Long term health-related quality of life after burns is strongly dependent on pre-existing disease and psychosocial issues and less due to the burn itself.

BACKGROUND: Health-related quality of life (HRQoL) is reduced after a burn, and is affected by coexisting conditions. The aims of the investigation were to examine and describe effects of coexisting disease on HRQoL, and to quantify the proportion of burned people whose HRQoL was below that of a reference group matched for age, gender, and coexisting conditions. METHOD: A nationwide study covering 9 years and examined HRQoL 12 and 24 months after the burn with the SF-36 questionnaire. The reference group was from the referral area of one of the hospitals. RESULTS: The HRQoL of the burned patients was below that of the reference group mainly in the mental dimensions, and only single patients were affected in the physical dimensions. The factor that significantly affected most HRQoL dimensions (n=6) after the burn was unemployment, whereas only smaller effects could be attributed directly to the burn. CONCLUSION: Poor HRQoL was recorded for only a small number of patients, and the decline were mostly in the mental dimensions when compared with a group adjusted for age, gender, and coexisting conditions. Factors other than the burn itself, such as mainly unemployment and pre-existing disease, were most important for the long term HRQoL experience in these patients.

Inhibition of connective tissue growth factor/CCN2 expression in human dermal fibroblasts by interleukin-1alpha and beta.

Connective tissue growth factor (CTGF/CCN2) is a matricellular protein induced by transforming growth factor (TGF)-beta and intimately involved with tissue repair and overexpressed in various fibrotic conditions. We previously showed that keratinocytes in vitro downregulate TGF-beta-induced expression of CTGF in fibroblasts by an interleukin (IL)-1 alpha-dependent mechanism. Here, we investigated further the mechanisms of this downregulation by both IL-1alpha and beta. Human dermal fibroblasts and NIH 3T3 cells were treated with IL-1alpha or beta in presence or absence of TGF-beta1. IL-1 suppressed basal and TGF-beta-induced CTGF mRNA and protein expression. IL-1alpha and beta inhibited TGF-beta-stimulated CTGF promoter activity, and the activity of a synthetic minimal promoter containing Smad 3-binding CAGA elements. Furthermore, IL-1alpha and beta inhibited TGF-beta-stimulated Smad 3 phosphorylation, possibly linked to an observed increase in Smad 7 mRNA expression. In addition, RNA interference suggested that TGF-beta activated kinase1 (TAK1) is necessary for IL-1 inhibition of TGF-beta-stimulated CTGF expression. These results add to the understanding of how the expression of CTGF in human dermal fibroblasts is regulated, which in turn may have implications for the pathogenesis of fibrotic conditions involving the skin.

Prediction of patient satisfaction with care one year after burn.

The aim of this prospective study was to find predictors of patient satisfaction with burn care. Sixty-nine consecutive adult patients undergoing acute treatment in a Burn Unit completed the following questionnaires: the Swedish universities Scales of Personality, the Impact of Event Scale-Revised, and the Hospital Anxiety and Depression Scale. Socio-demographic data and burn severity were registered. One year later they completed the Patient Satisfaction-Results and Quality (PS-RESKVA) questionnaire containing four subscales: quality of contact with nursing staff (QCN), quality of contact with medical staff (QCM), adequate treatment information (INF), and global satisfaction with treatment (GS). Each subscale was treated as a dependent variable in separate multiple regression models. Overall, the explained variance was low to moderate (range adjusted R(2)=0.06-0.19). Variables remaining in the models were: intrusive symptoms, and the personality trait stress susceptibility for QCN; age, education, and symptoms of hyperarousal for QCM; trait irritability for INF; and age and the personality traits detachment and social desirability for GS. In conclusion, psychological and socio-demographic variables predicted satisfaction to some degree, whereas injury severity did not. The low amount of explained variance suggests that other factors, hypothetically related to care itself, determine patient satisfaction as assessed by the PS-RESKVA.

Injury-related fear-avoidance, neuroticism and burn-specific health.

Dysfunctional beliefs such as fear-avoidance (i.e. fear of re-injury) and personality traits such as neuroticism are risk factors for poor health. However, there is little information regarding associations with poor perceived health after severe burn and what level of fear-avoidance is associated with poor health. In this study, we investigated fear-avoidance and neuroticism regarding their associations with post-burn health. Participants were 86 recovered burn patients and data were collected by a postal survey. Post-burn health was assessed with the nine subscales of the Burn Specific Health Scale-Brief (BSHS-B). In logistic regressions, fear-avoidance was related to poorer health in six subscales assessing both physical and psychosocial problems. Neuroticism was associated with poorer health in three subscales assessing mainly psychosocial problems. Chi-square analyses showed that participants with a moderate or high level of fear-avoidance >or=1.0 (out of 4) were more likely to describe their health as poor and had a longer sick leave than those with a fear-avoidance level of <1.0. In summary, fear-avoidance was associated with poorer health even at moderate levels and was associated with several aspects of post-burn health.

Use of healthcare a long time after severe burn injury; relation to perceived health and personality characteristics.

PURPOSE: The aim of the study was to evaluate which factors are associated with the use of healthcare a long time after severe burn injury. METHOD: After a review process based on clinical reasoning, 69 former burn patients out of a consecutive group treated at the Uppsala Burn Unit from 1980--1995 were visited in their homes and their use of care and support was assessed in a semi-structured interview. Post-burn health was assessed with the Burn-Specific Health Scale-Brief (BSHS-B) and personality was assessed with the Swedish universities Scales of Personality (SSP). RESULTS: The participants were injured on average eight years previously. Thirty-four had current contact with healthcare due to their burn injury and had significantly lower scores on three BSHS-B-domains: Simple Abilities, Work and Hand function, and significantly higher scores for the SSP-domain Neuroticism and the SSP-scales Stress Susceptibility, Lack of Assertiveness, and lower scores for Social Desirability. There was no relation to age, gender, time since injury, length of stay, or to the surface area burned. CONCLUSIONS: A routine screening of personality traits as a supplement to long-term follow-ups may help in identifying the patient's need for care.

Effects of commonly used immunosuppressants on graft-derived fibroblasts.

In acute rejection of transplanted organs intragraft fibroblasts increase their production of hyaluronan. Hyaluronan has strong water binding capacity and an increased tissue content of hyaluronan thus contributes to the development of interstitial oedema. The present study examined the effects of commonly used immunosuppressants (prednisolone, cyclosporin, tacrolimus, mycophenolic acid and sirolimus) on fibroblast proliferation, hyaluronan production and cell surface receptor expression. Fibroblasts isolated from rejecting tissue and from normal, non-transplanted tissue were studied in parallel. All substances investigated, except tacrolimus, were found to affect fibroblasts in one way or another. The most striking effect was the almost total inhibition of fibroblast proliferation in the presence of mycophenolic acid. Cyclosporin reduced the proliferation by about 50% and prednisolone had an inhibiting effect on hyaluronan production (50% reduction). These effects were observed on fibroblasts isolated from rat cardiac allografts undergoing rejection as well as on fibroblasts obtained from normal heart tissue. In contrast, sirolimus was found to stimulate the proliferation of fibroblasts from rejecting tissue (100% increase), but not that of normal fibroblasts. The majority of the fibroblasts expressed the hyaluronan receptor CD44, with a more intense expression in cultures of fibroblasts derived at rejection. None of the immunosuppressants affected the staining pattern (number of positive cells or intensity). The inhibitory effects of prednisolone, cyclosporin and mycophenolic acid on fibroblasts may contribute to the overall beneficial effects of these drugs when used for prevention or treatment of rejection.

Dupuytren's contracture and sarcoma.

In order to study possible connections between Dupuytren's contracture and sarcoma we analysed the records of 18 patients who developed sarcoma 5 years or more after surgery for Dupuytren's contracture. We found an increased frequency of fibrosarcoma and malignant fibrous histiocytoma, but these patients did not differ from the other patients in the study group. Our analysis suggests that neither smoking, diabetes nor cancer syndromes can explain why patients with Dupuytren's contracture have a higher incidence of sarcoma.

In vitro growth of human endolymphatic sac cells: a transmission electron microscopic and immunohistochemical study in patients with vestibular schwannoma and Ménière's disease.

HYPOTHESIS: Human endolymphatic sac cells have been notoriously difficult to maintain in culture. It was hypothesized that an in vitro environment intended for growth of keratinocytes would also be suitable for human endolymph sac cells. BACKGROUND: Studies on cell physiology of human endolymphatic sac cells have been hampered by difficulties in maintaining them in culture. METHODS: Human endolymphatic sac cells were taken from 10 patients during translabyrinthine skull base surgery for vestibular schwannoma, one of whom also had Ménière's disease. Cell lines of proliferating epithelial cells were obtained after trypsinization and growth in a 3:1 mixture of Dulbecco's modified Eagle medium and Ham's F12 medium supplemented with 10% fetal calf serum. Fibroblast overgrowth was counteracted by the use of so-called cloning rings. During various stages, cells were investigated with transmission electron microscopy and/or immunohistochemistry. RESULTS: Proliferation took place after 2 to 3 days of primary cell culture. The cells were cytokeratin-positive and pleomorphic, and they had abundant polarized microvillus-like projections, numerous coated cytoplasmic pits and vesicles, and a well-developed rough endoplasmic reticulum. CONCLUSION: Cell lines of proliferating human endolymphatic sac cells can be produced with the technique described here and may be a valid tool in studies of human endolymph sac physiology.

Development of a brief version of the Burn Specific Health Scale (BSHS-B).

BACKGROUND: The Burn Specific Health Scale (BSHS) is an outcome scale designed specifically for burn patients. The scale has been abbreviated (BSHS-A) and revised (BSHS-R). We used a factor analytic approach to further improve the scale for clinical use. METHODS: Two hundred forty-eight of 350 former patients (70.9%) treated at the Uppsala Burn Unit between 1980 and 1995 responded to 94 questions from previous versions of the BSHS. RESULTS: Principal components factor analyses were used to derive an instrument with 40 items called the Burn Specific Health Scale-Brief (BSHS-B), resulting in nine well-defined domains with intercorrelations ranging from 0.11 to 0.56, and Chronbach's factor alphas ranging from 0.75 to 0.93. The domains describe function with respect to Heat Sensitivity, Affect, Hand Function, Treatment Regimens, Work, Sexuality, Interpersonal Relationships, Simple Abilities, and Body Image. CONCLUSION: The BSHS-B is a valid but shorter alternative to the previously described BSHS-A. Important domains of postburn distress are captured better in the BSHS-B than in the BSHS-R.

Interferon-gamma-induced inhibition of wound healing in vivo and in vitro.

This work was undertaken to study the effects of various doses of interferon-gamma (IFN-gamma) on developing granulation tissue in rats and on granulation tissue-derived fibroblasts in culture. For in vivo studies cylindrical hollow sponge implants were used as an inductive matrix for the growth of granulation tissue. In the test groups the implants were injected daily for four days with a solution containing 160, 800, 4000, or 20000 units of IFN-gamma while the implants of the control group were treated correspondingly with the carrier solution only. Analyses of granulation tissue in the sponge cylinders, carried out 7 days after implantation, showed an IFN-gamma-related decrease in the formation of new granulation tissue. The largest, dose-dependent effect was seen in the accumulation of collagen. For in vitro studies, cultures of rat granulation tissue fibroblasts were treated with 100, 500, 1000, or 5000 units/ml of IFN-gamma. IFN-gamma decreased collagen synthesis to about 50 per cent of that in controls. IFN-gamma treatment also decreased type I procollagen mRNA levels maximally by 41 per cent from the control level. It is concluded that IFN-gamma inhibits the formation of new granulation tissue by decreasing collagen synthesis.

Interferon-gamma-induced inhibition of wound healing in vivo and in vitro.

This work was undertaken to study the effects of various doses of interferon-gamma (IFN-gamma) on developing granulation tissue in rats and on granulation tissue-derived fibroblasts in culture. For in vivo studies cylindrical hollow sponge implants were used as an inductive matrix for the growth of granulation tissue. In the test groups the implants were injected daily for four days with a solution containing 160, 800, 4000, or 20000 units of IFN-gamma while the implants of the control group were treated correspondingly with the carrier solution only. Analyses of granulation tissue in the sponge cylinders, carried out 7 days after implantation, showed an IFN-gamma-related decrease in the formation of new granulation tissue. The largest, dose-dependent effect was seen in the accumulation of collagen. For in vitro studies, cultures of rat granulation tissue fibroblasts were treated with 100, 500, 1000, or 5000 units/ml of IFN-gamma. IFN-gamma decreased collagen synthesis to about 50 per cent of that in controls. IFN-gamma treatment also decreased type I procollagen mRNA levels maximally by 41 per cent from the control level. It is concluded that IFN-gamma inhibits the formation of new granulation tissue by decreasing collagen synthesis.

Hyaluronan content in the kidney in different states of body hydration.

BACKGROUND: Growing evidence suggests that the interstitial hyaluronan (HA) content is a determinant of the fluid exchange barrier in tissues through its high resistance to water flow. This study addressed the possible involvement of renal papillary HA in water balance regulation. METHODS: In anesthetized rats during different states of renal water handling (euvolemia, water diuresis, antidiuresis), in desert rodents, and in Brattleboro rats (diabetes insipidus) with a hereditary difference in water handling, regional renal HA and water contents were measured. RESULTS: The intrarenal HA distribution is heterogeneous, with 100 times larger amounts in the papilla than in the cortex. Compared with control rats, two hours of water diuresis increased the papillary HA content by 48% and that in the outer medulla by 52%, leaving the cortex unaffected. After 24 hours of water deprivation, papillary HA was decreased by 17%, while outer medullary HA remained unchanged. In gerbils, papillary and outer medullary HA contents were only 25 and 13%, respectively, of those in normal rats, while the cortical content was similar. In Brattleboro rats, the outer medullary HA content was significantly higher (285%) than in the normal rat, while the papillary content was similar. Generally, papillary HA was positively correlated to water content but was inversely related to urine osmolality. CONCLUSIONS: The amount of renal papillary HA changes in response to water balance of the organism. When excess water needs to be excreted, increased papillary interstitial HA could antagonize water reabsorption. The opposite occurs during water conservation. HA may play a role in renal water handling by affecting physicochemical characteristics of the papillary interstitial matrix and influencing the interstitial hydrostatic pressure, thereby determining interstitial water diffusion.

Cancer incidence in patients treated surgically for Dupuytren's contracture.

Our aim was to study risk factors for Dupuytren's contracture (DC) by assessing cancer morbidity in a group of Swedish patients treated surgically for Dupuytren's contracture. The risk of cancer was determined in 15,212 patients operated on for Dupuytren's contracture, identified in the nationwide Swedish Inpatient Register during the period 1965 to 1994 by means of record linkage to the Swedish Cancer Register. Standardized incidence ratios (SIRs) were computed using age-, sex- and period-specific incidence rates derived from the entire Swedish population. The overall relative risk of cancer was increased by 24%. There were significantly increased risks for malignancies related to smoking such as buccal, oesophageal, gastric, lung and pancreatic cancers. Significantly increased risks were present for both prostate and rectal cancer in men and an increase risk for breast cancer in women was noted 1 year or more after surgery for Dupuytren's contracture. The present study confirms smoking and alcohol abuse as probable risk factors for DC. There are characteristics in patients with DC that alter the risks for other malignancies compared with the general population.

Intestinal mucosal secretion of basic fibroblast growth factor in patients with ulcerative colitis.

BACKGROUND: Basic fibroblast growth factor (bFGF) promotes angiogenesis and several other biologic processes, including proliferation of mesenchymal cells and tumor progression. We investigated whether bFGF could be detected in the intraluminal secretion of the small intestine, sigmoid colon, and rectum in healthy individuals and in patients with ulcerative colitis. METHODS: We used endoscopic perfusion techniques to obtain samples from well-defined intestinal segments. The perfusion fluid concentrations of bFGF, biochemical markers of inflammation, myeloperoxidase (MPO), interleukin-6 (IL-6), and permeability (albumin) were determined with immunochemical methods. RESULTS: In the perfusion fluids the albumin concentration, which reflects passive diffusion, was less than 1% of the plasma concentration, whereas the intestinal concentration of bFGF was similar to that in plasma. Among healthy subjects the concentration of bFGF was eightfold higher in the jejunum and twofold higher in the rectum than in the sigmoid colon. The perfusion fluid from colorectal segments in patients with ulcerative colitis had a significantly higher mean concentration of bFGF than that from healthy individuals; an almost 10-fold difference was found in rectal segments. There were strong correlations between the concentration of bFGF and the concentrations of MPO and IL-6. CONCLUSIONS: The high concentrations of bFGF in the intestinal perfusion fluid reflect either a local synthesis or an active secretion of bFGF within the mucosa. The bFGF concentration differs in intestinal anatomic location and increases significantly in patients with ulcerative colitis in close relationship with biochemical markers of inflammation and permeability.

Characterisation of cells in regenerating cartilage from autotransplanted perichondrium. immunohistochemical expression of smooth-muscle actin, desmin, vimentin, and Ki-67.

Autotransplanted perichondrium from rib and ear sutured to the knee joints of 26 rabbits has been examined with immunohistochemistry and shows certain structural, functional, and proliferative characteristics of regenerating cartilage. Cryostat sections have been examined for the expression of smooth-muscle actin (SMA), desmin, vimentin, and Ki-67. In this rabbit model of perichondrial grafting SMA staining showed vivid vessel regeneration, particularly in the proliferating stage about two to three weeks after grafting, and no vessels in more mature parts one month or more after transplantation. Desmin staining showed expression and distribution similar to SMA. Vimentin staining shows the cytoskeleton of regenerating cartilaginous tissue and makes cellular borders apparent. Immunohistochemical expression of Ki-67 is constantly negative in perichondrial tissue from rib and ear before transplantation, clearly positive in the proliferative stage, but there is no expression in maturing cartilage. The study also shows that all human antibodies used are applicable in a rabbit model.

The sex ratio and rate of reoperation for Dupuytren's contracture in men and women.

We identified all patients treated by local fasciectomy at the Department of Hand Surgery, Uppsala University Hospital between 1965 and 1996. A total of 2375 operations were performed on 1600 patients. We found a male:female ratio of 5.9:1. Women had a higher mean age at first operation (62.4 years) than men (59.8 years). One-third of the men required repeated surgery and one-quarter of the women. Early age at first operation was associated with recurrent disease.

Hyaluronidase ameliorates rejection-induced edema.

Hyaluronan, a glucosaminoglycan with unique water-binding capacity, is accumulated in the interstitial edematous tissue in rejecting organs. We here investigated whether the increased tissue content of water and hyaluronan seen during allograft rejection can be prevented by treatment with the hyaluronan-degrading enzyme hyaluronidase. Heterotopic heart transplantations between PVG and Wistar/Kyoto rats were performed. Recipient rats were treated with hyaluronidase prophylactically or therapeutically, either alone or in combination with cyclosporine. Daily intravenous injections of hyaluronidase induced a significant reduction of the cardiac content of both hyaluronan and water, as evaluated on day six after transplantation. Morphological examination revealed grafts with better preserved morphology and fewer infiltrating mononuclear cells, compared to untreated controls. Hyaluronidase therapy, alone or combined with cyclosporine, resulted in prolonged graft survival times. Hyaluronidase infusion for two hours also reduced already established edema five days after transplantation. This study confirms the hypothesis that hyaluronan accumulation plays a critical role in edema formation, and that hyaluronidase therapy can be used to reduce edema after organ transplantation.

Reduced mucosal perianastomotic capillary density in rat small intestine with chronic radiation damage.

Anastomoses in an intestine with chronic radiation damage are prone to leakage, possibly due to a reduced blood supply induced by a reduced capillary bed. In an animal model, the numerical capillary density in the perianastomotic area was investigated in intestine with or without chronic radiation damage. A 2-cm segment of rat ileum received a single dose of 21 Gy. Twenty weeks later, when the chronic radiation-induced changes were established, an anastomosis was constructed in this segment and in a corresponding segment in control rats. In situ perfusion fixation of the intestine was done 4 or 7 days after construction of the anastomosis, sections of the intestine were removed surgically, the specimens were embedded in methacrylate plastic and sectioned at 2.5 microm, and capillaries were counted under a light microscope. The circumferential mucosal capillary density was lower in irradiated than in nonirradiated animals at both 4 and 7 days (P < 0.001 and P = 0.04, respectively). This reduction was greater in the mesenteric quadrant than in the other quadrants around the circumference. These results are indicative of a reduced capillary bed in the vicinity of anastomoses in intestine with chronic radiation damage, which might lead to an impeded blood supply and subsequent leakage.

Anastomotic blood-flow reduction in rat small intestine with chronic radiation damage.

BACKGROUND/AIMS: Anastomoses in previously irradiated intestine are prone to leakage, possibly due to an impeded blood supply. Whether or not chronic radiation damage actually predisposes to a disturbed blood flow in the vicinity of anastomoses was investigated in the rat small bowel. METHOD: A 2-cm segment of rat ileum was irradiated with a single dose (21 Gy). After 20 weeks an anastomosis was created in the irradiated segment and in the corresponding segment of controls. Another 4 days later local blood flow was studied with the 14C-iodoantipyrine autoradiography technique in 16 sectors around the circumference both in the anastomotic segment and in a segment 4 mm apart. RESULTS: In the anastomotic segment, the average blood flow was reduced in irradiated compared with non-irradiated animals in the mucosal layer (p = 0.034), but not in the muscular layer (p = 0.08). In the mesenteric quadrant blood flow was reduced in irradiated compared with non-irradiated animals, both in the mucosal layer (p = 0.012) and in the muscular layer (p = 0.05). More irradiated than non-irradiated animals showed a blood-flow reduction to 15% or more in 13-16 sectors both in the mucosal (p = 0.015) and the muscular layer (p = 0.04). CONCLUSIONS: The results favor the hypothesis that anastomoses in previously irradiated intestine are vascularly compromized and thereby have an increased risk of leakage.

Eosinophil activation in ulcerative colitis: studies on mucosal release and localization of eosinophil granule constituents.

Activation of eosinophil granulocytes (eosinophils) seems to contribute to the pathophysiology of several inflammatory conditions. This process was evaluated in 18 patients with ulcerative colitis and in 18 healthy controls using intraluminal segmental perfusion of the sigmoid colon and rectum and immunoanalysis for eosinophil cationic protein (ECP) in the perfusate. Immunohistochemistry for eosinophils and neutrophils was made in simultaneously taken biopsies and in biopsies from surgical specimens taken from additional 10 patients. The mucosal release of ECP was increased severalfold in patients with UC. The bowel biopsies demonstrated a lamina propria infiltrated with eosinophils. The degree of eosinophil activation/degranulation was related to the intensity of the inflammatory reaction. Activated eosinophils and extracellular deposits of ECP were, in particular, seen in crypt abscesses and in areas with damaged surface epithelium. Since ECP is highly cytotoxic, its release at the site of inflammatory bowel lesions might reflect a potential pathophysiological mechanism.