The role of bone scintigraphy in patients with Erdheim-Chester disease.

Erdheim-Chester disease (ECD) is a rare disorder that has been reported fewer than 60 times in the literature. Although clinical findings seem to be specific at first sight, histologic classification remains unclear. It has not been decided whether ECD is part of the spectrum of histiocytoses or whether it may be a lipid storage disorder or even a primary macrophage cell disorder, although it does show a distinct histologic pattern. However, the clinical appearance alone shows several typical features, rendering the diagnosis very probable if present. This article illustrates the importance of bone scanning in ECD, because the scintigraphic pattern of involved skeletal sites may in themselves lead to the diagnosis. Several differential diagnoses are considered. The importance of bone scintigraphy as an imaging method in patients with an unclear diagnosis is discussed, as exemplary in ECD, as is its role for the detection of sites of skeletal involvement in other diseases.

Accurate differentiation of parkinsonism and essential tremor using visual assessment of [123I]-FP-CIT SPECT imaging: the [123I]-FP-CIT study group.

OBJECTIVE: To evaluate whether visual assessment of [123I]-FP-CIT (DaTSCAN, Nycomed Amersham, plc) single photon emission computerized tomography (SPECT) images can differentiate between parkinsonism and essential tremor (ET). METHODS: [123I]-FP-CIT SPECT imaging was conducted in a six-center study of 158 patients with a clinical diagnosis of parkinsonism compared with 27 ET cases and 35 healthy volunteers. Striatal uptake of the radioligand was graded normal or abnormal, and abnormal images were further graded to three levels of severity. An institutional read whereby each center visually assessed the images blinded to the clinical data and a consensus blinded read by a panel of five was undertaken. RESULTS: The institutional reading scored 154 of 158 cases of parkinsonism abnormal, all 27 cases of ET as normal, and 34 of 35 healthy volunteers as normal compared with the consensus blinded read scoring 150 cases of parkinsonism as abnormal, 25 ET cases as normal, and 33 healthy volunteers as normal. Sensitivity for the clinical diagnosis of parkinsonism was 97% and specificity for ET was 100% for the institutional read, whereas sensitivity was 95% and specificity 93% for the consensus blinded read. Semiquantitative analysis of specific: nonspecific caudate and putamen uptake were consistent with the results of visual inspection. CONCLUSION: Visual assessment of [123I]-FP-CIT SPECT images is an easily applied diagnostic test which is helpful in the differential diagnosis of tremor disorders and in confirming a clinical diagnosis of a hypokinetic-rigid syndrome.

Hepatic perfusion scintigraphy. Relationship of liver perfusion and ascites in patients with liver cirrhosis.

Radionuclide studies were performed on 38 patients with biopsy proven liver cirrhosis in an attempt to evaluate the interrelationship between liver perfusion and ascites in cirrhotic patients. Quantitative hepatic scintigraphy was used to evaluate the relative contribution of hepatic arterial and portal venous blood flow to the hepatic circulation. Using a gamma camera and on-line computer system, a bolus of 370 MBq Tc-99m pertechnetate was injected intravenously. Time activity curves of the abdominal aorta and right lobe of the liver were obtained using a region of interest analysis where arterial and portal components were calculated. Ascites was determined by clinical examination and by ultrasonography. Of 38 patients, 10 patients (26.3%) showed normal liver perfusion (group A), 22 patients (58%) showed reduced portal venous perfusion (group B), and 6 patients (15.7%) showed pure arterial hepatic perfusion (group C). The incidence, as well as the advancement, of ascites were significant (P < 0.05) and were most frequent in group C, frequent in group B, and less frequent in group A. The results of this study suggest that the development of ascites in patients with liver cirrhosis is closely correlated with the reduction in portal blood perfusion.

Refined 2.3 A X-ray crystal structure of bovine thrombin complexes formed with the benzamidine and arginine-based thrombin inhibitors NAPAP, 4-TAPAP and MQPA. A starting point for improving antithrombotics.

Well-diffracting crystals of bovine epsilon-thrombin in complex with several "non-peptidic" benzamidine and arginine-based thrombin inhibitors have been obtained by co-crystallization. The 2.3 A crystal structures of three complexes formed either with NAPAP, 4-TAPAP, or MQPA, were solved by Patterson search methods and refined to crystallographic R-values of 0.167 to 0.178. The active-site environment of thrombin is only slightly affected by binding of the different inhibitors; in particular, the exposed "60-insertion loop" essentially maintains its typical projecting structure. The D-stereoisomer of NAPAP and the L-stereoisomer of MQPA bind to thrombin with very similar conformations, as previously inferred from their binding to bovine trypsin; the arginine side-chain of the latter inserts into the specificity pocket in a "non-canonical" manner. The L-stereoisomer of 4-TAPAP, whose binding geometry towards trypsin was only poorly defined, is bound to the thrombin active-site in a compact conformation. In contrast to NAPAP, the distal p-amidino/guanidino groups of 4-TAPAP and MQPA do not interact with the carboxylate group of Asp189 in the thrombin specificity pocket in a "symmetrical" twin N-twin O manner, but through "lateral" single N-twin O contacts; in contrast to the p-amidino group of 4-TAPAP, however, the guanidyl group of MQPA packs favourably in the pocket due to an elaborate hydrogen bond network, which includes two entrapped water molecules. These thrombin structures confirm previous conclusions of the important role of the intermolecular hydrogen bonds formed with Gly216, and of the good sterical fit of the terminal bulky hydrophobic inhibitor groups with the hydrophobic aryl binding site and the S2-cavity, respectively, for tight thrombin active site binding of these non-peptidic inhibitors. These accurate crystal structures are presumed to be excellent starting points for the design and the elaboration of improved antithrombotics.

Crystal structure determination, refinement and molecular model of creatine amidinohydrolase from Pseudomonas putida.

The three-dimensional crystal structure of creatine amidinohydrolase (creatinase EC 3.5.3.3) from Pseudomonas putida, a dimeric enzyme with a molecular weight of 97,000, has been determined by multiple isomorphous replacement, averaging over the local dyad and restrained crystallographic refinement at 1.9 A with a crystallographic R-value of 17.7%. The asymmetric unit contains a dimer. The two chemically identical subunits consist of 403 residues each. A subunit is built up of two domains, a small N-terminal and a larger C-terminal domain. The small domain has a central seven-stranded beta pleated sheet with short helices on the outside. The large domain forms a six-stranded antiparallel beta half-barrel with helices on the outside. The two domains are connected by a segment that links two helices. The binding site of the competitive inhibitor carbamoyl sarcosine, a close analog of the substrate creatine, is located in the center of the large domain and partly covered by the small domain of the other subunit. The carbamoyl group is tightly co-ordinated to a water molecule, which presumably represents the nucleophile involved in hydrolysis of creatine. A catalytic mechanism is proposed on the basis of this structure.

[Therapy in metastasizing ovarian cancer--survival rate correlated with histological and cytological grading as prognostic factors]. / Therapie beim metastasierenden Ovarialkarzinom--Uberlebensrate in Abhängigkeit vom histologischen und zytologischen Grading als prognostischen Faktoren.

The histologic grading especially of the modified Broders'-Grading is a suitable prognostic factor in Ovarian Carcinoma. Our investigations show this to be especially true after failure with first line chemotherapeutic agents. These morphologic gradings should especially be used for the selection for high risk patients and for the treatment planning in ovarian carcinoma.

[Morphological and clinical aspects of the so-called sinus tumours of the ovary (author's transl)]. / Morphologische und klinische Aspekte der sogenannten endodermalen Sinustumoren des Ovars.

Data from literature as well as our own studies are used in the discussion of differential diagnosis of the so-called endodermal sinus tumours. Clinical and paraclinical aspects of this once lethal tumour species are reported. New therapeutic strategies are presented consisting of the introduction of new, effective combinations with adjuvant chemotherapy. Thus at early stages a conservative surgical approach seems to allow the preservation of fertility in these generally young women. But even in more advanced cases the administration of a modern adjuvant polychemotherapy is likely to result in higher survival rates.