[The management of acute pancreatitis according to the modern guidelines]. / Managementul pancreatitei acute conform ghidurilor terapeutice actuale.

Severe acute pancreatitis is a critical illness as the organism that produces a significant mortality despite diagnostic and therapeutic acquisitions. While new mechanisms have been identified for production and were crystallized management principles, a number of controversies remain awaiting resolution in the near future. Aim is to establish, based on their experience and literature data, place the current means of diagnosis and treatment in close correlation with the pathophysiological events of acute pancreatitis.

Carcinoembryonic antigen (CEA)-specific T-cell activation in colon carcinoma induced by anti-CD3 x anti-CEA bispecific diabodies and B7 x anti-CEA bispecific fusion proteins.

Two bispecific recombinant molecules, an anti-CD3 x anti-carcinoembryogenic antigen (CEA) diabody and a B7 x anti-CEA fusion protein, were tested for their capacity to specifically activate T cells in the presence of CEA-expressing colon carcinoma cells. T-cell activation by the anti-CD3 x anti-CEA diabody required close contact to CEA-positive cells and resulted in diabody-mediated cytotoxicity against the target cells. Additionally, CD28-mediated costimulation in combination with anti-CD3 x anti-CEA diabodies induced activation of autologous T cells in CEA-positive primary colon carcinoma specimens, as determined by flow cytometry. The high specificity of the bispecific diabody approach could be further enhanced by the use of B7 x anti-CEA fusion proteins because the costimulatory CD28-signaling to the T cells strictly depended on the expression of CEA on the target cells. We demonstrate that displaying engagement sites for the T-cell antigens CD3 and CD28 on the surface of colon carcinoma cells is a suitable way to activate and retarget T cells in a highly tumor-specific manner. For clinical purposes, B7 x anti-tumor-associated antigen (TAA) fusion proteins, which are equally effective but more specific compared with anti-CD28 monoclonal anti-bodies, thus may improve the tumor specificity of anti-CD3 x anti-TAA bispecific antibodies. Furthermore, B7-negative tumors can be converted into B7-positive tumors by B7 x anti-TAA fusion proteins without the need for B7 gene transfer to the malignant cells.

In vitro degradation of a biodegradable polyurethane foam, based on 1,4-butanediisocyanate: a three-year study at physiological and elevated temperature.

Biodegradable polyesterurethanes (PUs) may be used as scaffold materials for tissue regeneration applications, because of their excellent mechanical properties. In this study, the degradation of highly porous PU foams was evaluated in vitro. The PU had amorphous soft segments of DL-lactide/epsilon-caprolactone and uniform hard segments, synthesized from 1,4-butanediisocyanate and butanediol. The foams were degraded for 3 years in a Sörensen buffer solution (pH 7.4) at 37 and 60 degrees C. Dimensions of the foams, intrinsic viscosity, mass loss, thermal properties, and composition of the remaining material were evaluated. Copolyester (CP) foams of DL-lactide/epsilon-caprolactone served as controls. The PU foams kept their dimensions for 20 weeks at 37 degrees C, whereas CP foams collapsed after 3 weeks. PU mass loss reached a maximum of 80% at both 37 and 60 degrees C. CP mass loss reached 99.9% at 60 degrees , and 92% at 37 degrees C after 3 years. The degradation processes at 37 and 60 degrees C are initially the same, but eventually degradation products with different thermal properties are being formed. (1)H NMR studies showed that the hard urethane segments of the PU do not degrade in vitro at pH 7.4. It was concluded that the PU material has favorable characteristics for a scaffold material. Compared to long-term in vivo results of the same PU these in vitro results are not representative for the in vivo situation and therefore total resorption has to be investigated in long-term in vivo studies.

Local anesthesia for endovascular abdominal aortic aneurysm repair.

OBJECTIVES: This study reports the results of a prospective continuous cohort of patients treated for endovascular aneurysm repair (EVAR) with a unified anesthetic strategy based on the use of local anesthesia (LA) in all patients, while reserving regional (RA) or general anesthesia (GA) only for those with predefined individually or surgically specific indications. METHODS: All patients treated by EVAR for an elective aortic abdominal aneurysm (AAA) between April 1998 and December 2003 were included. The strategy of treatment generated three cohorts of patients (LA, RA, or GA). Primary outcome included all-cause mortality, nonfatal cardiac morbidity, respiratory complications, and renal failure. Secondary outcome measures included conversion to general anesthesia, use of analgesics, and time-related outcomes (operating time, length of stay in intensive care unit and hospital, time required to resume oral intake, and time to ambulation). RESULTS: A total of 239 patients underwent EVAR: 170 LA, 31 RA, and 38 GA. Overall mortality was one patient (0.4%). LA was associated with a lower incidence of complications compared with GA (P < .001). In the LA group, two patients had to be converted to GA, one because of a dissection and one because of anxiety. In 13% of the patients in the LA group, additional intravenous sedation or analgesia was required. Operating time and length of stay in intensive care was shorter in the LA and RA groups than in the GA group (P < .001). Length of stay in hospital and time to ambulation and regular diet was shorter in the LA group compared with the RA and GA groups (P < .001). CONCLUSIONS: A strategy based on the preferential use of LA for EVAR restricting RA or GA only to those with predefined contraindications is feasible and appears to be well tolerated.

Secondary prevention in patients several years after myocardial infarction: comparison of an outpatient and an inpatient rehabilitation programme.

OBJECTIVE: To compare the effectiveness of secondary preventive measures in patients after myocardial infarction participating in an outpatient rehabilitation programme at a university hospital with those of an inpatient programme in community hospitals. DESIGN: Cross-sectional study of patients several years after myocardial infarction. METHODS: Seven hundred patients who survived myocardial infarction in the period from 1 January 1989 to 31 December 1995 were chosen from archives of the university hospital (350 patients) and from archives of two community hospitals (350 patients). The patients from the university hospital attended an outpatient rehabilitation programme, while the patients from the community hospitals attended an inpatient rehabilitation programme. The data were obtained by questionnaire, clinical examination and laboratory blood analyses. RESULTS: One hundred and eighty patients attending an outpatient and 140 patients attending an inpatient rehabilitation programme responded to the invitation. Among those who were smokers at the time of myocardial infarction, 91% of patients from the outpatient programme versus 77% of patients from the inpatient programme (P < 0.05) gave up smoking and were still non-smokers; 69% versus 48% (P < 0.05) had a lipid-modified diet; 21% versus 36% (P < 0.05) were obese (BMI > 30 kg/m2). Blood pressure > 140/90 mmHg was found in 21% versus 58% (P < 0.05); total cholesterol > 5.0 mmol/l in 67% versus 87% (P < 0.05); and fasting glucose > 5.6 mmol/l in 43% versus 63% (P < 0.05) of patients from the outpatient and the inpatient programmes, respectively. Among prophylactic drug treatments higher usage of beta-blocking agents (56% versus 36%; P < 0.05) and lipolytic agents (43% versus 23%; P < 0.05) and no significant difference in usage of antiplatelet drugs (83% versus 75%) and angiotensin-converting enzyme inhibitors (30% versus 32%) was found in patients from the outpatient programme compared to patients from the inpatient programme. Only regular physical activity was performed better by patients from the inpatient programme than by patients from the outpatient programme (68% versus 50%; P < 0.05). CONCLUSIONS: The outpatient rehabilitation programme of the university hospital resulted in better application of secondary prevention than the inpatient rehabilitation programme of community hospitals.

A detailed analysis of K-ras point mutations in relation to tumor progression and survival in colorectal cancer patients.

Point mutations in codon 12, 13, and 61 of the K-ras gene are an early event in tumorigenesis of colorectal cancer, but the impact of number, type, and position of such mutations on the progression of adenomas as well as the clinical behaviour of colorectal carcinomas is not clearly established. A series of 35 adenomas and 117 carcinomas at various stages was subjected to single-strand conformation polymorphism (SSCP) to analyse type, position and number of exon-I K-ras point mutations and to relate the results with patients survival. From our data we conclude that the number of K-ras point mutated tumors shows a trend to increase with tumor progression. The number of multiple K-ras point mutations, however, significantly increases with stage. Most mutations occur in the 1st or 2nd base of codon 12, whereas point mutations in the 3rd base are rare. In adenomas mutations, particularly G-T transversions, in the K-ras gene could indicate a propensity to malignant transformation. G-A transitions and G-C transversions of the second base are associated with metastasized tumors. Regarding survival, patients with K-ras point mutated tumors did worse than their non-mutated counterparts. G-A transitions in the 1st and 2nd base and G-C transversions in the 2nd base were associated with a poor prognosis as compared with G-T transversions in both the 1st and 2nd base. Patient survival therefore is related to the occurrence and type, but not the location, of K-ras point mutations.

CD3X anti-nitrophenyl bispecific diabodies: universal immunotherapeutic tools for retargeting T cells to tumors.

We developed a universal recombinant bispecific molecule (BiMol) that is capable of redirecting cytotoxic T cells to tumor cells via tagged anti-tumor ligands such as antibody fragments or cytokines. A recombinant bispecific diabody with binding specificities for the CD3 molecule on T cells as well as for the hapten nitrophenyl (NIP) was produced. This bispecific molecule is capable of redirecting cytotoxic T cells to kill a series of malignant cells, including B cell lymphoma, Hodgkin's lymphoma, and colon carcinoma via NIP-conjugated ligands to tumor-associated antigens. Cytotoxic activity of the diabody was found to be comparable to tetradoma-derived bispecific antibodies with similar specificities. Our findings demonstrate that universal CD3xanti-NIP diabodies could be used for T cell based cellular immunotherapy in a variety of human malignancies. Additionally, these bispecific molecules allow fast and economic testing of tumor-associated antigens on malignant cells for their potential use as immunotherapeutic target structures if corresponding hapten-conjugated antibodies or ligands are available.