Hereditary deficiency of antithrombin III, protein C and protein S: prevalence in patients with a history of venous thrombosis and criteria for rational patient screening.

Data in the literature on the prevalence of hereditary deficiency of the natural coagulation inhibitors are conflicting. We conducted a prospective study on 680 consecutive patients with a history of venous thrombosis to determine the prevalence of hereditary deficiency of antithrombin III (AT III), protein C(PC) and protein S(PS) and to establish selection criteria for rational patient screening. The mean age of the patients at investigation was 44.3 +/- 15.4 years, while that at the first thrombotic event was 38.5 +/- 14.8 years. The total prevalence of inhibitor deficiency states was 48/680 (7.1%). 19/680 patients (2.8%) had AT III-deficiency, 17 (2.5%) PC-deficiency, nine (1.3%) PS-deficiency and three (0.4%) a combined deficiency. In 37/48 deficient patients family studies were performed and the hereditary nature was established in 19 cases (2.8% of total patient population, six with AT III-deficiency, eight with PC-deficiency, four with PS-deficiency and one with a combined deficiency). Family studies in these 19 patients revealed 46 additional individual patients with a hereditary deficiency state. A positive family history was found in 15/19 (79%) with a proven hereditary deficiency state, in 153/619 (25%) of non-deficient patients and in 11/29 (38%) of deficient patients without established hereditary nature. The mean age at the first thrombotic event was significantly lower in patients with a hereditary deficiency state (26.8 years) compared with the other two groups (39.0 and 39.7 years, respectively). In all patients with a hereditary deficiency the first thrombotic event occurred before the age of 45 years.(ABSTRACT TRUNCATED AT 250 WORDS)     

Changes in CSF pressures during experimental acute arterial subdural bleeding in pig

Summary The effects of acute arterial subdural bleeding on cerebrospinal fluid (CSF) pressure and 12 other vital parameters were studied in spontaneously breathing pigs (group 1, n=9) and in mechanically ventilated pigs (group 2, n=18) to analyze quantitatively the bleeding course and the lethal mechanism.Spontaneously breathing animals all succumbed after a mean bleeding volume of 45.6±8.9ml, corresponding to about 50 per cent of the intracranial volume, and a mean bleeding duration of 11.0±2.6 min. Rapid rise in CSF pressures, marked transtentorial pressure gradients, and progressive reductions of cerebral perfusion pressure leading to a permanently iso-electric EEG, apnoea and to a terminal rise in arterial pressure (Cushing response), was the rule in these animals.The mechanically ventilated animals had smaller bleeding volumes (34.3±8.1 ml), but longer bleeding durations (13.8±5.8 min). In this group 7 animals survived. They had no pressure gradients, and only moderate changes in arterial pressure and EEG. The 11 animals that succumbed had marked transtentorial pressure gradients, but smaller increments in arterial pressure than the spontaneously breathing animals.At autopsy, subdurally located blood was found throughout the intracranial and spinal subdural compartments and along the spinal nerve roots in both groups.The results of this study suggest that survival after acute subdural haematoma is influenced by the presence of transtentorial pressure gradients and by the spinal sac acting as a space for expansion. The beneficial effect of artificial ventilation is discussed.This study has been supported by the University of Oslo, The Anders Jahre Foundation for The Advance of Research, and by the Norwegian Society for fighting Cancer.     

Effects of polymerization heat and monomers from acrylic cement on canine bone

We investigated the effects of polymerization heat and toxicity of polymethyimetacrylate bone cement in the canine tibial diaphysis. Heat was studied by filling the tibias with either bone cement or bone wax contained in a monomer tight membrane pouch. Toxicity was studied by filling both tibias with cement, with the control side contained in the membrane pouch. Bone blood perfusion was measured by microsphere technic, and bone remodeling by ^99mTc-methylene diphosphonate uptake and by histologic technique. In bone exposed to the combination of polymerization heat and monomer, both perfusion and remodeling were impaired. We did not find any effects of polymerization heat alone.

We conclude that hot toxic chemicals from bone cement during polymerization may inhibit bone blood perfusion and remodeling, whereas heat alone seems to be of minor importance for the regenerative processes in cemented diaphyseal bone.     

Megestrol acetate versus aminoglutethimide for metastatic breast cancer

In this prospective, randomized study the clinical response and toxicity of megestrol acetate (MA) and aminoglutethimide (AG) as second-line treatment in patients with metastatic breast cancer was compared. 176 patients were included, and 150 received treatment greater than 8 weeks and are evaluable for treatment response. The two groups did not differ with regard to prognostic factors. Response rate for the AG and MA groups were 34% and 31% respectively, with duration of response of 13.1 and 13.0 months. Stable disease was obtained in 33% and 35% respectively. No difference was observed in survival. Side effects occurred more frequently in the AG group (42%) than in the MA group (18%).     

Inter- and intraobserver variability in the histopathological diagnosis of medullary carcinoma of the breast,and its prognostic implications

Summary One hundred thirty-one breast carcinomas with medullary features, registered in the Danish Breast Cancer Cooperative Group from 1977–1982, have been histopathologically reviewed by two senior pathologists and classified as typical medullary carcinoma (TMC), atypical medullary carcinoma (AMC), and non-medullary carcinoma (NMC). Diagnostic criteria were based on those put forward by Ridolfiet al. and Fisheret al. The procedure was repeated with an interval of about one year by both pathologists. The diagnostic interobserver agreement was 72% with a Kappa of 0.55. The intraobserver agreement was 77% and 63% with Kappa values of 0.64 and 0.44, respectively. To see whether the observed inter- and intraobserver variability had any prognostic implications, diagnostic subgroups for both pathologists were analyzed with Kaplan Meier plots for recurrence-free survival (RFS) and with log rank tests. In the first evaluation pathologist 1 segregated a group of TMC with a significantly better RFS than for the NMC group, and pathologist 2 segregated a group of TMC with a corresponding strong trend. These findings could not, however, be reproduced in the second evaluation. The study indicates that the criteria of TMC and AMC as proposed by Ridolfiet al. need to be sharpened and simplified in order to reduce inter-and intraobserver variability. Larger studies with a control group of infiltrating ductal carcinomas are mandatory to elucidate the clinical importance of the diagnoses of Typical and Atypical Medullary Carcinoma of the breast.     

Die verwendung der autologen vena femoralis bei vena-cava-superior-thrombose

We report on a 52-year old male patient who underwent implantation of an insulin pump because he had diabetes and in whom superior vena cava syndrome developed as a long-term complication. After unsuccessful lysis therapy superficial femoral vein was implanted to form a bypass from the internal jugular vein to the right atrium. The postoperative course was uneventful from the aspects of both the bypass and the leg after explantation of the superficial femoral vein. The bypass is still patent 7 months after the operation, and the patient has no symptoms. Autogenous superficial femoral vein can be used successfully in the reconstruction of large venous vessels. It should be the graft of choice for young patients with benign diseases. We compare our result and those obtained with different substitutes described in the literature that have been used for reconstruction in superior vena cava syndrome.

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Die verwendung der autologen vena femoralis bei vena-cava-superior-thromboseFallbericht mit literaturübersicht

Zusammenfassung Bei einem 52jährigen, männlichen Patienten trat nach Implantation einer Insulinpumpe als Spätkomplikation eine Thrombose der Vena cava superior auf. Nach erfolgloser Lysetherapie wurde ein Venajugularis-rechtsatrialer-Venenbypass mit autologer Vena femoralis durchgeführt. Der postoperative Heilungsverlauf war sowohl von Seiten des gefäßrekonstruktiven Eingriffs, als auch von Seiten der Venenentnahmestelle komplikationslos. Der Bypass ist 7 Monate postoperativ offen und der Patient beschwerdefrei. Die autologe Vena femoralis eignet sich zur Rekonstruktion großer venöser Gefäße ausgezeichnet. Sie sollte v. a. bei benignen Prozessen und jüngeren Patienten als autologes Bypassmaterial dem Kunststoff vorgezogen werden. Das Ergebnis wird mit verschiedenen Gefäßsubstituten, die bei Verschluß der oberen Hohlvene verwendet werden, verglichen.

     

Prognosis of fracture of the talus in children: 21 (7-34)-year follow-up of 14 cases

14 children suffering from a fracture of the talar neck or body were examined after 21 (7-34) years. The talar neck was fractured in 10 children and the talar body in 4. 3 fractures were displaced and primarily treated with reduction and immobilization. Nondisplaced fractures were treated conservatively. All fractures healed. All patients with displaced fractures had exercise-induced pain at follow-up. Of 11 patients with nondisplaced fractures only 1 had minor complaints.

CT and conventional radiographs showed arthrosis in the talocrural joint and normal subtalar joints in those with displaced fractures. The radio- graphic findings were normal after nondisplaced fractures.     

Dorsal root ganglia cocultured with macrophages: an in vitro model to study experimental demyelination

The present investigation introduces an in vitro model to study macrophage properties during demyelination. Rat dorsal root ganglia (DRG) were cultured for obtaining myelinated peripheral nerve fibers. These cultures were exposed to non-resident macrophages. In untreated control cultures, there was no indication of myelin removal by the added macrophages. DRG were exposed to enzymatically generated oxygen radicals using the xanthin/xanthin oxidase or the glucose/glucose oxidase system. Assessment of Schwann cell viability and ultrastructural morphology revealed different patterns of cell cytotoxicity and morphological changes in different experiments. High concentrations caused complete tissue necrosis of the DRG, while low concentrations did not affect either cell viability or ultrastructural morphology. Under intermediate experimental conditions, oxygen radicals caused non-lethal Schwann cell damage leading to Schwann cell retraction and myelin sheath rejection. Myelin lamellae were disrupted and decompacted. These changes were followed by a selective macrophage attack on myelin sheats, resulting in demyelination. Axons, Schwann cells and sensory ganglion cells survived this attack. The specificity of the oxygen radical effects was tested in experiments using the oxygen radical scavengers catalase and superoxide dismutase. Catalase prevented the described effects on cell morphology and subsequently blocked demyelination by non-resident macrophages.Supported by a grant from the Deutsche Forschungsgemeinschaft (DFG) (Br 1274/1-1)     

Phenotypes and spontaneous cell cytotoxicity of mononuclear cells from patients with seronegative spondyloarthropathies: Ankylosing spondylitis,psoriatic arthropathy and pauciarticular juvenile chronic arthritis — Analysis of mononuclear cells from peripheral blood,synovial fluid and synovial membranes

Summary T-cell subpopulations and natural killer (NK) cells from peripheral blood, synovial fluid and synovial membranes from patients with seronegative spondyloarthropathies were investigated. Thirty-four patients with ankylosing spondylitis, sixteen patients with psoriatic arthropathy and six patients with pauciarticular juvenile chronic arthritis were studied. All the patient groups had normal proportions of T4⁺ and T8⁺ cells as well as normal T4/T8 ratios in peripheral blood. In the synovial fluids the T4/T8 ratios were reduced in ankylosing spondylitis and psoriatic arthropathy (p<0.05). Although both the T4 and T8 subpopulations were reduced, the T4/T8 ratios in the synovial membranes of patients with these two disorders tended to be within the normal range of that of peripheral blood. Increased numbers of T-cells in the synovial fluid from patients with ankylosing spondylitis expressed class II MHC antigens. The natural killer cell activity was normal in peripheral blood and synovial fluids of patients with ankylosing spondylitis and psoriatic arthropathy while it tended to be reduced, although not significantly, in pauciarticular juvenile chronic arthritis. Synovial membranes were almost devoid of NK cell activity. The number of Leu 7⁺ cells were reduced in synovial fluid of patients with psoriatic arthropathy (p<0.04), but not as significantly as in the two other patient groups.