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Biomedical subjects

H Laursen

Publications and source records attributed to H Laursen.

At least 19 recordsLinked to original sources

Classification of surgical procedures for epidemiologic assessment of sporadic Creutzfeldt-Jakob disease transmission by surgery.

BACKGROUND: In this preparatory phase of a case-control study, we propose and evaluate a new tool for classifying surgical procedures (SPs) in categories useful for epidemiologic research on surgical transmission of sporadic Creutzfeldt-Jakob disease (sCJD). METHODS: All SPs reported to the Swedish National Hospital Discharge Registry in the period 1974-2002, and undergone by 212 Swedish patients with registered diagnosis of CJD at death, hospital discharge or notification, in the period 1987-2002, 1060 age-, sex- and residence-matched controls and 1340 randomly chosen population controls, were reclassified into one of six categories of hypothetical transmission risk level. For that purpose the following two attributes were used: non-disposable instruments involved; and highest assigned ad-hoc risk level for four tissues or anatomical structures contacting such instruments. RESULTS: A total of 1170 different SP codes were reclassified as follows: 3.1% in the high-risk, 59.1% in the lower-risk, 24.4% in the lowest-risk, and 2.1% in the no-risk groups, with 11.3% procedures negatively defined by rubric as "other than..." being assigned to two spurious diluted-high and diluted-lower risk categories. The high-risk group mainly comprised neurosurgical (53%) and ophthalmic (39%) procedures. Sensitivity of neurosurgery and of ophthalmic surgery excluding neurosurgery, for the high- and diluted-high risk vs. other categories was 46% and 84%, while specificity was 98% and 95%, respectively. Sensitivity analysis based on these indices revealed that non-significant odds ratio effects of 1.4 and 1.3 for neurosurgery and ophthalmic surgery corresponded to statistically significant values of 5.1 after reclassification. CONCLUSIONS: This classification might contribute to quantify effects masked by use of body-system SP-categories in case-control studies on sCJD transmission by surgery.

Case-Control Studies↗

Total number of cells in the human newborn telencephalic wall.

The total cell numbers were estimated in the neocortical part of the human telencephalon in 10 normal brains of newborn babies within four major developmental zones: the cortical plate/marginal zone, the subplate, the intermediate zone and the ventricular/subventricular zone. Furthermore, the total number of neuron and glial cells was estimated in the cortical plate. The gestational ages ranged from 38 + 0-42 + 5 weeks + days of gestation. The mean total cell number was 32.6 x 10(9) (coefficient of error = 0.04) and the total number of neurons in the cortical plate 19.8 x 10(9) (coefficient of error = 0.06). This indicates that the total number of neocortical neurons equals the total number in the adults, which, however, is not the case for the glial cells.

Cell Count↗

Short-term study of the uptake of PrP(Sc) by the Peyer's patches in hamsters after oral exposure to scrapie.

The disease-associated prion protein (PrP(Sc)) has been detected in the ileal Peyer's patches of lambs as early as one week after oral exposure to scrapie. In hamsters, the earliest reported time of PrP(Sc) detection in the Peyer's patches after oral exposure to scrapie is 69 days post-infection. To evaluate the acute uptake of inoculum and to investigate whether the Peyer's patches constitute the primary site of entry for scrapie after oral exposure, hamsters were each exposed orally to 1 ml of a 10% brain homogenate from hamsters in the terminal stage of infection with the 263 K strain of the scrapie agent. PrP(Sc) was demonstrated in the Peyer's patches only a few days after exposure, i.e., much earlier than previously reported. This study supports the view that the Peyer's patches constitute at least one of the primary entry sites of PrP(Sc) after oral exposure to scrapie.

Animals↗

New evidence for the origin of intracranial germ cell tumours from primordial germ cells: expression of pluripotency and cell differentiation markers.

Primary intracranial germ cell tumours are rare neoplasms that occur in children and adolescents. This study examined both the biology and the origin of these tumours, as it has been hypothesized that they originate from a totipotent primordial germ cell. We applied recent knowledge from gonadal germ cell tumours and analysed expression of a wide panel of stem cell-related proteins (C-KIT, OCT-3/4 (POU5F1), AP-2gamma (TFAP2C), and NANOG) and developmentally regulated germ cell-specific proteins (including MAGE-A4, NY-ESO-1, and TSPY). Expression at the protein level was analysed in 21 children and young adults with intracranial germinomas and non-germinomas, contributing to a careful description of these unusual tumours and adding to the understanding of pathogenesis. Stem cell related proteins were highly expressed in intracranial germ cell tumours, and many similarities were detected with their gonadal equivalents, including a close similarity with primordial germ cells. A notable difference was the sex-specific expression of TSPY, a gene previously implicated in the origin of gonadoblastoma. TSPY was only detected in germ cell tumours in the central nervous system (CNS) from males, suggesting that it is not required for the initiation of malignant germ cell transformation. The expression of genes associated with embryonic stem cell pluripotency in CNS germ cell tumours strongly suggests that these tumours are derived from cells that retain, at least partially, an embryonic stem cell-like phenotype, which is a hallmark of primordial germ cells.

Adolescent↗

Cavernous hemangioma of the spinal cord - conservative or operative management?

Once believed to be extremely uncommon, due to magnetic resonance imaging cavernous hemangiomas of the spinal cord are detected with increasing frequency. Management of both symptomatic and asymptomatic intramedullary cavernous hamangiomas is therefore of growing importance. However, experience with treatment and follow-up is very limited. In particular, patients with multiple central nervous system cavernous hemangiomas represent a therapeutical dilemma. We present a patient with a ruptured intramedullary and multiple cerebral cavernous hemangiomas and a survey of current knowledge of epidemiology, pathophysiology and treatment options. We conclude that the benefit of operative treatment possibly decreases with the number of clinically silent vascular malformations.

Adult↗

Autoprotection in acetaminophen intoxication in rats: the role of liver regeneration.

Autoprotection by acetaminophen, i.e. increased resistance to toxic effects caused by pretreatment, is a well-known phenomenon. The purpose of the present work was to identify mechanisms for increased acetaminophen tolerance induced by pretreatment of rats. One group of female Wistar rats (pretreated rats) received acetaminophen orally in increasing doses (1 to 4.3 g/kg) twice a week for 3 weeks, one group (naïve rats) received the vehicle. At time zero pretreated rats received a toxic dose of 7.5 g/kg (100% lethal in naïve rats), and naïve rats received a toxic dose of 4.3 g/kg. Blood and liver tissue were collected before and 12, 24, 36, and 48 hr after the toxic dose and were analysed for hepatic glutathione and cysteine contents, hepatic glutathione-S-transferase and blood alanine aminotransferase activity, as well as acetaminophen concentration in plasma. Steady-state mRNA levels of proteins involved in acetaminophen detoxification, cell division and acute phase response were measured, liver tissue was examined for proliferating cell nuclear antigen and degree of hepatocyte necrosis. Six naïve rats not receiving acetaminophen served as controls. The mortality was the same in pre-treated and naïve rats (33 percent). Thus, pretreatment increased the tolerance twice. Before the toxic dose pretreated rats compared to control rats had higher activity of glutathione-S-transferase (liver) and alanine aminotransferase (serum), higher hepatic mRNA level of glutathione-S-transferase and gamma-glutamylcysteine synthetase heavy and light chain subunits, and lower hepatic concentration of glutathione, cysteine and mRNA of CYP1A2 than control rats. After the toxic dose, the mRNA levels of glutathione-S-transferase, gamma-glutamylcysteine synthetase heavy and light chain subunits, and CYP1A2 in naïve rats rose, approaching those of pretreated rats. Proliferating cell nuclear antigen labelling was high in pretreated rats, while only slightly increased in a few of the naïve rats. Necrotic hepatocytes were found at all time intervals in pretreated rats, and in naïve rats they appeared after 12 hr, peaking after 36 hr. Pretreatment increased the tolerance to acetaminophen toxicity twice, as estimated by mortality. The data indicate that pretreatment may reduce the relative production of toxic metabolites, but it primarily enhances the protection against these metabolites by regenerating hepatocytes.

Acetaminophen↗

Transvaginal sonography combined with saline contrast sonohysterography in evaluating the uterine cavity in premenopausal patients with abnormal uterine bleeding.

OBJECTIVES: To evaluate whether saline contrast sonohysterography (SCSH) adds additional information to that obtained by transvaginal sonography (TVS) for predicting endometrial abnormality in premenopausal patients with abnormal uterine bleeding. PATIENTS AND METHODS: This was a two-center prospective study at a university clinic and a central hospital in Denmark. The uterine cavity was evaluated with TVS and SCSH in 470 premenopausal patients with abnormal uterine bleeding. One hundred and eighty-nine of the patients had operative hysteroscopy or hysterectomy within 4 months which provided a detailed description of the uterine cavity and was used as the true value for exclusion of polyps and submucous myomas. RESULTS: Based on normal endometrial morphology alone, the results for detection of an abnormal uterine cavity were as follows: sensitivities of TVS 0.92, SCSH 0.99; specificities of TVS 0.62, SCSH 0.72; positive predictive values of TVS 0.80, SCSH 0.85; negative predictive values of TVS 0.82, SCSH 0.98. Transvaginal sonography combined with SCSH was superior to TVS for detection of intracavitary abnormalities (McNemar test, P = 0.008). The post-test probability of there being an abnormal cavity after normal findings on TVS alone was 0.18 (0.10-0.32) and after TVS and SCSH it was 0.02 (0.01-0.11). When normal endometrial morphology was combined with an endometrial thickness of < 12 mm for evaluation of all abnormalities including hyperplasia, the diagnostic potential of TVS or SCSH was almost unchanged except for specificities, which were markedly lower (TVS 0.54; SCSH 0.57). In all the patients referred, TVS had a negative predictive value of 0.94 for identification of polyps and myomas when findings at subsequent SCSH were accepted as the true value. Transvaginal sonography reduced the pretest probability of polyps or submucous myomas from 0.35 to a post-test probability of 0.06, but missed 21% of the polyps. CONCLUSIONS: Sonohysterography was a sensitive tool and was superior to TVS used alone for evaluation of the uterine cavity in patients who underwent operative surgery for abnormal uterine bleeding. All abnormalities except one were found at SCSH, while TVS alone missed polyps and had almost one in four equivocal findings. The use of TVS, without saline contrast, left one in five of the polyps undiagnosed in referred patients with abnormal bleeding.

Adult↗

Increased acute phase reactants are associated with levels of lipoproteins and increased carotid plaque volume.

OBJECTIVES: to test the hypotheses that increased acute phase reactants predict elevated levels of lipoproteins and increased plaque volume as well as echolucency of carotid plaques. MATERIALS AND METHODS: the study included 258 patients with >or =50% carotid artery stenosis. Acute phase reactants (orosomucoid, C-reactive protein (CRP)) were measured in the fasting state, and ultracentrifugated lipoproteins before and after a standardised fat load test. Echogenicity of carotid plaques was detected using high-resolution B-mode ultrasound and computer-assisted image processing. A subgroup of 81 patients underwent carotid endarterectomy. RESULTS: on linear regression analysis orosomucoid levels were positively associated with fasting and postprandial levels of all triglyceride-rich lipoproteins, and negatively associated with HDL cholesterol (p -values <0.0001); results for CRP were less pronounced. Orosomucoid and CRP both predicted the presence of an increased carotid plaque volume on univariate analysis (p =0.01 and p =0.02). Finally, orosomucoid was negatively associated with echolucency of carotid plaques ( p =0.05). CONCLUSIONS: elevated levels of acute phase reactants are strongly associated with elevated levels of triglyceride-rich lipoproteins, increased plaque volume, and borderline significantly associated with echolucency of carotid plaques. Elevated acute phase reactants possibly predict severity of atherosclerosis, and presence of lipid-rich, rupture-prone plaques.

Aged↗

Can the endometrial thickness as measured by trans-vaginal sonography be used to exclude polyps or hyperplasia in pre-menopausal patients with abnormal uterine bleeding?

BACKGROUND: To combine findings of normal mid-line echoes from TVS (trans-vaginal sonography) with cut-off levels for endometrial thickness, in order to examine the associated risk of abnormalities in the uterine cavity. DESIGN AND SETTING: Two center prospective study at a university clinic and a central hospital in Denmark. PARTICIPANTS: Three hundred and fifty-five pre-menopausal patients with abnormal uterine bleeding, and indications for endometrial sampling or surgery. INTERVENTIONS: The thickness of the endometrium was measured, and the mid-line echoes were evaluated using TVS. The findings from the endometrial sampling, combined with the evaluation of the uterine cavity using operative hysteroscopy (115), hysterectomy (74) or HSE (hysterosonographic examination) (166), were used as the true values. RESULTS: The mean (+/-s.d.) endometrial thickness was significantly different in patients with hyperplasia 11.5 mm (+/-5.0), polyps 11.8 mm (+/-5.1), sub-mucous myomas 7.1 mm (+/-3.4) and in patients without these abnormalities 8.37 (+/-3.9) (p<0.001). Hyperplasia and/or polyps were present in 20% of all patients, and in 8% of 143 patients with an endometrial thickness of < or =7 mm. This proportion did not decrease with lower cut-off levels for endometrial thickness. Receiver operating characteristic (ROC) curves were not optimal for excluding hyperplasia or polyps by endometrial thickness. In 173 cases with a distinct, regular midline echo without echo-dense foci in TVS the proportion of patients with abnormalities was 16% (11-23). This proportion did not decrease with cut-off levels for endometrial thickness. CONCLUSIONS: Using TVS, low levels of endometrial thickness reduced the possibility of abnormalities such as polyps and hyperplasia, but did not exclude them. Low cut-off levels for endometrial thickness did not increase the diagnostic performance in cases with normal sonograms.

Adult↗

Correlation between N-acetylaspartate levels and histopathologic changes in cortical infarcts of mice after middle cerebral artery occlusion.

The aim of the present study was to evaluate the use of the endogenous neuronal compound N-acetylaspartate (NAA) as a marker of neuronal damage after focal cerebral ischemia in mice. After occlusion of the middle cerebral artery (MCAO) the ischemic cortex was sampled, guided by 2,3,5-triphenyltetrazolium chloride (TTC) staining, and the NAA concentration was measured by high-pressure liquid chromatography (HPLC). Conventional histology and immunohistological methods using antibodies against neuron-specific enolase (NSE), neurofilaments (NF), synaptophysin, glial fibrillary acidic protein (GFAP), and carbodiamide-linked NAA and N-acetylaspartylglutamate (NAAG). The level of NAA rapidly declined to 50% and 20% of control levels in infarcted tissue after 6 hours and 24 hours, respectively. No further decrease was observed during the observation period of 1 week. Within the first 6 hours the number of normal-appearing neurons in the infarcted cortical tissue decreased to 70% of control, of which the majority were eosinophilic. After 24 hours almost no normal-appearing neurons were seen. The number of eosinophilic neurons decreased steadily to virtually zero after 7 days. The number of immunopositive cells in the NSE, NF, and synaptophysin staining within the infarct was progressively reduced, and after 3 to 7 days the immunoreactions were confined to discrete granulomatous structures in the center of the infarct, which otherwise was infested with macrophages. This granulomatous material also stained positive for NAA. The number of cells with positive GFAP immunoreactions progressively increased in the circumference of the infarct. They also showed increased immunoreaction against NAA and NSE. The study shows that the level of NAA 7 days after ischemia does not decline to zero but remains at 10% to 20% of control values. The fact NAA is trapped in cell debris and NAA immunoreactivity is observed in the peri-infarct areas restricts its use as a marker of neuronal density.

Animals↗

Childhood medulloblastoma in Denmark 1960-1984. A population-based retrospective study.

Medulloblastoma is a common paediatric brain tumour, located in the cerebellum and in the IV ventricle, surpassed in frequency only by astrocytomas. 180 children below the age of 15 with a medulloblastoma of the posterior fossa were treated in Denmark in the 25-year period from 1960 to 1984 and followed up until the end of 1996, or until death. During the 25 years they accounted for 20% of all intracranial tumours in children in Denmark. All tumours were histologically verified. The mean annual incidence was 6.4x10(-6), decreasing slightly with a factor of 0.12x10(-6) per year. The male/female ratio was 2.1 - twice that of the background population of children (1.05). The 5-year survival rate following diagnosis, surgery and radiotherapy was 23%, and the 25-year survival rate was 16%. The 5-year survival rate was 8% in the first 5-year period of 1960-1964, increasing to 36% in the last period 1980-1984. Presumably the increase in survival depends on many factors, e.g. improved diagnostic methods and neuroanaesthesia, better operative technique (microscope), improvements in radiotherapy and the introduction of chemotherapy. The best predictive factors of a good prognosis were preoperative CSF shunting, radical tumour removal and complete radiotherapy, i.e. irradiation of the brain, tumour bed and spinal cord. The survival rate in the last five-year period was seven times higher than the survival rate found in a comparable Danish study from the years 1935-1959. Most of the children followed Collins law of risk index. The results of treatment in children with medulloblastoma remain unsatisfactory. Accordingly, participation in international prospective studies of multimodal treatment should be encouraged, possibly using chemotherapy prior to surgery.

Adolescent↗

Astroglia contain a specific transport mechanism for N-acetyl-L-aspartate.

N-Acetylaspartate (NAA) is the second most abundant amino acid in the adult brain. It is located and synthesized in neurons and probably degraded in the glia compartment, but the transport mechanisms are unknown. Rat primary neuron and astrocyte cell cultures were exposed to the L isomer of [3H]NAA and demonstrated concentration-dependent uptake of [3H]NAA with a Km approximately 80 microM. However, Vmax was 23+/-6.4 pmol/mg of protein/min in astrocytes but only 1.13+/-0.4 pmol/mg of protein/min in neurons. The fact that neuron cultures contain 3-5% astrocytes suggests that the uptake mechanism is expressed only in glial cells. The astrocyte uptake was temperature and sodium chloride dependent and specific for L-NAA. The affinity for structural analogues was (IC50 in mM) as follows: L-NAA (0.12) > N-acetylaspartylglutamate (0.4) > N-acetylglutamate (0.42) > L-aspartate (>1) > L-glutamate (>1) > or = DL-threo-beta-hydroxyaspartate > N-acetyl-L-histidine. The naturally occurring amino acids showed no inhibitory effect at 1 mM. The glutamate transport blocker trans-pyrrolidine-2,4-dicarboxylate exhibited an IC50 of 0.57 mM, whereas another specific glutamate transport inhibitor, DL-threo-beta-hydroxyaspartate, had an IC50 of >1 mM. The experiments suggest that NAA transport in brain parenchyma occurs by a novel type of sodium-dependent carrier that is present only in glial cells.

Animals↗

N-Acetylaspartate distribution in rat brain striatum during acute brain ischemia.

Brain N-acetylaspartate (NAA) can be quantified by in vivo proton magnetic resonance spectroscopy (1H-MRS) and is used in clinical settings as a marker of neuronal density. It is, however, uncertain whether the change in brain NAA content in acute stroke is reliably measured by 1H-MRS and how NAA is distributed within the ischemic area. Rats were exposed to middle cerebral artery occlusion. Preischemic values of [NAA] in striatum were 11 mmol/L by 1H-MRS and 8 mmol/kg by HPLC. The methods showed a comparable reduction during the 8 hours of ischemia. The interstitial level of [NAA] ([NAA]e) was determined by microdialysis using [3H]NAA to assess in vivo recovery. After induction of ischemia, [NAA]e increased linearly from 70 micromol/L to a peak level of 2 mmol/L after 2 to 3 hours before declining to 0.7 mmol/L at 7 hours. For comparison, [NAA]e was measured in striatum during global ischemia, revealing that [NAA]e increased linearly to 4 mmol/L after 3 hours and this level was maintained for the next 4 h. From the change in in vivo recovery of the interstitial space volume marker [14C]mannitol, the relative amount of NAA distributed in the interstitial space was calculated to be 0.2% of the total brain NAA during normal conditions and only 2 to 6% during ischemia. It was concluded that the majority of brain NAA is intracellularly located during ischemia despite large increases of interstitial [NAA]. Thus, MR quantification of NAA during acute ischemia reflects primarily changes in intracellular levels of NAA.

Acute Disease↗

A simple one-stop menstrual problem clinic with use of hysterosonography for the diagnosis of abnormal uterine bleeding.

BACKGROUND: The purpose of the present study was to evaluate a one-stop outpatient bleeding disorder clinic in a Scandinavian population. METHODS: One hundred and fourteen women under the age of 60 years referred to the clinic for bleeding disorders. The consultation included pelvic ultrasound, hysterosonography and, when indicated, endometrial sampling. RESULTS: In 93% of the patients a sufficient diagnosis of the uterine cavity was attained at a one-stop visit. Eighty-six percent of the patients were investigated according to the one-stop program, and in 73% of the patients a treatment plan could be formulated during the consultation. Twenty-one percent had selective resection of intracavitary abnormalities. In 3% no intracavitary abnormality was found at hysteroscopy, even though hysterosonography had indicated this. CONCLUSIONS: Most patients under the age of 60 with bleeding disorders can be investigated by a one-stop out-patient procedure with the use of hysterosonography and endometrial sampling. Diagnostic or operative hysteroscopy was needed in cases of insufficient hysterosonography and suspicion of intracavitary abnormalities. This procedure can assist in determining the therapeutic approach and can often lessen the extent of surgical intervention or obviate it altogether.

Adult↗

Clinical and autopsy findings in spinal cord compression due to metastatic disease.

Clinical and autopsy findings are described in 14 patients who had suffered from spinal cord compression due to metastatic disease. All patients were clinically examined at the time of diagnosis of spinal cord compression, and followed until death. Autopsy studies of the cord revealed microscopic tumors similar to the primary tumor in seven cases. There were white matter lesions varying from slight to severe loss of myelin in seven cases. A correlation between the myelin damage and the patients ambulation just before death was found. Copyright 1998 Lippincott Williams & Wilkins

Journal Article↗

Lung morphometry by unbiased methods in emphysema: bronchial and blood vessel volume, alveolar surface area and capillary length.

We have estimated lung volume, bronchial volume, vessel volume, alveolar surface area and capillary length in patients who died of lung failure due to emphysema and chronic obstructive pulmonary disease (COPD) and in patients with no clinical signs of respiratory disease. Unbiased morphometric methods were applied to the right lung. The patients with emphysema had equal lung volumes and bronchial and vessel volumes compared to the control group. The alveolar surface area and surface density were significantly decreased to about 67%, of control values. The capillary length and length density were significantly decreased to about 68% of control values. The proportional decreases in alveolar surface area and capillary length suggest that compensatory capillary proliferation has not occurred. These unbiased morphometric studies of emphysema have yielded results in end-stage emphysema that are comparable to those previously reported using biased methods. However, the unbiased methods may provide new insights when applied to earlier stages of the disease.

Aged↗