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PubMedDate not supplied

Dosimetry for 125I seed (model 6711) in eye plaques.

The effect of eye plaque materials (gold backing and silastic seed-carrier insert) on the dose distribution around a single 125I seed has been measured, using cubic lithium fluoride thermoluminescent dosimeters (TLDs) 1 mm on an edge, in a solid water eye phantom embedded in a solid water head phantom. With an 125I seed (model 6711) positioned in the center slot of the silastic insert for a 20-mm plaque of the design used in the collaborative ocular melanoma study (COMS), dose was measured at 2-mm intervals along the plaque central axis (the seed's transverse axis) and at various off-axis points, both with and without the COMS gold backing placed over the insert. Monte Carlo calculations (MORSE code) were performed, as well, for these configurations and closely the same geometry but assuming a large natural water phantom. Additional Monte Carlo calculations treated the case, both for 20- and 12-mm gold plaques, where the silastic insert is replaced by natural water. Relative to previous measurements taken in homogeneous medium of the same material (without the eye plaque), the dose reduction found by both Monte Carlo and TLD methods was greater at points farther from the seed along the central axis and, for a given central-axis depth, at larger off-axis distances. Removal of the gold backing from the plaque did not make measurable difference in the dose reduction results (10% at 1 cm).

Brachytherapy↗
PubMed1985

Dose-dependent reduction of lipopolysaccharide pyrogenicity by polymyxin B.

Lipopolysaccharides (LPS) from Gram-negative bacteria are potent pyrogens in mammals. Polymyxin B (PB), a cationic polypeptide antibiotic, binds lipid A, the active moiety of LPS, with high affinity and abrogates several biological responses to LPS. We studied the effect of PB on pyrogenicity of purified LPS from E. coli 0111:B4 in rabbits. PB reduced the pyrogenic response to LPS in a dose-dependent manner at mass ratios (PB:LPS) from 5:1 to 100:1. Previous reports have suggested that PB is effective only at much higher doses. In our hands, PB itself is pyrogenic, unless previously gamma-irradiated. Our results confirm in vivo the anti-endotoxic action of PB.

Animals↗
PubMed1985

[Reduction of doses in teleradiography of the spine. Criteria of radiation protection and studies of dosimetry].

To reduce the radiation exposure during full spine X-ray examinations, the following techniques were instituted: 72" tube to film distance; X-ray beam collimation; fast screen-film combination (rare earth gradual screens with high speed films); additional compensation filters; shielding of the most radiation-sensitive organs. Dosimetric measurements are reported. A very high reduction in exposure, above all of breasts and gonads, was obtained, without significant loss in the quality of radiographs.

Breast↗
PubMed1996

[Radiation exposure in abdominal radiography with digital luminescence radiography and conventional screen-film system: an experimental animal study].

PURPOSE: To determine and compare the minimum required radiation exposure for a.-p. abdominal radiographs with digital luminescence radiography (DLR) and a screen-film system (SFS) providing adequate image quality in clinical routine. MATERIAL AND METHOD: Abdominal radiographs a.-p. of a pig were produced with DLR and SFS systematically varying the tube current-time product. The image quality was assessed by eight experienced radiologists according to the criteria of visual resolution, mean optical density, perceptibility of the lateral edge of the psoas, the caudal edge of the liver, bone structures and intestinal wall. RESULTS: The image quality of the digital radiographs was better for each criterion except visual resolution if the same current-time product was used for both techniques. From the minimum tube current-time products providing an adequate image quality it follows that a dose reduction of 57% can be achieved by applying DLR instead of speed class 200 SFS. CONCLUSION: The recently published guide-lines for quality assurance in x-ray diagnostics issued by the German Federal Board of Physicians recommend using speed class 400 SFS. Since in that case an approximately halved radiation dose is necessary, dose reduction is hardly to be expected with DLR.

Animals↗
PubMed1990

Dose-dependent reduction of bone inductive properties by ethylene oxide.

Sterilisation of demineralised bone matrix with ethylene oxide has been claimed to destroy the ability of bone matrix to induce new bone formation on intramuscular implantation. Other workers have routinely used ethylene oxide sterilised bone matrix for assays in rodents without detrimental effects. We studied the effects of various lengths of exposure to ethylene oxide gas, and found that bone induction properties are destroyed in a dose-dependent manner. After a short exposure, bone induction properties were moderately diminished. However, this short ethylene oxide treatment did not kill Bacillus subtilis spores. A sterilisation procedure that killed these spores rendered the implants incapable of bone-induction.

Animals↗
PubMed2000

Neuroleptic reduction and/or cessation and neuroleptics as specific treatments for tardive dyskinesia.

BACKGROUND: Since the 1950s neuroleptic medication has been extensively used to treat people with chronic mental illnesses, such as schizophrenia. These drugs, however, have been also associated with a wide range of adverse effects, including movement disorders such as tardive dyskinesia (TD). Various strategies have been examined to reduce a person's cumulative exposure to neuroleptics. These studies include dose reduction, intermittent dosing strategies, such as drug holidays, and neuroleptic cessation. OBJECTIVES: To determine whether, for those people with both schizophrenia (or other chronic mental illnesses) and tardive dyskinesia (TD), a reduction or cessation of neuroleptic drugs was associated with reduction in TD symptoms. A secondary objective was to determine whether the use of specific neuroleptics for similar groups of people could be a treatment for already established TD. SEARCH STRATEGY: Electronic searches of Biological Abstracts (1982-1997), Cochrane Schizophrenia Group's Register of trials (1997), EMBASE (1980-1997), LILACS (1982-1996), MEDLINE (1966-1997), PsycLIT (1974-1997), and SCISEARCH (1997) were undertaken. References of all identified studies were searched for further trial citations. Principal authors of trials were contacted. SELECTION CRITERIA: Reports were included if they assessed the treatment of neuroleptic-induced tardive dyskinesia in people with schizophrenia or other chronic mental illnesses and already established TD, who had been randomly allocated to (a) neuroleptic cessation (placebo or no intervention) versus neuroleptic maintenance; b. neuroleptic reduction (including intermittent strategies) versus neuroleptic maintenance; or c. specific neuroleptics for the treatment of TD versus placebo or no intervention. DATA COLLECTION AND ANALYSIS: The reviewers extracted the data independently and the Odds Ratio (95% CI) or the average difference (95% CI) were estimated. The reviewers assumed that people who dropped out had no improvement. MAIN RESULTS: Two trials were able to be included in this review. Sixty two were excluded and 16 are awaiting assessment. Seven trials are still pending classification. No randomised controlled trial-derived data were available to clarify the role of neuroleptics as treatments for TD. This includes the atypical antipsychotics including clozapine. Despite neuroleptic cessation being a frequently first-line recommendation, there were no RCT-derived data to support this. Two studies ( approximately approximately Cookson 1987 approximately approximately , approximately approximately Kane 1983 approximately approximately ) found a reduction in TD associated with neuroleptic reduction. REVIEWER'S CONCLUSIONS: The lack of evidence to support the efficacy of neuroleptic cessation as a treatment for TD, combined with the accumulating evidence of an increased risk of relapse should antipsychotic drugs be reduced, makes this intervention a hazardous treatment for TD. Dose reduction may offer some benefit as a treatment for TD compared to standard levels of neuroleptic use. There is a need to evaluate the utility of clozapine and the 'atypical' antipsychotics as treatments for established TD.

Antipsychotic Agents↗
PubMed2000

Treatment of tacrolimus-related adverse effects by conversion to cyclosporine in liver transplant recipients.

When tacrolimus side effects persist despite dose reduction, conversion to cyclosporine-based immunosuppression (CyA) is necessary. We characterized tacrolimus side effects that warranted discontinuation of the drug, and outcomes after conversion. Of 388 liver recipients who received tacrolimus as primary immunosuppression, 70 required conversion to CyA. We recorded indication for conversion, whether conversion was early or late after transplantation, tacrolimus dose and trough blood level at conversion, and incidence of rejection after conversion. Conversion was early in 29 patients (41.4%) and late in 41 (58.6%). Indications for early conversion were neurotoxicity (20), (insulin-dependent) diabetes mellitus (IDDM) (5), nephrotoxicity (3), gastrointestinal (GI) toxicity (6), and cardiomyopathy (1), and for late conversion were neurotoxicity (15), IDDM (12), nephrotoxicity (3), GI toxicity (5), hepatotoxicity (6), post-transplant lmphoproliferate disease (PTLD) (2), cardiomyopathy (1), hemolytic anemia (1), and pruritus (1). All early-conversion patients showed improvement/resolution of symptoms. Among late-conversion patients, 37 (90.2%) had improvement/resolution; in 4 (9.8%), adverse effects persisted. The overall rejection rate was 30%. Sixty-two patients (88.6%) are alive with functioning grafts 686 +/- 362 days (range, 154-1433 days) after conversion. When tacrolimus side effects are unresponsive to dose reduction, conversion to CyA can be accomplished safely, with no increased risk of rejection and excellent long-term outcome.

Adolescent↗
PubMed1978

Effect of valproic acid on hepatic function.

Altered hepatic function tests occurred in four of 25 patients treated with valproic acid. An average dose reduction in three patients of 10 mg per kilogram per day resulted in reversion of serum glutamic oxaloacetic transaminase (SGOT) and serum glutamic pyruvic transaminase (SGPT) to normal. The drug was discontinued in one patient. Careful monitoring of hepatic function is required of patients being treated with valproic acid, but our experience suggests that dose reduction alone may be effective in preventing untoward hepatic side effects.

Adolescent↗
PubMedDate not supplied

Influence of flat-panel fluoroscopic equipment variables on cardiac radiation doses.

PURPOSE: To assess the influence of physician-selectable equipment variables on the potential radiation dose reductions during cardiac catheterization examinations using modern imaging equipment. MATERIALS: A modern bi-plane angiography unit with flat-panel image receptors was used. Patients were simulated with 15-30 cm of acrylic plastic. The variables studied were: patient thickness, fluoroscopy pulse rates, record mode frame rates, image receptor field-of-view (FoV), automatic dose control (ADC) mode, SID/SSD geometry setting, automatic collimation, automatic positioning, and others. RESULTS: Patient radiation doses double for every additional 3.5-4.5 cm of soft tissue. The dose is directly related to the imaging frame rate; a decrease from 30 pps to 15 pps reduces the dose by about 50%. The dose is related to [(FoV)(-N )] where 2.0 < N < 3.0. Suboptimal positioning of the patient can nearly double the dose. The ADC system provides three selections that can vary the radiation level by 50%. For pediatric studies (2-5 years old), the selection of equipment variables can result in entrance radiation doses that range between 6 and 60 cGy for diagnostic cases and between 15 and 140 cGy for interventional cases. For adult studies, the equipment variables can produce entrance radiation doses that range between 13 and 130 cGy for diagnostic cases and between 30 and 400 cGy for interventional cases. CONCLUSIONS: Overall dose reductions of 70-90% can be achieved with pediatric patients and about 90% with adult patients solely through optimal selection of equipment variables.

Acrylic Resins↗
PubMed1997

[5 years quality assurance in accordance with the roentgen regulation. Benefits, costs, necessary innovations].

Guidelines and standards supplementing the German "Röntgenverordnung" initiated a complex system of quality control in diagnostic radiology. Cost and profit are analysed for two hospitals of comparable size (Klinikum Buch and Klinikum Nürberg). The considerable expenses that must be incurred for measuring devices, equipment, working time and extra charges on the one hand, are the items that are opposed to achieving a higher image quality and dose reduction on the other. Public quality control enables to demonstrate the quality and to optimise imaging procedures in diagnostic radiology. A critical evaluation of the results of quality control suggests further developments. We should consider larger time intervals for quality tests in some cases, while focussing on techniques with high radiation exposure, e.g. computed tomography, where dose reductions are highly effective.

Adolescent↗
PubMed2005

A population-based study of severity of comorbidity among patients with non-Hodgkin's lymphoma: prognostic impact independent of International Prognostic Index.

Over 60% of patients aged over 70 years, diagnosed with non-Hodgkin's lymphoma (NHL) in the Netherlands have serious comorbidity. We studied the independent influence of comorbidity on choice of treatment, dose reductions, treatment-related toxicity and prognosis, using data from a random sample of 381 patients from the population-based Eindhoven Cancer Registry. About 45% of patients over 60 years of age with NHL had high impact comorbidity at the time of cancer diagnosis. The proportion of patients with aggressive NHL who received chemotherapy decreased from 85% in patients aged 40-60 years to 70% in those over 60 years. About 65% of systematically treated patients with aggressive NHL suffered from treatment-related toxicity. Toxicity appeared to be more common among females and those with high-intermediate or high International Prognostic Index (IPI) risk. Among patients with aggressive NHL, the chance of dying for those with high impact comorbidity was twice as high compared with those without comorbidity. This was independent of the IPI risk. Dose reductions are frequently unavoidable for patients with severe comorbidity, poor performance status or chemotherapy-related toxicity. Whether the less frequent prescription of (full dose) chemotherapy for patients with advanced age and/or with comorbidity is justified remains a question for debate.

Adult↗
PubMed2003

Posttransplantation diabetus mellitus under calcineurin inhibitor.

BACKGROUND: The development of postransplantation diabetes mellitus (PTDM) is a serious complication of kidney transplantation. PTDM has a major impact on quality of life decreasing rates of patient and graft survival. It is well known that some currently used immunosuppressants are diabetogenic. Greater diabetogenicity of FK-506 has been reported in multicenter trials. We initiated a study of conversion from tacrolimus (FK-506) to cyclosporine (CsA) among kidney allograft recipients presenting with PTDM to evaluate whether this maneuver would ameliorate a diabetic state. METHODS: This analysis of 20 adult, renal allograft recipients presenting with PTDM assumed the need for insulin therapy or oral hypoglycemics before and after conversion of the immunosuppressive regimen. The criteria for evaluating the outcome were as follows: dose reduction of insulin or oral hypoglycemic agents, adequacy of glucose control, C-peptide levels, and insulin concentration. RESULTS: During the follow-up, we observed an improvement in the control of blood glucose in the converted group. In 13 patients, satisfactory glucose control was obtained without insulin or any other agent. In 3 patients a significant dose reduction of required insulin was possible. In another 2 patients who were insulin-dependent, the switch to oral hypoglycemic treatment was clinically possible after conversion. After conversion we observed significantly lowered fasting blood glucose levels and increased C-peptide levels. CONCLUSIONS: The conversion from a tacrolimus to a CsA-based immunosuppressive regimen resulted in better glucose metabolism. We demonstrated a positive effect of conversion on the diabetic state of patients with PTDM.

Adult↗
PubMed1996

Individual variation in D2 dopamine receptor occupancy in clozapine-treated patients.

OBJECTIVE: The objectives of this study were 1) to pursue the question of clozapine's striatal D2 occupancy in relation to its clinical effectiveness; 2) to investigate the relation between schizophrenic symptoms, clozapine blood levels, and estimated D2 occupancy during clinically stable and unstable conditions; and 3) to examine long-term stability in D2 occupancy. METHOD: Specific binding of the D2 radioligand [123I]benzamide ([123I]IBZM) was studied with single photon emission computed tomography in 13 patients with schizophrenia when they were clinically stable during chronic clozapine treatment, after clozapine dose reduction of > or = 50%, and in a subgroup (N = 7) after restabilization on clozapine regimens. Clozapine's estimated D2 occupancy was based on comparison with values from drug-free normal subjects. RESULTS: A wide range of estimated D2 occupancies (18% to > or = 80%) were associated with sustained, favorable response to clozapine without correlation with residual symptoms. Clozapine blood levels were negatively related to [123I]IBZM specific binding. Acute dose reduction was associated with predicted worsening in positive and negative symptoms and increases in [123I]IBZM specific binding. Independent of clozapine blood level, patients with more symptoms showed lower [123I]IBZM specific binding, consistent with competition of endogenous dopamine for D2 binding sites in patients with greater symptoms. Restabilization on clozapine regimens produced D2 occupancies closely correlated with baseline values. CONCLUSIONS: There was no evidence for a critical degree of D2 occupancy required to sustain clozapine's therapeutic effects across subjects. Simple linear regression was the best-fit model for clozapine's D2 occupancy. Longitudinal follow-up suggests stability over time of D2 occupancy in relation to dose and clinical response within individual patients.

Adult↗
PubMed2006

Induction cisplatin and paclitaxel followed by combination chemoradiotherapy with 5-fluorouracil, cisplatin, and paclitaxel before resection in localized esophageal cancer: a phase II report.

BACKGROUND: Multimodality therapy for esophageal cancer holds promise for improving outcome in this lethal disease. On the basis of encouraging data from a phase I trial, we conducted a phase II study of preoperative chemotherapy, followed by concurrent chemoradiotherapy and surgery. METHODS: Patients with clinically staged resectable esophageal cancer were treated with induction cisplatin and paclitaxel, followed by 45 Gy of external beam radiation with concurrent infusional 5-fluorouracil and weekly cisplatin and paclitaxel. Four to eight weeks after multimodality induction, esophagectomy was performed in suitable patients. Study end points were survival, pathologic complete response, and toxicity. RESULTS: Twenty-one patients were enrolled with a median age of 58 years, and all patients were clinically staged II or III. Sixteen (76.2%) patients completed the trial, of whom four (25%) had a pathologic complete response. One patient died from postoperative complications. Grade 3 or 4 toxicity was observed in 76% of patients, and dose-limiting toxicity was seen in 6 of the first 14 patients, thus necessitating a planned dose reduction of paclitaxel. At a median follow-up of 30 months, 13 patients remain alive. The 2-year disease-specific survival for the study population was 78%. CONCLUSIONS: This regimen of multimodality therapy before resection resulted in an encouraging 2-year survival rate but a disappointing rate of pathologic complete response and was toxic, necessitating a predetermined paclitaxel dose reduction. The incorporation of taxanes into induction strategies for esophageal cancer seems promising, but the optimal schedule remains undefined.

Aged↗
PubMed2000

Patient positioning in prostate radiotherapy: is prone better than supine?

PURPOSE: To assess potential dose reductions to the rectum and to the bladder with three-dimensional conformal radiotherapy (3D-CRT) to the prostate in the prone as compared with the supine position; and to retrospectively evaluate treatment position reproducibility without immobilization devices. METHODS AND MATERIALS: Eighteen patients with localized prostate cancer underwent pelvic CT scans and 3D treatment planning in prone and supine positions. Dose-volume histograms (DVHs) were constructed for the clinical target volume, the rectum and the bladder for every patient in both treatment positions. "Comparative DVHs" (cDVHs) were defined for the rectum and for the bladder: cDVH was obtained by subtracting the organ volume receiving a given dose increment in the prone position from the corresponding value in the supine position. These values were then integrated over the entire dose range. The prescribed dose to the planning target volume (PTV) was 74 Gy using a 6-field technique. To evaluate reproducibility, portal films were subsequently reviewed in 12 patients treated prone and 10 contemporary patients treated supine (controls). No immobilization devices were used. Deviations in the anterio-posterior (X) and cranio-caudal (Y) axes were measured. Mean treatment position variation, total setup variation, systematic setup variation, and random setup variation were obtained. RESULTS: Prone position was associated with a higher dose to the rectum or to the bladder in 6 (33%) and 7 (39%) patients, respectively. A simultaneously higher dose to rectum and bladder was noted in 2 (11%) patients in prone and in 7 (39%) patients in supine. Rectal and bladder volumes were frequently larger in prone than in supine: mean prone/supine volume ratios were 1.21 (SD, 0.68) and 1.03 (SD, 1.32), respectively. In these cases cDVH analysis more often favored the prone position. Mean treatment position variation and total setup variation were similar for both prone and supine plans. A higher systematic setup variation was observed in prone positioning: 2.7 mm vs. 1.9 mm (X axis) and 4.1 mm vs. 2.2 mm (Y axis). The random variation was similar for both prone and supine: 4. 0 mm vs. 3.6 mm (X axis) and 3.7 mm vs. 3.6 mm (Y axis). CONCLUSIONS: Prone position 3D-CRT is frequently, but not always, associated with an apparent dose reduction to the rectum and/or to the bladder for prostate cancer patients. As suggested by the increased mean prone/supine rectal volume ratio, the advantage of prone positioning for the rectum may be artifactual, at least partly reflecting a position-dependent rectal air volume, which may significantly vary from treatment to treatment. In the absence of immobilization devices, daily setup reproducibility appears less accurate for the prone position, primarily due to systematic setup variations.

Aged↗
PubMed2002

Pharmacokinetic interactions of cyclosporine with etoposide and mitoxantrone in children with acute myeloid leukemia.

The purpose of this study was to assess the effect of the multidrug resistance modulator cyclosporine (CsA) on the pharmacokinetics of etoposide and mitoxantrone in children with de novo acute myeloid leukemia (AML). Serial blood samples for pharmacokinetic studies were obtained in 38 children over a 24-h period following cytotoxin treatment with or without CsA on days 1 and 4. Drug concentrations were quantitated using validated HPLC methods, and pharmacokinetic parameters were determined using compartmental modeling with an iterative two-stage approach, implemented on ADAPT II software. Etoposide displayed a greater degree of interindividual variability in clearance and systemic exposure than mitoxantrone. With CsA treatment, etoposide and mitoxantrone mean clearance declined by 71% and 42%, respectively. These effects on clearance, in combination with the empiric 40% dose reduction for either cytotoxin, resulted in a 47% and 12% increases in the mean AUC for etoposide and mitoxantrone, respectively. There were no differences in the rates of stomatitis or infection between the two groups. CsA treatment resulted in an increased incidence of hyperbilrubinemia, which rapidly reversed upon conclusion of drug therapy. The variability observed in clearance, combined with the empiric 40% dose reduction of the cytotoxins, resulted in statistically similar systemic exposure and similar toxicity.

Acute Disease↗
PubMed2005

Intravesical bacillus Calmette-Guèrin therapy: experience with a reduced dwell-time in patients with pronounced side-effects.

OBJECTIVE: To report the side-effects after a reduction in the dwell-time in patients who had pronounced symptoms after intravesical bacillus Calmette-Guèrin (BCG) treatment, as side-effects such as fever, haematuria, and frequency are common and sometimes severe after BCG treatment in patients with bladder cancer. PATIENTS AND METHODS: The dwell-time was reduced to < or = 30 min in 51 patients who had pronounced side-effects after the preceding BCG instillation. All patients self-reported side-effects after each instillation in a questionnaire. RESULTS: After reducing the BCG dwell-time, fever, chills, dysuria and the overall time-to-recovery were significantly reduced but frequency and haematuria were not influenced. Patients with carcinoma in situ had significantly less dysuria than patients with papillary tumours. There was no difference in the treatment results between patients who had a normal dwell-time and a reduced dwell-time, determined at the first and second follow-up cystoscopy. CONCLUSION: Reducing the BCG dwell-time to < or = 30 min could be an alternative to a dose reduction in patients who experience pronounced side-effects after BCG instillations. The long-term outcome after reducing dwell-time and after dose reduction has not been studied and warrants further investigation.

Adjuvants, Immunologic↗
PubMed2001

Effects of enzyme replacement therapy in thirteen Japanese paediatric patients with Gaucher disease.

UNLABELLED: To determine treatment effects in the unique and previously internationally unreported Japanese paediatric patient population with Gaucher disease (GD), we analysed six response parameters among 13 patients given enzyme replacement therapy (ERT). Also to obtain insights into optimising maintenance dosing, through subgroup analysis we retrospectively examined effects of three ERT dose reduction schedules from a starting regimen of 60 U/kg of body weight every 2 weeks. Our patients included 11 males and two females, 11 individuals with possible type 1 and two individuals with type 3b GD, six individuals with the L444P/F2131 genotype and five with the L444P/L444P genotype, and five who had been splenectomised. Despite different mutation prevalence, Japanese patients with GD, like their counterparts from other ethnic groups, generally benefitted from ERT. However, early and marked ERT dose reduction (from 60 U/kg to 30 or 15 U/ kg every 2 weeks within < or =6 months) was associated with insufficient improvement of mean haemoglobin level and relative height and with insufficient improvement or worsening of platelet count. Only the subgroup given 60 U/kg of ERT every 2 weeks for 36 months had significant improvement in mean haemoglobin, platelet count, angiotensin-converting enzyme and acid phosphatase levels and relative height at 36 months. CONCLUSION: These data suggest that long-term high dose enzyme replacement therapy may be required to obtain sufficient improvement to maintain health among paediatric patients with severe Gaucher disease.

Asian People↗