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Biomedical subjects

D Ludwig

Publications and source records attributed to D Ludwig.

At least 37 records · Page 2Linked to original sources
PubMed1999

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↗
PubMed1999

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↗
PubMed1999

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↗
PubMed1999

Efficacy of azathioprine in the treatment of chronic active Crohn's disease: prospective one-year follow-up study. German Imurek Study Group.

Azathioprine has been found effective in chronic active Crohn's disease. The aim of this open uncontrolled trial was an efficacy analysis in hospitals and private practices versus results of controlled trials. 89 patients with active Crohn's disease (CDAI > 150) were included in a multicenter trial of azathioprine therapy during one year. Follow-up evaluations were scheduled at three, six and twelve months and included self-assessment as well as physicians assessment of disease activity using CDAI and laboratory parameters. 65 patients (73%) completed the study per protocol until twelve months. At the end of the trial 75% of patients were in remission (CDAI < 150), 22% were ameliorated and two patients (3%) deteriorated. Corticosteroid dose was dropped from 0.46 mg/kg bw to 0.18 mg/kg bw during the study. Adverse events, primarily allergy, nausea and hyperlipasemia were frequent (21%), but only two patients had to be withdrawn from the trial. Everyday use of azathioprine for the treatment of chronic active Crohn's disease in hospital and private practice is equally effective compared to results of previous controlled trials. High doses of steroids at the beginning of azathioprine therapy may be associated with higher remission rates at one year.

Adolescent↗
PubMed1998

The postprandial portal flow is related to the severity of portal hypertension and liver cirrhosis.

BACKGROUND/AIMS: Diminished postprandial portal hyperemia has been demonstrated by echo-Doppler flowmetry in patients with liver cirrhosis, but its diagnostic role is unclear. This prospective study was therefore undertaken in patients with varying severity of portal hypertension and degree of liver cirrhosis. METHODS: Portal flowmetry was performed in 66 patients with cirrhosis and 20 healthy volunteers during fasting and 30 min after ingestion of a standardized meal. Hemodynamic parameters were related to the degree of esophageal varices, variceal bleeding, portal hypertensive gastropathy and Child-Pugh score. RESULTS: The postprandial portal blood velocity increment was low in patients with esophageal varices of any degree (22-24%), compared to patients without varices (49%, p<0.01) and healthy controls (65%, p<0.001), but was not different in patients with or without variceal bleeding (22% vs. 20%). In contrast, the congestion index (CI; ratio of portal vein cross-sectional area and portal blood velocity) pre-/postprandial decreased in the bleeding group only (CI pre/ CI post 1.30+/-0.23 (no bleeding) vs. 0.86+/-0.29 (bleeding); p<0.01). Portal hypertensive gastropathy was not related to any of the portal flow parameters. The portal blood velocity increment was comparable in controls (65%) and patients with Child-Pugh class A cirrhosis (56%), but lower in patients with class B (32%) and class C cirrhosis (15%, p<0.05 vs. class A). Also, there was no postprandial decrease in congestion index in patients with the most severe cirrhosis (p<0.01 class C vs. class A and B). CONCLUSIONS: The postprandial rise in portal flow is inversely related to the severity of portal hypertension and liver cirrhosis, and may be a valuable parameter with respect to the risk of variceal bleeding.

Adult↗
PubMed1998

Intestinal expression of human heat shock protein 90 in patients with Crohn's disease and ulcerative colitis.

Heat shock proteins are induced by several stress factors and are potential antigens in autoimmune disorders. Expression of heat shock protein 90 (HSP 90) was investigated in patients with inflammatory bowel disease and normal controls. We combined western blot analysis with laser densitometry for quantitation. Localization of HSP 90 was investigated by immunohistochemistry. Western blots showed a significant mucosal expression of HSP 90, which was comparable in patients and controls. There was also no difference between normal and inflamed mucosa in inflammatory bowel disease. In immunohistochemical staining studies, HSP 90 was detected in epithelial cells, mononuclear cells, giant cells, nerve cells, and endothelial cells of small vessels. There was no difference in the intensity of staining or localization in patients with inflammatory bowel disease compared to controls. These findings render a potential protective or immunogenic function of HSP 90 in inflammatory bowel disease unlikely.

Adult↗
PubMed1998

Steroid-unresponsive acute attacks of inflammatory bowel disease: immunomodulation by tacrolimus (FK506).

OBJECTIVE: Steroid treatment failure in acute Crohn's disease and ulcerative colitis frequently necessitates surgical intervention. Several alternative therapeutic strategies have been raised. The most promising so far has been intravenous cyclosporine, but the results in the long term have been discouraging. We assessed the efficacy and safety of the new macrolide immunomodulator tacrolimus as an alternative to cyclosporine A. METHODS: Eleven patients with steroid-refractory disease (six ulcerative colitis, two indeterminate colitis, two Crohn's disease, one pouchitis) and severe activity according to the Truelove and Witts criteria or Crohn's disease activity index > 150, respectively, were eligible for the study. All patients were treated with intravenous tacrolimus for 7-10 days followed by oral treatment over a median period of 7 months (range 0.25-16). Azathioprine and mesalamine were given concomitantly. Steroids were tapered according to clinical activity. RESULTS: Seven of 11 patients achieved remission rapidly, whereas a modest improvement was noted in two. Only two patients required an early and one a delayed colectomy. Moreover, a rectovaginal fistula closure in a case of Crohn's disease and an improvement of pouchitis was observed. A tapering to low dose steroids was possible during oral tacrolimus therapy in all nine responders and remission was maintained in five of them (mean follow-up 9.2 months). The drug was well tolerated and side effects were managed conservatively. CONCLUSION: Tacrolimus induced rapid remission in steroid resistant inflammatory bowel disease in the majority of cases. It appears to be an effective treatment modality that may be superior to cyclosporine with respect to maintenance of remission.

Adolescent↗
PubMed1998

Treatment of unresectable carcinoma of the esophagus or the gastroesophageal junction by mesh stents with or without radiochemotherapy.

The palliative treatment of malignant stenoses of the upper gastrointestinal tract by self-expanding metal stents is a novel procedure with effective relief of dysphagia in most patients. There is little follow-up information with respect to the factors influencing clinical outcome and survival rates. Survival rates of 40 consecutive patients treated with 53 mesh stents were analyzed with regard to their degree of dysphagia (grades 0-3), quality of life (Karnofsky score), and the effect of additional radiation and chemotherapy. Following stent placement dysphagia improved in 36 of 40 patients. Endoscopic reinterventions for worsening of dysphagia were necessary in 23 patients during a median follow-up period of 74 days (range 51-149). There was a trend towards superior survival time in younger patients (<60 years) with high Karnofsky score ( 70). Patients receiving concurrent radiation and chemotherapy (n=12) experienced prolonged survival (median 318 days after diagnosis, 225 days after stent) compared with patients of equal tumour staging, but without additional therapy (n=17; median 157 days after diagnosis, p<0.001; 138 days after stent, p<0.05). The combination of endoscopic stenting with additional radiation and chemotherapy was associated with improved survival. A randomized trial is warranted.

Adult↗
PubMed1997

Crohn's disease and sarcoidosis: systemic granulomatosis?

We report an unusual case of severe Crohn's disease with involvement of the lung. In 1993 at age 21 a male patient experienced a Helicobacter-negative duodenitis. A routine chest radiograph revealed spotted opacities in the right upper lobe without discomfort and normal pulmonary function except for a reduced diffusion capacity. Bronchoalveolar lavage showed mild lymphocytosis and biopsies from the macroscopically normal bronchi displayed non-caseating granulomas. In 1995 he had symptoms of peptic ulcer disease with a gastric outlet stenosis. He underwent Billroth I resection with only temporary improvement. Three months later the symptoms had recurred and a stenosing inflammatory process of the duodenum was seen on endoscopy suggesting Crohn's disease. A chest radiograph demonstrated infiltrations in parts of the left lung and bronchoalveolar lavage again revealed alveolar lymphocytosis (CD4/CD8 ratio 3.1). Both the gastrointestinal and pulmonary affections responded to corticosteroids but the duodenal stricture had to be resected. The association of Crohn's disease and pulmonary disorders is discussed.

Adrenal Cortex Hormones↗
PubMed1996

Surgical therapy of gastrointestinal non-Hodgkin's lymphomas.

Within a period of 13 years 39 patients underwent surgery for primary gastrointestinal non-Hodgkin's lymphoma. The stomach was the most frequent site of involvement (26 cases) followed by the small intestine (10 cases) and the large bowel (three cases). Operative procedures included: total gastrectomy (n = 19), subtotal gastrectomy (n = 5), partial gastrectomy (n = 2), small bowel resection (n = 7), right hemicolectomy (n = 5) and sigmoid resection (n = 1). According to Musshoff's modification of the Ann Arbor system, we found stage I in nine, stage II in 12, stage III in two and stage IV in 16 patients. Histological typing according to the Kiel classification showed low-grade malignancy in 11 cases and high-grade in 28. Twenty-eight patients received chemotherapy and/or radiation in accordance with the tumour staging and type of malignancy. The follow-up data were analysed by the method of Kaplan and Meier. Including five patients who died post-operatively from perforated or bleeding lymphomas, the overall 5-year survival rate was 53.8%.

Adult↗
PubMed1992

Epidemiology of blastomycosis in a region of high endemicity in north central Wisconsin.

The clinical and epidemiologic features of 73 patients with laboratory-confirmed blastomycosis who were identified over an 11-year period in North Central Wisconsin are presented. Pulmonary disease was the sole manifestation in 77% of patients. More than one-half of all patients had symptoms that included fever, cough, weight loss, night sweats, and pleuritic chest pain. Virtually all were previously healthy, and most did not have an outdoor occupation. However, 82% of these patients lived or had visited within 500 m of rivers or associated waterways. The majority experienced the onset of symptoms between December and April. The estimated mean annual incidence rate of infection for Vilas County was 40.4 cases per 100,000 persons, and that for the largest city in the county was 101.3 cases per 100,000 persons. Several areas with an exceptionally high incidence of the infection were observed. We suggest that, in regions where blastomycosis is hyperendemic, clinical disease is most often pulmonary and occurs in immunocompetent individuals and that residence near an ecological focus may be a greater risk factor for acquisition of blastomycosis than is occupation.

Adolescent↗
PubMed1992

Haemodynamic and renal effects of urodilatin bolus injections in patients with congestive heart failure.

Urodilatin (ANF(95-126)) is an analogue of the atrial natriuretic factor (ANF(99-126)), which has been isolated from human urine. Recently we have shown in healthy volunteers, that intravenous bolus injections of synthetic urodilatin produce more pronounced reductions of pulmonary arterial pressure than ANF(99-126). To compare haemodynamic and renal effects of synthetic urodilatin with those of ANF(99-126) in congestive heart failure (CHF), 12 patients (66.3 +/- 1.4 years) received either two high dose intravenous bolus injections of 4 micrograms kg-1 bw Urodilatin (URO) at a 30 min interval (n = 6) or the same doses of ANF(99-126) (n = 6). Prior to i.v. URO, no URO immunoreactivity was found in human plasma (specific RIA, no crossreactivity to ANF). Similar to ANF, the increase in diuresis (1.4 +/- 0.7 to 3.7 +/- 1.6 ml min-1) and natriuresis (169 +/- 114 to 430 +/- 197 mumol min-1) was moderate after URO in CHF. During the 90 min study period, mean plasma cyclic GMP levels increased much more after URO (by 53.4 +/- 15.1 nM) than after ANF (by 13.1 +/- 3.0 nM; P = 0.04). In contrast to ANF, i.v. bolus injections of URO produced sustained haemodynamic effects in CHF lasting up to 90 min: The average (0-90 min) reduction of systemic vascular resistance was more pronounced after URO (-578 +/- 148) than after ANF (-204 +/- 65 dyn*s*cm-5, P = 0.04).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1992

Haemodynamic and renal effects of urodilatin in healthy volunteers.

Urodilatin (ANF(95-126)), an analogue of the atrial natriuretic factor (ANF(99-126)), has recently been isolated from human urine. To study haemodynamic and renal effects of synthetic urodilatin, 18 healthy male volunteers (age 26.1 +/- 0.8 years; X +/- SEM) received i.v. bolus injections of urodilatin at doses of 1, 2 or 4 micrograms kg-1 body weight (bw) (n = 6 per dosage group). Urodilatin dose-dependently increased heart rate and cardiac index. A dose-dependent increase in plasma cyclic GMP levels was also observed. Urinary cyclic GMP excretion, urine flow and natriuresis increased 7-fold, 5-fold and 4-fold, respectively. Renal effects were not different between dosage groups. Compared with ANF(99-126), after urodilatin the reduction in mean pulmonary arterial pressure (PAP) was more pronounced (2 micrograms kg-1, n = 6; ANF -1.8 +/- 0.5, URO: -5.5 +/- 1.1 mmHg, P less than 0.05). Furthermore, after urodilatin the reduction of PAP lasted continuously from 2 up to 90 min after injection, while ANF(99-126) produced only a transient decrease of PAP. Similarly the reduction of pulmonary capillary wedge pressure (PCWP) by urodilatin from 9.3 +/- 1.2 to 3.8 +/- 0.9 mmHg (P less than 0.05) was also sustained up to 90 min post administration. These data in healthy volunteers suggest that, due to prolonged reduction of PAP and PCWP with increases of cardiac index and reduction of systemic vascular resistance, urodilatin might exhibit beneficial effects in cardiovascular disease.

Adult↗
PubMed1992

Secondary metabolites by chemical screening. 8. Decarestrictines, a new family of inhibitors of cholesterol biosynthesis from Penicillium. I. Strain description, fermentation, isolation and properties.

A family of new 10-membered lactones was detected by chemical screening. Taxonomic studies and fermentation conditions of the producing organisms, which belong to the species Penicillium simplicissimum and Penicillium corylophilum, are presented. The isolation as well as physico-chemical data of the new compounds named decarestrictines A to D are reported. In vitro testing using the HEP-G2 cell assay showed the decarestrictines to be inhibitors of cholesterol biosynthesis, which could be confirmed in vivo. In addition to the decarestrictines from P. corylophilum epoxyagroclavine-I (1) was isolated.

Animals↗