Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Dose reduction”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 469 records · Page 26Linked to original sources
PubMed1997

Clinical and genomic influence of sulindac on rectal mucosa in familial adenomatous polyposis.

PURPOSE: A study was performed to evaluate the antiproliferative effects of low doses of the nonsteroidal drug, sulindac, on adenomas and rectal mucosa in familial adenomatous polyposis and to analyze the influence on tumor-suppressor genes and on apoptosis. METHODS: This was a prospective, controlled, nonrandomized Phase II dose-finding study for sulindac. The study group (n = 28) and control group (n = 10) underwent colectomy and ileorectal anastomoses, with repeated proctoscopy with endoluminal ultrasound and biopsies every three months. Dose-reduction of sulindac according to adenoma reversion was predetermined. Proliferation marker, Ki-67 (MIB1 and 5), on frozen or paraffin sections evaluated the antiproliferative effects; mutant p21ras, pantropic p53, mutant p53, and anti-bcl-2 were performed as enzyme-linked immunosorbent assay procedures and/or immunohistochemistry on paraffin sections. RESULTS: All patients responded to sulindac after 24 weeks (at the latest). There was a significant reduction of adenomas and dose reduction to 67 mg/day after three years of therapy (Mann's test for trend, P < 0.001). Results consisted of 78 percent complete reversions, 22 percent partial reversions of adenomas at latest re-examination, and no influence on upper gastrointestinal tract adenomas. No influence was detected on repeated hemograms, liver, or renal function at high or low doses. There was a permanent antiproliferative effect (Ki-67) of low-dose sulindac, significant blocking of ras mutation activation, and a significant difference of untreated and treated mucosa in mutant p53 content (Wilcoxon's or Kruskal-Wallis each, P < 0.05). Reverse correlation of anti-bcl-2 and p53 immunostaining on mucosa sections was an indication of adenoma relapse. CONCLUSIONS: Low-dose antiproliferative sulindac therapy is highly effective in adenoma reversion in familial adenomatous polyposis patients. Sulindac shows influence on tumor-suppressor genes and on apoptosis markers. An immunostaining correlation indicates adenoma relapse in flat microadenomas in advance of macroscopic appearance. Low-dose sulindac treatment may develop into an additive permnanent therapy for colectomized familial adenomatous polyposis patients.

Adenomatous Polyposis Coli↗
PubMed1986

Effects of brain irradiation and chemotherapy on myelosuppression in small-cell lung cancer.

The effect of brain irradiation on myelosuppression was studied in patients with untreated small-cell lung cancer (SCLC) by comparing 24 patients who received brain irradiation for brain metastasis at presentation (irradiated patients) with 24 control patients who were selected by matching ages and non-CNS metastatic sites with those of irradiated patients. All patients were evaluated during the first three courses of chemotherapy. More irradiated patients than control patients had chemotherapy dose reductions from the starting dose level for the second (nine of 22 v two of 24; P = .03) and the third (nine of 18 v three of 20; P = .05) courses of chemotherapy. Overall, more irradiated patients had chemotherapy dose reductions than did control patients (11 of 22 v three of 24; P = .01). The difference was highly significant even after other variables were considered in a multivariate analysis (P less than .001). Myelosuppression was more severe in irradiated patients for WBCs (P = .01) and for platelets (P = .05). When the second course of chemotherapy was administered at the same dose levels as in the first course, irradiated patients had greater decreases in nadir counts after the second course compared with the first course than did control patients. Irradiated patients had a higher incidence of infectious complications than did control patients (14 of 24 v six of 24; P = .02), particularly after the second course of chemotherapy (seven of 22 v one of 24; P = .04). There were four treatment-related deaths due to sepsis in irradiated patients. Following brain irradiation given concurrently with intensive chemotherapy, close monitoring of myelosuppression and adjustments of chemotherapy doses are advised.

Adult↗
PubMed2002

Dose effect of guidewire position in intravascular brachytherapy.

It has been reported that the dose effects of metallic guidewires are significant in intravascular brachytherapy (IVBT) using a beta source. The purpose of this work is to investigate the dependence of these dose effects on guidewire position. The EGS4 Monte Carlo codes were used to perform the dose calculations for the 90Sr (NOVOSTE), 32P (Guidant) and 192Ir (BEST Ind.) sources with and without a guidewire in place. Guidewires were placed at various distances from the central axes of the sources. Due to the attenuation by the guidewires, a dose reduction of up to 70% behind a guidewire was observed for the beta sources, while the dose perturbation was found to be negligible for the gamma source. The dose reduction for the beta sources was found to be dependent on the guidewire location. For example, the dose reduction was 10% higher for a stainless steel guidewire located at 0.5 mm than that for the guidewire at 2 mm from the central axis of the source, The portion of the target volume affected (shadowed) dosimetrically by the guidewire was reduced when the guidewire was positioned farther away from the source. The shadow volume (in which the dose reduction occurs) can be reduced by up to 45% as the guidewire is moved away from the source axis from 0.5 mm to 2 mm. The dosimetric perturbations due to the presence of a metallic guidewire as well as their dependence on guidewire location should be considered in designing a new IVBT delivery device, in analysing the treatment efficacy, and/or in dose prescription for a beta source.

Algorithms↗
PubMed2003

Pharmacology of all-trans-retinoic acid in children with acute promyelocytic leukemia.

BACKGROUND: Due to severe side effects in virtually all children treated with a standard dose of 45 mg/m(2)/day all-trans-retinoic acid (ATRA) for acute promyelocytic leukemia (APL) the AML-BFM study group reduced the dosage to 25 mg/m(2)/day. For the lack of data on the use of ATRA at this dosage in children with APL, the study group further decided to evaluate the pharmacokinetics and metabolism of ATRA in children. PROCEDURE: Twenty-three pharmacokinetic and metabolic profiles of ATRA were studied in 14 children (aged 0.9-18.4 years) with APL. Eleven plasma samples were collected over a period of 8 hr and analyzed for ATRA and its metabolites by high-performance liquid chromatography. RESULTS: Peak plasma concentrations of ATRA were characterized by wide interpatient variability (range: 28.6-513.0 nM). Compared to adults the same metabolic pathways were observed in children. Even though peak plasma concentrations were in the lower range of those considered effective in vitro, ATRA side effects, notably neurotoxicity, still required dose reduction, treatment break, or drug withdrawal in eight patients. In this small number of patients, neurotoxicity could not be related to age or any specific level of ATRA or metabolites in the plasma. Plasma concentrations of vitamin A, however, were significantly higher in those patients, who developed signs of neurotoxicity (P = 0.03, Mann-Whitney Rank Sum test). CONCLUSIONS: Considering the low plasma concentrations and the persistence of toxicity in spite of dose reduction intermittent dosing schedules might be considered as an alternative to further dose reduction of ATRA in the treatment of APL especially in children, who might be at risk of ATRA-induced neurotoxicity.

Adolescent↗
PubMed2001

[Optimizing dosage in thoracic computerized tomography].

Radiation exposure in computed tomography (CT) by far exceeds radiation dose in chest radiography. Dose requirements in CT of the chest, however, are much smaller than for the abdomen because of low x-ray absorption in the lungs. This article describes scanner parameters that influence patient exposure and image quality. Suitable compromises will be explained that allow for dose reduction in chest CT without jeopardising image quality. Dose reduction in chest CT should be performed depending on the clinical indication and requires active reduction of mAs settings. For helical CT, a pitch of 1.5 to 2 should be employed. Dedicated low-dose techniques for screening of bronchogenic carcinoma are described. Dose reduction decreases image quality but the detrimental effects can be reduced by applying proper parameters for scanning and image reconstruction. Thus, images of the mediastinum should be reconstructed with a smoothing filter, while a higher resolution filter should be used for the lungs. In multislice CT, reconstruction of thicker axial or multiplanar sections retains spatial resolution but keeps image noise and thus dose requirements low. The effective, weighted CT dose index (CTDIw,eff) can serve as a rough estimate of the effective patient dose (E) in helical or multislice CT of the whole chest: for most scanners and age groups the conversion factors are 0.5 mSv/mGy for females and 0.4 mSv/mGy for males.

Artifacts↗
PubMed1997

Dose titration of nebulized budesonide in young children.

We compared the clinical effect of the glucocorticoid budesonide delivered from two nebulizers Aiolos and Pari LL in 38 children less than 4 years of age (mean age, 20.2 months) with chronic wheeze. The design was a controlled, single-blind, randomized, cross-over, dose titration study. After a 1-week run-in, patients were randomized to treatment with 1 mg budesonide b.i.d. for 2 weeks from either an Aiolos or a Pari LL nebulizer. This was followed by a gradual dose reduction period during which the budesonide dose was reduced at 2-week intervals until unacceptable asthma symptoms appeared or the placebo level was reached. The patient was then switched to budesonide 1 mg b.i.d. from the other nebulizer for 2 weeks, after which the dose was reduced at 2-week intervals as described for the first period. Patients who completed the study on placebo for 2 weeks without deterioration of their asthma were not included in the statistical analysis. During Period #1 the minimum effective dose of budesonide was 2 mg/day in 9 patients, 1 mg/day in 10 patients, and 0.5 mg/day in 13 patients. In Period #2 the corresponding figures were 14, 5, and 13 patients. Six patients were excluded after the first period because their asthma control did not deteriorate during dose reduction and when finishing on placebo for 2 weeks. For both nebulizers the reduction in budesonide dose was associated with a small increase in symptoms and use of rescue terbutaline. The mean dose of budesonide delivered to the patient by the Aiolos was twice as large as that delivered by the Pari LL: 26% vs. 13% of the nominal dose assessed by the filter method. Nevertheless, no statistically significant difference in clinical effect or mean minimal effective dose (1.1 mg for Aiolos and 1.2 mg for Pari LL) could be detected between the two nebulizers. No serious adverse events were observed. We conclude that the minimal effective dose of nebulized budesonide varies from 0.5 to 2.0 mg/day in young children with asthma. A higher drug delivery, as assessed by the filter method, does not necessarily result in better clinical control or lower minimal effective dose. Further studies are needed to assess whether this is due to insufficient sensitivity of the study design in detecting a difference in clinical effect, or whether measurements of drug delivery by the filter method do not reflect lung deposition or clinical effect in young children with wheezing.

Asthma↗
PubMed2004

The use of topotecan for relapsed ovarian cancer in accordance with the National Institute for Clinical Excellence Guidance 2001: the Nottingham experience.

AIMS: The topoisomerase-1 inhibitor, topotecan, is an established chemotherapy agent for the treatment of relapsed ovarian cancer after the failure of platinum-based chemotherapy, and is an established treatment choice at first relapse. In line with National Institute for Clinical Excellence (NICE) guidance, topotecan has been used at Nottingham City Hospital for the last 2 years. MATERIALS AND METHODS: A retrospective audit, over the period September 2001 to September 2002, was carried out to assess response rates and side-effects for patients with relapsed ovarian cancer who were treated with topotecan. Twenty-five patients received topotecan as a 30-min intravenous infusion for 5 consecutive days, every 21 days. The starting dose was either 1.5 mg/m2/day (n = 22) or 1.25 mg/m2/day (n = 3). Patient response was monitored by physical examination and serological CA125 tumour marker level. Radiological assessment was by computed tomography. RESULTS: Eighteen (72%) patients had their previous platinum-based treatment less than 6 months before topotecan therapy. Thirteen patients received topotecan therapy as second-line, seven as third-line and five as > or = fourth-line treatment. Twenty-two (88%) patients who received more than one cycle of chemotherapy were evaluable for response. A clinical benefit was observed in 11 (44%) patients (two [8%] partial response and nine [36%] stable disease). Seven patients achieving clinical benefit received topotecan as second-line treatment. Dose was reduced from 1.5 to 1.25 mg/m2/day in six patients after the first cycle of topotecan. Twelve (48%) patients had dose delay of at least 1 week. Grade 3/4 neutropenia, observed in nine (36%) patients, was the main dose-limiting toxicity. One patient died as a result of treatment. CONCLUSION: The Nottingham experience with topotecan in platinum-resistant ovarian cancer has been encouraging, even in such a heavily pre-treated patient population. There is a better chance of response if the patients receive topotecan at first relapse. The haematological toxicity is significant but manageable with dose reduction and dose delay.

Adult↗
PubMed2005

Phase II trial of capecitabine in recurrent squamous cell carcinoma of the cervix.

PURPOSE: To determine the efficacy and safety of capecitabine in women with inoperable, recurrent, or metastatic squamous cell cervical cancer. PATIENTS AND METHODS: In a phase II IRB approved trial, capecitabine was given at a dosage of 2000 mg/m2/day orally in a divided dose daily for 14 days followed by a 7-day rest period. A standard dose modification scheme was used with one allowed dose reduction or dose escalation. National Cancer Institute criteria for progression, response, and toxicity were utilized. Quality of life data were obtained using the Memorial Symptom Assessment Scale and Functional Assessment for Cancer Therapy, which included a subscale for cervical cancer. RESULTS: Twenty of 23 enrolled patients were evaluable for response. Stable disease was noted in 5 patients, with a median duration of response of 3.5 months (range, 3-6.5 months). No partial or complete responses were seen. Common grade 3 toxicities were fatigue (30.4%); abdominal pain, constipation, hand-foot syndrome, nausea, and vomiting (8.7% each); as well as dyspnea, headache, and coagulopathy (4.3% each). There were no grade 4 toxicities. All patients with previous exposure to infused 5-FU had evidence of progression. No statistically significant changes in quality of life were noted from baseline to post-cycle 2. CONCLUSION: Single-agent capecitabine in patients with recurrent cervical cancer resulted in no objective responses. Although capecitabine is a well-tolerated regimen, as a single agent, it offers minimal benefit in a poor-prognosis cervical cancer population.

Adult↗
PubMed2003

Phase I trial of docetaxel, carboplatin, and gemcitabine as first-line therapy for patients with high-risk epithelial tumors of müllerian origin.

OBJECTIVES: The aim of this study was to assess the feasibility of combining docetaxel, carboplatin, and gemcitabine (DoCaGem) as first-line treatment of ovarian and other müllerian origin tumors. METHODS: Four dose levels were planned for this phase I trial. Treatment consisted of carboplatin on day 1 only, docetaxel on days 1 and 8, and gemcitabine on days 1 and 8, every 21 days. RESULTS: Nineteen patients were enrolled, of whom 18 were evaluable for toxicity. The first 5 patients enrolled at dose level I (carboplatin AUC 5, 30 mg/m(2) docetaxel, 800 mg/m(2) gemcitabine) experienced no dose-limiting toxicity. At dose level II, 4/4 evaluable patients experienced significant bone marrow suppression that required dose reduction and/or dose delay. Further dose escalation was not attempted, and 9 additional patients were enrolled in dose level I. Of the 67 cycles administered on dose level I, day 8 treatment could not be administered due to bone marrow suppression in 16 cycles (24%), and prolongation of the cycle length from day 22 to day 29 was required in 13 cycles (19%). There were no episodes of febrile neutropenia in evaluable patients and no treatment-related deaths. Grade 3 nonhematologic toxicity (fatigue) occurred in 1 cycle. Response was determined in the 14 evaluable patients who tolerated 4 or more cycles of therapy, with 11 obtaining a complete clinical response and 3 obtaining a partial clinical response. CONCLUSIONS: The DoCaGem regimen is highly active, but myelosuppression at dose level I prevents full dose delivery. Other strategies to combine these three active agents are reasonable to explore.

Adult↗
PubMed2002

Role of supportive care in the treatment of NSCLC: supportive care for myelotoxicity.

Chemotherapy-associated myelosuppression is a major limitation of anticancer therapy in both local advanced and metastatic NSCLC. In the past, primary prophylactic use of hematopoietic growth factors was administered in these patients to reduce the incidence of febrile neutropenia, to avoid dose reduction and dose delay, and to improve patient quality of life. However, so far, for myeloid growth factors significance is missing that response to treatment can be improved in terms of better outcome. Therefore, the routine use of primary for secondary prophylactic CSF in patients with stage III or IV NSCLC is discouraged. This is due to the fact that there is no evidence that intensified chemotherapy schedules improve patients' prognosis. The application of CSF may be considered (but not given routinely) in patients with pre-existing neutropenia due to diseases or (extensive) prior chemotherapy, poor performance status, previous radiotherapy of areas with large amounts of bone marrow reserve or a history of recurrent febrile neutropenia while receiving earlier therapy. However, none of these indications has ever been proven in randomised clinical trial. In contrast, locally advanced NSCLC is a potentially curable disease. Future schedules may combine increased dose intensity of chemotherapy with sequential or simultaneous radiotherapy, where the primary or secondary use of myeloid growth factors may be justified. Chemotherapy-associated thrombopenia: So far, no thrombopoietic factors are available for clinical use.

Antineoplastic Agents↗
PubMed2003

[Chest examination protocol with a reduced dose using a multi-slice spiral CT].

PURPOSE: Comparison of multi-slice computed tomography (MSCT) for examination of the chest using two protocols differing in tube voltage (kV) and effective tube current (mAs), as to image quality, diagnostic quality and radiation dose. MATERIAL AND METHODS: Re-staging examinations of 20 patients with bronchial carcinoma on a MSCT (Somatom Volume Zoom, Siemens AG, Forchheim) with 140 kV/100 mAseff and again after an average interval of 4.5 months, a second examination using 120 kV/80 mAseff, employing identical detector width (4 x 2.5 mm), slice, pitch, increment, kernel and selecting the same use or non-use of contrast medium. Image quality, delineation of mediastinal and pulmonary anatomy and pathology, and frequency of artifacts were evaluated by two radiologists and the effective radiation doses were calculated. RESULTS: Subjective image quality was good to very good for both protocols, and no significant differences were found for visualizing anatomic and pathologic structures in mediastinum and lung. Only the region surrounded by the shoulder girdle showed significantly more artifacts with 120 kV/80 mAsff, but without loss of diagnostic quality. The effective doses were 8 mSv (women) and 6 mSv (men) for 140 kV/100 mAseff versus 4.3 mSv and 3.3 mSv for 120 kV/80 mAseff. CONCLUSIONS: In view of the equal diagnostic quality of both images, CT of the chest should be obtained with 120 kV and 80 mAseff rather than with 140 kV/100 mAseff, regardless of the slightly lower aesthetic quality of the former. This will keep the radiation dose as low as possible. Follow-up examinations should be obtained with even further dose reduction (low dose CT).

Aged↗
PubMed2006

Short communication: phase I clinical and gene modulatory evaluation of tamoxifen and IFN-alpha2b.

Preclinical studies had determined that tamoxifen and interferon-alpha2b (IFN-alpha2b) synergistically inhibited growth of both estrogen-receptor positive and negative murine tumor xenografts and had combined antiangiogenic effects and that tamoxifen potentiated IFN-stimulated gene (ISG) expression. A phase I trial in 26 patients was conducted using the combination to define tolerance and potentiation of ISG expression. IFN- alpha2b at a dose of 3 x 10(6) units/m(2) daily was given subcutaneously (s.c.), and tamoxifen was initiated as a loading dose of 150 mg/m(2) and then 60 mg/m(2) twice daily on day 8. At this initial dose, reduction of dose of IFN- alpha2b was required in 4 of 11 patients, primarily because of fatigue. Another group of patients was treated with an identical tamoxifen dose but with IFN-alpha2b reduced to 2 x 10(6)/m(2) U; this was better tolerated. As the projected serum tamoxifen level to reduplicate preclinical effects was 300 mg/m(2), dose escalation in a third cohort was undertaken; it had to be discontinued secondary to grade III or IV toxicity in 2 of 2 patients. Increases in products of transcriptionally regulated ISGs, beta (2)-microglobulin, neopterin, and ISG15 were assessed. All ISGs increased after IFN-alpha2b, but only ISG15 had a further significant rise after initiation of tamoxifen. Because at doses not limited by unacceptable toxicities, no marked potentiation of ISGs by tamoxifen could be identified, clinical evaluation of the combination was terminated.

Angiogenesis Inhibitors↗
PubMed1996

Phase II study of liposomal encapsulated daunorubicin in the treatment of AIDS-associated mucocutaneous Kaposi's sarcoma.

OBJECTIVE: To evaluate the efficacy and safety of liposomal encapsulated daunorubicin (DaunoXome) in the treatment of AIDS-associated mucocutaneous Kaposi's sarcoma. DESIGN: A Phase II, multicentre, European, non-comparative, open study to assess the use of DaunoXome in patients with no prior anthracycline chemotherapy for Kaposi's sarcoma. The response rate, time to disease progression, and the incidence and severity of adverse events were documented. SETTING: Hospital-based HIV units. PATIENTS: Thirty HIV-seropositive patients with mucocutaneous Kaposi's sarcoma were enrolled and treated. INTERVENTIONS: Treatment with DaunoXome at a dose of 40 mg/m2 intravenously once every 2 weeks. Treatment with antiretroviral agents and prophylaxis of opportunistic infections where indicated. RESULTS: Of the 30 evaluable patients, 22 patients (73%) achieved a partial response. Median time to treatment response was 30 days (range, 15-202). For patients with a partial response, median time to treatment failure was 153 days (range, 15-558). Patients received a median of 10 cycles (range, 1-44). Adverse events were minimal. The most common side effect was granulocytopenia in 16 patients (53%). CONCLUSION: DaunoXome is an effective and well-tolerated treatment for AIDS-associated mucocutaneous Kaposi's sarcoma and can be administered for prolonged periods. The myelosuppression can be managed by dose reductions and dose not preclude the concurrent use of antiretroviral therapies.

Acquired Immunodeficiency Syndrome↗
PubMed2005

Safe use of pegylated interferon/ribavirin in hepatitis C virus cirrhotic patients with hypersplenism after partial splenic embolization.

BACKGROUND AND AIMS: Partial splenic embolization (PSE) is a non-surgical alternative for the treatment of hypersplenism. Thrombocytopenia precludes the use of pegylated interferon (peg-IFN) and ribavirin in cirrhotic patients with hepatitis C virus (HCV). We aimed to evaluate the role of PSE as a procedure allowing combined HCV therapy in this setting. METHODS: A retrospective analysis of the safety and rate of sustained virological response (SVR) after a full-dose course of peg-IFN plus ribavirin in eight HCV cirrhotic patients with severe hypersplenism undergoing PSE at a tertiary centre in Madrid, Spain, from May 2002 to August 2004. RESULTS: Six patients (75%) were in Child-Pugh class B (median score 7). PSE significantly improved the mean platelet (P = 0.012), leucocyte (P = 0.017) and haemoglobin (P = 0.035) levels, and prothrombin activity (P = 0.012). After a mean of 20 weeks after PSE all patients started weight-adjusted ribavirin plus peg-IFN-alpha2b (n = 6) or 180 microg/week of peg-IFN-alpha2a (n = 2). Six subjects (75%) completed therapy with no peg-IFN dose reductions; the dose of ribavirin was reduced in two patients reaching haemoglobin levels of less than 10 g/dl (one also received erythropoietin and granulocyte colony-stimulating factor because of neutrophil counts < 300 cells/microl). Three patients (38%) achieved SVR. Portal vein thrombosis was observed in 50% of patients, but did not preclude antiviral therapy. The pathogenic mechanism was multifactorial. It was successfully managed with anticoagulant therapy in two cases. CONCLUSIONS: PSE allowed the safe use of peg-IFN plus ribavirin in HCV cirrhotic patients with severe cytopenias who otherwise would never have been treated. The rate of SVR was 38%.

Antiviral Agents↗
PubMed2004

Measurements of occupational exposure for a technologist performing 18F FDG PET scans.

Radiation doses to one PET technologist performing 100 18F FDG (18F fluorodeoxyglucose) imaging procedures were measured in a clinical setting using two types of thermoluminescent dosimeter (TLD) badges, one finger-ring TLD and one electronic pocket dosimeter (EPD). 18F FDG was handled either with unshielded or with viewing window tungsten shielded syringes. The resulting doses using unshielded syringes were 13.8 +/- 0.8 microSv/370 MBq and 14.3 +/- 0.4 microSv/370 MBq, measured with TLD 100 and with TLD 700H/600H, respectively. For the same series of measurements, the doses obtained using shielded syringes were 10.7 +/- 0.4 microSv/370 MBq and 7.2 +/- 2.1 microSv/370 MBq with TLD700H/600H and with EPD, respectively. The dose to the right hand from shielded syringes was 69.3 +/- 5.5 microSv/370 MBq. All these values are within the ICRP recommended dose limits. Extrapolated to 725 examinations per year, the resulting effective dose measured with TLD would be 10 mSv with unshielded and 7.5 mSv with shielded syringes, respectively (25% dose reduction). The doses measured by TLD were consistently higher than those measured by EPD, suggesting that EPD measurements might underestimate occupational doses.

Adult↗
PubMed1991

Should opiate addicts be involved in controlling their own detoxification? A comparison of fixed versus negotiable schedules.

This study compares the responses of opiate addicts at a London drug treatment centre to two outpatient methadone-based detoxification programmes. These involved either a fixed (non-negotiable) dose reduction schedule or a flexible, negotiable withdrawal schedule. In the negotiable condition, subjects were less likely to complete the detoxification programme and the mean reduction in dose achieved by the subjects in the negotiable condition was less than that in the fixed group. There was no difference between groups in programme retention at 6 weeks though subjects who remained in treatment in the negotiable group tended to extend their detoxification period beyond this point. The overall response of subjects in both groups was unsatisfactory. Only 13% of the subjects initially allocated to detoxification or 28% of those who actually started detoxification completed treatment; urine screening showed that heroin abuse was a continuing problem during treatment. The implications of these results for detoxification and drug treatment services are discussed.

Adult↗
PubMedDate not supplied

Comparison of computed radiography and conventional film-screen radiography of the equine stifle.

Major advantages of computed radiography are the potential reduction of dose and the possibility of postprocessing. In our study, we compared conventional radiographs to digital radiographs of the equine stifle by subjective evaluation of diagnostic quality when using a decreasing photon flux (mAs). Twelve equine stifle joints from horses of different weight and size were examined. Conventional and digital radiographs were performed identically in a caudocranial projection with the tube angled 15 degrees. A series of four radiographs was performed in each technique with an increasing photon flux starting with 2.5 mAs and going up to 5, 10, and 20 mAs. All radiographs were evaluated subjectively in a blinded fashion by seven readers in terms of contrast, bone structure, and diagnostic value and were graded using a 1-5 scale. Results from conventional and digitized radiographs were compared, and differences between the individual observers were analyzed statistically. Contrast, bone structure, and diagnostic value from digital images were rated significantly better than from conventional images (p < .001). For both techniques, a decrease in ranking was found with a decrease of photon flux. There was only slight interobserver variability. A dose reduction up to a factor of 4 compared to a 100 speed film-screen system seems to be possible without loss of information. Weight and size of the horse are not major influences.

Animals↗
PubMed2006

Phase I trial of bortezomib in combination with docetaxel in patients with advanced solid tumors.

PURPOSE: Bortezomib (PS-341), a first-in-class proteasome inhibitor, is metabolized by deboronation involving cytochrome P4503A (CYP3A), which also metabolizes docetaxel. Preclinical studies have shown synergy between bortezomib and taxanes. We conducted a phase I study combining bortezomib and docetaxel in refractory solid tumor patients. EXPERIMENTAL DESIGN: Patients received escalating doses of weekly docetaxel (days 1 and 8) and twice weekly bortezomib (days 2, 5, 9, and 12) in 3-week cycles. Two subjects were enrolled at each dose level, with cohort expansion to six for dose-limiting toxicity (DLT). Dose levels 1, 2, and 3 consisted of docetaxel/bortezomib 25/0.8, 25/1.0, and 30/1.0 mg/m(2), respectively. CYP3A activity and docetaxel pharmacokinetic studies were conducted, and proteasome inhibition was assessed. RESULTS: Fourteen patients received a total of 34 cycles of treatment. Dose level 2 was expanded for DLT that occurred in two of six patients consisting of febrile neutropenia in one patient and grade 3 thrombocytopenia in one patient. One patient received two cycles at dose level 3 with dose reduction to dose level 2, where grade 3 thrombocytopenia occurred at cycle 3. Both episodes of grade 3 thrombocytopenia were transient (<7 days). Dose level 1 was then expanded to six patients where no DLTs occurred. CYP3A activity and docetaxel clearance did not change between weeks 1 and 5. CONCLUSIONS: The maximum tolerated dose was docetaxel 25 mg/m(2) (days 1 and 8) with bortezomib 0.8 mg/m(2) (days 2, 5, 9, and 12) given every 21 days. Bortezomib treatment did not alter CYP3A activity and docetaxel clearance.

Adult↗