Access to N-cyanosulfoximines by transition metal-free iminations of sulfoxides.

A transition metal-free synthesis of N-cyanosulfoximines from sulfoxides using N-chlorosuccinimide (NCS) as oxidising agent and cyanamide as nucleophilic amine source is reported. The products are obtained in moderate to excellent yields. The protocol enables an easy access to N-cyanosulfoximines from readily available starting materials under inversion of configuration at a preexisting stereogenic center.

[Resuscitation of a patient in the computed tomography unit]. / Der reanimationspflichtige Patient auf dem CT-Patiententisch.

An 80-year-old male patient presented with acute chest pain. Clinically an aortic dissection or pulmonary embolism was suspected therefore non-ECG-gated multislice computed tomography was performed and despite the lacking ECG gating the causative high grade coronary stenosis could be identified.

[Thunderclap headache caused by cerebellar infarction]. / Thunderclap headache durch Kleinhirninfarkt.

Thunderclap headache is an acute and severe headache and is often the first sign of a life-threatening neurovascular disorder. The case of a 44-year-old man is described who presented with a thunderclap headache as the only clinical symptom. The clinical examination did not reveal any other focal deficits or signs of motor or sensory failures. Routine blood tests, cerebral CT as well as cerebrospinal fluid analysis showed no pathological results. A cerebral MRI to exclude a symptomatic thunderclap headache revealed a right cerebellar infarction. This case expands the differential diagnosis of thunderclap headache and reinforces the need for magnetic resonance imaging in the evaluation of such patients, even when neurological examination, cerebral CT, and cerebrospinal fluid analysis are normal.

The concept of the GPOH-HD 2003 therapy study for pediatric Hodgkin's disease: evolution in the tradition of the DAL/GPOH studies.

Today it is possible to cure more than 90 % of children and adolescents with Hodgkin's disease with a combination of radiotherapy and chemotherapy. Since the DAL-HD 82 study, the main scientific focus has been on avoiding late effects such as the OPSI syndrome, late complications involving the heart, lungs, thyroid and/or gonads particularly sterility in men and premature onset of menopause in women, and the prevention of secondary malignancies. The GPOH-HD 2003 study will introduce FDG-PET to the initial diagnostic program and the assessment of response to therapy in order to evaluate further possibilities for reducing therapy. In this context, the central review of all clinical and radiological findings, systematically done since the DAL-HD 90 study, will be increasingly relevant in maintaining standardised stage classification and therapy group assignment which was established by the preceding studies. Continuing in the direction of the earlier studies, the indications for radiotherapy will be restricted even further. In the early stages (treatment group 1) patients with CR or a negative FDG-PET at the end of chemotherapy will receive no radiotherapy in order to reduce the risk of a secondary malignancy. In a randomized comparison, procarbazine will be replaced by dacarbazine in the COPP cycles to determine whether sterility in men and premature onset of menopause in women can be avoided by elimination of procarbazine while retaining the same clinical efficacy. Finally, relapse therapy is to be tailored according to the time of relapse, the initial therapy group, and the patient's response to the relapse therapy with more patients receiving autologous transplantation in order to further improve the results of relapse treatment.

Importance of F18-fluorodeoxy-D-2-glucose positron emission tomography (FDG-PET) for staging and therapy control of Hodgkin's lymphoma in childhood and adolescence - consequences for the GPOH-HD 2003 protocol.

The prognosis for children and adolescents with Hodgkin's lymphoma is excellent. However, many patients will show secondary malignancies 15-30 years after the initial diagnosis, which appears to be connected with the intensity of treatment during primary disease. In the GPOH-HD 95 trial, the indication for radiotherapy was limited to patients who did not show a complete remission after chemotherapy, as determined radiographically. In the future protocol, the indication for radiotherapy in patients with early-stage Hodgkin's lymphoma should be further refined by using FDG-PET for evaluating the response to chemotherapy. Furthermore, in patients at an advanced stage of the disease, it should be determined if sequential FDG-PET research during chemotherapy can separate patients into subgroups with an excellent or a poor prognosis. This article gives a review of the current literature on FDG-PET in patients with Hodgkin's lymphoma and outlines the consequences for future protocols.

[A giant malignant tumour of the skull-Case report and differential diagnosis]. / Ein gigantischer maligner Tumor der Kalotte - Fallbericht und Differentialdiagnose.

The case of a 72-year-old woman with a high-partially located tumor grown within a half year to a magnitude of 8.5 x 11 x 11 cm is reported. The patient remembered a mastectomy and axillary lymphadenectomy followed by chemotherapy and radiation 8 years ago. Therefore we assumed a skeletal metastasis of a breast cancer. After wide excision, an unusual morphology was found, allowing only a classification as a pleomorphic sarcoma. Searching for the pathohistological evaluation of the former breast tumor, a cystosarcoma phylloides malignum could be found out. The tumor described here can be identified as a metastasis of this rare neoplasm.

Prospective value of perfusion and X-ray attenuation imaging with single-photon emission and transmission computed tomography in acute cerebral ischemia.

BACKGROUND AND PURPOSE: The aim of the present study was to test the hypothesis that perfusion single-photon emission computed tomography (SPECT), carried out in addition to transmission computed tomography (TCT), improves the predictive value of brain imaging within the therapeutically relevant time window after acute cerebral ischemia. METHODS: Using TCT and [(99m)Tc]ethyl cysteinate dimer (ECD)-SPECT within 6 hours after symptom onset, we examined 108 patients (44 women, 64 men; mean age 65+/-13 years) with acute ischemic stroke attributed to the territory of the middle cerebral artery (MCA). In each case, 3 experts prospectively evaluated the early SPECT and TCT images. We correlated these ratings with follow-up TCT findings for the final infarction as well as with clinical outcome (Scandinavian Stroke Scale, Barthel Index, Modified Rankin Scale) after 30 and 90 days. RESULTS: Severe activity deficits on SPECT, not caused by local atrophy on TCT, were the best predictors (positive predictive value [PPV ]94%, 95% CI 89% to 99%; negative predictive value [NPV] 90%, 95% CI 78% to 100%; P<0.001) for evolving cerebral infarction. Complete MCA infarctions were predicted with significantly higher accuracy with early SPECT (area under receiver operating characteristic curve [AUC] index 0.91) compared with early TCT (AUC index 0.77) and clinical parameters (AUC index 0.73, P<0.05). Logistic regression analysis revealed 1 independent predictor for completed MCA territory infarction: SPECT activity deficits in the corresponding areas (PPV 88%, 95% CI 65% to 100%; NPV 96%, 95% CI 92% to 100%; P<0.001). Furthermore, death after stroke was optimally predicted by [(99m)Tc]ECD-SPECT. Clinical outcome up to 90 days after the stroke event best correlated with the degree of activity deficits in early SPECT (r=0.53, P<0.001). CONCLUSIONS: [(99m)Tc]ECD brain perfusion SPECT that completes TCT definitely improves the predictive value of brain imaging after acute cerebral ischemia. Thus, the combined imaging of brain edema and of cerebral perfusion early after stroke is recommended for clinical use.

[Fusion of MRI, fMRI and intraoperative MRI data. Methods and clinical significance exemplified by neurosurgical interventions]. / Fusion von MRT-, fMRT- und intraoperativen MRT-Daten. Methode und klinische Bedeutung am Beispiel neurochirurgischer Interventionen.

The aim of this work was to realize and clinically evaluate an image fusion platform for the integration of preoperative MRI and fMRI data into the intraoperative images of an interventional MRI system with a focus on neurosurgical procedures. A vertically open 0.5 T MRI scanner was equipped with a dedicated navigation system enabling the registration of additional imaging modalities (MRI, fMRI, CT) with the intraoperatively acquired data sets. These merged image data served as the basis for interventional planning and multimodal navigation. So far, the system has been used in 70 neurosurgical interventions (13 of which involved image data fusion--requiring 15 minutes extra time). The augmented navigation system is characterized by a higher frame rate and a higher image quality as compared to the system-integrated navigation based on continuously acquired (near) real time images. Patient movement and tissue shifts can be immediately detected by monitoring the morphological differences between both navigation scenes. The multimodal image fusion allowed a refined navigation planning especially for the resection of deeply seated brain lesions or pathologies close to eloquent areas. Augmented intraoperative orientation and instrument guidance improve the safety and accuracy of neurosurgical interventions.

[Multimodal SPECT and MRT imaging data analysis for an improvement in the diagnosis of idiopathic Parkinson's syndrome]. / Multimodale SPECT- und MRT-Bilddatenanalyse zur Verbesserung der Diagnostik des idiopathischen Parkinson-Syndroms.

Parkinson's disease (PD) is characterized by a degeneration of nigrostriatal dopaminergic neurons, which can be imaged with 123I-labeled 2 beta-carbomethoxy-3 beta-(4-iodophenyl) tropane ([123I]beta-CIT) and single-photon emission computed tomography (SPECT). However, the quality of the region of interest (ROI) technique used for quantitative analysis of SPECT data is compromised by limited anatomical information in the images. We investigated whether the diagnosis of PD can be improved by combining the use of SPECT images with morphological image data from magnetic resonance imaging (MRI)/computed tomography (CT). We examined 27 patients (8 men, 19 women; aged 55 +/- 13 years) with PD (Hoehn and Yahr stage 2.1 +/- 0.8) by high-resolution [123I]beta-CIT SPECT (185-200 MBq, Ceraspect camera). SPECT images were analyzed both by a unimodal technique (ROIs defined directly within the SPECT studies) and a multimodal technique (ROIs defined within individual MRI/CT studies and transferred to the corresponding interactively coregistered SPECT studies). [123I]beta-CIT binding ratios (cerebellum as reference), which were obtained for heads of caudate nuclei (CA), putamina (PU), and global striatal structures were compared with clinical parameters. Differences between contra- and ipsilateral (related to symptom dominance) striatal [123I]beta-CIT binding ratios proved to be larger in the multimodal ROI technique than in the unimodal approach (e.g., for PU: 1.2 vs. 0.7). Binding ratios obtained by the unimodal ROI technique were significantly correlated with those of the multimodal technique (e.g., for CA: y = 0.97x + 2.8; r = 0.70; P < 0.001). Concerning the correlations between SPECT data and clinical parameters, the significance levels in the multimodal ROI technique, for example, for the correlation between CA and the UPDRScom subscore (r = -0.49 vs. -0.32). These results show that the impact of [123I]beta-CIT SPECT for diagnosing PD is affected by the method used to analyze the SPECT images. The described multimodal approach, which is based on coregistration of SPECT and morphological imaging data, leads to improved determination of the degree of this dopaminergic disorder.

In vivo [125I]-iodobenzovesamicol binding reflects cortical cholinergic deficiency induced by specific immunolesion of rat basal forebrain cholinergic system.

In this study, radiolabeled iodobenzovesamicol (IBVM), which is known to bind with high affinity to the vesicular acetylcholine transporter, was tested for its usefulness in imaging cortical cholinergic deficits in vivo. To induce reductions in cortical cholinergic input, the cholinergic immunotoxin 192IgG-saporin was employed. This has been shown to selectively and efficiently destroy basal forebrain cholinergic neurons in rats. The efficiency of the immunolesion was verified by histochemical acetylcholinesterase staining. [125I]-IBVM binding before and after lesioning was measured using autoradiography. Basal forebrain cholinergic cell loss resulted in a considerable reduction in [125I]-IBVM binding in the cholinoceptive target regions, but not in the striatum and cerebellum, brain regions that do not receive a cholinergic input by the basal forebrain cholinergic nuclei, suggesting that [123I]-IBVM has potential in imaging cortical cholinergic deficits in vivo, at least in animals.

Improvement of brain SPECT by stabilization of Tc-99m-HMPAO with methylene blue or cobalt chloride. Comparison with Tc-99m-ECD.

AIM: This present study was carried out to investigate whether stabilization of Tc-99m-HMPAO with methylene blue (MB) or cobalt chloride (CC) causes a sensible improvement in image quality and how cerebral to noncerebral activity ratios compare with those of Tc-99m-ECD. METHODS: 30 minutes after preparation 400-600 MBq unstabilized Tc-99m-HMPAO (N = 35 patients), Tc-99m-HMPAO added with MB (N = 24 patients), added with CC (N = 30 patients) or Tc-99m-ECD (N = 28 patients) were injected. Radiochemical stability was measured in vitro with three chromatographical methods. Image quality was assessed quantitatively using two ratios, one of them determined by count densities of brain/scalp (Os), the other one by count densities of brain/nose (QN). In addition, image quality (0 = bad, 3 = excellent) and background activity (0 = high, 3 = no) were visually assessed by three independent observers. RESULTS: In contrast to unstabilized Tc-99m-HMPAO the integrity of the complexes of MB-Tc-99m-HMPAO, CC-Tc-99m-HMPAO and Tc-99m-ECD decreased only by a few percent during a period of 2 hours after reconstitution (66.8 +/- 9.9 vs. 93.0 +/- 2.5, 91.8 +/- 1.9 and 96.9 +/- 1.4%, p < 0.001). Qs and Qn (m.v. +/- SD) differed significantly between studies using unstabilized Tc-99m-HMPAO (3.0 +/- 0.4 and 2.1 +/- 0.3), MB-Tc-99m-HMPAO (3.4 +/- 0.4 and 2.3 +/- 0.3), CC-Tc-99m-HMPAO (3.6 +/- 0.6 and 2.6 +/- 0.4) and those using Tc-99m-ECD (4.3 +/- 0.7 and 4.8 +/- 1.4, p < 0.05 and < 0.001). Stabilization with CC or MB resulted in significant higher scoring of image quality and lower scoring of background activity in comparison to that of unstabilized Tc-99m-HMPAO, without reaching the scores obtained with Tc-99m-ECD. CONCLUSIONS: It is concluded that stabilization of Tc-99m-HMPAO with MB or CC definitely improves image quality in rCBF-SPECT, without reaching that of Tc-99m-ECD. Improvement of image quality results from the reduction of the amount of decomposition products that contribute to considerable extracerebral activity.

Iodo-QNB cortical binding and brain perfusion: effects of a cholinergic basal forebrain lesion in the rat.

This study deals with the question of whether in vivo application of [125I]iodo-quinuclidinyl-benzilate (QNB) is able to demonstrate changes in cortical muscarinic receptor density induced by a cholinergic immunolesion of the rat basal forebrain cholinergic system, and whether the potential effects on IQNB distribution in vivo are also associated with effects on regional cerebral perfusion. Immunolesioned and control animals were injected with (R,S) [125]iodo-QNB and with [99mTc]-d,l-hexamethylpropyleneamine oxime (HMPAO). The cerebral distribution of both tracers was imaged using double tracer autoradiography. Impaired cholinergic transmission was paralleled by a 10-15% increase of [125I]iodo-QNB binding in the regions of cortex and hippocampus. The local cerebral blood flow remained unchanged after cholinergic lesion.

The prognosis of mild cognitive impairment in the elderly.

PURPOSE: To determine whether or not subtypes of intellectual functioning are suitable to predict further cognitive decline in individuals with mild cognitive impairment. DESIGN: Naturalistic longitudinal study (mean interval 2.7 years). PATIENTS: 41 subjects with mild cognitive impairment who attended a memory clinic. METHODS: SIDAM, CT, SPECT, and ApoE genotype. RESULTS: At follow-up, 8 out of 41 patients (19.5%) with MCI had progressed to dementia, 8 patients (19.5%) had improved to normal levels of cognitive functioning, 25 patients (61%) had remained stable within the MCI group. At baseline the two prognostic groups differed significantly with regard to age, memory functions, orientation, and the degree of atrophy of the left medial temporal lobe on CT scan. CONCLUSION: The majority of MCI patients in this study remained cognitively stable within the observation period. Patients with older age, poorer test performance on memory tasks and orientation deficits are at higher risk of progressive decline to dementia. CT measures of medial temporal lobe atrophy may be a sensitive parameter of group discrimination.

DNA typing for natural killer cell inhibiting HLA-Cw groups NK1 and NK2 by PCR-SSP.

Over the last few years, natural killer (NK) cells have been shown to express MHC molecule recognizing receptors which are thought to function primarily as negative signaling receptors. HLA-Cw seems to play a key role as the corresponding ligand. Two distinct HLA-Cw groups which differ in amino acid residues 77 and 80 inhibit separate subsets of NK cells. In order to classify target cells with respect to their expression of HLA-Cw groups we established a group specific PCR-SSP which directly amplifies the relevant epitope coding sequences. The PCR protocol was validated by retyping cell lines obtained from the International Histocompatibility Workshop and by comparing those results with those acquired from allele-specific genotyping and serotyping on 80 donor-recipient pairs from our kidney transplantation unit. In the context of inhibitory HLA-Cw receptors, our protocol which definitively discriminates the two alternative epitopes is the more direct and thus more reliable approach, and is less labor intensive compared to an allele specific PCR or serotyping. In addition serotyping does not detect at all certain alleles. Basic NK cell research and clinical transplantation immunology may benefit from this newly established PCR SSP technique.

Age-specific cerebral perfusion in 4- to 15-year-old children: a high-resolution brain SPET study using 99mTc-ECD.

This study addresses the question of whether the normal range for distribution of local cerebral blood flow (lCBF) in adults can be transferred to the 4- to 15-year-old age group. Twenty-three children (age: 4-15 years; mean 11+/-3 years, group I) and 10 adults (age: 27-56 years; mean 45+/-10 years, group II) without evidence of cerebrovascular disease or other brain diseases underwent technetium-99m ethyl cysteinate dimer single-photon emission tomography. Counts in cortical and subcortical regions of interest (ROIs) were related to those in cerebellar ROIs (= 100%). Relative cortical activity in group I exceeded that in group II, particularly in left parietal (107.6%+/-9.8% vs 84.1%+/-12.4%), left frontal (97. 7%+/-6.7% vs 79.4%+/-8.9%) and left temporal areas (99.7%+/-7.4% vs 84.9%+/-10.1%) and in the cingulate cortex (112.1%+/-9.1% vs 95. 9%+/-10.1%, P<0.05). Cerebral activity uptake per injected dose was inversely correlated with age in 19 children of group I (r = -0.77, P<0.001). In group I, there was also an inverse correlation between age and the relative local count density in the parietal (r = -0.42 to -0.57), frontal (r = -0.48), temporal (r = -0.42 to -0.58) and occipital cortex (r = -0.44). In these cortical regions relative counts differed when subgroups of children aged 4-10 and 11-15 years were analysed. It is concluded that there are systematic differences between 4- to 15-year-old children and adults with regard to normal lCBF. Diagnostic use of perfusion agents has to consider age-adjusted normal flow maps; normal ranges should be determined separately for the age groups 4-10 and 11-15 years.

[Age dependence of cerebral Tc-99m-ECD distribution between preschool and school-age children and adults]. / Altersabhängigkeit der zerebralen Tc-99m-ECD-Verteilung zwischen Klein- und Schulkindern und Erwachsenen.

AIM: This present study deals with the question whether normal distribution of local cerebral blood flow (ICBF) agents in adults can be transferred to the age group of 4 to 15 years old children. METHODS: 23 children (age: 4-15 years, mean 11 +/- 3 y) (group I) and 10 adults (age: 27-56 years, mean 45 +/- 10 y) (group II) without evidence of cerebrovascular disease or other brain diseases underwent Tc-99m-ECD-SPECT imaging. Counts in the cortical ROIs were related to those of cerebellar ROIs (= 100%). RESULTS: In group I, relative cortical activity exceeded that of group II, particularly in parietal (107.6 +/- 9.8 vs. 84.1 +/- 12.4%), frontal (97.7 +/- 6.7 vs. 79.4 +/- 8.9%), left temporal areas (99.7 +/- 7.4 vs. 84.9 +/- 10.1%) and in the singular cortex (112.1 +/- 9.1 vs. 95.9 +/- 10.1%, p < 0.05). Cerebral activity uptake/injected dose/acquisition period was linearly correlated with age in group I (r = -0.78, p < 0.001). There was also a correlation of the relative local count density with age in 5 parietal ROIs (r = -0.42 to -0.57), in 2 frontal ROIs (r = -0.48), in 7 temporal ROIs (r = -0.42 to -0.58) and in 2 occipital ROIs (r = -0.44). In 14 cortical regions relative counts differed when subgroups of children aged 4-10 and 11-15 years were analysed. CONCLUSION: There are systematic differences between 4 to 15 years old children and adults regarding the normal distribution of ICBF. Diagnostic use of perfusion agents has to consider the respective age-adjusted normal flow maps; respective normal ranges should be determined for age groups of 4-10 and of 11-15 years separately.

Changes in local cerebral blood flow by neuroactivation and vasoactivation in patients with impaired cognitive function.

Imaging of local cerebral blood flow (lCBF) may serve as an important supplementary tool in the aetiological assessment of dementias. In early or preclinical disease, however, there are less characteristic changes in lCBF. In the present study it was investigated whether vasoactivation or neuroactivation may produce more pronounced local lCBF deficits. Local CBF was investigated by using technetium-99m hexamethylpropylene amine oxime and single-photon emission tomography (SPET) in 80 patients (50 with mild cognitive impairment and 30 with dementia of Alzheimer type (DAT), all without evidence of cerebrovascular disease) at rest (baseline) and during activation. In 31 studies patients underwent vasomotor activation with acetazolamide, while 62 studies were performed under cognitive challenge (neuroactivation by labyrinth task). Cortical activity relative to that of cerebellum increased significantly in a right temporal region and tended to increase in other cortical regions upon vasoactivation. In contrast, neuroactivation reduced cortical activity relative to that of cerebellum in several left and right temporal and in left parietal regions. Visual classification of SPET images of patients with probable DAT by three observers resulted in a reduction of the number of definitely abnormal patterns from 9/12 to 4/12 by vasoactivation and an increase from 10/18 to 15/18 by neuroactivation. Correspondingly, abnormal ratings in patients with mild cognitive dysfunction were reduced from 7/19 to 5/19 by vasoactivation and were increased from 12/21 to 18/21 by neuroactivation. In conclusion, vasoactivation does not enhance local relative perfusion deficits in patients with cognitive impairment of non-vascular aetiology, whereas neuroactivation by labyrinth task produces more pronounced local flow differences and enhances abnormal patterns in lCBF imaging.

Localization of the undulin gene (UND) to human chromosome band 8q23.

Undulin, a large extracellular matrix (ECM) mosaic glycoprotein related to collagen type XIV, is associated with dense collagen matrices in soft tissues and is likely to be involved in the supramolecular organization of interstitial collagens. By fluorescence in situ hybridization (FISH), we have assigned the undulin locus (UND) to band q23 of human chromosome 8.