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Biomedical subjects

P Schlichting

Publications and source records attributed to P Schlichting.

At least 19 recordsLinked to original sources

Ascites fluid and plasma calprotectin concentrations in liver disease.

BACKGROUND: Calprotectin, a marker of neutrophil activation, has been associated with a poor prognosis in alcohol-induced cirrhosis. The aims were to study concentrations of calprotectin in patients with various liver diseases, and to further investigate the prognostic value of calprotectin in cirrhosis. METHODS: Plasma calprotectin concentrations were determined in 84 patients with alcohol-induced liver disease, 32 hepatitis B or C infected patients, 33 patients with liver disease of other aetiologies, 7 patients with combined aetiologies and in 24 patients with malignant disease. Thirty healthy individuals were included as controls. Ascites calprotectin concentrations were determined in patients with ascites (n = 75). Follow-up for survival was performed after a median observation period of 10 months. RESULTS: Increased plasma and ascites calprotectin concentrations were observed in malignant disease compared to non-malignant disease (P < 0.0001). Plasma calprotectin concentrations were low in viral liver disease compared to patients with non-viral liver disease (P = 0.02) and to controls (P = 0.0002). Plasma calprotectin (>median) was a highly significant marker of poor survival in alcohol-induced cirrhosis (P = 0.001), but was of no prognostic value in non-alcohol-induced cirrhosis (P = 0.88). In decompensated cirrhosis high (>upper quartile) ascites calprotectin concentrations were associated with an increased mortality (P = 0.002), as were high (>median) plasma calprotectin levels (P = 0.009). CONCLUSION: The prognostic importance of calprotectin in alcohol-induced cirrhosis is confirmed and demonstrated as specific for alcohol-induced liver disease. Low calprotectin levels are indicated in viral liver disease, and an association between high ascites calprotectin levels and malignant ascites was observed.

Ascitic Fluid↗

Inflammatory bowel disease evaluated by low-field magnetic resonance imaging. Comparison with endoscopy, 99mTc-HMPAO leucocyte scintigraphy, conventional radiography and surgery.

BACKGROUND: To evaluate the use of low-field magnetic resonance imaging (MRI) in active inflammatory bowel disease (IBD). METHODS: MRI was executed in a consecutive cohort of 28 patients with Crohn disease (CD) and in 17 with ulcerative colitis (UC) prior to glucocorticoid treatment (1 mg prednisolone orally/kg body weight/day). MRI was repeated after 2-3 weeks (22 CD, 12 UC), and again after treatment completion or prior to surgery (18 CD, 6 UC). Five bowel segments were evaluated separately. MRIs were blindly evaluated by two observers, and findings compared with 39 leucocyte scintigraphies, 38 endoscopies, 15 double-contrast barium enemas, 66 small-bowel radiographic examinations and surgery in 23 patients. RESULTS: In CD, blinded evaluation revealed a kappa (kappa) of 0.84 (95% confidence interval (CI) 0.78-0.91). In UC, kappa was 0.66 (95% CI 0.55-0.78). Agreements regarding disease extension between MRI and other modalities in CD were found in 345 bowel segments out of 391 (88.2%) at risk, and in UC in 209/235 (88.9%). Colonic disease activity gradings by radiography and endoscopy correlated significantly with T2-signal intensity (SI(T2)) and increments in T1-signal intensity (%SI(T1)) in both diseases. Significant correlations between MRI indices of disease activity and CDAI in CD (MRI-SI(T2): P <0.0001: MRI% SI(T1): P=0.0008) and the Powell-Tuck index in UC (MRI% SI(T1): P=0.008) were found. CONCLUSIONS: With low interobserver variation and high concordance of findings with other examinations. low-field MRI seems a valuable modality in active IBD. In addition, MRI expressions of disease activity correlate to clinical, radiographic and endoscopic disease activity.

Adult↗

Interferon alfa-2b alone or combined with recombinant granulocyte-macrophage colony-stimulating factor as treatment of chronic hepatitis C.

BACKGROUND: To compare the effect of combination therapy with interferon-alpha (INF-alpha) and granulocyte-macrophage colony-stimulating factor (GM-CSF) to monotherapy with INF-alpha in patients with chronic hepatitis C infection. METHODS: Forty-five consecutive patients with chronic hepatitis C, all presenting with elevated serum alanine aminotransferases and viremia, were randomized to receive either 1) INF-alpha + GM-CSF for 3 months followed by INF-alpha alone for 9 months (n = 23) or 2) INF-alpha for 12 months (n = 22). Both drugs were administered 3 times weekly in doses of 3 mU (INF-alpha) and 50-100 microg depending on body weight (GM-CSF). RESULTS: At baseline, there was no difference between the treatment groups in terms of age, sex, ALT level, viral load, genotype or histological activity and fibrosis in a pretreatment liver biopsy. After 12 months' treatment, more patients treated with GM-CSF+ INF-alpha compared to patients receiving monotherapy had normalized ALT, 65% and 32%, respectively (P = 0.03), but there was no difference in percentages of patients with viral clearance between the 2 groups, 48% and 32%, respectively (P = 0.27). At 6 months' follow-up, the biochemical response had declined to 35% in the combination therapy group and to 23% in the monotherapy group (P = 0.37); viral clearance had declined to 22% and 27%, respectively (P = 0.67), and the overall sustained response rate was 22% and 23%, respectively (P = 1.00). CONCLUSIONS: Even though patients receiving INF-alpha + GM-CSF had a significant better biochemical response during treatment compared to patients receiving monotherapy, the sustained biochemical and virological response was not increased. Thus, GM-CSF hardly plays any role in the future treatment of chronic hepatitis C.

Adult↗

Prevalence of hereditary haemochromatosis in late-onset type 1 diabetes mellitus: a retrospective study.

BACKGROUND: Although genotyping studies suggest that hereditary haemochromatosis is one of the most common genetic disorders in white people, it is still thought of as an uncommon disease. Our aim was to test the hypothesis that hereditary haemochromatosis is a disease often overlooked in patients with late-onset type 1 diabetes mellitus, a late manifestation of untreated iron overload. METHODS: We did a retrospective study in which we genotyped for the C282Y and H63D mutations in the haemochromatosis gene in 716 unselected Danish patients who developed type 1 diabetes mellitus after age 30 years and 9174 controls from the general Danish population. We also screened for hereditary haemochromatosis by assessment of transferrin saturation. FINDINGS: More patients with diabetes (n=9, relative frequency 1.26%, 95% CI 0.58-2.37) than controls (23, 0.25%, 0.16-0.38) were homozygous for C282Y (odds ratio 4.6, 2.0-10.1, p=0.0001). These patients had unrecognised signs of haemochromatosis. Transferrin saturation and ferritin concentrations ranged from 57% to 102% and 17 microg/L to 8125 microg/L, respectively. Frequency of compound heterozygosity (C282Y/H63D) did not differ between patients with diabetes (eight) and controls (131) (odds ratio 0.8, 95% CI 0.4-1.7). Positive and negative predictive values of transferrin saturation greater than 50%, in identification of C282Y homozygosity, were 0.26 and 1.00, respectively. A saturation of less than 50% therefore excluded C282Y homozygosity, whereas a saturation of more than 50% suggested C282Y homozygosity. INTERPRETATION: Measurement of transferrin saturation followed by genetic testing could prevent liver and heart problems and improve life expectancy in patients with diabetes. Population screening before the onset of diabetes might improve the outlook of patients even further, but will be less cost effective.

Adult↗

An open-labeled, randomized study comparing systemic interferon-alpha-2A and prednisolone enemas in the treatment of left-sided ulcerative colitis.

OBJECTIVE: The aim of this study was to compare the treatment efficacies of subcutaneous interferon-alpha-2A (IFN-alpha-2A) injections versus prednisolone enemas in active left-sided ulcerative colitis in an open-labeled, randomized study. METHODS: Sixteen ulcerative colitis patients received IFN-alpha-2A subcutaneously (dosage: first wk, 9 MIU three times weekly [t.i.w.]; second wk, 6 MIU t.i.w.; wk 3-12, 3 MIU t.i.w.), and 16 received prednisolone enemas for 30 days (100 ml once daily, 0.25 mg of prednisolone/ml). The Powell-Tuck Index, Inflammatory Bowel Disease Questionnaire (IBDQ) score, and rectal histological activities were assessed before and after treatment. Thirteen patients in the IFN-alpha-2A group and all 16 in the prednisolone enema group completed the treatment. RESULTS: IFN-alpha-2A treatment showed significant improvements in the Powell-Tuck Index (p = 0.0002), IBDQ score (p = 0.002), and rectal histological activity scores (p = 0.02). In the enema group, significant improvements were found in the Powell-Tuck Index (p = 0.0009), whereas no significant improvements were detected in the IBDQ scores (p = 0.055) or rectal histological scores (p = 0.052). There were no differences between scores of the two groups either before or after treatment. Only moderate side effects from the IFN-alpha-2A treatment were seen during the first 2-4 wk of treatment. CONCLUSION: IFN-alpha-2A treatment resulted in significant depression of the disease activity as reflected by the Powell-Tuck Index, IBDQ score, and histological disease activity scoring. The preliminary trial thus suggests that IFN-alpha-2A may be effective in the treatment of active left-sided ulcerative colitis. Larger, randomized trials are, however, warranted to confirm this finding, owing to possible type II errors in group comparisons.

Adult↗

Ethical aspects of clinical trials: the attitudes of participants in two non-cancer trials.

OBJECTIVES: To investigate attitudes to clinical trials in non-cancer trial participants. DESIGN: Questionnaires at entry, during, and after participation in a clinical study. SETTING: Participants in: (i) ROC: a clinical study comparing systemic interferon-alpha-2A treatment vs. prednisolone enemas in ulcerative colitis; and (ii) MRCRUC: a clinical study investigating low-field magnetic resonance imaging as a new modality for the evaluation of patients with inflammatory bowel disease. SUBJECTS: Thirty-two patients in ROC and 47 patients in MRCRUC. OUTCOME MEASURES: Attitudes towards different aspects of clinical research. RESULTS: The majority found scientific testing of clinical methods necessary, having positive attitudes towards both participation by themselves and others. The creation of a personal moral problem by denying participation was rejected by a large majority, and still both personal and altruistic motives for participation were highly rated. An important motive for accepting inclusion was the expectation of being 'a special patient' during the trial. The presence of research ethics committees controlling clinical research had a significant positive impact on decisions to participate, and drawing lots and blinding were found problematic by only a minority. Patients valued their satisfaction with participation in the trials highly, and would almost all accept a request to participate in future trials. The most important reason for this was a feeling of receiving better care and information than expected outside a trial setting, primarily determined by the patients seeing only one physician during the trials. A pronounced wish to obtain follow-up information was expressed. CONCLUSION: Attitudes towards medical research are positive with both altruistic and nonaltruistic motives for participation. Expectations of being treated as 'a special patient' in the trial were important in accepting to participate. Seeing the same physician at control visits was an important factor for satisfaction with participation.

Adult↗

A randomized, placebo-controlled, cross-over study of ginger extracts and ibuprofen in osteoarthritis.

OBJECTIVE: Alternative medicine is used extensively by patients with chronic pain due to e.g., osteoarthritis. Only few of these drugs have be tested in a controlled setting and the present study was undertaken to examine the effect of ginger extract, one of the most popular herbal medications. DESIGN: Ginger extract was compared to placebo and Ibuprofen in patients with osteoarthritis of the hip or knee in a controlled, double blind, double dummy, cross-over study with a wash-out period of one week followed by three treatment periods in a randomized sequence, each of three weeks duration. Acetaminophen was used as rescue medication throughout the study. The study was conducted in accordance with Good Clinical Practice (European Guideline for GCP). RESULTS: A ranking of efficacy of the three treatment periods: Ibuprofen>ginger extract>placebo was found for visual analogue scale of pain (Friedman test: 24.65, P< 0.00001) and the Lequesne-index (Friedman test: 20.76, P< 0.00005). In the cross-over study, no significant difference between placebo and ginger extract could be demonstrated (Siegel-Castellan test), while explorative tests of differences in the first treatment period showed a better effect of both Ibuprofen and ginger extract than placebo (Chi-square, P< 0.05). There were no serious adverse events reported during the periods with active medications. CONCLUSION: In the present study a statistically significant effect of ginger extract could only be demonstrated by explorative statistical methods in the first period of treatment before cross-over, while a significant difference was not observed in the study as a whole.

Adult↗

[Amyloidosis. A review].

Amyloidosis is a heterogenous group of diseases, all characterized by extracellular deposition of amyloid either systemically or localized. Of wellknown diseases are Alzheimer's dementia, AL-amyloidosis (e.g. in multiple myeloma) and AA-amyloidosis (e.g. in rheumatoid arthritis). Amyloid is composed of three components of which the fibrillary component is the basis of amyloid classification. Many types of amyloid have a systemic distribution and give rise to varying symptoms. The diagnosis is based on biopsy, preferably of abdominal subcutis. The prognosis is poor, however, recent investigations on the three-dimensional structure of the P-component provide hope for future therapy.

Amyloid↗

[Amyloidosis: rapid course of AL-amyloidosis in a patient without myelomatosis].

A case of severe AL-amyloidosis in a 72-year-old man is presented. Amyloid was especially deposited in the kidneys and the liver. The patient died one year after diagnosis with impaired kidney function and severe ascites. Despite the type of amyloid (AL-type), multiple myelomata or lymphoproliferative disease could not be demonstrated.

Aged↗

[Transjugular intrahepatic portosystemic shunt. Treatment of patients with recurrent bleeding from esophageal varices].

We report the results of transjugular intrahepatic portosystemic shunt (TIPS) procedure in six patients with liver cirrhosis and recurrent bleeding or acute intractable bleeding from oesophageal varices in spite of multiple sessions of sclerotherapy. Median follow-up was 15 months (range 1-24 months). The procedure was technically successful in all patients without procedure-related morbidity or mortality. Four of the procedures were performed electively and two as an emergency procedure. The portosystemic pressure gradient decreased to below 12 mmHg following TIPS implantation and the shunt bloodflow was one quarter to three-quarters of the portal bloodflow determined by Doppler ultrasound. Recurrent bleeding occurred in one patient but was amenable to endoscopic sclerotherapy. In this patient the shunt had developed a stenosis that was treated by balloondilatation and insertion of an additional stent six months following the initial procedure, and no further bleeding occurred. The remaining five patients had no rebleeding episodes. Repeated Doppler examinations in the followup period demonstrated patency of all shunts. None of the patients developed portosystemic encephalopathy. One patient died of cerebral haemorrhage, unrelated to TIPS, 16 months following implantation. Another patient died 14 months following TIPS due to acute mesenteric occlusion and septicaemia. We conclude that TIPS is feasible and effective in selected patients with liver cirrhosis and persistent or recurrent variceal bleeding following repeated endoscopic therapy.

Adult↗

Active Crohn's disease and ulcerative colitis evaluated by low-field magnetic resonance imaging.

BACKGROUND: Our aim was to evaluate low-field magnetic resonance imaging (MRI) in the assessment of disease extension and activity in inflammatory bowel disease. METHODS: Nineteen patients with Crohn's disease (CD), 8 with ulcerative colitis (UC), and 5 healthy controls (HC) were examined using MRI (0.1 T) before and after intravenously administered gadodiamide and glucagon. MRI images were evaluated in a blinded fashion and compared with findings at endoscopy, double-contrast barium enema, small-bowel follow-through, and surgery. RESULTS: Comparisons of diseased with both non-diseased bowel segments and segments from HC showed significant differences for both CD and UC with regard to signal intensity on T2-weighted (SI(T2)) images and post-contrast increment of signal intensity on T1-weighted images (%SI(T1). Agreements with regard to disease extension in CD between MRI and other examinations were 97%, underestimating the extension in two patients. For SI(T2) in CD a cut-off value of 1.0 showed a predictive value of a positive finding (PVpos) = 1.0 and a predictive value of a negative finding (PVneg) = 0.96. For %SI(T1) in CD a cut-off value of 15.0% showed values of PVpos = 0.95 and PVneg = 0.92. Agreements between MRI and conventional methods (disease extension) in UC was 87.5%. Extension was underestimated in two patients and overestimated in two patients as compared with barium enemas. Values of PVpos were 1.0 (SI(T2) >1.0) and 1.0 (%SI(T1) >15.0%), respectively, with corresponding values of PVneg being 0.94 and 0.94. CONCLUSION: Low-field MRI seems a promising non-invasive, non-radiating method in the evaluation of inflammatory bowel disease.

Adult↗

Doppler ultrasound assessment of TIPS patency and function--the need for echo enhancers.

PURPOSE: The aim of this study was to illustrate the versatility of an i.v. administered echo enhancer for Doppler US assessment of TIPS patency and function. MATERIAL AND METHODS: A total of 22 Doppler US evaluations of TIPS patency and function were performed in 5 patients with alcoholic cirrhosis and recurrent oesophageal bleeding who had been treated with TIPS. TIPS patency was evaluated by means of colour or power Doppler US. The volume flow (VF) was assessed in the TIPS and in the portal vein by spectral Doppler. The ratio of the VF in the TIPS to the VF in the portal vein (T/P ratio) was used to express the functional status of the TIPS. If Doppler signals were inconclusive or absent, echo-enhanced US was performed. RESULTS: In 22 follow-up Doppler US examinations, echo-enhanced Doppler US was required in 7 cases (29%). The Doppler enhancement persisted in the range of 3-5 min. No adverse effects were observed. An apparently normal TIPS function reflected a T/P ratio in the range of 0.44-1.10, median 0.78 +/- 0.20 (2SD). CONCLUSION: The i.v. administration of echo enhancers would seem to be indicated in the assessment of the TIPS function if conventional Doppler US fails to prove normal TIPS patency and function. The T/P ratio may be a convenient monitoring parameter for reflecting the TIPS function.

Adult↗

[Penicillin treatment of non-nosocomial pneumonia in Danish medical departments. A questionnaire].

This study describes the most common penicillin-regime for hospitalized patients with community-acquired pneumonia in Denmark. One hundred and seventy-one consultant physicians received an anonymous questionnaire, 85% were returned and 75% were evaluated. The most common regime is a treatment duration of six to ten days with 3-6 million IU of penicillin daily given in three doses. The most common route of administration is intravenously until the patient's body temperature drops. Then the same dose is given orally. Variations in strategy were revealed and call for further investigations to establish and maintain restrictive antibiotic regimes.

Denmark↗

Tolerability of interferon alpha-2b, a possible new treatment of active Crohn's disease.

BACKGROUND AND AIMS: Due to the need for new principles for the treatment of Crohn's disease and due to the documented immunomodulatory effects of interferon alpha, the tolerability and effect(s) of interferon alpha-2b (Introna) in active Crohn's disease were examined in a pilot study. METHODS: Five patients with active Crohn's disease (activity index (CDAI) scores of 235-517), were treated with interferon alpha-2b for 12 weeks. RESULTS: All patients tolerated the treatment, but developed influenza-like symptoms, which were fully controlled by paracetamol. Two patients obtained partial remission with a decline in activity index scores of 39% and 50%. The activity of 2',5'-oligoadenylate synthetase, which together with two other interferon-induced proteins, neopterin and beta 2-microglobulin were increased during treatment, indicated clearly an in vivo uptake of interferon. Sedimentation rate, C-reactive protein, orosomucoid, albumin, specific inflammatory markers: soluble interleukin-2 alpha-receptors (sIL-2R) and intercellular adhesion molecule-1 (ICAM-1) did not show any changes before or after treatment. CONCLUSION: Future multicentre investigations are required to evaluate the clinical effect of interferon alpha-2b treatment in active Crohn's disease.

2',5'-Oligoadenylate Synthetase↗

The treatment effect of alpha interferon in chronic hepatitis B is independent of pre-treatment variables. Results based on individual patient data from 10 clinical controlled trials. European Concerted Action on Viral Hepatitis (Eurohep).

Alpha interferon induces HBeAg seroconversion in about one third of treated patients and has become an established treatment of chronic hepatitis B. A number of smaller studies have suggested that response to treatment is more likely to occur in patients with higher levels of transaminases, with recent (adult) onset, a history of acute hepatitis, low levels of HBV DNA and in heterosexual males. The aim of this European co-operative study was to estimate the effect of alpha interferon more accurately and to evaluate the influence of host pre-treatment variables on the effect of interferon. Individual data were collected from 751 patients from 10 controlled clinical trials on alpha interferon (lymphoblastoid or recombinant) treatment for chronic hepatitis B. Alpha interferon was administered to 496 patients, while 255 were untreated controls. Individual patient data were analysed by survival analysis (log rank test and Cox regression analysis), stratified by trial, with the disappearance of HBeAg as the major endpoint. The results showed that the HBeAg disappearance rate with or without interferon treatment was higher in patients with high aminotransferase levels, with a history of acute hepatitis and in male heterosexual patients disregarding HIV status. If HIV-positive patients were excluded, the effect of sexual orientation was not significant. Therapy with alpha interferon increased the a priori HBeAg disappearance rate by a factor of 1.76; the relative treatment effect of alpha interferon was independent of the tested pretreatment host variables, but dependent on the total (intended) interferon dose (low dose < or = 200 MU/m2 increased HBeAg disappearance by a factor 1.37; medium/high dose > or = 200 MU/m2 increased HBeAg disappearance by a factor 2.05). In conclusion, this meta-analysis suggests that the effect of alpha interferon is less than previously assumed and independent of pretreatment host variables tested. It confirms the higher therapeutic benefit of a total dose exceeding 200 MU/m2 and of selection of patients based on disease activity and immune reactivity. Although all patient seem to have the same relative benefit, the absolute benefit of alpha interferon treatment seems to be greatest in patients with high transaminase levels and with a history of acute hepatitis.

Adult↗

[Plasmapheresis as life-saving treatment in acute hepatic failure].

Emergency liver transplantation is the treatment of choice in acute liver failure without signs of spontaneous regeneration. However, many patients rapidly contract irreversible neurological complications before transplantation can be performed. We used high-volume plasmapheresis to increase the time span to obtain a donor liver. Four patients with acute liver failure of unknown cause and a galactose elimination capacity indicative of a virtually extinct liver function were assigned maximum priority for liver transplantation. Plasmapheresis were performed daily until transplantation. Each time 8-10 liters of patient plasma were replaced with an equal volume of fresh donor plasma. There were no major complications. None of the patients developed irreversible neurological complications for 48-144 h at which time liver transplantation was performed. High volume plasmapheresis increases the time to obtain a donor liver for emergency liver transplantation and optimizes the condition for the surgical procedure.

Acute Disease↗

[Garcin syndrome. Clinical aspects and diagnosis of a rare cranial nerve syndrome with special reference to computerized tomography and nuclear magnetic resonance image findings].

Garcin syndrome is an ipsilateral step-by-step deterioration of all 12 brain cranial nerves, first described in 1927. The underlying cause is usually a sarcoma or carcinoma of the skull base. The pathogenesis of the Garcin syndrome is chiefly determined by the slow localized growth of these tumors, rather than by their histology and primary localisation. The prognosis is as a rule unfavourable. The findings on computed and magnetic resonance tomography are important for an early diagnosis. Two cases of Garcin syndrome are reported, one of which was probably due to a tonsillar carcinoma, while the other was caused by a mucinous adenocarcinoma of the nasopharynx.

Adenocarcinoma↗

Colonic epithelial dysplasia or carcinoma in a regional group of patients with ulcerative colitis of more than 15 years duration.

Colonoscopic screening for neoplasia was performed in a regional group of ulcerative colitis patients with a disease duration of greater than or equal to 15 years. A total of 121 patients, aged less than 80 years, were invited to participate, of whom 100 (83%) accepted colonoscopy, including biopsies in 15 standard locations of the entire colon, plus additional biopsies from all visible lesions. Unequivocal dysplasia was found in one patient with extensive colitis and a disease duration of 31 years. A polyp with highly differentiated adenocarcinoma was found in the sigmoid colon of a patient with intermittent rectum involvement, 37 years after the ulcerative colitis diagnosis had been made. Biopsy specimens from the remaining 98 patients showed no signs of dysplasia or cancer. Thus the frequency of pre-malignant or malignant changes is very low compared with the results of similar studies, and the rationale for general colonoscopic surveillance programmes for such patients is open to question.

Adenocarcinoma↗