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Biomedical subjects

C Lindholm

Publications and source records attributed to C Lindholm.

At least 19 recordsLinked to original sources

[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

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

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

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

Unstable and stable chromosomal aberrations in lymphocytes of people exposed to Chernobyl fallout in Bryansk, Russia.

Analyses of unstable and stable chromosomal aberrations in peripheral blood lymphocytes were used in the assessment of radiation exposure of residents of a village situated in the Chernobyl fallout-contamination zone of Bryansk, Russia. Blood samples were taken from subjects residing in villages with high (> 1100 kBq/m2 137 Cs; Mirnyi) and very low (< 37 kBq/m2 137 Cs; Krasnyi Rog) contamination, 7 years after the Chernobyl accident. The groups were matched by age, sex, smoking habits and previous medical radiological exposures. A total of 200 people (100 exposed, 100 controls) were analysed for the presence of unstable aberrations from Giemsa-stained slides. To study stable aberrations, chromosome painting analyses were performed on 100 subjects (50 exposed, 50 controls), using painting probes for chromosomes 1, 2 and 4 and a pancentromeric probe. People living in the contaminated area showed significantly higher rates of unstable chromosome-type aberrations but not chromatid-type aberrations in their lymphocytes, indicating radiation exposure as a causative factor for the observed difference. No significant differences were found in the aberration rates between the two areas by the chromosome painting method. The levels of chromosome exchanges were low in both populations, but consistently higher in Mirnyi compared with the control area. The magnitude of radiation exposure resulting from Chernobyl fallout was estimated on the basis of excess stable chromosomal aberrations in the lymphocytes of the Mirnyi population compared with the controls.

Adult

Quantification of conserved antigens in Helicobacter pylori during different culture conditions.

In this study, we raised monoclonal antibodies (MAbs) against three conserved Helicobacter pylori antigens, i.e., the N-acetylneuraminyllactose-binding fibrillar hemagglutinin, HpaA; the flagellin subunits, FlaA and FlaB; and a species-specific 26-kDa protein. The MAbs were used for the development of sensitive inhibition enzyme-linked immunosorbent assays for quantification of these antigens in H. pylori during various culture conditions. The quantities of these antigens varied considerably (up to 8-fold) during different culture procedures and between strains (up to 10-fold).

Antibodies, Bacterial

Pain in venous leg ulcers.

A prospective study was conducted to assess the prevalence, severity and diagnostic utility of pain in patients with venous leg ulcers. A semi-structured questionnaire was completed by 140 consecutive patients in two specialist centres caring for patients with leg ulcers. A high proportion (64%) of the 94 patients with ulcers of purely venous aetiology reported severe pain; 50% of these patients were taking either mild analgesia or none at all. In 10 of 72 cases, leg elevation made the pain worse. Venous ulcers are painful. Pain in three distinct locations was reported by patients-within ulcers, around ulcers and elsewhere in the leg. The presence of severe pain does not necessarily indicate arterial disease or infection. Pain is, in general, inadequately controlled in these patients.

Adult

Reduced meal-related gastrointestinal hormone response to adrenocorticotropic hormone stimulation test in female athletes.

This study was undertaken to elucidate the impact of hypercortisolism in meal-related gastrointestinal hormone secretion and appetite in female endurance athletes. Thirteen elite runners and seven sedentary women participated on two occasions, either receiving intravenous injection of 250 micrograms synthetic adrenocorticotropic hormone (ACTH) 1-24 or saline. Blood samples were collected before and after the injection, and then in connection with a standardized meal. Serum concentrations of cortisol, cholecystokinin (CCK), gastrin, insulin and glucose were analyzed. Self-ratings of appetite were assessed by visual analog scales. Elevated basal levels of cortisol and glucose were found in the athletes. ACTH-induced cortisol response was comparable between groups, but a negative correlation between basal cortisol levels and the ACTH-induced response was found. In sedentary women, ACTH challenge enhanced meal-related CCK and gastrin responses, whereas athletes showed a blunted response of these hormones combined with decreased satiety and reduced levels of insulin. Blunted meal-related response of gastrointestinal hormones and decreased satiety in female runners after ACTH stimulation compared to sedentary women are probably due to difference in the effect of cortisol, which could be explained by cortisol insensitivity as a result of basal hypercortisolism in the athletes. Decreased CCK response and satiety in female athletes may reflect increased nutritional requirements.

Adrenocortical Hyperfunction