Comparison of IMRT techniques in the radiotherapeutic management of head and neck cancer: is tomotherapy "better" than step-and-shoot IMRT?

Currently, the most common method of delivering intensity-modulated radiotherapy (IMRT) is through step-and-shoot, segmental multi-leaf collimator (SMLC)-based techniques. Although rotational delivery methods such as helical tomotherapy (HT) have been proposed as offering advantages in the treatment of head and neck cancer, a lack of clinical data exists on its potential utility. This study compared dosimetric, clinical, and quality-of-life endpoints among 149 patients treated by HT and SMLC-IMRT for head and neck cancer. Dosimetric analysis revealed that the use of HT resulted in significant improvements with respect to mean dose (23.5 versus 27.9 Gy, p = 0.03) and V30 (30.1 versus 43.9 Gy, p = 0.01) to the contralateral (spared) parotid gland. However, the incidence of grade 3+ xerostomia in the late setting was 10% and 8% among patients treated by HT and SMLC-IMRT, respectively (p = 0.46). There were no significant differences in any of the quality of life endpoints among patients treated by HT and SMLC-IMRT (p > 0.05, for all). Acknowledging the biases inherent in this retrospective analysis, we found that the dosimetric advantages observed with HT compared to SMLC-IMRT failed to translate into significant improvements in clinical outcome. Prospective studies are needed to further evaluate how HT may affect the therapeutic ratio.     

The Australian Intervention Randomized Control of Rate in Atrial Fibrillation Trial (AIRCRAFT)

OBJECTIVES: The Australian Intervention Randomized Control of Rate in Atrial Fibrillation Trial was a multicenter trial of atrioventricular junction ablation and pacing (AVJAP) compared with pharmacologic ventricular rate control (medication [MED]) in patients with mild to moderately symptomatic permanent atrial fibrillation (AF). BACKGROUND: There have been very few prospective randomized trials, undertaken in highly symptomatic patients, comparing AVJAP with pharmacologic methods of ventricular rate control for patients with permanent AF. METHODS: There were 99 patients (70 men, mean age 68 +/- 8.6 years) at five centers. Forty-nine patients were randomized to AVJAP while 50 patients were randomized to pharmacologic control. The primary end point was cardiac function measured by echocardiography and exercise tolerance. The secondary end points were ventricular rate control, evaluated by 24-h ambulatory electrocardiographic monitoring, and quality of life. Data were collected at randomization and then at one month, six months, and 12 months post-randomization. RESULTS: At 12 months follow-up there was no significant difference in left ventricular ejection fraction (AVJAP: 54 +/- 17%; MED: 61 +/- 13% [p = ns]) or exercise duration on treadmill testing (AVJAP: 4.1 +/- 2 min; MED: 4.6 +/- 2 min [p = ns]); however, the peak ventricular rate was lower in the AVJAP group during exercise (112 +/- 17 beats/min vs. 153 +/- 36 beats/min, p < 0.05) and activities of daily life (117 +/- 16 beats/min vs. 152 +/- 37 beats/min, p < 0.05). The CAST quality-of-life questionnaire revealed that patients in the AVJAP group had fewer symptoms at six months (p = 0.003) and at 12 months (p = 0.004). The observed relative risk reduction in symptoms at 12 months was 18%. Global subjective semiquantitative measurement of quality of life using the "ladder of life" revealed that the AVJAP group reported a 6% better quality of life at six months (p = 0.011). CONCLUSIONS: In this trial, AVJAP for patients with mild to moderately symptomatic permanent AF did not worsen cardiac function during long-term follow-up, and quality of life was improved.     

Altered glucocorticoid immunoregulation in treatment resistant depression

Alterations in cellular immune function are associated with depression and have been related to changes in endocrine function. We carried out a study to: (i) reliably assess the hypothalamic-pituitary-adrenal (HPA) axis function in treatment resistant depression (TRP); (ii) evaluate whether depression was associated with changes on T-cell proliferation and cytokine production; and (iii) assessed the sensitivity of lymphocytes to glucocorticoids (GC)s in vitro. Thirty-six pharmacologically treated inpatients diagnosed with TRP and 31 healthy controls took part in the study. Salivary cortisol was measured hourly from 0800 to 2200 h both before and after dexamethasone (DEX) intake and the patients were classified into HPA axis suppressors and nonsuppressors. The following were measured in vitro: (a) phytohemagglutinin-induced T-cell proliferation; (b) cytokine production (interleukin-2 and tumor necrosis factor-alpha, TNF-alpha); and (c) lymphocyte sensitivity to both cortisol and DEX. Basal morning cortisol levels from patients and controls did not differ nor did their T-cell proliferation and cytokine production. Ten out of 36 patients were classified as nonsuppressors and presented a significantly higher post-DEX salivary cortisol levels than suppressors, 82.0 vs 8.9 nM/l/h (p <0.001). Cells of nonsuppressors produced significantly less TNF-alpha compared to suppressors, 299.8 vs 516.9 pg/ml (p < 0.05). Remarkably, GC-induced suppression of lymphocyte proliferation and cytokine production were generally less marked in depressives compared with controls. Our data indicate that alterations in immune function and steroid regulation associated with depression are not related to elevated basal levels of cortisol and suggest that lymphocyte steroid resistance may be associated with TRP.     

The pattern of postoperative analgesic administration in non-English speaking Asian women following caesarean section

A survey of postoperative analgesic administration to non-English speaking Asian women following Caesarean section has shown significant differences when compared to English speaking Caucasian women. The main differences demonstrated were that analgesia was utilised for a shorter period (mean of 16 hours) and that a smaller number of doses were given to the Asian group.     

Plasma bradykininogen levels before and after ovulation: Studies in women and guinea pigs,with observations on oral contraceptives and menopause

In healthy women, there was a 41 per cent fall in plasma bradykininogen 48 (36 to 60) hours before ovulation. Similarly, guinea pigs showed a 79 per cent fall 24 (18 to 30) hours before ovulation; recovery of normal values occurred by the time of ovulation itself. The 59 per cent fall in rats took place 17 (15 to 20) hours before ovulation. The fall persisted in women using oral contraceptives containing norethindrone and mestranol (1.0:0.05 to 2.0:0.1 mg. per day); a 39 per cent fall occurred 48 hours before the calculated time of “ovulation”. The women using oral contraceptives showed a 38 per cent elevation in plasma bradykininogen levels throughout the rest of the cycle, as compared with normal women. The fall in kininogen could not be found in early postmenopausal women or in control male guinea pigs. The results show that the fall in plasma bradykininogen is essentially a preovulatory change; the possibilities that it is linked to early events in the mechanism of ovulation and that it is associated with a rhythmic mechanism more fundamental than the events obstructed by the oral contraceptives are discussed.