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Biomedical subjects

M Andersson

Publications and source records attributed to M Andersson.

At least 91 records · Page 5Linked to original sources
PubMed2001

Reduction of postoperative morbidity and mortality in patients with rectal cancer following the introduction of a colorectal unit.

BACKGROUND: Surgery for rectal cancer is associated with high morbidity and mortality rates. The reason for this has been much debated. This population-based study reports the findings on postoperative morbidity and mortality after rectal cancer surgery following the introduction of a centralized colorectal unit in a county central hospital, supervised by a colorectal surgeon using the most recent techniques. METHODS: All consecutive patients with rectal cancer who underwent surgery at four county hospitals in the Västmanland county in Sweden during 1993-1996 (n = 133) were compared with patients who underwent surgery at the new colorectal unit in the county central hospital from 1996 to 1999 (n = 144). RESULTS: The number of operating surgeons was reduced from 26 to four. The postoperative mortality rate decreased from 8 to 1 per cent (P = 0.002) and the total postoperative complication rate was reduced from 57 to 24 per cent (P < 0.001). Surgical complications dropped from 37 to 11 per cent (P < 0.001). The relaparotomy rate fell from 11 to 4 per cent (P < 0.05). Postoperative stay in hospital was reduced from a median of 13 to 9 days (P < 0.001). CONCLUSION: The new organization, with centralized rectal cancer surgery using modern techniques, reduced postoperative mortality and overall morbidity rates to less than half.

Adult↗
PubMed2001

Mucosal output of eotaxin in allergic rhinitis and its attenuation by topical glucocorticosteroid treatment.

BACKGROUND: Eotaxin is a chemokine that attracts and activates eosinophils. The present study examines the occurrence of eotaxin in nasal mucosal surface liquids in patients with seasonal allergic rhinitis without allergen exposure and during repeat allergen challenge with and without topical glucocorticosteroid treatment. The number of subepithelial eosinophils and mucosal outputs of bulk plasma (alpha2-macroglobulin) and eosinophil cationic protein (ECP) are also examined. METHODS: Twelve patients underwent daily allergen challenges for 6 days. Separately, 14 patients, who were receiving budesonide and placebo in a parallel group design, also underwent allergen challenge for 6 days. Nasal biopsies were obtained before and 24 h after the allergen challenge series, and lavages were carried out before and 15 min after selected allergen challenges. RESULTS: At baseline nasal lavage fluid levels of eotaxin correlated to levels of alpha2-macroglobulin and ECP. After the first allergen challenge there was a correlation between nasal lavage fluid levels of eotaxin and ECP. Repeat allergen exposure increased the mucosal output of eotaxin (P <0.05) and ECP (P <0.01) as well as eosinophil numbers (P <0.01), but no correlation was found between increased eosinophil numbers and eotaxin. Budesonide reduced eotaxin levels during repeat allergen challenge (P <0.05). CONCLUSIONS: Repeat allergen exposure in allergic rhinitis is associated with increased mucosal output of eotaxin. Topical budesonide attenuates this effect, suggesting the possibility that inhibitory effects on mucosal eotaxin may contribute to anti-eosinophilic actions of topical glucocorticosteroids.

Administration, Intranasal↗
PubMed2001

Dispersion in ventricular repolarization in patients with severe intraventricular conduction disturbances.

Increased dispersion of repolarization, measured invasively or by QT interval measurements, is associated with an increased risk for ventricular arrhythmias and sudden death. Most studies on this issue have included patients with normal intraventricular conduction, and it is not known if this finding has a predictive value also in patients with intraventricular conduction disorders. An invasive electrophysiological study, including programmed ventricular stimulation and assessment of effective refractory periods at two RV sites, was performed in 103 patients with bifascicular block (mean age 67 +/- 12 years). QT dispersion was measured from standard 12-lead ECGs. In patients with inducible sustained polymorphic VT or VF the dispersion in refractoriness between the two RV sites was significantly greater (46 +/- 11 ms, n = 13) than in noninducible patients (14 +/- 14 ms, n = 84) and in patients with inducible sustained monomorphic VT (16 +/- 5 ms, n = 6) (P < 0.01). Similarly, QT dispersion was 104 +/- 46 ms, 66 +/- 31 ms, and 77 +/- 33 ms, respectively, in the three groups (P < 0.05). Dispersion in repolarization, neither measured invasively nor by QT interval measurements, predicted sudden death, all cause mortality, or ventricular arrhythmia during a mean follow-up period of 3 years. In patients with bifascicular block, there is a relation between the degree of dispersion of ventricular repolarization and the inducibility of polymorphic ventricular arrhythmia, but this outcome did not occur during follow-up.

Adolescent↗
PubMed2001

Dual symptomatic and exudative nasal responses are not characteristics of perennial allergic rhinitis.

Acute and late phase (dual) symptomatic responses after allergen challenge commonly occur in allergic asthma. The aim of the present study was to explore the occurrence of allergen challenge-induced biphasic responses in patients with chronic perennial allergic rhinitis living in an area with high house dust mite (HDM) exposure. Fifteen patients with perennial rhinitis and evident allergy to HDM participated. Nasal challenges with HDM and sham were performed on separate days in a crossover design. Nasal symptoms, forced expiratory volume in 1 s (FEV1) and orally exhaled nitric oxide were recorded every hour for up to 8 h after each challenge. Alpha2-macroglobulin and eosinophil cationic protein (ECP) were analysed in hourly nasal lavages, and nasal histamine provocations were carried out after 8 h. HDM, but not sham, caused an immediate increase in nasal symptoms which gradually abated over the 8-h period. No reoccurrence of nasal late phase symptoms was seen. HDM, but not sham, induced an early increase in alpha2-macroglobulin and ECP levels: both indices remained elevated for up to 3 h after challenge. HDM challenge evoked hyper-responsiveness to histamine expressed as increased nasal symptoms (p < 0.05; HDM vs sham). No differences in exhaled nitric oxide or FEV1 were demonstrated at any one time point between the HDM- and sham-challenged days. It is concluded that nasal symptomatic and exudative late phase responses may not be a general feature, even in subjects with perennial rhinitis challenged with high, symptom-provoking, doses of HDM allergen.

Adolescent↗
PubMed2001

Allopurinol as prophylaxis against pouchitis following ileal pouch-anal anastomosis for ulcerative colitis. A randomized placebo-controlled double-blind study.

BACKGROUND: Pouchitis is the major long-term complication of restorative proctocolectomy for ulcerative colitis (UC). Allopurinol is a scavenger of oxygen-derived free radicals, which it is suggested play a role in the development of UC and pouchitis. The first aim was to test the hypothesis that the incidence of pouchitis can be reduced by prophylactic Allopurinol, and secondly to evaluate if Allopurinol influences the overall pouch function. METHODS: 273 patients with UC who were planned for proctocolectomy and ileal pouch-anal anastomosis at 12 centres in Sweden between October 1994 and June 1997 were offered the opportunity to participate. 184 patients (67%) were randomized to receive postoperative prophylactic Allopurinol 100 mg twice daily or placebo. All 273 patients had clinical and endoscopic follow-up at 1, 3, 6, 12, 18, 24 months after surgery. RESULTS: Of the 184 randomized patients, 94 were randomized to Allopurinol and 90 to placebo; 116 patients (63%) completed follow-up and the crude incidence of pouchitis among those patients fullfilling the protocol was 31% in the Allopurinol group and 28% in the placebo group (ns). The cumulative risk for a first attack of pouchitis was 30% and 26% after 24 months (ns). The overall pouch function improved over time and did not differ significantly between the two groups. CONCLUSIONS: Prophylactic Allopurinol did not reduce the risk of a first attack of pouchitis.

Adolescent↗
PubMed2001

In vitro activity of PR-39, a proline-arginine-rich peptide, against susceptible and multi-drug-resistant Mycobacterium tuberculosis.

We have investigated the in vitro activity of antimicrobial peptides against Mycobacterium tuberculosis using a radiometric method and cfu determinations. PR-39, a proline-arginine-rich antibacterial peptide from porcine leucocytes, was found to be active against drug-susceptible as well as multi-drug-resistant (MDR) clinical isolates of M. tuberculosis. The activity of PR-39 was concentration dependent, with 80% growth inhibition of M. tuberculosis H37Rv at 50 mg/L. The MDR M. tuberculosis strains E1380/94 and P34/95 were less susceptible to PR-39, with 39 and 49% growth inhibition at 50 mg/L peptide, respectively, suggesting a lower susceptibility than strain H37Rv and drug-susceptible clinical isolates. Reduction of counts of M. tuberculosis H37Rv and the MDR M. tuberculosis strain E1380/94 by PR-39 indicated that the growth inhibition seen in the radiometric assay is due to a mycobactericidal effect of the peptide. These observations suggest that antimicrobial peptides may play an important role in host defence against MDR M. tuberculosis.

Anti-Bacterial Agents↗
PubMed2001

Fast, nondestructive measurement of frost hardiness in conifer seedlings by VIS+NIR spectroscopy.

Frost hardiness development from mid-August to mid-November was evaluated in seedlings of three provenances of Norway spruce (Picea abies (L.) Karst.) and three provenances of Scots pine (Pinus sylvestris L.) raised at nurseries in north, central and south Sweden. Measurements of the visible + near infrared (VIS+NIR) spectra of shoots were made simultaneously with estimates of frost hardiness based on electrolyte leakage following artificial freezing. Nine physiological variables known to influence frost hardiness were measured throughout the experiment. Multivariate analysis showed that VIS+NIR spectra explained 69% and 72% of the variation in frost hardiness in Scots pine and Norway spruce, respectively. Stem lignification, dry weight fraction, and starch, glucose, fructose, galactose, sucrose, raffinose and stachyose concentrations together explained 80% and 85% of the variation in frost hardiness in Scots pine and Norway spruce, respectively when used as independent X variables in a partial least squares model. These physiological variables could be related to varying degrees with variation in the VIS+NIR spectra. We conclude that VIS+NIR spectroscopy provides a rapid nondestructive technique for measuring frost hardiness in conifer seedlings based on causal relationships between the spectra and the physiology of seedling frost hardiness.

Freezing↗
PubMed2001

Increased levels of proinflammatory cytokines and nitric oxide metabolites in neuropsychiatric lupus erythematosus.

OBJECTIVE: To investigate systemic and intrathecal production of proinflammatory cytokines in relation to cerebrospinal fluid (CSF) nitric oxide (NO) release in patients with neuropsychiatric lupus erythematosus (NPLE). METHODS: Thirty patients with NPLE rated as mild, moderate, or severe were studied and CSF was obtained from 21 of these. Cytokine mRNA expressing cells were detected by in situ hybridisation. Soluble cytokines were assessed by enzyme linked immunosorbent assay (ELISA). Nitrite and nitrate were determined by capillary electrophoresis. RESULTS: Patients with NPLE had high numbers of lymphocytes expressing mRNA for tumour necrosis factor alpha (TNFalpha), interferon gamma, and interleukin 10 in blood. The number of peripheral blood TNFalpha mRNA positive cells correlated strongly with the level of NO metabolites in the CSF (r(2)=0.69). Both the number of peripheral blood mononuclear cells expressing mRNA for TNFalpha as well as the CSF level of NO metabolites correlated with NPLE disease severity. CONCLUSION: These data suggest that increased peripheral production of proinflammatory cytokines such as TNFalpha may contribute both to an increased production of NO in the central nervous system and to generation of clinical NPLE. The data also support the possibility that measurements of NO metabolites in CSF may be of value in the diagnosis of neurological symptoms related to SLE.

Adult↗
PubMed2001

Effects on the nervous system in different groups of workers exposed to aluminium.

OBJECTIVE: To investigate possible neurotoxic effects in groups of aluminium pot room and foundry workers, aluminium welders, and a small group of workers exposed to aluminium in the production of flake powder. METHODS: Exposure to aluminium was evaluated with aluminium concentrations in blood and urine as well as a questionnaire. The groups exposed to aluminium were compared with a group of mild steel welders. Neurotoxic effects were studied with mood and symptom questionnaires and several psychological and neurophysiological tests. RESULTS: The pot room and foundry workers showed very low aluminium uptake as their aluminium concentrations in blood and urine were close to normal, and no effects on the nervous system were detected. The group of workers exposed to flake powder had high concentrations of aluminium in blood and urine, even higher than those of the aluminium welders. However, aluminium could not be shown to affect the functioning of the nervous system in flake powder producers. Although significant effects could not be shown in the present analysis of the data on welders, the performance of the welders exposed to high concentrations of aluminium was affected according to the analyses in the original paper from this group. CONCLUSIONS: For the pot room and foundry workers no effects related to the exposure to aluminium could be found. For the group of flake powder producers exposed for a short term no effects on the nervous systems were evident despite high levels of exposure. Due to the high concentrations of aluminium in the biological samples of this group, measures to reduce the exposure to aluminium are recommended, as effects on the central nervous system might develop after protracted exposures. However, this assumption needs to be verified in further studies.

Adult↗
PubMed2001

Degranulation patterns of eosinophil granulocytes as determinants of eosinophil driven disease.

BACKGROUND: Degranulation of eosinophils in target tissues is considered a key pathogenic event in major chronic eosinophilic diseases. However, because of a lack of appropriate methods, little is known about degranulation of eosinophils in common eosinophilic diseases. METHODS: Using transmission electron microscopic (TEM) analysis, a novel approach has been devised and validated to quantify eosinophil degranulation in human tissues (assessed in individual cells as percentage granules with structural signs of protein release). Biopsy specimens from patients with inflammatory bowel disease, allergic rhinitis, asthma, and nasal polyposis were evaluated. RESULTS: All conditions displayed a similar degree of local tissue eosinophilia, with no differences being observed in eosinophil numbers in the airway mucosa of patients with airway diseases and the colonic mucosa of those with inflammatory bowel disease (IBD). In contrast, marked differences in the mean (SE) extent of eosinophil degranulation were observed between the patient groups; IBD 9.3 (1.4)% altered granules, artificial and natural allergen challenge induced allergic rhinitis 67.8 (6.8)% and 86.6 (3.0)%, respectively, asthma 18.1 (2)%, and nasal polyposis 46.6 (7.6)%. CONCLUSIONS: This study provides the first quantitative data which show that different eosinophilic conditions, despite having similar numbers of tissue eosinophils, may exhibit markedly different degranulation patterns. The present assessment of piecemeal degranulation would thus make it possible to delineate the conditions under which eosinophils are likely to contribute to disease processes. This novel type of analysis may also guide and validate anti-eosinophilic treatment options.

Apoptosis↗
PubMed2001

Predictive markers of asthma exacerbation during stepwise dose reduction of inhaled corticosteroids.

To determine predictors for failed reduction of inhaled corticosteroids (ICS), in 50 subjects with well-controlled asthma (age 43.7 [18-69]; 22 males) taking a median dose of 1,000 microg ICS/d (100-3,600 microg/d), ICS were halved every 8 wk. Airway hyperresponsiveness (AHR) to a bronchial provocation test (BPT) with histamine was measured at baseline. AHR to BPT with mannitol, spirometry, exhaled nitric oxide (eNO), and, in 31 subjects, sputum inflammatory cells were measured at baseline and at monthly intervals. Thirty-nine subjects suffered an asthma exacerbation. Seven subjects were successfully weaned off ICS. Using a Kaplan- Meier survival analysis, the significant predictors of a failure of ICS reduction were being hyperresponsive to both histamine and mannitol at baseline (p = 0.039), and being hyperresponsive to mannitol during the dose-reduction phase of the study (p = 0.02). Subjects older than 40 yr of age tended to be at greater risk of ICS reduction failure (p = 0.059). Response to mannitol and percentage sputum eosinophils were significantly greater before a failed ICS reduction than before the last successful ICS reduction, whereas there were no significant differences in symptoms, spirometry, or eNO. These findings suggest that documentation of patient's AHR or sputum eosinophils may be useful in guiding the reduction of ICS doses.

Adolescent↗
PubMed2001

Markers of airway inflammation and airway hyperresponsiveness in patients with well-controlled asthma.

In steroid-naive asthmatics, airway hyperresponsiveness correlates with noninvasive markers of airway inflammation. Whether this is also true in steroid-treated asthmatics, is unknown. In 31 stable asthmatics (mean age 45.4 yrs, range 22-69; 17 females) taking a median dose of 1,000 microg inhaled corticosteroids (ICS) per day (range 100-3,600 microg x day(-1)), airway responsiveness to the "direct" agent histamine and to the "indirect" agent mannitol, lung function (forced expiratory volume in one second (FEV1), forced vital capacity (FVC), peak expiratory flow (PEF)), exhaled nitric oxide (eNO), and number of inflammatory cells in induced sputum as a percentage of total cell count were measured. Of the 31 subjects, 16 were hyperresponsive to mannitol and 11 to histamine. The dose-response ratio (DRR: % fall in FEV1/cumulative dose) to both challenge tests was correlated (r=0.59, p=0.0004). However, DRR for histamine and DRR for mannitol were not related to basic lung function, eNO, per cent sputum eosinophils and ICS dose. In addition, NO was not related to basic lung function and per cent sputum eosinophils. In clinically well-controlled asthmatics taking inhaled corticosteroids, there is no relationship between markers of airway inflammation (such as exhaled nitric oxide and sputum eosinophils) and airway responsiveness to either direct (histamine) or indirect (mannitol) challenge. Airway hyperresponsiveness in clinically well-controlled asthmatics appears to be independent of eosinophilic airway inflammation.

Adult↗
PubMed2001

Prevalence of nasal symptoms and their relation to self-reported asthma and chronic bronchitis/emphysema.

Little information is available on associations between rhinitis and chronic bronchitis/emphysema (CBE). Self-reported upper airway symptoms, asthma, and CBE were examined in 12,079 adults living in southern Sweden. The response rate was 70% (n=8,469), of whom 33% reported significant nasal symptoms: a blocked nose was reported by 21%; sneezing by 18%; nasal discharge by 17%; and thick yellow nasal discharge by 5.7%. Nasal symptoms and combined nasal and self-reported bronchial disease were generally more common among smokers than nonsmokers. There was little overlap between asthma and CBE, but 46% of those with asthma and 40% of those with CBE had significant nasal symptoms. Best predicting factors (odds ratios >3) for asthma and CBE were nasal symptoms due to exposure to animals and damp/cold air, respectively. One-third of an adult, southern Swedish population, had significant allergic and/or nonallergic nasal symptoms. Nasal symptoms were frequently found to coexist with both asthma and chronic bronchitis/emphysema, suggesting that pan-airway engagement is common in both diseases. Differing associations between types of nasal symptoms and allergic and irritant triggers of nasal symptoms, with regard to asthma and chronic bronchitis/emphysema, emphasize the different natures of these bronchial diseases.

Adult↗
PubMed2001

Mortality after cerebral angiography with or without radioactive Thorotrast: an international cohort of 3,143 two-year survivors.

There are few studies on the long-term sequelae of radionuclides ingested or injected into the human body. Patients exposed to radioactive Thorotrast in the 1930s through the early 1950s provide a singular opportunity, since the administration of this radiographic contrast agent resulted in continuous exposure to alpha particles throughout life at a low dose rate. We evaluated cause-specific mortality among an international cohort of 3,143 patients injected during cerebral angiography with either Thorotrast (n = 1,736) or a similar but nonradioactive agent (n = 1,407) and who survived 2 or more years. Standardized mortality ratios (SMRs) for Thorotrast and comparison patients were calculated, and relative risks (RR), adjusted for population, age and sex, were obtained by multivariate statistical modeling. Most patients were followed until death, with only 94 (5.4%) of the Thorotrast patients known to be alive at the closure of the study. All-cause mortality (n = 1,599 deaths) was significantly elevated among Thorotrast subjects [RR 1.7; 95% confidence interval (CI) 1.5-1.8]. Significantly increased relative risks were found for several categories, including cancer (RR 2.8), benign and unspecified tumors (RR 1.5), benign blood diseases (RR 7.1), and benign liver disorders (RR 6.5). Nonsignificant increases were seen for respiratory disease (RR 1.4) and other types of digestive disease (RR 1.6). The relative risk due to all causes increased steadily after angiography to reach a threefold RR at 40 or more years (P < 0.001). Excess cancer deaths were observed for each decade after Thorotrast injection, even after 50 years (SMR 8.6; P < 0.05). Increasing cumulative dose of radiation was directly associated with death due to all causes combined, cancer, respiratory disease, benign liver disease, and other types of digestive disease. Our study confirms the relationship between Thorotrast and increased mortality due to cancer, benign liver disease, and benign hematological disease, and suggests a possible relationship with respiratory disorders and other types of digestive disease. The cumulative excess risk of cancer death remained high up to 50 years after injection with >20 ml Thorotrast and approached 50%.

Adult↗
PubMed2001

Indomethacin and telomerase activity in tumor growth retardation.

It is well-recognized that cycloogygenase inhibitors attenuate tumor growth in tumor models, although underlying mechanisms are unclear. In the present study we report that indomethacin retards MCG-101 tumor growth on mice by induction of apoptosis/necrosis and inhibits telomere elongation. The inhibition of telomerase activity by NSAIDs (indomethacin, mobic, sulindac sulfone, suramin) was, however, not a universal finding, since a mouse melanoma (K1735-M2) did not respond. By contrast, a human cell line of colon carcinoma origin (HT-29), responded by both retarded growth and telomerase activity despite a low intrinsic production of prostaglandins, mainly PGE2. Therefore, it is not likely that indomethacin inhibition of tumor growth and telomere elongation is directly related to Cox-1/Cox-2 activities in tumor cells. Also, NSAIDs at 25 microM (sulindac sulfone) decreased growth and telomerase activity in MCG-101 cells, without any effects on PGE2 production, while ibuprofen reduced PGE2 production but had no effect on growth or telomerase activity. Our results demonstrate that cyclooxygenase inhibitors can retard tumor growth both in murine tumors and in human tumor cells by inhibition of telomerase activity in addition to previously recognized mechanisms as induction of apoptosis, inhibition of cell proliferation, influence on the expression of growth factors around growing tumors and attenuation of neoangiogenesis.

Animals↗
PubMed2001

The effect of intranasal budesonide spray on mucosal blood flow measured with laser Doppler flowmetry.

BACKGROUND: Recent reports have shown that, although rare, findings of mucosal ulcers and perforations of the nasal septum in some cases may be associated with the use of topical nasal glucocorticosteroids (GCS). It can been speculated that, a reduction in septal mucosal blood flow causing ischemia may eventually induce septal perforations. AIM: To evaluate whether a single dose of a potent nasal GCS given in a clinically recommended dose may acutely reduce the mucosal blood flow on the nasal septum. METHODS: Six healthy subjects received in a randomised double blind placebo controlled crossover procedure one dose of 64 micrograms budesonide aqueous nasal spray (Rhinocort aqua, AstraZeneca R&D, Lund, Sweden) and placebo. One dose was delivered into each nasal cavity by means of a pump spray. As a positive control 140 micrograms of xylometazoline (Nezeril, AstraZeneca R&D, Lund, Sweden) was sprayed in the same way, but in an open fashion. A wash-out period of at least 3 days followed each session. Blood flow was measured on the nasal septum with Laser Doppler flowmetry up to 20 min after administration. RESULTS: Budesonide did not affect the nasal septal mucosal blood flow as compared to placebo, but xylometazoline reduced the septal mucosal blood flow by 60.9 +/- 7.1% measured from baseline values. CONCLUSION: A single dose of intranasal budesonide aqueous nasal spray has no acute effects on nasal septal mucosal blood flow.

Administration, Intranasal↗
PubMed2001

The role of capsulin in the morphogenesis and differentiation of fetal rat gastric mucosa.

The signals that guide the morphogenesis and differentiation of rat fetal gastric mucosa remain largely unknown. We have investigated the role of capsulin in pit/gland formation and epithelial cell differentiation in cultured stomach tissue. Embryonic day 16.5 (E 16.5) stomach tissue cultured for three days in the presence of 1 microM hydrocortisone underwent dramatic transformation, from undifferentiated, stratified cells to differentiated epithelia composed of polarised columnar cells with mucous cells and pit/glands. In the presence of capsulin antisense oligonucleotides directed against capsulin mRNA, tissues do not undergo further development. Significantly, both mucous granules and pit/gland formation were inhibited compared to capsulin sense/scrambled oligonucleotide treated controls. However, in tissues treated with specific anti-rat HGF-antiserum to neutralise secreted HGF, pit/gland formation was inhibited, but the number of mucous granules remained unchanged compared to controls treated with non-specific antiserum (mouse monoclonal cytokeratin 8 antiserum). This data suggests that capsulin may have a role in the morphogenesis of pit/glands and mucin granule formation in the developing rat gastric mucosa. We discuss the possibility that this role of capsulin may be partly mediated through the actions of HGF.

Animals↗