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PubMed2003

Doxapram produces a dose-dependent reduction in the shivering threshold in rabbits.

Dopamine is a thermoregulatory neurotransmitter that provokes hypothermia when injected in or near the hypothalamus. Doxapram stimulates release of dopamine from carotid bodies, but is known to have central effects that are probably, at least in part, similarly mediated. We thus tested the hypothesis that doxapram produces a substantial, dose-dependent reduction in the shivering threshold in rabbits. Twenty-four rabbits, anesthetized with isoflurane, were randomly assigned to 1) saline (control), 2) 0.25 mg x kg(-1) x h(-1) doxapram, or 3) 0.50 mg x kg(-1) x h(-1) doxapram. These doses are within the recommended range for humans. Body temperature was reduced at a rate of 2 degrees to 3 degrees C/h by perfusing water at 10 degrees C through a U-shaped thermode positioned in the colon. Core temperatures were recorded from the distal esophagus. A blinded observer evaluated shivering. Core temperature at the onset of shivering defined the threshold. Data were analyzed with a one-way analysis of variance; P < 0.05 was considered statistically significant. Hemodynamic and respiratory responses were comparable in the groups. The control rabbits shivered at 36.3 degrees +/- 0.3 degrees C, those given 0.25 mg x kg(-1) x h(-1) doxapram shivered at 34.8 degrees +/- 0.5 degrees C, and those given 0.50 mg x kg(-1) x h(-1) shivered at 33.7 degrees +/- 0.6 degrees C. All the shivering thresholds significantly (P < 0.001) differed from one another. The magnitude of this inhibition, if similar in humans, would be clinically important.

Anesthesia, Inhalation↗
PubMed1998

[Dosage monitoring as a quality control instrument in digital radiography].

PURPOSE: Automatic image processing procedures ensure a constant image quality. Overexposed images constitute a danger zone on account of a subjectively better image appearance (improved signal-to-noise ratio). We have examined the software "Dose-Monitoring" both for the identification of false exposures and as a quality control tool. MATERIALS AND METHODS: Firstly the correlation between dose and present IgM (mean grey tone from the crude histogram of a 12-bit image) was examined by exposing phantoms. A further-reaching comparison of the present IgM values of some MTRAs with the department average (nominal IgM) should detect tendencies for over- and underexposure. Finally a dose reduction in 12 forms of X-ray examination was evaluated with regard to IgM course controls (median IgM). RESULTS: A high correlation (0.987) between dose and mean grey tone (IgM). In some MRTAs tendency for over-/underexposure was detected. The dose reduction of defined types of X-ray examination lead to a trend to lower mean IgM values. DISCUSSION: Numerous factors have an influence on the IgM value thus making its evaluation difficult, even so it is a suitable parameter for uncovering tendencies to incorrect exposure and for identifying processes requiring optimization. CONCLUSIONS: The value of this tool lies in the quality assurance of dose fluctuations and a possible dose reduction.

Humans↗
PubMed1991

Cyclosporin A renders target cells resistant to immune cytolysis.

Exposure of cytolytically susceptible human target cells with therapeutic concentrations of the immunosuppressive drug cyclosporin A renders these cells highly resistant to T cell-mediated, natural killer (NK) cell-mediated, and complement-mediated cytolysis. The resistance is dose dependent, time dependent and reversible. The resistance is accompanied by target cell growth inhibition as measured by thymidine uptake. Surprisingly, target cell growth inhibition induced by serum depletion is associated with cell-mediated cytolytic resistance. These data suggest that cyclosporin A (CsA) may block some target cell biochemical pathway(s) important in the suicidal cytolytic process which is (are) linked to some G0/G1 cell cycle events. In addition, these results suggest that the increased risk of Epstein-Barr virus (EBV)-associated lymphoproliferative disease in human organ transplant recipients may be contributed to by CsA-induced resistance of EBV-transformed B lymphocytes to immune cytolysis. In the post-transplant setting, CsA probably blocks T cell-dependent responses to EBV-transformed B lymphocytes (Bird, A.G., McLachlan, S.M. and Britton, S., Nature 1981, 289: 300) yet leaving the NK cell and antibody-dependent responses intact (Shao-Hsien, C. et al. Transplantation 1983. 35: 127). However, given the direct effect of CsA upon EBV-transformed B lymphocytes, these cells would be rendered resistant to nearly all forms of cytolytic immune control (cytotoxic T lymphocyte, natural killer, antibody-dependent cell-mediated cytotoxicity, complement). Unregulated EBV-transformed B lymphocytes may then proliferate in the CsA-treated host thus leading to a polyclonal B cell hyperplasia. Our data would suggest that this early pre-malignant process is likely to be reversible following CsA dose reduction. Indeed, EBV-dependent polyclonal B cell hyperplasia is seen in early post-transplant lymphoproliferative disorders (Hanto, D.W., et al., Transplantation 1989, 47: 458). Furthermore, in some cases CsA dose reduction does lead to disease regression (Starzl, T., et al., Lancet 1984. i: 583). However, further progression of the disease probably occurs following chromosomal changes leading to oncogene activation and might be resistant to CsA dose reduction.

B-Lymphocytes↗
PubMed1999

Immune tolerance therapy for haemophilia A patients with acquired factor VIII alloantibodies: comprehensive analysis of experience at a single institution.

Immune Tolerance Therapy for Haemophilia A Patients with Acquired Factor VIII Alloantibodies: Comprehensive Analysis of Experience at a Single Institution Eleven children with severe haemophilia A associated with the IVS 22 inversion and acquired high titre neutralising antibodies to factor VIII underwent immune tolerance induction. HLA class I and high resolution class II type is detailed for each patient. A three phase approach to immune tolerance induction was used. During phase 1, which lasted a median of six weeks, patients received factor VIII 100 IU/kg twice daily. Phase 2 comprised a factor VIII dose reduction to 100 IU/kg once daily, and continued for a median duration of 14 weeks. Subsequently 10 of the 11 patients satisfied the criteria of absent factor VIII neutralising activity by the Bethesda method, and a factor VIII elimination half life of greater than 5 h, allowing progression to phase 3, a further factor VIII dose reduction to 50 IU/kg three times weekly. A model for dose reduction as factor VIII tolerance evolves, based on pharmacokinetic analysis, is described.

Child, Preschool↗
PubMed2003

Tacrolimus for the treatment of fistulas in patients with Crohn's disease: a randomized, placebo-controlled trial.

BACKGROUND & AIMS: This study determined the effectiveness of tacrolimus for the treatment of Crohn's disease fistulas. METHODS: The study was a randomized, double-blind, placebo-controlled, multicenter clinical trial. Forty-eight patients with Crohn's disease and draining perianal or enterocutaneous fistulas were randomized to treatment with oral tacrolimus 0.2 mg. kg(-1). day(-1) or placebo for 10 weeks. The primary outcome measure was fistula improvement as defined by closure of >/=50% of particular fistulas that were draining at baseline and maintenance of that closure for at least 4 weeks. A secondary outcome measure was fistula remission as defined by closure of all fistulas and maintenance of that closure for at least 4 weeks. RESULTS: Forty-three percent of tacrolimus-treated patients had fistula improvement compared with 8% of placebo-treated patients (P = 0.004). Ten percent of tacrolimus-treated patients had fistula remission compared with 8% of placebo-treated patients (P = 0.86). Adverse events significantly associated with tacrolimus, including headache, increased serum creatinine level, insomnia, leg cramps, paresthesias, and tremor, were managed with dose reduction. CONCLUSIONS: Oral tacrolimus 0.2 mg. kg(-1). day(-1) is effective for fistula improvement, but not fistula remission, in patients with perianal Crohn's disease. Adverse events associated with tacrolimus can be managed by dose reduction. Lower doses of tacrolimus should be evaluated.

Adolescent↗
PubMed1999

Subcutaneous treatment with recombinant human erythropoietin--the influence of injection frequency and skin-fold thickness.

Subcutaneous treatment with erythropoietin (epoetin) in patients undergoing continuous ambulatory peritoneal dialysis (CAPD) is convenient, but the optimal injection frequency is under discussion. Epoetin was given subcutaneously to 22 stable anaemic CAPD patients in doses that adjust haemoglobin to 7.2+/-0.3 mmol/l during a correction period. During the maintenance period the frequency of injections in four randomized groups of patients was changed randomly to once, twice or three times a week or daily. Each period lasted more than 8 weeks. During the maintenance period the epoetin dose was almost unchanged, whether the patients were treated once, twice or thrice weekly. In 15 patients treated with daily injections, the overall dose reduction was 22%. These 15 patients were grouped arbitrarily into 7 patients with a skin-fold of more than 20 mm at the injection site, and 8 patients with a skin-fold of less than 20 mm at the injection site. The dose reduction correlated with skin-fold thickness; the reduction was seen only in the patients with skin-folds of less than 20 mm. Seven of the eight patients experienced an average dose reduction of 36+/-8%.

Adult↗
PubMed1999

Decreased topotecan platelet toxicity with successive topotecan treatment cycles in advanced ovarian cancer patients.

The dose-limiting toxicities of the DNA topoisomerase I inhibitor topotecan are hematological. We prospectively analyzed the platelet toxicity pattern in patients receiving topotecan to optimize the clinical management of topotecan hematotoxicity. Twenty-one advanced ovarian cancer patients, all pretreated with cisplatin and paclitaxel, were treated with 1.25 mg/m2/day topotecan as a 30 min infusion for 5 days, every 3 weeks. No prophylactic granulocyte colony stimulating factor (G-CSF) was given. No topotecan dose reduction was planned according to hematologic toxicity. One hundred and thirty-three topotecan courses were administered (median per patient 6; range: 1-15). Despite no dose reduction, the mean platelet nadir values were significantly less pronounced at cycle 2 than at cycle 1 (82 versus 46 x 10(3)/mm3, p=0.0007). Similar differences were found between cycle 1 and any following cycle. The percent of patients experiencing grade 4 thrombocytopenia decreased from 43% at the first cycle, to 15 and 19% at the second and third courses, respectively (p=0.058). We conclude that the currently recommended topotecan schedule is feasible in heavily pretreated ovarian cancer patients without prophylactic G-CSF. The severity of topotecan-induced thrombocytopenia is maximal at the first cycle but significantly decreases from the second cycle in the absence of dose reduction.

Adult↗
PubMed1998

Altered fractionation in the management of head and neck cancer.

Progress in radiation science led to the development of two classes of biologically sound fractionation schedules for the treatment of head and neck cancers. These altered fractionation regimens are referred to as hyperfractionation and accelerated fractionation schedules. Hyperfractionation exploits the difference in fractionation sensitivity between tumours and tissues manifesting late morbidity and only minor variations exist among regimens tested. In contrast, accelerated fractionation attempts to reduce tumour proliferation as a major cause of radiotherapy failure. Although there are major permutations, the existing schedules can conceptually be grouped into two categories, namely pure accelerated fractionation and hybrid accelerated regimens, depending on whether there are concurrent changes in other fractionation parameters. The results of completed phase III clinical trials addressing different types of altered fractionation schedules in head and neck carcinomas are summarized and examined in this review paper. The data from trials on hyperfractionation regimens applying 10-15% total dose increment consistently revealed a 10-15% improvement in the local control rate of a subset of intermediate-stage carcinomas without increasing the incidence of late complications. The available data on accelerated fractionation regimens already showed that tumour clonogen proliferation is a major cause of radiation failure. However, completed studies revealed that a 1-1.5 week treatment acceleration without total-dose reduction, achieved by administering 2 Gy fractions six times per week or concomitant boost schedule, yielded a 15% higher tumour control rate without increasing late toxicity. Shortening the overall time to below 2 weeks with an associated total-dose reduction did not seem to improve the tumour control rate but might decrease some late normal-tissue injury. A weekly dose accumulation rate of > or =14 Gy or delivery of three fractions of 1.6 Gy per day, with a 6 h interval, without total-dose reduction was found to increase morbidity significantly. Further treatment refinements are being pursued based on these findings.

Clinical Trials, Phase III as Topic↗
PubMed1999

Conversion of liver transplant recipients on cyclosporine with renal impairment to mycophenolate mofetil.

The management of liver transplant recipients with renal function impairment remains controversial because cyclosporine withdrawal from triple immunosuppression regimens may be followed by graft rejection. A nonnephrotoxic and powerful immunosuppressant such as mycophenolate mofetil (MMF) could allow a reduction of cyclosporine dosage or its withdrawal and an improvement in renal function in these patients. Eleven patients with serum creatinine levels greater than 1.5 mg/dL, normal graft function, and a rejection-free period of at least 1 year started MMF at a dose of 2000 mg/d (reduced in case of adverse events) while cyclosporine dosage was slowly reduced. At last follow-up (63 +/- 5 weeks), 7 patients remained free of cyclosporine (6 of those patients are also free of steroids), 2 patients reduced their cyclosporine dose, and 2 patients developed mild acute rejection that responded to a switch to tacrolimus therapy. Serum creatinine and urea levels in the 7 patients free of cyclosporine decreased from 2.22 +/- 0.13 to 1.90 +/- 0.19 mg/dL (P =.05) and 0.95 +/- 0.10 to 0.60 +/- 0.10 g/L (P <.001), respectively. Creatinine clearance increased from 38.16 +/- 5.60 to 47.01 +/- 6. 76 mL/min (P =.005). Control of arterial hypertension also improved. Tolerance to MMF was good, but 6 patients required dose reductions, mainly because of asymptomatic anemia. In conclusion, in liver transplant recipients with stable graft function, MMF may allow cyclosporine dose reduction or discontinuation, thus improving renal function and the control of arterial hypertension. This change of treatment must be carefully monitored because of the frequent need for MMF dose reduction and the risk for rejection.

Aged↗
PubMed1993

Dose intercomparison at the radiotherapy centers in The Netherlands. 3. Characteristics of electron beams.

Dosimetric characteristics of a number of clinically applied electron beams were analyzed as part of a dosimetry intercomparison program performed at the radiotherapy centers in The Netherlands. Absorbed dose values, determined under reference conditions, were compared during site visits with stated dose values. The mean deviation was 0.2% with a standard deviation (SD) of 2.5%. The maximum deviation was 5.7%. The largest differences were due to differences in the calibration procedures and differences in the numerical values of conversion factors adopted from different dosimetry protocols. In addition, a number of clinically relevant parameters of the dose distribution on the central beam axis were analyzed including the depth of the 85% and 50% relative dose, the dose reduction at the depth of the 50% relative dose and the surface dose. The average difference between the stated and measured therapeutic depth (85% dose level) was -0.4 mm with an SD = 1.2 mm. Due to this dosimetric uncertainty observed a safety margin of about 3 mm at the therapeutic depth is recommended. The maximum difference between stated and observed mean energy of the electron beams had only a small influence, < 1%, on the absorbed dose determination. The normalized dose gradient is not an adequate parameter to describe the dose reduction beyond the therapeutic depth. The depth of a low dose level is a better parameter. The relative dose at the surface showed differences up to 10% between scanning electron beams and beams from accelerators with a single scattering foil and closed wall collimating system.

Electrons↗
PubMed1998

Low-dose cyclosporine and mycophenolate mofetil in renal allograft recipients with suboptimal renal function.

BACKGROUND: Cyclosporine (CsA) nephrotoxicity can be identified by functional changes and chronic renal damage. CsA-associated renal fibrosis has been related to the overproduction of transforming growth factor (TGF)-beta1, a fibrogenic cytokine. Mycophenolate mofetil (MMF) may allow CsA dose reduction without increasing the risk of rejection. METHODS: We studied the impact of CsA dose reduction in association with MMF on renal function and TGF-beta1, production in 16 long-term renal allograft recipients with suspected CsA nephrotoxicity. Two grams/day of MMF were introduced, and CsA dose was reduced to reach whole-blood levels between 40 and 60 ng/ml within 1 month. CsA dose and levels, renal function parameters, and platelet-poor plasma TGF-beta1 levels were evaluated before and 6 months thereafter. RESULTS: MMF allowed a decrease in both the mean dose of CsA (3.8+/-1.35 vs. 2.2+/-0.73 mg/kg/day; P<0.01) and CsA levels (148+/-36 vs. 53+/-19 ng/ml; P<0.001). The reduction of CsA was associated with a decrement of serum creatinine levels (210+/-46 vs. 172+/-41 micromol/L; P<0.001) and an increase in both the glomerular filtration rate (32.9+/-12 vs. 39.1+/-14 ml/min/1.73 m2; P<0.02) and renal plasma flow (195+/-79 to 218.6+/-74.02 ml/min/1.73 m2; P<0.02). There was a reduction in plasma TGF-beta1 levels (4.6+/-4.2 vs. 2.0+/-1.4 ng/ml; P=0.003) and CsA levels correlated with TGF-beta1 (r=0.536, P=0.002). No rejection episodes occurred, and an improvement in both systolic (149+/-13 vs. 137+/-12 mmHg; P<0.01) and diastolic blood pressure (89+/-14 vs. 83+/-10 mmHg; P<0.04) were observed. CONCLUSIONS: These short-term results show that MMF introduction allows a CsA dose reduction, which improves renal function, reduces TGF-beta1 production, and improves the control of hypertension, without increasing the incidence of acute rejection.

Adult↗
PubMed1998

Altered fractionation trials in head and neck cancer.

Advancement in radiobiological concepts has led to the development of two classes of new fractionation schedules for the treatment of head and neck cancers. These altered fractionation regimens are referred to as hyperfractionation and accelerated fractionation schedules. Hyperfractionation exploits the difference in fractionation sensitivity between tumors and normal tissues manifesting late morbidity. In contrast, accelerated fractionations attempt to reduce tumor proliferation as a major cause of radiotherapy failure. Although there are many permutations in accelerating radiation treatment, the existing schedules can be conceptually grouped into two categories, pure accelerated fractionations and hybrid accelerated regimens, depending on whether there are concurrent changes in other fractionation parameters. The results of 10 completed phase III clinical trials addressing different types of altered fractionation schedules in head and neck carcinomas are examined and summarized in this review article. The data of trials on hyperfractionation regimens applying 10% to 15% total dose increment over the standard 66 to 70 Gy consistently revealed a 10% to 15% improvement in the local control rate of a subset of intermediate-stage carcinomas without an appreciable increase in the incidence of late complications. The available data on accelerated fractionation regimens showed that tumor clonogen proliferation is a major cause of radiation failure. Completed studies, however, revealed that a 1- to 1.5-week treatment acceleration without total dose reduction achieved by administering 2-Gy fractions 6 times per week or concomitant boost schedule yielded an approximately 15% higher tumor control rate without increasing late toxicity. Shortening the overall time to less than 2 weeks with an associated total dose reduction did not seem to improve tumor control rate, with an exception perhaps for a small subset of patients with laryngeal carcinomas, but might decrease some late normal tissue injury. A weekly dose accumulation rate of 14 Gy or greater, or delivery of 3 fractions of 1.6 Gy/d, with 6 hour intervals, without total dose reduction, was found to increase morbidity beyond the acceptable level. Further treatment refinements building on these findings are being pursued.

Dose Fractionation, Radiation↗
PubMed2004

The management of anticoagulants in the periendoscopic period for patients with atrial fibrillation: a decision analysis.

PURPOSE: The management of patients who undergo endoscopy while being treated with warfarin is challenging. We used decision analysis to determine the preferred strategy to manage anticoagulants in the periendoscopic period. METHODS: We designed a Markov model to estimate costs and quality-adjusted survival during a 10-year period in patients with nonvalvular atrial fibrillation undergoing screening colonoscopy. We compared six alternatives to the continue-warfarin strategy, which was to perform colonoscopy while the patient was taking full-dose warfarin. The hold-warfarin strategy was to stop warfarin 5 days before the colonoscopy. The repeat endoscopy strategy was to continue warfarin for a diagnostic colonoscopy, followed by a repeat procedure after cessation of warfarin if polypectomy was required. The dose-reduction strategy was to reduce the warfarin dose before colonoscopy. The low molecular weight heparin strategy was to administer subcutaneous low molecular weight heparin for 2 days before and 2 days after colonoscopy. The unfractionated heparin strategy was to administer intravenous unfractionated heparin for 2 days before and 2 days after the procedure. The vitamin K strategy was to hold warfarin for 4 days and to administer vitamin K if the international normalized ratio (INR) exceeded 2.0 the day before the procedure, or low molecular weight heparin if the INR was less than 1.5. RESULTS: For screening colonoscopy, assuming that polyps would be removed in 35% of examinations, the hold-warfarin and dose-reduction arms were both cost-effective strategies. The hold-warfarin arm was most cost-effective if the likelihood of polypectomy exceeded 60%, or if there was a low risk of stroke despite atrial fibrillation. The continue-warfarin strategy was preferred if the probability of polypectomy was 1% or less. CONCLUSION: Temporary warfarin cessation or halving the warfarin dose for several days before endoscopy was the preferred strategy for most patients. Periendoscopic heparin therapy was not cost-effective for patients with nonvalvular atrial fibrillation.

Aged↗
PubMed1993

Effect of oral cyclosporin on renal function in Crohn's disease.

Twenty-one patients with Crohn's disease were followed prospectively for 24 weeks to examine the effect of a low-dose cyclosporin regime on renal function (initial dose 5 mg/kg reduced by 1 mg/kg every two months to a maintenance of 2 mg/kg). Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were measured by radioisotope clearance at 0, 6 and 24 weeks. GFR and ERPF fell significantly (mean GFR at baseline: 120.9 ml/min/1.73 m2; at six weeks: 100.9 ml/min/1.73 m2; mean ERPF at baseline: 497.3 ml/min/1.73 m2; at six weeks: 398.5 ml/min/1.73 m2). Following dose reduction, the ERPF remained lower than baseline (mean 408.6 ml/min/1.73 m2), and there was a trend towards the GFR remaining low (mean 111.8 ml/min/1.73 m2). Serum creatinine rose significantly (median pretreatment 72 mumol/liter; median at four weeks 86 mumol/liter) but returned to baseline after dose reduction. Plasma cyclosporin levels and serum creatinine did not help predict the extent of changes in renal function. At low doses, cyclosporin causes changes in renal hemodynamics that may not be reversed by dose reduction.

Administration, Oral↗
PubMed2002

Flat panel digital radiography compared with storage phosphor computed radiography: assessment of dose versus image quality in phantom studies.

RATIONALE AND OBJECTIVE: To assess and quantify the dose reduction by use of a CsI-flat panel digital radiography (DR)-system compared with digital computed radiography (CR). MATERIALS AND METHODS: A TCDD-test using the CDRAD-phantom was performed at mAs-values of 5, 4, 2.5, 2, 1, and 0.5 mAs for both digital systems. Entrance surface doses were recorded for all images. Images were presented to four independent observers. For quantitative comparison the image quality figure (IQF) was calculated. Statistical analysis was performed using the Pearson correlation and the Wilcoxon test. A ROC analysis was performed using the TRG-phantom. Settings of 4, 2.5, 2 mAs for both systems were used. In addition, 1 and 0.5 mAs were used for the DR system only. Statistical significance was evaluated using Student test. RESULTS: The DR system provided equivalent results compared with CR with respect to high frequency information and superior results with respect to low contrast details. Compared with computed radiography, the flat panel detector demonstrated significantly lower IQFs, ensuring a better image quality with respect to contrast and detail detectability. IQFs for DR and CR were equal at a surface dose reduction of 87% for DR. ROC analysis revealed significantly higher values under the curve for DR up to a surface dose reduction of 70%. CONCLUSIONS: Image quality of DR proved to be far superior to CR in particular for low contrast details. The image quality of CR is similar to that of DR only at high dose levels.

Phantoms, Imaging↗
PubMed2006

Coronary artery calcium scoring with multislice computed tomography: in vitro assessment of a low tube voltage protocol.

OBJECTIVES: We sought to compare an 80-kVp coronary calcium scoring protocol with the standard protocol of 120 kVp in terms of accuracy and reproducibility and to assess its dose reduction potential. MATERIALS AND METHOD: An anthropomorphic heart phantom with calcium cylinders was scanned with different tube currents at 80 kVp and 120 kVp using a 16-slice multislice CT (MSCT) scanner. An adapted threshold for 80 kVp was calculated. Accuracy and reproducibility for calcium mass, volume, and Agatston score were analyzed using F-tests. The radiation doses needed to produce artifact-free images were determined. RESULTS: Accuracy (measurement errors: mass 120 kVp +4.6%, mass 80 kVp -6.9%, volume 120 kVp +78.8%, volume 80 kVp +58.2%) and reproducibility (F-tests: mass: P = 0.4998, volume: P = 0.9168, Agatston: P = 0.5422) were comparable at both tube voltages. Avoiding the appearance of artificial lesions, a CTDI(w,eff) of 10.7 mGy was needed at 120 kVp versus 4.6 mGy at 80 kVp (dose reduction of 57%). CONCLUSIONS: Using an 80-kVp protocol in coronary calcium scoring, a relevant dose reduction is possible without compromising reproducibility and accuracy.

Analysis of Variance↗
PubMed1991

[Perceptibility of details in conventional and digital teleradiography--a comparative study].

By introduction of rare earth film-screen combinations instead of classical screens dose reduction has already been possible. By this study the extent of dose reduction without loss of clinical information was to be examined by comparing conventional radiographic rare earth film-screen combinations to digital radiography. Statistical analysis proves for conventional lateral cephalograms that soft tissue reference points can better be localized if small radiation doses are used. The localization of reference points in areas of less radiographic transparency is better when applying higher doses. These results were not found in images by digital radiographic technique. Reference points both of soft tissue and of more dense areas of the skull were equally to be localized independent from radiation dose by the linear sensibility characteristics of digital radiography. This enables reduction of radiation doses and therefore a contribution to radioprotection.

Cephalometry↗
PubMed1994

Impact of clinical pharmacokinetics on neuroleptic therapy in patients with schizophrenia.

This review covers some recent work on: 1. The effects of route of administration on the pharmacokinetics of fluphenazine and some of its metabolites; 2. The clinical pharmacokinetics of fluphenazine in acute patients medicated with oral fluphenazine; 3. The clinical pharmacokinetics of haloperidol in acute patients medicated with oral haloperidol; 4. The clinical pharmacokinetics of fluphenazine in the maintenance of individuals with chronic schizophrenia with fluphenazine decanoate; 5. A systematic dose reduction study in maintenance treatment refractory patients with oral haloperidol. A study in which plasma levels of fluphenazine and fluphenazine sulfoxide were measured in a group of DSM-III-R patients with schizophrenia before and after switching from oral fluphenazine to depot fluphenazine, decanoate revealed much higher levels of fluphenazine sulfoxide with oral medication compared with those found with depot fluphenazine. These data illustrate the effect of "first pass" metabolism after oral fluphenazine. Thus in a group of 33 patients randomly assigned to receive 5 mg, 10 mg or 25 mg oral fluphenazine daily, steady state plasma fluphenazine levels at each dose were significantly lower that those of fluphenazine sulfoxide or 7-hydroxy-fluphenazine, although there were no significant differences between the levels of fluphenazine and fluphenazine N4-oxide. On the other hand, plasma levels of the parent drug were significantly higher than those of any metabolite in a corresponding group of patients at steady state on depot medication. These observations underscore the importance of route dependent differences in the pharmacokinetics of fluphenazine which can lead to problems when switching patients from oral to depot neuroleptics. The concept of "disabling side-effects" is an important development in understanding relationships between plasma levels of neuroleptic drugs and clinical response in patients with schizophrenia. Risk-benefit analysis shows clearly that evaluation of relationships between plasma levels and clinical response must take into account the consequences of side-effects which the patient feels have a negating effect on therapy. Emerging data on putative therapeutic plasma level ranges in maintenance therapy are potentially important and may be particularly useful in the maintenance of patients on low dose therapy. It is noteworthy that in a carefully executed dose reduction study in treatment resistant patients under medication with haloperidol, the mean lowest effective dose (8.7 ng/mL) lay within the optimal therapeutic range (5 ng/mL to 12 ng/mL) found in acutely psychotic patients. The study showed that gradual dose reduction of neuroleptic was possible in chronic treatment resistant patients with schizophrenia who were originally thought by ward staff to require high doses of neuroleptic.(ABSTRACT TRUNCATED AT 400 WORDS)

Antipsychotic Agents↗