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Polycystic ovary syndrome (PCOS) is an endocrinological and metabolic disorder widely diffused and diagnosed in women of reproductive age. The pathology exhibits alteration of the reproductive functions, including conditions as hyperandrogenism, menstrual cycle irregularity, type 2 diabetes. These conditions are visible in the patients through phenotypical manifestations as hirsutism, acne, and obesity. Even if the syndrome is characterized by common features among both adult and adolescent women, the diagnostic criteria are different for the two age categories and to date still controversial. We investigated different treatments in PCOS adolescents with non-severe metabolic conditions, to evaluate which could be the appropriate therapeutical approach for these patients.We enrolled lean teenagers with PCOS, and we divided the patients in two age ranges: 13-16 years old and 17-19 years old. They were treated for 3 months either with oral contraceptive pills (OCP) drospirenone/ethinylestradiol (group A), myo-Inositol (myo-Ins) (group B), or OCP plus myo-Ins (group C). Data were analyzed with a descriptive statistics summarizing quantitative variables including median, 25th and 75th percentiles.We pointed out that the group of 13-16 years old lean teenagers treated with myo-Ins exhibit a significant decrease of weight and body mass index (BMI), and an effective improvement the metabolic and hormonal parameters achieved with a non-pharmacological treatment. In the older teenagers aged 17-19 years, data highlights that myo-Ins treatment in combination with OCP prevents the increases of weight and BMI, improves the metabolic profile of the patients, and strongly ameliorates the hormonal parameters analyzed.The results indicate a different scenario in the two age ranges considered and interestingly suggest an important role of myo-Ins in the PCOS context. A therapy based on this natural compound alone or in combination with OCP seems effective to improve both metabolic and hormonal parameters of PCOS adolescents and thus could represent a novel and valid option to consider for the treatment of this syndrome.

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The aim of this clinical trial was to evaluate the efficacy of seven different ratios between two inositols stereoisomers, myo-inositol (MI) and D-chiro-inositol (DCI), in the therapy of polycystic ovary syndrome (PCOS).fifty-six PCOS patients (8 for each group) were treated by oral route using the following formulations: DCI alone, and 1:3.5; 2.5:1; 5:1; 20:1; 40:1, 80:1 MI/DCI ratio. They received 2 g of inositols twice a day for 3 months. The primary outcome was ovulation, the secondary outcome included the improvement of FSH, LH, Sex Hormone Binding Globulin (SHBG), 17-beta-Estradiol (E2), free testosterone, basal and postprandial insulin levels, as well as HOMA index, BMI and menses.We found that the 40:1 MI/DCI ratio is the best for PCOS therapy aimed at restoring ovulation and normalizing important parameters in these patients. The other formulations were less effective. In particular, a decreased activity was observed when the 40:1 ratio was modified in favour of DCI.Our data demonstrated that DCI activity is beneficial mainly at a specific ratio with MI, whereas the increase of DCI causes the loss of the beneficial effects at reproductive level. These results in humans validate a previous preclinical study with different MI/DCI ratios carried out in an experimental model of PCOS mice.

The anticancer effect of myo-inositol (MI) is catching researchers' attention worldwide. Thyroid nodules (TNs) have been detected by ultrasound (US) in up to 76% of the general population and, although most of them are benign, thyroid cancer is the most common malignancy of the endocrine system.A retrospective, observational study was conducted in 642 patients with suspected hypothyroidism undergoing US. The analysis was addressed exclusively to patients with subclinical hypothyroidism (SCH) or thyroid-stimulating hormone (TSH) levels borderline associated to TNs classified as class I and II; 1 group (control, no. 16) no treatment was prescribed; the other group (treated, no. 18) underwent treatment with 1 tablet containing MI plus selenium (Se) every day, for six months. Clinical data were collected to evaluate the nodular size, number, and elasticity, as well as TSH levels.Final data were analyzed from 34 patients: in 76% of mixed TNs was observed a significant reduction of their size and 56% of them significantly regressed nodule stiffness following oral supplementation with MI plus Se. The mean number of mixed nodules for patient shifted from 1.39 ± 0.16 to 1.05 ± 0.15 (p ≤ 0.05). TSH levels dropped from 4.2 ± 0.21 mIU/L at baseline to 2.1 ± 0.20 mIU/L post-treatment (p0.001). In the control group, 38% of TNs reduced their diameter but TSH levels significantly increased up to the threshold after six months (from 3.95 ± 0.18 mIU/L to 4.30 ± 0.22 mIU/L, p ≤ 0.05).In SCH patients undergoing treatment with MI plus Se, a reduction of the size, number and elasticity score of TNs as well as TSH levels was observed. Further studies are required, either in vitro and in vivo, to investigate the use of MI plus Se for the management of TNs.

Clinical evidence suggests that oral supplementation with myo-inositol (MI) and selenium (Se) is useful in the treatment of autoimmune thyroiditis. The purpose of this study was to highlight the positive response of Hashimoto's patients with subclinical hypothyroidism (SH) treated with MI and Se (MI-Se) in restoring a normal thyroid function.A total of 168 patients with Hashimoto's thyroiditis (HT) having Thyroid Stimulating Hormone (TSH) levels between 3 and 6 µIU/ml were randomized into 2 groups: one receiving MI-Se and the other one Se alone.TSH, anti-thyroid peroxidase (TPOAb) and anti-thyroglobulin (TgAb) levels were significantly decreased in patients treated with combined MI-Se after six months of treatment. Also, a significant free serum T4 increase was observed in MI-Se group, along with an amelioration of patients' quality of life.The administration of MI-Se is significantly effective in decreasing TSH, TPOAb and TgAb levels, as well as in enhancing thyroid hormones and personal wellbeing. Such treatment restored euthyroidism in patients diagnosed with autoimmune thyroiditis.

The definition itself of subclinical hyperthyroidism (SHyper) and, therefore, the therapeutic approach to patients with SHyper still remains undefined and controversial. Therefore, the interest of finding a novel and alternative therapy for SHyper has caught the attention. An observational pilot study was performed to assess the effects of l-carnitine and selenium in the management of SHyper symptoms and endocrine profile in patients affected by this disease.Patients with TSH levels between 0.1-0.4 mIU/L and positive antibodies were recruited in this study. Subjects received orally one tablet containing 500 mg of l-carnitine and 83 mcg of selenium (L-Carn + Se), daily for 1 month. The primary outcome was the improvement of the quality of life (QoL) with the disappearance of main symptoms (subjective symptomatology) associated to SHyper, evaluated through a 9-items short form survey. Secondary outcomes included TSH, fT3, and fT4, TPOAb, TgAb measurement. Primary and secondary outcomes were evaluated at baseline, after the completion of treatment and after a successive month without treatment.After 1-month treatment, the subjective symptomatology significantly dropped from 25.61 ± 1.19 to 12.11 ± 1.15 (p0.05). On the other hand, during the following 1-month period without treatment, it increased back to 23.33 ± 1.35 (p0.05). Thyroid hormones and auto-antibodies remained in their normal range.The present pilot study has shown that L-Carn + Se significantly reduced symptoms associated with SHyper, improving QoL of patients, without significant modifications of their endocrine profile. In addition, it is noteworthy that the extension of treatment seems necessary to prevent symptoms reappearance. Prospective randomized controlled trials are needed to address clinicians to define the appropriate treatment-settings for this disorder.

Women with Polycystic Ovarian Syndrome (PCOS) present several factors that increase the cardiovascular risk, such as insulin resistance and dyslipidemia. Myo-inositol and D-chiro-inositol have been shown to improve insulin resistance, hyperandrogenism and to induce ovulation in PCOS women. However, their effects on dyslipidemia are less clear. The aim of the present study was to evaluate whether the combined therapy myo-inositol plus D-chiro-inositol (in a in a physiological ratio of 40:1) improve the metabolic profile, therefore, reducing cardiovascular risk in PCOS patients.Twenty obese PCOS patients [BMI 33.7 ± 6 kg/m2 (mean ± SD)] were recruited. The lipid profile was assessed by measuring total cholesterol, LDL, HDL and triglycerides before and after 6 months treatment with the combined therapy. Secondary end points included changes in BMI, waist-hip ratio, percentage of body fat, HOMA-IR and blood pressure.The combined therapy myo-inositol and D-chiro-inositol improved LDL levels (3.50 ± 0.8 mmol/L versus, 3 ± 1.2 mmol/L p0.05), HDL (1.1 mmol/L ± 0.3 versus 1.6 mmol/L ± 0.4 p0.05) and triglycerides (2.3 ± 1.5 mmol/L versus 1.75 ± 1.9 mmol/L p0.05). Furthermore, significant improvements in HOMA-IR were also observed.The combined therapy myo-inositol plus D-chiro-inositol is able to improve the metabolic profile of PCOS women, therefore, reducing the cardiovascular risk.

This chapter introduces the fuzzy control approach for a dialysis session. Due to the complexity of the human system, the classical control methods, like PID, can fail to reach the target, mainly for what it concerns the stabilization of the system, which can induce sudden and undesired hypotensive collapses. To this purpose, a heuristic strategy based on expert rules, as fuzzy logic control, can help to reach the desired performances, reducing undesired collateral effects and increasing the potentiality of the dialysis session.

The paper proposes a fuzzy logic based procedure able to control as far as possible the behaviour of the blood pressure of a patient during a dialysis session, allowing him to reach the foreseen dry weight. A PI discrete-time fuzzy control is used in order to compare the controlled variables concerning the (blood pressure and blood volume) to the reference values. Two different reference tables, concerning the pressure and volume errors and rates are introduced, then the proposed control actions are mixed in order to obtain the final value (net ultrafiltration rate). A smooth function of volemia acts on the second control variable, Na concentration in the dialysate. The adaptive control system was simulated on an IBM-PC, rules and terms were expressed by linguistic judgements like: IF “situation”, THEN “action”. A pre-processor converts the rules into the numerical values of the reference tables. The obtained simulation results are satisfactory, the introduction of the Na control allows reaching the target dry weight of the patient with a stable blood pressure.

OBJECTIVE--To see whether cardiac morphological and functional abnormalities in uraemic patients are determined by high blood pressure or if they are an expression of a specific cardiomyopathy. DESIGN--Cross sectional study. SETTING--City general hospital in Italy. SUBJECTS--35 uraemic patients receiving haemodialysis (17 men, 18 women; mean age 60.3 (11.2); mean duration of dialysis 52 months) were selected from the 64 patients in Venice who were receiving dialysis; subjects with diabetes, haemochromatosis, valvar dysfunction, regional dyskinesias, and pericarditis were excluded. 19 control normotensive subjects (6 men and 13 women), matched for age. MAIN OUTCOME MEASURES--Echocardiographic measurements of left atrium, left ventricular end diastolic and end systolic volume, aortic root diameter, posterior wall and interventricular septum thickness, left ventricle mass index, and ejection fraction in controls and in patients according to whether they were normotensive (five men, eight women) or hypertensive (12 men, 10 women) on 48 hour ambulatory monitoring; left ventricular diastolic function by Doppler ultrasonography. RESULTS--Mean systolic and diastolic pressures, daytime systolic and diastolic pressures, and night time systolic and diastolic pressures were significantly higher in the hypertensive patients than in the normotensive patients. The normotensive patients had similar blood pressures to the controls. Left ventricular mass correlated significantly with the mean diastolic pressure and mean night time systolic and diastolic pressures. Parathyroid hormone concentrations were similar in the two groups of patients. Diastolic relaxation was impaired to the same degree in the two groups of patients. Parameters of diastolic function showed no relation to left ventricular mass, which was significantly higher in the hypertensive than in the normotensive patients. CONCLUSIONS--Uraemia is likely to induce specific changes in the relaxation properties of the myocardium. These changes are responsible for the impaired diastolic function independently of blood pressure, degree of hypertrophy, and metabolic changes, which suggests the existence of a specific cardiomyopathy. Hypertension remains a determinant of left ventricular mass.

Diet is a critical factor for the development of both embryo and fetus, as well as maternal health. In particular, two natural molecules have been shown to exert beneficial effects on fertility, pregnancy wellness and embryo development: myo-inositol and melatonin, whose requirements increase during pregnancy. In the present review, we summarize the most important functions of melatonin and myo-inositol on male and female reproductive systems (oocyte quality and development, sperm quality), on the maintenance of a physiological pregnancy and on embryo development.

Five hundred and sixty patients began renal replacement therapy in 2006, giving an incidence of 117.51 pmp; in 2007 there were 579 new patients, for an incidence rate of 120.01 pmp. Analysis of the incidence between 1998 and 2007 for both raw and age-standardized data (based on the 2001 census) shows a slow, gradual increase that is statistically significant. Most of the patients were between 55 and 85 years old; the modal class for males was between 65 and 70, and between 75 and 80 for females. The median age of the population beginning replacement therapy is clearly over 65 years old. The year 2000 was particularly significant because the incidence of new patients undergoing renal replacement therapy over the age of 75 definitively exceeded that of the next younger class (65-74 years old), a trend that remained constant until 2007. In 2006 and 2007, males account for 64.4% and 66.4%, respectively, of new patients, a proportion that is constant over the years. The greater incidence of males is also to be found across the other age groups and tends to be even more noticeable in the oldest age class. Incidence by province is highly variable, however, there is a constant trend within provinces during these years, since the incidence in some provinces is lower than the regional average and higher in others. After adjusting for age, there are no significant differences in the incidence between provinces: the age structure of the population accounts for the variability of the incidence of terminal uremia across the Veneto provinces. The conditions most responsible for renal insufficiency requiring replacement therapy are vascular diseases, diabetes and nephropathies of unknown origin. Although diabetic and vascular nephropathies are subject to wide fluctuations, they remain stable over the years, whereas the frequency of nephropathy of unknown origin appears to be on the rise. The first treatment for most of the patients is hemodialysis. In 2006, 436 patients (78%) were given extracorporeal dialysis as first treatment, compared to 122 patients (22%) who were given peritoneal dialysis and 2 (0.35%) who received live-donor kidney transplant. In 2007 the situation was very similar, with 435 patients treated with extracorporeal dialysis, 142 with peritoneal dialysis and 1 by a live-donor transplant. The proportion between patients treated with hemodialysis and peritoneal dialysis was constant from 1998 to 2007. The choice between hemodialysis or peritoneal dialysis as the initial treatment modality depends on many factors, ranging from clinical indications to cultural attitudes at the facility to individual patient preferences. Logistic regression of the factors influencing the choice of dialysis treatment shows that peritoneal dialysis is offered primarily to patients between the ages of 45 and 65 who do not have an underlying systemic or nephropathy of unknown origin and who do not have any comorbidities. This confirms the positive selection made with regard to these patients, widely described in the literature. Initial treatment by transplant is an exceptional event: starting from 2003, it was used in only 1 or 2 patients per year. Seventy-two percent of patients starting replacement therapy present with at least one comorbidity. Thirty-six percent of patients also present with more than one associated disease. The RVDT has been gathering data on the vascular access used for new dialysis patients since 2006. Roughly 43% of patients start treatment with an arteriovenous fistula, 38% with a temporary catheter, less than 1% with a prosthesis, 9% with a tunneled catheter, and 10% with a peritoneal catheter. Logistic regression was used to evaluate what role age, primary nephropathies and comorbidities present at the start of treatment play in determining the choice of a temporary catheter. The logistic model estimates a 29% probability of starting treatment with a temporary access. This probability decreases if the patient suffers from a familiar or hereditary nephropathy but increases if the patient has secondary glomerulonephritis or is affected by a group of various diseases (multiple myeloma or other pathologies) or if the patient suffers at the same time from cardiac insufficiency or an infection. The estimated probability of starting hemodialysis with a mature fistula is 40%, but this figure diminishes significantly in female patients, if the patient has secondary glomerulonephritis, cardiac insufficiency or infections.As of December 31, 2006, there were 4,071 patients being treated with extracorporeal or peritoneal dialysis or by kidney transplant, leading to a prevalence of 852.82 patients pmp; as of December 31, 2007, there were 4,200 patients treated, with a corresponding prevalence of 869.14 pmp. The breakdown in prevalence by age group shows that the increase in prevalence is highly significant in the top two age classes, namely, between 65 and 75 years of age and over 75, while remaining negligible in the other classes. Between 1998 and 2007, the prevalence increased by 40% in patients over 75 and increased by 20% in the class of 65-to-75 year olds. The elderly contribute a greater weight in the renal replacement therapy population, reflected in the gradual increase of the median age of the prevalent population from 1998 to 2007. During 2006 and 2007, males made up 63.99% and 64.36% of the patients, respectively. This relative frequency mirrors the findings for incidence and is constant over the years. The distribution of primary diseases is very different in the prevalent population compared to findings in the incident patients. Primary glomerulonephritis, at fourth place among incident patients, is the most frequent disease in the prevalent population (although there is a clearly downward trend over the years). The percentages of diabetes and vascular disease, on the other hand, are lower compared to what is observed in the incident population. The prevalence expressed by treatment modality pmp increased for all three types. In analyzing the annual percentage rise in prevalence, using 1998 as the baseline, the most significant figure regards transplant patients, whose prevalence increased by over 60% between 1998 and 2007. Prevalence of hemodialysis patients rose moderately by only slightly over 10%. Peritoneal dialysis shows a rather linear increase, similar to the transplant trend. Our study used longitudinal regression models to analyze factors predictive of a patient starting and continuing to undergo the same type of treatment over the years. The results show that a patient has a greater probability of being treated with hemodialysis based on several primary nephropathies, when aged45, and in the presence of the main comorbidities. The predictive factors for peritoneal dialysis mentioned earlier have a diametrically opposed role. The presence of comorbidities (except high blood pressure), the type of nephropathy, and age65 lead to a lower probability of receiving a transplant. We analyzed peritoneal dialysis failures - defined as changing over to extracorporeal dialysis for any reason (clinical, psychological or social) - and the cumulative incidence of failure, taking into account the two competing outcomes of transplant and death. The only variable associated with peritoneal dialysis failure was the presence of infections. Older patients, patients with peripheral vascular disease, and those with neoplasia are less frequently taken off peritoneal dialysis to receive a transplant, an event occurring more frequently, however, in patients with hypertension. Death is dependent on age, on the presence of peripheral vascular disease and is less frequent in hypertensives. As is the case for peritoneal dialysis, the natural history of kidney transplant can have two competing outcomes: return to dialysis and death. The risk factors associated with return to dialysis are the presence of peripheral vascular disease, hypertension and infections; risk factors associated with death include age, the presence of cerebral vascular disease and neoplasia. From 1998 to 2007, the prevalence of hepatitis C virus-antibody-positive patients decreased by almost one third. The number of antigen-positive hepatitis B patients is declining slowly, but the levels remain in any case very low. The association between the two infections is disappearing: already at very low levels in 1998, that figure was halved by 2007. MORTALITY AND SURVIVAL: The mortality of uremic patients on renal replacement therapy was calculated both as a cumulative incidence, expressed as the number of deaths over patients at risk (alive at the beginning of the study year) and as a mortality rate, expressed as the number of deaths per patients/year. The figure was constant over the years, at around 10%. The mortality of males was no different from that of females; this finding differs from what is observed in the general population where male mortality is markedly higher than that of females. The mortality rate is dependent on the age group of the patient at start of treatment and shows an upward trend that is growing exponentially. The mortality rate in hemodialysis patients remained stable at 15% between 2000 and 2007, while the mortality rate in peritoneal dialysis patients gradually decreased down to 13%. The mortality rate for transplant patients was low and constant, at under 2%. The trend for the various causes of death is stable over the years and shows that the main cause of death is cardiac, accounting for between 30% and 35%, while mortality due to vascular, neoplastic, infection or cachexia-related causes are all roughly at the same rate, between 10% and 15%. (ABSTRACT TRUNCATED)

Health and administrative databases are widely used in epidemiology, mostly in studies of chronic diseases, but biases may undermine the external validity of the results. In nephrology, the use of these data sources is in its early days and needs to be validated. The aim of this study was to compare the data on the incidence of ESRD and death in a cohort of patients with type 2 diabetes (DM2) obtained from administrative databases with the results of a traditional, well-performed cohort study. The study was conducted in the Health District of Venice (Italy) on a cohort of 18,416 DM2 patients on hypoglycemic drug therapy enrolled from 1 January 1998 to 31 December 2002 from administrative databases.Comorbid conditions were recorded from hospital discharge records, the database of death certificates was used to identify patients who died within 31 December 2004, and the database of the Dialysis and Transplantation Registry of the Veneto Region served to identify patients who started renal replacement therapy within 31 December 2004. Record linkage was performed using the unique personal identification codes (fiscal number) of Italian citizens. The cumulative incidence of ESRD was estimated using Gray's method for competing risks. The mortality rate was 50.95 per 1000 person-years, the ESRD incidence was 0.68 per 1000 person-years, with a relative risk of 2.62 with respect to all other causes of ESRD. The crude cumulative incidence of death was 22% and that of ESRD 0.33% at the end of follow-up. The results were similar to those obtained in traditional cohort studies. The results of our study prove the external validity of the administrative database approach in epidemiological studies in nephrology.

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The Italian Society of Nephrology (SIN) promoted a national survey of the Renal and Dialysis Units using an online questionnaire on some aspects of structural, technological and personnel resources, as well as organisation and activity. The major aim of this initiative was to obtain a reference benchmark on a national and regional basis. In this paper the data of the northestern regions of Italy (Veneto, Friuli-Venezia Giulia and Trentino-Alto Adige) are reported and compared with the recently published results of the northwestern regions (Piedmont, Liguria and Valle d'Aosta). From an epidemiologic point of view, the prevalence of dialysis patients was 534 pmp (per million population) in Veneto, 667 pmp in Friuli VG and 545 in Trentino AA, the prevalence of transplanted patients was 265, 294 and 404 pmp, respectively; the incidence of dialysis patients was 137, 182 and 130 pmp; gross mortality was 12.5, 14.3 and 16.5%; the distribution of vascular accesse in prevalently dialysis patients was: arteriovenous fistulas = 84.5, 70.4 and 80.9%, central venous catheters = 10.6, 20.0 and 10.2%, vascular graft = 4.9, 9.6 and 8.8%. Regarding structural resources, the distribution of hospital bed numbers was 38, 42 and 43 pmp; dialysis places were 137, 181 and 172 pmp. Human resources were given by renal physicians = 28.3, 38.2 and 23.6 pmp and renal nurses = 138, 200 and 172 pmp; each renal physician took care of 19, 17 and 23 dialysis patients and each renal nurse cared for 3.9, 3.3 and 3.2 dialysis patients. Activity data showed 1436, 1328 and 974 pmp hospital admissions, kidney biopsies were 106, 114 and 31 pmp. Overall, the Italian Northeast shows a significantly lower prevalence and incidence of end-stage renal disease patients than the Northwest; on the contrary, the incidence of patients with acute renal failure is significantly higher. In the Italian Northeast a significantly lower number of hospital beds devoted to renal patients is observed, while dialysis places are more frequent. In the Northeast fewer renal physicians are present than in the Northwest, whereas renal nurses are equivalent if related to the number of dialysis patients. Activity indexes, intended as amount of hospital admissions and renal biopsies standardised per population, are less significant in the Northeast. The results of the survey in Veneto, Friuli VG and Trentino AA show some discrepancies in the treatment of chronic kidney disease between the three regions and even more among different areas of Italy. Despite similar health care models, a relevant inequality in health care resources is evident.

The Italian Registry of Dialysis and Transplantation (RIDT) collects data concerning patients in renal replacement therapy (RRT) sent from Regional Registries. Until 2003, the data were sent in summary tables. From 2004, each region has been sending patient data as single non-summarized forms (i.e. one record for each patient). This paper summarizes the collection criteria and the ideal method to codify data ensuring that data sent to the RIDT are consistent. This standardization process is necessary to ensure the statistical analyzability of the data and their comparability with data from other registries. Moreover, the standardization process is the initial step in allowing the RIDT to obtain clinical data to transform the registry from an epidemiological registry to a clinical governance instrument.

Since its conception, proof-carrying code (PCC) woke up the interest of the research community and several methods based on this technique were developed. This technique guarantees that untrusted programs run safely in a host machine. In a PCC framework, the code producer equips the produced code with a formal proof establishing that the code satisfies the consumer's security policies. So, the code consumer only needs to verify such proof before the execution of the mobile code. On the other hand, static analysis is a technique useful for the production of the information required to construct the mentioned proof. Based on these two techniques, PCC and static analysis, we developed a framework that guarantees the safe execution of mobile code. This framework uses a high-level intermediate language to verify the security of the code. A control flow graph or an abstract syntax tree with type annotations could be used. Such intermediate representations of the code enable us to use static analysis techniques to generate and verify the type information needed. Moreover, we implemented a prototype as a proof of concept for our framework.

The study evaluates the circadian rhythm of melatonin in relation to sex and age and identified contemporary alterations in the secreton of some hypophyseal hormones, suggesting that melatonin may exert a modulatory action on the latter.The melatonin metabolite (6-hydroxymelatonin sulfate) was assayed in urine samples from 48 subjects of both sexes aged between 25 and 60 years old using the RIA method described by Arendt, modified for the ise of iodine markers. A blood sample was taken from the same subjects to assay hypophyseal hormones.Melatonin secretion does not remain constant over 24 hours in young subjects of both sexes, but instead is rhythmic. This rhythmic secretion is lacking in adults, revealing a daytime pineal secreton that is surprisingly higher than in younger persons. A difference in secretion levels was also found between sexes, a higher melatonin peak in females compared to males. Some young female subjects reveal a contemporary hypersecretion of the somatotropic hormone in line with the falling nocturnal peak of melatonin. Subjects with latent hypothyroidism show a diminished melatonin peak compared to that in euthyroid subjects.Changes in pineal secretion between the second and sixth decade of life are characterised by the loss of rhythmic secretion, linked not only to the loss of the nocturnal peak but an increased daytime secretion compared to younger subjects. The other finding that emerged from this study was the difference in secretion levels between the sexes. Lastly, we affirm that the pineal gland may exert a modulating influence on the hypophysis.

Thanks to the high progress in hardware evolution and the consequent economic cost fall-down, in the recent past some automatic systems have been developed to help the clinician during his activity. In this field, fuzzy logic was intensively applied [1], [4], [8], [9], [10], [11], [14]. In this paper, a fuzzy logic hierarchical controller for hemodialysis patients is proposed, with the aim to compute automatically the values of the therapeutic variables used during a dialysis session. The system, now in use in the Venice Central Hospital, showed good performances in the first experimental phase.

Patients in chronic dialysis have a higher prevalence of cardiovascular morbidity and mortality, together with higher prevalence of hypertension and valvular diseases. It is not clear whether aortic and mitral defects are linked to the effect of chronic dialysis (for instance hypercalcaemia or hyperparathyroidism) or to hypertension. In order to see whether these factors could independently affect the single valve diseases we studied 48 patients in chronic dialysis. Patients were divided into hypertensive and normotensive. A population of hypertensive and another of normotensive, non-dialyzed patients served as control. The presence of valvular disease was searched by mean of echocardiography. We also investigated the length of dialytic treatment and the levels of parathyroid hormone in order to see if any correlation with the single valve defects existed. Aortic stenosis and insufficiency were not related to hypertension suggesting that circulating factors are likely to be involved in the pathogenesis of this valvulopathy (chi 2 = 6, p0.01 between hypertensive and normotensive in dialysis; chi 2 = 6.1, p0.01 between patients in dialysis and normotensive non uremic, for aortic stenosis; chi 2 = 12.1, p = 0.02 between non uremic normotensive and dialyzed, for aortic insufficiency). On the contrary for mitral regurgitation we did not find differences between dialyzed patients and controls (chi 2 = 18.2, p0.0001 between uremic hypertensive and controls). There was a significant difference in both groups between hypertensive and normotensive subjects suggesting that hypertension plays an important role in this valvulopathy. Mitral and aortic calcifications were more frequent in the uremic patients (55% in hypertensive uremics, 33% in normotensive uremics, 16 and 25% in non uremics).

The paper proposes a fuzzy logic based procedure able to control as far as possible the behaviour of the blood pressure of a patient during a dialysis session, allowing him to reach the foreseen dry weight. A PI discrete-time fuzzy control is used in order to compare the controlled variables concerning the (blood pressure and blood volume) to the reference values. Two different reference tables, concerning the pressure and volume errors and rates are introduced, then the proposed control actions are mixed in order to obtain the final value (net ultrafiltration rate). A smooth function of volemia acts on the second control variable, Na concentration in the dialysate. The adaptive control system was simulated on an IBM-PC, rules and terms were expressed by linguistic judgements like: IF "situation", THEN "action". A pre-processor converts the rules into the numerical values of the reference tables. The obtained simulation results are satisfactory, the introduction of the Na control allows reaching the target dry weight of the patient with a stable blood pressure.

This paper presents a fuzzy adaptive control technique to automate the dialysis procedure. The main points of this research are: use of a data base of fuzzy inference rules to formalize the medical experience, use of pre-processed lookup tables to speed up the computation and to allow for run-time changes of the inference rules, implementation of adaptive concept by means a set of performance tables, and — finally — the smooth blending of different control actions to obtain a single output action.

The onset of cessation of oestrous cyclicity and associated organ and hormonal changes were compared in random-bred (RB) and inbred (IB) female Syrian hamsters kept either under short days (8 h light:16 h darkness; 8L:16D) or long days (14L:10D) and given daily afternoon injections of 25 μg melatonin. In response to short-day treatment, 100% of the IB hamsters exhibited vaginal acyclicity within 35 days; by comparison, none of the RB animals were acyclic at this time. The IB hamsters also exhibited other changes associated with exposure to short days, including increased body weight, enlarged ovaries, regressed uteri, elevated pituitary concentrations of FSH, and depressed pituitary and plasma concentrations of prolactin. At this time, only the pituitary FSH levels were increased in the RB animals kept under the same short-day conditions. In a second experiment, RB and IB female Syrian hamsters were maintained under long days (14L:10D) and the rate of reproductive regression in response to daily afternoon injections of melatonin was compared. After 8 weeks of melatonin injections, 80% of the IB females were anoestrous, while all RB hamsters were still exhibiting 4-day oestrous cycles. Other changes associated with melatonin administration in the IB females included a marked drop in uterine weight and a depression in pituitary and plasma prolactin levels. The RB hamsters, although they were all still cyclic after 8 weeks, had increased body and ovarian weights, increased pituitary concentrations of FSH, and lower pituitary and plasma prolactin levels. The results show that the IB strain of Syrian hamster, compared with the RB strain, responded more quickly with vaginal acyclicity to both exposure to short days and daily injections of melatonin. On the other hand, the IB hamsters responded more slowly in terms of oestrous acyclicity to melatonin injections than to treatment with short photoperiod. Journal of Endocrinology (1989) 120, 489–496

In this present study we evaluated the ability of a recently synthesized melatonin antagonist, N-(2,4-dinitrophenyl)-5-methoxytryptamine (ML-23), to antagonize the effects of afternoon injections of melatonin on the reproductive and thyroid axes in the female Syrian hamster. Thirty-six animals were divided into four groups and treated daily for 13 weeks with an afternoon injection of melatonin (25 micrograms/injection) or saline diluent. ML-23 was given via the drinking water to both melatonin- and saline-treated groups. The experiment was continued until 78% of melatonin-treated animals exhibited acyclicity. The results show that ML-23 partially reversed the effects of melatonin on pituitary follicle-stimulating hormone concentrations but was without effect on the decreased pituitary and plasma prolactin concentrations induced by melatonin treatment. Furthermore, ML-23 antagonized the effects of melatonin on plasma thyroxine levels and significantly increased plasma triiodothyronine concentrations and the free triiodothyronine index when used in combination with melatonin. The decrease in ovarian weight and plasma estradiol, but not progesterone, obtained with melatonin treatment also was reversed by ML-23. Our data suggest that ML-23 prevents the effects of melatonin treatment on ovarian weight, pituitary follicle-stimulating hormone levels, plasma estradiol, and thyroxine concentrations in the female Syrian hamster. Since ML-23 did not prevent the effects of melatonin on pituitary weight, plasma luteinizing hormone and prolactin, and pituitary prolactin concentrations, the actions of ML-23 may involve only peripheral sites of action of melatonin. Alternatively, the dose of ML-23 may not have been optimal to prevent all of the central effects of the indoleamine.

The effects of a drug with hemostatic action, "Vascular Factor" (V.F.), on platelet and vascular arachidonic acid metabolism were evaluated in man to establish the lack of side effects on platelet aggregation. Plasma levels of 6-keto PGF1 alpha and thromboxane B2 were determined by RIA in healthy volunteers undergoing treatment with V.F. Results indicate that basal values obtained in these compounds do not present significant variations following treatment with V.F. On the basis of these results, the possibility of administering this drug in atherosclerotic patients is further confirmed.

Harderian gland (HG) weight and lysosomal enzyme activity were evaluated after 2 1 -day-old female rats were singly caged in a long (LP 14: 10 LD) or short (SP; 8: 16 LD) photoperiod and fed on one of two dietary regimens (fed ad libitum or 50% underfed) for 50 days; an additional fed and an underfed group of animals in LP were injected every afternoon with 100 pg melatonin. Absolute HG weights were significantly lower in all underfed groups compared to their respective fed controls or to the LP fed control group. Absolute HG weights of underfed rats in SP were significantly lower than the underfed rats in LP. Relative HG weights (mg/100 g body wt) were significantly higher in the underfed saline or melatonin- treated groups compared to their respective fed controls; however, HG of the underfed SP group were not different from SP-fed controls. No significant differences in HG acid phosphatase, hexosaminidase, and P-glucuronidase activities were observed in any of the treatment groups maintained in LP. Acid phosphatase, hexosaminidase, and P-glucuronidase activities were significantly elevated in HG of underfed animals maintained in SP compared to their respective fed controls or to the LP-underfed group. Both the underfed control and the underfed-melato- nin treated groups had lower pineal protein values than their respective fed groups; underfed animals in 8: 16 LD had similar pineal protein values compared to those of the fed control group in SP. Significant effects of photoperiod and underfeeding with no interaction between these variables were observed on pineal acid phosphatase. The fed group maintained in 8: 16 LD had significantly higher acid phosphatase activity than the fed group kept in 14: 10 LD. In conclu- sion, underfeeding resulted in severely reduced body weights and absolute Harderian gland weights. Increased activity in certain lysosomal enzymes occurred in both the pineal and Harderian gland and in some instances this was dependent upon the light cycle and dietary regimen to which the animals were exposed. o 1988 Society for Experimental Biology and Medicine.

In the last years new highly permeables membranes have been introduced in dialysis practice, in order to improve the treatment effectiveness (1,2); moreover, the dialysis schedule has been often shortened (3,4). Both the innovations require a strict control of ultrafiltration (UF) during regular dialysis treatment (RTD), thus various automatic-UF-control monitors have been set up in order to ease new dialysis systems (5,6). The present study aims to test a new hemodialysis single patient unit (Monitral-S®, Hospal) in a little group of subjects who underwent short dialysis treatment.

Prepubertal (21-22 days) female Sprague-Dawley rats were caged singly in either long (LP; 14:10 LD) or short (SP; 8:16 LD) photoperiod and fed ad libitum or underfed (1/2 the food intake of controls). Additionally, a fed and underfed group in LP received a daily sc injection of saline or 100 micrograms melatonin at 1700 h. Food restriction delayed vaginal opening and resulted in a reduction in body weight and in the weights of the pituitary, ovary and uterus in all underfed groups. Melatonin treatment (but not SP exposure) significantly enhanced the reduction in pituitary, ovarian and uterine weight compared to the underfed saline-treated controls. Thyroid weights were significantly increased in underfed LP and SP groups compared to their respective controls where melatonin treatment in either fed or underfed animals was ineffective. Underfeeding caused a significant rise in pituitary LH (except for SP-underfed group) and FSH concentrations and a fall in pituitary prolactin concentrations and plasma T3 levels. Melatonin injections in underfed rats significantly increased pituitary LH and FSH and decreased prolactin concentrations compared to underfed saline-treated animals. Plasma prolactin levels increased after melatonin administration in both fed and underfed rats. These observations emphasize that environmental influences such as undernutrition can alter the physiological status of immature animals and enhance the sensitivity of the neuroendocrine axis to the pineal and one of its hormones, melatonin.

During the dialytic treatment, plasma phosphate (Pi) has a very specific time course. It reaches a nadir value approximately 90 minutes after the beginning of the treatment and then, despite the ongoing removal, it exhibits either a constant steady state or a slow rebound. In order to quantitatively describe the kinetics, the authors have proposed a set of different compartmental control models, which have been compared by using criteria based on mathematical indices and physiological considerations. The resulting best model has two compartments, which represent plasma and intra-cellular fluids (IF) respectively, In order to explain the Pi time course, it postulates two fluxes of Pi into plasma: one from IF, proportional to the decrease of plasma Pi from its pre-dialysis value, and one from an endogenous source (probably the bone surface), again proportional to the decrease of plasma Pi but also inversely proportional to Pi concentration in IF. This model was able to achieve a very good fit of all the experimental data (7 subjects) and good precision of parameter estimates. Moreover, it proved capable of correctly predicting also the qualitative time course of Pi in the post dialysis period.

This paper proposes a fuzzy logic based procedure able to control the behavior of a patient's blood pressure during a dialysis session, allowing him to reach the planned dry weight. A proportional integrative discrete-time fuzzy control is used to subject the controlled variables (blood pressure and blood volume) to the reference values. Two different tables that refer to pressure and volume errors and rates are consulted and the proposed control actions are taken to obtain the final value (net ultrafiltration rate). A saturation-threshold function of volemia acts on the second control variable, Na concentration in the dialysate. The adaptive control system was simulated on an IBM PC, and rules and terms were expressed by linguistic judgments such as: IF "situation," THEN "action." A pre processor converts the rules into the numerical values in the tables. The obtained simulation results are satisfactory, and the introduction of Na control allows achievement of the target dry weight of the patient with a stable blood pressure.

The aims of this study were to determine the frequency of dialysis and kidney transplantation and to estimate the regularity of comprehensive conservative management (CCM) for patients with kidney failure in Europe. This study uses data from the ERA-EDTA Registry. Additionally, our study included supplemental data from Armenia, Germany, Hungary, Ireland, Kosovo, Luxembourg, Malta, Moldova, Montenegro, Slovenia and additional data from Israel, Italy, Slovakia using other information sources. Through an online survey, responding nephrologists estimated the frequency of CCM (i.e. planned holistic care instead of kidney replacement therapy) in 33 countries. In 2016, the overall incidence of replacement therapy for kidney failure was 132 per million population (pmp), varying from 29 (Ukraine) to 251 pmp (Greece). On 31 December 2016, the overall prevalence of kidney replacement therapy was 985 pmp, ranging from 188 (Ukraine) to 1906 pmp (Portugal). The prevalence of peritoneal dialysis (114 pmp) and home hemodialysis (28 pmp) was highest in Cyprus and Denmark respectively. The kidney transplantation rate was nearly zero in some countries and highest in Spain (64 pmp). In 28 countries with five or more responding nephrologists, the median percentage of candidates for kidney replacement therapy who were offered CCM in 2018 varied between none (Slovakia and Slovenia) and 20% (Finland) whereas the median prevalence of CCM varied between none (Slovenia) and 15% (Hungary). Thus, the substantial differences across Europe in the frequency of kidney replacement therapy and CCM indicate the need for improvement in access to various treatment options for patients with kidney failure. European UnionEuropean Commission [PP-01-2016]; ERAEDTA This study was funded by the European Union (grant PP-01-2016) and ERAEDTA.

Background Previous US studies have indicated that haemodialysis with ≥6-h sessions [extended-hours haemodialysis (EHD)] may improve patient survival. However, patient characteristics and treatment practices vary between the USA and Europe. We therefore investigated the effect of EHD three times weekly on survival compared with conventional haemodialysis (CHD) among European patients. Methods We included patients who were treated with haemodialysis between 2010 and 2017 from eight countries providing data to the European Renal Association–European Dialysis and Transplant Association Registry. Haemodialysis session duration and frequency were recorded once every year or at every change of haemodialysis prescription and were categorized into three groups: CHD (three times weekly, 3.5–4 h/treatment), EHD (three times weekly, ≥6 h/treatment) or other. In the primary analyses we attributed death to the treatment at the time of death and in secondary analyses to EHD if ever initiated. We compared mortality risk for EHD to CHD with causal inference from marginal structural models, using Cox proportional hazards models weighted for the inverse probability of treatment and censoring and adjusted for potential confounders. Results From a total of 142 460 patients, 1338 patients were ever treated with EHD (three times, 7.1 ± 0.8 h/week) and 89 819 patients were treated exclusively with CHD (three times, 3.9 ± 0.2 h/week). Crude mortality rates were 6.0 and 13.5/100 person-years. In the primary analyses, patients treated with EHD had an adjusted hazard ratio (HR) of 0.73 [95% confidence interval (CI) 0.62–0.85] compared with patients treated with CHD. When we attributed all deaths to EHD after initiation, the HR for EHD was comparable to the primary analyses [HR 0.80 (95% CI 0.71–0.90)]. Conclusions EHD is associated with better survival in European patients treated with haemodialysis three times weekly.