A selective LC/RIA for dexamethasone and its prodrug dexamethasone-21-isonicotinate in biological fluids.

A combined LC/RIA procedure is described for the selective determination of dexamethasone (DEX) and its prodrug dexamethasone-21-isonicotinate (DIN) in plasma. The low affinity of the employed dexamethasone antiserum for DIN (cross-reactivity less than 0.5%) allowed the direct determination of DEX in plasma extracts. For the determination of DIN, both substances of interest were separated by LC, the DIN containing fraction was collected, hydrolysed and the generated DEX was consequently assayed by radioimmunoassay. The assay detection limits were 0.1 ng ml-1 for DEX and 0.75 ng ml-1 for DIN. For both substances, inter- and intra-day variabilities (RSDs) were 6 and 12%, respectively.     

Cultures of Langerhans cells and co-culture with lymphoid cells: Relevance to toxicology and pharmacology

Langerhans cells are an essential component of cutaneous immunological defence mechanisms. They are mononuclear dendritic cells derived from bone marrow, which are present in the squamous epithelia, particularly skin. Langerhans cells show marked changes in phenotype and function when epidermal cell suspensions are prepared according to a trypsinization protocol and placed in culture for 1–3 days. They seem to mature and acquire most of the features of lymphoid dendritic cells, especially the interdigitating dendritic cells present in lymph nodes. This observation supports the assertion that resident Langerhans cells take up foreign antigens and then migrate through dermal lymphatics to local lymph nodes where they function as antigen-presenting cells. Thus, Langerhans cells play a pivotal role in the primary immune response and in the pathogenesis of skin diseases. In the past, most therapeutic treatment of skin diseases was achieved by administration of pharmacological agents by epicutaneous application. More recently, the determination of the toxicity of drugs and their pharmacological mechanisms has required the development of in vitro models to explore their potential effects at the cellular level. The effects of different agents (physical and chemical) on the density and function of fresh or cultured Langerhans cells are reviewed.     

Prostate thermal therapy with high intensity transurethral ultrasound: the impact of pelvic bone heating on treatment delivery.

PURPOSE: This study was designed to assess pelvic bone temperature during typical treatment regimens of transurethral ultrasound thermal ablation of the prostate to establish guidelines for limiting bone heating. METHODS: Treatment with transurethral planar, curvilinear, and sectored tubular applicators was simulated using an acoustic and biothermal pelvic model that accommodates applicator sweeping, boundary temperature control, and changes in perfusion and attenuation with thermal dose to more accurately model ultrasound energy penetration. The effects of various parameters including power and frequency (5-10 MHz) on bone heating were assessed for a range of prostate cross-sections (3-5 cm) and bone distances (1-3 cm). RESULTS: All devices can produce significant bone heating (temperatures >50 degrees C, thermal dose >240 EM(43 degrees C)) without optimization of applied frequency or power for bone <3 cm from the prostate boundary. In small glands ( approximately 3 cm) increasing operating frequency of curvilinear and planar devices can increase bone temperatures, whereas the tubular applicator can be used at 10 MHz to avoid likely bone damage. In larger prostates (4-5 cm wide) increasing frequency reduces bone heating but can substantially increase treatment time. Lowering power can reduce bone temperature but may increase thermal dose by increasing treatment duration. All applicators can be used to treat glands 4-5 cm with limited bone heating by selecting appropriate power and frequency. CONCLUSIONS: Pubic bone heating during ultrasound thermal therapy of the prostate can be substantial in certain situations. Successful realization of this therapy will require patient-specific treatment planning to optimally determine power and frequency in order to minimize bone heating.     

Frühes Ovarialkarzinom

Patients with early ovarian carcinoma have a much better survival outcome than patients with more advanced disease. Comprehensive surgical staging is crucial for the determination of prognosis and treatment planning. During 2003, the first randomized trials were published demonstrating that adjuvant platinum based chemotherapy improves recurrence free and overall survival. Current treatment recommendations are largely based on the results of these studies. Accordingly, systemic adjuvant therapy should be offered to patients with disease stage Ib or higher and to patients with moderately differentiated or undifferentiated tumors. Due to incomplete surgical staging, the stage of disease in the patients included in these studies is probably underestimated, and only a fraction of the actual advanced stage patients is included.     

Systematic review of methods to diagnose infection in foot ulcers in diabetes.

AIM: To undertake a systematic review of the diagnostic performance of clinical examination, sample acquisition and sample analysis in infected foot ulcers in diabetes. METHODS: Nineteen electronic databases plus other sources were searched. To be included, studies had to fulfil the following criteria: (i) compare a method of clinical assessment, sample collection or sample analysis with a reference standard; (ii) recruit diabetic individuals with foot ulcers; (ii) present 2 x 2 diagnostic data. Studies were critically appraised using a 12-item checklist. RESULTS: Three eligible studies were identified, one each on clinical examination, sample collection and sample analysis. For all three, study groups were heterogeneous with respect to wound type and a small proportion of participants had foot ulcers due to diabetes. No studies identified an optimum reference standard. Other methodological problems included non-blind interpretation of tests and the time lag between index and reference tests. Individual signs or symptoms of infection did not prove to be useful tests when assessed against punch biopsy as the reference standard. The wound swab did not perform well when assessed against tissue biopsy. Semiquantitative analysis of wound swab might be a useful alternative to quantitative analysis. The limitations of these findings and their impact on recommendations from relevant clinical guidelines are discussed. CONCLUSION: Given the importance of this topic, it is surprising that only three eligible studies were identified. It was not possible to describe the optimal methods of diagnosing infection in diabetic patients with foot ulceration from the evidence identified in this systematic review.