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In order to explore the application of machine learning algorithm to intelligent analysis of big data in an artificial intelligence (AI) environment, make cognitive computing meet the requirements of AI and better assist humans to carry out data analysis, first, the theoretical basis of machine learning algorithm is elaborated. Then, a cognitive computational model based on the machine learning algorithm is proposed, including the essence, principle, function, training method of deep belief network (DBN) algorithm, as well as the joint use of DBN algorithm and multilayer perceptron. Finally, the proposed algorithm is simulated. The results show that under the same parameter conditions, the accuracy rate of the DBN algorithm combined with multilayer perceptron is higher than that of the DBN algorithm; when the number of units is >40, the accuracy rate of the DBN algorithm combined with multilayer perceptron is significantly higher than that of the DBN algorithm; when the number of units is 30, the best effect can be obtained, and the error rate is

Descripció del recurs: 27 juliol 2022 The aim of this book on artificial intelligence for architects and designers is to guide future designers, in general, and architects, in particular, to support the social and cultural wellbeing of the humanity in a digital and global environment. This objective is today essential but also extremely large, interdisciplinary and interartistic, so we have done just a brief introduction of the subject. We will start with the argument fixed by the Professor Jonas Langer in his web some years ago, that we have defined as: “The Langer’s Tree”.

Cognitive impairment is present in up to 65% of Relapsing Remitting Multiple sclerosis (RRMS) patients and can be extremely debilitating. Although deficits in episodic memory and processing speed occur more frequently than executive deficits, executive dysfunction tends to have a significant impact on MS patients' ability to generate strategies, think divergently, solve and estimate problems, and reason in abstract terms with substantial negative impacts on activities of daily living. In the present study we investigated perfusion detection rate and pattern, as well as the association between perfusion rates and cognitive dysfunction in cognitively impaired RRMS patients.We present findings from 17 cognitively impaired RRMS patients who were evaluated with a comprehensive neuropsychological battery and additionally evaluated by brain perfusion radiopharmaceutical technetium-99m hexamethyl-propylene amine oxime (RRMS patients had hypoperfusion in several predefined Brodmann areas and lobes of the brain, relatively to demographically matched healthy controls according to an established normative database NeuroGam™. However, we noted blood flow reduction, mainly in the frontal lobes and other related prefrontal areas, involving both hemispheres, but with asymmetric left hemisphere predominance. Moreover, associations between measures of response inhibition, set shifting (executive functions) and severity of hypoperfusion in the left frontal lobes were also established.Cerebral hypoperfusion is an integral feature of MS pathology. Executive dysfunction is associated with robust cerebral perfusion deficits in the frontal and prefrontal cortex of cognitively impaired RRMS patients.

Serum erythropoietin (Epo) levels are influenced by the integrity of renal function, the severity and etiology of anemia, the percentage of hemoglobin F and other factors. We aimed to create a parametric expression for the response to anemic/hypoxic stress and we evaluated serum Epo levels in 1096 subjects with normal renal function, of whom 837 were anemic (Hb 16.5 g/dl). Hb ranged between 3.6 and 23.8 g/dl and the corresponding Epo between

La reconsideración de la educación arquitectónica a la luz de una nueva realidad que surge de los rápidos cambios que se producen en nuestros entornos sociales, culturales y físicos es ahora imperativa. Para conocer las incompatibilidades de las estructuras educativas existentes con la dinámica actual del cambio, se examinan tres aspectos principales de nuestra educación arquitectónica contemporánea: el sistema de estudios, los contenidos de los estudios y la pedagogía del diseño arquitectónico implementado por las Escuelas de Arquitectura.En cuanto al sistema de estudios, entre otras cuestiones, especulamos sobre la agilidad limitada del sistema para albergar innovaciones, sus concepciones dominantes sobre el perfil del profesor, su forma poco clara de definir el perfil del graduado y la oscura relación entre la academia arquitectónica y la práctica profesional. En cuanto al contenido de los estudios, entre otras cuestiones, especulamos sobre el empobrecimiento de las humanidades en los estudios arquitectónicos que provocó un tecnicismo pasivo que, fascinado por las herramientas digitales, esteriliza la arquitectura de sus valores y significados culturales y humanos.Otras observaciones se refieren a la pedagogía actual y sus reservas sobre el temor a la confusión y la asunción de riesgos, a la rigidez metodológica de la educación basada en lo que está mal y no en lo especulativo, en la actitud hacia ) Simplifican la complejidad, la inclinación pasiva y la docilidad hacia las certezas, la resistencia al cambio, la revisión o la renovación de las prácticas docentes.El trabajo concluye presentando las líneas básicas de las prioridades que la educación arquitectónica tiene que considerar para poder seguir críticamente el nuevo paradigma surgido y impuesto por los nuevos entendimientos filosóficos de nuestro mundo y la consideración de la nueva normalidad que se atribuye a Como una nueva declaración ética que afecta profundamente la contemplación arquitectónica y la práctica. La reconsideració de l'educació arquitectònica a la llum d'una nova realitat que sorgeix dels ràpids canvis que es produeixen en els nostres entorns socials, culturals i físics és ara imperativa. Per conèixer les incompatibilitats de les estructures educatives existents amb la dinàmica actual del canvi, s'examinen tres aspectes principals de la nostra educació arquitectònica contemporània: el sistema d'estudis, els continguts dels estudis i la pedagogia del disseny arquitectònic implementat per les Escoles d'Arquitectura.Pel que fa al sistema d'estudis, entre altres qüestions, especulem sobre l'agilitat limitació sistema per albergar innovacions, les seves concepcions dominants sobre el perfil del professor, la seva forma poc clara de definir el perfil del graduat i la fosca relació entre l'acadèmia arquitectònica i la pràctica professional. Pel que fa al contingut dels estudis, entre altres qüestions, especulem sobre l'empobriment de les humanitats en els estudis arquitectònics que va provocar un tecnicisme passiu que, fascinat per les eines digitals, esterilitza l'arquitectura dels seus valors i significats culturals i humans.Altres observacions es refereixen a la pedagogia actual i les seves reserves sobre la por a la confusió i l'assumpció de riscos, a la rigidesa metodològica de l'educació basada en el que està malament i no en el especulatiu, en l'actitud cap) Simplifiquen la complexitat , la inclinació passiva i la docilitat cap a les certeses, la resistència al canvi, la revisió o la renovació de les pràctiques docents.El treball conclou presentant les línies bàsiques de les prioritats que l'educació arquitectònica ha de considerar per poder seguir el nou paradigma sorgit i imposat pels nous enteniments filosòfics del nostre món i la consideració de la nova normalitat que s'atribueix a Com una nova declaració ètica que afecta profundament la contemplació arquitectònica i la pràctica. The reconsideration of architectural education in light of a new reality emerging from the fast changes occurring in our social, cultural and physical environments is now imperative. In order to divulge the incompatibilities of the existing educational structures with the current dynamics of change, three main aspect of our contemporary architectural education are examined: the system of studies, the contents of studies and the architectural design pedagogy implemented by Schools of Architecture.Concerning the system of studies, amongst other issues we speculate on the limited agility of the system to host innovations, its dominant conceptions about the teacher’s profile, its unclear way to define the profile of the graduate and the obscure relationship between architectural academia and professional practice. As to the content of studies amongst other issues we speculate on the impoverishment of humanities in architectural studies that caused a passive technicality which, fascinated by the digital tools, sterilizes architecture from its cultural and human values and meanings.Further observations concern current pedagogy and its reservations on the fear for mistake-making and risk-taking, on the methodological rigidity of design education founded on what is wrong and on not what could be done on a speculative basis, on the attitude to (over)simplify complexity, on the passive inclination and docility towards certainties, on the resistance to change, revisit or renew teaching practices.The paper concludes by presenting the basic lines of the priorities architectural education has to consider in order to be able to critically follow the new paradigm emerging from and imposed by the new philosophical understandings of our world and the consideration of the new normal that is ascribed to them as a new ethical statement that profoundly affects architectural contemplation and practice.

Aim: KW-2170 is a novel pyrazoloacridone derivative that intercalates nucleic acids. It has promising in vitro properties against prostate and other cancers and is active in vivo against doxorubicin-resistant cell lines. We wished to investigate its activity and toxicity profile in this Phase II trial in androgen independent prostate cancer. Methods: Overall 44 men were recruited to this multicenter, open label, non-randomized study, with 35 evaluable for prostatic specific antigen (PSA) response. Results: Five patients had a PSA fall greater than 50% (overall RR 14.3%, 95% CI 4.8–30.3%). Overall median survival was 16 months. In the evaluable group (n = 35), median survival was 18.9 months. The drug was very well tolerated, with the most common toxicities being hematological (anemia, leucopenia, thrombocytopenia), alopecia, fatigue, and nausea. However, most of these were National Cancer Institute Grade 1 or 2; Grade 3 neutropenia occurred in only 11% of patients, and there was no Grade 4 neutropenia. Quality of life as measured by the FACT–P scale was not compromised. Conclusion: KW-2170 is a very well tolerated chemotherapy agent. It has a relatively low PSA response rate, and did not meet the pre-specifed criteria for further studies.

El material bàsic de l’arquitectura són les idees; idees sobre el món real i la posició de l’ésser humàen ell. Els canvis d’aquestes idees a mesura que avança el temps afecten la manera de com percebem,concebem i creem arquitectura. Les idees s’estructuren en els valors que guien la formulació de principis,a través dels quals es creen formes arquitectòniques. Per tal d’entendre l’arquitectura d’un cert períodede temps, cal entendre el sistema de valors que governa aquest període de temps específic i com afectales maneres en què la vida és representada en l’espai a través de l’arquitectura. En una invitació perdefinir la característica més significant del nostre temps que afecta la generació de noves idees i valors,la resposta podria trobar-se en tres nocions; les més importants: velocitat, complexitat i predictibilitat., Ideas are the primary material of architecture; ideas about the real world and the position of human beings in it. Changes in these ideas over time affect the way that architecture is perceived, conceived and created. These ideas are based on values that guide the way in which the principles for the creation of architectural forms are formulated. In order to understand the architecture of a certain period of time, it is necessary to understand the value system that governs the respective period and affects the ways in which life is represented in space by means of architecture. In an attempt to define the most significant feature affecting the generation of new ideas and values in our times, three central notions are identified: speed, complexity and predictability., El material básico de la arquitectura son las ideas; ideas sobre el mundo real y la posición delser humano en él. Los cambios de estas ideas a medida que avanza el tiempo afectan la manerade cómo percibimos, concebimos y creamos arquitectura. Las ideas se estructuran en los valoresque guían la formulación de principios, a través de los cuales se crean formas arquitectónicas.Para entender la arquitectura de un cierto período de tiempo, es necesario entender el sistemade valores que gobierna este período de tiempo específico y cómo afecta a las formas en que lavida es representada en el espacio a través de la arquitectura. En una invitación para definir lacaracterística más significante de nuestro tiempo que afecta a la generación de nuevas ideasy valores, la respuesta podría encontrarse en tres nociones; las más importantes: velocidadcomplejidad y predictibilidad.

Purpose: To test the hypothesis that therapy of intermediate- and high-grade (excluding Burkitt lymphoblastic) lymphoma with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) could be safely dose-intensified with routine filgrastim support. Patients and Methods: Eligible patients were those who were previously untreated and who had either bulky stage II, or stage III or IV lymphoma with working formulation histology D, E, F, G, H, or J; performance status ≤ 2; and acceptable end organ function. No upper age limit was specified. Therapy was dose-intensified CHOP (CHOP-DI) with filgrastim support. Each course was repeated every 14 days for six planned courses. Results: Eighty-eight eligible patients were treated with CHOP-DI and had a median follow-up of 5.1 years on this phase II study, designated Southwest Oncology Group (SWOG) 9349. The progression-free survival was 51% at 2 years and 41% at 5 years. The overall survival was 60% at 5 years. Three fatal treatment-related events occurred. One patient with myelodysplastic syndrome was reported. Conclusion: Treatment with CHOP-DI can be safely administered in the cooperative group setting and results in improved survival. Estimated overall survival at 5 years was 14% better than that of patients treated with standard-dose CHOP in an earlier SWOG study, although progression-free survival of 60% at 2 years—the prespecified end point—was not achieved. CHOP-DI, given every 2 weeks at escalated doses, is a strategy that should be tested in a future randomized clinical trial in lymphoma.

Purpose: To determine the efficacy of combination fludarabine and mitoxantrone (FN) in untreated stages III and IV low-grade lymphoma. The major end point was to estimate progression-free survival (PFS) in all eligible patients. Patients and Methods: Seventy-eight eligible patients were registered. Chemotherapy courses were administered every 4 weeks with mitoxantrone 10 mg/m2 on day 1 and fludarabine 25 mg/m2 on days 1, 2, and 3 for a total of six to eight cycles. Pneumocystis carinii prophylaxis was required. Results: Seventy-three patients (94%) attained an objective response. Complete remission was demonstrated in 34 patients (44%) and partial remission was demonstrated in 39 patients (50%). With a median follow-up time of 5.5 years, the median PFS was 32 months, with a 4-year PFS rate of 38%. Median survival has not been reached and 88% of all patients are alive at 4 years. The application of the International Prognostic Index and serologic staging showed significant differences in PFS in all risk groups, whereas overall survival was markedly worse for the highest-risk group in either prognostic model. Three prior Southwest Oncology Group trials using a regimen of cyclophosphamide, doxorubicin, vincristine, and prednisone or a combination of prednisone, vincristine, methotrexate, cytarabine, cyclophosphamide, etoposide, nitrogen mustard, vincristine, procarbazine, and prednisone in similar patient populations demonstrated comparable clinical outcome, although the 4-year survival for FN was better. FN was well tolerated, but mild to severe reversible myelosuppression was noted. Other complications were rare. Conclusion: FN is an effective, safe chemotherapy combination for patients with advanced-stage, low-grade lymphoma. Clinical outcomes were comparable to prior published data using anthracycline-based regimens.

PURPOSE Cisplatin has played a major role in the treatment of non-small-cell lung cancer (NSCLC). This randomized trial was performed by the Southwest Oncology Group (SWOG) to determine whether the combination of vinorelbine and cisplatin has any advantage with regard to response rate, survival, and time to treatment failure over single-agent cisplatin in the treatment of patients with advanced NSCLC. METHODS Between October 1993 and April 1995, 432 patients with advanced stage NSCLC were randomized to receive arm I (cisplatin 100 mg/m2 every 4 weeks) or arm II (cisplatin 100 mg/m2 every 4 weeks and vinorelbine 25 mg/m2 weekly). All patients were chemotherapy-naive, had performance status (PS) 0 or 1, and had adequate hematologic, renal, and hepatic function. RESULTS Four hundred fifteen patients were eligible and assessable. On arm I (cisplatin), there was a 12% partial response rate. Arm II (cisplatin and vinorelbine) had a 26% response rate (2% complete responses and 24% partial responses, P = .0002). There was a statistically significant advantage with regard to progression-free survival (median, 2 v 4 months; P = .0001) and overall survival (median, 6 v 8 months; P = .0018) for the cisplatin and vinorelbine arm. One-year survival was 20% for cisplatin alone and 36% for the combination arm. There was more hematologic toxicity on arm II of the study (81% grades 3 and 4 granulocytopenia v 5% on arm I). Other toxicities, such as renal insufficiency, ototoxicity, and nausea and vomiting, and neuropathy were similar. CONCLUSION The results of this study indicate that the combination of cisplatin and vinorelbine is a superior treatment when compared with single-agent cisplatin in the treatment of advanced NSCLC. Cisplatin and vinorelbine is the new standard for SWOG against which new therapies will be evaluated.

This phase II trial investigated the activity and toxicity of CODE (cisplatin, vincristine, doxorubicin, etoposide) chemotherapy with the addition of granulocyte colony-stimulating factor (G-CSF) in patients who had chemotherapy-naive, advanced, or metastatic non-small-cell lung cancer. Treatment consisted of cisplatin, 25 mg/m2, administered weeks 1 through 9; vincristine, 1 mg/m2, weeks 1, 2, 4, 6, and 8; doxorubicin, 40 mg/m2, weeks 1, 3, 5, 7, and 9; and etoposide, 80 mg/m2 intravenously day 1 and 160 mg/m2 orally, days 2 and 3 on weeks 1, 3, 5, 7, and 9. Granulocyte colony-stimulating factor, 5 microg/kg, was administered subcutaneously on all days that patients were not receiving chemotherapy. From April 1992 through April 1993, 42 patients were entered on study. The principal toxicities were hematologic. Grade 3-4 anemia was seen in 21 patients. Grade 3-4 thrombocytopenia was seen in 9 patients. Grade 3-4 neutropenia occurred in 29 patients. Eight patients experienced a neutropenic febrile episode requiring antibiotics. Nonhematologic toxicities included weight loss and fatigue. Responses were seen in 10 of 42 patients, for an overall response rate of 24% (95% confidence interval, 12%-39%) and a median survival of 7.1 months. The CODE chemotherapy regimen has activity similar to other previously described cisplatin-based regimens, with a significant amount of both hematologic and nonhematologic toxicity. Its continued use in patients who have previously untreated non-small-cell lung cancer cannot be recommended, based on the results of this study.

BACKGROUND. In patients with advanced esophageal adenocarcinoma, the efficacy and palliative role of systemic chemotherapy are not well defined. The primary objective of this Phase II trial was to evaluate the antitumor activity and toxicity of a multiday chemotherapy schedule of high dose cisplatin and etoposide in patients with unresectable or metastatic esophageal adenocarcinoma. A secondary objective was to assess the efficacy of this regimen in palliating dysphagia. METHODS. Twenty-seven eligible patients with unresectable locoregional or metastatic esophageal adenocarcinoma were treated with cisplatin, 30 mg/m 2 /day, and etoposide, 60 mg/m 2 /day, intravenously daily for 5 days, every 3 weeks. After three cycles of chemotherapy, all patients were assessed for response. Patients with responding metastatic disease were given one additional cycle of chemotherapy, and patients with locoregional disease received radiation and concurrent continuous infusion of 5-fluorouracil at 300 mg/m 2 /day for the duration of radiation therapy. Patients were questioned about dysphagia symptoms initially and then weekly during chemotherapy. RESULTS. The major toxicities included myelosuppression, nausea and vomiting, and peripheral sensory neuropathy, with one treatment-related death. Major responses were observed in 13 patients (48% ; 95% confidence intervals, 36-74%), including 5 complete and 8 partial responses. Dysphagia relief occurred in 89% of 18 symptomatic patients within a median time of 16 days. The median survival duration for all patients was 9.8 months, and the actuarial 3-year survival rate was 22%. CONCLUSIONS. Multiday chemotherapy with high dose cisplatin and etoposide is active in patients with advanced esophageal adenocarcinoma. Toxicities associated with this regimen are substantial but manageable.

Background. We wanted to determine factors affecting survival rates of benefits to, and complications in patients with esophageal cancer treated with photodynamic therapy. Methods. From 1982 to January 1994, we used photodynamic therapy to treat 77 patients with esophageal carcinoma and evaluated survival to July 1994. All patients had failed, refused, or were ineligible for surgical intervention, ionizing radiation therapy, or chemotherapy. Results. The only significant variable affecting survival was clinical stage. Median survival after photodynamic therapy was as follows: all patients, 6.3 months (mean survival, 9.2 months); stage I, not reached; stage II, 12 months; stage III, 6.2 months; and stage IV, 3.5 months. For stages III and IV, a Karnofsky performance status of 70 or higher had a significant effect. For stage III, the median survival was 6.3 months when the Karnofsky performance status was equal to or greater than 70 and 3.5 months when it was less than 70. For stage IV, the median survival was 5.5 months when the Karnofsky performance status was equal to or greater than 70 and 2.5 months when it was lower than 70. Seven stage I patients with no treatment prior to photodynamic therapy had an estimated 5-year survival rate of 62%. Three patients with stage I invasive adenocarcinoma and Barrett's mucosa diagnosed when they underwent endoscopy for dysphagia were alive with no evidence of disease 17, 44, and 59 months after photodynamic therapy. Conclusions. Photodynamic therapy for esophageal carcinoma caused minimal complications and no procedure-related deaths. Photodynamic therapy can be considered an alternative treatment for patients with Barrett's esophagus with severe dysplasia or patients with stage I carcinoma who are under consideration for operation but are high surgical risks. The length of palliation for patients having "noncurative" treatment was equal to or better than that reported historically for most other treatment regimens.

From January 1992 through May 1993, 31 patients with adenocarcinoma of the pancreas or hepatocellular carcinoma were treated with weekly oral methotrexate (7.5 mg/M2 every 6 hours for 6 doses) and continuous oral AZT (200 mg four times daily). Patients were treated for a total of 6 months or until disease progression. The median age was 66 (range 44-79) and the median KPS was 80. No patient had received prior chemotherapy. Hematologic toxicity was severe with 50% of patients developing hemoglobins less than 8 gm/dl and 70% with granulocyte counts less than 1000 per mm3. One patient achieved a radiographic complete remission and 2 had stable disease. Two-thirds of patients progressed within 2 months of beginning therapy. The combination of methotrexate and AZT is an inactive regimen in pancreatic and hepatocellular carcinoma and is associated with considerable toxicity.

Background. The assessment of treatment efficacy in nonsmall cell lung cancer (NSCLC) is limited by the lack of a clear association between clinical response and survival. The prognostic usefulness of treatment-induced tumor-marker declines in NSCLC has not been established. The authors investigated the prognostic significance of treatment-induced declination in tumor marker levels of carcinoembryonic antigen, CA 19-9, and CA 125 in a group of patients with NSCLC treated with a brief course of cisplatin-based chemotherapy. Methods. Eighty-three patients with NSCLC enrolled on 2 related treatment protocols had pretreatment tumor-marker determinations. Patients were restaged 10 to 12 weeks after study entry, and clinical and marker responses were determined. Results. Thirty-eight patients (46%) had elevated pretreatment tumor markers, 36 (42%) of whom were evaluable for both clinical and marker responses. Pretreatment, the latter 36 individuals had measurable or evaluable disease, and at least one elevated tumor marker (greater than twice normal) ; posttreatment, they had follow-up measurements of both parameters. Of the 36 patients, 8 had normalization of tumor marker levels, 13 had 50-99% marker level declination, and 15 had less than 50% or no declination. In the same group of 36 patients, there were, 1 patient with complete clinical response, 11 with partial response, 19 with stable disease, and 5 with progressive disease. Marker responses occurred with equal frequency in clinical responders and nonresponders. There was no association between clinical response and survival, but there was a strong association between marker response and survival. Conclusions. In patients with nonsmall cell lung cancer with elevated pretreatment tumor marker levels, treatment-induced marker level declination can be a surrogate indicator for survival. Cancer 1995 ; 75 :1586-93.

KW-2170 is a novel pyrazoloacridone derivative that intercalates nucleic acids. It has promising in vitro properties against prostate and other cancers and is active in vivo against doxorubicin-resistant cell lines. We wished to investigate its activity and toxicity profile in this Phase II trial in androgen independent prostate cancer.Overall 44 men were recruited to this multicenter, open label, non-randomized study, with 35 evaluable for prostatic specific antigen (PSA) response.Five patients had a PSA fall greater than 50% (overall RR 14.3%, 95% CI 4.8-30.3%). Overall median survival was 16 months. In the evaluable group (n = 35), median survival was 18.9 months. The drug was very well tolerated, with the most common toxicities being hematological (anemia, leucopenia, thrombocytopenia), alopecia, fatigue, and nausea. However, most of these were National Cancer Institute Grade 1 or 2; Grade 3 neutropenia occurred in only 11% of patients, and there was no Grade 4 neutropenia. Quality of life as measured by the FACT-P scale was not compromised.KW-2170 is a very well tolerated chemotherapy agent. It has a relatively low PSA response rate, and did not meet the pre-specified criteria for further studies.

Summary Purpose To evaluate the efficacy of a novel multiday schedule of vinorelbine and cisplatin in patients with advanced NSCLC. Patients and methods Thirty patients were enrolled, including 27 patients with stage IV disease, and 11 patients with performance status of 2. They received a maximum of four chemotherapy cycles with cisplatin 20 mg/m2/day and vinorelbine 15 mg/m2/day intravenously (i.v.) for four consecutive days, every three weeks, with prophylactic filgrastim. Results Sixteen patients responded (53%, 95% confidence interval (95% CI): 34%–72%), including two complete and fourteen partial confirmed responses. Median survival for all patients was 8.1 months, with actuarial one-year and two-year survival rates of 40% and 15%. Despite prophylactic filgrastim, the delivered vinorelbine dose intensity of 16.8 mg/m2/week caused febrile neutropenia in 48% of patients (16% of cycles), resulting in one treatment-related death. Common nonhematologic toxicities included delayed emesis, asthenia, and constipation. Conclusions This multiday vinorelbine-cisplatin schedule is highly active against advanced NSCLC but results in frequent neutropenic complications. The myelotoxicity and antitumor efficacy of vinorelbine in NSCLC patients may be schedule-dependent.

We report a case of thrombotic thrombocytopenic purpura (TTP) with cardiac involvement, imaged with Tc-99m depreotide. A 56-year-old man presented with fever, hematuria, and chest pain. Laboratory findings (angiopathic hemolytic anemia, thrombocytopenia, and uremia) were suggestive of TTP. Cardiac enzymes were elevated and diffuse left ventricular hypokinesis was demonstrated by echocardiography. Serum rheumatologic and virologic analysis were negative. A Tc-99m depreotide SPECT/CT study showed diffuse uptake in the myocardium, indicating inflammatory reaction to thrombotic/hemorrhagic myocardial damage. We suggest that Tc-99m depreotide imaging may reveal myocardial involvement in TTP; this could prompt further investigation for potential applications in myocarditis of other etiologies.

Background This phase II study (S9718) evaluated the antineoplastic activity and tolerability of the combination of gemcitabine and cisplatin in previously untreated patients with extensive stage small cell lung cancer (ES-SCLC). Methods Chemonaive patients with ES-SCLC, received gemcitabine 1250 mg/m 2 intravenously (IV) over 30 minutes on days 1 and 8 and cisplatin 75 mg/m 2 IV over 30 to 60 minutes on day 1. Treatments were repeated every 21 days for a maximum of six cycles. Results A total of 88 patients were enrolled in the study; seven patients were not eligible and one did not receive treatment; 80 patients were fully assessable for survival, response, and toxicity. Objective response was observed in 42 patients (53%; 95% confidence interval [CI]: 41%–64%) with two patients (3%; 95% CI: 0%–8%) achieving a complete response. Median PFS was 5 months (CI, 4.2-5.9 months), and median overall survival was 8.8 months (95% CI: 7.8–9.5 months). The 1- and 2-year survival rates were 27.5% (95% CI: 17.7%–37.3%) and 4% (95% CI: 0%–8%), respectively. The most common toxicity was neutropenia. Grade 3 and 4 neutropenia was noted in 17 (21%) and 17 (21%) patients, respectively. Two patients developed febrile neutropenia, with subsequent full recovery. Twenty-one patients (23%) developed grade 3 thrombocytopenia. Grade 4 thrombocytopenia was seen in only one patient. The most common nonhematologic toxicities included grade 3 and 4 vomiting in 12 (21%) patients and fatigue in nine (10%) patients. Two patients (3%) died of respiratory infections while on treatment. Conclusion The combination of gemcitabine and cisplatin is an active and reasonably well tolerated regimen for the treatment of ES-SCLC. It does not appear to offer any compelling advantages over other commonly used two drug regimens in this disease.

Diagnosis of septic loosening of hip endoprosthesis with antigranulocyte scintigraphy (AGS) was analysed. Twenty-one hip prostheses were studied using laboratory tests and, in cases of elevated values, three-phase bone scan (BS) and AGS. Elective SPECT/CT scans were performed. Histologic and microbiologic exams verified the diagnosis. The AGS analysis revealed sensitivity, specificity and accuracy of value 1, while positive and negative predictive values were also 1. BS showed sensitivity of 1 and specificity of 0.33. In three cases, SPECT/CT scans corroborated the AGS interpretation. This diagnostic algorithm proved effective in the detection of septic loosening of hip prostheses. AGS can be avoided without risk of infection being overlooked.

This study was designed to define the maximum tolerated dose of pegylated liposomal doxorubicin (Doxil) and multiday vinorelbine (VNB), without and with prophylactic filgrastim, and to identify antineoplastic effect.Patients with resistant cancers were treated with Doxil 50 mg/m2 every four weeks, and with VNB 15 mg/m2 on the same day. The VNB dose escalations were accomplished in subsequent patient cohorts by adding VNB doses on consecutive days. When the maximum tolerated dose (MTD) of VNB with Doxil was defined, prophylactic filgrastim was added to define a second MTD.Of 29 patients entered, two had early adverse events, and 27 received at least one full cycle with at least one month follow-up. The MTD of VNB, combined with Doxil 50 mg/m2, was 15 mg/m2 on day 1, with neutropenia as the dose-limiting toxicity. With prophylactic filgrastim, the MTD was 15 mg/m2 daily for two days, with neutropenia and stomatitis as dose-limiting toxicities. Palmar plantar erythrodysesthesia occurred frequently, usually after the third cycle. Objective responses were documented in six patients, all of whom received multiday VNB.Doxil 50 mg/m2 on day 1 of a 28-day cycle can be safely combined with VNB 15 mg/m2 day 1, or with VNB 15 mg/m2 days 1 and 2 with filgrastim prophylaxis. Antineoplastic activity was observed in this heavily pretreated population. Future studies of Doxil 35-40 mg/m2 with multiday VNB may be worthwhile, especially in metastatic breast cancer.

Both docetaxel and gemcitabine are active against chemotherapy-pretreated non small-cell lung cancer (NSCLC). We previously demonstrated that weekly gemcitabine can be safely combined with monthly docetaxel with promising antineoplastic activity. In a recently completed phase II trial, 38 NSCLC patients failing upfront chemotherapy were treated with gemcitabine 800 mg/m2 on days 1, 8, and 15 and docetaxel 100 mg/m2 on day 1 every 4 weeks. The intent-to-treat response rate was 33% (95% CI: 19%-55%), with one complete and 11 confirmed partial responses. Responses were seen at all disease sites and in 31% of patients refractory to front-line chemotherapy. The median time to disease progression for the responders was 8 months, and two have remained progression-free for longer than a year. Hematological toxicities included grade 4 neutropenia in half of patients, febrile neutropenia in 10%, and grade 3-4 thrombocytopenia in 25%. The most prominent nonhematological toxicity was asthenia. We conclude that this doublet is active and safe, producing durable responses at all disease sites and in patients with platinum-refractory NSCLC.

No abstract.

ContextMore persons in the United States die from non–small cell lung cancer (NSCLC) than from breast, colorectal, and prostate cancer combined. In preclinical testing, oral gefitinib inhibited the growth of NSCLC tumors that express the epidermal growth factor receptor (EGFR), a mediator of cell signaling, and phase 1 trials have demonstrated that a fraction of patients with NSCLC progressing after chemotherapy experience both a decrease in lung cancer symptoms and radiographic tumor shrinkages with gefitinib.ObjectiveTo assess differences in symptomatic and radiographic response among patients with NSCLC receiving 250-mg and 500-mg daily doses of gefitinib.Design, Setting, and PatientsDouble-blind, randomized phase 2 trial conducted from November 2000 to April 2001 in 30 US academic and community oncology centers. Patients (N = 221) had either stage IIIB or IV NSCLC for which they had received at least 2 chemotherapy regimens.InterventionDaily oral gefitinib, either 500 mg (administered as two 250-mg gefitinib tablets) or 250 mg (administered as one 250-mg gefitinib tablet and 1 matching placebo).Main Outcome MeasuresImprovement of NSCLC symptoms (2-point or greater increase in score on the summed lung cancer subscale of the Functional Assessment of Cancer Therapy-Lung [FACT-L] instrument) and tumor regression (>50% decrease in lesion size on imaging studies).ResultsOf 221 patients enrolled, 216 received gefitinib as randomized. Symptoms of NSCLC improved in 43% (95% confidence interval [CI], 33%-53%) of patients receiving 250 mg of gefitinib and in 35% (95% CI, 26%-45%) of patients receiving 500 mg. These benefits were observed within 3 weeks in 75% of patients. Partial radiographic responses occurred in 12% (95% CI, 6%-20%) of individuals receiving 250 mg of gefitinib and in 9% (95% CI, 4%-16%) of those receiving 500 mg. Symptoms improved in 96% of patients with partial radiographic responses. The overall survival at 1 year was 25%. There were no significant differences between the 250-mg and 500-mg doses in rates of symptom improvement (P = .26), radiographic tumor regression (P = .51), and projected 1-year survival (P = .54). The 500-mg dose was associated more frequently with transient acne-like rash (P = .04) and diarrhea (P = .006).ConclusionsGefitinib, a well-tolerated oral EGFR-tyrosine kinase inhibitor, improved disease-related symptoms and induced radiographic tumor regressions in patients with NSCLC persisting after chemotherapy.

This retrospective case-series review studied the effectiveness of epoetin alfa in community oncology practices, which until now has not been well documented.We reviewed the medical records of 118 cancer patients treated between 1999 and 2001 with cyclic chemotherapy plus epoetin alfa in 27 US community-based oncology practices. Two analysis sets were examined: one including all patients (n=118) and one including only those patients with no concurrent events impacting hemoglobin data interpretation (n=73). Efficacy of epoetin alfa was evaluated by hemoglobin response (aS2 g/dl increase in hemoglobin from baseline) at weeks 12 and 16, the time to hemoglobin response, and change in hemoglobin concentrations from baseline at specific time points.After 12 weeks of treatment, 43% (95% confidence interval [CI], 33-54%) of patients had a hemoglobin response, and the proportion of responders further rose to 61% (95% CI, 49-72%) after 16 weeks. The median time to response was 92 days (lower 95% confidence limit, 74 days; upper bound not estimable). Hemoglobin increased from baseline at all time points evaluated during epoetin alfa treatment, with a mean increase of 1.1 g/dl (95% CI, 0.77-1.4 g/dl) by the last observation.These results indicate that epoetin alfa is effective in community practice, but most patients take longer than 3 months to respond. Because slow responses may negatively impact on the quality of life in these patients, alternative treatment approaches providing faster and perhaps better responses may provide greater clinical benefit.

At the Antwerp meeting of the European Network of Heads of Schools of Architecture (ENHSA, March 2003) the need was felt to get a European-wide insight in the current situation of Architectural Higher Education, especially in relation to the Bologna process and the emerging Knowledge-Based Society. It was decided that each ENHSA Task Force would question the schools as to both the current situation and expected future trends. Each school received one package of questionnaires. In total 130 packages were sent and 52 were returned (40%). In 51 cases had the Curriculum Questionnaire be completed (39%). The returned questionnaires cover Northern, Western, Southern and Eastern Europe (Table 1). We are grateful that so many representatives of the Architectural Schools took part in this survey. In this presentation we will summarise the results of the Curriculum Task Force. The management of the ENHSA made the subject ECTS (European Credit Transfer System) part of the inquiry of the Task Force on Mobility. However, it is the opinion of the working group on Curriculum that ECTS is also an essential means to design a curriculum, make it transparent, and make the workload of students the starting point for discussions on the content of curricula. The inquiry on the content of the curriculum that started in 2002 is not included in this presentation.