[Improvement of Psychosomatic Rehabilitation after Prestationary Intervention]. / Verbesserung des Rehabilitationsergebnis durch prästationäre Intervention.

Aim of the study: Improvement of psychosomatic rehabilitation efforts with prestationary intervention. Method: The study is designed as a prospective and randomisized interventon study including 317 in patients. Result: Most of the patients were women (69.4 %), the mean age was 50.2 years. As measured with the BDI-II patients with prestationary intervention improved more than patients without intervention. The motivation has not been changed significantly in both treatment arms. Various independent cofactors like long duration of unemployment, disablement and patients who apply to pension were identified. Conclusion: Finally a prestationary telephon interview improves the results of psychosomatic rehabilitation measured with BDI.

Rheology of human blood plasma: viscoelastic versus Newtonian behavior.

We investigate the rheological characteristics of human blood plasma in shear and elongational flows. While we can confirm a Newtonian behavior in shear flow within experimental resolution, we find a viscoelastic behavior of blood plasma in the pure extensional flow of a capillary breakup rheometer. The influence of the viscoelasticity of blood plasma on capillary blood flow is tested in a microfluidic device with a contraction-expansion geometry. Differential pressure measurements revealed that the plasma has a pronounced flow resistance compared to that of pure water. Supplementary measurements indicate that the viscoelasticity of the plasma might even lead to viscoelastic instabilities under certain conditions. Our findings show that the viscoelastic properties of plasma should not be ignored in future studies on blood flow.

Oral glucose tolerance test and HbA1c for diagnosis of diabetes in patients undergoing coronary angiography: [corrected] the Silent Diabetes Study.

AIMS/HYPOTHESIS: The primary aim of this study was to compare the results of HbA(1c) measurements with those of an OGTT for early diagnosis of 'silent diabetes' in patients with coronary artery disease (CAD) undergoing angiography without prediagnosed diabetes. A secondary aim was to investigate the correlation between the extent of CAD and the glycaemic status of the patient. METHODS: Data from 1,015 patients admitted for acute (n = 149) or elective (n = 866) coronary angiography were analysed. Patients with known diabetes were excluded from the study. Using the OGTT results, patients were classified as having normal glucose tolerance (NGT), impaired fasting glucose (IFG), impaired glucose tolerance (IGT) or diabetes. According to the results of the HbA(1c) measurements, patients were classified into three groups: normal (HbA(1c) <5.7% [<39 mmol/mol]), borderline (HbA(1c) 5.7-6.4% [39-47 mmol/mol]) and diabetes (HbA(1c) ≥6.5% [≥48 mmol/mol]). RESULTS: Based on the OGTT, 513 patients (51%) were classified with NGT, 10 (1%) with IFG, 349 (34%) with IGT and 149 (14%) were diagnosed with diabetes. According to HbA(1c) measurements, 588 patients (58%) were classified as normal, 385 (38%) as borderline and 42 (4%) were diagnosed with diabetes. The proportion of patients with IGT and diabetes increased with the extent of CAD (IGT ρ = 0.14, p < 0.001, diabetes ρ = 0.09, p = 0.01). No differences in HbA(1c) were seen among the groups with different extents of CAD (p = 0.652). CONCLUSIONS/INTERPRETATION: An OGTT should be performed routinely for diagnosis of diabetes in patients with CAD undergoing coronary angiography, since HbA(1c) measurement alone appears to miss a substantial proportion of patients with silent diabetes. A limitation of the study is that the OGTT was not performed before the angiography.

Clonal growth of tumors on tissue-specific biomatrices and correlation with organ site specificity of metastases.

We have found that neoplastic transformation alters the ability of cells to grow on substrata of tissue extracts, "biomatrices", enriched in extracellular matrix. Tumor cells were able to survive and grow at lower densities and on more types of biomatrices than normal cells. When plated at high densities (greater than 10(5) cells/60 mm dish), tumor cells attached with equal efficiency and grew at similar rates and to equivalent saturation densities on biomatrices derived from all tissues. However, at low (10(2)-10(4)/60-mm dish) seeding densities, the tumor cells grew only on certain types of biomatrix. For the various hepatoma and mammary carcinoma cell lines tested, the tissue specificity in clonal growth on biomatrices correlated with their organ site specificity for metastasis in vivo in immunosuppressed, athymic nude mice. Analysis of the effects of purified matrix components (adhesion proteins, collagens, glycosaminoglycans) indicated that only the glycosaminoglycans influenced density-dependent survival and growth of tumor cells with effects that differed with respect to the cell's metastatic potential. The results indicate that the ability of tumor cells to colonize specific tissues represents, in part, regulation of low density survival and growth by extracellular matrix and are suggestive that one of the matrix components responsible may be proteoglycans or their glycosaminoglycan chains.

Role of asialo-GM1 positive liver cells from athymic nude or polyinosinic-polycytidylic acid-treated mice in suppressing colon-derived experimental hepatic metastasis.

Liver-derived (LD) murine colon adenocarcinoma MCA-38 cells injected into the ileocolic vein (ICV) of C57BL/6 mice developed distinct hepatic foci within 14-21 days and survived for an average of 19-35 days. In contrast, C57BL/6-nu/nu mice given injections of LD-MCA cells by the same route did not develop hepatic lesions. Furthermore, 111In-labeled LD-MCA-38 tumor cells were rapidly taken up by the liver of conventional mice within 1 h and 73% of the radioactivity remained after 24 h. However, about 60% of the 111In-labeled LD-MCA-38 tumor cells were cleared from the liver of nude mice after 24 h. Nonparenchymal liver cells isolated from untreated conventional mice displayed little cytotoxicity against freshly excised 51Cr-labeled LD-MCA-38 cells but did lyse the standard natural killer target, YAC-1 tumor cells, in 4 h chromium release assays. On the other hand, nonparenchymal liver cells but not spleen cells from nude mice were cytotoxic to 51CR-labeled LD-MCA-38 in vitro. The nonparenchymal liver cell population responsible for tumor killing was phenotypically nonadherent and asialo-GM1 (AsGM1) positive. C57BL/6 mice treated with polyinosinic-polycytidylic acid [poly(IC)] also displayed cytotoxic activity against LD-MCA-38 tumor cells in vitro. Furthermore, poly(IC) treatment of mice 1-8 days after tumor inoculation suppressed the number of hepatic foci and also significantly increased the life span of tumor-bearing mice. Treatment of athymic nude mice or poly(IC)-treated conventional mice with anti-AsGM1 induced significant numbers of foci and significantly decreased the life span of MCA-38-bearing mice suggesting that AsGM1-positive cells in the liver of these mice may inhibit tumor growth in vivo. In conclusion, the host defense system of the liver from athymic nude or poly(IC)-treated mice possess AsGM1-positive cells that can suppress tumor implantation or tumor growth in the early stages of metastasis in liver.

Early recovery of left ventricular function after thrombolytic therapy for acute myocardial infarction: an important determinant of survival.

Thrombolytic therapy for acute myocardial infarction reduces early mortality, but full recovery of left ventricular function after reperfusion is delayed. Therefore, the relations among reperfusion, survival and the time course of left ventricular functional recovery were examined in 226 patients treated with intracoronary streptokinase; 77% (134 patients) had sustained reperfusion and 31 patients had no reperfusion or had reocclusion by day 3. Wall motion was measured from contrast ventriculograms performed in the acute period and 3 days later in the central and peripheral infarct regions and the noninfarct region by the centerline method in 165 patients. Patients with reperfusion had better survival (p less than 0.05, mean follow-up 4.5 years) and a higher ejection fraction at 3 days (52 +/- 12 versus 46 +/- 10%, p less than 0.02) attributable to a significantly different change in peripheral infarct region function between the acute and 3 day studies (0.1 +/- 1.0 versus -0.3 +/- 0.9 SD, p less than 0.05). These early functional changes were significant in patients with anterior myocardial infarction and showed similar trends in those with inferior myocardial infarction. On Cox regression analysis, function measured at 3 days was more predictive of survival than was function measured acutely (chi square for acute ejection fraction = 11.48 versus 24.59 at 3 days). Although, as previously reported, greater than 45% of total recovery of left ventricular function occurs later, the ejection fraction achieved by day 3 is already predictive of survival. Thus, the mechanism by which successful thrombolytic therapy enhances survival is improvement of regional and global left ventricular function early after acute myocardial infarction.

Low density lipoproteins and Lovastatin modulate the organ-specific transendothelial migration of primary and metastatic human colon adenocarcinoma cell lines in vitro.

Tumor cell arrest and tumor migration are two of the critical steps in the metastatic cascade. We hypothesized that these steps may be facilitated by the low density lipoprotein (LDL)-induced activation of microvessel endothelial cells (MVEC). The purpose of our study was to investigate the biological effects of an LDL-enriched milieu and the effects of the anticholesterol drug Lovastatin on metastatic behavior. The SW480 and SW620 are primary and metastatic human colonic adenocarcinoma cell lines derived from the same patient. We investigated the effect of LDL on adhesion and migration of the two tumor cell lines across human brain, lung, liver and dermal endothelial monolayers. Adhesion and migration assays were done before and after pretreatment of the MVEC or tumor cells with LDL (100 microg/ml) for 24 h. Although metastatic SW620 cells were more adherent to MVEC compared with primary SW480 cells, LDL pretreatment of SW480 and SW620 cells did not affect tumor cell adhesion to MVEC. In contrast, tumor cell migration was significantly increased across endothelial monolayers when MVEC were pretreated with LDL. Transendothelial cell migration was not significantly affected by pretreatment of the tumor cells with LDL. Lovastatin is an inhibitor of HMG-CoA reductase, the rate-limiting enzyme in cholesterol biosynthesis. It has been shown to have anti-tumor activity in vitro. We investigated the effect of Lovastatin on tumor cell kinetics and tumor cell migration across MVEC. Growth curves and migration assays were done before and after pretreatment of the tumor cells with Lovastatin (30 microg/ml). Migration assays were also done after treatment of unstimulated or LDL-stimulated MVEC (100 microg/ml) for 24 h with Lovastatin. Lovastatin inhibited the in vitro growth of the metastatic SW620 cell line to a greater extent than the invasive SW480E cell line. On the other hand, pretreatment of tumor cells with Lovastatin (30 microg/ml) did not suppress transendothelial tumor cell migration of tumor cells. Finally, Lovastatin given to mice effectively suppressed the number of MCA-26 tumor colonies in the liver of Balb/c mice compared with untreated mice.

Indium-labeled anti-colorectal carcinoma monoclonal antibody accumulation in non-tumored tissue in patients with colorectal carcinoma.

Indium-111- (111In) labeled murine monoclonal antibodies ZCE 025 (against carcinoembryonic antigen) and CYT-103 MAb B72.3 (against tumor-associated glycoprotein - 72) have been used to image patients with colorectal cancers with encouraging results. The objectives of this study were to assess the frequency and causes of 111In MAb localization in tumor-free, benign tissues. Thus, scans of 75 patients who have undergone exploratory surgery following radioimmunoscintigraphy with 111In-ZCE 025 (n = 37) or 111In-CYT-103 (n = 38) were reviewed in conjunction with operative and histopathology reports. Localization in non-tumored tissues was seen in 10.8% and 13.1%, respectively, of patients receiving ZCE 025 and CYT-103. The most common sites involved were: degenerative joint disease, abdominal aneurysms, postoperative bowel adhesions, and local inflammatory changes secondary to surgery or external irradiation. Review of patients' medical history and results of concurrent diagnostic modalities is likely to lessen the false-positive rate of 111In-labeled MAb scan interpretation.

Gamma probe assisted ex vivo detection of small lymph node metastases following the administration of indium-111-labeled monoclonal antibodies to colorectal cancers.

This study evaluated the ability of ex vivo gamma-probe scanning to detect lymph node metastases in resected surgical specimens from primary colorectal carcinoma patients undergoing external scintigraphy following intravenous administration of 4.1-5.3 mCi of 111In-labeled anti CEA monoclonal antibodies. The ex vivo probe counting technique led to a twofold to fourfold increase in the number of detectable lymph nodes with the majority measuring 2-5 mm in diameter. Results indicate a potentially useful role for ex vivo probe counting in detection and mapping small (2-5 mm) lymph nodes metastases.

Safety and role of repeated administrations of Indium-111-labeled anti-carcinoembryonic antigen monoclonal antibody ZCE 025 in the postoperative follow-up of colorectal carcinoma patients.

The safety and clinical utility of repeated administrations of 111In-ZCE 025 were evaluated in 25 patients who have undergone colorectal carcinoma resection. Fifteen patients were clinically and radiologically free of recurrences and asymptomatic while 10 had rising CEA and/or symptoms. We repeatedly imaged the patients following intravenous administrations of 40 mg ZCE 025, every 4 to 6 mo. Side effects occurred in 16% of patients who received two or more infusions. Sixteen lesions were detected by immunoscintigraphy in 11 patients who were free of disease by CT scans or other imaging modalities. Ten recurrences were surgically confirmed in seven patients. Radiographic and clinical follow-up confirmed the remaining 6 Mab-positive lesions. Elevated human anti-mouse antibody (HAMA) titers were detectable in the sera of 30% and 64% of patients following the 1st and 2nd Mab injection respectively, but did not interfere with successful immunoscintigraphy nor correlated with the occurrence of side effects. This study suggests that a negative Mab scan indicates that a patient will remain free of recurrence; conversely, a positive scan was associated with recurrences of disease.

Intravascular ultrasound to assess aortocoronary venous bypass grafts in vivo.

In 20 consecutive patients (18 men and 2 women, aged 42 to 72 years) undergoing repeat coronary angiography because of new onset of angina pectoris 4 months to 11 years (mean 53 months) after aortocoronary saphenous venous bypass operation, the graft to the left anterior descending (n = 12), left circumflex (n = 4) or right coronary (n = 2) artery, or a diagonal branch (n = 2) was studied by both intravascular ultrasound and angiography. Sonographic images were obtained using a 4.8Fr catheter with a crystal mechanically rotated at 900 rpm; quantitative coronary angiograms were recorded in biplane projections. In 18 patients, qualitatively as well as quantitatively evaluable images could be recorded; no complications occurred. The venous wall in general appeared to be homogenous; there were no separate layers identifiable. Simultaneous ultrasound and angiographic measurements were performed at a total of 75 sites (2 to 6 per bypass). In 4 of these patients (10 of 75 sites), neither intravascular ultrasound nor angiography revealed any pathologic changes; these bypasses were classified as normal. At the remaining 65 sites, arteriosclerotic lesions were detected in each case by ultrasound, but at only 33 sites by angiography. Median wall thickness was 0.59 mm (95% confidence interval 0.54 to 0.63) in normal grafts and 1.02 mm (0.99 to 1.07; p less than 0.001) in diseased grafts. The cross-sectional luminal area determined by ultrasound correlated well with the angiographic assessment (r = 0.90; p less than 0.001), but the measured values were significantly higher (17 +/- 4 vs 14 +/- 4 mm2; p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Clinical applications of indium-111-labeled monoclonal antibody imaging in colorectal cancer patients.

During the past two decades, the in vivo application of monoclonal antibodies (MoAbs) in cancer diagnosis and therapy have been widely studied. This can be related to three main factors: (1) dramatic improvement in monoclonal antibody production, revolutionized by Kohler and Milstein; (2) improvement in radioisotopes and monoclonal antibody conjugation procedure and further simplification and ease of use of these procedures; and (3) the apparent safety of single or, in selected cases, multiple administration of MoAbs to humans. The development of radioimmunoscintigraphy or radioimmunodetection has added a significant new dimension to nuclear imaging, and it is very likely to broaden our approach to diagnosis and perhaps therapy of malignant diseases. The indications and limitation of radioimmunoscintigraphy must be clearly outlined to the referring oncologists and surgeons. The unique capability of radiolabeled MoAbs in detecting occult disease, upstaging patients, and, most importantly, changing patient management must be emphasized.

Duodenal lipoma causing intussusception.

Duodenal intussusception and duodenal lipomas are both rare clinical entities. A case of duodenal intussusception caused by a lipoma is presented. The diagnosis of lipoma may be made endoscopically and radiographically using both upper gastrointestinal series and computed tomographic scan. Intussusception in the duodenum may be partial and cause minimal symptoms, but it has distinctive roentgenographic findings. The treatment of symptomatic lipomas may be endoscopic removal, using snare and cautery, or local excision via duodenotomy. Intussusceptions must be reduced operatively.

Pancreaticoduodenectomy. University experience and resident education.

A radical pancreaticoduodenectomy offers the best chance for survival in patients with periampullary and pancreatic malignant neoplasms. A pancreaticoduodenectomy has educational value since complex pancreatic operations are demanding and important to the training of surgical residents. Increased pancreaticoduodenectomy experience (per surgeon) has been associated with improved outcomes. We examined the hypothesis that residents who are supervised by faculty surgeons can perform pancreaticoduodenectomies with acceptable outcomes. From 1976 to 1987, 127 pancreatic resections were performed by 81 residents who were supervised by 15 faculty surgeons in four teaching hospitals. A pancreaticoduodenectomy was performed on 61 patients. All residents served as an operating surgeon on a pancreatic resection, and 58 (82%) performed pancreaticoduodenectomies. The mortality for the pancreaticoduodenectomies was 8%, with a 36% major complication rate. A pancreaticoduodenectomy can be performed safely by residents under supervision. A review of the results identifies the means of improving outcomes. These results justify the preservation of a pancreaticoduodenectomy as an important experience for residents.

Indium 111 ZCE-025 immunoscintigraphy in occult recurrent colorectal cancer with elevated carcinoembryonic antigen level.

We investigated the utility of scanning with indium 111 labeled to monoclonal antibody in 13 patients after curative resection of colorectal cancer who had elevated carcinoembryonic antigen levels and negative results of clinical workup. Each patient received 1 mg of anti-carcinoembryonic antigen monoclonal antibody type ZCE 025 labeled with 5.5 mCi of 111In, plus 9 to 39 mg of the same antibody unlabeled. Patients underwent scanning 3 to 7 days after infusion by planar and emission computed tomography. ZCE-025 monoclonal antibody imaging detected tumor recurrence or metastasis in 11 of 13 patients. In one patient the monoclonal antibody scan gave a true-negative result, and in one patient the monoclonal antibody scan failed to disclose a metachronous cecal primary. Tumor sites identified were the pelvis (2 patients), abdominal wall (2), retroperitoneum (1), lymph nodes (3); liver (2), bone (2), and lung (1). The accurate localization of colorectal carcinoma recurrences by means of 111In ZCE-025 monoclonal antibody demonstrates the usefulness of this diagnostic agent in the setting of elevated carcinoembryonic antigen level and negative results of clinical and radiologic workup.

Detection of primary colorectal cancer with indium 111 monoclonal antibody B72.3.

B72.3 is a murine monoclonal antibody of the immunoglobulin subclass IgG1 directed against TAG-72, a cell surface antigen present on colorectal carcinoma cells. We investigated the utility of scanning with indium 111-labeled B72.3 in 16 patients with a high clinical suspicion of or biopsy-proven primary colorectal cancer. Each patient received 1 or 2 mg of B72.3 monoclonal antibody labeled with 152 MBq of indium 111. Patients underwent scanning 2 to 3 days and 7 days after infusion by planar and emission computed tomography. Nineteen lesions were confirmed in 12 patients. Three patients with benign polyps had true-negative monoclonal antibody scans. Indium 111-labeled imaging of B72.3 detected nine of 19 lesions. Unsuspected tumor sites were identified by monoclonal antibody scan in three patients. By detection of additional abdominal disease and extra-abdominal spread, indium 111-labeled scanning of B72.3 directly affected treatment in 18% of patients.

Partial hepatectomy augments the liver's antitumor response.

Despite adequate locoregional control, colorectal metastasis to the liver remains a significant cause of death. Resection of hepatic metastasis improves five-year survival 18% to 34%. A study of the impact of 40% partial hepatectomy on cytokine production in the liver was undertaken. Nonparenchymal liver cells (NPCs) were prepared by collagenase perfusion and metrizamide gradient from partially hepatectomized and laparotomized control C57BL/6Ros mice. Nonparenchymal cell from partially hepatectomized mice compared with laparotomized mice showed a twofold to threefold increase in interferon (IFN) activity. Both interferon alpha/beta and supernatants from cultured NPCs of partially hepatectomized mice suppressed the proliferation of liver-derived MCA-38 colon adenocarcinoma cells in vitro. This tumor has been shown to metastasize to the liver of C57BL/6Ros mice. The production of various cytokines by NPCs induced by partial hepatectomy may provide a possible antimetastatic mechanism.

Preoperative fasting improves survival after 90% hepatectomy.

OBJECTIVE: To assess whether alterations in preoperative fatty acid oxidation and gluconeogenesis induced by fasting will affect survival and liver regeneration following 90% hepatectomy in the rat. DESIGN: In a randomized, controlled trial, Wistar rats (N = 157) were separated into two groups. Rats in the first group fasted for 24 hours. Rats in the second group were allowed to eat ad libitum until the time of operation. These groups were further randomized to receive either 20% glucose or tap water ad libitum postoperatively. INTERVENTIONS: Ninety percent hepatectomy; 24-hour fast; 5% glucose feeding. MAIN OUTCOME MEASURES: Survival, DNA synthesis in the hepatic remnant along with glucokinase activity (GKA) and glycogen content, serum ketone bodies (KB), free fatty acid (FFA), glucose, and ad libitum glucose consumption (GC) were serially quantified. RESULTS: Fasting rats that were offered glucose (fasted/glucose) after hepatectomy demonstrated better survival at 48 hours than the rats that were fed before the procedure and given glucose following hepatectomy (fed/glucose), 95% vs 52% (P < .05). The fasted/glucose group also had a greater peak rate of DNA synthesis (550 +/- 110 vs 275 +/- 40 disintegrations per minute per 0.001 mg of DNA, P < .05). Survival was poor in both groups when only tap water was offered to the animals after hepatectomy (31% vs 12%). In the fasted/glucose group, GC 1 hour after hepatectomy was greater than that for fed rats (1.3 +/- 0.175 vs 0.73 +/- 0.176 g/h, P < .05), yet GKA was suppressed (3.4 +/- 0.42 vs 8.05 +/- 2.77 nmol/min per milligrams of protein, P < .05). Fasting before hepatectomy and consuming glucose after causes elevations in both FFA (1.26 +/- 0.19 vs 0.82 +/- 0.13 mol/mL., P < .05) and KB (18.96 +/- 2.82 vs 11.4 +/- 3.94 mmol/mL, P < .05). Normal glucose was maintained in the fasted/glucose group, but fell to 63 +/- 14 mg/dL at 8 hours after hepatectomy in the fed/glucose group. CONCLUSIONS: Fasting before hepatectomy shifts energy utilization to fat oxidation and gluconeogenesis, which appears to ameliorate liver failure after hepatectomy in this severe model of hepatic resection.

Hepatectomy prolongs survival of mice with induced liver metastases.

Resection of hepatic metastases from colorectal cancer has been shown to prolong survival in some patients. Whether this results from a reduction of tumor burden or is an indirect effect mediated by hepatectomy is questionable. Male C57BL/6Ros 8-week-old mice underwent ileocolic vein injection of a suspension of 0.3 mL of 2 x 10(5) viable liver-derived murine (MCA-38) colonic adenocarcinoma cells. This model produces hepatic metastases in all lobes of the liver. At 7, 14, or 21 days after tumor injection, mice were randomized to receive either 42% resection of the liver or laparotomy alone. Survival in the animals with hepatectomy was significantly prolonged when the hepatectomy was performed 14 or 21 days after tumor injection.

Hepatic metastasis alters the immune function of murine liver nonparenchymal cells.

To examine the effect of a single hepatic focus of metastatic colon tumor on the immune function of liver non-parenchymal cells (NPCs) from C57Bl/6 mice, we injected 2.5 x 10(5) liver-derived murine colon adenocarcinoma (LD-MCA-38) cells beneath the liver capsule. Three weeks following injection of the tumor cells, the immune function of the NPCs was studied. The NPCs from tumor-bearing mice exhibited increased cytotoxic and proliferative activity. The NPCs from tumor-bearing mice also contained a greater percentage of CD8+ and T-cell receptor gamma/delta+ liver-associated T lymphocytes. Levels of interleukin 6 and tumor necrosis factor were increased in the NPC supernatant, and interleukin 6 levels were increased in serum from tumor-bearing mice. We conclude that the presence of a single hepatic focus of metastatic tumor results in augmented immune function of murine liver NPCs.