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Biomedical subjects

D Otto

Publications and source records attributed to D Otto.

At least 19 recordsLinked to original sources
PubMed2004

Pre-operative localisation of hyperfunctional parathyroid tissue with 11C-methionine PET.

PURPOSE: Previous studies have shown high sensitivity of positron emission tomography (PET) with 11C-methionine in the pre-operative localisation of parathyroid adenoma and hyperplasia. Nonetheless, in secondary and tertiary hyperparathyroidism (HPT) and in patients with recurrent disease, pre-operative localisation of adenomatous (PTA) or hyperplastic tissue is still a problem with all available methods. The aim of this study was to define the optimal imaging protocol and to compare the diagnostic value of 11C-methionine PET and 99mTc-methoxyisobutylisonitrile (MIBI) single-photon emission computed tomography (SPECT): in particular, we wished to define the benefit of 11C-methionine in those patients with inconclusive or negative conventional imaging. METHODS: Thirty highly pre-selected patients with HPT were enrolled. Sixteen patients had primary HPT, 12 patients had secondary HPT, and two patients had recurrences of parathyroid carcinomas. All patients had ultrasound of the neck, dual-phase scintigraphy with 99mTc-MIBI and PET with 11C-methionine. SUV(parathyroid)/SUV(cervical soft tissue) (target-to-background) and SUV(parathyroid tissue)/SUV(thyroid tissue) (target-to-non-target) ratios were calculated. After surgery, histology of specimens was obtained in all patients but one. RESULTS: In 12 patients with secondary or tertiary HPT, 36 hyperplastic parathyroid glands were histologically verified. Twenty-five of 36 lesions (69%) were detected with 11C-methionine PET and 17 (47%) with 99mTc-MIBI scintigraphy. PET studies were positive in 17/18 (94%) cases in which HPT was related to adenomas or carcinomas. 99mTc-MIBI scintigraphy/SPECT yielded pathological lesions in 9/18 cases (50%). All eight atypical localisations of parathyroid glands were detected with PET but only six of the eight were detected with 99mTc-MIBI scintigraphy/SPECT. In 10/11 patients with recurrent HPT and non-diagnostic scintigraphy/SPECT, hyperfunctional parathyroid tissue was identified with 11C-methionine PET. The highest SUV(parathyroid)/SUV(cervical soft tissue) ratio was found 10 min, and the highest SUV(parathyroid tissue)/SUV(thyroid tissue) ratio 40 min post injection. In three patients clear delineation of hyperfunctional tissue was only achieved after 40 min post injection. CONCLUSION: 11C-methionine PET is a clinically useful method in highly pre-selected patients with recurrent primary HPT as well as in secondary and tertiary HPT if ultrasound and 99mTc-MIBI SPECT are inconclusive or negative. PET imaging of atypical PTA localisations is more accurate than conventional scintigraphy. In order to achieve optimal contrast of parathyroid glands versus thyroid tissue and adjacent soft tissue, imaging at both 10 min and 40 min is recommended.

Adult↗
PubMed2004

Phase I and pharmacokinetic study of TZT-1027, a novel synthetic dolastatin 10 derivative, administered as a 1-hour intravenous infusion every 3 weeks in patients with advanced refractory cancer.

BACKGROUND: TZT-1027 is a synthetic dolastatin 10 analog with antineoplastic properties in various cell lines and tumor xenografts. The purpose of this phase I study was to evaluate the safety and toxicity, maximum tolerated dose, pharmacokinetics and pharmacodynamics, clinical and metabolic antitumor activity of TZT-1027 when given as a 1-h intravenous infusion every 3 weeks in patients with refractory solid tumors. PATIENTS AND METHODS: Patients had a histologically verified refractory tumor with measurable disease, were > or = 18 years old, had an Eastern Cooperative Oncology Group performance status <2 and adequate bone marrow, liver, renal and cardiac function. Dose-limiting toxicity was defined as platelets <25 x 10(9)/l, neutrophils <0.5 x 10(9)/l for >5 days, febrile neutropenia > or = 38.5 degrees C with grade 4 (National Cancer Institute-common toxicity criteria) neutropenia, or grade 3/4 non-hematological toxicity excluding nausea and vomiting. The last dose was the dose where > or = 2 out of six patients experienced dose-limiting toxicity in cycle one. The maximum tolerated dose was one dose level below with less than two of six patients with dose-limiting events. RESULTS: Twenty-one non-selected, fully evaluable patients were enrolled. The majority were male (19) and the median age was 55 years (range 39-67). Dose levels of TZT-1027 ranged from 1.35 to 3.0 mg/m(2). The median number of cycles was two (range 1-4). Dose-limiting toxicities were observed in three patients at the 3.0 mg/m(2) dose level, including neutropenia, fatigue and a short lasting, reversible peripheral neurotoxic syndrome. The most common toxicities per patient were fatigue, anorexia, alopecia, nausea, constipation, leukopenia and neutropenia. Based on RECIST criteria, the best response was stable disease in seven patients. The pharmacokinetic evaluation revealed a T(1/2) of approximately 7 h and linear kinetics. CONCLUSIONS: The recommended dose of TZT-1027 for the 3-weekly administration is 2.7 mg/m(2). Neutropenia, fatigue and a reversible peripheral neurotoxic syndrome are dose-limiting with this schedule. TZT-1027 may be associated with neurological side-effects in patients previously exposed to neurotoxic compounds such as oxaliplatin.

Adult↗
PubMed2002

Influence of rhTSH on [(18)F]fluorodeoxyglucose uptake by differentiated thyroid carcinoma.

The influence of serum TSH levels on fluorine-18 fluorodeoxyglucose (FDG) uptake by recurrences or metastases of differentiated thyroid carcinomas has not yet been clarified. The aim of this study was to ascertain whether the administration of recombinant human thyrotropin (rhTSH) stimulates FDG uptake by such lesions. In this prospective study, 30 patients with positive or equivocal thyroglobulin (Tg) levels and negative or equivocal iodine-131 and/or morphological imaging results (ultrasound, MRI, CT) underwent FDG positron emission tomography (PET) under exogenous TSH suppression and under exogenous TSH stimulation of serum levels by injection of rhTSH. The mean interval between the FDG-PET studies under these two conditions was 9.3+/-8.8 weeks. Serum TSH levels and free thyroid hormones were determined on each occasion. FDG uptake was quantitated using tumour to background ratios (TBRs) and standardised uptake values (SUVs). Under TSH suppression there was focal FDG accumulation in nine subjects (22 tumour-like lesions). The total number of foci was 45. After exogenous TSH stimulation, the number of patients in whom FDG foci were detected was 19, and the number of foci identified was 82 (78 tumour-like lesions). TBR of regions showing positive FDG contrast with either of the modalities averaged 2.54+/-1.89, and under stimulated TSH levels, 5.51+/-2.99 ( P<0.0001). Corresponding SUVs were 2.05+/-1.45 versus 2.77+/-1.58 ( P<0.001). In a small number ( n=4) of foci related to inflammatory lymph nodes, TBR and SUV were only marginally increased under TSH stimulation (2.01+/-0.38 and 1.07+/-0.38, respectively), and the values did not differ significantly from those obtained under suppression. These results provide the first direct evidence that TSH stimulates FDG uptake by differentiated thyroid carcinoma and that, therefore, FDG-PET is more accurate under rhTSH than under suppression.

Adult↗
PubMed2002

Monitoring isotretinoin therapy in thyroid cancer using 18F-FDG PET.

Treatment with isotretinoin (13-cis-retinoic acid, 13-cis-RA) is a recent additional option in advanced, otherwise intractable differentiated thyroid cancers. The aim of this study was to evaluate fluorine-18 fluorodeoxyglucose positron emission tomography (18F-FDG PET) in the prediction and the monitoring of response to 13-cis-RA therapy. Twenty-one patients with advanced differentiated thyroid cancers were investigated using 18F-FDG PET and iodine-131 whole-body scans before and 3, 6 and 9 months after initiation of 13-cis-RA therapy. After 9 months, 13-cis-RA treatment was discontinued and imaging procedures repeated 3 months later. Average 18F-FDG uptake (SUV) decreased significantly during 13-cis-RA therapy but subsequently increased in five of eight patients after withdrawal of 13-cis-RA. 18F-FDG uptake (SUV) 3 months after onset of 13-cis-RA therapy was significantly lower in patients who developed increased 131I uptake in their tumour sites than in patients with no subsequent increase in 131I uptake. There was no relationship between serum thyroglobulin level on the one hand and simultaneously measured 131I or 18F-FDG uptake on the other hand. There was a tendency towards lower 18F-FDG uptake in tumour manifestations with a better outcome. Therefore, 18F-FDG PET at 3 months after the start of treatment promises to differentiate between those patients who will eventually benefit from 13-cis-RA and those who will not. In conclusion, these data indicate that 18F-FDG PET is a useful tool for the evaluation and monitoring of adjuvant therapy with 13-cis-RA in thyroid cancer.

Adenocarcinoma↗
PubMed2001

Early thrombolysis inhibits peri-infarct depolarizations in embolic MCA occlusion.

Rats submitted to middle cerebral artery (MCA) clot embolism were treated with tissue plasminogen activator (TPA) 1.5 and 3.5 h post-occlusion. Reperfusion patterns were monitored by measuring cortical laser-Doppler flow; the direct current potential was measured to detect peri-infarct depolarizations (PID), a known mechanism of ischemic injury. TPA treatment induced reperfusion in 58% of treated animals that was delayed by 41 +/- 7 min (mean +/- s.e.m.) from treatment onset. The probability of reperfusion did not differ significantly between the two treatment groups. TPA treatment led to a 3-fold reduced frequency of PID if administered early or if successful reperfusion was observed (each p < 0.001). Early thrombolysis inhibits, but does not block, PID as an important mechanism of ischemic injury in embolic stroke.

Animals↗
PubMed2001

The effect of instrumental and vocal music on adherence to a physical rehabilitation exercise program with persons who are elderly.

This study compared live, instrumental music, vocal music, and no music on the repetition frequencies for 14 prescribed physical therapy rehabilitation exercises. Male (N = 4) and female (N = 15) residents of care centers for older adults served as subjects. They ranged in age from 65 to 90 years (M= 84.3), and were either referred to physical therapy or were already involved in a physical therapy exercise pro-gram. All subjects (N = 19) participated in 6 treatment sessions under 3 conditions: Two sessions with live instrumental music, two with live vocal music, and two with no music. In all music sessions, familiar and recognizable songs were paired with specific exercises. Each exercise in all conditions had the same duration, and a metronome established consistent tempos. Each session was videotaped for later review and data collection. Analyses of variance were calculated for treatment effects and mean differences among the three conditions which yielded significant treatment effects and treatment differences among conditions for 6 of the 14 exercises. Unsolicited comments from subjects indicated preference for music over no music conditions while exercising. Further study is required to establish the relationship between music enhanced exercises and adherence to exercise regimens in populations of older adults.

Aged↗
PubMed2001

[Follow-up of differentiated thyroid cancer patients using rhTSH--preliminary results].

AIM: In the follow-up of patients with advanced stage thyroid cancer radioiodine scintigraphy, F-18-FDG PET and tumormarker hTg using stimulation with recombinant human TSH (rhTSH) were compared to the results of same diagnostic procedures during TSH-suppression or endogenous TSH-stimulation. METHODS: 30 patients were investigated in hypothyroidism and after application of rhTSH regarding the serum hormone concentrations, hTg, radioiodine scans and FGD-PET scans. RESULTS: Radioiodine avidity and FDG uptake were significantly higher in 7/30 and 3/5 patients, respectively, compared to endogenous stimulation or TSH-suppression. In about one third of patients hTg increased more than 30%. CONCLUSION: Our preliminary results indicate a sufficient feasibility and sensitivity of rhTSH not only in the follow-up by hTg and radioiodine scan but also in FDG-PET.

Adult↗
PubMed2001

[1-(11)C]Acetate as a quantitative perfusion tracer in myocardial PET.

UNLABELLED: Our objective was to investigate the properties of [1-(11)C]acetate as a quantitative perfusion tracer for myocardial PET studies. METHODS: We determined the flow dependence of the effective acetate extraction by a comparison with [(13)N]ammonia in 24 patients at rest (n = 8) and under pharmacologic vasodilation (n = 16). Furthermore, we compared the statistical quality of the perfusion values derived with both tracers. Quantification was based on an irreversible 2-compartment model for [(13)N]ammonia and a reversible 1-compartment model for [1-(11)C]acetate. Area-conserving polar maps were used to determine the correlation between the unidirectional uptake parameters of both tracers on a pixel-by-pixel basis for the whole left ventricular myocardium. RESULTS: A fit of a generalized Renkin-Crone formula to the data yielded the unidirectional acetate extraction fraction E(f) = 1 - 0.64e(-1.20/f). An extraction correction based on this formula led to good quantitative agreement of perfusion values derived with [(13)N]ammonia and [1-(11)C]acetate over the whole observed flow range (average difference of flow values, 3%; correlation coefficient, 0.96). This agreement proved the applicability of acetate as a quantitative perfusion tracer even under stress conditions. An analysis of the statistical properties of the parameter estimates showed, moreover, that statistical errors were reduced by a factor of nearly 2 in comparison with ammonia. CONCLUSION: [1-(11)C]acetate allows accurate quantification of myocardial perfusion with PET at rest as well as under stress conditions. The use of acetate leads to distinctly improved statistical accuracy for the perfusion estimates in comparison with ammonia. This accuracy facilitates the generation of reliable parametric polar maps, which are especially useful for clinical application of myocardial perfusion quantification.

Acetic Acid↗
PubMed2000

Increased resistance to acetaminophen hepatotoxicity in mice lacking glutathione S-transferase Pi.

Overdose of acetaminophen, a widely used analgesic drug, can result in severe hepatotoxicity and is often fatal. This toxic reaction is associated with metabolic activation by the P450 system to form a quinoneimine metabolite, N-acetyl-p-benzoquinoneimine (NAPQI), which covalently binds to proteins and other macromolecules to cause cellular damage. At low doses, NAPQI is efficiently detoxified, principally by conjugation with glutathione, a reaction catalyzed in part by the glutathione S-transferases (GST), such as GST Pi. To assess the role of GST in acetaminophen hepatotoxicity, we examined acetaminophen metabolism and liver damage in mice nulled for GstP (GstP1/P2((-/-))). Contrary to our expectations, instead of being more sensitive, GstP null mice were highly resistant to the hepatotoxic effects of this compound. No significant differences between wild-type (GstP1/P2((+/+))) mice and GstP1/P2((-/-)) nulls in either the rate or route of metabolism, particularly to glutathione conjugates, or in the levels of covalent binding of acetaminophen-reactive metabolites to cellular protein were observed. However, although a similar rapid depletion of hepatic reduced glutathione (GSH) was found in both GstP1/P2((+/+)) and GstP1/P2((-/-)) mice, GSH levels only recovered in the GstP1/P2((-/-)) mice. These data demonstrate that GstP does not contribute in vivo to the formation of glutathione conjugates of acetaminophen but plays a novel and unexpected role in the toxicity of this compound. This study identifies new ways in which GST can modulate cellular sensitivity to toxic effects and suggests that the level of GST Pi may be an important and contributing factor in the sensitivity of patients with acetaminophen-induced hepatotoxicity.

Acetaminophen↗
PubMed2000

Digital selenium radiography: detection of subtle pulmonary lesions on images acquired with and without an additional antiscatter grid.

OBJECTIVE: the objective of this ROC-study was to evaluate the diagnostic efficacy of images acquired with a grid in digital selenium radiography compared to that on images obtained with the integrated air gap only. MATERIALS AND METHODS: seven types of simulated lesions were superimposed onto an anthropomorphic chest phantom. Selenium radiography images were obtained either with or without an additional antiscatter grid. For images acquired with a grid either a similar or increased exposure level was used. Both normal and obese patients were simulated. RESULTS: When a grid was used with an equivalent detector dose and a higher exposure, diagnostic performance was significantly improved as compared to images obtained with only the air gap. ROC curve areas for mediastinal nodules and catheters were substantially higher for images acquired with a grid and the same exposure level compared to images obtained without a grid. However, detection of linear, net-shaped and reticulonodular structures in peripheral lung regions was significantly worse when a grid was used with an equivalent exposure level. Concerning the interpretation of images obtained from the normal and obese phantom models, no substantial differences were observed. CONCLUSION: a marked improvement in diagnostic performance could be achieved by means of the use of an additional antiscatter grid and an equivalent detector dose. However, when the same exposure was used, images acquired with the grid allowed a better detection of mediastinal structures although a worse performance was evident in radiolucent lung regions. Therefore, the routine use of a grid without increased exposure is not recommended.

Humans↗
PubMed1999

The Influence of Background Music on Task Engagement in Frail, Older Persons in Residential Care.

Colmery-O'Neil Veterans Affairs Medical CenterThe purpose of this study was to examine the effects of preferred background music on the engagement of residents of a nursing care facility in therapeutic recreation tasks. Eighteen subjects were assigned to one of two groups and both groups participated in a series of 12 weekly sessions in which the background conditions were randomly ordered. All subjects experienced four sessions each of 10 minutes of (a) silence, (b) preferred background music, and (c) nonpreferred background music. Videotapes were made of all sessions and an observer recorded the number of 30-second time intervals in which each subject was on task. A one-way analysis of variance calculated for frequencies of time intervals for the three conditions revealed no statistically significant differences. It was noted, however, that the therapist tended to prompt more conversations during the preferred music, and when subjects responded they generally dropped their task participation. The investigators concluded that background music may influence the therapists' behaviors which may, in turn, influence responses of their program participants. Further study of the effects of background music on task engagement among care home residents is recommended.

Journal Article↗
PubMed1999

Neuroprotection by estrogens in a mouse model of focal cerebral ischemia and in cultured neurons: evidence for a receptor-independent antioxidative mechanism.

Estrogens have been suggested for the treatment of neurodegenerative disorders, including stroke, because of their neuroprotective activities against various neurotoxic stimuli such as glutamate, glucose deprivation, iron, or beta-amyloid. Here, the authors report that 17beta-estradiol (0.3 to 30 mg/kg) and 2-OH-estradiol (0.003 to 30 mg/kg) reduced brain tissue damage after permanent occlusion of the middle cerebral artery in male NMRI mice. In vitro, 17beta-estradiol (1 to 10 micromol/L) and 2-OH-estradiol (0.01 to 1 micromol/L) reduced the percentage of damaged chick embryonic neurons treated with FeSO4. In these primary neurons exposed to FeSO4, the authors also found reactive oxygen species to be diminished after treatment with 17beta-estradiol (1 to 10 micromol/L) or 2-OH-estradiol (0.01 to 10 micromol/L), suggesting a strong antioxidant activity of the estrogens that were used. Neither the neuroprotective effect nor the free radical scavenging properties of the estrogens were influenced by the estrogen receptor antagonist tamoxifen. The authors conclude that estrogens protect neurons against damage by radical scavenging rather than through estrogen receptor activation.

Animals↗
PubMed1999

Detection of simulated interstitial lung disease and catheters with selenium, storage phosphor, and film-based radiography.

PURPOSE: To evaluate the diagnostic performance of storage phosphor and digital selenium radiography (DSR) with asymmetric and symmetric screen-film systems at different speeds in the detection of simulated interstitial lung disease and catheters. MATERIALS AND METHODS: Patterns of simulated interstitial lung disease and catheters were superimposed over an anthropomorphic chest phantom. Hard-copy images were generated at DSR (200-, 400-, and 600-speed), storage phosphor radiography (200- and 400-speed), and asymmetric (400-speed) and symmetric (200- and 400-speed) screen-film imaging. Surface doses were measured, and receiver operating characteristic analyses were performed. RESULTS: No statistically significant differences were found between the detector systems with the same speeds for each interstitial pattern. Significantly poorer results were found at 600-speed DSR than at 200-speed DSR. Detection of catheters and nodules over high-attenuation areas was significantly worse with the symmetric screen-film system than with the other detectors. The surface dose with the DSR system, without a grid, was about 50% less than that of the other detector systems, with grids, at the same speed. CONCLUSION: No significant difference was found in the diagnostic performance at DSR, storage phosphor radiography, and film-based radiography for simulated interstitial lung disease at corresponding speeds; there was a reduction in the surface dose of about 50% with the 400-speed DSR system.

Catheterization↗
PubMed1998

Subtle pulmonary abnormalities: detection on monitors with varying spatial resolutions and maximum luminance levels compared with detection on storage phosphor radiographic hard copies.

PURPOSE: The purpose of this receiver operating characteristic study was to compare diagnostic efficacy with images displayed on monitors of varying spatial resolutions and maximum luminance levels to that with storage phosphor radiographic hard copies. MATERIALS AND METHODS: Seven types of simulated lesions were superimposed onto an anthropomorphic chest phantom. Images were viewed by five radiologists on a 2,560 x 2,048 pixel monitor (maximum luminance, 75 foot-lamberts), on two 1,024 x 1,024 monitors with maximum luminance levels of 25 foot-lamberts and 75 foot-lamberts, respectively, as well as on hard copies. Monitor images were viewed both without and with systematic magnification. RESULTS: Overall visualization of the lesions was best on hard copies, but visualization on the 2,560 x 2,048 monitor was not found to be substantially different. Lines, reticular opacifications, and catheters were found to be particularly poorly visualized with the 1,024 x 1,024 monitor. These results could be statistically significantly improved only with a systematic magnification; however, this involved a considerable increase in viewing time. Observer performance was markedly inferior with the 1,024 x 1,024 monitor with the lower luminance. CONCLUSION: Diagnostic performance with a 1,024 x 1,024 monitor is statistically significantly inferior to that with hard copies. A statistically significant improvement can be achieved with a high-resolution 2,560 x 2,048 monitor with a maximum luminance of 75 foot-lamberts.

Angiography, Digital Subtraction↗
PubMed1998

[Unilateral pulmonary vein atresia in early adulthood].

Unilateral pulmonary vein atresia is a rare condition in adults that may cause serious diagnostic problems because of unspecific clinical findings. A 28-year old female patient is described who presented with signs of recurrent pulmonary embolism with shortness of breathing, unilateral thoracic pain and several episodes of haemoptysis. Ventilation and perfusion scans showed a total lack of perfusion in the right lung with only slight disturbance of ventilation. However, no marked increase of pulmonary artery pressure and no signs of a recent thrombosis of peripheral veins were found. Transoesophageal echocardiography and pulmonary angiography in combination with aortography revealed the diagnosis of unilateral pulmonary vein atresia with abnormal branches of bronchial arteries. There is a considerably left-to-right shunt with return of flow from the bronchial arteries to the right and afterwards to the left pulmonary artery. Clinical, radiological and nuclear medical findings as well as therapeutical options are described.

Adult↗
PubMed1997

Arthroscopic posterior cruciate ligament reconstruction using four-strand hamstring tendon graft and interference screws.

We describe an arthroscopic technique for reconstruction of the posterior cruciate ligament (PCL) using a four-strand hamstring tendon graft. The femoral tunnel is drilled via the anterolateral portal and the tibial tunnel through the skin incision from the graft harvest. The graft is pulled through the tunnels with pullout sutures and fastened with interference screws. The results to date are good and the procedure can often be performed as day surgery.

Ambulatory Surgical Procedures↗
PubMed1997

Transfusion of platelet-rich plasma from the organ donor during cardiac transplantation.

STUDY OBJECTIVE: To evaluate whether transfusion of platelet-rich plasma from the organ donor during cardiac transplantation can influence the amount of the needed homologous blood products. DESIGN: Randomized, controlled study. SETTING: University hospital. PATIENTS: 16 ASA physical status III patients undergoing orthotopic cardiac transplantation. INTERVENTIONS: Eight patients received donor plasma, while another 8 patients served as a control group. Blood from the organ donor was acquired during cardiac explantation. Thereafter platelet-rich plasma was separated by plasmapheresis (2400 turns per minute). The plasma was then transfused to the organ recipient at the end of the cardiac transplantation. The control group received a similar amount of albumin 5%. MEASUREMENTS AND MAIN RESULTS: In the patients who received donor plasma, the platelet count increased significantly from 98,000 +/- 49,000 mm-3 to 123,000 +/- 55,000 mm-3, the postoperative requirement of packed red blood cells (PRBCs) was 5.8 +/- 4.5 units, which was significantly lower as compared to the control group (10.8 +/- 5.9 units). CONCLUSIONS: Transfusion of platelet-rich plasma from the organ donor to the recipient was confirmed to be feasible, the number of postoperatively transfused PRBCs was reduced.

Blood Transfusion↗