stenosis degree, plaque surface irregularity, echolucency and texture, compounded in a Total Plaque Risk Score (TPRS), are predictors of the ischemic events in the San Daniele study, a general population-based study of 1,348 subjects followed for 12 years in average. In the 171 subjects with at least one plaque at baseline, high TPRS was the most powerful independent predictor of cerebrovascular events, which occurred in 115 subjects. Addition of plaque characteristics significantly increased the area under the ROC curve (0.90 vs. 0.88, p = 0.04) versus the Framingham risk score alone. The TPRS is a potential new tool to improve the stroke risk prediction.

Effects of the intensity of immunosuppressive therapy on outcome of treatment for CMV disease in organ transplant recipients.

An effective host immune response, critical for successful control of Cytomegalovirus (CMV) disease in solid organ transplant recipients, is affected by intensity and type of immunosuppressive therapy. We used information prospectively captured in the VICTOR-trial to investigate the impact of immunosuppressive therapy on short- and long-term outcomes of CMV treatment in organ transplant recipients. Dual, as compared to triple, immunosuppressive therapy ([odds ratios] OR of 2.55; 95% CI: 1.51-4.60; p = 0.002), lower blood concentrations of calcineurin inhibitors (OR of 5.53; CI: 1.04-29.35; p = 0.045), and longer time since transplantation (OR of 1.70; CI: 1.01-2.87; p = 0.047) all showed better early (Day 21) CMV DNAemia eradication. We observed no effect of the intensity of the immunosuppressive therapy on overall rates of viral eradication or recurrence. The type of calcineurin inhibitor (tacrolimus/cyclosporine) or use of mycophenolate did not affect treatment efficacy, although both tacrolimus and mycophenolate treated patients showed a lower rate of virological recurrence OR 0.51 (95% CI: 0.26-0.98; p = 0.044) and OR 0.45 (95% CI: 0.22-0.93; p = 0.031), respectively. Lower total intensity of immunosuppressive therapy was associated with more effective early, but not overall, CMV DNAemia eradication by valganciclovir/ganciclovir therapy. Both mycophenolate and tacrolimus (rather than cyclosporine) therapy seem to be associated with reduced risk of recurrence.

Long-term outcomes of CMV disease treatment with valganciclovir versus IV ganciclovir in solid organ transplant recipients.

Though an important cause of morbidity and mortality in solid organ transplantation (SOT), the long-term outcomes of cytomegalovirus (CMV) disease treatment have not been well studied. In a randomized trial, 321 SOT recipients with CMV disease were followed 1 year after treatment with either twice daily intravenous ganciclovir or oral valganciclovir (for 21 days) followed by once daily valganciclovir until day 49 in all patients. Clinical and viral eradication of CMV disease was similar between groups. Clinical recurrence beyond day 49 was found in 15.1% and virological recurrence in 30.0%, no difference between groups (p > 0.77). In a multivariable logistic regression analysis, the only independent predictor for recurrence was failure to eradicate DNAemia by day 21 (clinical: OR 3.9 [1.3-11.3], p = 0.012; virological: OR 5.6 [2.5-12.6], p < 0.0001). Eight patients developed ganciclovir resistance, with no difference between groups (p = 0.62). Twenty patients (valganciclovir: 11, ganciclovir: 9, p = 0.82) died, 12 due to infections, two involving CMV disease. There were no differences in long-term outcomes between treatment arms, further supporting the use of oral valganciclovir for treatment of CMV disease. Persistent DNAemia at day 21, CMV IgG serostatus and development of resistance may be relevant factors for further individualization of treatment.

Seroprevalence of hepatitis B virus markers and risk factors in patients and staff of an Italian residential institution for the mentally disabled.

We conducted a cross-sectional study to evaluate the prevalence rate and risk factors for hepatitis B virus (HBV) infection among residents and staff at the Fatebenefratelli Institute in San Colombano in the province of Milan. We tested serum from 510 patients and 165 staff members. In addition, a medical record and a completed questionnaire were obtained from each patient. A total of 338 (66.5%) residents were found to have markers of HBV infection, including 29 (5.7%) who were identified as carriers. Thirty-nine members of staff (24.1%) showed evidence of HBV infection but only 1 (0.6%) was identified as a carrier. Among patients the prevalence rate of HBV was significantly associated with length of stay and age at admission, as it was with length of employment among staff members. The hepatitis B vaccine was offered to all patients and staff in the institution during 1994. A total of 143 (84%) patients and 111 (90%) members of the staff were vaccinated in the same year. To prevent the further spread of HBV infection in this institution, all current and future residents and staff members should be screened for serological markers for HBV and subjects identified as being susceptible should be vaccinated according to a compulsory routine policy.

Effects of the administration of an angiotensin-converting enzyme inhibitor during the acute phase of myocardial infarction in patients with arterial hypertension. SMILE Study Investigators. Survival of Myocardial Infarction Long-term Evaluation.

A positive history of arterial hypertension (HBP) is present in as many as 30% of patients with acute myocardial infarction (AMI) and their clinical outcome could be greatly improved by drugs enhancing blood pressure control and preserving ventricular function. The aim of the present study was to evaluate the importance of a history of HBP on the clinical efficacy of early treatment with the angiotensin-converting enzyme (ACE) inhibitor zofenopril in patients with anterior AMI. We summarize the results of a post-hoc analysis of data from the Survival of Myocardial Infarction Long-term Evaluation (SMILE) study, which randomly evaluated the efficacy of zofenopril given within 24 h of symptom onset to patients with anterior AMI not undergoing thrombolysis. Of 1441 patients who entered the study, 565 (39.2%) had a history of HBP. The mean follow-up time was 12 months and the main outcome measures were 6-week combined occurrence of death and severe congestive heart failure (CHF) and 1-year mortality. After 6-week of treatment with zofenopril the relative risk of death or severe CHF was 0.60 (95% confidence interval [CI]: 0.45-0.81; 2P < .05) in the hypertensive group and 0.89 (0.74-1.08; 2P = .62) for normotensive patients, whereas the 1-year risk of death was 0.61 (95% CI: 0.23,0.89; 2P < .05) and 0.77 (95% CI: 0.52-1.17; 2P = .22), respectively. The 6-week prevalence of mild-to-moderate CHF was also significantly reduced by zofenopril in the hypertensive population (14.1% v 9.4%; 2P < .05). The present data suggest that treatment with zofenopril started within 24 h of the onset of anterior AMI could be highly beneficial in patients with a history of HBP.

Preliminary bioavailability study on protacine: a new, non-steroidal anti-inflammatory agent.

Time versus concentration curves of unchanged protacine were measured in the blood of 5 healthy volunteers by high pressure liquid chromatography after a single oral dose of 4 capsules (600 mg). These curves showed a maximum at 8 hours after administration, with an absorption half-life of 3.4 hours, and were interpreted according to the two-compartment open model with invasion. The elimination half-life was found to be 10 hours. This may allow a maintenance treatment, where necessary, with 1 capsule (150 mg) of protacine twice daily and strongly suggests that, apart from acute cases, protacine would be particularly well suited for long-term treatment.

Double-blind clinical evaluation of a new anti-inflammatory drug, protacine, versus indomethacin.

A double-blind clinical trial was carried out in 69 rheumatic in-patients to compare the efficacy and tolerance of a new, non-steroidal anti-inflammatory agent, protacine, with that of indomethacin. Patients received either 150 mg protacine or 50 mg indomethacin 3-times daily for 21 days. The time course of symptoms was recorded by semiquantitative scoring, as were side-effects. Uropepsinogen excretion, occult blood in faeces and standard physiological parameters were also monitored. Protacine globally decreased symptom scores by 58.5% and indomethacin by 24.3% (p less than 0.001). The computed time to reduce symptom scores by 50% was 17.2 days with protacine as compared to 39.2 days with indomethacin (p less than 0.001). Physiological parameters did not change, except white blood cells which decreased after protacine (each subject however, remaining well within the physiological range) and erythrocyte sedimentation rate, which decreased in both groups. Uropepsinogen excretion increased by 70% after protacine, and threefold after indomethacin (p less than 0.001). Occult blood search was positive in 1 patient receiving protacine, while 2 who were already positive before receiving protacine became negative during the treatment. Four patients taking indomethacin were found to be positive, 1 showing melaena. The one who was already positive before treatment showed increasing severity of occult bleeding during indomethacin administration. Frequency and severity of side-effects were significantly less with protacine (p = 0.004). In conclusion, protacine showed analgesic and anti-inflammatory actions significantly more potent and rapid than those of indomethacin, with significantly fewer and less severe side-effects.

The use of antisera ('Serocytol') in the management of gastritis: a double-blind clinical assessment versus placebo.

A double-blind, placebo-controlled study was carried out in 40 out-patients with endoscopically confirmed hypertrophic or erosive gastritis, without ulcer, to assess the effectiveness and tolerance of treatment with equine antisera (antidiencephalon and anti-stomach tissue). Patients were assigned at random to receive a single dose in suppository form on 2 days a week for 6 weeks of both antisera (anti-diencephalon on Days 1 and 4, anti-stomach tissue on Days 2 and 5) or placebo (saline solution). No other anti-ulcer treatment was allowed except standard antacid tablets, the consumption of which was recorded and used as an evaluation parameter. Endoscopy, haematology and haematochemistry were performed before and after treatment; symptoms (daytime and night-time pain, heartburn and dyspepsia) and possible adverse reactions were scored 0 to 4 in order of increasing severity before treatment and after 1, 2, 4 and 6 weeks. Five patients in the placebo group had to be withdrawn from the trial at the second week because of therapeutic failure. This proportion was significantly in favour of the antisera group, as was the proportion of patients endoscopically healed and the extent and rate of symptomatic improvement. Concomitant antacid consumption rapidly and significantly decreased in the antisera but not in the placebo group. Signs of intolerance were not observed with either treatment, nor were there any significant alterations in haematology or haematochemistry. In particular, the immune titre of patients did not increase after treatment, thus indicating that the administered heterologous proteins did not elicit an immunization of the patients against horse protein.(ABSTRACT TRUNCATED AT 250 WORDS)

Double-blind clinical comparison between a gastrin-receptor antagonist, proglumide, and a histamine H2-blocker, cimetidine.

A double-blind trial was carried out in 30 patients with peptic ulcers to assess the effects of treatment with a gastrin-receptor antagonist, proglumide, compared with a histamine H2-blocker, cimetidine. Patients received either 1200 mg proglumide or 1200 mg cimetidine per day for 28 days. The results showed that both drugs significantly reduced clinical symptoms and gastric secretion. In patients treated with cimetidine there was a significant increase in blood gastrin levels and marked hypertrophy and hyperplasia of the antral mucosa was observed in almost all patients. No such changes were found in the patients treated with proglumide.

A double-blind multicentre study of paroxetine and amitriptyline in depressed outpatients. Italian Paroxetine Study Group.

A comparative double-blind study of paroxetine and amitriptyline in the treatment of depressed hospital outpatients was undertaken at 15 centres in Italy. Three hundred and nine patients of either sex were admitted to the study. The starting dose of paroxetine was 20 mg daily and of amitriptyline 75 mg daily in divided doses; at week 3 these doses could be increased at the investigators' discretion. Efficacy was measured on the Hamilton Depression Rating Scale and on Clinical Global Impression. Both treatment groups showed significant improvement at week 6 with no significant between-group differences. Significantly fewer patients receiving paroxetine reported adverse events compared with those on amitriptyline (44% vs 62%; p < 0.01 in favour of paroxetine).

Posatirelin for the treatment of degenerative and vascular dementia: results of explanatory and pragmatic efficacy analyses.

In order to confirm the efficacy and safety of posatirelin (L-pyro-2-aminoadipyl-L-leucyl-L-prolinamide), a synthetic peptide having cholinergic, catecholaminergic and neurotrophic activities, a multicentre, double-blind, controlled study versus placebo was planned in elderly patients suffering from Alzheimer's disease and vascular dementia, according to National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) and National Institute of Neurological Disorders and Stroke/Association Internationale pour la Recherche et l'Enseignement en Neurosciences (NINDS-AIREN) criteria, respectively. The trial consisted of a 2-week run-in phase with placebo administered once a day orally, followed by a double-blind period of 3 months, with posatirelin or placebo administered once a day intramuscularly. Efficacy was assessed using the Gottfries-Bråne-Steen (GBS) Rating Scale (primary variable) and the Rey Memory Test (secondary variable). Laboratory tests, vital signs and adverse events were monitored. A total of 360 patients were randomized, the intent-to-treat sample (ITT) being made up of 357 patients and the per protocol sample (PP) of 260 patients. Both pragmatic and explanatory analyses showed significant differences between treatment groups in the GBS Rating Scale and the Rey Memory Test, with no difference in the two types of dementia. No difference between treatments was observed in safety variables, the incidence of adverse events in the posatirelin group being 7.3%. The study confirms previous results showing that treatment with posatirelin can improve cognitive and functional abilities of patients suffering from degenerative or vascular dementia.

Dietary calcium and mineral/vitamin supplementation: a controversial problem.

There is a consensus that adequate calcium intake during bone development, and possibly in adulthood and senescence, helps to prevent bone resorption and osteoporosis. The uptake of dietary calcium should be sufficient to maintain both normal serum calcium concentrations and parathyroid hormone levels in the low normal range throughout the day, otherwise, increased bone resorption occurs. Calcium intake varies with race and with environmental and dietary conditions. Estimating the appropriate amount of calcium to be added to dietary sources for an optimal supplementation regimen is therefore difficult. Few intervention studies have evaluated the dose-effect relationship for calcium supplementation conclusively. The mechanisms regulating fractional calcium absorption as a function of intake suggest that very high daily doses are probably useless. They may be unsafe in the long term because of the risks of hypercalciuria and kidney stones, and of an imbalance in the ratio of calcium to magnesium. Concomitant supplementation with limited amounts of magnesium may reduce this risk and improve mineralization. Dietary intake is 500-600 mg/day in most studies, making 400 mg/day an appropriate supplementary dose for most premenopausal women (RDA 1000 mg/day). After the menopause and during lactation (RDA 1200-1500 mg/day), 800 mg/day is probably appropriate, particularly if low doses of vitamin D are taken concomitantly.

[Nuclear medicine in pneumonology in the light of 9 year's experience at the S. Luigi Gonzaga Hospital]. / Medicina nucleare in pneumologia alla luce di 9 anni di sperimentazioni all'Ospedale S. Luigi Gonzaga.

An attempt is made to draw a picture of the results obtained with nuclear medicine in the pneumological field in the light of 9 years experience. An attempt is also made to identify from among recently introduced techniques (T.A.C., echotomography) which ones might be substituted for radioisotopes and when, and on what occasion they can be used as complementary treatment. It is concluded that nuclear medicine is of absolute value for functional examinations of the respiratory apparatus (perfusors and ventilators) and for lung onconscannning with Ga67 citrate and Bleomycin-Co57 under present circumstances and that in other fields certain morphological scans (bone scans) are still useful by virtue of their cost-benefit ratio.

[Indications for radiotherapy of lung cancer in the light of its clinical reality]. / Indicazioni del trattamento radiante del carcinoma del polmone alla luce della sua realtá clinica.

Reference is made to a large series and the literature in an attempt to single out cases where radiation management is indicated in the curative, palliative and anatalogic treatment of lung cancer, an in association with other therapies. It is pointed out that each case much be examined on its merits in the light of the histological type, the extent of the process, and its possible metastasis. The conclusion is drawn that radiotherapy plays a useful part in the albeit slight increase in survival of lung cancer patients under acceptable general conditions.