SEARCH · PubMed Health

Results for “Targeted dosing”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

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

At least 199 records · Page 11Linked to original sources

PubMed1995

Comparison of the effects of sub-hypnotic concentrations of propofol and halothane on the acute ventilatory response to hypoxia.

To compare the effects of sub-anaesthetic concentrations of propofol and halothane on the respiratory control system, we have studied the acute ventilatory response to isocapnic hypoxia (AHVR) in 12 adults with and without three different concentrations of propofol and halothane. Target doses for propofol were 0, 0.05, 0.1 and 0.2 of the effective plasma concentration (EC50 = 8.1 micrograms ml-1). Target doses for halothane were 0, 0.05, 0.1 and 0.2 minimum alveolar concentration (MAC = 0.77%). The doses achieved experimentally were 0.01, 0.06, 0.13 and 0.26 of the EC50 for propofol and 0, 0.05, 0.11 and 0.20 MAC for halothane. During the experiment subjects breathed via a mouthpiece from an end-tidal forcing system. End-tidal PO2 (PE'O2) was held at 13.3 kPa for 5 min, and then at 6.7 kPa for 5 min. End-tidal PCO2 (PE'CO2) was held constant at 0.13-0.27 kPa greater than the subject's natural level throughout. The mean values for AHVR with propofol were: 12.8 (SEM 2.4) litre min-1 (0.01 EC50), 10.0 (1.9) litre min-1 (0.06 EC50), 9.8 (2.3) litre min-1 (0.13 EC50) and 4.9 (1.2) litre min-1 (0.26 EC50). The values for AHVR with halothane were: 11.9 (2.4) litre min-1 (0 MAC), 7.8 (1.6) litre min-1 (0.05 MAC), 5.9 (1.2) litre min-1 (0.11 MAC) and 3.2 (1.6) litre min-1 (0.2 MAC). The decline in AHVR with increasing dose for both drugs was statistically significant (ANOVA, P < 0.001); there was no significant difference between the two drugs with respect to this decline. Normoxic ventilation with propofol declined from 13.2 (1.6) litre min-1 (0.01 EC50) to 8.3 (0.9 litre min-1 (0.26 EC50), and with halothane declined from 13.5 (2.0) litre min-1 (0 MAC) to 11.8 (1.6) litre min-1 (0.2 MAC). This was significant for both drugs (ANOVA, P < 0.001).

Adolescent↗

PubMed2006

Influence of organ at risk definition on rectal dose-volume histograms in patients with prostate cancer undergoing external-beam radiotherapy.

PURPOSE: To evaluate rectal dose-volume relations during three-dimensional conformal radiotherapy of patients with prostate cancer by means of different rectal volume contours. PATIENTS AND METHODS: 55 patients with prostate cancer underwent three-dimensional conformal external-beam radiotherapy. Rectal dose-volume histograms were calculated for four separately contoured rectal volumes in all patients resulting in four groups. In group 1 the outer rectal wall was contoured two CT slices above and below the planning target volume. The rectal contour of group 2 was drawn from the anal verge up to the sigmoid. Furthermore, the posterior half of the rectum was contoured for both volumes mentioned above (groups 1a and 2a). Statistical analysis was then performed using nonparametric Wilcoxon tests. RESULTS: The mean target dose was 72.9 Gy (standard deviation [SD] +/- 2.1 Gy). The minimum target dose was 70.2 Gy. Mean rectum dose (+/- SD) over all patients was 50.7 Gy (+/- 4.6 Gy), 45.2 Gy (+/- 5.4 Gy), 43.2 Gy (+/- 4.2 Gy), and 38.7 Gy (+/- 5.5 Gy) for group 1, 2, 1a, and 2a, respectively. The corresponding volumes receiving > or = 70 Gy for groups 1 and 2 were 14.0% (+/- 5.3%) and 11.9% (+/- 4.5%). These differences were statistically significant. Comparison of minimum and mean rectal dose also revealed a statistically significant difference toward higher doses in groups 1 and 1a (p < 0.001). Maximum rectal doses for groups 1 and 2 as well as for groups 1a and 2a revealed no statistically significant difference (p = 1.0). CONCLUSION: Data from the literature on normal-tissue complication probability (rectal bleeding) refer to different rectal contours. When applying dose restrictions to the rectum, contouring becomes a significant factor that determines the risk of rectal toxicity. The results of this study show that different ways of rectal contouring significantly influence doses to the rectum. The influence of organ at risk contouring should be considered thoroughly in conformal radiotherapy of prostate cancer patients, especially in dose escalation studies. It is recommended to calculate the doses for absolute rectal volumes and correlate these data with toxicity in order to be able to achieve comparable results among different institutions.

Data Interpretation, Statistical↗

PubMed1993

Targeting chemosensitizing doses of toremifene based on protein binding.

Toremifene is currently being evaluated as a chemosensitizing agent in doxorubicin-resistant patients. Although concentrations of > 2 microM reverse resistance in vitro, target concentrations required to reverse multidrug resistance (MDR) in vivo may be highly influenced by variables such as protein binding in serum. We examined the effects of high serum concentrations on the cellular accumulation of toremifene in an MDR MDA-MB-A-1 human breast-cancer cell line. We then examined the cellular accumulation of doxorubicin at various toremifene concentrations in 5% - 100% serum. We also measured the concentrations of toremifene and its major metabolites in plasma specimens obtained from two patients receiving 360 mg/day for 5 days in a phase I study. Our results show that (1) high serum concentrations decrease toremifene accumulation, (2) toremifene concentrations of < or = 2.5 microM enhance doxorubicin accumulation, and (3) patients achieve plasma toremifene concentrations of 10-15 microM following doses of 360 mg/day x 5 days. Our findings suggest that in vivo toremifene concentrations well above those used to reverse resistance in vitro are required to overcome the effect of high serum-protein binding.

Blood Proteins↗

PubMed1997

Design and analysis of an immobilization and repositioning system for treatment of neck malignancies.

Recent applications of three-dimensional treatment planning using non-coplanar treatment angles have demonstrated the potential for improved target dose homogeneity as well as normal tissue sparing for tissues in the neck, notably the parotid gland. Implementation of these highly targeted treatments requires a reliable method for accurate daily reproduction of the treatment position, as patient setup error could lead to significant decreases in target dose and normal tissue sparing. Additionally, the constrained geometry of this anatomic site requires the freedom to deliver treatments from any arbitrary angle in order to maximize the expected benefit. In order to permit accurate setup while maintaining access from most angles, a hybrid immobilization system has been developed, consisting of a custom thermoplastic mask with attachment to a foam cradle shaped to the back of the patient. To evaluate the accuracy of this system, setup errors were measured in 20 patients treated while immobilized with the positioning aide. Two orthogonal film sets consisting of anterior and lateral projections, one set taken at the beginning of treatment and a second 4-5 weeks into therapy, were compared to baseline simulator films or digitally reconstructed radiographs. The average setup deviation in any direction ranged from 0.8 to 1.4 mm and the largest single setup error observed was 4.5 mm. For the film sets taken late in treatment only 3 of the 20 patients required setup adjustment followed by repeat filming to obtain an acceptable film pair. This system has been implemented for routine clinical use since March 1995.

Equipment Design↗

PubMed1999

[The role of radiotherapy in the treatment of malignant meningiomas].

PURPOSE: Most malignant meningiomas will recur following surgical resection only. The role of irradiation and radiation dose levels is poorly defined. This study reviews a single institution experience using both, conventional and high doses > or = 60 Gy/CGE radiation regimen. PATIENTS AND METHODS: Between 1974 and 1995 16 patients with histologically proven malignant meningioma underwent radiation therapy (RT). Age at diagnosis ranged between 6 and 79 years (median: 49 years). Three patients reported previous irradiation to the head at least 14 years prior to diagnosis. Ten patients were treated for primary, and 6 patients for recurrent disease. Six patients underwent gross total and 10 patients subtotal resection (Table 1). RT was delivered using conventional, megavoltage photons or combined 160 MeV proton and photon irradiation. Except 1 patient, who died during RT, the radiation doses ranged between 40 and 70 Gy/CGE (= Cobalt Gray Equivalent) (median: 58 Gy/CGE, Table 2). RESULTS: With median observation time of 59 months (range: 10 to 155 months), actuarial local control rates at 5 and 8 years were 52% and 17%, respectively. Target doses > or = Gy/CGE resulted in significantly improved tumor control (100%) compared to < 60 Gy/CGE (17%) (p = 0.0006, Table 3 and Figure 1). Improved local control translated also in increased overall survival: 87% (> or = 60 Gy/CGE) versus 15% (< 60 Gy/CGE) at 5 years (p = 0.025, Figure 2). At time of analysis, 6/16 patients (38%) were alive. Two patients developed symptomatic brain damage at doses of 59.3 and 72 Gy/CGE. CONCLUSION: Conformal, radiation therapy with target doses > or = 60 Gy/CGE, in this study by use of combined proton and photon irradiation, can significantly improve chances of long-term local control and survival for patients diagnosed with these challenging tumors.

Adolescent↗

PubMed1998

Single-fraction stereotactic radiotherapy: a dose-response analysis of arteriovenous malformation obliteration.

PURPOSE: Stereotactic radiotherapy delivered in a high-dose single fraction is an effective technique to obliterate intracranial arteriovenous malformations (AVM). To attempt to analyze the relationships between dose, volume, and obliteration rates, we studied a group of patients treated using single-isocenter treatment plans. METHODS AND MATERIALS: From May 1986 to December 1989, 100 consecutive patients with angiographically proven AVM had stereotactic radiotherapy delivered as a high-dose single fraction using a single-isocenter technique. Distribution according to Spetzler-Martin grade was as follows: 79 grade 1-3, three grade 4, 0 grade 5, and 18 grade 6. The target volume was spheroid in 74 cases, ellipsoid in 11, and large and irregular in 15. The targeted volume of the nidus was estimated using two-dimensional stereotactic angiographic data and, calculated as an ovoid-shaped lesion, was 1900 +/- 230 mm3 (median 968 mm3; range 62-11, 250 mm3). The mean minimum target dose (Dmin) was 19 +/- 0.6 Gy (median 20 Gy; range: 3-31.5). The mean volume within the isodose which corresponded to the minimum target dose was 2500 +/- 300 mm3 (median 1200 mm3; range 75-14 900 mm3). The mean maximum dose (Dmax) was 34.5 +/- 0.5 Gy (median 35 Gy; range 15-45). The mean angiographic follow-up was 42 +/- 2.3 months (median 37.5; range 7-117). RESULTS: The absolute obliteration rate was 51%. The 5-year actuarial obliteration rate was 62.5 +/- 7%. After univariate analysis, AVM obliteration was influenced by previous surgery (p = 0.0007), Dmin by steps of 5 Gy (p = 0.005), targeted volume of the nidus (< or = 968 mm3 vs. >968 mm3; p = 0.015), and grade according to Spetzler-Martin (grade 1-3 vs. grade 4-6; p = 0.011). After multivariate analysis, the independent factors influencing AVM obliteration were the Dmin [relative risk (RR) 1.9; 95% confidence interval (CI) 1.4-2.5; p < 0.0001] and grade distribution according to Spetzler-Martin (RR 1.4; 95% CI 1.1-1.7; p = 0.010). Delayed complications were observed in eight patients. The 5-year actuarial rate of delayed complications was 7.4%. CONCLUSION: After stereotactic radiotherapy delivered in a single high dose using a single-isocenter technique, the success rate for complete obliteration is independently correlated to Dmin but does not seem to be influenced by Dmax and the targeted volume of the nidus.

Adolescent↗

PubMed2001

Optimal dosing with risperidone: updated recommendations.

BACKGROUND: Drug dosages utilized during controlled clinical trials are not always optimal for patients encountered in day-to-day practice. The original trials of risperidone, a novel antipsychotic, suggested that an initial target dose of 6 mg/day was appropriate, but these trials were necessarily conducted among patients who were chronically impaired, hospitalized, and often partly drug resistant. DATA SOURCES: Relevant data relating to the dosage of risperidone identified through an online (MEDLINE) search using the keywords risperidone, schizophrenia, schizoaffective disorder dementia, bipolar disorder, and dose were supplemented by a review of international and U.S. Congress abstracts in which the dose of risperidone was specifically described. CONCLUSION: On the basis of naturalistic studies, clinical audit, phase 4 trials, positron emission tomography data, and 5 years of clinical experience, the currently recommended target dose of risperidone is 4 mg/day for most patients, with less-rapid titration than previously recommended. Moreover, a lower dose than this and slower titration may be appropriate for elderly patients, young patients, and first-episode patients.

Adolescent↗

PubMed2003

[Utility of perindopril in mild-moderate heart failure in daily clinical practice. METRICA trial].

INTRODUCTION AND OBJECTIVES: Angiotensin II converting enzyme inhibitors have an unquestionable utility in heart failure, although these drugs are underused and rarely used at the recommended doses in the clinical practice. The objective of this investigation was to study the simplicity of perindopril use in the treatment of heart failure and to confirm its clinical and radiological efficacy. MATERIAL AND METHODS: Perindopril was orally administered at 2-4 mg/day doses to 180 patients with heart failure and functional class I-III who were not being treated with angiotensin II converting enzyme inhibitors. The percentage of patients who reached the target dose (4 mg/day) was studied as well as clinical (functional class of the NYHA) and radiological efficacy of this treatment in these patients. RESULTS: The target dose (4 mg/day) in heart failure was reached in 87.5% patients, with a rate of adverse effects of 18.9%. Eighty-nine percent of patients in the functional class III and 38.3% of patients in class II had clinical improvement. The cardio-thoracic index decreased from 0.57 to 0.54 (p < 0.05). A minimal irrelevant change was observed in the analytical levels of creatinine and potassium. Only three patients (1.7%) abandoned the trial early in its course. CONCLUSIONS: An efficient dose for heart failure is simply and safely obtained with perindopril, with a significant improvement in the NYHA functional class and in the radiological cardio-thoracic index.

Aged↗

PubMed2005

Under-utilization of evidence-based drug treatment in patients with heart failure is only partially explained by dissimilarity to patients enrolled in landmark trials: a report from the Euro Heart Survey on Heart Failure.

AIMS: Surveys on heart failure management suggest under-utilization of life-saving evidence-based treatment. Evidence-based medicine and clinical guidelines are based on the results of randomized controlled trials. Therefore, we investigated how patients who fulfilled the enrolment criteria of randomized trials were treated in real life. METHODS AND RESULTS: We selected three large placebo-controlled trials of patients with chronic heart failure, in which ACE-inhibitors (ACE-Is), beta-blockers, and spironolactone proved to be safe and effective. The major enrolment criteria of trials were identified and applied to patients enrolled in the Euro Heart Survey on Heart Failure to identify the proportion of patients eligible for treatment and also treated appropriately. Of the 10 701 patients who were enrolled in the Euro Heart Survey on Heart Failure, only a small percentage (13%) would have qualified for participation in at least one of the selected trials. Patients who fulfilled enrolment criteria of the identified trials were more likely to be treated with ACE-Is (83% of SOLVD-eligible patients), beta-blockers (54% of MERIT-HF-eligible patients), and aldosterone antagonists (43% of RALES-eligible patients) than trial-ineligible patients. Almost half of SOLVD-eligible patients who were treated with ACE-Is received the target dose as recommended in the guidelines, but only <10% of MERIT-HF eligible patients who were treated with beta-blockers received the target dose. CONCLUSION: ACE-Is are widely utilized but given in lower doses than proven effective in clinical trials. beta-Blockers are underused and given in lower doses to patients who fulfil the enrolment criteria of relevant landmark trials.

Adrenergic beta-Antagonists↗

PubMed2004

Limited long term effects of a management programme for heart failure.

OBJECTIVE: To evaluate the effects of a nurse based outpatient management programme for elderly patients discharged with heart failure from a university hospital. DESIGN: Patients with heart failure (New York Heart Association class II-IV) and left ventricular systolic dysfunction aged 60 years or more were randomly assigned to follow up within the management programme or to conventional follow up, usually in primary care. Of the 208 participants, 58% were men, mean age was 75 years, and mean ejection fraction 34%. All patients were scheduled for three observational study visits at six month intervals. The primary end point was quality of life (QoL) and secondary end points were hospitalisation and mortality. RESULTS: More patients achieved target doses of angiotensin converting enzyme (ACE) inhibitors in the intervention group than in the control group (82% v 69%, 88% v 69%, and 88% v 74% of recommended target doses at 6, 12, and 18 months of follow up, respectively, p < 0.05 for all). Patients with initial low QoL had a poor prognosis. After a mean 1122 days of follow up, 82% of all patients had been readmitted. There were on average 4.7 readmissions per patient and 66% were due to non-cardiac diagnoses. There were no differences in QoL or health care consumption between the two study groups during follow up. CONCLUSION: A nurse based management programme is more effective than follow up in primary care in optimising medication for elderly patients with heart failure. However, such a programme does not seem to have a favourable influence on QoL or readmission rate during long term follow up.

Aged↗

PubMed1988

The induction of chromosome aberrations during the course of radiation therapy for morbus Hodgkin.

In a patient with Morbus Hodgkin, structural aberrations of the chromosome type in peripheral lymphocytes were analyzed during radiation therapy (accumulated target dose 44.6 Gy: 22 fractions of 1.8 Gy each and 2 fractions of 2.5 Gy each at the end of the therapy). The blood was sampled about 5 min after a fraction and/or 24, 48, or 72 h thereafter. The frequency of dicentric chromosomes:acentric fragments:centric ring chromosomes is 37:14:1 throughout the therapy. Independent of the time of blood sampling after a fraction, the distributions of dicentrics and acentrics are overdisperse and represent negative binomial distributions. The yields from these aberrations, as determined during the course of radiotherapy, are best fitted to a linear-quadratic function with a negative quadratic term. The two dose-effect curves (blood sampling about 5 min and 24 to 72 h after a fraction) of dicentrics and acentrics do not differ significantly. Up to an accumulated target dose of about 20 Gy the percentages of cells with chromosome aberrations increase to about 48 to 65% and, at this level, remain constant until the end of therapy.

Adult↗

PubMed2002

A pilot study of thalidomide in patients with progressive metastatic renal cell carcinoma.

BACKGROUND: The highly vascular nature of renal cell carcinoma (RCC) suggests that angiogenesis inhibition may be therapeutic for patients with this disease. Thalidomide inhibits basic fibroblast growth factor and vascular endothelial growth factor (VEGF)-induced angiogenesis. METHODS: In a pilot study, we evaluated the safety and efficacy of escalating doses of thalidomide in patients with progressive metastatic RCC (mRCC), measurable disease, and good organ function. Patients received oral thalidomide starting at 200 mg per day and increasing by 100-200 mg per day weekly until a target dose of 1200 mg per day was reached. Study endpoints were objective tumor response and toxicity. RESULTS: Of the 20 patients enrolled, 19 were evaluable for response. Eighteen achieved the target dose. The most common, but reversible, toxicities were constipation, somnolence, and fatigue. Peripheral neuropathy was seen after prolonged therapy, necessitating dose reduction. Two patients achieved a partial response and nine had stable disease for a median of 14 months (range, 3-17 months). Median time to progression was 4.7 months (range, 0.7-31.3 months). Fifteen patients died (median survival, 18.1 months; 95% lower confidence bound 10.7). Survival was significantly longer in patients with higher hemoglobin level and longer time from first metastasis to start of thalidomide, but significantly shorter in patients with multiple organ involvement and previous treatments. CONCLUSIONS: Thalidomide at this dose is associated with manageable acute toxicities but long-term dose-limiting neuropathy. Objective responses are rare in patients with mRCC and are characterized by delay in achieving maximum tumor reduction. Prolonged stable disease is seen in some patients, but the benefit of thalidomide, as well as other angiogenesis inhibitors, in that setting needs to be studied in controlled, randomized trials.

Administration, Oral↗

PubMedDate not supplied

An algorithm for generation of implant plans for high-dose-rate irradiators.

An algorithm is described for generating a treatment plan with minimal input from the user for a remote high-dose-rate afterloading irradiator. The algorithm generates a plan after locating all catheters involved and an area of interest on each catheter, and two additional numbers are specified: a radial distance and a target dose. The treatment volume becomes the locus of all points that are within the specified radial distance from any point within the area of interest on any catheter (except for the end points). For a single catheter, the volume may be alternately outlined on an x-ray film of the implant. The routine uses a linear programming formulism to compute which dwell positions are to be used, as well as the dwell time at each position, to irradiate the treatment volume to the target dose while minimizing the total volume integrated dose to the patient.

Algorithms↗

PubMed1998

[First results of radioiodine therapy of multifocal and disseminated thyroid gland autonomy and use of a TcTUs-adapted dose concept].

AIM: The presented study examines prospectively the efficiency of a dose concept for radioiodine therapy (RIT) adapted to the pretherapeutic 99mTc-pertechnetate thyroid uptake under suppression (TcTUs) in patients with multifocal (MFA) and disseminated (DISA) autonomy. This concept considers the total thyroid as target volume and uses target doses from 150 Gy to 300 Gy according to the TcTUs, which is as a measure for the "autonomous volume" of the thyroid. METHODS: The data of 75 patients (54 female, 21 male; age 71 +/- 9 years) with MFA of DISA were evaluated. RIT was performed on patients presenting with normal values for free triiodothyronine and thyroxine and endogenous suppression of the basal thyrotropin (TSH). The following target dose were used for a TcTUs of 1.5-2.5% 150 Gy, for 2.51-3.5% 200 Gy, for 3.51-4.5% 250 Gy, and for > 4.5% 300 Gy. The radiation dose to be administered was calculated using a modified Marinelli formula. The therapy was considered as successful. When the basal TSH was above 0.5 mU/l and autonomous areas had disappeared in thyroid scintigraphy or the TcTU was below 1.5%, respectively. The average follow-up period was 8 +/- 4 months. RESULTS: The success rates average to 92%. Only in one case a subsequent subclinical hypothyroidism and in a further case an immunogenic hyperthyroidism occurred. CONCLUSION: The presented data indicate that even patients with a marked autonomy (TcTUs > 3.5%) can thus expected to be cured by of a one time therapy with success rate of over 90% using the presented dose concept. The rate of early hypothyroidism can altogether be estimated as very low.

Aged↗

PubMed1998

Measured lung dose correction factors for 50 MV photons.

Some clinically relevant measurements of lung tissue/water equivalent interfaces have been performed for a 50 MV therapeutic x-ray beam. The purpose was to investigate the severity of dose perturbation effects in lung tissue and adjacent tissues using an energy well above the common clinical practice in thoracic irradiations. The phantoms were constructed of solid water, PMMA and white polystyrene as soft tissue (water) equivalents, and cork was used as the lung tissue equivalent. Measurements were performed using radiographic film and a cylindrical ionization chamber. The results show that the degradation of the 20/80% beam penumbra in the lung region is severe, up to 2.5 times the penumbra in water for a 10 cm thick lung with a density of 0.30 x 10(3) kg m(-3). The lack of electronic equilibrium in the low-density region can cause underdosage at the lung/tumour interface of up to 30% of maximum target dose, and the build-up depth to 95% of target dose in unit density tissue behind the lung may be as large as 22 mm. It is also shown that these figures strongly depend on patient anatomy and beam size and why a careful calculation of the individual dose distribution is needed for optimal choice of photon beam energy in thoracic treatments.

Biophysical Phenomena↗

PubMed1999

Risk assessment of radiation-induced malignancies based on whole-body equivalent dose estimates for IMRT treatment in the head and neck region.

BACKGROUND AND PURPOSE: Intensity modulated radiation therapy (IMRT) has been introduced in our department for treatment of the head and neck region with the intention of reducing complications without compromising treatment outcome. However, these new treatment modalities inevitably require a substantial increase in monitor units per target dose yielding an increased risk of secondary malignancies induced by the treatment. This study aims at assessing the increased risk by means of in vivo measurements of the whole-body equivalent dose of both the conventional and the IMRT treatment techniques for head and neck lesions. MATERIAL AND METHODS: A conventional technique using parallel opposed, wedged treatment fields has been compared with a slice-by-slice arc rotation technique for IMRT. Both techniques were used to treat head and neck lesions with a 6-MV photon beam. Thermoluminescent badges and neutron bubble detectors designed for personnel monitoring have been applied to obtain the estimated whole-body equivalent dose on three patients for each treatment technique. The nominal probability coefficient for a lifetime risk of excess fatal cancer, recommended by the ICRP 60 has been used for risk estimates based on the estimated dose values. RESULTS: An estimated whole-body equivalent dose per monitor unit equal to 1.2 x 10(-2) mSv/MU and 1.6 x 10(-2) mSv/MU have been obtained with the conventional and IMRT technique, respectively. Applying the average amount of MU necessary to realize a 70 Gy target dose the estimated whole-body equivalent dose for both treatment techniques becomes 242 mSv (conventional) and 1969 mSv (IMRT), yielding an increase in the risk for secondary malignancies with a factor 8. CONCLUSIONS: Historically the risk of secondary malignancies has been accepted to take advantage of the possible benefits of improved local control and treatment outcome. However, the introduction of new and sophisticated treatment techniques will also increase the risk of radiation induced malignancies. Therefore, these risk estimates become important to assess whether the benefits of the treatment technique outweigh the possible risks.

Dose Fractionation, Radiation↗

PubMed1995

Hemoglobin adducts for in vivo dose monitoring and cancer risk estimation.

For the estimation of cancer risks from environmental chemicals, knowledge of the target dose is essential, dose being defined as the time integral of concentration in target tissues. In vivo doses from chronic or intermittent exposures are best determined from established steady-state levels of macromolecule adducts of reactive compounds or intermediates. For dose monitoring, hemoglobin (Hb) is preferred to DNA for several reasons: accessibility in large amounts, availability of methods for chemical identification, and well-determined life span due to absence of repair. For these reasons, and because of the proportionality of rates of DNA and Hb adduct formation, Hb adduct levels give better information on cumulative DNA adduct levels than do direct measurement of DNA adducts. The scientific background of Hb adduct measurement, target dose determination, and risk estimation based on the relative genotoxic potency, with gamma-radiation as reference standard, is reviewed and exemplified. The sensitivity of the method for Hb adduct measurement permits determination of exposures where the associated annual cancer risk is less than 1 per million. Besides application for studies of metabolism by determination of in vivo doses in exposed animals and humans, as a basis for risk estimation, Hb adduct measurement is used for hygienic surveillance of occupational exposures. Determination of Hb adducts by mass-spectrometric techniques gives a tool for identification of reactive metabolites, not only in individuals with known exposure, but also for characterization of adducts to Hb from compounds acting as mutagens (initiators) in the background carcinogenesis. This is the large fraction of the total number of cancer cases that occur among individuals without known exposure.

Carcinogens↗

PubMed1997

Behavioral, situational, and temporal effects of treatment of ADHD with methylphenidate.

OBJECTIVE: To determine the behavioral, situational, and temporal effects of 4 months of methylphenidate (MPH) treatment for attention-deficit hyperactivity disorder (ADHD). METHOD: Ninety-one children with ADHD were randomly assigned to receive either MPH (titrated to a target dose of 0.7 mg/kg twice a day) or a placebo. Treatment effects were investigated with measures sensitive to various behaviors (core and associated symptoms), situations (home and school), time periods (morning and afternoon, after reaching the target dose, and after 4 months of treatment), and side effects. RESULTS: MPH treatment improved symptoms of ADHD and oppositional behavior at school, both in the morning and afternoon, but not at home. Side effects (increase in physiological and effective symptoms, lack of weight gain) were significantly more frequent with MPH than with placebo treatment. Benefit was evident after titration, but the onset of some side effects was delayed. Side effects were reported by parents but not by teachers. CONCLUSIONS: Positive effects of MPH on behavior are evident in the classroom, but with MPH given twice daily, parents do not report that MPH improves behavior at home. Greater impact on home behavior may require three times daily MPH and combined treatments.

Affect↗