Thrombin activatable fibrinolysis inhibitor and hemostatic changes in patients with type I diabetes mellitus with and without microvascular complications.

We investigated thrombin activatable fibrinolysis inhibitor (TAFI) and its influence on fibrinolysis by measuring pro-TAFI activity and total TAFI antigen in 38 patients with type I diabetes mellitus (18 with and 20 without microvascular complications), as well as in 20 healthy controls. The pro-TAFI levels in the two groups of patients did not differ from those in the control group. Total TAFI antigen [i.e. pro-TAFI, TAFI and inactive carboxypeptidase U (TAFIi)] tended to decrease in both the patient groups (59.7 +/- 7.2 and 73.4 +/- 8.9% with and without microvascular complications, respectively) compared with controls (91.9 +/- 12.2%) (P = 0.12). We also assessed the overall hemostatic potential (OHP) in plasma, the clot lysis time and the overall fibrinolytic potential. The OHP was significantly higher in patients with complications compared with controls (8.9 +/- 0.9 versus 6.7 +/- 0.4; P < 0.05) and also higher in the diabetics without complications (7.8 +/- 0.6), although the latter difference did not reach statistical significance. Levels of clot lysis time and overall fibrinolytic potential were similar in the two groups of patients and the controls. The increased OHP in plasma from diabetic patients with microvascular complications indicates an imbalance of the hemostatic system towards a prothrombotic state. No signs of impaired fibrinolysis were observed in patients with diabetes. Using the OHP method for estimation of overall hemostasis, it seems that TAFI does not influence either fibrinolysis or the increased thrombotic potential observed in patients with type I diabetes mellitus.     

Could bipolar vessel sealers prevent bile leaks after hepatectomy?

BACKGROUND AND AIMS: The aim of this work was to test the feasibility of using a bipolar low thermal acting system inducing collagenic sealing but not protein coagulation to secure hepatic parenchyma cutting. MATERIALS AND METHODS: Thirty consecutive hepatectomies were carried out using kellyclasy plus ligatures and clips (controls), while the following 50 hepatectomies used kellyclasy plus bipolar vessels sealer (BVS). Blood loss, duration of hepatic pedicle clamping, length of hospital stay, and complications were recorded. RESULTS: There was no statistically significant difference in blood loss and duration of clamping between controls and BVS. Specific complications (9/21 in the control group vs 1/49 for the BVS group, p<0.00045) and length of hospital stay (14 days in the control group vs 11 days in the BVS group, p<0.014) were statistically lower in BVS group than in the controls, mainly due to prevention of bile duct leakages. CONCLUSIONS: Our data suggest that BVS may be particularly efficient to achieve bilistasis leading to the highest level of safety in performing hepatectomies. Further studies are now needed to confirm its superiority on the classical biliary ducts occlusion techniques.     

Synthesis procedure for routine production of 2-[18F]fluoro-3-(2(S)-azetidinylmethoxy)pyridine (2-[18F]F-A-85380).

2-[18F]Fluoro-3-(2(S)-azetidinylmethoxy)pyridine (2-[18F]F-A-85380) was among the first subtype selective radioligands to visualise the in vivo distribution of alpha4beta2-containing neuronal nicotinic acetylcholine receptors (nAChRs) in human brain. We developed a one-pot synthesis for the preparation of 2-[18F]F-A-85380 in a commercially available TRACERlab FXF-N synthesis module. The synthesis comprises a nucleophilic substitution followed by hydrolysis of a t-butyloxycarbonyl (BOC)-protected intermediate. After formulation for intravenous application up to 20 G Bq 2-[18F]F-A-85380 were produced from a starting activity of 100 G Bq [18F]fluoride in 60 min with a specific activity of about 4.10(5)GBq/mmol and a mean radiochemical purity of more than 99%.     

D2-40 immunohistochemistry in the differential diagnosis of seminoma and embryonal carcinoma: a comparative immunohistochemical study with KIT (CD117) and CD30.

The distinction between seminoma and embryonal carcinoma based on morphology alone can sometimes be problematic, requiring the use of immunohistochemistry to facilitate diagnosis. D2-40 is a monoclonal antibody that reacts with an oncofetal antigen expressed by fetal germ cells and testicular germ cell tumors. The diagnostic value of D2-40 immunohistochemistry in distinguishing seminoma from embryonal carcinoma has not been determined. D2-40 immunoreactivity was evaluated in a series of testicular germ cell tumors and compared with that of KIT (CD117) and CD30, to assess the relative utility of this marker in discriminating between seminoma and embryonal carcinoma. Forty testicular germ cell neoplasms were examined, which included 19 seminomas, three embryonal carcinomas, three teratomas, one yolk sac tumor, and 14 mixed germ cell tumors. The 14 cases of mixed germ cell tumors contained components of seminoma (n=7), embryonal carcinoma (n=11), teratoma (n=10), yolk sac tumor (n=2), and choriocarcinoma (n=1). All cases of pure seminoma and the seminomatous components of mixed germ cell tumors exhibited positive immunoreactivity for D2-40. Focal positivity for D2-40 was also observed in 29% of the embryonal carcinoma samples. D2-40 immunoreactivity in seminomas was characterized by diffuse membrane staining, whereas for embryonal carcinomas, staining was focal and distributed along the apical surfaces of the neoplastic cells. Immunohistochemical staining for KIT was observed in 92% of the seminoma samples and in none of the embryonal carcinomas. Conversely, CD30 expression was identified in 93% of the embryonal carcinoma samples and in none of the seminomas. Other germ cell components showed no immunoreactivity for D2-40, KIT, or CD30. KIT and CD30 are effective immunohistochemical markers in separating seminoma from embryonal carcinoma. Although a highly sensitive marker for seminomas, D2-40 positivity was also observed in a subset of embryonal carcinomas, thus limiting the utility of this antibody for discriminating between these two malignancies.     

Structural characterization of BPI-modulating 15 kDa proteins from rabbit polymorphonuclear leukocytes: Identification of a novel family of leukocyte proteins

We have previously described the isolation and initial characterization of 15 kDa protein isoforms (p15s) from rabbit polymorphonuclear leukocytes (PMN) that bind toEscherichia coli and modulate the antibacterial actions of other leukocyte proteins on this gram negative organism. We now report that the p15s differ in primary structure. The cloning and sequencing of two distinct p15 cDNAs from a rabbit bone marrow library reveal that two of the isoforms are closely similar in primary structure differing at only two amino acid positions. The p15 cDNAs encode putative signal sequences suggesting a granule-associated localization for these proteins. Analysis of the derived p15 primary structures reveals homology to two leukocyte proteins: CAP-18, an 18 kD lipopolysaccharide (LPS) binding protein from rabbit PMN and cathelin, an 11 kD cysteine protease inhibitor from porcine leukocytes. This structural similarity suggests the existence of a novel family of low molecular weight leukocyte proteins with potential roles in inflammation.     

Ethanol effects in an anxiety/defense test battery

Two tests, components of an Anxiety/Defense Test Battery, have been designed to measure risk assessment, inhibition of nondefensive behaviors, and movement arrest, all of which occur in the natural defense patterns of rats to threatening stimuli. In these tests, which used a nonpainful threat stimulus (a cat), ethanol (0.6 and 1.2 g/kg) increased two risk assessment behaviors on an initial test day, and produced a wider pattern of changes in all three patterns on a retest (no cat) day, 5 days later. The pattern of results obtained is compatible with a view that defensive behaviors occur in a fixed sequence with the decreasing intensity of threat an important factor in the transition from one defensive behavior to the next, and with ethanol at these doses producing a mild and relatively nonspecific anxiolytic effect. Comparison of male and female subjects on these tasks also suggested that females are more defensive than males, a finding which agrees with a variety of human anxiety studies but is at variance with previous rodent literature.     

Case report: Concordant traumatic brainstem contusion delayed diagnosis in a young man with Wilson's disease

Wilson's disease is a hereditary autosomal recessive disorder of copper metabolism. The corresponding gene locus has been localized on the long arm of chromosome 13. Three different clinical variants of the disease can be distinguished: hepato-cerebral, abdominal/hepatic, and central nervous type. The heterogeneity of symptoms can cause problems in differential diagnosis, especially when another concordant disorder can also explain the pathogenesis of symptoms. The case report of a young man who suffered from brainstem contusion demonstrates the possibilities of misinterpretation because presenting symptoms could be attributed either to traumatic brain injury followed by adjustment disorder or Wilson's disease. Clinical signs included leftsided hemiparesis, bilateral gaze direction nystagmus, marked dysarthria with consecutive pervasive mutism, choreo-athetoid movements, spasmodic torticollis and diplopia dependent on gaze direction. Slit lamp examination showed Kayser-Fleischer's corneal ring. EEG- and computer assisted tomography investigations revealed non-specific findings. The patient was treated with D-Penicillamine. Alternative treatment with oral zinc preparations is discussed.

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Zusammenfassung Beim Morbus Wilson handelt es sich um eine autosomal rezessiv vererbte Störung des Kupferstoffwechsels. Der Genort konnte auf dem langen Arm des Chromosoms 13 lokalisiert werden. Klinisch können aufgrund ihrer Symptomatik drei Verlaufsformen (hepato-zerebraler, abdominalhepatischer und zerebraler Typ) unterschieden werden. Die Vielfalt der Symptome kann differentialdiagnostische Schwierigkeiten bereiten. Das Beispiel eines jungen Mannes mit einer traumatischen Hirnstammkontusion zeigt, wie die Diagnose der hepato-lentikulären Erkrankung dadurch erschwert wurde, daß die Pathogenese der Symptome durch die Hirnstammkontusion und darauf folgende Anpassungsstörungen erklärt worden war. Die Symptomatik bestand aus linksseitiger Hemiparese, lateralem Blickrichtungsnystagmus, Dysarthrie mit nachfolgendem universalem Mutismus, choreo-athetodischen Bewegungsstörungen, Torticollis spasmoidicus und blickrichtungsabhängigem Auftreten von Doppelbildern. Bei der Spaltlampenuntersuchung stellte sich der Kayser-Fleischer Ring dar. EEG- und computertomographische Untersuchungen erbrachten nur unspezifische Befunde. Die Behandlung erfolgte mit D-Penicillamin. Die alternative Behandlung mit oraler Gabe von Zinksalzen wird diskutiert.

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Résumé La maladie de Wilson est une affection héréditaire autosomale recessive concernant le métabolisme cuivré. Le locus du gène a été situé sur le bras long du chromosome 13. Du point de vue clinique on distingue trois formes symptomatologiques: le type hepato-cérébral, hepato-abdominal et cérébral. La diversité des signes cliniques peut poser des problèmes de diagnostic différentiel, car d'autres affections peuvent se présenter avec cette même Symptomatologie. Nous rapportons ici l'exemple d'un homme jeune, porteur d'une maladie de Wilson et victime d'une contusion traumatique du tronc cérébral, dont les signes cliniques ainsi que les troubles du comportement pouvaient été autant rapportés à la contusion du tronc cérébral qu'à l'affection métabolique.La Symptomatologie comprenait une hemiparesie gauche, un nystagmus lateralisé, une dysarthrie avec mutisme secondaire universel, des mouvements choréo-athétosiques, un torticolis spasmodique et une diplopie dépendante de la direction du regard. L'examen à la lampe à fente permettait à mettre en evidence un anneau de Kayser Fleischer. L'EEG et le scanner cérébral ne montraient pas d'anomalies specifique.Le traitement a consisté en l'administration de D-Penicillamine. Traitment alternative avec les sels de zinc est discuté.

     

Postirradiation malignant fibrous histiocytoma expressing cytokeratin. Implications for the immunodiagnosis of sarcomas

A malignant fibrous histiocytoma of the sacrum complicating the course of radiation therapy for endometrial carcinoma is presented. Although the tumor fulfilled the clinical, radiologic, and histologic criteria for a postirradiation malignant fibrous histiocytoma of bone, it also expressed cytokeratin. That this immunoreactivity reflected keratin synthesis by the tumor and not an unusual pattern of cross-reactivity with another intermediate filament such as vimentin is strongly suggested by the reproducibility of the immunoreactivity utilizing both polyclonal and monoclonal antibodies and extinction of the immunoreactivity following absorption of the primary antiserum with keratin proteins. This is the first reported instance of keratin expression by a malignant fibrous histiocytoma; it indicates that sarcomas apart from synovial sarcoma and epithelioid sarcoma may sometimes express this protein.     

A phase I clinical and pharmacokinetic study of the topoisomerase I inhibitor topotecan (SK&F 104864) given as an intravenous bolus every 21 days.

Topotecan (SK&F 104864) is a novel antitumor agent whose mechanism of action is inhibition of the DNA unwinding protein topoisomerase I. An analog of camptothecin, topotecan was designed to be more water soluble in an effort to decrease the severe and sporadic toxicities experienced during phase I/II trials of the parent compound. In this phase I clinical and pharmacological trial, topotecan was given as a bolus intravenous (i.v.) infusion over 30 min every 21 days. A total of 42 patients entered the study, receiving doses ranging from 2.5 to 22.5 mg/m2. The maximum tolerated dose (MTD) of topotecan given in this schedule was 22.5 mg/m2. Myelosuppression, primarily neutropenia, was dose-limiting. The extent of prior therapy did not predict for more severe neutropenia. Non-hematologic toxicities were mild and included low-grade to moderate fever, nausea, vomiting, alopecia, diarrhea and skin rashes. There were no objective partial or complete responses, although there was a suggestion of antitumor activity in three patients. Topotecan undergoes pH-dependent hydrolysis of the lactone ring; only the closed, lactone form is active. The lactone form predominated during infusion, with hydrolysis occurring rapidly following the end of infusion. There were linear relationships between dose administered and peak plasma lactone concentrations as well as AUC lactone to AUC total. The lactone was rapidly cleared from plasma with a total body clearance of 25.7 (+/- 6.7) l/h/m2. The plasma lactone concentration declined rapidly with a harmonic mean terminal half-life of 3.4 (+/- 1.1)h. Lactone hydrolysis and renal excretion were the major routes of elimination.(ABSTRACT TRUNCATED AT 250 WORDS)