Quality of life in Klinefelter patients on testosterone replacement therapy compared to healthy controls: an observational study on the impact of psychological distress, personality traits, and coping strategies.

PURPOSE: We aimed to verify if 1 year-testosterone-replacement therapy could produce a psychopathological recovery and a satisfactory quality of life in Klinefelter syndrome (KS) patients compared to matched healthy controls. Further, we analyzed personality traits and coping strategies, an issue not yet examined in androgen-treated KS patients. We also enquired whether any of the sociodemographic and psychological variables might predict a patient's general and sexual life satisfaction. METHODS: The Quality of Life Enjoyment and Satisfaction Questionnaire and the Temperament and Character Inventory-Revised were administered to both 23 KS patients and matched healthy subjects. Psychopathology was investigated by the Symptom Checklist-90-Revised (SCL-90-R) and the Mini-mental State Examination. The COPE Inventory was used to identify cognitive and behavioral strategies to manage disease-related distress. RESULTS: In testosterone-treated KS patients, when compared with controls, SCL-90-R subscales analysis evidenced high psychological distress, mainly presented as obsessive thoughts, hanger-hostility, phobias, and psychoticism. Self-directedness and self-transcendence, along with the prevalent use of emotion-focused coping strategies, outlined the personality of our KS patients. Depression and somatization proved to be predictors of general life dissatisfaction. Depression, anger-hostility, and paranoid ideation, instead, emerged as predictors of sexual life dissatisfaction. CONCLUSION: Endocrinologists should cooperate with mental health providers to foster a better outcome of the disease in KS patients.

Patient characteristics and symptoms associated with perceived coercion during hospital treatment.

OBJECTIVE: Large numbers of psychiatric patients either are involuntarily admitted to hospital treatment or feel coerced despite a legally voluntary admission. For ethical and clinical reasons, their perceived coercion should be reduced as far as possible. There is however limited evidence on patient characteristics associated with perceived coercion during hospital treatment. This study aimed to identify i) sociodemographic and clinical characteristics associated with perceived coercion at admission and ii) changes in symptoms and global functioning associated with changes in perceived coercion over time. METHOD: Three thousand and ninety three in-patients who were involuntarily admitted or felt coerced to hospital treatment despite a legally voluntary admission were recruited in the European evaluation of coercion in psychiatry and harmonization of best clinical practice - EUNOMIA project in 11 European countries. Perceived coercion, global functioning and symptoms were assessed after admission and at a 3-month follow-up. RESULTS: Involuntary admission, female gender, poorer global functioning and more positive symptoms were associated with higher levels of perceived coercion at admission. Perceived coercion significantly decreased over time, and the improvements in global functioning and positive symptoms were associated with reduction in perceived coercion. CONCLUSION: Female patients perceive more coercion in psychiatric hospital treatment. Effective treatment for positive symptoms and improving patients' global functioning may lead to a reduction in perceived coercion.

[Erythropoiesis-stimulating agents in chronic kidney disease: which route of administration?]. / Agenti stimolanti l'eritropoiesi nell'insufficienza renale cronica: quale via di somministrazione?

In the last twenty years, erythropoiesis-stimulating agents (ESAs) have improved the management of renal anemia, with significant amelioration of quality of life in patients on hemodialysis. ESAs can be administered both intravenously and subcutaneously. In predialysis chronic kidney disease and in peritoneal dialysis, the administration route is necessarily subcutaneous. In hemodialysis the intravenous route was initially preferred because of the presence of ready vascular access for drug administration. Subsequent studies have demonstrated that the subcutaneous route allowed the achievement of optimal levels of hemoglobin with a reduction of mean administered dose, number of injections, and costs. A few years ago, the finding of a higher risk of pure red cell aplasia associated with subcutaneous administration of epoetin reopened the debate about the route of administration. We here review the studies on the preferable route of administration of epoetin and darbepoetin- alpha, in terms of efficacy and safety, and take a look at future perspectives.

[Treatment of HCV-associated cryoglobulinemic glomerulonephritis]. / Terapia della glomerulonefrite secondaria a crioglobulinemia HCV-correlata.

HCV-related membranoproliferative glomerulonephritis is the most common cause of hepatitis C-associated renal disease. Its treatment is still under debate and based on scant experimental evidence. The recommended therapeutic strategy depends on the severity of the kidney disease. The first-line treatment for patients with mild to moderate clinical and histological kidney damage is antiviral therapy with pegylated interferon alpha and ribavirin for 48 weeks combined with symptomatic treatment (diuretics, angiotensin converting enzyme inhibitors and angiotensin receptor blockers). In case of severe renal involvement (nephrotic syndrome, nephritic syndrome and/or progressive renal failure, high activity score of glomerulonephritis on light microscopy), the initial treatment may consist of sequential administration of immunosuppressive therapies (plasmapheresis, corticosteroids and cyclophosphamide) and antiviral agents, although no definitive data are yet available from the literature. B-cell depleting agents such as rituximab may be an alternative to conventional therapy in refractory or intolerant patients. Large randomized and controlled clinical trials are needed to establish guidelines for the treatment of HCV-related cryoglobulinemic glomerulonephritis.

In situ spacecraft observations of a structured electron diffusion region during magnetopause reconnection.

The electron diffusion region (EDR) is the region where magnetic reconnection is initiated and electrons are energized. Because of experimental difficulties, the structure of the EDR is still poorly understood. A key question is whether the EDR has a homogeneous or patchy structure. Here we report Magnetospheric Multiscale (MMS) spacecraft observations providing evidence of inhomogeneous current densities and energy conversion over a few electron inertial lengths within an EDR at the terrestrial magnetopause, suggesting that the EDR can be rather structured. These inhomogenenities are revealed through multipoint measurements because the spacecraft separation is comparable to a few electron inertial lengths, allowing the entire MMS tetrahedron to be within the EDR most of the time. These observations are consistent with recent high-resolution and low-noise kinetic simulations.

Perceived insecurity, mental health and urbanization: Results from a multicentric study.

AIMS: This article aims to (1) explore the levels of perceived insecurity in a sample of patients with mood or anxiety disorders and (2) assess whether living in 'big cities' can influence the levels of patients' perceived insecurity and social contacts compared to living in a non-urbanized context. METHODS: A total of 24 Italian mental health centers (MHCs) have been invited to participate. Twenty patients consecutively accessing the MHC have been recruited. All patients have been assessed using validated assessment tools. RESULTS: The sample consisted of 426 patients, mostly female, with a mean age of 45 years. Globally, 52.2% of patients had a diagnosis of mood disorders, and 37.8% had anxiety disorders. Half of the sample declared that the main feeling toward life is uncertainty; higher levels of pessimistic views toward life have been detected in patients living in urban areas. A positive association between negative attitudes toward life and higher levels of depressive and anxiety symptoms, poor social functioning and higher levels of perceived psychological distress has been found. CONCLUSION: Our findings confirm the presence of a common sense of perceived uncertainty among our sample. Such attitude toward life can have a detrimental impact on patients' psychological and physical well-being, contributing to high levels of distress.

Feasibility of a psychoeducational family intervention for people with bipolar I disorder and their relatives: Results from an Italian real-world multicentre study.

BACKGROUND: Despite several guidelines recommend the use of psychoeducational family interventions (PFIs) as add-on in the treatment of patients with bipolar I disorder, their implementation on a large scale remains limited. The aim of the present study is to identify obstacles for the feasibility of PFIs in routine care. METHODS: This was a multicentre, real-world, controlled, outpatient trial, carried out in 11 randomly recruited Italian mental health centres. Two mental health professionals from each center attended a modular training course on PFI and provided the intervention. Difficulties and benefits experienced by mental health professionals in implementing the intervention were assessed through the Family Intervention Schedule (FIS-R), which was administered six times. RESULTS: Sixteen out of the 22 recruited professionals completed the training and administered the PFI to 70 patients with bipolar I disorder and their relatives. The retention rate of families receiving the intervention was 93%. Mental health professionals reported high levels of organizational difficulties, several benefits in their daily clinical work and low levels of intervention-related difficulties. The most important organizational obstacles were related to the need to integrate the intervention with other work responsibilities and to the lack of time to carry out the intervention. These difficulties did not decrease over time. Intervention-related difficulties were rated as less problematic since the first time assessment and tended to improve over time. LIMITATIONS: Low number of recruited professionals; use of a not previously validated assessment instrument. CONCLUSIONS: PFIs are feasible in routine care for the treatment of patients with bipolar I disorder and their relatives, and main obstacles are related to the organization/structure of mental health centres, and not to the characteristics of the intervention itself.

Growth hormone secretagogue binding sites in peripheral human tissues.

The family of GH secretagogues (GHS) includes peptidyl (hexarelin) and nonpeptidyl (MK 0677) molecules possessing specific receptors in the brain, pituitary, and thyroid. GHS receptor subtypes have also been identified in the heart; and a gastric-derived peptide, named ghrelin, has recently been proposed as a natural ligand. Our aim was to investigate the presence of GHS receptors in a wide range of human tissues, by radioreceptor assay with [125I]Tyr-Ala-hexarelin. GHS receptors were detected mainly in the myocardium, but they were also present (in order of decreasing binding activity) in adrenal, gonads, arteries, lung, liver, skeletal muscle, kidney, pituitary, thyroid, adipose tissue, veins, uterus, skin, and lymphnode. In contrast, negligible binding was found in parathyroid, pancreas, placenta, mammary gland, prostate, salivary gland, stomach, colon, and spleen. Hexarelin, MK 0677, and human ghrelin completely displaced the radioligand from binding sites of endocrine tissues, but MK 0677 and ghrelin were less potent than hexarelin. In nonendocrine tissues, both MK 0677 and ghrelin were inactive in displacement of [125I]Tyr-Ala-hexarelin, whereas hexarelin was as active as a displacing agent in endocrine tissues. This study provides the first detailed analysis of the tissue localization of GHS receptors and suggests that a still unknown receptor subtype, specific for peptidyl GHS, may exist in the heart and in other tissues.

Identification, characterization, and biological activity of specific receptors for natural (ghrelin) and synthetic growth hormone secretagogues and analogs in human breast carcinomas and cell lines.

The family of GH secretagogues (GHS) includes synthetic peptidyl (hexarelin) and nonpeptidyl (MK-0677) molecules possessing specific receptors in the pituitary and central nervous system as well as in peripheral tissues, including the heart and some endocrine organs. A gastric-derived peptide, named ghrelin, has recently been proposed as the natural ligand of the GHS receptors (GHS-Rs). The presence of specific GHS-Rs has now been investigated in nontumoral and neoplastic human breast tissue using a radioiodinated peptidyl GHS ([(125)I]-Tyr-Ala-hexarelin) as ligand. Specific binding sites for GHS were detected in membranes from several types of breast carcinomas, whereas a negligible binding was found in fibroadenomas and mammary parenchyma. The highest binding activity was found in well-differentiated (G1) invasive breast carcinomas and was progressively reduced in moderately (G2) to poorly (G3) differentiated tumors. [(125)I]-Tyr-Ala-hexarelin bound to tumor membranes was displaced by different unlabeled GHS such as hexarelin, Tyr-Ala-hexarelin, human ghrelin, and MK-0677 as well as by desoctanoyl-ghrelin and hexarelin derivative EP-80317, which are devoid of GH-releasing properties in vivo. In contrast, no competition was seen between radiolabeled Tyr-Ala-hexarelin and some peptides (CRF and insulin-like growth factor I) structurally and functionally unrelated to hexarelin or when GHRH and SRIF were tested in the displacement studies. The presence of specific GHS binding sites was also demonstrated in three different human breast carcinoma cell lines (MCF7, T47D, and MDA-MB231), in which, surprisingly, no messenger RNA for GHS-R1a was demonstrated by RT-PCR. In these cell lines, ghrelin (as well as hexarelin, MK-0677, EP-80317, and even desoctanoyl ghrelin) caused a significant inhibition of cell proliferation at concentrations close to their binding affinity. In conclusion, this study provides the first demonstration of specific GHS binding sites, other than GHS-R1, in breast cancer. These receptors probably mediate growth inhibitory effects on breast carcinoma cells in vitro.

Plasma prolactin response to d-fenfluramine in obsessive-compulsive patients before and after fluvoxamine treatment.

The prolactin (PRL) responses to oral d-fenfluramine (30 mg) and placebo were assessed in 13 patients with obsessive-compulsive disorder (OCD) and in matched healthy subjects. After the neuroendocrine test, all patients were treated with fluvoxamine maleate (150-300 mg/day). At the end of the 10th week of treatment, 10 patients underwent again the neuroendocrine assessment. In drug-free patients, the PRL response to d-fenfluramine was significantly lower than in the comparison group. After 10-week fluvoxamine treatment, the PRL response to the serotonergic agent normalized. These findings suggest that, at least at the neuroendocrine level, central serotonergic responsivity is reduced in drug-free OCD patients, and that long-term fluvoxamine administration is associated with its normalization.

Specific binding sites for synthetic growth hormone secretagogues in non-tumoral and neoplastic human thyroid tissue.

The presence of specific receptors for synthetic growth hormone secretagogues (GHSs) has been investigated in non-tumoral and neoplastic human thyroid tissue using a radio-iodinated peptidyl GHS ((125)I-labelled Tyr-Ala-hexarelin) as ligand. Specific binding sites for Tyr-Ala-hexarelin were detected in membranes from non-tumoral and follicular-derived neoplastic thyroid tissue, but not in thyroid tumours (medullary carcinomas) of parafollicular (C cell) origin. The binding activity was greatest in well differentiated neoplasms (papillary and follicular carcinomas), followed by poorly differentiated carcinomas, non-tumoral thyroid parenchyma, follicular adenomas and anaplastic carcinomas. Both peptidyl (Tyr-Ala-hexarelin, hexarelin, growth hormone releasing peptide (GHRP6) and non-peptidyl (MK 0677) GHSs completely displaced the radioligand from binding sites of non-tumoral thyroid gland, but MK 0677 was significantly less potent. The IC(50) values were (1. 9+/-0.3)x10(-8) mol/l for Tyr-Ala-hexarelin, (2.1+/-0.2)x10(-8) mol/l for hexarelin, (2.4+/- 0.3)x10(-8) mol/l for GHRP6 and only (1. 5+/-0.4)x 10(-7) mol/l for MK 0677. Similar IC(50) values were found in neoplastic thyroid tissue. Scatchard analysis of the binding revealed a finite number of binding sites in non-tumoral (B(max): 1232+/-32 fmol/mg protein, n=3) and neoplastic (papillary carcinomas) thyroid tissue (B(max): 2483+/-380 fmol/mg protein, n=5), with dissociation constants (K(d)) of (3.8+/-0.3)x10(-9) and (4. 4+/-0.6)x 10(-9) mol/l, respectively. On the basis of this evidence, we investigated the effects of some GHS on the proliferation of three different human follicular thyroid carcinoma cell lines (NPA, WRO and ARO) in which the presence of specific GHS receptors was also demonstrated. Tyr-Ala-hexarelin, GHRP6 and MK 0677 were able to inhibit serum-stimulated [(3)H]thymidine incorporation in NPA cells at concentrations close to their binding affinity. These substances also caused a significant inhibition of cell proliferation, which was evident at the earliest time of treatment (24 h) in all the cell lines, and at the latest time (96 h) in NPA cells only. In conclusion, this paper confirms the existence of specific binding sites for GHS in normal thyroid tissue and demonstrates, for the first time, that these binding sites are present in papillary and follicular carcinomas, low in anaplastic carcinomas and absent in medullary carcinomas of the thyroid. This work also provides evidence of a growth-inhibitory effect of GHS on cell lines derived from follicular thyroid cancers.

Plasma melatonin and cortisol circadian patterns in patients with obsessive-compulsive disorder before and after fluoxetine treatment.

The circadian rhythms of melatonin and cortisol were evaluated in seven outpatients with obsessive-compulsive disorder (OCD) before and after 8 weeks of fluoxetine treatment (20 mg/day in the first 2 weeks, and 40 mg/day afterwards), and in seven healthy subjects matched to patients on age, sex and season of testing. The results confirm our previous findings of a decreased 24-h production of melatonin (p < .05; two-way ANOVA with repeated measures) and of an increased circadian secretion of cortisol (p < .01) in OCD patients with respect to matched controls, and show, for the first time, that these hormonal alterations do not significantly change after 2 months of fluoxetine administration, in spite of a good clinical improvement. These data suggest that the normalization of the biochemical changes underlying the altered endocrine parameters in obsessive-compulsive patients is not necessary for effective therapy or clinical remission.

Depression and cerebral stroke.

Behavioral and psychological changes following cerebrovascular pathology have long been known. Depression, often severe and long-lasting, is a common and often unrecognized component of stroke. Although many of the clinical characteristics of poststroke depression have been reported in the literature for years, systematic studies of the frequency, course, relationship to lesion location, and response to treatment have only recently been undertaken. In this review, the authors briefly examine these various aspects of poststroke depression.

Melatonin and cortisol secretion in patients with primary obsessive-compulsive disorder.

Plasma levels of melatonin and cortisol were measured over a 24-hour period in seven patients with primary obsessive-compulsive disorder (OCD) and seven matched healthy control subjects. In OCD patients, the 24-hour secretion of melatonin was reduced as compared with that in healthy control subjects, whereas its circadian rhythm was preserved. In addition, in OCD patients, the overall secretion of cortisol was higher than that in control subjects, but there was no change in the circadian pattern of cortisol secretion. No correlation was found between clinical parameters and hormone levels.

Burden on the families of patients with obsessive-compulsive disorder: a pilot study.

This study aimed to explore the burden on the key-relatives of a sample of patients with obsessive-compulsive disorder and a control sample of patients with major depression. The level of burden of relatives of obsessive-compulsive patients was moderate to severe in most of the explored situations, and did not differ significantly from that of the relatives of depressives. Social relationships were compromised in 74% of cases, and feelings of depression were recorded in 84% of cases. The level of subjective burden changed according to the relatives' sex, age and position in the family. The degree of objective burden correlated with the level of patients' disability, whereas that of subjective burden correlated with the severity of patients' obsessive-compulsive symptomatology.

[Effects of nimodipine on mental deterioration in subjects with chronic cerebrovascular pathology]. / Effetti della nimodipina sul deterioramento mentale in soggetti affetti da patologia cerebro-vascolare cronica.

In order to assess the efficacy of Nimodipine against a polymorphous pathology, such as chronic cerebrovascular insufficiency, the authors studied 96 subjects affected by chronic cerebrovascular diseases aged between 65 and 85 years old. The various symptoms were evaluated individually using tests and subjects were then divided into two groups on the basis of overall results. All subjects were followed for six months and then reassessed using the above-mentioned tests at the end of the study. From results obtained, it appears that Nimodipine is a useful tool for controlling the most common symptoms associated with mental deterioration in subjects affected by chronic cerebrovascular disorders.

[Isoproterenol in the emergency treatment of cardiac stimulus conduction]. / L'isoproterenolo nel trattamento di emergenza delle turbe della conduzione dello stimolo cardiaco

Continuous infusion with isoproterenol (mean dose 2 mug/min) was carried out for periods of a few hours to a few days in 22 patients recurrent Adams-Stokes syncope. In all cases, an improvement leading to or in the direction of physiological cardio-circulatory conditions was noted. Undesired side-effects foreseeable as the result of beta-adrenergic stimulation were not observed. Isoproterenol is more active than metaproterenol and is to be preferred on this account. It is indicated in Adams-Stokes crises due to conduction disturbances when pacemakers cannot or should not be fitted, or as a prelude to their application.

[Myxoma of the left atrium. General considerations and description of a case]. / Mixoma dell'atrio sinistro. Considerazioni generali e descrizione di un caso.

A case of left atrial myxoma is described. The neoplasia was observed in a female with no previous rheumatic history in whom cardiopathy was diagnosed only a few months before hospitalisation. The rapid and erratic course of the cardiopathy, the fact that changes of posture modified objective symptoms, the presence of dyspnoea and peripheral microembolisms were all clinical indicators of a possible myxoma, later confirmed by echography and cardiac catheterism. The anatomical and functional characteristics of myxomas are also discussed.

[Rupture of the chordae tendineae and mitral prolapse. General considerations and description of a case]. / Rottura di corda tendinea e prolasso mitralico. Considerazioni generali e descrizione di un caso.

A severe case of acute mitral insufficiency caused by a ruptured tendinous cord is described. The subject had an unrecognised mitral prolapse and had been suffering from tachycardia for years when an attack of pulmonary oedema occurred some days after apparently well tolerated exertion. The phenomena behind the event are discussed with particular reference to the mechanisms, closure and distribution of prolapses in so-called mixamatosic degeneration of the valve. The importance of body position and exertion in the creation and deterioration of prolapses is also emphasised.

[Effect of street noise on blood catecholamines, cyclic AMP and various cardiovascular and metabolic functions in a group of subjects with untreated essential hypertension]. / Effetti del rumore stradale sulle catecolamine ematiche, sul cAMP e su alcune funzioni cardio-vascolari e metaboliche in un gruppo di soggetti ipertesi essenziali non trattati.

The effect of road noise on blood catecholamines, cAMP and certain cardiovascular and metabolic parameters was studied in a group of young untreated essential hypertensives. It was found that the 10' stimulus increased both systolic and diastolic pressure values. Blood catecholamines rose only after 5'. The most significant increase was in adrenaline as opposed to noradrenaline and dopamine. Significant changes were noted in cAMP and triacylglycerols (10' and 15' after commencement of the stimulus respectively). Comparison with previous results in normotensives suggested that the catecholamine response to stress is primarily alpha-receptorial when blood pressure is normal and beta-adrenergic in hypertension.