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Biomedical subjects

J Larsen

Publications and source records attributed to J Larsen.

At least 19 recordsLinked to original sources
PubMed2001

[Tramadol and oxazepam. Effect on pulmonry function in elderly patients with chronic obstructive lung disease].

Many patients with chronic obstructive pulmonary disease (COPD) suffer from osteoporotic pain as a result of glucocorticoid treatment and nervous symptoms partly related to their lung disease. There seems to be som reluctance to treat these patients with an opioid or benzodiazepine. Upon request, the Drug Information Centre in Odense made an extensive literature search on the subject. No documentation was found that tramadol additionally depresses the respiration in patients with COPD, nor has oxazepam in clinically relevant doses been found to exacerbate their lung disease. The clinical effect is subject to large interindividual variability, and the use of these drugs should, to a greater extent, rest on experience with the individual patient. There seems to be no reason to maintain a priori this rigoristic reluctance to use tramadol and/or oxazepam in patients with COPD.

Aged↗
PubMed2000

First trimester biochemical screening for Down syndrome: free beta hCG versus intact hCG.

To compare free beta hCG versus intact hCG in first trimester Down syndrome screening we analysed 63 cases of Down syndrome and 400 unaffected control pregnancies between 10 and 13 weeks' gestation. The Down syndrome median multiple of the median (MoM) was significantly higher (p=0.001) for free beta hCG (1.89 MoM) than for intact hCG (1.37 MoM). Although distributions for free beta hCG (unaffected, 0.2157; DS, 0.2322) are wider than for intact hCG (unaffected, 0.1697; DS, 0.2158), overall 27% of Down syndrome cases were above the 95th percentile for free beta hCG compared to 19% for intact hCG. Combined with maternal age, free beta hCG detected 45% of Down syndrome pregnancies at a 5% false positive rate. Intact hCG combined with maternal age demonstrated a detection efficiency comparable to maternal age alone (35% versus 32%). In contrast, a recent study (Haddow et al., 1998-NEJM 338: 955-961) indicated that intact hCG yielded a higher first trimester Down syndrome detection efficiency than free beta hCG (29% versus 25% respectively). Re-analysis of distribution parameters in the Haddow et al. study, however, show that free beta hCG was actually the better marker (23% detection for intact hCG versus 29% for free beta hCG).

Adult↗
PubMed2000

Carcinoma in situ of the breast: correlation of histopathology to immunohistochemical markers and DNA ploidy.

In a consecutive and unselected series of 178 cases of carcinoma in situ of the breast (CIS), comprising both ductal (DCIS) and lobular type (LCIS), and a series of 48 cases of invasive carcinoma (IC) with predominance of DCIS, the association between histopathology, immunohistochemical markers (ER, PgR, MIB-1, c-erbB-2, and p53), and DNA ploidy was investigated, in order to discriminate biologically different groups. In DCIS, significant correlation was shown between large nuclear size and comedonecrosis, both of which showed also strong association to DNA aneuploidy, high proliferation activity, low steroid receptor content, and overexpression of c-erbB-2 and p53 factors that may indicate an aggressive behavior. Small nuclear CIS, whether LCIS or DCIS, on the contrary, were DNA diploid with low proliferation, and no cases showed overexpression of c-erbB-2 and p53. Heterogeneity with respect to the investigated parameters was also a frequent finding that may reflect a development complexity. In IC, comparison of the DCIS and the invasive component showed similar patterns. No significant differences were shown between DCIS without and with invasion. This may indicate that none of the investigated parameters on its own are essential for the event of invasion.

Biomarkers, Tumor↗
PubMed2000

Lack of adherence to lipid-lowering drug treatment. A comparison of utilization patterns in defined populations in Funen, Denmark and Bologna, Italy.

AIMS: The objective was to explore differences in lipid-lowering drug (LLD) prescribing in Italy and Denmark. METHODS: We used two geographical areas with computerized drug prescription records in defined populations, one in Funen, Denmark with 500 000 inhabitants, the other in Bologna, Italy with 400 000 inhabitants. Prescriptions for patients who had purchased a LLD from 1994 until 1996 were retrieved as well as coprescriptions of antidiabetic and cardiovascular drugs as markers for diabetes and cardiovascular disease. Only patients surviving and remaining in the area were included. Compliance was defined as percentage of DDDs purchased divided by the number of days within the time window. The limit between good and poor compliance was set at 82%. RESULTS: In Bologna, LLD consumption measured in DDD increased by 41% and in Funen by 129%. Annual prevalence increased from 36.9 to 46.3 users/1000 inhabitants from 1994 to 1996 and from 3.2 to 6.6 users/1000 inhabitants in Bologna and Funen, respectively. From 1995 to 1996, the incidence of use decreased slightly in Bologna from 19.3 to 18. 8/1000 inhabitants/year, whereas in Funen the incidence increased from 1.8 to 2.3/1000 inhabitants/year. In Bologna 48% and in Funen 91% of users persisted with treatment for 2 years or longer. In Bologna, 7% and in Funen 45% were good compliers. In Bologna, 61% and in Funen, 72% received other drugs indicating cardiovascular or diabetic comorbidity. CONCLUSIONS: Patterns of use differed substantially between the two areas. In contrast with Funen, where long-term use was common, Bologna LLD use was sporadic. Based on a higher rate of coprescription, LLDs seemed to be used for secondary prevention to a higher extent in Funen than in Bologna. In Funen it appeared that the correct patients, but an insufficient number of them, were being treated adequately according to guidelines. The higher discontinuation rate of lipid lowering drugs in the Bologna area indicates that a large proportion of patients use these drugs for too short a period of time to benefit from treatment. Since society's health care resources are limited it is difficult to justify public funding of these medications without at the same time giving appropriate attention to these problems.

Adult↗
PubMed2000

Mosaic characteristics of human endometrial epithelium in vitro: analysis of secretory markers and cell surface ultrastructure.

Specific terminal carbohydrate structures and mucin-associated glycans increase in expression within the human endometrial epithelium during the secretory phase of the menstrual cycle but exhibit wide intercellular variation. We postulated that variation in glycosylation between cells would produce differences in the glycocalyx and result in complex mixtures of cells bearing different combinations of glycans. MUC-1 mucin, keratan sulphate and fucosylated lactosaminoglycans were examined in epithelial gland fragment cultures with antibodies (HMFG1, 5D4) and a lectin (Dolichos biflorus agglutinin). The glycocalyx was examined by transmission and high resolution scanning electron microscopy. The data were related to patterns of expression seen in vivo. The MUC-1 mucin was expressed relatively uniformly in culture, but heterogeneity was evident in mucin sialylation within the epithelial cell population. Double labelling of gland explant cultures for combinations of fucosylated lactosaminoglycans, keratan sulphate and MUC-1 demonstrated cells expressing all combinations of these markers. Ultrastructural examination confirmed remarkable intercellular variation in the glycocalyx. Though the human endometrial epithelium is relatively morphologically homogeneous, these observations reveal complex variations of cell surface glycosylation between neighbouring cells and suggest that secretory function might vary in a similar fashion.

Adult↗
PubMed2000

A case of primary amenorrhea, diabetes and anosmia.

This case details a patient with primary amenorrhea with an unusual cause. She presented at age 16 with short stature, minimal sexual development and no prior menses. Her history was significant for poorly controlled type 1 diabetes. She had been evaluated previously for growth hormone deficiency, and had received a short course of growth hormone therapy. Of greatest significance was the fact that she had also had a decreased sense of smell since her youth. Although a previous computerized tomography scan had been reported as normal, follow-up magnetic resonance imaging demonstrated the absence of olfactory bulbs. Smell testing confirmed the absence of smell and testing of gonadotropin releasing hormone demonstrated an inadequate response. All of these features suggested Kallmann syndrome. This syndrome commonly presents with delayed onset of puberty and decreased or absent sense of smell. There are also many associated features, and the disease is remarkable for its great genotypic and phenotypic variability. Current understanding of its pathogenesis, the commonly associated features of Kallmann syndrome and the impact of diabetes on growth and sexual development are reviewed.

Adolescent↗
PubMed2000

Mathematical models behind advanced simulators in medicine.

The paper presents as an example the types of mathematical models that are used in a full scale anesthesia simulator. The models vary from detailed reference models, based on fundamental physiological laws and principles, to simple script based models. A few considerations on the implementation of the models are also given.

Anesthesiology↗
PubMed1999

Potent and orally bioavailable noncysteine-containing inhibitors of protein farnesyltransferase.

Potent and orally bioavailable nonthiol-containing inhibitors of protein farnesyltransferase are described. Oral bioavailability was achieved by replacement of the pyridyl ether moiety of 1 with a 2-substituted furan ether to give 4. Potency was regained with 2,5-disubstituted furan ethers while maintaining the bioavailability inherent in 4. p-Chlorophenylfuran ether 24 is 0.7 nM in vitro (FTase) and is 32% bioavailable in the mouse, 30% bioavailable in rats, and 21% bioavailable in dogs.

Alkyl and Aryl Transferases↗
PubMed1999

Generalizable patterns in neuroimaging: how many principal components?

Generalization can be defined quantitatively and can be used to assess the performance of principal component analysis (PCA). The generalizability of PCA depends on the number of principal components retained in the analysis. We provide analytic and test set estimates of generalization. We show how the generalization error can be used to select the number of principal components in two analyses of functional magnetic resonance imaging activation sets.

Algorithms↗
PubMed1999

Suppression of the biocontrol agent trichoderma harzianum by mycelium of the arbuscular mycorrhizal fungus glomus intraradices in root-free soil

Trichoderma harzianum is an effective biocontrol agent against several fungal soilborne plant pathogens. However, possible adverse effects of this fungus on arbuscular mycorrhizal fungi might be a drawback in its use in plant protection. The objective of the present work was to examine the interaction between Glomus intraradices and T. harzianum in soil. The use of a compartmented growth system with root-free soil compartments enabled us to study fungal interactions without the interfering effects of roots. Growth of the fungi was monitored by measuring hyphal length and population densities, while specific fatty acid signatures were used as indicators of living fungal biomass. Hyphal 33P transport and beta-glucuronidase (GUS) activity were used to monitor activity of G. intraradices and a GUS-transformed strain of T. harzianum, respectively. As growth and metabolism of T. harzianum are requirements for antagonism, the impact of wheat bran, added as an organic nutrient source for T. harzianum, was investigated. The presence of T. harzianum in root-free soil reduced root colonization by G. intraradices. The external hyphal length density of G. intraradices was reduced by the presence of T. harzianum in combination with wheat bran, but the living hyphal biomass, measured as the content of a membrane fatty acid, was not reduced. Hyphal 33P transport by G. intraradices also was not affected by T. harzianum. This suggests that T. harzianum exploited the dead mycelium but not the living biomass of G. intraradices. The presence of external mycelium of G. intraradices suppressed T. harzianum population development and GUS activity. Stimulation of the hyphal biomass of G. intraradices by organic amendment suggests that nutrient competition is a likely means of interaction. In conclusion, it seemed that growth of and phosphorus uptake by the external mycelium of G. intraradices were not affected by the antagonistic fungus T. harzianum; in contrast, T. harzianum was adversely affected by G. intraradices.

Journal Article↗
PubMed1999

Improved sensitivity in comparative genomic hybridization analysis of DNA heteroploid cell mixtures after pre-enrichment of subpopulations by fluorescence activated cell sorting.

Cytogenetic analysis of solid tumors with comparative genomic hybridization (CGH) is hampered by the dilution of DNA from individual tumor subpopulations with DNA from other cells. We investigated to what extent this dilution effect can be alleviated using fluorescence activated cell sorting (flow sorting) of experimental DNA heteroploid cell mixtures prior to CGH. From mixtures of normal lymphocytes with triploid K-562 cells the individual components were sorted according to stemline DNA content and processed by CGH in comparison with pure K-562 samples and the original mixtures. Compared with 30 autosome copy number imbalances found in pure K-562 samples, a mixture with 32% K-562 cells showed 16 imbalances, and none were detected in mixtures with 13% or 5% K-562 cells. In contrast, 29, 22 and 23 imbalances were detected in K-562 nuclei sorted from the 32%, 13% and 5% mixtures, respectively. This indicate that CGH analysis of flow sorted DNA aneuploid subpopulations enables a specific cytogenetic analysis of the individual subclones in a DNA heteroploid cell population.

Cell Separation↗
PubMed1998

Potent and selective non-cysteine-containing inhibitors of protein farnesyltransferase.

Potent and selective non-thiol-containing inhibitors of protein farnesyltransferase are described. FTI-276 (1) was transformed into pyridyl ether analogue 19. The potency of pyridyl ether 19 was improved by modification of the biphenyl core to that of an o-tolyl substituted biphenyl core to give 29. In addition to 0.4 nM in vitro potency, 29 displayed 350 nM potency in whole cells as the parent carboxylic acid. The o-tolyl biphenyl core dramatically and unexpectedly enhanced the potency of other compounds as exemplified by 46, 47, 48, and 49.

3T3 Cells↗
PubMed1998

[Antabus treatment in general practice. A pharmaco-epidemiological study of prescription patterns based on a prescription database].

Denmark has a long tradition for the use of alcohol-aversive drugs in the treatment of alcoholism, most commonly disulfiram (Antabuse). The purpose of this study was to examine the prescription patterns for disulfiram in Danish general practice on an individual level. By means of a prescription database we analysed 150,787 prescriptions on reimbursed medicine to persons who had redeemed prescriptions for alcohol-aversive drugs during the period 1.1.1993 to 31.12.1995 in the County of Funen. Prevalence of disulfiram treatment was 12 per 10,000 inhabitants, three-year prevalence 75 per 10,000 inhabitants and incidence 21 per 10,000 inhabitants per year. Eighty-seven percent of treatments were stopped at (or before) the expiration of one prescription, and relapse was frequent (46%).

Adult↗