Modal content measurements (S2) of negative curvature hollow-core photonic crystal fibers.

We present modal content measurements (S2) of two different negative curvature hollow-core photonic crystal fibers: a kagome fiber and an ice cream cone fiber. Their sensitivity towards mode matching, bending and polarization is analyzed. For the kagome fiber, a higher order mode suppression of 17dB under optimal conditions was achieved, and for the ice cream cone fiber there was a suppression of up to 42dB. Polarization turned out to be a critical parameter for good higher order mode suppression in both fibers.

Identification of the predicted 5s-4f level crossing optical lines with applications to metrology and searches for the variation of fundamental constants.

We measure optical spectra of Nd-like W, Re, Os, Ir, and Pt ions of particular interest for studies of a possibly varying fine-structure constant. Exploiting characteristic energy scalings we identify the strongest lines, confirm the predicted 5s-4f level crossing, and benchmark advanced calculations. We infer two possible values for optical M2/E3 and E1 transitions in Ir^{17+} that have the highest predicted sensitivity to a variation of the fine-structure constant among stable atomic systems. Furthermore, we determine the energies of proposed frequency standards in Hf^{12+} and W^{14+}.

BRM and BRG1 subunits of the SWI/SNF chromatin remodelling complex are downregulated upon progression of benign skin lesions into invasive tumours.

Background Nonmelanoma skin cancer is caused by exposure to ultraviolet radiation within sunlight. Actinic keratoses (AKs) are benign precursor lesions that can develop into invasive squamous cell carcinoma (SCC). Little is known about the molecular events that lead to human skin cancer progression from benign to invasive. Objectives To determine novel genes that may be involved in skin cancer progression based on data from an initial microarray screen of human skin cancers. Methods The SWI/SNF chromatin remodelling ATPase subunit BRM was identified as being downregulated in SCC but not AK compared with normal skin in our microarray screen. Therefore reverse transcription-polymerase chain reaction, gene methylation and protein expression was used to study BRM and its alternative ATPase subunit BRG1 in a range of human skin cancers. Results We found reduced levels of mRNA coding for BRM but not BRG1 in SCC. BRM mRNA levels in AK were similar to those in normal skin. Deregulation of BRM did not result from hypermethylation of CpG regions in the promoter of these genes. Both BRM and BRG1 protein was reduced by about 10-fold in 100% of SCC and basal cell carcinoma, but not in AK specimens examined. Conclusions BRM protein may be decreased due to low levels of mRNA, while BRG1 protein loss appears to be post-translational. BRM and BRG1 may be novel tumour suppressor genes for human skin cancer. They appear to be involved after development of benign lesions, and are downregulated during progression towards invasion.

Triamcinolone and prednisolone affect contractile properties and histopathology of rat diaphragm differently.

Diaphragm atrophy and weakness occur after administration of massive doses of corticosteroids for short periods. In the present study the effects of prolonged administration of moderate doses of fluorinated and nonfluorinated steroids were investigated on contractile properties and histopathology of rat diaphragm. 60 rats received saline, 1.0 mg/kg triamcinolone, or 1.25 or 5 mg/kg i.m. prednisolone daily for 4 wk. Respiratory and peripheral muscle mass increased similarly in control and both prednisolone groups, whereas triamcinolone caused severe muscle wasting. Maximal tetanic tension averaged 2.23 +/- 0.54 kg/cm2 (SD) in the control group. An increased number of diaphragmatic bundles in the 5-mg/kg prednisolone group generated maximal tetanic tensions < 2.0 kg/cm2 (P < 0.05). In addition, fatigability during the force-frequency protocol was most pronounced in this group (P < 0.05). In contrast, triamcinolone caused a prolonged half-relaxation time and a leftward shift of the force-frequency curve (P < 0.05). Histological examination of the diaphragm showed a normal pattern in the control and 1.25-mg/kg prednisolone group. Myogenic changes, however, were found in the 5-mg/kg prednisolone group and, more pronounced, in the triamcinolone group. Selective type IIb fiber atrophy was found in the latter group, but not in the prednisolone groups. In conclusion, triamcinolone induced type IIb fiber atrophy, resulting in reduced respiratory muscle strength and a leftward shift of the force-frequency curve. In contrast, 5 mg/kg prednisolone caused alterations in diaphragmatic contractile properties and histological changes without fiber atrophy.

[Somatic complaints in mothers of children with developmental language disorders]. / Körperliche Beschwerden bei Müttern von Kindern mit Sprachentwicklungsstörungen.

BACKGROUND: In preliminary studies of mothers of children with developmental language disorders it was found that the mothers' quality of life was diminished and that they suffered from increased emotional disorders. Studies have shown that women with emotional problems also experience increased somatic afflictions. This phenomenon has not yet been confirmed in the context of mothers of children with developmental language disorders. MATERIALS AND METHODS: Ninety mothers (aged 21-48 years) of 90 preschoolers diagnosed with a developmental language disorder, but otherwise of normal development, were questioned using the Giessen Complaint Questionnaire (Giessener Beschwerdebogen, GBB), to assess their level of somatic complaints. The multivariate statistical method used was the regression analysis. RESULTS: In comparison to women of the same age in the normal population, the mothers in this study had significantly more somatic symptoms. This was shown to be true even for those mothers who, though specifically asked, could not name any particular illness. In mothers of children being treated for developmental language disorders, psychosomatic complaints occurred more frequently. The same result can be observed in mothers who perceived a lack of adequate support in caring for their children as opposed to those who perceived support to be adequate. CONCLUSIONS: Physicians and health workers treating children with developmental language disorders must reckon with a considerable number of mothers with somatic complaints. As these complaints often occur without any specific illness, they must be considered psychosomatic in nature. These findings are in accordance with earlier studies looking at the relationship between specific emotional disorders and diminished quality of life of those affected. Specific channels of help include utilization of self-help groups or mothers' groups, educational enhancement programs and speech therapists.

[Critical factors for subjective burden of mothers of children with developmental language disorders]. / Bedingungen des Erlebens der Mütter von Kindern mit Sprachentwicklungsstörungen.

BACKGROUND: In earlier studies, it was found that mothers of children with developmental language disorders had a higher incidence of anxiety and depression in comparison to the normal population. This study concentrated on the following questions: is the perceived stress, anxiety and depression of mothers with children with developmental language disorders higher than in the normal population, even for those mothers who are not exposed to any further stressors? and what environmental factors play an important role in the mental health of the mothers? MATERIALS AND METHODS: A total of 90 mothers (aged 32.9+/-4.7 years) of preschoolers diagnosed with a developmental language disorder, but with otherwise normal development, participated in the study. The mental health of the mothers was assessed using the Perceived Stress Scale (PSS) and the German version of the Hospital Anxiety and Depression Scale (HASD-D). Environmental factors were captured by a structured anamnestic procedure. Predictors of mental health were determined using multivariate regression analysis. RESULTS: The entire sample demonstrated significant levels of stress, anxiety and depression. In comparison to the standardized values, those mothers of children with developmental language disorders who were not exposed to any further stressors, were also shown to have significantly higher rates of stress and depression on the scales used, although not significantly higher levels of anxiety. A significant predictor of positive overall mental health of the mothers was the extent of adequate support in child rearing. CONCLUSIONS: Health professionals dealing with children with developmental language disorders must reckon with a considerable number of mothers whose mental health is negatively affected. When treating a child with a developmental language disorder, measures to improve the mother's state of well-being should be considered, including counseling and self-help groups.

Long-term use of oseltamivir for the prophylaxis of influenza in a vaccinated frail older population.

OBJECTIVES: To investigate the efficacy of once-daily oral oseltamivir for 6 weeks (Tamiflu) in prophylaxis against laboratory-confirmed clinical influenza in frail older subjects living in homes for seniors and to determine the safety and tolerability of long-term oseltamivir. DESIGN: Double-blind, placebo-controlled, parallel-group, randomized, multicenter study. SETTING: Thirty-one residential homes for seniors across United States and Europe. PARTICIPANTS: Five hundred forty-eight frail older occupants (mean age 81 years, >80% vaccinated). INTERVENTION: Prophylaxis with oseltamivir 75 mg or placebo once daily for 6 weeks, beginning when influenza was detected locally. MEASUREMENTS: The primary efficacy endpoint was laboratory-confirmed clinical influenza. RESULTS: Oseltamivir administration resulted in a 92% reduction in the incidence of laboratory-confirmed clinical influenza compared with placebo (placebo 12/272 (4.4%), oseltamivir 1/276 (0.4%); P = .002). Of subjects vaccinated against influenza, oseltamivir was 91% effective in preventing laboratory-confirmed clinical influenza (placebo 11/218 (5.0%), oseltamivir 1/222 (0.5%); P = .003). Oseltamivir use was associated with a significant reduction in the incidence of secondary complications (placebo 7/272 (2.6%), oseltamivir 1/276 (0.4%); P = .037). Although nearly all subjects were taking concomitant medication both before and during the study, oseltamivir was well tolerated. A similar incidence of adverse events, including gastrointestinal effects, occurred in both groups. There was no suppression of antibody response in oseltamivir recipients. CONCLUSION: Oral oseltamivir 75 mg once daily for 6 weeks effectively prevented clinical influenza in vaccinated frail older subjects using significant concomitant medications in a residential care setting. The treatment was well tolerated and provided additional protection to that afforded by vaccination.

Effects of unilateral vagal stimulation on intrapulmonary neuroepithelial bodies.

We studied the influence of unilateral vagal stimulation on intrapulmonary neuroepithelial bodies (NEB) in rabbits. The left vagus nerve was cut and electrically stimulated for 10 min. Animals were killed and the lungs studied with fluorescence and electron microscopy. Intensity of formaldehyde-induced fluorescence, which reflects the serotonin content in NEB, was higher on the stimulated side than on the nonstimulated side (118 +/- 7 vs. 100%, n = 8, P less than 0.001). The latter difference was found to correlate with the stimulus amplitude (r = 0.9, P less than 0.05). Ultrastructurally a decrease in the number of exocytotic dense-cored vesicle (DCV) profiles at the level of the NEB basal epithelial cell membrane was found on the stimulated side (0.32 +/- 0.10 vs. 0.45 +/- 0.16 DCV/micron of basal epithelial cell membrane, n = 8, P less than 0.05). Section of the left vagus nerve without electrical stimulation affected neither the fluorescence intensity nor the number of exocytotic DCV profiles. In animals with supranodosal or infranodosal chronic vagotomy the observed effects of unilateral vagal stimulation were no longer present. We conclude that 1) vagal stimulation increases the serotonin content of NEB; 2) it decreases the number of exocytotic DCV profiles; 3) this effect depends on the amplitude of the stimulus; 4) it is obtained through efferent vagal fibers; 5) these results are the opposite of the effects seen after exposing normal NEB to acute hypoxia; and 6) these physiological experiments corroborate a vagal innervation of NEB, which may play an important role in modulating the sensitivity and reaction of NEB to various stimuli.

Theophylline minimally alters contractile properties of canine diaphragm in vitro.

We examined the effects of theophylline on contractile properties and high-frequency fatigue of canine diaphragm in vitro. Eighteen diaphragm muscle bundles were obtained from 10 anesthetized dogs and equilibrated in oxygenated Krebs solution to 100, 200, or 300 mg/l theophylline. These bundles were compared with 18 matched control bundles from the contralateral hemidiaphragm. No statistically significant differences in twitch tension, tetanic tension, twitch-to-tetanus ratio, time to peak tension, or half-relaxation time were observed. Concentrations of 300 mg/l theophylline, however, significantly (P less than 0.05) increased force production at 10 Hz by 32%. A similar tendency was present at lower concentrations and exhibited a clear dose-response behavior. High-frequency fatigue was similar in control and theophylline-treated bundles. We conclude that supratherapeutic in vitro concentrations of theophylline do not increase maximal tetanic tension and do not protect against muscle fatigue but potentiate relative force production at low stimulation frequencies. This relatively small effect cannot be explained by poor diffusion of the drug in the muscle bundle, because theophylline concentrations in the muscle bath and in the muscle bundle were virtually identical. Moreover, it remains unclear whether this potentially beneficial effect can be achieved at in vivo attainable serum concentrations.

Corticosteroid treatment and nutritional deprivation cause a different pattern of atrophy in rat diaphragm.

Triamcinolone (TR) causes type IIb fiber atrophy in the rat diaphragm, which is associated with changes in contractile properties. We investigated whether this is a direct effect of TR or the result of an accompanying loss of body and diaphragm weights. For 6 wk, adult rats received saline intramuscularly, TR (0.5 mg/kg im), or nutritional depletion (ND) that resulted in a similar (approximately 40%) reduction in body weight as TR. In these animals, the half-relaxation time of the diaphragm bundles increased, the force-frequency relationship shifted leftward, and the resistance to fatigue was increased. No histological changes were found in the ND diaphragm, in contrast to severe myogenic alterations in the TR diaphragm. Type IIb fiber cross-sectional area (CSA) in the TR diaphragm was reduced by 51%, whereas type I and IIa CSAs were unaffected. In the ND animals, the CSAs of type I, IIa, and IIb fibers were reduced by 31, 33, and 52%, respectively. Similar changes occurred in the deep part of the m. gastrocnemius. In conclusion, myogenic changes and selective type IIb fiber atrophy were caused by TR, whereas ND induced generalized fiber type atrophy without histological changes.

Effects of nandrolone decanoate on respiratory and peripheral muscles in male and female rats.

Thirty male and 18 female adult rats received weekly an intramuscular injection of either saline (control; C), 1.5 mg/kg (low-dose; LD) nandrolone decanoate or 7.5 mg/kg (high-dose; HD) nandrolone decanoate during 5 wk. Compared with respective C, growth rate was stunted in male HD rats from 2 wk of treatment on, whereas it was enhanced in female LD and HD rats after 1 wk. Mass of all muscles studied varied proportionally to body weight, except for the gastrocnemius (males: 0.49 +/- 0.04 vs. C: 0.52 +/- 0.03%, not significant; females: 0.17 +/- 0.01 vs. C: 0.15 +/- 0.01%, P < 0.05). In vitro contractile and fatigue properties of the diaphragm remained unchanged, except for a decrease in twitch kinetics (time to peak tension: C, 21 +/- 2; LD, 19 +/- 1; HD, 19 +/- 2 ms, P < 0.05; half-relaxation time: C, 26 +/- 5, LD, 25 +/- 5, HD, 23 +/- 3 ms, P < 0.01). Histochemistry of the diaphragm and the gastrocnemius revealed a significant increase in type IIx/b dimensions. In the gastrocnemius, type I fiber dimensions also increased. A pair-fed study, including another 24 female rats, showed that the changes in oral food intake only partly accounted for the observed anabolic effects.

Bombesin-like peptides in human small cell carcinoma of the lung.

The nature of bombesin-like immunoreactive peptides was studied in extracts of small cell carcinoma of the human lung. Three peaks, I, II and III, designated by their increasing retention times, were separated by reversed-phase high performance liquid chromatography (HPLC) with trifluoroacetic acid (TFA) as counter ion. None of the peaks corresponded to bombesin. Peak III was eluted at the same position as porcine gastrin releasing peptide (GRP) but was separated from it in another reversed-phase system using heptafluorobutyric acid (HFBA). Peak II material eluted in the position of bombesin in the HFBA system but not in the TFA system. The elution position of Peak I corresponded to that of the carboxyl terminal fragments of GRP, i.e. GRP18-27 and GRP19-27. This correspondence was observed in each of the reversed-phase and gel filtration systems used. The Peak III peptide was converted to peak I after incubation with trypsin. It was reasoned that this conversion could be one of the steps in the processing of bombesin-like peptides in human small cell carcinoma.

Serotonin content of rabbit lung and small intestine during perinatal development.

Serotonin (5-hydroxytryptamine, or 5HT) was measured in extracts of rabbit lung and intestine during perinatal development using high pressure liquid chromatography (HPLC) with electrochemical detection. Lung and intestine were extracted with HClo4 and the extract was loaded onto a Bio-Rex 70 resin column. After elution with acetic acid the samples were injected onto the HPLC column. Serotonin was detected in lung and intestine at 18 days of gestation (80 and 90 ng/mg protein). In lung serotonin content increased at day 28 (290 ng/mg protein) till day 30 (680 ng/mg protein) decreased at day 1 after birth (480 ng/mg protein) and then rose at day 10 of the newborn period (650 ng/mg protein). In intestine the serotonin content was always higher than in the lung. At the end of gestation the serotonin in the intestine remained constant (2410 ng/mg protein at day 28 and 2430 ng/mg protein at day 30), decreased slightly one day after birth (2150 ng/mg protein) and rose at day 10 (3300 ng/mg protein).

Origin of bombesin-like peptides in human fetal lung.

Four different forms of bombesin-like immunoreactive peaks were detected in extracts of human fetal lung by the use of reversed-phase high performance liquid chromatography (HPLC). Peaks I, II, III and IV, (increasing retention time), were eluted using a 14-38% of acetonitrile gradient containing 0.1% trifluoroacetic acid (TFA). Peak II was the major material found in the extract of human fetal lung obtained at 16-20 weeks gestation. None of the four compounds contained in the eluted peaks had the same retention time as amphibian bombesin or porcine gastrin releasing peptide (GRP). On reversed-phase HPLC using two different solvent systems TFA or heptafluorobutyric acid (HFBA) as a hydrophobic counter ion, and in gel filtration chromatography, the chromatographic behavior of the main peak (peak II) was the same as that of the carboxyl terminal fragments of GRP, GRP18-27 or GRP19-27. This suggested that the peptide(s) in peak II resembled in composition the carboxy terminal 9 or 10 amino acids of porcine GRP. Following tryptic digestion the material in peak IV was converted to the more polar compound present in peak II. Two other peptide peaks were eluted close to peak II and these were presumed to be a modification of this main peak. One of the possible biosynthetic steps in the formation of bombesin-like peptides in human fetal lung could be a tryptic conversion of a less polar peptide to a more polar form (peak IV to II).

Clostridium difficile infection in a geriatric ward.

In a prospective, longitudinal study we searched for the presence of Clostridium difficile in the stools of 100 consecutively hospitalized elderly patients (mean age: 82; SD: 9.5 years). C. difficile was found on admission in 6 patients, 3 of whom were asymptomatic carriers. Ten patients acquired C. difficile during hospitalization. Four different types of C. difficile were isolated. The various types were clustered in time, indicating that the infection was acquired from the environment.

Inhibition of the oxidative burst response of N-formyl peptide-stimulated neutrophils by serum amyloid-A protein.

Strong binding of the acute phase protein serum amyloid-A (SAA) to human neutrophils was found using flow cytometry. This binding was shown to be functionally relevant with respect to the oxidative burst reaction assayed on N-formyl peptide-stimulated neutrophils by the intracellular oxidation of non-fluorescent dihydrorhodamine to fluorescent rhodamine 123. The results show reduction of the oxidative burst response by isolated SAA (and recombinant SAA2). Inhibition was also demonstrated by acute phase as compared to normal human serum. This inhibitory effect was abolished by the purified monoclonal anti-amyloid A antibody mc29, strongly suggesting that SAA counteracts neutrophil responses to cytokines or bacterial products. This newly recognized function of SAA may help to prevent oxidative tissue destruction.

Pharmacokinetics of vancomycin in patients undergoing haemodialysis and haemofiltration.

Vancomycin is widely used for the treatment of infections with Gram-positive bacteria in patients with end-stage renal disease. The concentration of vancomycin in serum, in ultrafiltrate, and in dialysate was measured during nine haemofiltration and seven haemodialysis procedures with high-permeability membranes. The t1/2 of vancomycin was 101 +/- 19 h in the interdialytic and interhaemofiltration period. There was no significant difference between the haemodialysis clearance (55.2 +/- 18.5 ml/min) and the haemofiltration clearance (66.8 +/- 13.6 ml/min). The redistribution phenomenon was about 25% in the post haemofiltration period and only 10% in the post haemodialysis period. Approximately 270 mg of vancomycin was recovered in dialysate or ultrafiltrate. With high-permeability membranes more commonly used in patients with end-stage renal disease, continuous monitoring of vancomycin therapy is recommended.

Functional and histologic picture of steroid-induced myopathy in chronic obstructive pulmonary disease.

The functional and histologic picture of steroid-induced myopathy was systematically examined in eight patients with chronic obstructive pulmonary disease (COPD) and compared with control patients with COPD matched for age, sex, and degree of airflow obstruction. Steroid-induced myopathy was associated with severe peripheral muscle weakness, quadriceps force being 23 +/- 14 versus 71 +/- 23% in control patients with COPD (p < 0.001). In addition, clear ventilatory muscle weakness was present. PImax was 37 +/- 15 versus 67 +/- 24% in control patients (p < 0.001 ), and PEmax averaged 34 +/- 10 versus 74 +/- 23% (p < 0.001). Vital capacity tended to be slightly reduced compared with that in control patients (69 +/- 21 versus 80 +/- 16%, p = 0.11). The only biochemical abnormalities associated to steroid-induced myopathy were a moderately increased lactic dehydrogenase level (697 +/- 301 versus 421 +/- 128 IU/L, p < 0.001) and an increased creatine excretion in 24-h urine (990 +/- 609 versus 159 +/- 219 mg/24 h, p< 0.001). On quadriceps biopsy steroid-induced myopathy was characterized by increased variation in diameter of fibers, with several angular atrophic fibers and diffuse necrotic and basophilic fibers. In addition, increased amount of connective tissue in between fibers and increased number of subsarcolemmal and central nuclei were present. On ATPase stain diffuse fiber atrophy predominantly affecting fast fibers was present, but there was no indication that atrophy was confined to type IIb fibers in contrast to conventional thinking. On follow-up, survival of patients with steroid-induced myopathy was reduced in comparison with control patients with COPD with similar degree of airflow obstruction (p < 0.025).

Broxaterol increases force output of fatigued canine diaphragm more than salbutamol.

We previously demonstrated that broxaterol enhanced recovery of fatigued canine diaphragm. The aim of this study was to compare the inotropic effects of salbutamol and broxaterol on fatigued canine diaphragm. Low-frequency fatigue was induced in 14 mongrel dogs by electrophrenic stimulation, which was continued until transdiaphragmatic pressure (Pdi) at 20 Hz was reduced by 50% or for 1 h. After stabilization of fatigue, the animals received a bolus (18.5 microg/kg) of either broxaterol or salbutamol, followed by a continuous infusion (0.43 microg/kg/min). A second bolus of 74.0 microg/kg, followed by a continuous infusion of 1.72 microg/kg/min, was given after 90 min. Both drugs significantly increased twitch Pdi. Twitch Pdi measured 90 min after the first and second doses of broxaterol increased by 28 +/- 23% and 42 +/- 34%, respectively, whereas the salbutamol-induced increase was clearly smaller (9 +/- 10% and 17 +/- 15%, respectively). Broxaterol increased Pdi at 20 Hz by 25 +/- 28% with the first dose and by 29 +/- 21% with the second dose. In contrast, salbutamol did not alter Pdi at 20 Hz. Neither drug affected Pdi at 100 Hz. We conclude that broxaterol promoted recovery of low-frequency fatigue of the canine diaphragm in vivo in a dose-dependent manner, whereas salbutamol only minimally improved force production by the fatigued diaphragm.