Burow''s Triangle Advancement Flaps for Excision of Two Closely Approximated Skin Lesions

The Burow's triangle advancement flap can be adapted to simultaneously remove two closely approximated cutaneous lesions. Possible technical variants and their limitations are discussed. Four clinical cases are presented. This technique gives good cosmetic results and reduces operating time.     

Nefazodone, meta-chlorophenylpiperazine, and their metabolites in vitro: cytochromes mediating transformation, and P450-3A4 inhibitory actions

Rationale: Understanding of the mechanisms of biotransformation of antidepressant drugs, and of their capacity to interact with other medications, is of direct relevance to rational clinical psychopharmacology. Objectives: To determine the human cytochromes P450 mediating the metabolism of nefazodone, and the inhibitory activity of nefazodone and metabolites versus human P450–3A. Methods: Biotransformation of nefazodone to its metabolic products, and of meta-chlorophenylpiperazine (mCPP) to para-hydroxy-mCPP, was studied in vitro using human liver microsomes and heterologously expressed human cytochromes. Nefazodone and metabolites were also tested as inhibitors of alprazolam hydroxylation, reflecting activity of cytochrome P450–3A isoforms. Results: mCPP and two hydroxylated derivatives were the principal metabolites formed from nefazodone by liver microsomes. Metabolite production was strongly inhibited by ketoconazole or troleandomycin (relatively specific P450–3A inhibitors), and by an anti-P450-3A antibody. Only heterologously expressed human P450-3A4 mediated formation of nefazodone metabolites from the parent compound. Nefazodone, hydroxy-nefazodone, and para-hydroxy-nefazodone were strong 3A inhibitors, being more potent than norfluoxetine and fluvoxamine, but less potent than ketoconazole. The triazoledione metabolite and mCPP had weak or negligible 3A-inhibiting activity. Formation of para-hydroxy-mCPP from mCPP was mediated by heterologously expressed P450-2D6; in liver microsomes, the reaction was strongly inhibitable by quinidine, a relatively specific 2D6 inhibitor. Conclusion: The complex parallel biotransformation pathways of nefazodone are mediated mainly by human cytochrome P450-3A, whereas clearance of mCPP is mediated by P450-2D6. Nefazodone and two of its hydroxylated metabolites are potent 3A inhibitors, accounting for pharmacokinetic drug interactions of nefazodone with 3A substrate drugs such as triazolam and alprazolam. Received: 4 January 1999/Final version: 24 February 1999     

Targeted therapies in bronchioloalveolar carcinoma

Bronchioloalveolar carcinoma (BAC) is a subtype of adenocarcinoma with unique epidemiology, pathology, clinical features, radiographic presentation, and natural history compared with other non-small cell lung cancer (NSCLC) subtypes. According to criteria of the revised 2004 World Health Organization classification it accounts for only 5% of all cases of NSCLC. BAC cases are mostly represented by females and non-smokers and are diagnosed at a younger age. Patients with resected BAC have prolonged survival and a lower recurrence rate after surgical resection than other NSCLC subtypes. In advanced BAC cytotoxic chemotherapy seems as effective as in other NSCLC, although studies on pure BAC are based on small numbers of patients and mainly tested paclitaxel based regimens on preclinical activity on cell lines. A higher than expected response rate to the epidermal growth factor (EGFR) tyrosine kinase inhibitors gefitinib and erlotinib was recorded in BAC or in adenocarcinomas with BAC features compared with other NSCLC subtypes, mainly due to a higher rate of never-smoking patients. In fact, these agents demonstrated activity in the first-line setting especially in patients harboring EGFR mutations. The role of molecular predictors of response and survival such as EGFR gene amplification or EGFR mutations is an open field of research in fine-tuning BAC management. New drugs are being tested in advanced BAC, while more prospective data must be collected on predictive and prognostic factors.     

Evaluation of official instrumental methods for the determination of particulate matter contamination in large volume parenteral solutions

The distribution pattern of particle contamination in nine different types of LV parenteral solutions and the possibility of correlating the counts made with two official instruments (Coulter Counter and HIAC) were studied. Two hundred containers of LV parenteral solutions (corresponding to 40 batches) produced in Italy, were sampled. Each bottle was submitted to HIAC and Coulter Counter countings, for particle sizes ranging between 2 and 25 micron. For about 50% of the products, the two straight lines that represent the distribution of particle contamination obtained with the two methods did not cross-over within the studied size range, the Coulter Counter counts always proving higher than the HIAC ones. In the other cases, the cross-over point of the two lines occurred at varying size levels. Statistical analysis of the results pointed to a relationship between the contamination values obtained with the two counting methods for sizes ranging between 2 and 5 micron, but there was no correlation for sizes equal to, or higher than, 10 micron. From the maximum contamination levels established by the BP and the FU IX for the HIAC method, the corresponding values were calculated for the Coulter Counter method. Similarly the values were calculated the HIAC method based on the maximum values set for the Coulter Counter.     

Aplastic anaemia in childhood. Description of two cases and review of the literature

Childhood aplastic anaemia (AA) is an uncommon but potentially fatal haematological disorder. Patients with AA receive supportive care based on transfusions and timely treatment of opportunistic infections, along with specific therapies, which may be bone marrow transplantation and immunosuppressive therapy. Early diagnosis and supportive therapy are required to prevent fatal complications like overwhelming sepsis or life threatening haemorrhages. We report two cases of aplastic anaemia having a different aetiology. The diagnostic work-up and the therapeutic management for each case are described below.     

Sleep-related breathing impairment in myotonic dystrophy

Summary Respiratory failure has been described in myotonic dystrophy; it worsens during sleep but its central or peripheral origin has yet to be determined. Moreover, patients may present severely disturbed sleep and daytime somnolence. Eight patients with mild to moderate myotonic dystrophy were studied to assess breathing function while awake and during sleep by means of the pulmonary function tests, nocturnal polysomnographic examination and the multiple sleep latency test (MSLT). Three patients had restrictive respiratory defects; none had signs of airway obstruction. All patients had very disrupted nocturnal sleep. Of six patients who underwent the MSLT only two showed a mild tendency to sleep during the day. Six patients had pathological apnoea plus hypopnoea index [(A+H)I] and there was a prevalence of central apnoeas. The apnoeas occurred while resting but awake and throughout all sleep stages. Only two patients (the ones with the least vital capacity) had episodes of progressive oxygen desaturation during rapid eye movement sleep, similar to those found in other restrictive disorders and in chronic obstructive pulmonary disease. It is concluded that the breathing pattern characteristic of our myotonic dystrophy patients was the occurrence of central apnoeas both at rest while awake and during sleep.