Analysis of microtraces in invasive traumas using SEM/EDS.

Scanning electron microscopy in combination with energy-dispersive X-ray spectrometry (SEM/EDS) is a proven forensic tool and has been used to analyze several kinds of trace evidence. A forensic application of SEM/EDS is the examination of morphological characteristics of tool marks that tools and instruments leave on bone. The microtraces that are left behind by these tools and instruments on the bone are, however, often ignored or not noticed at all. In this paper we will describe the use of SEM/EDS for the analysis of microtraces in invasive sharp-force, blunt-force and bone-hacking traumas in bone. This research is part of a larger multi-disciplinary approach in which pathologists, forensic anthropologists, toolmark and microtrace experts work together to link observed injuries to a suspected weapon or, in case of an unknown weapon, to indicate a group of objects that could have been used as a weapon. Although there are a few difficulties one have to consider, the method itself is rather simple and straightforward to apply. A sample of dry and clean bone is placed into the SEM sample chamber and brightness and contrast are set such that bone appears grey, metal appears white and organic material appears black. The sample is then searched manually to find relevant features. Once features are found their elemental composition is measured by an energy dispersive X-ray spectrometer (EDS). This method is illustrated using several cases. It is shown that SEM/EDS analysis of microtraces in bone is a valuable tool to get clues about an unknown weapon and can associate a specific weapon with injuries on the basis of appearance and elemental composition. In particular the separate results from the various disciplines are complementary and may be combined to reach a conclusion with a stronger probative value. This is not only useful in the courtroom but above all in criminal investigations when one have to know for what weapon or object to look for.

Quantifying drug-related 5-HT1A receptor occupancy with.

RATIONALE: There is an increased interest in measuring the interaction of new or established drugs with their targets, in order to gain a better understanding of their mechanisms of action. PET can provide this information if an appropriate radioligand is available. [18F]MPPF (4-(2'-methoxyphenyl)-1-[2'-(N-2"-pyridinyl)-p-[18F]fluorobenzamido]ethylpiperazine) is a selective radioligand for serotonin 5-HT1A receptors. We have established that the binding potential (BP=Bmax/KD) of [18F]MPPF for cerebral 5-HT1A receptors can be assessed in human brain without arterial sampling. OBJECTIVES: The aim of this study was to assess if 5-HT1A receptor occupancy can be measured through calculation of a drug-related decrease in BP with [18F]MPPF and PET. METHODS: Six volunteers were scanned twice using a Siemens Exact HR+ camera following injection of 70+/-18 MBq [18F]MPPF (baseline and medicated conditions). Before the second scan, volunteers orally received either 3x10 mg pindolol at T=-15.5 h, T=-6.5 h, and T=-1.5 h (n=3) or 10 mg buspirone in a single dose at T=-1.5 h (n=3). Binding potentials were calculated using the simplified reference tissue model with the cerebellum as reference. RESULTS: Administration of 30 mg pindolol led to a significant reduction in [18F]MPPF binding potential of 42+/-17%. In contrast, no significant reduction of [18F]MPPF binding potential was observed following administration of buspirone (5+/-17%). CONCLUSIONS: These results show that [18F]MPPF can be used for measurement of drug-related 5-HT1A receptor occupancy and may be of particular interest in determining the 5-HT1A receptor interaction of new or established drugs in phase 1 and early phase 2 drug trials. Apparently, the 5-HT1A partial agonist buspirone is already clinically effective at low levels of 5-HT1A receptor occupancy.

L-3-[123I]iodo-alpha-methyl-tyrosine SPECT in non-small cell lung cancer: preliminary observations.

UNLABELLED: L-3-[123I]iodo-alpha-methyl-tyrosine (IMT) is a modified amino acid that is avidly taken up by many tumors. Uptake is based on the increased transmembrane transport of amino acids in malignancies. IMT is the only amino acid tracer suitable for SPECT. The aim of this study was to determine the feasibility of IMT SPECT in the detection, staging, and treatment evaluation of non-small cell lung cancer. METHODS: We evaluated 44 IMT SPECT studies in 17 patients with histologically proven non-small cell lung cancer, stage III. IMT SPECT and planar imaging of the chest was performed before, 2 wk after, and 3 mo after 60 Gy radiotherapy. Staging was based on the findings of bronchoscopy, chest CT, mediastinoscopy, or explorative thoracotomy. After radiotherapy, CT and bronchoscopy were repeated to assess tumor response. RESULTS: In 15 of 16 evaluable primary tumors, avid IMT uptake was present (sensitivity, 94%), with a mean (+/-SD) tumor-to-background ratio (T/B) of 2.95 +/- 0.78 (range, 1.7-4.9). In 12 of 14 patients (86%) with mediastinal involvement, IMT SPECT detected one or more mediastinal metastases. However, only 13 of 20 mediastinal metastases were detected in lesion analysis (lesion-based sensitivity, 65%). For lesions < 2 cm in diameter, sensitivity was 42%. FDG PET (available for 5 patients) detected more known and unknown lesions than did IMT SPECT. After radiotherapy, T/B had fallen to 1.84 +/- 0.29 (P < 0.001 vs. baseline), and 3 mo later to 1.61 +/- 0.41 (not statistically significant vs. second study). Considerable nonspecific uptake was found in irradiated normal lung tissue (mean ratio to nonirradiated tissue, 1.79 +/- 0.53), persisting for > 3 mo. No relationship was observed between various IMT uptake parameters and the presence of residual viable tumor tissue or survival. CONCLUSION: IMT SPECT has a high sensitivity for the detection of primary non-small cell lung cancer. Although patient-based sensitivity in detecting mediastinal spread was adequate, sensitivity for individual lesions, especially for small metastases (<2 cm in diameter) was too low to be clinically helpful. Radiotherapy caused considerable nonspecific IMT uptake, which also limits applicability in evaluating the results of treatment.

Imaging of beta-adrenoceptors in the human thorax using (S)-[(11)C]CGP12388 and positron emission tomography.

We report positron emission tomography studies of beta-adrenoceptors in the human thorax with (S)-[(11)C]CGP12388 (4-(3-(2'-[(11)C]-isopropylamino)-2-hydroxypropoxy)-2H-benzimidazol-2-one). Beta-adrenoceptors have previously been quantified using (S)-[(11)C]CGP12177 (4-(3-tert-butylamino-2-hydroxypropoxy)-2H-benzimidazol-2[(11)C]-one), but (S)-[(11)C]CGP12388 is more easily prepared and therefore more suitable in a clinical setting. (S)-[(11)C]CGP12388 was administered to five healthy volunteers on two separate days (control and pindolol block study). Arterial plasma samples were used to determine clearance, metabolites, and protein binding of the radioligand. Heart, lung and spleen showed high uptake of radioactivity, which was strongly suppressed (68-77%) by pindolol. Plasma clearance of (S)-[(11)C]CGP12388 was rapid, binding to plasma proteins was low (53+/-4%), and the radioligand was slowly metabolized. (S)-[(11)C]CGP12388 produces high-quality images of the human thorax. Uptake of (S)-[(11)C]CGP12388 in heart, lung and spleen represents binding to beta-adrenoceptors. (S)-[(11)C]-CGP12388 seems useful for imaging of beta-adrenoceptors in a clinical setting.

In vivo delineation of 5-HT1A receptors in human brain with [18F]MPPF.

UNLABELLED: Serotonin-1A (5-hydroxytryptamine-1A [5-HT1A]) receptors have been reported to play an important role in the pathophysiology of a variety of psychiatric and neurodegenerative disorders. Animal experiments have shown that 4-(2'-methoxyphenyl)-1-[2'-(N-2'-pyridinyl)-p-[18F]fluorobenzamido ]ethylpiperazine ([18F]MPPF) may be suitable for 5-HT1A receptor imaging in humans. The aim of this study was to determine if [18F]MPPF can be used for the quantitative analysis of 5-HT1A receptor densities in brain regions of healthy human volunteers. METHODS: [15O]H2O perfusion scanning was performed before intravenous injection of [18F]MPPF to obtain anatomic information. Cerebral radioactivity was monitored using a PET camera. Plasma metabolites of [18F]MPPF were determined by high-performance liquid chromatography. Binding potentials were calculated using the metabolite-corrected arterial input function and a linear graphic method (Logan-Patlak analysis). RESULTS: The highest levels of radioactivity were observed in the medial temporal cortex, especially in the hippocampal area. In contrast, the cerebellum and basal ganglia showed low uptake of 18F, in accordance with known 5-HT1A receptor distribution. The calculated binding potentials correlated well with literature values for 5-HT1A receptor densities. The binding potentials for [18F]MPPF were 4-6 times lower than those that have been reported for [carbonyl-1C]-(N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyrid yl) cyclohexane-carboxamide (WAY 100635), indicating that [18F]MPPF has a lower in vivo affinity for 5-HT1A receptors. CONCLUSION: These results confirm that [18F]MPPF can be used for the quantitative analysis of 5-HT1A receptor distribution in the living human brain. The rapid dissociation from the receptor makes this ligand a possible candidate to monitor changes in endogenous serotonin levels.

Quantitative imaging of 5-HT(1A) receptor binding in healthy volunteers with [(18)f]p-MPPF.

Animal experiments have shown that 4-(2'-methoxyphenyl)-1-[2'-(N-2"-pyridinyl)-p-[(18)F]fluorobenzamido+ ++] ethylpiperazine ([(18)F]p-MPPF) can be used for 5-hydroxytryptamine(1A) (5-HT(1A)) receptor imaging. The aim of this study was to develop a method for the quantitative imaging of 5-HT(1A) receptors in healthy volunteers with [(18)F]p-MPPF. After injection of [(18)F]p-MPPF radioactivity was rapidly taken up in the brain, with the highest accumulation in the medial temporal cortex. Low levels of radioactivity were found in cerebellum and basal ganglia. Plasma clearance and metabolism of [(18)F]p-MPPF resulted in only about 1% of the radioactivity in plasma as parent radioligand after 10 min. Using a linear graphical method (Logan-Patlak), binding potentials were calculated in several brain areas. A good correlation (r = 0.95) was found between the obtained binding potentials and literature values for 5-HT(1A) receptor densities. A good correlation (r = 0.96) was also found between the body weight-corrected region/cerebellum ratios and the respective binding potentials. Moreover, a blocking experiment with pindolol (n = 3) showed a decrease of 40% in the region/cerebellum ratios of the target areas. Compared to those of [carbonyl-(11)C]WAY-100635, the binding potentials were four to six times lower, indicating that [(18)F]p-MPPF has a lower in vivo affinity for 5-HT(1A) receptors. In conclusion, [(18)F]p-MPPF can be used for the quantitative analysis of 5-HT(1A) receptor distribution in human brain.

Preoperative staging of non-small-cell lung cancer with positron-emission tomography.

BACKGROUND: Determining the stage of non-small-cell lung cancer often requires multiple preoperative tests and invasive procedures. Whole-body positron-emission tomography (PET) may simplify and improve the evaluation of patients with this tumor. METHODS: We prospectively compared the ability of a standard approach to staging (computed tomography [CT], ultrasonography, bone scanning, and, when indicated, needle biopsies) and one involving PET to detect metastases in mediastinal lymph nodes and at distant sites in 102 patients with resectable non-small-cell lung cancer. The presence of mediastinal metastatic disease was confirmed histopathologically. Distant metastases that were detected by PET were further evaluated by standard imaging tests and biopsies. Patients were followed postoperatively for six months by standard methods to detect occult metastases. Logistic-regression analysis was used to evaluate the ability of PET and CT to identify malignant mediastinal lymph nodes. RESULTS: The sensitivity and specificity of PET for the detection of mediastinal metastases were 91 percent (95 percent confidence interval, 81 to 100 percent) and 86 percent (95 percent confidence interval, 78 to 94 percent), respectively. The corresponding values for CT were 75 percent (95 percent confidence interval, 60 to 90 percent) and 66 percent (95 percent confidence interval, 55 to 77 percent). When the results of PET and CT were adjusted for each other, only PET results were positively correlated with the histopathological findings in mediastinal lymph nodes (P<0.001). PET identified distant metastases that had not been found by standard methods in 11 of 102 patients. The sensitivity and specificity of PET for the detection of both mediastinal and distant metastatic disease were 95 percent (95 percent confidence interval, 88 to 100 percent) and 83 percent (95 percent confidence interval, 74 to 92 percent), respectively. The use of PET to identify the stage of the disease resulted in a different stage from the one determined by standard methods in 62 patients: the stage was lowered in 20 and raised in 42. CONCLUSIONS: PET improves the rate of detection of local and distant metastases in patients with non-small-cell lung cancer.

Practical reasons and reasonable practice: the case of euthanasia in The Netherlands.

Since the early 1970s the issue of euthanasia has been intensely debated in The Netherlands. Through these debates knowledge about medical practices involving the end of life was no longer confined to medical or legal quarters, but became public to a large extent. Following public opinion changes, the legal reaction to euthanasia changed. By prosecuting test cases the public prosecutors allowed the Dutch Supreme Court to formulate specific conditions in which euthanasia would go unpunished. The political debate about changing the criminal law, which still holds that euthanasia is a serious crime, developed at a much slower pace. Several extensive empirical studies were undertaken to gain valid knowledge about the medical practices. This article is concerned with a presentation of the various debates and the changes that took place in the fields of criminal law, politics, and medicine. The main conclusion is the hypothesis that a more open climate for medical practices concerning the end of life allows society to better control these practices.