Chronic leg ulcers: the impact of venous disease.
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Chronic Disease↗
Biomedical subjects
C Lindholm
Publications and source records attributed to C Lindholm.
Expression of tissue-type and urokinase-type plasminogen activator activities in chronic venous leg ulcers.
BACKGROUND: Chronic wounds have been shown to exhibit elevated levels of several classes of proteinases. Plasminogen activators (PAs) are proteinases which play a major role in the biological processes involved in wound healing and abnormalities in PAs may play a role in the pathology associated with chronic wounds. Here, we investigated the expression of tPA and uPA activities in chronic venous ulcer biopsies. PATIENTS AND METHODS: In 22 patients with chronic venous leg ulcers, punch biopsies were taken from the ulcer base, ulcer margin and uninvolved skin from the thigh of the affected limb and PA activities were assessed using in situ histological zymography. RESULTS: tPA is the main PA activity in uninvolved skin but was reduced in ulcer margin skin and venous leg ulcer tissue compared to normal skin. uPA activity appeared throughout the ulcer margin skin but was at low levels in normal skin. Ulcer base tissue appeared to exhibit a plasminogen-independent proteinase activity not seen in normal or ulcer margin skin. CONCLUSION: PA activities are altered in and around chronic venous leg ulcers and their distribution suggests that blood vessels in CVI may be damaged and that the tissue is in an inflamed state.
Aged↗
Implementation of risk assessment and classification of pressure ulcers as quality indicators for patients with hip fractures.
The aims of the study were (i) to investigate the prevalence of pressure ulcers in patients with hip fracture, on arrival at a Swedish hospital, at discharge, and two weeks post-surgery; (ii) to test whether clinical use of the Modified Norton Scale (MNS) could identify patients at risk for development of pressure ulcers; and (iii) to compare the reported prevalence of pressure ulcer in the experimental group, where risk assessment and classification of pressure ulcers was performed on a daily basis, with that of the control group, where it was not. The study design was prospective, with an experimental and a control group. The intervention in the experimental group consisted of risk assessment, risk alarm and skin observation performed by the nurse on duty, in the A & E Department, and daily throughout the hospital stay. To facilitate the nurse's assessment, a 'Pressure Ulcer Card' was developed, consisting of the MNS and descriptions of the four stages of pressure ulcers. On arrival at the hospital, approximately 20% of patients in both groups had pressure ulcers. At discharge, the rate had increased to 40% (experimental) and 36% (control). Clinical use of the MNS made it possible to identify the majority of patients at risk for development of pressure ulcers. Patients who were confused on arrival developed significantly more pressure ulcers than patients who were orientated to time and place. No significant difference was found in the reported prevalence of pressure ulcers between the experimental and control groups.
Aged↗
Distribution of radiation-induced exchange aberrations in human chromosomes 1, 2 and 4.
PURPOSE: To examine the distribution of radiation-induced breakpoints in chromosomes 1, 2 and 4 both in relation to their DNA content and by localization of the breaks along each chromosome. MATERIAL AND METHODS: The work consisted of two studies, one with chromosomal aberrations found in persons after accidental exposure in Estonia in 1994 and another involving aberrations seen in in vitro-irradiated lymphocytes. Localization of breakpoints in painted chromosomes involved in complete exchange-type aberrations was conducted by applying a computerized measuring system on stored image-files. RESULTS AND CONCLUSIONS: The yield of exchanges in chromosomes 1, 2 and 4 in both studies was equal to that expected from their DNA content. In contrast, the breakpoint location of complete exchanges within these chromosomes was not random. Chromosomes 1 and 4 contained more breaks in the middle parts of the p and q arms, whereas breaks were observed more uniformly along chromosome 2. Complete exchanges, however, were very rare in the terminal regions of all three chromosomes, most probably resulting from limitations in the resolution of small painted pieces.
Cell Culture Techniques↗
Domestic radon exposure and the frequency of stable or unstable chromosomal aberrations in lymphocytes.
PURPOSE: To clarify the relationship between domestic radon exposure and the occurrence of chromosomal aberrations, stable translocations especially, in peripheral blood lymphocytes. MATERIALS AND METHODS: The study comprised a total of 84 nonsmoking individuals, divided into three groups according to radon concentration measurements performed in their homes: low radon concentration (<100Bq/m3, mean 67Bq/m3), medium (200-400Bq/m3, mean 293Bq/m3) or high (>800Bq/m3, mean 1737Bq/m3). Minimum residence in the present low-rise house was 10 years. The groups were matched with regard to age, gender and medical exposure. Fluorescence in-situ hybridization (FISH) was performed using chromosome paints for chromosomes 1, 2 and 4; 1500 metaphases were scored from each individual. RESULTS: Equal frequencies of translocations and also other aberrations, e.g. dicentrics and complex rearrangements, were obtained in each group. Significant correlation of translocations with age was observed, and due to the high mean age (50 years) the genome-corrected frequency of translocations was high: about one translocation in 100 metaphases. CONCLUSIONS: Chronic exposure to high concentrations of domestic radon did not increase the rate of stable or unstable chromosomal aberrations in peripheral blood lymphocytes detected by FISH chromosome painting. A strong age effect was observed.
Adult↗
Role of local cytokines in increased gastric expression of the secretory component in Helicobacter pylori infection.
Using immunohistochemical staining, we examined the presence of secretory component (SC) on epithelial cells in gastric and duodenal biopsy specimens collected from Helicobacter pylori-infected individuals and healthy controls. Gastric epithelial cells from healthy volunteers expressed low, but detectable, levels of SC. In contrast, significantly higher level of expression of SC (P < 0.001) was observed on epithelial cells in the antra of H. pylori-infected individuals. The antral SC expression correlated with staining for gamma interferon of intraepithelial and lamina propria lymphocytes (r(s) = 0.76 and 0.69, respectively, P < 0.001) and correlated weakly with production of tumor necrosis factor alpha (r(s) = 0.43, P < 0.05), but it did not correlate at all with interleukin-4 production.
Adult↗
Chronic wounds and nursing care.
This study has collated data on the prevalence of chronic wounds and the demography of patients with these wounds. Diagnostic methods, nursing care, the presence of diabetes and pain are analysed, as well as data on healing, amputation and mortality three months post-study. A total of 694 patients were identified: 406 with leg or foot ulcers, 117 with pressure ulcers and 171 with other wounds. Most patients were treated in the community. Leg ulcer aetiology was verified with ultrasound Doppler examination. There was a correlation between low Norton score (< 20) and severity of pressure ulcer (Stage III or IV). The use of 113 different wound dressings or combinations of products was reported. Time spent on dressing changes was the equivalent of full-time employment for 57 nurses. Wound cleansing was not predominantly performed with tap water, as recommended, but with saline. Almost all patients with venous leg ulcers (88%) were treated with compression but in 35% of these support stockings were used. Pain was present in almost half of all patients, more commonly in Stage III or IV pressure ulcers than in Stages I and II, and was most often reported in older patients. Diabetes was present in 25% of all patients with leg and pressure ulcers, and in 57% of patients with foot ulcers. At three-month follow-up, 28% of pressure ulcers, 40% of leg ulcers and 61% of other wounds had healed. Mortality was 35% in patients with pressure ulcers, 4% in those with leg ulcers and 7% in those with foot ulcers. These data have been presented to politicians in the county, resulting in allocation of resources for a wound healing centre.
Adult↗
A follow-up study of leg ulcer patients in south Stockholm.
The objective of this study was to follow up patients with leg ulcers, previously identified in an epidemiological study in South Stockholm. Rate of healing, non-healing, recurrence, amputation and mortality were recorded. A total of 254 patients were identified for follow-up after 18 months, 217 of whom were included. The use of a questionnaire revealed that, during this period, 43 (20%) of the patients had died; of the remaining 174 patients, 61% had healed, 29% were unhealed, 8% had recurring ulceration after healing; 2% had required amputation. Venous aetiology was found to be more common than arterial aetiology. However, among those who had died, arterial disease was found to be more common than venous insufficiency. A further objective was to investigate 21 patients with non-healed venous leg ulcers who had been treated in community care. They were assessed by means of a standardised form and given a triple-layer bandaging treatment for a three-month period. Two ulcers had healed and nine ulcers had improved and were healing. In the group of patients with healed or improved ulcers, five had normal mobility.
Adult↗
Aspirin-induced gastritis, like Helicobacter pylori-induced gastritis disinhibits acid secretion in humans: relation to cytokine expression.
BACKGROUND: Helicobacter pylori infection contributes to hypergastrinemia and hypersecretion of acid by blocking inhibitory reflex pathways to gastrin and parietal cells normally activated by antral distention. Our aim was to investigate whether a similar blockade of inhibitory responses could be provoked by inducing gastritis with aspirin, thus implicating a common inflammatory component, possibly a proinflammatory cytokine(s). METHODS: We studied the effects of antral distention on stimulated acid secretion and gastrin release in H. pylori-negative volunteers, before and after 3 days of aspirin therapy (2 g daily). Immediately before the examinations, the severity of gastric mucosal injury was evaluated macroscopically and histologically, and the production of interleukin (IL)-1beta, IL-6, IL-8, tumor necrosis factor (TNF)-alpha, and interferon (IFN)-gamma was determined by immunohistochemistry. RESULTS: Most subjects had severe gastric injury after aspirin therapy, resulting in a substantially increased production of IL-1beta, IL-6, and IL-8 but not of TNF-alpha and IFN-gamma in the antral mucosa. In these subjects the acid-inhibitory response was abolished or markedly reduced. Conversely, aspirin therapy failed to affect the gastrin release in all subjects studied. CONCLUSIONS: The disinhibition of acid secretion in response to antral distention is a joint feature of the gastritis induced by aspirin and H. pylori infection, possibly related to the increased production of IL-1beta, IL-6, and IL-8. The H. pylori-related hypergastrinemia apparently has a different background.
Adult↗
Chromosomal instability in in vivo radiation exposed subjects.
PURPOSE: To investigate whether delayed chromosomal instability arises in human peripheral T lymphocytes exposed in vivo to gamma-irradiation. MATERIALS AND METHODS: Long-term cultures were established from lymphocytes obtained from subjects involved in the radiological accident in Estonia in 1994. Two individuals exposed to a high dose, one individual with low exposure and one apparently unexposed person were studied. Two Estonian controls not involved with the accident were also analysed. Cells were grown for 6-42 days and chromosomal aberrations were assessed from G-banded metaphases. In addition, FISH chromosome painting analysis was performed on short-term cultures established from whole blood. RESULTS: No obvious sign of chromosomal instability was observed in the in vivo follow-up of the frequencies of chromosomal aberrations in lymphocytes of radiation accident victims performed by the FISH technique (48 h cultures established at different time intervals after the exposure). However, when the lymphocytes were cultured long term in vitro, chromosomal instability was observed. There was no dose-response, and the appearance of chromosomally unstable cells in long-term cultures was also observed in a subject exposed to a dose of less than 0.1 Gy. Moreover, in contrast with previous findings, chromosomal instability was also observed in cells from non-exposed control individuals. The chromosomal changes observed in the controls were less complex than the aberrations in the cultures derived from individuals exposed to high doses. CONCLUSIONS: Chromosomal instability was observed in long-term cultures of donors with in vivo exposure to gamma-radiation. No dose-response was apparent. However, in contrast with previous findings, signs of chromosomal instability were observed also in long-term cultures from non-exposed controls. Further studies are needed to assess possible inter-individual differences in the induction of chromosomal instability.
Adolescent↗
The incidence of cytogenetically abnormal rogue cells in peripheral blood.
PURPOSE: To compare the occurrence of cytogenetically abnormal rogue cells, characterized by a high frequency of chromosome-type aberrations, in people exposed to ionizing radiation and in non-exposed subjects. MATERIALS AND METHODS: Data on rogue cells from a total of nine cytogenetic studies on radiation-exposed populations and controls were collected from three laboratories in the United Kingdom, France and Finland. The studies were conducted on first-division metaphases of peripheral blood lymphocytes. Solid Giemsa-stained, G- or R-banded and FISH chromosome-painted material was included. RESULTS: Rogue cells were found both from controls and from exposed subjects. The highest incidence of these cells was observed in a control group of young trainees (1:400), whereas the lowest incidence of rogue cells (1:36 500) was demonstrated in a follow-up study of people accidentally exposed to high levels of ionizing radiation. Rogue cells were found to be distributed non-randomly among individuals; the highest individual frequency was 1 in 50 analysed metaphases. CONCLUSIONS: The origin of rogue cells is still unclear. The incidence of rogue cells showed a large variability between studies and individuals. No correlation between long-term radiation exposure and the occurrence of rogue cells was demonstrated. Although the presence of rogue cells in astronauts after a 6 month space flight may be attributable to high-LET radiation, the frequencies were not remarkable when compared with those in the other studies in this review.
Azure Stains↗
Persistence of translocations after accidental exposure to ionizing radiation.
PURPOSE: To assess the validity of translocations for retrospective biodosimetry using FISH chromosome painting of peripheral lymphocytes in repeated samples of people accidentally exposed to radiation. MATERIALS AND METHODS: Blood samples from five people exposed to mainly whole-body irradiation of gamma-rays from a radiation accident in Estonia in 1994 were taken at 2-4 month intervals. A total of eight samplings were carried out, including one directly after the accident. Fluorescence in situ hybridization with probes for chromosomes 1, 2 and 4 was performed on metaphase preparations from 48 h whole blood cultures; 1500 cells were scored from each individual per time point. RESULTS: Translocations remained relatively stable during 2 years after exposure in all subjects. A noticeable decrease in complete translocation yields and a significant decrease in incomplete translocations were observed in one person. In addition to whole-body exposure, he had also been exposed to partial-body irradiation. Due to the overall persistence of translocations, dose estimates were very similar throughout the 2 year period. A rapid decline in dicentric frequencies was noted during the first year after exposure. CONCLUSIONS: The results suggest that during 2 years the yield of translocations in peripheral lymphocytes remained at a constant level after whole-body exposure. This finding supports the use of translocations for retrospective dosimetry, at least within this relatively short period of follow-up. In the case of partial-body irradiation, however, the elimination of co-existing unstable aberrations reduced the translocation yield over time. Follow-up will be continued in order to determine the stability of translocations over longer times.
Cesium Radioisotopes↗
Comparison of dose-response curves for chromosomal aberrations established by chromosome painting and conventional analysis.
PURPOSE: To establish 60Co gamma-ray dose-response curves for dicentrics and translocations visualized by chromosome painting and for dicentrics analysed after conventional solid staining. MATERIALS AND METHODS: Analysis of chromosomal aberrations was performed on peripheral blood lymphocytes obtained from 48 h old cultures of irradiated whole blood. Dicentrics were scored from Giemsa-stained preparations, and bi-coloured dicentrics and translocations after FISH painting of chromosomes 1, 2 and 4. RESULTS: Equal frequencies of complete dicentrics and translocations, where both members of the exchanges were seen, were observed in the chromosome painting analysis at all doses, resulting in similar calibration curves. Due to differences in scoring criteria, dicentrics scored in conventionally Giemsa-stained slides agreed better with data for total than for complete exchanges. Donor differences for translocations at the control level and at low doses were seen and large uncertainty surrounds the linear component of the dose-response for total translocations. CONCLUSIONS: Dose reconstruction of past exposures in cases of low doses is very dependent on the linear coefficient of the curve. Results indicate that total translocations would give less reliable dose estimates and therefore complete translocations are preferred.
Adult↗
Contingent valuation as a method for measuring the effects of rehabilitation.
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Adolescent↗
Local cytokine response in Helicobacter pylori-infected subjects.
The host immune response to Helicobacter pylori infection might be of importance with regard to the outcome of infection by this organism, e.g., to explain why only a proportion of infected subjects develop peptic ulcers. In this study we have analyzed the local response of different cytokines-i.e., the proinflammatory interleukin-1beta, (IL-1beta), IL-6, tumor necrosis factor alpha, and IL-8; the immunoregulatory gamma interferon (IFN-gamma); and IL-4; and the anti-inflammatory transforming growth factor beta (TGF-beta)-in antral biopsy specimens from H. pylori-infected duodenal ulcer (DU) patients and asymptomatic (AS) carriers (i.e., with chronic gastritis only). For comparison, biopsy specimens from uninfected healthy individuals were also analyzed. An immunohistochemical technique was used to allow quantification of the cytokine responses as well as identification of the cell types associated with the cytokine expression. We found that the levels of all of the studied cytokines except IL-4 were increased in the H. pylori-infected subjects compared to the levels in the healthy individuals. Our results indicate that the antral cytokine response is of the Th1 type since IFN-gamma, but not IL-4, was up-regulated both in H. pylori-infected DU patients and in AS carriers. However, there were no significant differences in either proinflammatory or immunoregulatory cytokine levels when H. pylori-infected subjects with and without peptic ulcers were compared. Some of the cytokines, particularly IL-1beta and TGF-beta, were also found in the gastric mucosae of healthy, uninfected subjects. We also showed that the gastric epithelium contributes substantially to the antral cytokine response of the proinflammatory cytokines IL-1beta and IL-6 in addition to IL-8.
Adult↗
Chronic ulcers and antibiotic treatment.
This study analysed 656 wound samples from patients with chronic wounds in order to determine the bacterial flora and patterns of antibiotic use and resistance. Almost all wounds (95.1%) were colonised with at least one bacterial species; 26% of all patients were on antibiotic treatment. The total number of bacterial isolates resistant to antibiotics was low.
Adolescent↗
Do recorded doses overestimate true doses received by Chernobyl cleanup workers? Results of cytogenetic analyses of Estonian workers by fluorescence in situ hybridization.
Studies of workers who were sent to Chernobyl after the 1986 reactor accident are being conducted to provide a better understanding of the effects of chronic low-dose radiation exposures. A crucial component to these investigations is an accurate assessment of the radiation doses received during the cleanup activities. To provide information on biological measurements of dose, fluorescence in situ hybridization (FISH) with whole-chromosome painting probes has been applied to quantify stable chromosome aberrations (translocations and insertions) among a defined cohort of 4,833 cleanup workers from Estonia. Cytogenetic analysis of 48-h lymphocyte cultures from 118 Estonian cleanup workers (10.3 cGy mean recorded dose; 25 cGy maximum), 29 Estonian population controls and 21 American controls was conducted by three laboratories. More than 258,000 painted metaphases were evaluated. Overall, we observed lower translocation frequencies than has been reported in previous studies using FISH among Chernobyl cleanup workers. In our data, a clear association with increased levels of translocations was seen with increasing age at blood drawing. There was no correlation, however, between aberration frequency and recorded measurements of physical dose or any category of potential high-dose and high-dose-rate exposure such as being sent to Chernobyl in 1986, working on the roof near the damaged nuclear reactor, working in special zones or having multiple tours. In fact, the translocation frequency was lower among the exposed workers than the controls, though not significantly so. To estimate the level of effect that would have been expected in a population of men having an average dose of approximately 10 cGy, blood from six donors was exposed to low-LET radiation, and more than 32,000 metaphases were scored to estimate dose-response coefficients for radiation-induced translocations in chromosome pairs 1, 2 and 4. Based on these results, we estimate that had this group of 118 men received an average whole-body dose of 10-11 cGy, as chronic or acute exposures, an increase in the mean frequency of chromosome translocations of more than 40-65% would have been observed in their lymphocytes compared to findings in nonirradiated controls. In spite of evaluating more than a quarter of a million metaphases, we were unable to detect any increase in the mean, median or range in chromosome aberrations in lymphocyte cultures from a group of Estonian men who took part in the cleanup of the Chernobyl nuclear power site and those who did not. We conclude that it is likely that recorded doses for these cleanup workers overestimate their average bone marrow doses, perhaps substantially. These results are consistent with several negative studies of cancer incidence in Chernobyl cleanup workers and, if borne out, suggest that future studies may not be sufficiently powerful to detect increases in leukemia or cancer, much less distinguish differences between the effects of chronic compared to brief radiation exposures.
Adult↗
Methods for improving the yield and quality of metaphase preparations for FISH probing of human lymphocyte chromosomes.
Procedures are described for the in vitro culture of human lymphocytes, which have been concentrated by density gradient centrifugation, and for a modified slide-making technique for the fixed cells. The method yields improved percentages of mitotic cells which are largely synchronized at harvest. Controlled placement of fixed cells on slides produces well-spread metaphase preparations with little background material to interfere with fluorescence in situ hybridization (FISH) probe procedures. The FISH reagents and microscope scanning time required are minimized by concentrating cells in a defined area of the slide.
Cell Culture Techniques↗