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Biomedical subjects

M Bolli

Publications and source records attributed to M Bolli.

13 recordsLinked to original sources
PubMed2006

[Incision and closure of the abdominal wall].

Access to the abdominal cavity must be performed in such a way that surgical treatment procedures can be performed safely. For skin incision, scalpel and electrocautery are equivalent. Subcutaneous tissue and fascias must be divided by electrocautery to minimize blood loss. The best way to close the abdominal cavity is by an all layer, slowly absorbable, running suture with a suture: wound length ratio of at least 4:1. Closing the peritoneal layer is not necessary. Subcutaneous sutures and drains do not reduce the risk of wound complications. Staples should be used for closing the skin.

Abdominal Wall↗
PubMed2006

[Ileus disease].

Intestinal obstruction may be mechanical or non-mechanical (adynamic ileus). Adhesions and external hernias are the most common causes of obstruction in small intestine, whereas carcinoma, sigmoid diverticulitis, and volvulus are the most common causes in large intestine obstruction. Distension of the intestine caused by gas and fluid accumulation in the obstructed segment is the key pathophysiological mechanism initiating ileus with subsequent multiorgan failure and death. Surgery should always be undertaken if complete obstruction or strangulation is suggested and ileus is established. Before operation, the fluid and electrolyte balance should be restored and decompression instituted by means of a nasogastric tube. Delaying the operation because of improvement in patient well-being during resuscitation is only justified in those suffering from large intestine obstruction due to colorectal carcinoma. Purely nonoperative treatment is safe only in the presence of incomplete obstruction and best utilized in patients with postoperative adynamic ileus or repeated episodes of partial obstruction.

Diagnosis, Differential↗
PubMed2004

Encapsulation into sterically stabilised liposomes enhances the immunogenicity of melanoma-associated Melan-A/MART-1 epitopes.

Tumour-associated antigens (TAA)-specific vaccination requires highly immunogenic reagents capable of inducing cytotoxic T cells (CTL). Soluble peptides are currently used in clinical applications despite an acknowledged poor immunogenicity. Encapsulation into liposomes has been suggested to improve the immunogenicity of discrete antigen formulations. We comparatively evaluated the capacity of HLA-A2.1 restricted Melan-A/MART-1 epitopes in soluble form (S) or following inclusion into sterically stabilised liposomes (SSL) to be recognised by specific CTL, to stimulate their proliferation and to induce them in healthy donors' peripheral blood mononuclear cells (PBMC), as well as in melanoma-derived tumour-infiltrating lymphocytes (TIL). HLA-A2.1(+), Melan-A/MART-1-NA-8 melanoma cells served as targets of specific CTL in 51Cr release assays upon pulsing by untreated or human plasma-treated soluble or SSL-encapsulated Melan-A/MART-1 27-35 (M27-35) or 26-35 (M26-35) epitopes. These reagents were also used to stimulate CTL proliferation, measured as 3H-thymidine incorporation, in the presence of immature dendritic cells (iDC), as antigen-presenting cells (APC). Induction of specific CTL upon stimulation with soluble or SSL-encapsulated peptides was attempted in healthy donors' PBMC or melanoma-derived TIL, and monitored by 51Cr release assays and tetramer staining. Na-8 cells pulsing with SSL M27-35 resulted in a five-fold more effective killing by specific CTL as compared with equal amounts of S M27-35. Encapsulation into SSL also provided a partial (50%) protection of M27-35 from plasma hydrolysis. No specific advantages regarding M26-35 were detectable in these assays. However, at low epitope concentrations (</=100 ng ml(-1)), SSL M26-35 was significantly more effective in inducing CTL proliferation than S M26-35, in the presence of iDC, as APC. Preincubation with iDC for 6 h virtually abolished the capacity of S M26-35 to stimulate specific CTL proliferation, but only partially affected that of SSL M26-35. Most importantly, SSL M26-35 was able to enhance the induction of specific CTL in healthy donors PBMC and in melanoma-derived TIL as compared to S M26-35. Taken together, our data indicate that encapsulation of TAA epitopes into SSL results in effective immunogenic formulations suitable for clinical use in active specific tumour immunotherapy.

Antigens, Neoplasm↗
PubMed2004

The incidence of iliac aneurysms in patients with abdominal aortic aneurysms: comparison of four centers in Europe and the USA.

BACKGROUND: The purpose of this study was to compare the anatomy of the aortoiliac vessels in patients scheduled for infrarenal abdominal aortic aneurysm (AAA) repair in four different countries. MATERIAL AND METHODS: Consecutives series of 100 preoperative CT-scans were evaluated at each center. Diameters of the suprarenal aorta, maximal diameter of the aneurysm, right and left common and external iliac artery as well as the hypogastric arteries were recorded and compared between each center. RESULTS: Configuration of the AAA above bifurcation was similar at each center. The dimensions of the aortic bifurcation and the common iliac arteries were different among the centers. Common iliac arteries with diameters over 25 mm were significantly more common at center 1 (p < 0.001, p = 0.002 and p < 0.001). Among centers 2, 3 and 4 there was no significant difference in common iliac diameters. CONCLUSIONS: Configuration of the iliac arteries in AAA was significantly different for Swiss patients compared to American, Austrian and German patients. Reasons for these differences are unclear, epidemiological or genetic factors may be responsible.

Adult↗
PubMed2003

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↗
PubMed2003

[Swiss surgery: quo vadis? Reader and market analysis for strategic positioning of a specialty journal].

UNLABELLED: Scientific journals currently face challenges including cost pressures caused by economic constraints, increasing rivalry among competitors, limited market potential of non-english speaking journals, increasing medical specialization with resulting market fragmentation, and internet-based competition. We therefore analyzed strategic opportunities of the journal Swiss Surgery on the basis of customer surveys and of a market analysis. RESULTS: Swiss surgeons expressed their interest in the continuation of the journal but also indicated their support for changes in its concept and for an increased use of electronic media. An international market analysis points-out the difficulties of national, non-english speaking journals in gaining impact points and in attracting authors and readers of scientific medical articles. Therefore, a journal such as Swiss Surgery should identify and use publication niches. RECOMMENDATION: The demand for a concept addressing surgical training including continuous postgraduate education was confirmed by the customers of Swiss Surgery. A corresponding offer does not presently exist in the area and could become the new focus of the journal. This change of concept may have a number of consequences: A journal focusing on surgical training and education should use the results of readers' surveys rather than impact point assignment to evaluate quality. The journal should increasingly use electronic services including data bases, pictures, videos and closed user groups to supplement the print version. At short term, however, the printed version should be continued and not be substituted by the electronic version in order to maintain the established brand "Swiss Surgery".

Attitude of Health Personnel↗
PubMed2002

Endothelin receptor antagonists: structures, synthesis, selectivity and therapeutic applications.

Endothelin (ET) was discovered in 1988 and is the most potent vasoconstrictive peptide known to date. It exists in three isoforms (ET-1 to ET-3) and acts on two endothelin receptor subtypes, the endothelin-A (ET(A))-receptor and the endothelin-B (ET(B))-receptor. Endothelin receptor antagonists are novel therapeutics in clinical development for different cardiovascular, cerebrovascular, and renal diseases. Several different structural classes of endothelin receptor antagonists have been discovered within the last decade, starting from peptidic- and peptidomimetic structures to small organic molecules suitable as therapeutics for oral administration. Focussing on the small organic molecules, the different structural classes of ET-receptor antagonists are described with respect to synthesis, structure-activity-relationships, receptor-subtype-selectivity profile, and where possible, intended therapeutic indications.

Drug Design↗
PubMed2001

Pentopyranosyl oligonucleotide systems. Part 11: Systems with shortened backbones: (D)-beta-ribopyranosyl-(4'-->3')- and (L)-alpha-lyxopyranosyl-(4'-->3')-oligonucleotides.

The (L)-alpha-lyxopyranosyl-(4'-->3')-oligonucleotide system-a member of a pentopyranosyl oligonucleotide family containing a shortened backbone-is capable of cooperative base-pairing and of cross-pairing with DNA and RNA. In contrast, corresponding (D)-beta-ribopyransoyl-(4'-->3')-oligonucleotides do not show base-pairing under similar conditions. We conclude that oligonucleotide systems can violate the 'six-bonds-per-backbone-unit' rule by having five bonds instead, if their vicinally bound phosphodiester bridges can assume an antiperiplanar conformation. An additional structural feature that seems relevant to the cross-pairing capability of the (L)-alpha-lyxopyranosyl-(4'-->3')-oligonucleotide system is its (small) backbone/basepair axes inclination. An inclination which is similar to that in B-DNA seems to be a prerequisite for an oligonucleotide system's capability to cross-pair with DNA.

Base Pairing↗
PubMed1999

L-alpha-lyxopyranosyl (4'-->3') oligonucleotides: a base-pairing system containing a shortened backbone.

[formula: see text] The L-alpha-lyxopyranosyl (4'-->3') oligonucleotide system shows cooperative base-pairing in spite of containing only five instead of the usual six covalent bonds per repetitive backbone unit. In contrast, corresponding D-beta-ribofuranosyl (4'-->3') oligonucleotides do not show adenine-thymine pairing under comparable conditions. The difference in pairing behavior relates to the conformation of the two systems' vicinal 3',4'-phosphodiester substituents, which is diaxial in the lyxopyranosyl system and 3'-axial-4'-equatorial in the ribopyranosyl system.

Base Pairing↗
PubMed1997

Pyranosyl-RNA: chiroselective self-assembly of base sequences by ligative oligomerization of tetranucleotide-2',3'-cyclophosphates (with a commentary concerning the origin of biomolecular homochirality).

BACKGROUND: Why did Nature choose furanosyl-RNA and not pyranosyl-RNA as her molecular genetic system? An experimental approach to this problem is the systematic comparison of the two isomeric oligonucleotide systems with respect to the chemical properties that are fundamental to the biological role of RNA, such as base pairing and nonenzymic replication. Pyranosyl-RNA has been found to be not only a stronger, but also a more selective pairing system than natural RNA; both form hairpin structures with comparable ease. Base sequences of pyranosyl-RNA can be copied by template-controlled replicative ligation of short activated oligomers (e.g. tetramer-2',3'-cyclophosphates) under mild and potentially natural conditions. The copying proceeds with high regioselectivity as well as chiroselectivity: homochiral template sequences mediate the formation of the correct (4'-->2')-phosphodiester junction between homochiral tetramer units provided they have the same sense of chirality as the template. How could homochiral template sequences assemble themselves in the first place? RESULTS: Higher oligomers of pyranosyl-RNA can self-assemble in dilute solutions under mild conditions by ligative oligomerization of tetramer-2',3'-cyclophosphates containing hemi self-complementary base sequences. The only side reaction that effectively competes with ligation is hydrolytic deactivation of 2',3'-cyclophosphate end groups. The ligation reaction is highly chiroselective; it is slower by at least two orders of magnitude when one of the (D)-ribopyranosyl units of a homochiral (D)-tetramer-2',3'-cyclophosphate is replaced by a corresponding (L)-unit, except when the (L)-unit is at the 4' end of the tetramer and carries a purine, when the oligomerization rate can be approximately 10% of that shown for a homochiral isomer. The oligomerization of homochiral tetramers is not, or only weakly, inhibited by the presence of the non-oligomerizing diastereomers. CONCLUSIONS: Available data on the chiroselective self-directed oligomerization of tetramer-2',3'-cyclophosphates allow us to extrapolate that sets of tetramers with different but mutually fitting base sequences can be expected to co-oligomerize stochastically and generate sequence libraries consisting of predominantly homochiral (D)- and (L)-oligomers, starting from the racemic mixture of tetramers containing all possible diastereomers. Such a capability of an oligonucleotide system deserves special attention in the context of the problem of the origin of biomolecular homochirality: breaking molecular mirror symmetry by de-racemization is an intrinsic property of such a system whenever the constitutional complexity of the products of co-oligomerization exceeds a critical level.

Biopolymers↗
PubMed1996

Watson-Crick base-pairing properties of bicyclo-DNA.

A series of sequences of the DNA analog bicyclo-DNA, 6-12 nucleotides in length and containing all four natural nucleobases, were prepared and their Watson-Crick pairing properties with complementary RNA and DNA, as well as in its own series, were analyzed by UV-melting curves and CD-spectroscopy. The results can be summarized as follows: bicyclo-DNA forms stable Watson-Crick duplexes with complementary RNA and DNA, the duplexes with RNA generally being more stable than those with DNA. Pyrimidine-rich bicyclo-DNA sequences form duplexes of equal or slightly increased stability with DNA or RNA, whereas purine-rich sequences show decreased affinity to complementary DNA and RNA when compared with wild-type (DNA-DNA, DNA-RNA) duplexes. In its own system, bicyclo-DNA prefers antiparallel strand alignment and strongly discriminates for base mismatches. Duplexes are always inferior in stability compared with the natural ones. A detailed analysis of the thermodynamic properties was performed with the sequence 5'-GGATGGGAG-3'x 5'-CTCCCATCC-3' in both backbone systems. Comparison of the pairing enthalpy and entropy terms shows an enthalpic advantage for DNA association (delta deltaH = -18 kcal x (mol)-1)) and an entropic advantage for bicyclo-DNA association (delta deltaS = 49 cal x K(-1) x mol(-1), leading to a delta deltaG 25 degrees C of -3.4 kcal x mol(-1) in favor of the natural duplex. The salt dependence of Tm for this sequence is more pronounced in the case of bicyclo-DNA due to increased counter ion screening from the solvent. Furthermore bicyclo-DNA sequences are more stable towards snake venom phosphodiesterase by a factor of 10-20, and show increased stability in fetal calf serum by a factor of 8 compared with DNA.

Base Composition↗
PubMed1996

Bicyclo-DNA: a Hoogsteen-selective pairing system.

BACKGROUND: The natural nucleic acids (DNA and RNA) can adopt a variety of structures besides the antiparallel double helix described by Watson and Crick, depending on base sequence and solvent conditions. Specifically base-paired DNA structures with regular backbone units include left-handed and parallel duplexes and triple and quadruple helical arrangements. Given the base-pairing pattern of the natural bases, preferences for how single strands associate are determined by the structure and flexibility of the sugar-phosphate backbone. We set out to determine the role of the backbone in complex formation by designing DNA analogs with well defined modifications in backbone structure. RESULTS: We recently developed a DNA analog (bicyclo-DNA) in which one (gamma) of the six torsion angles (alpha-zeta) describing the DNA-backbone conformation is fixed in an orientation that deviates from that observed in B-DNA duplexes by about + 100 degrees , a shift from the synclinal to the antiperiplanar range. Upon duplex formation between homopurine and homopyrimidine sequences, this analog preferentially selects the Hoogsteen and reversed Hoogsteen mode, forming A-T and G-C+ base pairs. Base-pair formation is highly selective, but degeneracy is observed with respect to strand orientation in the duplex. CONCLUSIONS: The flexibility and orientation of the DNA backbone can influence the preferences of the natural bases for base-pairing modes, and can alter the relative stability of duplexes and triplexes.

Adenine↗