Use of probiotics for the treatment of constipation in Parkinson's disease patients.

AIM: The aim of this paper was to assess the effects of milk fermented with the probiotic strain Lactobacillus casei Shirota on constipation in Parkinson's disease patients. Constipation is a common secondary symptom in patients suffering from Parkinson's Disease (PD), generally treated with dietary therapy, soluble fiber supplements and macrogol laxatives without sodium sulfate. There are no studies on the use of probiotics in the treatment of constipation in these patients. The effects of the administration of Lactobacillus casei Shirota on gastrointestinal symptoms have been assessed in two randomized controlled trials on patients suffering from chronic constipation. METHODS: Forty PD patients suffering from constipation according to Rome III criteria were recruited. We compared the characteristic of intestinal function during two periods with different treatments: in the first week the patients treated constipation only with dietetic therapy; in the following 5 weeks the patients treated constipation not only with dietetic therapy, but also taking a 65 mL fermented milk drink containing 6.5×109 CFU of Lactobacilus casei Shirota daily.They completed a daily diary for 6 weeks, recording details related to their intestinal function. RESULTS: After probiotic intake we observed a statistically significant increase in the number of days per week in which stools were of normal consistency (P<0.01) and significant reductions in the number of days per week in which patients felt bloated (P<0.01), experienced abdominal pain (P<0.01) and sensation of incomplete emptying (P<0.01). CONCLUSION: This pilot study showed that a regular intake of probiotics can significantly improve stool consistency and bowel habits in Parkinson's disease patients.

Subclinical hypercortisolism: correlation between biochemical diagnostic criteria and clinical aspects.

OBJECTIVE: Subclinical hypercortisolism (SH) has been associated with increased prevalence of hypertension, type 2 diabetes mellitus, dyslipidaemia, central obesity, osteoporosis and vertebral fractures. We aimed to investigate the accuracy of different SH diagnostic criteria in predicting the presence of complications. DESIGN: This was a retrospective study. PATIENTS: We evaluated data from 231 patients (120 women and 111 men) affected with adrenal incidentalomas (AI). MEASUREMENTS: We studied the accuracy of different SH diagnostic criteria (cortisol after 1 mg overnight dexamethasone suppression test - 1mg-DST - at different cut-off such as 49.7, 82.8, 137.9 nmol/l, elevated urinary free cortisol, reduced adrenal corticotroph hormone (ACTH) levels alone or various combination of these parameters) in predicting the concomitant presence of the following three complications: hypertension, type 2 diabetes and vertebral fractures. RESULTS: The criterion characterized by the presence of two of 1mg-DST >82.8 nmol/l, elevated UFC and reduced ACTH struck the best balance between sensitivity and specificity, reaching a good accuracy in predicting the cluster of complications (61.9%; 77.1% and 75.8%, respectively). The presence of this cluster was associated with this criterion (OR 4.75, 95%CI 1.8-12.7, P = 0.002) regardless of gonadal status, body mass index (BMI) and age. CONCLUSIONS: The SH criterion characterized by the presence of two of 1mg-DST >82.8 nmol/l, elevated UFC and reduced ACTH seems the best in predicting the presence of chronic manifestations of subtle cortisol excess.

Relationship of thyroid function with body mass index and insulin-resistance in euthyroid obese subjects.

BACKGROUND AND AIMS: It is recognized that overt thyroid dysfunction is associated with weight changes, but the influence of a minor alteration of thyroid function remains unclear. This study aimed to further investigate the relationship between obesity and thyroid function and to examine the possible role of insulin resistance on the hypothalamic-pituitary- thyroid axis. METHODS AND RESULTS: Serum TSH and free T4 (FT4) levels, anthropometric and metabolic parameters were evaluated in 581 obese patients. In all patients TSH values progressively increased according to the severity of obesity and were positively correlated with body mass index (p=0.001, r=0.13) and waist circumference (p=0.02, r=0.11). Patients with insulin resistance showed higher TSH (1.8±1.0 vs 1.6±0.9 µUI/l; p=0.03) and lower FT4 levels (13.8±2.3 vs 15.0±2.2 pmol/l; p<0.001), as compared with patients with normal insulin sensitivity. Moreover, TSH was positively correlated with fasting insulin (p<0.001, r=0.152) and homeostasis model assessment of insulin resistance (HOMA-IR; p<0.001, r=0.148), and negatively correlated with Quantitative Insulin Sensitivity Check Index (QUICKI; p<0.001, r=-0.148); FT4 was negatively associated with fasting insulin (p<0.001, r=-0.287) and HOMA-IR (p<0.001, r=-0.295), and positively associated with QUICKI (p<0.001, r=0.295). CONCLUSIONS: A relationship between thyroid function and overweight/ obesity condition seems to exist, mainly influenced by insulin resistance. Whether variations in TSH and/or thyroid hormones, within a normal range, can influence body weight or whether obesity per se can alter thyroid function cannot be stated so far. Further studies are needed to assess the link between thyroid function and body weight, by considering not only changes in thyroid hormones, but also body fat distribution, obesity duration and low-grade inflammation.

[Thyroid function and obesity]. / La funzione tiroidea in corso di obesità.

A relationship between thyroid function and obesity seems likely, mainly influenced by the insulin resistance. Whether variations in TSH and/or thyroid hormones, within a normal range, can influence body weight or if obesity per se can alter thyroid function has not been clarified so far. Further studies are necessary to assess the link between thyroid function and body weight, that must consider not only changes of thyroid hormones, but also body fat distribution, obesity duration and the state of low grade inflammation. It is recognized that thyroid function is linked not only to body mass index, but also to body composition and, particularly, to the amount and percentage of fat mass.

Effects of marine noise pollution on Mediterranean fishes and invertebrates: A review.

Marine noise pollution (MNP) can cause a multitude of impacts on many organisms, but information is often scattered and general outcomes difficult to assess. We have reviewed the literature on MNP impacts on Mediterranean fish and invertebrates. Both chronic and acute MNP produced by various human activities - e.g. maritime traffic, pile driving, air guns - were found to cause detectable effects on intra-specific communication, vital processes, physiology, behavioral patterns, health status and survival. These effects on individuals can extend to inducing population- and ecosystem-wide alterations, especially when MNP impacts functionally important species, such as keystone predators and habitat forming species. Curbing the threats of MNP in the Mediterranean Sea is a challenging task, but a variety of measures could be adopted to mitigate MNP impacts. Successful measures will require more accurate information on impacts and that effective management of MNP really becomes a priority in the policy makers' agenda.

[Risk factors for renal disease in cardiac patients]. / Fattori di rischio nefrologico del paziente cardiopatico.

There are interconnections between the kidney, which regulates the extracellular volume, and the heart, which regulates the systemic circulation. In normal and minor pathological conditions or in those with a slow onset, a self-regulatory mechanism between the two systems is created in our organism to maintain a balance that permits good survival. In acute or severe pathological conditions, this reciprocal correlation between the two systems may fail, creating situations where it is necessary to intervene rapidly to bring the organism back to a condition of balance compatible with life. Moreover, many disorders, such as acute or chronic inflammation of the endothelium, vascular alteration processes of metabolic origin, arteriosclerosis, and vascular calcifications, involve both the cardiocirculatory system and the kidney. Therefore, the cardiologist often has to treat cardiac patients who, besides their cardiocirculatory problems, present kidney involvement, a situation which significantly complicates patient management and may increase the mortality.

[Long-term sustained low efficiency dialysis in eight patients with class IV NYHA heart failure resistant to high-dose diuretic treatment]. / Dialisi prolungata intermittente a basso flusso (SLED) in otto pazienti con scompenso cardiaco classe IV NYHA resistente ad alte dosi di diuretico.

Many of the patients hospitalized for congestive heart failure have concurrent renal failure. Most patients with heart failure present NYHA class III dysfunction, but when the heart failure progresses to NYHA class IV, replacement therapy may be necessary to remove the salt and water overload and mitigate the clinical, prevalently respiration-related symptoms. We report the clinical cases of 8 patients with NYHA class IV heart failure resistant to multidrug treatment and high-dose diuretics who were treated with sustained low efficiency dialysis (SLED). We evaluated the survival rates of the patients, their clinical improvement and cardiac performance. The obtained results suggested that treatment with SLED is the most indicated in NYHA class IV heart failure.

[Effectiveness of daptomycin in the treatment of patients on hemodialysis affected by CVC infection]. / Efficacia della daptomicina in terapia empirica nel trattamento di 5 pazienti in emodialisi affetti da infezione del CVC.

The use of tunneled central venous catheters (CVCs) has grown exponentially in recent years. It has increased particularly for elderly patients, patients with severe heart failure, and patients on chronic hemodialysis. In such patients there is a great risk of infection. This led us to search for a new-generation antibiotic able to resolve infection rapidly and effectively. In our experience, administration of daptomycin resulted in rapid resolution of infection without the necessity of CVC removal or its replacement by another system.

Underwater operational noise level emitted by a tidal current turbine and its potential impact on marine fauna.

Marine renewable energy development raised concerns over the impact of underwater noise. Here we assess the acoustic impacts of an operating tidal current turbine (Paimpol-Bréhat site, France) on marine fauna. Its source level (SL) has been measured in situ using 19 drifting transects at distances between 100 m to 2400 m from the turbine. SL ranged from 118 to 152 dB re1 µPa@1 m in third-octave bands at frequencies between 40 and 8192 Hz. It is comparable to the SL of a 19 m boat travelling at 10kt speed. This SL was used to estimate the impact of this noise type based on acoustic propagation simulations. The acoustic footprint of the device corresponds to a 1.5 km radius disk. Our results show that within this area of greatest potential impact, physiological injury of the hearing apparatus of invertebrates, fishes and marine mammals is improbable. Behavioral disturbance may occur up to 1 km around the device for harbor porpoises only. This is of little concern for a single turbine. However, greater concern on turbine noise impact, particularly on behavioral reactions has to be granted for a farm with up to 100 turbine. The lack of consolidated knowledge on behavioral disturbances identifies the needs for specific research programs.

[Renal failure and cardiovascular risk]. / Carta del rischio vascolare renale.

Prevalent studies concerning chronic renal failure (CRF) in the general adult population, using the Crockroft-Gault formula correcting serum creatinine values for calibration factors, indicate that about 22.8% have initial CRF. If the albuminuria itself is considered as an index of renal damage, we find a prevalence rate in the adult population of about 8.5%, with slight differences between females and males. Considering only this second more optimistic statistic and comparing it with the number of patients on dialysis, evidenced by the different specific registers, we observe that only 2% of the population with renal failure reach terminal uremia; and therefore, require substitutive therapy or renal transplantation. For many years, statistical analyzes have been carried out on the prevalence of pathologies present in patients who arrive at dialysis; to date, little has been done for patients with initial or average renal failure. Few of these studies are prospective. The data of studies concerning the elderly population suffering from CFR of varying degrees, as well as the data of longitudinal studies concerning patients controlled for a few years, have shown that cardiovascular diseases (CVD) are more responsible for the mortality of patients with even modest renal failure before reaching uremia compared to patients without renal failure. On the contrary, statistics on the prevalence of CVD in patients who arrive at dialysis are well-known, it can be >70%. Different organizations such as the National Kidney Foundation, the American Heart Association and the Seventh Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure have considered the presence of CRF a cardiovascular risk factor.

[Sustained low-efficiency dialysis (SLED) in patients with prevalent systolic heart failure refractory to medical treatment and with chronic renal failure]. / Dialisi prolungata a bassa efficienza (SLED) in pazienti affetti da insufficienza cardiaca prevalentemente sistolica (IV NYHA) refrattaria al trattamento polifarmacologico e insufficienza renale cronica.

Systolic heart failure refractory to conventional medical therapy is the principal cause of the high hospitalization rates and of high mortality risks. When this condition is associated with chronic renal failure it is necessary to treat the body liquid composition alterations, and the alterations in the hemodynamic state without creating low flow conditions, trying to achieve an electrolytic and an acid-base balance to reduce the plasmatic volume and permit refilling between the interstitium and plasm. Sustained low-efficiency dialysis (SLED) is a dialysis technique allowing the maintenance of hemodynamic stability through a reduced ultrafiltration rate, it allows an adequate clearance of small solutes, and with sustained treatment it maximizes the dialysis dose and determines a clinical improvement through the removal of the hydric overload. Our experience suggests that SLED is a substitutive treatment for acute dialysis in patients with systolic heart failure refractory to conventional medical treatment.

[Quality of life in patients with combined treatments for heart failure]. / Qualità di vita nei pazienti con trattamenti combinati nello scompenso di cuore.

The low quality of life in patients with end-stage heart failure is correlated, above all, to frequent hospitalization and to the awareness of having an illness that limits survival. The quality of life in these patients with heart failure using treatment with sustained low efficiency dialysis (SLED) is determined through the Minnesota Living with Heart Failure (MLHF) Questionnaire. The reliability of this evaluation system has been examined through consultation with international trials. After 1 yr of this treatment, we observed an improvement in quality of life.

[Dialytic treatment in patients with renal insufficiency and heart failure refractory to combined drug therapy]. / Trattamento emodialitico in pazienti affetti da insufficienza renale cronica e scompenso cardiaco refrattario alla terapia polifarmacologica.

The incidence and prevalence of heart failure are continuously on the increase. Pharmacological therapy is not sufficient in the advanced stages of the illness to control the signs and symptoms, especially when stressing factors intervene and complicate the illness course. Dialytic treatments are always indicated more than necessary in the severe forms of heart failure, but the optimal treatment has not yet been established. In our division, 24 patients with heart failure (III-IV NYHA) and renal failure (III-IV NKF-DOQI) were treated with low flux bicarbonate dialysis, variable dialysate and limited ultra-filtration. Arrhythmia, pericarditis, ischemic cardiopathy and hyponatremia were the stressing factors that determined acute heart failure. Fifteen patients presented with diastolic failure, whereas nine patients had systolic heart failure. The first group of patients had higher arterial pressure, better ejection fraction and better prognosis regarding renal function and survival rate. The results obtained with this treatment in prevalently diastolic heart failure are satisfactory in terms of survival, as well as in renal function recovery, whereas they are not adequate in systolic failure where other approaches are being studied. Therefore, we believe that the therapeutic choice must always be determined in relation to the type of heart failure.

Central nervous system activity of 7-substituted 1-azaphenoxathiin analogues and their oxidation products.

A number of 7-substituted 1-azaphenoxathiins and their sulfone oxidation products have been synthesized and screened for central nervous system activity. Some of the compounds have antidepressant activity, with the most active, 7-(trifluoromethyl)-1-azaphenoxathiin 10,10-dioxide (8), having similar potency to imipramine.

Synthesis and central nervous system depressant activity of some bicyclic amides.

A series of aryl bicyclic analogs of succinimide and glutarimide was prepared and evaluated for CNS depressant activity. The 8a-aryl-3,4,6,7,8,8a-hexahydro-2H-pyrrolo[2,1-beta][1,3]oxazin-6-ones possessed the best overall spectrum of activity relative to the standard agents glutethimide and phenobarbital.

Synthesis and biological evaluation of some 10-substituted 2,3-dihydroimidazo[2,1-b]quinazolin-5(10H)-ones, a new class of bronchodilators.

On treatment of N-substituted isatoic anhydrides with 2-methylmercaptoimidazolines, 10-substituted imidazo[2,1-b]quinazolin-5(10H)-ones are obtained. Several members of this class exhibited pronounced broncholytic activity. The structure-activity relationships (based on results obtained in the guinea pig histamine aerosol test) of these nonsympathomimetic bronchodilators are discussed. In addition, the detailed pharmacological evaluation of two analogs found to be five to ten times more active than theophyline as bronchodilators without having central nervous system or cardiovascular side effects is described.

Synthesis and central nervous system evaluation of some 5-alkoxy-3H-1,4-benzodiazepin-2(1H)-ones.

A series of 1-R-5-alkoxy-3H-1,4-benzodiazepin-2(1H)-ones was prepared and evaluated for central nervous system depressant activity. Several of these compounds, in particular, 7-chloro-5-ethoxy-1-methyl-3H-1,4-benzodiazepin-2(1H)-one (2), gave a profile and activity level similar to diazepam when measured in mice.

Comparative effects of abrupt withdrawal of propranolol and verapamil in angina pectoris.

The potential hazards of abrupt withdrawal of propranolol have been described in patients with angina pectoris; however, the effects of abrupt withdrawal from long-term therapy with verapamil have not previously been investigated. The comparative effects of withdrawal from long-term treatment with propranolol and verapamil were assessed in a placebo-controlled double-blind randomized crossover study of 20 patients received placebo for 2 weeks, then increasing doses of propranolol (60 to 320 mg/day) or verapamil (240 to 480 mg/day) for 3 weeks. Patients were then abruptly withdrawn from drug onto placebo for 1 week, followed by crossover to the other drug treatment and a second withdrawal period. All 20 patients were withdrawn from verapamil without evidence of a rebound increase in frequency of anginal attacks, blood pressure, heart rate, or rate-pressure product and without a rebound deterioration in exercise tolerance. In contrast, with propranolol withdrawal, 2 patients (with the highest baseline angina attack rate) had a severe exacerbation of their anginal syndrome and could not undergo formal exercise testing; the other 18 patients were withdrawn from propranolol without incident. Plasma catecholamines were increased during exercise compared with rest during all treatments; however, the levels of catecholamines during exercise were significantly higher with propranolol than with verapamil and placebo (p less than 0.05). Levels of exercise catecholamines returned to placebo baseline values after withdrawal of propranolol.

The heart in uremia: role of hypertension, hypotension, and sleep apnea.

Cardiovascular disease is the leading cause of morbidity and mortality in end-stage renal disease. Causes include those usually found in the general population, those related to the uremic status, and those related to dialytic treatment. Hypertension, hypotension, anemia, hypoalbuminemia, malnutrition, dyslipidemia, reactive C protein, calcium-phosphate product, dialysis modalities, and hyperhomocysteinemia are discussed extensively. Special emphasis is put on hyperparathyroidism as a traditional toxin. The emergent role of sleep apnea has been confirmed in animal models as well as in humans studied using polysomnography. There are difficulties in diagnosing coronary disease, because angiography is not risk-free, is expensive, and should be reserved for patients having symptoms of heart failure and/or patients having diabetes mellitus, and/or patients entering a transplantation list. This allows patients with coronary disease to undergo coronary artery bypass (preferably) or percutaneous transluminal angioplasty. Patients for whom surgery is not appropriate should be treated using more traditional medical procedures.