Simultaneous bilateral occurrence of a mixed mesodermal tumor and cystadenocarcinoma in the ovary

The mixed mesodermal tumor is a very uncommon malignancy. The aggressiveness of this lesion is illustrated by extremely poor prospects for afflicted patients: postoperative survival is usually shorter than 24 months. According to the literature, malignant mixed tumor of the ovary is rather rare and its occurrence with other malignancy is exceptional. We report here a case of a 62-years old woman with serous cystadenocarcinoma in the right ovary and a heterologous malignant mixed mesodermal tumor in the left one. Both tumors expressed cytokeratins, while only the mesodermal tumor expressed S-100 and focal NSE.(Pathology Oncology Research Vol 10, No 2, 117–120)     

Combined typical carcinoid and acinic cell tumor of the lung: a heretofore unreported occurrence

We report a primary combined typical carcinoid and acinic tumor of the lung in a 70-year-old man. Although a similar case was reported previously, to the best of our knowledge this is the first case in which the diagnosis is supported by both immunohistochemical and ultrastructural findings. We review the literature and discuss the implications of this finding.     

Molecular investigation of hepatitis E virus infection in patients with acute hepatitis in Kathmandu,Nepal

One hundred fifty-four consecutive patients with sporadic acute hepatitis, who were seen at a city hospital in the Kathmandu valley of Nepal in 1997, were studied. IgM antibodies to hepatitis A virus were detected in four patients (3%), IgM antibodies to hepatitis B core in four patients (3%), hepatitis B surface antigen in 20 (13%), and hepatitis C virus RNA in four patients (3%). IgM antibodies to hepatitis E virus (HEV) (anti-HEV IgM) and HEV RNA were detected in 77 (50%) and 48 (31%), respectively. Consequently, 86 patients (56%) including nine HEV-viremic patients without anti-HEV IgM, were diagnosed with hepatitis E. The cause of hepatitis was not known in 53 patients (34%). All 48 HEV RNA-positive samples were genotyped as 1, and subtyped further as 1a in 17 (35%), 1c in 29 (60%), and mixed infection of 1a and 1c in 2 (4%). A seasonal difference in the prevalence of HEV subtypes was recognized. Before the rainy season (January to July), both 1a and 1c isolates were found: the intrasubtypic difference was up to 9.0% and 1.7%, respectively, in the 412-nucleotide sequence of open reading frame 2. During the rainy season (August), only 1c isolates (n = 17) with 99.5-100% identity were found; 13 of 17 isolates had the same sequence, being identical to the 3 isolates that emerged at the end of July. These results suggest that a particular HEV 1c strain spread widely during the rainy season and was implicated in a small epidemic in the Kathmandu valley in August 1997.     

Malignant mixed mullerian tumour of the ovary: prognostic factor and response of adjuvant platinum-based chemotherapy

OBJECTIVES: The purpose of the present study was to analyse retrospectively the data of a series of patients presenting to our unit with malignant mixed mullerian tumour (MMMT) of the ovary to identify the prognostic factors and relate them to survival. The role of platinum-based chemotherapy in the adjuvant treatment of this tumour was also evaluated. METHODS: All patients diagnosed with MMMT of the ovary from 1987 to 2000 were identified from the gynaecological tumour registry of King George V Hospital, Australia. The effect of clinical and histopathological variables on survival was analysed. The response of platinum-based adjuvant chemotherapy after surgery was also evaluated. RESULTS: Twenty patients with MMMT of the ovary were identified. Of the six patients with measurable disease, two (33%) had complete response after adjuvant platinum-based chemotherapy. The median survival of all patients was 8 months, while that of the patients receiving adjuvant platinum-based chemotherapy was 23 months. Women who were older (> 65 years) had a significantly worse survival rate than those who were younger (P = 0.02). The patients with optimal debulking had a better median survival than those with suboptimal debulking, but this difference was not statistically significant (P = 0.21). Sarcomatous component (homologous vs heterologous) was not found to be a significant prognostic factor for predicting survival. CONCLUSIONS: Malignant mixed mullerian tumour of the ovary is a rare and aggressive gynaecological tumour. The current study indicates that patient age was a significant prognostic factor for survival and surgical cytoreduction combined with platinum-based chemotherapy is the most effective management regimen identified to date to treat MMMT of the ovary.     

Sterically Stabilized Phospholipid Mixed Micelles: In Vitro Evaluation as a Novel Carrier for Water-Insoluble Drugs

Purpose. Sterically stabilized phospholipid micelles (SSMs) composed of poly(ethylene glycol-2000)-grafted distearoyl phosphatidylethanolamine (PEG(2000)-DSPE) are new and promising lipid-based carriers for water-insoluble drugs. This study investigates and compares sterically stabilized mixed micelles (SSMM), composed of (PEG(2000)-DSPE) plus egg-phosphatidylcholine, with SSM as a novel delivery system for improved solubilization of water-insoluble drugs using paclitaxel as a model. Methods. Paclitaxel was solubilized in SSM (P-SSM) and SSMM (P-SSMM) by coprecipitation and rehydration with isotonic 0.01M HEPES buffer, pH 7.4. After separation of excess drug by centrifugation, mean particle size and morphology of particles in the supernatant were determined by quasi-elastic light scattering and transmission electron microscopy. The solubilization potentials of SSMM and SSM for paclitaxel were determined by reverse phase high pressure liquid chromatography (RP-HPLC). Cytotoxic activity of paclitaxel in SSMM, SSM, and dimethyl sulfoxide (10% DMSO) was determined against human breast cancer cells (MCF-7). Results. Mean hydrodynamic diameter of P-SSMM and P-SSM were 13.1 ± 1.1 nm and 15 ± 1 nm (n = 3), respectively. SSMM solubilized 1.5 times more paclitaxel than SSM for the same total lipid concentration. Solubilized paclitaxel amount increased linearly with an increase in lipid concentration. A therapeutically relevant lipid concentration (15 mM) of SSMM solubilized 1321 ± 48g/ml of paclitaxel. Paclitaxel in the absence of sufficient SSM aggregated to form lipid-coated crystals. P-SSMM, P-SSM, and paclitaxel in DMSO had comparable cytotoxic activities against MCF-7 cells. Conclusions. SSMM showed increased solubilization potential compared with SSM while retaining all of its own advantages. Therefore, it can be used as an improved lipid-based carrier for water-insoluble drugs.     

Optimization of Individual and Population Designs Using Splus

We address the problem of design optimization for individual and population pharmacokinetic studies. We develop Splus generic functions for pharmacokinetic design optimization: IFIM, a function for individual design optimization similar to the ADAPT II software, and PFIM_OPT, a function for population design optimization which is an extension of the Splus function PFIM for population design evaluation. Both evaluate and optimise designs using the Simplex algorithm. IFIM optimizes the sampling times in continuous intervals of times; PFIM_OPT optimizes either, for a given group structure of the population design, only the sampling times taken in some given continuous intervals or, both the sampling times and the group structure, performing then statistical optimization. A combined variance error model can be supplied with the possibility to include parameters of the error model as parameters to be estimated. The performance of the optimization with the Simplex algorithm is demonstrated with two pharmacokinetic examples: by comparison of the optimized designs to those of the ADAPT II software for IFIM, and to those obtained using a grid search or the Fedorov-Wynn algorithm for PFIM_OPT. The influence of the variance error model on design optimization was investigated. For a given total number of samples, different group structures of a population design are compared, showing their influence on the population design efficiency. The functions IFIM and PFIM_OPT offer new efficient solutions for the increasingly important task of optimization of individual or population pharmacokinetic designs.     

Hepatobiliary elimination of bile acid-modified oligodeoxynucleotides in Wistar and TR- rats: evidence for mrp2 as carrier for oligodeoxynucleotides

As therapeutic antisense tools, oligonucleotides (ODNs) must enter cells to bind to their target structures. ODNs distribute in nearly each tissue with relatively high concentrations in kidney and liver from where excretion into urine and bile occurs. To investigate mechanisms involved in hepatic ODN transport, normal mixed backbone phosphodiester/phosphorothioate ODNs (n-ODN) and two different bile acid-conjugated mixed backbone ODNs (1BA-ODN and 2BA-ODN) were applied to two different rat strains, normal Wistar rats and Wistar TR- rats. In normal Wistar rats, concentration-dependent hepatobiliary elimination of the ODNs was observed with a remarkable increase of excretion of the cholic acid BA-ODN conjugates. In contrast to normal Wistar rats, n-ODN excretion into bile by TR- rats, a mutant Wistar rat strain lacking a functional multidrug resistance-associated protein 2 (mrp2) at the canalicular membrane, was strongly diminished, whereas these rats excreted an ODN conjugated with two cholic acid molecules (2BA-ODN) into bile. Concomitant application of substrates transported by mrp2 such as bromosulfophthalein (BSP) or the synthetic chlorogenic acid derivative S 3025 significantly reduced the biliary appearance of normal ODN and 2BA-ODN in Wistar rats and also in TR- rats. To inhibit the expression of cRNA derived from the Na+ -dependent taurocholate cotransporting polypeptide (Ntcp), antisense ODNs were constructed which fully retained the antisense properties when coupled with two bile acid molecules. The results indicate that ODNs are secreted via the mrp2 into bile. In the absence of mrp2, further excretory transport systems with affinity for bile acids seem to be relevant for their excretion. The results further indicate that bile acid tagged ODNs are useful tools for liver specific antisense therapy.     

北京地区108例SARS患者临床特征、治疗效果及转归分析

目的　分析北京地区SARS的临床特征及转归。方法　分析 2 0 0 3年 3月 1 1日至 4月1 5日收治的 1 0 8例SARS患者的临床资料。结果　男性 35例 (32 4% ) ,女性 73例 (67 6 % )。年龄1 3～ 83(37± 9)岁。医务人员 31例 (2 8 7% )。 94例 (87 0 % )有明确接触史。 2 2例 (2 0 4% )并存其他内科疾病。主要临床表现为发热、咳嗽、胸痛、胸闷、头痛等。多脏器受累多见。潜伏期 2～ 1 4d。有隐性感染者。轻型 5例 (4 6 % ) ,普通型 43例 (39 8% ) ,重型 2 2例 (2 0 4% ) ,极重型 38例(35 2 % )。典型病程临床呈早期、进展期、极期、恢复期四期经过。发病早期白细胞总数、淋巴细胞总数和比值、前白蛋白、转铁蛋白明显下降 ,C反应蛋白、α酸性糖蛋白和α2 球蛋白明显升高 ,CD+ 3、CD+ 4、CD+ 8细胞下降。X线胸片早期见肺内单发或多发局灶性渗出改变 ,多位于肺下野 ;进展期磨玻璃影或实变影增大。高分辨率CT表现为单发或多发“棉花团”样磨玻璃影或实变影。低氧血症较多。在疾病的进展期、极期合理使用激素和早期使用无创机械通气可阻止病情进展。抗生素可预防继发感染。 4例 (3 7% )遗留肺间质纤维化。 94例好转恢复出院 ,1 4例死亡。中医认为SARS属于温病 ,中西医结合治疗能减轻中毒症状 ,有助于恢复期患者     

北京地区首批SARS病人的发病特点和临床诊治

目的 总结北京地区首批发病的传染性非典型肺炎(SARS)的流行特点、发病特征和临床诊治的体会。方法 对2003年3—4月间我院收治的29例SARS患者(男11例,女18例,年龄范围20～74岁)的发病病程、临床诊断和治疗以及实验室检测方面的资料进行分析。结果 北京地区首批输入性的SARS病例具有明显的家庭和医护人员聚集发病的特点,潜伏期2—14d,20—50岁之间的青壮年人占发病人数的89．4％(26／29);患者以呼吸道飞沫和密切接触方式为主;首发症状为高热(38℃以上),并伴有文献报道的临床症状。进行肺部胸片或CT的动态检查有利于揭示肺部进行性病变,在指导诊断、治疗和疗效的判断等方面有重要帮助。包括利巴韦林抗病毒治疗在内的综合治疗(包括一般支持治疗、对症治疗、给氧、抗生素和激素的应用)具有较好的治疗效果。除了2例病人死亡以外,其余26例患者全部康复出院(死亡率为6．89％)。我们对1例患者(74岁)回输SARS病人恢复期的血浆(50ml),患者在发病的第21天完全恢复,但有关机制问题尚待研究。结论 临床观察表明SARS是一种急性、自限性传染病。我们认为早期特异性诊断、包括抗病毒和激素应用在内的综合治疗可能直接影响SARS的病程和预后;此外加强有效的防护措施,能显著减少医务人员的感染率。