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Biomedical subjects

R Löfberg

Publications and source records attributed to R Löfberg.

At least 37 records · Page 2Linked to original sources

The prevalence and clinical significance of alpha 1-antitrypsin deficiency (PiZ) and ANCA specificities (proteinase 3, BPI) in patients with ulcerative colitis.

Our aim was to determine the prevalence of the PiZ allele for alpha 1-antitrypsin (AAT) deficiency and some relevant antineutrophil cytoplasmic antibody (ANCA) specificities in patients with ulcerative colitis (UC), and explore a possible association between these markers. In addition, we studied the relation to disease extension and activity. Sera from 141 patients with UC (72 women) were analyzed while 50 blood donors and 54 patients with acute myocardial infarction served as controls. Serum samples were screened for PiZ with ELISA and phenotyped by isoelectric focusing. BPI-ANCA and PR3-ANCA were detected by ELISA. Results were that 8.5% (12/141) of the patients with UC were PiZ carriers, higher than expected in the general Swedish population (4.7%) (p = 0.03). There was a significant difference between PiZ-carriers and non-PiZ-carriers in the extension and severity of colitis (odds ratio = 4.1, confidence interval = 1.1, 14.9; p = 0.028, and odds ratio = 9.0, confidence interval = 1.1, 73.3; p = 0.015; respectively). BPI-ANCA and PR3-ANCA were detected in 20.5% (29/141) and 12% (17/141) (p < 0.05 compared with controls for all parameters). Occurrence of BPI-ANCA and PR3-ANCA was not related to extension or severity of colitis (p > 0.05 for both variables). We observed no association between PiZ-carrier status and occurrence of BPI-ANCA or PR3-ANCA. The increased frequency of heterozygosity for the PiZ variant of AAT deficiency among patients with UC might imply a role played by protease inhibitors for regulation of inflammation and immunologic response in UC.

Adolescent↗

Increased risk of cancer in ulcerative colitis: a population-based cohort study.

OBJECTIVE: There is an increased risk of colorectal cancer among patients with ulcerative colitis (UC). However, the overall and site specific cancer risks in these patients have been investigated to a limited extent. To study the association between UC and cancer, a population-based study of 1547 patients with UC in Stockholm diagnosed between 1955 and 1984 was carried out. METHODS: The patients were followed in both the National Cancer Register and the National Cause of Death Register until 1989. For comparisons, regional cancer incidence rates in Stockholm County were used together with individually computed person-years at risk in the UC disease cohort. RESULTS: A total of 121 malignancies occurred among 97 individuals as compared with 89.8 expected (standardized morbidity ratio [SMR] = 1.4; 95% confidence interval (CI), 1.1-1.6). Overall, an excess number of colorectal cancers (SMR, 4.1; 95% CI, 2.7-5.8), and hepatobiliary cancers in men (SMR = 6.0; 95% CI, 2.8-11.1) associated with primary sclerosing cholangitis, was observed. The risk of pulmonary cancer was decreased (SMR = 0.3; 95% CI, 0.1-0.9). In all, 91 extracolonic malignancies were observed, compared with the 82.3 expected (SMR = 1.11; 95% CI, 0.9-1.3). CONCLUSIONS: In UC patients, the overall cancer incidence is increased mainly because of an increased incidence of colorectal and hepatobiliary cancer. This increase is partly counterbalanced by a decreased risk of pulmonary cancer compared with that in the general population.

Adult↗

An international survey of the use and attitudes regarding alternative medicine by patients with inflammatory bowel disease.

OBJECTIVE: There is a perception of increasing and widespread use of alternative medicine for inflammatory bowel disease (IBD). We assessed the usage of alternative therapies among patients with IBD, whether there were similar or contrasting variables that were predictive of such use, and contrasted the use in four different centers in North America and Europe. METHODS: Patients in four IBD centers completed a self-administered questionnaire regarding alternative medicine. The centers were in Cork, Los Angeles, Stockholm, and Winnipeg. Patient demographics, the use of 18 types of alternative medicine, and attitudes towards alternative and conventional medicine were compared. A multiple logistic regression analysis was used. RESULTS: Fifty-one percent of 289 patients used some form of alternative medicine. The percentages of use by site were Cork = 31%, Los Angeles = 68%, Stockholm = 32%, and Winnipeg = 57%. The six most commonly used therapies in descending order were: exercise (28%), prayer (18%), counseling (13%), massage (11%), chiropractic (11%), and relaxation (10%). Only 7% used acupuncture or homeopathy and 5% used herbal medicine. The highest odds ratios (confidence intervals [CIs]) for using any form of alternative medicine were associated with: being single 3.1 (1.7-5.7), Los Angeles patient 4.4 (2.3-8.3), Winnipeg patient 2.7 (1.3-5.9), and an increase of alternative medicine use of 2.7% for every M.D. visit (CI, 2-11%/visit). The patient age, gender, disease diagnosis, or duration of disease were not predictive of any type of alternative medicine use. Regarding attitudes, respondents from Cork were most favorable toward alternative medicine use and least favorable toward conventional medicine. Based on attitudes, subjects were more likely to use alternative medicine if they were not satisfied with conventional therapy, viewed hospitals as dangerous places, thought that alternative medicine practitioners should have a role in hospitals, and felt their medical situation was hopeless. CONCLUSIONS: Fifty-one percent of respondents used some form of alternative medicine. The use was greater among the North American patients than the European ones. Respondents were more likely to use alternative medicine if they were single, in a higher income bracket, and an urban dweller.

Attitude↗

[New knowledge of heredity in inflammatory bowel disease. Specific gene mapping in a EU-project].

Chronic inflammatory bowel diseases, ulcerative colitis and Crohn's disease, are steadily increasing in prevalence, and one half to one per cent of the Swedish population are currently estimated to be affected. The aetiology remains unknown, but is probably multifactorial. Both dietary, microbiological and immunological causes have been discussed. Clinical studies, including several Swedish studies, have also shown genetic factors to be crucially involved. Findings in sophisticated molecular biological studies suggest certain specific genes to be involved, and a current EU project in which Sweden is participating has been launched to map the mode of inheritance in detail.

Chromosome Mapping↗

Sialyl-Tn antigen as a marker of colon cancer risk in ulcerative colitis: relation to dysplasia and DNA aneuploidy.

BACKGROUND & AIMS: Expression of the mucin-associated carbohydrate antigen sialyl-Tn (STn) and DNA aneuploidy has each been shown to correlate with malignant transformation in patients with sporadic colon cancer and in those with ulcerative colitis (UC). This study aimed to determine how STn expression topographically and temporally relates to aneuploidy and neoplasia in patients with long-standing UC. METHODS: Twenty-six patients enrolled in a cancer surveillance program were studied, and 1691 mucosal specimens from repeated colonoscopies and colectomies were assessed in a standardized, prospective fashion for the presence of dysplasia, aneuploidy, and STn antigen. RESULTS: STn was expressed in 47% of specimens from 6 patients who underwent colectomy for dysplasia and 7% of specimens from 6 well-matched patients who underwent surgery for medical intractability. Seven other patients who never developed dysplasia or aneuploidy expressed STn in 6% of biopsy specimens. STn expression was independent of aneuploidy in colons both with and without dysplasia. Of 5 patients with aneuploidy but without dysplasia, 4 expressed STn earlier than aneuploidy. CONCLUSIONS: In UC, STn antigen and DNA aneuploidy are independent markers of neoplastic transformation. Determination of STn expression may complement dysplasia and aneuploidy for identification of risk for colonic neoplasia in UC.

Adolescent↗

Clinical course of colorectal Crohn's disease: a 35-year follow-up study of 507 patients.

BACKGROUND & AIMS: Crohn's disease (CD) confined to the colon and rectum is an increasing clinical entity. The aim of this study was to assess the features and clinical course of colorectal CD. METHODS: This was a retrospective cohort study of 507 patients in whom colonic or rectal CD had been diagnosed between 1955 and 1989. RESULTS: Colonic distribution was segmental in 40%, total in 31%, and left-sided in 26%. Perianal/rectal fistulas occurred in 37%. In patients who attained clinical remission, the 5-year cumulative relapse rate after diagnosis was 67% (95% confidence interval [CI], 62-72). At the initial presentation of CD, the frequency of major surgery decreased from 24% to 14% (P < 0.005) over time. Still, the overall long-term probability of major surgery after 10 years was unaltered (49% vs. 47%). The presence of fistulas increased the probability of surgical resection (relative risk [RR], 1.7 [95% CI, 1.3-2.2]), whereas left-sided disease was associated with a decrease (RR, 0.6 [95% CI, 0.4-0.8]). Twenty-four percent of the patients developed inflammation in the small bowel. The cumulative risk for a permanent ileostomy was 25% (95% CI, 21-29) 10 years after diagnosis. CONCLUSIONS: Colorectal CD is an increasing entity carrying substantial morbidity. Half of the patients will undergo surgical resection within the first 10 years, and half of those will ultimately undergo ileostomy. Changed management at diagnosis has not affected the long-term probability of resection.

Adolescent↗

Early predictors of glucocorticosteroid treatment failure in severe and moderately severe attacks of ulcerative colitis.

OBJECTIVE: To analyse the ability of simple clinical and biochemical parameters to predict glucocorticosteroid (GCS) treatment failure in patients with acute attacks of ulcerative colitis. DESIGN/METHODS: Retrospective analysis of clinical and biochemical data. SETTING: Four Swedish university hospitals. PATIENTS: Ninety seven patients with acute attacks of ulcerative colitis severe enough to warrant treatment with intravenous GCS, hospitalized during the years 1988-93. MAIN OUTCOME MEASURE: Colectomy within the first 30 days after hospitalization, defined as 'clinical steroid resistance'. RESULTS: Thirty days after admission, 39 patients (40%) were in complete clinical and endoscopic remission while 33 (34%) had undergone colectomy. During follow-up for 24 months, four patients among the 39 initially in remission underwent colectomy. Among the 25 patients (26%) not attaining remission after 30 days, an additional nine patients subsequently required colectomy. Steroid resistance was associated with duration of disease (2.7 vs 8.1 years, P=0.0037) and steroid treatment before hospitalization (70 vs 42%, P=0.010). In particular, elevation of body temperature (37.4 vs 36.9 degrees C, P=0.012), persistence of diarrhoea (6.8 vs 3.6 bowel movements/day, P<0.0001) and passage of blood (83 vs 42%, P=0.0003) as well as CRP elevation (36.3 vs 18.0 mg/l, P=0.007) on day 3 after treatment initiation were identified as predictors of a poor response. CRP > or = 25 mg/l and > 4 bowel movements/day on day 3 of hospitalization independently predicted a high risk for colectomy within 30 days. CONCLUSIONS: Sustained elevation of body temperature, persistent bloody diarrhoea and continued CRP elevation on day 3 of intravenous GCS treatment strongly predict clinical steroid resistance in acute attacks of ulcerative colitis. In the group of poor or non-responders, colectomy or more aggressive medical treatment should be considered at an early stage.

Adolescent↗

Life threatening diarrhoea ultimately cured by surgery.

A 30-year-old previously healthy woman was diagnosed as having a vasoactive intestinal polypeptide (VIP)-producing tumour of the pancreas. Her medical history was typical for neuroendocrine gastrointestinal tumours, presenting initially with non-specific symptoms but eventually she developed life-threatening manifestations requiring intensive care due to severe dehydration. She immediately recovered following surgical resection. The patient had elevated serum concentrations of VIP as well as pancreastatin, and post-operatively elevated concentrations of three growth factors, IGF-I, EGF and TGF-alpha, were seen. The importance of the alterations in plasma concentrations of the different peptides for her symptomatology are discussed.

Adult↗

Is colonoscopic surveillance reducing colorectal cancer mortality in ulcerative colitis? A population based case control study.

BACKGROUND: Colonoscopic surveillance is a standard procedure in many patients with long standing, extensive ulcerative colitis (UC), in order to avoid death from colorectal cancer. No conclusive proof of its benefits has been presented however. AIMS: To evaluate the association between colonoscopic surveillance and colorectal cancer mortality in patients with UC. PATIENTS: A population based, nested case control study comprising 142 patients with a definite UC diagnosis, derived from a study population of 4664 patients with UC, was conducted. METHODS: Colonoscopic surveillance in all patients with UC who had died from colorectal cancer after 1975 was compared with that in controls matched for age, sex, extent, and duration of the disease. Information on colonoscopic surveillance was obtained from the medical records. RESULTS: Two of 40 patients with UC and 18 of 102 controls had undergone at least one surveillance colonoscopy (relative risk (RR) 0.29, 95% confidence interval 0.06 to 1.31). Twelve controls but only one patient with UC had undergone two or more surveillance colonoscopies (RR 0.22, 95% confidence interval 0.03 to 1.74), indicating a protective dose response relation. CONCLUSION: Colonoscopic surveillance may be associated with a decreased risk of death from colorectal cancer in patients with long standing UC.

Adolescent↗

Effects of environmental stress on tissue survival and neutrophil recruitment in surgical skin flaps in relation to plasma corticosterone levels in the rat.

OBJECTIVE: Because glucocorticoid treatment can improve the survival of surgical skin flaps, we examined the influence of environmental stress on skin flap survival in the rat. MATERIAL: Female Sprague-Dawley rats. TREATMENT: Dexamethasone (1 mg/kg i.p.). METHODS: A standardized dorsal skin flap was raised and sutured back into position, and six days latter the percentage of flap survival was assessed. Corticosterone in rat plasma was measured using radioimmuno assay, and skin flap myeloperoxidase accumulation (reflecting neutrophil recruitment) was determined spectrophotometrically. RESULTS: Skin flap survival decreased gradually during a 10 day acclimatization period after transportation of the animals from the supplier, and plasma corticosterone levels were increased during the first 5 days of acclimatization compared to day 7 and 10. Dexamethasone treatment of rats accustomed to their new environment for 10 days increased flap survival to a level close to that observed in animals operated at day 1 after arrival. Flap surgery induced pronounced neutrophil recruitment into flap tissue, and this cell accumulation was greatly reduced in both the dexamethasone treated rats and in rats with elevated corticosterone levels. CONCLUSIONS: Skin flap survival in rats exposed to environmental stress may be significantly increased as compared to animals accustomed to their new environment for one week, possibly as a consequence of anti-inflammatory actions exerted by stress-induced elevations in plasma corticosterone. These findings emphasize the importance of strictly controlling environmental stress factors in studies of inflammation and tissue damage after surgical skin trauma.

Animals↗

Neoplastic transformation of the pelvic pouch mucosa in patients with ulcerative colitis.

BACKGROUND & AIMS: Some patients with ulcerative colitis (UC) receiving an ileal pelvic pouch with ileoanal anastomosis (IPAA) develop persistent severe villous atrophy in the pouch mucosa. To investigate if mucosal atrophy indicates a risk for subsequent neoplastic transformation of the ileal pouch mucosa, a follow-up study was undertaken. METHODS: Seven patients with UC and an IPAA in whom persistent severe atrophy (type C) developed and 14 control patients with no or only slight atrophy (type A) were prospectively surveyed by flexible videoendoscopy with multiple biopsies for assessment of possible neoplastic changes. RESULTS: The median time of the pouch in function was 9 years for both groups. Dysplasia was found in 5 of 7 patients in the type C group (71%) compared with none in the type A group (P < 0.001). Four patients had low-grade dysplasia, and 1 patient had sequential multifocal development into high-grade dysplasia. Multifocal DNA aneuploidy was found in 2 patients, 1 with low-grade and 1 with high-grade dysplasia. CONCLUSIONS: Patients with UC and a long-standing IPAA who develop persistent severe mucosal atrophy are at risk also of neoplastic transformation of the pouch mucosa.

Adolescent↗

Incidence of Crohn's disease in Stockholm County 1955-1989.

AIM: To evaluate the incidence of Crohn's disease in Stockholm County between 1955 and 1989. METHODS: A cohort of 1936 patients with Crohn's disease was retrospectively assembled. Incidence rates and changes in disease distribution were assessed. RESULTS: The mean increase in incidence was 15% (95% confidence intervals 12% to 18%) per five year period with a mean annual incidence rate at 4.6/10(5) during the last two decades. The mean incidence for the entire study period was similar for men and women. The mean age at diagnosis increased from 25 years in 1960-64 to 32 years in 1985-89, partly because of an increasing proportion of patients aged at least 60 years at diagnosis. The proportion of patients with colonic Crohn's disease at the time of diagnosis increased from 15% to 32% (17% difference; 95% confidence intervals 12% to 23%) whereas the proportion of patients with ileocaecal disease decreased from 58% to 41% (17% difference; 95% confidence intervals 10% to 24%) during the study period. Elderly patients had a higher proportion of small bowel disease and a lower proportion of ileocolonic disease compared with the younger patients. CONCLUSION: The incidence rate of Crohn's disease in Stockholm has stabilised at 4.6/10(5) and the proportion of elderly patients has increased during a 35 year period. Colonic Crohn's disease has increased in frequency with a reciprocal decrease in ileocaecal disease.

Adolescent↗

Leukocyte migration in acute colonic inflammatory bowel disease: comparison of histological assessment and Tc-99m-HMPAO labeled leukocyte scan.

UNLABELLED: Noninvasive leukocyte scintigraphy for assessment of localization, extent, and degree of active inflammation in acute colonic inflammatory bowel disease have been shown to correlate well with endoscopy. This study compared findings of mucosal leukocyte migration assessed histologically with those of technetium 99m hexamethylpropylene-amineoxime-labeled leukocyte scintigraphy. PATIENTS AND METHODS: Twenty-one patients hospitalized because of a first attack or a relapse of known inflammatory bowel disease were investigated using leukocyte scintigraphy followed by total colonoscopy with multiple biopsies within 24 h. Histological interpretation focused on the degree of segmental mucosal leukocyte infiltration. RESULTS: Fourteen patients with ulcerative colitis (UC) and seven with colonic Crohn's disease (CD) were included. With the use of histology as the reference method, maximal proximal disease extent was correctly assessed by the leukocyte scan in 11 patients (8 with UC, 3 with CD), although the rectal involvement was not visualized in 5. In seven patients, the extent assessments almost matched (+/- one segment), and in the remaining three patients (two UC, one CD) the scan grossly misinterpreted active histological inflammation (> or = +/- two segments). In patients with UC, the sensitivity, specificity, and diagnostic accuracy concerning the extent of inflammation were 0.84, 0.79, and 0.83, respectively. In patients with CD, the sensitivity was 0.79, and the diagnostic accuracy was 0.78. The relative leukocyte scan activity score was less concordant with the degree of mucosal leukocyte infiltration but still significantly correlated (r = 0.616, p < 0.0001 in UC patients and r = 0.441, p < 0.003 in CD patients). CONCLUSION: Images created by the technetium 99m hexamethylpropylene-amineoxime-labeled leukocyte scan in acute colonic inflammatory bowel disease correlate to mucosal leukocyte migration in terms of proximal disease extent and, to a lesser degree, also to the intensity of mucosal inflammatory infiltration.

Acute Disease↗

Pouchitis following pelvic pouch operation for ulcerative colitis. Incidence, cumulative risk, and risk factors.

AIM: This study was undertaken to assess the risk for pouchitis in patients with ulcerative colitis who underwent surgery with colectomy, restorative pelvic pouch, and ileoanal anastomosis and to evaluate possible factors predictive for pouchitis development. PATIENTS AND METHODS: All patients receiving a pelvic pouch because of ulcerative colitis at Huddinge University Hospital between 1980 and 1993 (n = 149; 89 men) were prospectively evaluated for symptoms suggestive of pouchitis. Diagnosis of pouchitis was based on occurrence of certain symptoms in combination with endoscopic findings. Pouchitis was divided into mild and severe, and the time span until the first attack of mild or severe pouchitis was calculated for each patient. RESULTS: Median follow-up time was 54 (5-152) months. The absolute cumulative risk of developing mild pouchitis was 21, 26, and 39 percent at 6, 12, and 48 months, respectively. The corresponding cumulative risk of developing severe pouchitis was 9, 11, and 14 percent, respectively. Risk for both groups together was 51 percent at 48 months. The occurrence of pouchitis, calculated at six-month intervals after closure of the loop ileostomy, was highest (23.1 percent) during the first six months. Incidence during the next six-month period was 11.4 percent and then only 3.1 percent thereafter. Thirty-two patients (21.5 percent) had chronic continuous symptoms requiring long-term metronidazole treatment, and 14 (9.4 percent) of those had chronic severe pouchitis. In two patients, removal of the pouch and permanent ileostomy became necessary. Extracolonic manifestations and early onset of ulcerative colitis were predictive factors for developing pouchitis. Former smoking seemed to be a protective factor. CONCLUSION: The risk for pouchitis was highest during the initial six-month period. Cumulative risk leveled off after two years but was substantial (51 percent) at four years. Less than 10 percent of patients had severe, chronic pouchitis, and only two patients (1.3 percent) had their pouches removed.

Adolescent↗