We examined the effect of sleep state on the response of genioglossus muscle (EMGgg) activity to total airway occlusion applied at 1) nasal (N) airway [and thus exposing the upper airway (UAW) to pressure changes] and 2) tracheal (T) airway (thus excluding UAW from pressure changes). A total of 233 tests were performed during wakefulness (W), 98 tests in slow-wave sleep (SWS), and 72 tests in rapid-eye-movement (REM) sleep. Prolongation of inspiratory time (TI) of the first occluded effort occurred in all tests irrespective of behavioral state, with the greatest increase seen in awake N tests. Nasal tests augmented EMGgg activity in the first occluded breath and produced a linear increase in EMGgg during occlusion. The EMGgg activity at any given time during nasal occlusion in SWS was less than that recorded during W tests. There was a marked reduction in EMGgg response to N occlusion during REM sleep. The EMGgg activity during awake T tests was significantly less than that of N tests at any given time during occlusion. There was no relationship between the level of EMGgg activity and asphyxia in T tests performed during SWS and REM sleep. Nasal tests decreased the force generated by the inspiratory pump muscles and the central drive to breathing compared with T tests. These results confirm the important role of the UAW in regulating breathing pattern and indicate that both immediate and progressive load-compensating responses during nasal occlusion are influenced by information arising from the UAW.

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colorectal cancers have responded to braf kinase inhibitor monotherapy in early-phase trials 14 , raising the possibility that effective treatment may require blockade of one or more additional pathways 15 . Conversely, the clinical response of colorectal cancers to regimens including epidermal growth factor receptor (egfr) inhibitors appears to require both wild-type BRAF and KRAS status [16][17][18] .Because recent laboratory studies have confirmed that de novo resistance to braf inhibitors in BRAF V600E -mutated colorectal cancer is caused by egfr signalling 19,20 , we hypothesised that dual blockade of the braf and egfr pathways might be therapeutically useful, as has been suggested by preclinical data 15 . Moreover, a previous randomized trial of cetuximab combined with the nonspecific Raf inhibitor sorafenib indicated a doubling of the response rate in patients with metastatic colon cancer 21 . Here, we report an end-stage colorectal cancer patient benefiting from combination noncytotoxic drug therapy simultaneously targeting the egfr and braf signalling pathways. CASE REPORTA 78-year-old man presented in 2006 with anemia caused by an obstructive mucinous colorectal cancer of the hepatic flexure. The 75-mm tumour was resected en bloc. Vascular invasion and perineural infiltration were present, and 9 of 21 nodes contained metastases. The mismatch repair proteins mlh1 and pms2 were not detectable by immunohistochemistry.After surgery and biweekly oxaliplatin-based (folfox) adjuvant chemotherapy, our patient remained well until 2010, when rising serum carcinoembryonic antigen (cea) and fluorodeoxyglucose positron-emission tomography heralded recurrence in the right external iliac and inguinal nodes, with involvement of the anterior abdominal wall. Palliative use of oral capecitabine was poorly tolerated because of severe diarrhea and hand-foot syndrome, and it failed to stem the rising cea. Treatment was ABSTRACT Mismatch-repair-deficient colorectal cancers often contain kinase-activating V600E BRAF mutations, but no clinical utility has yet been demonstrated in this setting for monotherapy using oral braf kinase inhibitors such as vemurafenib or dabrafenib. Recent studies have indicated that tumour resistance to braf inhibition is mediated by upregulated epidermal growth factor receptor (egfr) signalling, disruption of which is a routine treatment strategy in KRAS wildtype colorectal cancer. In this report, we describe the clinical course of a heavily pretreated patient who elected to receive off-label dual-targeted braf-and egfr-inhibitory therapy with good tolerance and apparent clinical benefit.

(18)F-FDG-PET/CT imaging should be performed as late as reasonably possible after tracer administration in order to increase tumour-to-background contrast and thereby improve the sensitivity of demonstrating additional sites of disease. Dual-time-point (18)FDG-PET/CT may be of benefit in the evaluation of intra-abdominal lesions but does not improve the overall evaluation of pulmonary lesions.

A 66-year-old woman was referred for a bone scan to assess back pain on a background of breast cancer, melanoma, and rheumatic heart disease. The scan appearance was suspicious for a localized soft tissue neoplasm. An FDG coincidence positron emission tomography (PET) study demonstrated a large FDG-avid soft tissue abnormality. Staphylococcus aureus was isolated from a subsequent needle biopsy. This case illustrates the use of FDG-PET in infection imaging, as well as demonstrating the potential pitfalls in nuclear oncology. Because FDG is not tumor-specific, accumulation in benign lesions may give rise to false-positive results despite a high pretest probability for malignancy.

A 68-year-old woman reported acute severe pain in both lower limbs during a dipyridamole sestamibi myocardial perfusion scan. The pain was rapidly relieved by the administration of intravenous aminophylline. A review of the literature on the adverse effects of dipyridamole did not include this symptom.

The aim of this study was to determine if attenuation correction (AC) in a dual-head, coincidence, positron emission tomography imaging system (Co-PET) improved image quality, lesion detection, patient staging and management of various malignant neoplasms, compared to non-attenuation corrected (NAC) images. Thirty patients with known or suspected malignant neoplasms underwent fluorodeoxyglucose (FDG) Co-PET, which was correlated with histopathology, computed tomography (CT) and other conventional imaging modalities and clinical follow-up. The number and location of FDG avid lesions detected on the AC images and NAC Co-PET images were blindly assessed by two independent observers. Semi-quantitative grading of image clarity and lesion-to-background quality was performed. This revealed markedly improved image clarity and lesion-to-background quality in the AC versus NAC Co-PET images. AC Co-PET was statistically superior to NAC Co-PET in relation to lesion detection (P<0.01) and tumour staging (P<0.01). NAC Co-PET demonstrated 51 of the 65 lesions (78%) detected by AC Co-PET. AC Co-PET altered tumour staging in five additional patients (16%) compared to NAC Co-PET. Management was altered in two of these five patients.

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