From the Cover: PNAS Plus: Amygdala lesions disrupt modulation of functional MRI activity evoked by facial expression in the monkey inferior temporal cortex

Significance

Successful social interaction depends on the ability to recognize others, evaluate their mental states (e.g. intentions, desires, and beliefs), and “read” their emotional states. Here, we show that, in monkeys, damage to the amygdala, a brain structure that is central to the expression of emotion, significantly disrupts the processing of emotional facial expression in high-level visual cortical areas involved in face recognition. These findings suggest that the projections of the amygdala to visual cortical areas likely enhance the sensory processing of biologically important signals, including those related to potential environmental threats and social contexts.     

Randomised trial of standard 2D radiotherapy (RT) versus intensity modulated radiotherapy (IMRT) in patients prescribed breast radiotherapy.

BACKGROUND: Radiation dose distributions created by two dimensional (2D) treatment planning are responsible for partial volumes receiving >107% of the prescribed dose in a proportion of patients prescribed whole breast radiotherapy after tumour excision of early breast cancer. These may contribute to clinically significant late radiation adverse effects. AIM: To test three dimensional (3D) intensity modulated radiotherapy (IMRT) against 2D dosimetry using standard wedge compensators in terms of late adverse effects after whole breast radiotherapy. METHODS: Three hundred and six women prescribed whole breast radiotherapy after tumour excision for early stage cancer were randomised to 3D IMRT (test arm) or 2D radiotherapy delivered using standard wedge compensators (control arm). All patients were treated with 6 or 10MV photons to a dose of 50Gy in 25 fractions to 100% in 5 weeks followed by an electron boost to the tumour bed of 11.1Gy in 5 fractions to 100%. The primary endpoint was change in breast appearance scored from serial photographs taken before radiotherapy and at 1, 2 and 5 years follow up. Secondary endpoints included patient self-assessments of breast discomfort, breast hardness, quality of life and physician assessments of breast induration. Analysis was by intention to treat. RESULTS: 240 (79%) patients with 5-year photographs were available for analysis. Change in breast appearance was identified in 71/122 (58%) allocated standard 2D treatment compared to only 47/118 (40%) patients allocated 3D IMRT. The control arm patients were 1.7 times more likely to have a change in breast appearance than the IMRT arm patients after adjustment for year of photographic assessment (95% confidence interval 1.2-2.5, p=0.008). Significantly fewer patients in the 3D IMRT group developed palpable induration assessed clinically in the centre of the breast, pectoral fold, infra-mammary fold and at the boost site. No significant differences between treatment groups were found in patient reported breast discomfort, breast hardness or quality of life. CONCLUSION: This analysis suggests that minimisation of unwanted radiation dose inhomogeneity in the breast reduces late adverse effects. Incidence of change in breast appearance was statistically significantly higher in patients in the standard 2D treatment arm compared with the IMRT arm. A beneficial effect on quality of life remains to be demonstrated.     

Blood lactate and mixed venous-arterial PCO2 gradient as indices of poor peripheral perfusion following cardiopulmonary bypass surgry

Conventional indices of tissue perfusion after surgery involving cardiopulmonary bypass (CPB) may not accurately reflect disordered cell metabolism. Venous hypercarbia leading to an increased veno-arterial difference in CO₂ tensions (V-aCO₂ gradient) has been shown to reflect critical reductions in systemic and pulmonary blood flow that occur during cardiorespiratory arrest and septic shock. We therefore measured plasma lactate levels and V-aCO₂ gradients in 10 patients (mean age 57.2 years) following CPB and compared them with conventional indices of tissue perfusion. Plasma lactate levels, cardiac index (CI) and oxygen uptake all increased significantly (p<0.05 vs baseline levels) up to 3h following surgery. Oxygen delivery did not change. Plasma lactate levels correlated significantly with CI (r=0.47,p<0.01). V-aCO₂ fell significantly with time (p<0.01 vs baseline). There was an inverse relationship between V-aCO₂ and cardiac index and V-aCO₂ and lactate (r=–0.37,p<0.05;r=–0.3,p<0.05 respectively). We conclude that blood lactate, CI and increase progressively following CPB. An increase in lactate was associated with a decrease in V-aCO₂. An increase in V-aCO₂ was not therefore associated with evidence of inadequate tissue perfusion as indicated by an increased blood lactate concentration.     

Voriconazole for serious fungal infections

Voriconazole is a new second generation triazole effective against a wide spectrum of fungal pathogens. A randomised, controlled trial has shown it to be superior to amphotericin B in invasive aspergillosis, and it is a potential alternative to amphotericin B in neutropenic sepsis and to fluconazole in oesophageal candidiasis. Early clinical reports and in vitro susceptibility data suggest that it may also be a valuable antifungal against fluconazole-resistant Candida species and certain emerging fungal pathogens, which cause infections that are often refractory to conventional therapies. There is limited evidence of azole cross-resistance of clinical importance. Voriconazole is available as intravenous and oral formulations and has excellent tissue penetration and a good safety profile, the main problems being transient visual impairment and hepatotoxicity in patients with liver disease. It is metabolised by cytochrome P-450 isoenzymes causing important drug interactions but, in contrast to amphotericin B, is safe in renal failure and rarely causes infusion-related reactions. This review outlines the pharmacology of voriconazole and focuses on its clinical applications and safety profile.     

Anesthetic considerations for patients with anterior mediastinal masses

Anterior mediastinal tumors can cause severe airway and vascular compression, and these effects are exacerbated by general anesthesia. Tumor biopsy using a local anesthetic technique is preferable. General anesthesia for a biopsy procedure or resection of an anterior mediastinal mass should be undertaken only after a thorough preoperative assessment. Treatment protocols for surgery and anesthesia vary from institution to institution, and management remains operator dependent. Some consider the maintenance of spontaneous respiration during anesthesia optimal. Others advocate airway stenting. Cardiopulmonary bypass, instituted at the outset of surgery under local anesthetic, may be used as a fall-back technique in extreme circumstances.     

Detection of defects in myocardial perfusion imaging in patients with early breast cancer treated with radiotherapy.

BACKGROUND AND PURPOSE: To evaluate radiation-induced defects in myocardial perfusion imaging in early breast cancer patients treated with modern technique radiotherapy. PATIENTS AND METHODS: Twenty-four patients with left-breast tumours and 12 control patients with right-breast tumours, relapse-free since treatment for primary disease, who had undergone radiotherapy at least 5 years previously and with no history of ischaemic heart disease prior to radiotherapy underwent study. In left-breast patients, at least 1 cm of heart was required to have been in the treatment field. Patients underwent cardiac assessment and single photon emission computerized tomography myocardial perfusion imaging. RESULTS: Myocardial perfusion tracer uptake was abnormal in 17 (70.8%) left-breast and two (16.7%) right-breast patients (P = 0.002). Of the 17 abnormal scans in left-breast patients, abnormalities were confined to the cardiac apex in 16 patients, and perfusion defects were reversible (n = 7), fixed (n = 7) or mixed (n = 3). Reversible perfusion defects that were not confined to the cardiac apex were observed in two right-breast patients. Left ventricular ejection fraction was normal in all 33 patients in whom it was measured, and no myocardial perfusion abnormalities were judged to require treatment or follow-up. CONCLUSIONS: In this selected study population modern technique radiotherapy to the left breast was associated with a significantly greater number of myocardial perfusion abnormalities than radiotherapy to the right breast. These abnormalities were both reversible and irreversible, suggesting that radiotherapy can lead to both myocardial damage and to epicardial coronary disease. With a minimum of 5 years follow-up since treatment, no abnormalities were considered to be clinically significant.     

Double-blind, placebo-controlled, randomised phase II trial of IH636 grape seed proanthocyanidin extract (GSPE) in patients with radiation-induced breast induration.

BACKGROUND AND PURPOSE: Tissue hardness (induration), pain and tenderness are common late adverse effects of curative radiotherapy for early breast cancer. The purpose of this study was to test the efficacy of IH636 grape seed proanthocyanidin extract (GSPE) in patients with tissue induration after high-dose radiotherapy for early breast cancer in a double-blind placebo-controlled randomised phase II trial. PATIENTS AND METHODS: Sixty-six eligible research volunteers with moderate or marked breast induration at a mean 10.8 years since radiotherapy for early breast cancer were randomised to active drug (n = 44) or placebo (n = 22). All patients were given grape seed proanthocyanidin extract (GSPE) 100 mg three times a day orally, or corresponding placebo capsules, for 6 months. The primary endpoint was percentage change in surface area (cm(2)) of palpable breast induration measured at the skin surface 12 months after randomisation. Secondary endpoints included change in photographic breast appearance and patient self-assessment of breast hardness, pain and tenderness. RESULTS: At 12 months post-randomisation, > or =50% reduction in surface area (cm(2)) of breast induration was recorded in 13/44 (29.5%) GSPE and 6/22 (27%) placebo group patients (NS). At 12 months post-randomisation, there was no significant difference between treatment and control groups in terms of external assessments of tissue hardness, breast appearance or patient self-assessments of breast hardness, pain or tenderness. CONCLUSIONS: The study failed to show efficacy of orally-administered GSPE in patients with breast induration following radiotherapy for breast cancer.