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Biomedical subjects

K Larsen

Publications and source records attributed to K Larsen.

At least 55 records · Page 3Linked to original sources
PubMed1997

Glucocorticoid treatment for nasal polyps. The use of topical budesonide powder, intramuscular betamethasone, and surgical treatment.

BACKGROUND: The treatment of nasal polyps is controversial, and medical treatment alone has been little investigated to our knowledge. OBJECTIVE: To examine the efficacy of therapy using only topical budesonide powder and topical budesonide powder supplemented with surgical removal or intramuscular betamethasone. DESIGN: Randomized, double-blind comparison of 2 dosages and additional treatment, if therapy failed. After 1 year, treatment with medication was stopped, and the demand for renewed treatment was monitored for another year. PATIENTS: Patients with bilateral nasal polyps who demanded treatment were consecutively enrolled in a hospital outpatient clinic or specialty private practice. During a 15-month period from 1990 to 1992, a total of 126 patients entered the 2-year study. INTERVENTIONS: In phase 1, randomized and double-blind treatment with a topical medication, budesonide powder, 800 micrograms or 400 micrograms daily, or a placebo was given for 1 month. In phase 2, randomized and double-blind treatment with budesonide powder, 800 micrograms or 400 micrograms daily, was given. At the end of phase 1, failed therapy was supplemented by randomly assigned treatment of either surgical removal or a single injection of sustained released betamethasone. In phase 3, treatment with the medication was discontinued, and patients were monitored for another year. The time when treatment was required again was noted. The present article deals with phases 2 and 3. MAIN OUTCOME MEASURES: Patients' scores of treatment efficacy as well as symptoms and signs. Semiquantitative measurement of sense of smell and calculation of peak expiratory flow rate index based on nasal and oral peak expiratory flow. RESULTS: In all outcome measures, a comparison of the data before treatment with the corresponding figures during phase 2 showed statistically significant efficacy. The clinical course was described at the end of phase 2. About 85% of the patients, including those who received additional therapy because the initial therapy failed, rated total or substantial control over the symptoms. The 2 dosages investigated showed equal results. These findings were consistent with the signs recorded and the peak expiratory flow rate index. The results of phase 3 showed that 50% of patients had demanded treatment after 4 months, while 34% managed without medication after 1 year. CONCLUSIONS: The clinical course in this study showed that most patients with nasal polyps do well with medical treatment. Therefore, surgery was required in few patients. However, the potential of medical treatment should be further explored in future studies.

Administration, Inhalation↗
PubMed1997

A long-term follow-up study of nasal polyp patients after simple polypectomies.

A long-term follow-up study was performed on randomly selected patients after simple snare polypectomies. There were 243 patients, of whom 211 underwent endoscopic examination. There were 154 males and 57 females and median age was 57.7 years. Median period of follow-up was 8 years (range, 38-145 months). The median number of polypectomies was 1.6 (range, 1-15). Polyp eosinophilia was recorded in 97% of the cases. From life-table analysis the 5-year rate for two or less polypectomies was 80% (95% confidence intervals, 75-86%). Symptoms and findings were recorded at a median time of 56 months from the last polypectomy. At this time 70% of the patients denied blocked nose or excessive secretions. Seventeen per cent of the group claimed loss of sense of smell, while 28% stated that it was poor. At follow-up, large polyps were found in 3% of the patients, moderately sized ones in 30% and small in 42%. No polyps were visible in 25%. Patients with asthma (26%) had more polypectomies than those without (median, 2.4 versus 1.4). Patients with a history of non-steroidal antiinflammatory drug intolerance (7%) had the highest number of polypectomies. Previous troublesome sinusitis and allergy seemed not to exert major influence on the number of polypectomies needed. In the primary care of nasal polyp patients, the majority only need minor or limited surgery or only medical treatment.

Adult↗
PubMed1997

Chlamydia pneumoniae in children with otitis media.

In this study the polymerase chain reaction was used to test for the presence of Chlamydia pneumoniae DNA in 118 middle-ear aspirates from 20 children with acute otitis media (AOM) and 53 children with otitis media with effusion (OME). C. pneumoniae was detected in 8 samples obtained from 5 children with OME and, together with Streptococcus pneumoniae, in a sample from 1 child with AOM. The mean age of these five children (6.6 +/- 1.4 years) was significantly higher than that of the 48 children with OME in whom C. pneumoniae could not be detected (4.3 +/- 1.9 years). The presence of C. pneumoniae in 9.4% of the examined children with OME suggests that C. pneumoniae might be a significant supplementary factor in the etiology of this common children's disease.

Acute Disease↗
PubMed1997

Interleukin-8 and chemotactic activity of middle ear effusions.

The importance of interleukin (IL)-8 in the chemotactic activity of middle ear effusions (MEEs) was evaluated. There was a significantly higher IL-8 concentration in MEEs of children with acute otitis media (AOM) (n = 17; 136 ng/mL) than in children with otitis media with effusion (OME) (n = 28; 65 ng/mL). The IL-8 concentration in MEEs with bacteria (149 ng/mL) was significantly higher than in MEEs without bacteria (66 ng/mL). MEEs from children with AOM and OME had equally higher chemotactic activity than the diluent alone (23.3% and 24.8% vs. 9.2%). The chemotactic activity was not altered by the presence of bacteria nor did it correlate with IL-8 concentration. Fractionation of MEEs by gel chromatography demonstrated that the main chemotactic activity could clearly be separated from the IL-8 activity, thus excluding IL-8 as a main chemotactic component in MEEs.

Bacterial Infections↗
PubMed1997

Influenza virus M1 protein binds to RNA through its nuclear localization signal.

The RNA-binding activity of influenza A virus M1 protein was studied by cross-linking the protein to viral RNA followed by sequence analysis of the oligoribonucleotide bound to the protein as well as sequence analysis of the M1 peptide bound to the RNA. M1 was found to bind to RNA without any RNA sequence specificity, as verified in a series of filter-binding experiments using a large variety of nucleic acids including DNA. The peptide sequence that bound to the RNA was the RKLKR nuclear localization signal of M1. Site-specific mutagenesis of recombinant M1 showed that most of the basic residues in that region had to be mutated in order to inhibit RNA-binding. We also constructed an M1 mutant that no longer bound to RNA but which was still able to inhibit the in vitro transcription activity of isolated viral ribonucleoprotein, albeit to a lower extent. Mutation of the zinc-binding sequence had no effect on RNA-binding or transcription-inhibition activity.

Amino Acid Sequence↗
PubMed1997

Plasminogen activators in human nasal polyps and mucosa.

Fibrinolysis is one of the processes that are involved in inflammation. In this study we have investigated if it is also involved in bilateral nasal polyposis, a disease with an inflammatory component. Fibrinolytic activity in the nasal mucosa and nasal polyps has been studied in 10 patients with bilateral nasal polyposis. Tissue-type plasminogen activator (t-PA) and urokinase-like plasminogen activator (u-PA) activities and antigen levels have been determined in polyp tissue and control nasal mucosa. t-PA activity is higher in nasal mucosa (median: 4.26 i.u./mg) as compared with nasal polyps (median: 0.65 i.u./mg; p = 0.03); u-PA activity is slightly lower in nasal mucosa (median: 0.040 i.u./mg) as compared to polyps (median: 0.065 i.u./mg; not significant). The percentage of u-PA to t-PA is 7.9% in nasal mucosa and 22.8% in nasal polyps (p < 0.01). The shift towards a higher u-PA/t-PA ratio in nasal polyps suggests an inflammatory process. Plasma levels of C-reactive protein are all within normal limits, which may suggest that PA activity is restricted to a local inflammatory reaction in the airway mucosa. The higher u-PA/t-PA ratio in nasal polyps and the higher levels of u-PA, when compared with the findings in other organs affected by inflammation, indicate that u-PA plays a part in the inflammatory events resulting in nasal polyps.

Adult↗
PubMed1997

Regulations as Prevention Strategies for Shiftwork Problems.

The study examines how the Danish system of regulations stemming from collective agreements and legislation and its associated participatory structures operate at the local level in relation to shiftwork and health and safety issues in a regional hospital system consisting of seven hospitals. The study analyzed ward reports of each employee's employment and working hours, local agreements about working time for deviations from legislation, and accounts from meetings in Co-operation Committees and Health and Safety Committees with respect to shiftwork issues from 1980 to 1994. The results showed that part-time employment, especially for those working on fixed evening and night shifts, was a dominant feature in the shiftwork arrangements. A majority of wards were found to have mixtures of employees working rotating or fixed shifts. Each hospital had local agreements that extended the number of work days between periods with days off and reduced the daily resting period to its minimum. None of the meetings of the Health and Safety Committees dealt with shiftwork, and when shiftwork and working time were on the agendas of the Co-operation Committees, health and safety aspects did not feature in the conclusions. The absence of consideration of health and safety aspects is discussed in relation to the uncertainty of the general regulatory principles for work organization and scheduling. The paper concludes that in order to utilize the potential af the participatory structures in developing prevention strategies for shiftwork problems, it is important to clarify responsibilities and cooperation between the two participatory committees.

Journal Article↗
PubMed1996

A novel type of DNA-binding protein interacts with a conserved sequence in an early nodulin ENOD12 promoter.

The pea genes PsENOD12A and PsENOD12B are expressed in the root hairs shortly after infection with the nitrogen-fixing bacterium Rhizobium leguminosarum bv. viciae or after application of purified Nod factors. A 199 bp promoter fragment of the PsENOD12B gene contains sufficient information for Nod factor-induced tissue-specific expression. We have isolated a Vicia sativa cDNA encoding a 1641 amino acid protein, ENBP1, that interacts with the 199 bp ENOD12 promoter. Two different DNA-binding domains were identified in ENBP1. A domain containing six AT-hooks interacts specifically with an AT-rich sequence located between positions -95 and -77 in the PsENOD12B promoter. A second domain in ENBP1 is a cysteine-rich region that binds to the ENOD12 promoter in a sequence non-specific but metal-dependent way. ENBP1 is expressed in the same cell types as ENOD12. However, additional expression is observed in the nodule parenchyma and meristem. The presence of three small overlapping ORFs in the 5'-untranslated region of the ENBP1 cDNA indicates that ENBP1 expression might be regulated at the translational level. The interaction of ENBP1 with a conserved AT-rich element within the ENOD12 promoter and the presence of the ENBP1 transcript in cells expressing ENOD12 strongly suggest that ENBP1 is a transcription factor involved in the regulation of ENOD12. Finally, the C-terminal region of ENBP1 shows strong homology to a protein from rat that is specifically expressed in testis tissue.

Amino Acid Sequence↗
PubMed1995

The effect of a stroke unit: reductions in mortality, discharge rate to nursing home, length of hospital stay, and cost. A community-based study.

BACKGROUND AND PURPOSE: Treatment of stroke patients in specialized stroke units has become more frequent, yet the effect of this treatment has not been determined. METHODS: In a community-based, prospective, and consecutive study of 1241 unselected acute stroke patients, we compared outcome of stroke treatment between two neighboring communities within Greater Copenhagen: the Bispebjerg community, where all acute stroke patients are treated and rehabilitated on a stroke unit, and Frederiksberg community, where all acute stroke patients are treated and rehabilitated on general neurological and medical wards. Except for the different organization of stroke treatment, the two communities and the two patient groups were comparable. Specifically, age, sex, marital status, prestroke residence, and stroke severity were not statistically different between patients treated on the stroke unit and those treated on the general neurological and medical wards. Multivariate regression analyses were used to estimate the independent influence of stroke unit treatment on outcome. RESULTS: Stroke unit treatment significantly reduced in-hospital mortality (odds ratio [OR], 0.50; 95% confidence interval [CI], 0.34 to 0.74; P < .001), case-fatality rate (OR, 0.45; CI, 0.28 to 0.71; P < .001), 6-month mortality (OR, 0.57; CI, 0.39 to 0.82; P = .002), 1-year mortality (OR, 0.59; CI, 0.42 to 0.84; P = .003), and discharge rate to a nursing home (OR, 0.61; CI, 0.38 to 0.98; P = .04). Discharge rate to the patient's own home was significantly increased (OR, 1.90; CI, 1.30 to 2.70; P < .001). The length of hospital stay (including rehabilitation) was reduced significantly by 30% in patients treated on the stroke unit despite their lower mortality (P < .001). The savings due to stroke unit treatment were estimated at 1313 bed-days and three places at a nursing home per 100 stroke patients. CONCLUSIONS: Treatment of unselected acute stroke patients on a stroke care unit saved lives, reduced the length of hospital stay, reduced the frequency of discharge to a nursing home, and potentially reduced cost.

Aged↗
PubMed1995

Genetic anticipation in Parkinson's disease.

We studied age at onset and family history of 137 patients (probands) with the diagnosis of idiopathic Parkinson's disease (PD). Probands (N = 21) who had an affected parent, aunt, or uncle were younger (p = 0.0001) at the onset of PD (47.7 +/- 8.8 years) than were probands (N = 11) who had an affected sib only (60.3 +/- 12.9 years) and probands (N = 105) who had no affected sib, parent, aunt, or uncle (59.2 +/- 11.4 years). Age at onset of affected family members differed significantly between generations (p = 0.0001). Age at onset was earlier, by an average of 17 years, in the proband generation than in the parental generation. The intrafamily variation in the calendar year of onset was too great to suggest a common point of exposure. Our data are most compatible with genetic anticipation, which could suggest involvement of an unstable trinucleotide repeat.

Age Factors↗
PubMed1994

[Congenital fructose intolerance. New molecular aspects].

Hereditary fructose intolerance is a human autosomal recessive disease caused by a deficiency of aldolase B that results in an inability to metabolize fructose and related sugars. Molecular analyses have shown that most defects are caused by point mutations in critical regions of the aldolase B gene. We have performed PCR-based DNA analysis of members of two Norwegian families with hereditary fructose intolerance. The affected individuals from both families contained a point mutation (A149P) in exon 5 of the aldolase B gene. Molecular diagnosis of fructose intolerance is rapid and specific, and causes no inconvenience to the patient. It should be preferred to conventional fructose intolerance tests and visceral biopsy analyses.

Adult↗
PubMed1994

Crystal structures at 2.5 angstrom resolution of seryl-tRNA synthetase complexed with two analogs of seryl adenylate.

Crystal structures of seryl-tRNA synthetase from Thermus thermophilus complexed with two different analogs of seryl adenylate have been determined at 2.5 A resolution. The first complex is between the enzyme and seryl-hydroxamate-AMP (adenosine monophosphate), produced enzymatically in the crystal from adenosine triphosphate (ATP) and serine hydroxamate, and the second is with a synthetic analog of seryl adenylate (5'-O-[N-(L-seryl)-sulfamoyl]adenosine), which is a strong inhibitor of the enzyme. Both molecules are bound in a similar fashion by a network of hydrogen bond interactions in a deep hydrophilic cleft formed by the antiparallel beta sheet and surrounding loops of the synthetase catalytic domain. Four regions in the primary sequence are involved in the interactions, including the motif 2 and 3 regions of class 2 synthetases. Apart from the specific recognition of the serine side chain, the interactions are likely to be similar in all class 2 synthetases.

Adenosine↗
PubMed1994

Increased risk of Parkinson's disease in parents and siblings of patients.

We studied the incidence of Parkinson's disease in 586 first-degree relatives (parents and siblings) of 114 randomly ascertained white patients with idiopathic Parkinson's disease and in 522 first-degree relatives of 114 age-matched unrelated white control subjects. Sixteen percent of patients had a family history as compared to 4% of control subjects (p < 0.01). The age-specific cumulative incidence was higher in the first-degree relatives of patients than in the first-degree relatives of control subjects (p = 0.007). The age-adjusted odds ratio was 3.5 (95% confidence interval: 1.3-9.4; p = 0.014). These results suggest that genes contribute to the etiology of Parkinson's disease.

Aged↗
PubMed1994

Formation of otoconia in the Japanese red-bellied newt, Cynops pyrrhogaster.

Pre-mated adult female newts and fertilized eggs will be flown on the International Microgravity Laboratory-2 flight, in 1994. One objective of the flight will be to observe the influence of microgravity on the development of the gravity-sensing organs in the inner ear. These organs contain sensory hair cells covered by a layer of dense stones (otoconia). Gravity and linear acceleration exert forces on these masses, leading to excitation of the nerve fibers innervating the hair cells. If the production of the otoliths is regulated to reach an optimal weight, their development might be abnormal in microgravity. Ground-based control experiments are reported describing the developmental sequence in which both the otoliths and their associated sensory epithelium and the semicircular canals appear and develop. Three-dimensional reconstruction of serial sections through the otic vesicle of newt embryos at stages 31 through 58 demonstrate the first appearance, relative position and growth of the otoliths. Reports of experiments in which fertilized frog eggs were flown on a Russian Cosmos mission conclude that the utricular otolith is increased in volume, whereas the saccular otolith maintains normal size, suggesting that at least in the utricle, the weight of the otolith might be regulated.

Acceleration↗
PubMed1994

A small percentage of influenza virus M1 protein contains zinc but zinc does not influence in vitro M1-RNA interaction.

A peptide containing the CCHH motif, the putative zinc-binding sequence of influenza virus M1 protein, was found to bind zinc in a one-to-one complex with the characteristics of a typical zinc-binding peptide. Intact influenza virus also contained zinc and we show that this zinc is bound to the M1 protein in the virus. However, only a small proportion of M1 contained zinc: 4% in virus and 6 to 9% in isolated protein. One strain, B/Yamagata/16/88, consistently contained more zinc: 15 to 20% both in virus and in isolated protein. We also determined the RNA binding and transcription inhibition activities of various M1 proteins and found that the zinc content of M1 had no influence on either activity. We suggest that the zinc in M1 has a structural role in the virion other than nucleic acid binding.

Amino Acid Sequence↗