First-principles evaluation of dopant impact on structural deformability and processability of Li7La3Zr2O12.

Li7La3Zr2O12 (LLZO) and related ceramic solid electrolytes feature excellent stability and reasonable ionic conductivity, but processing remains challenging. High-temperature co-sintering is required for successful integration with the electrode, which is energetically costly and can lead to unacceptable cathode degradation. The introduction of dopants can promote lower-temperature processing by improving deformability and disrupting lattice integrity; however, an unbiased, systematic study correlating these properties to the dopant chemistry and composition is lacking. Here, we rely on a set of static and dynamic metrics derived from first-principles simulations to estimate the impact of doping on LLZO processability by quantifying LLZO structural deformability. We considered three distinct dopants (Al, Ba, and Ta) as representatives of substitutional incorporation on Li, La, and Zr sites. Our descriptors indicate that doping in general positively impacts lattice deformability, although significant sensitivities to dopant identity and concentration are observed. Amongst the tested dopants, Al doping (on the Li site) appears to have the greatest impact, as signaled across nearly the entire set of computed features. We suggest that these proxy descriptors, once properly calibrated against well-controlled experiments, could enable the use of first-principles simulations to computationally screen new ceramic electrolyte compositions with improved processability.

Effects of normal hematocrit on ambulatory blood pressure in epoetin-treated hemodialysis patients with cardiac disease.

BACKGROUND: Hypertension is a recognized complication of partial correction of anemia with recombinant human erythropoietin (epoetin) in hemodialysis patients. We used interdialytic ambulatory blood pressure (ABP) monitoring to study the effects of partially corrected anemia versus normal hematocrit (hct) on BP in hemodialysis patients. METHODS: Repeated interdialytic ABP monitoring was performed for up to one year in 28 chronic hemodialysis patients with cardiac disease who were randomized to achieve and maintain normal hct levels (42 +/- 3%, group A) or anemic hct levels (30 +/- 3%, group B) with epoetin. Routine BP measurements obtained at dialysis treatments were also evaluated. RESULTS: Mean hct levels were 30.7 +/- 0.7% in group A and 30.6 +/- 0.7% in group B at baseline, then 39.3 +/- 1.2% (group A) and 33.5 +/- 0.6% (group B) at four months, and 42.0 +/- 1.1% (group A) and 30.4 +/- 1.0% (group B) at 12 months. Baseline ABP and routine dialysis unit BP levels were not different between the groups. At 2, 4, 8, and 12 months of follow-up, there were no statistically significant differences in any BP parameters between groups or increases in any BP parameters in either group A or group B patients compared with baseline. At 12 months, the mean nighttime diastolic BP (DBP) in group A patients was slightly but significantly lower than the mean daytime DBP (daytime DBP 76.6 +/- 1.9 mm Hg vs. nighttime DBP 72.9 +/- 2.1 mm Hg, P < 0.05). The mean daytime and nighttime BPs were not different from each other at two, four, and eight months in group A or at any time in group B, and in both groups, most patients had little diurnal change in BP. CONCLUSION: Correction of hct to normal with epoetin in chronic hemodialysis patients with cardiac disease did not cause increased BP as assessed by interdialytic ABP monitoring or by the measurement of routine predialysis and postdialysis BP. There was little diurnal change in systolic or diastolic BP at baseline or after correction of anemia to normal levels, and although mean nighttime DBP was lower than mean daytime DBP at 12 months in group A, the maintenance of normal hct levels did not affect the abnormal diurnal BP pattern seen at moderately anemic hct levels in most patients.

Long-term efficacy, tolerability, and safety of the combination of enalapril and felodipine ER in the treatment of hypertension. Enalapril-Felodipine ER Factorial Study Group.

A recent 8-week, double-masked, placebo-controlled, 3 x 4 factorial-design study demonstrated that enalapril-felodipine extended-release (ER) combinations had statistically significant additive effects for reducing both sitting systolic blood pressure (SiSBP) and sitting diastolic blood pressure (SiDBP) and were generally well tolerated in hypertensive patients with SiDBPs ranging from 95 to 115 mm Hg. The present open-label study was undertaken to assess the long-term efficacy, tolerability, and safety of such combinations. Patients from the factorial study were eligible for the 1-year, open-label extension. Initially, all patients received enalapril 5 mg-felodipine ER 2.5 mg once daily; if SiDBP was not controlled (< 90 mm Hg) after 4 weeks of treatment, the dose was titrated upward at 2- to 4-week intervals to a maximum of enalapril 10 mg-felodipine ER 10 mg. Hydrochlorothiazide (HCTZ) 12.5 mg was added to the regimen of patients whose hypertension was not controlled at the highest enalapril-felodipine ER dose. A total of 507 patients were enrolled, of whom 502 were assessable. At their last study visit, 391 (78%) of the assessable patients were receiving only an enalapril-felodipine ER combination. The enalapril-felodipine ER combinations resulted in mean trough SiDBPs of 85 to 89 mm Hg (decreases of 13 to 16 mm Hg from baseline) and SiSBPs of 137 to 140 mm Hg (decreases of 13 to 21 mm Hg). Overall, 407 (81%) of the 502 assessable patients achieved an SiDBP < 90 mm Hg or a reduction from baseline > or = 10 mm Hg (responders); such a response was recorded in 331 patients (66%) taking a combination of enalapril-felodipine ER alone and 76 patients (15%) taking the combination with the addition of HCTZ 12.5 mg. Blood pressure reductions were maintained throughout the treatment period. Drug-related adverse events were relatively infrequent, often transient, usually mild, and apparently not dose related. The most frequently reported drug-related adverse events were edema/swelling, asthenia/fatigue, dizziness, cough, and headache. These results suggest that combination therapy with enalapril-felodipine ER is effective for long-term blood pressure reduction, has an excellent safety profile, and is generally well tolerated. Addition of low-dose HCTZ to the enalapril-felodipine ER combination appears to provide further blood pressure control without increasing drug-related adverse events.

Combined enalapril and felodipine extended release (ER) for systemic hypertension. Enalapril-Felodipine ER Factorial Study Group.

This multicenter, placebo-controlled, double-blind trial of factorial design evaluated the safety and efficacy of combination treatment with the angiotensin-converting enzyme inhibitor, enalapril, and the vascular selective calcium antagonist felodipine extended release (ER) in patients with essential hypertension. After a 4-week, single-blind placebo baseline period, 707 patients with sitting diastolic blood pressures (BPs) in the range of 95 to 115 mm Hg received placebo, enalapril (5 or 20 mg), felodipine ER (2.5, 5, or 10 mg), or their combinations for an 8-week double-blind treatment period. All doses of enalapril and felodipine ER had a statistically significant (p < 0.05) additive effect in reducing both systolic and diastolic BP. The trough to peak ratios for the combinations ranged from 0.63 (enalapril 5 mg-felodipine ER 2.5 mg) to 0.79 (enalapril 20 mg-felodipine ER 10 mg) and were consistent with effective BP control with 1 dose/day. Patients aged > or = 65 years demonstrated a greater reduction in diastolic BP. Combinations of enalapril-felodipine ER were associated with less drug-induced peripheral edema (4.1%) compared to felodipine ER monotherapy (10.8%). There were no serious drug-related adverse effects observed during the study. In this trial, the combination of enalapril and felodipine ER effectively lowered BP and was generally well tolerated with an excellent safety profile when used in the treatment of hypertension.

Problem-solving therapy in palliative care.

Emotional syndromes of depression and anxiety are common among palliative care patients. This pilot study evaluated the feasibility and acceptability of using a brief psychological treatment (problem-solving therapy) to treat these syndromes in patients receiving palliative care. Results were encouraging, particularly as regards acceptability to patients. Problems encountered during the study are discussed in the context of planning future research into the efficacy of treatments for emotional disorders in palliative care.

Hormone treatments in the common 'hormone-dependent' carcinomas.

Current understanding of the mechanisms of action of hormonal therapies in carcinomas of the breast, prostate, endometrium and ovary is briefly reviewed. The range of available hormonal therapies for each disease is considered together with response rates, toxicity and any evidence for survival benefit. Practical guidelines for the palliative use of hormonal therapies are suggested.

Elective conversion from cyclosporine to azathioprine in sensitized patients following cadaveric renal transplantation.

The safety of conversion from cyclosporine to azathioprine following renal transplantation in patients generally considered to be at immunologic risk for allograft loss has not been established. We examined a group of 59 patients who underwent cadaveric renal transplantation and elective conversion from cyclosporine to azathioprine 8.3 +/- 3.8 months following transplantation. Forty-three of these patients received a first transplant and had panel-reactive antibodies (PRA) less than 40% (unsensitized). Sixteen patients received at least their second allograft or had PRA of 40% or more (sensitized). Average follow-up was 17.9 +/- 8.2 months. Nine patients (15%) failed conversion as manifested by the need to restart cyclosporine 1 to 10 months following conversion. All were in the unsensitized group. Of those successfully converted, there were six allograft failures, two from patient death, one from acute rejection, one from recurrent diabetic nephropathy, and two from patient noncompliance. All were in the unsensitized group, although the difference from the sensitized group was not statistically significant (P = 0.051). There were three rejection episodes, all successfully reversed, in the sensitized group and six rejection episodes in the unsensitized group, five of which were reversed. Overall renal function improved in both groups as shown by a significant decrease in serum creatinine. Neither group required increased doses of steroid to compensate for lack of cyclosporine. From these data we can recommend conversion from cyclosporine to azathioprine in patients with cytotoxic antibodies or those undergoing retransplantation.

Neuropsychological rehabilitation after closed head injury in young adults.

Cognitive and personality disturbances following severe closed head injury in young adults are associated with poor rehabilitation outcome. Yet systematic programmes for dealing with these disturbances have generally not appeared. The present report briefly describes the Neuropsychological Rehabilitation Program (NRP) at Presbyterian Hospital in Oklahoma City and the initial outcome data on eighteen closed head injury patients and seventeen untreated controls. Greater improvement in neuropsychological functioning occurred in the NRP patient group on selected variables, but generally the effects were modest. Emotional distress, however, substantially decreased in treated patients. Fifty percent of the NRP patients maintained productivity 75% of the time or more following rehabilitation, compared to 36% of the controls. Treatment successes showed less personality disturbances than treatment failures and better learning and memory scores post-treatment.

Drug and chemical-induced metabolic acidosis.

Metabolic acidosis produced by drugs and/or chemicals can be conveniently divided into those with an increase in the anion gap (anion gap = Na- (Cl + HCO3)) and those with a normal anion gap. The increase in the anion gap is due to the accumulation of unmeasured organic anions, such as lactate or acetoacetate and beta-hydroxybutyrate, as occurs in ketoacidosis and lactic acidosis, or the accumulation of toxic anions such as formate or glycolate, as occurs with the ingestion of methanol or ethylene glycol. Increased concentrations of lactic acid may also be present in the toxic forms of metabolic acidosis. The most common drugs and chemicals that induce the anion gap type of acidosis are biguanides, alcohols, polyhydric sugars, salicylates, cyanide and carbon monoxide. In normal anion gap acidosis the reduction in bicarbonate is balanced by a reciprocal increase in the chloride concentration so that the sum of the two remains unchanged. Normal anion gap acidosis is caused by carbonic anhydrase inhibitors, hydrochloride salts of amino acids, toluene, amphotericin, spironolactone and non-steroidal anti-inflammatory drugs. The mechanism by which these substances produce metabolic acidosis and the therapy are discussed.

Gallium citrate Ga 67 imaging in noninfectious interstitial nephritis.

Gallium citrate Ga 67 has been reported to be of value in the diagnosis of both malignant and infectious intra-abdominal diseases. The drug may also be taken up by mononuclear phagocytes in noninfectious tubulo-interstitial disease of the kidney. Positive renal scans from patients with these diseases either become negative or show decreased uptake following treatment. With further support of these findings, gallium citrate Ga 67 may become a valuable tool in both diagnosis and follow-up of noninfectious interstitial nephritis.

Adult polycystic kidney disease and lattice corneal dystrophy: occurrence in a single family.

Most ophthalmologic disorders reported with renal cystic disease have been associated with either medullary cystic disease or juvenile nephrophthisis. A family we investigated demonstrated two previously unreported autosomal dominant disorders: adult polycystic kidney disease and lattice corneal dystrophy.