The Radiation Injury Severity Classification system: an early injury assessment tool for the frontline health-care provider

Our goal was to adapt current diagnostic methods for radiation overexposure patients into a practical system that can be implemented rapidly and reliably by responders unfamiliar with the effects of radiation. Our Radiation Injury Severity Classification (RISC) system uses clinical and haematological parameters from the prodromal phase of the acute radiation syndrome (ARS) to classify acute radiation injury for purposes of managing treatment disposition. Data from well-documented ARS cases were used to test the RISC system. Three-day summaries were generated for each case. These were individually reviewed by the three physicians most involved with the development of the system to establish both a consensus case score (CCS) and disposition category ranges. 30 volunteer raters from varying health disciplines using the RISC system then each independently rated a random selection of 12 cases for injury severity in a self-trained field-simulation exercise. The CCS identified discrete cut-off ranges for the three disposition categories in both manageable and mass casualty events. The group of raters, after a modest period of self-training, achieved overall levels of pairwise agreement with the CCS category of 0.944 for manageable events and 0.947 for mass casualty situations. In conclusion, an early assessment of the severity of the ARS injury is required for an appropriate disposition determination. The RISC system should produce reasonably accurate and reliable assessments of radiation injury severity within 6-12 hours post exposure despite the probable absence of physical dosimetric data.     

Mechanistic applicability domains for nonanimal-based prediction of toxicological end points: general principles and application to reactive toxicity

In light of new legislation (e.g., the REACH program in the European Union), several initiatives have recently emerged to increase acceptance of (quantitative) structure-activity relationships [(Q)SARs] to reduce reliance on animal (in vivo) testing. Among the principles for assessing the validity of (Q)SARs is the need for a defined domain of applicability, i.e., identification of the range of compounds for which the (Q)SAR can confidently be applied for purposes of toxicity prediction. Here, we attempt to develop a "natural" classification into applicability domains based on considering how a compound and the target organism between them "decide" on the nature and extent of the toxic effect. With particular emphasis on reactive toxicity, we present rules, based on organic reaction mechanistic principles, for classifying reactive toxicants into their appropriate mechanistic applicability domains.     

The efficacy of 99mTc-HIG for sentinel lymph node mapping in breast cancer patients

OBJECTIVE: To evaluate the efficacy of Tc-HIG on SLN identification in patients with early-stage breast cancer. MATERIALS AND METHODS: Seventeen women (18 tumours) with early-stage breast cancer were included. On the day of the operation, 111 MBq Tc-HIG was injected around the tumour or biopsy scar in all patients. Subsequently, dynamic lymphoscintigraphic images were taken for 30 min. After this, static images were recorded at 15-20 min intervals until the SLN was visualized. Patients were taken to the operating room 2-4 h after radiopharmaceutical injection. Before the incision, 5 ml of isosulfan blue dye solution was injected peritumourally in all subjects. Aided by blue dye and gamma probe SLN detection was done during the operation. RESULTS: In 17/18 tumours, SLN was detected with Tc-HIG lymphoscintigraphy. The mean visualization time for axillary SLNs was 49.94+/-11.25 min and for internal mammary SLNs was 52.50+/-10.60 min. In 15 of the tumours, only one SLN was detected in the axillary region. However, in two tumours, SLNs were found in both axillary and internal mammary regions. With blue dye mapping, axillary SLNs were found in 17/18 tumours. With the application of intraoperative gamma probe, all axillary and internal mammary SLNs were detected in 18 tumours. CONCLUSION: We conclude that Tc-HIG may be a suitable agent for SLN detection by lymphoscintigraphy and intraoperative gamma probe application in early-stage breast cancer patients.     

The influence of post-exercise cardiac changes on thallium-gated myocardial perfusion scintigraphy findings in normal subjects

BACKGROUND AND AIM: During recovery after exercise, the heart rate and blood pressure return to a resting state more rapidly than the end-systolic left ventricular dimensions and fractional shortening. The aim of this study was to assess how exercise-related cardiac changes affect the interpretation of myocardial perfusion images in normal subjects. Systolic cardiac parameters on gated stress and rest images were evaluated in healthy young and elderly subjects. METHODS: Twenty-six healthy young and 20 healthy elderly subjects participated in the study. An injection of 111-130 MBq of thallium-201 (201Tl) was given at peak exercise. Rest images were acquired 2.5 h after stress acquisition, 15 min after a second injection of 18.5-37 MBq of 201Tl. Data were analysed using automatic-processing software for quantitative gated single photon emission computed tomography (SPECT) (QGS). The parameters derived from QGS were the end-systolic volume (ESV), end-diastolic volume (EDV), left ventricular ejection fraction (LVEF), end-systolic surface area (ESSA) and end-diastolic surface area (EDSA). The difference between wall thickening in the basal and apical segments (Delta WT) was also calculated. Perfusion images were visually assessed for differences in cardiac size, evidence of reversible hypoperfusion and hot spots. RESULTS: In the young group, LVEF was approximately 6% higher at stress than at rest. EDV, ESV, ESSA and EDSA were all significantly lower, and Delta WT was significantly higher, at stress than at rest. In the elderly group, the mean LVEF at stress was slightly higher than the finding at rest (P<0.05). Visual evaluation of perfusion images revealed mild reversible stress hypoperfusion in the inferoseptal region in eight young male subjects. CONCLUSIONS: In healthy young subjects, post-exercise cardiac changes affect systolic functions detected on gated thallium myocardial perfusion scintigraphy, resulting in a smaller heart size during stress. This finding, accompanied by a significant difference in apex to base counts during stress, may cause basal portions of the heart to appear ischaemic. The absence of these findings in the elderly suggests a decrease in contractility with age.     

A comparison of fentanyl-propofol with a ketamine-propofol combination for sedation during endometrial biopsy

STUDY OBJECTIVE: The purpose of this study was to compare the clinical activities of ketamine and fentanyl when used in combination with propofol for outpatients undergoing endometrial biopsy. The investigated parameters were respiration, sedation, recovery rate, side effects, time to discharge, and patient satisfaction. DESIGN: Prospective, randomized, double-blind study. SETTING: University hospital. PATIENTS: Forty American Society of Anesthesiologists physical status I and II patients (age range 38-61 years) scheduled for elective endometrial biopsy. INTERVENTIONS: Patients received intravenous bolus doses of either fentanyl 1 microg/kg and propofol 1 mg/kg in (group 1 n = 20) or ketamine 0.5 mg/kg and propofol 1 mg/kg in (group 2 n = 20). MEASUREMENTS: Heart rate, systolic and diastolic blood pressure, respiratory rate, and peripheral O(2) saturation were monitored in all patients. Depth of sedation was assessed by the Ramsay sedation score. The Aldrete score was used for postoperative recovery evaluation. The time to Aldrete score >/=8, side effects, and time to discharge were recorded. MAIN RESULTS: Respiratory depression was observed in 5 patients from group 1 and 1 patient from group 2, but the difference was not significant (P > .05). Nausea, vertigo, and visual disturbances were more frequent in group 2 (P < .05). The time to Aldrete score >/=8 was similar in the 2 groups (6.2 +/- 3.5 minutes in group 1 and 7.0 +/- 3.1 minutes in group 2); the time to discharge was significantly longer in group 2 (71.2 +/- 9.7 minutes in group 1 and 115.2 +/- 25.6 minutes in group 2). Frequency of patient satisfaction was 95% in group 1 and 60% in group 2. CONCLUSIONS: Hemodynamic change and degrees of sedation showed that fentanyl-propofol and ketamine-fentanyl combinations can be used safely in patients undergoing endometrial biopsy. However, with regard to side effects and patient satisfaction, the fentanyl-propofol was superior.     

Generation of anti-idiotypic antibodies that mimic HBsAg and vaccination against hepatitis B virus

The advent of hybridoma technology has opened up a new avenue in vaccine development, and antigen-mimicking properties of anti-idiotypic antibodies have provided promising alternatives in the generation of experimental anti-idiotypic vaccines. In the present study, mice were immunized with anti-hepatitis B virus (HBV) mouse monoclonal and anti-HBV goat polyclonal antibody to produce anti-idiotypic antibodies. Two mouse monoclonal antibodies (6C9, 6H9) were obtained from the fusions, and the immunogenic properties and specificity of antibodies were analyzed. BALB/c mice were immunized with varying concentrations of anti-idiotypic antibodies (25, 50, 75, and 100 micrograms of anti-Id), and it was shown that anti-idiotypic antibodies generated hepatitis B surface antigen (HBsAg), as well as a BSA-specific antibody response. A simple method for the purification of monoclonal antibodies by dialyzing antibody against water has also been reported.     

Radial artery graft for bypass of the maxillary to proximal middle cerebral artery: an anatomic and technical study

OBJECTIVE: In this study, we aimed to investigate the use of a radial artery graft for bypass of the maxillary artery (MA) to the proximal middle cerebral artery (MCA) as an alternative to superficial temporal artery-to-MCA anastomosis or extracranial carotid-to-MCA bypass using long grafts. METHODS: Five adult cadavers were used bilaterally. After a frontotemporal craniotomy and a zygomatic arch osteotomy, the MA was found easily 1 to 2 cm inferior to the infratemporal crest. A hole was created with a 4-mm-tip drill in the sphenoid bone 2 to 3 mm lateral to the foramen rotundum extradurally, and the dura over the hole was opened. After the carotid and sylvian cisterns had been opened, the M2 segment of the MCA was exposed. The graft was passed through the hole to reach the M2 segment. Then, the MA was freed from the surrounding tissue and was transected before the infraorbital artery branch. The radial artery graft was anastomosed end-to-end to the MA proximally and end-to-side to the M2 segment of the MCA distally. RESULTS: The mean thickness of the MA before the infraorbital artery branch was 2.6 +/- 0.3 mm. The mean thickness of the largest trunk of the MCA was 2.3 +/- 0.3 mm. The average length of the graft was 36 +/- 5.5 mm. CONCLUSION: MA-to-MCA bypass is as feasible as proximal MCA revascularization using long vein grafts. The thickness of the MA provides sufficient flow; the length of the graft is short, and it has a straight course. MA-to-proximal MCA bypass may be an alternative to superficial temporal artery-to-MCA as well as extracranial carotid-to-MCA bypasses.     

Effects of lipid peroxidation on structure of human plasma lipoproteins (magnetic resonance spectroscopy)

Magnetic resonance spectroscopy revealed structural modifications of human plasma lipoproteins during peroxidation induced by copper sulfate in vitro. Decreased molecular mobility of fatty acid chains in lipoprotein lipids was demonstrated.