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1.
Most discussions on modern research ethics--particularly the formation of research ethics committees (institutional review boards)--focus on the revelations of the dreadful practices in the Nazi concentration camps at the Nuremberg trial after the second world war, with the subsequent production of the Nuremberg and Helsinki Codes. In fact, however, these trials were not pivotal: there was a long history of such concerns, going back at least to the 1830s, when William Beaumont introduced a contract with his patient Alexis St Martin, as well as the later part of the century when the celebrated leprosy worker Hansen was prosecuted in Bergen for having experimented on a patient without her consent, losing his post as a result. Probably, had it not been for the entry of the USA into the First World War, public indignation at the growing number of reports of unethical experimentation in public hospitals would have resulted in regulations, while official codes were introduced in Prussia at the turn of the century and in Berlin again in 1931. Nevertheless, the impetus for modern developments came principally from the furore aroused by the proselytising of two physicians: Henry Beecher, an anesthesiologist at Harvard, and Maurice Pappworth in London, whose respective books Experimentation in Man and Human Guinea Pigs, documented case histories of egregiously less than ethical research practices that went largely unquestioned by other clinical research workers. Here I shall discuss the reactions to and influence of some of these episodes, as well as more recent developments.  相似文献   

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Q-switched ruby laser (QSRL) and Q-switched Nd-YAG laser (QSNYL) treatment of dermal melanocytosis, especially nevus of Ota, has produced favorable results that are mediated by selective photothermolysis. However, the precise effects of irradiation on melanosomes and cells containing melanosomes remain unclear, and an optimal method of irradiation has not been found. In this study synthetic melanin powder and pigmented dermal tissue obtained from five blue nevus lesions, also classified as dermal melanocytosis, were used as targets to identify the specific effects of these forms of irradiation in vitro. Morphological changes were assessed by microscopy after irradiation with QSRL and QSNYL at a fluence of 5 J/cm2, the fluence ordinarily utilized in clinical applications. Light microscopy revealed that most of the synthetic melanin powder retained in 1% agar was no longer visible after QSRL irradiation. In contrast, melanin powder particles were partly crushed by QSNYL irradiation. Electron microscopic examination of melanosomes in the blue nevus tissue after irradiation showed expansion and various other forms of disruption. Statistical analysis by 2-way analysis of variance (ANOVA) of the length of the major axis of the melanosomes indicated that QSRL irradiation caused significantly greater melanosome expansion than QSNYL irradiation. These findings indicate that QSRL irradiation had a greater photothermal effect on dermal melanosomes than QSNYL irradiation. This suggests that QSRL is more efficacious in the treatment of dermal melanocytosis than QSNYL.  相似文献   

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Metabolism of xenobiotics such as alcohol and organic solvents can be divided roughly into two types: functional and conjugation reactions. Cytochrome P450 (CYP) is the primary group of enzymes involved in the former. Therefore, CYP analysis is essential for the study of the metabolism and toxicity of these chemicals. Of the isozymes, CYP2E1 is a low-km isozyme and has a high affinity for volatile hydrocarbons of low molecular mass, and is primarily involved in the metabolism of alcohol and organic solvents. There are many methods for analysis of CYPs including CYP2E1. The measurement of the metabolic rate of the target chemical in the liver is the most common. When combined with monoclonal or polyclonal antibody to CYP, contribution of the isozymes to the metabolism can be resolved, and the expression level is also identified by western blot analysis. The use of the reconstituted system of purified CYP isozymes is useful to determine the true activity (specific activity), but not common especially in that of human tissue. There are sometimes species differences in the enzymatic character of CYP isoforms, which causes difficulties in extrapolating to humans. In these case, the use of a cDNA expression system of human CYPs can cover the difficulties. The use of transgenic animals can answer the contribution of each CYP isoform in the in vivo metabolism and toxicity. The genotype of each isozyme is analyzed by PCR method, which can identify the polymorphism as well as the susceptibility to the chemicals.  相似文献   

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Tetrandrine, an alkaloid isolated from the plant Stephania tetrandra, at low concentration (2 micrograms/ml) was shown to protect normal human mononuclear cells in vitro against damage due to a single high-dose of ionizing irradiation (10 Gy). The cell survival rate increased from 58.3 +/- 2.2% in the irradiated group to 78.0 +/- 2.6% in the tetrandrine-pretreated group, and similarly, the percentage of necrotic cells declined from 20.7 +/- 2.5% to 10.7 +/- 1.9%, respectively. This protective effect of tetrandrine for cell surviving fraction increased in a dose-dependent manner. Tetrandrine was also found to inhibit inflammatory responses induced by irradiation including the release of superoxide (NBT [nitroblue tetrazolium] reduction decreased from 21.3 +/- 2.3% to 10.2 +/- 2.5%) and phagocytic activity (decreased from 80.7 +/- 3.8% to 50.7 +/- 2.3%, the same range level as that of the control group). However, the alkaloid demonstrated no effect on the production of nitric oxide. In terms of cell morphology, only two types were observed-normal or necrotic cells, and there were no characteristics of programmed cell death. These results indicate that tetrandrine possesses radioprotective activity against 10 Gy of ionizing irradiation and could suppress irradiation-induced inflammatory processes.  相似文献   

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The aim of the present study was to study the tissue reaction and gingival healing in pulsed laser gingival retraction in comparison with chemico-mechanical gingival retraction technique. This work was applied on six patients recommended for orthodontic extraction of first premolars upper and lower. The patients were divided into three groups (two patients each). -One group with laser tissue retraction. -Another group with ferric sulphate (13.3%). -Third group with aluminium chloride (25%). The present histologic findings revealed that with the application of pulsed Nd: YAG laser the gingival tissues showed faster healing with less hemorrhage and less inflammatory reaction in comparison with the other two groups. In conclusion it was evident that pulsed laser is a surgical device increasingly important to dentistry. The present study can support with the clinical application of laser in gingival retraction as a simple convenient, painless method.  相似文献   

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OBJECTIVE: To determine the relative efficacy and morbidity of Ho:YAG versus Nd:YAG laser treatment of bullous lung disease in an animal model. SUMMARY BACKGROUND DATA: Laser coagulation procedures for treatment of emphysematous pulmonary bullae and heterogeneous emphysema continue to evolve. The role of lasers in lung volume reduction surgery remains controversial due to issues of relative efficacy and morbidity. The Nd:YAG laser is most commonly used for these procedures. We hypothesized that the shallower penetration of the Ho:YAG laser may be better suited for laser bullae coagulation and emphysema lung volume reduction with increased efficacy and reduced lung injury. METHODS: Thirty New Zealand White rabbits (15 normal rabbits; 15 with bullous lung disease) were evaluated with Ho:YAG compared to Nd:YAG laser exposures. Bullae were coagulated by either Ho:YAG or Nd:YAG treatment. In all animals (bullous-induced and normals), unaffected lung tissue in the upper lobes and contralateral lungs were treated with 5 spot exposures of Nd:YAG and Ho:YAG, each to assess depth of lung injury. Animals were sacrificed at Days 0, 7, and 21 and their lungs were examined histologically. RESULTS: Ho:YAG and Nd:YAG exposures caused equivalent lung injury to normal lung tissue. In the acute phase, parenchymal necrosis depth was similar for both Ho:YAG and Nd:YAG (850 +/- 273 microns vs. 900 +/- 270 microns respectively, p = 0.7). By Day 7, lung necrosis depth was 925 +/- 133 microns Ho:YAG vs. 1225 +/- 235 microns Nd:YAG (p = 0.33), and lung fibrosis depth was 300 +/- 134 microns Ho:YAG vs. 558 +/- 127 microns Nd:YAG (p = 0.11). By Day 21, pulmonary parenchymal necrosis was not seen. Pleural fibrosis depth was maximal at Day 21, reaching 250 +/- 102 microns for Ho:YAG vs. 300 +/- 156 microns Nd:YAG (P = 0.88). Pleural necrosis depth was 67 +/- 42 microns Ho:YAG vs 48 +/- 34 microns Nd:YAG (p = 0.42) on Day 7 and resolved by Day 21. During surgical coagulation procedures, the Ho:YAG laser was dramatically more efficient in coagulating bullae. The Ho:YAG laser required less exposure at equivalent power and resulted in immediate desiccation of bullae, in sharp contrast to the Nd:YAG laser. CONCLUSIONS: Because the Ho:YAG was more effective and did not result in more acute lung injury than the standard Nd:YAG laser in this study, Ho:YAG lasers may have improved potential for laser treatment of bullae or lung volume reduction surgery (LVRS) compared to Nd:YAG lasers.  相似文献   

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OBJECTIVE: This study aimed to simulate the effects of lasing dentine on pulpal nerve function. METHODS: Rat spinal nerve roots were threaded through the prepared pulp canal of a 10 mm long tooth root segment which was mounted in a perspex bath. The protruding ends of the nerve were placed on platinum wire electrodes used to elicit and to record compound nerve action potentials (CAPs). Laser energy (average power = 0.3-3.0 W) was applied to the surface of the root segment using a pulsed Nd:YAG dental laser (dLase 300). RESULTS: With the laser probe tip placed in static contact with the tooth surface, the nerve CAP was irreversibly abolished within 60 s of lasing at 1.0-3.0 W power. When the laser tip was moved to and fro over the root surface in a scanning mode, similar levels of radiation produced less marked effects. In the latter mode, CAP attenuation increased with increasing power and duration of lasing. After 60 s lasing at 0.3 W, the CAP size was 95% (+/- 5, S.D.) of the prelasing controls value; with 2.0 W the CAP was reduced to 54% (+/- 33). The CAP recovered to 90% of control levels after lasing at powers up to 1.5 W, but reached only 72% of control values after lasing at 2.0 W power. CONCLUSIONS: Laser radiation applied to dentine caused a dose-dependent block of action potential conduction in nerve fibres in the underlying pulp chamber.  相似文献   

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Round enamel and dentin surfaces of sound and carious extracted human teeth were irradiated by an ArF:excimer laser for up to 180 sec. Thermographic measurements indicated that the temperature rise due to heat accumulation caused by laser irradiation on these enamel and dentin surfaces was up to 19 degrees C (10 HZ with 540 J/cm2), and the temperature returned to the preirradiation value within 10 sec after the irradiation was stopped. Under light microscopy, no carbonization was evident on these surfaces, and a simple recess was formed by abrasion or vaporization in the irradiated regions. In the secondary SEM, uniformly distributed fine pores and prism structures appeared slightly on the enamel surfaces. Between the peritubular and the intertubular dentin, there appeared a distinct difference in the dissolved area. The laser almost completely removed carious regions of the enamel and the dentin, and penetration extended beyond the carious regions. In the backscattered electron SEM, highly mineralized layers were observed on the enamel and dentin surfaces dissolved by the laser.  相似文献   

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Class II major histocompatibility complex (MHC) antigen-expressing cells are generally associated with the early phase of the immune response. We have studied the distribution of class II-expressing cells in developing, normal, and carious human teeth to clarify when human pulp acquires an immunologic defense potential and how this reacts to dental caries. Antigen-expressing cells were identified immunohistochemically by means of HLA-DR monoclonal antibody. In the pulp of unerupted developing teeth, numerous HLA-DR-positive cells were distributed mainly in and around the odontoblast layer. In erupted teeth, HLA-DR-positive cells were located, for the most part, just beneath the odontoblast layer, with slender cytoplasmic processes extending into the layer. Superficial caries lesions caused an aggregation of HLA-DR-positive cells in dental pulp corresponding to the lesion. In teeth with deeper caries lesions, this aggregation of cells expanded to include the odontoblast layer. Also noted were HLA-DR-positive cells lying along the pulp-dentin border, with cytoplasmic processes projecting deep into the dentinal tubules, where they co-localized with odontoblast processes. These findings suggest that: (1) human dental pulp is equipped with immunologic defense potential prior to eruption; (2) in the initial stage of caries infection, an immunoresponse mediated by class-II-expressing cells is initiated in human dental pulp; and (3) HLA-DR-positive cells trespass deep into dentinal tubules as the caries lesion advances.  相似文献   

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OBJECTIVE: The protective effect of dexamethasone against radiation damage is unclear. We examined the effect of early treatment of high-dose dexamethasone on iridium-192-induced damage to normal brain tissue. METHODS: Brain damage induced by interstitial irradiation with iridium-192 was evaluated with sequential magnetic resonance imaging and proton magnetic resonance spectroscopy in 11 adult monkeys, with or without short-term high-dose dexamethasone treatment. Dexamethasone (1 mg/kg of body weight/d) was administered intramuscularly to five irradiated animals every 24 hours, beginning 2 days before and ending 7 days after irradiation. Magnetic resonance imaging and proton magnetic resonance spectroscopy were performed 1 week, 1 month, and 3 months after irradiation. RESULTS: Magnetic resonance imaging performed 1 week after irradiation revealed marked edema in five nontreated animals. In dexamethasone-treated animals, the volume of edema was reduced significantly, compared to that of nontreated animals, 1 week and 1 month after irradiation. The volume of ring enhancement in dexamethasone-treated animals was also reduced significantly, compared to that of nontreated animals, 3 months after the irradiation. Proton magnetic resonance spectroscopy spectra revealed that N-acetylaspartate and choline peaks were reduced 1 week after irradiation in both groups. However, there were no statistically significant differences between the two groups at any time points. CONCLUSION: These results suggest that dexamethasone treatment may have an antiedema effect at an early stage and may modify subsequent development of vascular and inflammatory changes but may have no effect of preventing radiation-induced necrosis and the reduction of N-acetylaspartate after brachytherapy.  相似文献   

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Pseudotumoral mediastinal and pulmonary amyloidosis occur infrequently and may be confused with other tumors that are found more commonly in this region. Enlargement of hilar lymph nodes in the absence of pulmonary involvement is extremely rare. We report a case of nodular amyloidosis of the hilar lymph nodes that was studied using different diagnostic and radiologic methods. A previously healthy 79-year-old man presented with a large right hilar mass detected on routine chest roentgenography. The extensive mass behaved like a solid tumor and mimicked a bronchogenic carcinoma. At thoracotomy, frozen sections revealed the tumor to consist of kappa-light-chain amyloid. In light of the irresectibility of the tumor, thoracotomy was ended as open biopsy. Immunoelectrophoretic analyses of the plasma and urine showed no evidence of a paraprotein immunoglobulin or light chains. The patient was discharged without symptoms of disease. Different diagnostic procedures before and after surgery are discussed.  相似文献   

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The effects of the welding parameters on weld-bead morphology and the microstructural evolution of autogenous conduction-mode melted laser welds in gallium delta-stabilized plutonium were investigated. This investigation demonstrates that delta-stabilized plutonium is easily welded with a pulsed Nd:YAG laser. Variations in the welding parameters created a range of heat inputs that had a significant effect on the size and morphology of the resultant weld and associated heat-affected-zone (HAZ) microstructure. Unlike other low-melting-temperature materials such as aluminum alloys, neither fusion-zone porosity nor hot cracking was observed. The reactivity of plutonium promotes the rapid formation of surface oxides that inhibit complete weld-joint fusion. The high viscosity of the plutonium molten pool impeded the breakup of the surface oxide by fluid motion, thus further impeding joint fusion. Modifications to input parameters to affect changes in the weld-pool flow were only partially successful in improving joint fusion. Analysis of the weld region using optical and electron microscopy and electron microprobe analysis revealed fusion-zone microstructures consisting of fine acicular delta grains, with a limited amount of retained alpha phase. The Pu6Fe, the low-melting-point intermetallic phase, was observed in the base material and the partially melted HAZ. Further investigation into the solid/solid phase transformations, specifically the effect of the cooling rate, during the cooling of the weld will be required to describe fully the microstructural development of the fusion zone.  相似文献   

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BACKGROUND AND OBJECTIVES: To study tissue effects and thresholds of efficacy in producing a full-thickness scleral fistula in human eyes obtained from cadavers. The effect of laser sclerostomies created with indocyanine green (ICG) was also evaluated. MATERIALS AND METHODS: Ab externo laser sclerostomies were produced in 12 fresh human eyes obtained from cadavers using a 200-micron diameter fiber optic connected to a diode laser system. Power settings were 500, 750, 1000, 1250, 1500, and 2000 mW with a constant duration of 100 and 200 ms. The same diode laser settings were repeated in the tissues injected with ICG. RESULTS: The laser sclerostomies were associated with heat coagulation damage adjacent to the burn margins, with disruption of stromal collagen. Tissue damage was greater at higher power and longer duration. Scleral injection of ICG prior to laser sclerostomy did not enhance laser penetration. CONCLUSION: The diode laser can create a sclerostomy in human sclera with an optimum level of 1500 mW and 100 ms. ICG did not significantly enhance the ease of penetration or reduce the association thermal damage to the sclera.  相似文献   

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