Crystal structure of the human alpha-thrombin-haemadin complex: an exosite II-binding inhibitor.

The serine proteinase alpha-thrombin plays a pivotal role in the regulation of blood fluidity, and therefore constitutes a primary target in the treatment of various haemostatic disorders. Haemadin is a slow tight- binding thrombin inhibitor from the land-living leech Haemadipsa sylvestris. Here we present the 3.1 A crystal structure of the human alpha-thrombin- haemadin complex. The N-terminal segment of haemadin binds to the active site of thrombin, forming a parallel beta-strand with residues Ser214-Gly216 of the proteinase. This mode of binding is similar to that observed in another leech-derived inhibitor, hirudin. In contrast to hirudin, however, the markedly acidic C-terminal peptide of haemadin does not bind the fibrinogen-recognition exosite, but interacts with the heparin-binding exosite of thrombin. Thus, haemadin binds to thrombin according to a novel mechanism, despite an overall structural similarity with hirudin. Haemadin inhibits both free and thrombomodulin-bound alpha-thrombin, but not intermediate activation forms such as meizothrombin. This specific anticoagulant ability of haemadin makes it an ideal candidate for an antithrombotic agent, as well as a starting point for the design of novel antithrombotics.

[Quality assurance by improved cooperation structures. The example of decentralized early detection mammography]. / Qualitätssicherung durch bessere Kooperationsstrukturen. Das Beispiel der dezentralen Früherkennungs-Mammographie.

The German Mammography Study investigated into quality assurance measures for screening mammography, proceeding in a decentralised manner and focussing especially on structure, process and outcome of the study. The field phase lasted for three years, and during this period the technology of the equipment used in mammography improved, also to the indicators of process and of early outcome. The annual interval of examinations was well received. To include mammography into the German cancer screening programme is no easy matter: it requires a comprehensive cooperative quality assurance programme incorporating various institutions of medical care. Appropriate recommendations have been made to the Federal Committee of Physicians and Sickness Insurance Bodies.

[Determinants of observer variability in early diagnostic mammography--a ROC analysis]. / Determinanten der Beobachter-Variabilität bei der Früherkennungsmammographie--eine ROC-Analyse.

As part of the German mammographic study, the participating doctors were given test films of 30 histologically confirmed cases. Regarding the indications for biopsy there was good sensitivity (the median amongst 25 doctors was 0.87). Specificity (median 0.86) could be improved. Comparison of individual results with the majority showed considerable variability within the group of doctors performing mammography. ROC analysis indicated that there was considerable observer variability which was independent from the specialty or praxis characteristics of the participants. The inclusion of mammography in an early diagnostic programme requires continuing education of the participants in this technique. This should be supported by further methods of quality assurance.

Computerized tomography of breast cancer and regional lymph nodes.

Technique, advantages and disadvantages of computerized tomographic (CT) mammography are described in various pre- and postoperative conditions. The value of CT mammography is discussed.

Growth rate of 147 mammary carcinomas.

In 147 cases of mammary carcinoma, 388 serial mammographies were performed before final treatment. The average retrospective observation time was 27 months with a range of two months to 11 years. The number of serial mammographies per case ranged between two and 11. The tumor volume doubling times (TV); obtained by measuring the growth of the tumor nucleus shadow in the mammographies, ranged from 44 to 1869 days with an average of 212 days. No correlation between volume doubling time and histologic differentiation could be found. One hundred of these cancer patients were found in a screening population of 22,000 women receiving serial mammographies in a time period ranging from two to 16 years. An additional 40 cancer patients surfaced in this group without roentgenologic but with foregoing clinical or thermographic abnormalities before final diagnosis. An additional 21 cancer patients surfaced without any foregoing abnormalities. The follow-up tumor ranged between three months and two years with a mean time of one year and nine months. Not considering tumor size, pathologic-thermographic signs appeared with greater frequency the faster the tumor grew. Theoretically, an average of more than 16 years should elapse before an initial tumor cell develops into a 10-mm primary mammary carcinoma (30 doubling times). Therefore the length of time necessary for a 2-mm tumor to grow to a size of 10-mm is, on the average, four years.

CT-visualization of an intraspinal osteoma-like mass in Paget's disease.

Neuroradiological examination in a case of polyostotic Morbus Paget with compression of the thoracic spinal cord was extended to spinal computed tomography. The use of radiography, myelography, and skeletal scintigraphy as regards diagnostic information is compared to CT. Obviously the use of CT provides a valuable completion for the evaluation of extradural space-occupying spinal lesions. Undisturbed by overlying structures of CT has the potential to differentiate various types of tissues. CT clearly depicts the lesion and aids in the recognition of the type of the compressing foreign body, which in this case was an osteoma-like protrusion.

Hyperperfusion and enhancement in dynamic computed tomography of ischemic stroke patients.

The passage of contrast medium was observed using serial computed tomography (CT) in 24 stroke patients. Density--time profiles of various brain regions were plotted. In normal brain tissue, X-ray attenuation showed a maximum increase during the arterial phase (16.4 +/- 11.0%) and was 2.8 +/- 2.2% above control during stable distribution. In hypoperfusion, increase in attenuation was always below 10% in the arterial phase, while hyperperfusion was characterized by an attenuation increase of 25 to 70%. Enhancement was defined by a density increase of 16.8 +/- 14.8% and a tissue/blood ratio between 7 and 60%. An attempt was made to establish a relationship between the serial CT pattern and the prognosis. Enhancement tended to indicate severe morphological changes followed by permanent neurological deficit, whereas hyperperfusion was generally an indicator of probably recovery.

[Proposals for standardizing the image quality of mammography (author's transl)]. / Vorschläge zur Qualitätsnormierung der Mammographie.

The radiography of phantoms is not sufficient to test the image quality of mammography. In addition, patients mammograms have to be evaluated using our proposed quality criteria.

[Spontaneous Visibility of the Mammary Ducts in Plain Mammography (author's transl)]. / Spontane Milchgangsdarstellung bei der Mammographie.

Mammary ducts become visible as negative contrast in the mammogram. This is caused by an increased contents of fat or oil in the mammary secretion. The secretion of lipides can indicate hormonal disregulation.

[Introduction to x-ray diagnosis of primary malignant bone tumor (author's transl)]. / Einführung in die Röntgen-Diagnose der primär malignen Knochentumoren

Diagnosis of primary malignant bone tumors is based on a synopsis of X-ray findings, clinical symptoms, gross pathology and histology. Osteosarcoma, chondrosarcoma, fibrosarcoma and myelogenic sarcomas have a typical symptomatology and can be diagnosed in the radiograph by localisation, mode of extension, alterations of bone and periosteum.

X-ray therapy of primary bone tumors.

Radiotherapy of bone tumors can now be performed exclusively by megavolt therapy. Giant cell tumors hsould be resected. If the lesion is not completely resectable, surgery should be followed by the administration of a target dose of 3000 rads in 4-6 weeks. Inoperable giant cell tumors are irradiated to a tumor dose of 5000 rads, inoperable giant cell tumors of grade III receive a dose of 8000 rads as do osteosarcomas. Ewing's sarcoma and reticulum cell sarcoma can be totally destroyed by a tumor dose of 6000 rad with sufficient reliability. Combination with chemotherapy may offer a chance of improvement. Osteosarcoma should be resected. If surgery is too late (early distant metastases), a tumor dose of 8000 to 10000 rads would be able to destroy the tumor cells. Histologic control investigations have proved this.