Our results suggest that AUR, I3C, ACA, NOB, and ACE might exert tumor-preventive action through apoptosis- and/or cell proliferation-dependent mechanisms and, on the other hand, CGA, PA, SIN, HE, DIO, and GL might be apoptosis- and cell proliferation-independent. These assays provided an initial tool for further mechanical studies of tumor-preventive agents and future applications to mechanism-based chemopreventive studies.

No abstract

The effects of dietary administration of capsaicin and rotenone on 4-nitroquinoline 1-oxide (4-NQO)-induced tongue tumorigenesis were investigated in male F344 rats. In pilot studies, gavage with capsaicin and rotenone elevated the phase II enzymes glutathione S-transferase (GST) and quinone reductase (QR), in the liver and tongue. Also, a 10 week period of feeding of 500 p.p.m. capsaicin or rotenone together with 4-NQO exposure inhibited the occurrence of tongue dysplasia. Subsequently, a long-term study was conducted to test the protective effects of both compounds on 4-NQO-induced tongue carcinogenesis. One group was treated with 4-NQO alone (20 p.p.m. in drinking water for 8 weeks) and four other groups received the carcinogen treatment plus diets containing 500 p.p.m. test compounds for 10 weeks (initiation phase) or for 28 weeks (post-initiation phase). At the termination of the study (38 weeks), feeding of rotenone during the initiation phase, but not during the post-initiation phase, was found to significantly reduce the incidence of tongue squamous cell carcinoma (53% vs. 16%, 70% reduction, P b=e 0.0250) and severe dysplasia (80% vs. 42%, 70% reduction, P = 0.028). Capsaicin feeding during either the initiation or promotion phase and rotenone feeding during the promotion phase also reduced the frequency of tongue carcinoma without statistical significance. The treatment with two compounds especially rotenone lowered cell proliferation activity in the tongue, elevated phase II enzymes' activities of the liver and tongue, and increased the apoptotic index of tongue carcinoma. Although our results suggest that rotenone feeding during the initiation stage prevented 4-NQO-induced tongue carcinoma, chronic intravenous exposure of rotenone reproduces several features of human Parkinson's disease in rats (Nat. Neurosci., 3, 1301-1306, 2000), suggesting that additional studies to confirm the safety of rotenone are warranted.

The health care-associated pneumonia (HCAP) criteria have a limited ability to predict pneumonia caused by drug-resistant bacteria and favor the overutilization of broad-spectrum antibiotics. We aimed to derive and validate a clinical prediction score with an improved ability to predict the risk of pneumonia due to drug-resistant pathogens compared to that of HCAP criteria.

No abstract

In recent years, advances in PCR techniques have aided in the rapid and accurate detection of common respiratory pathogens from patient specimens. Multiplex PCR can identify and differentiate a large panel of viral and bacterial targets simultaneously. Published studies have shown that multiplex PCR panels are more rapid and more sensitive methods of virus detection than cultures or antigen detection (1, 2). One such method, the FilmArray respiratory panel (FARP) (BioFire Diagnostics, Inc.), is a multiplex, nested PCR technique that can detect 17 common respiratory viruses and 3 bacterial targets in a single reaction in just over 1 h (3). Published studies have shown that for both immunocompetent and immunocompromised patients, the FARP identifies significantly more viral pathogens in both bronchoalveolar lavage (BAL) fluid and nasopharyngeal (NP) samples than viral cultures and direct fluorescent antibody staining and that the FARP is among the most sensitive of the available multiplex assays (1, 4-10). In addition, the FARP has a low hands-on time and very fast turnaround time. Since the FARP is associated with a significant cost to the laboratory and the patient, its judicious use is necessary.Choosing the least invasive, highest yield, and most cost-effective investigations in a stepwise manner has always been central to the practice of medicine. Patients who present with symptoms of a respiratory tract infection often undergo testing for respiratory viruses. The initial testing at our center may involve collection of an NP sample for influenza A and B and respiratory syncytial viruses. The comprehensive FARP is obtained for patients with complex conditions or those who are immunocompromised and have symptoms of upper or lower respiratory tract infections. In the presence of concurrent pulmonary infiltrates, fever, and hypoxia, patients (especially if immunocompromised) may then undergo a bronchoscopy with BAL with repeat FARP testing on the BAL sample. To date, no studies have compared the yield of FARP on BAL samples with the yield on NP samples. Whether additional microbiologic information is obtained from FARP testing on a BAL sample after testing on a NP swab is not known. This retrospective case-control study evaluates the concordance between FARP testing on NP and BAL samples.(Part of this research was presented as a poster at the American Thoracic Society International Conference, Denver, CO, 15 to 20 May 2015.) MATERIALS AND METHODSWe retrospectively reviewed the electronic medical records of all patients evaluated at the Mayo Clinic in Arizona between 1 June 2013, and 31 May 2014, who had FARP testing on both NP and BAL samples. All patients who were included had a BAL sample FARP (BAL FARP) performed within 7 days after an NP swab FARP (NP FARP) during the same hospitalization or illness episode. FARP results obtained on tracheal aspirates were excluded.Patient electronic medical records were reviewed, and the following information was obtained: demographics (age and sex) and the presence of immun...

Ligands for peroxisome proliferator-activated receptor (PPAR) γ γ γ γ have been implicated in growth inhibition and cell differentiation in certain malignancies. In this study, the effects of troglitazone, a PPARγ γ γ γ ligand, given during the postinitiation phase of oral carcinogenesis initiated with 4-nitroquinoline 1-oxide (4-NQO) were investigated in male F344 rats. Rats aged 6 weeks were given 4-NQO at 20 ppm for 8 weeks to induce tongue neoplasms. Starting 1 week after the cessation of 4-NQO exposure, animals were fed diets containing 0, 30 or 100 ppm troglitazone for 22 weeks. At the end of the study (week 32), the incidences of 4-NQO-induced tongue neoplasms and preneoplasms were determined histopathologically and cell proliferation activity was estimated by counting bromodeoxyuridine (BrdU)-labeling indices and cyclin D1-positive cell ratios. In addition, immunohistochemical expression of cyclooxygenase (COX)-2 and PPARγ γ γ γ was assessed in the tongue lesions. Feeding with 100 ppm troglitazone significantly decreased the incidence of squamous cell carcinoma when compared to the group without troglitazone treatment (5.0% vs. 45.8%, P < < < <0.005). Interestingly, the BrdU-labeling index and cyclin D1-positive cell ratio assessed in the non-lesional tongue squamous epithelium were reduced by dietary administration of troglitazone (P < < < <0.0001-0.005). Additionally, the immunoreactivity of COX-2 in the tongue lesions was also decreased by the treatment (P < < < <0.01-0.05). These results clearly showed that dietary troglitazone inhibits 4-NQO-induced tongue carcinogenesis and such inhibition is related to suppression of increased cell proliferation and/or COX-2 expression. This study warrants further investigation on the use of PPARγ γ γ γ ligands as a novel preventive approach for oral malignancy. (Cancer Sci 2003; 94: 365-371) he nuclear receptor superfamily acts as ligand-responsive transcription factors that participate in many processes important for cell and tissue homeostasis. Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear receptor superfamily that includes receptors for steroids, thyroid hormone, vitamin D or retinoic acid.1) At present, several PPARs including PPARα, PPARβ (PPARδ, NUC-1, or FAAR), and PPARγ have been identified.2) Of these, PPARγ was initially shown to have regulatory roles in insulin sensitization. 3,4) The receptor binds to the promoter region of target genes involved in adipocyte differentiation and lipid storage [4][5][6] as a heterodimer with the retinoid X receptor.7) Activation of this receptor has been implicated in glucose metabolism, cell cycle control, and macrophage development and function. [8][9][10][11][12] In addition, recent studies suggest that PPARs play an important role in carcinogenesis. 13) 15-Deoxy-δ-prostaglandin J 2 , a natural-occurring metabolite of prostaglandin D 2 , and troglitazone, a thiazolidinedione analogue and a synthetic anti-diabetic drug, have been reported to be selective ligands for PPARγ.9, 14, 15) Re...

A persistent air leak (PAL) can be caused by either an alveolar-pleural fistula (APF) or bronchopleural fistula (BPF). Complications from PAL lead to an increase in morbidity and mortality, prolonged hospital stay, and higher resource utilization. Pulmonary physicians and thoracic surgeons are often tasked with the difficult and often times frustrating diagnosis and management of PALs. While most patients will improve with chest tube thoracostomy, many will fail requiring alternative bronchoscopic or surgical strategies. Herein, we review the bronchoscopic and surgical diagnostic and treatment options for PAL as it pertains to the field of interventional pulmonology and thoracic surgery.