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Results for “Acceleration”

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PubMed1994

Accelerated G1-transit following transient inhibition of DNA replication is dependent on two processes.

Accelerated G1 transit in HeLa cells develops after a temporary inhibition of DNA synthesis in the previous generation. G1 acceleration has been found to be dependent on (1) the cell-cycle position at the time of the inhibition and (2) the duration of the inhibition. The degree of G1 acceleration correlates with the position in S-phase at which DNA synthesis is blocked. G1 transit time decreases gradually beginning with early S blocks and reaches a minimum when DNA synthesis is inhibited at mid S-phase. A minimum of 4 h continuous inhibition at this position resulted in maximum G1 acceleration. Unbalanced growth, i.e., the nonspecific increase in total protein or RNA levels that results from inhibition of DNA synthesis, did not correlate with the decrease in G1 transit time. On the other hand, one-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis showed specific changes in four nuclear proteins of molecular weights 120, 66, 57, and 51 kDa in cells immediately following release from inhibition of DNA synthesis at mid S-phase. A Western blot analysis of cyclins D and E showed an increased accumulation of cyclin E at 0, 1, 5, 7, and 12 h following cell release from the mid S-phase block. Therefore, it is unlikely that changes in the ratio of protein/DNA or RNA/DNA are responsible for the decrease in G1 transit times as suggested by the unbalanced growth model of G1 acceleration. Instead, G1 acceleration may result from the accumulation during S-phase blockage, and subsequent retention through G2 and mitosis, of specific proteins required for cell transit through G1 in the next cell cycle.

Aphidicolin↗

PubMed1999

Estradiol accelerates extinction of a conditioned taste aversion in female and male rats.

Exogenous testosterone treatment prolongs extinction of conditioned taste aversions and estradiol treatment prevents testosterone from prolonging extinction in both gonadectomized males and females. Estradiol could require the presence of testosterone for its effect or its action alone could accelerate extinction. The first series of experiments were designed to test the hypothesis that estradiol accelerates extinction when it is given in the absence of testosterone. The results showed that estradiol accelerates extinction of conditioned taste aversions in the absence of testosterone in gonadectomized Sprague-Dawley females and Fischer 344 females and males. The second series of experiments were designed to determine whether estradiol and testosterone differ in the temporal requirements for their opposite effects on extinction. The results showed that estradiol can accelerate extinction when it is present before and during acquisition (from 8 days before until 3 days after acquisition) or when it is present before and during extinction (from 2 days after acquisition, which was 23 days before extinction, until extinction trials were terminated). This is in contrast to a previous finding that testosterone prolongs extinction only when it is present before and during extinction. The following two hypotheses were suggested to account for the temporal effects of estradiol on extinction of conditioned taste aversions: (1) the presence of estradiol during acquisition reduces the effectiveness of LiCl through its action on the opioid system, and the presence of estradiol during extinction activates a neural pathway, such as that associated with activity levels, that accelerates extinction of passive avoidance tasks in general or (2) the presence of estradiol before, not during, acquisition or extinction accelerates extinction because of its illness-inducing properties. Most of the evidence supports the second hypothesis.

Animals↗

PubMed1995

Human eye movement response to z-axis linear acceleration: the effect of varying the phase relationships between visual and vestibular inputs.

We investigated the effect of systematically varying the phase relationship between 0.5-Hz sinusoidal z-axis optokinetic (OKN) and linear acceleration stimuli upon the resulting vertical eye movement responses of five humans. Subjects lay supine on a linear sled which accelerated them sinusoidally along their z-axis at 0.4 g peak acceleration (peak velocity 1.25 m/s). A high-contrast, striped z-axis OKN stimulus moving sinusoidally at 0.5 Hz, 70 degrees/s peak velocity was presented either concurrently or with the acceleration stimulus or alone. Subjects' vertical eye movements were recorded using scleral search coils. When stimuli were paired in the naturally occurring relationship (e.g., visual stripes moving upward paired with downward physical acceleration), the response was enhanced over the response to the visual stimulus presented alone. When the stimuli were opposed (e.g., visual stripes moving upward during upward physical acceleration, a combination that does not occur naturally), the response was not significantly different from the response to the visual stimulus presented alone. Enhancement was maximized when the velocities of the visual and motion stimuli were in their normal phase relationship, while the response took intermediate values for other phase relationships. The phase of the response depended upon the phase difference between the two inputs. We suggest that linear self-motion processing looks at agreement between the two stimuli-a sensory conflict model.

Adult↗

PubMed1996

[Gamma knife versus stereotactic linear accelerator. Utilization, clinical results and cost-benefit relations].

INTRODUCTION: The principles of radiosurgery were developed in 1951 by Leksell. Their technical realization led to the development of the gamma knife and stereotactically modified linear accelerator. METHODS: In addition to the gamma knife, we present the different principles of convergent beam irradiation (radiosurgery with linear accelerator), the further development to fractionated stereotactic conformal radiotherapy, and the necessary quality-assurance steps. RESULTS: The greatest uncertainties in the precision of radiosurgery result from medical imaging (CT 0.7 x 0.7 x 1 mm; DSA 1-5 mm; MR angiography < 2 mm). The focusing accuracy of the gamma knife (+/- 0.3 mm) can also be achieved today by linear accelerators using a stereotactic floorstand. For the same indication and the same dosage for the target volume, there are no clinical differences between the gamma knife and the linear accelerator (AVM: 80% complete obliteration; metastases: 85% local tumor control; AN: 90% tumor control). However, there are greater differences in costs. There is no constellation where the gamma knife is just as expensive or more cost-effective than the linear accelerator treatment. The most cost-effective solution is modification of an available linear accelerator, resulting in treatment costs per patient of 9,201.25 DM (50 patients/year). CONCLUSION: There seem to be no methodological, physical, clinical or cost reasons for using a gamma knife, especially because the trend is going towards fractionated conformation radiotherapy instead of the application of high single doses.

Brain Neoplasms↗

PubMed2005

Accelerated myelination associated with venous congestion.

Magnetic resonance imaging is currently the gold standard in the assessment of brain myelination. The normal pattern of brain myelination conforms to a fixed chronological sequence. Focal accelerated myelination is a usual pathological state and previously has only been associated with Sturge-Weber syndrome. The purpose of our study is to describe alternate causes for accelerated myelination. We retrospectively reviewed serial MR scans, MR angiography, conventional angiography and the clinical progress of three children with accelerated myelination. Two patients with accelerated myelination had an underlying cerebral sinovenous thrombosis. The third patient had Sturge-Weber syndrome. Our study strongly suggests that cerebral venous thrombosis with the consequent restriction of venous outflow could be a key factor in the induction of accelerated myelination. We recommend that in patients with accelerated myelination, the search for an underlying etiology should include careful evaluation of the intracranial vascular pathology, especially cerebral venous thrombosis.

Brain↗

PubMed2004

Heat-accelerated fixation and rapid dissection of the pediatric brain at autopsy: a pragmatic approach to the difficulties of organ retention.

We investigated whether it is possible to accelerate the examination of a pediatric brain at autopsy and thus facilitate its return to the body before a funeral without compromising the quality of the neuropathologic examination. Accelerated fixation and next-day dissection of the brain was performed in selected cases over a 2-year period by using a microwave histologic tissue processor (MicroMed T/T MEGA, Milestone, Sorisole, Italy). Direct comparison of the histologic appearance and immunohistochemical reactivity of 2 cases, 1 fixed by conventional methods and 1 fixed with the accelerated method, was performed in a blinded fashion by a specialist neuropathologist. Examination of rapidly fixed brain by conventional thin coronal sections was readily achieved. There was no appreciable difference between tissue sections stained with hematoxylin and eosin and prepared from conventional formalin-fixed cortical and cerebellar brain tissue and that fixed by rapid heat acceleration. Immunocytochemical studies were not adversely affected by the accelerated heat-fixation process of tissue. Heat-accelerated fixation is a potential method of speeding up the examination of the brain at autopsy without unduly compromising the quality of the neuropathologic examination.

Adolescent↗

PubMed2006

Accelerated time-resolved 3D contrast-enhanced MR angiography at 3T: clinical experience in 31 patients.

PURPOSE: To evaluate whether time-resolved 3D MR-angiography at 3T with a net acceleration factor of eight is applicable in clinical routine and to evaluate whether good image quality and a low artifact level can be achieved with a temporal update rate that allows for additional information on pathologies. MATERIALS AND METHODS: Thirty-one consecutive patients underwent time-resolved 3D contrast-enhanced MR-angiography on a 3T system. Imaging consisted of accelerated 3D gradient echo sequences combining parallel imaging with an acceleration factor of four, partial Fourier acquisition along phase and slice encoding direction, and twofold temporal acceleration using view sharing. Data volumes representing the arterial and venous contrast phases were independently evaluated by two experienced radiologists by grading of image quality and artifact level on a 0-3 scale. RESULTS: Time-resolved MR-angiography was successfully performed in all subjects without the need for contrast agent bolus timing. Excellent arterial (average score = 2.65 +/- 0.32) and good venous (average score = 2.56 +/- 0.28) diagnostic image quality and little image degrading due to artifacts (average score = 2.20 +/- 0.16) were confirmed by both independent readers (agreement in 65.2% of all evaluations). In 14 patients vascular pathologies were identified in the arterial phases. In eight examinations temporal resolution and depiction of contrast agent dynamics provided additional information about pathology. DISCUSSION: Without the necessity for additional bolus timing, time-resolved 3D contrast-enhanced MR-angiography with imaging acceleration along both the spatial encoding direction and temporal domain revealed excellent diagnostic image quality in neurovascular and thoracic imaging. Despite the limited spatial resolution as compared to high-resolution imaging of the carotid artery bifurcation, the results demonstrate the applicability of contrast-enhanced MR-angiography in thoracic and abdominal MRA as well as cervical imaging with a temporal update rate allowing for additional information on pathologies. Future studies may include an evaluation of optimal trade-offs between spatial and temporal resolution, different acceleration factors and a comparison to the gold-standard for accuracy.

Adolescent↗

PubMed2006

Electroacupuncture elicits dual effects: stimulation of delayed gastric emptying and inhibition of accelerated colonic transit induced by restraint stress in rats.

Acupuncture has been used for treating functional gastrointestinal (GI) disorders. Animal studies have demonstrated that acupuncture antagonized various stress-induced responses. We investigated the effects of electroacupuncture (EA) at ST-36 (Zusanli; lower limb) on stress-induced alteration of GI motor activities. Solid gastric emptying was significantly delayed by restraint stress (29.6+/-2.4%; n=7) compared to that of controls (60.0+/-2.5%; n=8). Delayed gastric emptying was significantly improved by EA at ST-36 (47.2+/-1.8%). Intracisternal (IC) injection of corticotropin releasing factor (CRF; 1 microg) delayed gastric emptying to 25.4+/-3.1%, which was also improved by EA at ST-36, to 53.0+/-7.1% (n=8). The stimulatory effect of EA on stress-induced delayed gastric emptying was abolished by atropine (17.6+/-1.9%) but not by guanethidine (42.2+/-2.3%). Colonic transit was significantly accelerated by restraint stress (GC=7.2+/-0.3; n=8) compared to that of controls (GC=5.2+/-0.2; n=8). Accelerated colonic transit was significantly reduced by EA at ST-36 (GC=4.9+/-0.3). IC injection of CRF accelerated colonic transit (GC=6.9+/-0.2), which was also normalized by EA at ST-36 (GC=4.7+/-0.2). The inhibitory effect of EA on stress-induced acceleration of colonic transit was not affected by guanethidine (GC=4.6+/-0.3). In conclusion, EA at ST-36 showed dual effects: stimulation of stress-induced delayed gastric emptying and inhibition of stress-induced acceleration of colonic transit. The stimulatory effect of EA on stress-induced delayed gastric emptying is mediated via cholinergic pathways. The inhibitory effect of EA on stress-induced acceleration of colonic transit is independent of the sympathetic pathway.

Animals↗

PubMed2000

Accelerated and blastic phase of chronic myeloid leukemia.

There is currently no standard treatment for the blastic phase of chronic myeloid leukemia (CML-BC), which is a chemoresistant form of acute leukemia. Current approaches include using standard acute myeloid leukemia (AML) regimens in an effort to induce remission, variations of these approaches with drugs that seem more active in this specific leukemia, and the direct entry of patients into studies of investigational agents. Although the likelihood of achieving remission is small, immediate bone marrow transplantation in remission should be considered because it provides the only opportunity for long-term survival at this time. Allogeneic transplantation is preferred, but autologous transplantation of an early chronic phase marrow may provide benefit. Often, however, the duration of chemotherapy-induced remission of blast crisis is very short and may preclude entry into a transplant program. In addition, the patient may not be a candidate due to donor issues, age, or medical problems. If transplant is not an option, maintenance interferon is often used, although its benefit is uncertain. For patients in the accelerated phase of the disease, which is characterized by a variety of clinical presentations and cytogenetic abnormalities, the possibility of favorably manipulating the disease is greater. Again, there is no standard treatment, and clinical trials are recommended as first-line therapy. Treatment in the accelerated phase includes standard AML chemotherapy regimens, combinations of new agents, and the combination of cytostatic agents with interferon. Patients whose accelerated phase reverts to chronic phase after treatment may become candidates for bone marrow transplantation. However, current new approaches to the chronic phase applied in accelerated phase as well as new approaches directed specifically toward accelerated phase may lead to prolonged stabilization without bone marrow transplantation. In view of a median age of 55 at diagnosis of chronic phase, nontransplant regimens for accelerated phase that produce long-term benefit are urgently needed.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1993

The effects of centrally administered adenosine on fetal sheep heart rate accelerations.

OBJECTIVE: We examined the effect of administering a long-acting adenosine analog, L-2-N6-(phenylisopropyl) adenosine, into the cerebrospinal fluid of the fourth ventricle on fetal sheep heart rate accelerations. STUDY DESIGN: Pregnant ewes between 123 and 130 days' gestation were anesthetized, and the fetal head was exteriorized. Catheters were placed in the fourth cerebral ventricle through the foramen magnum and in the brachial artery to record fetal heart rate. Studies were performed in unanesthetized fetuses 4 to 7 days after surgery. Accelerations were defined as a 10 beats/min rise in heart rate for at least 5 seconds. RESULTS: The mean number of accelerations before administration of L-2-N6- (phenylisopropyl) adenosine was 3.9 +/- 0.7 (mean +/- SE) per 10-minute epoch, decreasing to 2.0 +/- 0.7 and 1.4 +/- 0.8 after instillation of 0.2 microgram and 0.5 micrograms of L-2-N6-(phenylisopropyl) adenosine, respectively (p < 0.05). Increasing the L-2-N6-(phenylisopropyl) adenosine dose to 10.0 micrograms resulted in loss of heart rate accelerations. Accelerations were not reduced when theophylline, an adenosine receptor blocker, was given before L-2-N6-(phenylisopropyl) adenosine. CONCLUSION: Increasing amounts of a centrally administered adenosine analog progressively decreased the number of fetal sheep heart rate accelerations, most probably by suppression of brainstem sympathetic outflow.

Animals↗

PubMed1981

[Accelerating effect of heterocyclic quaternary ammonium salts on neutral ester hydrolysis by acetylcholinesterase and butyrylcholinesterase (author's transl)].

Some heterocyclic cations (1-methylacridinium, 1-methyl-2-hydroxyiminomethylpyridinium and 1-methyl-3-methoxy-pyridinium) cause acceleration of hydrolysis of alkyl acetates (methyl, ethyl or n-propyl acetate) by acetylcholinesterase (acetylcholine acetylhydrolase EC 3.1.1.7) (Barnett, P. and Rosenberry, T.L. (1977) J. Biol. Chem. 252, 7200-7206). In this study, it is shown that (a) other mono- and bisquaternary ligands of pyridinium, quinolinium and benzoquinolinium series accelerate methyl-, ethyl- and n-propyl-acetate hydrolysis by acetylcholinesterase, (b) these ligands generally accelerate methyl-, and ethyl- and n-propyl-acetate, -propionate and -butyrate, 2-methoxyethyl- and furfuryl-acetate, and ethylene-glycol diacetate hydrolysis by butyrylcholinesterase (acylcholine acylhydrolase, EC 3.1.1.8). At the present time, the ability to accelerate enzymatic hydrolysis of neutral substrates appears to be restricted to some heterocyclic quaternary ammonium compounds. Acceleration which occurs at physiological ionic strength (T/2 = 0.155) involves ternary enzyme-substrate-ligand complex formation and interaction of ligands with the catalytic anionic subsite. It concerns the step leading to the enzyme-substrate complex formation and/or the acylation step of enzymes. Kinetic behaviour analogy of acetylcholinesterase and butyrylcholin-esterase in the presence of the same ligands suggests that an identical acceleration mechanism arises for both enzymes.

Acetylcholinesterase↗

PubMedDate not supplied

Analysis of flow acceleration during erythrocyte filtration: dependence of hematocrit and cell rigidity.

At flow onset the blood filtration rate accelerates to a steady state, this may affect the interpretation of red blood cell (RBC) filterability. We studied the acceleration of flow while the pressure is built up across the filter to analyse effects of various hematocrits and RBC rigidity by glutaraldehyde (GA) hardening. This was analysed by a new filtration system with high time resolution and unlimited filtration volume. The system uses a digital balance that samples the accumulated weight (e.g., filtration rate through 5 microns Nucleopore membranes) with on-line computer communication. The filtration is computer controlled via a pneumatic valve. White blood cells (WBC) were removed prior to filtration by a WBC-eliminating filter to avoid clogging artifacts. When flow is initiated a steady state is reached at 0.3-0.4 s. This timing was also tested and confirmed by a video monitoring technique of filtration flow into a horizontal pipette. The digital balance has a mathematical function to reduce the effects of vibration noise; when this function was activated the apparent acceleration was retarded to 1.2 s. With any of these techniques the steady state timing did not vary with the hematocrit, however, the volume of filtered suspension during acceleration varied with both the hematocrit and the GA hardening (p < 0.001). Extrapolation to yield the initial filtration rate from the relative flow curve (RBC suspension divided by buffer flow) varied depending on if the acceleration phase was included or not. In the most unfavourable situation, with GA-hardened RBC, this difference was 340% (p < 0.01). The slope to calculate clogging rate was affected in a similar way. Moreover, with the most GA-hardened RBC a delay in flow onset was observed with this technique. The acceleration phenomenon may cause artifacts in systems employing volume-derived filtration kinetics because of fixed volumes of filtrated medium.

Erythrocyte Aggregation↗

PubMed1991

Accelerated recovery of antigen-presenting cell activity by the administration of interleukin 1 alpha in 5-fluorouracil-treated mice.

In this study, we investigated the effect of human recombinant interleukin-1 alpha (IL-1 alpha) on antigen-presenting cell (APC) activity of spleen cells in mice treated with 5-fluorouracil (5-FU). APC activity was determined by the antigen-specific proliferation of T cell clone D10.G4.1 cells. When mice were injected with 5-FU, APC activity of spleen cells was suppressed. The administration of IL-1 alpha accelerated the recovery from this suppression. The most accelerated recovery was observed when these mice were administered with IL-1 alpha both before and after the 5-FU treatment. The recovery was also accelerated when the mice were injected with IL-1 alpha after the 5-FU treatment, but not when injected before the 5-FU treatment. The injection of 5-FU also decreased the cell numbers of whole spleen cells, B cells, and non-T non-B cells (Ig- and Thy-1- cells). The administration of IL-1 alpha accelerated the recovery of the decreased cell numbers. Both B cells and non-T non-B cells possessed APC activity, but most APC activity of unseparated spleen cells was carried by non-T non-B cells. B cells possessed only 1/20 of the APC activity of non-T non-B cells. The injection of 5-FU decreased APC activity of both B cells and non-T non-B cells, but the administration of IL-1 alpha accelerated its recovery. Thus, the accelerated recovery of APC activity by IL-1 alpha was suggested to be due to the recovery in the numbers of APC activity-bearing cell subpopulations and also due to the recovery of the APC activity of each subpopulation. Possible mechanisms for the recovery were discussed.

Animals↗

PubMed1993

Antibody response to accelerated immunisation with diphtheria, tetanus, pertussis vaccine.

From May, 1990, a new schedule of immunisation against diphtheria, tetanus, and pertussis (at 2, 3, and 4 months) replaced the previous more widely spaced schedule. A report that children had lower concentrations of diphtheria and tetanus antibodies a month after an accelerated schedule led us to undertake a controlled study to assess antibody response and the persistence of antibodies a year after immunisation in children receiving vaccine according to widely spaced and accelerated schedules. Concentrations of antibodies to diphtheria and tetanus toxoids and to Bordetella pertussis filamentous haemagglutinin (FHA) were measured by solid-phase radioimmunoassay (SP-RIA). We studied 57 children who received accelerated immunisation at median ages of 11, 16, and 21 weeks and two control cohorts (total n = 82) who received vaccine at median ages of 15, 21, and 45 weeks. 6-8 weeks after the third dose the accelerated-schedule group had lower (p < 0.0001) geometric mean concentrations of antibody to tetanus (0.522 [95% CI 0.383-0.710] vs 3.43 [2.45-4.81] IU/mL), diphtheria (0.266 [0.179-0.396] vs 2.39 [0.616-3.53] IU/mL), and FHA (0.044 [0.030-0.063] vs 0.270 [0.196-0.374] units/mL) than the longer-schedule group. 12 months after the third dose the differences between the groups had narrowed (tetanus 0.197 vs 0.341 IU/mL, p = 0.29; diphtheria 0.100 vs 0.131 IU/mL, p = 0.64; FHA 0.014 vs 0.016 units/mL, p = 0.72). At that time all children had tetanus antibody concentrations above protective levels (0.01 IU/mL); only 2 of 31 in the accelerated-schedule group and 3 of 31 in the longer-schedule group had diphtheria antibody concentrations below the protective level. The use of an accelerated schedule of diphtheria, tetanus, and pertussis vaccination is unlikely to lead to an increase in the proportion of children unprotected against these diseases before the preschool booster.

Antibodies, Bacterial↗

PubMed1987

Accelerated radiotherapy followed by chemotherapy for locally recurrent small-cell carcinoma of the lung. A phase II study of Cancer and Leukemia Group B.

Recurrent or persistent small-cell carcinoma of the lung (SCCL) after chemotherapy (CT) alone has shown a poor response to conventional salvage radiotherapy (RT). Accelerated RT is judged more effective than conventional RT for rapidly growing tumors such as SCCL. The objectives of this study were: to determine the tolerability of accelerated RT; and to test the ability of accelerated RT plus CT to achieve local tumor control (LTC) of SCCL recurrent after CT. Patients whose localized tumor was not controlled were selected from Arm III of the Cancer and Leukemia Group B (CALGB) protocol 8083 (Proc. ASCO 2:230, 1984) as eligible for this study. The program of accelerated RT consisted of the delivery of 50.1 Gray (Gy) in 30 fractions over a period of 21 days to the chest. New chemotherapy different from the first began 2 weeks after the completion of RT and was repeated every 3 weeks for 18 months (M). Of 29 potentially eligible patients with locally recurrent SCCL after the first line CT alone from Arm III of the CALBG protocol 8083, 12 were enrolled initially in this study. The analysis of LTC included 11 patients excluding one patient who died 4 weeks after the start of RT from liver metastases. The LTC achieved was as follow: complete remission in 8/11 (72%) and partial remission in 3/11 patients. None of the patients was converted to CR by subsequent chemotherapy. Survival ranged from 2 to 20 M, with a median survival time of 6 M. Tolerance to the subsequent CT, normal tissue reaction to accelerated RT, and the theoretical advantage of accelerated RT over conventional RT for SCCL were evaluated.

Aged↗

PubMed1992

Accelerated fractionation radiotherapy for laryngeal cancer, acute, and late toxicity.

The acute toxicity of an accelerated radiotherapy scheme was compared with a conventional schedule. Eighteen patients with squamous cell carcinoma of the larynx were treated with accelerated fractionation radiotherapy. An average reduction of overall treatment time of 11 days was accomplished by giving 2 fractions a day during the last part of the treatment. Total dose and fraction dose were left unchanged. Acute reactions of skin and mucosa in these patients were compared with those in 40 patients treated with a conventional fractionation scheme, that is, 2 Gy per fraction, 5 fractions per week, to a total dose of 64-70 Gy. Acute reactions were maximal between 5 and 7 weeks after the start of treatment. Complete healing occurred within 3 months in all patients. Mucosal reactions and, as a consequence, dysphagia were clearly increased in those patients treated with accelerated fractionation. For confluent mucositis an ED50 of 66 Gy was calculated compared to 69 Gy for conventional fractionation. To a lesser degree, skin toxicity was also enhanced in the patients treated with the accelerated schedule. Severe edema of the laryngeal mucosa occurred only in patients treated to a total dose of 68 or 70 Gy and was somewhat more frequent with accelerated fractionation (4/10) than with conventional fractionation (4/24). One patient in the accelerated fractionation group underwent laryngectomy for persistent edema and laryngeal necrosis. No severe late skin reactions were observed. It can be concluded that the fractionation schedule tested in this study is feasible. Further shortening of overall treatment time without reduction of total dose will likely lead to unacceptable acute and, possibly, also late toxicity.

Carcinoma, Squamous Cell↗

PubMed1995

Combined modality treatment of the rhabdomyosarcoma R1H of the rat: tumor and normal tissue response after cisplatin and conventional or accelerated irradiation treatment.

PURPOSE: To test the importance of the sequence of cisplatin and irradiation, either conventional or accelerated fractionated. METHODS AND MATERIALS: 30 fractions of 2 Gy were given in 6 or 3 weeks preceded or followed by (time interval between cisplatin and radiotherapy: 3 days) a single IP dose of 5 mg/kg cisplatin in the rhabdomyosarcoma R1H of the rat. Survival curves were generated, and comparisons were made by the log-rank test. RESULTS: After 60 Gy in 6 weeks, no local tumor controls were observed. If cisplatin was injected 3 days before start of 60 Gy/6 weeks, 11 +/- 10% (mean +/- SE) of the tumors were controlled. Cisplatin after radiotherapy resulted in 50 +/- 14% local controls. The difference was significant (p = 0.01) for cisplatin after radiotherapy in comparison to radiotherapy alone where no local controls were observed. After accelerated fractionation, 57 +/- 19% of the animals were cured with or without cisplatin before radiotherapy. If the drug was injected after end of 60 Gy/3 weeks, 86 +/- 13% survived recurrence free. The difference to accelerated radiotherapy alone was not significant. Accelerated radiotherapy produced significantly higher control rates than conventional radiotherapy (p < 0.001). CONCLUSIONS: Accelerated radiotherapy resulted in higher local tumor control rates as compared to conventional fractionated irradiation. Cisplatin combined with radiotherapy showed significantly better results if given after but not before irradiation, either conventional or accelerated fractionated.

Animals↗

PubMed1996

Accelerated repopulation during fractionated irradiation of a murine ovarian carcinoma: downregulation of apoptosis as a possible mechanism.

PURPOSE: To test whether accelerated tumor clonogen repopulation occurs during continuous fractionated radiotherapy of a slow-growing mouse ovarian tumor, and if so whether the accelerated rate of repopulation is predicted by the pretreatment potential doubling time, and whether changes in apoptotic response are a possible mechanism for this change. METHODS AND MATERIALS: The rate of clonogen production during fractionated radiotherapy was followed using the tumor-control assay, with an independent determination of the sensitivity to repeated dose fractions in vivo in the absence of repopulation. The pretreatment potential doubling time was measured by bromodeoxyuridine (BrdUrd) labeling and fluorescence measurements. The apoptotic and mitotic indices at various times during treatment were scored histologically. RESULTS: The slow-growing (pretreatment volume doubling time 6 days) ovarian tumor OCA responds to daily irradiation with 6 Gy under hypoxia by negligible tumor clonogen production in the first few days, followed by a change at about 9 days to accelerated repopulation, after which the effective clonogen doubling time Tclon was about 2 days, near the pretreatment Tpot of 1.7 days. Alternative interpretations of the data, such as a change in radiosensitivity vs. a change in the repopulation rate or acceleration at 3 days as opposed to 9 days, were shown to be unlikely. This change was accompanied by a reduced apoptotic response (measured morphometrically). CONCLUSIONS: When sensitivity to fractionated doses has been corrected for in vivo, this slow-growing mouse tumor exhibits a change to accelerated clonogen production during a continuous radiotherapy regimen that is accompanied or preceded by a reduced histologic apoptotic response. Tclon during accelerated repopulation was slightly longer than the pretreatment Tpot.

Animals↗