Prolactinoma: a condition associated with hypoadiponectinemia.

Prolactinomas are prolactin-secreting neoplasias accounting for 40% of the pituitary adenomas. Much is known about the effects of prolactinomas on the reproductive system, but few data are yet available regarding their induced changes on metabolism. This study was aimed at evaluating patients with prolactinomas for insulin resistance and adiponectinemia. Forty patients with prolactinoma were allocated to 2 different groups according to disease control: 20 with uncontrolled disease (UPRL) and 20 with controlled disease in the last 6 months (CPRL). Forty healthy individuals (CG) matched for age, sex, and body mass index were taken as controls. Patients with prolactinoma were compared both as a one group and according to disease control with CG. All subjects were evaluated for waist/hip ratio (WHR), blood pressure, lipid profile, fasting glucose, homeostasis assessment model of insulin resistance (HOMAIR), and adiponectin. Patients with prolactinomas (UPRL+CPRL) showed higher insulin (p<0.05) and HOMAIR (p<0.05), alongside with lower adiponectin levels (p<0.01) than matched controls. When UPRL was compared to CPRL and CG, UPRL was disclosed as a subgroup of significant altered metabolic profile as related to WHR (p<0.01 for comparisons), high-density lipoprotein cholesterol (p<0.05 for comparisons), triglycerides (p<0.05 for comparisons), HOMAIR (p<0.05 and p<0.01, respectively), and adiponectin (p<0.01 for comparisons). All these metabolic abnormalities, except hypoadiponectinemia (p<0.01), were not observed in CPRL. These data suggest that prolactinomas are associated with hypoadiponectinemia, which is further exacerbated in uncontrolled patients when insulin resistance is also prominent.

Clinical activity of trastuzumab and vinorelbine in women with HER2-overexpressing metastatic breast cancer.

PURPOSE: To determine the response rate and toxicity profile of trastuzumab administered concurrently with weekly vinorelbine in women with HER2-overexpressing advanced breast cancer. PATIENTS AND METHODS: Forty women with HER2-positive (+3 by immunohistochemistry, n = 30; +2 or positive, n = 10) breast cancer were enrolled onto a study of trastuzumab (4 mg/kg x 1, 2 mg/kg weekly thereafter) and vinorelbine (25 mg/m2 weekly, with dose adjusted each week for neutrophil count). Eighty-two percent of women had received prior chemotherapy as part of adjuvant (30%), metastatic (25%), or both (28%) treatment, including substantial portions of patients who had previously received either anthracyclines (20%), taxanes (15%), or both types (38%) of chemotherapy. RESULTS: Responses were observed in 30 of 40 patients (overall response rate, 75%, conditional corrected 95% confidence interval, 57% to 89%). The response rate was 84% in patients treated with trastuzumab and vinorelbine as first-line therapy for metastatic disease, and 80% among HER2 +3 positive patients. High response rates were also seen in women treated with second- or third-line therapy, and among patients previously treated with anthracyclines and/or taxanes. Combination therapy was feasible; patients received concurrent trastuzumab and vinorelbine in 93% of treatment weeks. Neutropenia was the only grade 4 toxicity. No patients had symptomatic heart failure. Grade 2 cardiac toxicity was observed in three patients. Prior cumulative doxorubicin dose in excess of 240 mg/m2 and borderline pre-existing cardiac function were associated with grade 2 cardiac toxicity. CONCLUSION: Trastuzumab in combination with vinorelbine is highly active in women with HER2-overexpressing advanced breast cancer and is well tolerated.

Study of mandibular head volume in rats submitted to occlusal alterations.

The possible alterations caused by occlusal modifications in mandibular head volume were studied in rats by morphometric techniques. The results permitted the authors to conclude that, within the conditions of the experiments, the total volume of the mandibular head was unchanged, although alterations in the direction of growth may occur.

Effect of polishing burs and stones on the micro-hardness of dental amalgam.

Square standard cavities were prepared in human teeth and restored with amalgam obtained from alloys of different trade-marks. Twenty-four hours after condensation, excess amalgam was removed from three of the four margins, each with a different rotatory instrument (number 4 bur, multiblade finishing bur, and fine green stone). No rotatory instrument was used on the fourth margin (control), and this control was polished with pumice and zinc-oxide pastes and Sweeney's brushes. Vickers' tests for micro-hardness of the amalgam were performed on the four margins of the restorations. The restorations were then submitted to metallographic polishing, and a second micro-hardness measurement was made seven days later. The statistical analysis of the data showed that micro-hardness values were higher at the margins on which no rotatory instruments were used. The lowest micro-hardness values were found at the margins where finishing and/or round burs were used. Polishing with fine green stones gave intermediate values.

Mekuido: intervención en línea para escolares chilenos de apoyo a la prevención del sobrepeso / Mekuido: on line intervention for chilean school children to support prevention of overweight

Se describe la intervención MeKuido disenada para el proyecto "Prevención del sobrepeso y de la obesidad en escolares chilenos: Apuesta a la capacidad emprendedora de los niños" (FONIS SA10I20016). Sujetos y Método: Estudio descriptivo de la intervención realizada a población seleccionada mediante muestreo aleatorio por conglomerado del 50% de los colegios municipalizados de la comuna de La Pintana, conformada por los niños/as que en marzo de 2011, cursaban 5° y 6° año básico, (n=468) y aceptaron participar. Mekuido elemento central de la intervención, es un software con cuatro secciones construidas según marco referencial Orem. Post intervención, se aplicó cuestionario de satisfacción. Resultados: La implementación en el contexto de las actividades escolares demostró ser factible, pero no exenta de dificultades. El cuestionario de satisfacción fue respondido por 355 niños/as (90,8%). En todas las preguntas cerradas más del 80% muestran satisfacción con la intervención y recomendarían su uso. Conclusiones. El marco de referencia de Orem permite diseñar intervenciones para cambio de conductas asociadas a alimentación. Su uso es factible en el contexto escolar, requiere de decisión y compromiso de los profesores. La estrategia puede ser incorporada al curriculum y contribuir al desarrollo de objetivos transversales. La satisfacción con la intervención fue alta.

The MeKuido intervention is described, designed for the project "Prevention of overweight and obesity in Chilean children: Bettinhg on the enterprising capacity of children" (FONIS SA10I20016). Subjects and Method: A descriptive intervention study on a randomly selected population by cluster at 50% of municipal schools in the district of La Pintana, with children enrolled in 5th and 6th grade of primary school who agreed to participate (n = 468). Mekuido, central element is a software with four sections built according to Orem's referential framework. Post intervention, a satisfaction questionnaire was applied. Results: The implementation in the context of school activities proved feasible but not without difficulties. The satisfaction questionnaire was answered by 355 children (90.8%). All closed questions showed over 80% of satisfaction with the intervention and would recommend their use. Conclusion: The Orem framework allows the design of interventions to change behaviors related to feeding. Its use is feasible in the school context, requires determination and commitment of teachers. The strategy can be incorporated into the curriculum and contribute to the development of transversal objectives.

A phase II study of fixed dose rate gemcitabine in patients with relapsed müllerian tumors.

Gemcitabine (2',2'-difluorodeoxycytidine) is a novel purine analog with clinical activity against ovarian cancer. Accumulation of gemcitabine triphosphate (dFdCTP) increases in a linear fashion with prolonged infusions of gemcitabine, and there is a strong relationship between intracellular accumulation of dFdCTP and DNA damage. Women with ovarian, fallopian tube, or primary peritoneal carcinoma and documented recurrent disease were eligible for the study. Patients could not have received more than four prior lines of chemotherapy and had to have measurable or evaluable disease. Gemcitabine 800 mg/m2 administered by intravenous infusion at 10 mg/m2/min (fixed dose rate [FDR]) on days 1 and 8 of a 21-day schedule. Twenty-eight patients with a median age 60 (range, 40-77) years were treated. Although 43% were Eastern Cooperative Oncology Group 0, 50% had liver metastases. Eighty-eight cycles of therapy were delivered (median 2 [range, 1-6]). Five of the first ten patients treated at 800 mg/m2 could not receive day 8 FDR-gemcitabine because of neutropenia, and the starting dose was reduced to 700 mg/m2. Even at this dose there was cumulative hematologic toxicity resulting in dose reductions. Vomiting, mucositis, diarrhea, allergy, rash, fever, and alopecia were mild. In 28 patients, there was only one partial response (4%, 95% CI 0-18%) and median time to progression was 1.7 (interquartile range, 1.2-3.9) months. FDR-gemcitabine 700 mg/m2 administered by intravenous infusion at an FDR of 10 mg/m2/min had minimal activity against heavily pretreated recurrent tumors of müllerian origin. The optimal dose and schedule of gemcitabine is yet to be defined in this population.

A phase I clinical trial of continual alternating etoposide and topotecan in refractory solid tumours.

The goal of this phase I study was to develop a novel schedule using oral etoposide and infusional topotecan as a continually alternating schedule with potentially optimal reciprocal induction of the nontarget topoisomerase. The initial etoposide dose was 15 mg m(-2) b.i.d. days (D)1-5 weeks 1,3,5,7,9 and 11, escalated 5 mg per dose per dose level (DL). Topotecan in weeks 2,4,6,8,10 and 12 was administered by 96 h infusion at an initial dose of 0.2 mg m(-2) day(-1) with a dose escalation of 0.1, then at 0.05 mg m(-2) day(-1). Eligibility criteria required no organ dysfunction. Two dose reductions or delays were allowed. A total of 36 patients with a median age of 57 (22-78) years, received a median 8 (2-19) weeks of chemotherapy. At DL 6, dose-limiting toxicities consisted of grade 3 nausea, vomiting and intolerable fatigue. Three patients developed a line-related thrombosis or infection and one subsequently developed AML. There was no febrile neutropenia. There were six radiologically confirmed responses (18%) and 56% of patients demonstrated a response or stable disease, typically with only modest toxicity. Oral etoposide 35 mg m(-2) b.i.d. D1-5 and 1.8 mg m(-2) 96 h (total dose) infusional topotecan D8-11 can be administered on an alternating continual weekly schedule for at least 12 weeks, with promising clinical activity.

The clinical utility of liposomal doxorubicin in recurrent ovarian cancer.

OBJECTIVES: The aim of this study was to determine the efficacy and toxicity of single agent off-protocol, liposomal doxorubicin (Doxil Alza), in consecutive patients with recurrent ovarian cancer and to investigate the influence of HER-2/neu expression on response to liposomal doxorubicin. PATIENTS AND METHODS: Retrospective analysis of 72 consecutive patients treated, typically with liposomal doxorubicin 40 mg/m(2) q28 days between January 1997 and December 1998. Results. Twenty-nine patients (40%) had platinum- and taxane-resistant tumors. Nineteen patients (27%) responded with clinical or radiological evidence of response with reduction in CA-125 of >50%. One complete response (CR) and 7 partial responses (PRs) occurred in platinum- and taxane-resistant patients (radiological response (RR) 29%) and 8 PRs occurred in patients with visceral metastases (RR 28%). Time to progression was 5.3 (2.1-12.1) months. Only 7 dose delays (3%) and 20 dose reductions (8%) were necessary in 265 cycles of treatment. Hematological toxicity was generally mild with grade (Gr) > or =III neutropenia in 1 (2%), Gr > or =III thrombocytopenia in 1 (1%), and Gr > or =III anemia in 8 patients (11%). One patient (1%) was admitted with fever and neutropenia. Other toxicity was minimal with Gr > or =III mucositis occurring in 3 patients (4%). Gr > or =III cutaneous toxicity was seen in 6 patients (8%). Three patients (4%) had a >10% fall in ejection fraction but there was no unequivocal clinical heart failure. CONCLUSIONS: The data suggest that liposomal doxorubicin is an active drug in both taxane- and platinum-sensitive and resistant recurrent ovarian cancer. Liposomal doxorubicin is associated with tolerable toxicity and is particularly well tolerated in patients with multiple prior lines of treatment.

A Phase I-II study of 96-hour infusional topotecan and paclitaxel for patients with recurrent Müllerian tumors.

BACKGROUND: Topotecan and paclitaxel are schedule dependent chemotherapeutic agents with activity against ovarian carcinoma. A Phase I-II study in which both drugs were administered concurrently by 96-hour, continuous, intravenous infusion was performed to determine the maximum tolerated dose (MTD), toxicities, pharmacokinetics, and efficacy of the combination. METHODS: Women with ovarian or primary peritoneal carcinoma and documented recurrent disease were eligible for the study. The dose of topotecan was escalated from 1.6 mg/m(2) while maintaining the paclitaxel dose constant at 100 mg/m(2). Plasma concentrations of both drugs were monitored daily during the first cycle of therapy. RESULTS: Forty-five patients with a median age of 54 years (range, 42-70 years) received 181 cycles of therapy. Five patients were recruited to each of four dose levels (topotecan 1.6 mg/m(2), 2.0 mg/m(2), 2.8 mg/m(2), and 3.6 mg/m(2)), and an additional 25 patients were treated at the MTD (Phase II). Neutropenia and thrombocytopenia became dose limiting toxicities (DLT) at the fourth dose level. Emesis, mucositis, peripheral neuropathy, diarrhea, and alopecia were mild. Twenty patients (44%) had line-related occlusion, thrombosis, or infection. The mean values (+/- standard deviation) of the apparent steady-state plasma concentrations at the Phase II doses were 2.3 nM +/- 0.5 nM for topotecan lactone, 5.6 nM +/- 2.1 nM for total topotecan, and 40.1 nM +/- 16.8 nM for paclitaxel. There were seven partial responses (Phase II) contributing to an objective response rate of 28% and a median survival time of 11.7 months (range, 0.6-20.1 months). CONCLUSIONS: Topotecan at a dose of 2.8 mg/m(2) and paclitaxel at a dose of 100 mg/m(2) administered by concurrent, 96-hour, continuous intravenous infusions shows activity against tumors of Müllerian origin.