ABSTRACT
The oral cavity is densely populated with microorganisms. As a result, intraoral surgical sites are prone to contamination by pathogens, potentially triggering surgical site infections (SSIs). Prophylactic antibiotics have proven beneficial in reducing the rate of SSIs. However, no consensus has been reached regarding the most effective regimen. The purpose of this study was to investigate two different antibiotic regimens - single-dose and prolonged antibiotic prophylaxis - regarding the rate and severity of postoperative SSIs in patients undergoing orthognathic surgery. Data were analysed retrospectively. Patients who underwent bilateral sagittal split ramus osteotomy or bimaxillary surgery in the study department in 2017 were screened for eligibility. Ninety-nine patients were included in the study and were divided into two groups. The prolonged-antibiotic prophylaxis group (PAP; n = 49) received a 5-day antibiotic prophylaxis regimen, while the single-dose antibiotic prophylaxis group (SDAP; n = 50) received single-dose antibiotic prophylaxis. The groups were assessed for the rate and severity of SSIs following orthognathic surgery. Five patients (10.2%) in the PAP group and seven (14%) in the SDAP group developed infections; no statistically significant difference in the occurrence of SSIs was found (P = 0.380). Single-dose antibiotic prophylaxis is as effective as a 5-day antibiotic prophylaxis regimen in preventing SSIs in orthognathic surgery and is a suitable antibiotic prophylaxis option when considering the risk of antibiotic resistance.
Subject(s)
Orthognathic Surgery , Surgical Wound Infection , Humans , Surgical Wound Infection/epidemiology , Antibiotic Prophylaxis , Retrospective Studies , Anti-Bacterial Agents/therapeutic useABSTRACT
The amount of blood loss determined in orthognathic surgery differs greatly among studies. This can be attributed to the inhomogeneity in study cohorts analysed, but may also be a result of the varying methodologies used for blood loss determination. However, this has yet to be explored. Thus, the aim of this study was to investigate the extent to which the formula and time point used to measure blood loss affect the blood loss volume, determined in a homogeneous cohort undergoing bimaxillary surgery. Blood loss was calculated at 24 and 48 hours postoperatively using the haemoglobin balance method and the formula of Hurle et al. The estimated total blood volume was established based on the formulae of Nadler et al. and Choi et al. Differences in blood loss volume with respect to time point and formula were analysed and compared. Fifty-four patients were included in the final analysis. Statistically significant differences in blood loss were observed: a significant increase in the blood loss volume from 24 hours to 48 hours postoperatively was detected. When comparing the formulae used, blood loss differed significantly at 24 hours after surgery; however no such difference resulted at 48 hours postoperatively. These findings imply that the time point of measuring blood loss is highly relevant, whereas the formulae applied seem to have less of an impact on the blood loss volumes calculated.
Subject(s)
Orthognathic Surgery , Orthognathic Surgical Procedures , Blood Loss, Surgical , Humans , Orthognathic Surgical Procedures/methodsABSTRACT
Patient dissatisfaction with labial appearance in the adult cleft lip is frequently linked to poor upper lip projection. Other areas of concern include asymmetry and impaired upper lip height. Different surgical techniques are available to address volumetric deficiencies, according to extent and localization. However, data comparing outcomes in these different areas are limited. The main aim of this study was to assess the relative gains in upper lip projection. An evaluation of upper vermilion height and symmetry was also performed. Thirty-seven consecutive patients treated by a single surgeon had their pre- and postoperative results measured using standardized photographs; these were analysed using subjective and objective outcome measures. Seven examiners evaluated anonymized pre- and postoperative side and front views for subjective evaluation. The objective analysis was performed using Adobe Photoshop. Fifteen lip revisions, four Abbe flaps, 12 dermal grafts, and six PermaLip implants were performed. In bilateral cleft lip and palate patients, Abbe flaps showed the most significant improvement in labial projection, followed by PermaLip implants and dermal grafts. In unilateral cleft lip and palate patients, PermaLip implants best addressed impaired lip projection, followed by dermal grafts. Overall, functional lip revisions showed excellent outcomes for upper lip symmetry; however, only minor changes in labial projection were found.
Subject(s)
Cleft Lip/surgery , Plastic Surgery Procedures , Adult , Humans , Mouth Mucosa , Reoperation , Skin Transplantation , Surgical FlapsABSTRACT
Orbital tumours, located in the medial extraconal and intraconal compartment of the orbit, represent a challenge, with regard to surgical exposure. In the present paper removal of a cavernous haemangioma, located in the medial intraconal compartment was accomplished by combining lateral orbitotomy, midfacial degloving and LeFort-I osteotomy. Resection of the tumour could be performed under direct vision. Surgical exposure and removal of the lesion were obtained, without causing damage to surrounding tissues. Aesthetical results and postoperative eye function proved to be highly satisfactorily. With regard to limitations, concerning the combination of these methods, extended surgery duration and invasiveness have to be named. According to the technical feasibility and postoperative results, this new surgical approach represents a reliable and fully viable alternative method for the removal of medial orbital tumours.
Subject(s)
Craniotomy/methods , Hemangioma, Cavernous/diagnostic imaging , Hemangioma, Cavernous/surgery , Orbital Neoplasms/diagnostic imaging , Orbital Neoplasms/surgery , Osteotomy, Le Fort , Female , Humans , Magnetic Resonance Imaging , Middle AgedABSTRACT
BACKGROUND AND AIM: Removal of polyps during colonoscopy effectively prevents the development of colorectal cancer. So far, snare resection with high frequency current with or without prior submucosal saline injection is the method of choice. The aim of this study was to evaluate the feasibility, safety, and outcome of cold snare resection during routine endoscopy. METHODS: In this prospective study, 522 patients undergoing outpatient colonoscopy were included. Cold snare resection for diminutive (<â6âmm), small (6â-â9âmm), and larger polyps (>â9â-â15âmm) was performed using a dedicated cold snare device (Exacto ® ) without prior submucosal injection. Outcome parameters included bleeding rate, perforation rate, procedure time, histologic evaluation of polyp margins, and success rates. The data were compared to a group of patients undergoing hot snare resection. RESULTS: Overall, 1233 polyps were removed using cold snare resection with an overall success rate of 99.4â%. All failures of cold snare resection occurred in the cecum (8/82, failure rate 9.8â%). In the remaining colon, the success rate was 100â%. Immediate post-polypectomy bleeding occurred in 0.49â% of all patients and was most frequently seen in polyps larger than 9âmm. The procedure time was significantly shorter using cold snare resection compared with hot snare resection (27.6âmin vs. 35.7âmin, P â<â0.01). CONCLUSION: Cold snare resection can be performed safely in outpatients for removal of small polyps in screening colonoscopy. It does not require prior saline injection and reduces procedure time without an increased risk of bleeding.
ABSTRACT
BACKGROUND: Providing end of life care for dying patients and those with life-threatening diseases is one of the core competences of physician. During the course of training all physicians should develop a sharpened perception of symptoms and acquire competence in the relief and therapy of pain. OBJECTIVES: The Hospital of Saint John of God in Vienna, Austria, provides an educational program for residents concerning end of life care. Treatment of pain is one of the major topics. A questionnaire (PKT) was designed in order to evaluate the efficiency of this program. MATERIAL AND METHODS: The Japanese PEACE questionnaire for assessing palliative knowledge of physicians was translated into German and the items checking specific self-efficacy expectations in palliative care in the Bonn palliative knowledge test (Bonner Palliativwissenstests) were transformed into physician duties. The new combination of 52 items was validated by testing groups of physicians with different levels of palliative education and experience. RESULTS: The 37 physicians who had received palliative education scored better in the knowledge section than the 46 without palliative education: 21 vs. 16 correct answers out of 28 (p < 0.001). In these two groups we also found a differences in self-efficacy expectations in palliative care: 46 vs. 35 points out of 54 (p < 0.001). Having worked in a specialized palliative setting (n = 33) was associated with higher scores in palliative knowledge 23 vs. 16 points (p < 0.001) as well as in self-efficacy expectations 47 vs. 35 (p < 0.001). CONCLUSION: The PKT is a German questionnaire that was validated to assess the efficiency of palliative education for physicians.
Subject(s)
Clinical Competence , Education, Medical , Educational Measurement , Palliative Care/psychology , Physician's Role/psychology , Self Efficacy , Surveys and Questionnaires , Austria , Cross-Cultural Comparison , Curriculum , Humans , Psychometrics , Reproducibility of Results , TranslatingABSTRACT
Linac4, a 160 MeV normal-conducting H(-) linear accelerator, is the first step in the upgrade of the beam intensity available from the LHC proton injectors at CERN. The Linac4 Low Energy Beam Transport (LEBT) line from the pulsed 2 MHz RF driven ion source, to the 352 MHz RFQ (Radiofrequency Quadrupole) has been built and installed at a test stand, and has been used to transport and match to the RFQ a pulsed 14 mA H(-) beam at 45 keV. A temporary slit-and-grid emittance measurement system has been put in place to characterize the beam delivered to the RFQ. In this paper a description of the LEBT and its beam diagnostics is given, and the results of beam emittance measurements and beam transmission measurements through the RFQ are compared with the expectation from simulations.
ABSTRACT
Modern intensive care is responsible both for curative interventions in critical health situations and palliative terminal care for the dying ICU patient. By applying an integrated ethics approach, this article examines organizational and cultural factors shaping good terminal care in the ICU. Starting with a reflection on what it means to be human, ethical goals for care of the dying are formulated. Among them, the article focuses on practices ensuring a dignified dying process, on the structured engagement of patients' families, on respecting cultural and spiritual values, and on a clinical pathway for terminal care as an institutional framework. In conclusion, it becomes evident that good terminal care in the ICU not only depends on ethically sound decisions on withholding or withdrawing medical interventions but also on organizational and cultural aspects which must be acknowledged and shaped.
Subject(s)
Ethics, Medical , Intensive Care Units/ethics , Palliative Care/ethics , Terminal Care/ethics , Critical Pathways/ethics , Cultural Competency , Germany , Humans , Patient Care Planning , Professional-Family Relations , Right to Die/ethics , SpiritualityABSTRACT
Surgically assisted rapid maxillary expansion (SARME) is commonly used to correct maxillary transverse deficiency. The aim of this study was to analyse the need for intraoperative liberation of the nasal septum during the procedure. SARME was performed in 25 patients by combining a lateral osteotomy with an inter-radicular maxillary osteotomy. The deviation of the nasal septum after SARME was evaluated by comparing measurements between radiologically defined landmarks on pre- and postoperative computed tomographic images. Two defined angles (angle I, between crista galli-symphysis mandibulae and crista galli-septum nasi; angle II, between maxillary plane and septum nasi) were measured based on four representative planes and septal movement was analysed. The mean changes in angles I (0.03° ± 0.78°) and II (0.25° ± 1.04°) did not differ significantly from zero (p=0.87 and p=0.24, respectively). Observed variations and displacements were considered to be acceptable because they were insignificant in every respect. Intranasal airway function was also examined pre- and postoperatively to evaluate any loss of ventilation. The described surgical technique is a successful method of maxillary segment distraction. The authors found no compelling reason to release the nasal septum in the context of SARME.
Subject(s)
Malocclusion/surgery , Maxillary Osteotomy/methods , Nasal Septum/surgery , Orthodontics, Corrective/methods , Palatal Expansion Technique , Adolescent , Adult , Airway Remodeling , Female , Humans , Male , Maxillary Osteotomy/instrumentation , Orthodontics, Corrective/instrumentation , Orthognathic Surgical Procedures/instrumentation , Orthognathic Surgical Procedures/methods , Palatal Expansion Technique/instrumentation , Retrospective Studies , Time FactorsABSTRACT
The MedAustron Ion therapy center will be constructed in Wiener Neustadt (Austria) in the vicinity of Vienna. Its accelerator complex consists of four ion sources, a linear accelerator, a synchrotron, and a beam delivery system to the three medical treatment rooms and to the research irradiation room. The ion sources shall deliver beams of H(3)(1+), C(4+), and light ions with utmost reliability and stability. This paper describes the features of the ion sources presently planned for the MedAustron facility, such as ion source main parameters, gas injection, temperature control, and cooling systems. A dedicated beam diagnostics technique is proposed in order to characterize electron cyclotron resonance (ECR) ion beams; in the first drift region after the ion source, a fraction of the mixed beam is selected via moveable aperture. With standard beam diagnostics, we then aim to produce position-dependant observables such as ion-current density, beam energy distribution, and emittance for each charge states to be compared to simulations of ECR e-heating, plasma simulation, beam formation, and transport.
Subject(s)
Radiotherapy/instrumentation , Carbon , Light , Mechanical Phenomena , Models, Theoretical , Protons , Radiotherapy/methods , Reproducibility of Results , TemperatureABSTRACT
BACKGROUND: Many decisions in neonatology are complex and demanding. Consequently, the involved persons can expect guidance which is provided to them by specialist organisations of the scientific community. Their documents deal with such substantial questions as how to treat extremely premature newborns and severely ill infants. They also address procedural aspects of the decision-making process; however, they could be made more transparent in this respect. OBJECTIVE: This paper aims to address those factors which may facilitate or hinder the neonatal decision-making process; regarding the legal framework, the countries Germany, Austria, and Switzerland are in the focus of this analysis. Thus, transparency, clarity, and predictability of the decision-making shall be enhanced. RESULTS: The following components of the decision-making process will be addressed: decisional framework factors, decision makers, decision types, decision steps, and decision consequences. Emphasis is placed on a compact visualisation of the process in order to communicate it more easily to younger team members. CONCLUSIONS: Good decision making in neonatology must be context sensitive. General guidelines can be a helpful resource for carefully developing such a process. By taking the factors described in this paper into consideration, this task will be completed more efficiently.
Subject(s)
Decision Making/ethics , Delivery of Health Care/ethics , Ethics, Clinical , Intensive Care Units, Neonatal/ethics , Neonatology/ethics , Physician's Role , EuropeABSTRACT
OBJECTIVE: To identify and gain an understanding of the influenza viruses circulating in wild birds in Australia. DESIGN: A total of 16,303 swabs and 3782 blood samples were collected and analysed for avian influenza (AI) viruses from 16,420 wild birds in Australia between July 2005 and June 2007. Anseriformes and Charadriiformes were primarily targeted. PROCEDURES: Cloacal, oropharyngeal and faecal (environmental) swabs were tested using polymerase chain reaction (PCR) for the AI type A matrix gene. Positive samples underwent virus culture and subtyping. Serum samples were analysed using a blocking enzyme-linked immunosorbent assay for influenza A virus nucleoprotein. RESULTS: No highly pathogenic AI viruses were identified. However, 164 PCR tests were positive for the AI type A matrix gene, 46 of which were identified to subtype. A total of five viruses were isolated, three of which had a corresponding positive PCR and subtype identification (H3N8, H4N6, H7N6). Low pathogenic AI H5 and/or H7 was present in wild birds in New South Wales, Tasmania, Victoria and Western Australia. Antibodies to influenza A were also detected in 15.0% of the birds sampled. CONCLUSIONS: Although low pathogenic AI virus subtypes are currently circulating in Australia, their prevalence is low (1.0% positive PCR). Surveillance activities for AI in wild birds should be continued to provide further epidemiological information about circulating viruses and to identify any changes in subtype prevalence.
Subject(s)
Anseriformes , Bird Diseases/virology , Charadriiformes , Influenza A virus/isolation & purification , Influenza in Birds/virology , Animals , Antibodies, Viral/blood , Australia/epidemiology , Bird Diseases/epidemiology , DNA, Viral/chemistry , DNA, Viral/genetics , Enzyme-Linked Immunosorbent Assay/veterinary , Influenza A virus/genetics , Influenza in Birds/blood , Influenza in Birds/epidemiology , Polymerase Chain Reaction/veterinary , Prevalence , Viral Matrix Proteins/chemistry , Viral Matrix Proteins/geneticsABSTRACT
Because P-glycoprotein expression might be associated with a more aggressive behaviour of colorectal carcinomas (Weinstein et al., Cancer Res, 1991, 51, 2720-2726), we determined the relationship between MDR1 RNA expression of the carcinomas and the survival of the patients. At a median duration of follow-up of 86 months, event-free survival of patients with MDR1 RNA-negative tumours (n = 35) was not significantly different to that of patients with MDR1 RNA positive tumours (n = 67). Among the different tumour stages, event-free survival of the patients was also independent of MDR1 gene expression of the tumours. Thus, these findings do not support the hypothesis that local aggressiveness of P-glycoprotein positive tumour cells translates into worse clinical outcome.
Subject(s)
ATP Binding Cassette Transporter, Subfamily B, Member 1/metabolism , Biomarkers, Tumor/metabolism , Colorectal Neoplasms/metabolism , Neoplasm Proteins/metabolism , ATP Binding Cassette Transporter, Subfamily B, Member 1/genetics , Biomarkers, Tumor/genetics , Colorectal Neoplasms/genetics , Follow-Up Studies , Gene Expression , Genes, MDR , Humans , Neoplasm Proteins/genetics , Prognosis , RNA, Neoplasm/genetics , Survival RateABSTRACT
We examined the efficacy of a group of drugs that stabilize the cell membrane and can potentially prevent cytotoxicity in cultured fetal chick cardiac myocytes exposed to hydrogen peroxide (H2O2). The effects of various membrane-protective agents were determined by analysis of the kinetics of lactic dehydrogenase (LDH) release. The kinetic parameters calculated from the data include a rate constant for release of LDH (kb) and the fraction of total LDH that is released from the cells (CIIMax). The CIIMaxs derived from a range of H2O2 concentrations reveal that the mean toxic concentration of H2O2 is 1.1 mM and that the pattern of toxicity is consistent with the damage being directly proportional to the concentration of the free radicals generated from the H2O2. Maximum nontoxic concentrations of three amphiphilic membrane protective agents had no effect upon cytotoxicity from H2O2. The slightly polar lipophilic agent, Trolox C, a vitamin E derivative, was also without protective effect at a maximum nontoxic concentration. The highly lipophilic agent, probucol, had a small protective effect at 50 microM, the maximum concentration we succeeded in solubilizing in the culture medium. However, the lipophilic 21-aminosteroid U74500, delivered to the cells in an emulsion, markedly reduced cytotoxicity from H2O2. The CII Max was significantly reduced and the protection was concentration dependent over a range of concentrations from 50-400 nmol/ml. Furthermore, the inhibition by U74500 was fully consistent with a mechanism of scavenging of free radicals formed during lipid peroxidation. In support of this hypothesis, a dose of 400 nmoles/ml completely prevented an increase in lipid peroxides due to H2O2 exposure, whereas there was a sixfold increase during exposure to H2O2 in untreated myocytes. Thus, a lipid soluble 21-aminosteroid prevented lipid peroxidation and reduced cardiac myocyte injury during exposure to H2O2, probably by scavenging of free radicals formed during lipid peroxidation in the cell membrane, whereas amphiphilic agents, which probably altered the physicochemical structure of the cell membrane but did not scavenge free radicals, were not protective.
Subject(s)
Antioxidants/pharmacology , Cell Membrane/drug effects , Hydrogen Peroxide/toxicity , Lipids , Pregnatrienes/pharmacology , Solubility , Animals , Cell Death/drug effects , Cells, Cultured , Chick Embryo , Chromans/pharmacology , Diltiazem/pharmacology , Dose-Response Relationship, Drug , Free Radical Scavengers , Kinetics , L-Lactate Dehydrogenase/metabolism , Lidocaine/pharmacology , Lipid Peroxidation/drug effects , Probucol/pharmacology , Propranolol/pharmacologyABSTRACT
The MDR1 gene, a multidrug resistance gene, codes for P-glycoprotein which pumps hydrophobic drugs out of the cells. Since cyclosporins also bind to P-glycoprotein and might be pumped by this transmembrane protein, we determined the expression of the MDR1 gene in the lymphocytes of 32 patients with renal transplants. MDR1 RNA expression of lymphocytes was measured by slot blot analysis and compared to the expression of drug-sensitive KB-3-1 cells and multidrug-resistant KB-8-5 cells. MDR1 RNA expression was detected in the lymphocytes of 9 (28%) patients, whereas no expression was seen in the remaining 23 patients. No association between MDR1 RNA expression and transplant function or hematological parameters was observed. However, none of the 6 patients who had transplants for more than 40 months expressed the MDR1 gene in their lymphocytes. In conclusion, expression of the MDR1 gene does occur in lymphocytes of patients with renal transplants and might reduce the immunosuppressive efficacy of cyclosporins through enhanced efflux of cyclosporins.
Subject(s)
ATP Binding Cassette Transporter, Subfamily B, Member 1/genetics , Drug Resistance, Multiple/genetics , Kidney Transplantation , Lymphocytes/physiology , ATP Binding Cassette Transporter, Subfamily B, Member 1/analysis , ATP Binding Cassette Transporter, Subfamily B, Member 1/metabolism , Adult , Aged , Cyclosporine/blood , Cyclosporine/pharmacokinetics , Cyclosporine/therapeutic use , Gene Expression , Graft Survival/physiology , Humans , Immunohistochemistry , Kidney Transplantation/pathology , Lymphocytes/chemistry , Lymphocytes/metabolism , Middle Aged , RNA/geneticsABSTRACT
The expression of the MDR1 gene, a multidrug resistance gene, was determined in patients (N = 24) with myelodysplastic syndrome or acute myeloid leukemia evolving from it. MDR1 RNA expression of the mononuclear cells was detected in 14 (58%) patients. Among patients who had progressed to acute myeloid leukemia (sAML) (N = 14), MDR1 RNA expression was seen in 8 (57%) patients. Expression was observed in the 2 patients who had been pretreated with MDR drugs. These findings indicate that the MDR1 gene is frequently expressed in MDS or sAML and suggest that multidrug resistance might be involved in the clinical drug resistance of these diseases.
Subject(s)
Carrier Proteins/genetics , Drug Resistance/genetics , Leukemia, Myeloid, Acute/genetics , Membrane Glycoproteins/genetics , Myelodysplastic Syndromes/genetics , ATP Binding Cassette Transporter, Subfamily B, Member 1 , Adult , Aged , Aged, 80 and over , Female , Gene Expression , Humans , Leukemia, Myeloid, Acute/etiology , Male , Middle AgedABSTRACT
In order to assess the clinical role of the MDR1 gene in chronic lymphocytic leukemia (CLL), we determined its expression in the leukemic cells of 39 patients with CLL and compared this with other clinical and laboratory parameters. MDR1 RNA expression was detected in 29 patients. MDR1 RNA transcripts were independent of age, treatment status of the patients and the clinical stage of CLL, but correlated with the white blood cell count and MDR2 RNA transcripts. Expression of the tumor suppressor gene p53 was found in 30 out of 37 patients and was associated with MDR1 RNA expression (P < 0.001). Immunocytochemistry using the monoclonal antibody C219 was performed in 38 patients, and in 28 cases, more than 5% of the leukemic cells were found to express cell surface P-glycoprotein. P-glycoprotein expression correlated with the expression of MDR1 RNA (P = 0.048).
Subject(s)
Carrier Proteins/genetics , Gene Expression Regulation, Leukemic , Leukemia, Lymphocytic, Chronic, B-Cell/genetics , Membrane Glycoproteins/genetics , ATP Binding Cassette Transporter, Subfamily B, Member 1 , Adrenal Cortex Hormones/administration & dosage , Adrenal Cortex Hormones/pharmacology , Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/pharmacology , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carrier Proteins/biosynthesis , Chlorambucil/administration & dosage , Chlorambucil/pharmacology , Cyclophosphamide/administration & dosage , Cyclophosphamide/analogs & derivatives , Cyclophosphamide/pharmacology , Female , Genes, p53 , Humans , Immunoenzyme Techniques , Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy , Leukemia, Lymphocytic, Chronic, B-Cell/pathology , Male , Membrane Glycoproteins/biosynthesis , Middle Aged , Prednisone/administration & dosage , Prednisone/pharmacology , RNA, Messenger/biosynthesis , RNA, Messenger/genetics , RNA, Neoplasm/biosynthesis , RNA, Neoplasm/genetics , Vincristine/administration & dosage , Vincristine/pharmacologyABSTRACT
Because of its potential importance in injury during myocardial ischemia and reperfusion, we assessed mechanisms of hydrogen peroxide (H2O2) cytotoxicity in cultured chick embryo cardiac myocytes. Injury was quantitated by release of lactate dehydrogenase (LDH) or 51Cr, both of which correlated with loss of cell viability assessed by trypan blue exclusion. The iron chelator deferoxamine (0.25-2 mM), but not equimolar iron-loaded deferoxamine, markedly reduced LDH and 51Cr release. Injury was also prevented or attenuated by the diffusible reactive oxygen metabolite scavengers dimethylthiourea (10-20 mM) and N-(2-mercaptopropionyl)-glycine (20 mM). The hydroxyl radical scavenger, dimethyl sulfoxide (200-400 mM), also reduced injury. Other scavengers that probably remained extracellular, superoxide dismutase and mannitol, were ineffective. Thus, with exposure of cardiac myocytes to H2O2, cytotoxicity requires reactions catalyzed by intracellular iron.
Subject(s)
Heart/drug effects , Hydrogen Peroxide/pharmacology , Iron/physiology , Animals , Cell Survival , Cell-Free System , Cells, Cultured , Chick Embryo , Diffusion , Dimethyl Sulfoxide/pharmacology , Free Radical Scavengers , Myocardium/cytology , Reactive Oxygen Species/metabolism , Thiourea/analogs & derivatives , Thiourea/pharmacology , Tiopronin/pharmacologyABSTRACT
The expression of the MDR1 gene, a multidrug resistance gene, was prospectively determined in 113 primary colorectal carcinoma specimens and correlated with clinical data including survival durations of the patients. MDR1 RNA was detected in 65% of the carcinomas. No expression of the MDR2 gene was seen, MDR1 gene expression was independent of age and sex of the patients, size and histologic grading of the tumour, lymph node involvement and distant metastasis. Kaplan-Meier analysis revealed that the durations of both relapse-free survival and overall survival were not different between patients with MDR1 RNA positive tumours and those with MDR1 RNA negative tumours.
Subject(s)
Adenocarcinoma/chemistry , Colonic Neoplasms/chemistry , Drug Resistance/genetics , RNA, Neoplasm/analysis , Rectal Neoplasms/chemistry , Adenocarcinoma/genetics , Adenocarcinoma/mortality , Adult , Aged , Aged, 80 and over , Colonic Neoplasms/genetics , Colonic Neoplasms/mortality , Female , Follow-Up Studies , Humans , Male , Middle Aged , Prospective Studies , Rectal Neoplasms/genetics , Rectal Neoplasms/mortality , Survival AnalysisABSTRACT
BACKGROUND: Drug resistance remains a major problem in gastric carcinomas. To evaluate the mechanisms involved in this resistance, the authors determined the expression of the MDR1 gene, a multidrug resistance gene, in primary gastric carcinomas. METHODS: MDR1 RNA levels of gastric carcinoma specimens (n = 22) were determined by slot blot analysis. An MDR1 cDNA (probe 5A) was used for the hybridization. RESULTS: MDR1 RNA was detected in 41% of the gastric carcinomas, with high levels in 18% of the specimens. No expression of the MDR3 gene was observed in these tumors. MDR1 gene expression was independent of patient age, tumor localization, and lymph node involvement. However, MDR1 RNA expression was less frequent in locally advanced tumors and was absent in the primary tumors of all six patients who had distant metastases. CONCLUSIONS: The data indicate that multidrug-resistant cells are present in primary gastric carcinomas and suggest that multidrug resistance might contribute to the clinical drug resistance of these tumors.