Biomedical subjects

C Lindholm

Publications and source records attributed to C Lindholm.

At least 37 records · Page 2Linked to original sources

PubMed2001

Induction of chemokine and cytokine responses by Helicobacter pylori in human stomach explants.

BACKGROUND: The cytokine response during the acute phase of Helicobacter pylori infection in humans has not been studied. The aim of this study was therefore to investigate the early cytokine responses against H. pylori using cultured human stomach explants as a model of acute infection. METHODS: Gastric corpus tissue obtained from 13 adult uninfected and 3 H. pylori-infected patients undergoing gastric surgery due to obesity was used for preparation of mucosal explants. The cultured explants were exposed to different H. pylori strains or antigens, that is, lipopolysaccharides (LPS), urease and heat-shock protein (Hsp) B. The responses of the CXC chemokines interleukin (IL)-8, growth-related oncogene alpha (GROalpha) and interferon-inducible protein (IP) 10 as well as the CC chemokine regulated on activation normal T-cell expressed and secreted (RANTES) were determined by ELISA. In addition, IL-4, IL-6, IL-10, IL-12, interferon gamma (IFNgamma), tumour necrosis factor alpha (TNFalpha) and granulocyte-macropage-colony stimulating factor (GM-CSF) were studied. RESULTS: In vitro H. pylori infection of the explants preferentially induced responses of the CXC chemokines GROalpha (P < 0.05) and IL-8 (P < 0.05), whereas the CC chemokine response (RANTES) was weak. In addition, the production of IL-6 was increased after H. pylori infection. Stimulation of the explants with different LPS preparations also induced strong GROalpha, IL-8 and IL-6 responses; the GROalpha responses being significantly higher after stimulation with rough than smooth H. pylori LPS (P < 0.05). CONCLUSIONS: GROalpha, IL-8 and IL-6 are increased early during acute H. pylori infection and may influence the development of gastric disease.

Adult↗

PubMed2001

Reduced incidence of pressure ulcers in patients with hip fractures: a 2-year follow-up of quality indicators.

OBJECTIVE: The aims of the present study were to (i) investigate the incidence of pressure ulcers in 1997 and 1999 among patients with hip fracture, (ii) study changes of nursing and treatment routines during the same period and (iii) to identify predictors of pressure ulcer development. DESIGN: The present comparative study was based partly on data collected in two prospective, randomized, controlled studies conducted in 1997 and 1999. SETTING: The study was carried out in the Accident & Emergency (A&E) Department and the Department of Orthopaedics at the University Hospital in Uppsala, Sweden. STUDY PARTICIPANTS INCLUSION CRITERIA: patient with hip fracture, > or = 65 years, admitted without pressure ulcers. Forty-five patents were included in 1997 and 101 in 1999. INTERVENTIONS: Risk assessment, pressure ulcer grading, pressure-reducing mattress and educational programme. MAIN OUTCOME MEASURES: Incidence of pressure ulcers. RESULTS: There was a significant reduction of the overall incidence of pressure ulcers from 55% in 1997 to 29% in 1999. The nursing notes had become significantly more informative. Nursing and treatment routines for patients with hip fractures had changed both in the A&E Department and the orthopaedic ward through initiatives developed and implemented by pressure ulcer nurses. CONCLUSION: In the framework of a quality improvement project, where research activities were integrated with practice-based developmental work, the incidence of pressure ulcers was reduced significantly in patients with hip fractures. The best predictor of pressure ulcer development was increased age.

Age Factors↗

PubMed2001

Stable and unstable chromosomal aberrations among Finnish nuclear power plant workers.

Twenty nuclear power plant workers with relatively high recorded cumulative doses were studied using FISH chromosome painting and dicentric analysis after solid Giemsa staining. The results indicated that chronic exposure to ionising radiation can be detected on the group level using translocation analysis after chromosome painting, although the mean cumulative dose was approximately 100 mSv. A significant association between translocation frequency and cumulative dose was observed. Variability in the translocation yields among workers with similar recorded doses was large, resulting in a poor correlation between translocation frequencies and documented doses on the individual level. The yields of dicentric and acentric chromosomes were not correlated with the cumulative dose, indicating the inability of unstable aberrations to monitor long-term exposures. It was also shown that the unstable aberrations were not correlated with the most recent annual dose.

Adult↗

PubMed2001

Homing commitment of lymphocytes activated in the human gastric and intestinal mucosa.

BACKGROUND: Gastric infection with the human pathogen Helicobacter pylori results in a large accumulation of IgA and IgM secreting cells in the gastric mucosa. The molecular mechanisms resulting in B cell migration to the gastric mucosa in H pylori infection are however not known. AIMS: To examine expression of the mucosal homing receptor integrin alpha4beta7 and the homing receptor for secondary lymphoid tissues, L-selectin, on lymphocytes activated by gastric, intestinal, or systemic antigens. Furthermore, to examine gastric expression of the mucosal addressin cellular adhesion molecule 1 (MAdCAM-1), the endothelial counter-receptor to integrin alpha4beta7. SUBJECTS AND METHODS: H pylori infected individuals were immunised by either gastric (n=8) or intestinal (n=8) delivery of an inactivated cholera vaccine. The resulting circulating vaccine specific B cells were sorted according to alpha4beta7 and L-selectin expression and assayed for production of IgA and IgG using an enzyme linked immunospot assay. In addition, circulating CD4+ T cells from seven H pylori infected individuals were fractionated according to alpha4beta7 and L-selectin expression. The resulting T cell fractions were then assayed for specific proliferation against H pylori or the systemic antigen tetanus toxoid. Finally, gastric expression of MAdCAM-1 was determined by immunohistochemistry in H pylori infected (n=16) and uninfected (n=8) individuals. RESULTS: Virtually all B cells induced by both gastric and intestinal antigen delivery expressed alpha4beta7 whereas less then half coexpressed L-selectin. Furthermore, H pylori reactive T cells were mainly found in the alpha4beta7+L-selectin+ T cell fraction whereas tetanus specific T cells were largely alpha4beta7-L-selectin+. MAdCAM-1 was present in similar amounts in gastric mucosa from H pylori infected and uninfected individuals. CONCLUSIONS: B cells and T cells activated by antigens delivered to the gastric mucosa express the mucosal homing receptor integrin alpha4beta7, as do cells activated in the intestine. Together with the observation that gastric endothelial cells express MAdCAM-1, this may partly explain the homing of lymphocytes activated in the stomach or in the small intestine to the gastric mucosa.

ATPases Associated with Diverse Cellular Activitie↗

PubMed2001

Does chronic illness cause adverse social and economic consequences among Swedes?

BACKGROUND: In an international comparison, the Swedish welfare system has been known for universal coverage and high benefit levels. Perhaps this is the reason why very few studies recently have dealt with the social and economic consequences of long-term illness in Sweden. AIMS: The research question raised here is therefore to examine chronic illness (defined as limiting longstanding illness. LLSI) as a causal factor contributing adverse financial conditions, unemployment or labour market exclusion. METHODS: A longitudinal design was employed with data from a sample of 27,773 people interviewed twice (Swedish Surveys of Living Conditions performed by Statistics Sweden), including subjects (n = 12,556) at interview I, without chronic illness or adverse socioeconomic conditions. RESULTS: The odds ratios for labour market exclusion, unemployment, and financial difficulties among people who had acquired LLSI at interview II varied between 1.4 and 4.0 for the outcomes. The elevated OR decreased after testing for the mediating effect of social context and the labour market position for financial difficulties but remained significantly elevated. CONCLUSIONS: The results suggest that LLSI increases the risk of adverse financial conditions, unemployment, and of not being economically active.

Adult↗

PubMed2000

Long term results of a randomized study by the Swedish Melanoma Study Group on 2-cm versus 5-cm resection margins for patients with cutaneous melanoma with a tumor thickness of 0.8-2.0 mm.

BACKGROUND: Large, prospective, randomized trials with long term follow-up are required to obtain an unbiased evaluation of the significance of resection margins in patients with cutaneous melanoma. METHODS: The Swedish Melanoma Study Group performed a prospective, randomized, multicenter study of patients with primary melanoma located on trunk or extremities and with a tumor thickness > 0.8 mm and </= 2 mm. Patients were allocated randomly to a 2-cm excision margin or a 5-cm excision margin. In total, 989 patients were recruited during the period 1982-1991. The median follow-up was 11 years (range, 7-17 years) for estimation of survival and 8 years (range, 0-17 years) for evaluation of recurrent disease. RESULTS: The crude rate of local recurrence, defined as a recurrence in the scar or transplant, was < 1% (8 of 989 patients). Twenty percent of the patients (194 of 989 patients) experienced any disease recurrence, and 15% (146 of 989 patients) died of melanoma. There were no statistically significant differences between the two treatment arms. In a multivariate Cox analysis with patients allocated to wide excision as the reference group, the estimated relative hazards for overall survival and recurrence free survival among those allocated to a 2-cm resection margin were 0.96 (95% confidence interval, 0.75-1.24), and 1.02 (95% confidence interval, 0.80-1.30), respectively. CONCLUSIONS: In this long term follow-up study, local recurrences were found to be rare among patients with tumors > 0.8 mm thick and </= 2.0 mm thick. No difference in recurrence rate or survival between the two treatment groups was found. Patients in this category can be treated with a resection margin of 2 cm as safely as with a resection margin of 5 cm.

Adolescent↗

PubMed2000

Improvement of urge- and mixed-type incontinence after acupuncture treatment among elderly women - a pilot study.

The aim of this study was to investigate if sensory stimulation in the form of manual acupuncture could influence urge- or mixed-type incontinence among elderly women who were not satisfactorily relieved by standard pharmacological and non-pharmacological treatments given at a specialised incontinence unit. The study is an open clinical follow-up study. The study included 15 elderly women who were treated with manual acupuncture 12 times. Both subjective scorings and objective measurements in the form of leakage in grams (48 h Inco-test) were used. Evaluations were performed at discharge and 1 and 3 months thereafter. Almost all outcome measurements were significantly improved even at follow-up 3 months after the last treatment. Global scorings showed that 12 of the 15 women considered themselves improved even at the follow-up 3 month after treatments were completed. The possible mechanisms of action are discussed, as is the way to perform more studies in this field.

Acupuncture Therapy↗

PubMed2000

Prevalence of non-healed and healed chronic leg ulcers in an elderly rural population.

OBJECTIVE: To estimate the prevalence of non-healed and healed chronic leg ulcers in an elderly rural population. DESIGN: All persons 70 years or older were asked about present and previous leg ulcers. SETTING: A rural village in mid-west Sweden with 4000 inhabitants. PARTICIPANTS: 541 persons aged 70 years and above. OUTCOME MEASURES: The prevalence of healed or non-healed chronic leg ulcers in the population aged > or = 70. RESULTS: Healed or non-healed leg ulcers were reported by 53 persons (9.8%). Examination of these patients and also 100 individuals who had negated present or previous leg ulceration, giving the total prevalence of 12.6%. CONCLUSION: The result indicates a certain risk for overestimation of prevalence, as well as underestimation and decreased reliability when basing the figures only on telephone interviews or posted questionnaires.

Aged↗

PubMed2000

Localization of radiation-induced chromosomal breakpoints along human chromosome 1 using a combination of G-banding and FISH.

PURPOSE: To determine the exact location of radiation-induced chromosomal breakpoints along the euchromatic or heterochromatic regions: G-light and G-dark bands, respectively. MATERIALS AND METHODS: The distribution of radiation-induced chromosomal breakpoints was scored in human lymphocytes irradiated in vitro with 3 Gy of gamma-radiation. Image analysis was applied to combine G-banded and FISH-painted images of the human chromosome 1. RESULTS: A total of 195 chromosomal breakpoints in 176 cells with structural chromosomal aberrations was used for the present analysis. Radiation-induced breakpoints were found to be distributed randomly with respect to the p or q arms of chromosome 1 and specific band or band length, but more breakpoints were mapped to G-light than to G-dark bands, the difference being statistically significant. CONCLUSIONS: The results can well be interpreted in terms of concepts of existing models of nuclear architecture, chromatin structure and transcriptional activities of the chromatin, which can influence the induction of primary chromosomal aberrations by gamma-rays. Differential repair of randomly produced primary aberrations may also explain the non-random distribution of radiation-induced breakpoints.

Chromosome Aberrations↗

PubMed2000

Kinetics of formation of exchanges and rejoining of breaks in human G0 and G2 lymphocytes after low-LET radiation.

PURPOSE: To study the kinetics of chromosomal break rejoining and exchange formation in human G0 and G2 lymphocytes after low-LET irradiation using the premature chromosome condensation (PCC) technique. METHODS: For the G0 experiments, isolated human lymphocytes were irradiated (1, 3 and 8 Gy) and immediate and delayed fusions (1, 3, 5, 8 and 24 h) were performed with CHO-cells, and 48-h cultures were set up simultaneously. Interphase and metaphase human chromosomes were hybridized with dual colour combination probes for chromosomes 2 and 4. For the G2 experiments, isolated lymphocytes from the same donor were cultured for 69 h, irradiated with 3 Gy 60Co gamma rays and fused with CHO cells immediately and after 1, 2 and 3 h. Chromatid breaks and exchanges were scored after Giemsa staining. RESULTS: In both G0 and G2 cells, exchanges were already observed at the first fusion and, at lower doses, their frequencies remained relatively stable over time. The exchange-type aberrations seen in G0 cells were mostly incomplete, especially in the first fusions, while the exchanges seen in metaphase were mostly complete. The frequency of complete exchanges increased by time during incubation, while the frequency of incomplete exchanges showed more variation and a general decline by time in the G0-PCC experiment. The number of breaks declined rapidly by time both in G0 and G2. The break rejoining rate was higher at 8 Gy than in the two lower doses in the G0-PCC. The overall aberration frequencies in G0 and G2 cells studied by PCC were higher than in the corresponding metaphase. The initial number of breaks in G2 was higher than in G0 and the break rejoining rate in the G2 was two-fold. CONCLUSIONS: The formation of complete exchanges in G0 is a delayed process. The incomplete exchanges appear unstable in G0. The decreasing proportion of incomplete exchanges and simultaneous increase in complete exchanges in G0-PCC indicates that formation of exchanges is not coordinated in time.

Adult↗

PubMed2000

The value of cysteinyldopa in the follow-up of disseminated malignant melanoma.

In a series of 92 patients with malignant melanoma, clinical stage III or IV, both 5-S-cysteinyldopa (5SCD) and 6-hydroxy-5-methoxyindole-2-carboxylic acid (6H5MI2C) were measured in urine during chemotherapy. A total of 434 urine specimens were analysed. The sensitivity of 5SCD for the detection of stage III-IV melanoma was 83%, while the corresponding sensitivity of 6H5MI2C was 52%. Fifty per cent of patients with one metastatic site had increased 5SCD excretion, while all patients with four or more metastatic sites had increased excretion. A significant correlation was found between 5SCD decrease and clinical regression (P<0.001) and between 5SCD increase and clinical progression (P<0.001). Corresponding correlations were not found for 6H5MI2C. Increments in 5SCD excretion (median 269 micromol/mol creatinine) were seen for 83% of the occasions when clinical progression was recorded, and decrements in 5SCD excretion (median 145 micromol/mol creatinine) were seen for 85% of the occasions when clinical regression was seen. During clinical 'stable disease' increases in 5SCD excretion were seen in 59% and decreases in 41%. The median value of 5SCD changes for stable disease was 7.0 micromol/mol creatinine, indicating a chemical marker stability in many cases. We recommend the use of 5SCD in urine as a valuable, reliable and simple biochemical marker to use in the clinical follow-up of melanoma patients with advanced disease.

Adult↗

PubMed2000

Helicobacter pylori modulates lymphoepithelial cell interactions leading to epithelial cell damage through Fas/Fas ligand interactions.

Helicobacter pylori causes a common chronic infection of humans that leads to epithelial cell damage. Studies have shown that apoptosis of the gastric epithelium is increased during infection and this response is associated with an expansion of gastric T-helper type 1 (Th1) cells. We report that gastric T cells contribute to apoptosis of the epithelium by a Fas/Fas ligand (FasL) interaction. Fas receptor expression was detected on freshly isolated gastric epithelial cells by flow cytometry and immunohistochemistry, and this level of expression was increased during infection with H. pylori. The expression of Fas receptor on three gastric epithelial cell lines was increased by H. pylori, either alone or in combination with gamma interferon or tumor necrosis factor alpha. The role of Fas in apoptosis of gastric epithelial cell lines was evidenced by DNA fragmentation after cross-linking of Fas with specific antibodies. FasL expression was detected by immunohistochemistry on mononuclear cells in gastric biopsy specimens of infected but not uninfected subjects. Gastric T-cell lines were also shown to express FasL, as evidenced by reverse transcription-PCR and killing of target cells expressing Fas receptor. Moreover, these T-cell lines were capable of killing cultured gastric epithelial target cells and antibodies that block the interaction between Fas receptor and FasL inhibited this cytotoxic activity. These observations demonstrate that local Th1 cells may contribute to the pathogenesis of gastric disease during H. pylori infection by increasing the expression of Fas on gastric epithelial cells and inducing apoptosis through Fas/FasL interactions.

Adult↗

PubMed2000

Effect of visco-elastic foam mattresses on the development of pressure ulcers in patients with hip fractures.

This study had three aims: to investigate if visco-elastic foam mattresses are more effective than standard hospital mattresses in reducing the incidence of pressure ulcers in patients with hip fractures; to compare pressure ulcer grade and location and documented nursing prevention and treatment interventions in patients using the two types of mattresses; to identify possible predictors of pressure ulcer development. Using a prospective randomised controlled trial design 101 patients (mean age: 84 years) were randomly allocated either a visco-elastic foam mattress or a standard mattress. There was no significant difference in the incidence of pressure ulcers between the two groups, but patients on standard mattresses tended to develop more severe pressure ulcers. Furthermore, according to the documentation, patients with grade I pressure ulcers who were allocated a standard mattress received more preventive interventions, which may have reduced the differences in outcomes between the two groups. The researchers concluded that the results support the use of the test mattress. Significant predictors of pressure ulcer development were long waiting times for surgery and low haemoglobin levels at hospital admission.

Aged↗

PubMed2000

Role of tyrosine kinase signaling for beta-cell replication and survival.

Diabetes mellitus is commonly considered as a disease of a scant beta-cell mass that fails to respond adequately to the functional demand. Tyrosine kinases may play a role for beta-cell replication, differentiation (neoformation) and survival. Transfection of beta-cells with DNA constructs coding for tyrosine kinase receptors yields a ligand-dependent increase of DNA synthesis in beta-cells. A PCR-based technique was adopted to assess the repertoire of tyrosine kinases expressed in fetal islet-like structures, adult islets or RINm5F cells. Several tyrosine kinase receptors, such as the VEGFR-2 (vascular endothelial growth factor receptor 2) and c-Kit, were found to be present in pancreatic duct cells. Because ducts are thought to harbor beta-cell precursor cells, these receptors may play a role for the neoformation of beta-cells. The Src-like tyrosine kinase mouse Gtk (previously named Bsk/Iyk) is expressed in islet cells, and was found to inhibit cell proliferation. Furthermore, it conferred decreased viability in response to cytokine exposure. Shb is a Src homology 2 domain adaptor protein which participates in tyrosine kinase signaling. Transgenic mice overexpressing Shb in beta-cells exhibit an increase in the neonatal beta-cell mass, an improved glucose homeostasis, but also decreased survival in response to cytokines and streptozotocin. It is concluded that tyrosine kinase signaling may generate multiple responses in beta-cells, involving proliferation, survival and differentiation.

Adaptor Proteins, Signal Transducing↗

PubMed2000

Inequality in the social consequences of illness: how well do people with long-term illness fare in the British and Swedish labor markets?

The demand for unskilled labor has collapsed across industrialized societies, including Britain and Sweden, and rates of unemployment and economic inactivity have increased. The result is a reduction in total employment, primarily among men. These trends could be expected to hit particularly hard those people with chronic illness. The study tests two opposing hypotheses: (1) the increasingly flexible, deregulated labor market in Britain would result in an increased number of new jobs, and thus better employment opportunities for unskilled workers, including those with chronic illness; (2) the more regulated labor market in Sweden, with the associated health and social policies, would provide greater opportunities for jobs and job security for workers with chronic illness. Analysis of data on men from the British General Household Survey and the Swedish Survey of Living Conditions, 1979-1995, showed that employment rates were higher and rates of unemployment and economic inactivity were lower in Sweden than in Britain, and the differences in these rates across socioeconomic groups and between those with and without chronic illness were smaller in Sweden. The results support the hypothesis that active labor market policies and employment protection may increase the opportunities for people with chronic illness to remain in work.

Adult↗

PubMed2000

The development of pressure ulcers in patients with hip fractures: inadequate nursing documentation is still a problem.

The aims of the study were to investigate, on a daily basis: (i) the development and progress of pressure ulcers, (ii) the documented nursing interventions for prevention and treatment of pressure ulcers, and (iii) when nursing interventions regarding prevention and treatment of pressure ulcers were documented, in relation to patient risk status and the development of pressure ulcers. The study design was prospective, comparative and descriptive. A total of 55 patients with hip fracture were included. To facilitate the nurse's assessment, a 'pressure ulcer card' was developed, consisting of the Modified Norton Scale (MNS) and descriptions of the four stages of pressure ulcers. The incidence of pressure ulcers was 55%. The mean rank of the lowest MNS score was significantly lower for patients who developed pressure ulcers than for patients without pressure ulcers. The majority of the pressure ulcers occurred between admission to the ward and the fourth day after surgery. Documented interventions regarding prevention and treatment were: repositioning, overlays, cushions, use of lotion and observation. The mean number of interventions per patient was 2.2 for patients who developed pressure ulcers during their hospital stay. The comprehensiveness and quality of the nursing record was unsatisfactory, and only three nursing records reached the level required by Swedish law. Preventive interventions such as repositioning were documented when the pressure ulcer had already occurred. The lack of nursing documentation regarding prevention and treatment of pressure ulcers may indicate that nurses did not identify pressure ulcers as a prioritized nursing problem for this patient group. The Modified Norton Scale could be a valuable tool for nurses, both identifying the patient at risk and acting as a guide for nursing interventions. The study was approved by the ethics committee of the Faculty of Medicine at Uppsala University.

Aged↗

PubMed2000

Quantitative analysis of tyrosinase and tyrosinase-related protein-2 mRNA from melanoma cells in blood by real-time polymerase chain reaction.

Several studies have evaluated the use of polymerase chain reaction (PCR) amplification of tyrosinase mRNA to detect melanoma cells in blood. However, contradictory results have been obtained from different groups. We therefore have developed and validated a quantitative PCR method for tyrosinase and tyrosinase-related protein-2 (TRP-2) mRNA. An important methodological finding was that high concentrations of reverse transcriptase or RNA sample inhibited the following PCR. This could be abolished by dilution of the cDNA sample before the PCR. Standard curves with a linear range over at least five logs were obtained with dilutions of melanoma cell cDNA. Controls (RNA and cDNA) consisting of melanoma cells (1000/ml) added to blood were analysed repeatedly over 3 months, resulting in means between 880 and 1074 AU/ml. The RNA controls were stable, whereas the cDNA controls, as well as the calibrators, showed a tendency to change over time. The variation in the RNA controls was 25% for tyrosinase and 22% for TRP-2. Seven stage III-IV melanoma patients were tested for tyrosinase and TRP-2 transcripts in blood drawn from a peripheral vein and from a Port-a-cath. Tyrosinase mRNA was found in three patients (0.8-12.4 AU/ml). For TRP-2, the same amount was found in the patients as in healthy donors. No differences were seen between blood from a peripheral vein and from the Port-a-cath. We here present fast and sensitive methods for the quantification of tyrosinase and TRP-2 mRNA in blood.

Evaluation Studies as Topic↗

PubMed1999

[Infections and treatment of chronic leg ulcers: the use of antibiotics is too excessive, restrictive prescription is recommended].

Chronic venous leg ulcers are contaminated or colonised with bacteria that seldom affects ulcer healing. Signs of clinical infection appear in only a minority of chronic ulcers. In spite of this, data show a high consumption of antibiotics in this group of patients. Treatment with antibiotics is indicated only when clinical signs of infection or obvious risk factors are present or when Streptococcus pyogenes is isolated from the ulcer. In these cases an oral antistaphylococcal agent (semisynthetic penicillinase-resistant penicillin or first generation oral cephalosporin) is recommended as the first choice. Enterococci, anaerobic bacteria and gram-negative bacteria including pseudomonas spp. often colonise chronic ulcers, but do not usually cause antibiotic requiring infection.

Anti-Bacterial Agents↗