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Biomedical subjects

S Andersen

Publications and source records attributed to S Andersen.

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

Glomerular permselectivity in early stages of overt diabetic nephropathy.

BACKGROUND: Impairment of glomerular size selectivity has been demonstrated by the dextran-sieving technique in nephropathic diabetics with heavy, but not mild proteinuria. The purpose of the present study was to determine whether such a barrier defect could be demonstrated with mild proteinuria by substituting Ficoll 70, a polysucrose, for dextran as a probe of the filtration barrier. METHODS: Differential solute clearances were performed in 12 individuals with early diabetic nephropathy on two occasions: after 60 days of treatment with losartan 50 mg daily or a placebo. An uncharged preparation of nonreabsorbable Ficoll 70 was infused along with inulin. Fractional clearance (theta) of Ficoll of discrete size was determined after separating molecules in urine and plasma in narrow 2 A fractions over a 20 to 60 A radius interval by size exclusion high-performance liquid chromatography (HPLC). A hydrodynamic theory of hindered ficoll transport through water-filled pores was used to characterize the pore size distribution of the glomerular barrier. RESULTS: The theta for Ficoll molecules with radii> 50 A was selectively enhanced in placebo-treated diabetic nephropathy versus corresponding theta in healthy control subjects (N = 12). Computations revealed a lower distribution of glomerular pores that was unaltered in nephropathic diabetics. However, an upper distribution of large, shunt-like pores was more prominent, exceeding healthy controls by one order of magnitude in diabetic nephropathy (P = 0.01). A trend to lower theta for Ficoll in the 56 to 60 A radius range during losartan therapy is computed to have lowered the fraction of shunted filtrate by 26 to 44%, depending on whether glomerular pressure declined. The corresponding reduction in theta for endogenous albumin, IgG, and IgG4 was by 19 to 23% (P < 0.05). CONCLUSION: Our findings suggest that shunt-like defects, partially reversible by angiotensin II blockade, are present early in the course of diabetic nephropathy. We estimate that such defects can account for immunoglobulinuria in this disorder. Additional impairment of either charge- or shape-selectivity must be invoked to explain the observed level of albuminuria, however.

Adult↗
PubMed2000

Presence of group IIa secretory phospholipase A2 in mast cells and macrophages in normal human ileal submucosa and in Crohn's disease.

Secretory group IIa phospholipase A2 (PLA2-II) is an important regulator of proinflammatory lipid mediator production and may play a role in ileal inflammation in Crohn's disease. The enzyme has previously only been detected in epithelial Paneth cells. However, one characteristic feature of Crohn's disease is the transmural inflammation. Full thickness ileal sections from nine patients with Crohn's disease, and histologically normal sections from patients with colonic cancer (n=7) and chronic severe constipation (n=1) as controls, were used in this study. PLA2-II-positive cells were detected by immunofluorescence and in situ hybridization. Metachromatic staining and esterase staining were used to identify mast cells and macrophages, respectively. It was shown that mast cells and macrophages in the ileal submucosa in both patients and controls showed positive PLA2-II staining. The number of PLA2-II-labeled cells that did not react with metachromasia, e.g. macrophages, was significantly greater in inflamed Crohn's disease compared to controls. This is, to our knowledge, the first study that has described the presence in healthy, while presence and upregulation of PLA2-II-positive cells in inflamed human ileal submucosa. Our findings suggest a proinflammatory potential for secretory PLA2-II in submucosa, while proinflammatory stimulation of mast cells and macrophages in vitro has shown that the enzyme is responsible for delayed prostaglandin formation.

Adolescent↗
PubMed2000

Role of patient factors in therapy resistance to antiproteinuric intervention in nondiabetic and diabetic nephropathy.

Reduction of proteinuria is a prerequisite for successful long-term renoprotection. To investigate whether individual patient factors are determinants of antiproteinuric efficacy, we analyzed individual responses to different modes of antiproteinuric intervention in nondiabetic and diabetic patients, obtained in prior studies comparing the efficacy of various pharmacological regimens. The individual antiproteinuric response to angiotensin-converting enzyme (ACE) inhibition positively correlated to the response to angiotensin type I (AT1) receptor blockade in diabetic (r = 0.67, P < 0.01, N = 16) as well as nondiabetic patients (r = 0.75, P < 0.01, N = 12). This corresponded to the correlations for antihypertensive efficacy between ACE inhibition and AT1 receptor blockade in diabetic (r = 0.73, P < 0.001) as well as nondiabetic patients (r = 0.55, P < 0.05). Remarkably, the antiproteinuric response to ACE inhibition also correlated positively to the antiproteinuric response to indomethacin (r = 0.63, P < 0.05, N = 9). Thus, patients responding favorably to one class of antiproteinuric drugs also respond favorably to other classes of available drugs, supporting a main role for individual patient factors in responsiveness or resistance to antiproteinuric intervention. In the search for strategies to improve response in these high risk patients, combination-treatment (combining different drugs, and combining drugs with dietary measures like sodium and protein restriction), and the use of higher doses may provide more fruitful strategies to optimize renoprotection than shifting to other classes of the available drugs.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1999

Smoking cessation: the state of the science. The utility of the Transtheoretical Model in guiding interventions in smoking cessation.

Smoking remains the most significant modifiable risk factor for the leading causes of death in the United States. The most frequently used theoretical model used to guide interventions directed toward smoking cessation has been the Transtheoretical Model (TTM) (Prochaska and DiClemente, 1983), although the effectiveness and efficacy of the model's use in guiding smoking cessation interventions has not been fully evaluated. A non-statistical meta-analytic approach was used to examine reports of the use of the TTM in smoking cessation interventions. Three elements were considered for inclusion in this integrated review: the clear specification of the use of a theoretical framework, a specified intervention directed towards changing smoking behavior, and a specified outcome of smoking behavior change. From 1,500 research articles, 16 reports fit these criteria. The assessment of the research reviewed indicates that the TTM has not been fully tested in smoking cessation interventions, nor have process mediators been used to determine the mechanism of smoking behavior change.

Journal Article↗
PubMed1999

Evaluation of two automated enzyme-immunoassays for detection of thermophilic campylobacters in faecal samples from cattle and swine.

We evaluated the performance of two enzyme-immunoassays (EIA) for the detection of naturally occurring, thermophilic Campylobacter spp. found in faecal samples from cattle (n = 21 and n = 26) and swine (n = 43) relative to the standard culture method, and also assuming that none of the tests was the definitive standard. The primary isolation both for the culture and the EIA methods was carried out by overnight selective enrichment in Preston broth. The results showed good sensitivities for both EIA methods in cattle (95% and 84%) and swine (88% and 69%) samples. However, when testing cattle samples, EIA-2 method resulted in a rather low specificity (32%). This seemed to be partially due to the isolation of nonthermophilic species. In conclusion, EIA-1 method may provide a simple and fast tool with good accuracy in cattle and swine samples for automated screening of large number of samples.

Animals↗
PubMed1999

Iodine in drinking water varies by more than 100-fold in Denmark. Importance for iodine content of infant formulas.

The iodine intake level of the population is of major importance for the occurrence of thyroid disorders in an area. The aim of the present study was to evaluate the importance of drinking water iodine content for the known regional differences in iodine intake in Denmark and for the iodine content of infant formulas. Iodine in tap water obtained from 55 different locations in Denmark varied from <1.0 to 139 microg/l. In general the iodine content was low in Jutland (median 4.1 microg/l) with higher values on Sealand (23 microg/l) and other islands. Preparation of coffee or tea did not reduce the iodine content of tap water with a high initial iodine concentration. A statistically significant correlation was found between tap water iodine content today and the urinary iodine excretion measured in 41 towns in 1967 (r=0.68, P<0.001). The correlation corresponded to a basic urinary iodine excretion in Denmark of 43 microg/24h excluding iodine in water and a daily water intake of 1.7 l. The iodine content of infant formulas prepared by addition of demineralized water varied from 37 to 138 microg/l (median 57 microg/l, n=18). Hence the final iodine content would depend heavily on the source of water used for preparation. We found that iodine in tap water was a major determinant of regional differences in iodine intake in Denmark. Changes in water supply and possibly water purification methods may influence the population iodine intake level and the occurrence of thyroid disorders.

Adult↗
PubMed1999

Patient perspective and self-help.

Effective adaptation to PD demands that patients and their caregivers elaborate coping strategies that empower them and promote a more salutary orientation to formidable psychosocial difficulties and thus, perhaps, blunt or prevent depressive responses. Patients and their loved ones should be encouraged to seize the initiative in terms of promoting an acceptable life-style: in short, "breaking through" rather than "breaking down." The notion of a "healthy" PD patient is not necessarily a contradiction in terms if the patient and family can be encouraged to view organic disease as a learning opportunity, continuing to find meaning in life despite the inevitable threats to identity posed by PD (e.g., loss of work). PD patients and their families may benefit by grieving (over a finite interval) or observing other rituals associated with universal life changes. These adaptive processes should be promoted in the context of a trusting physician-patient alliance that addresses both the biochemical foundations and adverse psychosocial consequences of PD; the latter problems require that the clinician or nurse furnish both education and emotional support. Three well-established phenomena from the depression literature must be combatted: a normal depression reaction associated with the failure to attain closely held life goals; outer locus of control, in which PD patients may perceive that the disease is dictating their existences; and learned helplessness, which may result when coping behaviors are not positively reinforced.

Caregivers↗
PubMed1999

Graves' disease in the Inuit population of Greenland. Presentation of five cases observed during a two month period.

Thyroid hormones are important for metabolic regulation. A number of studies have dealt with the effect of arctic living on thyroid hormone secretion and metabolism in healthy animals and humans. Little is however known of the effect of arctic living on the occurrence of thyroid diseases. In a study from Upernavik, Greenland no cases of hyperthyroidism were observed over the 25 years period from 1950 to 1974. We present five cases of hyperthyroidism due to Graves' disease observed during a two month period in Nuuk Greenland. The discrepancy could be due to improved diagnostic methods and activity or to a real increase in incidence. Systematic studies of thyroid disorders in Greenland are warranted.

Adult↗
PubMed1998

Opioid analgesics as noncompetitive N-methyl-D-aspartate (NMDA) antagonists.

Much evidence points to the involvement of N-methyl-D-aspartate (NMDA) receptors in the development and maintainance of neuropathic pain. In neuropathic pain, there is generally involved a presumed opioid-insensitive component, which apparently can be blocked by NMDA receptor antagonists. However, in order to obtain complete analgesia, a combination of an NMDA receptor antagonist and an opioid receptor agonist is needed. Recent in vitro data have demonstrated that methadone, ketobemidone, and dextropropoxyphene, in addition to being opioid receptor agonists, also are weak noncompetitive NMDA receptor antagonists. Clinical anecdotes suggest that the NMDA receptor antagonism of these opioids may play a significant role in the pharmacological action of these compounds; however, no clinical studies have been conducted to support this issue. In the present commentary, we discuss evidence for the NMDA receptor antagonism of these compounds and its relevance for clinical pain treatment; an overview of structure-activity relationships for the relevant opioids as noncompetitive NMDA receptor antagonists also is given. It is concluded that although the finding that some opioids are weak noncompetitive NMDA receptor antagonists in vitro has created much attention among clinicians, no clinical studies have been conducted to evaluate the applicability of these compounds in the treatment of neuropathic pain conditions.

Analgesics, Opioid↗
PubMed1998

Prediction of axillary lymph node involvement of women with invasive breast carcinoma: a multivariate analysis.

BACKGROUND: The increasing use of systemic therapy for women with lymph node negative breast carcinoma and earlier stage of disease at mammographic detection raises questions regarding the need for routine axillary lymph node dissection. Predictive modeling for lymph node involvement may be one way to reduce the need for axillary lymph node dissection and its morbidity. METHODS: A multivariate analysis of 12 factors predictive of axillary lymph node involvement was conducted in a population-based cohort of 4312 women with invasive breast carcinoma diagnosed between January 1, 1993 and December 31, 1996. RESULTS: Clinical palpability, lymphatic or vascular invasion, lesion size, margin status, histology, and patient age were independent predictors of axillary lymph node involvement. The model correctly identified lymph node status in 76.6% of cases. Model accuracy and fit were equally high when applied to randomly selected halves of the study subjects. Approximately 32.0% of the patients in the study sample (1363/4312) were identified as having an extremely high (91%; n = 1102) or low (10%; n = 261) risk of lymph node involvement. In a second analysis, a clinically useable, three-variable model identified a very low risk group of patients (n = 147) with a 4.8% risk of lymph node metastasis and a high risk group of patients (n = 1008) with a 74.2% risk of lymph node metastasis. Greater than 90% of subjects in the high risk group received adjuvant systemic therapy even if they were lymph node negative pathologically. CONCLUSIONS: A clinically useable, three-variable model employing tumor and lymph node palpability, size, and lymphatic or vascular invasion can identify women with invasive breast carcinoma in whom axillary lymph node dissection is very unlikely to alter recommendations regarding adjuvant systemic therapy.

Adult↗
PubMed1998

Quality evaluation of plateletpheresis using the new AMICUS (Baxter) cell separator: evolution of CD 62 expression.

The purpose of this study was to evaluate the new AMICUS (Baxter-Fenwal Division) cell separator in terms of donor safety, efficiency, and quality of the product obtained. One hundred eighty-three single-donor plateletpheresis procedures were performed, using a collection of 4-4.5 x 10(11) platelets as endpoint. During the first part of the study, the mean volume processed was 3,225 ml and the mean procedure duration 69.5 min. During the second part, after a software change, the mean volume and mean procedure time were 3,071 ml and 68.3 min, respectively. According to local policy, every collection bag was separated into two therapeutic units each containing a mean of 1.87 (1.83) x 10(11) platelets. The white blood cell (WBC) contamination per therapeutic unit was less than 5 x 10(6) in 91% of phereses performed in part one of the study and in 98% of phereses performed in part two. During the recommended 5 days storage, sequential in vitro analyses were performed in 27 units, showing limited platelet activation according to CD62 expression and morphological changes on electron microscopy (EM). Furthermore, there was a correlation between CD62 expression and the degree of WBC contamination (P = 0.03). In conclusion, platelet collection with the new Amicus allows for high platelet yields of adequate quality as judged by WBC content, CD62 expression, and electron microscopic morphological changes.

Humans↗
PubMed1998

Dextropropoxyphene acts as a noncompetitive N-methyl-D-aspartate antagonist.

In order to elucidate whether opioid analgesics available on the Scandinavian market also act as noncompetitive N-methyl-D-aspartate (NMDA) antagonists, a series of commercially available opioids were screened for their affinity in [3H](RS)-5-methyl-10, 11-dihydro-5H-dibenzo[a,d]cycloheptene-5,10-imine ([3H]MK-801) binding assays and potential inhibitory actions on responses to NMDA in the rat cortical wedge preparation. Of the screened compounds (codeine, dextropropoxyphene, etorphine, fentanyl, and morphine), only dextropropoxyphene, with an IC50 value in [3H]MK-801 binding of 5 microM, was found to be active. Further characterization of the interaction of dextropropoxyphene with the NMDA response in the rat cortical wedge preparation illustrated the noncompetitive NMDA antagonist activity of dextropropoxyphene. Analysis of the dextropropoxyphene inhibition curve of NMDA gave an IC50 value of 190 microM and a Hill slope of 0.8.

Analgesics, Opioid↗
PubMed1998

Ketobemidone plus (RS)-3-dimethylamino-1,1-diphenylbut-1-ene (A29) is more potent at NMDA receptors than ketobemidone alone: evidence for A29 as a non-competitive NMDA receptor antagonist.

The opioid, ketobemidone, has previously been shown to be a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist. In Denmark, ketobemidone is available in a formulation which contains ketobemidone and a spasmolytic compound, (RS)-3-dimethylamino-1,1-diphenylbut-1-ene, hydrochloride (A29), in a one to five ratio. Using in vitro receptor binding techniques and an in vitro electrophysiological preparation consisting of rat cerebral cortex, we have characterized the interaction between A29 and the different glutamate receptor subtypes. A29 selectively inhibited binding of the non-competitive NMDA receptor antagonist 3H-MK-801 with a Ki value 16 +/- 4.5 microM, but was inactive in assays measuring affinities for other glutamate receptors. In agreement with the binding studies, A29 was found to selectively inhibit responses to NMDA in the rat cortical wedge preparation, whereas responses to kainate and AMPA were unaffected. Analysis of dose response curves showed A29 to be a NMDA receptor antagonist with an IC50 value of 100 microM versus responses to 10 microM NMDA. The inhibitory effects of ketobemidone and A29 on responses to 10 microM NMDA were additive. These data show that the combination of A29 and ketobemidone exert more potent antagonism at the NMDA receptor than does ketobemidone alone.

Allylamine↗
PubMed1997

Localization of nonpancreatic secretory phospholipase A2 in normal and atherosclerotic arteries. Activity of the isolated enzyme on low-density lipoproteins.

Secretory nonpancreatic type II phospholipase A2 (snpPLA2) hydrolyzes fatty acids at the sn-2 position in phospholipids releasing free fatty acids (FFAs) and lysophospholipids. These products may act as intracellular second messengers or can be further metabolized into proinflammatory lipid mediators. The presence of snpPLA2 in extracellular fluids and serum during inflammation has suggested a role of the enzyme in this process. However, the presence of snpPLA2 in a variety of normal tissues suggests that snpPLA2 may also have physiological functions. Atherosclerosis appears to have an inflammatory component. Here we report on the snpPLA2 localization in normal and atherosclerotic lesions and on the properties of the isolated enzyme. A strong snpPLA2 immunoreactivity was observed in the arterial media that was colocalized with alpha-actin-positive vascular smooth muscle cells (SMCs) in both normal and atherosclerotic vessels. In aortic atherosclerotic lesions, snpPLA2 was observed colocalized with CD68-positive macrophages and HHF-35-positive SMCs and extracellularly in the lipid core. snpPLA2 was isolated from human normal arteries and from aorta with lesions. The enzyme was isolated by acid extraction of normal arterial tissues followed by immunoaffinity chromatography. The purified snpPLA2 had an expected molecular weight of 14 kD by polyacrylamide gel electrophoresis and appeared as a single band in immunoblotting. The enzymatic activity was followed by measuring release of fatty acids from phospholipid liposomes or LDL as substrates. The enzymatic activity was inhibited with two specific inhibitors for human snpPLA2: (1) monoclonal antibody 187 and (2) LY311727, a synthetic selective inhibitor. The mRNA for snpPLA2 was detected with reverse transcriptase polymerase chain reaction. These results indicate that snpPLA2 is present in human arteries and that it is able to hydrolyze phospholipids in LDL. The results support the hypothesis that snpPLA2 can release proinflammatory lipids at places of LDL deposition in the arterial wall.

Adult↗
PubMed1996

[Mortality among Norwegian addicts after admission to different types of institutions. A 10-year follow-up study 1985-94].

Ten years after enrollment in six different treatment and rehabilitation facilities in 1984-85, 482 drug addicts (158 women) were followed-up by means of official death records. 97 drug addicts (20%) had died, i.e. an incidence rate of 2.3 per 100 observation years. The incidence rate among those enrolled in psychiatry-oriented institutions was 2.8 for men and 2.0 for women. Among those enrolled in rehabilitation-oriented institutions the corresponding incidence rate was 2.0 and 0.6. The ratio between the incidence rates for the two types of institutions was 1.6 (95% CI 1.0-2.6). Excluding those who were 21 to 25 years of age in 1984-85, the death rate was significantly higher among the drug addicts in psychiatry-oriented institutions than among the addicts at institutions focusing on rehabilitation(relative risk 2.1, 95% CI 1.1-4.1).

Adult↗