Clinical and diagnostic imaging findings predict anesthetic complications in children presenting with malignant mediastinal masses

BACKGROUND: The presence of a mediastinal mass in a child poses significant anesthesia-related risks including death. To optimize outcome clinicians must be able to predict which patients are at highest risk of anesthetic complications. METHODS: We conducted a retrospective review of 118 pediatric patients who presented with mediastinal masses. We investigated their medical records for clinical symptoms and signs at presentation and reviewed their chest radiographs, computed tomography scans, and echocardiograms and electrocardiograms when available. We then conducted analyses to identify clinical and diagnostic imaging features associated with anesthesia-related complications. RESULTS: Eleven of 117 [9.4%, 95% confidence interval (CI) 4.1-14.7%] patients experienced an anesthesia-related complication. Four preoperative features were significantly associated with anesthetic complications: orthopnea (P = 0.033, odds ratio (OR) 5.31, 95% CI, 1.15-24.56), upper body edema (P = 0.035, OR 8.00, 95% CI, 1.16-55.07), great vessel compression (P = 0.037, OR 5.41, 95% CI, 1.11-26.49), and main-stem bronchus compression (P = 0.044, OR 5.11, 95% CI, 1.05-24.92). The presence of pleural effusion (P = 0.060, OR 4.53, 95% CI, 0.94-21.96) or tracheal compression (P = 0.061, OR 5.09, 95% CI, 0.93-27.81) also appeared to be risk factors. Although the rate of anesthesia-related complications detected in our cohort was comparable with that found in earlier studies, the events were less severe. CONCLUSIONS: Patients who present with orthopnea, upper body edema, great vessel compression and main stem bronchus compression are at risk of anesthesia-related complications. The low severity of complications in our series may reflect a combination of factors: use of the least invasive method such as interventional radiology to obtain tissue for diagnosis, completion of a thorough preoperative assessment and minimal anesthesia intervention.     

Clinicians' attitudes to prostate cancer peer-support groups

OBJECTIVE: To assess clinicians' knowledge and attitudes to prostate cancer peer-support groups, essential in improving support services for men with prostate cancer, as patients' perceptions of their clinicians' attitudes to such groups predict patients' positive and negative perceptions of their experiences at such groups. SUBJECTS AND METHODS: In all, 36 clinicians (75% response) across Australia, of whom 27 were urologists and nine were radiation oncologists, were interviewed in-depth using a key-informant approach. Nine clinicians were from regional Australia, with the remaining 27 from major metropolitan settings. Subsequently, 30 clinicians (69% response) completed surveys to confirm identified themes. RESULTS: Peer support was rated positively by most clinicians and most report a fair to good knowledge of such groups. However, less than a quarter regularly refer their patients to these groups. While clinicians can describe positive aspects of peer support, many are concerned that biased viewpoints and misinformation within these groups might potentially contribute to patients' decisional uncertainty and regret. CONCLUSIONS: Further research is needed to establish for whom these support groups are most helpful. Concerns about misleading information that might be proffered in support groups is a barrier to clinician referral to these groups. Dialogue between prostate cancer interest groups and clinicians to resolve concerns presents as a key strategy to improve support for men with prostate cancer.     

Phosphoprotein pathway mapping: Akt/mammalian target of rapamycin activation is negatively associated with childhood rhabdomyosarcoma survival

Mapping of protein signaling networks within tumors can identify new targets for therapy and provide a means to stratify patients for individualized therapy. Despite advances in combination chemotherapy, the overall survival for childhood rhabdomyosarcoma remains approximately 60%. A critical goal is to identify functionally important protein signaling defects associated with treatment failure for the 40% nonresponder cohort. Here, we show, by phosphoproteomic network analysis of microdissected tumor cells, that interlinked components of the Akt/mammalian target of rapamycin (mTOR) pathway exhibited increased levels of phosphorylation for tumors of patients with short-term survival. Specimens (n = 59) were obtained from the Children's Oncology Group Intergroup Rhabdomyosarcoma Study (IRS) IV, D9502 and D9803, with 12-year follow-up. High phosphorylation levels were associated with poor overall and poor disease-free survival: Akt Ser(473) (overall survival P < 0.001, recurrence-free survival P < 0.0009), 4EBP1 Thr(37/46) (overall survival P < 0.0110, recurrence-free survival P < 0.0106), eIF4G Ser(1108) (overall survival P < 0.0017, recurrence-free survival P < 0.0072), and p70S6 Thr(389) (overall survival P < 0.0085, recurrence-free survival P < 0.0296). Moreover, the findings support an altered interrelationship between the insulin receptor substrate (IRS-1) and Akt/mTOR pathway proteins (P < 0.0027) for tumors from patients with poor survival. The functional significance of this pathway was tested using CCI-779 in a mouse xenograft model. CCI-779 suppressed phosphorylation of mTOR downstream proteins and greatly reduced the growth of two different rhabdomyosarcoma (RD embryonal P = 0.00008; Rh30 alveolar P = 0.0002) cell lines compared with controls. These results suggest that phosphoprotein mapping of the Akt/mTOR pathway should be studied further as a means to select patients to receive mTOR/IRS pathway inhibitors before administration of chemotherapy.     

Repair pathways evident in human liver organ slices

The extension of human liver slice culture viability for several days broadens the potential of this ex vivo model for characterizing pathways of organ injury and repair, and allows for the multiple dosing of compounds. Extended viability is demonstrated by continued synthesis of GSH and ATP, and maintenance of intracellular K⁺ levels. Gene expression profiling revealed the activation of regeneration pathways via increased expression of collagens (I, IV, and V), laminins, ninjurin, growth factors (EGF, epiregulin, and TGF-β1), matrix metalloproteinase-7, and insulin like growth factor 5. Collagen IV protein levels began to increase by day 4 of culture. Some markers of hepatic stellate cells, detected by RT-PCR, were up-regulated (HSP47, αSMA, pro-collagen 1a1, PDGF receptor, thrombospondin-2) with time in culture, while other markers exhibited no change or were down-regulated (αB-crystallin, synaptophysin), suggesting that the induction of regenerative pathways may in part be the role of the stellate cells as well as resident fibroblasts. Complimentary to the gene expression was evidence of regeneration in the human liver slices, as evaluated by histopathology. Improvements in organ acquisition, organ slice preparation and culture methods demonstrates that organ slice viability, integrity and morphology can be extended reproducibly for several days in culture which allows for the investigation of injury and repair processes.     

SOCS1 deficiency results in accelerated mammary gland development and rescues lactation in prolactin receptor–deficient mice

Prolactin is essential for proliferation and differentiation of the developing mammary gland. We have explored a role for Suppressor of Cytokine Signaling 1 (SOCS1) as a modulator of the prolactin response using mice deficient in SOCS1, which were rescued from neonatal death by deletion of the Interferon gamma (IFN gamma) gene. SOCS1(-/-)/IFN gamma(-/-) mice exhibited accelerated lobuloalveolar development in the mammary gland during late pregnancy and precocious lactation. Significantly, the lactogenic defect in prolactin receptor heterozygous females could be rescued by deletion of a single SOCS1 allele. These findings establish a role for SOCS1 as a negative regulator of prolactin signaling and suggest that SOCS1 is required for the prevention of lactation prior to parturition.     

Characterization of potentially chemopreventive phenols in extracts of brown rice that inhibit the growth of human breast and colon cancer cells.

Rice is a staple diet in Asia, where the incidence of breast and colon cancer is markedly below that in the Western world. We investigated potential colon and breast tumor-suppressive properties of rice, testing the hypothesis that rice contains phenols that interfere with the proliferation or colony-forming ability of breast or colon cells. Brown rice, its white milled counterpart, and bran from brown rice were boiled and extracted with ethyl acetate. The extracts were analyzed by high pressure liquid chromatography-mass spectrometry. Eight phenols, protocatechuic acid, p-coumaric acid, caffeic acid, ferulic acid, sinapic acid, vanillic acid, methoxycinnamic acid, and tricin, were identified in the extracts of bran and intact brown rice. These extracts were separated into nine fractions by column chromatography. The effect of bran extract and its fractions at 100 microg/ml on cell viability and colony-forming ability of human-derived breast and colon cell lines was assessed. Bran extract decreased numbers of viable MDA MB 468 and HBL 100 breast cells and colon-derived SW 480 and human colonic epithelial cells as judged by the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4 -sulfophenyl)-2H-tetrazolium assay. It also reduced colony formation of SW 480 colon and MDA MB 468 breast cells. Of the eight phenols identified in the brown rice bran, when applied at 50 microM, caffeic acid decreased numbers of all cell types except HBL 100. Tricin, ferulic acid, and methoxycinnamic acid interfered with cell viability in one or more cell lines. Tricin (50 microM) and the other phenols (200 microM) inhibited colony formation of SW 480 cells. Clonogenicity of MDA MB 468 cells was inhibited by caffeic acid, ferulic acid, and tricin (50 microM). Tricin was the most potent anticlonogenic of the compounds with IC50s of 16 microM in the SW 480 colon cells and 0.6 microM in the MDA MB 468 breast cells. The results suggest that: (a) brown rice and bran contain compounds with putative cancer chemopreventive properties; (b) certain phenols contained in brown rice bran, e.g., tricin, may be associated with this activity; and (c) these phenols are present at much lower levels in white than in brown rice. Thus, the consumption of rice bran or brown rice instead of milled white rice may be advantageous with respect to cancer prevention.     

Reactive arthritis: preliminary microbiologic analysis of the human temporomandibular joint.

PURPOSE: The presence of Chlamydia trachomatis has been previously shown in the temporomandibular joint (TMJ). This study investigated whether the presence of other bacteria associated with reactive arthritis (ReA) can be identified in the TMJ. MATERIALS AND METHODS: Posterior bilaminar tissue removed during TMJ surgery from 26 patients (24 F, 2 M) was evaluated for the presence of C. trachomatis, Mycoplasma fermentans, Mycoplasma genitalium, Campylobacter jejuni, Yersinia enterocolitica, Salmonella spp, and Shigella spp by highly specific polymerase chain reaction (PCR) assays. RESULTS: Bacterial DNA was identified in the TMJ as follows: C. trachomatis, 11 of 26 (42%); M. fermentans/orale, 6 of 26 (23%); M. genitalium, 9 of 26 (35%). Nine of 26 TMJs (35%) had the presence of a single bacterial species. Eight of 26 TMJs (31%) had more than 1 species, as follows: C. trachomatis with either M. genitalium or M. fermentans/orale in 5 of 26 (19%), M. fermentans/orale with M. genitalium 2 of 26 (8%), and C. trachomatis/M. fermentans/orale/M. genitalium, 1 of 26 (4%). A total of 17 of 26 (65%) of TMJs had the presence of bacteria identified in the TMJ. Campylobacter jejuni, Y. enterocolitica, Salmonella spp, and Shigella spp were not identified in any samples. CONCLUSIONS: The presence of M. genitalium in the human TMJ has not been previously reported. The presence of bacteria in the TMJ, either singly or concurrently with other bacteria, may serve as the pathogenetic mechanism of TMJ inflammation. The presence of 2 bacteria from the urogenital tract in the TMJ suggests that internal derangement of the TMJ may occur as a result of a sexually acquired infection.