HMPV infections are frequently accompanied by co-infections.
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Biomedical subjects
Publications and source records attributed to Andreas Müller.
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We describe a case of bronchiolitis associated with the newly detected human bocavirus (hBoV) in a child with a suspected Noonan syndrome. This is the first report of a bronchiolitis probably linked to hBoV that required intensive care while being accompanied by a congenital heart disease and a history of several episodes of severe respiratory symptoms.
Six cell lines routinely used in laboratories were tested for permissiveness to the infection with the newly identified human coronavirus NL63. Two monkey epithelial cell lines, LLC-MK2 and Vero-B4, showed a cytopathic effect (CPE) and clear viral replication, whereas no CPE or replication was observed in human lung fibroblasts MRC-5s. In Rhabdomyosarcoma cells, Madin-Darby-Canine-kidney cells and in an undefined monkey kidney cell line some replication was observed but massive exponential rise in virus yield lacked The results will lead to an improved routine diagnostic algorithm for the detection of the human coronavirus NL63.
Maillard products, such as Nepsilon-carboxymethyllysine (CML), are readily formed during the manufacturing of infant formulas. Little has been known, however, about the presence of CML in human breast milk and about the uptake of CML by infants. In this study, CML was measured in the serum and breast milk of 32 healthy mothers by ELISA. CML concentrations in breast milk (137 +/- 82.7 ng/mL) were significantly lower than in the serum (399 +/- 67.8 ng/mL, p < 0.001) and on average 35-fold lower than in infant formulas (4754 +/- 4299.5 ng/mL). CML was also measured in the urine of 21 infants, which were fed with breast milk or formulas. Although there was a tendency toward higher urinary CML excretion in infants fed with hypoallergenic formulas compared to breast-fed ones, the differences were not significant. Neonates that were delivered by vaginal birth had significantly higher concentrations of CML compared to those delivered by caesarean section (1306 +/- 653 vs 601 +/- 220 ng/mL, p = 0.012). It is concluded that CML passes from the serum into the breast milk, but the levels are by far lower than in infant formulas. In very young neonates (< or =3 days), the mode of delivery has a greater influence on urinary CML excretion than the nutrition.
2-Pyridone (pyridin-2-one) is a mimic of the uracil and thymine nucleobases, with only one N--H and C==O group. It provides a single H-bonding site, compared to three for the canonical pyrimidine nucleobases. Employing the supersonically cooled 9-methyladenine2-pyridone (9MAd x 2PY) complex, which is the simplest base pair to mimic adenine-uracil or adenine-thymine, we show that its gas-phase UV spectrum consists of contributions from two isomers. Based on the H-bonding sites of 9-methyladenine, these are the Watson-Crick and Hoogsteen forms. Combining two-color two-photon ionisation (2C-R2PI), UV-UV depletion and laser-induced fluorescence spectroscopies allows separation of the two band systems, revealing characteristic intermolecular in-plane vibrations of the two isomers. The calculated S(0) and S(1) intermolecular frequencies are in good agreement with the experimental ones. Ab initio calculations predict the Watson-Crick isomer to be slightly more stable (D(0)=-16.0 kcal mol(-1)) than the Hoogsteen isomer (D(0)=-15.0 kcal mol(-1)). The calculated free energies Delta(f)G(0) of the Watson-Crick and Hoogsteen isomers agree qualitatively with the experimental isomer concentration ratio of 3:1.
BACKGROUND: Nosocomially acquired respiratory syncytial virus (RSV) infections cause serious problems in hospitalized patients. An increased effort should be made to describe the problems connected with such infections in pediatric hospitals, with the aim of reducing the occurrence of nosocomial RSV infections (NI). METHODS: A specialized database was introduced for surveillance and a multifaceted barrier concept based on the CDC recommendations was developed for the control of NI in a university children's hospital in Germany. RESULTS: Between 1999 and 2002 (November 1-April 30), 283 RSV infections (general population) were prospectively documented. Thirty-nine cases (13.8%) were nosocomial infections (NI) with an incidence density (ID) of 0.99/1000 patient days; 48.7% of all NI were found in prematurely born infants. Following the introduction of a surveillance and prevention policy, a 9-fold decrease of the ID (1.67 vs. 0.18/1000 patient-days) was found when comparing the first and the last season. Intensive care treatment was required in 18% of all documented RSV-infections, in 48.7% of all NI cases and in 43.5% of all RSV-infected prematurely born infants. Overall RSV-related mortality was 0.71%. CONCLUSIONS: Early diagnosis, a strict cohorting and contact isolation policy, and prospective surveillance contribute to the reduction of nosocomial RSV infection.
Oxytocin is one of the most potent uterotonic agents and is known to fluctuate throughout the menstrual cycle, showing an increase during sexual stimulation and arousal, with a peak during orgasm in women. To date, limited data are available on the effects of oxytocin on the regulation of uterine contractility and transport mechanisms in human reproduction. The goal of this study was to evaluate the effects of oxytocin on uterine contractility and peristalsis in estrogen-primed non-pregnant uteri. In an extracorporeal perfusion model of the swine uterus the effect of dynamic changes in uterine contractility and peristalsis in response to oxytocin and estrogen administration was observed. Spontaneous uterine contractility and oxytocin-induced uterine contractility and peristalsis with and without estrogen perfusion were assessed using an intrauterine double-chip microcatheter. Spontaneous peristalsis and oxytocin induced contraction waves without estrogen perfusion resulted in a slightly higher intrauterine pressure in the isthmus uteri in comparison with the corpus uteri, while the peristaltic waves were seen to start mostly in the corpus uteri, moving in the direction of the cervix. While after estrogen perfusion oxytocin produced a significant increase in intrauterine pressure in the isthmus uteri compared to the corpus uteri, and 80% of the peristaltic waves started in the isthmus uteri, moving in the direction of the corpus uteri. This observation strengthens the view that oxytocin is able to support directed transport mechanism in the female genital tract only in the presence of estrogens. The biological role of oxytocin increase during sexual stimulation and arousal with a peak during orgasm for the mechanisms of reproduction may be to stimulate directed uterine transport mechanisms in the presence of estrogens.
To investigate the relationship between ionized calcium and disease activity, parameters of bone metabolism and bone mineral density (BMD) at the lumbar spine (BMD-LS) and the femoral neck (BMD-FN) measured by dual X-ray absorptiometry in rheumatoid arthritis (RA). In 146 patients with RA, the following parameters were investigated: serum levels of ionized calcium, total calcium, vitamin D metabolites 25-hydroxyvitamin D3 (25D3) and 1,25-dihydroxyvitamin D3 (1,25D3), intact parathyroid hormone (iPTH), interleukin-6, osteocalcin, erythrocyte sedimentation rate (ESR) and c-reactive protein (CRP); renal excretion of pyridinolin (PYD)- and desoxypyridinolin (DPD)-crosslinks. A total of 30.1% of the patients were hypercalcemic (ionized calcium >1.30 mmol/l). In comparison with normocalcemic patients, those with hypercalcemia had significantly higher ESR (P<0.01) and CRP values (P<0.05) and significantly lower serum levels of both iPTH (P<0.01) and 1,25D3 (P<0.05) and a significantly lower BMD-LS (P<0.05). The results indicate that a substantial part of RA patients is hypercalcemic. Hypercalcemia is associated with high disease activity and may contribute to suppression of PTH secretion and vitamin D hormone synthesis. High levels of ionized calcium may be a reflection of disease-activity-related systemic bone loss, and could be a predictor of BMD at the lumbar spine in RA.
PURPOSE: Although diabetes increases the risk of becoming visually impaired or blind, a large proportion of people with diabetes are not receiving the recommended eye care to detect and prevent retinopathy. Assessing a broad range of demographic, health behavior, and societal characteristics in relation to eye care utilization, the present study aims to increase knowledge about the potential impact of such factors on eye care utilization. METHODS: In 2003, for the first time, the annual Victorian Population Health Survey (VPHS) incorporated various eye health-related questions. Approximately 12,600 primary approach letters were mailed to all eligible and randomly selected households. Using computer-assisted telephone interviewing (CATI), the interviewer selected the person aged 18 years or over with the most recent birthday within the contacted household. RESULTS: The mean age of all 7500 participants was 47.7 years (range, 18-99 years). Six percent (n = 424) of all participants had diabetes, of whom 80% (n = 345) reported a visit to an eye care specialist within the last 2 years. People with diabetes were more likely to have had an eye test within the last 2 years if they had seen a healthcare provider or had one of various health checks, including checks not related to diabetes, within the same time. CONCLUSION: Results suggest that people who take an interest in their general health may also be more aware of the importance of eye examinations to avoid vision loss. Eye health promotion activities therefore need to broaden their reach to approach from outside the health sector, targeting people with diabetes who normally do not receive health checks. The importance of dilated eye examinations for people with diabetes needs to be further promoted for eye care providers.
PURPOSE: To determine baseline eye care utilization by older Victorians in order to assess change in 2 years after an eye health promotion campaign. METHODS: A letter of invitation to participate was sent to all people aged 70-79 years in randomly selected Melbourne postcode areas. A questionnaire was designed to allow gathering of eye health-related information. Eye exams included autorefraction, frequency doubling technology and non-mydriatic fundus photography. Results were compared with the Melbourne Vision Impairment Project . RESULTS: A total of 1695 people with a mean age of 74 years were recruited. The overall proportion with visual impairment was 8% (134/1695), of which 27% (36/134) was due to non-refractive causes. Only 31% (11/36) of visually impaired people knew about low-vision services, of whom 20% (7/36) had used them. Of all people with diabetes, only 52% (96/184) had a dilated eye exam within the recommended 2 years (Melbourne Vision Impairment Project 44%). CONCLUSIONS: Compliance rates with recommendations for 2-yearly eye exams for people with diabetes have not improved since the last major eye health study in Victoria 10 years ago. The same is true for the rate of undiagnosed glaucoma, suggesting that messages about eye examinations need to be promoted for older people at high risk of vision loss, for example, those with diabetes and at risk of vision loss from glaucoma.
PURPOSE: The aim was to develop a means of rapidly assessing eye health in a cost- and time-effective way to monitor changes over time. METHODS: Key features of the five main eye diseases that cause vision loss in Australia were assessed. Participation was volunteer-based from randomly selected Melbourne suburbs. Recruitment was by mail. Anterior segments and fundi were photographed with a digital non-mydriatic fundus camera. Visual fields were tested with Frequency Doubling Technology. A questionnaire collected information about demographics, general health and lifestyle. Findings from this rapid assessment were compared with those from a population-based study. RESULTS: A total of 1695 people, aged between 70 and 79 years (mean 74), were recruited. The rates and causes of visual impairment were similar between the rapid assessment method and the population-based study. Among the 134 people (8%) with visual impairment at presentation, 98 (73%) had undercorrected refractive error, 17 (13%) had age-related macular degeneration, 11 (8%) had cataract, 2 (2%) had diabetic retinopathy and 2 (2%) had glaucoma. Screening costs per participant were only about AU$145, compared with AU$433 in the Melbourne Visual Impairment Project (VIP). The application of Frequency Doubling Technology as well as the use of a non-mydriatic digital camera for fundus and lens photography resulted in an average examination time of less than half the time needed in the VIP. Data collection took 3 months rather than 4 years in the VIP. CONCLUSION: The rapid assessment method was efficient in time and cost and produced results comparable to a normal population-based survey. Repeating the study design for a similarly sampled group every 2 years would allow the assessment of changes in the prevalence of undiagnosed eye disease.
AIM: To compare two freezing protocols in an automatic open-vessel freezing system for cryopreservation of rat ovarian tissue. METHODS: Ovarian tissue was transplanted heterotopically into the neck muscle, either without cryopreservation (group 1, n = 6) or with cryopreservation after equilibration with 1.5 mol/L dimethyl sulfoxide and propanediol (protocol A, group 2, n = 6) or 1.5 mol/L ethyl glycol (protocol B, group 3, n = 6). The ovarian tissue was examined with LIVE/DEAD fluorescent viability staining and histologically after isotransplantation. RESULTS: The healthy follicular loss (intact oocyte and >50% granulosa cells alive) due to cryopreservation was 15.5% with protocol A and 12.2% with protocol B. Histological examination showed follicles in all developmental phases in all groups: group 1, 35.5 +/- 5.7/mm(2) (mean +/- SD); group 2, 16.0 +/- 5.0/mm(2); group 3, 17.3 +/- 5.7/mm(2). The differences between groups 1 and 2 and between groups 1 and 3 were significant (P < 0.001). The difference between groups 2 and 3 was not significant (P = 0.33). CONCLUSIONS: These results demonstrate that the use of an open freezing system with both freezing protocols allows cryopreservation of rat ovarian tissue with equally good survival rates.
PURPOSE: To determine the repeatability and agreement between a digital camera (monoscopic and stereoscopic images) and the Heidelberg Retina Tomograph (HRT; Heidelberg Engineering, Heidelberg, Germany) in determining cup-to-disc ratio. A secondary purpose was to determine the monoscopic and stereoscopic thresholds that maximize specificity and sensitivity when compared with the HRT. METHODS: Community living participants aged between 70 and 79 years had their optic discs imaged with a digital nonmydriatic retinal camera (NMRC) and the HRT. Intraclass correlation coefficients (ICCs) and 95% tolerance limits of change were used to determine repeatability characteristics of the instruments. The agreement between the HRT- and NMRC-derived area cup-to-disc ratios was assessed using weighted kappa statistics and receiver operator characteristic (ROC) curves. RESULTS: The agreements between the monoscopic and stereoscopic images and HRT were assessed for 1238 and 1173 eyes, respectively. The reliability measures for both NMRC techniques and HRT were almost perfect (ICC = 0.84-0.99) with narrow tolerance limits of change (9.2%-18.4%) and very small systemic biases (P < 0.05). The agreement between the HRT and both NMRC techniques was substantial, with a weighted kappa = 0.83. The HRT gave a marginally larger area cup-to-disc ratio than the monoscopic and stereoscopic images by 0.008 and 0.006, respectively (P < 0.001). The areas under the ROC curves for both NMRC techniques were 0.98, indicating excellent discriminating characteristics (P < 0.001). An area cup-to-disc ratio cutoff of > or =0.5 for the monoscopic and stereoscopic NMRC was highly specific (94.1% and 91.6%) and sensitive (87.5% and 97.2%, respectively) in determining an HRT-derived area cup-to-disc ratio >0.6. CONCLUSIONS: The monoscopic and stereoscopic digital images showed excellent repeatability and demonstrated substantial agreement with the HRT. The results indicate that the digital NMRC could be a reliable and useful instrument for assessing area cup-to-disc ratio and screening for glaucoma-suspect eyes in the community.
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Pollinator specificity has traditionally been considered the main reproductive isolation mechanism in orchids. Among Mediterranean orchids, however, many species attract and deceive pollinators by mimicking nectar-rewarding plants. To test the extent to which deceptive orchid species share pollinators, we collected and identified hemipollinaria-carrying insects, and used ribosomal sequences to identify the orchid species from which hemipollinaria were removed. We found that social and solitary bees, and also flies, carried hemipollinaria belonging to nine orchid species with different degrees of specialization. In particular, Anacamptis morio, Dactylorhiza romana and Orchis mascula used a large set of pollinator species, whereas others such as Orchis quadripunctata seemed to be pollinated by one pollinator species only. Out of the insects with hemipollinaria, 19% were found to carry hemipollinaria from more than one orchid species, indicating that sympatric food-deceptive orchids can share pollinators. This sharing was apparent even among orchid sister-species, thus revealing an effective overlap in pollinator sets among closely related species. These results suggest varying degrees of pollinator specificity in these orchids, and indicate that pollinator specificity cannot always act as the main isolation mechanism in food-deceptive temperate orchids.
The nucleobases uracil (U) and thymine (T) offer three hydrogen-bonding sites for double H-bond formation via neighboring N-H and C=O groups, giving rise to the Watson-Crick, wobble and sugar-edge hydrogen bond isomers. We probe the hydrogen bond properties of all three sites by forming hydrogen bonded dimers of U, 1-methyluracil (1MU), 3-methyluracil (3MU), and T with 2-pyridone (2PY). The mass- and isomer-specific S1 <-- S0 vibronic spectra of 2PY.U, 2PY.3MU, 2PY.1MU, and 2PY.T were measured using UV laser resonant two-photon ionization (R2PI). The spectra of the Watson-Crick and wobble isomers of 2PY.1MU were separated using UV-UV spectral hole-burning. We identify the different isomers by combining three different diagnostic tools: (1) Selective methylation of the uracil N3-H group, which allows formation of the sugar-edge isomer only, and methylation of the N1-H group, which leads to formation of the Watson-Crick and wobble isomers. (2) The experimental S1 <-- S0 origins exhibit large spectral blue shifts relative to the 2PY monomer. Ab initio CIS calculations of the spectral shifts of the different hydrogen-bonded dimers show a linear correlation with experiment. This correlation allows us to identify the R2PI spectra of the weakly populated Watson-Crick and wobble isomers of both 2PY.U and 2PY.T. (3) PW91 density functional calculation of the ground-state binding and dissociation energies De and D0 are in agreement with the assignment of the dominant hydrogen bond isomers of 2PY.U, 2PY.3MU and 2PY.T as the sugar-edge form. For 2PY.U, 2PY.T and 2PY.1MU the measured wobble:Watson-Crick:sugar-edge isomer ratios are in good agreement with the calculated ratios, based on the ab initio dissociation energies and gas-phase statistical mechanics. The Watson-Crick and wobble isomers are thereby determined to be several kcal/mol less strongly bound than the sugar-edge isomers. The 36 observed intermolecular frequencies of the nine different H-bonded isomers give detailed insight into the intermolecular force field.
OBJECTIVE: Hyperhomocysteinemia is associated with atherosclerotic risk. Although vitamins can lower homocysteine (Hcy), information about effects on atherosclerosis is scarce. METHODS: We used carotid intima-media thickness (IMT) as an accepted marker of atherosclerotic changes. Fifty patients (60 +/- 8 years) with IMT> or =1 mm were included. In a double blind, randomized trial they received daily 2.5 mg folic acid, 25 mg Vitamin B6, and 0.5mg Vitamin B12 or placebo for 1 year. RESULTS: In the treatment group, Hcy decreased from 10.50 +/- 3.93 to 6.56 +/- 1.53 micromol/l (P < 0.0001), whereas it remained unchanged in the placebo group (10.76 +/- 2.36 versus 10.45+/-3.30 micromol/l). IMT decreased from 1.50 +/- 0.44 to 1.42 +/- 0.48 mm (P = 0.034) in the treatment group, whereas it increased from 1.47 +/- 0.57 to 1.54 +/- 0.71 mm in the placebo group. The mean individual changes of IMT between both groups differed significantly (-0.08 +/- 0.17 versus 0.07 +/- 0.25 mm, P = 0.019). Multiple regression analysis revealed that the observed effect on IMT depended only on medication. CONCLUSIONS: Vitamin supplementation significantly reduces IMT in patients at risk. This effect is independent of Hcy concentration.