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Biomedical subjects

L Olsen

Publications and source records attributed to L Olsen.

At least 19 recordsLinked to original sources

[Circumcision of boys--a child's right versus parents' right].

Male circumcision was practiced long before Abraham established a covenant with God to the effect that he should circumcize himself and all male members of his house. Thereafter it has become a potent religion-ethnic commandment also in the Islamic world, although it is not mentioned in the Koran. Several million boys are circumcised yearly in for instance traditional Africa and the USA (in the USA originally as prophylaxis against masturbation). In Sweden the yearly figure is some 3000 boys. A comprehensive review of the literature reveals that there are no or only marginal medical benefits of the operation, particularly in view of the fact that up to 10% suffer complications, and also that newborns both experience pain and will respond more strongly to new pain stimuli for years to come. There are two opposing interests--those related to the religious tradition and those related to the welfare of the child as expressed in the United Nations Convention on the Rights of the Child.

Child Welfare↗

Induction of micronuclei in V79 cells by fractions of roofing asphalt fume condensate.

More than 50,000 workers in the United States are exposed to roofing asphalt fumes that may pose genotoxic and potential carcinogenic hazards. The Type III roofing asphalt is most frequently used in roof-application. Results of our previous studies showed that fume condensates of Type III roofing asphalts induced micronuclei (MN) in vitro in cultured V79 cells and DNA adduct formation in vivo in rat lung cells. In this study, the genotoxicity of whole fume condensates (WFC) of Type III roofing asphalt and its five chemical fractions (A, B, C, D and E) was determined by the micronucleus assay using V79 cells. Linear regressions were determined for the dose response of MN frequencies and percent of binucleated and multinucleated cells (MTC) following the treatment. Results showed that the numbers of micronucleated cells in cultures treated with Type III roofing asphalt WFC and its fractions B, C, D and E were significantly higher than that in the control culture, and that the slopes of the linear regression line for fractions B and C were greater than those for the WFC and fractions D and E. A clear dose response of binucleated cells was also induced by the WFC and fractions B and C. These findings indicate that: (1) WFC and all fractions, except fraction A, induced MN formation in cultured V79 cells; (2) fractions B and C possess the highest genotoxic activity; (3) the roofing asphalt WFC contains chemicals or chemical classes that induce not only chromosomal aberrations but also binucleation in V79 cells.

Animals↗

Pressure-flow studies: short-time repeatability.

The within and between examination variation in selected test parameters and test results in repeated pressure-flow studies was determined in a prospective study of consecutive pressure-flow examinations in 22 patients. The patients were pressure-flow tested twice within a month. Furthermore, it was evaluated whether there was a systematic change in the measured parameters during retesting. By using the Abrams-Griffiths nomogram, patients were classified as obstructed, equivocal, or unobstructed. Within and between examination variations in classification were evaluated. We found a systematic variation in P(det.Qmax) during testing, which in the absence of statistically significant systematic variations in P(det.Close) and Qmax, indicates a physiological effect of repeated pressure-flow studies, resulting in a less-obstructed second voiding. Supporting this, we found that all patients who changed group of classification of bladder outlet obstruction in the first examination shifted to a group of less obstruction, as did 66% of the patients who changed group of classification of bladder outlet obstruction in the second examination. Still, 80, respectively 85%, of the patients remained in the same group of classification of bladder outlet obstruction during retesting in the first and second examinations, respectively. Classifying the degree of bladder outlet obstruction by Qmax, P(det.Qmax), and P(det.Close) 85% of the patients reproduced their test results accurately in both examinations and taking only the first voiding in both examinations into account 95% reproduced their test results.

Aged↗

Mathematical modelling of anisotropy in fibrous connective tissue.

We present two modelling frameworks for studying dynamic anistropy in connective tissue, motivated by the problem of fibre alignment in wound healing. The first model is a system of partial differential equations operating on a macroscopic scale. We show that a model consisting of a single extracellular matrix material aligned by fibroblasts via flux and stress exhibits behaviour that is incompatible with experimental observations. We extend the model to two matrix types and show that the results of this extended model are robust and consistent with experiment. The second model represents cells as discrete objects in a continuum of ECM. We show that this model predicts patterns of alignment on macroscopic length scales that are lost in a continuum model of the cell population.

Anisotropy↗

Safe biotechnology 9: values in risk assessment for the environmental application of microorganisms. The Safety in Biotechnology Working Party of the European Federation of Biotechnology.

Risk assessment for the deliberate release of microorganisms into the environment is traditionally carried out on a case-by-case basis. In a similar approach to that used when assessing human pathogenicity, we propose an alternative approach by introducing risk classes to facilitate or complement this type of risk assessment. These consider several sets of scenarios that address the different values that need to be protected. Examples of this approach include risk-class definitions for soil fertility and biodiversity.

Bacteria↗

Accessory wandering spleen associated with short pancreas. A pediatric case report.

We present an extremely rare case of a 5-year-old girl with short pancreas associated with three accessory spleens, one of which was a large wandering spleen. The diagnosis was established by US and CT. A large accessory wandering spleen is considered to be at risk of torsion and infarction as well as susceptible to abdominal trauma. The authors discuss the difficulty of establishing the diagnosis and underline the importance of US and CT as pre-operative diagnostic tools.

Abdominal Pain↗

Interstitial cells of Cajal in the human fetal small bowel as shown by c-kit immunohistochemistry.

BACKGROUND: Interstitial cells of Cajal (ICCs) express the tyrosine kinase receptor c-kit, which is required for their development and spontaneous pacemaker activity in the bowel. From murine models it has been proposed that ICCs do not develop until after birth, but more recent findings indicate that c-kit is expressed early in the embryonic period. The temporal development of ICCs in the human gut remains unknown. AIM: To investigate ICCs in the human fetal small bowel using c-kit immunohistochemistry. SUBJECTS: Small bowel specimens were obtained at post mortem examination of 16 fetuses and nine neonates, eight of whom were premature, born at gestational ages of 13 to 41 weeks, without gastrointestinal disorders. METHODS: Immunohistochemical analysis was performed on material fixed in formalin and embedded in paraffin. The specimens were exposed to antibodies raised against c-kit (an ICC marker) and neurone specific enolase (a general neuronal marker). The ABC complex method was used to visualise binding of antibodies to the corresponding antigens. RESULTS: c-kit immunoreactive cells were visualised from 13 weeks of gestation. The immunoreactivity was mainly localised in association with the myenteric plexus. From about 17-18 weeks of gestation, the ICCs formed a layer along the myenteric plexus, whereas this layer appeared to be disrupted at 13-16 weeks of gestation. CONCLUSIONS ICCs are c-kit immunoreactive at least from a gestational age of 13 weeks in the human fetal small intestine. From 17-18 weeks of gestation until birth, they form a continuous layer around the myenteric ganglia.

Embryonic and Fetal Development↗

Attention-deficit hyperactivity disorder in children and youth: a quantitative systematic review of the efficacy of different management strategies.

OBJECTIVE: To obtain estimates of the relative efficacy of 3 main treatment strategies for attention-deficit hyperactivity disorder (ADHD) in children and youth (age < 18 years). METHODS DESIGN: quantitative systematic review of randomized trials. SUBJECTS: 999 patients with ADHD from 26 randomized trials. INTERVENTIONS: medications alone, behavioural interventions alone, and a combination of these 2 modalities. MAIN OUTCOME MEASURE: differences in scores between treatment groups on commonly used teacher- and parent-completed behaviour rating scales. RESULTS: Medication-only therapy was efficacious in ADHD. Behavioural therapies used alone appeared not to be efficacious in ADHD. Combination therapy was more efficacious than placebo or no treatment for parent but not teacher ratings, not more efficacious than drug therapy alone, and more efficacious than behavioural treatments alone based on parent but not teacher ratings. CONCLUSION: Though stimulant medications were found to be an effective treatment strategy for ADHD in children and youth, it proved difficult to assess the relative benefits of behavioural interventions alone and combined medication and behavioural therapy because of the paucity of treatment studies other than medication-only treatment studies and heterogeneity of various kinds that exist in relation to ADHD studies and treatments.

Adolescent↗

Expression of bcl-2 in enteric neurons in normal human bowel and Hirschsprung disease.

OBJECTIVE: The bcl-2 protein has the functional role of blocking apoptosis, ie, programmed cell death. This protein is widely expressed in the developing central and peripheral nervous systems. The purpose of this study was to map bcl-2 expression in the human enteric nervous system, as this has not previously been done. METHODS: Rectal specimens were obtained at autopsy of 13 fetuses at 13 to 31 weeks of gestation. Normal colon was also obtained from 5 children and 2 adults, and, in addition, ganglionic and aganglionic bowel resected in 11 patients with Hirschsprung disease was examined. Specimens were fixed in formalin, embedded in paraffin, and analyzed with immunohistochemical methods, using antibodies raised against bcl-2 and neuron-specific enolase (NSE). RESULTS: The bcl-2 protein was expressed in myenteric and submucous ganglion cells in fetuses, children, and adults. Nerve fibers of the enteric plexuses that were bcl-2 immunoreactive were few compared with the number of NSE-immunoreactive nerve fibers. In aganglionic bowel no bcl-2-or NSE-immunoreactive ganglion cells were revealed. Results of NSE immunohistochemistry showed clearly stained hypertrophic nerve bundles, known to be of extrinsic origin, which were only weakly bcl-2 immunoreactive. CONCLUSION: Expression of bcl-2 in enteric ganglion cells of the myenteric and submucous plexuses is displayed in the fetus and during childhood and is also retained in adult bowel. Immunohistochemical analysis of bcl-2 provides a good marker for identification of ganglion cells in Hirschsprung disease and may also be valuable for the diagnosis of disorders characterized by hypoganglionosis or hyperganglionosis.

Aged↗

Differential expression of inducible nitric oxide synthase in septic shock.

During cardiopulmonary bypass (CPB), the septic patient has markedly decreased peripheral vascular resistance as a consequence of endotoxin release from microorganisms. This decrease in peripheral vascular resistance is the result of endotoxin-induced nitric oxide (NO) produced by inducible nitric oxide synthase (iNOS) and endothelial nitric oxide synthase (eNOS). iNOS and eNOS are responsible for the synthesis of NO because of various stimuli, including the bacterial endotoxin, lipopolysaccharide (LPS). We tested the hypothesis that a differential expression of iNOS among human endothelial cells and murine macrophage is dependent upon exposure to endotoxin and various pro-inflammatory cytokines. Using a human endothelial cell line, ECV-304 and murine macrophage cell line, RAW 264.7, we quantified the expression of iNOS with specific FITC-conjugated antibodies using fluorescence activated cell sorter (FACS) and NO production with a Bioxytech nitric oxide spectrophotometric assay. This in vitro septic model utilized LPS supported with species-specific interferon-gamma, interleukin-1 beta, and tumor necrosis factor-alpha. The cell type were stimulated for 8 hours with combinations of the cytokines mentioned. The FACS data demonstrated a significant stimulus-dependent increase in iNOS expression among the macrophage groups; however, the stimulated endothelial cells showed no significant change in iNOS expression. The nitric oxide production data demonstrated significant increases in NO production among macrophage stimulated groups; whereas, endothelial stimulated groups exhibit no significant change. We conclude that NO secreted during septic shock is the result of activated macrophage, not the endothelium. The clinical relevance is that the more severe the infectious process, the lower the PVR may be during CPB because of increased NO production from activated macrophage.

Animals↗

Spatially varying equilibria of mechanical models: application to dermal wound contraction.

Mechanochemical models based on the Oster-Murray continuum framework have been applied to a variety of biological settings to obtain an understanding of the morphogenesis of living tissues. Wound-healing in mammalian skin is an important example, because a complex sequence of biochemical and biomechanical responses are orchestrated to close a wound by a combination of new tissue formation and wound contraction. Mechanical interactions between dermal fibroblastic cells and the collagen-rich extracellular matrix are crucial in the development of a contracted wound state. We and others have previously proposed mechanochemical models for wound repair to gain a greater understanding of both normal and abnormal healing. In the present work, the existence of spatially varying equilibria of these models is investigated by using a small-stain approximation and phase-plane techniques, with numerical simulations to confirm the analytical predictions. These results are sources of novel insight into the roles of key biological parameters in determining the mechanical properties of a contracted wound. These methods may also be relevant to other morphogenetic scenarios for which similar mechanochemical models have been proposed.

Animals↗

The effect of addition of calcipotriol ointment (50 micrograms/g) to acitretin therapy in psoriasis.

Our purpose was to find out whether the addition of calcipotriol ointment (50 micrograms/g) to systemic treatment with acitretin produces additional therapeutic effects and thereby an acitretin-sparing effect, and further to investigate the safety and tolerability of this combination. A multicentre, randomized, double-blind placebo-controlled study was designed. Patients were randomized to receive calcipotriol or placebo. All patients were treated with a starting dose of 20 mg acitretin per day and doses were adjusted at 2-weekly intervals with increments of 10 mg per day up to a maximum of 70 mg per day. The dose requirement for acitretin, clinical signs and adverse events were recorded. Seventy-six patients were randomized to treatment with calcipotriol 50 micrograms/g ointment twice daily and 59 patients to treatment with the vehicle only twice daily. Clearance or marked improvement was achieved by 67% of the patients in the calcipotriol group and by 41% of the patients in the placebo group (P = 0.006). Calcipotriol treatment proved to have a statistically significant additional effect to acitretin on the Psoriasis Area and Severity Index, redness, thickness and scaliness as compared with placebo. Clearance or marked improvement was achieved with a statistically significantly lower cumulative dose of acitretin by the patients in the calcipotriol group as compared with the placebo group. The number of patients reporting adverse events was pronounced and largely related to acitretin. No significant differences were observed between the two treatment groups with respect to adverse events. Laboratory assessments were essentially normal. The addition of calcipotriol ointment to acitretin treatment contributes to the efficacy, reduces the cumulative dose of acitretin to reach marked improvement or clearance, and is well-tolerated and safe.

Acitretin↗

Developmental gene expression of sympathetic nervous system tumors reflects their histogenesis.

Comparisons of the developing human sympathetic nervous system (SNS) to tumors presumed to derive from these cells may suggest tumor progenitors and predict tumor biologic behavior. Classic neuroblastoma (NB) and its more highly differentiated stroma-rich subtypes, extra-adrenal sympathetic paraganglioma, and pheochromocytoma were examined for the presence of the developmentally characterized gene products NSE, S-100, CD44, Bcl-2, HNK-1, PNMT, TrkA, IGF2, and tyrosine hydroxylase. The marker gene expression profiles of these tumors were compared with those similarly determined for a number of normal prenatal and postnatal human SNS cell types. Sympathetic paraganglioma, pheochromocytoma, and stroma-rich NB display marker expression profiles mimicking those of childhood sympathetic paraganglia, adrenal chromaffin cells, and sympathetic neurons, respectively. A selection of differentiating, extra-adrenal NB tumors with prognostically favorable features possess marker gene expression profiles paralleling that observed for fetal extra-adrenal sympathetic paraganglia/small intensely fluorescent cells. In contrast, undifferentiated, clinically aggressive NB tumors manifest characteristics mirroring that of embryonic/early fetal sympathetic neuroblasts of sympathetic ganglia and of the adrenal gland. These findings suggest that clinical features, such as primary tumor location and age at diagnosis, provide prognostic information for NB patients by virtue of the existence and biology of the presumed tumor progenitor cell type.

Adrenal Gland Neoplasms↗

Pressure-flow studies: an evaluation of within-testing reproducibility--validity of the measured parameters.

The within-examination variation in selected test parameters in repeated pressure-flow studies was determined in a retrospective study of consecutive pressure-flow examinations in 105 patients. It was further evaluated to see whether there was a systematic change in the measured parameters during retesting. To see if variation and reproducibility were influenced by the procedure of investigation, i.e., transurethral or suprapubic, patients were grouped according to the method employed. Finally, the effect of detrusor instability on the measurements was evaluated. Using the Abrams-Griffiths nomogram, patients were classified as obstructed, equivocal, or unobstructed. The test-retest variations in classification were evaluated. We found a systematic variation in Pdet.Qmax' Pdet.Open' and Qmax during testing, indicating a physiological effect of repeated pressure-flow studies resulting in a less obstructed second voiding. Accordingly, 69% of the patients who shifted group of classification during retesting shifted to a group of lesser obstruction at the second voiding. Still, 88% of patients remained in the same group of classification of bladder outlet obstruction. Within- and between-patient variations and reproducibility of the test results were not influenced by the procedure of investigation, i.e., the transurethral or suprapubic method. However, we found variations suggesting a decrease in urethral resistance and bladder contractility from test to test in the transurethral group, whereas variations suggesting an isolated decrease in bladder contractility were seen in the suprapubic group. Detrusor instability per se does not seem to cause any systematic changes during repeated testing.

Adult↗

Spatial association of apoptosis-related gene expression and cellular death in clinical neuroblastoma.

Several unique features of neuroblastoma (NB), including the capacity for spontaneous regression and maturation to benign pathology, suggest that genes that regulate cellular proliferation, survival and differentiation may be involved in directing clinical tumour aggressiveness. The in situ expression of Bcl-2, Rb, p21, p53 and Bax proteins, as well as the proliferation marker proliferating cell nuclear antigen (PCNA) were examined immunocytochemically in a selection of 38 stage- and outcome-identified NB tumours. Apoptotic cells were identified morphologically and by a DNA fragmentation labelling technique (TUNEL). Although the tumour cell density of Bcl-2, p53, Bax, PCNA and TUNEL positivity correlated with patient survival, a spatially organized expression pattern was further recognized in stroma-poor differentiating tumours. Immature tumour cells adjacent to thin fibrovascular stroma are proliferating, as evidenced by PCNA positivity, and often express Bcl-2. At increasing distance from this fibrovascular stroma, intermediately differentiated tumour cells express Rb, while with more advanced differentiation, proliferation ceases and Bcl-2 immunoreactivity is lost. The most differentiated tumour cells, which often express p53, and occasionally p21 and Bax, lie adjacent to TUNEL-positive, morphologically apoptotic cells. This spatial organization in favourable outcome NB tumours suggests that physiological regulation of differentiation and apoptosis may be involved in tumour regression.

Apoptosis↗