多发性骨髓瘤肾损害10例临床分析

目的：探讨多发性骨髓瘤（multiple myeloma,MM)肾损害的误漏诊原因并提出避免误漏诊的要点。方法：对1989年6月－1999年6月住院的MM患者中10例并肾损害者进行临床分析。结果：首发症状缺乏特异性，误诊率80％，结论：对于有原因不明的贫血，骨痛，蛋白尿，高球蛋白血症和骨折，应及时进行本周氏蛋白，免疫球蛋白及免疫电泳测定，多部位的骨髓穿刺和骨X线摄片，避免误漏诊。     

多发性骨髓瘤肾损害的临床特征和相关因素分析

目的分析多发性骨髓瘤肾损害的临床特征,探讨其发生肾损害的相关因素。方法对84例多发性骨髓瘤患者的实验室检查结果和临床特征进行回顾性分析。结果多发性骨髓瘤患者的肾损害发生率为53.6%。临床症候群为孤立性蛋白尿、肾功能不全、溶骨性损害、中重度贫血、M蛋白阳性、高血压和尿苯周氏蛋白阳性。发生肾损害的独立危险因素为中重度贫血、高钙血症、血清M蛋白水平和男性。结论多发性骨髓瘤肾损害临床特征以孤立性蛋白尿最为常见,其次为肾功能不全。中重度贫血、高钙血症、血清M蛋白水平及男性是多发性骨髓瘤肾损害主要危险因素。     

多发性骨髓瘤相关肾损害的危险因素

目的:分析多发性骨髓瘤相关肾损害的危险因素。方法:回顾性分析2009年1月-2013年12月我院收治的多发性骨髓瘤89例患者资料。将患者分为A组（肾功能正常）57例,B组（肾功能损害）32例,各因素首先采取单因素分析,对具有统计学意义的因素进一步采取非条件多因素Logistic回归分析。结果:单因素分析显示,两组患者Hgb、血Ca、血P、血URIC、血清β2-MG、尿本周氏蛋白、轻链类型、感染以及肾毒性药物九个因素比较,差异具有统计学意义（P＜0.05）。对上述单因素具有统计学意义的八个因素进行多因素Logistic回归分析,血Ca、轻链类型以及Hgb三个因素进入回归模型（P＜0.05）。结论:肾损害是多发性骨髓瘤患者的主要表现,高血钙、单克隆免疫球蛋白游离轻链类型以及贫血是多发性骨髓瘤患者发生相关性肾损害的独立危险因素。     

多发性骨髓瘤肝占位1例报道

多发性骨髓瘤（MM）是一种以骨髓浆细胞异常增生为特征的恶性肿瘤。并伴有单克隆免疫球蛋白和轻链蛋白异常增高。MM起病隐匿,症状多样,临床上容易误诊,主要临床表现为转移性骨痛、贫血、肾脏损害和感染等,其侵袭部位以骨和淋巴结多见,但以肝转移和黄疸为主要表现的非常少见。现报道1例,并结合国内外文献对其临床特点进行分析,以加强对本病的认识。     

多发性骨髓瘤误诊3例临床分析

目的：研究多发性骨髓瘤（MM）的临床特征,误诊原因。方法：对我院误诊的3例多发性骨髓瘤病例进行回顾性分析。结果：MM首发症状与临床表现复杂多变,极易误诊、漏诊。结论：对MM的临床表现要综合分析,外周血涂片形态学检查可为临床提供重要参考,骨髓细胞学检查及骨髓活组织检查是确诊的首要方法。完善MM相关检测对避免误诊有重要意义。     

多发性骨髓瘤误诊原因探讨(附34例分析)

目的　探讨多发性骨髓瘤误诊原因 ,提高对其临床表现的认识 ,减少误诊。方法　回顾性分析 34例多发性骨髓瘤误诊经过。结果　 18例误诊为腰肌劳损、老年人退行性骨质增生、风湿性关节炎 ,5例误诊为冠心病 ,3例上呼吸道感染、肺炎 ,4例误诊为慢性肾炎、肾功能不全 ,3例误诊为缺铁性贫血 ,1例误诊为原发性甲状腺功能亢进症。结论　由于浆细胞侵犯骨髓部位不同 ,致使其临床表现多种多样。故凡具有药物不能抑制的骨关节疼痛 ,不明原因的中老年人贫血、血沉加快、蛋白尿、高钙血症、反复发生的感染等均应作必要实验室检查、X线检查及SPECT全身骨扫描 ,以免误诊     

多发性骨髓瘤诊断与治疗进展

骨髓瘤常为多发,偶有单发,一般系指多发性骨髓病(MM),为与孤立性骨髓瘤区别,有人称MM为骨髓瘤病.本病起源于骨髓腔组织,由浆细胞的恶变而来的恶性肿瘤,故又称浆细胞肉瘤.肿瘤局限于骨内,浸润骨骼,引起骨骼破坏,高血钙,产生M蛋白,主要是球蛋白的增高和出现异常球蛋白,同时还可因蛋白物质阻塞肾小管,引起肾功能损害(骨髓瘤肾),并引起相应的临床表现如贫血,免疫缺陷而发的感染及并发的淀粉样变和凝血障碍以及骨外病变等一系列复杂问题.     

多发性骨髓瘤肾损害10例临床分析

目的 :探讨多发性骨髓瘤 (multiplemyeloma ,MM)肾损害的误漏诊原因并提出避免误漏诊的要点。方法 :对 1989年 6月～ 1999年 6月住院的MM患者中 10例并肾损害者进行临床分析。结果 :首发症状缺乏特异性 ,误诊率 80 %。结论 :对于有原因不明的贫血、骨痛、蛋白尿、高球蛋白血症和骨折 ,应及时进行本周氏蛋白、免疫球蛋白及免疫电泳测定 ,多部位的骨髓穿刺和骨X线摄片 ,避免误漏诊。     

硼替佐米在多发性骨髓瘤治疗中的应用

摘 要：多发性骨髓瘤（MM）是一种浆细胞恶性肿瘤,其特征是骨髓中浆细胞克隆性增殖,分泌单克隆免疫球蛋白或其片段（M蛋白）,同时伴有广泛的溶骨病变及贫血、感染、肾功能损害等临床表现。硼替佐米是一种新型的蛋白酶体抑制剂,通过全新机制达到抗骨髓瘤作用。临床上硼替佐米单药及同其他常规化疗药物组成的联合方案对初治、复发/难治的MM患者均取得了良好的疗效。全文就硼替佐米治疗多发性骨髓瘤的临床进展作一综述。     

多发性骨髓瘤误诊原因探讨（附34例分析）

目的 探讨多发性骨髓瘤误诊原因，提高对其临床表现的认识，减少误诊。方法 回顾性分析34例多发性骨髓瘤误诊经过。结果 18例误诊为腰肌劳损、老年人退行性骨质增生、风湿性关节炎，5例误诊为冠心病，3例上呼吸道感染、肺炎，4例误诊为慢性肾炎、肾功能不全，3例误诊为缺铁性贫血，1例误诊为原发性甲状腺功能亢进症。结论 由于浆细胞侵犯骨髓部位不同，致使其临床表现多种多样。故凡具有药物不能抑制的骨关节疼痛，不明原因的中老年人贫血、血沉加快、蛋白尿、高钙血症、反复发生的感染等均应作必要实验室检查、X线检查及SPECT全身骨扫描，以免误诊。     

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.     

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.     

Large-scale molecular characterization and analysis of gastric cancer

The recent effort by The Cancer Genome Atlas （TCGA） Network has revealed that gastric cancer, which is a leading cause of cancerrelated deaths worldwide with a 5-year survival rate less than 25%, is a much more heterogeneous disease than previously thought. And yet, conventional treatment approaches and clinical trials have assumed it is a single disease. Although it is well known that under the microscope, gastric cancer cells appear quite different, the current classification scheme recognizes two main categories of gastric cancer： diffuse and intestinal.     

A conceptually new treatment approach for relapsed glioblastoma: Coordinated undermining of survival paths with nine repurposed drugs (CUSP9) by the International Initiative for Accelerated Improvement of Glioblastoma Care

To improve prognosis in recurrent glioblastoma we developed a treatment protocol based on a combination of drugs not traditionally thought of as cytotoxic chemotherapy agents but that have a robust history of being well-tolerated and are already marketed and used for other non-cancer indications. Focus was on adding drugs which met these criteria: a) were pharmacologically well characterized, b) had low likelihood of adding to patient side effect burden, c) had evidence for interfering with a recognized, well-characterized growth promoting element of glioblastoma, and d) were coordinated, as an ensemble had reasonable likelihood of concerted activity against key biological features of glioblastoma growth. We found nine drugs meeting these criteria and propose adding them to continuous low dose temozolomide, a currently accepted treatment for relapsed glioblastoma, in patients with recurrent disease after primary treatment with the Stupp Protocol. The nine adjuvant drug regimen, Coordinated Undermining of Survival Paths, CUSP9, then are aprepitant, artesunate, auranofin, captopril, copper gluconate, disulfiram, ketoconazole, nelfinavir, sertraline, to be added to continuous low dose temozolomide. We discuss each drug in turn and the specific rationale for use- how each drug is expected to retard glioblastoma growth and undermine glioblastoma''s compensatory mechanisms engaged during temozolomide treatment. The risks of pharmacological interactions and why we believe this drug mix will increase both quality of life and overall survival are reviewed.     

Endometrial cancers and predisposition

As nearly 5% of all endometrial cancers occur because of a predisposition, this possibility has systematically to be explored. The hallmarks of predisposition, a young age at diagnosis, a personal or a familial history of cancer, have to be searched systematically. The identification of a predisposition in a family has a major impact on the management of the proband or his relatives. The endometrial cancer main predisposition is Lynch's syndrome. In this review, we will focus on this condition and describe its clinical manifestations, the underlying molecular mechanisms, the cancer risks and the management guidelines. We will also get onto some far less frequent other predispositions.