Biomedical subjects

C Möller

Publications and source records attributed to C Möller.

At least 37 records · Page 2Linked to original sources

PubMed2001

Comparison of the cost-effectiveness of budesonide and sodium cromoglycate in the management of childhood asthma in everyday clinical practice.

BACKGROUND: Budesonide and sodium cromoglycate are both recommended as maintenance therapy for childhood asthma. OBJECTIVE: To compare the cost-effectiveness of these two treatment strategies in clinical practice, in an open-label, pharmacoeconomic clinical trial. METHODS: Health economics were evaluated in 138 children, ages 5 to 11 years, with unstable asthma not previously treated with corticosteroids or cromones. The asthma was stabilized during 4 to 6 weeks with budesonide 200 to 400 microg twice daily. The children were then randomly allocated to one of the two treatment strategies aiming at maintaining asthma control for 12 months; budesonide 400 microg/day (N = 69) or sodium cromoglycate 60 mg/day (N = 69). If asthma control was judged unsatisfactory, the doses were increased or the children were switched to the alternate treatment. RESULTS: In children continuing on the same treatment, the degree of asthma control was similar in the two groups at study end. To maintain asthma control, 42% of cromoglycate children switched to budesonide, and then experienced a 14% increase in symptom-free days. No budesonide patient had to switch therapy because of lack of asthma control. Although not statistically significant, total annual cost per patient was 24% (Swedish kronor 4195; US $487; Euro 485) lower in the budesonide than the cromoglycate group, mainly due to a lower cost for asthma medication. CONCLUSIONS: A budesonide strategy for continued maintenance treatment, after an initial period of stabilizing treatment with budesonide, resulted in lower costs and less drug switches than did a strategy with sodium cromoglycate.

Anti-Asthmatic Agents↗

PubMed2000

Atomic force microscopy of native purple membrane.

Atomic force microscopy (AFM) allows the observation of surface structures of purple membrane (PM) in buffer solution with subnanometer resolution. This offers the possibility to classify the major conformations of the native bacteriorhodopsin (BR) surfaces and to map the variability of individual polypeptide loops connecting transmembrane alpha-helices of BR. The position, the variability and the flexibility of these loops depend on the packing arrangement of BR molecules in the lipid bilayer with significant differences observed between the trigonal and orthorhombic crystal forms. Cleavage of the Schiff base bond leads to a disassembly of the trigonal PM crystal, which is restored by regenerating the bleached PM. The combination of single molecule AFM imaging and single molecule force-spectroscopy provides an unique insight into the interactions between individual BR molecules and the PM, and between secondary structure elements within BR.

Bacteriorhodopsins↗

PubMed2000

Reversible loss of crystallinity on photobleaching purple membrane in the presence of hydroxylamine.

Structural changes of purple membrane during photobleaching in the presence of hydroxylamine were monitored using atomic force microscopy (AFM). The process of bleaching was associated with the disassembly of the purple membrane crystal into smaller crystals. Imaging steps of the photobleaching progress showed that disassembly proceeds until the sample is fully bleached and its crystallinity is almost lost. As revealed from high resolution AFM topographs, the loss of crystallinity was initiated by loss of lattice forming contact between the individual bacteriorhodopsin trimers. The bacteriorhodopsin molecules, however, remained assembled into trimers during the entire photobleaching process. Regeneration of the photobleached sample into intact purple membrane resulted in the reassembly of the bacteriorhodopsin trimers into the trigonal lattice of purple membrane. The data provide novel insights into factors triggering purple membrane formation and structure.

Bacteriorhodopsins↗

PubMed2000

[Diagnostic value of s-100 protein and neuron-specific enolase as serum markers for cerebral deficiency after general anesthesia. Study in patient with hip or knee replacement].

UNLABELLED: S-100 protein and neuron-specific enolase (NSE) serum concentrations serve as markers of cerebral damage in cardiac surgery, neurology, or after head injury. In these circumstances, S-100 and NSE levels correspond with the results of neuropsychological tests. The present study investigated the diagnostic value in orthopaedic patients after joint replacement. METHODS: Forty patients scheduled for elective hip or knee arthroplasty were investigated. Serum values of NSE and S-100 were determined preoperatively and 30 min and 4, 18, and 36 h postoperatively. Neuropsychological tests (syndrome short test, SKT, delirium assessment according to DSM IV) were performed preoperatively and two, three, and four days following surgery. General anaesthesia was induced with fentanyl and etomidate and maintained with isoflurane in oxygen/air. FINDINGS: The S-100 increased from a median of 0.04 ng/ml (range 0.004-0.19 ng/ml) preoperatively to 1.03 ng/ml (range 0.18-3.65 ng/ml) at 30 minutes postoperatively (P < 0.0001). These levels returned to normal in the course of the following 2 days. NSE values were 8.55 ng/ml (range 4.6-14.9 ng/ml) preoperatively and 7.07 ng/ml (range 4-16.4 ng/ml) postoperatively (P = 0.167). There were no differences in serum concentrations of S-100 and NSE between normal patients and those with postoperative cognitive deficit. Furthermore, no correlation was found between the serum marker and neuropsychological tests. INTERPRETATION: Obviously, increased NSE levels seem to indicate cerebral damage only in more severe cases. S-100 does not seem to be brain-specific in patients undergoing orthopaedic surgery. Therefore, the value of S-100 in the assessment of brain disorders is limited.

Aged↗

PubMed2000

Treatment with diazoxide causes prolonged improvement of beta-cell function in rat islets transplanted to a diabetic environment.

Prolonged hyperglycemia desensitizes beta cells. A role for hyperglycemia-induced excessive stimulation can be tested by diazoxide, which inhibits glucose-induced insulin secretion. Using diazoxide, we have investigated in a rat transplantation model whether excessive stimulation can induce lasting effects on beta cells. One batch with 150 islets and another with 20 islets isolated from Wistar-Furth rats were transplanted under the left-kidney capsule of syngeneic streptozotocin-diabetic recipients. In a first series, recipients were treated for 8 weeks with or without 0.2% diazoxide in the food. Graft-bearing kidneys were then perfused and excised. Diazoxide treatment increased by 5.5-fold the insulin response to 10 mmol/L arginine, by 4.1-fold the graft insulin content, and by 2.3-fold the preproinsulin mRNA versus nontreated diabetic controls. The persistence of these effects was assessed in a second series in which 8 weeks of diazoxide treatment was followed by 1 week of no treatment. Again, perfusion experiments showed a higher insulin response to arginine in diazoxide-treated rats (136.0 +/- 25.7 v 62.3 +/- 11.8 fmol/min, P < .05). Also, the response to 27.8 mmol/L glucose was increased (54.0 +/- 17.1 v 13.6 +/- 7.8 fmol/min, P < .05). The insulin content was increased (2.2 +/- 0.6 v 1.0 +/- 0.4 pmol/islet, P < .05), as well as the preproinsulin mRNA (0.60 +/- 0.08 v0.22 +/- 0.02 pg/islet, P < .05). In a third series, we tested the impact of diazoxide treatment when given only during the first 2 weeks following transplantation. When tested 6 weeks later, insulin secretion was unaffected, whereas there was a strong tendency for a higher preproinsulin mRNA and insulin content in grafts of diazoxide-treated rats. In conclusion, this study demonstrates that beta-cell function in transplanted islets is improved by diazoxide long after the end of treatment, an effect that is likely due to removal of hyperglycemia-induced excessive stimulation.

Animals↗

PubMed2000

Changes in balance performance in physically active elderly people aged 73-80.

In our hospital in 1989 a series of 30 healthy elderly people participated in a study to evaluate the effect of physical training on improving balance. Thereafter, the majority of the people in this group continued with some kind of balance training. Seven years later we followed up 17 of the people who had participated in the original study. We wanted to evaluate the balance performance of these physically active elderly people (mean age 80.5 years) and compare it with their balance performance 7 years previously. Balance was found to be significantly impaired compared with 1989 in four out of six static balance tests. The time required to walk 30 m had increased significantly. The subjective ratings of vertigo and balance problems had not changed significantly, neither had the number of correct steps when walking forwards on one line and backwards between two lines. In dynamic posturography, the test with sway-referenced visual cues showed improved postural control, but no change in sway was seen in the other five sensory conditions. When sudden backward translations of the platform occurred, increased latencies of force response were seen.

Aged↗

PubMed1999

Endogenous histamine reduces plasma insulin-like growth factor I via H1 receptor-mediated pathway in the rat.

Endotoxin has been recently shown to reduce plasma insulin-like growth factor I. As it was reported that histamine can induce gut-derived endotoxemia, we wanted to determine whether histamine has a similar effect on plasma insulin-like growth factor I. Compound 48/80 (a histamine releaser) was injected subcutaneously into rats, then blood was taken for plasma insulin-like growth factor I assay and the livers were assayed for insulin-like growth factor I mRNA. Like endotoxin, injection of compound 48/80 significantly reduced plasma insulin-like growth factor I. Six hours post-injection, plasma insulin-like growth factor I was reduced by 61% (P < 0.001), and 24 h post-injection, it was still lower (by 35% P < 0.001) than in the control group. Hepatic insulin-like growth factor I mRNA was not reduced by this treatment. The effect of compound 48/80 on plasma insulin-like growth factor I was significantly attenuated by oral administration of the histamine H1 receptor antagonist (chlorpheniramine), but not by the histamine H2 receptor antagonists (cimetidine and ranitidine). Oral administration of polymyxin B (an antiendotoxin antibiotic) did not attenuate the effect of compound 48/80 on plasma insulin-like growth factor I at all. In conclusion, endogenous histamine reduces plasma insulin-like growth factor I via H1 receptor-mediated pathway. Our study suggests a novel role of histamine in the regulation of insulin-like growth factor I metabolism in vivo.

Animals↗

PubMed1999

Efficacy of once-daily versus twice-daily administration of budesonide by Turbuhaler(R) in children with stable asthma.

We evaluated the efficacy of once-daily versus twice-daily treatment with budesonide, delivered by a Turbuhaler(R), in the management of children with stable asthma in a randomized, double-blind, parallel-group study involving 206 children (age 5-15 years). After a 2-week run-in period during which the children were maintained on their usual dose of budesonide (200 microg or 400 microg/day), patients were randomized to receive the same daily dose in either two daily administrations (morning and evening) or as a single dose in the morning over a period of 12 weeks. The primary efficacy variable was morning peak expiratory flow (PEF). The mean morning PEF during the run-in phase was 271 L/min in patients randomized to once-daily treatment and 264 L/min in those randomized to twice-daily treatment. The mean change from baseline to the last 2 weeks of the treatment period in the two groups was -0.3 L/min (95% confidence limits -6.6 to +6.0) and 2.5 L/min (-4.3 to +9.3). The estimated difference between the groups was -2.8 L/min, with 90% confidence limits of -10.4 + 4.5; these were close to the limits regarded as indicative of equivalence (-10 to +10), and hence the difference was not regarded as clinically relevant. Similarly, there were no significant differences between the groups in regard to secondary efficacy measures such as spirometric tests and symptom scores. Both treatments were well tolerated. We conclude that once-daily administration of budesonide by Turbuhaler(R) is as effective as twice-daily treatment in the management of stable asthma in children treated with inhaled steroids at doses of 200-400 microg/day.

Administration, Inhalation↗

PubMed1999

Growth characteristics and influence of antibiotics on rough/smooth phenotypic variants of Helicobacter pylori.

Helicobacter pylori shows a rather high variability of several biochemical markers including lipopolysaccharide structures. This study aimed to determine whether Helicobacter pylori has a potential for phenotypic variability and to describe its effects on bacterial pathogenesis. From colonies of three clinical strains of Helicobacter pylori with rough (R) colony morphology, spontaneous phenotypic variants with smooth (S) colony morphology were isolated that occurred with a frequency of 10(-2) to 10(-3), irrespective of growth conditions. R-variant bacteria produced exclusively low-molecular-mass lipopolysaccharide. They exhibited increased lysis in the presence of plain air. In contrast, the S variants produced low- and high-molecular-mass lipopolysaccharide and did not exhibit increased lysis in the presence of plain air. Cocultivation of bacterial cells with AGS stomach cancer cells revealed that R-variant bacteria but not S-variant bacteria effected an inhibition of high molecular-weight glycoprotein biosynthesis and secretion by the host cells. Skirrow supplement added as selective agent to liquid and/or solid media was tolerated to a similar extent among R- and S-variant bacteria, while all variants proved sensitive to metronidazole, amoxicillin and clarithromycin except for the R and S isolates of strain Hp57, which showed resistance to the latter compound. It was concluded that R- and S-variants of Helicobacter pylori may have distinct roles in pathogenesis; nevertheless, these bacteria may be isolated by traditional methods and eradicated by conventional anti-infective therapy.

Anti-Bacterial Agents↗

PubMed1999

Tapping-mode atomic force microscopy produces faithful high-resolution images of protein surfaces.

Compared to contact-mode atomic force microscopy (CMAFM), tapping-mode atomic force microscopy (TMAFM) has the advantage of allowing imaging surfaces of macromolecules, even when they are only weakly attached to the support. In this study, TMAFM is applied to two different regular protein layers whose structures are known to great detail, the purple membrane from Halobacterium salinarum and the hexagonally packed intermediate (HPI) layer from Deinococcus radiodurans, to assess the faithfulness of high-resolution TMAFM images. Topographs exhibited a lateral resolution between 1.1 and 1. 5 nm and a vertical resolution of approximately 0.1 nm. For all protein surfaces, TMAFM and CMAFM topographs were in excellent agreement. TMAFM was capable of imaging the fragile polypeptide loop connecting the transmembrane alpha-helices E and F of bacteriorhodopsin in its native extended conformation. The standard deviation (SD) of averages calculated from TMAFM topographs exhibited an enhanced minimum (between 0.1 and 0.9 nm) that can be assigned to the higher noise of the raw data. However, the SD difference, indicating the flexibility of protein subunits, exhibited an excellent agreement between the two imaging modes. This demonstrates that the recently invented imaging-mode TMAFM has the ability to faithfully record high-resolution images and has sufficient sensitivity to contour individual peptide loops without detectable deformations.

Bacterial Proteins↗

PubMed1999

Anxiogenic-like action of galanin after intra-amygdala administration in the rat.

The neuropeptide galanin is expressed in brain structures implicated in regulation of emotionality. The amygdala is known to play a central role in mechanisms of fear and anxiety. We therefore examined the effects of galanin (0.2 and 0.6 nmol/side) on experimental anxiety upon microinjection into the amygdala. Two established animal models of anxiety were used: a punished drinking test, and the elevated plus-maze. Punished responding was dose dependently suppressed by intra-amygdala galanin, whereas unpunished responding, drinking motivation, locomotor activity, and shock thresholds were unaffected. No effects on experimental anxiety were seen in the plus-maze following galanin injection. When injected into parietal cortex, no anxiety promoting properties of galanin were detected. These data suggest that activation of galanin receptors in amygdala modulates neurotransmission involved in fear and experimental anxiety.

Amygdala↗

PubMed1999

Mite fauna in the home and sensitivity to house-dust and storage mites.

In search of potential new indoor allergen sources, all mites in dust from homes of 55 asthmatic children living in three climatic regions in Sweden were counted and identified by light microscope. Antibodies of the IgE class against three house-dust mites and three storage mites were measured in corresponding serum samples. Mites were found in all but two homes from the northernmost area, where levels also were lower than in the other regions. The highest mite densities were most often found in bedrooms (50%) and living rooms (40%). Mite density was increased in homes with high humidity and was higher in bungalows than in flats. House-dust mites predominated in the south and storage mites in the east central area, particularly in kitchens and bathrooms. Mite-density and IgE-antibody levels against house-dust mites were significantly associated. The same association applied to storage mites. Other species numbered around 100 mites/g dust in some homes. Microscopy helps to identify potentially important mites. Analysing home dust only for house-dust mites will underestimate mite exposure. Storage mites may be as relevant to sensitivity as house-dust mites. As other species occasionally were found in high numbers, their relevance should also be assessed.

Allergens↗

PubMed1999

Acute and short-term effects of growth hormone on insulin-like growth factors and their binding proteins: serum levels and hepatic messenger ribonucleic acid responses in humans.

We investigated the acute (4-5 h) and short-term (5 days) effects of GH treatment on hepatic messenger RNA (mRNA) levels of the genes for the insulin-like growth factors (IGFs), insulin-like growth factor binding protein-1, -2, and -3 (IGFBPs), and the acid labile subunit (ALS), as well as serum levels of these proteins in humans. At the mRNA level, we observed an increase in IGF-1 transcription (+173%) following GH treatment in the acute group, which remained elevated in the short-term treatment group. IGFBP-2 mRNA decreased after short-term GH treatment, without changes in IGFBP-1 or -3 expression. The ALS transcript level increased after 5 days. In serum, we found increased levels of IGF-I and insulin, and decreased levels of IGF-II, in the short-term treatment group. IGFBP-1 decreased in both treatment groups, whereas IGFBP-2 was reduced after 5 days treatment. ALS increased in the short-term group. We observed increased IGFBP-3 serum levels after 5 days of GH treatment, likely due to increased formation of the ternary complex. Our results show that the metabolic effects by GH on the IGF axis are complex. In addition to a direct stimulation of IGF-I and ALS expression, GH inhibits IGFBP-1 serum levels and IGFBP-2 expression in an indirect manner, possibly facilitating enhanced IGF bioavailability to target tissues.

Adult↗

PubMed1999

Once-daily inhaled corticosteroids in children with asthma: dry powder inhalers.

The cornerstone of pharmacological management of asthma in childhood is inhaled corticosteroids. These drugs are intended for long term treatment and, consequently, compliance is a major issue. Once-daily administration of maintenance medication would simplify treatment and it is likely that it would lead to better compliance. Moreover, the excellent safety profile of inhaled corticosteroid treatment tailored to disease severity may, theoretically, be further improved with once-daily administration. Studies comparing inhaled corticosteroids given once or twice daily to patients with asthma indicate that unstable asthma is best treated with at least 2 daily doses. On the other hand, it has been demonstrated that, if the asthma is stabilised, most children can be treated with inhaled corticosteroids once daily without loss of efficacy. Thus, the data suggest that newly diagnosed asthma, or asthma after deterioration, should first be reliably controlled with inhaled corticosteroids divided into at least 2 daily doses. Once-daily maintenance treatment should then be tried with the aim of improving compliance and quality of life. A dry powder inhalation device is probably the best choice for children from the age of 5 years.

Adrenal Cortex Hormones↗

PubMed1999

Early prophylaxis with recombinant human interleukin-11 prevents spontaneous diabetes in NOD mice.

We evaluated the effects of recombinant human (rh) interleukin (IL)-11 on the development of spontaneous and cyclophosphamide-induced diabetes in female NOD mice. Prolonged treatment with rhIL-11 10 microg i.p. five consecutive times a week between the 4th and 22nd weeks of age significantly suppressed both development and cumulative incidence of type 1 diabetes. Disease protection was transient because most of the animals developed type 1 diabetes within 3 months of treatment withdrawal. In contrast, rhIL-11 failed to prevent type 1 diabetes when administered for the first time to euglycemic 18-week-old NOD mice. Most likely, this discrepancy was not due to age-dependent differences in the immunological responses of NOD mice to rhIL-11 because staphylococcus aureus enterotoxin B-induced tumor necrosis factor (TNF) and IL-12 production were equally suppressed by rhIL-11 in 12- and 25-week-old NOD mice. Relative to controls, NOD mice pretreated with rhIL-11 also showed significantly diminished blood levels of TNF, interferon-gamma, and IL-12 induced by anti-CD3 antibody and/or lipopolysaccharide. The results demonstrate that rhIL-11 has powerful anti-inflammatory effects that are capable of down-regulating early immunodiabetogenic pathways in NOD mice.

Aging↗

PubMed1998

Audiological disturbances caused by long-term exposure to industrial solvents. Relation to the diagnosis of toxic encephalopathy.

Sixty workers, consecutively admitted due to suspicion of solvent-induced chronic toxic encephalopathy (CTE), were investigated with pure-tone audiometry, determination of speech recognition of monosyllabic words and distorted speech and cortical response audiometry (CRA). Eighteen workers not exposed to occupational solvents and noise were also investigated. The scores in the distorted speech test were significantly lower and the CRA latencies were significantly longer in the solvent group than in the control group. There was no difference between the groups in the pure-tone and monosyllabic speech recognition tests. In the solvent group, 19 subjects had one or several pathological audiological test results (values exceeding the mean result of the control group by 2 SD). Independently of the audiological examination all the workers in the solvent group underwent the traditional clinical assessment of CTE, which is based on symptoms, history of exposure, clinical neurological examination and a neuropsychological investigation. They were classified in three groups--CTE, incipient CTE and non-CTE. There was no correlation between these groups and the audiological test results. A previous report on vestibular pathology in the same group of subjects and the present investigation on hearing deficits suggest that long-term exposure to solvents causes disturbances of the central pathways in the otovestibular system. Hitherto, no attention has been paid to these disturbances in the definition of the CTE syndrome.

Adult↗

PubMed1998

Environmental assessment of Dermatophagoides mite-allergen levels in Sweden should include Der m 1.

The major allergen of Dermatophagoides microceras, Der m 1, as well as the allergens of D. pteronyssinus and D. farinae, Der p 1 and Der f 1, were analyzed in the homes of 111 asthmatic children in three climatic regions in Sweden. The numbers and species of mites were determined by microscopy, and circulating IgE antibodies against mites were measured. Der f 1 was the predominant house-dust-mite (HDM) allergen, Der p 1 the least often found, and Der m 1 represented 31% of the allergen load. However, in the Linköping area, Der m 1 was the major HDM allergen (58%). Mite counts and allergen levels correlated well. Current exposure to HDM allergens at home was associated with the serum IgE antibody response to HDM in the children with no threshold level. Of the children with IgE antibodies against HDM, 67% reacted to all three mites. Mite sensitization rates were marginally increased (7%) by the addition of IgE analysis of D. microceras to the routine analysis of IgE antibodies against D. pteronyssinus and D. farinae. Thus, Der m 1 may be an important HDM allergen and should be considered when HDM exposure data are assessed in areas with a climate like that of Sweden.

Adolescent↗

PubMed1997

Identification, isolation, and characterization of daintain (allograft inflammatory factor 1), a macrophage polypeptide with effects on insulin secretion and abundantly present in the pancreas of prediabetic BB rats.

A bioactive macrophage factor, the polypeptide daintain/allograft inflammatory factor 1 (AIF1), has been isolated from porcine intestine. It was discovered when searching for intestinal peptides with effects on insulin release, and its purification was monitored by the influence of the peptide fractions on pancreatic glucose-induced insulin secretion. Daintain/AIF1 is a 146-aa residue polypeptide with a mass of 16,603 Da and an acetylated N terminus. An internal 44-residue segment with the sequence pattern -KR-KK-GKR- has a motif typical of peptide hormone precursors, i.e., dibasic sites for potential activation cleavages and at the sequentially last such site, the structure GKR. The latter is a signal for C-terminal amide formation in the processing of peptide hormones. Daintain/AIF1 is immunohistochemically localized to microglial cells in the central nervous system and to dendritic cells and macrophages in several organs. A particularly dense accumulation of daintain/AIF1-immunoreactive macrophages was observed in the insulitis affecting the pancreatic islets of prediabetic BB rats. When injected intravenously in mice, daintain/AIF1 at 75 pmol/kg inhibited glucose (1 g/kg)-stimulated insulin secretion, with a concomitant impairment of the glucose elimination, whereas at higher doses (7.5 and 75 nmol/kg), daintain/AIF1 potentiated glucose-stimulated insulin secretion and enhanced the glucose elimination. Its dual influence on insulin secretion in vivo at different peptide concentrations, and the abundance of macrophages expressing daintain/AIF1 in the pancreatic islets of prediabetic rats, suggest that daintain/AIF1 may have a role in connection with the pathogenesis of insulin-dependent diabetes mellitus.

Amino Acid Sequence↗