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Biomedical subjects

K Larsen

Publications and source records attributed to K Larsen.

At least 19 recordsLinked to original sources
PubMed2006

BALF-derived fibroblasts differ from biopsy-derived fibroblasts in systemic sclerosis.

Growth of fibroblasts from bronchoalveolar lavage fluid (BALF) in patients with systemic sclerosis (SSc) has previously been described. The purpose of the present study was to characterise fibroblasts from BALF and bronchial biopsies from SSc patients with alveolitis and from controls, to analyse fibroblast proliferation, migration, stress fibres and proteoglycan production. BALF and bronchial biopsies were collected from 10 patients with SSc and alveolitis and from 15 controls. Outgrowth of fibroblasts was observed from the BALF of four patients, particularly in those with a markedly increased percentage of eosinophils in BALF, but not in any member of the control group. Increased levels of granulocyte-macrophage colony-stimulating factor, correlating with the percentage of eosinophils in BALF, were found in patients when compared with controls. Fibroblasts from BALF showed an elongated, mobile phenotype and increased proteoglycan production compared to the corresponding biopsy fibroblasts. In conclusion, outgrowth of fibroblasts with an altered phenotype is reported from bronchoalveolar lavage fluid in systemic sclerosis patients with alveolitis and an increased percentage of eosinophils in the bronchoalveolar lavage fluid. These findings indicate a possible role for eosinophil-fibroblast interaction in pulmonary fibrosis in systemic sclerosis.

Adult↗
PubMed2006

Reproducibility of ultrasound and magnetic resonance imaging measurements of tendon size.

PURPOSE: To investigate the intra- and inter-tester reproducibility of measurements of the Achilles tendon, tibialis anterior tendon, and the tibialis posterior tendon in football players using ultrasound (US) and magnetic resonance imaging (MRI). MATERIAL AND METHODS: Eleven asymptomatic football players were examined. Using a standardized US scanning protocol, the tendons were examined by two observers with US for thickness, width, and cross-sectional area. One observer conducted the procedure twice. The subjects also underwent an MRI examination, and the assessment of tendon size was conducted twice by two observers. RESULTS: The best reproducibility judged by coefficient of variation (CV) and 95% confidence interval was determined for the Achilles tendon on both US and MRI. The variability of US on measurements on the tibialis anterior and tibialis posterior tendons was less than that when using MRI. In 12 out of 18 measurements, there were systematic differences between observers as judged by one-sided F-test. CONCLUSION: The reproducibility of the three tendons was limited. Precaution should be taken when looking for minor quantitative changes, i.e., training-induced hypertrophy, and when doing so, the Achilles tendon should be used.

Achilles Tendon↗
PubMed2006

Dosage dependent hormonal counter regulation to combination therapy in patients with left ventricular dysfunction.

UNLABELLED: The present study attempts to assess the efficacy combination therapy for heart failure. Genuine dose-response studies on combination therapy are not available and published studies involved adding one drug on top of 'usual treatment'. Sixteen different dosage combinations of trandolapril and bumetanide was tested in a double blind, double placebo-controlled, randomized, multiple cross-over study in a 16 times six balanced incomplete Latin square design. Patients reported optimal quality of life on the sub maximal dose bumetanide. Bumetanide decreased left ventricular function and increased heart rate and plasma noradrenaline in a dose dependent manner. Doses of bumetanide of more than 0.5 mg, given twice daily significantly decreased the quality of life and increased diuresis. Weight loss was maximal on 0.5 mg bumetanide twice daily. Trandolapril significantly reduced systolic blood pressure with the maximal effect at 0.5 mg daily. Both drugs significantly increased renin concentration with a significant potentiating interaction. It was not possible to detect beneficial effects of combination therapies. The optimal dosage of Bumetanide appeared to be 0.5 mg twice daily based on its effect on quality of life and weight loss. Estimated by the reduction in systolic blood pressure the optimal dosage of Trandolapril appeared to be 0.5 mg once daily. CONCLUSIONS: It appears that patients should be given less than the usually recommended dosages. Patients may be treated with a low dose loop diuretic, if signs of water retention are present or if symptomatic relief is desired.

Aged↗
PubMed2006

Risk factors for asthma in young adults: a co-twin control study.

BACKGROUND: The liability to asthma is influenced both by genetic and environmental factors. The objective of this study was to identify risk factors for asthma in young adult twin pairs during an 8-year period. METHODS: From the birth cohorts 1953-1982 of the Danish Twin Registry, 6,090 twin pairs who were initially unaffected with respect to asthma at a nationwide questionnaire-based study in 1994 participated in a similar follow-up study in 2002. Subjects were regarded incident asthma cases when responding affirmatively to the question 'Do you have, or have you ever had asthma'? in 2002. Pairs in which only one twin developed asthma -- discordant pairs -- were identified and conditional logistic regression was applied to detect effects of risk factors. RESULTS: A total of 126 monozygotic (MZ) and 273 dizygotic (DZ) discordant twin pairs were identified. In MZ twins hay fever (OR = 3.16, 95% CI: 1.29-7.73, P = 0.007) and exercise (OR for inactivity = 0.35, 95% CI: 0.13-0.91, P = 0.023) were significantly associated with asthma, whereas in DZ twins, hay fever (OR = 2.44, 95% CI: 1.44-4.13, P = 0.001), eczema (OR = 1.96, 95% CI: 1.02-3.78, P = 0.040), female sex (OR between males and females = 0.54, 95% CI: 0.36-0.80, P = 0.002), and increasing levels of body mass index (BMI; OR per unit = 1.11, 95% CI: 1.02-1.20, P = 0.009) were significant predictors of asthma. CONCLUSIONS: Hay fever, eczema, female sex, exercise and increasing levels of BMI were risk factors for asthma in young adults. The different risk profile observed in MZ twins compared with DZ twins may reflect an underlying genetic vulnerability shared between those risk factors and asthma.

Adolescent↗
PubMed2006

A brief conceptual tutorial of multilevel analysis in social epidemiology: using measures of clustering in multilevel logistic regression to investigate contextual phenomena.

STUDY OBJECTIVE: In social epidemiology, it is easy to compute and interpret measures of variation in multilevel linear regression, but technical difficulties exist in the case of logistic regression. The aim of this study was to present measures of variation appropriate for the logistic case in a didactic rather than a mathematical way. DESIGN AND PARTICIPANTS: Data were used from the health survey conducted in 2000 in the county of Scania, Sweden, that comprised 10 723 persons aged 18-80 years living in 60 areas. Conducting multilevel logistic regression different techniques were applied to investigate whether the individual propensity to consult private physicians was statistically dependent on the area of residence (that is, intraclass correlation (ICC), median odds ratio (MOR)), the 80% interval odds ratio (IOR-80), and the sorting out index). RESULTS: The MOR provided more interpretable information than the ICC on the relevance of the residential area for understanding the individual propensity of consulting private physicians. The MOR showed that the unexplained heterogeneity between areas was of greater relevance than the individual variables considered in the analysis (age, sex, and education) for understanding the individual propensity of visiting private physicians. Residing in a high education area increased the probability of visiting a private physician. However, the IOR showed that the unexplained variability between areas did not allow to clearly distinguishing low from high propensity areas with the area educational level. The sorting out index was equal to 82%. CONCLUSION: Measures of variation in logistic regression should be promoted in social epidemiological and public health research as efficient means of quantifying the importance of the context of residence for understanding disparities in health and health related behaviour.

Adolescent↗
PubMed2005

Cognitive and motor deficits associated with HIV-2(287) infection in infant pigtailed macaques: a nonhuman primate model of pediatric neuro-AIDS.

Lentivirus-infected nonhuman primates exhibit behavioral and neurological pathology similar to human immunodeficiency virus (HIV)-infected humans and offer a means to examine the effects of lentivirus infection while controlling for confounding factors inherent in human populations. The purpose of this study was to examine cognitive and motor development in infant macaques vertically infected with HIV-2287. Subjects were 20 infant pigtail macaques (Macaca nemestrina); 8 controls born to uninfected dams, and 12 infants whose dams had been inoculated and infected with HIV-2287 in the third trimester of pregnancy. Eight of these pregnancies had undergone surgical procedures in the form of maternal amniotic catheters or maternal amniotic and fetal carotid artery and jugular vein catheters. Data indicated that catheterization had little or no impact on behavioral development. Seven infants were vertically infected (as measured by polymerase chain reaction (PCR) at birth) and five were not infected (as measured by PCR and coculture on repeated testing). Infected infants attained cognitive and motor milestones at significantly later ages than controls. Uninfected infants, born to infected dams, attained developmental milestones at later ages than controls on all tasks, but this reached statistical significance only for the Fine Motor Task. Attainment of milestones was not correlated with viral dose, maternal CD4+ levels at parturition or infant viral RNA levels at birth. Attainment of milestones was negatively correlated with infants' proportions of CD4+ lymphocytes at birth and significantly correlated with proportions of CD4+ lymphocytes 2 weeks after birth, indicating poorer performance in those infants with a more rapid CD4+ depletion. These cognitive and motor deficits closely resemble those observed in human infants and children infected with HIV and indicate that HIV-2287-infected infant macaques represent an excellent model of pediatric neuro-acquired immunodeficiency syndrome (neuroAIDS).

AIDS Dementia Complex↗
PubMed2003

Loss of expression of MLH1, MSH2, MSH6, and PTEN related to endometrial cancer in 68 patients with endometrial hyperplasia.

Derangements in the tumor suppressor gene PTEN and the mismatch-repair genes, hMLH1, hMSH2, and hMSH6, have an important role in endometrial carcinogenesis. The purpose of this study was to assess immunohistochemically the pattern of protein expression for these genes in 68 patients with endometrial hyperplasia and to determine the relation of protein expression to cancer development or coexistence of cancers. Loss of expression of these genes also was evaluated as potential tumor markers for clinical use. PTEN and hMLH1 both showed loss of expression in 55% of specimens from 18 patients with subsequent or coexisting carcinoma. D&C specimens from 50 patients who did not develop cancer (10 patients underwent hysterectomy within 2 years; 40 had no hysterectomy; follow-up of 10-20 years), expressed protein at a much higher frequency (92% for PTEN and 98% for hMLH1). The parameter with the strongest independent relation to subsequent or coexisting carcinoma in a stepwise multiple logistic regression analysis was hMLH1. Evaluation of the investigated factors as prognostic markers for tumor development showed high specificity (92% for PTEN, 98% for MLH1) at the expense of sensitivity (56% for PTEN, 56% for MLH1). The results were compared with the results of the computerized image analysis algorithm, the D-score.

Adaptor Proteins, Signal Transducing↗
PubMed2002

Causes of ambient toxicity in the Calleguas Creek watershed of southern California.

A combination of toxicity tests, chemical analyses, and Toxicity Identification Evaluations (TIEs) were used to investigate receiving water toxicity in the Calleguas Creek watershed of southern California. Studies were conducted from 1995 through 1999 at various sites to investigate causes of temporal variability of toxicity throughout this system. Causes of receiving water toxicity varied by site and species tested. Investigations in the lower watershed (Revolon Slough, Santa Clara Drain, Beardsley Wash) indicated that toxicity of samples to the cladoceran Ceriodaphnia dubia was due to elevated concentrations of the organophosphate pesticide chlorpyrifos, while causes of intermittent toxicity to fathead minnows (Pimephales promelas) and the alga Selanastrum capricornutum were less clear. Investigations at sites in the middle and upper reaches of the watershed (Arroyo Simi and Conejo Creek) indicated that the pesticide diazinon was the probable cause of receiving water toxicity to Ceriodaphnia. Elevated ammonia was the cause of toxicity to fathead minnows in the upper watershed sites. Results of these and previous studies suggest that biota are impacted by degraded stream quality from a variety of point and non-point pollution sources in the Calleguas Creek watershed. Water quality resource manager's efforts to identify contaminant inputs and implement source control will be improved with the findings of this study.

Ammonia↗
PubMed2002

Design, organization and management of a controlled population screening study for detection of colorectal neoplasia: attendance rates in the NORCCAP study (Norwegian Colorectal Cancer Prevention).

BACKGROUND: In the past three decades, the incidence of colorectal cancer (CRC) in Norway has doubled, surpassing all other Nordic countries for both men and women to become the most frequently diagnosed cancer. A small-scale, randomized study on flexible sigmoidoscopy (FS) screening in Telemark, Norway, has shown a reduction in accumulated CRC incidence after 13 years. The aim of our study was to evaluate the effect on CRC mortality and morbidity by screen detection of CRC and removal of precursor lesions (polypectomy), and to test out the management and organization mimicking a countrywide screening service. A total of 13,823 men and women (1:1), age 55-64 years, were drawn randomly from the population registries in Oslo (urban) and the county of Telemark (mixed urban and rural) and invited to have a screening examination. The rest of the relevant age cohorts constituted the control groups. In the screening group, 535 individuals were excluded according to exclusion criteria, rendering 13,288 individuals eligible for screening examination. METHODS: A once only screening model was used. In the screening group, individuals were randomized to have a once only FS or a combination of FS and faecal occult blood test (FOBT). RESULTS: The overall attendance rate was 8,849 out of 13,288 (67%); 73% in Telemark and 60% in Oslo. Attendance for FS only was 68% and 65% for combined FS&FOBT. CONCLUSIONS: The present FSIFS&FOBT screening study obtained a high acceptance rate for both screening modalities. The attendance rate was stable throughout the trial, suggesting an acceptable model for management of future countrywide screening.

Colonic Polyps↗
PubMed2001

The assessment of postoperative cognitive function.

Postoperative cognitive function (POCD) has been subject to extensive research. In the literature, large differences are apparent in methodology such as the test batteries, the interval between sessions, the endpoints to be analysed, statistical methods, and how neuropsychological deficits are defined. Traditionally, intelligence tests or tests developed for clinical neuropsychology have been used. The tests for detecting POCD should be based on well-described sensitivity and suitability in relation to surgical patients. In tests using scores, floor/ceiling effects may compromise the evaluation if the tests are either too easy or to difficult. Uncontrolled testing facilities and change of test personnel may affect the test performance. Practice effects are pronounced in neuropsychological tests but have generally been ignored. The use of a suitable normative population is essential to allow correction for practice effects and variability between sessions. Missing follow-up may severely compromise valid conclusions since subjects unable or unwilling to be examined are particularly prone to suffer from POCD. In the statistical analysis of the test results, the evaluation should be based on differences between pre- and postoperative performance. Parametric statistical tests are not relevant unless the appropriate Gaussian distributions are present, perhaps after transformation of data. The definition of cognitive dysfunction should be restrictive and the criteria should be fulfilled in only a small proportion of volunteers. In the literature, these requirements often have not been fulfilled. This precludes a reasonable estimation of the incidence of POCD and the conclusions of comparative studies should be interpreted with great caution. In this review article, we present a number of recommendations for the design and execution of studies within this area. In addition, the critical reader may use these recommendations in the evaluation of the literature.

Affect↗
PubMed2001

Characterization of a maternal-fetal HIV transmission model using pregnant macaques infected with HIV-2(287).

To study mechanisms involved in mother-to-fetus transmission of human immunodeficiency virus (HIV) in utero, we have developed a chronically catheterized pregnant macaque model that permits simultaneous and sequential determination of virus in maternal and fetal blood and amniotic fluid during pregnancy. In this report, we have characterized this model using three groups of pregnant macaques designed to sample: (1) maternal blood, fetal blood, and amniotic fluid (n = 6); (2) maternal blood and amniotic fluid (n = 6); or (3) maternal blood only (n = 2). After inoculation with the highly pathogenic HIV-2(287), all pregnant macaques developed brief but intense viremias followed by precipitous CD4+ T-cell declines within 2-3 weeks. While all the infants born to dams of the three groups were HIV positive, the degree of infection and outcome of HIV infection varied. All infants were shown to be HIV-RNA-positive by reverse transcriptase-polymerase chain reaction (RT-PCR). However, HIV-infected cells were detected only in the blood of those born to dams enrolled in groups 1 and 2: most of these infants progressed to CD4+ T-cell depletion. The infants in group 3 exhibited HIV-RNA in plasma, although neither HIV-infected cells nor CD4+ T-cell depletion was detectable. However, all infants developed HIV-2-specific antibody at various levels by 2 months of age. Together, the data suggest that, while the degree of instrumentation may modulate intensity of virus transmission to fetus, the highly pathogenic HIV-2(287) exhibited a high frequency of virus transmission from the mother to fetus.

Amniotic Fluid↗
PubMed2001

Evidence for early local viral replication and local production of antiviral immunity upon mucosal simian-human immunodeficiency virus SHIV(89.6) infection in Macaca nemestrina.

Transmission of human immunodeficiency virus type 1 (HIV-1) is largely a result of heterosexual exposure, leading many investigators to evaluate mucosal vaccines for protection against intravaginal (i.vag.) transmission in macaque models of AIDS. Relatively little is known, however, about the dynamics of viral replication and the ensuing immune response following mucosal infection. We have utilized a simian-human immunodeficiency virus (SHIV) to study the differences in viremia, CD4 T-cell percentages, and mucosal and systemic anti-SHIV humoral and cellular immune responses during primary infection of animals infected either intravenously (i.v.) or i.vag. Positive viral cocultures, peripheral blood mononuclear cell viral load peaks, and CD4 cell declines were delayed by 1 week in the i.vag. inoculated animals compared to the animals infected i.v., demonstrating delayed viral spreading to the periphery. In contrast, mucosal anti-SHIV antibody levels were greater in magnitude and arose more rapidly and mucosal CD8(+) T-cell responses were enhanced in the i.vag. group animals, whereas both the magnitudes and times of onset of systemic immune responses for the animals in the two groups did not differ. These observations demonstrate that compartmentalization of viral replication and induction of local antiviral immunity occur in the genital tract early after i.vag. but not i.v. inoculation. Induction of mucosal immunity to target this local, contained replication should be a goal in HIV vaccine development.

Animals↗
PubMed2001

Formation of strong airway irritants in mixtures of isoprene/ozone and isoprene/ozone/nitrogen dioxide.

We evaluated the airway irritation of isoprene, isoprene/ozone, and isoprene/ozone/nitrogen dioxide mixtures using a mouse bioassay, from which we calculated sensory irritation, bronchial constriction, and pulmonary irritation. We observed significant sensory irritation (approximately 50% reduction of mean respiratory rate) by dynamically exposing the mice, over 30 min, to mixtures of isoprene and O3 or isoprene, O3, and NO2. The starting concentrations were approximately 4 ppm O3 and 500 ppm isoprene (+ approximately 4 ppm NO2. The reaction mixtures after approximately 30 sec contained < 0.2 ppm O3. Addition of the effects of the residual reactants and the identified stable irritant products (formaldehyde, formic acid, acetic acid, methacrolein, and methylvinyl ketone) could explain only partially the observed sensory irritation. This suggests that one or more strong airway irritants were formed. It is thus possible that oxidation reactions of common unsaturated compounds may be relevant for indoor air quality.

Air Pollution, Indoor↗
PubMed2001

Incidence and management of ulcers in diabetic Charcot feet.

This study followed 115 patients with diabetes--who between them had 140 feet with Charcot's arthropathy--over six to 114 months (median: 48). A total of 43 patients (37%) developed ulcers in 53 feet. Their treatment was multifactorial. An offloading regimen was adopted, with the use of crutches and therapeutic sandals with soft, individually moulded insoles, followed by adjusted or bespoke shoes. Recalcitrant ulcers were treated with surgery in 16 patients (37%). Antibiotics were needed by 21 patients (49%). The incidence of ulceration was 17% per year. The median time interval between the acute component of Charcot's arthropathy and ulcer development was 36 months (range: 0-120 months). In seven patients, the ulcer developed during the acute phase. In 12 patients the ulcers were localised to the rockerbottom deformity in the mid-foot region, but in 31 patients other regions were affected. Dynamic footprint analysis was used to help adjust the offloading shoe/insole on the rockerbottom deformity. Such ulcers took twice as long to heal as other ulcers. Surgical treatment comprised: major amputation (two patients), arthrodesis for unstable ankle (three patients), toe amputations (seven patients), resection of the rockerbottom deformity (one patient) and other revisions (three patients). One patient died with an unhealed ulcer. There is a four-fold risk of ulcers in diabetic Charcot deformity compared with the overall risk of foot ulcers in diabetic feet. Healing was achieved in 40 patients (93%). The surgical intervention rate of 37% in ulcer cases in Charcot feet was low compared with the literature.

Adult↗
PubMed2000

Suppression of maternal virus load with zidovudine, didanosine, and indinavir combination therapy prevents mother-to-fetus HIV transmission in macaques.

Recently, we developed a maternal-fetal macaque model using a highly pathogenic HIV-2 strain, HIV-2287, to study the time course of HIV transmission in utero. Most pregnant macaques (Macaca nemestrina) infected with HIV-2287 (10-103 infective doses) transmitted HIV to their fetuses, as verified by positive identification of virus-infected mononuclear cells and free viral RNA in fetal blood. To determine whether an antiretroviral drug combination therapy composed of two dideoxynucleosides, azidothymidine (15 mg/kg) and dideoxyinosine (15 mg/kg), and a protease inhibitor, indinavir (25 mg/kg), could completely inhibit mother-to-fetus HIV transmission, we administered these drugs orally through gastric catheters to five pregnant macaques infected with 10 infective doses of HIV-2287. Beginning 30 minutes after HIV inoculation, the dams were given the combination antiviral therapy three times daily until delivery by cesarean section. Drug treatment reduced the maternal virus load to a minimally detectable level but did not prevent primary HIV-2287 infection. All fetal and infant blood samples were virus negative by internally controlled RNA polymerase chain reaction (QC-RNA-PCR) and virus coculture assays. Fetal and infant CD4+ T-cell levels remained normal throughout the experiment. These findings strongly suggest that combination chemotherapy with azidothymidine, dideoxyinosine, and indinavir can suppress maternal viral load enough to prevent mother-to-fetus transmission of HIV.

Animals↗
PubMed2000

CPP1, a DNA-binding protein involved in the expression of a soybean leghemoglobin c3 gene.

Nodulin genes are specifically expressed in the nitrogen-fixing root nodules. We have identified a novel type of DNA-binding protein (CPP1) interacting with the promoter of the soybean leghemoglobin gene Gmlbc3. The DNA-binding domain of CPP1 contains two similar Cys-rich domains with 9 and 10 Cys, respectively. Genes encoding similar domains have been identified in Arabidopsis thaliana, Caenorhabditis elegans, the mouse, and human. The domains also have some homology to a Cys-rich region present in some polycomb proteins. The cpp1 gene is induced late in nodule development and the expression is confined to the distal part of the central infected tissue of the nodule. A constitutively expressed cpp1 gene reduces the expression of a Gmlbc3 promoter-gusA reporter construct in Vicia hirsuta roots. These data therefore suggest that CPP1 might be involved in the regulation of the leghemoglobin genes in the symbiotic root nodule.

Amino Acid Sequence↗
PubMed2000

Volatile metabolites from mold growth on building materials and synthetic media.

Mold species which were isolated from damp buildings were grown on sterile building materials and some synthetic media in order to study the microbial volatile organic compounds produced. Patterns of the microbial volatile organic compounds (MVOC) were very media dependent but media which favor terpene biosynthesis may give patterns unique enough for identification of dominant indoor molds.

Air Pollutants↗