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Biomedical subjects

M Ström

Publications and source records attributed to M Ström.

At least 37 records · Page 2Linked to original sources
PubMed1997

Restoration of the growth suppression function of mutant p53 by a synthetic peptide derived from the p53 C-terminal domain.

We demonstrate here that synthetic 22-mer peptide 46, corresponding to the carboxy-terminal amino acid residues 361-382 of p53, can activate specific DNA binding of wild-type p53 in vitro and can restore the transcriptional transactivating function of at least some mutant p53 proteins in living cells. Introduction of peptide 46 in Saos-2 cells carrying a Tet-regulatable His-273 mutant p53 construct caused growth inhibition and apoptosis in the presence of mutant p53 but not in its absence, confirming that the effect of the peptide is mediated by reactivation of mutant p53. Moreover, peptide 46 caused apoptosis in mutant as well as wild-type p53-carrying human tumor cell lines of different origin, whereas p53 null tumor cells were not affected. These findings raise possibilities for developing drugs that restore the tumor suppressor function of mutant p53 proteins, thus selectively eliminating tumor cells.

Apoptosis↗
PubMed1997

Immediate repeat course of amoxycillin, metronidazole and omeprazole to eradicate Helicobacter pylori.

AIM: To investigate a repeat treatment regimen with the same antibiotic combination of amoxycillin and metronidazole in patients with continuing Helicobacter pylori infection. METHODS: Eighty-two patients with severe peptic ulcer disease and concurrent Helicobacter pylori infection were treated with a two week regimen of omeprazole (40 mg once daily), amoxycillin (750 mg t.d.s.) and metronidazole (400 mg t.d.s.). Upper gastrointestinal tract endoscopy was performed before, and approximately 2 months after, completion of antibiotic therapy. Biopsies were taken for rapid urease testing and the histological demonstration of H. pylori infection. Patients with persistent H. pylori infection at follow-up endoscopy were re-treated with a second and identical antibiotic treatment course. A subsequent endoscopic examination with accompanying biopsies was performed at least 6 weeks after the second treatment course and after a further 6, 18 and 30 months. RESULTS: Eradication of H. pylori was achieved in 69 patients (84%, 95% CI: 75-90%) after the first treatment. Four patients (4/82 = 5%) were withdrawn from the study because of side-effects. All of the remaining nine patients had their H. pylori infection eradicated after the second treatment course (95% CI: 70-100%). Seventy-eight patients had a follow-up examination after a median 30 months of the initial eradication of H. pylori, and all but one remained free of infection and none had an ulcer relapse. CONCLUSIONS: This study demonstrates that patients with persistent H. pylori infection after completing a primary course of omeprazole (40 mg once daily), amoxycillin (750 mg t.d.s.) and metronidazole (400 mg t.d.s.) will probably respond to a repeat course of treatment with the same antibiotic combination.

Adult↗
PubMed1997

Evaluation of the RFIPC, a disease-specific health-related quality of life questionnaire, in Swedish patients with ulcerative colitis.

BACKGROUND: We wanted to characterize a Swedish version of the Rating Form of Inflammatory Bowel Disease Patient Concerns (RFIPC) with regard to validity, reliability, and responsiveness. METHODS: Two hundred and three consecutive patients with ulcerative colitis were studied. Health-related quality of life (HRQOL) was measured with the disease-specific questionnaire, the RFIPC, and a general questionnaire, the Sickness Impact Profile (SIP). Concerns about general well-being were also reported. Disease activity was measured by means of symptom cards, laboratory tests, and two clinical indices for disease activity. RESULTS: Test-retest reliability using Spearman's r (rs) was 0.79, and internal consistency measured with Cronbach's alpha was 0.95. RFIPC had a fair correlation with concerns about general well-being (rs = 0.69, P < 0.001). There was also a stronger correlation with another measure of HRQOL, the overall SIP score (rs = 0.43), than with measures of disease activity such as stool frequency (rs = 0.28) and sigmoidoscopic grading (NS). The group of patients in relapse had a higher RFIPC sum score than patients in remission (P = 0.001). Measures of HRQOL had a low correlation with disease activity and did not respond to changes in disease activity. CONCLUSION: The Swedish version of the RFIPC is a valid and reliable measure of HRQOL. The SIP and the RFIPC have a good discriminative ability between groups of patients in remission and in relapse. However, they do not seem to be useful in predicting the disease activity or change in disease activity over time in the individual patient.

Adult↗
PubMed1997

The diagnostic value of enzyme immunoassay and immunoblot in monitoring eradication of Helicobacter pylori.

55 patients with severe ulcer disease and H. pylori infection, successfully treated with antimicrobials, were followed-up with repeated blood samples for up to 32 months. Sera were analysed by enzyme immunoassay (EIA) for IgG and IgA antibodies and by IgG immunoblot. The EIA for IgG antibodies showed a high sensitivity (100%), while IgA antibodies above the cut-off level were found in 55% of the patients. At a median of 77 days after onset of treatment, approximately 50% of the patients showed a significant decrease (> or = 50%) of IgG or had titres below the cut-off level. All patients but 1 had a significant decrease of IgG after 6-12 months. The decrease was slower for IgA. The H. pylori-specific 116 kDa and 19.5 kDa bands were found in all pre-treatment samples, but the decrease in median intensity of the bands was slower than for the IgG EIA. In the 32-months post-treatment samples, both bonds had an intensity still above 50% of the pre-treatment value. The study showed that the IgG EIA is a useful method for monitoring eradication of H. pylori. Immunoblot can detect previous H. pylori infection in EIA negative Individuals.

Enzyme-Linked Immunosorbent Assay↗
PubMed1996

The single-stranded DNA end binding site of p53 coincides with the C-terminal regulatory region.

p53 is a transcription factor that binds double-stranded (ds) DNA in a sequence-specific manner. In addition, p53 can bind the ends of single-stranded (ss) DNA. We previously demonstrated that ssDNA oligonucleotides interact with the C-terminal domain of p53 and stimulate binding to internal segments of long ssDNA by the p53 core domain. Here we show that the p53 C-terminal domain can recognize staggered ss ends of dsDNA. We have mapped the binding site for ssDNA ends to residues 361-382 in human p53 using a p53 deletion mutant (p53-delta 30) lacking the 30 C-terminal amino acid residues and a series of 22mer peptides. The binding site for DNA ends coincides with a region previously implicated in regulation of sequence-specific DNA binding by the core domain. The interaction of the C-terminal regulatory domain with the ends of ssDNA or with the protruding ends of dsDNA stimulates both sequence-specific and non-specific DNA binding via the core domain. Electron microscopy demonstrated the simultaneous binding of p53 to dsDNA and a ssDNA end. These results suggest a model in which interaction of the p53 C-terminal tail with DNA ends generated after DNA damage causes activation of sequence-specific p53 DNA binding in vivo and may thus provide a molecular link between DNA damage and p53-mediated growth arrest and apoptosis.

Amino Acid Sequence↗
PubMed1996

Use of air enema radiography to assess depth of ulceration during acute attacks of ulcerative colitis.

BACKGROUND Acute colitis is usually assessed by means of plain abdominal radiographs, the diagnostic utility of which can be enhanced by barium enema. Colonoscopy can also be useful. The latter methods may be laborious and carry risk. We describe a radiographic technique using air as the contrast medium to show mucosal or deeper ulceration. METHODS Of 60 patients undergoing colectomy for acute ulcerative colitis, 35 had air enema radiography and 14 had plain films with sufficient amount of spontaneously occurring gas to allow visualisation of the mucosa, during the 10 days before surgery. The degree of inflammation on air enema films and the extent of histopathological ulceration in colectomy specimens were independently graded and compared with each other. Depth of ulceration was compared with clinical data including a preoperative risk stratification, the APACHE II score. FINDINGS The degree of inflammation on air enema radiography correlated significantly with depth of ulceration at histopathological examination (rs 0.61, p<0.001). Presence of mucosal changes had a close association with deep ulceration extending into the muscularis propria layer or beyond (p<0.001). Air enema radiography had a high sensitivity (0.91) for presence of and specificity (0.75) in the exclusion of deep ulceration, with positive and negative predictive values of 0.88 and 0.80. 42 of 49 patients were correctly classified as regards deep ulcers. The correlation between higher preoperative APACHE II scores and severity of histopathological colitis was weak (rs 0.30, p<0.05). INTERPRETATION Air enema radiography reliably assesses the presence of colonic ulceration in patients with an acute attack of ulcerative colitis. It is a first-line investigation to assess the presence of deeper ulceration in acute colitis.

APACHE↗
PubMed1996

Technetium-99m scintigraphy: more accurate assessment of ulcerative colitis with exametazime-labelled leucocytes than with antigranulocyte antibodies.

To compare two technetium-99m scintigraphic techniques - 99mTc-labelled antibodies against granulocyte non-specific cross-reacting antigen-95 and 99mTc-exametazime labelled leucocytes in ulcerative colitis - 23 consecutive patients undergoing colonoscopy were investigated in a prospective and randomized study. In each patient the two scans and colonoscopy and biopsy were performed within 10 days. Scans, endoscopy and histology were independently graded for degree of inflammation in eight different colorectal segments for each patient. Active inflammation in one or more segments was present on endoscopy in 22 patients and on histology in 17 patients. Twenty-two patients had increased uptake on the antibody scan and 21 patients on the exametazime scan. Twelve patients showed the same disease extent with both scan methods (total colitis, n=10; distal colitis, n=2). Compared with endoscopy, sensitivity for inflammation in individual segments was 0.51 for antibody scan and 0.87 for exametazime scan; specificity was 0.67 and 0.55, respectively. The predictive value for presence of inflammation was 0.66 for antibody scan and 0.72 for exametazime; the predictive value for absence of inflammation was 0.52 and 0.77, respectively. Segmental scan uptake of endoscopically or histologically visualized inflammation was consistently lower for antigranulocyte antibodies than for exametazime. It is concluded that in patients with active ulcerative colitis, inflammation is better visualized with 99mTc-exametazime labelled leucocytes than with 99mTc-labelled antigranulocyte antibodies. The antibody technique offers the advantage of in vivo labelling, but is less reliable than the exametazime method for imaging of colonic inflammation.

Adolescent↗
PubMed1996

Is small bowel biopsy necessary in adults with suspected celiac disease and IgA anti-endomysium antibodies? 100% positive predictive value for celiac disease in adults.

The comparative diagnostic value of IgA anti-endomysium and IgA antigliadin antibodies in adults with histologically confirmed celiac disease is reported. Sera from 144 adult patients (without concurrent dermatitis herpetiformis or IgA deficiency) who underwent small bowel biopsy were analyzed for both IgA anti-endomysium and IgA anti-gliadin antibodies. Nineteen patients (13%) had celiac disease. The presence of IgA antiendomysium antibodies had a sensitivity of 74% and a specificity of 100%. The positive and negative predictive values were 100% and 96%, respectively, and the diagnostic accuracy was 97%. In contrast, IgA anti-gliadin antibodies had positive and negative predictive values of 28% and 96%, respectively, with a diagnostic accuracy of 71%. Based on these data, we suggest that small bowel biopsy is not necessary to diagnose celiac disease in symptomatic adults with IgA antiendomysium antibodies. Due to a negative predictive value of 96%, some symptomatic adults lacking anti-endomysium antibodies will not be correctly diagnosed without small bowel biopsy.

Adolescent↗
PubMed1996

Reversal of osteopenia with diet in adult coeliac disease.

To evaluate the effects of a gluten free diet on bone mineral density in untreated adult patients with coeliac disease, 63 patients (17-79 years, 35 women) were examined at diagnosis and after one year taking a gluten free diet. Bone mineral density was measured in the forearm using single photo absorptiometry and in the lumbar spine, femoral neck, and trochanter using dual energy x ray absorptiometry. The values for each patient were compared with those of 25 healthy controls, matched for sex, age, and menopausal state. Before being given a gluten free diet bone mineral density in the total group was reduced at all sites (p < 0.001). Age adjusted bone mineral density was inversely correlated with age. During the first year taking a gluten free diet bone mineral density increased at all sites (p < 0.01). This was seen in patients of all ages and in patients who were without symptoms of malabsorption (weight loss or diarrhoea) before treatment. Low bone mineral density in patients with untreated coeliac disease increases rapidly when treatment with a gluten free diet is followed. These findings emphasise the importance of early diagnosis and treatment in all patients with coeliac disease.

Adult↗
PubMed1996

Concentrations of platelet activating factor in rectal mucosa in patients with ulcerative colitis.

OBJECTIVE: To find out if concentrations of platelet activating factor (PAF), which has been proposed as a mediator in the pathogenesis of ulcerative colitis and Crohn's disease, are increased in the rectal mucosa of patients with ulcerative colitis. DESIGN: Open study. SETTING: University hospital, Sweden. SUBJECTS: 45 Patients with ulcerative colitis (19 with active disease and 26 in remission), and 6 control patients and 11 healthy volunteers who acted as controls. INTERVENTIONS: Rectal biopsy. MAIN OUTCOME MEASURE: PAF content of rectal biopsy specimens. RESULTS: There were no differences between the PAF content of rectal mucosa in patients with active disease (median 47 pmol/g wet weight), patients in remission (47 pmol/g), and controls (51 pmol/g). There was no correlation between PAF content and inflammation seen endoscopically or histologically. 13 Patients who had active disease were investigated on a second occasion 9 weeks later (range 7-17), when in remission having received steroids but steroid-free at that time. There was a slight but not significant trend towards lower concentrations of PAF (median 33 pmol/g) compared with their previous results, possibly as a result of treatment. PAF concentrations were significantly lower than those of a group of patients in clinically stable remission of longer duration (p < 0.05). CONCLUSIONS: We did not find high concentrations of PAF in the rectal mucosa of patients with active ulcerative colitis compared with patients in remission or controls. We therefore have no evidence that PAF has an important role as a mediator in the inflammation of ulcerative colitis.

Adult↗
PubMed1995

Is computer-aided interpretation of 99Tcm-HMPAO leukocyte scans better than the naked eye?

In order to compare visual interpretation of inflammation detected by leukocyte scintigraphy with that of different computer-aided quantification methods, 34 patients (25 with ulcerative colitis and 9 with endoscopically verified non-inflamed colonic mucosa), were investigated using 99Tcm-hexamethylpropyleneamine oxime (99Tcm-HMPAO) leukocyte scintigraphy and colonoscopy with biopsies. Scintigrams were obtained 45 min and 4 h after the injection of labelled cells. Computer-generated grading of seven colon segments using four different methods was performed on each scintigram for each patient. The same segments were graded independently using a 4-point visual scale. Endoscopic and histological inflammation were scored on 4-point scales. At 45 min, a positive correlation was found between endoscopic and scan gradings in individual colon segments when using visual grading and three of the four computer-aided methods (Spearman's rs = 0.30-0.64, P < 0.001). Histological grading correlated with visual grading and with two of the four computer-aided methods at 45 min (rs = 0.42-0.54, P < 0.001). At 4 h, all grading methods correlated positively with both endoscopic and histological assessment. The correlation coefficients were, in all but one instance, highest for the visual grading. As an inter-observer comparison to assess agreement between the visual gradings of two nuclear physicians, 14 additional patients (9 ulcerative colitis, 5 infectious enterocolitis) underwent leukocyte scintigraphy. Agreement assessed using kappa statistics was 0.54 at 45 min (P < 0.001). Separate data concerning the presence/absence of active inflammation showed a high kappa value (0.74, P < 0.001). Our results showed that a simple scintigraphic scoring system based on assessment using the human eye reflects colonic inflammation at least as well as computer-aided grading, and that highly correlated results can be achieved between different investigators.

Adolescent↗
PubMed1995

Plain X-ray films and air enema films reflect severe mucosal inflammation in acute ulcerative colitis.

In a prospective study of 34 patients with active ulcerative colitis, the findings of inflammation on plain abdominal films and air enema films were compared to those at colonoscopy including biopsy within 10 days. The degree of inflammation on X-ray films was graded independently by two radiologists, at colonoscopy by one gastroenterologist and from histological slides from 6 different colon segments by one pathologist for each patient. Air enema films had a high sensitivity for endoscopically confirmed friable or ulcerated mucosa (0.91). There was a high specificity (0.86) when excluding inflammation in individual colon segments. Absence of fecal residue as an indication of active inflammation had the same positive predictive value, 0.95, as an abnormal air enema film, 0.98 for endoscopically confirmed inflamed mucosa. The presence of fecal residue or a normal air enema film excluded a friable or ulcerated mucosa at endoscopy with negative predictive values of 0.83 and 0.86, respectively. Patients who had had a complete colonoscopy (n = 16) were divided into groups with total, extensive or distal colitis. Air enema films underestimated the extent of inflammation in 8 of 16 patients compared to colonoscopy. Of 6 patients with distal disease only on air enema films, 5 had disease above the splenic flexure at endoscopy. In patients with ulcerative colitis (1) the presence of fecal residue and a normal air enema film exclude a friable or ulcerated mucosa with a high degree of certainty, and (2) the absence of fecal residue and an abnormal air enema film are predictors of the presence of endoscopically confirmed inflammation.

Adult↗
PubMed1995

Air enema radiology compared with leukocyte scintigraphy for imaging inflammation in active ulcerative colitis.

OBJECTIVE: To compare air enema radiology with a leukocyte scintigraphy technique using technetium-99m-hexamethyl propylene amine oxime-labelled leukocytes for imaging colonic inflammation in ulcerative colitis. DESIGN: Prospective study in a University hospital. One radiologist and one nuclear physician independently graded the degree of inflammation in six colon segments per patient using radiographs and leukocyte scans. PATIENTS: Twenty consecutive patients with symptoms of active ulcerative colitis requiring corticosteroids, inflammation on rigid sigmoidoscopy and a positive leukocyte scan above the rectum. RESULTS: Using air enema radiology, inflammation above the rectum was observed in 17 of the 20 patients. Eleven patients had the same extent of disease with both imaging techniques (total n = 5; extensive n = 3; distal n = 3). Seven patients had more widespread colitis using leukocyte scintigraphy. In the remaining two patients with extensive inflammation at scintigraphy, air enema films showed total colitis. When the colon was subdivided into six different segments, prediction of the presence of inflammation in individual segments was 0.88 for air enema radiology compared with leukocyte scintigraphy and 0.60 for the prediction of absence of inflammation. All segments with an irregular mucosal contour or ulceration on air enema films had intense inflammation at scintigraphy. CONCLUSIONS: In patients with active ulcerative colitis, air enema radiology underestimates the extent of inflammation because this investigation shows secondary patho-anatomical changes, while leukocyte scintigraphy visualizes the acute cellular infiltrate. In patients with more severe inflammation, there is excellent agreement between the two methods.

Adolescent↗
PubMed1994

Bone mineral density in coeliac disease.

Patients with coeliac disease may have osteomalacia or osteoporosis, even in the absence of abdominal symptoms. Little is known about the effects of a gluten-free diet and villous restitution on the bone mineral density in adult patients with coeliac disease. Of the 288 patients with coeliac disease in our unit, 13 (5%) had persistent villous atrophy of the small bowel despite dietary recommendations over at least the previous 4 years. For each of these 13 patients, 1 or 2 controls with coeliac disease, matched for age, gender, menopausal state, and dermatitis herpetiformis, whose intestinal mucosa had normalized at least 4 years earlier, were identified (n = 17). Bone mineral density was measured in the forearm using single-photon absorptiometry and in the femoral neck and trochanter using dual-energy X-ray absorptiometry. Bone mineral density was reduced at all sites in patients with persistent villous atrophy compared with patients responsive to diet and healthy controls. Bone mineral density in patients responsive to diet did not differ from that in healthy controls. Persistent villous atrophy is associated with low bone mineral density, underlining the importance of keeping to a proper diet.

Adult↗
PubMed1993

Increased absorption of polyethylene glycol 600 deposited in the colon in active ulcerative colitis.

A defect in the barrier function of the intestinal mucosa has been proposed as important in both the pathogenesis and systemic manifestations of inflammatory bowel disease. After colonoscopy, polymers of polyethylene glycol (PEG) with molecular weights of 414-810 (mean 600), were instilled in the descending colon of patients with ulcerative colitis (n = 17) and in controls without intestinal inflammation (n = 8). The patients with active ulcerative colitis (n = 6) had a significantly increased uptake of PEGs in the molecular weight range 458-810, measured as urinary excretion over the first 6 hours after instillation. The median values for their excretion were 2.85-3.80% of PEGs instilled compared with 0.32-0.94% for patients in remission (n = 11) (p < 0.05-0.01) and 0.17-0.60% for the controls (p < 0.05-0.01). The differences in absorption of PEG 414 did not reach the present level of statistical significance. There was a positive correlation between PEG absorption and the endoscopic and histological grading of inflammatory activity in the sigmoid colon (p < 0.01-0.001). These findings support a correlation between the presence of active inflammation and PEG absorption. There was little evidence to support the presence of a primary defect in the colonic barrier in patients with ulcerative colitis.

Adolescent↗
PubMed1992

Pharmacokinetics of tranexamic acid in patients with ulcerative colitis and in healthy volunteers after the single instillation of 2 g rectally.

Topically applied antifibrinolytic drugs may be of value in the control of bleeding in active ulcerative colitis. Any impairment of systemic fibrinolysis in this condition, however, is potentially harmful. Since pharmacokinetic data after the rectal administration of tranexamic acid are non-existent, plasma concentration and recovery in the urine were recorded after a single dose of 2 g tranexamic acid given rectally to five patients with ulcerative colitis and to five healthy volunteers. The median area under the curve was, for the volunteers, 7.64 mg/L x hr (range: 4.43-11.56) and, for the patients, 13.84 mg/L x hr (range: 9.32-50.22) (P less than .05). The median 24-hour recovery in the urine was 0.8% (0.3-1.1) and 2.7% (1.1-4.0), respectively (P less than .05). The median peak plasma concentration was, for the volunteers, 0.40 mg/L (range: 0.20-0.69) 6 hours after administration and, for the patients, 1.10 mg/L (range: 0.53-2.90) 5 hours after administration (P less than .05). The plasma concentrations and recovery in the urine that were observed in the patients and volunteers were low compared with those seen after oral intake of the same dose. The plasma concentrations did not reach levels that were considered liable to impair systemic fibrinolysis.

Administration, Rectal↗
PubMed1992

Do technetium-99m hexamethylpropylene amine oxime-labeled leukocytes truly reflect the mucosal inflammation in patients with ulcerative colitis?

Twenty-five patients with ulcerative colitis and nine controls with macroscopically non-inflamed colon were investigated with technetium-99m hexamethylpropylene amine oxime-labeled leukocyte scintigraphy and colonoscopy with biopsies. The interval between leukocyte scintigraphy and colonoscopy was < or = 14 days in all patients with ulcerative colitis and < or = 30 days in eight of nine controls. Scintigrams were obtained at approximately 45 min and 4 h after injection of labeled leukocytes. One nuclear physician, one internist, and one pathologist graded blindly and independently of each other the degree of active inflammation in seven different colonic segments for each patient, using 4-grade scales for scans and macroscopically and histologically viewed inflammation, respectively. A positive correlation between endoscopic and histologic grading of all colonic segments and scan gradings for all subjects and for ulcerative colitis patients separately was found (all, p < 0.001). By means of kappa statistics, the inter-observer agreement between scintigraphic grading at 45 min and endoscopy was, for all subjects, 0.32 (95% confidence interval (CI), 0.20-0.44; p < 0.001) and, for patients with ulcerative colitis, 0.19 (CI, 0.07-0.31; p < 0.001). When 17 patients who had complete colonoscopies were divided into those with total, extensive, or distal colitis, leukocyte scintigraphy underestimated the extension of active inflammation. A simple scintigraphic scoring system reflects the colonic inflammation viewed endoscopically and histologically in patients with ulcerative colitis but underestimates the presence of active inflammation in individual colonic segments.

Adolescent↗