Suicide risk in epilepsy: Clinical variables, psychiatric disorders, and social support.

OBJECTIVE: To explore the relationship between suicide risk, the perception of social support and quality of life (QoL), and with the clinical variables of adult people with epilepsy (PWEs). METHODOLOGY: A total of 98 consecutive PWEs cared for in the outpatient setting, with a mean age of 48.1±15.9 years, having had epilepsy for 26.4±16.4 years and 48 (48.9%) female cases participated in this study. The MINI suicide module, the Social support satisfaction scale (SSSS), the Quality of life in epilepsy inventory (QOLIE-31), and the Hospital anxiety and depression scale (HADS) were used. A logistic regression was conducted to assess the factors associated with the suicide risk. RESULTS: Suicide risk was present in 33 cases. Younger age, earlier age at epilepsy onset, depression and anxiety in the HADS scale, and lower MMSE, QOLIE-31, and SSSS scores were significantly associated with suicide risk in the univariate analysis. The logistic regression analysis identified that lower scores in the MMSE (OR 0.826, 95%CI 0.705-0.969), presence of anxiety (OR 0.197, CI 0.073-0.530), and a low perception regarding satisfaction with family (OR 0.953, CI 0.920-0.988) are the factors associated with the highest risk of suicide. CONCLUSION: Suicide risk and recurrence of a suicide attempt was high in the PWEs. Suicide risk was associated with clinical variables, the presence of anxiety and the perception of less social support from the family.

Vitamin D status and non-alcoholic fatty liver disease in patients with type 1 diabetes.

PURPOSE: In patients with type 1 diabetes (T1D), the prevalence of non-alcoholic fatty liver disease (NAFLD) ranges from 10 to 53% and contrasting evidence suggests that vitamin D deficiency may favor liver fat accumulation. Here, we investigated the association between vitamin D status and NAFLD in adults with T1D. METHODS: 220 consecutive adult T1D patients on multiple daily injections or continuous subcutaneous insulin infusion and not taking calcium or vitamin D supplements were included. Patient characteristics, 25(OH)D serum levels, and metabolic parameters were analyzed. Vitamin D status was defined as sufficiency ( ≥ 75 nmol/L; 30 ng/ml), insufficiency (50-75 nmol/L; 20-30 ng/ml), or deficiency ( < 50 nmol/L; 20 ng/ml). NAFLD was diagnosed at ultrasound examination and graded 0-3. RESULTS: NAFLD was present in 57 patients (29.5%): 51 grade 1, 5 grade 2, and 1 grade 3. Median 25(OH)D levels were 53 nmol/L (IQR 38-70) in patients with NAFLD and 50 nmol/L (34-69) in patients without (p = 0.46). At multivariable analysis, NAFLD was not associated with 25(OH)D levels (p = 0.42) or vitamin D deficiency (p = 0.55), while BMI (OR 1.16, 95% CI 1.07-1.27) and serum triglycerides (OR 1.02, 95% CI 1.01-1.03) were independently associated with NAFLD. CONCLUSIONS: Vitamin D status appears to have no link with low-grade NAFLD in patients with type 1 diabetes.

Effects of subcutaneous interleukin-2 therapy on CD4 subsets and in vitro cytokine production in HIV+ subjects.

HIV infection is characterized by the reduction of the CD4+, CD45RA+, CD26+, and CD28+ lymphocyte subsets and of the in vitro production of IL-2, IL-4, and interferon-gamma; on the contrary, chemokine production is usually increased. These abnormalities are only partially restored by antiretroviral chemotherapy. Therapy with interleukin-2 has been proposed to restore the functions of the immune system, but the mechanisms by which IL-2 exerts its activities are unknown. The aim of this study was to define the effects of rIL-2 administration on CD4+, CD45RA+, CD45R0+, and CD26+ lymphocytes and on the in vitro production of IL-2, IL-4, IL-10, IFN-gamma, RANTES, and sCD30 in HIV+ patients. 10 HIV+ patients with CD4 cell counts between 200 and 500 cells/mm3 were treated with six cycles of subcutaneous recombinant IL-2 administration, in combination with zidovudine and didanosine. This therapeutic regimen resulted in a remarkable increase in the number of CD4+ cells and in the prolonged reduction of the levels of viremia. CD45R01 cells were expanded during the first cycle of therapy, while CD45RA+/CD26+ cells predominated after the third cycle. At this time, the in vitro production of IL-2, IL-4, IFN-gamma, and sCD30 were significantly upregulated. These results demonstrate that rIL-2 in HIV+ patients induces the reconstitution of the CD4/CD45RA lymphocytes subtype. This expanded cell population recovered the ability to produce in vitro IL-2, IL-4, and IFN-gamma. These effects may be beneficial to HIV+ patients by improving their immune response to microorganisms or vaccines.

Integration of blood volume, blood pressure, heart rate and bioimpedance monitoring for the achievement of optimal dry body weight during chronic hemodialysis.

BACKGROUND: Achieving optimal dry body weight in hemodialysis is challenging. Clinical assessment alone is inadequate, and methods such as bioimpedance monitoring may be impractical for every patient treatment. Continuous blood volume monitoring, blood pressure and heart rate variability inform clinical decision-making, but integrated use of multiple methodologies to achieve dry weight and understand patient factors has not yet been described. METHODS: Nineteen chronic hemodialysis patients underwent thrice-weekly treatments for two weeks. Baseline hydration status and target weight were determined by bioimpedance. During subsequent treatments, ultrafiltration was adjusted and relative blood volume, blood pressure and pulse were recorded non-invasively. Bioimpedance was repeated to assess hydration. Response of variables to progressive change in weight was assessed and selected patients underwent additional autonomic function testing. RESULTS: Four distinct hemodynamic patterns emerged. Profile A: 4 patients demonstrated overhydration at baseline. With decreasing target, pulse and blood pressure remained stable while blood volume and bioimpedance demonstrated achievement of dry weight. Profile B: 8 patients demonstrated overhydration at baseline. With decreasing target, blood pressure remained stable while pulse increased. Profile C: 5 patients were overhydrated, but as weight decreased, blood pressure became unstable and heart rate failed to compensate. Further testing confirmed autonomic dysfunction. Profile D: 2 patients were dehydrated, and with increasing target demonstrated stable pulse and pressure, while blood volume and bioimpedance revealed achievement of dry weight. CONCLUSIONS: Integrating existing non-invasive, continuous monitoring during hemodialysis enabled achievement of dry weight and identified distinct profiles of the patients, some with autonomic dysfunction. This strategy may contribute to achieving optimum dry weight while improving cardiovascular tolerability of hemodialysis.

Coronary Microvascular Dysfunction Predicts Long-Term Outcome in Simultaneous Pancreas-Kidney Transplantation.

BACKGROUND: Patients with diabetes are at increased cardiovascular risk. Simultaneous pancreas-kidney transplantation (SPKT) is the treatment of choice in patients with type 1 diabetes mellitus and diabetic nephropathy. We assessed coronary flow reserve (CFR) by transthoracic echocardiography as a marker of major adverse cardiac events (MACE) in SPKT patients. METHODS: We studied 48 consecutive SPKT patients (28 male, age at SPKT 54 ± 8 years). Time from transplantation was 8.5 ± 3 years. Follow-up was 4.6 ± 1.8 years. Coronary flow velocity in the left anterior descending coronary artery was detected by Doppler echocardiography at rest and during adenosine infusion. CFR was the ratio of hyperemic diastolic flow velocity (DFV) to resting DFV. A CFR ≤ 2 was considered abnormal and a sign of coronary microvascular dysfunction. MACE were cardiac death, myocardial infarction, and heart failure. RESULTS: CFR was 2.55 ± 0.8. CFR was ≤2 in 13 (27%) patients. CFR was lower in SPKT patients with MACE (2.1 ± 0.7 vs 2.7 ± 0.8, P = .03) and patients with MACE had a higher incidence of CFR ≤ 2 (P = .03). Time from transplantation was shorter in patients with MACE (P < .0001). Patients with CFR ≤ 2 had a lower MACE-free survival (P = .03). CFR ≤ 2 predicted the risk of MACE (P = .007) independently from coronary artery disease and metabolic control. However, this predicted role is lost when adjusted for the time from transplantation, which plays a protective role (P = .001). CONCLUSIONS: In SPKT, CFR ≤ 2 may be a reliable marker for MACE, independent of coronary artery disease diagnosis. However, this role seems to be reduced over time. This finding suggests a gradual reduction of cardiovascular risk in SPKT patients.

The hemodynamic abnormalities in short-term insulin deficiency: the role of prostaglandin inhibition.

It has been suggested that the hemodynamic derangements present in diabetic ketoacidosis are the results not only of profound volume depletion but also of the effects of increased production of vasodilating prostaglandins (PGs), principally PGI2, released by adipose tissue. In animal and in vitro models, prostaglandin synthesis is increased during insulin deficiency. We assessed the effects of short-term ketosis on the metabolic and hemodynamic variables of 10 IDDM patients free from long-term complications and of 9 normal control subjects after a 7-day randomized double-blind indomethacin (INDO) (50 mg q.i.d.) or placebo treatment period. Calf blood flow (CBF), postocclusive reactive hyperemia (PORH), and recovery half-time (an index of overall perfusion) after PORH were measured by plethysmography. Left ventricular and myocardial functions were also studied in each different condition during placebo and INDO treatment in IDDM patients. During placebo treatment, the increase in CBF during ketosis was higher (1.75 +/- 0.29 ml / min / 100 ml muscle) than during INDO (0.85 +/- 0.17 ml / min) / 100 ml muscle; P = 0.007). PORH was similar in baseline conditions, during ketosis, and in recovery in both the placebo and INDO arms. Recovery half-time significantly increased during placebo (10 +/- 2; 200%; P < 0.01) but not during INDO (1 +/- 1; 106%; NS) treatment. In normal control subjects, insulin deficiency did not induce any significant effect on hemodynamic variables. In IDDM patients, during placebo treatment, ketosis increased both the cardiac index (from 3.4 +/- 0.7 to 4.1 +/- 0.81 / min / m; P < 0.01) and the stroke index (from 42 +/- 8 to 49 +/- 7 ml/m2; P < 0.01) without changes in left ventricular ejection fraction but with a significant increase in both left and right ventricular end-diastolic volumes. Metabolic recovery induced a normalization of these parameters. INDO treatment significantly blunted these alterations. In summary, we showed that during acute insulin deficiency, INDO-sensitive mechanisms mediate vascular disturbances. Moreover, INDO treatment was capable of completely preventing the cardiac venous return and the left ventricular alterations. INDO does not interfere with the overall ketogenetic process or with insulin-induced metabolic recovery.

Alcohol intake impairs glucose counterregulation during acute insulin-induced hypoglycemia in IDDM patients. Evidence for a critical role of free fatty acids.

In this study, we assessed the effects of alcohol intake on glucose counterregulation in response to acute insulin-induced hypoglycemia in IDDM patients and in normal control subjects. Nine euglycemic IDDM patients and 9 normal control subjects were studied. After a baseline period, insulin (0.15 U/kg) was administered subcutaneously to induce hypoglycemia. Each IDDM patient was studied 3 times. In the first study, alcohol was orally administered as wine. In the second (control) study, water was administered instead of wine. In the third study, wine was given; however, a continuous infusion of heparin plus intralipid was administered to prevent the fall in plasma free fatty acid. Normal control subjects underwent only the alcohol and the control studies. In IDDM patients alcohol intake impairs, whereas in normal subjects it supports glucose counterregulation. Alcohol intake is associated with normal catecholamine responses in both IDDM diabetic patients and normal subjects. In both IDDM patients and normal subjects, hepatic glucose production in the recovery phase of the alcohol study was normal. Plasma glucose rate of disappearance was significantly increased by alcohol intake in IDDM (13.72 +/- 0.82 vs. 11.84 +/- 0.53 mumol.kg-1 x min-1; P < 0.05). Alcohol intake in both normal subjects and IDDM patients decreased plasma free fatty acid (267 +/- 22 vs. 156 +/- 20 microM; P < 0.01 and 356 +/- 29 vs. 96 +/- 12 microM; P < 0.01). We hypothesized that in IDDM patients, deficient glucose recovery during alcohol intake is the result of the ability of alcohol to depress lipolysis.

Myocardial dysfunction and adrenergic cardiac innervation in patients with insulin-dependent diabetes mellitus.

BACKGROUND: Insulin-dependent diabetes mellitus (IDDM) is associated with an increased incidence of heart failure due to several factors, and in some cases a specific cardiomyopathy has been suggested. OBJECTIVES: This study sought to assess the mechanisms of exercise-induced left ventricular (LV) dysfunction in asymptomatic patients with IDDM in the absence of hypertensive or coronary artery disease. METHODS: Fourteen consecutive patients with IDDM were enrolled (10 men, 4 women; mean [+/- SD] age 28.5 +/- 6 years); 10 healthy subjects matched for gender (7 men, 3 women) and age (28.5 +/- 3 years) constituted the control group. LV volume, LV ejection fraction (LVEF) and end-systolic wall stress were calculated by two-dimensional echocardiography at rest and during isometric exercise. LV contractile reserve was assessed by post-extrasystolic potentiation (PESP) obtained by transesophageal cardiac electrical stimulation and dobutamine infusion. Myocardial iodine-123 metaiodobenzylguanidine (MIBG) scintigraphy was performed to assess adrenergic cardiac innervation. RESULTS: Diabetic patients were classified into group A (n = 7), with an abnormal LVEF response to handgrip (42 +/- 7%), and group B (n = 7), with a normal response (72 +/- 8%). Baseline LVEF was normal in both group A and B patients (60 +/- 6% vs. 61 +/- 7%, p = NS). In group A patients, the LV circumferential wall stress-LVEF relation showed an impairment in LVEF disproportionate to the level of LV afterload. No significant changes in LVEF occurred during dobutamine (60 +/- 6% vs. 64 +/- 10%, p = NS), whereas PESP significantly increased LVEF (60 +/- 6% vs. 74 +/- 6%, p < 0.001); PESP at peak handgrip normalized the abnormal LVEF (42 +/- 7% vs. 72 +/- 5%, p < 0.001); and MIBG uptake normalized for body weight or for LV mass was lower than that in normal subjects (1.69 +/- 0.30 vs. 2.98 +/- 0.82 cpm/MBq per g, p = 0.01) and group B diabetic patients (vs. 2.79 +/- 0.94 cpm/MBq per g, p = 0.01). Finally, a strong linear correlation between LVEF at peak handgrip and myocardial MIBG uptake normalized for LV mass was demonstrated in the study patients. CONCLUSIONS: Despite normal contractile reserve, a defective blunted recruitment of myocardial contractility plays an important role in determining exercise LV dysfunction in the early phase of diabetic cardiomyopathy. This abnormal response to exercise is strongly related to an impairment of cardiac sympathetic innervation.

Sequential convective therapies (SCT): a prospective study on feasibility, safety, adequacy and tolerance of on-line hemofiltration and hemodiafiltration in sequence.

Sequential dialysis techniques (i.e pure ultrafiltration followed by dialysis) have been used in the past, due to their capability to remove large volumes of fluids without inducing hemodynamic instability. The disadvantages of inadequate efficiency and lack of technology lead to the decline of such methods. Hemofiltration (HF) and hemodiafiltration (HDF) are recently being utilized in a greater proportion thanks to on-line fluid preparation systems. Each process (HF and HDF) has its own benefits in the removal of small, medium and high-molecular weight substances and in hemodynamic stability. Sequential convective therapies (SCT) such as hemofiltration-hemodiafiltration in sequence (HF-HDF) may combine the benefits and eliminate the disadvantages of each method and should be studied in order to explore their potential application in modern dialysis. Furthermore they can be easily applied nowadays, due to the development of new sophisticated dialysis machines. In order to evaluate the feasibility, safety, efficiency and tolerance of different SCT methods we studied 3 schedules: SCT1: 1h pre-dilution HF followed by 3h of post-dilution HDF (in the HF mode we lost 25% of the total fluid that had to be removed). SCT2: 1h pre-dilution HF followed by 3h of post-dilution HDF (in the HF mode we lost 50% of the total fluid that had to be removed). SCT3: 2h pre-dilution HF followed by 2h of post-dilution HDF (in the HF mode we lost 50% of the total fluid that had to be removed). We studied 6 chronic hemodialysis patients using the same machine (AK200 ULTRA), with on-line fluid preparation system and the same type of dialyzer (Polyflux 210). SCT schedules were compared to on-line HF, on-line HDF and high flux dialysis performed with the same dialyzers. The treatments resulted safe, easy, feasible and well tolerated with an improved hemodynamic response to high volume convective therapies. Adequacy of treatment was satisfactory in all SCT schedules while middle molecular weight solute clearance and removal resulted higher in treatments with higher convective component. SCT might represent an interesting option for the future especially in patients with hemodynamic instability and requirements for interventions during treatment.

Dialytic performance evaluation of Rexeed: a new polysulfone-based dialyzer with improved flow distributions.

New dialyzers are designed to optimize the convective and diffusive components of solute transport. Asahi Kasei Medical Co.,Ltd.has developed a new high flux dialyzer series called Rexeed with improved flow distributions. We evaluated the in vivo dialytic performance of two dialyzers of the Rexeed series: Rexeed-18A and Rexeed-25A (1.8 m2 and 2.5 m2 ). We calculated the clearance for urea,creatinine,phosphate and b2-microglobulin both in high flux dialysis (HFD)and in 15 liter postidiluitional on-line hemodiafiltration (HDF)mode. With n = 3 patients in high flux HD at blood flow 450, 400, 350 and 250 ml/min we found remarkably high clearance for urea (347 +/- 4%, 305 +/- 0%, 288 +/- 5%, 230 +/- 3%, for Rexeed-18A and 361 +/- 3%, 329 +/- 0%, 313 +/- 1%, 234 +/- 3%for Rexeed-25A),creatinine (282 +/- 10%, 234 +/- 0%, 221 +/- 8%, 174 +/- 8%, for Rexeed-18A and 276 +/- 6%, 245 +/- 0%, 226 +/- 9%, 172 +/- 13% for Rexeed-25A),phosphate (347 +/- 0%, 316 +/- 0%, 275 +/- 4%, 202 +/- 16%, for Rexeed-18A and 364 +/- 3%, 365 +/- 0%,286 +/- 3%, 224 +/- 2% for Rexeed-25A)and b2-microglobulin (133 +/- 21%, 124 +/- 0%,118 +/- 12%, 98 +/- 11%, for Rexeed-18A and 159 +/- 8%, 169 +/- 0%,157 +/- 8%, 129 +/- 7% for Rexeed-25A) With n = 2 patients in HDF at blood flow 300 ml/min we found remarkably high clearance for urea (268 +/- 2%, for Rexeed-18A and 283 +/- 2% for Rexeed-25A),creatinine (183 +/- 6%for Rexeed-18A and 205 +/- 9% for Rexeed-25A),phosphate (245 +/- 3%, for Rexeed-18A and 270 +/- 2% for Rexeed-25A)and b2-microglobulin (166 +/- 12%, for Rexeed-18A and 192 +/- 4% for Rexeed-25A). Our preliminary evaluation describes the characteristics and the performances of a new polysulfone-based hemodialyzer series called Rexeed. Several innovative features have been implemented by the manufacturer. These constructive approaches seem to have produced a positive effect on the dialyzer performance at the bedside.

Short-term diabetic ketosis alters n-6 polyunsaturated fatty acid content in plasma phospholipids.

At present, no information is available about the possibility that acute loss of metabolic control might be able to modify fatty acid composition in IDDM patients. Therefore, the aim of this study was to determine whether a short-term period of ketosis has any effect on the composition of fatty acid of plasma phospholipids in a group of insulin-dependent diabetes mellitus (IDDM) patients. Eleven IDDM patients and nine healthy volunteers were studied. Patients were studied over a 2-day period; each 2-day period consisted of initial baseline measurements followed by a day of hyperglycemia and mild ketosis, which was promptly alleviated by insulin infusion. No significant difference in baseline percent fatty acid composition was observed between normal controls and IDDM patients. In IDDM patients, ketosis induced a significant decrease in percent arachidonic acid (20:4 n-6) content, with a significant parallel decline in n-6 total polyunsaturated fatty acids. A significant inverse correlation between the prevailing plasma glucose and the relative content of arachidonic acid in plasma phospholipids was observed (r = -0.35; P = 0.0488). A highly significant inverse correlation was observed between the change from baseline condition to ketosis of the ratio C20:4/C20:3, the product/precursor ratio for the reaction catalyzed by delta5-desaturase, and the values of hemoglobin A1c,(r = -0.855; P = 0.0015). In conclusion, short term diabetic ketosis is associated with a significant decrease in n-6 polyunsaturated fatty acid content in plasma phospholipids, especially arachidonic acid. This decrease in arachidonic acid appears to be related to the degree of metabolic derangement, whereas the influence of short-term diabetic ketosis on the ratio of C20:4 to C20:3 seems to be due to the degree of long-term metabolic control.

Ethanol impairs insulin-mediated glucose uptake by an indirect mechanism.

The effect of ethanol (ETOH) on muscle metabolism was assessed in both normal (NC) and noninsulin-dependent (NIDDM) subjects in the basal state and during isoglycemic hyperinsulinemia (450 pmol/L) clamp studies carried out either with systemic (NC, n = 5; NIDDM, n = 5) or intrabrachially (NC, n = 5; NIDDM, n = 5)ETOH infusion. On a repeat study, each subject underwent the same experimental procedures, except that saline was infused instead of ETOH. Systemic ETOH significantly decreased whole body glucose disposal in both NC and NIDDM patients. In NC, ETOH infusion decreased basal forearm glucose uptake (FGU) from 1.22 +/- 0.20 to 0.32 +/- 0.04 mumol/min.100 mL tissue (P < 0.01), whereas in NIDDM, this decrement was not significant (from 0.95 +/- 0.31 to 0.66 +/- 0.23). With saline infusion, hyperinsulinemia significantly stimulated FGU to 4.09 +/- 0.46 mumol/min.100 mL tissue in NC and to 2.50 +/- 0.76 in NIDDM. During ETOH, FGU was depressed by 81% in NC (delta = 3.32 mumol/min.100 mL tissue) and by 48% (P < 0.05) in NIDDM (delta = 1.21 mumol/min.100 mL tissue). Local ETOH infusion did not affect FGU in either NC (1.18 +/- 0.23 vs. 1.1 +/= 0.11 mumol/min.100 mL tissue in the baseline condition and 4.12 +/- 0.65 vs. 3.97 +/- 0.35 in insulin-stimulated conditions) or NIDDM (1.05 +/- 0.29 vs. 1.1 +/- 0.19 mumol/min.100 mL tissue in baseline condition and 2.72 +/- 0.82 vs. 2.83 +/- 0.51 in insulin-stimulated conditions) subjects. With systemic ETOH, but not local infusion, there was a reduction in baseline plasma free fatty acid level and an increase in blood lactate concentration during isoglycemic hyperinsulinemia. In summary, systemic ETOH infusion impairs both whole body and forearm glucose uptake in NC and NIDDM subjects; this effect was more apparent in NC than in NIDDM at both the whole body and forearm level. On the contrary, intrabrachial ETOH infusion did not affect forearm glucose balance in either group. These results suggest that the reduction in muscle glucose disposal associated with increased systemic ETOH concentrations is not caused by a direct ETOH effect on muscle glucose metabolism.

Plasma free fatty acids and endothelium-dependent vasodilation: effect of chain-length and cyclooxygenase inhibition.

Free fatty acids (FFA) are known to interfere with glucose metabolism. Moreover, it has been shown that they are able to impair the endothelium-dependent vasodilation. Therefore, we sought to determine whether their negative effect on endothelial function depends on their chain length or on their ability to modify PG production. Fourteen normal volunteers were studied under baseline conditions and then randomly allocated to two of the following four studies: 1) long chain triglyceride (LCT) emulsion and heparin infusion (n = 7), 2) infusion of an emulsion containing 56% medium chain triglycerides (MCT) and 44% LCT plus heparin (n = 7), 3) infusion of LCT and heparin preceded by an i.v. bolus of 900 mg lysine-salicylate (ASA; n = 7), and 4) after an i.v. bolus of ASA (n = 7). Basal forearm blood flow (FBF), endothelium-dependent vasodilation in response to intraarterial acetylcholine (Ach), and endothelium-independent vasodilation in response to intraarterial nitroprusside were assessed by venous occlusion plethysmography. Both LCT and MCT infusions significantly increased basal FBF from 1.58 +/- 0.35 to 2.60 +/- 0.76 and 2.28 +/- 0.56 mL/min 100 mL tissue, respectively (both P < 0.05). This increase was also observed for LCT plus heparin, but not after ASA alone. The percent increase in FBF during Ach was lowered during both LCT (252 +/- 34% of the ratio infused/control arm at maximal Ach dose) and MCT (255 +/- 41%) compared to the baseline conditions (436 +/- 44%; both P < 0.05). The response to Ach was also lower during LCT plus ASA, whereas it was similar to baseline with ASA alone. No differences were observed in the response to nitroprusside among the experimental conditions. In conclusion, 1) the effect of FFA on endothelium-dependent vasodilation is independent of their chain length; 2) both LCT and MCT increase baseline FBF, independently from cyclooxygenase inhibition; and 3) acute ASA administration does not affect endothelium-dependent vasodilation. The FFA effect on the endothelial response to Ach may contribute to altered endothelial function and, hence, to the development and progression of atherosclerotic cardiovascular disease.

Practice pattern and treatment options for kidney patients in a single North Italian nephrology center.

The experience and the current practice of a single center located in northern Italy is reported. The center of Vicenza is a self-standing nephrologic unit serving a population of about 300,000 individuals. The overall province counts approximately 800,000 individuals and some of them are referred to our center from peripheral hospitals for renal transplantation and/or particular pathologic conditions. The center offers an integrated approach to the treatment of uremia including hemodialysis (HD), peritoneal dialysis (PD), and renal transplantation. In HD and PD, the most peculiar aspect is the treatment personalization that leads to numerous types of applied therapies and technologies. The policy of the center is based on the belief that the nephrology team has a substantial influence on the outcomes of dialysis patients. A large number of treatment options are available. Special care is placed on the delivery of an adequate amount of dialysis, but the fractional clearance of urea in relation to volume (Kt/V) is seen as a prerequisite and other factors are considered important. Reduction in mortality and morbidity is largely dependent on beginning therapy early in the course of renal treatment. The attainment of appropriate hemoglobin concentrations, good nutrition, good control of calcium and phosphorus metabolism, lipids, and blood pressure, is considered of great importance. Beyond all these factors the time spent by the physician with the patient is considered one of the major factors influencing quality of care. The particularly low mortality of the center (6%/yr) may also be ascribed to a lower incidence of diabetes and other comorbidities.

Effects of interleukin-2 therapy on the proliferation and differentiation of CD4/CD25 positive and CD4/CD25 negative cells in HIV+ patients.

Interleukin-2 has been widely used in HIV-1+ subjects as an immunoactivating agent. In this study, we investigated cytokine production, Ki67 antigen expression and the modulation of the surface phenotype of the CD4/CD25+ subset as compared to the reciprocal CD4/CD25- subset in IL-2-treated HIV+ patients. Our findings suggest that CD4 T cells are heterogeneous in responding to IL-2, because CD4/CD25+ cells sharply increased their "memory" phenotype, their Ki67 antigen expression and were the main in vivo targets for IL-2-dependent proliferation during therapy, while the percentages of IFN-gamma+ (terminally differentiated) cells remained unchanged at the end of therapy. Conversely, the CD4+/CD25- subpopulation showed an expansion of differentiated cells and a slight increase in the proliferation rate. The use of anti-retroviral therapy alone (HAART) reduced the proliferation and increased the differentiation of both CD4 subsets. Our data suggest that IL-2 has a moderate capacity to activate resting T cells in vivo and is probably unable to boost HIV-1 from latency to the replicative state.

Analysis of outcome of pregnancy in type 1 diabetics treated with insulin pump or conventional insulin therapy.

We evaluated the outcome of pregnancies followed between 1990 and 2000 in 93 women with type 1 diabetes, treated with conventional intensive insulin therapy (n=68) or continuous subcutaneous insulin infusion (n=25). We evaluated metabolic control (fasting and 1-hour post-prandial plasma glucose and HbA1c levels), spontaneous or induced abortions, time and mode of delivery, maternal outcome (pregnancy-induced hypertension, preeclampsia, placental insufficiency, hydramnios, hypoglycemic coma, ketoacidosis) and fetal outcome (weight, hypoglycemia, hypocalcemia, hyperbilirubinemia, fetal distress, asphyxia, hyaline membrane disease, polycythemia, shoulder dystocia, malformations). Patients treated with insulin pump more frequently had background retinopathy and clinical neuropathy. No significant differences were observed between the two groups in metabolic control and maternal outcome. Glycemic control, non-optimal in the prepregnancy state, improved significantly during pregnancy, as shown by the progressive reduction in HbA1c levels. As regards fetal outcome, no differences were observed between the two groups in morbidity and especially in malformation rate. Patients with malformed babies did not have optimal metabolic control at conception. Thus, maternal and perinatal outcomes were comparable in patients treated with insulin pump and continuous subcutaneous insulin therapy, and depended on metabolic control. In patients in higher White's class and with more unstable glycemia, we achieved metabolic control and outcomes comparable with those of women of lower White's class and more stable glycemic values using the insulin pump. Our data suggest that insulin pump therapy is useful in problematic, complicated cases of women who want a baby.

Double pass dialysis: a new method of renal replacement in patients with malfunctioning vascular access.

Several patients undergoing chronic renal replacement therapy present problems related to their vascular access. Low blood flows and high rates of recirculation are common in such patients in which, for this reason, it becomes difficult to apply highly efficient techniques or techniques where diffusion and convection are combined as in hemodiafiltration. In these patients we studied the possibility of partially recirculating the blood in the extracorporeal circuit in order to increase the flow rate per single hollow fiber; we defined our system "double pass dialysis". We evaluated the system's efficiency in 12 patients during 24 dialysis sessions: 12 high flux dialysis sessions (without reinfusion) and 12 hemodiafiltration sessions (9 liters reinfusion). Different surfaces of polyacrylonitrile dialyzers were utilized (1.3-1.7-2.1 sqm) at 250 and 350 ml/min of blood flow with or without 100 ml/min of recirculation. During each dialysis session blood and dialysate samples were taken in order to calculate BUN, Creatinine, Phosphate and Inuline clearances from both the blood and dialysate side. The clearances of low molecular weight solutes were not really influenced by the artificial increase of the blood flow, but on the other hand, the clearances of higher molecular weight solutes increased from 10 to 30% during both high flux dialysis and hemodiafiltration with recirculation. This increase was evident mostly in hemodiafiltration suggesting that the cleaning effect on the membrane has a positive impact on the permeability. The good clinical results obtained with the double pass dialysis show that the system is safe and reliable and may become a valid support in critical situations in order to reach adequate dialysis treatment.

Impact of spacing filaments external to hollow fibers on dialysate flow distribution and dialyzer performance.

A new type of dialyzer (PAN 650 SF Asahi) is analyzed in terms of hydraulic properties, solute clearances and dialysate flow distribution. The new type of dialyzer is a polyacrylonitrile hollow fiber filter, equipped with spacing filaments placed externally to the fibers to facilitate dialysate distribution and avoid channeling. The new filter is compared with a similar filter without spacing filaments. For this purpose, blood and dialysate side clearances have been measured in sequential dialysis session carried out randomly in the same patients. Furthermore, a last generation helical scanner (X-Press/HS1, Toshiba) has been utilized to analyze in vitro the flow distribution of dialysate inside the dialyzer. A contrast medium was injected and a sequence of images has been achieved on a longitudinal section of the dialyzer. This new method permits to avoid any bias due to the cylindrical shape of the dialyzer, since a 10 mm thick rectangular section is analyzed and not the entire body of the filter. The dialyzers equipped with spacing filaments displayed a significant improvement of the dialysate distribution as demonstrated by the radiological pattern. In detail, despite a channeling phenomenon in the peripherical region of the bundle is still present, this is remarkably reduced in comparison with the channelling phenomenon observed in the standard dialyzers. This improved distribution is confirmed by a significant improvement of the solute clearances.

Ultrafiltration and pressure profiles in continuous arterio-venous hemofiltration studied by computerized scintigraphic imaging.

Clotting of the filters in continuous arterio-venous hemofiltration (CAVH) has been frequently related to filtration pressure equilibrium (FPE). The geometry of the filter and the blood flow, together with filtration fraction, are the factors affecting FPE. A new method based on scintigraphic imaging of the filter is described to demonstrate FPE and identify the operational conditions influencing it. A radiolabelled marker molecule (albumin macroaggregates + Tc99) is added to the blood circulating at various flows through the filter. Changes in the concentration of this molecule detected by a gamma camera are used to calculate the water fluxes in different sections of the filter. When the curve reaches a plateau, no further changes occur and FPE is achieved. The study used Amicon D-30 hemofilters and FPE points were achieved for blood flows of 75, 110 and 150 ml/min respectively 8 cm, 12 cm and 18 cm from the inlet. The study not only demonstrates the occurrence of FPE, but also identifies the length of the filter required at a given blood flow to avoid FPE (achieving less clotting and lower heparin requirement). The Amicon diafilter family, having filters of different length, is useful for "personalizing" the filter in CAVH.

Technical and clinical evaluation of a new asymmetric polysulfone membrane (Biosulfane).

First generation asymmetric polysulfone membranes had high hydraulic permeability (kf = 40 ml/h/mmHg/sqm) but a low diffusive permeability due to the hydrophobic nature and wall thickness of 75-100 microns. We have tested a new polysulfone membrane with a wall thickness of 40 microns in a series of in vitro and in vivo dialysis session experiments. The new "Biosulfane" membrane presented a Kf of 45.8 with constant performance up to 240 mins. The koA was 760 and the clearance value at 350 ml/min of Qb in hemodiafiltration was 255 ml/min for urea, 210 for creatinine, 225 for phosphate, 76 for inulin. In high flux dialysis the clearances were similar except for inulin which was 32% lower due to the lower convection amount. Beta-2 microglobulin clearance was 22 ml/min in high flux dialysis and 37 in hemodiafiltration. Solute sieving coefficients were close to 1 for the majority of the studied solutes in a wide range of molecular weights and slight variations were observed for charged solutes due to Donnan's effect. The sieving for Inulin was 0.96 while that for Beta-2 microglobulin was not measurable due to a large molecule adsorption on the inner structure of the fibres. The good performances of this membrane are probably due to reduced wall thickness and a consequent improvement in diffusive permeability to small size solutes.