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2-Chloro-2'-deoxyadenosine synergistically enhances azidothymidine cytotoxicity in azidothymidine resistant T-lymphoid cells.

This report presents quantitative analysis of the synergistic interaction of azidothymidine (AZT) and cladribine (CdA) in human H9-lymphoid cell lines sensitive and resistant to AZT (H9-araC cells). H9-araC cells obtained by cultivation of H9 cells in the presence of 0.5 microM arabinosyl-cytosine (araC) had lower deoxycytidine kinase and thymidine kinase (TK) activities and expressed cross-resistance to araC and AZT. The IC(50) values of AZT and CdA were calculated by using median-effect analysis and CalcuSyn software. The IC(50) values were 0.44 and 0.82 microM for CdA and 67.8 and 30,310 microM for AZT in H9 and H9-araC cells, respectively. However, when the drugs were used in combination the IC(50) values of CdA and AZT were reduced to 0.12 and 15.5 microM in H9 cells and to 0.19 and 24.9 microM in H9-araC cells, respectively. Calculation of dose reduction index (DRI) indicated that at 50-90% growth inhibition level, the combination of the drugs caused 3.6-5.8- and 4.1-11.5-fold reduction in the dose of CdA and 4.4-37.6- and > 1000-fold reduction in the dose of AZT in H9 and H9-araC cells, respectively. The combination index (CI) values simulated from these data suggested synergistic to very strong synergistic lymphocytotoxic effects of AZT combined with CdA. These findings suggest the potential usefulness of a double-targeted approach for designing efficacious therapeutics for the kinase deficient drug resistant tumors.

Antineoplastic Agents↗

Radiotherapy of testicular intraepithelial neoplasia (TIN): a novel treatment regimen for a rare disease.

PURPOSE: Testicular intraepithelial neoplasia (TIN) is a consistent precursor of most invasive germ cell tumors, currently treated by radiotherapy with 20 Gy, which destroys TIN but preserves Leydig cells. Nevertheless, analysis has shown dose-dependent dysfunction even with low therapeutic doses of 20 Gy in some cases. Therefore, we tested a dose reduction regimen by delivering smaller fractional doses to enhance the tolerance of Leydig cells. METHODS AND MATERIALS: Between 1993 and 1999, 9 patients were treated for TIN in a prospective multicenter trial. A total dose of 13 Gy was administered in 10 fractions of 1.3 Gy. Hormonal levels of follicle-stimulating hormone, luteinizing hormone, and testosterone were assayed serially. RESULTS: During a median follow-up time of 36 months, no patient showed evidence of local disease. A first postradiation biopsy was obtained 3-12 months after radiotherapy; 5 patients underwent a second biopsy 2-3 years after treatment. All biopsies showed a Sertoli cell-only pattern. Follicle-stimulating hormone levels continued to increase 1 year after radiotherapy, signaling eradicated spermiogenesis. Luteinizing hormone and testosterone remained within the normal range 2 years after radiotherapy. CONCLUSIONS: In the treatment of TIN, there seems to be a dose reduction potential to 13 Gy by lowering single fractional doses, which enhances the therapeutic ratio in favor of the Leydig cells.

Adult↗

Dose-dependent reduction of N-2-fluorenylacetamide-induced liver cancer and enhancement of bladder cancer in rats by butylated hydroxytoluene.

The modifying effect of four dose levels of butylated hydroxytoluene (BHT) on liver and bladder carcinogenesis by N-2-fluorenylacetamide (FAA) was studied in rats. FAA (200 ppm) was fed simultaneously with four levels of BHT (300, 1000, 3000, and 6000 ppm) to male F344 Fischer strain rats. Groups of animals were killed at 6, 12, 18, and 25 weeks. Hepatocellular-altered foci in the liver were identified histochemically by the exclusion of cellular iron after iron loading and by reaction for gamma-glutamyltranspeptidase. FAA alone induced altered hepatocellular foci which increased in number with duration of exposure, and by 25 weeks of feeding, 100% of rats had liver neoplasms. Concurrent feeding of BHT produced a dose-dependent reduction in the numbers of altered foci and the areas of liver sections occupied by histochemically altered cells, as well as a reduction in the incidence of liver neoplasms and the number of neoplasms per animal. These findings indicate that reduction of the number of foci at an early stage is predictive of reduced incidence of neoplasms at a late stage. Thus, BHT inhibited in a dose-dependent manner the hepatocarcinogenesis of concurrently fed FAA. However, although no bladder neoplasms occurred in rats given either BHT or FAA alone, groups fed BHT and FAA together developed bladder neoplasms in proportion to the dose of BHT. The effect of BHT on both liver and bladder carcinogenesis could be explained by BHT causing an alteration of the metabolism of FAA in the liver, resulting in less activation and greater urinary excretion of carcinogenic metabolites. In addition, BHT at high dose levels may exert a promoting effect on bladder carcinogenesis. Accordingly, it is suggested that the chemopreventive effect of phenolic antioxidants should be investigated with attention to the possibility that they not only inhibit carcinogenesis in the main target organs but also modify carcinogenesis in other organs.

2-Acetylaminofluorene↗

Comparison of dose homogeneity effects due to electron equilibrium loss in lung for 6 MV and 18 MV photons.

PURPOSE: Loss of electronic equilibrium within and adjacent to low density materials can result in a dose reduction along the central axis and near the beam edge for megavoltage photon beams. In this context, Radiation Therapy Oncology Group (RTOG) protocol #91-05 recommends the use of photon beams of energy 12 MV or less for nonsmall cell lung cancer therapy. This work presents data to support the use of higher energy photons for some clinical lung field setups. METHODS AND MATERIALS: Beam profiles were obtained from films inserted into homogeneous (polystyrene) and heterogeneous (polystyrene and lung-equivalent material) phantoms and irradiated in both single-field and parallel-opposed setups with 6 and 18 MV photon beams. Depth-dose curves were obtained with a parallel-plate ion chamber in the heterogeneous phantom to determine the range of field sizes over which the dose reduction at the lung/polystyrene interface becomes clinically significant. RESULTS: Opposed field profiles show less degradation in the penumbra (50-90% width) at the lung/polystyrene interface than single-field profiles. The difference between 6 and 18 MV penumbra widths at the interface also reduced when an opposed field is added. The central axis dose reduction at the interface was negligible for single fields of a width of 8 cm or more. CONCLUSION: Our results show that for opposed fields, the difference in penumbra degradation of the 6 and 18 MV photon beams is clinically insignificant compared to daily setup errors and patient motion. The central axis dose reduction is also shown to be small. Our data support the use of higher energy beams to obtain lower peripheral dose maxima in small clinical geometries.

Carcinoma, Non-Small-Cell Lung↗

Single-drug parenteral estrogen treatment in prostatic cancer: a study of two maintenance-dose regimens.

Treatment of 17 patients with prostatic cancer with 320 mg polyestradiol phosphate (PEP) as intramuscular injections every fourth week suppressed serum testosterone (T) values to orchidectomy levels within 1 month, and serum estradiol-17 beta (E2) rose to a mean level of 2,456 pmol/liter after 6 months. Following 6 months of treatment, the PEP dose was reduced to 80 mg/4 weeks in 9 and 160 mg/4 weeks in eight patients. Mean T levels, increased significantly after dose reduction in both groups and were above the upper orchidectomy limit at 1 month after dose reduction in the 80 mg group. Mean T levels, however, remained below this level at 5 months in the 160 mg group. Dose reduction caused a rise in gonadotropin levels in the 80 mg but not in the 160 mg group. While 320 mg/4 weeks may be a suitable initial dosage, doses less than or equal to 160 mg/4 weeks are insufficient as maintenance dosages if orchidectomy values of T are required.

Aged↗

Hepatic spiral CT: reduction of dose of intravenous contrast material.

PURPOSE: To assess the potential for reduction of contrast material dose in hepatic spiral computed tomography (CT). MATERIALS AND METHODS: Four hundred eighty-seven outpatients were randomized prospectively into nine biphasic and eight uniphasic injection protocols: 75, 100, or 125 mL of 240, 300, or 350 mg of iodine per milliliter of iohexol (18-44 grams of iodine). Protocols were compared according to the maximum hepatic enhancement (MAX) and the contrast enhancement index (CEI). RESULTS: Uniphasic injection was superior to biphasic injection for all protocols. No statistically significant difference in contrast enhancement was present for 38-44 grams of iodine with the uniphasic technique. Adequate enhancement thresholds (MAX > 50 HU, CEI at 30 HU > 300 HU x sec) were exceeded in more than 70% of heavy patients ( > 183 lb [83 kg]) with uniphasic injection of 38 g. For thin patients ( < 183 lb [83 kg]), uniphasic injection of 26 g produced adequate enhancement. CONCLUSION: Contrast material dose may be reduced by up to 40% in thin patients undergoing hepatic spiral CT after uniphasic injection of contrast material; this may result in substantial cost savings.

Adult↗

Detailed analysis of a randomized phase III trial: can the tolerability of capecitabine plus docetaxel be improved without compromising its survival advantage?

BACKGROUND: In a phase III trial, 3-weekly capecitabine (1250 mg/m(2) twice daily days 1-14) plus docetaxel (75 mg/m(2) day 1) demonstrated significantly superior overall survival to 3-weekly docetaxel (100 mg/m(2) day 1). We report a retrospective analysis of the impact of capecitabine/docetaxel dose reduction on safety and efficacy. PATIENTS AND METHODS: Safety and efficacy data were analyzed retrospectively according to the actual doses of capecitabine and docetaxel administered. RESULTS: More patients receiving capecitabine/docetaxel (65%) had dose reductions for adverse events than docetaxel alone (35%). In most patients requiring dose reduction with the combination (80%), capecitabine and docetaxel were simultaneously reduced to 950 mg/m(2) and 55 mg/m(2), respectively. Subsequently, there were fewer cycles (17%) with grade 3/4 adverse events than with the full doses (34%). Time to progression and overall survival appeared to be similar in patients starting the second cycle with reduced doses of capecitabine/docetaxel and those who continued to receive full doses of capecitabine/docetaxel for at least the first four cycles. CONCLUSIONS: Capecitabine/docetaxel dosing flexibility allows management of side-effects without compromising efficacy. This retrospective analysis, as well as multiple phase II studies of taxanes with reduced-dose capecitabine, shows that reducing the starting dose of capecitabine with docetaxel is a reasonable strategy for the treatment of patients with metastatic breast cancer. In addition, reducing the dose of both agents may be appropriate.

Adult↗

Dose-dependent reduction of myocardial infarct mass in rabbits by the NHE-1 inhibitor cariporide (HOE 642).

The aim of this study was to investigate the dose-dependent effect of pretreatment with the selective sodium-hydrogen exchange NHE-subtype 1 inhibitor cariporide on myocardial infarct mass in a rabbit model of coronary ligation and reperfusion. Furthermore, in a second part of the study, we tested the effect of cariporide in the rabbits when given prior to reperfusion. Rabbits (n=49) were randomized in 7 groups: saline vehicle, cariporide: 0.01, 0.03, 0.1 and 0.3 mg/kg, and subjected to a 30 min occlusion of a branch of the left coronary artery followed by 2 h reperfusion. Cariporide was given as a bolus intravenously 10 min before occlusion or 5 min before reperfusion. After reperfusion, myocardial infarct mass was determined by triphenyl tetrazolium chloride staining and expressed as a percent of area at risk. Cariporide given intravenously 10 min before occlusion in doses of 0.01, 0.03, 0.1, 0.3 mg/kg, led to a dose-dependent reduction in infarct mass from 58+/-6% in controls to 48+/-4% (-17%, NS), 36+/-5% (-38%, p<0.05), 26+/-6% (-55%, p<0.05), 11+/-4% (-81%, p<0.05) respectively, whereas area at risk did not differ in between the groups. The effect of the lowest dose of 0.01 mg/kg did not reach significance. Plasma levels at different doses of cariporide were correlated to the respective infarct mass. After coronary occlusion left ventricular end-diastolic pressure (LVEDP) significantly increased throughout occlusion and reperfusion. Cariporide in the doses of 0.3, 0.1 and 0.03 mg/kg normalized LVEDP when measured after 2 h reperfusion. In controls hemodynamic parameters such as mean arterial blood pressure (MAP), heart rate (HR), left ventricular pressure (LVP) and LV dP/dt(max) were not significantly changed by ischemia/reperfusion with the exception of MAP, LVP and LV dP/dt(max) which were significantly decreased after 120 min reperfusion. Cariporide at doses of 0.1, 0.03 and 0.01 mg/kg did not significantly influence these parameters, whereas the highest dose of 0.3 mg/kg prevented the decrease of MAP and LVP. Cariporide (0.3 mg/kg i.v.) administered 5 min before reperfusion significantly reduced infarct mass by 31%. Under these conditions the increase of LVEDP after coronary occlusion was not influenced by cariporide. As in the pretreatment experiments, the decrease of MAP and LVP was prevented when measured 2 h after reperfusion. The results show that pretreatment with the NHE-subtype 1 inhibitor cariporide is cardioprotective by reducing infarct mass in rabbits in a dose-dependent manner. While the cardioprotective effect of pretreatment could be demonstrated over a broad range of doses, the efficacy of the compound when given only on reperfusion was significant but more limited.

Animals↗

Dose-dependent reduction in renal magnesium clearance by amiloride during frusemide-induced diuresis in rats.

The effects of the potassium-sparing diuretic, amiloride, on fractional magnesium excretion were investigated at four doses (0.02, 0.08, 0.20 and 2.00 mg kg-1 h-1) during frusemide-induced diuresis. Amiloride caused a dose-dependent reduction in the fractional excretion of both magnesium and potassium, whereas the effects of amiloride, over the same dose range, on fractional sodium and calcium excretion were not dose-dependent. The results indicate that amiloride exerted a specific renal action to alter magnesium and potassium transport dissociated from effects on sodium excretion.

Amiloride↗

Analysis of low-dose digital lateral cephalometric radiographs.

OBJECTIVE: To examine the effects of the dose reduction obtained with photostimulable phosphor computed radiography (CR) on the identification of cephalometric landmarks. METHODS: Dose reductions of 50% and 75% respectively were obtained by placing three storage phosphor image plates in the same cassette. Lateral cephalograms were exposed on ten patients. Seven observers identified 14 anatomical landmarks on the images. RESULTS: The location of anatomical landmarks on the lateral cephalograms was not effected by the decreased dose (P > 0.05). Interobserver variation was the major influence. CONCLUSION: A dose reduction of 75% does not effect the localization of anatomical landmarks in lateral cephalograms obtained with CR.

Adolescent↗

First-line oral capecitabine therapy in metastatic colorectal cancer: a favorable safety profile compared with intravenous 5-fluorouracil/leucovorin.

PURPOSE: To evaluate the safety profile of capecitabine using data from a large, well-characterized population of patients with metastatic colorectal cancer treated in two phase II studies. In these trials, capecitabine achieved significantly superior response rates, equivalent time to disease progression and equivalent survival compared with 5-fluorouracil (5-FU)/leucovorin. PATIENTS AND METHODS: Patients (n = 1207) were randomized to either oral capecitabine (1250 mg/m2 twice daily, on days 1-14 every 21 days) or intravenous (i.v.) bolus 5-FU/leucovorin (Mayo Clinic regimen). RESULTS: Capecitabine demonstrated a safety profile superior to that of 5-FU/leucovorin, with a significantly lower incidence of diarrhea, stomatitis, nausea, alopecia and grade 3 or 4 neutropenia leading to significantly fewer neutropenic fever/sepsis cases and fewer hospitalizations. All patients in the capecitabine group received a starting dose of 1250 mg/m2 twice daily and the majority (66%) did not require dose modification for adverse events. In the 5-FU/leucovorin group, 58% of patients did not require dose reduction for toxicities. The capecitabine dose-modification scheme reduced the recurrence of key toxicities without compromising efficacy. In both treatment arms, patients with moderate renal impairment at baseline (estimated creatinine clearance 30-50 ml/min) experienced a higher incidence of grade 3 or 4 toxicities. This increase was more pronounced with 5-FU/leucovorin. CONCLUSIONS: Capecitabine is at least as effective, better tolerated and more convenient than i.v. 5-FU/leucovorin as treatment for patients with metastatic colorectal cancer. Analysis of data from two large phase III trials demonstrates that efficacy is not compromised in patients requiring a dose reduction for adverse events. The phase III data and an additional pharmacokinetic study support a lower starting dose in patients with moderate renal impairment at baseline (calculated creatinine clearance 30-50 ml/min) and a contra-indication in patients with severely impaired creatinine clearance at baseline (<30 ml/min). For patients with normal or mildly impaired renal function at baseline, the standard starting dose is well tolerated. The incidence and severity of adverse events in patients with moderate renal impairment at baseline who were treated with 5-FU/leucovorin was more pronounced, indicating that capecitabine provides a better-tolerated alternative.

Administration, Oral↗

On the determination of the effective transmission factor for stainless steel ovoid shielding segments and estimation of their shielding efficacy for the clinical situation.

Commercially available ovoid tubes for gynecological applications used in conjunction with the microSelectron-HDR (Nucletron International B.V., Waardegelder 1, 3905 TH Veenendaal, The Netherlands) for 192Ir sources, allow for shielding. Publications concerning the transmission properties of these 4.5-mm thick stainless steel (AISI number 303/304) shielding segments are scarce and not compatible for implementation in treatment planning. Therefore the effect of shielding on dose distribution is unknown. The effective transmission factor has been measured and implemented in the planning computations. Screening efficacy was evaluated on 20 actual treatment plans, analyzing dose reduction to critical tissue and comparing dose distribution in planes relevant for this particular application. Due to high transmission (effective transmission factor = 0.85), stainless steel screening segments only provide low, local dose reductions of maximum 15%. A new approach with regard to optimization and source configuration is needed to reduce dose to vulnerable tissue, exploiting the screening segments to a maximum extent. Better shielding, especially at the midline (plane bisecting the ovoids) could be expected by using shielding segments with other geometrical characteristics.

Biophysical Phenomena↗

Management of hand-foot syndrome induced by capecitabine.

INTRODUCTION: Capecitabine (Xeloda) is a systemic prodrug of 5-fluorouracil (5-FU), which is administered in an oral formulation. Hand-foot syndrome (HFS) has proven to be a chronic dose-limiting toxicity of capecitabine, leading to significant morbidity in patients receiving this agent. The purpose of this review is to define the pathophysiology, risk factors, incidence and management of capecitabine-induced HFS. METHODS: Literature for this review article was collected from the following databases: PubMed, CINAHL, and the proceedings of the American Society of Clinical Oncology (ASCO) confined to the years 1995-2006. The following key terms were used in the search: hand-foot syndrome, palmar-plantar erythrodysesthesia, capecitabine, Xeloda, colorectal cancer, and metastatic breast cancer. RESULTS: HFS associated with capecitabine is a serious dose-limiting toxicity. Incidence of grade 3/4 toxicity is of extreme significance, and introduces the need for dose reductions and/or interruptions in capecitabine therapy. Drug-related therapies studied include topical emollients and creams, systemic and topical corticosteroids, nicotine patch, vitamin E, pyridoxine, and COX-2 inhibitors. However, due to the lack of randomized, controlled trials with these therapies, the current mainstay of treatment for the management of this toxicity is interruption of therapy and, if necessary, dose reduction. CONCLUSION: Treatment interruption or dose reduction remain the only methods shown to effectively manage HFS, but supportive measures to reduce pain and discomfort and prevent secondary infection are very important. Many other prophylactic and treatment strategies have been investigated, with pyridoxine and COX-2 inhibitors being the most promising in case reports and retrospective studies; therefore, prospective, randomized, controlled trials are needed to prove their efficacy.

Antimetabolites, Antineoplastic↗

Shielding performance and clinical applicability of lead-free materials in computed tomography.

Owing to the high radiation exposure associated with computed tomography (CT) examinations and the image quality degradation caused by conventional radiation shielding materials, this study evaluated the dose reduction performance and image quality maintenance potential of a newly developed lead-free composite shielding material. This material was composed of bismuth, tungsten, tungsten carbide, aluminium, and polyurethane. Phantom-based dose measurements demonstrated that the shielding material achieved dose reduction rates ranging from 17.6% to 37.6%, depending on tube voltage. Signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and changes in tube current-time product (mAs) under a scout-based automatic exposure control (AEC) protocol were analysed according to the presence or absence of the shielding material across regions. For the clinical evaluation, CT scans were performed on four patients. Furthermore, the images were reviewed to evaluate whether this material affected image quality. The shielding material exhibited radiation reduction levels comparable to those reported in previous studies. SNR and CNR analyses showed minor statistical variations in certain regions; however, most differences were not statistically significant, and even significant differences remained within a range that did not compromise diagnostic image quality. Under the scout-based AEC protocol, the use of the shielding material resulted in less than 1% variation in mAs values. No visually perceptible artefacts or clinically significant image quality degradation were observed. The proposed composite shielding material demonstrated the potential to mitigate some limitations of conventional shielding materials and showed preliminary clinical feasibility as an adjunctive strategy for radiation dose reduction in CT examinations.

Radiation Protection↗

Conversion from tacrolimus to neoral for postrenal transplant diabetes.

Diabetes mellitus (DM) is a well-recognized complication of immunosuppressive therapy in the post-transplant (Tx) period. The DM encountered in the setting of tacrolimus therapy has been managed in the past by tacrolimus dose reduction and a rapid corticosteroid taper; frequently insulin therapy is also required to maintain normoglycemia. However, the dose reduction of immunosuppressive agents has often resulted in acute allograft rejection. We are reporting our experience in managing three pediatric renal Tx recipients who developed DM in the post-Tx period while on triple immunosuppressive therapy including tacrolimus and corticosteroids. All of our patients were managed by substitution of tacrolimus with conventional doses of neoral while maintaining their usual corticosteroid dose. All three patients had resolution of hyperglycemia and none experienced acute rejection. Tacrolimus was then successfully reinitiated 4.6 months later; at last follow-up, all of our patients have good allograft function and have maintained a normal blood sugar. In conclusion, we feel that conversion of patients from tacrolimus to neoral should be attempted as a safer alternative to tacrolimus dose reduction, for managing post-Tx DM in tacrolimus treated patients.

Adrenal Cortex Hormones↗

Hematologic abnormalities in liver-transplanted children during medium- to long-term follow-up.

OBJECTIVE: Hematologic abnormalities as adverse effects related to immunosuppressive drugs in liver-transplanted children are rarely reported. We have observed anemia, neutropenia, and thrombocytopenia in our pediatric liver-transplant population. The aim of this study was to exclude all suspected etiologies to define the association of immunosuppressants with these abnormalities. METHODS: Patients under 18 years old who still attend periodic controls at liver-transplant outpatient clinics were considered. Seventy patients met the inclusion criteria, 36 girls and 34 boys. Mean patient age was 5.6 years (range: 7 months to 17 years) and mean follow-up 6 years (range: 1-10 years). Medical records were reviewed beginning 1 month posttransplant. Treatment exposures, irradiation, blood product administration, and all laboratory studies were reviewed. When a hematologic abnormality was detected, we recorded the management for its resolution, the clinical response to therapy and the length of treatment. RESULTS: Twenty-five of the 70 children suffered 26 abnormal hematologic episodes (anemia 14, neutropenia 2, thrombocytopenia 3, simultaneous anemia and neutropenia 5, and pancytopenia 2). Eleven episodes (42%) had unclear etiologies and the process of elimination suggested an association with the immunosuppressant. Switching immunosuppressant was required in four patients and dose reduction in seven. CONCLUSIONS: Hematologic abnormalities in liver-transplanted children are common. The etiology is readily attributable to several causes. When the immunosuppressant appears to be a possible cause, the first step is dose reduction. If the hematologic abnormality persists despite dose reduction, a trial switch may be required.

Adolescent↗

Oral cyclosporin A in the treatment of psoriasis: an overview of studies performed in The Netherlands.

This is a review of the clinical studies performed so far in The Netherlands of the treatment of psoriasis with cyclosporin A (CyA), a selective immunosuppressive drug that has caused a major breakthrough in transplant medicine. Data derived from a double-blind placebo-controlled study (5 mg/kg/day of CyA), dose-finding studies (2.5 mg vs 5 mg/kg/day and 1 mg, 2 mg or 3 mg/kg/day), and long-term treatment of chronic plaque-type psoriasis (1.1-7.2 mg/kg/day) suggest an initial starting dose of 3 mg/kg/day irrespective of the severity of the disease. Long-term treatment brought about dose- and time-dependent (reversible) side-effects, including renal dysfunction and hypertension. Efforts to reduce the dose included concomitant administration of drugs known to have anti-psoriatic efficacy. Only combination with topical steroids appeared to add to the clinical efficacy of CyA, but did not allow a dose reduction sufficient to restore renal function. Dose reduction through intermittent treatment, however, postponed exacerbations sufficiently to permit at least partial normalization of serum creatinine levels. A similar effect was seen in the treatment of pustular palmoplantar psoriasis, which responded to doses of 1.1-6.1 mg/kg/day.

Administration, Oral↗

Techniques for reducing interventional neuroradiologic skin dose: tube position rotation and supplemental beam filtration.

PURPOSE: To limit the side effects of interventional neuroradiologic radiation, such as epilation, by applying a technique involving tube position rotation and by adding a supplemental inexpensive primary beam filter; and to show the dose effect of modifying technical factors. METHODS: Combined skin dose from fluoroscopy and digital subtraction angiography was measured with an array of 16 thermoluminescent dosimeters during interventional neuroradiologic procedures in 12 control subjects, in 18 patients whose procedures included addition of an inexpensive primary beam filter (0.5 mm aluminum/0.076 mm copper), and in 10 patients in whom the tube position was rotated, additional primary beam filtration was used, and close attention was paid to technique. RESULTS: Maximum thermoluminescent dosimetric measurements obtained with existing machine filtration ranged from 0.31 to 2.70 Gy in the control group (mean, 1.51 +/- 0.88); 0.25 to 2.42 Gy in the group with additional filtration alone (mean 0.96 + 0.64; average dose reduction, 36%); and 0.13 to 1.23 Gy in the group with additional filtration, tube position rotation, and close attention to technique (mean, 0.58 +/- 0.34; average dose reduction, 63%). Differences were statistically significant. CONCLUSIONS: Greater than 50% skin dose reductions were documented during interventional neuroradiologic procedures by combining tube position rotation, supplemental primary beam filtration, and technical modifications.

Adolescent↗