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Biomedical subjects

L Søndergaard

Publications and source records attributed to L Søndergaard.

At least 19 recordsLinked to original sources

Mental illness in new neurological patients.

OBJECTIVE: To determine the prevalence of psychiatric disorders in new neurological inpatients and outpatients, and examine whether they are recognised, treated, or referred to psychiatric consultation. METHODS: 198 consecutive patients referred for the first time to a neurologist were studied using a two phase design. ICD-10 psychiatric diagnoses were established by means of the SCAN (Schedules for Clinical Assessment in Neuropsychiatry). RESULTS: The overall prevalence of current mental disorders was 55.1% (95% CI: 46.2 to 63.8), and 65.0% (95% CI: 56.1 to 73.0) had at least once in their life had a psychiatric disorder. The most frequent current diagnoses were somatoform disorders (33.8%, (95% CI: 25.9 to 42.7%)), followed by phobias (21.8%; 95% CI: 15.3 to 30.0), substance use disorders (13.3%; 95% CI: 8.3 to 20.6) and depression/dysthymia (14.4; 95% CI: 9.1 to 21.8). The psychiatric morbidity markedly declined with increasing age. Compared with 63.5% of the women, 46.4% of the men had a psychiatric disorder. Substance use disorders were more frequent in men than women (p=0.002). Patients with a psychiatric disorder were more frequently seen in the outpatients' clinic than those without. The neurologists detected 14%-40% of the cases, 16.9% were in treatment, and only 4.6% were referred to mental health care. CONCLUSION: Psychiatric disorders, in particular somatoform disorders, are extremely common in neurological patients, especially in young and middle aged patients, outpatients, and women. The results call for more research on mental illness' impact on care and outcome in neurological patients.

Ambulatory Care↗

[Primary cardiac lymphoma].

Primary cardiac non-Hodgkin lymphoma is very rare. Results recently published suggest that the prognosis is good, if the lymphoma is diagnosed early. The symptoms are nevertheless unspecific and a clinical investigation is often inconclusive. We report a case of a woman with symptoms of severe dyspnoea at rest, chest pain, and fatigue. The ECG showed a complete atrioventricular block. Magnetic resonance imaging (MRI) revealed a tumour in the right atrium and ventricle. A myocardial biopsy showed malignant non-Hodgkin lymphoma of the diffuse, large cell B-type. The patient was treated with chemotherapy and control MRI after four treatments showed complete regression of the tumour.

Antineoplastic Agents↗

Mental disorders among internal medical inpatients: prevalence, detection, and treatment status.

OBJECTIVE: To determine the prevalence of ICD-10 mental disorders among internal medical inpatients, the relation between mental disorder, age, and gender, and the recognition and referral of the disordered patients. METHOD: 294 consecutive medical inpatients were examined with a two-phase design using the SCAN (Schedules for Clinical Assessment in Neuropsychiatry) for ICD-10 psychiatric diagnoses. Information from questionnaires and interviews with patients, doctors, nurses, and from medical records. RESULTS: The prevalence of current mental disorders was 38.7%, being heavily increased in young patients. Main diagnoses were somatoform disorders (17.6%), phobias (12.9%), substance use disorders (10.9%), and depression (8.3%). Psychiatric consultations were very few. About 38-56% of the cases were recognized by medical doctors and nurses, and only about 20% were in mental health treatment. CONCLUSION: The prevalence of mental disorders among internal medical inpatients is high and increased in young patients and women. Detection and referral are low, and few are treated.

Adult↗

Molecular cloning and genomic organization of a novel receptor from Drosophila melanogaster structurally related to mammalian galanin receptors.

We screened the Berkeley "Drosophila Genome Project" database with "electronic probes" corresponding to conserved amino acid sequences from the five known rat somatostatin receptors. This yielded alignment with a Drosophila genomic clone that contained a DNA sequence coding for a protein, having amino acid sequence identities with the rat galanin receptors. Using PCR with Drosophila cDNA as a template, and oligonucleotide probes coding for the exons of the presumed Drosophila gene, we were able to clone the cDNA for this receptor. The Drosophila receptor has most amino acid sequence identity with the three mammalian galanin receptors (37% identity with the rat galanin receptor type-1, 32% identity with type-2, and 29% identity with type-3). Less sequence identity exists with the mammalian opioid/nociceptin-orphanin FQ receptors (26% identity with the rat micro opioid receptor), and mammalian somatostatin receptors (25% identity with the rat somatostatin receptor type-2). The novel Drosophila receptor gene contains ten introns and eleven exons and is located at the distal end of the X chromosome.

Amino Acid Sequence↗

Functional expression of a multisubstrate deoxyribonucleoside kinase from Drosophila melanogaster and its C-terminal deletion mutants.

The occurrence of a deoxyribonucleoside kinase in Drosophila melanogaster (Dm-dNK) with remarkably broad substrate specificity has recently been indicated (Munch-Petersen, B., Piskur, J., and Søndergaard, L. (1998) J. Biol. Chem. 273, 3926-3931). To prove that the capacity to phosphorylate all four deoxyribonucleosides is in fact associated to one polypeptide chain, partially sequenced cDNA clones, originating from the Berkeley Drosophila genome sequencing project, were searched for homology with human deoxyribonucleoside kinases. The total sequence of one cDNA clone and the corresponding genomic DNA was determined and expressed in Escherichia coli as a glutathione S-transferase fusion protein. The purified and thrombin cleaved recombinant protein phosphorylated the four deoxyribonucleosides with high turnover and K(m) values similar to those of the native Dm-dNK, as well as the four ribonucleosides and many therapeutical nucleoside analogs. Dm-dNK has apparently the same origin as the mammalian kinases, thymidine kinase 2, deoxycytidine kinase, deoxyguanosine kinase, and the herpes viral thymidine kinases, but it has a unique C terminus that seems to be important for catalytic activity and specificity. The C-terminal 20 amino acids were dispensable for phosphorylation of deoxyribonucleosides but necessary for full activity with purine ribonucleosides. Removal of the C-terminal 20 amino acids increased the specific activity 2-fold, but 99% of the activity was lost after removal of the C-terminal 30 amino acids.

Amino Acids↗

Vasodilatation with felodipine in chronic asymptomatic aortic regurgitation.

BACKGROUND: Afterload reduction decreases volume overload on the left ventricle and may thereby delay the need for valve replacement in chronic asymptomatic aortic regurgitation. The aims of this randomized double-blind, placebo-controlled trial were to examine short- and long-term hemodynamic effects of felodipine in chronic asymptomatic aortic regurgitation. METHODS: Sixteen patients were randomly assigned to an intravenous infusion of either felodipine 0. 3 mg or placebo followed by 3 months' treatment with felodipine 10 mg or placebo orally once daily. Magnetic resonance imaging was performed at baseline, immediately after intravenous treatment, and after 3 months of oral treatment. RESULTS: Intravenous felodipine caused a statistically significant reduction in the systemic vascular resistance from (mean +/- SD) 1160 +/- 400 to 970 +/- 320 dynes. s. cm(-5) (P <.05), in the regurgitant volume index from 1.5 +/- 0.8 to 1.3 +/- 0.8 L. min(-1). m(-2) (P <.05), and in the regurgitant fraction from 0.31 +/- 0.15 to 0.26 +/- 0.14 (P <.05). The forward cardiac output index increased significantly from 3.2 +/- 0.9 to 3.5 +/- 0.7 L. min(-1). m(-2) (P <.05). Three months of oral treatment with felodipine caused a corresponding but more pronounced decrease in systemic vascular resistance of 880 +/- 330 dynes. s. cm(-5) (P <.05), regurgitant volume index of 1.2 +/- 0.7 L. min(-1). m(-2) (P <.05), and regurgitant fraction 0.25 +/- 0.11 (P <.05), whereas the forward cardiac output index increased to 3.6 +/- 0.7 L. min(-1). m(-2) (P <.05). No significant changes were found in the placebo group. Left ventricular volumes and ejection fraction remained unaffected by treatment, but compared with the placebo group left ventricular myocardial mass decreased significantly from 137 +/- 24 to 132 +/- 21 g. m(-2) (P <.01). CONCLUSION: In chronic asymptomatic aortic regurgitation, felodipine causes beneficial hemodynamic effects that may postpone the need for valve replacement.

Adult↗

Molecular cloning, genomic organization, developmental regulation, and a knock-out mutant of a novel leu-rich repeats-containing G protein-coupled receptor (DLGR-2) from Drosophila melanogaster.

After screening the Berkeley Drosophila Genome Project database with sequences from a recently characterized Leu-rich repeats-containing G protein-coupled receptor (LGR) from Drosophila (DLGR-1), we identified a second gene for a different LGR (DLGR-2) and cloned its cDNA. DLGR-2 is 1360 amino acid residues long and shows a striking structural homology with members of the glycoprotein hormone [thyroid-stimulating hormone (TSH); follicle-stimulating hormone (FSH); luteinizing hormone/choriogonadotropin (LH/CG)] receptor family from mammals and with two additional, recently identified mammalian orphan LGRs (LGR-4 and LGR-5). This homology includes the seven transmembrane region (e.g., 49% amino acid identity with the human TSH receptor) and the very large extracellular amino terminus. This amino terminus contains 18 Leu-rich repeats-in contrast with the 3 mammalian glycoprotein hormone receptors and DLGR-1 that contain 9 Leu-rich repeats, but resembling the mammalian LGR-4 and LGR-5 that each have 17 Leu-rich repeats in their amino termini. The DLGR-2 gene is >18.6 kb pairs long and contains 15 exons and 14 introns. Four intron positions coincide with the intron positions of the three mammalian glycoprotein hormone receptors and have the same intron phasing, showing that DLGR-2 is evolutionarily related to these mammalian receptors. The DLGR-2 gene is located at position 34E-F on the left arm of the second chromosome and is expressed in embryos and pupae but not in larvae and adult flies. Homozygous knock-out mutants, where the DLGR-2 gene is interrupted by a P element insertion, die around the time of hatching. This finding, together with the expression data, strongly suggests that DLGR-2 is exclusively involved in development.

Alternative Splicing↗

Magnetic resonance imaging of valvular heart disease.

The optimum management of patients with valvular heart diseases requires accurate and reproducible assessment of the valvular lesion and its hemodynamic consequences. Magnetic resonance imaging (MRI) techniques, such as volume measurements, signal-void phenomena, and velocity mapping, can be used in an integrated approach to gain qualitative and quantitative information on valvular heart disease as well as ventricular dimensions and functions. Thus, MRI may be advantageous to the established diagnostic tools in assessing the severity of valvular heart disease as well as monitoring the lesion and predicting the optimal timing for valvular surgery. This paper reviews the validation of these MRI techniques in assessing valvular heart disease and discusses some typical pitfalls of the techniques, including suggestions for solutions.J. Magn. Reson. Imaging 1999;10:627-638.

Blood Flow Velocity↗

Molecular cloning, genomic organization and developmental regulation of a novel receptor from Drosophila melanogaster structurally related to gonadotropin-releasing hormone receptors for vertebrates.

After screening the data base of the Berkeley Drosophila Genome Project with a sequence coding for the transmembrane region of a G protein-coupled receptor, we found that Drosophila might contain a gene coding for a receptor that is structurally related to the Gonadotropin-Releasing Hormone (GnRH) receptors from vertebrates. Using the polymerase chain reaction, with Drosophila cDNA as a template, and oligonucleotide probes coding for the presumed exons of this gene, we were able to clone the cDNA coding for this receptor. The transmembrane region of the receptor shows 36% amino acid residue identity with the transmembrane region of the catfish and 31% amino acid residue identity with that of the rat GnRH receptor. The Drosophila receptor gene contains six introns, whereas the rat gene contains two: one intron in the Drosophila gene occurs at exactly the same position and has the same intron phasing as one intron in the rat gene, suggesting that the Drosophila and mammalian GnRH receptor genes are evolutionarily related. Northern blot analyses show that the Drosophila receptor gene is progressively expressed during larval development with a prominent maximum at the 3rd instar larval stage. Pupae contain low amounts of receptor mRNA, while adult flies contain higher levels, with males having about five times more receptor mRNA than females flies. Southern blot analyses show that Drosophila contains only one copy of the receptor gene, which is located at position 27A2-B1 of chromosome 2. This paper is the first report on the molecular cloning of a member of the GnRH receptor family from invertebrates.

Amino Acid Sequence↗

Capillary transfer constant of Gd-DTPA in the myocardium at rest and during vasodilation assessed by MRI.

The purpose of this study was to determine whether the capillary transfer constant (Ki) of gadolinium-DTPA was sensitive to perfusion changes and whether ischemic regions in the myocardium could be identified using the modified Kety formula. Ki was measured at rest and during dipyridamole-induced vasodilation in 10 healthy volunteers and in 10 patients with ischemic heart disease. Ki increased by a factor of 2.5+/-1.2 (mean +/- SD) from 55+/-16 ml 100 g(-1)min(-1) at rest to 136+/-46 ml 100 g(-1)min(-1) (P < 0.01) during vasodilation in the healthy subjects. In the patients, there were no changes in Ki during vasodilation in ischemic regions (50+/-18 versus 49+/-30 ml 100 g(-1)min(-1) (P > 0.4)). Ki increased in nonischemic regions by a factor of 2.0+/-0.8 from 44+/-17 to 81+/-32 ml 100 g(-1)min(-1) during vasodilation (P < 0.02). It is concluded that the capillary transfer constant is sensitive to perfusion changes and that regional ischemia can be detected with MRI. This noninvasive and quantitative method may prove useful in the evaluation of patients with ischemic heart disease.

Adult↗

Functional characterization of HLA-DRA1*0101/DRB1*0401 molecules expressed in Drosophila melanogaster cells.

We have expressed the human MHC class II molecule, HLA-DRA1*0101/-DRB1*0401 (DRB1*0401), in Drosophila melanogaster Schneider 2 cells under control of the Drosophila metallothionein promoter. Upon induction with CuSO4, flow cytometry revealed expression of DRB1*0401 on the surface of the Drosophila cells at high levels. The membrane-bound class II molecules could present peptides specifically to DRB1*0401-restricted T cells. Drosophila-expressed DRB1*0401 molecules revealed a decreased N-linked glycosylation as compared to DRB1*0401 molecules purified from a human B-cell line. The purified DRB1*0401 molecules from Drosophila cells were dissociated into subunits in SDS-PAGE but could be stabilized with a peptide known to bind DRB1*0401 with a high affinity, indicating that the recombinant class II molecules from Drosophila cells are either empty or occupied by low affinity endogenous peptides. This assumption was further substantiated by the observation that the class II molecules from Drosophila cells had a much higher peptide-binding capacity than DRB1*0401 molecules derived from the human B-cell line. Otherwise, the two species of DRB1*0401 had similar peptide-binding specificities and affinities. The purified recombinant DRB1*0401 molecules also showed biological activity because immobilized complexes of DRB1*0401 and synthetic peptides specifically stimulated DRB1*0401-restricted T cells.

Amino Acid Sequence↗

Myocardial perfusion modeling using MRI.

In the present study, it is shown that it is possible to quantify myocardial perfusion using magnetic resonance imaging in combination with gadolinium diethylenetriaminopentaacetic acid (Gd-DTPA). Previously, a simple model and method for measuring myocardial perfusion using an inversion recovery turbo-FLASH (fast low-angle shot) sequence and Gd-DTPA has been presented. Here, an extension of the model is presented taking into account fast and slow water exchange between the compartments, enabling the calculation of the unidirectional influx constant (Ki) for Gd-DTPA, the distribution volume of Gd-DTPA (lambda), the vascular blood volume (Vb), and the time delay through the coronary arteries (delta T). The model was evaluated by computer simulation and used on experimental results from seven healthy subjects. The results in the healthy volunteers for a region of interest placed in the anterior myocardial wall were (mean +/- SD) Ki = 54 +/- 10 ml/100 g/min, lambda = 30 +/- 3 ml/100 g, Vb = 9 +/- 2 ml/100 g, delta T = 3.2 +/- 1.1 s. These results are in good agreement with similar results obtained by other methods.

Adult↗

Measurement of the arterial concentration of Gd-DTPA using MRI: a step toward quantitative perfusion imaging.

A noninvasive method using an inversion recovery turbo-FLASH for dynamic measurement of the arterial input function represented by the bolus passage of Gd-DTPA in the descending aorta is presented, and the results are compared with the input function obtained by arterial blood samples. A good accordance between the two input functions was found, indicating that it is possible to measure the input function to the myocardium using MRI. A variation between the two concentration curves of 5% at upslope, 2.7% at peak point, and < 7% at downslope was found. The study also indicates that a short inversion time < 250 ms has to be used to ensure correct measurement of peak concentration.

Adult↗

MR velocity mapping measurement of renal artery blood flow in patients with impaired kidney function.

Renal blood flow (RBF) was measured in 9 patients with chronic impaired kidney function using MR velocity mapping and compared to PAH clearance and 99mTc-DTPA scintigraphy. An image plane suitable for flow measurement perpendicular to the renal arteries was chosen from 2-dimensional MR angiography. MR velocity mapping was performed in both renal arteries using an ECG-triggered gradient echo pulse sequence previously validated in normal volunteers. Effective renal plasma flow was calculated from the clearance rate of PAH during constant infusion and the split of renal function was evaluated by 99mTc-DTPA scintigraphy. A reduction of RBF was found, and there was a significant correlation between PAH clearance multiplied by 1/(1-hematocrit) and RBF determined by MR velocity mapping. Furthermore, a significant correlation between the distribution of renal function and the percent distribution of RBF was found.

Aged↗

Acute midtarsal sprains: frequency and course of recovery.

In a prospective consecutive registration of 711 ankle inversion sprains, the dorsal ligaments and capsule of the midtarsal joints were involved in 237 of the cases (33%), and in 172 cases (24%) only these joints seemed to be injured. A total of 162 isolated midtarsal injuries and 161 cases of isolated lateral talocrural lesions selected at random were followed using questionnaires 1, 3, 6, 9, and 12 months after injury. The frequencies of pain after 1 month and swelling after 1 and 3 months were significantly lower in isolated dorsal midtarsal sprains compared with isolated lateral talocrural sprains. At the following controls, frequencies of both pain and swelling were the same for both groups. Functional instability appeared with the same frequency in both groups during the 12 months of follow-up. Regarding the social impact of the sprains, absence from work and sports did not differ between groups. When avulsions were present in midtarsal injuries recovery was slow, with two thirds of the patients experiencing pain after 6 months. We conclude that the dorsal midtarsal sprain is a common entity with a course of recovery and a frequency of residual symptoms very like the lateral talocrural lesions.

Acute Disease↗

Nutritional response in a Drosophila yolk protein gene promoter.

The yolk protein genes (yps) of Drosophila melanogaster are only expressed in the ovary and fat body of female flies if they are supplied with proteinaceous food. This nutritional response is specific to the yp genes. We have used transgenic flies transformed with a series of constructs bearing deletions in the upstream region of the yp1 and yp2 genes attached to a reporter gene to search for DNA sequences responsible for the nutritional induction specific for yp1 and yp2 genes. Several regions were shown independently of each other to confer nutritional regulation on the expression of the yp1 and yp2 genes. This regulation can be induced both on the yp promoter and the heterologous Drosophila heat-shock 70 (hsp 70) promoter. The redundancy of sequences conferring a nutritional response on the yp genes is similar to that observed for the female specificity of these genes and suggest that several DNA binding proteins interact to provide the correct regulation of these genes. These results suggest that nutrition acts to modify the level of a trans-acting factor in the fat body. Northern blot analysis showed that the transcript levels from the dsx gene are not affected by nutrition, indicating that the response is not mediated via the dsx gene.

Alcohol Dehydrogenase↗

Decreased right heart blood volume determined by magnetic resonance imaging: evidence of central underfilling in cirrhosis.

Whether the central blood volume is reduced or expanded in cirrhosis is still under debate. Accordingly, the current study was undertaken to assess the volume of the heart cavities. Ten cirrhotic patients and matched controls had their right and left ventricular end-diastolic volumes (RVDV and LVDV), and end-systolic volumes (RVSV and LVSV) determined by magnetic resonance imaging (MRI). RVDV (122 vs. control 166 mL, P < .02), RVSV (41 vs. 80 mL, P < .02) and right atrial volume (47 vs. 64 mL, P < .05) were significantly reduced in the patients. In contrast, LVDV (134 vs. 129 mL, NS), LVSV (54 vs. 40 mL, NS), and left atrial volume (70 vs. 57 mL, P = .08) were normal or slightly increased. The right ejection fraction (68% vs. 53%, P < .05) was significantly increased, but the left ejection fraction was slightly reduced (61% vs. 69%, NS). The central and arterial blood volume (CBV), assessed as the cardiac output (CO) multiplied by the central circulation time, was significantly decreased (1.47 vs. 1.81 L, P < .05). The noncentral blood volume (4.43 vs. 3.64 L, P < .02), plasma volume (4.05 vs. 3.27 L, P < .02), and CO (7.11 vs. control 5.22 L/min, P < .01) were significantly increased in the patients. CCT (13.1 vs. 20.0 sec, P < .005) and the right ventricular transit time (0.79 vs. 1.35 sec, P < .005) were significantly reduced, but the left ventricular transit time was normal (0.91 vs. 0.88 sec, NS). Systemic vascular resistance was reduced (991 vs. 1,490 dyn.sec/cm5, P < .01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗