Prognostic factors for survival in systemic lupus erythematosus associated pulmonary hypertension.

OBJECTIVE: Pulmonary hypertension (PH) is a rare but severe manifestation of systemic lupus erythematosus (SLE) that can ultimately result in death. The identification of factors that prognosticate survival in SLE-PH is necessary for appropriate monitoring, timing of therapeutics and lung transplantation. The primary objective of this study was to identify prognostic factors for survival in SLE-PH through review of the literature. The methodological quality of the prognostic studies was also evaluated. METHODS: A systematic review of the literature was performed to identify studies evaluating prognostic factors for survival in SLE-PH. Medline, EMBASE, CINAHL, and Cochrane Central Registry of Controlled Trials (inception - week 2 2010) were searched. A standardized abstraction form was used by two independent reviewers to extract prognostic factors. Methodological quality was evaluated using a validated quality index. RESULTS: Twenty-three observational studies from 375 citations were evaluated. Elevated mean pulmonary artery pressure, Raynaud's phenomenon, thrombocytopenia, plexiform lesion, infection, thrombosis, pregnancy, pulmonary vasculitis and anticardiolipin antibodies were associated with decreased survival. Lupus disease activity, nephritis and central nervous system disease were not associated with survival. The sample sizes were small and methodological quality of the studies was variable. CONCLUSION: This study summarizes factors that may be associated with decreased survival in SLE-PH. The small sample sizes and variable methodological quality preclude definitive conclusions. This study provides the groundwork for further research using large cohorts.

Diagnostic accuracy of a prototype rapid chlamydia and gonorrhoea recombinase polymerase amplification assay: a multicentre cross-sectional preclinical evaluation.

OBJECTIVES: Rapid and accurate sexually transmitted infection diagnosis can reduce onward transmission and improve treatment efficacy. We evaluated the accuracy of a 15-minute run-time recombinase polymerase amplification-based prototype point-of-care test (TwistDx) for Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG). METHODS: Prospective, multicentre study of symptomatic and asymptomatic patients attending three English sexual health clinics. Research samples provided were additional self-collected vulvovaginal swab (SCVS) (female participants) and first-catch urine (FCU) aliquot (female and male participants). Samples were processed blind to the comparator (routine clinic CT/NG nucleic acid amplification test (NAAT)) results. Discrepancies were resolved using Cepheid CT/NG GeneXpert. RESULTS: Both recombinase polymerase amplification and routine clinic NAAT results were available for 392 male and 395 female participants. CT positivity was 8.9% (35/392) (male FCU), 7.3% (29/395) (female FCU) and 7.1% (28/395) (SCVS). Corresponding NG positivity was 3.1% (12/392), 0.8% (3/395) and 0.8% (3/395). Specificity and positive predictive values were 100% for all sample types and both organisms, except male CT FCU (99.7% specificity (95% confidence interval (CI) 98.4-100.0; 356/357), 97.1% positive predictive value (95% CI 84.7-99.9; 33/34)). For CT, sensitivity was ≥94.3% for FCU and SCVS. CT sensitivity for female FCU was higher (100%; 95% CI, 88.1-100; 29/29) than for SCVS (96.4%; 95% CI, 81.7-99.9; 27/28). NG sensitivity and negative predictive values were 100% in FCU (male and female). CONCLUSIONS: This prototype test has excellent performance characteristics, comparable to currently used NAATs, and fulfils several World Health Organization ASSURED criteria. Its rapidity without loss of performance suggests that once further developed and commercialized, this test could positively affect clinical practice and public health.

A 30-Min Nucleic Acid Amplification Point-of-Care Test for Genital Chlamydia trachomatis Infection in Women: A Prospective, Multi-center Study of Diagnostic Accuracy.

BACKGROUND: Rapid Point-Of-Care Tests for Chlamydia trachomatis (CT) may reduce onward transmission and reproductive sexual health (RSH) sequelae by reducing turnaround times between diagnosis and treatment. The io® single module system (Atlas Genetics Ltd.) runs clinical samples through a nucleic acid amplification test (NAAT)-based CT cartridge, delivering results in 30min. METHODS: Prospective diagnostic accuracy study of the io® CT-assay in four UK Genito-Urinary Medicine (GUM)/RSH clinics on additional-to-routine self-collected vulvovaginal swabs. Samples were tested "fresh" within 10days of collection, or "frozen" at -80°C for later testing. Participant characteristics were collected to assess risk factors associated with CT infection. RESULTS: CT prevalence was 7.2% (51/709) overall. Sensitivity, specificity, positive and negative predictive values of the io® CT assay were, respectively, 96.1% (95% Confidence Interval (CI): 86.5-99.5), 97.7% (95%CI: 96.3-98.7), 76.6% (95%CI: 64.3-86.2) and 99.7% (95%CI: 98.9-100). The only risk factor associated with CT infection was being a sexual contact of an individual with CT. CONCLUSIONS: The io® CT-assay is a 30-min, fully automated, high-performing NAAT currently CE-marked for CT diagnosis in women, making it a highly promising diagnostic to enable specific treatment, initiation of partner notification and appropriately intensive health promotion at the point of care.

Acid-suppressive therapy use associated with antihypertensive agents.

Nitrates and calcium channel blockers (CCBs) have been shown to decrease lower esophageal sphincter pressure and theoretically may precipitate or aggravate gastroesophageal reflux. Thus, the authors hypothesized that patients who receive these agents would have greater use of acid-suppressive drug use, defined as histamine2 antagonists or proton pump inhibitors. A retrospective cohort design was used to assess the use of acid-suppressive drug use in hypertensive patients with respect to both nitrates and antihypertensive therapy. Of 15,662 treated hypertensive patients, 20% received acid-suppressive therapy. An increased use of acid-suppressive therapy was associated with nitrate (odds ratio [OR] = 1.71), CCB (OR = 1.46), and alpha 1 antagonist (OR = 1.32) treatment, which appeared to be additive when patients received two or more of the agents. Within the class of CCBs, there was no significant difference among the individual agents. As the clinical and economic burden may be substantial, further study is warranted.

Iconic memory, location information, and partial report.

It has been suggested that the systematic decline of partial report as the delay of the partial-report cue increases is due to a time-related loss of location information. Moreover, the backward masking effect is said to be precipitated by the disruption of location information before and after identification. Results from three experiments do not support these claims when new indices of location information and of item information are used. Instead, it was found that the systematic decline in partial report was due to a time-related loss of item information, and location information was affected neither by the delay of the partial-report cue nor by the delay of backward masking. Subjects adopted the "select-then-identify" mode of processing.

Effect of simethicone on the accuracy of the rapid urease test.

OBJECTIVE: Simethicone, which is a principal ingredient in the defoaming agent used during gastroscopy, can inhibit the growth of Helicobacter pylori (MIC, 64-128 mg/l). This prospective study was designed to evaluate the in vivo and in vitro effects of simethicone on the accuracy of the rapid urease test (RUT). METHODS: In the in vivo study, three sets of gastric biopsies (two from the antrum, and one from the corpus) were taken from 75 patients. The first set was examined histologically, and the second set was used for the RUT (pre-simethicone RUT). Then, 25 ml simethicone (1200 mg/l) was introduced into the stomach for a contact time of 1 min. A third set of gastric biopsies was taken for the RUT (post-simethicone RUT). In the in vitro clinical study, 41 patients were recruited. The first set of gastric biopsies was used for the RUT (pre-incubation RUT). The second set was incubated in 1 ml of simethicone for 5 min before being used for the RUT (post-incubation RUT). In the spectrophotometric study, urease activity before and after incubation in simethicone for 5 min was quantified in 12 patients by measuring the absorbance at 560 nm. RESULTS: Reading at 15 min, the concordance rate between the pre-simethicone and post-simethicone RUT was 98%. In the in vitro clinical study, the concordance rate between the pre-incubation and post-incubation RUT was 97%. The spectophotometric study showed a significant reduction of 43% in urease activity after incubation in simethicone. CONCLUSION: The application of a defoaming agent containing simethicone does not affect the accuracy of the RUT. However, simethicone modestly suppresses urea hydrolysis.

Elucidation of the role of hydrophobic bonding in influencing intestinal absorption of model sulfonamides and revealing possible mechanism of drug absorption in rat model.

A recirculation technique was used to study the first-order kinetics of intestinal absorption of un-ionized sulfadiazine, sulfamerazine, and sulfamethazine in rats in situ at 32, 35, and 38 degrees C. The absorption rate constant (Kab) of each sulfonamide increased with increase in temperature and, at each temperature, Kab was the highest for sulfamethazine and the lowest for sulfadiazine. Applying the activated complex formation theory, the energy of activation (Ea), free energy of activation (delta F*), enthalpy of activation (delta H*), and entropy of activation (delta S*) of absorption were determined for the sulfonamides to gain some insight into the mechanism of their intestinal absorption. The high values of delta F* indicated that the barrier for sulfonamide absorption was great. For each drug, the value of delta H* was positive and that the delta S* negative. However, delta H* and delta S* were the highest for sulfamethazine and the lowest for sulfadiazine, thus revealing the influence of hydrophobic bonding in increasing Kab of the sulfonamides with the increase in methyl group content of their molecules. By considering the facts that (1) the microvillus membrane of the intestinal absorptive cells regulates the rate of passive absorption of drugs, (2) the microvillus membrane is rich in proteins, which are located external to the membrane and exposed to the intestinal fluid, and (3) hydrophobic bonding contributes to the activation parameters of absorption, it was postulated that the activated complex formed in the absorption process consisted of a transient association of the sulfonamide molecules with some protein component of the microvillus membrane.

Micellar solubilization of cetaben sodium in surfactant and lipid solutions.

Cetaben sodium solubilities were evaluated by micellar solubilization in various surfactants and lipid solvents. At pH 8, the relationship between cetaben sodium solubility and surfactant concentration delineated apparent saturable kinetics; at pH 4.9, the relationship between the two parameters was linear. In the presence of 0.5% sodium taurocholate and polysorbate 80, cetaben sodium solubility increased as the medium pH was increased; however, in the presence of 0.5% poloxamer 188, cetaben sodium solubility revealed a hyperbola when the pH was changed from 4.9 to 8.0. Cetaben sodium solubility was enhanced greatly by mixed physiological surfactants, full-strength caprylic-capric monodiglycerides or monodiglycerides, when compared to a single surfactant system. Cetaben sodium solubility is influenced by pH, surfactant type, surfactant concentration, lipid solvent type, and the simultaneous presence of surfactants or phospholipids.

Possible changes in luminal surface charge densities of small intestine membrane in the 4-7.4 pH range exhibit varied influence on the absorption rate constants of the ionized and un-ionized species of sulfadiazine in rats.

The overall apparent first-order rate constants (Kab) of small intestinal absorption of sulfadiazine were determined in rats in situ at various pHs (4.01-7.42) of the recirculation fluids at 32 degrees. The purpose of the study was to verify our hypothesis that the rate-determining step for the absorption of sulfonamides involves the formation of an "activated complex" consisting of a transient association of the sulfonamide molecules with the surface protein of the microvillus membrane. The Kab versus Fu (where Fu is the fraction of un-ionized sulfadiazine at a given pH) profile prepared according to the equation Kab = Ki+Fu(Ku-Ki), where Ki and Ku are the first-order rate constants of absorption of the ionized and un-ionized species, respectively, was clearly resolvable into two linear segments: one based on the data in the 4.01-6.43 pH range and the other based on the data in the 6.43-7.42 pH range. In view of the fact that the combined molar concentration of aspartic acid and glutamic acid in the microvillus membrane protein is about twice that of arginine and lysine, the resolution of the data into two linear segments suggested that the negative charge density of the microvillus surface membrane protein in the 6.43-7.42 pH range is greater than that in the 4.01-6.43 pH range. The Ku and Ki values of sulfadiazine were determined in each pH range. It was noted that Ku was greater than Ki in each pH range, and that Ki in the 4.01-6.43 pH range was greater than that in the 6.43-7.42 pH range.(ABSTRACT TRUNCATED AT 250 WORDS)

Linoleic acid absorption in the unanesthetized rat: mechanism of transport and influence of luminal factors on absorption.

Linoleic acid intestinal absorption was studied in the unanesthetized rat. At low (21-1260 micrometer) intraluminal concentrations, absorption took place by facilitated diffusion; while at high (1.26-2.5 mM) concentrations, simple diffusion was the predominant mechanism of transport. At low concentrations (840 micrometer), the equimolar additions of oleic, linolenic, and arachidonic acids or lecithin inhibited the absorption of linoleic acid. Substitution of potassium for sodium in the buffer solution, substitution of Tween 80 for sodium taurocholate, or decrease in the hydrogen ion concentration all resulted in decreased rate of linoleic acid absorption. Increase in sodium taurocholate concentration, or perfusate flow rate increased linoleic acid's absorption. These experiments demonstrate that linoleic acid is absorbed by a concentration-dependent dual mechanism of transport. The absorption rate is modified by the pH, surfactant type and concentration, the simultaneous presence of other polyunsaturated fatty acids, and the thickness of the unstirred water layer.

Arachidonic acid intestinal absorption: mechanism of transport and influence of luminal factors of absorption in vitro.

The mechanism and characteristics of intestinal absorption of arachidonic acid were studied in vitro using everted intestinal sacs of the rat. Arachidonic acid absorption was studied at concentrations of 5 micron to 8.36 mM. The plot of absorption rate vs. concentration fitted best to a rectangular hyperbola at low micron concentrations and to a straight linear relationship in the mM range of concentrations. Metabolic inhibitors and uncouplers did not change absorption in either range of concentrations. The absorption of arachidonic acid increased with thinning of the unstirred water-layer, decrease in the pH, or the substitution of sodium taurocholate by Pluronic F 68 OR Tween 80. Absorption decreased following the equimolar additions of oleic, linoleic, and linolenic acids. Absorption rate did not change when the taurocholate concentration was varied from 5-15 mM or following the additions of butyric or glutamic acids, leucine, lysine, or dextrose. It was concluded that arachidonic acid is absorbed by a concentration-dependent dual mechanism of transport which is not energy dependent. At the low micron range of concentrations, facilitated diffusion is predominant, while at mM concentrations, simple diffusion is the dominant mechanism of absorption. Changes in the intestinal fluid composition, flow rate, and pH can modify the rate of absorption of arachidonic acid.

Initial cholesterol uptake by everted sacs of rat small intestine: kinetic and thermodynamic aspects.

The kinetics of initial cholesterol uptake by everted rat proximal and distal small intestinal sacs were evaluated in vitro. The mucosal incubation solution consisted of 0.05 mM cholesterol solubilized in 4.8 mM sodium taurocholate micellar solution at pH 7.4 Experiments were performed at temperatures from 26 to 38 C. The rate of cholesterol uptake followed a linear relationship when plotted against time indicating an apparent zero-order kinetics mechanism for initial uptake. An Arrhenius plot of the results of uptake versus temperature remained linear over the entire range of temperatures studied. The large free energy of activation (20 kcal/mole) suggests that an energy barrier for cholesterol uptake exists at the enterocyte luminal cell membrane and may be an important limiting step in cholesterol uptake. It is proposed that a transient association between cholesterol and a component of the enterocyte luminal cell membrane is formed during initial uptake of cholesterol. The transient association may be an activated complex formed with proteins present at or within the luminal enterocyte cell membrane.

Nonsecretory immunoglobulin-derived amyloidosis of the heart: diagnosis by immunohistochemistry of the endomyocardium.

Primary amyloid light chain (AL) amyloidosis of the heart is a rare cause of congestive heart failure. Approximately 15% of patients with primary AL amyloidosis demonstrate no monoclonal proteins on serum or urine immunoelectrophoresis:(so-called nonsecretory immunoglobulin-derived amyloidosis). The histologic findings of endomyocardial biopsy from these patients may be indistinguishable from those with senile cardiac amyloidosis. However, the AL type may respond favourably to chemotherapy while the latter type does not. The prognosis is also better in the senile cardiac amyloid type. The precise diagnosis in the present case was made by applying immunohistochemical techniques on cardiac tissues.

Parametric modelling of a knee joint prosthesis.

This paper presents an approach for the establishment of a parametric model of knee joint prosthesis. Four different sizes of a commercial prosthesis are used as an example in the study. A reverse engineering technique was employed to reconstruct the prosthesis on CATIA, a CAD (computer aided design) system. Parametric models were established as a result of the analysis. Using the parametric model established and the knee data obtained from a clinical study on 21 pairs of cadaveric Asian knees, the development of a prototype prosthesis that suits a patient with a very small knee joint is presented. However, it was found that modification to certain parameters may be inevitable due to the uniqueness of the Asian knee. An avenue for rapid modelling and eventually economical production of a customized knee joint prosthesis for patients is proposed and discussed.

Partial report: iconic store or two buffers?

Selective recall of a subset of letters from a multiletter array declines systematically with increases in the delay of the partial report cue. The issues addressed were (a) whether such a decline is due to progressive loss of location information or to systematic loss of features and (b) whether partial report is the result of a select-then-identify or an identify-then-select process. Instructing the subjects to guess or not to guess had an effect of intra-array, displacement, and extra-array errors. Emphasizing on recall location affected both intra- and extra-array errors. The interstimulus interval manipulation had an effect on extra-array errors as well as on intra-array errors. These observations are contrary to the suggestions that intra-array errors are due to loss of location information and that extra-array errors are indicative of a joint effect on misidentification due to chance and the ratio of extra-array errors to intra-array errors. Some other results are difficult for a dual-buffer model but can readily be accounted for by the orthodox view of the iconic store.

Plasma biomarkers and echocardiographic indices of left ventricular function in very low birth weight infants.

OBJECTIVE: Evaluate plasma markers of myocardial function and ischemia [B-type natriuretic peptide] (BNP) and cardiac troponin T (cTnT)] in relationship to echocardiographic indices of left ventricular (LV) function and severity of illness score (SNAPPE-II) in Very-Low-Birth-Weight-Infants (VLBWIs) prospectively. STUDY DESIGN: Serial echocardiography studies, clinical data, BNP and cTnT were obtained in thirty VLBWIs on postnatal days 1, 2, 3 and 7. RESULTS: BNP increased and cTnT decreased significantly day 1 through 3. BNP was significantly associated with patent ductus arteriosus (PDA), but did not correlate with LV function or cTnT and did not reflect use of inotropic medication. Cardiac troponin T increased with severity of illness, SNAPPE-II, score and was highest in babies receiving inotropic medication; Low cardiac output (CO) was common in the first seventy two hours and correlated negatively with cTnT (p < 0.01). A contractility index, the corrected LV mean velocity of circumferential fiber shortening, (mVcfc) was not related to cTnT. The LV mVcfc was inversely related to LV end systolic wall stress (p < 0.001) in all subgroups, and this index of contractility (mvcfc-ess) did not differ with large caliber PDA or use of inotropic medication. CONCLUSION: Cardiac troponin T exclusively rather than a combined biomarker approach may be useful in assessing myocardial injury. Cardiac output was low in sick VLBWIs with myocardial ischemia. Left ventricular contractile state was apparently preserved in significantly ill babies with elevated cTnT. Further research is needed to define the complex relationship between biomarkers and echocardiographic indices.

The significance of elevated CSF lactate.

The final diagnosis of 158 patients who had a cerebrospinal fluid (CSF) lactate concentration greater than 2 mmol/l was ascertained. The conditions included seizures, inflammatory changes, and proven metabolic disorders. For the diagnosis of congenital lactic acidoses, CSF lactate should ideally be measured in a seizure free patient after any acute illness.

Acute aortic dissection in a patient with Marfan's syndrome complicated by gestational hypertension.

OBJECTIVE: To present a case of aortic dissection in a pregnant woman with Marfan's syndrome. CLINICAL FEATURES: A 34-year-old woman with Marfan's syndrome developed gestational hypertension and Type III aortic dissection during the third trimester. The diagnosis was confirmed by computed tomography and aortography. OUTCOME: Although the dissection progressed, the woman was treated successfully. Elective caesarean section was performed. At follow-up the dissection had healed. CONCLUSION: Marfan's syndrome introduces a high risk of aortic dissection during pregnancy and the treatment chosen is crucial. As dilatation of the aorta is progressive, patients with Marfan's syndrome should be followed up closely and offered prophylactic surgery if necessary.

Departure from the onset-onset rule.

Using a signal-detection task, the generality of Turvey's (1973) onset-onset rule was tested in our experiments. After seeing, in succession, (1) one or two letters (target display), (2) a multiletter detection display, and (3) a mask display, subjects decided whether or not the letter or letters in the target display reappeared in the succeeding detection display at different levels of detection-display duration in various situations. The subjects' sensitivity was inconsistent with the onset-onset rule. More specifically, sensitivity increased with increases in display duration within a fixed stimulus onset asynchrony of 150 msec. Display duration, however, had no effect on response bias. Nor was there any interaction between display duration and display size in terms of either sensitivity or response bias. The more complicated relationship between display duration and display size does not invalidate the departure from the onset-onset rule.

Précis of statistical significance: rationale, validity, and utility.

The null-hypothesis significance-test procedure (NHSTP) is defended in the context of the theory-corroboration experiment, as well as the following contrasts: (a) substantive hypotheses versus statistical hypotheses, (b) theory corroboration versus statistical hypothesis testing, (c) theoretical inference versus statistical decision, (d) experiments versus nonexperimental studies, and (e) theory corroboration versus treatment assessment. The null hypothesis can be true because it is the hypothesis that errors are randomly distributed in data. Moreover, the null hypothesis is never used as a categorical proposition. Statistical significance means only that chance influences can be excluded as an explanation of data; it does not identify the nonchance factor responsible. The experimental conclusion is drawn with the inductive principle underlying the experimental design. A chain of deductive arguments gives rise to the theoretical conclusion via the experimental conclusion. The anomalous relationship between statistical significance and the effect size often used to criticize NHSTP is more apparent than real. The absolute size of the effect is not an index of evidential support for the substantive hypothesis. Nor is the effect size, by itself, informative as to the practical importance of the research result. Being a conditional probability, statistical power cannot be the a priori probability of statistical significance. The validity of statistical power is debatable because statistical significance is determined with a single sampling distribution of the test statistic based on H0, whereas it takes two distributions to represent statistical power or effect size. Sample size should not be determined in the mechanical manner envisaged in power analysis. It is inappropriate to criticize NHSTP for nonstatistical reasons. At the same time, neither effect size, nor confidence interval estimate, nor posterior probability can be used to exclude chance as an explanation of data. Neither can any of them fulfill the nonstatistical functions expected of them by critics.