Novel experimental setup for megahertz X-ray diffraction in a diamond anvil cell at the High Energy Density (HED) instrument of the European X-ray Free-Electron Laser (EuXFEL).

The high-precision X-ray diffraction setup for work with diamond anvil cells (DACs) in interaction chamber 2 (IC2) of the High Energy Density instrument of the European X-ray Free-Electron Laser is described. This includes beamline optics, sample positioning and detector systems located in the multipurpose vacuum chamber. Concepts for pump-probe X-ray diffraction experiments in the DAC are described and their implementation demonstrated during the First User Community Assisted Commissioning experiment. X-ray heating and diffraction of Bi under pressure, obtained using 20 fs X-ray pulses at 17.8 keV and 2.2 MHz repetition, is illustrated through splitting of diffraction peaks, and interpreted employing finite element modeling of the sample chamber in the DAC.

The Fe-FeSi phase diagram at Mercury's core conditions.

Mercury's metallic core is expected to have formed under highly reducing conditions, resulting in the presence of significant quantities of silicon alloyed to iron. Here we present the phase diagram of the Fe-FeSi system, reconstructed from in situ X-ray diffraction measurements at pressure and temperature conditions spanning over those expected for Mercury's core, and ex situ chemical analysis of recovered samples. Under high pressure, we do not observe a miscibility gap between the cubic fcc and B2 structures, but rather the formation of a re-entrant bcc phase at temperatures close to melting. Upon melting, the investigated alloys are observed to evolve towards two distinct Fe-rich and Fe-poor liquid compositions at pressures below 35-38 GPa. The evolution of the phase diagram with pressure and temperature prescribes a range of possible core crystallization regimes, with strong dependence on the Si abundance of the core.

Ankle-brachial pressure index: a simple tool for assessing cardiovascular risk in patients with systemic vasculitis.

OBJECTIVE: Cardiovascular disease may be increased in patients with systemic vasculitides (SV). The Ankle-Brachial Pressure Index (ABPI) is a non-invasive tool for the assessment of cardiovascular risk (CV). Our aim was to determine the prevalence of an abnormal ABPI in patients with SV and healthy controls and to correlate with clinical and serological parameters. METHODS: We studied 54 consecutive vasculitis patients (20 males) attending the vasculitis clinic and 49 healthy subjects. Patients were classified according to the ACR 1990 criteria and the Chapel Hill Consensus definitions. There were 18 patients with Wegener's granulomatosis, eight with Behcet's disease, seven with Churg-Strauss Syndrome, three with Henoch-Schonlein purpura, three with polyarteritis nodosa, three with Takayasu's disease, three with p-ANCA associated vasculitis, three with urticarial vasculitis, two with cutaneous leucocytoclastic angiitis, one with microscopic polyangiitis, one with primary central nervous system angiitis, one giant cell arteritis and one with cutaneous vasculitis secondary to Sjogren's syndrome. Traditional risk factors as well as glucose, lipid profile, CRP, hsCRP, ANCA and aPL were assessed. ABPI was measured according to a consensus statement on the methodology. RESULTS: The ABPI was abnormal in 11/54 (20.4%) of SV patients and 2/49 (4%) of the control group (chi(2) with Yates correction = 4.8, P

Nateglinide, alone or in combination with metformin, is effective and well tolerated in treatment-naïve elderly patients with type 2 diabetes.

AIM: The aim of this work was to assess the efficacy and tolerability of nateglinide alone or in combination with metformin in elderly patients with type 2 diabetes (T2DM). METHODS: Study 1 was a 12-week, multicentre, randomized, double blind and placebo-controlled study of nateglinide monotherapy (120 mg, before meals) in 66 drug-naïve patients with T2DM aged >or=65 years. Study 2 was a 104-week, multicentre, randomized, double blind and active-controlled study of nateglinide (120 mg, before meals) or glyburide (up to 5 mg bid) in combination with metformin (up to 1000 mg bid) in 69 treatment-naïve patients with T2DM aged >or=65 years. HbA(1c), fasting and postprandial glucose levels, and safety assessments were made. RESULTS: In Study 1, nateglinide significantly reduced HbA(1c) from baseline (7.6 +/- 0.1% to 6.9 +/- 0.1%; Delta = -0.7 +/- 0.1%, p < 0.001) and compared with placebo (between-group difference = -0.5%, p = 0.004 vs. nateglinide). No hypoglycaemia was reported. In Study 2, combination therapy with nateglinide/metformin significantly reduced HbA(1c) from baseline (7.8 +/- 0.2% to 6.6 +/- 0.1%; Delta = -1.2 +/- 0.2%, p < 0.001), as did glyburide/metformin (7.7 +/- 0.1% to 6.5 +/- 0.1%; Delta = -1.2 +/- 0.1%, p < 0.001). There was no difference between treatments (p = 0.310). One nateglinide/metformin-treated patient experienced a mild hypoglycaemic episode compared with eight episodes in eight patients on glyburide/metformin; one severe episode led to discontinuation. Target HbA(1c) (<7.0%) was achieved by 60% of patients receiving nateglinide (Study 1) and 70% of nateglinide/metformin-treated patients (Study 2). CONCLUSION: Initial drug treatment with nateglinide, alone or in combination with metformin, is well tolerated and produces clinically meaningful improvements in glycaemic control in elderly patients with T2DM.

Effects of vildagliptin on glucose control in patients with type 2 diabetes inadequately controlled with a sulphonylurea.

AIM: To compare the efficacy and tolerability of vildagliptin vs. placebo in patients with type 2 diabetes mellitus (T2DM) who are inadequately controlled [haemoglobin A(1c) (HbA(1c)) 7.5 to 11%] with prior sulphonylurea (SU) monotherapy. METHODS: This 24-week, multicentre, randomized, double-blind, placebo-controlled study assessed the effects of the dipeptidyl peptidase-4 inhibitor vildagliptin (50 mg given once or twice daily) vs. placebo added to glimepiride (4 mg once daily) in 515 patients with T2DM. Adjusted mean changes from baseline to end-point (AMDelta) in HbA(1c), fasting plasma glucose, fasting lipids and body weight were compared by analysis of covariance. RESULTS: The between-group difference (vildagliptin - placebo) in AMDelta HbA(1c) was -0.6 +/- 0.1% in patients receiving vildagliptin 50 mg daily and -0.7 +/- 0.1% in those receiving 100 mg daily (p < 0.001 vs. placebo for both). Greater efficacy was seen in patients > or =65 years of age (-0.7 +/- 0.1% and -0.8 +/- 0.2% for 50 and 100 mg daily respectively) and in patients with baseline HbA(1c) > 9% (Delta = -1.0 +/- 0.2% and -0.9 +/- 0.2% for 50 and 100 mg daily respectively). Relative to placebo, patients receiving vildagliptin also had improvements in beta-cell function and postprandial glucose, with small changes in fasting lipids and body weight. The incidences of adverse events (AEs) (67.1, 66.3 and 64.2%) and serious AEs (2.9, 2.4 and 5.1%) were similar in patients receiving 50 mg vildagliptin, 100 mg vildagliptin or placebo respectively. The incidence of hypoglycaemic events was low but slightly higher in the group receiving vildagliptin 100 mg (3.6%) than in the group receiving vildagliptin 50 mg (1.2%) or placebo (0.6%). CONCLUSIONS: In patients with T2DM inadequately controlled with prior SU monotherapy, addition of vildagliptin (50 or 100 mg daily) to glimepiride (4 mg once daily) improves glycaemic control and is well tolerated. Addition of vildagliptin 50 mg daily to SU monotherapy may be a particularly attractive therapy in elderly patients.

[Helicobacter pylori infection (13C-UBT), and its relationship with nutritional and socioeconomic factors in low income school children from Valencia, Venezuela]. / Infección por helicobacter pylori (13C-UBT) y factores nutricionales y socioeconómicos asociados en escolares de estratos bajos de la ciudad de Valencia, Venezuela.

Helicobacter pylori infection (Hp) is widely spread around the world, and it is considered one of the main causes of chronic gastritis, peptic and duodenal ulcers, and gastric cancer. Recent research has shown that it can be associated with nutritional disorders, mainly with iron and other micronutrient deficiencies. The objective of this study was to assess the prevalence of Hp infection, and infection pattern according to age, sex, nutritional status, and socioeconomic conditions in children who attended the Unidad Educativa "Valentin Espinal" in the city of Valencia. 170 children, between 3 and 14 years of age were studied to assess Hpylori infection (13C-urea breath test), age, nutritional status according to BMI and Height for age, hemoglobin (cianometahemoglobin), serum ferritin (ELISA), socioeconomic status (Graffar-Méndez-Castellano), housing conditions, number of families and of people cohabitating in the same household, and quality of services. 78.8% of the children were infected with Hp, witch was significantly correlated with age but not gender. 25.9% of the sample had undernutrition, and 46.5% were stunted. 98.1% of the families lived in poverty, and 98% of the households showed sanitary deficiencies. A mean of 6.0 +/- 2.4 persons lived in each household (range: 2-15), and an average of 3.2 person shared bedrooms. The odds of being infected were higher in those children who were stunted. Also, socioeconomic status, mother's education level, and poor hosing conditions were significantly associated to being infected. Hpylori is highly prevalent among socially and economically deprived children, and age, overcrowding, and a low education level of the mother increases the risk of being infected.

Bacteremia in private pediatric practice.

The capillary white blood cell count and differential, a test easily done in office practice, was used in unexplained febrile illness of infants and toddlers to help distinguish those babies most likely to have bacteremia who would benefit from blood culture and early bacteriologic diagnosis. Four criteria were used as indicators suggestive of bacterial infection: white blood cell count greater than or equal to 15,000/cu mm, total segmented neutrophils greater than or equal to 10,000/cu mm, total band cells greater than or equal to 500/cu mm, and total polymorphonuclear leukocytes (segmented neutrophils plus band cells) greater than or equal to 10,500/cu mm. These measurements were found helpful in separating a small group of bacteremic babies at high risk of complications from a large group of babies who recovered without antibiotic treatment and without complications. There were 146 febrile illnesses recorded in babies 3 to 24 months of age; bacteremia was proven in eight of these. Three or four blood cell count criteria were fulfilled in seven of the eight bacteremic babies and in only ten (7.2%) of the remaining 138 febrile illnesses (P < .001 by chi 2 test).

Predictive value of abnormal physical examination findings in ill-appearing and well-appearing febrile children.

In order to study the occurrence and positive predictive value of history and physical examination findings suggestive of serious illness in ill-appearing and well-appearing febrile children, 103 consecutive children aged less than or equal to 24 months with fever greater than or equal to 38.3 degrees C were evaluated from July 1, 1982 to Nov 24, 1982. Patients were initially classified by an attending physician (A) as to whether they appeared ill (Yale Observation Scale score greater than 10) or well (scale score less than or equal to 10). The history was then taken by two attending physicians (A and B) and a resident; the physical examination was performed by attending physician B and the same resident. As history and physical examination findings were elicited, they were scored as to whether they did or did not suggest a serious illness. Serious illness was defined as the presence of a positive laboratory test. Ill-appearing patients had a significantly greater (P less than .001, Fisher's exact test) occurrence of physical examination findings suggesting serious illness (14 of 22, 64%) than well-appearing children (12 of 81, 15%). The positive predictive values of abnormal physical examination findings for serious illness in ill-appearing (11 of 14, 79%) and well-appearing children (3 of 12, 25%) were significantly different (P = .02 by Fisher's exact test). The trends for abnormal history findings in ill-appearing and well-appearing children were similar to those for abnormal physical examination findings but did not achieve statistical significance. The results, indicating an important interaction between a febrile child's appearance and physical examination findings, are discussed in terms of probability reasoning in clinical decision making.

Demographic, clinical, and psychosocial predictors of the reliability of mothers' clinical judgments.

The purpose of this study was to investigate to what extent selected adverse demographic, clinical, and psychosocial data measured at the 2-week well child visit could predict poorer reliability of mothers' judgments during acute illness episodes over the next 32 months. The study was a randomized trial of the Acute Illness Observation Scales (AIOS); 369 mothers participated, 183 in the intervention group using the Acute Illness Observation Scales and 186 in the control group using a three-point global assessment scale. There were 704 acute illnesses judged simultaneously and independently by mothers and pediatricians. Standard Pearson r correlations were performed between the independent variables, taken singly and in all possible combinations, and the dependent variable, reliability of mothers' judgments as measured by weighted kappa (kappa W). Group assignment was entered as an independent variable. Analyses were performed separately for all first, second, and third acute illness visits to control for any "practice effect" (analysis 1). To control for consistency of observers, the first, second, and third visits of mothers with three visits were also analyzed (analysis 2). Depending on the visit number, adverse demographic, clinical, and psychosocial characteristics did correlate with poorer reliability independent of group assignment. The correlations ranged from small (analysis 1, first visit, multiple variable r2 = 4%) to large (analysis 2, second visit, multiple variable r2 = 29%). Controlling for both visit number and consistency of observers vs visit number alone (analysis 2 vs analysis 1) increased multivariate correlations to kappa W. The results support the untoward impact that adverse demographic, clinical, and psychosocial factors have on mothers' clinical judgment. These data may assist pediatricians in identifying parents who might benefit from more intensive teaching and support about acute illness episodes in their children.

Further definition of history and observation variables in assessing febrile children.

The experienced clinician makes a judgment (hereafter called overall assessment [OA]) about the degree of illness of a febrile child prior to physical examination. In order to define the history and observation variables on which OA is based, 262 febrile children less than or equal to 24 months of age were evaluated simultaneously by multiple observers including attending pediatricians, practicing pediatricians, pediatric house officers, and nurses. The observer listed history and observation variables he/she thought most important in making an OA on a blank, lined form and then scored those variables and OA as normal, or mildly, moderately, or severely impaired. Scoring for observation rather than history variables was better correlated with scoring for OA and serious illness. The observation variables most frequently mentioned by all observers were the child's "looking at the observer" and "looking around the room." There were 20 observation variables frequently mentioned, the scoring of which significantly correlated with scoring for OA; four of these 20 variables related to eye function. The child's response to a stimulus was noted in 105/186 different observation variables listed; both the attending pediatrician and the house officer scored these stimulus-response variables significantly different in children with, vs those without, serious illnesses. For attending pediatricians, house officers, and nurses, serious illness was five to seven times as likely if an OA of moderate or severe impairment was made than if it were not made. OA is a key skill in evaluating febrile children; these data identify variables on which OA is based, document the importance of assessing eye function in young, febrile children, and demonstrate that eye function is one key type of stimulus-response behavior on which the pediatrician as clinician and developmentalist relies to make judgments about febrile children.

Blood cultures in private pediatric practice: an eleven-year experience.

We describe an 11-year experience with bacteremia in a two-physician suburban private pediatric practice. Patients studied were ages 3 to 24 months with a body temperature of greater than or equal to 39.4 degrees C and nonfocal illness. During these 11 years, 23 such babies had bacteremia, 21 with Streptococcus pneumoniae. Three risk factors for bacteremia were identified: absolute neutrophil counts greater than or equal to 10,500/microliters; cool season (November to April), and Yale observation score greater than 10. The positive predictive values for bacteremia were 33, 41 and 57%, respectively, when (1) absolute neutrophil count was greater than or equal to 10,500, (2) absolute neutrophil count was greater than or equal to 10,500 and it was the cool season, and (3) all 3 risk factors existed. Of 158 babies at low risk for bacteremia by these criteria, none was treated and none developed serious complications of bacteremia. Eight of the 23 bacteremic infants received no expectant antibiotic therapy and 15 received presumptive amoxicillin treatment in dosages ranging from 20 to 174 mg/kg/day. Twelve bacteremic infants either were not treated or received dosages of 100 mg/kg/day or less; complications developed in 5 of the 12 (persistent bacteremia, 2; facial cellulitis, 3). The remaining 11 bacteremic babies received approximately 150 mg/kg/day (range, 136 to 174) and none had complications (P = 0.03 by Fisher's exact test). The costs of identifying and treating infants suspected of having possible occult bacteremia were examined.

Plasma immunoreactive TSH: spurious elevation due to antibodies to bovine TSH which cross-react with human TSH.

A patient with thyroid carcinoma treated by thyroidectomy who received multiple injections of bovine (bTSH) exhibited elevated and nonsuppressible levels of plasma "immunoreactive TSH." Antibodies to TSH of the IgG class which bound bTSH and human TSH (hTSH) were demonstrated using specific radioimmunoassay and radioimmunoelectrophoretic techniques. Antibodies were present for more than one year and binding of bTSH was greater than that of hTSH throughout this period. Characterization of the antibodies with respect to the binding of human and bovine glycoprotein hormones and subunits revealed two populations of antibodies, one of which bound both bTSH and hTSH and the other which bound only bTSH. Both antibodies appeared to be directed toward antigenic sites on the beta subunit of TSH as both hTSH-beta and bTSH-beta displaced the binding of intact TSH from antibodies whereas the alpha subunits were virtually unreactive. The binding studies suggest that the cross-reactivity of the antibody to hTSH occurred on the basis of common antigenic determinants on the beta subunits of the two species. Documentation of a true elevation of plasma hTSH was achieved by gel filtration of plasma in which a peak of immunoreactivity co-eluting with [125I]-hTSH could be shown. Evidence for suppression of TSH secretion by thyroxine administration in the presence of interfering antibody was obtained by demonstrating that the level of plasma "immunoreactive TSH" did not change in response to TRH administration.

Hypoglycemic potential of nateglinide versus glyburide in patients with type 2 diabetes mellitus.

Antidiabetic agents that augment insulin secretion can cause hypoglycemia. With the current trend toward early and aggressive treatment of patients with type 2 diabetes, the hypoglycemic potential of insulinotropic agents is of concern. This study aimed to compare the propensity of the "glinide," nateglinide, and the sulfonylurea (SU), glyburide, to elicit hypoglycemia in type 2 diabetic patients with moderately elevated fasting plasma glucose (FPG). Hyperglycemic clamps (target plasma glucose = 11.1 mmol/L) were initiated, and 30 minutes later patients received a single oral dose of nateglinide (120 mg, n = 15) or glyburide (10 mg, n = 12) in a double-blind fashion. At the end of the 2-hour clamp when the glucose infusion was terminated, plasma glucose and insulin levels were measured for 4 additional hours. The minimum plasma glucose level achieved after terminating the glucose infusion (glucose nadir) was used as an index of hypoglycemic potential. The mean (+/-SEM) glucose nadir was significantly lower in patients given glyburide (3.3 +/- 0.2 mmol/L) versus nateglinide (4.4 +/- 0.3 mmol/L, P = .025). Confirmed hypoglycemia (plasma glucose < or = 2.8 mmol/L) occurred in 2 of 12 patients given glyburide and in none of those given nateglinide. Plasma insulin levels were significantly higher from 100 to 240 minutes after clamp termination in patients given glyburide versus nateglinide. Nateglinide has less hypoglycemic potential than glyburide, suggesting that nateglinide may be a more appropriate insulinotropic agent for patients with moderate fasting hyperglycemia, such as elderly patients and those with comorbid cardiac ischemia.

Do mothers overestimate the seriousness of their infants' acute illnesses?

The purpose of this study was to determine if mothers generally perceive their infants as more ill than do pediatricians, and if the presence of fever has an impact on the perceptions of either the mother or pediatrician. One hundred eighty-seven mothers and their infants, from a primary care clinic (n = 109) and private practice (n = 78), were enrolled at the 2-week well-child visit and were asked to contact a physician participating in the study whenever their infants became acutely ill. The mothers were asked to rate the severity of their infants' illness according to a 3-point scale, first at home and then simultaneously, but independently, with a physician in the office. In general, mothers rated their infants equally as ill at home as in the office (kappa = 0.59). However, both their home ratings (kappa = 0.15) and office ratings (kappa = 0.29) were in poor agreement with the ratings of the physicians. The mothers consistently rated their infants as more ill than did the pediatricians (p less than 0.0001). Both the mothers and physicians perceived infants with higher temperatures (greater than or equal to 38.9 degrees C) as significantly (p = 0.0004) more ill than infants with lower temperatures (less than 38.9 degrees C). We conclude that mothers generally perceive their infants as more ill than do pediatricians, and that it is important for pediatricians to address the perceptions of mothers in order to establish effective communication with them.

Abdominal wall metastasis from ovarian cancer after laparotomy. A case report.

A 27-year-old woman underwent surgery for an abdominal wall mass later confirmed to be a relapse of Stage I ovarian mucinous adenocarcinoma. The authors stress that caution should be observed during laparotomy to remove a malignant neoplasm in order to avoid parietal dissemination.

New property of vitamin A and beta-carotene on human iron absorption: effect on phytate and polyphenols as inhibitors of iron absorption.

One hundred and seventy four human subjects were studied to find out the interaction of vitamin A or beta-carotene with the inhibitors of iron absorption, from a basal breakfast containing bread from either 100 g of precooked corn flour or 100 g of white wheat flour, 50 g of cheese and 10 g of margarine. Bread was labeled with either 55Fe or 59Fe. This bread was made from commercially flours fortified with iron as ferrous fumarate and vitamins. It was noticed that the percentage of iron absorption from the breakfast prepared with precooked corn flour given alone and with different concentrations of coffee was practically the same, while the iron absorption from the breakfast prepared from wheat flour decreased from 6% when the breakfast was given alone, to less than 2% when it was given with different concentrations of coffee. The only ingredient present in precooked corn flour and not in wheat flour was vitamin A. This difference encouraged the authors to perform further experiments using precooked corn and wheat flours fortified only with ferrous fumarate. These studies demonstrated that vitamin A inhibits the effect of the polyphenol and partially inhibits the effect phytate on iron absorption. HPLC and spectrophotometric studies demonstrated an interaction between vitamin A and iron. Other experiments, which included 100 volunteers, were performed to test the effect of vitamin A and beta-carotene on iron absorption from corn, wheat and rice. The presence of vitamin A increased iron absorption up to 3 times for rice, 2.4 times for wheat and 1.8 times for corn. beta-carotene increased absorption almost 3 times for the three cereals tested, showing that both compounds were capable of preventing the inhibitory effect of phytates on iron absorption. This information suggest that vitamin A and beta-carotene form a complex with iron keeping it soluble in the intestinal lumen and preventing the inhibitory effect of phytates and polyphenols on iron absorption.

[Pro-hepcidin, its relation with indicators of iron metabolism and of inflammation in patients hemodialyzed treated or not with recombinant erythropoietin]. / Pro-hepcidina, su relación con indicadores del metabolismo del hierro y de inflamación en pacientes hemodializados tratados o no con eritropoyetina recombinante.

UNLABELLED: Hepcidin, an antimicrobial peptide which synthesis is regulated by iron status and inflammation, plays an important role in iron homeostasis in hemodialysed (HD) patients. It is measured by measuring serum prohepcidin. OBJECTIVE: To determine serum prohepcidin levels and their relationship with serum ferritin, C reactive protein (CRP), and albumin in HD patients treated or not with recombinant erythropoietin (EPO) that attended the Health Centre of the Carabobo State in Venezuela. METHODOLOGY: This is a descriptive, correlational, and field investigation with a sample comprised by 71 HD patients of whom 57 were treated with EPO. Serum prohepcidin, ferritin, haemoglobin, hematocrit, CRP, and albumin were determined. Anaemia (haemoglobin < 10 g/dL) and iron deficiency (ferritin < 100 ng/mL) were defined according to the criteria recommended by the K/DOQUI group. Reference values: Albumin 3.5-4.8 g/dL, and for acute inflammatory conditions (CRP > 10 mg/L.). RESULTS: The mean value for prohepcidin was 397.5 ng/mL. A high percentage of anaemia was observed (87.3%) and 22.5% of the patients had low levels of serum ferritin. There were no statistically significant differences for ferritin, albumin, CRP, or prohepcidin, between patients with and without EPO therapy. Only the CRP value was significantly correlated (rho = 0.276; p = 0.020) with prohepcidin. CONCLUSION: HD patients present high levels of prohepcidin, and this may be due to the common ongoing inflammatory process in these patients and not to the iron status measured through serum ferritin levels.