Objective To provide an updated and expanded analysis of clinical outcome and immunohistochemical (IHC) findings unique to primary dermal melanoma (PDM) that may be used to differentiate this entity from primary nodular melanoma (PNM) and cutaneous metastatic melanoma (MM).
Design Cohort analysis and extensive IHC panel comparing PDM with PNM and cutaneous MM.
Setting Melanoma clinics and pathology departments of academic and VA medical centers.
Patients Thirteen patients with a solitary dermal or subcutaneous nodule of histologically proven melanoma, prospectively followed through April 30, 2007.
Interventions Clinical, pathologic, and IHC assessment of patients diagnosed as having PDM.
Main Outcome Measures Long-term clinical outcome and determination of unique clinical and IHC features in the study cohort compared with other melanoma subtypes.
Results Histologically, there was no evidence of an overlying in situ component, ulceration, or regression, and there was no associated nevus in any cases. Clinical history and findings from workup, including imaging studies, skin examination, and sentinel lymph node biopsy, were negative for evidence of melanoma elsewhere. The mean Breslow depth was 9.6 mm. Two patients developed satellite or in-transit recurrences, 1 developed pulmonary metastasis, and another died of liver metastases. Overall, the cohort showed a 92% melanoma-specific survival rate at a mean duration of follow-up of 44 months. The IHC findings showed that PDM exhibited lower levels of staining for the antigens p53 (P = .02), Ki-67 (Mib-1) (P = .002), cyclin D1 (P = .001), and podoplanin (recognized by D2-40 antibody) lymphovascular staining (P <.001) compared with MM and PNM. All other markers were comparable.
Conclusions Patients with PDM have remarkably prolonged survival compared with patients with MM or PNM of similar thickness. Preliminary results suggest that PDM may be characterized by lower levels of p53, Ki-67, cyclin D1, and D2-40 compared with histologically similar MM and PNM.
Pharmacokinetic variability of extended interval tobramycin in burn patients.
Burns. 2008 Apr 4;
Authors: Bracco D, Landry C, Dubois MJ, Eggimann P
BACKGROUND: Aminoglycosides are mandatory in the treatment of severe infections in burns. However, their pharmacokinetics are difficult to predict in critically ill patients. Our objective was to describe the pharmacokinetic parameters of high doses of tobramycin administered at extended intervals in severely burned patients. METHODS: We prospectively enrolled 23 burned patients receiving tobramycin in combination therapy for Pseudomonas species infections in a burn ICU over 2 years in a therapeutic drug monitoring program. Trough and post peak tobramycin levels were measured to adjust drug dosage. Pharmacokinetic parameters were derived from two points first order kinetics. RESULTS: Tobramycin peak concentration was 7.4 (3.1-19.6)mug/ml and C(max)/MIC ratio 14.8 (2.8-39.2). Half-life was 6.9 (range 1.8-24.6)h with a distribution volume of 0.4 (0.2-1.0)l/kg. Clearance was 35 (14-121)ml/min and was weakly but significantly correlated with creatinine clearance. CONCLUSION: Tobramycin had a normal clearance, but an increased volume of distribution and a prolonged half-life in burned patients. However, the pharmacokinetic parameters of tobramycin are highly variable in burned patients. These data support extended interval administration and strongly suggest that aminoglycosides should only be used within a structured pharmacokinetic monitoring program.
PMID: 18395988 [PubMed - as supplied by publisher]
(Source: Burns : Journal of the International Society for Burn Injuries)