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Biomedical subjects

P A Larsson

Publications and source records attributed to P A Larsson.

At least 19 recordsLinked to original sources
PubMed2000

Sense of coherence: quality of life before and after coronary artery bypass surgery--a longitudinal study.

The attention to patient outcome has nowadays extended from morbidity and mortality to an aspect of patients' benefits in terms of quality of life. One factor crucial for quality of life is coping capacity, in this study represented by the sense of coherence concept. Physical status and emotional state (often measured by comprehensive instruments not always suitable for clinical use) are also additionally used to reflect quality of life. The purpose was therefore to study sense of coherence and emotional state as indirect measures of quality of life in relation to coronary artery bypass grafting surgery. One hundred and eleven patients were studied by a developed questionnaire on five occasions in relation to the surgery: the week before the angiography, the day before surgery and then at 3, 6, and 12 months post-operatively. The main findings were: (1) The sense of coherence was changed (more than +/-10%) from before to 1 year after surgery in 41% of the patients, which is contrary to the theory of sense of coherence as a stable personality characteristic in adults. (2) Experience of depressed mood, stress, and anxiety decreased significantly from before to after surgery. (3) Beneficial outcome with regard to sense of coherence was significantly related to less experience of loneliness, depressed mood, stress and anxiety, and to less experience of chest pain 1 year after surgery. In conclusion, sense of coherence and emotional state variables, are suggested to be valuable as measurements of quality of life in relation to coronary artery bypass grafting surgery.

Adaptation, Psychological↗
PubMed2000

Presence of human papilloma viruses in intraosseous ameloblastoma.

PURPOSE: This study investigated the possibility that human papilloma virus (HPV) is a possible etiologic agent in the development of ameloblastoma. MATERIALS AND METHODS: DNA was extracted from 18 formalin-fixed, paraffin-embedded biopsy specimens and assayed for the presence of HPV DNA by PCR using the L1 consensus primer and specific primers for HPV types 6/11, 16 and 18. RESULTS: Eight samples (67%) were positive for HPV. Of the 8 HPV-positive samples, 7 were positive for HPV 18. Four of the HPV 18-positive samples were also positive for HPV 6/11. One HPV-positive sample was not positive for any of the type-specific primers. CONCLUSIONS: No conclusions can be drawn about the etiologic role of HPV from this study, but surgical manipulation is suggested to be one of the reasons for HPV presence attributable to contamination from the surface mucosal epithelium in these tumors.

Adolescent↗
PubMed2000

Epstein-Barr virus and human papillomavirus in snuff-induced lesions of the oral mucosa.

Epstein-Barr virus (EBV) and human papillomavirus (HPV) have been associated with benign as well as malignant oral lesions. We examined 43 patients with snuff-induced lesions and 22 control patients with clinically healthy oral mucosa for the presence of HPV and EBV. Polymerase chain reaction was performed on fresh frozen oral biopsies with degenerate consensus primers for HPV and nested primers for EBV. None of the 43 snuff-induced lesions or the 22 control biopsies were HPV-positive. Seven of the 43 (16.3%) snuff-induced lesions and one of the 22 (4.5%) controls were positive for EBV. The snuff-induced lesions were classified according to clinical severity, grade 1 lesions being the least severe and grade 4 the most severe. Eleven percent of grade 2 lesions, 15.8% of grade 3 lesions and 20% of grade 4 lesions were EBV-positive. Neither EBV nor HPV seem to be associated with snuff-induced lesions.

Adult↗
PubMed2000

A pharmacokinetic study of 5-FU/leucovorin and alpha-interferon in advanced cancer.

The present study was designed to study 5-FU pharmacokinetics after interferon. Weekly bolus 5-FU (500 mg/m2), immediately followed by leucovorin (60 mg/m2) was given in 14 weekly cycles to 55 gastrointestinal and breast cancer patients. Interferon-alpha was given on days 2, 4 and 6, starting from cycle 2 at a dose of 0.5 million units (MU) and stepwise increased to 12 MU in cycles 12 and 13. Five patients could not tolerate the treatment even at the lowest dose of interferon and 22 patients were unavailable for the pharmacokinetic analysis because of dose reductions of 5-FU. Five patients were able to follow the protocol to 12 MU, whereas most patients were unable to continue owing to toxicity. 5-FU pharmacokinetics was analysed every second cycle. Peak concentration and AUC were increased after 12 MU of interferon, but no other significant influence of interferon on pharmacokinetic parameters of 5-FU was observed.

Adult↗
PubMed1999

Rapid method for relative gene expression determination in human tissues using automated capillary gel electrophoresis and multicolor detection.

The aim of this study was to evaluate a direct and automated post-polymerase chain reaction (PCR) detection system to simultaneously determine the relative gene expression levels of nine cancer-related human genes. Total RNA was prepared from flash-frozen biopsies derived from human colorectal tumors or normal mucosa and reverse-transcribed to cDNA which was PCR-amplified using primer pairs corresponding to the studied genes. In each reaction, the forward primer was labeled with a fluorescent dye. The PCR products were pooled and an internal size standard with a uniquely colored fluorescent dye was added. The samples were then subjected to automated capillary gel electrophoresis. Fragment analysis software was used to calculate the relative gene expression using beta-actin as the reference gene. We found that automated capillary gel electrophoresis with multicolor detection is a rapid, accurate and highly reproducible method for separation and quantification of PCR-amplified cDNA.

Autoanalysis↗
PubMed1999

Predictors of chest pain after coronary artery bypass grafting.

To identify preoperative biopsychosocial factors characterizing patients who will experience chest pain (self-reported) one year after coronary artery bypass grafting (CABG), 111 patients under 61 years of age were evaluated by questionnaire before CABG and 12 months postoperatively. A "Coronary Health Profile" was evolved to study quality-of-life indicators, e.g. "Sense of Coherence" (SOC), emotional state (loneliness, depressed mood, stress, anxiety) and social support as well as experience of chest pain, and the results were correlated to biomedical data. Chest pain was experienced in the first postoperative year by 34% of the patients. These patients, who were younger than those without chest pain, generally had a body mass index >25, as well as lower preoperative values for SOC, poorer emotional state and social support. Independent predictors in a multivariate stepwise logistic regression analysis were moderate/weak SOC, ejection fraction <50%, and moderate/severe mood depression. We conclude that biomedical as well as psychosocial factors have a significant impact as predictors of chest pain (of any origin) after CABG, and must be considered in preoperative evaluation. The findings indicate the need for biopsychosocial support/intervention before as well as after CABG.

Adult↗
PubMed1999

High-throughput DNA extraction from old paraffin-embedded biopsies.

We have developed a rapid and reliable microporous spin-column-based method for high-throughput extraction of DNA from old paraffin-embedded biopsies. The method was developed specifically for PCRs and molecular genetic studies. De-waxing and DNA extraction from tissues is performed in only one vessel, minimizing pipetting steps and eliminating supernatant/pellet procedures. All steps are performed at 60 degrees, 55 degrees and 95 degrees C minimize deleterious DNase activity. The amount of the extracted DNA was measured spectrophotometrically, and the quality of the extracted DNA and the PCR products was controlled on ethidium bromide-stained 3% agarose gel. The presented method for DNA extraction is less laborious and more convenient than previously published methods. It provides means by which extensive, paraffin-embedded material can be subjected to molecular genetic studies.

Actins↗
PubMed1998

Rapid quantitative PCR determination of relative gene expression in tumor specimens using high-pressure liquid chromatography.

A reverse transcriptase polymerase chain reaction (rt-PCR) for quantification of gene expression has been optimized for analysis of folylpolyglutamate synthase (FPGS) and thymidylate synthase (TS), using beta-actin as an internal standard (house-keeping gene). Total RNA was isolated from tumor tissue, reversely transcribed to cDNA and PCR amplified with primers specific for TS, FPGS and beta-actin in separate vials. PCR products were separated and quantified by high-pressure liquid chromatography (HPLC) without addition of radioactive or fluorescent markers, which minimizes labor and occupational hazards. The day-to-day variation in the HPLC analysis was 2.7% and the within sample variations for rt-PCR/HPLC analysis of TS and FPGS were 18.5% for both assays. This method provides a tool for convenient gene expression analysis in clinical biopsies.

Chromatography, High Pressure Liquid↗
PubMed1998

Chemical stability and human plasma pharmacokinetics of reduced folates.

The in vitro stability and plasma pharmacokinetics of 5,10-methylenetetrahydrofolic acid (CH2FH4), tetrahydrofolic acid (FH4), 5-methyltetrahydrofolic acid (CH3FH4), and 5-formyltetrahydrofolic acid (5-CHOFH4) were studied in view of their potential usefulness in cancer chemotherapy. Analysis of reduced folates was done on a high-performance liquid chromatography (HPLC) system. The high sensitivity of FH4 and CH2FH4 to oxidation can be circumvented by use of high concentrations of the folates, addition of ascorbate, and by thorough exclusion of atmospheric O2. Intravenous injection of 200 mg FH4 or CH2FH4 resulted in average peak concentrations of 69.2 +/- 3.2 nmol/ml and 46.3 +/- 2.6 nmol/ml, respectively. The plasma concentration curves support the concept that these highly oxygen-sensitive reduced folates can be reliably administered as pharmaceuticals to cancer patients through the use of a suitable air-occlusive system for their preparation and administration.

Colorectal Neoplasms↗
PubMed1997

[Diverticulitis is increasing among the elderly. Significant cause of morbidity and mortality].

The prevalence of diverticulosis in western countries has increased and two-thirds of the population over the age of 85 are now affected. Diverticulitis results from inflammation and subsequent perforation of a colonic diverticulum. Mild forms of diverticulitis usually present with gradually increasing symptoms from the lower left quadrant of the abdomen, whereas acute complicated disease is characterised by dramatic onset of abdominal pain, followed by fever within a few hours. The standard treatment for uncomplicated diverticulitis is bowel rest, with liquid diet or intravenous fluids in combination with antibiotics. Patients not responding to conservative treatment within the first 24 hours require further evaluation by computed tomography or ultrasonography. If an abscess is present, it can often be drained percutaneously. In cases of perforation and peritonitis, surgical intervention is mandatory, though no consensus exists as to the choice of procedure. Fistula formation and intestinal obstruction are also indications for surgical intervention, although the frequent recurrent attacks which commonly afflict these patients are seldom associated with severe complications. Prophylactic resection is not to be recommended for patients with diverticular disease, but a high-fibre diet may afford protection by preventing further complications.

Aged↗
PubMed1997

Detection of thymidylate synthase gene expression levels in formalin-fixed paraffin embedded tissue by semiquantitative, nonradioactive reverse transcriptase polymerase chain reaction.

We describe a new, simple and reliable semiautomated strategy for quantifying mRNA from archival specimens by using oligo(dT)25 paramagnetic beads and the reverse-transcriptase polymerase chain reaction (PCR) coupled with quantitative digital image analysis (Q-DIA). To evaluate the experimental conditions, we examined thymidylate synthase (TS) gene expression in mRNA isolated from both flash-frozen and formalin-fixed paraffin-embedded human biopsy samples using biopsy material obtained from 2 patients prior to chemotherapy with 5-fluorouracil. Following the electrophoretic separation of the PCR products through a 20% polyacrylamide gel, quantitation of the perimeters of the silver-nitrate-stained PCR products will be done by Q-DIA using a video frame-grabber board attached to a CCD camera using Image-Pro+ software. Validation of this approach will involve a comparison of the observed gene expression levels to TS protein levels obtained by tissue homogenization assays of TS, tetrahydrofolate, 5,10-methylenetetrahydrofolate, 2'-deoxyuridine-5'-monophosphate and 5-fluoro-2'-deoxyuridylate (FdUMP), by established [3H]FdUMP ligand-binding assays. The novelty of this method is that it offers a low-cost means whereby Q-DIA is performed directly from the gel to rapidly and accurately determine the level of TS gene expression, which is standardized against the beta-actin housekeeping gene. In the protocol described herein, gene expression studies can be done quickly and without the use of radioactive substances in both normal clinical samples shock frozen at the time of surgical excision and in formalin-fixed paraffin-embedded archival samples, which are commonly available in all hospital pathology departments. To demonstrate the utility of this method, mRNA was extracted from both nonpathological and tumor biopsies originating from both types of material from the same patients. TS gene expression in the flash-frozen and archival materials was compared to the level of TS intracellular enzyme activity in the same samples and a correlation of 89 and 80% between the shock-frozen and archival material relative to TS intracellular enzyme activity levels was observed. These findings suggest that routine semiautomated quantitative analysis of rare mRNA transcripts, e.g. TS, from archival material can be applied for retrospective studies.

DNA, Complementary↗
PubMed1996

The role of reactive oxygen metabolites in the transcriptional regulation of IFN-gamma gene expression by histamine in NK cells following IL-2 stimulation.

The secretion of interferon-gamma (IFN-gamma) by natural killer (NK) cells following in vitro stimulation with interleukin-2 (IL-2) is inhibited by co-incubation with autologous monocytes at a transcriptional level by more than sixty-fold. In this study, we investigate the nature of the inhibitory signal and particularly the role of reactive oxygen metabolites (ROMs). It was found that the inhibition of IFN-gamma was operating at a pre-translational level, this was indicated by the inability of CD 56(+)-enriched natural killer cells to accumulate IFN-gamma mRNA in the presence of elutriated monocytes. Both catalase, a scavenger of hydrogen peroxide and histamine, a biogenic amine which inhibits the generation of ROMs by monocytes, strongly abrogated the inhibition of IFN-gamma production. We thereby conclude that histamine behaves synergistically with IL-2 at a transcriptional level to induce IFN-gamma even in an admixture of NK cells and monocytes.

Base Sequence↗
PubMed1996

Rapid detection of thymidylate synthase gene expression levels by semi-quantitative competitive reverse transcriptase polymerase chain reaction followed by quantitative digital image analysis.

We describe a simplified and reliable polymerase chain reaction (PCR) method to quantify thymidylate synthase (TS) gene expression levels from clinical human tumor biopsy samples as small as 100 mg using the beta-actin housekeeping gene as a reference standard. The semiquantitative RT-PCR is carried out by the coamplification of the target template and an external competitor using primer pairs common to both templates in the same reaction vessel. Quantitative digital image analysis is performed directly after electrophoresis, thus mRNA quantification is done quickly and without the use of radioactive substances. The observed relative TS gene expression levels varied between 3- and 40-fold, but most of the values were grouped within a 10-fold range. There is an observed 89% correlation between TS mRNA expression and protein levels. These findings suggest that preliminary experiments used to determine the linear range of RT-PCR amplification in non-competitive semiquantitative PCR experiments, and the use of radioactive substances to quantify PCR products may be unnecessary.

Base Sequence↗
PubMed1996

Different intravenous administration techniques for 5-fluorouracil. Pharmacokinetics and pharmacodynamic effects.

The pharmacokinetics after 20 min intravenous infusion or a 2 min bolus (push) injection of 5-fluorouracil (500 mg/m2) were studied in 14 colorectal cancer patients. Treatment effects and toxicity related to the administration technique of 5-fluorouracil were retrospectively analysed in 198 colorectal cancer patients. The AUC after bolus injection was 6158 +/- 874 micromol/l*min compared to 3355 +/- 428 micromol/l*min after short-time infusion of 5-fluorouracil (p < 0.01). The mean peak-level after bolus injection was 341 +/- 34 microM versus 161 +/- 17 microM after a short-time infusion (p < 0.01). Patients receiving bolus injections had significantly better treatment result (32% partial remission) than patients receiving infusion (10% partial remissions, p < 0.001). Toxic side-effects were more frequently encountered after bolus injection but subjective improvement was also more frequently experienced by these patients. Bolus 5-fluorouracil push injection rather than a short-time infusion appears to be the more efficient administration technique.

Aged↗
PubMed1996

Thymidylate synthase in advanced gastrointestinal and breast cancers.

Knowledge of population thymidylate synthase (TS) levels in malignant tumors and normal tissues is essential for the use of TS as a predictor for 5-fluorouracil treatment. Tumor tissue TS levels in fresh frozen surgical biopsies from 136 patients with gastrointestinal or breast cancer, not previously subjected to chemotherapy, were analysed by [3H]FdUMP radioligand binding assay. TS levels were 2.4 +/- 0.31 pmol/g in liver metastases of colorectal cancer (n = 87), 4.2 +/- 1.0 pmol/g in primary colorectal cancer (n = 13), 2.7 +/- 0.93 pmol/g in gastric cancer (n = 13), 3.1 +/- 1.7 pmol/g in pancreatic cancer (n = 10), 3.4 +/- 1.4 pmol/g in breast cancer (n = 13) and 0.58 +/- 0.075 pmol/g in normal liver parenchyma (n = 24). TS levels were significantly higher in malignant tumor tissues compared to normal liver parenchyma.

Antimetabolites, Antineoplastic↗
PubMed1995

Antitumour effects of pure diastereoisomers of 5-formyltetrahydrofolate in hepatic transplants of a rodent colon carcinoma model.

The effects of the two diastereoisomers of 5-formyltetrahydrofolate on tumour growth, thymidylate synthase (TS, EC 2.1.1.45) levels, and potentiation of 5-fluorouracil cytotoxicity were studied in an in vivo rat colon carcinoma model, transplanted to liver. The animals were randomized into eight groups, treated with daily i.v. tail vein injections of racemic (d,l)-5-formyltetrahydrofolate (5-CHO-FH4), 15 mg/kg, (1)-5-CHO-FH4 7.5 mg/kg, and (d)-5-CHO-FH4 7.5 mg/kg, 5-fluorouracil (FUra) 30 mg/kg, (d,l)-5-CHO-FH4 15 mg/kg+FUra 30 mg/kg, (l) 5-CHO-FH4 7.5 mg/kg+FUra 30 mg/kg, and (d)-5-CHO-FH4 7.5 mg/kg+FUra 30 mg/kg, and a sham-treated control group. The average tumour size of the groups was equal at the start of treatment. After six days' treatment the average tumour sizes were at laparotomy 3.3 +/- 1.0 g in the (d/l)-5-CHO-FH4 treated group, compared to 2.0 +/- 0.1 g in the FUra treated group and 7.1 +/- 3.1 g in the controls. Natural (l)-5-CHO-FH4 promoted tumour growth (average tumour weight 10.8 +/- 4.0 g), whereas the unnatural (d)-5-CHO-FH4 alone retarded it (average tumour weight 1.2 +/- 0.40 g). (l)-5-CHO-FH4 induced a significant increase in tumour tissue TS levels by [3H]FdUMP radioligand assay (27.5 +/- 8.4 pmol/g tumour tissue) compared to controls (16.8 +/- 6.1 pmol/g tumour tissue). Increases in 5,10-methylenetetrahydrofolate and tetrahydrofolate occurred with FUra alone, with a further statistically significant increase in both folates with the addition of (d)-5-CHO-FH4 to FUra.

Animals↗