应用锥形束CT对盆腔肿瘤放疗计划靶区外放距离的研究

Objective To analyze setup errors for irradiation of pelvic carcinoma by online conebeam CT (CBCT) scanning and to calculate the external margins from clinical target volume (CTV) to planning target volume (PTV) in treatment planning. Methods Twelve patients with rectal or prostate cancer were enrolled in this study. Translational errors (x,y,z) and rotational errors (u,v,w) were obtained by using CBCT in radiotherapy. Results The set-up errors were gathered from 229 sets of CBCT in 12patients. The systemic ± random errors on x,y,z, u,v and w axes were (0.49 ± 1.18) mm, (-0. 11 ±3.45) mm, (-2. 00 ± 1.59) mm, 1.14°±0. 67°, 0. 42°±O. 94°and -0. 32°±±0. 68°, respectively. Setup errors in the left-right, anterior-posterior, and superior-inferior directions were 4. 6 mm, 12. 5 mm, and 6. 2 mm, respectively. Conclusions Set-up errors were unavoidable in pelvic carcinoma irradiation. To minimize the influence of set-up errors, we suggest a PTV margin of 5 mm, 15 mm and 10 mm in the leftright, anterior-posterior and superior-inferior directions, respectively.     

图像引导鼻咽癌调强放疗位置误差导致剂量差异分析

Objective To discuss the set-up isocenter error based on kilovolt cone beam computed tomography (KVCBCT) and to investigate dose deviation led to set-up isocenter error. Methods 21 cases of nasopharyngeal carcinoma ( NPC ) treated with image guided intensity modulated radiotherapy (IG-IMRT)were investigated. The online KVCBCT scan, rigid image registration, set-up error was gained for 376 sets before radiotherapy. We sampled ten and fifteen setup isocenter error in the 376 sets randomly. Without changing beam angle,fields size and leaf sequences and dose weight et al. , we only replaced new isocenter and accumulated the new plan for ten or fifteen plans. We compared the percentage deviation between ten,fifteen times accumulated plans and normal ten , fifteen times plans. Results All 376 sets of KVCBCT image were analyzed for 21 cases. Under the condition of non-correction, the setup isocenter errors are 0. 75mm ± 1.13 mm, 0. 92 mm ±2. 15 mm,0. 82 mm ± 1.24 mm in left-right, superior-inferior and anteriorposterior directions respectively. So, we developed the margins which were 4 mm,6 mm、4 mm in three directions respectively from clinical tumor volume to planning tumor volume (PTV) calculated by two parameters model. In the fifteen accumulated plan, the deviation in the dose of 95% PTV (D95) was -7. 5% - - 11.9%, and the deviation in the D50 was -5. 1% - -8. 2%. Conclusions It is possible of small effects to normal organs and targets because of small error of patient displacement in one fraction.However, many small errors can led to considerable dose difference in targets and normal tissue in thirty fractions of all treatments period. So, according to two parameters model, PTV margin can be designed new planning and depended on IG-IMRT technique, which it will be significantly reduced these dose differences.     

图像引导调强放疗头颈部肿瘤摆位误差对靶区外扩边界大小的影响

目的 利用锥形束CT (CBCT)图像分析跟踪头颈部恶性肿瘤调强放疗分次治疗间和分次治疗内肿瘤中心误差情况,并以此误差探讨临床靶体积(CTV)外放边界大小.方法 51例头颈部肿瘤经图像引导调强放疗,其中治疗前CBCT引导464次,治疗后CBCT 126次.根据CBCT图像与计划CT图像匹配实现在线和离线分析得到位移偏差.按不同在线校正次数(15次、11～15次、5～10次)和3个方向偏差依照双模型参数计算CTV外扩边界大小.结果 464次摆位未校正的左右、前后、上下方向偏差分别为0.37、-0.43、0.47 mm,CTV外扩边界分别为6.41、6.15、7.10 mm;校正后偏差分别为0.08、-0.03、0.03 mm,CTV外扩边界分别为1.78、1.80、1.97 mm.在线校正次数>15次,11～15次,5～10次者左右、前后、上下方向外扩分别为3.8、3.8、4.0 mm,4.0、4.0、5.0 mm,5.4、5.2、6.1 mm.结论 利用CBCT引导头颈部恶性肿瘤的调强放疗可确定确切的CTV外扩边界大小,保证肿瘤区域得到准确剂量和减小正常组织受量.

Abstract：

Objective To determine the planning target volume margins of head and neck cancers treated by image guided radiotherapy (IGRT).Methods 464 sets cone beam computed tomography (CBCT) images before setup correction and 126 sets CBCT images after correction were obtained from 51 head and neck cancer patients treated by IGRT in our department.The systematic and random errors were evaluated by either online or offline correction through registering the CBCT images to the planning CT.The data was divided into 3 groups according to the online correction times.Results The isocenter shift were 0.37 mm±2.37 mm, -0.43 mm±2.30 mm and 0.47 mm±2.65 mm in right-left (RL), anterior-posterior (AP) and superior-inferior (SI) directions respectively before correction, and it reduced to 0.08 mm±0.68 mm, -0.03 mm±0.74 mm and 0.03 mm±0.80 mm when evaluated by 126 sets corrected CBCT images.The planning target volume (PTV) margin from clinical target volume (CTV) before correction were:6.41 mm,6.15 mm and 7.10 mm based on two parameter model, and it reduced to 1.78 mm,1.80 mm and 1.97 mm after correction.The PTV margins were 3.8 mm,3.8 mm,4.0 mm;4.0 mm,4.0 mm,5.0 mm and 5.4 mm,5.2 mm,6.1 mm in RL, AP and SI respectively when online-correction times were more than 15 times, 11-15 times,5-10 times.Conclusions CBCT-based on online correction reduce the PTV margin for head and neck cancers treated by IGRT and ensure more precise dose delivery and less normal tissue complications.     

图像引导鼻咽癌调强放疗位置误差导致剂量差异分析

目的 分析千伏特锥形束CT(CBCT)对鼻咽癌调强放疗靶区中心位置变化及由位置偏差导致的剂量变化.方法 对21例鼻咽癌患者调强放疗,全程376次CBCT得到每次靶区中心变化值.在上述变化值中随机抽取10、15次值输入逆向调强放疗计划系统中,照射角度、子野序列、权重等均不变,只对中心发生变化;累积10、15次偏差计划得到新的剂量分布,通过偏差公式得到相对应次数标准计划剂量偏差情况.结果 未经校正的376次CBCT在左右、上下、前后方向的系统误差和随机误差分别为0.75 mm和1.13 mm,0.92 mm和2.15 mm,0.82 mm和1.24 mm,利用双参数模型计算CTV外扩4、6,4 mm生成PTV,左右、上下、前后方向＜2 mm的偏差比例分别为82.8%、76.0%、81.8%,＞3 mm偏差分别为6.2%、9.8%、7.1%.在15次累积计划时靶区接受95%处方剂量(D95)偏差为-7.5%～-11.9%,D50的为-5.1%～-8.2%.结论 每次较小的摆位误差可能对靶区或正常器官的剂量影响较小,但整个疗程累计30余次的误差结果可能导致较大剂量差异,通过双参数模型计算生成PTV并按PTV实现的计划和图像引导放疗可弥补这些剂量的不足.

Abstract：

Objective To discuss the set-up isocenter error based on kilovolt cone beam computed tomography (KVCBCT) and to investigate dose deviation led to set-up isocenter error. Methods 21 cases of nasopharyngeal carcinoma ( NPC ) treated with image guided intensity modulated radiotherapy (IG-IMRT)were investigated. The online KVCBCT scan, rigid image registration, set-up error was gained for 376 sets before radiotherapy. We sampled ten and fifteen setup isocenter error in the 376 sets randomly. Without changing beam angle,fields size and leaf sequences and dose weight et al. , we only replaced new isocenter and accumulated the new plan for ten or fifteen plans. We compared the percentage deviation between ten,fifteen times accumulated plans and normal ten , fifteen times plans. Results All 376 sets of KVCBCT image were analyzed for 21 cases. Under the condition of non-correction, the setup isocenter errors are 0. 75mm ± 1.13 mm, 0. 92 mm ±2. 15 mm,0. 82 mm ± 1.24 mm in left-right, superior-inferior and anteriorposterior directions respectively. So, we developed the margins which were 4 mm,6 mm、4 mm in three directions respectively from clinical tumor volume to planning tumor volume (PTV) calculated by two parameters model. In the fifteen accumulated plan, the deviation in the dose of 95% PTV (D95) was -7. 5% - - 11.9%, and the deviation in the D50 was -5. 1% - -8. 2%. Conclusions It is possible of small effects to normal organs and targets because of small error of patient displacement in one fraction.However, many small errors can led to considerable dose difference in targets and normal tissue in thirty fractions of all treatments period. So, according to two parameters model, PTV margin can be designed new planning and depended on IG-IMRT technique, which it will be significantly reduced these dose differences.     

肺癌锥形束CT图像不同配准方式的误差分析

Objective To analyze the influencing factors of cone-beam CT (CBCT) imagine registration in lung cancer. Methods From Mar. 2007 to Dec. 2007, 20 patients with lung cancer were treated with IGRT. The imagines of CBCT were collected from 6 to 19 fractions during the patients' radiotherapy. To compare the difference of set-up errors between the two groups according to the distance from the lesion in lung to the centrum. At the same time, CBCT imagines from the first, middle and the last fraction of these patients' radiotherapy were registrated in bone and grey methods by four doctors. The difference of set-up errors between different doctors and registrated methods were compared. Results The mean values of set-up errors were ＜2 mm in the two groups without significant difference (x:-1.31mm vs 0. 10 mm (t=0. 07,P=0.554);y:1.24 mm vs 1.37 mm (t=0. 05,P=0. 652);z: - 1.88mm vs -1.26mm (t= -0. 12,P=0.321)). The mean values of set-up errors were ＜ 1.3 mm in four doctors and registrated methods without significant difference, for bone registration,x: -0. 05 mm, -0. 01 mm,0. 05 mm, -0.12 mm and -1.31 mm ( F=-0.01,P=0.887) ;y:0.56 mm,0.35 mm,0.51 mm and 0.43 mm (F= -0.01,P=0.880);z: -1.16 mm, -1.20 mm, -0.88 mm and -1.03 mm (F= -0.04,P=0. 555 ), for grey registration ,x: -0.32 mm, -0.341 mm, -0.395 mm and - 0.37 mm(F=-0.01, P=0.874);y:0.34 mm,0.54 mm, -0.04 mm and 0.27 mm (F= -0.03,P=0.622);x:-1.12 mm,- 1.15 mm, - 1.13 mm and - 1.04 mm (F=0. 00,P=0. 812). Conclusions With the same registrated box and imagine quality, the location of the lesions in lung, registred methods and different doctors are not the influencing factors for CBCT imagine registration.     

胸段食管癌三维适形放疗摆位误差研究

Objective To study the setup errors in three-dimensional conformal radiotherapy (3DCRT) for thoracic esophageal carcinoma using electronic portal imaging device(EPID) and calculate the margins from CTV to PTV. Methods Forty-one patients with thoracic esophageal carcinoma who received 3DCRT were continuously enrolled into this study. The anterior and lateral electronic portal images (EPI) were aquired by EPID once a week. The setup errors were obtained through comparing the difference between EPI and digitally reconstructed radiographs(DRR). Then the setup margins from CTV to PTV were calculat-ed. By using self paired design,22 patients received definitive radiotherapy with different margins. Group A: the margins were 10 mm in all the three axes;Group B: the margins were aquired in this study. The differ-ence were compared by Paired t-test or Wilcoxon signed-rank test. Results The margins from CTV to PTV in x,y and z axes were 8.72 mm, 10.50 mm and 5.62 mm, respectively. Between the group A and group B, the difference of the maximum dose of the spinal cord was significant(4638.7 cGy±1449.6 cGy vs. 4310.2 cGy±1528.7 cGy; t=5.48, P=0.000), and the difference of NTCP for the spinal cord was also significant (4.82%±5.99% vs. 3.64%±4.70%;Z=-2.70,P=0.007). Conclusions For patients with tho-racic esophageal carcinoma who receive 3DCRT in author's department,the margins from CTV to PTV in x, y and z axes were 8.72 mm, 10.50 mm and 5.62 mm, respectively. The spinal cord could be better protected by using these setup margins than using 10 mm in each axis.     

胸段食管癌三维适形放疗摆位误差研究

Objective To study the setup errors in three-dimensional conformal radiotherapy (3DCRT) for thoracic esophageal carcinoma using electronic portal imaging device(EPID) and calculate the margins from CTV to PTV. Methods Forty-one patients with thoracic esophageal carcinoma who received 3DCRT were continuously enrolled into this study. The anterior and lateral electronic portal images (EPI) were aquired by EPID once a week. The setup errors were obtained through comparing the difference between EPI and digitally reconstructed radiographs(DRR). Then the setup margins from CTV to PTV were calculat-ed. By using self paired design,22 patients received definitive radiotherapy with different margins. Group A: the margins were 10 mm in all the three axes;Group B: the margins were aquired in this study. The differ-ence were compared by Paired t-test or Wilcoxon signed-rank test. Results The margins from CTV to PTV in x,y and z axes were 8.72 mm, 10.50 mm and 5.62 mm, respectively. Between the group A and group B, the difference of the maximum dose of the spinal cord was significant(4638.7 cGy±1449.6 cGy vs. 4310.2 cGy±1528.7 cGy; t=5.48, P=0.000), and the difference of NTCP for the spinal cord was also significant (4.82%±5.99% vs. 3.64%±4.70%;Z=-2.70,P=0.007). Conclusions For patients with tho-racic esophageal carcinoma who receive 3DCRT in author's department,the margins from CTV to PTV in x, y and z axes were 8.72 mm, 10.50 mm and 5.62 mm, respectively. The spinal cord could be better protected by using these setup margins than using 10 mm in each axis.     

胸段食管癌三维适形放疗摆位误差研究

Objective To study the setup errors in three-dimensional conformal radiotherapy (3DCRT) for thoracic esophageal carcinoma using electronic portal imaging device(EPID) and calculate the margins from CTV to PTV. Methods Forty-one patients with thoracic esophageal carcinoma who received 3DCRT were continuously enrolled into this study. The anterior and lateral electronic portal images (EPI) were aquired by EPID once a week. The setup errors were obtained through comparing the difference between EPI and digitally reconstructed radiographs(DRR). Then the setup margins from CTV to PTV were calculat-ed. By using self paired design,22 patients received definitive radiotherapy with different margins. Group A: the margins were 10 mm in all the three axes;Group B: the margins were aquired in this study. The differ-ence were compared by Paired t-test or Wilcoxon signed-rank test. Results The margins from CTV to PTV in x,y and z axes were 8.72 mm, 10.50 mm and 5.62 mm, respectively. Between the group A and group B, the difference of the maximum dose of the spinal cord was significant(4638.7 cGy±1449.6 cGy vs. 4310.2 cGy±1528.7 cGy; t=5.48, P=0.000), and the difference of NTCP for the spinal cord was also significant (4.82%±5.99% vs. 3.64%±4.70%;Z=-2.70,P=0.007). Conclusions For patients with tho-racic esophageal carcinoma who receive 3DCRT in author's department,the margins from CTV to PTV in x, y and z axes were 8.72 mm, 10.50 mm and 5.62 mm, respectively. The spinal cord could be better protected by using these setup margins than using 10 mm in each axis.     

胸段食管癌三维适形放疗摆位误差研究

Objective To study the setup errors in three-dimensional conformal radiotherapy (3DCRT) for thoracic esophageal carcinoma using electronic portal imaging device(EPID) and calculate the margins from CTV to PTV. Methods Forty-one patients with thoracic esophageal carcinoma who received 3DCRT were continuously enrolled into this study. The anterior and lateral electronic portal images (EPI) were aquired by EPID once a week. The setup errors were obtained through comparing the difference between EPI and digitally reconstructed radiographs(DRR). Then the setup margins from CTV to PTV were calculat-ed. By using self paired design,22 patients received definitive radiotherapy with different margins. Group A: the margins were 10 mm in all the three axes;Group B: the margins were aquired in this study. The differ-ence were compared by Paired t-test or Wilcoxon signed-rank test. Results The margins from CTV to PTV in x,y and z axes were 8.72 mm, 10.50 mm and 5.62 mm, respectively. Between the group A and group B, the difference of the maximum dose of the spinal cord was significant(4638.7 cGy±1449.6 cGy vs. 4310.2 cGy±1528.7 cGy; t=5.48, P=0.000), and the difference of NTCP for the spinal cord was also significant (4.82%±5.99% vs. 3.64%±4.70%;Z=-2.70,P=0.007). Conclusions For patients with tho-racic esophageal carcinoma who receive 3DCRT in author's department,the margins from CTV to PTV in x, y and z axes were 8.72 mm, 10.50 mm and 5.62 mm, respectively. The spinal cord could be better protected by using these setup margins than using 10 mm in each axis.     

胸段食管癌三维适形放疗摆位误差研究

Objective To study the setup errors in three-dimensional conformal radiotherapy (3DCRT) for thoracic esophageal carcinoma using electronic portal imaging device(EPID) and calculate the margins from CTV to PTV. Methods Forty-one patients with thoracic esophageal carcinoma who received 3DCRT were continuously enrolled into this study. The anterior and lateral electronic portal images (EPI) were aquired by EPID once a week. The setup errors were obtained through comparing the difference between EPI and digitally reconstructed radiographs(DRR). Then the setup margins from CTV to PTV were calculat-ed. By using self paired design,22 patients received definitive radiotherapy with different margins. Group A: the margins were 10 mm in all the three axes;Group B: the margins were aquired in this study. The differ-ence were compared by Paired t-test or Wilcoxon signed-rank test. Results The margins from CTV to PTV in x,y and z axes were 8.72 mm, 10.50 mm and 5.62 mm, respectively. Between the group A and group B, the difference of the maximum dose of the spinal cord was significant(4638.7 cGy±1449.6 cGy vs. 4310.2 cGy±1528.7 cGy; t=5.48, P=0.000), and the difference of NTCP for the spinal cord was also significant (4.82%±5.99% vs. 3.64%±4.70%;Z=-2.70,P=0.007). Conclusions For patients with tho-racic esophageal carcinoma who receive 3DCRT in author's department,the margins from CTV to PTV in x, y and z axes were 8.72 mm, 10.50 mm and 5.62 mm, respectively. The spinal cord could be better protected by using these setup margins than using 10 mm in each axis.     

The medically important dematiaceous fungi and their identification

Dematiaceous fungi include a large group of organisms that are darkly pigmented (dark brown, olivaceous, or black). In most cases the pigment is melanin, and specifically, dihydroxynaphthalene melanin. The diseases produced include chromoblastomycosis, eumycotic mycetoma, and phaeohyphomycosis. Phaeohyphomycosis is a new classification for a diverse group of previously known entities grouped together on the basis of finding dematiaceous hyphal and/or yeast-like forms in tissue; tissue involvement may be superficial, cutaneous and corneal, subcutaneous, or systemic. Identification of these fungi is based mostly upon morphology. Important structures include annellides (Phaeoannellomyces, Exophiala), phialides (Phialophora, Wangiella), adelophialides (Phialemonium without collarettes, Lecythophora with collarettes), differentiation of conidiophores (Xylohypha versus Cladosporium) and conidial hilum, septation and germination (Bipolaris, Drechslera, Exserohilum). Useful laboratory tests include the 12% gelatin test (controversial), nitrate assimilation (W. dermatitidis is negative, most other species are positive), and determination of temperature maxima (especially 37 degrees C for E. jeanselmei, 40 degrees C for W. dermatitidis and B. spicifera, 42 degrees C for X. bantiana, and 45 degrees C for Dactylaria constricta var. gallopava and Scedosporium inflatum).     

Orale Langzeitbehandlung von Onychomykosen mit Ketoconazol

Zusammenfassung: An der Studie zur Wirksamkeit und Anwendungssicherheit von Ketoconazol nahmen 27 Männer im Alter von 20 bis 80 (Median: 57) Jahre, davon 18 mit Onychomykosen und 9 als KontroUen bei den Laborwertbestimmungen, teil. Während des ersten Behandlungsmonats erhielten je 9 Patienten 200 mg und 400 mg Ketoconazol täglich. Danach wurden beide Gruppen 6 Monate mit 200 mg/d weiterbehandelt. Die klinische Beurteilung sowie hämatologische, biochemische und Plasmaspiegeluntersu-chungen erfolgten mindestens monafich, mykologische Untersuchungen wurden vor Aufnahme und bei Beendigung der Therapie vorgenommen. Erne letzte klinische Unter-suchung erfolgte 1 Jahr nach Beginn der Studie. Nach 7 Monaten Behandlung wurden 23 von 30 Nägeln mit “gebessert” bis “stark gebessert” beurteilt, nach dem behandlungsfreien Intervall galt dies für 28 von 30 Nägeln. Die Plasmaspiegel waren mit 200 mg/d ausreichend und uber den Behandlungszeit-raum konstant. Dies spricht für gute orale Resorption und Abwesenheit von Enzyminduktion. Die Laborwerte zeigten im Vergleich zu den Kontrollen und den Werten vor Behandlung keine signifikanten Abweichungen, so daß myelo-, nephro- und hepatotoxische Wirkungen von 400 bzw. 200 mg/d ausgeschlossen werden können. Der Lipidhaushalt wurde nicht beeinfluat und es trat unter Therapie als Folge der Ketoconazolwirkung lediglich Lanosterin im Serum auf. Nach Beendigung der Therapie ging der Lanosteringehalt schnell zurück. Damit erweist sich Ketoconazol in den angewandten Dosen als ein gut verträgliches und zur Langzeitbehandlung von Onychomykosen geeignetes Antimykotikum. Summary: Twenty-seven males with a median age of 57 (range: 20 to 80) years took part in this study on the efficacy and safety of ketoconazole. Eighteen men suffered from onychomycosis; nine served as controls in the safety evaluation. During the first month of treatment, nine patients received 200 mg and the nine other 400 mg ketoconazole daily. Then the treatment was uniformly continued with 200 mg/d for 6 months. Clinical evaluation and haematological, biochemical and plasma level investigations were carried out at least at monthly intervals; mycological controls were performed at the start and end of therapy. A final clinical evaluation was carried out one year after the start of the study. After 7 months of treatment, moderate or definite clinical improvement was obtained in 23 out of 30 nails. After 5 more months without antimycotic treatment this was the case in 28 of 30 nails. Plasma levels obtained with 200 mg ketoconazole daily were adequate and constant during the entire treatment period. This indicates a good oral resorption as well as the absence of induction of hepatic enzymes. The laboratory values did not show significant deviations as compared with the controls or with the pretreatment values. This excludes myelo-, nephro- and hepatotoxic effects of 400 and 200 mg ketoconazole daily. The lipid metabolism was not influenced, the only difference was the occurrence of lanosterol in the serum, which is a result of the mechanism of action of ketoconazole. After the medication period the lanosterol levels subsided rapidly. In the applied doses ketoconazole is a well-tolerated and effective drug for the systemic long-term treatment of onychomycosis.     

Laboratory Techniques Alternative to In Vivo Experiments for Studying the Liberation, Penetration and Fungicidal Action of Topical Antimycotic Agents in the Skin, Including Ciclopiroxolamine

Summary: Short-term experiments on excised skin (human, pig) gave the following results: 1. In the tissue activity test with direct inoculation (D-TAT) commercial preparations of the non-azole antimycotics ciclopiroxolamine, tolnaftate and naftifine, produced higher inhibitory activity against Trichophyton mentagrophytes (standard strain) in various levels of the horny layer than were produced by the azole antimycotics econazole, miconazole, clotrimazole, oxiconazole and bifonazole. Fast drying solutions of antimycotics invariably gave higher inhibitory activities than creams. In the ultrafiltration tissue activity test (UFT- TAT) against Candida albicans (2 strains), antimycotic agents ranked in order of effectiveness as follows: ciclopiroxolamine – most of the azole antimycotics – bifonazole and naftifine. 2. In tests of fungicidal activity against T. mentagrophytes (2 strains) and Microsporum gypseum (1 strain) the first step was to inoculate the skin surface. After the horny layer had been penetrated by fungal mycelia, antimycotic agents of documented fungicidal potency, chiefly in the form of creams, were applied to the skin surface and left to act for up to 18 hours. The horny layer and epidermis were then scraped off and the concentration of viable fungi was determined. Ciclopiroxolamine cream and lotion produced by far the greatest diminution in viable fungi; creams containing oxiconazole and naftifine were moderately effective and those containing tioconazole and bifonazole produced a relatively small decrease in viable fungi. To avoid erroneous results it is important to homogenize and dilute the skin scrapings; if this is not done certain antimycotics will give misleadingly high fungal killing rates. At this early stage the scatter of results is still wide and minor differences in efficacy cannot as yet be detected with certainty. 3. From the results of various comparative tests it is evident that pig skin can be used as a substitute for human skin in the tests listed under 1. and 2. above. This discovery may make a valuable contribution towards limiting the need for experiments on living animals and trials on human beings. Zusammenfassung: In Kurzzeitversuchen an exzidierter Haut (Mensch, Schwein) wurde gefunden: 1. Im Gewebeaktivitätstest mit direkter Inokulation (D-GAT) wurde mit Handelspräparaten der Nichtazol-Antimykotika Ciclopiroxolamin, Tolnaftat und Naftifin in verschiedenen Hornschichtniveaus eine höhere Hemmaktivität gegenüber Trichophyton mentagrophytes (Standard-Stamm) erzielt als mit solchen der Azol-Antimykotika Econazol, Miconazol, Clotrimazol, Oxiconazol und Bifonazol. Rasch trocknende Lösungen von Antimykotika ergaben durchweg höhere Hemmaktivitäten als Cremes. Im Ultrafiltrations-Gewebeaktivitätstest (UFT-GAT) gegenüber Candida albicans (2 Stämme) ergab sich nach erzielter Wirksamkeit die Rangfolge Ciclopiroxolamine – Mehrzahl der Azolantimykotika – Bifonazol und Naftifin. 2. In Fungizidie-Testen gegenüber T. mentagrophytes (2 Stämme) und Microsporum gypseum (1 Stamm) wurde zunächst die Hautoberfläche inokuliert. Nach Durchdringung der Hornschicht mit Pilzmyzelien wirkten auf die Hautoberfläche bis zu 18 Stunden lang überwiegend Cremes von als fungizid publizierten Antimykotika ein. Während sich in abgeschabter Hornschicht und Epidermis der so bearbeiteten Hautoberflächen mit Ciclopiroxolamin-Creme und -Lotion die weitaus höchste Verminderung lebensfähiger Keime ergab, bewirkten Cremes mit Oxiconazol und Naftifin eine mittlere und solche mit Tioconazol und Bifonazol eine relativ niedrige Keimeliminierung. Zur Vermeidung von fehlerhaften Ergebuissen mußten Homogenisierung und Verdünnung der Hautschabsel erfolgen, anderenfalls bei mehreren Antimykotika eine zu hohe Keimabtötung vorgetäuscht worden wäre. Wegen der vorerst noch hohen Streuung der Ergebnisse können kleinere Wirksamkeitsunterschiede noch nicht sicher erfaßt werden. 3. Nach dem Ergebnis verschiedener Vergleichstests kann in den Testen zu 1. und 2. Schweinehaut als Ersatz für Haut vom Menschen dienen und dürfte damit wesentlich zur Einschränkung von Versuchen am lebenden Tier und von Prüfungen am Menschen beitragen.     

Pharmacogénétique des fluoropyrimidines. La méthylènetétrahydrofolate réductase

Résumé: Lefficacité optimale des fluoropyrimidines nécessite des concentrations élevées en 5-10 méthylènetétrahydrofolate (CH₂FH₄), contrôlées par la méthylènetétrahydrofolate réductase (MTHFR) qui convertit irréversiblement le CH₂FH₄ en 5-méthyltétrahydrofolate (CH₃FH₄). Les polymorphismes 677CT et 1298AC du gène MTHFR sont associés à une baisse dactivité de lenzyme. Les tumeurs «MTHFR mutées» devraient donc être plus sensibles aux fluoropyrimidines que les tumeurs «MTHFR sauvages». Les études expérimentales et cliniques publiées à ce jour tendent à montrer une plus grande sensibilité au 5-FU (associé ou non à lacide folinique) dans les tumeurs MTHFR mutées par rapport aux tumeurs sauvages. Ces résultats montrent la nécessité de poursuivre ces recherches afin de confirmer limpact de ces polymorphismes sur lefficacité des fluoropyrimidines.     

Efficiency of crude and purified fungal antigens in serodiagnosis to discriminate mycotic from other respiratory diseases

Mycotic immunodiagnosis was performed in 186 hospitalized patients with different respiratory diseases, mostly considered as tuberculosis and others with a doubtful diagnosis. Crude histoplasmin, coccidioidin, paracoccidioidin, blastomycin, candidin, aspergillin, and sporotrichin, as well as purified polysaccharide-protein complexes (PPC) of Histoplasma capsulatum, Coccidioides immitis, and Paracoccidioides brasiliensis were used as antigens. Immune tests used included skin test (ST), gel immunodiffusion (ID), counterimmunoelectrophoresis (CIE), complement fixation (CF), and ELISA. A possible association with candidosis was observed in 17% of patients with tuberculosis and diabetes; one presumptive paracoccidioidomycosis, one confirmed aspergillosis, and six cases of active histoplasmosis were determined. Candidin ST showed 29% of positive reactions with an increased frequency in patients between 31 and 55 years of age. CF test showed the highest positivity percentages with crude antigens, specially for Candida antigen (26.3%) and histoplasmin (18.2%). Cross reactions were evident with crude antigens but decreased when PPC's were used in ELISA.     

Isoconazole nitrate in the treatment of tropical dermatomycoses

Summary. A total of 54 patients with culturally proven tropical dermatomycoses, comprising 23 with various types of dermatophytoses, one with foot infection due to Trichosporon beigelii and one with foot infection due to Geotrichum candidum , two with candidoses of the groin and 27 with pityriasis versicolor, were included in a clinical trial of efficacy of 1% isoconazole cream (Travogen^R, Schering, Berlin, Germany). Five patients were not evaluable. A clinical and mycological cure was achieved in 29 cases in 3–4 weeks. In 15 (31%) of the remaining patients treatment was required for 5–6 weeks, while another three patients required treatment for 8 weeks. In two patients the disease proved to be resistant to treatment with the drug.
Zusammenfassung. Insgesamt 54 Patienten mit kulturell gesicherter Dermatomykose, (23 unterschiedliche Dermatophytosen, eine Trichosporon beigelii - und eine Geotrichum candidum -Fußinfektion, 2 Candidosen der Leistengegend und 27 Pityriasis versicolor) wurden in einer klinischen Wirksamkeits-studie mit 1% iger Isoconazol-Creme (Travogen^R, Schering, Berlin, Deutschland) behandelt. Fünf Patienten waren nicht auswertbar. Eine klinische und mykologische Heilung wurde bei 47 von 49 Patienten (96%) erreicht. Bei 29 patienten (59%) wurde die Heilung bereits nach 3–4 Wochen Behandlung erreicht. Weitere 15 Patienten (31%) benötigten 5–6 Wochen und drei Patienten 8 Wochen Behandlungsdauer. Zwei Mykosesituationen erwiesen sich als therapieresistent.     

Oncogénétique et psycho-oncologie, une collaboration recommandée...

Résumé: La possibilité depuis 1994, de connaître la probabilité individuelle de développer certains cancers a permis de proposer de nouvelles modalités de prévention, de traitements et contribué au développement actuel de loncogénétique. Une meilleure connaissance des répercussions psychologiques tant pour les patients que pour les apparentés est désormais possible et limplication des psycho-oncologues dans ce cadre de la réalisation des tests prédictifs, recommandée. La mission de «messager» qui incombe au «cas-index» doit faire lobjet dune attention particulière. La complexité de linformation et la dimension paradoxale que peut avoir parfois la communication à propos des choix, rend difficile lévaluation de la qualité du consentement. La situation particulièrement délicate dune aide à la décision à légard de la chirurgie prophylactique, exige une collaboration étroite des généticiens et des psycho-oncologues.Les soins de support en oncologie     

The role of papillomaviruses in human cancers

This review comprehensively evaluates the influence of gene-gene, gene-environment and multiple interactions on the risk of colorectal cancer (CRC). Methods of studying these interactions and their limitations have been discussed herein. There is a need to develop biomarkers of exposure and of risk that are sensitive, specific, present in the pathway of the disease, and that have been clinically tested for routine use. The influence of inherited variation (polymorphism) in several genes has been discussed in this review; however, due to study limitations and confounders, it is difficult to conclude which ones are associated with the highest risk (either individually or in combination with environmental factors) to CRC. The majority of the sporadic cancer is believed to be due to modification of mutation risk by other genetic and/or environmental factors. Micronutrient deficiency may explain the association between low consumption of fruit/vegetables and CRC in human studies. Mitochondrial modulation by dietary factors influences the balance between cell renewal and death critical in colon mucosal homeostasis. Both genetic and epigenetic interactions are intricately dependent on each other, and collectively influence the process of colorectal tumorigenesis. The genetic and environmental interactions present a good prospect and a challenge for prevention strategies for CRC because they support the view that this highly prevalent cancer is preventable.     

PSA-Test zur Früherkennung des Prostatakarzinoms

Zusammenfassung Prostatakrebs ist hierzulande seit einigen Jahren die häufigste Krebserkrankung bei Männern. Da über die Ätiologie wenig gesichertes Wissen vorliegt und daher kaum Möglichkeiten zur primären Prävention bestehen, konzentrieren sich die Anstrengungen auf die Suche nach wirksamen Verfahren zur sekundären Prävention. Hierbei gilt die Verwendung des PSA-Tests zur Früherkennung des Prostatakarzinoms als derzeit aussichtsreichstes Verfahren. Bevor ein neues Früherkennungsverfahren zur breiten Anwendung empfohlen oder in das gesetzliche Früherkennungsprogramm aufgenommen wird, muss jedoch seine Wirksamkeit in hierfür geeigneten wissenschaftlichen Untersuchungen nachgewiesen werden. Bis jetzt gibt es bereits eine ganze Reihe epidemiologischer Studien zur Effektivität des PSA-Screenings, doch konnte ein Wirksamkeitsnachweis bisher nicht erbracht werden. Zwei große randomisierte Studien in Europa und den USA lassen für die Jahre 2005–08 erste Ergebnisse erwarten. Da epidemiologische Arbeiten belegen, dass durch PSA-Screening eine nicht unerhebliche Überdiagnostik und Übertherapie eintritt, d. h. Schaden angerichtet werden kann, ist das Ergebnis der genannten randomisierten Studien vor weitergehenden Entscheidungen unbedingt abzuwarten. Bis dahin sollte von der Anwendung des PSA-Tests zur Prostatakrebsfrüherkennung unmissverständlich abgeraten werden. Da für den Test bereits ausgiebig Werbung betrieben wurde, kommt einer gründlichen ärztlichen Aufklärung von an dem Test interessierten Personen eine Schlüsselrolle zu.