PubMed Health⌕ Search

Biomedical subjects

W Marti

Publications and source records attributed to W Marti.

10 recordsLinked to original sources

Phase I/II clinical trial of a nonreplicative vaccinia virus expressing multiple HLA-A0201-restricted tumor-associated epitopes and costimulatory molecules in metastatic melanoma patients.

We performed a phase I/II clinical trial in metastatic melanoma patients with an ultraviolet (UV)-inactivated nonreplicating recombinant vaccinia virus enabling the expression, from a single construct, of endoplasmic reticulum-targeted HLA-A0201-restricted Melan-A/MART-1(27-35), gp100(280-288), and tyrosinase(1-9) epitopes, together with CD80 and CD86 costimulatory proteins. Corresponding soluble peptides were used to boost responses and granulocyte-macrophage colony-stimulating factor was used as systemic adjuvant. Safety and immunogenicity, as monitored with in vitro-restimulated peripheral blood mononuclear cells by cytotoxic T lymphocyte precursor (CTLp) frequency analysis and tetramer staining, were specifically addressed. Of 20 patients entering the protocol, 2 had to withdraw because of rapidly progressing disease. Immune responses were evaluated in 18 patients (stage III, n = 5; stage IV, n = 13) and increases in specific CTLp frequencies were observed in 15. In 16 patients responsiveness against all 3 antigens could be analyzed: 7 (43%), including all stage III cases, showed evidence of induction of CTLs specific for the three epitopes, and 2 (12%) and 4 (25%), respectively, showed reactivity against two or one tumor-associated antigen. In three stage IV patients no specific CTL reactivity could be induced. Increases in CTLp frequency were detected mostly after viral vaccine injections. However, in a majority of patients final CTLp levels were comparable to initial levels. Tetramer characterization of Melan-A/MART-1(27-35)-specific CTLs during the protocol also suggested preferential expansion after recombinant virus administration. Vector-specific humoral responses, frequently undetectable in stage IV patients, did not appear to prevent tumor-associated antigen-specific CTL induction. Aside from a single occurrence of transient grade 3 leukopenia, no major clinical toxicity was reported. Seventeen of 18 patients completed the 3-month trial (one patient died before the last delayed-type hypersensitivity test). Three displayed regression of individual metastases, seven had stable disease, and progressive disease was observed in seven patients. This is the first report on the administration of a UV-inactivated recombinant vaccinia virus coexpressing five transgenes in cancer patients. The results described here, in terms of safety and immunogenicity, support the use of this reagent in active specific immunotherapy.

Adult↗

[Small breast carcinomas--less axillary surgery?].

In view of introducing less invasive or selective axillary procedures for small breast cancers we investigated our own pT1 tumor patients. The incidence of pT1 carcinoma, the nodal involvement of pT1a, b and c, the axillary relapse and the overall survival were analyzed. From 1983 till 1997 185 consecutive patients have been treated for breast cancers with a diameter of < or = 20 mm. The survival data after Kaplan-Meier are based on a cohort of 117 patients with a median follow up of at least seven years. There were seven patients with a pT1a carcinoma, 30 with a pT1b and 148 with pT1c carcinoma. On an average 16 axillary lymph nodes were counted by the pathologists. The axillary involvement clearly depends on the size of the primary tumor: no nodal involvement in patients with pT1a carcinoma, 10% in patients with pT1b carcinoma and 30% in patients with pT1c carcinoma. Not one single axillary relapse was detected after this follow up time. The overall ten years survival for patients with pT1a was 100%, 91% for pT1b, but only 74% for pT1c carcinoma. Screening mammography is expected to detect more small breast cancers in pN0 stage. Risks and benefits of axillary dissection have to be carefully evaluated. Axillary involvement of small breast cancers is rare. Only a minority of patients will benefit from routine axillary lymphadenectomy, while the majority runs the risk of complications. The sentinel lymph node (SLN) procedure offers a selective approach to this dilemma.

Adult↗

Efficacy of specific aseptic precautions for preventing propofol-related infections: analysis by a quality-assurance programme using the explicit outcome method.

Specific aseptic precautions have been recommended for preventing infectious complications of propofol because its lipid base can support bacterial growth if contaminated. To study whether the precautions used at our institution prevent propofol-related infections, we retrospectively analysed the data covering 1 January, 1995 until 30 June, 1996 held in our quality-assurance database. The database contains prospectively collected, detailed and standardized information of each patient's risk factors, anaesthetic and surgical data, and postoperative outcome. Surgical patients who had received propofol for anaesthesia did not have a higher incidence of postoperative infection, thus demonstrating the efficacy of our aseptic precautions.

Adult↗

Gene expression and cytopathic effect of vaccinia virus inactivated by psoralen and long-wave UV light.

Induction of the cytopathic effect (CPE) in cells infected with poxvirus seems ubiquitous in that it has been associated with all different strains and preparations of poxviruses, regardless of the replicating status of these viruses. The study of the mechanisms by which CPE is induced by nonreplicating poxviruses is hampered by the lack of any noncytopathic mutant strains and preparations. In this paper, we report on the patterns of gene expression and induction of CPE by vaccinia viruses treated by limited cross-linking with psoralen and long-wave UV light (PLWUV). We show that treatment of cell-free virus with PLWUV could inactivate viral replication without abolishing the ability of the virus to infect cells. Viral transcription as indicated by reporter genes was generally enhanced and prolonged under early viral promoters and abolished under late promoters. Furthermore, increasing the levels of cross-linking with PLWUV resulted in a decrease and abolishment of viral expression of a large reporter gene and a concomitant loss of the induction of CPE. Cells infected with such a virus were able to express the reporter genes and proliferate. The generation of nonreplicating and noncytopathic recombinant vaccinia viruses may help in studies of the mechanisms of CPE induction by poxvirus and may facilitate the use of poxviral vectors in broader areas of research and clinical applications.

Animals↗

[Cholecystectomy today. A prospective study].

Between 13 June 1990 and 12 June 1993, we performed 1145 consecutive cholecystectomies. 127 patients who had undergone additional surgery were excluded from the prospective study. Of the remaining 1018 patients, 806 (78.2%) underwent laparoscopic cholecystectomy. The conversion rate to open procedure was 11.2% (90/806). The operative morbidity associated with laparoscopic cholecystectomy was 2.1% (17/806) and with open surgery 1.9% (4/212); mortality was 0.12% (1/806) and 0.47% (1/212) respectively. The reoperation rate after laparoscopic cholecystectomy was 0.6% (5/806). Reoperation was performed for lesions of the common bile duct, bleeding, and abscess formation. If the indications for open cholecystectomy are respected the morbidity and mortality were low for both laparoscopic and conventional cholecystectomy.

Adolescent↗

[Labor without prenatal care--an unnecessary challenge].

A group of 431 patients who had given birth, but had not attended regular check-ups during their pregnancy, are compared with a cumulative comparative group. The data is from a databank, belonging to the Swiss gynaecological working group. The following results are striking: Very young women, relatively older childbearing women, a noticeably high number of unmarried women and women from the Mediterranean countries. The number of women with heavy nicotine abuse is significant. The general progress of the pregnancy is however not noticeably different from the comparative group. The premature birth rate is higher in the group without pregnancy check-ups, as are birth deficiences and clinical foetal distress. Particularly noticeably is the high number of perinatal deaths. The pointlessness and the possible reasons for lack of regular pregnancy check-ups are discussed.

Adolescent↗

[The muscles and blood supply of the stomach].

Using human gastric specimens, figures are presented for gastric muscle thickness and the myoarchitecture is described. The study shows that the blood supply to the cardia, gastric fundus and body is excellent, due to the many anastomosing arteries, but is less good at the curvatures of the gastric antrum and poor at the anterior and posterior walls of this area, due to absent or minute anastomoses.

Cardia↗

[Status of dental preventive efforts in Switzerland].

Regarding schools, the first endeavours of preventive dentistry based on the results of modern scientific results were made in the early fifties in the Canton of St. Gall. Great efforts have been made since then and it is impossible to keep track of all activities. At the schools it is the teachers on one hand and specialized or lay auxiliary personnel on the other who organize and perform supervised toothbrushing exercises with fluorides. In Switzerland there are now some 30 full-time positions for auxiliaries charged with preventive measures at Kindergarten or school. An estimate of the population reached by the various methods of prevention is presented. The costs of prevention are but a small fraction of the cost of conservative treatment. In the majority of the private dental offices prevention is part of the activity, but with varying intensity. As to public clinics, the preventive programm run by the Volkszahnklinik Basel is most advanced. It is important that prevention is introduced in all regions of Switzerland and that it reaches the children of all ages. The future depends strongly on the availability of auxiliary personnel working at the schools and in the dental offices.

Child↗

Glutamine peptide-supplemented long-term total parenteral nutrition: effects on intracellular and extracellular amino acid patterns, nitrogen economy, and tissue morphology in growing rats.

Glutamine (GLN) is a nonessential amino acid that is not included in current regimens for parenteral nutrition because of its chemical instability. This study tested the hypothesis that GLN supplementation during long-term total parenteral nutrition (TPN) (3 weeks) would enhance GLN availability, thereby improving nitrogen economy and growth in a growing rat model: Standard TPN delivering 300 kcal/kg per day (lipid:carbohydrate = 1.1) including 2.1 g of nitrogen per kilogram per day in an all-in-one solution was compared with an isonitrogenous, isocaloric, and isovolemic TPN regimen with 0.29 g of nitrogen per kilogram per day substituted by GLN derived from the dipeptides glycyl-GLN and alanyl-GLN (TPN GLN). Enterally fed controls were included. Analysis was confined to nonbacteremic animals with negative blood culture, in which extracellular and intracellular amino acid concentrations including GLN, nitrogen balance, serum protein concentrations, growth, and histologic sections of liver and small-bowel mucosa (light and scanning electron microscopy) were evaluated. Hepatic intracellular GLN concentrations were significantly lower, in animals receiving GLN-free TPN (11.7 +/- 1.6 nmol/mg fat-free dry and solid tissue mass, n = 9) compared with both GLN-supplemented TPN (16.0 +/- 3.0, n = 7) and enteral feeding (18.2 +/- 1.8, n = 6) (p < .001). Corresponding results were found for intracellular GLN concentrations in skeletal muscle (TPN standard 12.5 +/- 3.1, TPN GLN 14.7 +/- 3.1, enteral control 17.3 +/- 2.3, p < .05), intestinal mucosa, and spleen as well as for plasma concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids↗