Type I intestinal lymphangiectasia treated successfully with slow-release octreotide.
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Adult↗
Biomedical subjects
D Ludwig
Publications and source records attributed to D Ludwig.
Alterations in pulmonary function in inflammatory bowel disease are frequent and persist during remission.
OBJECTIVES: Information on the occurrence and frequency of pulmonary involvement in patients with inflammatory bowel disease (IBD) is inconsistent. The aim of this prospective study was to determine the frequency and type of pulmonary dysfunction in patients with IBD. METHODS: Sixty-six patients with IBD (35 with Crohn's disease [CD] and 31 with ulcerative colitis [UC]) and 30 control patients were investigated with respect to the following pulmonary function tests: forced expiratory volume in 1 s (FEV1), inspiratory vital capacity (IVC), Tiffeneau value (FEV1/IVC), and lung CO transfer capacity (D(LCO)). Disease activity in IBD patients was assessed by the CD activity index for CD and the Truelove index for UC, respectively. Smoking habits and medication were documented in every patient. RESULTS: Fourteen of 36 CD patients (39%) and 14 of 31 UC patients (45%) but only one of the controls exhibited at least one pathological (<80% of predicted value) pulmonary function test. In both CD and UC lung function tests were significantly decreased in comparison to the control group. This could be shown for FEV1 (-14% of predicted value in CD and -17% in UC, p < 0.01), IVC (-10% in CD and -12% in UC, p < 0.05), and DLCO (-20% in CD and -31% in UC, p < 0.01) without significant differences between both disease entities. The impairment of pulmonary function tests was more pronounced in patients with active disease than in those with inactive disease (FEV1, 81.4% vs 93.4% predicted, p < 0.02; IVC, 84.4% vs 93.7%, p < 0.05; DLCO, 80.4% vs 95.8%, ns). CONCLUSIONS: IBD patients show significantly decreased lung function tests in comparison to healthy controls. The impairment in active disease exceeded that during remission.
Adult↗
[Sweet syndrome and erythema nodosum in ulcerative colitis, refractory to steroids: successful treatment with tacrolimus].
BACKGROUND: Inflammatory bowel disease is accompanied by cutaneous manifestations in about 10% of cases. Erythema nodosum and pyoderma gangraenosum are most frequently observed, which often subside on treatment of the underlying disease. CASE REPORT: A 30-year-old male with a history of long-standing ulcerative colitis experienced an acute attack despite treatment with azathioprine. Further he noticed dull red, elevated and tender maculae on the forelegs. A disseminated and papulosquamous exanthema arose on the back of the trunk and the upper extremities without pruritus. Well-being was compromised and blood sampling revealed an inflammatory response. High-dose steroids with antibiotics were without benefit until they were combined with tacrolimus, an immunosuppressive agent acting similar to ciclosporin. Remission occurred rapidly and the skin lesions resolved. Six months later the patient is currently still in remission and developed no signs of recurrent exanthema. CONCLUSION: The cutaneous lesions are thought to be related to ulcerative colitis and were classified as erythema nodosum and Sweet syndrome. This is the first report on the successful use of tacrolimus in steroid-refractory ulcerative colitis with extraintestinal cutaneous involvement.
Adult↗
Tacrolimus: a new immunosuppressant for steroid refractory inflammatory bowel disease.
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Dose-Response Relationship, Drug↗
Ulcerative colitis and colorectal carcinoma: DNA-profile, laminin-5 gamma2 chain and cyclin A expression as early markers for risk assessment.
BACKGROUND: Ulcerative colitis patients are at increased risk for developing colorectal carcinomas. Despite expensive surveillance programmes, clinical practice reflects an uncertainty in individual risk assessment. The aim of the study was to evaluate independent cellular features with possible predictive value. METHODS: Two patient groups were selected: group A comprised 8 patients with ulcerative colitis-associated colorectal carcinomas, group B comprised 16 ulcerative colitis patients with risk factors (duration of disease, extent of inflammation, epithelial dysplasias). A total of 683 paraffin-embedded mucosal biopsies were retrospectively evaluated for inflammatory activity, grade of dysplasia, ploidy status, laminin-5 gamma2 chain and cyclin A expression. RESULTS: Mild or moderate inflammatory activity was present in 78% of all biopsies, low- or high-grade dysplasia in 5.5%. There was no difference in inflammatory activity and dysplasia between patient groups. In group A, 75% of the biopsies exhibited aneuploid DNA distribution patterns. Group B showed mainly proliferative-diploid cell populations (85% / P = 0.006). Laminin-5 gamma2 chain was expressed in 13% of all biopsies, with a higher frequency in group A (P = 0.002). Cyclin A expression was found in 98% of all biopsies, with a higher number of immunopositive cells in group A biopsies (P = 0.014). CONCLUSIONS: Combined nuclear DNA assessment, laminin-5 gamma2 chain and cyclin A expression may help to identify ulcerative colitis patients with an increased risk for cancer development.
Adult↗
Conservation in the real world.
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Animals↗
cDNA cloning, chromosomal mapping, and expression analysis of human VE-Cadherin-2.
Murine vascular endothelial cadherin-2 (VE-cad-2) is a cellular adhesion molecule that is distinct from vascular endothelial cadherin 1 (VE-cad-1) in that it does not interact with catenins and does not appear to affect cell migration or growth. In this study, we have cloned a full-length cDNA of the human homolog of VE-cad-2 and used it to map the chromosomal locus of the VE-cad-2 gene. Human VE-cad-2 maps to Chromosome (Chr) 5q31. The cDNA of human VE-cad-2 is highly homologous to mouse VE-cad-2, except for a C-terminal tail. The genomic structure of VE-cad-2 is strikingly similar to that reported for a large family of neuronal protocadherin genes mapped to Chr 5q, yet the amino acid sequences between VE-cad-2 and the protocadherins are substantially divergent. The promoter of human VE-cad-2 contains two TATA boxes and transcription initiates from a single site 3' to these elements. Similar to mouse VE-cad-2, the human gene is expressed primarily in highly vascularized tissues.
5' Untranslated Regions↗
48-hour hemodynamic effects of octreotide on postprandial splanchnic hyperemia in patients with liver cirrhosis and portal hypertension: double-blind, placebo-controlled study.
Octreotide is effective during 48 h in the treatment of acute variceal bleeding, probably by reducing variceal blood flow and pressure. Its basal and postprandial effects on splanchnic and systemic hemodynamics, and hormonal changes over this time interval have not yet been studied. Twenty-four patients with cirrhosis and portal hypertension were randomized to receive a liquid meal and either octreotide (Oct, 100 microg bolus intravenous, followed after 2 h by a continuous infusion of 25 microg/hr for 20 hr) or placebo (Plac) given at three consecutive days. Splanchnic (Doppler ultrasound) and systemic hemodynamics (noninvasive cardiac monitoring) were assessed on four consecutive days (one control day and three treatment days) during 2 hr. The postprandial increase in mean blood velocity of the superior mesenteric artery (SMA-V(mean) +44%), portal blood velocity (PV-V(mean), +44%) and total hepatic blood flow (HBF, +40%) observed in the placebo group during the control day was abolished during the first day of treatment (SMA-V(mean), +3%, P < 0.01; PV-V(mean), +6%, P < 0.05; HBF, -25%, P < 0.01) and still reduced after 48 hr in the octreotide group (SMA-V(mean) +28%, P < 0.05; PV-V(mean), +22%, P > 0.05; HBF, -8%, P < 0.05). The postprandial increase in cardiac index (CI, + 10%) and decrease in systemic vascular resistance index (SVRI, -6%) were blunted after the initial injection of octreotide only (CI, -8%, P < 0.05; SVRI, +18%, P < 0.01). Endothelin-1-levels, which were increased at baseline (Plac 25 +/- 17, Oct 16 +/- 13 ng/liter, P > 0.05) decreased significantly after 48 hr of treatment with octreotide (Plac 27 +/- 20, Oct 8 +/- 4 ng/liter, P < 0.05). Octreotide is effective during 48 hr in the prevention of postprandial hyperemia in cirrhotics, even if its efficacy is decreasing over time. Moreover it may have positive effects on systemic vasodilation in cirrhotics. These findings suggest a potential role of this drug in the chronic treatment of portal hypertension.
Aged↗
Mycophenolate mofetil: lack of efficacy in chronic active inflammatory bowel disease.
BACKGROUND: Mycophenolate mofetil (MMF) is a new immunosuppressant with pharmacodynamic properties comparable to azathioprine. Recent reports found MMF to be effective in inflammatory bowel disease (IBD). METHODS: An open-label prospective and uncontrolled multicentre 6 month trial of MMF in combination with steroids was conducted in 24 chronic active IBD patients. A daily steroid demand of >/= 10 mg prednisone in the preceding 2 months and a Crohn's disease activity index (CDAI) > 150, or moderate to severe activity according to Truelove, served as criteria for chronic activity. The treatment consisted of a steroid pulse and tapering protocol in combination with MMF 2 g/day. A prednisone dose of 5 mg/day was maintained during months 4-6. The primary end-point was induction and maintenance of remission. RESULTS: Only 10 of 24 patients had achieved remission after 3 months. All but one Crohn's disease patient had relapsed by the end of the study at 6 months. Depression and migraine necessitated drug withdrawal in two patients. CONCLUSION: In conclusion, MMF 2 g/day was unable to induce and maintain remission for a period of 6 months in 23 of 24 chronic active IBD patients. Further controlled investigations are required in view of recent conflicting reports.
Adult↗
[Ulcerative colitis-associated colorectal carcinoma. DNA ploidy as indicator of impending malignant transformation?].
The onset of a malignant transformation in long-standing ulcerative colitis is difficult to predict. The value of the clinical and histomorphological parameters in current use is limited. It was thus aim of the present study to investigate the value of DNA-ploidy for the early detection of a malignant transformation in long-standing ulcerative colitis. This retrospective study comprised 20 patients with long-standing ulcerative colitis. The average observation time was 7.3 years (range: four to twelve years). All patients took part in a surveillance program and had between four and seven colonoscopies within a minimum period of time of five years. At these instances mucosal biopsies were taken in a standardized manner at eight different locations throughout the colon. These paraffin-embedded specimens (n = 542) were analyzed histomorphologically and DNA-cytometrically. During the observation time five patients developed an ulcerative colitis-associated colorectal carcinoma (UCA). In these patients epithelial dysplasias were not more common than in the remaining 15 cases. The vast majority of the specimen of the patients with UCA showed distinct DNA-cytometrical alterations, i.e. they were aneuploid. Such aneuploid mucosal cell populations were distributed over the whole colon, irrespectively of the later site of the carcinoma. These aneuploid lesions were found in one case eleven years, in an average seven years prior to the final diagnosis of a UCA. In contrast, the colon epithelium of the patients without UCA showed only proliferative-diploid DNA-distribution patterns during the observation time. In summary, affected patients had multiple highly aneuploid lesions of the colon mucosa at an average of seven years prior to the final diagnosis of UCA. These lesions came from macroscopically chronic inflamed tissue, and where histomorphologically without signs of dysplastic transformation. DNA-cytometrical investigations could thus be of additional predictive value for the individual risk assessment as regards an impending malignant transformation.
Adult↗
Treatment of infected pancreatic pseudocysts by endoscopic ultrasonography-guided cystogastrostomy.
It has been appreciated for a long time that surgery is the treatment of choice for symptomatic, and especially infected, pancreatic pseudocysts. This paradigm is now being challenged by endoscopic cystoenterostomy and cystogastrostomy, which have both been employed with success in selected patients. We present three cases in which infected pancreatic pseudocysts resolved following endoscopic cystogastrostomy guided by endoscopic ultrasonography (EUS).
Adult↗
Transjugular intrahepatic portosystemic shunt for trauma?
We report a case of successful emergency TIPS placement to control intra-abdominal bleeding after blunt abdominal trauma in a patient with severe cirrhosis and portal hypertension.
Abdominal Injuries↗
Enhanced intestinal expression of heat shock protein 70 in patients with inflammatory bowel diseases.
Heat shock protein (Hsp) 70 is stress-inducible and exhibits both protective and antigenic properties. This study investigated the mucosal expression of the constitutive (Hsp70c) and inducible form (Hsp70i) as well as antibodies against human Hsp70 in inflammatory bowel disease and controls. Biopsies were assessed by immunoblot and immunofluorescence, resection specimens by immunohistochemistry, and mucosal antibody content by isoelectric focusing. Compared to controls, expression of Hsp70 was enhanced in ulcerative colitis (P<0.05), less so in Crohn's disease and infectious colitis. Strong epithelial staining was found for Hsp70c and Hsp70i in both diseases. Mucosal and submucosal mononuclear cells showed enhanced Hsp70c expression in Crohn's disease and to a lesser degree in ulcerative colitis. Antibodies of isotypes A or M were detected in nearly all patients and controls. The different pattern of Hsp70 expression in Crohn's disease compared to ulcerative colitis points to a distinct protective and immunological function, whereas a role in autoimmunity seems unlikely.
Adult↗
Long-term haemodynamic effects of octreotide on postprandial splanchnic hyperemia in humans: a placebo-controlled echo-doppler study.
BACKGROUND: Octreotide is a potent splanchnic hypotensive somatostatin analogue effective in the treatment of acute variceal bleeding. AIM: To study the effects of octreotide on basal and postprandial splanchnic and systemic haemodynamics, and hormonal changes in humans. METHODS: Twenty-four healthy volunteers were randomized to receive a liquid meal and either octreotide (OCT, 100 microg bolus) or placebo repeatedly every 4 h for 48 h. Splanchnic (Doppler ultrasound) and systemic haemodynamics (non-invasive cardiac monitoring) were assessed for 2 h on four consecutive days: one control day and after doses 1 (0 h), 7 (24 h) and 13 (48 h). RESULTS: The maximum postprandial increases in mean blood velocity of the superior mesenteric artery (SMA-Vmean +72%), portal (PBF +52%) and total hepatic blood flow (HBF +50%) observed in the placebo group, were abolished after the first dose of octreotide (SMA-Vmean -23%, P<0.01; PBF -22%, P<0.01; HBF -21%, P<0.01). Postprandial hyperemia was restored at the end of the 48-h study period, but baseline SMA-Vmean (placebo 40+/-12, OCT 29+/-11 cm/s, P<0.05) and PBF (placebo 1200+/-971, OCT 743+/-449 mL/min, P<0.05) remained significantly lower in the octreotide group. The postprandial decrease of systemic vascular resistance and increase of cardiac index were prevented by octreotide for 48 h. CONCLUSIONS: Repeated 4-hourly bolus injections of octreotide reduce splanchnic blood flow for at least 48 h, but the prevention of food-induced splanchnic hyperemia is short-lasting.
Adult↗
Elevated serum thrombopoietin and interleukin-6 concentrations in thrombocytosis associated with inflammatory bowel disease.
Reactive thrombocytosis is a typical feature in inflammatory bowel disease (IBD). The question arose as to whether the normal negative feedback regulation of the concentration of thrombopoietin (TPO) in blood was altered in IBD patients. We measured serum immunoreactive TPO in 30 patients with active IBD, 29 patients with inactive IBD, and 56 healthy controls. The results were related to platelet and leukocyte counts and to the serum concentration of interleukin 6 (IL-6). Patients with active IBD exhibited significantly increased TPO levels (medians 112 pg/ml vs. 90 pg/ml in controls, p < 0.05) in association with thrombocytosis (428 platelets/nl blood vs. 241 platelets/nl blood in controls), leukocytosis, and increased IL-6 levels (12.9 pg/ml vs. 2.5 pg/nl in controls). In patients with inactive IBD, only platelets (322/nl) and leukocytes were above normal. Although the observation of increased TPO and IL-6 levels provides an explanation for the occurrence of thrombocytosis in IBD, the pathogenetic mechanisms underlying the elevated TPO level still need to be identified.
Adolescent↗
Mucosal cytokine expression, cellular markers and adhesion molecules in inflammatory bowel disease.
OBJECTIVE: To relate proinflammatory cytokines to leukocyte surface markers and adhesion molecules in the same paraffin-embedded biopsy specimen in inflammatory bowel disease (IBD) of varying activity. METHODS: Biopsies of seven cases of Crohn's disease, seven patients with ulcerative colitis, one case of intestinal infection and six control subjects were studied. We performed in situ hybridization on sections of tissue using probes specific to interleukin-1beta (IL-1beta), interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF alpha). Leucocyte markers and adhesion molecules were investigated in subsequent slides of selected specimens by immunohistochemistry. RESULTS: Cytokine mRNA was found in large numbers of cells throughout the inflamed intestine but also in some macroscopically unaffected tissue specimens. Transcripts were predominantly located within the lamina propria where immunohistochemistry of parallel sections revealed numerous macrophages and the presence of endothelial adhesion molecules. The expression of the different cytokines was closely related to each other and to histological but not to macroscopic (endoscopic) activity. CONCLUSIONS: The synthesis of IL-1beta IL-6 and TNF alpha mRNA is coordinately regulated. Cytokine production is located mostly in the lamina propria at sites that are rich in macrophages and show abundant staining of vascular adhesion molecules. This cascade of immune events is related to inflammatory cell infiltration in both Crohn's disease and ulcerative colitis.
Adult↗
Mesenteric blood flow is related to disease activity and risk of relapse in Crohn's disease: a prospective follow-up study.
OBJECTIVE: The diagnostic significance of increased splanchnic blood flow in Crohn's disease is unclear. This prospective study was therefore undertaken to define the role of Doppler sonography in the assessment of disease activity and in the prediction of early relapse. METHODS: Splanchnic flowmetry was performed in 59 patients with Crohn's disease and 20 healthy volunteers during fasting and 30 min after ingestion of a standardized meal. Twenty-one patients measured during the active state and in clinical remission were followed-up for 6 months. Hemodynamic parameters of the superior and inferior mesenteric arteries and the portal vein were related to clinical (Crohn's disease activity index [CDAI]), laboratory (C-reactive protein), and endoscopic (Crohn's Disease Endoscopic Index of Severity) parameters of disease activity. RESULTS: The postprandial mean velocity of the superior mesenteric artery correlated closest with clinical activity (CDAI, p < 0.005) and C-reactive protein (p < 0.01), but was unrelated to endoscopic activity. All patients in remission after 6 months (9/9) showed an increase in postprandial pulsatility index of the superior mesenteric artery, compared with an initial measurement during active disease (+28%). In contrast, the majority of patients with later relapse or surgery (11/12) had decreased pulsatility index during initial remission (-20%). The positive predictive value of this index for maintenance of remission was 0.82. CONCLUSIONS: Postprandial flow measurements in the superior mesenteric artery are closely related to clinical but not endoscopic disease activity in patients with Crohn's disease. The repeated measurement of the postprandial pulsatility index allows estimation of the risk of recurrence.
Adult↗
Mesenteric blood flow is related to disease activity and risk of relapse in ulcerative colitis: a prospective follow up study.
BACKGROUND: The diagnostic significance of increased splanchnic blood flow in ulcerative colitis is unclear. This prospective study was therefore undertaken to define the role of Doppler sonography in the assessment of disease activity and in the prediction of early relapse. SUBJECTS/METHODS: Splanchnic flowmetry was performed in 76 patients with ulcerative colitis (47 with active disease and 29 in remission), six with infectious colitis, and 13 healthy controls during fasting and 30 minutes after ingestion of a standardised meal. Twenty seven of the patients with ulcerative colitis and all patients with infectious colitis were investigated during the active state as well as in clinical remission and followed up for six months. Flow velocity and pulsatility index (PI) of the superior (SMA) and inferior (IMA) mesenteric arteries and the portal vein were related to clinical (Truelove index), laboratory (C-reactive protein), and endoscopic (Sutherland index) parameters of disease activity. RESULTS: The mean flow velocity of the IMA correlated closest with clinical activity (Truelove, r = 0.41, p<0.005), the PI with C-reactive protein (r = 0.30, p<0.05), and endoscopic activity (r = 0.45, p<0.001). All patients in remission after six months (14/14) or with infectious colitis (6/6) showed an increase in PI of the IMA compared with the initial measurement during active disease (mean increase for ulcerative colitis +36% and for infectious colitis +77%). In contrast, most patients with later relapse or surgery (11/13) had decreased PI during initial remission (mean decrease -12%). The positive predictive value of this index for maintenance of remission was 0.77. Flow variables of the SMA and portal vein displayed weaker correlations. CONCLUSIONS: Flow measurements in the IMA are closely related to clinical and endoscopic disease activity in patients with ulcerative colitis. Repeated measurement of the PI allows estimation of the risk of recurrence.
Adolescent↗