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Biomedical subjects

L Andersson

Publications and source records attributed to L Andersson.

At least 55 records · Page 3Linked to original sources

Effect of CO(2) pneumoperitoneum on ventilation-perfusion relationships during laparoscopic cholecystectomy.

BACKGROUND: Previous studies have shown that pneumoperitoneum transiently reduces venous admixture as assessed by a calculation based on the shunt formula, and increases arterial oxygen tension (PaO(2)) in patients without heart or lung disease. The aim of the present study was to further explore the relationship between ventilation-perfusion (V(A)/Q) before and during pneumoperitoneum by using the multiple inert gas technique. METHODS: Nine patients without heart or lung disease (ASA I), with a mean age of 42 years, scheduled for laparoscopic cholecystectomy were included. After premedication and induction of anaesthesia, radial artery and pulmonary artery catheters were introduced percutaneously. The V(A)Q relationships were evaluated by the multiple inert gas elimination technique before and during pneumoperitoneum to obtain a direct measure of the pulmonary shunt. RESULTS: Induction of pneumoperitoneum decreased the pulmonary shunt from 5.8 (4.5) to 4.1 (3.2)% (P<0.05) and increased PaO(2) from 21.7 (5.9) to 24.7 (4.8) kPa (P<0.01). During surgery, the shunt increased from 3.2 (2.8) to 5.2 (3.4)% to the same level as before pneumoperitoneum induction. No area with low V(A)Q was seen. Dead space ventilation amounted to 20.0 (1.2)% in the supine position and did not change during the investigation. CONCLUSIONS: In patients without heart or lung disease, pneumoperitoneum at an intra-abdominal pressure level of 11-13 mmHg causes a transient reduction of the pulmonary shunt. The mechanisms underlying the present finding remain to be elucidated.

Adult↗

Approaches to interval mapping of QTL in a multigeneration pedigree: the example of porcine chromosome 4.

Quantitative trait loci (QTLs) have been mapped in many studies of F2 populations derived from crosses between diverse lines. One approach to confirming these effects and improving the mapping resolution is genetic chromosome dissection through a backcrossing programme. Analysis by interval mapping of the data generated is likely to provide additional power and resolution compared with treating data marker by marker. However, interval mapping approaches for such a programme are not well developed, especially where the founder lines were outbred. We explore alternative approaches to analysis using, as an example, data from chromosome 4 in an intercross between wild boar and Large White pigs where QTLs have been previously identified. A least squares interval mapping procedure was used to study growth rate and carcass traits in a subsequent second backcross generation (BC2). This procedure requires the probability of inheriting a wild boar allele for each BC2 animal for locations throughout the chromosome. Two methods for obtaining these probabilities were compared: stochastic or deterministic. The two methods gave similar probabilities for inheriting wild boar alleles and, hence, gave very similar results from the QTL analysis. The deterministic approach has the advantage of being much faster to run but requires specialized software. A QTL for fatness and for growth were confirmed and, in addition, a QTL for piglet growth from weaning at 5 weeks up to 7 weeks of age and another for carcass length were detected.

Alleles↗

Melanocortin-4 receptor (MC4R) genotypes have no major effect on fatness in a Large White x Wild Boar intercross.

The melanocortin-4 receptor (MC4R), a G-protein coupled receptor, is implicated in mediating the effect of leptin on food intake and energy balance. A previous candidate gene study reported an association between an MC4R missense mutation (Asp298Asn) and fatness, growth and feed intake in pigs. To assess this association further, we analysed the segregation of this missense mutation in relation to variation in fatness traits using a Wild Boar x Large White intercross. The Wild Boar and Large White founders were homozygous for different MC4R alleles. The MC4R was assigned to the expected region on pig chromosome 1. The statistical evaluation did not reveal any indication of a significant effect on fatness related traits in this pedigree.

Animals↗

Unexpectedly high allelic diversity at the KIT locus causing dominant white color in the domestic pig.

Mutations in KIT encoding the mast/stem cell growth factor receptor (MGF) are responsible for coat color variation in domestic pigs. The dominant white phenotype is caused by two mutations, a gene duplication and a splice mutation in one of the copies leading to skipping of exon 17. Here we applied minisequencing and pyrosequencing for quantitative analysis of the number of copies with the splice form. An unexpectedly high genetic diversity was revealed in white pigs. We found four different KIT alleles in a small sample of eight Large White females used as founder animals in a wild boar intercross. A similar number of KIT alleles was found in commercial populations of white Landrace and Large White pigs. We provide evidence for at least two new KIT alleles in pigs, both with a triplication of the gene. The results imply that KIT alleles with the duplication are genetically unstable and new alleles are most likely generated by unequal crossing over. This study provides an improved method for genotyping the complicated Dominant white/KIT locus in pigs. The results also suggest that some alleles may be associated with negative pleiotropic effects on other traits.

Alleles↗

Canine leucocyte adhesion deficiency in Irish red and white setters.

Seventy-six Irish red and white setter samples were tested for the recently documented CD18 point mutation which manifests as canine leucocyte adhesion deficiency (CLAD) in Irish setters. Six carrier dogs were identified, all originating from a lineage within which sporadic deaths from symptoms consistent with CLAD had been observed. This is the first demonstration that the CLAD mutation exists outside the Irish setter population, confirming that the mutation is present in a significant minority of Irish red and white setters. Routine testing by breeders to identify carrier animals will enable the eradication of CLAD from the Irish red and white setter population.

Animals↗

Phase II study assessing the effectiveness of Biafine cream as a prophylactic agent for radiation-induced acute skin toxicity to the breast in women undergoing radiotherapy with concomitant CMF chemotherapy.

PURPOSE: To assess the efficacy of Biafine cream in preventing Grade 2 acute radiation dermatitis, according to the National Cancer Institute of Canada skin radiation toxicity criteria in patients undergoing concomitant adjuvant chemotherapy and radiotherapy to the breast. METHODS AND MATERIALS: Sixty patients participated in this study. Patients were treated with a lumpectomy followed by concomitant chemotherapy and radiotherapy to the breast. Biafine cream was applied daily, starting on the first day and ending 2 weeks post-radiotherapy. Patients underwent weekly skin assessments throughout radiotherapy and at 2 and 4 weeks after treatment. Outcome measures were assessed using a Skin Assessment Questionnaire that was scored according to the National Cancer Institute of Canada skin radiation toxicity criteria and a self-administered questionnaire that evaluated skin symptoms. RESULTS: The maximum skin toxicity observed during the course of treatment was as follows: less than Grade 2 toxicity, 15% (9 patients); Grade 2, 83% (50 patients); Grade 3, 2% (1 patient); Grade 4, 0% (0 patients). The majority of the radiation dermatitis was observed after 3 weeks of radiotherapy. CONCLUSION: The majority of patients who underwent concomitant chemo- and radiotherapy for breast cancer developed Grade 2 radiation dermatitis with the use of Biafine cream. However, no treatment delays or interruptions were observed because of skin toxicity.

Adult↗

Direct observation of localized parallel electric fields in a space plasma.

We report direct measurements of parallel electric fields related to particle acceleration in a collisionless space plasma. The electric field is that of a monotonic potential ramp localized to approximately 10 debye lengths along the magnetic field. Electrons accelerated by the parallel electric field are accompanied by intense electrostatic waves and nonlinear structures interpreted as electron phase-space holes.

Journal Article↗

Comparative analysis of a BAC contig of the porcine RN region and the human transcript map: implications for the cloning of trait loci.

The poorly developed transcript maps and the limited resources for genome analysis hamper positional cloning of trait loci in farm animals. This study demonstrates that this will now be easier by the combined use of BAC contigs and the import of the near complete human transcript map. The conclusion was obtained by a comparative analysis of a 2.4-Mb BAC contig of the RN region in pigs. The contig was constructed as part of a successful positional cloning project, which identified PRKAG3 as the causative gene for the RN phenotype. A comparative map including the corresponding regions on human chromosome 2q35 and mouse chromosome 1 (region 36-44 cM) is reported. Sixteen coding sequences were mapped on the BAC contig. The majority of these were identified by BLAST searches of BAC end sequences and BAC shotgun sequences generated during the positional cloning project. Map data for the orthologues in humans were available for 12 of the 16 coding sequences, and all 12 have been assigned to 2q35. Furthermore, no evidence for any rearrangement in gene order was obtained. The extensive linkage conservation indicates that the near complete human transcript map will be an invaluable resource for positional cloning projects in pigs and other domestic animals.

Animals↗

Flow cytometric analysis of apoptotic subpopulations with a combination of annexin V-FITC, propidium iodide, and SYTO 17.

BACKGROUND: We have previously characterized apoptotic cell death induced in a follicular lymphoma cell line, HF-1, after triggering via the B-cell receptor (BCR) or treatment with Ca(2+) Ionophore A23187. We analyzed the kinetics of apoptosis induced by these two treatments, as two alternative models of classical apoptosis, by flow cytometry using a novel combination of cytofluorometric stains. METHODS: Cells were stained with a combination of Annexin V-FITC, propidium iodide (PI), and SYTO 17 and analyzed by a two-laser flow cytometry system using 488-nm argon and 633-nm HeNe air-cooled lasers. RESULTS: In both apoptotic models, the first apoptotic cells were detected by SYTO 17 staining. The alteration in SYTO 17 staining intensity was followed by an increased uptake of PI. Finally, the apoptotic cells were labeled with Annexin V in BCR-induced apoptosis. On the contrary, on treatment with Ca(2+) Ionophore A23187, cells became positive for Annexin V earlier than for PI. CONCLUSIONS: The novel cytofluorometric dye, SYTO 17, discriminates apoptotic alterations before Annexin V and PI. PI also discriminates apoptotic alterations before the loss of plasma membrane asymmetry by BCR but not by Ca(2+) Ionophore A23187-induced apoptosis. Finally, the combination of these three cytofluorometric dyes allows effective detection of apoptotic subpopulations and ordering of apoptotic events by flow cytometry.

Annexin A5↗

A phylogenetic study of the origin of the domestic pig estimated from the near-complete mtDNA genome.

The near-complete pig mtDNA genome sequence (15,997 bp) was determined from two domestic pigs (one Chinese Meishan and one Swedish Landrace) and two European wild boars. The sequences were analyzed together with a previously published sequence representing a Swedish domestic pig. The sequences formed three distinct clades, denoted A, E1, and E2, with considerable sequence divergence between them (0.8-1.2%). The results confirm our previous study (based on the sequence of the cytochrome B gene and the control region only) and provide compelling evidence that domestication of pigs must have occurred from both an Asian and a European subspecies of the wild boar. We estimated the time since the divergence of clade A (found in Chinese Meishan pigs) and E1 (found in European domestic pigs) at about 900,000 years before present, long before domestication about 9,000 years ago. The pattern of nucleotide substitutions among the sequences was in good agreement with previous interspecific comparisons of mammalian mtDNA; the lowest substitution rates were observed at nonsynonymous sites in protein-coding genes, in the tRNA and rRNA genes, while the highest rates were observed at synonymous sites and in the control region. The presence of Asian clade A in some major European breeds (Large White and Landrace) most likely reflects the documented introgression of Asian germplasm into European stocks during the 18th and 19th centuries. The coexistence of such divergent mtDNA haplotypes for 100+ generations is expected to lead to the presence of recombinant haplotypes if paternal transmission and recombination occur at a low frequency. We found no evidence of such recombination events in the limited sample studied so far.

Amino Acid Sequence↗

Construction of a high-resolution RH map of the human 2q35 region on TNG panel and comparison with a physical map of the porcine homologous region 15q25.

This article describes the construction of a high-resolution radiation hybrid map of Hsap 2q35 by using the TNG RH panel generated by irradiation with 50,000 rads. We were able to build a framework map of 1300 cR(50,000) including 34 markers ordered with odds higher than 1000:1. The comprehensive map includes 77 loci and describes a region of 3 Mb around the SLC11A1 gene. Because of the very small size of the fragments retained and a reduced retention frequency, it was difficult to build a high-resolution multi-point map of this region by using the TNG RH panel. Nevertheless, this study confirmed the very high potential of this RH panel for constructing a human, high-resolution physical map (2.3 kb/cR(50,000)). Moreover, human ESTs from Hsap 2q35 were hybridized with porcine BAC contigs to establish a porcine transcript map of the homologous region Sscr 15q25 (greater than 2.5 Mb). We identified 17 new genes in this porcine chromosomal region. We were able to compare the location of 26 genes mapped in both species. The gene order was similar except for two possible minor discrepancies in the Desmin sub-region, suggesting the existence of a porcine micro-region between TNP1 and IL8RB with an unknown origin.

Animals↗

Prospective patient-based assessment of effectiveness of palliative radiotherapy for bone metastases.

PURPOSE: The primary objective of this report is to prospectively evaluate pain control provided by palliative radiotherapy for all irradiated patients with bone metastases by using their own assessments. MATERIALS AND METHODS: A prospective database was set up for all patients referred for palliative radiotherapy for bone metastases. Patients were asked to rate their pain intensity using an 11 categorical point scale (0=lack of pain, 10=worst pain imaginable). Analgesic consumption during the preceding 24 h was recorded and converted into equivalent total daily dose of oral morphine. For those who received radiotherapy, follow-up was conducted via telephone interviews at week 1, 2, 4, 8 and 12 post treatment using the same pain scale and analgesic diary. Radiotherapy outcome was initially assessed by pain score alone. Complete response (CR) was defined as a pain score of 0. Partial response (PR) was defined as a reduction of score > or =2 or a> or =50% reduction of the pre-treatment pain score. We further analyzed outcomes using integrated pain and analgesic scores. Response was defined as either a reduction of pain score > or =2 with at least no increase in analgesics or at least stable pain score with a > or =50% reduction in analgesic intake. RESULTS: One hundred and five patients were treated with palliative radiotherapy. When response evaluation was by pain score alone, the PR rates at 2, 4, 8 and 12 weeks were 44, 42, 30 and 38%, respectively; while the CR rates were 24, 32, 31 and 29%, respectively. The overall response rate at 12 weeks was 67%. When assessed by the integrated pain and analgesic scores, the response rates were 50, 46, 43 and 43%, respectively. CONCLUSION: The response rate in our patient population is comparable with those reported in clinical trials. This is important when counselling our patients on the expected effectiveness of radiotherapy outside of clinical trials. Our observations confirm the generalizability of the trials conducted to date. While randomized trials still remain the gold standard of research, observational studies can serve as useful adjuncts to randomized trials to confirm the efficacy and guide the design of new controlled trials.

Adult↗

Use of the CAGE questionnaire for screening problem drinking in an out-patient palliative radiotherapy clinic.

To determine the positive rate of the CAGE questionnaire in an outpatient palliative radiotherapy clinic and to examine the association between problem drinking, pain control, and analgesic consumption, patients referred for palliative radiotherapy were screened with the CAGE questionnaire and asked to rate their symptom distress using the modified Edmonton Symptom Assessment System (ESAS). The latter instrument uses 11-point numeric scales (0 = best, 10 = worst). Their daily analgesic consumption in oral morphine equivalent was recorded. A total of 128 patients participated in the study. Only 9 patients answered one of the four CAGE questions affirmatively (positive group). All the rest answered negatively (negative group). The mean pain intensity at index site/overall pain was 4.97 +/- 3.31/3.27 +/- 2.76 for the negative group and 6.29 +/- 4.42/2.89 +/- 3.37 for the positive group. The mean total daily oral morphine equivalent for the negative and positive group were 112.35 +/- 233.58 mg and 36.82 +/- 58.85 mg, respectively. There was no significant difference found in other symptoms in the modified ESAS between these two groups. The positive rate of the CAGE in patients with advanced cancer attending an out-patient radiotherapy clinic was only 7%, and analyses were limited by the small sample size of those with a positive CAGE. Whether our observed low positive rate of CAGE represents the true prevalence of problem drinking or the CAGE questionnaire is an insensitive tool for screening problem drinking in an outpatient palliative radiotherapy clinic requires further investigation. We did not find a statistically significant worse pain intensity nor higher analgesic consumption in patients who screened positive for CAGE questionnaire.

Adult↗

Prospective assessment of symptom palliation for patients attending a rapid response radiotherapy program. feasibility of telephone follow-up.

Clinical trials generally include motivated patients with relatively good performance status. This can result in an overestimation of the effectiveness of an intervention. Clinic follow-up protocols for outcome assessment after palliative treatments suffer from high attrition rates. In this study, the feasibility of telephone follow-up for the assessment of symptom palliation in patients receiving outpatient palliative radiotherapy as a tool to evaluate outcome was examined. Patients referred for palliative radiotherapy were asked to rate their symptom distress using the modified Edmonton Symptom Assessment System (ESAS) at initial consultation. Patient demographics and analgesic consumption were collected. For those who received radiotherapy, follow-up was conducted through telephone interviews at week 1, 2, 4, 8, and 12 post-treatment using the same modified ESAS and analgesic diary. One hundred ninety patients received radiotherapy to 256 sites from January to August 1999. Seventy-eight patients (41%) died during the 12-week follow-up period. The percentage of surviving patients responding to the telephone interview ranged from 63% to 68% during the 12-week study. Telephone follow-up is a feasible tool for the prospective outcome assessment of symptom palliation in this population. It compares well to clinic visits or mailed questionnaires. However, to improve the follow-up rates, other modalities may also need to be implemented.

Adult↗

Genetic dissection of phenotypic diversity in farm animals.

Farm animal populations harbour rich collections of mutations with phenotypic effects that have been purposefully enriched by breeding. Most of these mutations do not have pathological phenotypic consequences, in contrast to the collections of deleterious mutations in model organisms or those causing inherited disorders in humans. Farm animals are of particular interest for identifying genes that control growth, energy metabolism, development, appetite, reproduction and behaviour, as well as other traits that have been manipulated by breeding. Genome research in farm animals will add to our basic understanding of the genetic control of these traits and the results will be applied in breeding programmes to reduce the incidence of disease and to improve product quality and production efficiency.

Animals↗

Comparison of starch branching enzyme I and II from potato.

The in vitro activities of purified potato starch branching enzyme (SBE) I and II expressed in Escherichia coli were compared using several assay methods. With the starch-iodine method, it was found that SBE I was more active than SBE II on an amylose substrate, whereas SBE II was more active than SBE I on an amylopectin substrate. Both enzymes were stimulated by the presence of phosphate. On a substrate consisting of linear dextrins (chain length 8-200 glucose residues), no significant net increase in molecular mass was seen on gel-permeation chromatography after incubation with the enzymes. This indicates intrachain branching of the substrate. After debranching of the products, the majority of dextrins with a degree of polymerization (dp) greater than 60 were absent for SBE I and those with a dp greater than 70 for SBE II. To study the shorter chains, the debranched samples were also analysed by high-performance anion-exchange chromatography. The products of SBE I showed distinct populations at dp 11-12 and dp 29-30, whereas SBE II products had one, broader, population with a peak at dp 13-14. An accumulation of dp 6-7 chains was seen with both isoforms.

1,4-alpha-Glucan Branching Enzyme↗

Patients with advanced cancer: a survey of the understanding of their illness and expectations from palliative radiotherapy for symptomatic metastases.

We conducted a pilot study to examine patients' understanding of their illness and their expectations for palliative radiotherapy for symptomatic metastases. Participants were asked to complete a survey consisting of seven questions prior to the initial consultation. Demographic details and information on extent of disease were collected. Patients were asked to score their symptom distress using the modified Edmonton Symptom Assessment System. Sixty patients participated in the pilot study between January and April 1999. Their median age was 68 years (range 46-90). The most common primary tumours were lung, prostate and breast. Twenty-one patients (35%) believed that their cancer was curable. Twelve (20%) expected that palliative radiotherapy would cure their advanced cancer and 23 (38%) believed that palliative radiotherapy would prolong their lives. Twenty-one patients (35%) had concerns about the effectiveness of radiation therapy and twenty (33%) had concerns about the side-effects of radiotherapy. Fifty-two (87%) were not familiar with the concept of radiation treatment. Forty-seven patients (78%) reported that they were not given information about the radiation treatment; 51 (85%) were not satisfied with the information that their own doctors had provided regarding radiation treatment prior to the consultation at our clinic. A significant proportion of the patients in this pilot study had misconceptions regarding their illness and unrealistic expectations from palliative radiotherapy. We plan to provide educational pamphlets for use in referring doctors' surgeries and clinics in order to inform patients of the nature, rationale and anticipated benefits and side-effects of palliative radiotherapy.

Aged↗