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Biomedical subjects

Peter Huber

Publications and source records attributed to Peter Huber.

At least 19 recordsLinked to original sources

Antibiotic treatment of exacerbations of COPD: a randomized, controlled trial comparing procalcitonin-guidance with standard therapy.

BACKGROUND: Therapy with antibiotics influences recovery only in selected cases of COPD exacerbations. We evaluated the efficacy and safety of procalcitonin guidance compared to standard therapy with antibiotic prescriptions in patients experiencing exacerbations of COPD. METHODS: A total of 208 consecutive patients requiring hospitalization for COPD exacerbation were randomized at the index exacerbation to procalcitonin-guided or standard antibiotic therapy. Patients receiving procalcitonin-guided therapy were treated with antibiotics according to serum procalcitonin levels; standard-therapy patients received antibiotics according to the attending physician. The primary outcome was the antibiotic exposure at the index exacerbation and the subsequent antibiotic requirement for COPD exacerbation within 6 months. Secondary outcomes were clinical recovery, symptom scores, length of hospitalization, ICU stay, death, lung function, exacerbation rate, and time to next exacerbation. RESULTS: At the index exacerbation, procalcitonin guidance reduced antibiotic prescription (40% vs 72%, respectively; p < 0.0001) and antibiotic exposure (relative risk [RR], 0.56; 95% confidence interval [CI], 0.43 to 0.73; p < 0.0001) compared to standard therapy. Moreover, procalcitonin guidance at the index exacerbation allowed a significant sustained reduction in total antibiotic exposure for up to 6 months (RR, 0.76; 95% CI, 0.64 to 0.92; p = 0.004). Clinical outcome and improvement in FEV(1) at 14 days and 6 months did not differ between groups. Within 6 months, the exacerbation rate (0.62 vs 0.64, respectively), the rehospitalization rate (0.21 vs 0.24, respectively), and mean (+/- SD) time to the next exacerbation (70.0 +/- 46.1 vs 70.4 +/- 51.9 days, respectively; p = 0.523) were similar in both groups. CONCLUSIONS: Procalcitonin guidance for exacerbations of COPD offers a sustained advantage over standard therapy in reducing antibiotic use for up to 6 months with a number-needed-to-treat of 3.

Acute Disease↗

Changes in salivary gland function after radiotherapy of head and neck tumors measured by quantitative pertechnetate scintigraphy: comparison of intensity-modulated radiotherapy and conventional radiation therapy with and without Amifostine.

PURPOSE: The aim of this study was to compare changes in salivary gland function after intensity-modulated radiotherapy (IMRT) and conventional radiotherapy (RT), with or without Amifostine, for tumors of the head-and-neck region using quantitative salivary gland scintigraphy (QSGS). METHODS AND MATERIALS: A total of 75 patients received pre- and post-therapeutic QSGS to quantify the salivary gland function. In all, 251 salivary glands were independently evaluated. Changes in the maximum uptake (DeltaU) and relative excretion rate (DeltaF) both pre- and post-RT were determined to characterize radiation-induced changes in the salivary gland function. In addition, dose-response curves were calculated. RESULTS: In all groups, maximum uptake and relative excretion rate were reduced after RT (DeltaU <or=0 and DeltaF <or=0). The reduction was significantly lower for IMRT than for conventional RT. For the parotid glands, the reduction was smaller for the IMRT-low than for the IMRT-high group. For the Amifostine-high and the conventional group the difference was significant only for one parameter (DeltaU, parotid and submandibular glands, p < 0.05). In contrast to this, the difference between the Amifostine-low and the conventional group was always significant or at least showed a clear trend for both changes in U and F. In regard to the endpoint "reduction of the salivary gland excretion rate of more than 50%," the dose-response curves yielded D50-values of 34.2 +/- 12.2 Gy for the conventionally treated group and 36.8 +/- 2.9 Gy for the IMRT group. For the Amifostine group, an increased D50-values of 46.3 +/- 2.3 Gy was obtained. CONCLUSION: Intensity-modulated RT can significantly reduce the loss of parotid gland function when respecting a certain dose threshold. Conventional RT plus Amifostine prevents reduced salivary gland function only in the patient group treated with <40.6 Gy.

Adult↗

Effect of radiotherapy and hyperthermia on the tumor accumulation of HPMA copolymer-based drug delivery systems.

Copolymers of N-(2-hydroxypropyl)methacrylamide (HPMA) are prototypic and well-characterized polymeric drug carriers that have been broadly implemented in the delivery of anticancer therapeutics. In an attempt to improve the tumor accumulation of HPMA copolymer-based drug delivery systems, their in vivo application was combined with radiotherapy and hyperthermia. As the effects of radiotherapy and hyperthermia were considered to depend significantly on the tumor model used, we first analyzed the accumulation of two differently sized HPMA copolymers in three different types of tumors, based on the syngeneic Dunning rat prostate carcinoma model. Subsequently, in these three models, the effects of different doses of radiotherapy and hyperthermia on the tumor accumulation of 31 kDa poly(HPMA), 65 kDa poly(HPMA) and 28 kDa poly(HPMA)-GFLG-doxorubicin were evaluated. It was found that the polymeric drug delivery systems accumulated effectively in all three tumor models. In addition, as opposed to hyperthermia, radiotherapy was found to improve the concentrations of the copolymers independent of the tumor model used. Based on these findings, we conclude that radiotherapy is an effective means for increasing the tumor accumulation of (polymeric) drug delivery systems, and we propose that the combination of carrier-based chemotherapy with radiotherapy holds significant potential for improving the treatment of advanced solid malignancies.

Animals↗

Correction of patient positioning errors based on in-line cone beam CTs: clinical implementation and first experiences.

BACKGROUND: The purpose of the study was the clinical implementation of a kV cone beam CT (CBCT) for setup correction in radiotherapy. PATIENTS AND METHODS: For evaluation of the setup correction workflow, six tumor patients (lung cancer, sacral chordoma, head-and-neck and paraspinal tumor, and two prostate cancer patients) were selected. All patients were treated with fractionated stereotactic radiotherapy, five of them with intensity modulated radiotherapy (IMRT). For patient fixation, a scotch cast body frame or a vacuum pillow, each in combination with a scotch cast head mask, were used. The imaging equipment, consisting of an x-ray tube and a flat panel imager (FPI), was attached to a Siemens linear accelerator according to the in-line approach, i.e. with the imaging beam mounted opposite to the treatment beam sharing the same isocenter. For dose delivery, the treatment beam has to traverse the FPI which is mounted in the accessory tray below the multi-leaf collimator. For each patient, a predefined number of imaging projections over a range of at least 200 degrees were acquired. The fast reconstruction of the 3D-CBCT dataset was done with an implementation of the Feldkamp-David-Kress (FDK) algorithm. For the registration of the treatment planning CT with the acquired CBCT, an automatic mutual information matcher and manual matching was used. RESULTS AND DISCUSSION: Bony landmarks were easily detected and the table shifts for correction of setup deviations could be automatically calculated in all cases. The image quality was sufficient for a visual comparison of the desired target point with the isocenter visible on the CBCT. Soft tissue contrast was problematic for the prostate of an obese patient, but good in the lung tumor case. The detected maximum setup deviation was 3 mm for patients fixated with the body frame, and 6 mm for patients positioned in the vacuum pillow. Using an action level of 2 mm translational error, a target point correction was carried out in 4 cases. The additional workload of the described workflow compared to a normal treatment fraction led to an extra time of about 10-12 minutes, which can be further reduced by streamlining the different steps. CONCLUSION: The cone beam CT attached to a LINAC allows the acquisition of a CT scan of the patient in treatment position directly before treatment. Its image quality is sufficient for determining target point correction vectors. With the presented workflow, a target point correction within a clinically reasonable time frame is possible. This increases the treatment precision, and potentially the complex patient fixation techniques will become dispensable.

Automation↗

Pediatric cerebral arteriovenous malformations: the role of stereotactic linac-based radiosurgery.

PURPOSE: To evaluate retrospectively clinical outcome and obliteration rates after linac-based radiosurgery (RS) in children with cerebral arteriovenous malformations (AVM). METHODS AND MATERIALS: Between 1996 and 2002, 22 children with cerebral AVM were treated at our institution. Mean age at treatment was 11.8 years (range, 4.4-16.4 years). Classification according to Spetzler-Martin was 1 child grade I (4%), 7 grade II (32%), 12 grade III (56%), 1 grade IV (4%), and 1 grade V (4%). Median single dose was 18 Gy/80%-isodose. Median AVM volume was 4.2 mL (range, 0.4-26.5 mL). Median RS-based AVM-score was 1.07 (range, 0.61-3.55). Fifty-nine percent of children experienced intracranial hemorrhage before RS. Median follow-up was 3.1 years (range, 1.7-7.3 years). RESULTS: Actuarial complete obliteration rate (CO) was 54% after 3 years and 65% after 4 years, respectively. Median time interval to CO was 27.1 months. Intracranial hemorrhage after RS was seen in five children after median 13.9 months. Annual bleeding risk was 9.1% after 1 year and 13.6% after 2 years. Maximum diameter>or=3 cm and AVM-volume>or=6 mL were significant predictors for intracranial hemorrhage. Neurologic deficits were improved/completely dissolved in 58% of children and remained stable in 42%. No new onset of neurologic dysfunction was seen after RS. CONCLUSIONS: RS is safe and effective in pediatric cerebral AVM with high obliteration rates. Size and volume of AVM are significant predictors for intracranial bleeding. The same treatment guidelines as in adults should be applied. Careful long-term follow-up observation is required after RS from long life expectation.

Adolescent↗

The influence of breathing motion on intensity modulated radiotherapy in the step-and-shoot technique: phantom measurements for irradiation of superficial target volumes.

For intensity modulated radiotherapy (IMRT) of deep-seated tumours, dosimetric variations of the original static dose profiles due to breathing motion can be primarily considered as blurring effects known from conventional radiotherapy. The purpose of this dosimetric study was to clarify whether these results are transferable to superficial targets and to quantify the additional effect of fractionation. A solid polystyrene phantom and an anthropomorphic phantom were used for film and ion chamber dose measurements. The phantoms were installed on an electric driven device and moved with a frequency of 6 or 12 cycles per minute and an amplitude of 4 mm or 10 mm. A split beam geometry of two adjacent asymmetric fields and an IMRT treatment plan with 12 fields for irradiation of the breast were investigated. For the split beam geometry the dose modifications due to unintended superposition of partial fields were reduced by fractionation and completely smoothed out after 20 fractions. IMRT applied to the moving phantom led to a more homogeneous dose distribution compared to the static phantom. The standard deviation of the target dose which is a measure of the dose homogeneity was 10.3 cGy for the static phantom and 7.7 cGy for a 10 mm amplitude. The absolute dose values, measured with ionization chambers, remained unaffected. Irradiation of superficial targets by IMRT in the step-and-shoot technique did not result in unexpected dose perturbations due to breathing motion. We conclude that regular breathing motion does not jeopardize IMRT of superficial target volumes.

Breast↗

Improved target volume definition for fractionated stereotactic radiotherapy in patients with intracranial meningiomas by correlation of CT, MRI, and [68Ga]-DOTATOC-PET.

PURPOSE: To evaluate the influence of 68-Ga-labeled DOTA (0)-D-Phe (1)-Tyr (3)-Octreotide positron emission tomography ([68Ga]-DOTATOC-PET) for target definition for fractionated stereotactic radiotherapy (FSRT) as a complementary modality to computed tomography (CT) and magnetic resonance imaging (MRI). Because meningiomas show a high expression of somatostatin receptor subtype 2, somatostatin analogs such as DOTATOC offer the possibility of receptor-targeted imaging. PATIENTS AND METHODS: Twenty-six patients received stereotactic CT, MRI, and [68Ga]-DOTATOC-PET as part of their treatment planning. Histology was: World Health Organization (WHO) Grade 1 61.5%, WHO Grade 2 7.7%, WHO Grade 3 3.9%, and undetermined 26.9%. Six patients received radiotherapy as primary treatment, 2 after subtotal resection; 17 patients were treated for recurrent disease. Dynamic PET scans were acquired before radiotherapy over 60 min after intravenous injection of 156 +/- 29 MBq [68Ga]-DOTATOC. These PET images were imported in the planning software for FSRT. Planning target volume (PTV)-I outlined on CT and contrast-enhanced MRI was compared with PTV-II outlined on PET. PTV-III was defined with CT, MRI, and PET and was actually used for radiotherapy treatment. RESULTS: PTV-III was smaller than PTV-I in 9 patients, the same size in 7 patients, and larger in 10 patients. Median PTV-I was 49.6 cc, median PTV-III was 57.2 cc. In all patients [68Ga]-DOTATOC-PET delivered additional information concerning tumor extension. PTV-III was significantly modified based on DOTATOC-PET data in 19 patients. In 1 patient no tumor was exactly identified on CT/MRI but was visible on PET. CONCLUSION: These data demonstrate that [68Ga]-DOTATOC-PET improves target definition for FSRT in patients with intracranial meningiomas. Radiation targeting with fused DOTATOC-PET, CT, and MRI resulted in significant alterations in target definition in 73%.

Adult↗

Linac-based radiosurgery or hypofractionated stereotactic radiotherapy in the treatment of large cerebral arteriovenous malformations.

PURPOSE: We investigate retrospectively clinical outcome after radiosurgery (RS) or hypofractionated stereotactic radiotherapy (HSRT) in patients with large cerebral arteriovenous malformations (AVMs). METHODS AND MATERIALS: This analysis is based on 48 patients with cerebral AVM greater than 4 cm treated with HSRT or RS at our institution. Fifteen patients received HSRT, with 26 Gy median total dose in 4 to 5 fractions, and 33 patients received RS with 17 Gy median total dose in 4 to 5 fractions. Median target volume was 27 cc in HSRT and 7 cc in RS; median maximum diameter was 6 cm and 5 cm, respectively. Seventeen patients experienced intracranial hemorrhage before treatment. Median follow-up was 2.6 years. RESULTS: The 3-year and 4-year actuarial complete obliteration (CO) after HSRT was 17% and 33% and after RS was 47% and 60%, respectively. Actuarial CO was higher in AVMs less than 5 cm (66% vs. 37% after 4 years). Intracranial hemorrhage after HSRT occurred in 3 of 15 patients after 18 months median, and after RS in 7 of 33 patients after 17 months median. Bleeding risk was significantly higher in patients with prior hemorrhage (p < 0.04). Preexisting neurologic dysfunction improved/dissolved in 50% and remained stable in 45%. CONCLUSIONS: Large AVMs need a long time period to obliterate and show a high bleeding risk. Multimodal treatment strategies are required to reduce treatment volume before radiotherapy.

Adolescent↗

Fractionated stereotactic radiation therapy in the management of benign cavernous sinus meningiomas : long-term experience and review of the literature.

PURPOSE: To analyze own long-term results with fractionated stereotactic radiotherapy (FSRT) in patients with benign meningiomas of the cavernous sinus and to review the literature on these rare lesions. PATIENTS AND METHODS: 57 patients were treated with FSRT for benign meningiomas of the cavernous sinus between 01/1990 and 12/2003 at the authors' institution. Histology was WHO grade I in 28/57 lesions, and undetermined in 29/57 lesions. 29 patients received radiotherapy as primary treatment, ten following surgery, and 18 patients were irradiated for recurrent disease. Median target volume was 35.2 cm3. Median total dose was 57.6 Gy with 1.8 Gy per fraction. 51/57 patients showed clinical symptoms before radiotherapy like reduced vision (n = 19), diplopia (n = 25), or trigeminal hyp-/dysesthesia (n = 17). RESULTS: Median follow-up period was 6.5 years. 50/57 patients were followed for > 36 months. Overall local tumor control was 100%. 39/57 patients had stable disease based on CT/MRI, while 18/57 had a partial remission of tumor volume. Overall survival for patients with WHO grade I meningiomas was 95.5% after 5 and 10 years. Two patients died 2.8 and 4.1 years after radiotherapy due to cardiac failure. In 11/57 patients, preexisting neurologic deficits improved. There was one patient with recurrent hyperlacrimation of one eye on the side of the irradiated meningioma. Three patients complained about subjective visual deterioration after FSRT without any objective findings in an ophthalmologic examination. No late toxicity RTOG >/= degrees III was seen. CONCLUSION: These data demonstrate that FSRT is an effective and safe treatment modality for local control of benign cavernous sinus meningiomas with a minimal risk of significant late toxicity.

Cavernous Sinus↗

Linac-integrated kV-cone beam CT: technical features and first applications.

One of the most prominent imaging techniques in image-guided radiotherapy (IGRT) is the acquisition of cone beam computed tomographies (CBCTs) at the linac with the patient in treatment position. CBCTs provide accurate 3-dimensional (3D) knowledge about the patient's anatomy for every treatment fraction and are therefore well suited for all adaptive corrections of errors related to interfractional uncertainties of the treatment process. In this paper, we first describe the technical development and implementation of this new imaging technique at our linac, i.e., the hardware components and their operating parameters are discussed in detail for a standard image acquisition of CBCTs. Then, an extension of this approach for the acquisition of complete images for extended field of views--the "shifted detector" technique--is presented followed by a first investigation of how CBCTs can be reliably used for adaptive dose calculations. Finally, a first clinical application, the process of automatic patient positioning based on CBCT images, is discussed. From our investigations, we conclude that the technical development of linac-integrated CBCTs bears an enormous potential for the correction of interfractional treatment errors. However, image quality and reconstruction speed of the images leave room for improvement. The development of clinical strategies for the optimal application of this new image modality in a clinical environment is one the major tasks for the future.

Humans↗

[Sound-field modification with acoustic lenses for high-intensity focused ultrasound therapy].

High-intensity focused ultrasound (HIFU) therapy is a minimally invasive method for precise thermal tissue destruction. Most applications make use of spherical, sharply focused fixed-focus transducers. These allow only small ablation rates, thus the treatment of large tumours is a very time-consuming process. The present paper describes the design of ancillary lenses, which combined with a spherical focused ultrasound transducer can be employed to reduce treatment time. The ancillary lenses shift the phase of the focused ultrasound waves, so that instead of one ellipsoidal focus multiple foci are generated. Thus, a single sonication can achieve a larger ablated area. To estimate the therapeutic benefits of the designed lenses, the lesion development during sonication was numerically simulated. Two "optimal" lenses were made of polystyrene and acoustically analysed. Using the designed lenses the theoretical lesion rate was increased by a factor of 3.7-5. There was a good correlation between simulated and measured ultrasound pressure field. The lenses reduced the system efficiency by only 13%. Thus, ancillary lenses present a technically simple and cost-effective method to accelerate ablative ultrasound therapy.

Computer Simulation↗

Effect of intratumoral injection on the biodistribution and the therapeutic potential of HPMA copolymer-based drug delivery systems.

The direct intratumoral (i.t.) injection of anticancer agents has been evaluated extensively in the past few decades. Thus far, however, it has failed to become established as an alternative route of administration in routine clinical practice. In the present report, the impact of i.t. injection on the biodistribution and the therapeutic potential of N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer-based drug delivery systems was investigated. It was found that, compared to intravenous injection, both the tumor concentrations and the tumor-to-organ ratios of carriers improved substantially. In addition, compared to intravenously and intratumorally applied free doxorubicin and to intravenously applied poly(HPMA)-glycylphenylalanylleucylglycine-doxorubicin, intratumorally injected poly(HPMA)-glycylphenylalanylleucylglycine-doxorubicin presented a significantly increased antitumor efficacy, as well as an improved therapeutic index. Based on these findings, we propose intratumorally injected carrier-based chemotherapy as an interesting alternative to routinely used chemotherapy regimens and routes of administration.

Acrylamides↗

Stereotactic linac-based radiosurgery in the treatment of cerebral arteriovenous malformations located deep, involving corpus callosum, motor cortex, or brainstem.

PURPOSE: To evaluate patient outcome and obliteration rates after radiosurgery (RS) for cerebral arteriovenous malformations (AVM) located deep, in the motor cortex or brainstem and those involving corpus callosum. METHODS AND MATERIALS: This analysis is based on 65 patients. AVM classification according to Spetzler-Martin was 13 patients Grade 2, 39 Grade 3, 12 Grade 4, and 1 Grade 5. Median RS-based AVM score was 1.69. Median single dose was 18 Gy. Mean treatment volume was 5.2 cc (range, 0.2-26.5 cc). Forty patients (62%) experienced intracranial hemorrhage before RS. Median follow-up was 3.0 years. RESULTS: Actuarial complete obliteration rate (CO) was 50% and 65% after 3 and 5 years, respectively. CO was significantly higher in AVM <3 cm (p < 0.02) and after doses >18 Gy (p < 0.009). Annual bleeding risk after RS was 4.7%, 3.4%, and 2.7% after 1, 2, and 3 years, respectively. AVM >3 cm (p < 0.01), AVM volume >4 cc (p < 0.009), and AVM score >1.5 (p < 0.02) showed a significant higher bleeding risk. Neurologic dysfunction improved, completely dissolved, or remained stable in 94% of patients. CONCLUSIONS: Surgically inaccessible AVM can be successfully treated using RS with acceptable obliteration rates and low risk for late morbidity. The risk of intracranial hemorrhage is reduced after RS and depends on RS-based AVM score.

Adolescent↗

Effect of physicochemical modification on the biodistribution and tumor accumulation of HPMA copolymers.

Copolymers of N-(2-hydroxypropyl)methacrylamide (HPMA) are prototypic and well-characterized polymeric drug carriers that are being broadly implemented in the delivery of anticancer therapeutics. To better predict the in vivo potential of the copolymers and to describe the biodistributional consequences of functionalization, 13 physicochemically different HPMA copolymers were synthesized, varying in molecular weight and in the nature and amount of functional groups introduced. Upon radiolabeling, the copolymers were injected i.v., and their circulation kinetics, tissue distribution and tumor accumulation were monitored in rats bearing subcutaneous Dunning AT1 tumors. It was found that increasing the average molecular weight of HPMA copolymers resulted in prolonged circulation times and in increased tumor concentrations. Conjugation of carboxyl and hydrazide groups, as well as introduction of spacer, drug and peptide moieties reduced the long-circulating properties of the copolymers and as a result, lower levels were found in tumors and in all organs other than kidney. Interestingly, however, in spite of the reduced (absolute) tumor concentrations, hardly any reduction in the relative levels localizing to tumors was found. Tumor-to-organ ratios were comparable to unmodified control for the majority of chemically modified copolymers, indicating that functionalization does not necessarily affect the tumor targeting ability of the copolymers and suggesting that HPMA copolymer-based drug delivery systems may prove to be attractive tools for more effectively treating various forms of advanced solid malignancy.

Animals↗

Procalcitonin-guided antibiotic use versus a standard approach for acute respiratory tract infections in primary care: study protocol for a randomised controlled trial and baseline characteristics of participating general practitioners [ISRCTN73182671].

BACKGROUND: Acute respiratory tract infections (ARTI) are among the most frequent reasons for consultations in primary care. Although predominantly viral in origin, ARTI often lead to the prescription of antibiotics for ambulatory patients, mainly because it is difficult to distinguish between viral and bacterial infections. Unnecessary antibiotic use, however, is associated with increased drug expenditure, side effects and antibiotic resistance. A novel approach is to guide antibiotic therapy by procalcitonin (ProCT), since serum levels of ProCT are elevated in bacterial infections but remain lower in viral infections and inflammatory diseases. The aim of this trial is to compare a ProCT-guided antibiotic therapy with a standard approach based on evidence-based guidelines for patients with ARTI in primary care. METHODS/DESIGN: This is a randomised controlled trial in primary care with an open intervention. Adult patients judged by their general practitioner (GP) to need antibiotics for ARTI are randomised in equal numbers either to standard antibiotic therapy or to ProCT-guided antibiotic therapy. Patients are followed-up after 1 week by their GP and after 2 and 4 weeks by phone interviews carried out by medical students blinded to the goal of the trial. Exclusion criteria for patients are antibiotic use in the previous 28 days, psychiatric disorders or inability to give written informed consent, not being fluent in German, severe immunosuppression, intravenous drug use, cystic fibrosis, active tuberculosis, or need for immediate hospitalisation. The primary endpoint is days with restrictions from ARTI within 14 days after randomisation. Secondary outcomes are antibiotic use in terms of antibiotic prescription rate and duration of antibiotic treatment in days, days off work and days with side-effects from medication within 14 days, and relapse rate from the infection within 28 days after randomisation. DISCUSSION: We aim to include 600 patients from 50 general practices in the Northwest of Switzerland. Data from the registry of the Swiss Medical Association suggests that our recruited GPs are representative of all eligible GPs with respect to age, proportion of female physicians, specialisation, years of postgraduate training and years in private practice.

Adult↗

Reproducibility of nighttime salivary cortisol and its use in the diagnosis of hypercortisolism compared with urinary free cortisol and overnight dexamethasone suppression test.

BACKGROUND/METHODS: Nighttime salivary cortisol (NSC) has been suggested to be a useful diagnostic test for Cushing's syndrome (CS). In the absence of published data on its day-to-day variability, we assessed the reproducibility of NSC by repeated measurements in healthy volunteers. Its diagnostic performance was compared with 24-h urinary free cortisol (UFC) and 1 mg overnight dexamethasone suppression test in 12 patients with CS, 20 healthy volunteers, 14 referred patients in which CS was excluded or not firmly established, 16 obese patients, and 20 women in late pregnancy. RESULTS: NSC showed a superior reproducibility in healthy volunteers with a low day-to-day variability as reflected by an intraclass correlation coefficient of 0.78. The receiver operating characteristic curve-estimated cutoff of 6.1 nmol/liter (0.22 microg/dl) demonstrated a sensitivity and specificity of 100% (area under the receiver operating characteristic curve, 1.0; 95% confidence interval, 0.94-1.0) in the diagnosis of CS. NSC, 24-h UFC [after adjusting the local laboratory cutoff to 504 nmol/d (183 microg/d)], and the urinary cortisol/creatinine ratio showed a tendency to be superior to 1 mg dexamethasone suppression test in correctly identifying CS. In late pregnancy, the preserved diurnal variation at a higher level of salivary cortisol reduced the specificity of NSC to 75%. CONCLUSION: Based on its remarkable reproducibility, easy noninvasive nature, and at least similar diagnostic performance, NSC appears to be a preferable alternative to 24-h UFC as a first-line screening test for CS. The cutoff values of NSC, 24-h UFC, and urinary cortisol/creatinine ratio have to be carefully adjusted using assay and center-specific reference ranges of sufficiently large populations.

Adult↗

Influence of different breathing maneuvers on internal and external organ motion: use of fiducial markers in dynamic MRI.

PURPOSE: To investigate, with dynamic magnetic resonance imaging (dMRI) and a fiducial marker, the influence of different breathing maneuvers on internal organ and external chest wall motion. METHODS AND MATERIALS: Lung and chest wall motion of 16 healthy subjects (13 male, 3 female) were examined with real-time trueFISP (true fast imaging with steady-state precession) dMRI and a small inductively coupled marker coil on either the abdomen or thorax. Three different breathing maneuvers were performed (predominantly "abdominal breathing," "thoracic breathing," and unspecific "normal breathing"). The craniocaudal (CC), anteroposterior (AP), and mediolateral (ML) lung distances were correlated (linear regression coefficient) with marker coil position during forced and quiet breathing. RESULTS: Differences of the CC distance between maximum forced inspiration and expiration were significant between abdominal and thoracic breathing (p < 0.05). The correlation between CC distance and coil position was best for forced abdominal breathing and a marker coil in the abdominal position (r = 0.89 +/- 0.04); for AP and ML distance, forced thoracic breathing and a coil in the thoracic position was best (r = 0.84 +/- 0.03 and 0.82 +/- 0.03, respectively). In quiet breathing, a lower correlation was found. CONCLUSION: A fiducial marker coil external to the thorax in combination with dMRI is a new technique to yield quantitative information on the correlation of internal organ and external chest wall motion. Correlations are highly dependent on the breathing maneuver.

Abdomen↗