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Biomedical subjects

H Lippert

Publications and source records attributed to H Lippert.

At least 109 records · Page 6Linked to original sources
PubMed2001

Induction and expression of cyclin D3 in human pancreatic cancer.

PURPOSE: Cyclins play a key role in the control and regulation of the cell cycle. The role of cyclins in the pathogenesis of pancreatic cancer is largely unknown. METHODS: Using Northern blot analysis, polymerase chain reaction (PCR) and immunohistochemistry, we examined the expression of cyclins D1, D2, and D3 in human pancreatic cancer and studied the induction of these cyclins by growth factors in pancreatic cancer cell lines. RESULTS: We now report that cyclin D1 and D3 mRNAs are expressed in human pancreatic cancer cell lines, and that the expression of cyclin D3 is enhanced in pancreatic cancer cells by amphiregulin, a member of the epidermal growth factor family. Cyclins D1 and D3 are also expressed in normal and malignant pancreatic tissues. However, while the normal pancreas and pancreatic cancers express cyclin D2 as determined by reverse-transcriptase PCR, we could not detect cyclin D2 mRNA by either Northern blot analysis or reverse transcriptase PCR in the two pancreatic cancer cell lines. Immunohistochemical analysis revealed the expression of cyclin D3 in pancreatic cancer cells. CONCLUSIONS: These findings suggest that D-type cyclins are differentially expressed in pancreatic cancer and that the aberrant activation of the EGF receptor in human pancreatic cancer by amphiregulin may lead to the progression of the cell cycle via induction of cyclin D3 expression, thus contributing to the growth advantage of these transformed cells.

Amphiregulin↗
PubMed2001

Combination chemotherapy with docetaxel and cisplatin for locally advanced and metastatic gastric cancer.

BACKGROUND: Poor treatment results obtained with palliative chemotherapy for advanced gastric cancer indicate the need for new effective and well-tolerated regimens. PATIENTS AND METHODS: Forty-three patients with locally advanced or metastatic gastric cancer were enrolled in a phase II study to evaluate the efficacy and safety of combination chemotherapy with doxetacel 75 mg/m2 and cisplatin 75 mg/m2 given every three weeks. RESULTS: Thirty-nine patients were evaluable for response. Four achieved a complete response and twelve a partial response, for an overall response rate of 37.2% (16 of 43 patients; 95% confidence interval (CI): 22.98-53.72). Median time to progression was 6.1 months and median overall survival 10.4 months. Forty-two percent of all patients were still alive at one year and twelve percent at two years. The major toxicity was leukopenia which reached grade 3-4 in 18.6% (n = 8) of the patients. However, no febrile neutropenia occurred. Non-haematological toxicities were usually mild to moderate. Grade 3 toxicities included diarrhea (9% of the patients), nausea and vomiting (7%), and alopecia (7%). Severe ototoxicity with or without peripheral neuropathy developed after completion of chemotherapy in two patients. CONCLUSIONS: These results suggest that the combination of docetaxel and cisplatin has moderate toxicity and is an effective regimen for the treatment of advanced gastric cancer, both with regard to response rate and survival.

Adult↗
PubMed2001

Differential oxidative injury in extrapancreatic tissues during experimental pancreatitis: modification of lung proteins by 4-hydroxynonenal.

Oxidative stress is considered to be a pathogenic factor for multisystem organ failure during acute pancreatitis. Infusion of 3% and 5% sodium taurocholate into the pancreatic duct of rats resulted in a 24-hr lethality of 8% and 82%, respectively. Kidney tissue showed a long-lasting significant elevation of malondialdehyde (lipid peroxidation). Only small amounts of this aldehyde were formed in the liver. In the lung malondialdehyde was increased during the first 6 hr after pancreatitis induction. Malondialdehyde levels were not different for pancreatitis initiated by 3% or 5% taurocholate. Protein-bound carbonyls (protein oxidation) in the tissues were not significantly changed at any time point. However, after infusion of 5% taurocholate, lung proteins were oxidatively modified by the product of lipid peroxidation, 4-hydroxynonenal. Another parameter characteristic for pancreatitis with high lethality was the high number of neutrophils in the lungs. We conclude that oxidative stress is important for the injury of extrapancreatic tissues during pancreatitis, but survival is determined by the degree of systemic inflammation.

Aldehydes↗
PubMed2001

Hospital caseload and the results achieved in patients with rectal cancer.

BACKGROUND: The aim of the study was to investigate the impact of hospital caseload on the short-term postoperative outcome of patients with rectal carcinoma. METHODS: A multicentre study involving 75 German hospitals was carried out between January and December 1999. Some 1463 patients with rectal carcinoma were studied. RESULTS: The hospitals were divided into three groups by annual caseload as follows: less than 20 (group 1), 20-40 (group 2) and more than 40 (group 3). The groups were identical in terms of age, gender, height, weight, tumour stage, risk factors and American Society of Anesthesiologists classification. Postoperative morbidity was less in hospitals with a case volume of more than 20 patients per year (41.7 per cent in group 2 versus 49.9 per cent in group 1). The proportion of patients undergoing abdominoperineal resection with a permanent stoma was less in hospitals with a case volume of more than 40 patients per year (26.4 per cent in group 3 versus 34.0 per cent in group 2). CONCLUSION: A large caseload in rectal surgery results in a significant reduction in permanent stoma formation and postoperative morbidity.

Anastomosis, Surgical↗
PubMed2001

[Quality assurance study of benign and malignant goiter. Prospective multicenter data collection regarding 7,617 patients].

A quality control study was undertaken on 7,265 patients with benign goitre and 352 patients with malignant goitre who were surgically treated between 1.1.98 and 31.12.98. 3 hospital groups were defined according to surgical workload: Group 1: < 50 operations/yr; Group 2: 50-150 operations/yr; Group 3: > 150 operations/yr. The temporary rate of recurrent laryngeal nerve (RLN) palsies for benign goitre was 3.9% and the permanent 1.1%. For malignant goitre the rates were 12.8% and 6.8% respectively. The rate of temporary (p < 0.040) and permanent (0.003) palsies after surgery for benign goitre was lower in group 3 compared to group 1 and 2. There were too few cases for statistical analysis of the malignant goitres. After benign goitre surgery a transient hypocalcaemia rate of 6.3% and a permanent of 1.1% were observed. For malignant goitre the incidence was 23.8% and 7.1%, respectively. A significantly increased rate of permanent hypocalcaemia (p < 0.003) was demonstrated in group 3 after surgery for multinodular goitre. Centres in group 3 made more extended (smaller thyroid remnants) resections (p < 0.01) with the equivalent rate of general complications. The average inpatient stay for malignant goitres was 13.1 days and for benign goitres 8.7 days. On average, patients with bilateral resections for benign goitre stayed 0.4 days longer in hospital than those with unilateral procedures. Prophylactic antibiotics were administered to 2.1% of patients and 94.6% received thrombosis prophylaxis.

Adult↗
PubMed2001

[Enzymatic and histological alterations in the isolated perfused rat pancreas in the taurocholate and cerulein model of acute pancreatitis].

METHODS: The pancreas of 24 male Wistar rats was perfused extracoporally by modified Krebs-Ringer-buffer for 80 minutes (including a 20 minutes equilibration period). To verify any organ damage we measured the activity of pancreatic enzymes like amylase, lipase and lactatdehydrogenase in the portal effluent. Furthermore histological changes were analysed after perfusion. Organ damage was induced by adding cerulein in a physiological dose (10(-10) M, n = 6) and in a supramaximal dose (10(-8) M, n = 6) and by intraductal injection of taurocholate (3.5 %, n = 6). RESULTS: Already 10 minutes after stimulation with cerulein (10(-8) M) and after intraductal injection of taurocholate increased activities (p < 0.01) of amylase and lipase were measured in the portal effluent compared to the group without any treatment. Lactatdehydrogenase levels did not changed. Apart from marked oedema in both groups considerable zones of necrosis could be noticed especially in the taurocholate group. CONCLUSION: Our data suggest that the isolated perfused rat pancreas (IPRP) is a valuable experimental tool to verify pathophysiological changes in the early phase of acute pancreatitis (AP). Various established models of AP such as by cerulein hyperstimulation or intraductal injection of taurocholate, could be applied to the IPRP. We conclude that this method enlarges the spectrum of established experimental models of acute pancreatitis.

Acute Disease↗
PubMed2001

[The isolated perfused rat pancreas - an experimental model for investigation the early events in the pathogenesis of acute pancreatitis].

METHODS: External perfusions of the pancreatic glands of Wistar-rats were done, using a modified Krebs-Ringer-Buffer (KRB). We looked for an elevation of amylase, lipase and lactate-dehydrogenase in the effusion fluid (portal outflow fluid). We investigated a normal perfusion (KRB, 60 minutes), a long term perfusion (KRB, 240 minutes) and a perfusion (60 minutes) including an additive of the detergents triton x-100 or the cholecystokinin analogue ceruletid (10(-8) M). RESULTS: An isolated external perfusion of a rat pancreas is possible without inducing any increase of parameters of damage such as amylase, lipase or lactate-dehydrogenase in the outflow medium. The perfusion time should be limited to 80 minutes including a 20 minutes equilibration period. A damage of pancreatic parenchyma is indicated by increased levels of pancreatic enzymes in the perfusion medium. Such damage can be induced by various noxious substances like detergents or cerulein, which has a significance in the pathophysiology of experimental acute pancreatitis. A significant increase (p < 0.01) of lactate-dehydrogenase, lipase and amylase was found 10, 20 and 30 minutes after an application of triton x-100. During a perfusion with the cholecystokinin analogue ceruletid (10(-8) M) we found an increase of lipase (p < 0.05) after 30 minutes and an increase of amylase (p < 0.05) after 50 minutes perfusion. CONCLUSIONS: The isolated perfused rat pancreas is a valuable experimental model to investigate the early phase of pathophysiology in acute pancreatitis.

Acute Disease↗
PubMed2001

Real-time assessment of intraperitoneal tumor growth in a rat model using CEA immunoscintigraphy.

BACKGROUND: In most preclinical models, assessment of intraperitoneal tumor location and size require killing the animal. The dynamics of postoperative intraperitoneal tumor implantation and growth remain unclear. A noninvasive method allowing reliable in vivo, real-time assessment of tumor growth is desirable. METHODS: An intraperitoneal tumor homograft using cultured CC531 colorectal cells was created by laparotomy in 24 Wistar Albino Glaxo rats. Eight additional rats were used as controls. Then, 10 MBq technetium 99m-labeled anticarcinoembryonic antigen (anti-CEA) monoclonal antibodies were administrated intravenously and radioactivity uptake was measured by using extracorporeal gamma counting at various time points. Subsequently, the animals were killed for tumor weighting. In 2 more groups of 8 animals, real-time, repeated measures were performed. RESULTS: Correlation between gamma counting and tumor weight was highly significant (P <.001). The regression equation obtained by using the least squares method was: tumor weight (g) = 2.422 + 0.267 x counts. It was possible to obtain real-time tumor growth curves when repeated measurements of radioactivity were performed. At day 25, the predicted tumor weight was 8.49 +/- 0.76 g, the measured weight was 8.16 +/- 0.99 g. CONCLUSIONS: Immunoscintigraphic measurements with technetium 99m anti-CEA antibodies are highly correlated with tumor weight in this model. As opposed to other tumor graft models based on autopsy findings, real-time monitoring is possible. This will allow dynamic studies of intraperitoneal tumor implantation and growth and will reduce the number of animals used in further studies.

Animals↗
PubMed2001

Randomized, placebo-controlled trial of lazaroid effects on severe acute pancreatitis in rats.

OBJECTIVES: To evaluate the therapeutic potential of lazaroids in severe necrotizing acute pancreatitis and to investigate the association between oxidative stress, protease activation, and local production of proinflammatory cytokines and the severity and lethality of the disease. BACKGROUND: Oxidative stress is a crucial factor in the pathophysiology of acute pancreatitis and its systemic complications. Treatment with antioxidants, however, failed to improve survival in most studies performed so far. Lazaroids are a novel class of antioxidants that potently protect pancreatic acinar cells against oxidant attack in vitro. DESIGN: Prospective, randomized, controlled experimental study. SETTING: University research laboratory. SUBJECTS: Seventy-five anesthetized male Wistar rats (300-350 g). INTERVENTIONS: Severe acute pancreatitis was induced by retrograde injection of 3.5% taurocholate-sodium into the common bile-pancreatic duct. Interventions were performed to mimic the clinical situation, including continuous intravenous fluid substitution and administration of lazaroids in a therapeutic protocol. Therapy was started 1 hr after injection of the bile salt by using three different lazaroids, lactated Ringer's solution (placebo), and methylprednisolone as a corticosteroid control (n = 15 in each group). All the substances were given by continuous intravenous infusion throughout the 20-hr trial period. MEASUREMENTS AND MAIN RESULTS: Pancreatic homogenates and ascites were analyzed for indicators of oxidative stress, antioxidants, proteases, and proinflammatory cytokines. Pancreatic edema, morphologic pancreatitis severity, and pancreatic histopathology also were assessed. All three lazaroids and methylprednisolone diminished pancreatic tumor necrosis factor-alpha concentrations. Lethality was 33% in the placebo group. Neither the lazaroids nor methylprednisolone influenced survival. The local pancreatic and peritoneal concentrations of lipid peroxidation products, antioxidants, and proteases did not differ among the five groups. Nonsurviving rats, however, had a higher total protease activity in the pancreas and higher concentrations of trypsinogen activation peptide in ascites, as compared with surviving animals. There were no differences between survivors and nonsurvivors with regard to variables of oxidative stress and cytokines. CONCLUSIONS: Lazaroid application under clinically relevant conditions (i.e., after induction of fulminant acute pancreatitis) does not influence lethality or biochemical variables relevant to this disease. Protease activation rather than oxidative stress or local pancreatic cytokine production is an important determinant of disease severity and survival in acute pancreatitis. In experimental studies evaluating novel therapeutics, the same strict criteria should be applied as in the human setting.

Animals↗
PubMed2001

Prognostic parameters determining survival in pancreatic carcinoma and, in particular, after palliative treatment.

Prognosis and outcome of patients with pancreatic carcinoma is poor. The aim of the study was to investigate (1) which factors of medical history and clinical status as well as which laboratory parameters determine survival in pancreatic carcinoma and (2) whether specific data can be used as prognostic parameters or for early diagnosis of pancreatic carcinoma. In total, 287 patients with pancreatic carcinoma were enrolled in the study. In 193 subjects, only palliative treatment was possible. Survival was assessed using univariate survival probability curves by Kaplan-Meier. Comparison of patient groups with regard to survival was achieved using the log-rank test. Multivariate analysis was carried out using the Cox regression model. Overall, 22 factors, showing a significant impact on survival in pancreatic carcinoma were found, e.g., tumor-associated factors such as (1) tumor stage according to the UICC classification including TNM-based staging, grading, tumor site, and vascular infiltration; (2) preoperative habits and signs and symptoms (physical condition, pain, loss of appetite, ethanol consumption); (3) change of laboratory parameters (CA 19-9, bilirubin, prothrombin time, urea, C-reactive protein), and (4) type of intervention (surgical approach, R0/1/2 resection). Using multivariate analysis, seven factors (UICC tumor stage and site, surgical intervention including number of resected lymph nodes, chemotherapy, occurence of a carcinoma in relatives, preoperative physical condition, night sweat) were determined. In the 193 patients with palliative treatment, only ten factors (among them UICC tumor stage including the presence of metastases; data from the medical history such as physical condition, loss of appetite, and carcinoma in relatives, and laboratory parameters including prothrombin time, protein content, and aspartate aminotransferase levels) were found to be important. Chemotherapy had the strongest impact on survival which was confirmed by multivariate analysis, followed by tumor stage (UICC) and preoperative appetite. Besides tumor-associated determinants, data from the medical history, and pathological laboratory parameters, the prognosis in pancreatic carcinoma is considerably determined by the treatment such as interventional and/or using antineoplastic agents.

Adult↗
PubMed2001

Ergotamine-induced acute vascular insufficiency of the lower limb--a case report.

Ergotamine-containing drugs are widely used in the treatment of acute migraine attacks. Spastic vasoconstriction is one of the possible side effects usually affecting the lower extremities and sometimes leading to gangrene. A 28-year-old woman was hospitalized for severe acute arterial insufficiency of the limbs. The initial surgical approach was not successful since the diagnosis was missed. Overuse of ergotamine derivative was acknowledged by the patient, who had a long history of migraine headaches. Therefore, the patient was treated conservatively with intravenous heparin and prostaglandin infusion and sympatheticolysis via epidural catheter. The vascular complications, angiographic findings, and different modalities of treatment of ergotamine-induced peripheral vascular insufficiency of the lower limb are reviewed.

Acute Disease↗
PubMed2001

[History of lymphadenectomy].

The present reflection of lymphadenectomy's history shows that the following questions have been discussed since about 100 years: How does the lymph node dissection affect the treatment of cancer? Does it reduce the local recurrence rate? Does a lymph node dissection improve the survival rate or permit a more specific staging of the tumour's extension? The principles of metastatic ways as well as their mechanisms have already been discussed in the 1920s.

Germany↗
PubMed2001

[The status of port-site recurrence].

Since laparoscopic surgery has been applied to cancer, an increased number of secondary tumors implanted in the abdominal wall have been reported. Quality of surgery is paramount in the incidence of port-site recurrences. In large prospective series of laparoscopic colorectal surgery, their incidence (around 0.85%) was similar to that reported in open surgery (0.6 to 1.6%) while it is higher for unapparent gallbladder cancer (around 15%) due to direct wound contamination. Viable tumor cells are seeded by inadequate surgical technique or released by advanced tumors. Tumor cells are carried across the abdominal cavity by peritoneal fluid currents and surgical instruments, not by CO2 pneumoperitoneum. CO2 modifies the morphology of mesothelial cells and inhibits peritoneal macrophages. Differences in retroperitoneal/subserosal/intraluminal tumor xenograft models show that CO2 laparoscopy reduces tumor growth when compared to gasless laparoscopy and laparotomy. The local effects of pneumoperitoneum in the wound might be counteracted by using inert gases such as helium, drug-loaded CO2 or various antiadhesive or cytotoxic agents. In clinical practice, port-site recurrences can be effectively prevented by careful surgical technique and prophylactic wound irrigation.

Abdominal Neoplasms↗
PubMed2001

[Treatment strategy in iatrogenic perforation of the large intestine].

Iatrogenic perforation of the colon is a rare but feared complication of coloscopy with an incidence of up to 0.3%. During a period of 12 years we saw 14 perforations of this kind. The therapeutic approach varies with the state of peritonitis and type of perforation. Conservative primary therapy should only be chosen in rare cases. Classic operative therapy ranges from simple suturing to partial resection of the colon, in cases including even formation of a colostomy. In case of diffuse peritonitis discontinuity resection following Hartmann is still recognized as a secure procedure. Lethality of 7.1% in our own patients confirms the effectivity of conventional operating methods.

Aged↗
PubMed2000

[Leben im Eismeer - Tauchuntersuchungen zur Biologie arktischer Meerespflanzen und Meerestiere]

Die Maske wird nochmals auf Dichtigkeit überprüft, der Knoten der Sicherungsleine mit zwei halben Schlägen fixiert, dann rutscht die Taucherin von der Eiskante in das kalte Wasser. Eine halbe Stunde vergeht, bevor ihr Kopf wieder aus dem Eisloch auftaucht und sie ein großes Sammelnetz nach oben reicht, gefüllt mit verschiedenen Arten von Makroalgen. Obwohl noch große Flächen des Kongsfjordes im arktischen Spitzbergen zugefroren sind und das Festland von einer dicken Schneedecke bedeckt ist, hat unter Wasser in den Algenwäldern bereits der Sommer und damit die Saison der Meeresbiologen begonnen.

Journal Article↗
PubMed2000

[Multiple metachronous metastases of renal cell carcinoma in the pancreas. Case report and review of the literature].

Isolated pancreatic metastases from renal-cell carcinomas (RCC) are extremely rare. Only 96 cases of clinically diagnosed renal-cell carcinoma metastatic to the pancreas have been reported in the world literature, and 70 of the patients (including ours) underwent a definitive surgical resection. In many cases the time between the nephrectomy and diagnosis of metachronous metastases is reported to exceed 10 years. Therefore, the initial diagnosis may be overlooked when there is a prolonged disease-free interval. When it does occur simultaneously or metachronously, aggressive surgical resection, when possible, seems to be the most effective treatment for this metastatic lesion. Surgical resection can provide long-term survival in selected cases. We present the case of a 69-year-old woman in whom two pancreatic metastases were treated by a left-sided subtotal pancreatectomy with splenectomy, 12 years after radical nephrectomy for a RCC. The patient simultaneously presented with both a mass in the body of the pancreas and a right-sided colon cancer. Thus, the diagnosis of pancreatic metastasis of colon cancer was suspected initially. Both tumors were radically resected, and histological examination revealed two pancreatic metastases from the previous RCC. In the world literature this report represents the eighth case of multiple pancreatic metastases due to RCC. It illustrates a rare indication of pancreatic resection because of pancreatic metastasis. The need for prolonged follow-up of patients is emphasized. The few reports on surgically treated pancreatic metastases from RCC are reviewed after the presentation of this case.

Adenocarcinoma↗
PubMed2000

Multivariate analysis of risk factors for postoperative complications in benign goiter surgery: prospective multicenter study in Germany.

Risk factors for postoperative complications of benign goiter surgery have not been investigated systematically. To this end, a prospective multicenter study (January 1 through December 31, 1998) was conducted involving 7266 patients with surgery for benign goiter from 45 East German hospitals. High-volume providers (>150 operations per year) performed 69% (5042/7266), intermediate-volume providers 27% (50-150), and low-volume providers 4% (258/7266) of operations. Among the hospital groups, the pattern of thyroid disease did not vary significantly, but there was a trend that small-volume providers tended to perform more operations for uninodular goiter and high-volume providers treated more patients with Graves' disease and recurrent goiter. Extent of resection (p < 0.0001) and remnant size (multinodular goiter and recurrent goiter, p < 0.001), differed significantly, with total thyroidectomy being performed more often in hospitals with more than 150 operations compared to hospitals with an operative volume of less than 150 procedures per year. Despite the larger extent of resection and smaller remnant size, rates of recurrent laryngeal nerve (RLN) palsy or hypoparathyroidism were not increased. When the logistic regression analyses were fitted to evaluate the impact of risk factors on transient and permanent RLN palsy and hypoparathyroidism, larger extent of resection [relative risk (RR) 1.5-2.1] and recurrent goiter (RR 1.8-3.4) consistently evolved as independent risk factors. With hypoparathyroidism, additional significant factors included patient gender (RR 2.1-2.4), hospital operative volume (RR 0.8-1.5), and Graves' disease (RR 2.8). Unlike parathyroid gland identification during hypoparathyroidism, RLN identification (RR 1.6) significantly (p = 0.01) reduced permanent RLN palsy rates. The multivariate analyses clearly confirmed the pivotal role of routine RLN identification, independent of the extent of the thyroid resection. These findings might help hospitals with lower operative volumes to identify patients at increased risk whom they might consider for specialist care.

Adult↗