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Dynamic enhancement of upper abdominal organs in normal volunteers with MRI and effects of contrast dose reduction.

BACKGROUND: To quantify enhancement parameters of the upper abdominal organs over time during magnetic resonance (MR) examinations and to evaluate the effect of a dose reduction of contrast medium on these parameters. METHODS: Ten volunteers underwent two separate dynamic enhanced MR examinations with 0.1 and 0.075 mmol/kg of contrast medium, respectively. Breath-hold gradient-echo T1-weighted images were acquired every second for 118 s followed by delayed images. The percentages of enhancement, the time to maximum enhancement, and the area under the time-versus-enhancement curve were calculated for each organ. RESULTS: The mean times to maximum percentage of enhancement were less than 25 s for the pancreas, kidneys, and spleen and 50 s for the liver. The mean values of maximum percentage of enhancement for the standard/reduced doses were 72%/62% (pancreas), 165%/155% (kidneys), 114%/87% (spleen), and 67%/53% (liver). This difference was significant when liver enhancement was considered (p = 0.02). In addition, when the areas under the time-versus-enhancement curves were compared, the difference between the standard dose and reduced dose was significant for all organs tested (p < 0.05). CONCLUSIONS: Dynamic scanning of the upper abdomen should start early after contrast injection. Injection parameters should be standardized to capture arterial and venous enhancements in liver examinations. A 25% dose reduction did not significantly affect peak enhancement (except for the liver) but did significantly reduce overall enhancement.

Adult↗

Benefits of pre-emptive dose reduction for Sandimmune to Neoral conversion in stable renal transplant recipients.

In an effort to minimize nephrotoxicity resulting from greater exposure to cyclosporine after Sandimmune to Neoral conversion, we compared two conversion regimens using different dosing ratios. Serial serum creatinine concentrations and trough cyclosporine levels were measured in 26 patients converted from Sandimmune to Neoral using a 1:0.8 dosing ratio (Group 1) and compared to those of 26 patients converted using a 1:1 dosing ratio (Group 2). The percentage change in peak serum creatinine concentration after conversion was greater in Group 2. However, at last follow-up, the dose reductions in each group were comparable. Following conversion, patients in Group 1 required fewer dose adjustments and follow-up blood tests. Compared to conversion using a 1:1 dosing ratio, conversion from Sandimmune to Neoral using a 1:0.8 ratio results in comparable dose reductions and less short-term nephrotoxicity, while requiring less frequent laboratory monitoring.

Adult↗

Cyclophosphamide allows for in vivo dose reduction of a potent oncolytic virus.

The success of cancer virotherapy depends on its efficacy versus toxicity profile in human clinical trials. Progress towards clinical trials can be hampered by the relatively elevated doses of oncolytic viruses administered in animal models to achieve an anticancer effect and by the even higher doses required in humans to approximate an animal bioequivalent dose. Such elevated doses of injected viral proteins may also lead to undesirable toxicities and are also very difficult to produce in a biotechnological setting. We report that a relatively potent herpes simplex virus type 1 oncolytic virus (rQNestin34.5) produces 45% survivors at a dose of 3 x 10(4) plaque-forming units (pfu) in a 9-day-old mouse model of human glioma. Unlike our previous findings with less potent oncolytic viruses, though, the preadministration of cyclophosphamide did not enhance this survival or affect oncolytic virus tumor distribution and tumor volume. However, when oncolytic virus doses were reduced (3 x 10(3) and 3 x 10(2) pfu), cyclophosphamide significantly enhanced both animal survival and oncolytic virus tumor distribution and also reduced tumor volumes. These findings thus show that cyclophosphamide allows for dose reduction of doses of a relatively potent oncolytic virus, a finding with implications for the development of clinical trials.

Animals↗

Dose reduction in dental radiography.

All exposures to ionizing radiation for medical and dental purposes carry risks to both the patient and staff. It is now accepted practice that all exposures should be kept as low as reasonably practicable to minimize these risks. The various methods currently available for dose limitation in intraoral and panoramic radiography and their effects on image quality are considered. In intraoral radiography the use of fast (E-speed) film and rectangular collimation offer dose reductions of approximately 50 per cent and 60 per cent respectively. Constant potential X-ray units, longer focus-to-skin distances and rare-earth filtration will permit further dose reductions. In panoramic radiography the radiation dose to the patients can be reduced by up to one-eighth by combining the use of constant potential X-ray units, rare-earth intensifying screens and rare-earth filtration.

Humans↗

A 1-year randomized study to evaluate the effects of a dose reduction in oral contraceptives on lipids and carbohydrate metabolism: 20 microg ethinyl estradiol combined with 100 microg levonorgestrel.

OBJECTIVES: To evaluate the impact on lipid and carbohydrate variables of a combined one-third ethinyl estradiol (EE)/levonorgestrel (LNG) dose reduction in oral contraceptives. METHODS: In an open-label, randomized study, a dose-reduced oral contraceptive containing 20 microg EE and 100 microg LNG (20 EE/100 LNG) was compared with a reference preparation containing 30 microg EE and 150 microg LNG (30 EE/150 LNG). One-year data from 48 volunteers were obtained. RESULTS: We found a decrease of HDL2 cholesterol and increases of low-density lipoprotein cholesterol, very low-density lipoprotein cholesterol and total triglycerides in both treatment groups from baseline to the 13th treatment cycle. Although for four of six variables, the changes in the 20 EE group were lower compared with the 30 EE group, none of the differences between the two treatments were statistically significant. The median values for the fasting levels of insulin, C-peptide and free fatty acids slightly increased or remained unchanged while the fasting glucose levels slightly decreased after 13 treatment cycles. While the glucose area under the curve (AUC) (0-3 h) was similar in both groups during the OGTT, the insulin AUC(0-3 h) was less increased in the 20 EE/100 LNG group compared with the 30 EE/150 LNG group. None of the differences between the treatment groups for any of the carbohydrate metabolism variables were statistically significant at any time point. Both study treatments were safe and well tolerated by the volunteers. CONCLUSION: Similar effects on the lipid and carbohydrate profiles were found for both preparations. The balanced one-third EE dose reduction in this new oral contraceptive caused slightly lower, but insignificant, changes in the lipid and carbohydrate variables compared with the reference treatment.

Adult↗

[Dose reduction by several measures in X-ray angiographic system].

"The radiation protection measures from equipment side, from a maker's point of view."TAKAJI SAITO Medical Solutions Marketing Division, Siemens-Asahi Medical Technologies Ltd. Taking care of limited fluoro and acquisition time during every case is an important prerequisite for dose reduction. Latest technology provides us with a number of means for dose savings regarding patients and staff. Here, the practical techniques of the radiation control function in angiography system are addressed. Last Image Hold (LIH). Collimation without radiation on LIH. Pulsed fluoroscopy at high and low rates. Additional spectral filters in the X-ray beam. Display of applied dose during the procedure These technological measures will definitely contribute for dose reduction for interventional procedures.

Angiography↗

A global phase III randomized controlled trial of etanercept in psoriasis: safety, efficacy, and effect of dose reduction.

BACKGROUND: In previous studies, etanercept significantly improved plaque psoriasis and was well tolerated. OBJECTIVES: To examine further the efficacy and safety of etanercept and to assess maintenance of treatment effect after dose reduction of etanercept. METHODS: In this multicentre 24-week study in the U.S.A., Canada and Western Europe, patients were at least 18 years old; had active, clinically stable plaque psoriasis involving at least 10% of body surface area; had a minimum Psoriasis Area and Severity Index (PASI) of 10 at screening; and had received or were a candidate to receive systemic psoriasis therapy or phototherapy. During the first 12 weeks of the study, patients were randomly assigned to receive by subcutaneous injection etanercept twice weekly (BIW) at a dose of 50 mg or 25 mg, or placebo BIW in a double-blind fashion. During the second 12 weeks, all patients received etanercept 25 mg BIW. The primary endpoint was a 75% or greater improvement from baseline in PASI (PASI 75) at 12 weeks. RESULTS: Five hundred and eighty-three subjects were randomized and received at least one dose of study drug. At week 12, a PASI 75 was achieved by 49% of patients in the etanercept 50 mg BIW group, 34% in the 25 mg BIW group, and 3% in the placebo group (P < 0.0001 for each etanercept group compared with placebo). At week 24 (after 12 weeks of open-label 25 mg etanercept BIW), a PASI 75 was achieved by 54% of patients whose dose was reduced from 50 mg BIW to 25 mg BIW, by 45% of patients in the continuous 25 mg BIW group, and by 28% in the group that received placebo followed by etanercept 25 mg BIW. Etanercept was well tolerated throughout the study. CONCLUSIONS: Etanercept provided clinically meaningful benefit to patients with chronic plaque psoriasis, with no apparent decrease in efficacy after dose reduction.

Adolescent↗

Lead shielding thickness for dose reduction of 7- to 28MeV electrons.

The relative percent dose reduction by lead of 7- to 18-MeV electrons with a Siemens betatron and of 19- to 28-MeV electrons with a Sagittaire linear accelerator has been measured with a thin-wall buildup chamber for 6.3 X 6.3- and 10.5 X 10.5-cm field sizes at the chamber position for the normal treatment source-to-skin distance (SSD) of each machine. The thickness of lead necessary to attenuate the open beam by 95-98% was then determined of 7- to 28-MeV electrons. The required thickness of lead to attenuate 95% of the 7- to 28-MeV electron beam ranged from 2.3 to 18 mm for the 6.3 X 6.3-cm field and from 2.4 to 23 mm for the 10.5 X 10.5-cm field, respectively. For 98% attenuation, thicknesses from 2.6 to 25.0 mm for the 6.3 X 6.3-cm field and from 2.8 to 27.5 mm of lead for the 10.5 X 10.5-cm field were necessary.

Electrons↗

[Dose reduction in spiral-CT: detection of pulmonary coin lesions with and without anatomically adjusted modulation of tube current].

PURPOSE: To investigate the potential of projection angle-dependent anatomical adaptation of tube current to reduce dose in spiral CT examinations of the thorax without loss in detectability of pulmonary nodules and image quality. PATIENTS AND METHODS: Dose can be reduced for non-circular patient cross-sections without an increase in noise if the tube current is reduced at those angular positions where the patient diameter and, consequently, attenuation are small. The examinations were dose with SOMATOM Plus 4 (Siemens AG). CT projection data were analysed to determine the optimum tube current for each projection angle in real time. We compared image quality, done, and detection rates of pulmonary nodules for thoracic spiral CT examinations with and without online anatomically adapted tube current control in a group of 38 patients. Three radiologists counted all intrapulmonary nodules in consensus separated in three different groups (< 5 mm, 5-10 mm, > 10 mm). Image quality was evaluated in a scale from 1-3 (1 = very good, 2 = good, 3 = worse). RESULTS: On average, the dose was reduced by 21% (15-34%). With a constant tube current, 704 pulmonary nodules were detected, with tube current modulation 707 pulmonary nodules. For three patients we saw more pulmonary nodules (five) with tube current modulation, for two patients we saw less pulmonary nodules (two). In a direct comparison, the missed intrapulmonary nodules were also detected in the respective method. Thus, the detection rate of intrapulmonary nodules was uninfluenced. In general, no deterioration of image quality was observed. CONCLUSION: On average, 21% dose reduction was achieved by an anatomically adapted tube current modulation in spiral CT examinations of the thorax without a loss in detectability of pulmonary nodules and image quality. This method is an important contribution to dose reduction in spiral CT.

Diagnosis, Differential↗

Maintenance treatment of schizophrenia: a review of dose reduction and family treatment strategies.

Maintenance treatment in schizophrenia requires the integration of both medication and psychosocial treatment interventions for maximum effect. We review the recent evidence for strategies drawn from both domains. For the use of anti-psychotic medication we focus on studies of dose reduction using two strategies that differ in assumptions regarding the action of medication. They are: continuous low-dose and targeted, early intervention or intermittent treatment. For psychosocial interventions we focus on studies of family treatment. Regarding dose reduction, we conclude that both strategies are feasible but the targeted strategy incurs higher relapse and rehospitalization rates. Regarding family treatment, we conclude that family treatment provides benefits beyond other psychosocial interventions or usual care, but that there is no evidence for differences in efficacy among family treatments.

Antipsychotic Agents↗

Clinical application of a flat-panel X-ray detector based on amorphous silicon technology: image quality and potential for radiation dose reduction in skeletal radiography.

OBJECTIVE: The purpose of this study was to compare images obtained with a self-scanning, flat-panel X-ray detector based on amorphous silicon technology with conventional screen-film radiographs and to evaluate the possibility of radiation dose reduction in skeletal radiography. SUBJECTS AND METHODS: One hundred twenty patients were examined prospectively using a conventional screen-film system (speed, 400; detector dose, 2.5 microGy) and a prototype digital amorphous silicon detector (simulated speed, 400 and 800, n = 120; simulated speed, 1600, n = 40). The resulting 400 images were evaluated independently by six radiologists using a subjective five-point preference scale that rated overexposure, underexposure, contrast resolution, spatial resolution, and soft-tissue presentation. Image quality was ranked on a scale from 0 to 10 according to subjective criteria. Statistical significance of differences was determined using Student's t test and confidence intervals (95% confidence level). RESULTS: Comparison of conventional radiographs with digital images revealed a statistically significant preference for the digital system for soft-tissue presentation (speed 400 and 800) and visualization of osteoarthrotic changes (speed 400). A small but statistically significant preference for conventional images was found with respect to contrast and spatial resolution when digital speed was 800 or 1600; and the visibility of arthrosis at digital speed 1600, osteolysis at digital speed 800 and 1600, and fractures at digital speed 1600. CONCLUSION: The amorphous silicon-based system with a simulated speed of 400 provided images equivalent to screen-film radiographs. For clinical tasks such as routine follow-up studies, assessment of instability, or orthopedic measurements, a radiation dose reduction of up to 75% may be possible.

Aged↗

A study of dose reduction using digital luminescence radiography for lateral skull radiography.

For lateral skull radiography the minimum required radiation patient exposure to ensure adequate image quality was determined for digital luminescence radiography (DLR) in comparison with a screen-film system (speed class 200). Radiographs were produced with a grid technique on conventional X-ray equipment. A real prepared female head including a true fracture above the pars petrosa ossis temporalis was imaged. The tube current-time product (mAs), and thus the surface entrance dose, was varied systematically. Surface entrance dose was measured with TLD-100 rods. Image quality was judged by experienced radiologists according to the criteria: visual resolution, mean optical density, contrast and perceptibility of specific bone structures. Surface entrance dose was reduced from 0.46 to 0.20 mGy by application of DLR instead of speed class 200 screen-film system without loss of diagnostic information in clinical routine. This corresponds to a dose reduction potential of 57% showing a good agreement with the dose reduction potential of 52% obtained in a previous study using the Alderson head phantom.

Female↗

Flat-panel x-ray detector based on amorphous silicon versus asymmetric screen-film system: phantom study of dose reduction and depiction of simulated findings.

PURPOSE: To compare a large-area amorphous silicon flat-panel detector with an asymmetric screen-film system for the depiction of simulated patterns of interstitial lung disease, nodules, and catheters, as well as for evaluation of dose reduction. MATERIALS AND METHODS: Ground-glass, linear, miliary, and reticular patterns; nodules; and catheters were superimposed over an anthropomorphic chest phantom. Hard copies were generated at different dose levels (speeds: 400, 800, and 1,600) with a flat-panel detector and were compared with copies generated with an asymmetric screen-film system (speed, 400). Detection performance of eight radiologists was compared with a receiver operating characteristic analysis of 19,200 observations per pattern. A difference was significant with a P value of.05. RESULTS: There was no statistically significant difference between the flat-panel detector and the asymmetric screen-film system at the same speed (P >.05) and between the flat-panel detector at a speed of 800 and the asymmetric screen-film system at a speed of 400 (P >.05). The visibility of linear, miliary, and reticular patterns over lucent lung and of nodules smaller than 10 mm and catheters over obscured chest regions on copies generated at a speed of 1,600 with the flat-panel detector decreased, compared with the visibility of these features on copies generated with the asymmetric screen-film system (P <.05). CONCLUSION: The diagnostic performance of the flat-panel detector is comparable to that of the asymmetric screen-film system for depiction of all simulated patterns of interstitial lung diseases, nodules, and catheters at the same speed and offers the potential of dose reduction to a speed of 800.

Humans↗

Trial of maintenance neuroleptic dose reduction in schizophrenic outpatients: two-year outcome.

BACKGROUND: An open trial was undertaken to assess the feasibility of reducing maintenance doses in a public clinical setting and to identify eventual predictors of outcome after dose reduction in schizophrenia. METHOD: Forty-one remitted and chronically psychotic schizophrenic outpatients were assigned, on the basis of their previously clinically determined maintenance dosages, to one of two reduced fluphenazine decanoate regimens: 35 mg/4 wk (19 patients) or 10 mg/4 wk (22 patients). Subsequently, patients were assessed, for a 2-year period, by means of the Brief Psychiatric Rating Scale, the Scale for the Assessment of Positive Symptoms, the Scale for the Assessment of Negative Symptoms, the Simpson-Angus Scale, and the Abnormal Involuntary Movement Scale. RESULTS: Chronically psychotic patients, who represented 74% of the high-dose group and only 14% of the low-dose group, had a significantly higher cumulative relapse rate (81%) than remitted patients (38%). For most remitted patients a dose of 10 mg of fluphenazine decanoate, injected every 4 weeks, was satisfactory. Both remitted and chronically psychotic patients displayed reductions in the severity of neuroleptic side effects. CONCLUSION: Maintenance dose reductions may be beneficial for many schizophrenic outpatients. Chronically psychotic and remitted patients maintained on lowered dosages differ significantly in the stability of their course of illness.

Adolescent↗

The Dose Reduction in Schizophrenia (DORIS) Study: a final report.

Twenty-one medication-free chronic schizophrenics were randomly assigned to three treatment groups: 50% blockade of the bromocriptine growth hormone (GH) response, 100% blockade or 10 ng/ml haloperidol. Only seven of the 21 patients showed a significant improvement after 6 weeks in positive psychotic symptoms; six of the seven responders came from the 50 and 100% blockade groups, suggesting greater efficacy at lower doses. Fifty percent blockade was associated with an average daily haloperidol dose of 3.2 mg and plasma haloperidol levels below the limit of detection (< 1 ng/ml). 100% blockade was associated with a daily dose of 6.5 mg and a plasma haloperidol level of 1 ng/ml. Negative symptoms significantly improved in only four of the 21 patients, and three of these patients were from the 100% blockade group. Twenty-nine patients currently receiving 20 mg/day haloperidol were randomly assigned to three treatment groups: placebo, 100% blockade of the GH response and 10 ng/ml. Patients in the placebo group showed significant deterioration along both the positive and negative symptom dimensions. There were no significant symptom differences between the 100% blockade and the 10 ng/ml groups. The patients in the 100% blockade group had on average a daily dose reduction from 20 to 11 mg/day and a 65% reduction in the plasma haloperidol level. There was a 70% difference in the average daily dose for 100% blockade between the two study arms. The higher daily dose in the dose-reduction arm may reflect receptor up-regulation and/or other "tolerance'-like mechanisms associated with chronic neuroleptic administration.

Adult↗

Leaded shields for thyroid dose reduction in intraoral dental radiography.

This study evaluated the radiation dose reduction, operator acceptance, and patient acceptance of two types of leaded thyroid shields designed for use during intraoral dental radiography. Exposure levels were measured with thermoluminescent dosimeters on three groups of 20 patients undergoing complete mouth (20-film) surveys. Skin entrance dose to the thyroid was 20 mR per complete mouth survey without a shield in place, 12 mR per complete mouth survey with the experimental shield in place, and 9 mR with the commercial shield. Patients and radiologic technologist were surveyed to determine patient comfort and operator acceptability. Patient and operator acceptability were higher for the experimental shield than for the commercial shield.

Adolescent↗

Cyclosporine dose reduction by ketoconazole administration in renal transplant recipients.

Cyclosporine metabolism occurs in the liver via hepatic cytochrome P-450 microsomal enzymes. Ketoconazole, an imidazole derivative, has been shown to inhibit the cytochrome P-450 enzyme system. Thirty-six renal transplant recipients receiving cyclosporine as part of a triple immunosuppressive drug regimen were started on 200 mg/day of oral ketoconazole. The dose of cyclosporine was reduced by 70% at the start of ketoconazole; this dose reduction was based on our previous experience with concomitant cyclosporine-ketoconazole therapy. Ketoconazole was started in patients who had been on cyclosporine for between 10 days and 74 months. The mean cyclosporine dose was 420 mg/day (5.9 mg/kg/day) before starting ketoconazole and 66 mg/day (0.9 mg/kg/day) one year after the addition of ketoconazole; this represents a cyclosporine dose reduction of 84.7% (P less than 0.0001). The mean trough whole-blood cyclosporine concentrations measured by HPLC, were 130 ng/mL preketoconazole and 149 ng/mL after 1 year of combination therapy. Mean serum creatinine and BUN levels were unchanged before and during ketoconazole administration, and no changes in liver function tests were noted. Cyclosporine pharmacokinetics were performed before and after at least three weeks of ketoconazole. Hourly whole-blood samples were measured by HPLC (parent cyclosporine only) and TDX (parent + metabolites). Combination therapy resulted in decreases in the maximum blood concentration and the steady-state volume of distribution divided by the fractional absorption, and increases in mean residence time and the parent-to-parent plus metabolite ratio (calculated by dividing the HPLC by the TDX value). The addition of ketoconazole to cyclosporine-treated patients resulted in a significant inhibition of cyclosporine metabolism and decrease in the dosage. There was minimal nephrotoxicity, and only four rejection episodes occurred on combined therapy. The concomitant administration of the two drugs was well tolerated, and there was no deleterious effect on the immunosuppressive activity of cyclosporine. This drug interaction provides a significant reduction in the costs associated with organ transplantation.

Adult↗

Radiation dose reduction in diagnostic x-ray procedures.

The performance of K-edge filters to modify the x-ray spectrum is investigated experimentally in a variety of clinical situations involving bone/soft tissue imaging, with the aim of improving the optimization between image contrast and patient exposure. The results show that simultaneous improvement of contrast and reduction of exposure is possible for a wide range of patient sizes. For conditions of fixed contrast skin exposure reductions of better than 50% and integrated dose reductions of up to 30% have been achieved with tolerable increases in tube load. Rare earth salt solutions were used as an inexpensive alternative source of K-edge filtration, and their performance was found to be in no way inferior to that of expensive metal foils.

Filtration↗