The Clinical Impact of Increasing the Hemodialysis Dose

Good evidence suggests that improvements in dialysis efficiency reduce morbidity and mortality of hemodialysis (HD) patients. Dialysis efficiency has also been related to better control of arterial blood pressure (BP), anemia, and serum phosphorus levels, and to improvement in patients' nutritional status. Over a 2‐year period, the present self‐controlled study of 34 HD patients (23 men, 11 women; age, 52.6 ± 14.5 years; HD duration, 55.9 ± 61.2 months) looked at the effect on clinical and laboratory parameters of increasing the delivered dialysis dose under a strict dry‐weight policy. Dialysis dose was increased without increasing dialysis time and frequency. A statistically significant increase was seen in delivered HD dose: the urea reduction ratio (URR) increased to 60% ± 10% from 52% ± 8%, and then to 71% ± 7% (p < 0.001); Kt/V_urea increased to 1.22 ± 0.28 from 0.93 ± 0.19, and then to 1.55 ± 0.29 (p < 0.001). A statistically significant increase in hemoglobin concentration also occurred—to 10.8 ± 1.9 g/dL from 10.4 ± 1.7 g/dL, and then to 11.0 ± 1.3 g/dL (p < 0.05 as compared to baseline)—with no significant difference in weekly erythropoietin dose. Statistically significant decreases occurred in the systolic and diastolic blood pressures during the first year; they then remained unchanged. Systolic blood pressure decreased to 131 ± 23 mmHg from 147 ± 24 mmHg (p < 0.001); diastolic blood pressure decreased to 65 ± 11 mmHg from 73 ± 12 mmHg (p < 0.001). Serum albumin increased insignificantly to 4.4 ± 0.4 g/dL from 4.3 ± 0.4 g/dL, and then significantly to 4.6 ± 0.3 g/dL (p = 0.002 as compared to both previous values). Normalized protein catabolic rate increased significantly to 1.16 ± 0.15 g/kg/day from 0.93 ± 0.16 g/kg/ day (p < 0.001), and then to 1.20 ± 0.17 g/kg/day (p < 0.001 as compared to baseline). We conclude that the increases achieved in average Kt/V_urea per hemodialysis session by increasing dialyzer membrane area, and blood and dialysate flows, without increasing dialysis time above 4 hours, in patients hemodialyzed thrice weekly, coupled with strict dry‐weight policy, resulted in improvements in hypertension, nutritional status, and anemia.     

HCO3 increment in arterial line can reveal significant vascular access recirculation in high-flux hemodialysis: a preliminary report

We report a new and simple way that can reveal the presence of vascular access recirculation (VAR) in patients undergoing hemodialysis (HD). Acid-base and blood gas parameters (pH, pO(2), pCO(2), and HCO(3)) were measured in blood samples drawn from an arterial fistula needle before the initiation of HD and from arterial and venous lines simultaneously 5 min later, in 31 patients (group A). Vascular access recirculation was measured using the glucose infusion test (GIT) immediately after the withdrawal of the 5-min samples. The same study was repeated in 30 patients in whom HD lines were reversed (group B). A comparison with baseline (predialysis) values of an analysis of the arterial line in group A at 5 min revealed that pCO(2) increased by 1.14+/-2.5 mmHg and HCO(3) by 0.6+/-0.6 mM/L (p<0.02 and p<0.00001, respectively). The corresponding pO(2) and pH values did not show significant differences. Glucose infusion test at 5 min (GITa) was -0.058+/-0.03%. A comparison with baseline (predialysis) values of an analysis of the arterial line in group B at 5 min revealed that pCO(2) increased by 7.7+/-3.5 mmHg and HCO(3) by 2.9+/-1.0 mM/L (p<0.000001 in each case). The pH level was significantly lower in comparison with baseline values (p<0.00001), while pO(2) did not show a significant difference. Glucose infusion test at 5 min (GITb) was 12.0+/-6.1% (p<0.000001 in comparison with GITa values). Clinically significant VAR was defined as HCO(3) increment >1.8 mM/L, based on the receiver-operating characteristics curve, which showed a threshold value of HCO(3) increment >1.8 mmol/L as a predictor of GIT recirculation. Five minutes after the initiation of high-flux HD with a 0 ultrafiltration rate, there is a small increment in arterial HCO(3) values relative to predialysis values. Clinically significant VAR is present when this increment is higher than 1.8 mM/L.     

Longitudinal micro-incision creation prior to balloon angioplasty for treatment of arteriovenous access dysfunction in a real-world patient population: 6-month cohort analysis

Introduction

Routine hemodialysis depends on well-functioning vascular access. In the event of vascular access dysfunction, percutaneous transluminal balloon angioplasty (PTA) is conducted to restore patency. Although an angioplasty procedure can provide an excellent immediate result by opening the access to allow dialysis to continue, the long-term patency rates are less than satisfactory. The goal of this study was to assess the outcomes of patients who underwent a novel vessel preparation via longitudinal, controlled-depth micro-incisions prior to PTA.

Methods

This multicenter, prospective, observational registry enrolled hemodialysis patients scheduled to undergo PTA of their arteriovenous fistula or graft due to clinical or hemodynamic abnormalities. A primary endpoint was anatomic success, defined as angiographic confirmation of <30% residual stenosis post-procedure without an adverse event. Additional assessments included device technical success, clinical success, freedom from target lesion revascularization, target lesion primary patency, and circuit primary patency at 6 months.

Findings

A total of 148 lesions were treated with the FLEX Vessel Prep™ System (FLEX VP) prior to PTA in 114 subjects at eight clinical sites. Target lesions were 21 ± 25 mm in length with mean pre-procedure stenosis of 75.2% ± 4.7%. Five procedural complications were recorded without serious adverse events. Two subjects did not complete the follow-up evaluation. Target lesion primary patency across all subjects at 6-months was 62.2% with mean freedom from target lesion revascularization of 202.7 days. Target lesion primary patency and freedom from target lesion revascularization for AVF cases (n = 72) were 67.5% and 212.9 days, respectively. Target lesion primary patency and freedom from target lesion revascularization for AVGs (n = 42) were 52.4% and 183.3 days, respectively. In cases treating AVF cephalic arch stenosis (n = 25), 6-month target lesion primary patency was 70.6% and freedom from target lesion revascularization was 213.4 days.

Discussion

This FLEX-AV registry demonstrates safety and effectiveness, notably in the cephalic arch and AVGs, when FLEX VP is used prior to PTA for treatment of vascular access dysfunction in a population of end-stage renal disease subjects.     

Outcomes of Severe Methanol Intoxication Treated with Hemodialysis: Report of Seven Cases and Review of Literature

To identify factors associated with the outcome of severe methanol intoxication treated with hemodialysis, we analyzed the clinical course of 7 patients admitted with serum methanol level higher than 50 mg/dL, and therefore requiring hemodialysis. Four patients (group A) had adverse outcomes (1 death, 3 severe neurological deficits and/or blindness) and 3 patients (group B) had no adverse outcomes. Compared to group B, group A appeared to have a longer delay between ingestion of methanol and arrival at the emergency department (ED), a longer wait in the ED until ethanol infusion was started (3.6 ± 2.7 vs 1.3 ± 0.9 hr, p < 0.05), and, on admission, higher serum methanol (504 ± 219 vs 321 ± 228 mg/dL, p < 0.05), higher serum osmolality (460.5 ± 98.2 vs 397.6 ± 52.3 mOsm/kg, p < 0.05), higher serum osmolal gap (162.6 ± 76.7 vs 105.6 ± 52.9 mOsm/kg, p < 0.05), lower arterial pH (6.86 ± 0.08 vs 7.38 ± 0.16, p < 0.01), lower serum bicarbonate (4.6 ± 1.6 vs 19.9 ± 5.7 mmol/L, p < 0.01), and higher serum anion gap (36.5 ± 1.3 vs 14.3 ± 6.7 mEq/L, p < 0.01). Delay in the ED until hemodialysis was started did not differ (group A 6.4 ± 2.6 hr, group B 5.3 ± 3.5 hr), while duration of hemodialysis until serum methanol levels became permanently undetectable was longer in group A (15.0 ± 0.5 vs 8.4 ± 4.4 hr, p < 0.01). The ingested dose of methanol and the delay between ingestion and initiation of therapy to block methanol metabolism (ethanol infusion) and remove methanol from the body (hemodialysis) appear to be the critical factors influencing the outcome of methanol intoxication. Early diagnosis and initiation of treatment before substantial parts of the ingested methanol have been metabolized are of paramount importance in ensuring a favorable outcome.     

Regional Anticoagulation with Sodium Citrate in Pediatric Patients on Intermittent Hemodialysis Therapy with Bleeding Risks

Heparin‐free anticoagulation in hemodialysis (HD) is advocated for patients with clotting abnormalities and risk of bleeding. Objective: First publication on regional citrate anticoagulation (RCA) in children. RCA is free from systemic effects, guarantees excellent dialyzer life, but requires careful monitoring. Methods: We report on 3 patients treated by intermittent RCA HD (4 h each, high‐flux dialyzer F40, Fresenius): (1) 17‐year‐old boy (renal transplant failure, access via cubital Cimino fistula) after hypertensive intra‐cerebral hemorrhage (2 sessions); (2) 13‐year‐old girl (hemolytic uremic syndrome, access via jugular vein Shaldon catheter) after abdominal surgery and bleeding (8 sessions); and (3) 7‐year‐old boy (hyperoxaluria, access via PermCath^® jugular vein catheter) after renal transplant biopsy (3 sessions). Sodium citrate 30% was infused into the extra corporeal circuit (blood flow 150 mL/min) before dialyzer (initial flow 30 mL/min) and calcium gluconate 10% for antidote into venous line near of catheter or fistula (initial flow 40 mL/min). Post‐dialyzer extracorporeal serum Ca⁺⁺ (aim < 0.3 mmol/L) and pre‐dialyzer intra‐corporeal Ca⁺⁺ (aim > 0.9) were measured for every 30 min. Serum Na⁺, K⁺, base excess (BE), blood flow, blood pressure, heart rate, and blood out‐flow and in‐flow pressure were also monitored. Results: For adequate RCA (mean extracorporeal serum Ca⁺⁺ 0.24 ± 0.04 mmol/L), a mean citrate flow of 36.1 ± 5.9 mL/h and a mean calcium substitution rate of 40.8 ± 3.4 mL/h were needed. Intra‐corporeal Ca⁺⁺ was kept at 1.10 ± 0.07 mmol/L. Extracorporeal activated clotting time (ACT) was 194 ± 41 and intra‐corporeal ACT 90 ± 12 sec. Serum Na⁺, K⁺, and BE during HD were 138 ± 2, 3.5 ± 0.3, and ?0.6 ± 1.1 mmol/L, respectively. Mean arterial blood pressures of patients 1–3 were 117 ± 5, 103 ± 5, and 102 ± 6 mmHg. All patients were stable and without any bleeding during HD. The only adverse event was 1 episode of hypocalcemia (Ca⁺⁺ < 0.6 mmol/L) cured by stopping dialysis. Conclusions: Local anticoagulation with sodium citrate during intermittent HD can be applied safely in children and adolescents.     

Sigma-2 receptor ligand anchored telmisartan loaded nanostructured lipid particles augmented drug delivery,cytotoxicity, apoptosis and cellular uptake in prostate cancer cells

Recently, the anticancer activity of telmisartan (TEL) has been discovered against prostate cancer. Nevertheless, despite favorable therapeutic profile, poor aqueous solubility and suboptimal oral bioavailability hamper the anticancer efficacy of TEL. Therefore, in this investigation, sigma-2 receptor ligand, 3-(4-cyclohexylpiperazine-1-yl) propyl amine (CPPA) anchored nanostructured lipid particles of telmisartan (CPPA-TEL-NLPs) were engineered using stearic acid for targeting prostate cancer, PC-3 cells. The mean particle size of TEL-NLPs was measured to be 25.4?±?3.2?nm, significantly (p?p?p?In vitro drug release study was conducted to determine the drug delivery potential of tailored nanoparticles. TEL-NLPs released 93.36% of drug significantly (p?50 of CPPA-TEL-NLPs was measured to be 20.3?µM significantly (p?50 of 41.3?µM, significantly (p?>?0.05) not different from 43.4?µM, exhibited by TEL-NLPs in PNT-2 cells. We elucidated that CPPA-TEL-NLPs entered the PC-3 cells via receptor mediated endocytosis pathway and thus exhibited superior cytotoxicity, apoptosis and greater extent of cellular uptake in PC-3 cells. In conclusion, CPPA-TEL-NLPs may be a promising nanomedicine and warrant further in vivo investigations for gaining clinical success.     

Long-term patency of arteriovenous fistulas for hemodialysis: A decade's experience in a transplant unit

Background

The heterogeneous quality of studies on arteriovenous fistulas outcome, with variable clinical settings and large variations in definitions of patency and failure rates, leads to frequent misinterpretations and overestimation of arteriovenous fistula patency. Hence, this study aimed to provide realistic and clinically relevant long-term arteriovenous fistula outcomes.

Methods

We retrospectively analyzed all autologous arteriovenous fistulas at our center over a 10-year period (2012–2022). Primary and secondary patency analysis was conducted using the Kaplan–Meier method; multivariate analysis of variance was used to detect outcome predictors. Vascular access-specific endpoints were defined according to the European guidelines on vascular access formation.

Findings

Of 312 arteriovenous fistulas, 57.5% (n = 181) were radio-cephalic (RC_AVF), 35.2% (n = 111) brachio-cephalic (BC_AVF), and 6.3% (n = 20) brachio-basilic (BB_AVF). 6, 12, and 24 months follow-up was available in 290 (92.1%), 282 (89.5%), and 259 (82.2%) patients, respectively. Primary patency rates at 6, 12, and 24 months were 39.5%, 34.8%, and 27.2% for RC_AVF, 58.3%, 44.4%, and 27.8% for BC_AVF, and 40.0%, 42.1%, and 22.2% for BB_AVF (p = 0.15). Secondary patency rates at 6, 12, and 24 months were 65.7%, 63.8%, and 59.0% for RC_AVF, 77.7%, 72.0%, and 59.6% for BC_AVF, and 65.0%, 68.4%, and 61.1% for BB_AVF (p = 0.29). Factors associated with lower primary and secondary patency were hemodialysis at time of arteriovenous fistula formation (p = 0.037 and p = 0.024, respectively) and higher Charlson Comorbidity Index (p = 0.036 and p < 0.001, respectively). Previous kidney transplant showed inferior primary patency (p = 0.005); higher age inferior secondary patency (p < 0.001).

Discussion

Vascular access care remains challenging and salvage interventions are often needed to achieve maturation or maintain patency. Strict adherence to standardized outcome reporting in vascular access surgery paints a more realistic picture of arteriovenous fistula patency and enables reliable intercenter comparison.     

Improved nursing home end-stage renal disease patient participation in physical therapy with onsite,more frequent dialysis

Introduction

For end-stage renal disease (ESRD) patients residing in skilled nursing facilities (SNFs), the logistics and physical exhaustion of life-saving hemodialysis therapy often conflict with rehabilitation goals. Integration of dialysis care with rehabilitation programs in a scalable and cost-efficient manner has been a significant challenge. SNF-resident ESRD patients receiving onsite, more frequent hemodialysis (MFD) have reported rapid post-dialysis recovery. We examined whether such patients have improved Physical Therapy (PT) participation.

Methods

We conducted a retrospective electronic medical records review of SNF-resident PT participation rates within a multistate provider of SNF rehabilitation care from January 1, 2022 to June 1, 2022. We compared three groups: ESRD patients receiving onsite MFD (Onsite-MFD), ESRD patients receiving offsite, conventional 3×/week dialysis (Offsite-Conventional-HD), and the general non-ESRD SNF rehabilitation population (Non-ESRD). We evaluated physical therapy participation rates based on a predefined metric of missed or shortened (<15 min) therapy days. Baseline demographics and functional status were assessed.

Findings

Ninety-two Onsite-MFD had 2084 PT sessions scheduled, 12,916 Non-ESRD had 225,496 PT sessions scheduled, and 562 Offsite-Conventional-HD had 9082 PT sessions scheduled. In mixed model logistic regression, Onsite-MFD achieved higher PT participation rates than Offsite-Conventional-HD (odds ratio: 1.8, CI: 1.1–3.0; p < 0.03), and Onsite-MFD achieved equivalent PT participation rates to Non-ESRD (odds ratio: 1.2, CI: 0.3–1.9; p < 0.46). Baseline mean ± SD Charlson Comorbidity score was significantly higher in Onsite-MFD (4.9 ± 2.0) and Offsite-Conventional-HD (4.9 ± 1.8) versus Non-ESRD (2.6 ± 2.0; p < 0.001). Baseline mean self-care and mobility scores were significantly lower in Onsite-MFD versus Non-ESRD or Offsite-Conventional-HD.

Discussion

SNF-resident ESRD patients receiving MFD colocated with rehabilitation had higher PT participation rates than those conventionally dialyzed offsite and equivalent PT participation rates to the non-ESRD SNF-rehabilitation general population, despite being sicker, less independent, and less mobile. We report a scalable program integrating dialysis and rehabilitation care as a potential solution for ESRD patients recovering from acute hospitalization.     

Role of bicarbonate dialysis in prevention of serious arrhythmias in high‐risk cardiac patients undergoing regular hemodialysis

Background: Cardiac arrhythmias are considered as one of the most important causes of mortality in patients on hemodialysis. Arrhythmias frequently occur in patients with chronic renal failure on regular hemodialysis with reported incidences varying from 30–48% of patients. These abnormalities can span from supraventricular to severe ventricular arrhythmia. There is an increased frequency of occurrence and clustering of arrhythmias around the dialysis time. Aim of the study: To detect the difference between acetate and bicarbonate dialysis as regard to the type and frequency of arrhythmia in those patients. Study design: This study was done on 20 male patients age 51–73, all have history of heart disease. Patients were divided into 2 equal groups using acetate in group 1 and bicarbonate in group 2. All patients were on regular hemodialysis (4 hours, thrice weekly). Careful history and clinical examination were done. Pre‐dialysis investigations included serum creatinine, blood urea nitrogen, serum sodium, potassium, calcium and phosphorus, serum albumin, hemoglobin, and arterial blood gases. Post‐dialysis serum potassium and arterial blood gases were measured. ECG and forty‐eight hours ambulatory monitor (Holter monitor)(before, during, and after hemodialysis, till the end of the dialysis day and throughout the following day) were performed. Results: Group 1 showed significantly less post‐dialysis supraventricular arrhythmias than in dialysis day (210.9 ± 236 and 62.3 ± 14.4), respectively. Significantly less ventricular arrhythmias in post‐dialysis than in dialysis day (30.7 ± 50.4, and 106.2 ± 128.4), respectively. While in Group 2 there were insignificant differences regarding supraventricular arrhythmias (21.9 ± 28.9 and 16.6 ± 36.3) and ventricular arrhythmias (22.9 + 7.8 and 29.6 + 12.8) in dialysis day than in post‐dialysis day. There was significantly higher frequency of supraventricular and ventricular arrhythmias in the dialysis day in acetate hemodialysis in comparison to bicarbonate hemodialysis. Conclusion: Bicarbonate hemodialysis is less arrhythmogenic in comparison to acetate hemodialysis and has better effect on the blood pH and greater degree of base repletion. Continuous ambulatory ECG recording (Holter) is a useful tool in detecting arrhythmias in dialysis patients.     

Phosphorus Clearance Using Two Hemodialyzers Placed in Parallel

Control of hyperphosphatemia is a major goal in patients with end‐stage renal disease. However, removal of retained inorganic phosphorus during hemodialysis remains a major problem. We compared clearances and total phosphate removal in large patients treated with two F‐80 dialyzers (Fresenius Medical Care of North America, Lexington, MA, U.S.A.) placed in parallel, and small patients dialyzed with a single F‐80 dialyzer (SD). Clearances were obtained using total dialysate collections. Eight dialysate collections (5 patients) using double parallel dialyzers (DD group) were compared with 5 dialysate collections (4 patients) using single dialyzers (SD group). Blood and dialysate flow rates and time of dialysis treatment were identical between the groups. The DD group's Kt/V _urea was 1.46 ± 0.13; SD group's Kt/V _urea was 1.35 ± 0.09 (p = 0.2). Absolute phosphorus removal was 1594 ± 300 mg for the DD group, compared to 1108 ± 285 mg in the SD group (p = 0.03). Urea clearance in the DD group was 285 ± 25 mL/minute and 251 ± 27 mL/ min in the SD group (p = 0.082). Phosphorus clearance was 178 ± 32 mL/min in the DD group and 149 ± 38 mL/min in the SD group (p = 0.039). There was no correlation between phosphorus clearance and dialyzer reuse. The bulk of phosphorus removal was achieved during the first 2 hours of hemodialysis. This finding is consistent with the hypothesis that there are at least two pools of body phosphorus. Using hemodialyzers placed in parallel led to higher phosphate clearance and total phosphorus removal. This higher phosphate removal may be related in part to increasing the concentration gradient for transfer out of a second compartment.     

Long-Term Transport Study of Bioartificial Tubule Devices in the Development of a Bioartificial Kidney

Introduction: A bioartificial kidney, which consists of a continuous hemofilter and a bioartificial tubule device using proximal tubular epithelial cells (LLC‐PK₁), is desired to develop for preventing long‐term complications in hemodialysis patients. A bioartificial tubule device should function for a long duration in terms of the simplicity and the economy. Continuous hemofiltration with 10 L/day of filtrate could maintain plasma urea, creatinine and β₂‐microglobulin in patients at low levels compared to those in standard hemodialysis patients. Methods: 6 bioartificial tubule devices, in which LLC‐PK₁ cells were grown on the inner surfaces of hollow fiber capillaries (membrane area: 0.4 m², 1600 fibers), were used to evaluate the transport ability of H₂O, glucose and Na⁺, and leak rates of urea and creatinine for 2 weeks when the medium containing 50 mg/dL of urea and 5.0 mg/dL of creatinine was perfused inside of the cell‐attached membranes and another medium containing 2.5 g/dL of albumin was perfused outside of the membranes. Scanning electron micrograph of cross‐sectional findings of the hollow fibers was taken at 6, 10, and 14 days after formation of confluence. Results: By conversion into 1 m² of membrane area, transport of H₂O, glucose, and Na⁺ was 6266 ± 995 mL/day, 22832 ± 7240 mg/day, and 941.3 ± 180 mEq/day, respectively at 6 days after confluence. Leak rates of urea and creatinine across the cell‐attached membranes were 22 ± 6.1% and 19.2 ± 4.9 with albumin addition, whereas 13.1 ± 1.9% and 12.2 ± 1.6 without albumin addition. Transport capacity of these components and the leak rates had continued for 10–13 days, and decreased thereafter because of the formation of the multilayers. Bioartificial tubule devices with membrane area 1.0 m² can reach the targeted amounts of H₂O, glucose, and Na⁺ transports when 6 L of 10 L/day of hemofiltrate has to be regenerated, substituting 4 L with meal and drinks.     

Interaction of hydrogen with the intermetallic compound Nd<Subscript>2</Subscript>Fe<Subscript>17</Subscript> studied by calorimetry

Interaction of hydrogen with the intermetallic compound Nd₂Fe₁₇ has been studied for the first time by calorimetry using a differential heat conduction calorimeter coupled to a Sieverts apparatus. Hydrogen absorption and desorption reactions were run at 200°C, and two types of data were obtained: p–C–T and ΔH–C–T (where p is the equilibrium hydrogen pressure, C = H/Nd₂Fe₁₇, ΔH is the reaction enthalpy, and T is the measurement temperature). The p–C–T curves obtained for the hydrogen absorption and desorption processes have no plateau or two-phase region, in contrast to what is characteristic of the formation of a hydride phase. At the same time, the ΔH(C) curves have a few portions where the enthalpy of reaction between hydrogen and the intermetallic compound remains constant: 0 < C < 2.0, with ΔH _abs =–85.05 ± 0.65 kJ/mol H ₂; 2.0 < C < 2.7, with ΔH _abs =–80.64 ± 1.00 kJ/mol H₂; and 1.9 < C < 2.7, with ΔH _des = 76.48 ± 0.85 kJ/mol H₂. The data obtained in this study suggest that positions 9e and 18g in the intermetallic compound are occupied by hydrogen in a particular order.     

Disproportionation of Pu(V) in K<Subscript>10</Subscript>P<Subscript>2</Subscript>W<Subscript>17</Subscript>O<Subscript>61</Subscript> solutions

In solutions of unsaturated heteropolytungstate K₁₀P₂W₁₇O₆₁, Pu(V) disproportionates in a wide pH range; it is a first-order reaction with respect to Pu(V), and its rate only slightly changes in the pH range from 0.7 to 4.0. The activation energy E _a of Pu(V) disproportionation was determined as 78.6±2.0 and 64.2±3 kJ mol^?1 at pH 2.0±0.1 and 4.0±0.2, respectively. The thermodynamic parameters of activation ΔH ^≠ and ΔS ^≠ were evaluated. Published data on disproportionation of Np(V) and Am(V) in K₁₀P₂W₁₇O₆₁ solutions were analyzed.     

Unphysiology Is the Major Factor Influencing Cardiovascular Instability during Hemodialysis

Background: Hemodialysis is often complicated by cardiovascular instability (CVI). We studied factors contributing to this problem during 720 hemodialyses (HDs) in 20 patients; 480 dialyses were 6/week and 240 were 3/week. Methods: Dependent variables were increase in pulse rate (PR) and maximal (MAX) and overall (OV) fall of systolic blood pressure (BP). Independent variables were dialyses/week (DIAL), ultrafiltration (Uf), % of body weight (BW), pre‐post BUN (ΔBUN), time on dialysis (T), speed of dialysis (K/V in mL min^–1 kg^–1 BW), target‐postdialysis BW (Ta‐Po BW), Kt/V, ΔPO4, Δbicarbonate, Δpotassium, ΔBUN, an ‘unphysiology index’ summing up changes in electrolytes, and BUN and BW during dialysis (UPI). The relations were analyzed by backward multiple regression analysis. Results: PR increased 0.5 ± 11/min; MAX BP fall was 23 ± 17 mmHg; OV BP fall was 12 ± 19 mmHg. In multiple stepwise backward regression analysis, independents in order of importance: PR = 38 – DIAL × 4 + T × 0.1 + Uf × 1.8 +ΔPO4 × 1.8 – UPI× 0.2 – K/V × 2, r = 0.30, p < 0.0001; MAX BP = UPI × 0.4 – ΔBUN × 0.3 + ΔPO4 × 2.6 + 11, r = 0.34, p < 0.0001; OV BP = UPI × 0.4 – ΔBUN × 0.3 +ΔPO4 × 2.7 + 1, r = 0.33, p < 0.0001. Conclusion: To prevent BP fall and tachycardia during hemodialysis, the most important factor to decrease is unphysiology, i.e., the oscillations in electrolytes, fluid spaces, and osmolality that occur during dialysis. The best way to do this is to dialyze patients daily. An unexpected finding worthy of further investigation was the large detrimental influence of ΔPO4 on CVI.     

High–temperature phase chemistry of the system Gd–Pd–O

Anisothermal sectionof the phase diagram for the system Gd–Pd–O at 1223 K has been established by equilibrationof samples and phase identification after quenching by optical and scanning electron microscopy, X–ray powder diffraction, and energy dispersive spectroscopy. Three ternary oxides Gd₄PdO₇,Gd₂PdO₄ and Gd₂Pd₂O₅ were identified. Liquid alloys, the four inter–metallic compounds and Pd–rich solid solutionwere found to be inequilibrium with Gd₂O₃.

Based on the phase relations, four solid–state cells were designed to measure the Gibbs energies of formation of the three ternary oxides in the temperature range from 920 to 1320 K. Although three cells are sufficient to obtain the properties of the three compounds, the fourth cell was deployed to cross check the data. An advanced version of the solid–state cell incorporating a buffer electrode with yttria–stabilized zirconia solid electrolyte and pure oxygen gas at a pressure of 0.1 MPa as the reference electrode was used for high–temperature thermodynamic measurements. The standard Gibbs energy of formation of the inter–oxide compounds from their component binary oxides can be represented by the following equations:

Gd₄PdO₇(s) : Δ_f(ox)G⁰/J mol^–1 = –25,030 + 0.33T (±140), Gd₂PdO₄(s) : Δf(ox)_f(ox)G⁰/J mol^–1 = –25,350 + 0.84T (±135), Gd₂Pd₂O₅(s) : Δf(ox)_f(ox)G⁰/J mol^–1 = –48,700 + 0.38T (±270)

Based on the thermodynamic information, isothermal chemical potential diagrams and isobaric phase diagrams for the system Gd–Pd–O are developed.     

Application of Flow-Through Dissolution Method for the Evaluation of Oral Formulations of Nifedipine

Abstract

The drug release characteristics of three oral formulations (one conventional and 2 extended-release) of nifedipine were evaluated using a flow-through apparatus. The experiments were conducted for 4 to 24 hours using water or phosphate buffer (0.05 or 0.1 M; pH 7.4) with or without solubilizing agent, Tween, as a dissolution medium at a flow rate of 12.5 mL/min. The drug concentrations were determined using an HPLC method based on ratios of peak heights corresponding to UV absorbances at 254 nm for nifedipine and nitrendipine (internal standard). Dissolution characteristics in various media correspond to the nifedipine solubility in the medium. Peak nifedipine concentrations with 0.05 M phosphate buffer containing 0.5% Tween were significantly higher than those in the medium without Tween (21.5±1.0 vs 8.3±0.2 μg/mL, p c 0.001). Using a 0.05 M phosphate buffer with no Tween, the products tested showed distinct dissolution profiles representative of the respective formulation type. The conventional release product (10 mg) showed a higher mean peak nifedipine concentration (C_max,d) of 49.5±2.4 pg/mL (p < 0.001) attained at (t_max,d) 0.46±0.05 h as compared to those of modified-release products. The corresponding mean values for the modified-release tablets were 8.3±0.2 and 2.6±.3 μg/mL for C_max,d, and 0.28±0.03 and 12.0±3.8 h for t_max,d for the 20 and 30 mg tablets, respectively. Area under the concentration-time curves (AUC_o-t,d) for the 10, 20 and 30 mg formulations were 12.3±0.4,20.5±2.6 and 32.6±3.7 μg.h/mL, respectively (p < 0.001). As the dissolution profiles are similar to those of plasmakerum drug concentrations-time profiles obtained from clinical studies, application of this dissolution method, along with the derived in vitro drug-release kinetics parameters for potential correlation with in vivo parameters are discussed. The results of this study show that, compared to the USP dissolution method using apparatus 1 or 2, the flow-through dissolution system offers a potentially better alternative to assess drug release characteristics for different types of formulations, especially for drugs of low aqueous solubility such as nifedipine.     

Non-isothermal crystallization of As2Se3 glass

The results of non-isothermal crystallization studies performed at different heating rates on batches of As₂Se₃ glasses prepared from melts at 400°C, 600°C and 800°C are reported. The peak temperature of crystallizationT _p, the enthalpy of crystallization ΔH _c and the activation energy for crystallizationE _c are independent of the melt temperature used in the preparation. Bulk nucleation with three-dimensional growth of crystals is indicated for As₂Se₃. The values of ΔH _c andE _c are found to be respectively 23·3 ± 0·9 cal/g and 36·5 ± 0·9 kcal/mol for As₂Se₃.     

Stimulated sweating as a therapy to reduce interdialytic weight gain and improve potassium balance in chronic hemodialysis patients: A pilot study

Controlling the extracellular volume in hemodialysis patients is a difficult task. The aim of this study was to evaluate the capacity of different methods of stimulated sweating to reduce mean interdialytic weight gain (IWG), to improve blood pressure regulation, and potassium/urea balance. Two center, crossover pilot study. In Lausanne, hemodialysis patients took four hot‐water baths a week, 30 minutes each, on nondialysis days during 1 month. In Sfax, patients visited the local Hammam Center four times a week. Hemodynamic parameters were recorded, and weekly laboratory analysis was performed. Results were compared with a preceding 1‐month control period. In Lausanne, five patients (all men, median age 55 years) participated. Bathing temperature was (mean ± standard deviation) 41.2 ± 3°C and sweating‐induced weight loss 600 ± 500 g. Mean IWG (control vs. intervention period) decreased from 2.3 ± 0.9 to 1.8 ± 1 kg (P = 0.004), Systolic blood pressure from 139 ± 21 to 136 ± 22 mmHg (P = 0.4), and diastolic blood pressure form 79 ± 12 to 75 ± 13 mmHg (P = 0.08); antihypertensive therapy could be reduced from 2.8 ± 0.4 to 1.9 ± 0.5 antihypertensive drugs per patient (P = 0.01). In Sfax (n = 9, median age 46 years), weight loss per Hammam session was 420 ± 100 g. No differences were found in IWG or BP, but predialysis serum potassium level decreased from 5.9 ± 0.8 to 5.5 ± 0.9 mmol/L (P = 0.04) and urea from 26.9 ± 6 to 23.1 ± 6 mmol/L (P = 0.02). Hot‐water baths appear to be a safe way to reduce IWG in selected hemodialysis patients. Hammam visits reduce serum potassium and urea levels, but not IWG. More data in larger patient groups are necessary before definite conclusion can be drawn.     

Hemodialysis decreases carotid‐brachial and carotid‐femoral pulse wave velocities: A 5‐year follow‐up study

Aortic stiffness is a prognostic parameter associated with patient mortality. Vascular access creation has been shown to have effects on arterial stiffness both in the aorta and in the upper limb arteries in chronically hemodialyzed patients (CHPs). However, no longitudinal studies have been conducted in order to characterize the evolution of arterial stiffness in CHPs. The aims of this work were (a) to measure baseline pulse wave velocity (PWV) in the carotid‐femoral and in right and left carotid‐brachial pathways in a cohort of CHP and (b) to conduct a 5‐year prospective study on the same cohort to determine possible time‐related differences. Pulse wave velocity was measured both in the carotid‐femoral and in the carotid‐brachial pathways, and clinical and biochemical parameters were collected in 25 CHPs, which were followed up after a 5‐year lapse. Right and left carotid‐brachial pathway PWV values showed significant decreases after the 5‐year follow‐up, independently of the presence of the vascular access (P < 0.001). Additionally, baseline carotid‐brachial PWV was significantly higher (P < 0.001) than values measured 5 years later for upper limbs with vascular access (11.97 ± 2.97 m/sec vs. 6.76 ± 1.48 m/sec, respectively) and without vascular access (12.25 ± 2.38 m/sec vs. 7.18 ± 1.88 m/sec, respectively). Similarly, PWV values in the carotid‐femoral pathway decreased significantly (P < 0.001) over the same period (13.27 ± 2.96 m/sec vs. 9.75 ± 2.99 m/sec, respectively). The 5‐year follow‐up of PWV showed significant decreases in both carotid‐brachial and carotid‐femoral pathways. The general changes in arterial stiffness could be related to the vascular access creation, hemodialysis therapy, and to the improvement of arterial pressure management.