Hazelnut allergy differs between children and adults in frequency of severity, aetiology and relevance of diagnostic parameters.

BACKGROUND: Hazelnut allergy in adults is often birch pollen related, whereas in children, non-pollen-related hazelnut allergy is more frequent. OBJECTIVE: To compare the differences in hazelnut allergy between children and adults with regard to severity, aetiology and diagnostic value of routinely available data. METHODS: Adults (n = 120) who underwent a double-blind placebo-controlled food challenge (DBPCFC) for hazelnut were selected and compared to 151 hazelnut-challenged children from a previous study. Univariate and multivariate logistic regression analyses were performed to build a prediction model. The area under the curve (AUC) of the ROC curve was determined for level of hazelnut-specific IgE, skin prick test (SPT) and the prediction model. RESULTS: Hazelnut allergy was confirmed by DBPCFC in 95/120 (79%) adults, 77% had only subjective and 23% objective symptoms, whereas in children, 63% had objective symptoms to hazelnut. Within the group of children, the frequency of severe hazelnut allergy was higher in younger than in older children. A concomitant birch pollen allergy was more common in adults (82%) than in children (39%) with a hazelnut allergy. A detailed history with allergic symptoms to previous ingestion of hazelnut had the highest diagnostic value in adults, while in children, SPT to hazelnut extract showed the highest level of discrimination between clinical reactivity and tolerance to hazelnut. CONCLUSIONS AND CLINICAL RELEVANCE: Hazelnut allergy differs between children and adults with respect to frequency of severity, aetiology and relevance of diagnostic parameters. Therefore, age has to be taken into account in the diagnostic work-up of a hazelnut allergy.

First trimester trophoblast and placental bed vascular volume measurements in IVF or IVF/ICSI pregnancies.

STUDY QUESTION: Are first trimester trophoblast volume (TV) and placental bed vascular volume (PBVV) different in IVF or IVF/ICSI pregnancies in comparison with spontaneously conceived pregnancies? SUMMARY ANSWER: Any possible abnormal placentation in IVF or IVF/ICSI pregnancies in comparison with spontaneously conceived pregnancies is not detected by a difference in PBVV or TV at an early gestational age (GA). WHAT IS KNOWN ALREADY: Assisted reproductive technology pregnancies have been associated with an increased risk of placenta-related adverse pregnancy outcomes. It is unclear whether these effects originate from infertility or from the technique itself. STUDY DESIGN, SIZE, DURATION: We performed a retrospective cohort study in which 154 pregnant patients qualified for participation. PARTICIPANTS/MATERIALS, SETTING, METHODS: Out of 154 pregnant patients, 84 conceived spontaneously and 70 conceived after IVF or IVF/ICSI. We determined the TV at 10 weeks GA by Virtual Organ Computer-aided AnaLysis measuring application and the PBVV at 12 weeks GA by the virtual reality operating system of BARCO I-Space in both subgroups. The investigators were blinded to the mode of conception during the measurements. Analysis was limited to singleton pregnancies with only one sac ever detectable. MAIN RESULTS AND THE ROLE OF CHANCE: There were no differences in TV (mean 42.7, SD 15.9 versus mean 41.2, SD 13.9, P = 0.70) and PBVV (mean 27.6, SD 16.9 versus mean 24.8, SD 19.9, P = 0.20) between IVF or IVF/ICSI pregnancies and spontaneously conceived pregnancies. There was a significant correlation between TV and PBVV (rs = 0.283, P = 0.004). LIMITATIONS, REASONS FOR CAUTION: The limitations of the present study concern the small size of the study groups. WIDER IMPLICATIONS OF THE FINDINGS: IVF or IVF/ICSI does not seem to be associated with abnormal placentation. STUDY FUNDING/COMPETING INTERESTS: This study was financially supported by the Erasmus Trustfonds, the Meindert de Hoop foundation and the Fonds NutsOhra. No competing interests are declared.

Early first-trimester trophoblast volume in pregnancies that result in live birth or miscarriage.

OBJECTIVES: To assess the validity of trophoblast volume measurements on three-dimensional ultrasound (3D-US) with Virtual Organ Computer-aided AnaLysis (VOCAL(TM) ), to create reference values between 6 and 12 weeks of gestation and to compare trophoblast volume between pregnancies ending in miscarriage and those resulting in live birth. METHODS: In a prospective periconceptional cohort, we performed weekly 3D-US in 112 singleton pregnancies resulting in a non-malformed live birth and in 56 ending in miscarriage. Scans were performed between 6 and 12 weeks. Trophoblast volumes were calculated by subtracting the gestational sac volume from the volume of the total pregnancy. The interobserver and intraobserver agreement of measurements were determined to assess validity. Reference values were created for trophoblast volume in relation to crown-rump length and gestational age. RESULTS: A total of 722 3D-US examinations were available for offline VOCAL measurements, but measurements could be performed in only 53% of these due to non-targeted scanning and incomplete framing. Interobserver and intraobserver agreement for trophoblast volume measurements were excellent, with intraclass correlation coefficients > 0.97. Trophoblast volumes of pregnancies ending in miscarriage were significantly smaller (P < 0.01) than were those of pregnancies that resulted in live birth. Trophoblast growth in pregnancies ending in miscarriage was also reduced compared with that in pregnancies that resulted in live birth. CONCLUSION: VOCAL is a valid technique for measuring trophoblast volume during the early first trimester of pregnancy. Pregnancies ending in miscarriage have smaller trophoblast volumes as well as reduced trophoblast growth compared with those that result in live birth.

Safety evaluation of Evesse EPC, an apple polyphenol extract rich in flavan-3-ols.

The safety of the apple polyphenol extract EvesseEPC, which is rich in flavan-3-ols, particularly epicatechin, was evaluated. Both in a bacterial reverse mutation test and a mouse lymphoma assay, EvesseEPC showed a positive response in vitro. In vivo studies (UDS test in hepatocytes, bone marrow micronucleus test and comet assay in intestinal cells) were all negative and hence Evesse EPC is considered not to have genotoxic properties in vivo. In a 90-day study in rats, EvesseEPC was administered at dietary levels of 0%, 1.25%, 2% and 3.25%. Body weights were decreased in the high-dose group in both sexes without effects on feed or water intake. In the high-dose group, thrombocytes (males) and creatinine (both sexes) were decreased, prothrombin time (males) was increased, and liver, kidneys and spleen weights were increased (males), without histological correlates. Diffuse acinar cell hypertrophy, observed in the parotid salivary glands in all treatment groups, was not considered as adverse and presumably reflected a local, reversible and adaptive response to direct contact with EvesseEPC. The NOAEL for EvesseEPC in rats was 2% in the diet, equivalent to an overall average intake of 1.3 and 1.5 g/kg body weight/day for males and females, respectively.

Pregnancy outcome in a Spanish population of women beyond age 40 delivered above 32 weeks' gestation.

OBJECTIVE: To investigate the effect of age and parity on obstetric outcome in a Spanish population of pregnants aged 40 years or older delivered above 32 weeks'gestation. METHODS: A retrospective cohort of 16764 singleton pregnancies delivered above 32 weeks'gestation between 2000 and 2007 in a nontertiary community hospital was studied. Obstetric outcomes in women aged 40 years or above (n = 335) were compared to women aged 20-29 years (n = 347) delivered at the same period. RESULTS: During the study period, the prevalence of mothers aged 40 or above increased from 1.6% to 3%. Older pregnants were more likely to be multiparous and to have used assisted reproductive techniques. They were more likely to develop gestational diabetes (OR 7.77, 3.50-17.94) and preeclampsia (OR 2.60, 1.13-6.16) and to have a higher rate of cesarean delivery (OR 2.95, 1.98-4.42). Elective was the most frequent cause of cesarean delivery in this group. Newborns were at higher risk to suffer diabetes-related complications but no differences neither in 5-min Apgar score of <7 nor in the need for admission into special care baby unit were found. No perinatal deaths were registered. CONCLUSION: Our Spanish population of older mothers showed a higher risk for being delivered by cesarean section and for developing either preeclampsia or gestational diabetes. The overall neonatal outcome was unaffected. These data may be helpfull to counsel patients about their pregnancy expectations and possible outcomes.

Formation and removal of genotoxic activity during UV/H(2)O(2)-GAC treatment of drinking water.

The objective of this study was to determine the genotoxic activity of water after UV/H(2)O(2) oxidation and GAC filtration. Pre-treated surface water from three locations was treated with UV/H(2)O(2) with medium pressure (MP) lamps and passed through granulated activated carbon (GAC). Samples taken before and after each treatment step were extracted and concentrated by solid phase extraction (SPE) and analyzed for genotoxicity using the Comet assay with HepG2 cells and the Ames II assay. The Comet assay showed no genotoxic response in any of the samples. In the Ames II, no genotoxic response was obtained with the TAMix (a mix of six strains), but the TA98 strain showed an increase in genotoxic activity after MP-UV/H(2)O(2) for all three locations. GAC post treatment effectively reduced the activities to control levels at two of the three locations and to below the level of the pre-treated water at one site. The results indicate that UV/H(2)O(2) treatment may lead to the formation of genotoxic by-products, which can be removed by subsequent GAC filtration.

Gastritis eosinofílica y estenosis hipertrófica de píloro / Eosinophilic gastritis and pyloric estenosis

Paciente intervenido quirúrgicamente de estenosis hipertrófica de píloro, con reaparición de clínica después de un período asintomático. El caso obliga a su estudio hasta llegar al diagnóstico de gastritis eosinofílica. Se realiza una revisión de esta entidad: síntomas, métodos diagnósticos y tratamiento. (AU)

Tumor de Wilms bilateral metacrónico / Metachronous bilateral Wilms' tumor

La incidencia del tumor de Wilms bilateral es entre el 5 y 10% de los casos de nefroblastoma. La forma metacrónica representa el 2-3%. El 96,2% de las formas metacrónicas aparecen durante los primeros 5 años tras el tumor primario. Las malformaciones asociadas son más frecuentes en las formas bilaterales. La aparición de un tumor metacrónico constituye una dificultad terapéutica. Se describe el caso de una niña de 11 años con hemihipertrofia izquierda diagnosticada de recidiva metacrónica de tumor de Wilms tras 7 años del primer diagnóstico. Recibió 5 ciclos de quimioterapia preoperatoria. Se realizó tumerectomía. Por complicación posquirúrgica se realizó nefrectomía del único riñón. La paciente se encuentra en insuficiencia renal crónica por su condición de anéfrica, dependiente de hemodiálisis. Se continuó el tratamiento posquirúrgico con carboplatino y etopósido. Actualmente se encuentra en remisión completa. Es excepcional la presentación de las formas metacrónicas del tumor de Wilms después de los primeros 5 años del tumor primitivo. Cuando aparece el tumor contralateral la quimioterapia debe mantenerse hasta conseguir la reducción del tamaño tumoral para poder preservar la función renal y evitar la diálisis. En los casos de insuficiencia renal crónica secundaria a una nefrectomía bilateral la elección de los quimioterápicos efectivos y el conocimiento de la farmacocinética y farmacodinámica de éstos hace posible continuar el tratamiento en estos pacientes con el soporte adecuado de hemodiálisis (AU)

[Metachronous bilateral Wilms' tumor]. / Tumor de Wilms bilateral metacrónico.

Wilms' tumor occurs in 5-10 % of all cases of nephroblastoma. The metachronous form represents 2-3 % of cases. Most (96.2 %) metachronous tumors appear within the first 5 years of the primary tumor. Associated malformations are more common in bilateral cases. Metachronous tumors are a therapeutic challenge. We describe the case of an 11-year-old girl with left hemihypertrophy. The diagnosis was metachronous relapse of Wilms' tumor 7 years after the first diagnosis. The patient received five courses of preoperative chemotherapy and tumorectomy was performed. Because of post-surgical complications, nephrectomy was performed on her only kidney. Since she is anephric, the patient is in chronic renal failure and is dependent on dialysis. Treatment with carboplatin and etoposide was continued after surgery and the patient is currently in complete remission. The appearance of a metachronous Wilms' tumor 5 years after that of the primary tumor is rare. When a contralateral tumour develops, chemotherapy must be given until the size of the tumor is reduced in order to preserve renal function and avoid dialysis. In patients with chronic renal failure caused by bilateral nephrectomy, ongoing treatment with dialysis support can be achieved through the choice of effective drugs and knowledge of their pharmacokinetics and pharmacodynamics.

Protective immunisation against hepatitis B with an internal antigen of the virus.

Preparations of hepatitis B virus (HBV) core antigen (HBcAg) synthesised in Escherichia coli have been shown previously to confer partial immunity against infection by the virus [Murray, Bruce, Hinnen, Wingfield, van Eerd, de Reus, and Schellekens: EMBO Journal 3:645-650, 1984]. In a further experiment reported here, immunisation of chimpanzees with a similar preparation of HBcAg that had been treated with sodium dodecyl sulphate in order to expose e antigen epitopes was found to protect one animal completely and another quite substantially upon challenge with the virus. The results are used to support the argument for trials in humans of a vaccine against HBV based upon or containing HBcAg and its e antigen derivative, and in discussion of a more general role for internal antigens in generating immunity against viral infection.

The protection of chimpanzees against hepatitis B viral infection using a recombinant yeast-derived hepatitis B surface antigen.

In order to determine the efficacy of the SmithKline Biologicals recombinant DNA yeast-derived hepatitis B vaccine in inducing protection against hepatitis B infection, two chimpanzees were injected intramuscularly with 20 micrograms according to a 0-, 1-, and 2-month schedule. After the second dose, the vaccinated animals already showed a significant antibody response. One month after the last injection, the animals were challenged with hepatitis B virus. The vaccinated animals were protected while the two unvaccinated controls showed all signs of hepatitis B infection. One year after vaccination, antibodies remained high and were comparable with levels produced by plasma-derived vaccines.

Hepatitis B virus antigens made in microbial cells immunise against viral infection.

Chimpanzees have been vaccinated successfully against hepatitis B virus with preparations of the viral antigens made in microbial cells by genetic engineering methods.

Antiviral activity of interferon in rats and the effect of immune suppression.

The antiviral effect of interferon was studied in a number of experimental virus infections in the rat. Interferon was shown to protect rats infected with pseudorabies virus, herpes simplex virus or vesicular stomatitis virus. The antiviral activity was not inhibited by immune suppression induced by azothioprine, prednisolone or cyclosporin A treatment. Cyclophosphamide completely blocked the in vivo activity of interferon in rats.

Structure and expression in Escherichia coli of a cloned rat interferon-alpha gene.

DNA synthesized by in vitro transcription on rat interferon (IFN) mRNA has been cloned and amplified as recombinant DNA. The nucleotide sequence of these rat IFN cDNA clones revealed i. the partial presence of the coding region of the gene and ii all cDNA clones were derived from the same subtype of rat IFN-alpha mRNA. Purified inserted fragments were used as a hybridisation probe against chromosomal "Southern blots" to show that at least twelve rat IFN-alpha-related sequences are present in the genome. A lambda-linked rat gene library was screened with the cDNA probes, resulting in an equivalent number of rat IFN-alpha-related hybrid phages. By use of a 3'-noncoding region as a probe, the chromosomal counterpart of the cDNA clones could be detected and the nucleotide sequence of its coding region has been determined. Expression of the coding region in E. coli yielded biologically active IFN, when tested for in vitro or in vivo antiviral activity.

The chimpanzee as a model to test the side effects of human interferons.

Interferon are naturally occurring proteins that are currently under evaluation as potential antiviral and antitumor agents. Currently all human interferons can in principle be produced in adequate amounts by recombinant DNA technology. Human interferons produce side effects, but because they are species-specific the toxicity cannot be tested in lower mammals. The chimpanzee is the only species in which the side effects of human interferon can be reproduced, and only in this species the toxicity of human interferons can be screened.

Circulating interferon in rabbits and monkeys after administration of human gamma interferon by different routes.

Rabbits and rhesus monkeys were injected with 3 X 10(5) units of human gamma interferon (IFN) prepared in human leukocyte suspensions. Circulating IFN was detected up to 4 h after intravenous administration. Intramuscular injection maintained a relatively stable serum IFN level of about 50 units/ml for 7 to 9 h. The results in both species were similar. Little or no circulating IFN was detected after subcutaneous injection of 3 X 10(5) units, but 1.5 X 10(6) units maintained about 50 units per ml of serum for 30 h. Pharmacokinetically, human gamma IFN resembled human alpha interferons rather than human beta IFN.