This survey confirms that TMZ is established as first-line chemotherapeutic treatment of APT/PC. Clinically functioning tumours, low MGMT and concurrent radiotherapy were associated with a better response. The limited long-term effect of TMZ and the poor efficacy of other drugs highlight the need to identify additional effective therapies.
Background: Cabergoline is a long-acting dopamine receptor agonist used to treat prolactinomas. Identification of D 2 receptors in corticotroph tumors led to clinical trials of cabergoline therapy in limited cases of Nelson's syndrome, ectopic ACTH-secreting tumors, and recently Cushing's disease (CD). Objective: To evaluate the long-term efficacy of cabergoline monotherapy in patients with CD. Methods: Retrospective analysis of non-randomized clinical therapy with cabergoline in 30 patients with CD treated in academic centers of Buenos Aires and Montreal. Cabergoline was initiated at 0.5-1.0 mg/week and adjusted up to a maximal dose of 6 mg/week based on urinary free cortisol (UFC) levels. Complete response to cabergoline was defined as a sustained normalization of UFC with at least two normal values measured at 1-3 months interval; partial response was defined as a decrease of UFC to !125% of the upper limit of normal, and treatment failure as UFC R125% of it. Results: Within 3-6 months, complete response was achieved in 11 patients (36.6%) and partial response in 4 patients (13.3%). After long-term therapy, nine patients (30%) remain with a complete response after a mean of 37 months (range from 12 to 60 months) with a mean dose of 2.1 mg/week of cabergoline. Two patients escaped after 2 and 5 years of complete response, but one patient transiently renormalized UFC after an increase in cabergoline dosage. No long-term response was maintained in four initial partial responders. Conclusions: Cabergoline monotherapy can provide an effective long-term medical therapy for selected patients with CD, but requires close follow-up for dose adjustments.
Freshwater blooms of cyanobacteria (blue-green algae) in source waters are generally composed of several different strains with the capability to produce a variety of toxins. The major exposure routes for humans are direct contact with recreational waters and ingestion of drinking water not efficiently treated. The ultra high pressure liquid chromatography tandem mass spectrometry based analytical method presented here allows simultaneous analysis of 22 cyanotoxins from different toxin groups, including anatoxins, cylindrospermopsins, nodularin and microcystins in raw water and drinking water. The use of reference standards enables correct identification of toxins as well as precision of the quantification and due to matrix effects, recovery correction is required. The multi-toxin group method presented here, does not compromise sensitivity, despite the large number of analytes. The limit of quantification was set to 0.1 μg/L for 75% of the cyanotoxins in drinking water and 0.5 μg/L for all cyanotoxins in raw water, which is compliant with the WHO guidance value for microcystin-LR. The matrix effects experienced during analysis were reasonable for most analytes, considering the large volume injected into the mass spectrometer. The time of analysis, including lysing of cell bound toxins, is less than three hours. Furthermore, the method was tested in Swedish source waters and infiltration ponds resulting in evidence of presence of anatoxin, homo-anatoxin, cylindrospermopsin and several variants of microcystins for the first time in Sweden, proving its usefulness.
Our pilot study suggests that decreasing the glucocorticoid replacement dose to approximately 15 mg/day is beneficial in terms of patients' body composition, lipid profile and quality of life.
Although there are international guidelines orienting physicians on how to manage patients with acromegaly, such guidelines should be adapted for use in distinct regions of the world. A panel of neuroendocrinologists convened in Mexico City in August of 2007 to discuss specific considerations in Latin America. Of major discussion was the laboratory evaluation of acromegaly, which requires the use of appropriate tests and the adoption of local institutional standards. As a general rule to ensure diagnosis, the patient’s GH level during an oral glucose tolerance test and IGF-1 level should be evaluated. Furthermore, to guide treatment decisions, both GH and IGF-1 assessments are required. The treatment of patients with acromegaly in Latin America is influenced by local issues of cost, availability and expertise of pituitary neurosurgeons, which should dictate therapeutic choices. Such treatment has undergone profound changes because of the introduction of effective medical interventions that may be used after surgical debulking or as first-line medical therapy in selected cases. Surgical resection remains the mainstay of therapy for small pituitary adenomas (microadenomas), potentially resectable macroadenomas and invasive adenomas causing visual defects. Radiotherapy may be indicated in selected cases when no disease control is achieved despite optimal surgical debulking and medical therapy, when there is no access to somatostatin analogues, or when local issues of cost preclude other therapies. Since not all the diagnostic tools and treatment options are available in all Latin American countries, physicians need to adapt their clinical management decisions to the available local resources and therapeutic options.
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