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Biomedical subjects

R Mayer

Publications and source records attributed to R Mayer.

At least 37 records · Page 2Linked to original sources
PubMed2000

Optimized synthesis of phosphorothioate oligodeoxyribonucleotides substituted with a 5'-protected thiol function and a 3'-amino group.

A new deprotection procedure enables a medium scale preparation of phosphodiester and phosphor-othioate oligonucleotides substituted with a protected thiol function at their 5'-ends and an amino group at their 3'-ends in good yield (up to 72 OD units/micromol for a 19mer phosphorothioate). Syntheses of 3'-amino-substituted oligonucleotides were carried out on a modified support. A linker containing the thioacetyl moiety was manually coupled in two steps by first adding its phosphor-amidite derivative in the presence of tetrazole followed by either oxidation or sulfurization to afford the bis-derivatized oligonucleotide bound to the support. Deprotection was achieved by treating the fully protected oligonucleotide with a mixture of 2,2'-dithiodipyridine and concentrated aqueous ammonia in the presence of phenol and methanol. This proced-ure enables (i) cleavage of the oligonucleotide from the support, releasing the oligonucleotide with a free amino group at its 3'-end, (ii) deprotection of the phosphate groups and the amino functions of the nucleic bases, as well as (iii) transformation of the 5'-terminal S -acetyl function into a dithiopyridyl group. The bis-derivatized phosphorothioate oligomer was further substituted through a two-step procedure: first, the 3'-amino group was reacted with fluorescein isothiocyanate to yield a fluoresceinylated oligo-nucleotide; the 5'-dithio-pyridyl group was then -quantitatively reduced to give a free thiol group which was then substituted by reaction with an N alpha-bromoacetyl derivative of a signal peptide containing a KDEL sequence to afford a fluoresceinylated peptide-oligonucleotide conjugate.

Amides↗
PubMed2000

Transition of nitro musks and polycyclic musks into human milk.

Synthetic musks are widely used in various consumer products. The identification of nitro musks in human milk in the early 1990s in connection with evidence for cancerogenicity in animal experiments have caused public concern. However, the validity of previously reported quantitative data has been questioned. Polycylic musks have hardly been investigated so far. The present study aimed at providing accurate current data on the occurrence of nitro and polycyclic musks in human milk. Samples from 40 healthy breast feeding mothers were analysed under carefully controlled conditions avoiding secondary contamination. As in earlier studies, among the nitro compounds musk xylene and ketone were the most frequently detected substances. However, much lower concentrations (roughly by a factor of 10) were found (musk xylene: median 6.1 ng/kg fat). Among the polycylic musks HHCB was found in most samples (median 64 ng/kg fat). Scientific knowledge on possible routes of exposure and health risk aspects is summarized and discussed.

Adult↗
PubMed2000

Radiotherapy as adjunct to surgery for malignant carotid body paragangliomas presenting with lymph node metastases.

PURPOSE: Three cases of malignant carotid body paragangliomas with nodal metastases are reported. PATIENTS AND METHODS: Between 1985 and 1994, 3 female patients (51 to 65 years of age) were referred for postoperative radiotherapy after complete (2) or incomplete (1) surgical excision of a malignant carotid paraganglioma (Shamblin III). Preoperative angiographic embolization of the tumor-supplying arteries was performed in all cases. In 2 patients resection of the internal carotid artery and reconstruction by saphenous vein graft was necessary. Continuous course radiotherapy of the tumor bed (50 to 56 Gy/2 Gy) and regional lymph nodes (50 Gy) using photon beams was delivered in 2 patients. The third patient having had incomplete resection cancelled radiotherapy after 4 Gy. RESULTS: Within an observation time of 110 and 119 months no evidence of recurrence was obtained in both patients irradiated postoperatively. The third patient died of progressive disease. Twelve months after the withdrawn irradiation she presented with a tumor progression into the brain and an ulcerated mass on the right side of the neck and was irradiated consecutively for palliation (Figures 1a to 1f). In none of the patients severe acute or late radiation-induced complications were observed. CONCLUSION: In patients with malignant paraganglioma moderate dose postoperative radiotherapy of the tumor bed and regional lymph nodes is well tolerated. It seems to be effective to prolong local control after surgery, to eradicate microscopic lymphatic disease and eventually to postpone further spreading.

Aged↗
PubMed2000

Spacer length dependence on the efficiency of dimeric anionic peptides in gene transfer by glycosylated polylysine/plasmid complexes.

Amphiphilic anionic peptides have been used to enhance the efficiency of transfection by helping plasmids to escape from endosomes to the cytosol. It has been shown that efficiency of an eicosamers containing five glutamyl residues (E5), can be considerably enhanced either by transforming it into a dimer or by adding a tripeptide WYG in a C-terminal position (E5WYG). The dimerization of the peptide E5WYG leads to a more efficient tool when the dimerization device includes the tripeptide WYG unit and a longer spacer arm made of Gly-betaAla-betaAla residues, but to a 10-fold less efficient tool when the dimerization device includes a shorter spacer, a glycyl residue. Both dimers are taken up by the cells to a similar extent. Both dimers seem to be surrounded similarly as far as the environmental pH is concerned. In contrast, we found a correlation between the propensity of the peptides to adopt a helical structure at neutral pH and the gene transfer efficiency.

Amino Acid Sequence↗
PubMed2000

Use of danaparoid sodium (Orgaran) as an alternative to heparin sodium during cardiopulmonary bypass: a clinical evaluation of six cases.

Heparin-induced thrombocytopenia (HIT) has become more prevalent in today's cardiac setting and has resulted in the need for alternative anticoagulant therapies. Danaparoid sodium, one alternative to heparin, has been used in six cardiopulmonary bypass procedures in this hospital. This clinical experience has resulted in the progressive refinement of a protocol for the 'safe' clinical use of danaparoid sodium. Although there were six positive outcomes with the use of danaparoid sodium, alternatives must be explored in order to find the optimal anticoagulant for the treatment of HIT.

Adult↗
PubMed2000

Immigration and health: the Italian National Focal Point experience.

This report is a description of the situation of migrant populations in Italy. It was written by a committed team of experts from public institutions, non-governmental organisations (NGO) and volunteer associations that for three years have been part of the Italian National Focal Point (NFP) within the European Project "AIDS & Mobility", which is being co-ordinated by the Netherlands Institute for Health Promotion and Disease Prevention (the Netherlands) and financed by the European Commission DG/V. This year the Italian National Focal Point, co-ordinated by the Telefono Verde AIDS of the Istituto Superiore di Sanità, has produced a second report (the first one was published in 1998) on health issues related to migrant populations. Besides providing an updated picture on the presence of foreigners in Italy, such report illustrates the present legislative situation within the sanitary area and some interventions regarding prevention, treatment and rehabilitation provided by each structure in the Italian NFP to foreign citizens. The initiatives carried out during the year 1999 by public institutions, NGO and volunteer associations are also reported in order to detect the psycho-social-sanitary needs of immigrants and target prevention programmes to their particular and specific needs.

Acquired Immunodeficiency Syndrome↗
PubMed2000

[Teaching the history of medicine in Switzerland, past and present].

This article covers the teaching of the history of medicine at the Swiss universities of Basel, Bern, Geneva, Lausanne and Zurich and from its initially modest proportions until it reached the standard it achieved in the Twentieth Century. Brief biographies are provided of the principal protagonists from earliest times to the current holders of the chairs of the history of medicine. It concludes with a brief account of the current structure and organization of the various institutes, together with their fields of research and education.

Education, Medical↗
PubMed1999

The nuclear export signal-dependent localization of oligonucleopeptides enhances the inhibition of the protein expression from a gene transcribed in cytosol.

Upon endocytosis, most oligodeoxynucleotides (ODNs) accumulate in vesicular compartments; a tiny number of them cross the vesicle membrane, reach the cytosol and by passive diffusion enter the nucleus where they are entrapped. So far, the compartment in which an antisense ODN interacts with its mRNA target has not been precisely characterized. In an attempt to answer this question, ODN-peptides were designed with the aim of maintaining them in the cytosol. This has been achieved by a short peptide sequence called the nuclear export signal (NES). Upon microinjection, ODN-NES peptide conjugates were efficiently and rapidly exported from the nucleus to the cytosol whereas ODN-peptides containing an inactive NES were found to be located in the nucleus. The inhibitory activity of antisense ODN was tested in a system allowing the specific transcription of a luciferase reporter gene in the cytosol. Antisense propynylated ODN-NES peptide conjugates, directed against the luciferase gene, efficiently inhibited (75%) the cytosolic expression of luciferase whereas at the same concentration the peptide-free propynylated ODN or the propynylated ODN-peptides containing an inactive NES were nearly inactive.

Animals↗
PubMed1999

Colorectal cancer in inflammatory bowel disease: a continuing problem.

PURPOSE: Because of the increased risk of colorectal cancer in patients with inflammatory bowel disease, surveillance colonoscopy with mucosal biopsies for dysplasia has been advocated to prevent malignancy or permit its early diagnosis. However, despite adoption of colonoscopic surveillance programs by many clinicians, we have noted a pattern of continued referrals for inflammatory bowel disease-associated malignancy. This study was undertaken in an effort to characterize this cohort of patients. METHODS: We reviewed the operative records of a large metropolitan colorectal practice from 1983 to 1995. During this period 40 large-bowel resections were performed for patients with documented inflammatory bowel disease and concomitant carcinoma. A retrospective analysis was conducted with emphasis on clinical presentation, pathologic description, and most recent follow-up. RESULTS: Mean age at the time of diagnosis of cancer was 48 years with an average inflammatory bowel disease duration of 19 years. Seven patients had documented inflammatory bowel disease for less than eight years before their cancer diagnosis. Carcinomas were identified preoperatively by colonoscopy in 92 percent of patients. One-half of these patients had the colonoscopy to investigate a recent change in inflammatory bowel disease symptoms or signs, whereas the other half underwent endoscopy as routine surveillance. For the remaining 8 percent of patients, operated on for worsening symptoms, the carcinoma was detected in the pathological specimen only. The majority of patients (68 percent) did not have a preoperative diagnosis of dysplasia. Twenty-five percent of tumors were mucinous, 20 percent were multicentric, and 70 percent were located distal to the splenic flexure. Among the seven patients who died, four had pancolitis, six had a recent worsening of symptoms, and all had cancer involving the rectum. CONCLUSION: Cancer occurs at a younger age in patients with long-standing inflammatory bowel disease. The tumors are often mucinous, multiple, and located in the left colon. Despite increasing acceptance of surveillance colonoscopy as a recommended strategy in cancer prevention, almost one-half of the patients in this study had their cancer diagnosed because increased colitis symptoms led to colonoscopic examination. Eighteen percent of patients developed cancer with less than an eight-year history of inflammatory bowel disease. These data call into question the effectiveness of dysplasia surveillance as a population-based strategy to decrease the colorectal cancer mortality in inflammatory bowel disease patients.

Adult↗
PubMed1999

Radiotherapy for invasive thymoma and thymic carcinoma. Clinicopathological review.

PURPOSE: This study reports clinicopathological features and outcome of thymic tumors. Twenty-seven patients with invasive thymoma and 6 patients with thymic carcinoma who had received radiotherapy either primary or postoperatively were analyzed retrospectively. PATIENTS AND METHODS: All 33 patients were irradiated with a mean dose of 50 Gy after complete resection (16 patients), partial resection (9 patients) or biopsy (8 patients). Staging was done according to the Masaoka classification; there were 12 Stage II, 12 Stage III and 9 Stage IV patients. RESULTS: In patients with invasive thymoma Stage II to IV (median follow-up 54.4 months) Kaplan-Meier estimates of overall survival (OS), disease-specific (DSS) and disease-free survival (DFS) at 5 years were 63.7% (95% confidence interval [CI], 42 to 84%), 88.3% (CI, 75 to 100%) and 77.4% (CI, 58 to 95%), respectively. Among the prognostic factors tested, such as age, myasthenia gravis, completeness of surgery and histologic subclassification, total radiation dose, and Masaoka Stage, the latter was the only significant predictor of improved survival (p = 0.04). Considering local control, radiation dose was a significant prognostic factor (p = 0.0006). In patients with thymic carcinoma (median follow-up 43.4 months) 5-year DSS, and DFS were 22.2% (CI, 0 to 60%) and 16.7% (CI, 0 to 46%), respectively. Thymoma as compared to thymic carcinoma had a statistically significant better DSS (p = 0.007) and DFS (p = 0.0007). CONCLUSION: Postoperative radiotherapy with sufficient doses plays an important role as adjuvant treatment in complete or incomplete resected invasive Stage II to III thymoma. In unresectable thymoma Stage III to IV as well as in thymic carcinoma a multimodality approach should be considered to improve survival.

Actuarial Analysis↗
PubMed1999

[The effect of low droperidol dosages on postoperative anxiety, internal tension, general mood and PONV].

BACKGROUND: Droperidol even in low doses such as 0.5 mg to 1.25 mg can increase postoperative anxiety and state of tension. The aim of this study was to determine whether these side effects occur frequently following low-dose droperidol and to see whether these are dose related. METHODS: 184 female in- and outpatients ASA grade 1 and 2 undergoing gynaecological laparoscopy were recruited to this prospective, double-blind study. General anaesthesia was standardized (induction with thiopentone, fentanyl 2 micrograms/kg and vecuronium 0.1 mg/kg, tracheal intubation, maintainance with enflurane in N2O/O2). Patients were randomly allocated to receive saline (n = 45), 0.625 mg (n = 46), 1.25 mg (n = 47) or 2.5 mg (n = 46) droperidol i.v. 10 minutes before the end of surgery. 1,3,6, and 24 hours postoperatively, the patients' anxiety, state of tension and overall mood was evaluated using two psychological questionnaires which had been tested for the perioperative period (Erlanger anxiety and tension-scale/BSKE-EWL-test). Sedation was evaluated by the staff of the recovery room. In addition, postoperative nausea and vomiting (PONV) was assessed using a 100 mm visual analogue scale and by counting the episodes of retching or vomiting. PONV was then rated over the whole observation period as none, mild, moderate or severe using a fixed scoring algorithm. Statistical analysis was performed using the ANOVA and the chi2-test. RESULTS: The patients did not differ with regard to biometric data, duration of surgery and anaesthesia. The postoperative scores for anxiety, state of tension and overall mood were not different between the groups at any observation time (Fig. 1: anxiety and tension: P = 0.5687; figure 2: overall mood: P = 0.0647). Quality of sleep in the first night after surgery was the same in all groups (Table 2 and 3). Sedation was not significantly different (Table 4; P = 0.0704). Furthermore, duration of stay in the recovery room did not differ (P = 0.4353). On the other hand, three patients from the 2.5 mg droperidol group had to stay unexpectedly on the ward overnight, because they had been too much sedated to be discharged at home. This was not the case with any patient from the other groups. Compared to placebo, PONV over the whole 24 h observation period was significantly reduced by droperidol (Fig. 3; P = 0.0338): completely free from PONV: placebo: 41.3%, 0.625 mg droperidol: 67.4%, 1.25 mg droperidol: 53.2%, 2.5 mg droperidol: 71.7%. Also the severity of PONV was reduced. CONCLUSION: In gynaecological laparoscopy under general anaesthesia with tracheal intubation, we recommend droperidol 0.625 mg in the prevention of PONV, as it reduces PONV as well as 2.5 mg with no severe sedation in this dosage. Psychological side effects did not occur more frequently after droperidol compared to placebo in any of the investigated dosages.

Adjuvants, Anesthesia↗
PubMed1999

Adjuvant radiotherapy in male breast cancer.

PURPOSE: To determine retrospectively the outcome of postoperative radiation therapy in male breast cancer. Local/distant control was assessed with attention to age, stage, lymph node involvement, histopathological differentiation and hormone receptor status. MATERIALS AND METHODS: Thirty-one male patients were irradiated postoperatively at the chest wall (mean dose 50 Gy) and 16 patients received radiation to regional lymph nodes. Tumour distribution by stage was: stage 0 (9.7%), stage I (22.6%), stage II (32.2%) and stage III (35.5%). Nine patients were subjected to additional hormone therapy and three patients to chemotherapy. RESULTS: Local control was achieved in 30/31 (96.8%) patients. Kaplan-Meier estimates of overall survival (OS), disease specific (DSS) and disease free survival (DFS) at 5 years were 77% (95% confidence interval (CI), 0.61-0.93), 84% (CI, 0.69-0.98) and 73% (CI, 0.57-0.91), respectively. Five-year DFS for stage 0 + I, II and III was 100, 56.3 and 67.3%, respectively. Favourable results were observed in patients with negative axillary nodes with 5-year OS/DFS of 90.9% (CI, 0.74-1.0). For lymph node positive patients DFS was 71% (CI, 0.4-1.0). Patients who presented lymph node metastases with extracapsular extension the 5-year OS was 80% (CI, 0.45-1.00), but the DFS was 0%. Stage of disease, lymph node involvement and histological differentiation were found to have statistically significant influence on DFS, but not on OS. CONCLUSION: Application of postoperative radiotherapy approved in females resulted in one local relapse in our study population. Other treatment modalities (hormone therapy/chemotherapy) should continue to be considered a necessary treatment option for appropriately selected patients.

Adult↗
PubMed1999

Calycopterones and calyflorenones, novel biflavonoids from Calycopteris floribunda.

Neocalycopterone (1) and its methyl ether (2), along with two new biflavonoids, calyflorenones A (3) and B (4), were isolated from dried leaves of Calycopteris floribunda (Combretaceae). Structures 1-4 were investigated by spectroscopic methods. The relative stereochemistry of 3 and 4 was deduced through NOE and ROESY experiments, comparative CD and optical rotation evaluations. Cytotoxicity test results of 1 and 2 are reported. The monoflavonoid penduletin was isolated as a minor component from C. floribunda for the first time.

Antineoplastic Agents, Phytogenic↗
PubMed1999

Glycotargeting: influence of the sugar moiety on both the uptake and the intracellular trafficking of nucleic acid carried by glycosylated polymers.

Nucleic acids (plasmids as well as oligonucleotides) used to specifically express or modulate the expression of a gene, must reach the cytosol and/or the nucleus. Several systems have been developed to increase their uptake and their efficiency. Glycosylated polylysines have been shown to specifically help nucleic acids to be taken up in cells expressing a given cell surface membrane lectin. However, it appeared that the efficiency of the imported nucleic acid was not directly related to the extent of the uptake. Indeed, some glycosylated polylysines bearing sugar moities which are poor ligands of the cell surface lectins of a given cell were found to be more efficient than those bearing better sugar ligands. The interpretation of this paradoxal result is discussed with regards to the nature of the compartment allowing the nucleic acid to cross the membrane and to be delivered in the cytosol on the one hand, and to the presence of intracellular lectins on the other hand.

Animals↗
PubMed1999

Contrast-enhanced spiral CT of the head and neck: comparison of contrast material injection rates.

BACKGROUND AND PURPOSE: Contrast-enhanced spiral CT studies of the head and neck are performed frequently using contrast material volumes of approximately 30 g iodine and a scan delay of 30-45 seconds. Because little is known about the effects of contrast material injection rates on tissue enhancement, this was prospectively investigated in our study. METHODS: Ninety-seven patients underwent spiral CT of the head and neck. Each patient was assigned randomly to one of four groups who received 100 mL of nonionic contrast material (300 mg I/mL) at different monophasic injection flow rates with 1.5, 2, 3, and 4 mL/s. Scanning started after a constant delay of 35 seconds. The attenuation of the carotid artery, jugular vein, and sternocleidomastoid muscle was measured over time and the attenuation of the submandibular and thyroid gland was evaluated. Vascular attenuation of at least 150 HU was considered to be sufficient. RESULTS: The mean scan time was 33+/-5 seconds. The study, using an injection rate of 2 mL/s, showed the longest time of sufficient overall (arterial and venous) vessel attenuation (27+/-4 seconds, P< or =.008). The injection flow rate did not influence significantly muscular attenuation (mean enhancement during scan time: 9+/-7 HU). The 1.5 mL/s protocol showed the lowest attenuation values of the submandibular gland (81+/-12 HU) and the highest attenuation values of the thyroid gland (164+/-22 HU), but the attenuation of the thyroid gland was not statistically different from that revealed by the 2 mL/s protocol. CONCLUSION: Using 100 mL of intravenous contrast material with 300 mg I/mL for spiral CT studies of the entire head and neck, the optimal injection flow is 2 mL/s, whereas lower flow rates resulted in insufficient venous enhancement.

Adult↗
PubMed1998

A Plasmodium falciparum aminopeptidase gene belonging to the M1 family of zinc-metallopeptidases is expressed in erythrocytic stages.

A new single copy gene has been isolated from Plasmodium falciparum, by immunoscreening a genomic DNA expression library. The gene appears devoid of introns, displays the classical A + T richness and codon usage of P. falciparum genes, and is transcribed into a 4 kb mRNA in erythrocytic stages. The deduced amino acid sequence corresponds to a 1056 residue protein (122 kDa) containing the canonical HExxHx18E signature of zinc-metallopeptidase active sites of the M1 family at position 467-490, a downstream conserved tyrosine residue involved in catalysis in position 551, and the GAMEN conserved motif characteristic of aminopeptidases in the M1 family, at position 431-435. The greatest similarities were found with aminopeptidases N of Escherichia coli and Haemophilius influenza (more than 80% identical residues in the canonical signature of the active site) but significant similarities centred on the active site region exist with all other members of the M1 family such as other prokaryotic aminopeptidases, eukaryotic aminopeptidases A and N and leukotriene A4 hydrolases (40-50% identical residues in the canonical signature of the active site). A polyclonal serum raised to a synthetic peptide deduced from the gene labelled schizont proteins of 96 and 68 kDa purified to homogeneity and both displaying aminopeptidase activity, as well as cytoplasmic structures in schizont stages.

Amino Acid Sequence↗