Effectiveness of chemical pleurodesis in spontaneous pneumothorax recurrence prevention: a systematic review.

OBJECTIVES: Spontaneous pneumothorax is a common pathology. International guidelines suggest pleurodesis for non-resolving air leak or recurrence prevention at second occurrence. This study comprehensively reviews the existing literature regarding chemical pleurodesis efficacy. DESIGN: We systematically reviewed the literature to identify relevant randomised controlled trials (RCTs), case-control studies and case series. We described the findings of these studies and tabulated relative recurrence rates or ORs (in studies with control groups). Meta-analysis was not performed due to substantial clinical heterogeneity. RESULTS: Of 560 abstracts identified by our search strategy, 50 were included in our systematic review following screening. Recurrence rates in patients with chest tube drainage only were between 26.1% and 50.1%. Thoracoscopic talc poudrage (four studies (n=249)) provided recurrence rates of between 2.5% and 10.2% with the only RCT suggesting an OR of 0.10 compared with drainage alone. In comparison, talc administration during video-assisted thoracic surgery (VATS) from eight studies (n=2324) recurrence was between 0.0% and 3.2%, but the RCT did not demonstrate a significant difference compared with bleb/bullectomy alone. Minocycline appears similarly effective post-VATS (recurrence rates 0.0-2.9%). Prolonged air leak and recurrence prevention using tetracycline via chest drain (n=726) is likely to provide recurrence rates between 13.0% and 33.3% and autologous blood patch pleurodesis (n=270) between 15.6% and 18.2%. CONCLUSIONS: Chemical pleurodesis postsurgical treatment or via thoracoscopy appears to be most effective. Evidence for definitive success rates of each agent is limited by the small number of randomised trials or other comparative studies.

Role of CT in assessing pleural malignancy prior to thoracoscopy.

The definitive diagnosis of pleural malignancy depends upon histological confirmation by pleural biopsy. CT is reported to have a high sensitivity and specificity for the diagnosis of malignant pleural disease, and is part of the routine diagnostic workup of these patients. The aim of this study was to assess the sensitivity and specificity of CT in detecting pleural malignancy prior to definitive histology obtained via thoracoscopy in a large cohort of patients with suspected malignant pleural disease. Retrospective review of thoracoscopies between January 2008 and January 2013 at two UK tertiary referral centres: Oxford and Preston. The histological results were compared with the CT reported diagnosis before the procedure. CT scan reports were assessed by independent respiratory physicians as to whether the radiologist concluded evidence of malignant pleural disease or benign features only. 211 (57%) of 370 patients included in the analysis had malignant disease: CT scans were reported as 'malignant' in 144, giving a sensitivity of 68% (95% CI 62% to 75%). Of the 159 patients with benign disease, 124 had CT scans reported as benign: specificity 78% (72% to 84%). The positive predictive value of a malignant CT report was 80% (75% to 86%), with a negative predictive value of 65% (58% to 72%). A significant proportion of patients being investigated for malignant disease will have malignancy despite a negative CT report. The use of CT alone in determining which patients should have invasive pleural biopsies should be re-evaluated, and further studies to define the diagnostic pathway are now required.

An in vitro model for the pro-fibrotic effects of retinoids: mechanisms of action.

BACKGROUND AND PURPOSE: Retinoids, including all-trans retinoic acid (tRA), have dose-dependent pro-fibrotic effects in experimental kidney diseases. To understand and eventually prevent such adverse effects, it is important to establish relevant in vitro models and unravel their mechanisms. EXPERIMENTAL APPROACH: Fibrogenic effects of retinoids were assessed in NRK-49F renal fibroblasts using picro-Sirius red staining for collagens and quantified by spectrophotometric analysis of the eluted stain. Other methods included RT-qPCR, immunoassays and matrix metalloproteinase (MMP) activity assays. KEY RESULTS: With or without TGF-ß1, tRA was dose-dependently pro-fibrotic, notably increasing collagen accumulation. tRA and TGF-ß1 additively suppressed expression of mRNA for MMP2, 3 and 13 and suppressed MMP activity. tRA, in the presence of TGF-ß1, induced plasminogen activator inhibitor-1 (PAI-1) mRNA and they additively induced PAI-1 protein expression. A PAI-1 inhibitor, a pan-retinoic acid receptor (RAR) antagonist and a pan-retinoid X receptor (RXR) antagonist each partially prevented the pro-fibrotic effect of tRA. The dose-dependent pro-fibrotic effects of a pan-RXR agonist were similar to those of tRA. A pan-RAR agonist showed weaker, less dose-dependent pro-fibrotic effects and the pro-fibrotic effects of RARα and RARß-selective agonists were even smaller. An RARγ-selective agonist did not affect fibrogenesis. CONCLUSIONS AND IMPLICATIONS: An in vitro model for the pro-fibrotic effects of retinoids was established in NRK-49F cells. It was associated with reduced MMP activity and increased PAI-1 expression, and was probably mediated by RXR and RAR. To avoid or antagonize the pro-fibrotic activity of tRA, further studies on RAR isotype-selective agonists and PAI-1 inhibitors might be of value.

Retinoic acid receptor-α signalling antagonizes both intracellular and extracellular amyloid-ß production and prevents neuronal cell death caused by amyloid-ß.

Alzheimer's disease (AD) is characterized by amyloid-ß (Aß) deposition in the brain, neuronal cell loss and cognitive decline. We show here that retinoic acid receptor (RAR)α signalling in vitro can prevent both intracellular and extracellular Aß accumulation. RARα signalling increases the expression of a disintegrin and metalloprotease 10, an α-secretase that processes the amyloid precursor protein into the non-amyloidic pathway, thus reducing Aß production. We also show that RARα agonists are neuroprotective, as they prevent Aß-induced neuronal cell death in cortical cultures. If RARα agonists are given to the Tg2576 mouse, the normal Aß production in their brains is suppressed. In contrast, neither RARß nor γ-agonists affect Aß production or Aß-mediated neuronal cell death. Therefore, RARα agonists have therapeutic potential for the treatment of AD.

RA regulation of keratin expression and myogenesis suggests different ways of regenerating muscle in adult amphibian limbs.

Formation of a regeneration blastema following limb amputation is believed to occur through a process of dedifferentiation. It has been suggested, however, that the cells contributed to the blastema by the stump muscle are satellite-like cells, rather than cells originated by dedifferentiation. We have previously shown that simple epithelial keratins 8 and 18 are expressed in the mesenchymal progenitor cells of the regenerating amphibian limb and in cultured cells with myogenic potential, and that their expression appears to be causally related to changes in proliferation and differentiation. We show here that retinoic acid (RA) affects the expression of these keratins differently in myogenic cells originated from normal limb and limb blastema. Furthermore, we find that the effects of RA on proliferation, myogenic differentiation and adhesion of these cells also differ. In fact, whereas RA does not affect keratin expression, proliferation or myogenic differentiation in blastemal cells, it does decrease keratin levels and thymidine incorporation and increase myogenesis in cells from normal limb. Conversely, RA increases cell adhesion only in blastemal cells. Significantly, these effects of RA on cultured cells are consistent with those observed in vivo. Overall the results presented here suggest that in the urodele limb there are two distinct cell populations with myogenic potential, one originating from dedifferentiation and one equivalent to the satellite cells of the mammalian muscle, which are likely to be primarily involved in blastema formation and muscle repair, respectively.

Fatal septicaemia in a previously healthy man following a dog bite.

A rare case of fatal septicaemia after a dog bite in a previously healthy individual is presented and discussed. Capnocytophaga canimorsus (DF-2 bacterium) was isolated from blood cultures. Our case shows the importance of immediate antibiotic treatment for all dog and cat bites, regardless of severity.

Keratin 8 and 18 expression in mesenchymal progenitor cells of regenerating limbs is associated with cell proliferation and differentiation.

Keratins are considered markers of epithelial differentiation. In lower vertebrates, however, immunoreactivity for keratin 8 and 18 has been reported in nonepithelial cells, particularly in mesenchymal progenitor cells of regenerating complex body structures. To confirm that such reactivity does indeed reflect keratin expression and to investigate their possible role in regeneration, we have isolated clones coding for the newt homologues of keratin 8 and 18 (NvK8 and NvK18, respectively) and studied their distribution and changes in their expression following experimental manipulations. Analysis of NvK8 and NvK18 transcripts confirms that K8 and K18 are expressed in the blastemal cells of regenerating newt limbs and that their expression is first observed 3-5 days after amputation, when the blastemal cells start to proliferate under the influence of the nerve, whose presence is essential for regeneration to proceed. In contrast, no induction of these keratins is observed following amputation of a larval limb at a stage when organogenesis is proceeding in a nerve-independent manner. To establish whether there is a causal relationship between keratin expression and cell proliferation in the adult limb blastema, we have investigated whether their expression is nerve-dependent and whether suppression of their expression in cultured blastemal cells affects cell division and differentiation. Analysis of keratins in denervated limbs demonstrates that the nerve is not necessary to induce their expression. However, treatment of cultured blastemal cells with K8 and K18 anti-sense oligonucleotides significantly decreases DNA synthesis and induces changes in cell morphology, suggesting that expression of these keratins during regeneration may be necessary for the maintenance of the undifferentiated and proliferative state of blastemal cells.

Chronic sinusitis and zinc-containing endodontic obturating pastes.

Several researchers have reported a link between the development of a solitary antral aspergillus sinusitis and the presence of zinc-containing root canal obturating paste within the antrum. If diagnosed correctly, it is generally accepted that this type of sinusitis can be treated effectively using surgical techniques alone. However, previous reports have shown that this is not always the case and may result in prolonged and inappropriate treatment of the condition. It is hoped that the reported case and literature review will assist both dental and medical practitioners in identifying affected patients and in the subsequent instigation of correct treatment regimes.

Psychological treatment of anabolic-androgenic steroid-dependent individuals.

Anabolic-androgenic steroids (AAS) are synthetic derivatives of the sex hormone testosterone. Anabolic refers to the "growth-promoting" effect while androgenic refers to the "masculinizing" effect. It is becoming more evident that nonathletes as well as athletes are abusing AAS. Although the abuse of alcohol and other drugs contribute significantly to current chemical use problems in American society, AAS abuse is one of the fastest growing "new drug" problems facing secondary and higher education institutes of learning. The purpose of this discussion is to present working hypotheses regarding the psychological treatment of AAS dependent individuals. The treatment approach presented incorporates the approaches used with eating disorders, substance abuse/dependence, and narcissistic personality disorders. This paper considers some of the preliminary considerations for the first phase of treatment, some pitfalls to avoid, and therapist characteristics, as well as treatment modalities that might be helpful in the treatment of AAS-dependent individuals.