Characterization of buried interfaces using Ga Kα hard X-ray photoelectron spectroscopy (HAXPES).

The extension of X-ray photoelectron spectroscopy (XPS) to measure layers and interfaces below the uppermost surface requires higher X-ray energies and electron energy analysers capable of measuring higher electron kinetic energies. This has been enabled at synchrotron radiation facilities and by using lab-based instruments which are now available with sufficient sensitivity for measurements to be performed on reasonable timescales. Here, we detail measurements on buried interfaces using a Ga Kα (9.25 keV) metal jet X-ray source and an EW4000 energy analyser (ScientaOmicron GmbH) in the Henry Royce Institute at the University of Manchester. Development of the technique has required the calculation of relative sensitivity factors (RSFs) to enable quantification analogous to Al Kα XPS, and here we provide further substantiation of the Ga Kα RSF library. Examples of buried interfaces include layers of memory and energy materials below top electrode layers, semiconductor heterostructures, ions implanted in graphite, oxide layers at metallic surfaces, and core-shell nanoparticles. The use of an angle-resolved mode enables depth profiling from the surface into the bulk, and is complemented with surface-sensitive XPS. Inelastic background modelling allows the extraction of information about buried layers at depths up to 20 times the photoelectron inelastic mean free path.

Fasting and postprandial spot urine calcium-to-creatinine ratios do not detect hypercalciuria.

SUMMARY: Clinicians can diagnose high urine calcium by asking patients to collect urine for 24 h or to provide a random urine specimen. In this study, random urine calcium levels were not as accurate as those from the 24-h collection. Clinicians should only use 24-h collections to diagnose high urine calcium. INTRODUCTION: Clinicians diagnose hypercalciuria using a 24-h urine calcium (24HUC) or a spot urine-calcium-to-creatinine ratio (SUCCR) specimen. The SUCCR is reportedly interchangeable with the 24HUC. However, studies to date show mixed results when comparing SUCCR and 24HUC values. We systematically compared fasting and postprandial SUCCR measurements to 24HUC measurements using Bland-Altman analysis. METHODS: Twenty-one postmenopausal women aged 58 ± 7 years came to the research ward for three 24-h inpatient stays. At each study visit, research nurses collected fasting morning (n = 62) and postprandial (n = 62) spot urine specimens along with carefully timed and complete 24-h urine specimens (n = 63) from each woman. RESULTS: Hypercalciuria was present in 13 24HUC samples (21%) using an upper limit of 250 mg/24-h. The fasting SUCCR underestimated the 24HUC (Bland-Altman bias -71 mg/24-h), with a sensitivity and specificity for diagnosing hypercalciuria of 0% and 98%, respectively. The postprandial SUCCR overestimated the 24HUC (Bland-Altman bias +61 mg/24-h), with a sensitivity and specificity of 77% and 61%, respectively. The average of fasting and postprandial SUCCR measurements had a lower Bland-Altman bias of -3 mg/24-h but demonstrated a sensitivity and specificity of only 42% and 78%, respectively. CONCLUSIONS: The SUCCR is not interchangeable with the 24HUC. The fasting SUCCR systematically underestimates, and the postprandial SUCCR systematically overestimates, 24HUC. The average SUCCR demonstrates low sensitivity and specificity for hypercalciuria. Clinicians must use the 24HUC to diagnose hypercalciuria in postmenopausal women.

Vitamin D and calcium levels in Ugandan adults with human immunodeficiency virus and tuberculosis.

BACKGROUND: Vitamin D increases cathelicidin production, and might alter mortality due to tuberculosis (TB) in human immunodeficiency virus (HIV) coinfection. However, due to abundant sun exposure, vita min D levels might be excellent among Ugandans with HIV and TB. METHODS: We measured 25(OH)D and calcium levels in 50 HIV-negative, 50 HIV-infected and 50 TB-HIV coinfected Ugandan adults. RESULTS: Mean ± standard deviation 25(OH)D levels were 26 ± 7 ng/ml in HIV-negative, 28 ± 11 ng/ml in HIV-infected and 24 ± 11 ng/ml in TB-HIV co-infected adults (P > 0.05 all comparisons). Vitamin D deficiency (< 12 ng/ml) was present in 10% of the HIV-infected subjects, 12% of the TB-HIV co-infected and none of the healthy controls (P = 0.03 for healthy vs. TB, P > 0.05 for other comparisons); 20% of the healthy controls, 22% of the HIV-positive and 38% of the TB-HIV co-infected subjects (P = 0.047 for healthy vs. TB, P > 0.05 for other comparisons) had suboptimal vitamin D levels (< 20 ng/ml). No participant had hypercalcemia. Serum 25(OH)D levels correlated positively with body mass index (r = 0.22, P = 0.03) and serum calcium levels (r = 0.18, P = 0.03). CONCLUSIONS: Ugandan HIV-infected adults with and without TB commonly had suboptimal vitamin D levels. Clinical trials are needed to evaluate the effect of vitamin D on health outcomes in HIV-infected patients with low vitamin D levels.

Adjustment for body mass index and calcitrophic hormone levels improves the diagnostic accuracy of the spot urine calcium-to-creatinine ratio.

SUMMARY: Providers diagnose hypercalciuria using a 24-hour or random urine samples. We compared calcium measurements from paired 24-hour and morning urine samples; measurements correlated poorly. We developed a formula to correct random urine calcium levels. Corrected levels showed excellent agreement with 24-hour measurements. Until validation, providers should diagnose hypercalciuria using 24-hour tests. INTRODUCTION: Hypercalciuria is a risk factor for osteoporosis and nephrolithiasis. The 24-hour urine calcium (24HUC) measurement is the gold standard to diagnose hypercalciuria, but the spot urine calcium-to-creatinine ratio (SUCCR) is more convenient. Although authors claim they are interchangeable, we observed inconsistencies during the conduct of a clinical trial. Therefore, we systematically evaluated agreement between the tests. METHODS: During a 28-inpatient calcium absorption studies in 16 postmenopausal women, we simultaneously collected paired fasting morning and 24-hour urine specimens. RESULTS: We found moderate correlation between paired SUCCR and 24HUC specimens (r = 0.57, p = 0.002), but the SUCCR underestimated 24HUC by a mean of 83 mg (Bland-Altman). We diagnosed hypercalciuria (24HUC >250 mg) in eight specimens using the 24HUC, but only in two specimens using the SUCCR (25% sensitivity). We developed a regression model to predict 24HUC using SUCCR, parathyroid hormone, body mass index, and 1,25(OH)(2)D. The model improved diagnostic sensitivity to 100% and decreased Bland-Altman bias of the SUCCR to +0.06 mg/kg/24-hour. CONCLUSIONS: We conclude that the SUCCR underestimates urine calcium loss and does not reliably diagnose hypercalciuria. A formula derived from multivariate regression incorporating other readily measurable variables greatly improved the SUCCR's accuracy. Future studies must verify this correction before clinical implementation.

Adherence to alendronate in male veterans.

UNLABELLED: In one Veterans Affairs' medical center, alendronate non-adherence was more likely in male veterans who smoke or report side effects, and less likely in men undergoing bone densitometry during therapy. Providers urgently need programs to increase adherence to osteoporosis medications. Initial programs should target patients with risk factors for non-adherence. INTRODUCTION: Adherence to osteoporosis therapy in men is unknown. We hypothesized that ca. 50% of men at one center would be adherent to alendronate and one or more patient-specific factors would associate with adherence. METHODS: We conducted a retrospective chart review study of male veterans to determine the rates and predictors of alendronate adherence over two years. We excluded women, men who received primary care elsewhere and those who took alendronate for indications other than low bone mass. We defined adherence as a medication possession ratio > or =80% in the first 24 months of therapy. RESULTS: Adherence in the first 12 and 24 months of therapy was 59% and 54%, respectively. In multivariate analyses, non-adherence was more likely in men using tobacco (OR 2.08, 95% CI 1.13, 3.84, p = 0.02) and reporting side effects (OR 2.06, 95% CI 1.14, 3.73, p = 0.02) and less likely in men undergoing bone density during therapy (OR 0.49, 95% CI 0.26, 0.90, p = 0.02). CONCLUSIONS: Alendronate non-adherence is more likely in male veterans who smoke or report side effects, and less likely in men having bone densitometry during therapy. Providers urgently need programs to increase adherence to osteoporosis medications. Initial programs should target patients with risk factors for non-adherence.

Decreased expression of smooth muscle alpha-actin results in decreased contractile function of the mouse bladder.

PURPOSE: Smooth muscle alpha-actin (SMalphaA) is an important actin isoform for functional contractility in the mouse bladder. Alterations in the expression of SMalphaA have been associated with a variety of bladder pathological conditions. Recently, a SMalphaA-null mouse was generated and differences in vascular tone and contractility were observed between wild-type and SMalphaA-null mice suggesting alterations in function of vascular smooth muscle. We used SMalphaA-null mice to explore the hypothesis that SMalphaA is necessary for normal bladder function. MATERIALS AND METHODS: Reverse transcriptase polymerase chain reaction, Western blotting and immunohistochemical staining were used to confirm the absence of SMalphaA transcript and protein in the bladder of SMalphaA-null mice. In vitro bladder contractility compared between bladder rings harvested from wild-type and SMalphaA-null mice was determined by force measurement following electrical field stimulation (EFS), and exposure to chemical agonists and antagonists including KCl, carbachol, atropine and tetrodotoxin. Resulting force generation profiles for each tissue and agent were analyzed. RESULTS: There was no detectable SMalphaA transcript and protein expression in the bladder of SMalphaA-null mice. Nine wild-type and 9 SMalphaA-null mice were used in the contractility study. Bladders from SMalphaA-null mice generated significantly less force than wild-type mice in response to EFS after KCl. Similarly, bladders from SMalphaA-null mice generated less force than wild-type mice in response to pretreatment EFS, and EFS after carbachol and atropine, although the difference was not significant. Surprisingly, the bladders in SMalphaA-null mice appeared to function normally and showed no gross or histological abnormalities. CONCLUSIONS: SMalphaA appears to be necessary for the bladder to be able to generate normal levels of contractile force. No functional deficits were observed in the bladders of these animals but no stress was placed on these bladders. To our knowledge this study represents the first report to demonstrate the importance of expression of SMalphaA in force generation in the bladder.

The absorption, distribution, metabolism and excretion of rofecoxib, a potent and selective cyclooxygenase-2 inhibitor, in rats and dogs.

Absorption, distribution, metabolism, and excretion studies were conducted in rats and dogs with rofecoxib (VIOXX, MK-0966), a potent and highly selective inhibitor of cyclooxygenase-2 (COX-2). In rats, the nonexponential decay during the terminal phase (4- to 10-h time interval) of rofecoxib plasma concentration versus time curves after i.v. or oral administration of [(14)C]rofecoxib precluded accurate determinations of half-life, AUC(0-infinity) (area under the plasma concentration versus time curve extrapolated to infinity), and hence, bioavailability. After i.v. administration of [(14)C]rofecoxib to dogs, plasma clearance, volume of distribution at steady state, and elimination half-life values of rofecoxib were 3.6 ml/min/kg, 1.0 l/kg, and 2.6 h, respectively. Oral absorption (5 mg/kg) was rapid in both species with C(max) occurring by 0.5 h (rats) and 1.5 h (dogs). Bioavailability in dogs was 26%. Systemic exposure increased with increasing dosage in rats and dogs after i.v. (1, 2, and 4 mg/kg), or oral (2, 5, and 10 mg/kg) administration, except in rats where no additional increase was observed between the 5 and 10 mg/kg doses. Radioactivity distributed rapidly to tissues, with the highest concentrations of the i.v. dose observed in most tissues by 5 min and by 30 min in liver, skin, fat, prostate, and bladder. Excretion occurred primarily by the biliary route in rats and dogs, except after i.v. administration of [(14)C]rofecoxib to dogs, where excretion was divided between biliary and renal routes. Metabolism of rofecoxib was extensive. 5-Hydroxyrofecoxib-O-beta-D-glucuronide was the major metabolite excreted by rats in urine and bile. 5-Hydroxyrofecoxib, rofecoxib-3',4'-dihydrodiol, and 4'-hydroxyrofecoxib sulfate were less abundant, whereas cis- and trans-3,4-dihydro-rofecoxib were minor. Major metabolites in dog were 5-hydroxyrofecoxib-O-beta-D-glucuronide (urine), trans-3, 4-dihydro-rofecoxib (urine), and 5-hydroxyrofecoxib (bile).

Synthesis and evaluation of furan, thiophene, and azole bis[(carbamoyloxy)methyl] derivatives as potential antineoplastic agents.

A series of bis(hydroxymethyl)-substituted heterocycles were synthesized and converted to the corresponding bis(methylcarbamate) derivatives. The heterocyclic systems studied were based on 2-phenyl-3-methylfuran (2-4), 1-phenylpyrazole (5-7), 1-phenyl-5-methylpyrazole (9-11), 1-phenyl-5-methylthiophene (13), 1-phenyl-1,2,3-triazole (14), 3-phenylisoxazole (15), 3-phenylisothiazole (16), 2-phenylthiazole (17), and 2-phenyloxazole (18). None of the bis(carbamates) prepared was active against murine P388 lymphocytic leukemia. Pyrrole bis(carbamates) 20 and 21, which exhibited antileukemic activity, also showed reactivity toward 4-(p-nitrobenzyl)pyridine while the inactive bis(carbamates) were unreactive in the 4-(p-nitrobenzyl)pyridine assay.

Vinylogous carbinolamine tumor inhibitors. 8. Activity of bis(acyloxymethyl) derivatives of pyrroles and pyrrolizines against a panel of murine leukemias and solid tumors.

The activity of three pyrroles and four pyrrolizines is compared in several different experimental leukemias and solid tumors in mice. Two compounds were particularly noteworthy, the bis(N-cyclohexylcarbamate) and the bis[N-(2-propyl)] derivatives of 2,3-dihydro-5-(3,4-dichlorophenyl)-6,7-bis(hydroxymethyl)-1H-pyrrolizine. These two compounds showed a very high level of activity against B16 melanocarcinoma, CD8F1 mammary tumor, colon tumor 26, and colon tumor 38, and a significant number of "cures" were recorded. The isopropyl compound was more potent than the cyclohexyl compound, but both showed a similar profile of activity.

Effect of restrictions on prescribing patterns for dextropropoxyphene.

Prescribing of compound analgesics containing dextropropoxyphene was limited to consultants only in a teaching hospital. Inpatient prescribing (mainly by junior staff) fell immediately to very low levels but outpatient prescribing (by consultants) fell more slowly to about one-third of the original level, suggesting that patients and doctors find dextropropoxyphene compounds useful. Prescriptions for paracetamol increased but so did those for other compound analgesics, particularly those containing high doses of codeine, indicating a belief that compound analgesics have a role in treatment. Restrictions may produce unexpected results and monitoring is essential, but the method of audit used by pharmacies is not suitable for detailed analysis.

Pathology of radiation myelopathy.

After nothing the rarity of papers describing the pathology of delayed radiation necrosis of the spinal cord, the clinical and pathological findings from four cases are presented. The main pathological features are asymmetric demyelination of the lateral columns and to a lesser degree the posterior and anterior columns of white matter, with coagulative necrosis at the level of irradiation which affected the grey matter to a lesser degree. There is ascending and descending secondary tract degeneration, and poor glial response in the lesions themselves. Vascular changes, mainly hyalilne thickening of arteriolar walls, are present, but not in degree sufficient to explain the primary lesion. The discussion of the pathogenesis of the myelopathy weighs the merits of a primary vascular lesion against those of a primary effect of the radiation on neural tissue. The latter is favoured.