Serum sex hormone-binding globulin levels are reduced and inversely associated with intrahepatic lipid content and saturated fatty acid fraction in adult patients with glycogen storage disease type 1a.

PURPOSE: De novo lipogenesis has been inversely associated with serum sex hormone-binding globulin (SHBG) levels. However, the directionality of this association has remained uncertain. We, therefore, studied individuals with glycogen storage disease type 1a (GSD1a), who are characterized by a genetic defect in glucose-6-phosphatase resulting in increased rates of de novo lipogenesis, to assess the downstream effect on serum SHBG levels. METHODS: A case-control study comparing serum SHBG levels in patients with GSD1a (n = 10) and controls matched for age, sex, and BMI (n = 10). Intrahepatic lipid content and saturated fatty acid fraction were quantified by proton magnetic resonance spectroscopy. RESULTS: Serum SHBG levels were statistically significantly lower in patients with GSD1a compared to the controls (p = 0.041), while intrahepatic lipid content and intrahepatic saturated fatty acid fraction-a marker of de novo lipogenesis-were significantly higher in patients with GSD1a (p = 0.001 and p = 0.019, respectively). In addition, there was a statistically significant, inverse association of intrahepatic lipid content and saturated fatty acid fraction with serum SHBG levels in patients and controls combined (ß: - 0.28, 95% CI: - 0.47;- 0.09 and ß: - 0.02, 95% CI: - 0.04;- 0.01, respectively). CONCLUSION: Patients with GSD1a, who are characterized by genetically determined higher rates of de novo lipogenesis, have lower serum SHBG levels than controls.

Association of culture medium with growth, weight and cardiovascular development of IVF children at the age of 9 years.

STUDY QUESTION: Is embryo culture media used during an IVF/ICSI treatment associated with differences in growth, body composition and cardiovascular development as determined in 9-year-old singleton IVF children? SUMMARY ANSWER: The choice of in vitro culture medium for human embryos is associated with differences in body weight, BMI, truncal adiposity, waist circumference and waist/hip ratio at the age of 9, while no significant differences were observed in cardiovascular development. WHAT IS KNOWN ALREADY: Children born after IVF/ICSI have an increased risk of low birthweight, which is correlated with a higher risk of cardiovascular diseases. Some studies show that IVF children exhibit a significantly higher systolic and diastolic blood pressure and higher fasting glucose levels compared to naturally conceived children. After alternating assignment to G1™ Version 3 (Vitrolife) or K-SICM (Cook) embryo culture media, birthweight of the resulting children was significantly higher in the Vitrolife group and they remained heavier during the first 2 years of life. STUDY DESIGN, SIZE, DURATION: In this observational cohort study (MEDIUM-KIDS), parents of singletons from a previous study were approached for further follow-up after the ninth birthday of their child. The singletons were born after fresh embryo transfer of cleavage stage embryos resulting from an IVF/ICSI treatment performed between July 2003 and December 2006 in our clinic, when two different culture media were used alternately: either G1™ Version 3 (Vitrolife) or K-SICM (Cook). Follow-up measurements were performed between March 2014 and December 2016. PARTICIPANT/MATERIALS, SETTINGS, METHODS: Parents were invited to attend our clinic with their child for a single visit lasting ~2.5 h. Two experienced clinicians performed all measurements as part of the MEDIUM-KIDS study in a standardized way. Height and weight of the child was measured using calibrated scales, 4-point skinfold thickness measurements were measured in triplicate and waist and hip circumference were measured using a tape measure. The following cardiovascular parameters were measured in a standardized way: blood pressure, heart rate and endothelial function by skin laser-Doppler with iontophoresis using vasodilatory drugs. Cortisol and cortisone concentrations in hair were measured. A blood sample was taken after an overnight fast for insulin, glucose, TSH and lipid analysis. Blood samples of the IVF children were compared with a non-IVF control group. Differences between culture medium groups were analysed by Student's t-test and effects of confounders were analysed using multivariable regression analysis. MAIN RESULTS AND THE ROLE OF CHANCE: Of the 294 eligible children (168 Vitrolife and 126 Cook), 136 children (75 Vitrolife and 61 Cook) participated in the study. Baseline characteristics of the participating children from the Vitrolife and Cook group were similar. Birthweight was higher in the Vitrolife group, in keeping with the full cohort. After correction for confounders, the difference in weight and BMI attributable to culture medium was 1.58 kg (95% CI: 0.01-3.14) and 0.84 kg/m2 (95% CI: 0.02-1.67), respectively, with the Vitrolife children being heavier. Height and height corrected for age and gender (SDS scores) were similar in both groups. Furthermore, waist circumference was significantly higher in the Vitrolife group with a corrected difference of 3.21 cm (95%CI: 0.60-5.81) leading to a 0.03 increase (95% CI: 0.01-0.05) in waist/hip ratio. Subscapular skinfolds combined with suprailiacal skinfolds (defined as truncal adiposity), was also significantly higher in Vitrolife children (adjusted difference 3.44 cm [95% CI: 0.27-6.62]). Both systolic (adj. beta 0.364 [95% CI: -2.129 to 2.856],) and diastolic (adj. beta 0.275 [95% CI: -2.105 to 2.654]) blood pressures (mmHg) were comparable for the two groups. After an overnight fast, cholesterol, glucose, insulin, low and high-density lipoprotein, triglycerides and TSH were normal and similar in the two groups. Endothelial function in the microcirculation was compared by using maximum perfusion units corrected for the baseline value as a measure for vasodilatory capacity. There were no significant differences between the two groups. Cortisol and cortisone concentration in hair samples were comparable. LIMITATIONS, REASONS FOR CAUTION: A limitation of the original study was its pseudo-randomized design. This and the dwindling enthusiasm of families for participation (47.7% after 9 years) prevent us from drawing robust causal conclusions from the observed association. Nevertheless, to date this is oldest cohort of IVF/ICSI children where culture medium was allocated alternatingly and used in a blinded setting, to be studied. We believe that our participants are representative for the full cohort. The current number of participants was sufficient to rule out differences as little as 3 mmHg in systolic and diastolic blood pressures. WIDER IMPLICATIONS OF THE FINDINGS: This study underlines the importance of structured follow-up of IVF/ICSI children to further elucidate possible long-term health effects. Health professionals and culture medium manufacturers should be aware that small changes in culture conditions and culture medium composition for the early embryo can have long-term health effects. The similar cardiovascular results for the two groups are reassuring but the children may still be too young to detect differences in cardiovascular development. Prolonged follow-up and structured investigations up until adulthood are necessary to gain more insight and reassurance in the cardiovascular development of IVF offspring, although long-term follow-up will become more complicated by confounding life-style and environmental factors possibly influencing development. STUDY FUNDING/COMPETING INTEREST(S): The study was financially supported by the March of Dimes (Grant number #6-FY13-153). The sponsor of the study had no role in study design, data collection, data analysis, data interpretation or writing of the report. The authors have no conflicts of interest to declare. TRIAL REGISTRATION NUMBER: NTR4220.

Diagnostic ANCA algorithms in daily clinical practice: evidence, experience, and effectiveness.

Detection of antineutrophil cytoplasmic antibodies (ANCA) for ANCA-associated vasculitides (AAV) is based on indirect immunofluorescence (IIF) on ethanol-fixed neutrophils and reactivity toward myeloperoxidase (MPO) and proteinase 3 (PR3). According to the international consensus for ANCA testing, presence of ANCA should at least be screened for by IIF and, if positive, followed by antigen-specific immunoassays. Optimally, all samples are analyzed by both IIF and quantitative antigen-specific immunoassays. Since the establishment of this consensus many new technologies have become available and this has challenged the positioning of IIF in the testing algorithm for AAV. In the current paper, we summarize the novelties in ANCA diagnostics and discuss the possible implications of these developments for the different ANCA algorithms that are currently applied in routine diagnostic laboratories. Possible consequences of replacing ANCA assays by novel methods are illustrated by our data obtained in daily clinical practice. Eventually, it is questioned if there is a need to change the consensus, and if so, whether IIF can be discarded completely, or be used as a confirmation assay instead of a screening assay. Both alternative options require that ANCA requests for AAV can be separated from ANCA requests for gastrointestinal autoimmune diseases.

The association between first trimester placental biomarkers and placental lesions of maternal vascular malperfusion.

INTRODUCTION: Abnormal levels of first trimester placental biomarkers are associated with the development of placental syndrome (PS). However, prediction performance is moderate, possibly explained by the clinical heterogeneity of PS. Aim of this study is to investigate the association between first trimester biomarkers and the presence of maternal vascular malperfusion (MVM), as a marker for placental insufficiency. METHODS: This retrospective study included 195 women with available first trimester blood sample and placenta histological sections for examination at the Maastricht University Medical Centre. Women were divided into 4 groups, based on the presence of having MVM lesions and/or PS. Levels of PAPP-A, PlGF and sFlt-1 were measured and MVM lesions were classified according to the Amsterdam Placental Workshop Group Consensus Statement. RESULTS: MVM occurrence was observed in 32% of the uncomplicated pregnancies. Women with MVM (regardless of the PS) had lower levels of PAPP-A (p = 0.038) and sFLt-1 (p = 0.006), and a non-significant trend for lower PlGF and sFlt-1/PlGF ratio compared to women without MVM. Low PAPP-A levels individually and in combination with the presence of PS was significantly associated with MVM lesions (aOR = 3.0 and 6.1, respectively), as did the combination of low PlGF levels and PS (aOR = 4.6). In women with PS, having MVM increased the incidence of fetal growth restriction, small for gestational age neonates, lower birthweight and adverse neonatal outcome. DISCUSSION: Our findings suggest that MVM lesions were found to be associated with increased obstetric risks due to early placental dysfunction that can potentially be predicted by the use of first trimester biomarkers.

[Don't be guided purely by numbers: false increased TSH values due to analytical interference]. / Vaar niet alleen op een getal.

BACKGROUND: Physicians are often guided by laboratory values. When a clinical presentation does not match laboratory values, one must consider the possibility that these values may be falsely increased or decreased. A common cause is analytical interference. CASE DESCRIPTION: A 57-year-old male, presenting with fatigue and palpitations, had high TSH and normal FT4 values. Although there were no fitting clinical symptoms for these values, the patient was treated with levothyroxine assuming he had subclinical hypothyroidism. TSH levels remained high, however, whereas FT4 levels increased and the patient developed thyrotoxicosis. Eventually, it was discovered that the TSH was falsely elevated. CONCLUSION: The patient turned out to have macro TSH, where TSH forms conjunctions with IgG into larger molecules. These conjugates cause a rarely occurring interference during laboratory analysis, resulting in a falsely increased TSH value.

'Postnatal growth during the first five years of life in SGA and AGA neonates with reduced fetal growth'.

BACKGROUND: Even though a lot of research has been done on postnatal growth and the occurrence of catch-up growth in small-for-gestational age (SGA) neonates, this phenomenon has not been studied well in appropriate-for-gestational age (AGA) neonates. Postnatal catch-up growth may also occur in AGA neonates indicating a compensatory mechanism for undiagnosed intrauterine growth restriction, especially in AGA neonates with reduced fetal growth velocity. AIMS: To describe postnatal growth during the first 5 years of life in SGA and AGA neonates and evaluating the role of fetal growth velocity in catch-up growth. STUDY DESIGN: Retrospective study in a Dutch tertiary hospital. SUBJECTS: 740 singleton neonates, without congenital anomalies, with ultrasound fetal growth data from 20 weeks and 32 weeks of pregnancy. OUTCOME MEASURES: Postnatal growth measurements of height (cm) and weight (kg) from birth until five years of age. Postnatal catch-up growth defined as difference (delta) in both height and weight between 4 weeks and 3 years of age. RESULTS AND CONCLUSIONS: SGA neonates had a significantly lower height and weight compared to the AGA group for all available measurement moments till 3 years. The catch-up growth between the SGA and AGA groups from 4 weeks up to 3 years after birth was not different between the two groups. However, neonates with reduced fetal growth velocity had a significantly higher risk for catch-up growth in height during the first 3 years after birth. This suggests a role for fetal growth velocity measurement in predicting fetal and subsequent postnatal growth potential.

PREMIUM: A French prospective multicenter observational study of factors impacting on efficacy and compliance to cetuximab treatment in first-line KRAS wild-type metastatic colorectal cancer.

BACKGROUND: Cetuximab improves progression-free survival (PFS) and overall survival (OS) in patients with KRAS wild type (wt) metastatic colorectal cancer (mCRC). Few data are available on factors impacting both efficacy and compliance to cetuximab treatment, which is, in combination with chemotherapy, a standard-of-care first-line treatment regimen for patients with KRAS wt mCRC. PATIENTS AND METHODS: PREMIUM is a prospective, French multicenter, observational study that recruited patients with KRAS wt mCRC scheduled to receive cetuximab, with or without first-line chemotherapy, as part of routine clinical practice, between October 28, 2009 and April 5, 2012 (ClinicalTrials.gov Identifier: NCT01756625). The main endpoints were the factors impacting on efficacy and compliance to cetuximab treatment. Predefined efficacy endpoints were PFS and safety. RESULTS: A total of 493 patients were recruited by 94 physicians. Median follow-up was 12.9 months. Median progression-free survival was 11 months [9.6-12]. In univariate analyses, ECOG performance status (PS), smoking status, primary tumor location, number of metastatic organs, metastasis resectability, surgery, folliculitis, xerosis and paronychia maximum grade, and acne preventive treatment were statistically significant. In multivariate analysis (Hazard Ratios of multivariate stepwise Cox models), ECOG PS, surgery, xerosis and folliculitis were positive prognostics factors for longer PFS. Among all patients, 69 (14%) were non-compliant. In multivariate analysis, no variables were statistically significant. The safety profile of cetuximab was consistent with previous studies. CONCLUSIONS: ECOG PS <2, surgical treatment performed, and maximum grade xerosis or folliculitis developed were predictive factors of cetuximab efficacy on KRAS wt mCRC patients. Unfortunately, we failed in identifying predictive factors for compliance in these patients.

Maternal vascular malformation in the placenta is an indicator for fetal growth restriction irrespective of neonatal birthweight.

INTRODUCTION: To study the association between placental pathology and neonatal birthweight and outcomes, and whether a combination of first trimester biomarkers and fetal growth velocity can predict placental lesions. METHODS: The presence of maternal vascular malperfusion (MVM) lesions (Amsterdam criteria) was recorded in a retrospective cohort of singleton pregnancies in the Maastricht University Medical Centre, 2011-2018. First trimester maternal characteristics and PAPP-A, PlGF and sFlt-1 levels were collected. Fetal growth velocities were calculated (mm/week) from 20 to 32 weeks for abdominal circumference, biparietal diameter, head circumference and femur length. Data were compared between neonates with 'small for gestational age' (SGA < p10) and different categories of 'appropriate for gestational age (AGA)': AGAp10-30, AGAp30-50 and AGA > p50 (reference), using one-way ANOVA and post hoc test. RESULTS: There were significantly more MVM lesions in the SGA group (94.6% p < .0001), but also in the AGAp10-30 (67.3% p < .0001) and AGAp30-50 (41.6% p = 0.002), compared to the reference AGA group (19.3%). The prediction of MVM for a 20% false-positive rate, with maternal characteristics was25.2%. The addition of birthweight percentile gave a prediction of 51.7% for MVM. However adding placental biomarkers and fetal growth velocities (instead of birthweight percentile) to the maternal characteristics, gave a prediction of 81.8% (PPV 49.5%, NPV 53.7%). DISCUSSION: Placental MVM lesions correlated inversely with birthweight even in AGA neonates, and was associated with slower fetal growth and more adverse outcome in SGA neonates. A combination of first trimester biomarkers and fetal growth velocity had good prediction of placental MVM lesions, as an indicator of fetal growth restriction irrespective of neonatal weight.

A randomized double-blind comparison of ondansetron and metoclopramide in the prophylaxis of emesis induced by cyclophosphamide, fluorouracil, and doxorubicin or epirubicin chemotherapy.

Seventy-five breast cancer patients scheduled to receive a first course (in a new cycle) of cyclophosphamide, fluorouracil, and doxorubicin (FAC) or epirubicin (FEC) participated in a double-blind crossover study to compare the antiemetic efficacy and safety of ondansetron (GR38032), a 5-hydroxytryptamine3 (5-HT3) receptor antagonist, and metoclopramide. Ondansetron was given as an 8 mg loading dose (4 mg intravenously [IV] plus 4 mg orally) before chemotherapy followed by 8 mg every 8 hours orally for 3 to 5 days. Metoclopramide was given as an 80 mg loading dose (60 mg IV plus 20 mg orally) before chemotherapy followed by 20 mg every 8 hours orally for 3 to 5 days. A "period" interaction in the analysis of emetic response in the first 24 hours necessitated a parallel group analysis of first treatments only, 68 patients being assessable for this parameter. In the first 24 hours, complete or major control (zero to two emetic episodes) of emesis was achieved in 30 of 35 (86%) patients receiving ondansetron and in 14 of 33 (42%) patients receiving metoclopramide (P less than .001). Ondansetron was also more effective in reducing acute nausea. On days 2 to 3, the complete or major responses were significantly better with ondansetron (81% v 65%; P = .033), but there was no statistical difference in the control of nausea. There was a significant patient preference for ondansetron (63% v 26%; P = .001). Extrapyramidal reactions were observed in two metoclopramide treatments; both treatments were otherwise well tolerated. These results are consistent with serotonin (5-HT), being a significant neurotransmitter of cyclophosphamide/doxorubicin- or epirubicin/fluorouracil-induced emesis.

Calcium blocker lacidipine and carotid arteriolar vasodilation in healthy volunteers.

Systemic and carotid hemodynamics were studied in 10 healthy male volunteers before and after short-term administration of a 4 mg dose of the calcium entry-blocker lacidipine in a placebo-controlled, double-blind, crossover study. Hemodynamic parameters of the right common carotid artery were measured before and at 1 1/2 and 3 hours after dose administration by means of pulsed Doppler flowmetry. In addition, systemic hemodynamic parameters were calculated from cardiac impedance measurements at the same time. In comparison with placebo, lacidipine produced a significant decrease in blood pressure, together with systemic and carotid arteriolar dilatation. Heart rate increased sharply, whereas carotid arterial diameter and tangential tension did not change. The study provided evidence that the calcium entry-blocker lacidipine produces systemic and carotid arteriolar vasodilation and that the heart rate baroreflex response after administration of calcium inhibitor is not associated with a significant modification of the geometry of carotid arterial wall.

An improved incubation apparatus for Western blots used for the detection of antinuclear antibodies.

To facilitate the use of Western blots for the detection of antibodies, we have developed an incubation apparatus. The use of this apparatus simplifies the incubation of blots with antisera, permits the testing of large numbers of sera and eliminates artefacts caused by the use of loose strips. The introduction of a pressure bag in the lower lid of the apparatus secures a steady pressure over the entire blot, a feature lacking in currently available commercial equipment. The detection of antinuclear antibodies is presented as an example of the use of this incubator.

Evaluation of nasopharyngeal cultures for bacteriologic assessment of acute otitis media in children.

BACKGROUND: The recent emergence of penicillin-resistant Streptococcus pneumoniae, particularly in acute otitis media (AOM), has increased interest in the development of noninvasive procedures that might help to predict the bacterial etiology of this condition. We conducted an open multicenter study to evaluate the predictive value of the nasopharyngeal (NP) sampling in children with AOM by comparing the bacteriologic results of NP cultures with those of pus collected by myringotomy in the same patients. METHODS: The NP secretions and the pus obtained by myringotomy were collected concomitantly in 354 children younger than 6 years of age with clinical signs of AOM. The clinical usefulness of NP culture was determined by calculating its sensitivity and specificity, and especially its positive and negative predictive values for the three main pathogens responsible for AOM, Haemophilus influenzae, S. pneumoniae and Moraxella catarrhalis. RESULTS: A positive NP culture was found to have little predictive value for H. influenzae (52%), S. pneumoniae (43%) and M. catarrhalis (19%). In contrast the negative predictive value of NP cultures was much greater and was accompanied by negative middle ear fluid cultures in more than 95% of children, especially for S. pneumoniae. Furthermore the incidence of beta-lactamase-producing strains of H. influenzae at both sampling sites was similar (30 and 35%, respectively), as was the incidence of penicillin-resistant S. pneumoniae (50 and 54%). CONCLUSION: It appears that the correlation between results of NP and middle ear fluid cultures in children with AOM is too weak to allow NP culture to be recommended for the bacteriologic documentation of this disease. However, these results should not overshadow the considerable epidemiologic value of NP cultures, particularly with reference to the monitoring of pneumonococcal susceptibility in children. The collection of NP cultures should therefore be promoted for their collective epidemiologic value.

rhGM-CSF vs placebo following rhGM-CSF-mobilized PBPC transplantation: a phase III double-blind randomized trial.

In this placebo-controlled randomized trial we evaluated the hematological and clinical effects of r-Hu GM-CSF after high-dose chemotherapy (HDC) followed by GM-CSF-mobilized PBPC transplantation. Fifty patients with poor prognosis malignancies were randomized in a double-blind study to receive either GM-CSF or placebo after HDC followed by PBPC rescue. For all patients, PBPCs were recruited using a combination of VP-16 (300 mg/m2 on days 1 and 2), cytoxan (3 g/m2 on days 3 and 4) and GM-CSF (5 micrograms/kg from day 5). No differences were demonstrated between the two groups in median time to neutrophil or platelet recoveries. There was no significant difference between the GM-CSF group and the placebo group in the median duration of post-transplant hospitalization, in the number of days of antibiotic treatment, in the number of infections and in red blood cell or platelet transfusion requirements. There was a significant difference with an advantage for the placebo group in the mean duration of febrile days (P = 0.01). We conclude that the administration of GM-CSF in patients transplanted with GM-CSF-mobilized PBPC is not associated with a clinical benefit in term of tempo of engraftment, numbers of documented infections, transfusion requirements and mucositis grading.

An analysis of the diagnostic methods for acute pulmonary embolism.

In spite of numerous sophisticated investigative procedures, acute pulmonary embolism (PE) is very frequently misdiagnosed. In order to improve the diagnostic approach to PE, the sensitivity and specificity of the commonly used methods were reviewed in a group of 421 patients with angiographically proved PE without associated cardio-pulmonary disease. The specificity of diagnostic procedures was, by decreasing order: positive pulmonary angiography (to affirm) = negative perfusion lung scan (to eliminate) greater than chest X-ray much greater than clinical symptoms, positive perfusion lung scan, ECG, blood gas, serum enzymes.

GR38032F, a 5HT3 receptor antagonist, in the prophylaxis of acute cisplatin-induced nausea and vomiting.

A total of 28 patients receiving cancer chemotherapy with cisplatin-containing regimens (70-120 mg/m2) participated in an evaluation of the efficacy and safety of GR38032F for the prevention of acute nausea and vomiting. GR38032F, a 5HT3 receptor antagonist, was given 30 min prior to cisplatin as an 8-mg loading dose by i.v. infusion over 15 min, followed by continuous infusion at a rate of 1 mg/h for 24 h. Efficacy was assessed by measurement of the number of episodes of retching and vomiting occurring in the 24 h after cisplatin administration and by an assessment of nausea during the same period. In all, 26 patients were evaluable for efficacy: overall, complete control was achieved in 12 patients (46%), major control (1-2 emetic episodes), in 6 (23%); minor control (3-5 episodes), in 1 (4%); control could not be achieved (failure; greater than 5 episodes) in 7 patients (27%). GR3832F was the tolerated, with no significant drug-related adverse events. These encouraging results should be confirmed in comparative trials.

Clinical efficacy and safety of fluticasone propionate 250 microg twice daily administered via a HFA 134a pressurized metered dose inhaler to patients with mild to moderate asthma. French study group.

This study compared the efficacy and safety of the fluticasone propionate 125 microg pressurized metered dose inhaler (pMDI) propelled by either hydrofluoroalkane (HFA) 134a or chlorofluorocarbon (CFC) propellants, in adult patients with asthma. HFA 134a is a non-ozone depleting propellant used as a replacement for the CFC propellants 11 and 12 which are being phased out in accordance with the Montreal Protocol. Three hundred and eighty patients with mild to moderate asthma and 'room for improvement' in their treatment were randomized to receive fluticasone propionate 250 microg twice daily via pMDIs propelled by either CFC propellants 11 and 12 (n = 195) or HFA 134a (n = 185). Fluticasone propionate significantly improved lung function over the 4-week treatment period in both treatment groups. The improvement in mean morning peak expiratory flow (PEF) after 7 days of treatment was approximately 12 l min(-1) in both groups, rising to approximately 22 l min(-1) at the end of the 4-week treatment period. The adjusted mean difference between the two formulations over weeks 1-4 was -1 l min(-1) (90% confidence interval: -7, 5 l min(-1)), confirming their equivalence. Clinical comparability was also demonstrated with respect to secondary efficacy variables, including daily symptom scores, evening PEF and clinic visit expiratory measurements. There were no clinically relevant differences in adverse events or serum cortisol levels between the two groups. The fluticasone propionate 125 microg HFA 134a pMDI is an effective and well tolerated product and is a suitable replacement for the fluticasone propionate 125 microg CFC pMDI at a microgram equivalent dose.

Progressive transmission of line drawings using the wavelet transform.

This paper presents a method to apply progressive transmission to line drawings using the wavelet transform. Experiments have been conducted and showed that the wavelet transform, combined with a quantization step, performs progressive transmission using a data rate comparable to standard chain coding at the expense of almost no visually perceptible distortion.

[Ondansetron: a specific 5-HT3 serotonin receptor inhibitor, a new antiemetic in oncology]. / Ondansétron: un nouvel antiémétique en oncologie, inhibiteur spécifique des récepteurs à la sérotonine du type 5-HT3.

Serotonin (5-Hydroxytryptamine) seems to play a dominant role in triggering vomiting induced by cytotoxic agents through the stimulation of 5-HT3 receptors. They have been observed in the GI tract as well as in the brain (area postrema). Ondansetron is a specific antagonist of 5-HT3 serotonin receptors. Its anti-emetic activity is very powerful in the ferret. The availability of an injectable or oral form of this product allows the overall treatment of acute and delayed emesis and its administration is in accordance with different schedules: single IV injection or a continuous 24 hour infusion or repeated IV injection followed by oral treatment. The pharmacokinetics of the drug are as follows: absorption begins about 30 minutes after the administration per os, its biodisponibility is about 60%, its clearance: 20 ml/minute and its elimination half life about 3 hours. Different double blind studies, carried out in parallel groups or in cross over, demonstrated the superiority of ondansetron over metoclopramide in the control of nausea and vomiting, whether or not the chemotherapy contained cisplatin; a more recent study shows also that ondansetron was superior to alizapride and methylprednisolone in combination. Side effects of ondansetron do not include extrapyramidal symptoms but only headaches and constipation. The use of ondansetron improves the well-being of patients receiving chemotherapy and increases protocol compliance.

[Effect on atrioventricular conduction of a new calcium antagonist: lacidipine. Evaluation by the Holter method]. / Effet sur la conduction atrioventriculaire d'un nouvel antagoniste calcique: la lacidipine. Evaluation par la méthode de Holter.

The modification of AV conduction induced by 4 mg b.i.d. of lacidipine (L), a new calcium antagonist, was assessed by studying the changes in ventricular rhythm in 10 patients with stable chronic atrial fibrillation (mean age 71 +/- 15) by daily Holter recordings. The study was single blind versus placebo (P), nifedipine (N) 10 mg b.i.d. and for five patients diltiazem (D) 120 mg b.i.d. Five or seven consecutive 24 hours Holter were recorded in the following order: P, P, N or L, P, N or L, D, D. For each hour, an RR histogram was drawn and the 10 per cent and 90 per cent values of the cumulative cycle length curve were computed, as were the total number of QRS, and the mean value of RR intervals. The correlation coefficient between the number of QRS from the same hour on different days, the Student t test between the mean hourly RR interval values and the comparison between the histograms did not demonstrate a significant difference between the placebo, the nifedipine and the lacidipine periods. The only significant changes were induced by diltiazem (p less than 0.01), with a significant prolongation of the RR intervals. This suggests that lacidipine, like nifedipine, has no effect on AV conduction.