Split-dose Technique Research Articles

Comparison of Gastric Residual Volume and pH between Single and Split-Dose Bowel Preparation in Patients Undergoing Esophago-Gastro-Duodenoscopy and Colonoscopy: A Randomized Controlled Trial

Background: Colonoscopy is an effective surveillance for the diagnosis and screening of colorectal cancer (CRC). Prior to the procedure, people would take laxatives for a good visualization of bowel texture. Although a split-dose bowel preparation has become popular, many anesthesiologists are concerned about pulmonary aspiration. Objective: To study the gastric residual volume and pH in patients taking split-dose bowel preparation as compared to those having laxatives on the day before the procedure. Materials and Methods: One hundred patients were randomized equally into two groups, as A for a single-dose, and B for a split-dose regimen. All patients underwent endoscopy under standard anesthetic care. The total gastric residual volume was suctioned, and pH was measured through the endoscope. The surgical team was unaware of the study protocol. The quality of bowel cleansing was assessed by the endoscopist using the Boston Bowel Preparation Scale (BBPS). Results: The bowel cleansing, the latency period, the endoscopist and patients’ satisfaction of single-and split-dose group were 7.06±1.4 and 8.14±1.1, 13.3±1.1 and 4.2±0.4 hours, 62.0% and 94.0%, and 90.0% and 74.0%, respectively. They all showed statistically significant differences between the two groups (p<0.05). Conclusion: The gastric residual volume and pH were not different between the split and single-dose preparations. Therefore, it might not increase the risk of aspiration pneumonitis. However, the split-dose technique was more effective in colon cleansing, patients’ tolerability, acceptability, and compliance than the preparations administered entirely the day or evening before the surgical procedure. Keywords: Gastro-colonoscopy; Single-dose bowel preparation; Split-dose bowel preparation; Gastric residual volume; Anesthesia

Split-Dose Technique for FDG PET/CT–guided Percutaneous Ablation: A Method to Facilitate Lesion Targeting and to Provide Immediate Assessment of Treatment Effectiveness

To describe a split-dose technique for fluorine 18 fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT)-guided ablation that permits both target localization and evaluation of treatment effectiveness. Institutional review board approved the study with a waiver of consent. From July to December 2011, 23 patients (13 women, 10 men; mean age, 59 years; range, 35-87 years) with 29 FDG-avid tumors (median size, 1.4 cm; range, 0.6-4.4 cm) were targeted for ablation. The location of the lesion was the liver (n = 23), lung (n = 4), adrenal gland (n = 1), and thigh (n = 1). Radiofrequency ablation was performed in 17 lesions; microwave ablation, in six; irreversible electroporation, in five; and cryoablation, in one. The pathologic condition of the tumor was metastatic colorectal adenocarcinoma in 18 lesions, primary hepatocellular carcinoma in one lesion, and a variety of metastatic tumors in the remaining 10 lesions. A total of 4 mCi (148 MBq) of FDG was administered before the procedure for localization and imaging guidance. At completion of the ablation, an additional 8 mCi (296 MBq) of FDG was administered to assess ablation adequacy. Results of subsequent imaging follow-up were used to determine if postablation imaging after the second dose of FDG reliably helped predict complete tumor ablation. Descriptive statistics were used to summarize the results. Twenty-eight of 29 (97%) ablated lesions showed no residual FDG activity after the second intraprocedural FDG dose. One patient with residual activity underwent immediate biopsy that revealed residual viable tumor and was immediately re-treated. Follow-up imaging at a median of 155 days (range, 92-257 days) after ablation showed local recurrences in two (7%) lesions that were originally negative at postablation PET. Split-dose FDG PET/CT may be a useful tool to provide both guidance and endpoint evaluation, allowing an opportunity for repeat intervention if necessary. Further work is necessary to validate these concepts.

Partusinductie bij de zeug

Partusinductie verhoogt het toezicht tijdens het werpen, waardoor het geboortegetal kan toenemen. Wanneer partusinductie echter niet correct wordt toegepast, kan dit leiden tot vroeggeboorte. Daarom mag partusinductie pas ten vroegste twee dagen vóór de gemiddelde drachtduur van de zeugen op een bedrijf worden uitgevoerd. Voor partusinductie bestaan verschillende protocols, zoals de eenmalige toediening van prostaglandinen, de dubbele toediening van prostaglandinen met zes uur interval (split-dose-techniek) en de combinatie van prostaglandinen met oxytocine 24 uur later en verschillende toedieningswegen, zoals intramusculaire injectie in de nekregio en injectie in de buurt van de vulva. Andere strategieën bestaan maar zijn minder effectief en/of worden minder frequent gebruikt. Na een eenmalige injectie van prostaglandinen werpt 60% van de zeugen binnen de werkuren (22-32 uur na injectie). Met de split-dose-techniek of de combinatie van prostaglandinen en oxytocine 24 uur later is dit 80%. Bij incorrect gebruik is oxytocine echter een risicofactor voor asfyxie bij biggen. Het wel of niet toepassen van partusinductie en welk protocol het beste wordt gebruikt hangen af van het bedrijf en de wensen van de veehouder.

Central noradrenergic responsiveness to a clonidine challenge in Generalized Anxiety Disorder: a Single Photon Emission Computed Tomography study

Generalized Anxiety Disorder (GAD) may involve hypo-responsiveness of noradrenaline a2 receptors. To test this hypothesis, we used (99m)Tc-hexa-methyl-propylene-amine-oxime (HMPAO) Single Photon Emission Computed Tomography to measure regional cerebral perfusion in patients with untreated GAD, venlafaxine-treated patients and healthy controls during word generation before and after clonidine. Concurrent psychological and physiological measures supported noradrenergic hypofunction in GAD in some cases. A single-day split-dose technique was used. Images were processed using SPM5 (Institute of Neurology). Factorial analysis revealed no significant results. Exploratory analyses were done. Regional perfusion during verbal fluency differed by group pre-clonidine. Compared with healthy controls, patients with untreated GAD displayed increased perfusion in the left Broca's area and left occipitotemporal region. Treated GAD patients displayed increased cerebellar perfusion bilaterally. Clonidine was associated with different changes in cerebral perfusion in each group. Increases were seen in the right supra-marginal gyrus in healthy subjects, in the left pre-central gyrus in treated GAD patients and in the right cerebellum and middle frontal gyrus in untreated GAD patients. Despite these differences, the findings were not consistent with a noradrenergic hypo-responsiveness hypothesis, as the treated group showed a different pattern of response rather than a normalization of response.

Stability of cerebral blood flow measures using a split-dose technique with 99mTc-exametazime SPECT

To determine whether there is stability of cerebral blood flow (CBF) measures using single photon emission computed tomography (SPECT) imaging in healthy controls in a test-retest split-dose paradigm. Such a paradigm is frequently used in the clinical and research setting to assess various brain states. Five healthy volunteers underwent two brain SPECT scans after the administration of low and high doses of (99m)Tc-exametazime. The first SPECT scan was acquired approximately 30 min after the intravenous injection of approximately 259 MBq of (99m)Tc-exametazime. The second SPECT scan was acquired approximately 30 min after the intravenous injection of 925 MBq of (99m)Tc-exametazime. Both scans were acquired over approximately 30-45 min and the images were reconstructed using filtered backprojection, a low-pass filter and Chang's first-order attenuation correction. Values were obtained for regions of interest (ROIs) in major brain structures and normalized to whole brain activity. Counts on the second SPECT scan were also decay corrected for activity from the first scan. The results demonstrated a strong correlation between the low-dose and high-dose scans for all regions (r = 0.86, P<0.0001). Symmetries were preserved with a strong correlation between low-dose and high-dose scans (r = 0.70, P<0.0001). Finally, most regions demonstrated less than a 5% difference between the low-dose and high-dose scans. The results of this study demonstrate that the split-dose technique can be employed for clinical and research applications to measure CBF in different brain states using two SPECT scans on the same day.

THE INFLUENCE OF DOSE FRACTIONATION ON RADIATION-INDUCED HAEMOLYSIS OF HUMAN ERYTHROCYTES

In this paper the radioresistance of human erythrocytes to radiation-induced haemolysis was studied by means of the split-dose technique. Human erythrocytes suspended in an isotonic Na-phosphatase buffer, pH7.4 were exposed under air to gamma radiation. Erythrocytes were irradiated with a single dose of 2.7kGy and with the same total dose split into two fractions with an interval between the subsequent exposures. It seems that postradiation processes initiated by the first radiation dose of definite magnitude can lead to an increase in the resistance of erythrocytes to haemolysis under the influence of subsequent dose. The maximal effect of the fractionation (50% decrease of haemolysis) was observed when the first fraction was equal to 0.3–0.4kGy and the interval between exposures was equal to 3h.

The effects of acute hypoglycemia on relative cerebral blood flow distribution in patients with type I (insulin-dependent) diabetes and impaired hypoglycemia awareness

To examine the hypothesis that in diabetic patients with impaired hypoglycemia awareness the relative regional distribution of cerebral blood flow (rCBF) would be abnormal in a specific area, namely the frontal lobes, rCBF was examined in 20 type I diabetic patients, of whom 10 had a normal awareness of hypoglycemia and 10 had a history of impaired hypoglycemia awareness. rCBF was determined sequentially using single photon emission computed tomography (SPECT) during (1) normoglycemia (arterialized blood glucose 4.5 mmol · L −1) and (2) hypoglycemia (blood glucose 2.5 mmol · L −1) induced by a hyperinsulinemic glucose clamp technique. Distribution of the isotope, 99mTc-Exametazime, was detected using a single-slice multi-detector head scanner. A split-dose technique was used, with 250 MBq being injected during steady-state normoglycemia and 250 MBq during subsequent hypoglycemia. rCBF was estimated in 30 regions of interest, derived from a standard neuroanatomical atlas on two parallel slices at 40 and 60 mm above the orbitomeatal line (OML). No between-group differences in the pattern of overall rCBF or changes in regional tracer uptake were demonstrated. In comparison to the rCBF during normoglycemia, both patient groups exhibited significant changes in the pattern of rCBF during hypoglycemia, with increments of rCBF to both superior frontal cortices and the right thalamus and reduced rCBF to the right posterior cingulate cortex and the right putamen. This pattern of relative redistribution of rCBF during hypoglycemia was preserved in patients who had impaired hypoglycemia awareness.

Analyzing the role of biochemical processes in determining response to ionizing radiations.

The interaction of biochemical processes and radiation damage appears to play a major role in determining long-term biological effects. It is responsible for both the removal of radiation-induced alterations in macromolecules and for the time-dependent changes in survival of irradiated cells. Restoration of macromolecules by such means as the rejoining of strand breaks in DNA suggests a variety of possible mechanisms which could lead to the observed enhancement of cell survival. However, even though a number of molecular repair mechanisms have been identified, specific links between any such mechanisms and a subsequent modification of cell survival have proved difficult, if not impossible, to demonstrate. Models of cellular response provide a means of attempting to establish this connection. Although details of radiation chemistry, chromatin structure, enzymatic repair, molecular genetics, and cell cycle kinetics are generally simplified, each individual model incorporates features based on a set of assumed mechanisms. For example, one group of models assumes that all damage is potentially lethal (capable of killing the cell unless it is repaired), while another assumes that part of the damage is sublethal (innocuous until it interacts with other damage). Using split-dose, dose-rate, and delayed-plating techniques, we have demonstrated two distinct components of repair in plateau-phase Chinese hamster ovary cells. One process has a characteristic time of about 1 h; the other, about 18 h. In both cases, the reaction rates and the fractions of damage repaired appear to be independent of the initial amounts of damage produced. These observations suggest that none of the simpler models adequately describes cell inactivation; i.e., reproductive death is inconsistent with all assumptions regarding any of them. Consequently, more-complex models involving combinations of sublethal and potentially lethal damage or multiple-step damage processes may be required. These findings help to define the effects of exposure at low doses and dose rates and to develop an understanding of the underlying biochemical mechanisms involved.

Radiobiologic response of CHO-KI cells treated with vitamin A.

Treatment of CHO-KI cells with vitamin A altered their response to subsequent gamma irradiation. In general longterm preincubation with low doses of the vitamin caused a relative increase in the number of cells surviving a given radiation dose. The effect resulted in an increase in the D0 of the survival curve. Long or short term exposure to high concentrations of the vitamin caused a decrease in the number of surviving cells leading to a decrease in the extrapolation number of the survival curve. Recovery of cells from radiation damage, assessed using the split dose technique, was also impaired by vitamin A pretreatment. A mechanism involving repair of potentially lethal damage may explain the protective effect of vitamin A since this was highly dependent on the cell density of cultures at the time of irradiation. However, in view of the data showing that the vitamin A concentrations necessary to alter the radiation survival curve shoulder caused a significant release of sialic acid into the medium, a mechanism involving membrane stability may account for both the reduction in repair/recovery capacity of the treated cells and the radioprotective effect.

Response of Lymphosarcoma LS/BL Cells to Continuous Irradiation

Mouse lymphosarcoma LS/BL cells growing as an ascites tumor in the peritoneal cavity of C57BL mice were continuously irradiated in vivo at a low exposure rate of 1.2 Gy per day (5 rad/hr). The growth of the ascites tumor evaluated by direct counting of the cells in the peritoneal cavity and their capacity to form colonies in livers declined with increasing time of continuous irradiation. The radiosensitivity and repair ability of LS/BL cells were studied by a serial dilution method using host survival time as the end point and by the liver colony assay. The radiosensitivity of continuously irradiated LS/BL-CI cells showed no remarkable change as measured by the Do values, but from the 150th week of irradiation the initial shoulder on the survival curves appeared and its width increased with time of exposure. The extrapolation number (n) increased from 1.0 to 8.4 after 350 weeks of irradiation. The reappearance of the initial shoulder was proved with the split-dose technique.

Response of Cultured Normal Human Mammary Epithelial Cells to X Rays

The effect of X rays on the reproductive death of cultured normal human mammary epithelial cells was examined. Techniques were developed for isolating and culturing normal human mammary epithelial cells which provide sufficient cells at second passage for radiation studies, and an efficient clonogenic assay suitable for measuring radiation survival curves. It was found that the survival curves for epithelial cells from normal breast tissue were exponential and had D0 values of about 109-148 rad for 225 kVp X rays. No consistent change in cell radiosensitivity with the age of donor was observed, and no sublethal damage repair in these cells could be detected with the split-dose technique.

Rapid Repair of Ionizing Radiation Injury in Chlamydomonas reinhardi

Repair of sublethal damage is an important factor affecting the survival of irradiated cells. An understanding of this phenomenon is fundamental to understanding the action of ionizing radiations. Although multiple components of such repair have been detected in plateau-phase mammalian cells, processes having different repair rates have never been observed previously in proliferating eucaryotic cell systems. This report describes experiments used to study repair of sublethal damage in cells exposed to fast electrons. Split-dose techniques, utilizing two equal doses given at 100 krad/min and separated by intervals as short as 15 sec, followed by clonogenic cell assay, have been used throughout. These experiments demonstrate the existence of at least two independent repair processes in synchronous, exponentially growing cultures of Chlamydomonas reinhardi. Furthermore, each process probably represents repair of a distinctly different kind of damage. The rapid process described in this report is characterized by a mean repair time on the order of 2 to 4 min in contrast to 20 to 30 min for the well-known Elkind-Sutton type repair. Both processes are nearly temperature independent at temperatures above 25/sup 0/C.

Comparison of Repair Rates Determined by Split-Dose and Dose-Rate Methods

BRABY, L. A., NELSON, J. M., AND ROESCH, W. C. Comparison of Repair Rates Determined by Split-Dose and Dose-Rate Methods. Radiat. Res. 82, 211-214 (1980). Both split-dose and dose-rate techniques have been used to investigate sublethal damage repair in Chlamydomonas reinhardi irradiated with fast electrons. Repair rates, measured by these two methods, were found to depend on temperature over the range 7.5 to 32.50C. However, no significant differences were found between values determined by the two methods.

Studies on the Division Cycle of Mammalian Cells VII. X-Ray Sensitivity and Repair Capacity of Synchronously Dividing Murine Mastocytoma Cells

Partially synchronous cell populations of a transplantable murine mastocytoma exhibiting a cell cycle time of 8 to 8.5 h were prepared by density gradient centrifugation and reincubation of slowly sedimenting early interphase cells. The single-dose survival curve of such cultures indicated that x-ray sensitivity was high in early S and in G2 + M, and low in late S and G1 although these cells have a short G1 period. Survival curves of cells irradiated at different stages showed pronounced changes in extrapolation number n, whereas the slope Do did not vary markedly. In order to assess the cellular ability to repair sublethal damage, the survival ratio was measured at various times after incubation of early interphase cells by the split-dose technique with a 1-h interval. Marked cyclic changes were observed, indicating that mastocytoma cells repair radiation damage most effectively in the middle and second part of S, and to a lesser extent in G1. These fluctuations in survival ratio were in good correlation with the variations in n. These findings support the view that relative incroase in survival after split doses and extrapolation number both are the expression of one single type of cellular repair activity. This is in agreementmore » with the concept originally proposed by Elkind and Sutton that the extrapolation number reflects the extent of cellular recovery from sublethal injury.« less

Recovery Studies of X-Irradiated Tribolium castaneum ("Flour Beetle") Larvae

By means of the split-dose technique, a rapid recovery from a portion of radiation-induced damage was found in T. castaneum larvae. After irradiation at 30°C, recovery reached a maximum, or peak, at around 5 hours with a time to half-maximum recovery between 1 and 2 hours and dropped to a minimum around 8 hours. The rate of recovery, however, is strongly temperature-dependent. At low temperature (10°C), no peak could be detected within 8 hours. The arrest of recovery by low temperature is, nevertheless, reversible. In this study, although larvae showed a fast recovery from sublethal radiation damage, no complete or over-recovery was observed. From the slope of Arrhenius plot of the time of half-maximum of recovery vs reciprocal absolute temperature, the activation energy for the recovery of 14-day-old larvae was determined to be about 20.1 kcal/mole. The residual injury at 6 hours at 30°C was found to be proportional to the 7/4 power of the conditioning dose.

Acute Lethality and Recovery of Goats after 1 MVp X-Irradiation

The ${\rm LD}_{50/60}$ and recovery pattern after a sublethal radiation exposure have been determined for the Angora goat, exposed to 1 MVp x-rays at 450 R/hour. The ${\rm LD}_{50/60}$ was 327 R (95% confidence interval: 292-378). The split-dose technique was utilized for measurement of the amount of recovery from the initial conditioning exposure of 150 R. At 7 days, minimal recovery had taken place, as 84% of the initial injury remained. By 14 days, rapid recovery had occurred and the animals' LD50 had returned to normal. At 21 days, 16% of the initial injury remained. At 30 days, the animals exhibited a reversion in radiosensitivity to the extent that the injury present at that time appeared to be greater than that produced by the conditioning exposure. The recovery pattern in the goat is marked by three distinct phases and does not fit a simple linear or exponential pattern. Routine hematological sampling for 160 days after 150 R, while showing definite depression of the leukocytes and very slow recov...

Effect of Exposure Rate on the Gastrointestinal LD 50 of Mice Exposed to 60 Co Gamma Rays or 250 kVp X-Rays

The LD50 in mice due to gastrointestinal radiation injury from exposure to either60 Co gamma rays or 250 kVp x-rays has been measured for exposure rates ranging from over 100 R/minute down to less than 1 R/minute. The LD50 for60 Co gamma rays was greater than the LD50 for x-rays, but at all exposure rates there was a nearly constant ratio of LD50 for the two kinds of radiation. Measurements of rate of recovery of radiation injury were made with x-rays, using the split-dose technique. The recovery was exponential, with a half-time of 23 minutes. The amount of repairable injury was about half of the exposure given for exposures up to 470 R, but became nearly constant and independent of exposure between 470 and 700 R. A model for repair of injury during exposure was constructed on the basis of the measured recovery kinetics. The increase of LD50 with decreasing exposure rate of either type of radiation was shown to be reasonably accounted for by the model for repair of radiation injury.

Acute Mortality and Recovery Studies in Burros Irradiated with 1 MVP X-Rays

Abstract : With 1 Mvp X-rays, the acute LD50/30 (midline air exposure) of adult female burros was determined to be 369 R; the acute LD50/60 was determined to be 344 R. The split-dose technique, which consists of conditioning animals with a sublethal exposure and redetermining the LD50 at various times thereafter, was used to determine the recovery pattern after an exposure to 250 R. By this method, the burro appeared to have recovered from 48% of the initial injury at 60 days and from 85% at 90 days. A bimodal death pattern was seen in the normal burros, with peaks at 2.4 and 24.2 days. The early death response was dose related. When the LD50 for 1 Mvp X-rays was compared with earlier reported LD50's, it was found that there is an apparent exposure-rate-effectiveness relationship for the burro. The pattern of recovery at 60 and 90 days was found to closely parallel the return of white blood cells to normal values. The slow recovery has been suggested to be a reflection of the small numbers of circulating lymphocytes that were present after the radiation exposures. (Author)

The Effect of Radioprotective Agents on Stem Cell Recovery after Irradiation

Abstract : Erythropoietic stem cell damage and recovery after treatment with radio-protective agents followed by gamma irradiation was measured in transfusion-induced polycythemic mice in conjunction with 59Fe red cell incorporation as the indicator of erythropoietic activity. In irradiated mice, the administration of S-2 aminoethyl isothiourea dihydrobromide (AET) prior to irradiation results in less initial damage to the blood and spleen, and this is responsible for the earlier recovery of the erythropoietic system. Blood and spleen 59Fe values at 1 or 7 days after irradiation with 200 or 700 rads, respectively, can be used to compare the relative value of different sulfhydryl agents in aiding survival. Using the split-dose technique, it was shown that AET given prior to the second radiation dose provided protection to the hematopoietic system and increased survival. However, AET, prior to the first radiation dose (200 rads), did not produce any increased protective effect over that produced by the first radiation dose when the mice were irradiated 10 days later. (Author)

Repair of Sublethal Radiation Injury in Hypoxic Cells of a C 3 H Mouse Mammary Carcinoma

The cells of a C3H mouse mammary carcinoma were examined for their ability to repair sublethal radiation injury using the split-dose technique and ${\rm TCD}_{50}$ as the end point ( ${\rm TCD}_{50}$ = radiation dose that yields local control of half of the irradiated tumors). Radiation was administered either under conditions of local tissue hypoxia (application of a clamp across the root of the thigh bearing the tumor for 2 minutes prior to and during irradiation) or under ${\rm O}_{2}30 {\rm psi}$ conditions (respiring pure oxygen at 3 atmospheres of pressure absolute for 15 minutes prior to and during irradiation). The ${\rm TCD}_{50}$ values were 5372 rads for v = 1 (single dose) and 6853 rads for v = 2 ( $D_{1}=3000$ rads, hypoxia; $t_{i}=6 \text{hours}$ ; $D_{2}=\text{variable}$ , hypoxia). Thus, these acutely hypoxic mammary carcinoma cells repaired rad...