Biomedical subjects
Publications and source records attributed to W Müller.
The aim of this study was to analyse changes in peripheral oxygenation in healthy term neonates within the first week of life with near-infrared spectroscopy and venous occlusion. Oxygen delivery did not change with increasing age. Oxygen consumption and fractional oxygen extraction increased, whereas tissue oxygenation index decreased with increasing age.
We studied monocytic differentiation of primary mouse progenitor cells to understand molecular mechanisms of differentiation. We found a tightly controlled non-apoptotic activation of caspase-3 that correlated with differentiation. Although caspase activity was already detected during monocytic differentiation, a caspase-3 target has not been identified yet. We show that hematopoietic progenitor kinase 1 (HPK1) is processed towards its N- and C-terminal fragments during monocytic differentiation. While HPK1 is an immunoreceptor-proximal kinase in T and B cells, its role in myeloid cells is elusive. Here, we show that the N-terminal cleavage product, HPK1-N, comprising the kinase domain, confers progenitor cell survival independent of the growth factor IL-3. Furthermore, HPK1-N causes differentiation of progenitor cells towards the monocytic lineage. In contrast to full-length kinase, HPK1-N is constitutively active causing sustained JNK activation, Bad phosphorylation and survival. Blocking of caspase activity during differentiation of primary mouse progenitor cells leads to reduced HPK1-N levels, suppressed JNK activity and attenuated monocytic differentiation. Our work explains growth factor-independent survival during monocytic differentiation by caspase-mediated processing of HPK1 towards HPK1-N.
For the first time a multimodal approach to NEC prophylaxis is reported, consisting of early trophic feeding with human breast milk, and enteral administration of an antibiotic, an antifungal agent, and probiotics. A retrospective analysis of local protocol of NEC prophylaxis is presented. Included were all VLBWI admitted to the NICU, including transfers within the first 28 days of life. These infants were divided into two groups, an "inborn group" (infants admitted within the first 24 h of life) and an "outborn group" (infants admitted after the onset of their second day of life). Prophylaxis of NEC according to protocol was started at the day of admission, and was continued until discharge. Between 1998 and 2004, 405 VLBWI were admitted, including all transfers within the first 28 days of life. A total of 334 (82%) infants were admitted within the first 24 h of life (inborn group), and 71 (18%) were admitted after 24 h of life (outborn group). Five infants developed clinical features of necrotizing enterocolitis. The inborn group showed a NEC incidence of 0.7% (two infants), whereas the outborn group showed a NEC incidence of 4.5% (three infants), respectively. This difference was significant (P=0.049, Fisher's exact test). A surgical treatment with bowel resection was performed in two infants (both from the outborn group). The present study used a combination of different strategies, all having shown to have some beneficial effect, but not having brought a clinical breakthrough in single administration studies. Combinated were the beneficial effects of human breast milk feeding, oral antiobiotics, oral antifungal agents, and the administration of probiotics. In a homogenous group of preterm infants, using this protocol of multimodal NEC prophylaxis, there was a very low incidence of NEC, when started within the first 24 h of life.
Underweight is becoming increasingly prevalent in many sports. Among world class ski jumpers, the body mass index BMI has decreased by 4 units since 1970. The BMI ignores different body properties of individuals. Particular care should be taken in groups with unusual leg length to avoid classifying them inappropriately as thin or overweight (WHO). The improved measure MI (mass index) for relative body weight overcomes this shortcoming. Anthropometric data of ski jumpers was collected during the Olympic Games in Salt Lake City (2002; participation 81 %, n = 57), during the Summer Grand Prix in Hinterzarten (2000; participation 100 %, n = 92), and during the World Cup in Planica (2000; n = 56). The BMI and the MI were determined. The MI considers the individual leg length: A person with longer legs than average has an MI > BMI, and vice versa: MI = 0.28 m/s2 (m: mass in kg, s: sitting height in meters). BMI classes of ski jumpers in the season 2004/2005 were calculated from their official individual ski length limitation which is a function of their BMI. BMI means were 19.84 in Planica, 19.58 in Hinterzarten, and 19.43 kg m(-2) in SLC. Lowest BMI was 16.4 kg m(-2). The percentage of underweight ski jumpers (BMI < 18.5 kg m(-2)) decreased from 22.8 % at the Olympic Games 2002 to 8.7 % in the season 2004/2005 due to the new ski jumping regulations. The ratio s/h = C (s = sitting height, h = height, C = cormic index) ranged from 0.49 to 0.57. Accordingly, the MI values (which are leg length corrected BMI values according to MI = BMI (C /C) (k) with k = 2 and C = 0.53) deviated remarkably from BMI values. For the 49 cases with BMI or MI or both below 18.5 kg m(-2), the classification to be underweight or not changed in 69 % when the MI was used instead of the BMI. Underweight or overweight is not only a question of cut-off points; the measure used determines the classification accuracy. A substantial improvement of weight analyses in sports medicine, public health, and general medicine as well can be obtained by using the MI instead of the BMI.
UNLABELLED: The assessment of forearm oxygen consumption (VO(2)) and forearm blood flow (FBF) by means of near infrared spectroscopy has become widespread in adults, whereas in children and adolescents no data are available. The aim of the present study was to analyze VO(2) and FBF in healthy children and adolescents. METHODS: In a prospective cohort study, 20 male and 20 female healthy children and adolescents were investigated. The measurements of VO(2) and FBF were performed by means of near infrared spectroscopy in combination with the venous occlusion method. RESULTS: Mean VO(2) was 0.08 +/- 0.04 ml 100 g(-1) min(-1) in male and 0.09 +/- 0.05 ml 100 g(-1) min(-1) in female subjects. Mean FBF was 1.95 +/- 1.25 ml 100 g(-1) min(-1) in male and 1.82 +/- 0.98 ml 100 g(-1) min(-1) in female subjects. No significant difference was found between male and female subjects. A significant negative correlation of VO(2) and FBF to age was observed in both groups. CONCLUSION: In the present study we were able to show that VO(2) and FBF decreased with increasing age in children and adolescents without significant differences between male and female subjects.
BACKGROUND: Assessment of neurologic and developmental outcome at 2 years age of infants with gestational age (GA)<27 weeks, born between 1996-2001. PATIENTS: A total of 110 live-born preterm infants with GA<27 weeks. METHODS: Main outcome criterions: Neurologic examination (according to Touwen) and classification of cerebral palsy by using the Gross Motor Function Classification System (GMFCS) at the corrected age of 1 and 2 years; assessment of mental and psychomotor development by using the Griffith Mental Development scales at the corrected age of 2 years; growth assessment at birth, 1 and 2 years. RESULTS: Mortality was 52%. Regular follow up was performed in 48 (91%) of the 53 surviving infants. Neurologic outcome: at 1 year age: 2% nonambulant cerebral palsy, 25% mild neurologic signs and 73% normal; at 2 years age: 4% nonambulant cerebral palsy, 2% ambulant cerebral palsy, 4% mild neurologic signs and 90% normal neurology. Developmental outcome at 2 years age: 40% DQ>-1 SD, 6% DQ between -1 SD and -2 SD (mild delay), 35% DQ between -2 SD and -3 SD (moderate delay) and 19% DQ<-3 SD (severe delay). Overall disability was found in 64%, severe disability in 27% of the infants. Profound growth failure in weight and head circumference<3rd centile at 2 years age was recorded in 39 and 19% of the infants, respectively. CONCLUSION: Developmental delay is very common in preterm infants<27 GA and exceeds the number of neurological disabilities (including cerebral palsy).
The initial care of a fractured bone provided by the general physician includes reduction followed by immobilization and the treatment of pain. Open fractures must be covered by a sterile dressing, prior to the transportation of the patient to a hospital. Depending upon the severity of the injury, further treatment is provided by an orthopedic surgeon or in an appropriate hospital.
When a fracture of an extremity has been established, the question immediately arises: should it be treated conservatively or surgically? For each of these options the three "R's" of fracture treatment apply "reduction, retention, rehabilitation". In humans, the most common fracture is that of the distal radius, which is usually amenable to conservative treatment. A fracture of the ankle is treated conservatively only when it is stable with no syndesmotic injury, and the fragments are in good alignment. Should surgical treatment be necessary, stabilization is accomplished with a plate and screws. The advantages and disadvantages of each of the options must be weighed up on an individual basis.
Today, early mobilization is recommended, irrespective of whether a patient with a fracture of the extremities has been treated conservatively or surgically. In this way, morbidity and mortality risks can be considerably reduced, in particular in the elderly patient. As a result of the continuing trend towards an ever shorter hospital stay, the general physician is faced with the task of providing aftercare to such patients at an early stage in the healing process of the fracture. This includes wound care, prevention of thromboembolism, the timely initiation of physiotherapeutic measures, and the requesting of x-ray follow-up.
Mallory bodies (MBs) and intracellular hyaline bodies (IHBs) are cytoplasmic hepatocellular inclusions that consist of aggregated proteins. MBs are characteristically associated with alcoholic and non-alcoholic steatohepatitis, but may also be found in chronic cholestatic and metabolic (eg copper intoxication) diseases and hepatocellular neoplasms, particularly hepatocellular carcinomas. IHBs have hitherto only been described in hepatocellular carcinoma cells. In the present study hepatocellular carcinomas (HCCs) and a case of idiopathic copper toxicosis were evaluated with respect to the presence and mutual relationship of MBs and IHBs. IHBs alone were present in 8.6%, MBs alone in 16.1% and both types of inclusion in 7.5% of HCCs. It is shown that IHBs may also occur in non-neoplastic hepatocytes in association with idiopathic copper toxicosis, together with MBs. In HCCs and idiopathic copper toxicosis, MBs and IHBs may be present within the same cell. Moreover, hybrid inclusions holding an intermediate position between MBs and IHBs regarding light microscopy, ultrastructure and composition exist. MBs and IHBs contain p62, a stress-inducible adapter protein, as the major constituent. In MBs p62 is associated with keratins, whereas classical IHBs lack keratins. Light microscopic, electron microscopic and immunohistochemical data suggest a close pathogenetic relationship between MBs and IHBs. Both types of inclusion are the result of over-expression and accumulation of the stress protein p62. If p62 is induced alone, or at least prevails, IHBs may arise by aggregation. However, if abnormal keratins are present in addition to p62, p62 associates and co-aggregates with keratins, finally leading to classical MBs.
The Streptococcus milleri group, which also includes S. anginosus, S. intermedius and S. constellatus, is found in the oropharynx and gastrointestinal tract mucosa. Recent isolations of S. milleri DNA sequences have been made from both gastric and oesophageal carcinoma. There are only a few publications on the isolation of viable bacteria and S. milleri DNA, and their role in carcinogenesis, in otorhinolaryngologic malignoma. We present four patients with a cervical abscess and the isolation of S. milleri -group bacteria, without signs of malignancy or other risk factors. After a delay of several months, squamous cell carcinoma of the oropharynx was diagnosed in three patients and a neck metastasis without primary tumor in the fourth.
Hypertrophic cranial pachymeningitis is an uncommon, fibrosing, inflammatory process that involves the dura mater. The condition is being reported more frequently owing to the use of cranial MRI. The main clinical feature is headache, whereas cranial nerve lesions, cerebellar symptoms, and epileptic seizures occur more rarely. A variety of autoimmune and infectious diseases can result in this condition, which is labeled as idiopathic in the absence of any definite inciting factor. The diagnosis of hypertrophic cranial pachymeningitis is based on neuroimaging of thickened and enhancing dura mater. It can be defined pathologically on biopsy. A specific treatment is indicated in some cases of secondary hypertrophic cranial pachymeningitis. Mostly, treatment relies on corticosteroids and immunosuppressive agents. This review summarizes the current knowledge on causes, clinical presentation, diagnosis, and treatment of this disorder.
Various rheumatic diseases like fibromyalgia, systemic inflammatory rheumatic disorders and localized diseases, such as arthritides and activated arthroses, tendinopathies and periarthropathies, as well as trigger points can be improved considerably by treatment with the 5-HT3 receptor antagonist tropisetron. Particularly in the latter group of diseases, local injections have done surprisingly rapid analgesic action. This effect matches that of local anesthetics, but lasts considerably longer and is comparable to local injections of local anesthetics combined with corticosteroids. The action of the 5-HT3 receptor antagonists can be attributed to an antinociceptive effect that occurs at the same time as an antiphlogistic and probably also an immunosuppressive effect. Whereas an inhibited release of substance P from the nociceptors, and possibly some other neurokins as well, seems to be the most likely explanation for the antinociceptive action, the antiphlogistic effect is primarily due to an inhibited formation of various different phlogistic substances; in some conditions, like systemic inflammatory rheumatic diseases, for example, the 5-HT3 receptor antagonists may exert an immunosuppressive effect in addition to this.
We investigated in the black-headed gull whether female deposition of antioxidants and immunoglobulins (enhancing early immune function), and testosterone (suppressing immune function and increasing early competitive skills) correlate suggesting that evolution has favoured the mutual adjustment of different pathways for maternal effects. We also took egg mass, the position of the egg in the laying sequence and offspring sex into account, as these affect offspring survival. Yolk antioxidant and immunoglobulin concentrations decreased across the laying order, while yolk testosterone concentrations increased. This may substantially handicap the immune defence of last-hatched chicks. The decrease in antioxidant levels was greater when mothers had a low body mass and when the increase in testosterone concentrations was relatively large. This suggests that female black-headed gulls are constrained in the deposition of antioxidants in last-laid eggs and compensate for this by enhanced testosterone deposition. The latter may be adaptive since it re-allocates the chick's investment from costly immune function to growth and competitive skills, necessary to overcome the consequences of hatching late from an egg of reduced quality.
Changes in gene expression are known to occur between closely related species, but it is not yet clear how many of these are due to random fixation of allelic variants or due to adaptive events. In a microarray survey between subspecies of the Mus musculus complex, we identified the mitogen-activated protein-kinase-kinase MKK7 as a candidate for change in gene expression. Quantitative PCR experiments with multiple individuals from each subspecies confirmed a specific and significant up-regulation in the testis of M. m. domesticus. Northern blot analysis shows that this is due to a new transcript that is not found in other tissues, nor in M. m. musculus. A cis-trans test via allele specific expression analysis of the MKK7 gene in F1 hybrids between domesticus and musculus shows that the expression change is mainly caused by a mutation located in cis. Nucleotide diversity was found to be significantly reduced in a window of at least 20 kb around the MKK7 locus in domesticus, indicative of a selective sweep. Because the MKK7 gene is involved in modulating a kinase signalling cascade in a stress response pathway, it seems a plausible target for adaptive differences between subspecies, although the functional role of the new testis-specific transcripts will need to be further studied.
Rabies continues to be a major public health concern both in Europe and worldwide. In the greater part of the European continent the disease has been eradicated, or its incidence drastically reduced, by oral vaccination of wildlife reservoirs. Yet, 'hot spots' still remain in north-eastern and south-eastern Europe with a high temporal variation of disease distribution in the previous decade. Rabies is predominantly transmitted by the red fox; but in recent years, especially in Eastern European countries, an independent infection cycle in raccoon dogs seems to have developed. Although countries such as the Czech Republic, Slovenia and Poland achieved very impressive rabies control results and trend analyses of rabies occurrence showed a long- and short-term decrease, there is still need for improved rabies surveillance and control in Europe. The Rabies Bulletin Europe (RBE), a quarterly, printed and on-line publication, aims to improve this situation. Besides the need to improve the quality of data in some countries, it will provide a public domain rabies database in the near future. Further strategic cooperation is necessary to control the disease in areas of European public health concern.
In this study, the presence of 20 putative virulence genes was examined in 11 Campylobacter jejuni isolates with different colonization and invasion abilities as determined in a chick colonization model and on Caco-2 cells, respectively. The majority of the genes were detected in all strains. Among them, there were genes of the flagellar secretion apparatus like flhA, flhB, flgB, flgE2, the flagellin genes flaA and flaB, invasion-associated genes like ciaB and iamA, the cytotoxin genes cdtA-C, the adhesion related gene cadF, and some genes involved in the colonization process (docA, docB). The plasmid gene virB11 could not be detected in any strain. Specific differences between the isolates were observed only in genes cgtB and wlaN involved in lipo-oligosaccharide (LOS) biosynthesis. The gene cgtB was only detectable in three of five strains with strong colonization and invasion abilities. Probably, wlaN can overcome the lack of cgtB in the two cgtB- isolates.
The long-favored paradigm for the development of continental crust is one of progressive growth beginning at approximately 4 billion years ago (Ga). To test this hypothesis, we measured initial 176Hf/177Hf values of 4.01- to 4.37-Ga detrital zircons from Jack Hills, Western Australia. epsilonHf (deviations of 176Hf/177Hf from bulk Earth in parts per 10(4)) values show large positive and negative deviations from those of the bulk Earth. Negative values indicate the development of a Lu/Hf reservoir that is consistent with the formation of continental crust (Lu/Hf approximately 0.01), perhaps as early as 4.5 Ga. Positive epsilon(Hf) deviations require early and likely widespread depletion of the upper mantle. These results support the view that continental crust had formed by 4.4 to 4.5 Ga and was rapidly recycled into the mantle.