Phase I study of non-pegylated liposomal doxorubicin in combination with ifosfamide in adult patients with metastatic soft tissue sarcomas.

OBJECTIVE: The aim of this study was to evaluate the maximum tolerated dose (MTD) and safety of the combination of non- pegylated liposomal doxorubicin (Myocet) and ifosfamide in patients with metastatic soft tissue sarcomas. METHODS: Cohorts of four patients with metastatic soft tissue sarcomas received up to five cycles of intravenous ifosfamide 3000 mg/m2 on days 1- 3 in combination with escalating doses of intravenous Myocet on day 1 every 3 weeks until dose limiting toxicity (DLT) in at least one patient. Starting dose of Myocet was 40 mg/m2 to be escalated through 10 mg/m2 increase up to 80 mg/m2. Toxicity was graded according to the National Cancer Institute Common Toxicity Criteria v3.0 (NCI-CTC v3.0). RESULTS: Ten patients were enrolled in the study and 8 of them received the treatment. Median age was 45 years, 3 patients were male and 5 were female. DLT, consisting of neutropenic fever, was reached in one patient at dose level 2 (Myocet 50 mg/m2). Therefore, the MTD and the recommended phase II dose is 40 mg/m2. CONCLUSIONS: The combination of intravenous Myocet 40 mg/m2 on day 1 and ifosfamide 3,000 mg/m2 on days 1-3 every 3 weeks is safe and feasible; a phase II study is ongoing.

Dietary fat intake as risk factor for the development of diabetes: multinational, multicenter study of the Mediterranean Group for the Study of Diabetes (MGSD).

OBJECTIVE: To investigate the role of dietary factors in the development of type 2 diabetes. RESEARCH DESIGN AND METHODS: In the context of the Multinational MGSD Nutrition Study, three groups of subjects were studied: 204 subjects with recently diagnosed diabetes (RDM), 42 subjects with undiagnosed diabetes (UDM) (American Diabetes Association criteria-fasting plasma glucose [FPG] > or =126 mg/dl), and 55 subjects with impaired fasting glucose (IFG) (FPG > or =110 and <126 mg/dl). Each group was compared with a control group of nondiabetic subjects, matched one by one for center, sex, age, and BMI. Nutritional habits were evaluated by a dietary history method, validated against the 3-day diet diary. In RDM, the questionnaire referred to the nutritional habits before the diagnosis of diabetes. Demographic data were collected, and anthropometrical and biochemical measurements were taken. RESULTS: Compared with control subjects, RDM more frequently had a family history of diabetes (49.0 vs. 14.2%; P < 0.001), exercised less (exercise index 53.5 vs. 64.4; P < 0.01), and more frequently had sedentary professions (47.5 vs. 27.4%; P < 0.001). Carbohydrates contributed less to their energy intake (53.5 vs. 55.1%; P < 0.05), whereas total fat (30.2 +/- 0.5 vs. 27.8 +/- 0.5%; P < 0.001) and animal fat (12.2 +/- 0.3 vs. 10.8 +/- 0.3%; P < 0.01) contributed more and the plant-to-animal fat ratio was lower (1.5 +/- 0.1 vs. 1.8 +/- 0.1; P < 0.01). UDM more frequently had a family history of diabetes (38.1 vs. 19.0%; P < 0.05) and sedentary professions (58.5 vs. 34.1%; P < 0.05), carbohydrates contributed less to their energy intake (47.6 +/- 1.7 vs. 52.8 +/- 1.4%; P < 0.05), total fat (34.7 +/- 1.5 vs. 30.4 +/- 1.2%; P < 0.05) and animal fat (14.2 +/- 0.9 vs. 10.6 +/- 0.7%; P < 0.05) contributed more, and the plant-to-animal fat ratio was lower (1.6 +/- 0.2 vs. 2.3 +/- 0.4; P < 0.05). IFG differed only in the prevalence of family history of diabetes (32.7 vs. 16.4%; P < 0.05). CONCLUSIONS: Our data support the view that increased animal fat intake is associated with the presence of diabetes.

ICSD diagnostic criteria for narcolepsy: interobserver reliability. Intemational Classification of Sleep Disorders.

STUDY OBJECTIVES: To estimate the reliability of the diagnosis of narcolepsy after clinical interview and polysomnographic evaluation among sleep medicine doctors, before and after training in application of the International Classification of Sleep Disorders (ICSD). SETTING: Videotaped semi-structured interviews of 10 patients complaining of daytime sleepiness of different etiologies. Questions referred to ICSD criteria for narcolepsy. A further series of 10 cases of narcolepsy without cataplexy were simulated, with at least a random one to three of the ICSD polysomnographic criteria at pathological levels. PARTICIPANTS AND DESIGN: Seventeen doctors were required to classify each videotaped case as "ascertained," "possible," or "excluded" narcolepsy, in two sessions: one before and one after discussion of ICSD criteria. The observers were invited to confirm or exclude the diagnosis of narcolepsy in the 10 simulated cases, according to the given polysomnographic findings, before and after an agreed proposal of the interpretation of ICSD polysomnographic criteria. Interobserver reliability was calculated using Kappa statistics. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: Interobserver reliability of clinical judgement improved from "substantial" at baseline (Kappa 0.61) to "almost perfect" after training (Kappa 0.95). Interobserver reliability of polysomnographic findings was "fair" at baseline (Kappa 0.24), unanimous after the proposed interpretation of ICSD polysomnographic criteria. CONCLUSIONS: Baseline reliability of diagnostic judgement in suspected narcolepsy was found satisfactory among Italian sleep medicine doctors. Educational training, based on discussion of ICSD criteria, further improved agreement. Diagnosis based on polysomnographic findings, not reliable at baseline, needed a strict interpretation of ICSD criteria to attain standardization.