Search PubMed⌕ Search

Biomedical subjects

C Lindholm

Publications and source records attributed to C Lindholm.

At least 19 recordsLinked to original sources
PubMed2006

Chromosomal aberrations and SCEs as biomarkers of cancer risk.

Previous studies have suggested that the frequency of chromosomal aberrations (CAs), but not of sister chromatid exchanges (SCEs), predicts cancer risk. We have further examined this relationship in European cohorts comprising altogether almost 22,000 subjects, in the framework of a European collaborative project (CancerRiskBiomarkers). The present paper gives an overview of some of the results of the project, especially as regards CAs and SCEs. The results confirm that a high level of CAs is associated with an increased risk of cancer and indicate that this association does not depend on the time between CA analysis and cancer detection, i.e., is obviously not explained by undetected cancer. The present evidence indicates that both chromatid-type and chromosome-type CAs predict cancer, even though some data suggest that chromosome-type CAs may have a more pronounced predictive value than chromatid-type CAs. CA frequency appears to predict cancers at various sites, although there seems to be a particular association with gastrointestinal cancers. SCE frequency does not appear to have cancer predictive value, at least partly due to uncontrollable technical variation. A number of genetic polymorphisms of xenobiotic metabolism, DNA repair, and folate metabolism affect the level of CAs and might collectively contribute to the cancer predictivity of CAs. Other factors that may influence the association between CAs and cancer include, e.g., exposure to genotoxic carcinogens and internal generation of genotoxic species. Although the association between CA level and cancer is seen at the group level, an association probably also exists for the individual, although it is not known if an individual approach could be feasible. However, group level evidence should be enough to support the use of CA analysis as a tool in screening programs and prevention policies in occupational and environmental health.

Chromosome Aberrations↗
PubMed2006

Prediction of and risk factors for surgical wound infection in the saphenous vein harvesting leg in patients undergoing coronary artery bypass.

BACKGROUND: Surgical wound infection (SWI) of the leg after saphenous vein harvesting is an important complication of coronary artery bypass graft (CABG) procedures. SWIs may restrict mobility in the postoperative period and increase costs of postoperative hospitalisation and antibiotic treatment. METHODS: A total of 356 patients were followed. Surgical risk factors were evaluated for SWI following saphenous vein harvesting, and the effectiveness of an occlusive glycerinated hydrogel dressing in reducing postoperative SWIs was assessed. In addition, the ability of postoperative clinical wound assessment to predict SWI following CABG 30 and 60 days after operation was investigated. RESULTS: The most important risk factor for SWI after saphenous vein harvesting was the use of a monofilament suture for skin closure (glycomer 4-0 Biosyn Tyco Healthcare, Stockholm, Sweden) (p > 0.001). The hydrogel dressing did not prevent the development of SWIs. The clinical wound assessment showed that wound gap was associated with leg infection, but other signs were poor predictors of SWI. CONCLUSION: The choice of suture and suturing technique is important to prevent SWI following saphenous vein harvesting. More precise definitions of wound signs are necessary if they are to be used as predictors of SWI.

Adult↗
PubMed2005

Differential mechanisms for T lymphocyte recruitment in normal and neoplastic human gastric mucosa.

Worldwide, gastric adenocarcinoma (GC) is the second most common cause of death from malignant disease. The reason why immune responses are unable to clear the tumour is not fully understood, although aberrant lymphocyte recruitment to the tumour site might be one factor. Therefore, we investigated the homing phenotype of mucosal T lymphocytes in GC, compared to tumour-free mucosa. We could detect significantly decreased frequencies of mucosal homing alpha4beta7+ T cells in the tumour tissues and increased frequencies of L-selectin+ T cells. This was probably due to the correlated decrease in MAdCAM-1 positive and increase in PNAd positive blood vessels in the tumour mucosa. There were also fewer CXCR3+ T lymphocytes in the tumour tissue. These findings provide evidence that endothelial cells within tumours arising at mucosal sites do not support extravasation of typical mucosa-infiltrating T cells. This may be of major relevance for future immunotherapeutic strategies for treatment of GC.

Adenocarcinoma↗
PubMed2005

Peri-operative glucose control and development of surgical wound infections in patients undergoing coronary artery bypass graft.

Elevated blood glucose following coronary artery bypass graft (CABG) is associated with an increased risk of surgical wound infection (SWI). It is unclear whether hyperglycaemia, the diabetic state, the longstanding vascular effects of diabetes, or the systematic inflammatory response confers the increased vulnerability to SWI. This study was designed to examine the significance of postoperative blood glucose control as a risk factor for SWI after vein graft harvesting on the leg and sternotomy. Patients with and without diabetes had a CABG within 60 days to be eligible. The present study was part of a larger protocol investigating SWI following CABG in a total of 374 patients. Potential risk factors, duration of diabetes, pre-operative glycated haemoglobin (HbA(1c)) and presence of long-term complications were recorded. All patient records were reviewed retrospectively to record 10% glucose infusions during the operation, and blood glucose concentrations and insulin therapy on postoperative days 0, 1 and 2. Patients were contacted by telephone 30 and 60 days after surgery and interviewed in accordance with a questionnaire about symptoms and signs of wound infection. In the present study, it was not possible to separate the effect of diabetes as a risk factor for SWI from that of hyperglycaemia. However, in the subgroup of patients without a pre-operative diagnosis of diabetes, increased blood glucose concentrations during postoperative days 0, 1 and 2 was associated with an increased risk of mediastinitis.

Aged↗
PubMed2005

Translocation yields in peripheral blood lymphocytes from control populations.

PURPOSE: To record the latest information on control levels of translocations in cultured human lymphocytes. MATERIALS AND METHODS: Control-level data from seven European laboratories that are using fluorescence in situ hybridization (FISH) techniques for retrospective biological dosimetry have been combined in a meta-analysis. After correction for the differing probe combinations used, tests of consistency are performed. The combined data have been used to test for individual variation, systematic variation with age, gender and smoking habits. RESULTS: There is a strong variation of translocation yield with age but no variation was detectable with gender or smoking habits. After correction for age, homogeneity tests showed that about 10% of individuals were outside the 95% confidence limits as opposed to 5% expected. From a total of 385, there is an excess of about 20 individuals most of whom have an unexpectedly high yield of translocations. CONCLUSIONS: For retrospective biological dosimetry purposes a generic age-dependent control level can be assumed. No other lifestyle factors such as smoking appear to have a significant effect on translocation yield.

Adolescent↗
PubMed2005

Review of translocations detected by FISH for retrospective biological dosimetry applications.

Several European laboratories have combined their research efforts to arrive at a consensus view on using fluorescence in situ hybridisation (FISH) for retrospective dosimetry. The aim of this review is to report these views and to highlight some areas where further work is needed. Translocations in the stable cells should be measured only in the cells that contain the full complement of the painted material. Two-way and one-way translocations should be combined with equal weight. The control level of translocations has a strong dependence on age, which has now been measured and the system has been calibrated. In conclusion, the technique works and a lifetime dose to the bone marrow from low-linear energy transfer radiation of 0.5 Gy above normal background levels can be measured for any individual. The main application is considered to provide an independent verification of lifetime doses to individuals who might form a part of an epidemiological study.

Calibration↗
PubMed2005

Down-regulation of epithelial IL-8 responses in Helicobacter pylori-infected duodenal ulcer patients depends on host factors, rather than bacterial factors.

Helicobacter pylori infection is one of the most common gastrointestinal infections worldwide. Although the majority of the infected individuals remain asymptomatic carriers of the bacteria, approximately 15% develop peptic ulcers, which are most prevalent in the duodenum. H. pylori induce a vigorous immune response which, however, fails to clear the infection. Instead, the chronic inflammation that arises in the infected gastroduodenal mucosa may be involved in the development of H. pylori-associated peptic ulcers. We have previously shown that duodenal ulcer (DU) patients have a significantly lower epithelial cytokine, e.g. IL-8, response in the duodenum than asymptomatic (AS) carriers. In this study we have further investigated the mechanisms behind this finding, i.e. whether it can be explained by bacterial factors, down-regulation of epithelial cytokine production by regulatory T cells, or an impaired ability of the duodenal epithelium in DU patients to produce cytokines. Gastric AGS, and intestinal T84 epithelial cell lines were stimulated with H. pylori strains isolated from DU patients and AS carriers, respectively. All strains were found to induce comparable cytokine and cytokine receptor expression in epithelial cells. Regulatory T cells (CD4+ CD25(high)), isolated from human peripheral blood and cocultured with H. pylori stimulated AGS cells, were found to slightly suppress H. pylori-induced epithelial cytokine production. Furthermore, primary cultures of duodenal epithelial cells from DU patients were found to produce markedly lower amounts of cytokines than epithelial cells isolated from AS carriers. These results suggest that the lower epithelial cytokine responses in the duodenum of DU patients, which may be of importance for the pathogenesis of H. pylori-induced duodenal ulcers, most likely can be explained by host factors, i.e. mainly a decreased ability of the duodenal epithelium to produce cytokines, but possibly partly also down-regulation by regulatory T cells.

CD4-Positive T-Lymphocytes↗
PubMed2005

Wounds scrutiny in a Swedish hospital: prevalence, nursing care and bacteriology, including MRSA.

OBJECTIVE: To identify all wounds, wound types and wound characteristics; to identify bacteria in all wounds, particularly MRSA, VRE and multi-resistant Gram-negative rods;. METHOD: All patients admitted to or visiting hospital clinics were examined. If the patient had a wound, a questionnaire was filled in by a nurse, and if the wound met the inclusion criteria swabs were taken. RESULTS: A total of 2172 patients were admitted to or visited the hospital; 408 (19%) had a total of 668 wounds. Of this number, 248 were cultured. Thirty-seven patients had pressure ulcers, 83 had leg and foot ulcers and 288 patients had other types of wounds. Nursing care varied according to wound type and ward. Fifty-eight different types of wound dressings were used. Cleansing was performed with saline in 58% of the wounds. The mean number of dressing changes was once daily. Wounds were painful in 37% of the cases, with a predominance of leg and foot ulcers (51%). Many patients did not receive analgesia. MRSA was identified in two patients. No VRE was identified, and there was a low prevalence of multi-resistance in Enterobacteriaceae and Pseudomonas aeruginosa. CONCLUSION: The study provided important information for future improvement of wound care in a university hospital. Fewer resistant bacteria, particularly MRSA, were identified than expected.

Adolescent↗
PubMed2004

Surgical-site infections within 60 days of coronary artery by-pass graft surgery.

Surgical wound infections (SWIs) after coronary artery by-pass graft (CABG) within 30 and 60 days of operation were registered. Already known risk factors and possible risk factors for wound infection were studied. SWIs of sternal and/or leg wounds have been reported to occur in 2-20% of patients after CABG. Deep sternal infection, mediastinitis, occurs after 0.5-5% of CABG procedures. The duration and methods of follow-up, as well as definitions of SWI, vary in different studies. Previously known and possible new risk factors were registered for 374 patients. Patients were contacted by telephone 30 and 60 days after surgery and interviewed in accordance with a questionnaire about symptoms and signs of wound infections. Our definition of SWI was based on the Centers for Disease Control and Prevention (CDC) definition. SWIs were diagnosed in 114 of 374 (30.5%) of the patients. In total SWI were diagnosed in 120 surgical-site incisions. Almost all SWIs of the sternum (93.3%) were diagnosed within 30 days of surgery. Most of the SWIs of the leg (73%) were diagnosed within 30 days of surgery and 27% were diagnosed within 31 to 60 days of surgery. Being female was the most important risk factor for SWI of the leg. Low preoperative haemoglobin concentrations were the most important risk factor for superficial SWI on the sternum. Patients with mediastinitis had higher BMI and had more often received erythrocyte transfusions on postoperative day two or later than those without infections.

Adult↗
PubMed2004

Long-term persistence of translocations in stable lymphocytes from victims of a radiological accident.

PURPOSE: To investigate whether translocations in 'stable' lymphocytes, i.e. those not containing unstable aberrations in any chromosome including counterstained ones, would have a longer persistence with time compared with those measured in all cells. MATERIALS AND METHODS: The time-course of chromosomal aberrations in the three most highly exposed radiation victims of an Estonian accident in November 1994 was followed for 7 post-accident years encompassing 15 samples. Chromosome painting was performed using probes for chromosomes 1, 2 and 4 with a pan-centromeric probe, and chromosomal aberrations involving the painted chromosomes were scored using a developed version of the Protocol for Aberration Identification and Nomenclature Terminology (PAINT) nomenclature. Metaphases containing aberrations were captured with an image analyser and stored on a computer. An earlier analysis of aberrations in the painted portion of the genome was performed in all cells, irrespective of the possible aberrations in the unpainted part of the genome. The present analysis has taken into account the 'stable/unstable' nature of the complete cell. Evaluation was performed on images, counting all chromosomes and checking the counterstained chromosomes for unstable aberrations, i.e. dicentrics, acentrics or ring chromosomes. RESULTS: In the original analyses of all cells, a decrease in translocation frequency in the early samples was observed. In the present study of stable cells, the results showed that the yield of translocations is constant with time. CONCLUSIONS: The results show that translocations observed in stable cells are persistent with time. This implies that retrospective dosimetry and calibration should be performed using stable cells. To obtain more information on this issue, the stability status of all cells in any future fluorescence in situ hybridization follow-up of a radiation accident should be noted.

Humans↗
PubMed2003

O6-methylguanine-DNA-methyltransferase expression and gene polymorphisms in relation to chemotherapeutic response in metastatic melanoma.

In a retrospective study, O(6)-methylguanine-DNA-methyltransferase (MGMT) expression was analysed by immunohistochemistry using monoclonal human anti-MGMT antibody in melanoma metastases in patients receiving dacarbazine (DTIC) as single-drug therapy or as part of combination chemotherapy with DTIC-vindesine or DTIC-vindesine-cisplatin. The correlation of MGMT expression levels with clinical response to chemotherapy was investigated in 79 patients with metastatic melanoma. There was an inverse relationship between MGMT expression and clinical response to DTIC-based chemotherapy (P=0.05). Polymorphisms in the coding region of the MGMT gene were also investigated in tumours from 52 melanoma patients by PCR/SSCP and nucleotide sequence analyses. Single-nucleotide polymorphisms (SNPs) in exon 3 (L53L and L84F) and in exon 5 (I143V/K178R) were identified. There were no differences in the frequencies of these polymorphisms between these melanoma patients and patients with familial melanoma or healthy Swedish individuals. Functional analysis of variants MGMT-I143V and -I143V/K178R was performed by in vitro mutagenesis in Escherichia coli. There was no evidence that these variants decreased the MGMT DNA repair activity compared to the wild-type protein. All melanoma patients with the MGMT 53/84 polymorphism except one had tumours with high MGMT expression. There was no significant correlation between any of the MGMT polymorphisms and clinical response to chemotherapy, although an indication of a lower response rate in patients with SNPs in exon 5 was obtained. Thus, MGMT expression appears to be more related to response to chemotherapy than MGMT polymorphisms in patients with metastatic melanoma.

Adult↗
PubMed2003

Increased frequency of activated T-cells in the Helicobacter pylori-infected antrum and duodenum.

Helicobacter pylori colonize the human stomach and duodenum. The infection has been shown to induce a strong T-cell response in the stomach, whereas the response within the duodenum has been poorly characterized. Furthermore, it remains to be elucidated whether the T-cell response may contribute to ulcer formation in the host. In this study, the frequency of different T-cell subsets, their degree of activation and expression of co-stimulatory receptors in biopsies from the duodenum as well as the antrum were studied by immunohistochemistry and flow cytometry. It was also evaluated whether there are differences in the T-cell responses between duodenal ulcer patients and asymptomatic carriers that might explain why only 10-15% of the infected subjects develop duodenal ulcers. The frequencies of CD4+, CD8+ and CD45RO+, i.e. memory T-cells, were significantly increased in the antrum, and the number of CD25+ cells was considerably higher in both the antrum and duodenum of duodenal ulcer patients and asymptomatic carriers as compared to uninfected individuals. Interestingly, the levels of immunosuppressive CTLA-4+ cells were significantly higher in the duodenum of duodenal ulcer patients, as compared to the asymptomatic carriers. H. pylori cause activation of T-cells in the duodenum as well as in the stomach. Our observation of higher levels of CTLA-4+ cells in the duodenum of duodenal ulcer patients than in the asymptomatic carriers suggests that a suppressive T-cell response may be related to the development of duodenal ulcers.

Adult↗
PubMed2003

Decreased epithelial cytokine responses in the duodenal mucosa of Helicobacter pylori-infected duodenal ulcer patients.

Helicobacter pylori colonizes the human stomach and areas of gastric metaplasia in the duodenum, but only a minority of those that are infected develop symptoms, e.g., peptic ulcers. Although most ulcers occur in the duodenum, almost all studies of mucosal immune responses against the infection have been limited to responses in the stomach. In the present study we evaluated whether there are differences in the levels of proinflammatory cytokines as well as immunoregulatory cytokines in the duodenal mucosa of duodenal ulcer (DU) patients and asymptomatic (AS) carriers which may be related to the development of duodenal ulcers. Duodenal biopsy specimens collected from normal mucosa as well as metaplastic mucosa of DU patients, AS carriers, and uninfected controls were analyzed for a number of cytokines by immunohistochemistry. Interestingly, the level of epithelial staining for several cytokines, e.g., interleukin-8 (IL-8), transforming growth factor beta (TGF-beta), and gamma interferon (IFN-gamma), was found to be significantly lower in DU patients than in AS carriers and uninfected individuals. No differences were observed when cytokine staining in normal and metaplastic biopsy specimens was compared. However, larger numbers of IL-8-, IL-6-, TGF-beta-, and IFN-gamma-positive mononuclear cells were observed in the duodenal lamina propria of both DU patients and AS carriers than in that of the uninfected controls. Our finding that a number of cytokines that may be important for the mucosal host defense against H. pylori are strongly decreased in the duodenal epithelium of ulcer patients suggests that a down-regulated immune response plays a role in the development of duodenal ulcers.

Adult↗
PubMed2002

Intercomparison of translocation and dicentric frequencies between laboratories in a follow-up of the radiological accident in Estonia.

PURPOSE: To perform an interlaboratory comparison of FISH chromosome painting and to study the time-course of translocations and dicentrics in three accident victims exposed to radiation. Also, to use the data in the validation of the FISH technique as a retrospective dosimeter. MATERIALS AND METHODS: Twelve blood samples were collected during 4 years from three subjects exposed to radiation in an accident in Estonia in 1994 involving gamma-radiation from a 137Cs source. Two of the subjects were exposed during approximately 7 h, both receiving a protracted dose of about 1 Gy and also localized exposure. The third subject received a protracted whole-body dose of 2.7 Gy during 4 weeks as well as a short-term partial-body dose. Preparations from 48-h metaphase cultures were painted by the FISH technique using routine methods and probe cocktails in four laboratories. Samples from each subject were analysed in two different laboratories that used different combinations of whole chromosome probes. The PAINT nomenclature was applied when recording chromosome aberrations. RESULTS: The intercomparison of FISH analysis data showed reasonable similarities between laboratories, the largest discrepancy being 21% in the frequency of two-way translocations in subject 3. Half-time calculations, based on combined data sets from two laboratories, showed that dicentrics decreased rapidly with half-times of approximately 2 years. In all cases, the initial dicentric yields were lower than the initial translocation yields. During the 4-year follow-up, the frequencies of all translocations in cells containing only simple rearrangements fell on average to about 65% of their initial value. Two-way translocations were slightly more persistent than all translocations. The average half-time was about 8 years for two-way translocations and around 6 years for all translocations. Cells containing complex rearrangements were few in number and they disappeared with time. In general, the inclusion of complex cells caused a more rapid fall in aberration yield. CONCLUSIONS: In general, the results imply that relatively consistent scoring data were obtained with different chromosome painting protocols. They also support the idea that the reduction of translocations with time is associated with partial-body irradiation.

Adolescent↗
PubMed2002

Class differences in the social consequences of illness?

STUDY OBJECTIVE: To investigate adverse social consequences of limiting longstanding illness and the modifying effect of socioeconomic position on these consequences. DESIGN: Cohort study on the panel within the annual Swedish Survey of Living Conditions where participants were interviewed twice with eight years interval 1979-89 and 1986-97. Sociodemographic characteristics, self reported longstanding illness, employment situation and financial conditions were measured at baseline. Social consequences (economic inactivity, unemployment, financial difficulties) of limiting longstanding illness were measured at follow up eight years later. SETTING: National sample for Sweden during a period that partly was characterised by high unemployment and reduction in insurance benefits. PARTICIPANTS: PARTICIPANTS were 13 855 men and women, economically active, not unemployed, without financial difficulties at the first interview and aged 25-64 years at the follow up. MAIN RESULTS: Persons with limiting longstanding illness had a higher risk of adverse social consequences than persons without illness. The effect was modified by socioeconomic position only for labour market exclusion while the effects on unemployment and financial difficulties were equal across socioeconomic groups. CONCLUSIONS: Labour market policies as well as income maintenance policies that deal with social and economical consequences of longstanding illness are important elements of programmes to tackle inequalities in health. Rehabilitation within health care has a similar important part to play in this.

Activities of Daily Living↗
PubMed2002

Towards a standardization of biological dosimetry by cytogenetics.

When individuals are accidentally overexposed to ionising radiations, follow-up investigations may include dose assessment by cytogenetics. Scoring of unstable chromosome aberrations (dicentrics, centric rings and acentrics) in peripheral blood lymphocytes is regarded as the most specific method to estimate the exposure dose. It has acquired, in some countries, a medico-legal recognition. Paradoxically, there is no universally adopted technique and so important variations occur in methods and these may influence the quality of results. The only published documents supplying some standardization background are International Atomic Energy Agency (IAEA) Technical Reports No 260 (1986) and 405 (2001). Even they do not address crucial areas such as the organization of service laboratories and the need for quality assurance programmes. The significant role of biological dosimetry in many countries has proved the need for a standardized technique that is compatible with national radiological protection programmes. Thus, an International Standards Organization working group for the standardization of biological dosimetry by cytogenetics was created. This group comprises 13 scientists from 11 countries plus an IAEA representative. On the basis of a group consensus, a text defining minimal constraints on all the steps of the process was proposed. A working draft was submitted to ISO in 2001 and its structure is presented here.

Animals↗
PubMed2001

Risk, prevention and treatment of pressure ulcers--nursing staff knowledge and documentation.

The aims were to investigate (i) registered nurses' and nursing assistants' knowledge of risk, prevention and treatment of pressure ulcer before implementing a system for risk assessment and pressure ulcer classification for patients with hip fracture (ii) interventions documented in the patient's records by registered nurses, and (iii) to what extent reported and documented interventions accord with the Swedish quality guidelines. Nursing staff (n=85) completed a questionnaire, and patient's records (n=55) were audited retrospectively. The majority of the nursing staff reported that they performed risk assessment when caring for a patient with hip fracture. These risk assessments were, however, not comprehensive. The most frequently reported preventive interventions were repositioning, use of lotion, mattresses/overlays and cushions for the heels. These interventions were to some extent documented in the patient's records. Nutritional support, reduction of shear and friction, hygiene and skin moisture, and patient's education were reported to a small extent and not documented at all. The Swedish quality guidelines regarding prevention and treatment of pressure ulcers were not fully implemented in clinical practice. It was concluded that nursing staff's knowledge and documentation of risk, prevention and treatment of pressure ulcers for patients with hip fractures could be improved.

Aged↗