Axillary lymphadenectomy with muscular padding, without drainage

OBJECTIVE: Axillary padding without drainage appeared to be a valuable alternative technique to vacuum drainage. The technique employs local muscles or the axillary aponeurosis for padding. We report here the clinical evaluation of muscular padding without drainage. The analysis of these results prompted us to also do a literature search for other alternatives aimed at reducing morbidity due to vacuum drainage. PATIENTS AND METHODS: Muscular padding was prospectively performed by 8 different surgeons on a total of 152 patients at the Centre Rene-Huguenin (Saint-Cloud, France). Follow-up has attained 3.5 years. A comparative assessment of pain was conducted in 30 patients operated on with vacuum drainage. RESULTS: This technique is easy to learn and reproducible. It facilitates post-operative follow-up, always allowing discharge at the 2nd or 3rd post-operative day without any home nursing. The late sequels are not increased. In contrast, pain was twice more intense during the first post-operative weeks compared with vacuum drainage, and the seroma rate was also increased. DISCUSSION AND CONCLUSION: Despite good efficacy, this worsening of pain is a major obstacle to the routine use of muscular padding. A technical improvement has been published very recently where the axillary aponeurosis was used to pad the axilla. It seems to be equally efficient but less painful than muscular padding. This technique is under clinical evaluation and could appear as a valuable option to vacuum drainage. Other alternatives are discussed. Most studies lack a direct comparison with vacuum drainage and a satisfactory evaluation of quality of life is also omitted. New studies with quality of life scales are ongoing. They should allow us to choose options that take this aspect into account in the future.     

Appropriateness of requests for therapeutic drug monitoring of antiepileptic drugs: the experience in southwestern Saudi Arabia

The purpose of this study was to evaluate request forms of therapeutic drug monitoring of antiepileptic drugs for appropriateness criteria according to published data. Request forms received by the laboratory were sampled as all requests in one day per week on an alternating basis. Drugs monitored were phenytoin (PHT), phenobarbital (PB), carbamazepine (CBZ) and valproic acid (VPA). A total of 420 request forms were collected. Age, gender and weight were provided in 95.5%, 97.1% and 56.9% of request forms, respectively. The diagnosis, seizure type and the indication for therapeutic drug monitoring were provided in 81.6%, 3.2% and 55.5%, respectively. Sampling times were provided in 45% and were considered appropriate in 25.2% of the request forms. The indications for therapeutic drug-monitoring were considered appropriate in 28.6% of the request forms, and only 19.2% of these were appropriately sampled. Only 37.9% of all samples were drawn at steady-state. Serum albumin and creatinine concentrations were lacking in 93.6% and 53.3% of requests, respectively. The potential for drug-drug interactions was detected in 28.6% of all requests. Thus, the information needed for the proper interpretation of therapeutic drug monitoring results and that was provided in the request forms was surprisingly scarce. Most of the appropriateness criteria for therapeutic drug monitoring were not met.     

Differential effects of rapamycin, cyclosporine A, and FK506 on human coronary artery smooth muscle cell proliferation and signalling

BACKGROUND: Immunosuppressive agents are at the forefront of preventing organ rejection after transplantation. However, their effects on vascular smooth muscle cell-mediated intimal hyperplasia that occurs in post-transplant coronary artery disease are less well known. METHODS AND RESULTS: We investigated the in vitro effects of three immunosuppressive agents cyclosporine A (CsA), FK506 (tacrolimus), and rapamycin (sirolimus, Rapa) on cultured human coronary artery smooth muscle cells (cSMC). CsA inhibited both platelet-derived growth factor (PDGF)-stimulated DNA synthesis and serum-induced proliferation at high concentrations (> or =1000 ng/ml). The growth-inhibitory effect of CsA was not altered by anti-TGF-beta neutralising antibodies nor was autocrine TGF-beta release detected in CsA-treated culture medium. At inhibitory doses, CsA inhibited ERK kinase activation by PDGF, although cytotoxicity was also apparent. Most notably, CsA visibly prevented PDGF-induced altered cell morphology. Rapa was a highly potent and effective inhibitor of cSMC proliferation (reduction in DNA synthesis by >50% from 0.01 ng/ml), acting through inhibition of 70-kDa S6 kinase (p70S6k). FK506 (1-1000 ng/ml) did not affect cSMC proliferation alone, although a > or =250-fold excess of FK506 over Rapa completely reversed the inhibitory effect of Rapa, confirming that these two agents share a common intracellular receptor, the FK506-binding protein (FKBP). CONCLUSION: Rapa is a powerful inhibitor of cSMC proliferation, while CsA slighly inhibits cSMC proliferation, although only at higher concentrations that may be toxic. These results indicate that therapeutic immunosuppression with Rapa may be additionally useful in prevention or delay of posttransplant coronary artery disease.     

Kallikrein gene downregulation in breast cancer

Recent evidence suggests that many members of the human kallikrein gene family are differentially regulated in breast cancer and other endocrine-related malignancies. In this study, we utilised the serial analysis of gene expression (SAGE) and expressed sequence tag (EST) databases of the Cancer Genome Anatomy Project (CGAP) to perform in silico analyses of the expression pattern of the 15 human kallikrein genes in normal and cancerous breast tissues and cell lines using different analytical tools such as Virtual Northern blotting, Digital Differential Display and X-profiler. Our results indicate that at least four kallikrein genes (KLK5, 6, 8, 10) are downregulated in breast cancer. Probing eight normal and 24 breast cancer SAGE libraries with gene-specific tags for each of the above kallikreins indicated moderate-to-high expression densities in normal breast (27-319 tags per million; tpm, in two to five out of eight libraries), compared to no or low expression (0 - 34 tpm in zero to two libraries out of 24) in breast cancer. These data were verified by screening the EST databases, where all mRNA clones isolated for these genes, except for one in each, were from normal breast libraries, with no clones detected from breast cancer tissues or cell lines (with the exception of KLK8). X-profiler comparison of two pools of normal and breast cancer libraries further verified the presence of significant downregulation of expression levels of 4 of the kallikreins genes (KLK5, 6, 10, 12). We experimentally verified the downregulation of these four kallikreins (KLK5, 6, 8, 10 and 12) by RT - PCR analysis.     

Primary antiphospholipid syndrome presenting as complicated Henoch-Schönlein purpura

A child showing signs of Henoch-Sch?nlein purpura developed a right tibiofibular vascular thrombosis. Antiphospholipid antibody tests were positive for both lupus anticoagulant and anticardiolipin antibodies. This suggests that an antiphospholipid syndrome should be considered in cases of Henoch-Sch?nlein purpura and antiphospholipid antibodies should be measured to determine whether prophylactic antithrombotic measures are needed to prevent thrombotic manifestations.     

Revascularization in multivessel disease: comparison between two-year outcomes of coronary bypass surgery and stenting

OBJECTIVE: The recent appreciation that stenting has improved the short- and long-term outcomes of patients treated with coronary angioplasty has made it imperative to reconsider the comparison between surgery and percutaneous interventions in patients with multivessel disease. METHODS: One thousand two hundred five patients were randomly assigned to undergo bypass surgery or angioplasty with stent implantation when there was consensus between the cardiac surgeon and interventional cardiologist as to equivalent treatability. The primary clinical end point was freedom from major adverse cardiac and cerebrovascular events at 1 year. Major adverse cardiac and cerebrovascular events at 2 years constituted a secondary end point. RESULTS: At 2 years, 89.6% of the surgical group and 89.2% of the stent group were free from death, stroke, and myocardial infarction (log-rank test P =.65). Among patients who survived without stroke or myocardial infarction, 19.7% in the stent group underwent a second revascularization, as compared with 4.8% in the surgical group (P <.001). At 2 years, 84.8% of the surgical group and 69.5% of the stent group were event-free survivors (log-rank test P <.001), and 87.2% in the surgical cohort and 79.6 % in the stent group were angina-free survivors (P =.001). In the diabetes subgroup, 82.3% of the surgical group and 56.3% of the stent group were free from any events after 2 years (log-rank test P <.001). CONCLUSION: The difference in outcome between surgery and stenting observed at 1 year in patients with multivessel disease remained essentially unchanged at 2 years. Stenting was associated with a greater need for repeat revascularization. In view of the relatively greater difference in outcome in patients with diabetes, surgery clearly seems to be the preferable form of treatment for these patients.     

Early detection of myocardial dysfunction in Chagas disease using novel echocardiographic indices

The first manifestation of cardiac involvement in Chagas disease could be sudden death or rapid deterioration in cardiac function. The aim of this study was to identify a non-invasive method for early detection of cardiac involvement in patients with Chagas disease. During a 6-month period in 2001, 133 people were studied using echocardiography and electrocardiography in Honduras; 88 were seropositive for Trypanosoma cruzi, of which 31 were asymptomatic, and 45 were seronegative controls. The echocardiographic assessment included geometrical and time interval derived indices. Patients with asymptomatic Chagas disease had increased left and right myocardial performance index (MPI) when compared with seronegative controls (P= 0.003 and P= 0.023, respectively) with 36% having a left MPI above the upper limit of the normal range. They also had a reduced diastolic posterior wall thickness (P= 0.005) and lower posterior wall thickness to left ventricular cavity (PWT:LVC) ratio (P= 0.002). Our results show that the MPI, a simple Doppler parameter, and the PWT:LVC ratio are useful in the early detection of myocardial involvement in asymptomatic patients with Chagas disease. These parameters could serve as useful screening tools and monitor the disease progression in these patients.     

mda-7 (IL-24) Inhibits growth and enhances radiosensitivity of glioma cells in vitro via JNK signaling

Despite therapeutic interventions including surgery, chemotherapy and radiotherapy, glioblastoma multiforme (GBM) has a very poor prognosis and novel therapies are required. MDA-7 (IL-24), when expressed via a recombinant replication defective adenovirus, Ad.mda-7, has profound anti-proliferative and cytotoxic effects in a variety of tumor cells, but not in non-transformed cells. The present studies examined the combined impact of Ad.mda-7 and ionizing radiation on the proliferation and survival of GBM cells. Ad.mda-7 reduced the proliferation of rodent and human glioma cells in MTT assays and in colony formation assays. The anti-proliferative effects of Admda-7 were enhanced by radiation in a greater than additive fashion. In vitro, this cellular change correlated with enhanced cell numbers in G1/G0 and G2/M phases of the cell cycle, implying Ad.mda-7 radiosensitizes tumor cells in a cell cycle-independent manner. The radiosensitizing effects were not observed in cultures of non-transformed primary astrocytes. The enhanced reduction in growth correlated with increased necrosis and DNA degradation. Ad.mda-7 enhanced p38 and ERK1/2 activity but did not alter JNK or Akt activity. Irradiation of cells expressing MDA-7 suppressed ERK1/2 activity and dramatically enhanced JNK1/2 activity without altering either Akt or p38 activity. Inhibition of JNK1/2, but not p38, signaling abolished the radiosensitizing properties of MDA-7. Inhibition of neither ERK1/2 nor PI3K signaling enhanced the anti-proliferative effects of Ad.mda-7, whereas combined inhibition of both pathways enhanced cell killing, suggesting that ERK and PI3K signaling can be protective against MDA-7 lethality.