The current evidence fails to identify a superior regimen in terms of relative efficacy or safety for the treatment of HIV-associated cerebral toxoplasmosis. Use of TMP-SMX as preferred treatment may be consistent with the available evidence and other real-world considerations. Larger comparative studies are needed.
Seventeen pediatric patients (mean age at diagnosis 10 yr and 9 mo +/- 2 yr and 9 mo) with Graves' disease treated with 0.3-0.7 mg/kg/day methimazole and followed for at least three years, during which drug suspension was attempted on attainment of good clinical and metabolic compensation, were retrospectively studied to look for factors predictive of lasting remission present at onset. Lasting remission was defined as a clinical and laboratory picture of euthyroidism lasting at least one year in the absence of treatment at the end of the follow-up. A distinction was drawn between patients who reached remission after one or two courses (groups 1 and 2) and those who never attained a lasting remission (group 3). TRAb (TBIAb) levels at onset were the only factor significantly correlated with the response to treatment. Age at diagnosis, goiter size and fT3 and fT4 concentrations were not significantly correlated with the clinical picture. The series was too small to allow any assessment of the real importance of these factors, though a generally better response was displayed by children over 11 years old, without appreciable or with very small goiter and moderately increased thyroid hormone levels at onset (fT3 < 25 pg/ml in 10/10 in groups 1 and 2 and 2/7 in group 3 patients; fT4 < 40 pg/ml in 7/10 in groups 1 and 2 and 3/7 in group 3 patients). It was also found that better results were obtained when the initial drug course was protracted for at least two years.
RT-PCR is more sensitive than PATH to detect SLN metastases and it is a reliable predictor of disease relapse in stage I-II melanoma patients.
The aim of this study was to optimize a protocol for radioguided biopsy of the sentinel lymph node (SLN) in patients with melanoma. The protocol was based on a combination of ex vivo counting of the nodes detected intraoperatively and analysis of the harvested nodes by hematoxylin and eosin staining plus immunohistochemistry (conventional histopathology [PATH]) and by molecular biology (reverse-transcriptase polymerase chain reaction [RT-PCR]). Methods: A total of 124 patients with primary clinical stage I-II (according to the American Joint Committee on Cancer) cutaneous melanoma underwent successful radioguided SLN biopsy. SLNs harvested for analysis included any additional nodes whose ex vivo counting rate exceeded 20% of the hottest node. All removed SLNs were examined by conventional PATH and with RT-PCR analysis for the expression of messenger RNA for tyrosinase and the melanoma antigens recognized by T cells. Complete lymph node dissection (CLND) was performed only in the case of SLN metastasis detected by PATH. Different combinations of the intraoperative parameters (only the hottest node and all nodes harvested) and of analysis (PATH and RT-PCR) were tested as predictors of clinical outcome on the basis of long-term follow-up (12-81 mo; median, 55 mo). Results: A total of 197 SLNs were harvested, 41 of which harbored metastasis as detected by RT-PCR analysis; PATH detected metastasis in only 24 of 41 metastatic SLNs. In 5 of 41 instances, metastasis was not in the hottest SLN. The main factor determining correct classification of the SLN status was RT-PCR, which significantly improved detection of metastasis, even if applied only to the hottest node (P , 0.0001 vs. PATH analysis of either the hottest SLN or all nodes above the 20% threshold). Metastatic disease recurred locally in 5 patients who had not undergone CLND; RT-PCR analysis showed metastasis in 4 of these patients. The false-negative rate of SLN biopsy progressively decreased when applying PATH only to the hottest node (32.1%), additional RT-PCR to the hottest node (21.4%), PATH to all nodes (17.9%), and RT-PCR to all nodes (3.6%, P 5 0.015 vs. PATH analysis of only the hottest SLN). Conclusion: On the basis of long-term follow-up (the gold standard for final clinical outcome of SLN biopsy), both 20% threshold and RT-PCR analysis should be applied for optimal detection of nodal metastases in patients with melanoma.
The presence of lymph node metastases is the best prognostic factor for predicting relapse or survival in melanoma patients. It has been demonstrated that melanoma metastases spread through the first lymph node(s) draining the tumor (sentinel lymph node, SN) to the lymphatic system and that detection of melanoma cells in peripheral blood directly correlates with prognosis in melanoma. To identify lymph node metastases and circulating melanocytes, we developed a single-step reverse transcriptase-polymerase chain reaction assay (RT-PCR) for detection of two melanoma-specific markers: the tyrosinase gene, which encodes an enzyme associated with melanin synthesis, and melanoma antigen-related T-cells, which are present in tumor infiltrating T-lymphocytes. This method detects two tumor cells in a background of 10(7) lymphocytes. Thirty patients with stage I-IV cutaneous melanoma entered the study. Blood samples were taken preoperatively, one month after excision of the primary melanoma lesion and the SN or total lymphadenectomy, and before the start of chemotherapy and every three months thereafter in metastatic patients. SNs were collected from 22 patients, bisected and analyzed by RT-PCR and routine pathological and immunohistochemical tests. The preliminary results indicate that RT-PCR for melanoma markers is a sensitive and valuable method for the detection of micrometastases and for early diagnosis and staging of melanoma.
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