Epidemiologische Beobachtungen bei Erkrankungen durch Salmonella infantis

Zusammenfassung Es werden mehrere Erkrankungen durch Salmonella infantis beschrieben und die bakteriologischen und serologischen Ergebnisse besprochen. Bei einer Gruppenerkrankung konnte aus einer Kükenkot-probe des Hühnerhofes Salmonella infantis gezüchtet werden. Ebenfalls wurden in einer benachbarten Hühnerfarm, wo die Küken ausgebrütet waren, in mehreren Fällen aus Hühnerkotproben diese Bakterien isoliert. Es wird auf den möglichen Infektionsweg und auf die Gefahren, die durch den Genuß ungenügend gekochter Hühnereier entstehen können, hingewiesen.     

A dinucleotide mutation in the endothelin-B receptor gene is associated with lethal white foal syndrome (LWFS); a horse variant of Hirschsprung disease

Lethal white foal syndrome (LWFS) is a congenital anomaly of horses characterized by a white coat colour and aganglionosis of the bowel, which is similar to Hirschsprung disease (HSCR). We decided to investigate possible mutations of the endothelin-B receptor gene ( EDNRB ) in LWFS as recent studies in mutant rodents and some patients have demonstrated EDNRB defects. First, we identified a full-length cDNA for horse EDNRB . This cDNA fragment contained a 1329 bp open reading frame which encoded 443 amino acid residues. The predicted amino acid sequence was 89, 91 and 85% identical to human, bovine and mouse as well as rat EDNRB respectively, but only 55% identical to the human, bovine and rat endothelin A receptor (EDNRA). Secondly, sequence analysis, together with allele-specific PCR and the amplification- created restriction site (ACRS) technique, revealed a dinucleotide TC-- >AG mutation, which changed isoleucine to lysine in the predicted first transmembrane domain of the EDNRB protein. This was associated with LWFS when homozygous and with the overo phenotype when heterozygous.      

Relationship between HLA-DRB1 and DQ alleles and the genetic susceptibility to type 1 diabetes

Objective　To study the relationship between human leukocyte antigen (HLA)-DRB1 and DQ alleles and the genetic susceptibility of type 1 diabetes in North Chinese children. Methods　Polymerase chain reaction (PCR) techniques were used to amplify the second exon of DRB1 and DQ alleles, after which sequence specific olignucleotide probe (SSOP) dot blot hybridization techniques were used to analyze the amplified products. Results　DRB1*0301, DQA1*0301, DQB1*0201 alleles and DRB1*0301-DQA1*0501-DQB1*0201 haplotype were significantly increased in patients, while DQA1*0103 and DQB1*0601 alleles were significantly increased in controls. The distribution of DR4 and DR9 haplotypes in patients and controls were not significantly different, but DR3/DR4 and DR4/DR9 heterozygotes were significantly increased in patients. Conclusions　DRB1*0301, DQA1*0301 and DQB1*0201 confer susceptibility while DQA1*0103 and DQB1*0601 confer protection to type 1 diabetes. DRB1*0301-DQA1*0501-DQB1*0201 haplotype offers a predisposition to type 1 diabetes in North Chinese. Although the distribution of DR4 and DR9 in patients and controls had no significant difference, DR3/DR4 and DR3/DR9 heterozygotes were significantly increased in patients, showing that the susceptive effects of DR3 and DR4 or DR4 and DR9 haplotypes could be added up.     

Efficacy of "high-intensity" blue-light and "standard" daylight phototherapy for non-haemolytic hyperbilirubinaemia

We report our clinical experience with phototherapy in 3802 infants; 3629 were exposed to "standard" daylight phototherapy and 173 to "high-intensity" blue-light phototherapy. High-intensity blue-light phototherapy was twice as effective as standard daylight phototherapy in decreasing bilirubin concentrations. No failures occurred with high-intensity phototherapy compared with an overall failure rate of 1.84/1000 with daylight lamps; these cases were transferred to high-intensity phototherapy with prompt response. Rebound after cessation of phototherapy was greater in those exposed to high-intensity blue light with a significantly greater number requiring a second exposure. However, the incidence was still low. No third exposure was required in any infant. Nursing of infants under high-intensity blue light was more difficult and inconvenient as was clinical monitoring. The light also caused more stress on the nursing and medical personnel. However, the infants tolerated both types of phototherapy equally well. High-intensity blue-light phototherapy would seem to be the treatment of choice for infants with rapidly increasing or very high bilirubin levels, as well as in those not responding adequately to daylight phototherapy.     

Identification of cytochrome p450 enzymes involved in the metabolism of 4'-methyl-alpha-pyrrolidinopropiophenone, a novel scheduled designer drug, in human liver microsomes.

4'-Methyl-alpha-pyrrolidinopropiophenone (MPPP) is a new drug of abuse. It is believed to have an abuse potential similar to that of amphetamines. Previous studies with Wistar rats had shown that MPPP was metabolized mainly by hydroxylation in position 4' followed by dehydrogenation to the corresponding carboxylic acid. The aim of the study presented here was to identify the human hepatic cytochrome p450 (p450) enzymes involved in the biotransformation of MPPP to 4'-hydroxymethyl-pyrrolidinopropiophenone. Baculovirus-infected insect cell microsomes and human liver microsomes were used for this purpose. Only CYP2C19 and CYP2D6 catalyzed this hydroxylation. The apparent Km and Vmax values for the latter were 9.8 +/- 2.5 microM and 13.6 +/- 0.7 pmol/min/pmol p450, respectively. CYP2C19 was not saturable over the tested substrate range (2-1000 microM) and interestingly showed a biphasic kinetic profile with apparent Km,1 and Vmax,1 values of 47.2 +/- 12.5 microM and 8.1 +/- 1.4 pmol/min/pmol p450, respectively. Experiments with pooled human liver microsomes also revealed biphasic nonsaturable kinetics with apparent Km,1 and Vmax,1 values of 57.0 +/- 20.9 microM and 199.7 +/- 59.7 pmol/min/mg of protein for the high affinity enzyme, respectively. Incubation of 2 microM MPPP with 3 microM of the CYP2D6-specific inhibitor quinidine resulted in significant (p < 0.01) turnover inhibition (11.8 +/- 1.6% of control). Based on kinetic data corrected for the relative activity factors, CYP2D6 is the enzyme mainly responsible for MPPP hydroxylation, confirmed by CYP2D6 inhibition studies.     

Informed consent, parental awareness, and reasons for participating in a randomised controlled study

BACKGROUND: The informed consent procedure plays a central role in randomised controlled trials but has only been explored in a few studies on children. AIM: To assess the quality of the informed consent process in a paediatric setting. METHODS: A questionnaire was sent to parents who volunteered their child (230 children) for a randomised, double blind, placebo controlled trial of ibuprofen syrup to prevent recurrent febrile seizures. RESULTS: 181 (79%) parents responded. On average, 73% of parents were aware of the major study characteristics. A few had difficulty understanding the information provided. Major factors in parents granting approval were the contribution to clinical science (51%) and benefit to the child (32%). Sociodemographic status did not influence initial participation but west European origin of the father was associated with willingness to participate in future trials. 89% of participants felt positive about the informed consent procedure; however, 25% stated that they felt obliged to participate. Although their reasons for granting approval and their evaluation of the informed consent procedure did not differ, relatively more were hesitant about participating in future. Parents appreciated the investigator being on call 24 hours a day (38%) and the extra medical care and information provided (37%) as advantages of participation. Disadvantages were mainly the time consuming aspects and the work involved (23%). CONCLUSIONS: Parents' understanding of trial characteristics might be improved by designing less difficult informed consent forms and by the investigator giving extra attention and information to non-west European parents. Adequate measures should be taken to avoid parents feeling obliged to participate, rather than giving true informed consent.     

Evaluation of three risk scores to predict postoperative nausea and vomiting

BACKGROUND: So far there are three different scores to predict postoperative vomiting (PV: Apfel et al., 1998) or postoperative nausea and vomiting (PONV: Koivuranta et al., 1997; Palazzo and Evans, 1993). All three scores used logistic regression analysis to identify and create weights for the risk factors for PV or PONV. In short, these were sex, age, history of previous PONV, motion sickness, duration of anaesthesia, and use of postoperative opioids. However, an external evaluation and a comparison of these scores has not been performed so far. METHODS: Patients undergoing a variety of surgical procedures under general anaesthesia were studied prospectively. Preoperatively, they completed a questionnaire concerning potential risk factors for the occurrence of PV or PONV implemented in the three risk scores. Balanced anaesthesia (induction agent, nondepolarising neuromuscular blocker, opioid, and inhalation agent in nitrous oxide/oxygen) was performed. No intravenous anaesthesia or any antiemetic prophylaxis was applied. Postoperatively, the patients were observed in the recovery room for the occurrence of PV and PONV and were visited twice on the ward within the 24-h observation period. Both the patients and the nursing staff were asked whether PV or PONV was present. The severity of PONV was categorised using a standardised scoring algorithm. A total of 1,444 patients was finally included into the analysis. Using information of the predicted risk for the individual patients and the actual occurrence of PV or PONV, Receiver Operator Characteristics (ROC-curves) were drawn. The area under each ROC-curve was calculated as a means of the predictive properties of each score and was compared for statistical differences. RESULTS: For prediction of PONV (any severity) the AUC-values (AUC=area under the curve) and the corresponding 95%-confidence intervals were: Apfel: 0.70 (0.67-0.72); Koivuranta: 0.71 (0.69-0.73); Palazzo: 0.68 (0.65-0.70). For prediction of PV: Apfel: 0.73 (0.71-0.75); Koivuranta: 0.73 (0.70-0.75); Palazzo: 0.68 (0.65-0.70). Thus, all three scores appeared to have a moderate accuracy as measured by the AUC. The score of Koivuranta predicts PONV (P=0.007) and also PV (P=0.002) significantly better than Palazzo's score. Furthermore, for predicting of PV the score of Apfel was also superior to Palazzo's score (P=0.005). All three scores predict PV with the same accuracy as PONV. CONCLUSION: The occurrence of PV and PONV in patients undergoing surgery under balanced anaesthesia can be predicted with moderate but acceptable accuracy using one of the available risk scores, regardless of local surgical or anaesthesiological circumstances. For clinical practice, we recommend the score published by Koivuranta, since its calculation is very simple.     

Impact of Caffeine on Overactive Bladder Symptoms

Caffeine consumption is highly prevalent in the adult population. First-line treatment of overactive bladder (OAB) symptoms involves behavioral modification, which includes reduction of caffeine consumption. A literature review over the last 3 years has identified 10 peer-reviewed articles that investigated the effects and mechanisms of caffeine on OAB symptoms. The literature describes that caffeine can be associated to de novo OAB symptoms or their exacerbation. Those effects have been found to be dose dependent. Significant associations to age and gender cannot be made at this point due to limited studies. This review raises awareness of caffeine’s potential causal impact on OAB symptoms, which is important when counseling the general population and patients suffering from OAB. Since there is a lack of evidence-based data to support clinical recommendations, more controlled-randomized prospective studies are needed to assess the impact of caffeine on OAB symptoms that also control for dose, gender, and age.     

A monokine regulates colony-stimulating activity production by vascular endothelial cells

Human umbilical vein endothelial cells were cultured in supernatants of peripheral blood monocytes that had been cultured for 3 days with and without lactoferrin. Colony-stimulating activity (CSA) was measured in supernatants of the endothelial cell cultures and appropriate control cultures using normal, T-lymphocyte-depleted, phagocyte-depleted, low- density bone marrow cells in colony growth (CFU-GM) assays. Monocyte- conditioned medium contained a nondialyzable, heat labile factor that enhanced 4-15--fold the production of CSA by endothelial cells. The addition of lactoferrin to monocyte cultures reduced the activity of this monokine by 69%. Lactoferrin did not inhibit CSA production by monokine-stimulated endothelial cells. Therefore, vascular endothelial cells are potent sources of CSA, the production of CSA by these cells is regulated by a stimulatory monokine, and the production and/or release of the monokine is inhibited by lactoferrin, a neutrophil- derived putative feedback inhibitor of granulopoiesis. Inasmuch as a similar monokine is known to stimulate CSA production by fibroblasts and T lymphocytes, we suggest that mononuclear phagocytes play a pivotal role in the regulation of granulopoiesis by recruiting a variety of cell types to produce CSA.