A Dosimetric Comparison of Breast Radiotherapy Techniques to Treat Locoregional Lymph Nodes Including the Internal Mammary Chain.

AIMS: Radiotherapy target volumes in early breast cancer treatment increasingly include the internal mammary chain (IMC). In order to maximise survival benefits of IMC radiotherapy, doses to the heart and lung should be minimised. This dosimetry study compared the ability of three-dimensional conformal radiotherapy, arc therapy and proton beam therapy (PBT) techniques with and without breath-hold to achieve target volume constraints while minimising dose to organs at risk (OARs). MATERIALS AND METHODS: In 14 patients' datasets, seven IMC radiotherapy techniques were compared: wide tangent (WT) three-dimensional conformal radiotherapy, volumetric-modulated arc therapy (VMAT) and PBT, each in voluntary deep inspiratory breath-hold (vDIBH) and free breathing (FB), and tomotherapy in FB only. Target volume coverage and OAR doses were measured for each technique. These were compared using a one-way ANOVA with all pairwise comparisons tested using Bonferroni's multiple comparisons test, with adjusted P-values ≤ 0.05 indicating statistical significance. RESULTS: One hundred per cent of WT(vDIBH), 43% of WT(FB), 100% of VMAT(vDIBH), 86% of VMAT(FB), 100% of tomotherapy FB and 100% of PBT plans in vDIBH and FB passed all mandatory constraints. However, coverage of the IMC with 90% of the prescribed dose was significantly better than all other techniques using VMAT(vDIBH), PBT(vDIBH) and PBT(FB) (mean IMC coverage ± 1 standard deviation = 96.0% ± 4.3, 99.8% ± 0.3 and 99.0% ± 0.2, respectively). The mean heart dose was significantly reduced in vDIBH compared with FB for both the WT (P < 0.0001) and VMAT (P < 0.0001) techniques. There was no advantage in target volume coverage or OAR doses for PBT(vDIBH) compared with PBT(FB). CONCLUSIONS: Simple WT radiotherapy delivered in vDIBH achieves satisfactory coverage of the IMC while meeting heart and lung dose constraints. However, where higher isodose coverage is required, VMAT(vDIBH) is the optimal photon technique. The lowest OAR doses are achieved by PBT, in which the use of vDIBH does not improve dose statistics.

Umbilical arterial blood flow in the mouse embryo during development and following acutely increased heart rate.

In anesthetized, pregnant ICR mice, we measured embryonic umbilical arterial velocity at baseline and during bipolar atrial or ventricular pacing. Pregnant mice were anesthetized with pentobarbital (60 mg/kg intraperitoneal) and ventilation was mechanically supported via a tracheotomy. Embryos were exposed through a mid-line laparotomy and regional hysterotomy. We recorded umbilical velocity using a 1-mm diameter piezoelectric crystal and 20-MHz, pulsed Doppler velocimeter at embryo day (ED) 10.5 (n = 8), 12.5 (n = 10), 13.5 (n = 27), 14.5 (n = 12), and 16.5 (n = 17). We then acutely altered embryonic heart rate in n = 8 ED 13.5 mouse embryos by bipolar atrial and ventricular pacing. Embryonic heart rate in this experimental preparation increased from 123+/-7 to 193+/-11 beats/min from ED 10.5 to 16.5 (p<0.05). Peak instantaneous average velocity increased from 21+/-2 to 55+/-6 mm/s from ED 10.5 to 16.6 (p<0.05), as did stroke volume and blood flow (p<0.05 for each). In contrast to human umbilical arterial velocity profiles, significant forward diastolic flow was not seen at these stages, suggesting higher placental resistance in mice versus humans at comparable developmental time points. As previously noted for the chick embryo, murine embryonic umbilical arterial velocity decreased after atrial pacing and disappeared after ventricular pacing. Thus, we can determine embryonic umbilical blood flow during the overlapping periods of murine cardiac and placental morphogenesis.

Nonpainful swelling of the palate and loosening of the maxillary incisors.

Bone lesions in the maxilla have rarely been described in relation to sarcoidosis. This patient exhibited many of the classic signs of sarcoidosis, including lack of symptoms at the time of presentation, which resulted in the diagnosis of sarcoidosis being made serendipitously. The presence of musculoskeletal lesions is often regarded as a poor prognostic sign and, in general, sarcoidosis follows a more virulent course in black patients. Sadly, the course of the disease in this patient continues to march onward despite a 1-year therapeutic trial of corticosteroids.

Hemodynamic response to anesthesia in pregnant and nonpregnant ICR mice.

Mean arterial blood pressure (BP) and heart rate (HR) during and after recovery from anesthesia in pregnant and nonpregnant ICR mice were evaluated. Mice were evaluated during mechanical ventilation, from 15 to 60 min after induction of anesthesia. The anesthetic protocols were pentobarbital (80 mg/kg, given intraperitoneally [i.p.]); two low doses of ketamine and xylazine (90 mg/kg, 7.5 mg/kg, respectively, i.p., with a second dose given 20 min after the initial dose); and a single high dose of ketamine and xylazine (150 mg/kg, 12.5 mg/kg, respectively, i.p.). The BP was measured in the right carotid artery, using a fluid-filled catheter connected to a chamber containing a solid-state pressure transducer. Mechanical ventilation was performed via tracheotomy, using a normalized minute ventilation of 3.5 ml*min-1*g-1 for nonpregnant mice and 3.0 ml*min-1*g-1 for pregnant mice. Mean BP was lower and HR was higher in pregnant than in nonpregnant mice for each anesthetic protocol. Pentobarbital induced significantly greater tachycardia and hypotension than did the other protocols. The average BP and HR were similar between two low doses and a single high dose of ketamine and xylazine. During spontaneous breathing from 30 to 180 min after recovery from anesthesia by use of a single low dose, ketamine and xylazine induced similar HR profiles, but mean BP in pregnant mice recovered earlier than did that in nonpregnant mice. These results suggest that ketamine and xylazine induced adequate anesthesia for superficial surgical procedures in pregnant and nonpregnant mice while inducing small changes in HR and BP, and pregnancy resulted in a different hemodynamic reaction in response to ketamine and xylazine. These data will be useful for the design and interpretation of physiologic protocols using pregnant and nonpregnant genetically targeted mice.

In vivo assessment of embryonic cardiovascular dimensions and function in day-10.5 to -14.5 mouse embryos.

Embryonic cardiovascular function has been extensively studied in vivo in the chick embryo. However, the geometry of mammalian and avian hearts differs; the mammalian cardiovascular system is coupled to both yolk sac and placental circulations, and unique murine genetic models associated with structural and functional cardiovascular defects are now available. We therefore adapted techniques validated for the chick embryo to define cardiovascular dimensions and function in the mouse embryo. We bred C3HeB female and C57B1/J6 male mice and ICR pairs for experiments on embryonic days (EDs) 10.5 to 14.5 (n = 130 dams). After maternal anesthesia (pentobarbital, 60 mg/kg IP), laparotomy, and sequential regional hysterotomy, we exposed and then imaged individual embryos at 60 Hz (video) in the ventral and/or left anterior oblique views while maintaining uteroplacental continuity. We measured epicardial chamber dimensions and then calculated right and left ventricular elliptical volumes from ares. In addition, we measured pulsed-Doppler blood velocity across the atrioventricular cushions and ventricular outflow tract. We maintained embryonic temperature with a heated surgical platform, topical oxygenated and warmed buffer, and warming lamps. Embryonic heart rate increased from 124.7 +/- 5.2 to 194.3 +/- 13.2 bpm from EDs 10.5 to 14.5 (P < .01). Right and left ventricular end-diastolic and end-systolic dimensions increased (P < .05 by ANOVA for each). Maximal ventricular mean inflow and outflow velocities increased from 62.33 +/- 4.06 to 106.23 +/- 11.59 and from 55.79 +/- 6.11 to 91.61 +/- 6.93 mm/s, respectively (P < .05 by ANOVA for each). Thus, as has been done for chick and rat embryos, the maturation of murine embryonic cardiovascular function can be quantified in vivo, setting the stage for the investigation of structure-function relations in mouse models of cardiovascular development and disease.

Salivary calcium, magnesium, phosphate, chloride, sodium and potassium in pregnancy and labour.

Pregnancy and labour produce significant changes in salivary calcium, magnesium, phosphate and chloride when pregnant patients in labour are compared with non-pregnant patients. There is a decrease in concentration of these constituents in the 3rd trimester of pregnancy followed by a marked increase when labour occurs. Magnesium and chloride are the constituents most significantly affected and show the largest increase during labour. Changes in saliva flow rate were accounted for and are not responsible for these changes noted. Sodium and potassium follow a similar pattern. When their levels are corrected for saliva flow rate changes, both show a significant increase with the onset of labour.