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D Uhlmann

Publications and source records attributed to D Uhlmann.

At least 37 records · Page 2Linked to original sources
PubMed2000

[Treatment concept of adenomas of Vater's ampulla].

INTRODUCTION: The most common benign ampullary tumors are adenomas (80%). They are considered as premalignant lesions with a transformation rate to carcinoma of up to 30%. METHODS: From 1 January 1997 to 28 February 1999 we treated 11 patients with adenoma of the ampulla of Vater. An ampullectomy was performed in 10 cases. One poor-risk patient could not be operated on. RESULTS: No operative mortality occurred. In two patients a pT1 adenocarcinoma was diagnosed postoperatively. One of the two patients with a high-risk carcinoma underwent a second operation, a Whipple pancreatoduodenectomy. Nine of 10 patients had no recurrence with a median follow-up of 12 months. CONCLUSION: One patient died of glioblastoma. We would therefore recommend ampullectomy as the first-line treatment for benign tumors of the ampulla of Vater. In low-risk pT1 carcinoma (G1/G2, L0) and R0 resection, local excision is acceptable. In high-risk pT1 carcinoma (G3 and/or L1) Whipple pancreatoduodenectomy is mandatory.

Adenocarcinoma↗
PubMed2000

Endothelin/nitric oxide balance influences hepatic ischemia-reperfusion injury.

During ischemia-reperfusion an imbalance between endothelin (ET) and nitric oxide (NO) can be responsible for microcirculatory disturbances. The aim of this study was to restore the ET/NO balance to reduce the ischemia-reperfusion injury. Hepatic ischemia was induced for 30 min in 56 Wistar rats. Sham operation, ischemia and treatment groups with the ET receptor antagonist (ERA) bosentan (1 mg/kg body weight i.v.) and the NO donor L-arginine (400 mg/kg body weight i.v.) were performed. For evaluation of hepatic microcirculation in vivo microscopy was carried out 30-90 min after reperfusion. Local hepatic tissue PO2, laser Doppler flow and aspartate aminotransferase/alanine aminotransferase (AST/ALT) levels were measured. Increased ET caused sinusoidal constriction after reperfusion to 76% of the sham group (p < 0.05), leading to significant decrease in perfusion rate (82%), liver tissue PO2 (6.9 mmHg) and erythrocyte flux (45.2% of sham group). Hepatocellular damage could be detected 6 h after reperfusion by AST/ALT increase (p < 0.05). Sinusoidal diameters were maintained at baseline in the ERA (98%) and NO (102%) groups (p < 0.05). Increased percentage of leukocytes sticking in sinusoids (144%) and venules (435%) was reduced by therapy to 110/253% (ERA) and 111/324% (NO), respectively (p < 0.05). Perfusion rate was increased to 93 and 94% (p < 0.05 vs ischemia). Local hepatic tissue PO2 was improved 30 min after reperfusion in the ERA (11.0 mmHg) as well as in the NO group (11.5 mmHg; p < 0.05 vs ischemia). Measurement with a laser Doppler flow meter revealed significant improved erythrocyte flux in both therapy groups (p < 0.05 vs ischemia). Also, the post-ischemic AST/ALT increase was reduced by therapy. In conclusion, ET evokes strong constriction of post-ischemic sinusoids, leading to microcirculatory disturbances. The maintenance of the ET/NO balance by blocking ET receptors, or providing an NO donor, protects liver microcirculation and reduces hepatic ischemia-reperfusion injury.

Animals↗
PubMed2000

Endothelin receptor blockade as a therapeutic strategy in ameliorating postischemic damage to the liver microcirculation.

Ischemia leads to profound endothelin- (ET) related constriction of hepatic microvessels, causing disturbances in blood and oxygen supply. The aim of the study was to modulate hepatic microvascular diameters by blocking ET receptors to find the optimal therapeutic vessel width for reduction of ischemia-reperfusion injury. In an in vivo model (84 female Wistar rats, 250-300 g) with portal decompression by means of a splenocaval shunt, normothermic hepatic ischemia was induced for 30 min by crossclamping of the hepatoduodenal ligament. The ET receptor antagonist (ERA) bosentan was administered before induction of ischemia in different dosages [0.1, 1.0 and 10.0 mg/kg body weight (BW) i.v. and 10 mg/kg BW intraportally (i.p.)]. The effect on microcirculation was assessed by in vivo microscopy and influence on hepatocellular function by measurement of aspartate aminotransferase (AST) levels. Sinusoidal diameters were reduced as a result of ischemia to 76.3 +/- 7.4% compared with values received from sham-operated animals. After application of 0.1 mg/kg of bosentan, sinusoids remained constricted (89.7 +/- 9.9%, AST 255.0 +/- 12.8 U/l). Blocking ET receptors with 1 mg/kg bosentan avoided sinusoidal constriction (99.0 +/- 8.8%, p < 0.05) and led to the most effective reduction of AST level peak after 6 h of reperfusion (244.0 +/- 34.2 U/l vs 422.9 +/- 163.3 U/l in untreated ischemia). Bosentan (10 mg/kg i.v.) caused an increase in sinusoidal diameter to 109.1 +/- 6.4% (AST 311.7 +/- 33.6 U/l) and 10 mg/kg i.p. to 136.8 +/- 19.3% and even increase AST levels (618.90 +/- 209.32 U/l). After intravenous application of 1 and 10 mg/kg BW bosentan the perfusion rate was significantly increased and sticking of leukocytes in sinusoids and venules reduced (p < 0.05). In our model, diameters of sinusoids and postsinusoidal venules could be regulated gradually. We conclude that the avoidance of constriction, but not an excessive vasodilation leads to increased perfusion rate and hence improved hepatocellular function.

Animals↗
PubMed2000

Frequency of p16(INK4A) alterations and K-ras mutations in intrahepatic cholangiocarcinoma of the liver.

BACKGROUND: Inactivation of the tumour suppressor gene p16 (CDKN2/MTS-1/INK4A) and K-ras mutations are among the most frequent genetic alterations in human malignancies. AIMS: To investigate the tumour suppressor gene p16 and its possible association with K-ras mutations in intrahepatic cholangiocarcinomas of the liver. METHODS: The status of p16 was evaluated in 41 cholangiocarcinomas by methylation specific polymerase chain reaction, microsatellite analysis, DNA sequencing, and immunohistochemical staining. K-ras mutations were determined by direct DNA sequencing analyses after microdissection. The results obtained were correlated with histopathological variables and patient survival. RESULTS: Hypermethylation of the 5' CpG island of the p16 gene was found in 34 of 41 (83%) carcinomas. Homozygous deletion at the p16 region was present in two (5%), and loss of heterozygosity (LOH) in eight cases (20%). We failed to detect p16 gene missense mutations. K-ras mutations were found in 22 of 41 (54%) cholangiocarcinomas and in two cases of tumour surrounding non-neoplastic liver tissue. All 22 cancers with K-ras mutations also exhibited methylated p16. We failed to observe a correlation between K-ras or p16 status and histopathological factors or prognosis of patients. CONCLUSION: These data suggest that inactivation of the p16 gene is a frequent event in cholangiocarcinoma. The most common somatic alteration is promotor methylation of the p16 gene which is closely associated with K-ras mutations. We failed to establish p16 or K-ras status as independent prognostic factors in these tumours.

Bile Duct Neoplasms↗
PubMed2000

[Hepatocellular carcinoma: resection versus transplantation].

For decision of adequate surgical therapy and comparison of results differentiation of hepatocellular carcinomas (HCC) in cirrhotic and noncirrhotic livers is important. Liver resection is the treatment of choice for HCC in noncirrhotic liver. Between 4/94 and 8/99 we treated 54 patients with hepatocellular carcinoma (HCC) by subtotal hepatic resection (n = 40) and orthotopic liver transplantation (n = 14). Overall 1- and 3-year survival rates of the resection group were 45 and 25% (median follow up: 3.5 years). One-year survival in the transplantation group was 72% (median follow up: 2.2 years). In patients with HCC in cirrhosis in UICC stage I to III the optimal therapy is a controversial issue. In these patients the results after liver resection are poor due to high operative mortality and recurrence (3-year recurrence-free survival: 30%). Regarding the literature, liver transplantation is the treatment of choice in small (< 3-5 cm, < or = 2 tumors) HCCs arising in cirrhosis with better outcome compared to resection. The data in the literature report 3-year-survival rates after liver transplantation of 60-80%. However, consequent patient selection is necessary for this treatment modality. Due to the limited donor resources liver transplantation is rarely justified in advanced tumors.

Carcinoma, Hepatocellular↗
PubMed1999

Involvement of endothelin/nitric oxide balance in hepatic ischemia/reperfusion injury.

INTRODUCTION: Endothelin (ET) and nitric oxide (NO) act as opponents in the regulation of the hepatic microcirculation. During ischemia/reperfusion (I/R) ET levels are increased, whereas no rise in NO levels is observed. This imbalance may be responsible for microcirculatory disturbances. The aim of this study was to restore the delicate ET/NO balance to maintain the integrity of the hepatic microcirculation and to reduce I/R injury. METHODS: Ischemia was induced by crossclamping of the hepatoduodenal ligament for 30 min with portal decompression using a splenocaval shunt (56 Wistar rats, 200-250 g). Sham operation, ischemia and treatment groups with the endothelin receptor antagonist (ERA) bosentan (1 mg/kg body weight i.v.) and the NO donor L-arginine (400 mg/kg body weight i.v.) were performed. For assessment of the microcirculation, sinusoidal perfusion rate, diameters of sinusoids and postsinusoidal venules, leukocyte endothelium interactions and velocity of free-flowing leukocytes were investigated by means of in vivo microscopy 30-90 min after reperfusion. Local hepatic tissue PO2 was measured prior to ischemia, 30 min and 60 min after reperfusion and aspartate aminotransferase (AST)/alanine aminotransferase (ALT) levels were investigated 2 h and 6 h after reperfusion. RESULTS: After ischemia, sinusoidal and venular diameters were reduced to 76% and 85%, respectively, of sham operation group values (P<0.05), but were maintained at baseline in ERA (98/102%) and NO (102/105%) groups (P<0.05). Increased postischemic leukocyte sticking in sinusoids (144%) and venules (435%) was reduced by therapy to 110/253% (ERA) and 111/ 324% (NO), respectively (P<0.05). Perfusion rate was increased to 93% and 94% compared with 82% in the ischemia group (P<0.05). Concomitant with the improved microcirculation in therapy groups, local hepatic tissue pO2 was improved 30 min after reperfusion in the ERA (11.0 mmHg) and the L-arginine group (11.5 mmHg) relative to the ischemic group (6.9 mmHg) (P<0.05). In addition, postischemic AST/ALT increase was reduced by therapy. CONCLUSION: Our results indicate that maintenance of ET/NO balance by blocking ET receptors, as well as providing a NO donor, protects the liver microcirculation and reduces hepatic I/R injury.

Alanine Transaminase↗
PubMed1998

[Intra-abdominal abscess].

In more than 80% of cases, intra-abdominal abscesses derive from an intra-abdominal organ, and in most cases they develop after operative procedures. Regarding anatomy, intra-abdominal abscesses can be divided into intra-peritoneal and visceral abscesses and those located in the anterior retroperitoneal space. Despite improvements in ultrasonography, CT is still the most effective method in diagnosis and therapy. Percutaneous ultrasound or CT-guided drainage is a therapy characterized by low procedural morbidity and is successful in 80% of cases if strict criteria are met. Complicated abscesses and those cases in which the underlying disease has to be treated require surgical intervention. Most liver abscesses are treated interventionally; in abscesses of the pancreas or spleen and in Crohn's disease, surgery is necessary. The combination with sufficient antibiotic drug therapy is very important. Specific infectious diseases appearing as intra-abdominal conglomerates (tuberculosis, actinomycosis, amebiasis) lead to a delay in diagnostics because of their scarcity and are characterized by special patho-anatomical, diagnostic and therapeutic features. The crucial thing is to take a specific infection into consideration.

Abdominal Abscess↗
PubMed1998

Spondyloenchondrodysplasia: several phenotypes--the same syndrome.

We present details of a dwarfing skeletal dysplasia in two boys. Radiographs show multiple enchondromas of tubular and flat bones together with abnormalities of the spinal column. Clinical, laboratory and radiological findings enable this entity to be grouped within the spectrum of enchondromatoses with vertebral changes. A literature review suggests heterogeneity of this group of conditions.

Adolescent↗
PubMed1998

Exogenous L-arginine protects liver microcirculation from ischemia reperfusion injury.

UNLABELLED: Hepatic ischemia followed by reperfusion evokes an imbalance between the vasoregulatory compounds endothelin and nitric oxide (NO) followed by constriction of the vascular bed, leading to microcirculatory disturbances and reduced blood flow, thereby causing hypoxia and liver damage. The aim of this study was to protect the liver microcirculation by maintaining this delicate balance. MATERIAL AND METHODS: In an in vivo ischemia/reperfusion model with portal decompression by a splenocaval shunt, hepatic ischemia was induced for 30 min by Pringle's maneuver. The effect of the NO donor L-arginine (400 mg/kg b.w. i.v.) was assessed by in vivo microscopy. Microhemodynamic studies, including the sinusoidal perfusion rate, diameters of hepatic sinusoids and postsinusoidal venules, leukocyte endothelium interactions and leukocyte velocity were performed. Microcirculatory data were compared with local tissue pO2 and serum transaminase levels. RESULTS: After ischemia the diameters of sinusoids and postsinusoidal venules were significantly reduced to 76+/-7 and 86+/-10% respectively in the nontreatment group, but dilated to 102+/-3 and 105+/-7% in the group treated with L-arginine (p < 0.001). The percentage of permanently adherent leukocytes in sinusoids and venules was increased by ischemia, but L-arginine reversed this increase (p < 0.001). Perfusion rate was improved to 90+/-2 compared with 83+/-5% in the untreated group (p < 0.01). Systemic arterial blood pressure was not affected by administration of the NO donor. The postischemic increase in serum transaminase levels was diminished in the treatment group (ASAT: p < 0.05). Local postischemic hepatic tissue pO2 was significantly decreased to 45% of basal values after 30 min and to 55% after 60 min of reperfusion (p < 0.05). Administration of L-arginine results in a significant increase in local tissue pO2 to 86 and 106% of basal values respectively (p < 0.05). CONCLUSION: These data indicate that L-arginine improves hepatic microcirculation after warm ischemia by increasing sinusoidal perfusion rate and by diminishing leukocyte endothelium interactions. Maintained integrity of microcirculation is associated with sufficient oxygen supply and improved hepatocellular function.

Animals↗
PubMed1998

[Role of endothelin-nitrogen monoxide equilibrium in ischemia/reperfusion damage of the liver].

Elevated levels of endothelin (ET) are measured during ischemia and reperfusion, but no adequate increase of nitric oxide (NO) can be observed. Thus, the balance of both substances, which occurs under physiological conditions and regulates microcirculatory vessel widths, is disturbed. This leads to microcirculatory damages. As well ET receptor blocking using a mixed ET receptor antagonist as increase of NO production after L-arginine treatment influenced this pathomechanism. The preischemic sinusoidal diameters were maintained and leukocyte endothelial interactions reduced. Concomitantly, sinusoidal perfusion rate and local hepatic tissue pO2 were increased. Because of significant reduced hepatocellular damage in both therapy groups both therapeutical ways might exert beneficial effects to attenuate ischemia/reperfusion induced microvascular and tissue injury.

Animals↗
PubMed1996

Effect of the endothelin receptor antagonist bosentan on postischemic liver microcirculation.

UNLABELLED: One mechanism evoked by ischemia is endothelin mediated vasoconstriction of the hepatic vascular bed. Postischemic sinusoidal constriction leads to microcirculatory disturbances and reduced blood flow, thereby causing local hypoxia and liver damage. The aim of the study was to avoid the constrictive response of sinusoids by blocking endothelin receptors. MATERIAL AND METHODS: In an in vivo ischemia-reperfusion-model (21 Wistar rats, 250-300 g) with portal decompression by a splenocaval shunt, hepatic ischemia was induced for 30 min by cross clamping of the hepatoduodenal ligament. The effect of the endothelin receptor antagonist bosentan (10 mg/kg bw i.v.) injected before ischemia was assessed by in vivo microscopy. Microhemodynamic studies, including the sinusoidal perfusion rate, diameters of hepatic sinusoids and postsinusoidal venules, leukocyte endothelium interactions and leukocyte velocity were performed. RESULTS: After ischemia sinusoidal diameters and diameters of postsinusoidal venules were significantly reduced to 76 +/- 7% and 86 +/- 10%, respectively, in the non-treatment group, but dilated to 109 +/- 6% and 118 +/- 8% in the group treated with endothelin receptor antagonist (p < 0.001). Increased percentage of postischemic permanent adherent leukocytes could be diminished in sinusoids and more markedly in venules by therapy (p < 0.001). Leukocyte velocity was decreased to 69 +/- 9% in the treatment group ( p < 0.001). Perfusion rate could be improved to 90 +/- 2% compared to 83 +/- 5% in the untreated group (p < 0.01). Systemic arterial blood pressure was not affected by administration of the receptor antagonist. CONCLUSION: These data indicate that the endothelin receptor antagonist treatment results in prevention of postischemic sinusoidal constriction. Perfusion rate could be improved due to dilation of sinusoids and diminished leukocyte adhesion, but leukocyte velocity was reduced by 31%.

Animals↗
PubMed1989

[The reliability of angiographic volume determination of the left ventricle using digital image subtraction--significance in stress tests].

Using the technique of digital subtraction angiography (DSA), left ventricular volumes can be determined after intravenous injection of contrast medium at rest and during exercise. The significance of the well known errors of angiographic determination of left ventricular volumes was investigated in 22 patients before and during a bicycle exercise test. Before and after exercise 40 ml of contrast medium were injected (18 ml/s) intravenously to calculate left ventricular volumes. Enddiastolic and endsystolic contours of the left ventricle were traced by two investigators (A and B) on five different days. Using these contours, volumes were calculated by a computer system. The first calculation of both investigators (single measurement) and the mean value of all five calculations (repetitive measurements) were compared. In the same procedure left ventricular contours of six patients were calculated after conventional contrast ventriculography (40 ml of contrast medium). No systematic deviations were found in comparing the results of both investigators using the single or repetitive method by means of DSA: (VolB = 0.86 VolA + 12.2, r = 0.97 versus VolB = 0.96 VolA + 9.1, r = 0.99). Compared to single method the residuals (Syx) of the repetitive method were significantly smaller: Syx = +/- 16.3 ml vs +/- 8.9 ml (p less than 0.01). Similar results were found in conventional ventriculography: single method Syx = +/- 18.7 ml and repetitive method Syx = +/- 8.8 ml (p less than 0.01). Comparing the volumes determined by DSA and by conventional ventriculography, respectively, no significant differences were found.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiography↗
PubMed1985

[Left ventricular function at rest and by stress in patients with aortic valve diseases. Study using digital subtraction angiocardiography].

Using digital subtraction angiocardiography left ventricular (LV) function and mean pulmonary artery pressure (PPA) at rest and during exercise were examined in 49 patients with aortic valve disease, 23 patients with aortic stenosis (AS), 12 patients with combined aortic valve lesions (kAV) and 14 patients with aortic regurgitation (AI). Muscular hypertrophy was present in all patients. LV-mass-to-volume ratio was significantly higher in patients with AS and kAV than in patients with AI. There was no significant difference in heart rate at rest or during exercise among the three groups. During exercise PPA increased significantly in all groups. The increase was significantly higher in patients with AS than in those with AI. End-diastolic and end-systolic volumes increased significantly in patients with AS and kAV on the average, showing no change in patients with AI. Ejection fraction decreased significantly in patients with AS and kAV and remained unchanged in patients with AI. Due to the increase in heart rate cardiac index increased significantly during exercise in all groups. In patients with pressure overloaded left ventricles (AS and kAV) the increase in filling pressure partly results in a decrease of compliance caused by hypertrophy. Thus in these ventricles LV function cannot be judged by LV filling pressures alone. In those patients in whom the indication for valve replacement was given without knowing the results of the exercise test, the changes of LV volumes and ejection fraction were abnormal during exercise on the average.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMedDate not supplied

Controlled vasoregulation of postischemic liver microcirculation--a therapeutic approach.

One of the changes produced by ischemia and reperfusion is endothelin (ET)-mediated constriction of the hepatic vascular bed. This leads to microcirculatory disturbances and reduced blood flow, thereby causing local hypoxia and liver damage. Our aim was to induce stepwise changes of microvascular vessel diameters so as to define the best protective vessel width that could be produced by drug therapy and thereby to minimize ischemia/reperfusion injury. The mixed ET receptor antagonist bosentan was used in different dosages in a rat liver ischemia/reperfusion model with splenocaval shunt. In vivo microscopy was performed 30-90 min after reperfusion and local hepatic tissue pO2 was determined, together with aspartate aminotransferase/alanine aminotransferase (AST/ALT). After ischemia, sinusoidal diameters were significantly reduced to 76 +/- 7% of those in the control group. After the administration of bosentan in dosages of 0.1, 1, and 10 mg/kg body weight iv and 10 mg/kg body weight intraportally we found diameters of 83 +/- 4, 98 +/- 2, 109 +/- 6, and 137 +/- 19%, respectively. Perfusion rate and leukocyte-endothelium interactions showed dependence on sinusoidal diameters, with the best results in the group where preischemic sinusoidal vessel width had been maintained. Local tissue pO2 and transaminase levels also showed that oxygen supply was sufficient and that hepatocellular injury was most minimized in this group. Graduated blocking of ET receptors allows stepwise regulation of sinusoidal and postsinusoidal venular vessel width and offers a treatment strategy for pathophysiological situations that are associated with ET-induced vasoconstriction. The results suggest that maintenance of preischemic microvascular diameter is the best therapeutic approach.

Animals↗