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K Larsen

Publications and source records attributed to K Larsen.

At least 37 records · Page 2Linked to original sources
PubMed2000

Interpreting parameters in the logistic regression model with random effects.

Logistic regression with random effects is used to study the relationship between explanatory variables and a binary outcome in cases with nonindependent outcomes. In this paper, we examine in detail the interpretation of both fixed effects and random effects parameters. As heterogeneity measures, the random effects parameters included in the model are not easily interpreted. We discuss different alternative measures of heterogeneity and suggest using a median odds ratio measure that is a function of the original random effects parameters. The measure allows a simple interpretation, in terms of well-known odds ratios, that greatly facilitates communication between the data analyst and the subject-matter researcher. Three examples from different subject areas, mainly taken from our own experience, serve to motivate and illustrate different aspects of parameter interpretation in these models.

Animals↗
PubMed2000

Inhibition of human gastric H(+)-K(+)-ATPase alpha-subunit gene expression by Helicobacter pylori.

Clinical studies and in vitro data from isolated parietal cells suggest that acute Helicobacter pylori infection inhibits acid secretion. Gastric acidification is mediated by H(+)-K(+)-ATPase, an integral protein of parietal cell apical membranes. To test the hypothesis that H. pylori downregulates H(+)-K(+)-ATPase alpha-subunit (HKalpha) gene expression and to identify potential intracellular signaling pathways mediating such regulation, we transfected human gastric adenocarcinoma (AGS) cells with human and rat HKalpha 5'-flanking DNA fused to a luciferase reporter plasmid. Histamine caused dose-dependent, cimetidine-sensitive (10(-4) M) increases in cAMP, free intracellular Ca(2+), and HKalpha promoter activation in AGS cells. H. pylori infection of transfected AGS cells dose dependently inhibited basal and histamine-stimulated HKalpha promoter activity by 80% and 66%, respectively. H. pylori dose dependently inhibited phorbol myristate acetate-induced (10(-7) M) and staurosporine- (10(-7) M) and calphostin C-sensitive (5 x 10(-8) M) activation of HKalpha promoter. Also, H. pylori inhibited epidermal growth factor (EGF) (10(-8) M), genistein-sensitive (5 x 10(-5) M) activation of HKalpha promoter, reducing activity to 60% of basal level. These data suggest that H. pylori inhibits HKalpha gene expression via intracellular pathways involving protein kinases A and C and protein tyrosine kinase, AGS cells have functional histamine H(2) and EGF receptors, and transiently transfected AGS cells are a useful model for studying regulation of HKalpha gene expression.

Animals↗
PubMed2000

Who benefits from treatment and rehabilitation in a stroke Unit? A community-based study.

BACKGROUND AND PURPOSE: The beneficial effects of treatment and rehabilitation of patients with acute stroke in a dedicated stroke unit (SU) are well established. We wanted to examine if these effects are limited to certain groups of patients or if they apply to all patients independent of age, sex, comorbidity, and initial stroke severity. METHODS: This was a community-based study of outcome in 1241 consecutive stroke patients from 2 communities in Copenhagen: In one (Frederiksberg), treatment and rehabilitation were given in general neurological and medical wards (GW), and in the other (Bispebjerg) in one single large SU. Outcome measures were initial, 1-year, and 5-year mortality rates, a poor outcome (initial death or discharge to a nursing home), and length of hospital stay (LOHS). Multivariate regression analyses were used to examine the independent effect of SU treatment on the various subgroups. RESULTS: The relative risks of initial death, poor outcome, and 1-year and 5-year mortality rates were reduced by 40% on average in patients treated in the SU compared with the GW. A beneficial effect of SU treatment was observed regardless of the patient's age, sex, comorbidity, and initial stroke severity. Those who benefited most appeared to be the patients with the most severe strokes (poor outcome: OR 0.17; 95% CI 0.05 to 0.58). Those who benefited least were patients with mild or moderate strokes (poor outcome: OR 0.66; 95% CI 0.41 to 0.98) and patients <75 years of age (poor outcome: OR 0.66; 95% CI 0.36 to 1.19). LOHS was reduced by 2 to 3 weeks in all who had their treatment in the SU except in patients with the most severe strokes. LOHS in these patients was similar to LOHS in the GW. CONCLUSIONS: A beneficial effect of treatment in a SU is achieved in completely unselected patients independent of their age, sex, comorbidity, and stroke severity. Those who had the most severe strokes appeared to benefit most. All patients with acute stroke should therefore have access to treatment and rehabilitation in a dedicated SU.

Acute Disease↗
PubMed2000

Long-term follow-up in diabetic Charcot feet with spontaneous onset.

OBJECTIVE: To assess the long-term results after Charcot breakdown with spontaneous onset in diabetic feet. RESEARCH DESIGN AND METHODS: This study was retrospective. A total of 115 patients (140 feet), 107 with acute deformity and 8 with chronic Charcot deformity, were followed for a median of 48 months (range 6-114). The routine treatment for acute cases was a weight-off regimen with crutches and foot protection with therapeutic shoes until skin temperature had normalized followed by increased weightbearing and the use of bespoke shoes or modification of conventional shoes. RESULTS: The incidence of Charcot deformity was 0.3%/year in the diabetic population investigated. About half of the patients were active in their jobs. Major complications were encountered in 5 (4%) of the patients that required surgical intervention: arthrodesis for unstable malaligned ankles in 3 subjects (1 bilaterally) and major amputation in 2 subjects for unstable ankle and pressure sores. Minor complications were recorded in 43% of subjects: new attacks of Charcot breakdown in 41 patients (36%) and/or foot ulceration in 43 patients (37%) that required minor surgical procedures for 11 patients. All healed except in 2 patients: 1 patient died before the Charcot fractures had healed, and 1 patient died with an unhealed ulcer. No patient lost the ability to walk independently. CONCLUSIONS: Major surgical procedures in only 4% were particularly related to patients with Charcot deformities in the ankle. Minor complications were recorded in about half of the patients. Lifelong foot care is required for diabetic patients with Charcot feet.

Adult↗
PubMed1999

Coagulation factors VIIa and Xa induce cell signaling leading to up-regulation of the egr-1 gene.

Intracellular signaling induced by the coagulation factors (F) VIIa and Xa is poorly understood. We report here studies on these processes in a human keratinocyte line (HaCaT), which is a constitutive producer of tissue factor (TF) and responds to both FVIIa and FXa with elevation of cytosolic Ca(2+), phosphorylation of extracellular signal-regulated kinase (Erk) 1/2, p38(MAPK), and c-Jun N-terminal kinase, and up-regulation of transcription of the early growth response gene-1 (egr-1). Using egr-1 as end point, we observed with both agonists that phosphatidylinositol-specific phospholipase C and the mitogen-activated protein kinase/Erk kinase/Erk pathway were mediators of the responses. The responses to FVIIa were TF-dependent and up-regulation of egr-1 mRNA did not require presence of the TF cytoplasmic domain. Antibodies to EPR-1 and factor V had no effect on the response to FXa. We have provided evidence that TF is not the sole component of the FVIIa receptor. The requirement for proteolytic activity of both FVIIa and FXa suggests that protease-activated receptors may be involved. We now report evidence suggesting that protease-activated receptor 2 or a close homologue may be a necessary but not sufficient component of this particular signal transduction pathway. The up-regulation of egr-1 describes one way by which the initiation of blood coagulation may influence gene transcription. The ability of these coagulation proteases to induce intracellular signals at concentrations at or below the plasma concentrations of their zymogen precursors suggests that these processes may occur also in vivo.

Animals↗
PubMed1999

[Pregnancy and drug abuse].

The antenatal care of pregnant women with drug abuse is very complex and costly both in money and in time. The women often live under different circumstances than non-abusing women, and their personal and social resources are often very small. Collaboration between the hospital and the social system is essential in order to obtain a positive outcome of the pregnancy. Retrospective records of pregnancy, outcome and follow-up on 18 morphine-abusing women referred for delivery at Glostrup hospital in Copenhagen county over the three year period 1992-1994 are reported here. The study show the children are born in relatively good condition, although almost all needed postnatal detoxification, since their mothers was not able to stop their drug abuse during pregnancy. The pregnancy was with few complications because of tight antenatal care for these women. The study also shows a need for defining a common goal for the care of these women and their children and binding political commitments in order to obtain this goal.

Adult↗
PubMed1999

Interferon-gamma elicits a G-protein-dependent Ca2+ signal in human neutrophils after depletion of intracellular Ca2+ stores.

Interferon-gamma (IFN-gamma) has multiple effects on Ca2+ signalling in polymorphonuclear neutrophils (PMNs), including evoked cytosolic Ca2+ transients, increased capacitative calcium influx and increased sequestration of Ca2+ in intracellular stores. The present study was conducted to elucidate the mechanism behind the Ca2+ transients. As observed before, the IFN-gamma-evoked Ca2+ signals were apparent when extracellular Ca2+ was removed. A new finding was that the proportion of responding cells and the extent of calcium release increased with increasing time in EGTA buffer. As assessed by N-formyl-methionyl-leucyl-phenylalanine (fMLP)-stimulated Ca2+ release, the intracellular stores were depleted during this incubation period, and the extent of depletion correlated well with the appearance of IFN-gamma-induced Ca2+ signals. This store dependence of the IFN-gamma-induced Ca2+ signals was confirmed by the appearance of IFN-gamma-evoked Ca2+ signals in the presence of extracellular Ca2+ after store depletion by thapsigargin. The appearance of IFN-gamma-mediated Ca2+-signals in the presence of EGTA indicates that IFN-gamma stimulates Ca2+ release from intracellular stores. This was confirmed by the inability of the calcium transportation blocker La3+ to abolish the IFN-gamma response and the total abrogation of the response by the phospholipase C inhibitor U73122. Although these latter results imply a role for inositol 1,4,5-trisphosphate(IP3) in IFN-gamma signalling, comparison of IFN-gamma-evoked responses with fMLP responses revealed clear differences that suggest different signal-transduction pathways. However, responses to fMLP and IFN-gamma were both depressed by pertussis toxin, and the IFN-gamma responses were, in addition, inhibited by the tyrosine kinase inhibitor genistein. Further evidence of the involvement of tyrosine kinase was a slight stimulatory effect of the protein tyrosine phosphatase inhibitor sodium orthovanadate. The PI-3K activity was of minor importance. In conclusion, we present evidence of a novel signal-transduction mechanism for IFN-gamma in PMNs, dependent on tyrosine kinase activity, a pertussis toxin-sensitive G protein and phospholipase C activity.

Adult↗
PubMed1999

A new class of plant homeobox genes is expressed in specific regions of determinate symbiotic root nodules.

A cDNA containing a homeobox sequence was isolated from a soybean nodule-specific expression library. This homeobox cDNA, Ndx (nodulin homeobox), represents a small gene family with at least two members in soybean (Glycine max) and three in Lotus japonicus. One complete 3304 bp Ndx cDNA from L. japonicus encodes a protein, NDX, of 958 amino acids. An unusual type of homeodomain that differs in two of the most conserved amino acid positions in the consensus sequence is located close to the C-terminal and appears to be the only DNA-binding domain. Weak Ndx gene expression in the root increases very shortly after infection with Rhizobium and remains throughout nodule development. In situ hybridizations show cell-specific expression patterns that suggest developmentally separate regions in maturing determinate nodules. Thus in the maturing nodule Ndx and leghemoglobin genes are expressed in a mutually exclusive fashion. The Ndx transcript is also detectable in the young nodule primordium. Ndx expression is not confined to the root nodule since Ndx is also expressed in shoot and root meristems, indicating that the Ndx gene products might also be involved in developmental processes in other plant tissues.

Amino Acid Sequence↗
PubMed1999

Bradykinin elevates cytosolic Ca2+ concentration in smooth muscle cells isolated from rat duodenum.

The effect of bradykinin on the cytosolic Ca2+ concentration were measured in single, Fura-2 loaded, smooth muscle cells isolated from rat duodenum. All cells responded with a Ca2+ signal when exposed to bradykinin. The bradykinin response consisted of an initial Ca2+ spike followed by a plateau. Pre-treatment of single muscle cells with either the phospholipase C blocker U-73122 or thapsigargin, which is a potent inhibitor of the endoplasmic reticulum Ca2+-ATPase, inhibited the response to bradykinin. Pre-treatment of the cells with EGTA or La3+ to inhibit the Ca2+ influx, abolished the response induced by bradykinin. We conclude that bradykinin applied to single smooth muscle cells from rat duodenum, increases cytosolic Ca2+ by emptying intracellular Ca2+ stores, and by contribution from extracellular Ca2+. In contrast to bradykinin-induced response in isolated rat duodenum (a relaxation followed by a contraction), we did not observe a biphasic effect of bradykinin on cytosolic Ca2+ in single muscle cells. Bradykinin may thus cause relaxation of duodenal smooth muscle indirectly through an effect on neighbouring cells as dilatation is brought about by this agent in blood vessels.

Animals↗
PubMed1999

Treatment and rehabilitation on a stroke unit improves 5-year survival. A community-based study.

BACKGROUND AND PURPOSE: We have previously reported a marked reduction in mortality up to 1 year after treatment and rehabilitation on a stroke unit versus on general neurological and medical wards in unselected stroke patients. In the present study we wanted to test the hypothesis that this mortality-reducing effect is not temporary but is long lasting. METHODS: We performed a community-based comparison of outcome in 1241 stroke patients from 2 adjacent communities in Copenhagen: in one (Frederiksberg), treatment and rehabilitation were provided on general neurological and medical wards, and in the other (Bispebjerg), treatment and rehabilitation were provided on a single large stroke unit. RESULTS: The 2 stroke populations were comparable regarding age, sex, initial stroke severity, lesion diameter on CT, and stroke subtype (hemorrhage/infarct), but patients treated on the stroke unit had a higher frequency of comorbidity and lower incomes. One-year mortality was 39% (general wards) versus 32% (stroke unit) (P=0.01). This difference was still present 5 years after stroke (71% versus 64%; P=0.02). In a multiple logistic regression model of 5-year mortality, treatment on a stroke unit reduced the relative risk of death by 40% (odds ratio, 0.60; 95% CI, 0.42 to 0.85; P<0.01), independent of age, sex, stroke severity, and comorbidity. CONCLUSIONS: The mortality-reducing effect of treatment and rehabilitation on a dedicated stroke unit is long lasting rather than temporary. Stroke unit treatment reduced the relative risk of death within 5 years after stroke by 40% in an unselected, community-based stroke population. These results emphasize the need for organization of treatment and rehabilitation of unselected stroke patients on dedicated stroke units.

Aged↗
PubMed1999

Epidemiology of juvenile chronic arthritis: risk dependent on sibship, parental income, and housing.

OBJECTIVE: We studied the socioeconomic background of children with juvenile chronic arthritis (JCA) diagnosed during the years 1988-91 in Denmark. The working hypothesis is that JCA may be triggered by one or several different infectious agents and that the amount of exposure to infectious agents in infancy and childhood affects the risk of JCA. METHODS: In this case-control study, we investigated socioeconomic variables prior to disease onset from national registers, primarily the Fertility Database of Statistics Denmark, in a national cohort of all 220 known cases of JCA fulfilling the EULAR criteria incident during the years 1988-91, identified from national and local diagnosis registers. There were 4 controls per case, matched for sex, age, and county of residence. Socioeconomic variables as risk factors were quantified by odds ratios, which are equivalent to relative risks of contracting JCA if exposed to a risk factor. RESULTS: Three socioeconomic variables were significantly and mutually independently associated with the risk of developing JCA during the following year. An only child had a risk of JCA 1.6 times that of a child with siblings. Children whose parents had a high income had a relative risk of 1.9. Children living in an urban flat had a risk 2.7 times that of children living on a farm. We found no space-time clustering of cases and no cyclical variations of incidence rates. CONCLUSION: The absence of clustering and of seasonal variation does not support a theory of triggering by infection. The hitherto unreported effects of the socioeconomic variables on the risk of JCA are of the same order of magnitude as reported for certain HLA alleles. Our findings do not lend full support to either of the 2 mechanisms, that growing up under either hygienic or unhygienic conditions increases the risk of JCA, and lack an obvious biological explanation.

Adolescent↗
PubMed1999

Effects of feeding on the circadian rhythm of Ceratophyllus s. sciurorum (Siphonaptera: Ceratophyllidae).

Circadian rhythm in newly emerged blood-fed individuals of the flea Ceratophyllus s. sciurorum was studied in a constant environment, using an insect activity monitor. The results of trials run continuously over seven days confirmed the finding that C. s. sciurorum has a self-sustaining clock. Statistical tests confirm that feeding weakens the rhythm but does not eliminate it. There was a significant difference in the mean activity between the fed and unfed fleas, reflecting the difference in the number of hours over which this activity took place. A possible commercial application for the monitor and also for the method of analysis is discussed.

Animals↗
PubMed1998

Intestinal parasites in swine in the Nordic countries: prevalence and geographical distribution.

In Denmark (DK), Finland (FIN), Iceland (I), Norway (N), and Sweden (S), 516 swine herds were randomly selected in 1986-1988. Individual faecal analyses (mean: 27.9 per herd) from eight age categories of swine showed that Ascaris suum, Oesophagostomum spp., Isospora suis, and Eimeria spp. were common, while Trichuris suis and Strongyloides ransomi-like eggs occurred sporadically. Large fatteners and gilts were most frequently infected with A. suum with maximum prevalences of 25-35% in DK, N and S, 13% in I and 5% in FIN. With the exception of the remarkably low A. suum prevalence rates in FIN, no clear national differences were observed. Oesophagostomum spp. were most prevalent in adult pigs in the southern regions (21-43% in DK and southern S), less common in the northern regions (4-17% adult pigs infected), and not recorded in I. I. suis was common in piglets in DK, I, and S (20-32%), while < 1% and 5% were infected in N and FIN, respectively. Eimeria spp. had the highest prevalences in adult pigs (max. 9%) without clear geographical differences. I. suis and Eimeria spp. were recorded for the first time in I, and I. suis for the first time in N.

Age Factors↗
PubMed1998

Long-term postoperative cognitive dysfunction in the elderly ISPOCD1 study. ISPOCD investigators. International Study of Post-Operative Cognitive Dysfunction.

BACKGROUND: Long-term postoperative cognitive dysfunction may occur in the elderly. Age may be a risk factor and hypoxaemia and arterial hypotension causative factors. We investigated these hypotheses in an international multicentre study. METHODS: 1218 patients aged at least 60 years completed neuropsychological tests before and 1 week and 3 months after major non-cardiac surgery. We measured oxygen saturation by continuous pulse oximetry before surgery and throughout the day of and the first 3 nights after surgery. We recorded blood pressure every 3 min by oscillometry during the operation and every 15-30 min for the rest of that day and night. We identified postoperative cognitive dysfunction with neuropsychological tests compared with controls recruited from the UK (n=176) and the same countries as study centres (n=145). FINDINGS: Postoperative cognitive dysfunction was present in 266 (25.8% [95% CI 23.1-28.5]) of patients 1 week after surgery and in 94 (9.9% [8.1-12.0]) 3 months after surgery, compared with 3.4% and 2.8%, respectively, of UK controls (p<0.0001 and p=0.0037, respectively). Increasing age and duration of anaesthesia, little education, a second operation, postoperative infections, and respiratory complications were risk factors for early postoperative cognitive dysfunction, but only age was a risk factor for late postoperative cognitive dysfunction. Hypoxaemia and hypotension were not significant risk factors at any time. INTERPRETATION: Our findings have implications for studies of the causes of cognitive decline and, in clinical practice, for the information given to patients before surgery.

Abdomen↗
PubMed1998

The effect of catalase amplification on immortal lens epithelial cell lines.

Utilizing a human beta-actin promoter, a catalase cDNA expression vector was constructed. This construct was used to transfect two immortal cell lines, mouse alpha TN4-1 and rabbit N/N 1003A. The catalase activity was increased about 3.4 fold in the alpha TN4-1 cells and 38 fold in the N/N 1003A cells. Some changes in other enzyme activities were also observed as a result of the transfections. Surprisingly, the ability to degrade H2O2 in the extracellular environment of the cells did not markedly change as a result of the catalase amplification. However, the ability to resist H2O2 stress was dramatically altered. Non-protein thiol (NP-SH) levels, choline uptake and glyceraldehyde phosphate dehydrogenase (GPD) activity were all markedly decreased in the non-transfected cells when they were subjected to 300 microM H2O2. However, in both transfected cell lines, these parameters remained in the normal range during H2O2 stress. The results obtained upon observing aspects of DNA metabolism were more complicated. While on H2O2 stress, non-transfected cell lines showed a marked decrease in thymidine incorporation, only the transfected alpha TN4-1 line remained in the normal range. Thymidine incorporation in transfected rabbit N/N 1003A cells was decreased compared to normal cells. In contrast, studies on single strand DNA breaks indicated that transfected rabbit cells had little damage compared to the significant DNA damage observed in the normal cells. The normal N/N 1003A cells were also much more susceptible to H2O2 induced damage than normal alpha TN4-1 cells, suggesting that the high GSH peroxidase activity observed in the rabbit cells may be detrimental since the low glutathione reductase activity in such cells results in an accelerated depletion of glutathione. The overall results suggest that augmenting lens catalase may prevent cataract development caused by H2O2 stress.

Animals↗
PubMed1998

Glucose metabolism in chronic diabetic foot ulcers measured in vivo using microdialysis.

Ten subjects with diabetes mellitus and unilateral chronic foot ulcer were investigated. Local tissue concentrations of glucose and lactate were measured using the microdialysis method at a distance of 0.5-1 cm from the edge of the ulcer and in normal skin in the contralateral foot. Subcutaneous blood flow in the area investigated was measured using the 133Xewashout technique. The interstitial glucose concentration in the ulcer was found to be lower than in intact skin (8.0 +/- 1.0 mmol l-1 vs. 8.5 +/- 1.1 mmol l-1) (P < 0.02), and the interstitial lactate concentration was higher in the ulcer than in intact skin (3.2 +/- 0.2 mmol l-1 vs. 2.1 +/- 0.3 mmol l-1) (P < 0.01). The subcutaneous blood flow was on average 40% higher in the ulcer than in the intact skin. The calculated local glucose uptake and lactate outputs were twofold higher in the ulcer than in the intact skin. However, the molar ratio between lactate output and glucose uptake was approximately two, both in the ulcer and in the intact skin, indicating that the glucose metabolism was qualitatively the same in the two regions.

Aged↗
PubMed1998

IFN-gamma induces calcium transients and increases the capacitative calcium entry in human neutrophils.

We have previously reported that long-term priming of human polymorphonuclear neutrophilic granulocytes (PMN) with interferon-gamma (IFN-gamma) increased the fMLP-stimulated calcium influx. We now show that also after short-term incubation with IFN-gamma, PMN calcium metabolism is modulated. Single adherent cells in three different calcium-containing buffers (high, normal, and low [Ca2+]) were stimulated with the bacterial peptide fMLP or the Ca-ATPase inhibitor thapsigargin (Tg) after about 5 min preincubation with IFN-gamma. The results of this protocol indicated that IFN-gamma increases both calcium influx and calcium sequestration. Store dependent Ca2+ influx, directly measured on readdition of calcium to Tg-treated cells incubated in EGTA buffer, was significantly enhanced in IFN-gamma-treated cells. This effect of IFN-gamma was enhanced by the tyrosine kinase inhibitor herbimycin A. Strikingly, in low extracellular calcium concentrations, IFN-gamma induced calcium transients in 20%-60% of the cells. The proportion of PMN responding with Ca2+ transients increased with decreasing extracellular calcium concentration. Average lagtime from addition of IFN-gamma to a response that could be measured was 7.3 sec, and average increase in [Ca2+] above the basal level was 790 nM. These IFN-gamma-induced transients could not be depressed by herbimycin A. Thus, IFN-gamma can increase capacitative calcium influx, induce calcium transients, and possibly affect calcium sequestration in human PMN.

Calcium↗