Recombinant activated factor VII in patients with cancer and hemorrhagic disseminated intravascular coagulation.

Hemorrhagic disseminated intravascular coagulation (DIC) associated with the presence of underlying advanced or metastatic tumors are often difficult to control by conventional methods. We report the use of recombinant activated factor VII (rFVIIa) in patients with cancer and bleeding secondary to DIC. A total of 18 patients with cancer met pre-defined criteria for DIC. All patients had failed to respond to transfusion with blood products and treatment of the underlying malignancy prior to the introduction of rFVIIa. The median laboratory data at the time of treatment with rFVIIa were as follows: hemoglobin, 7.7 g/dl; platelets, 54 x 10(9)/l; prothrombin time, 21 s; activated partial thromboplastin time, 41 s fibrinogen, 83 mg/dl; D-dimer, 17 microg/ml; and antithrombin, 32%. The dose of rFVIIa was 90 microg/kg and the median number of doses administered was 5 (range, 3-10). Serial measurements of coagulation parameters were obtained at frequent intervals during treatment with rFVIIa. Of the 18 patients, 15 responded with cessation of bleeding and improvement in coagulation data. The prothrombin time and activated partial thromboplastin time normalized in all responding patients within 24 h of treatment. The median fibrinogen was 214 mg/dl while the median D-dimer was 6 microg/dl at 48 h following the administration of rFVIIa. No thromboembolic complications were observed following rFVIIa. Our data provide evidence that rFVIIa can be used successfully to control the hemorrhagic episodes associated with DIC. Although this type of treatment appears to be safe, close monitoring of the patients is warranted.     

Septal-lateral annnular cinching perturbs basal left ventricular transmural strains.

OBJECTIVE: Septal-lateral annular cinching ('SLAC') corrects both acute and chronic ischemic mitral regurgitation in animal experiments, which has led to the development of therapeutic surgical and interventional strategies incorporating this concept (e.g., Edwards GeoForm ring, Myocor Coapsys, Ample Medical PS3). Changes in left ventricular (LV) transmural cardiac and fiber-sheet strains after SLAC, however, remain unknown. METHODS: Eight normal sheep hearts had two triads of transmural radiopaque bead columns inserted adjacent to (anterobasal) and remote from (midlateral equatorial) the mitral annulus. Under acute, open chest conditions, 4D bead coordinates were obtained using videofluoroscopy before and after SLAC. Transmural systolic strains were calculated from bead displacements relative to local circumferential, longitudinal, and radial cardiac axes. Transmural cardiac strains were transformed into fiber-sheet coordinates (X(f), X(s), X(n)) oriented along the fiber (f), sheet (s), and sheet-normal (n) axes using fiber (alpha) and sheet (beta) angle measurements. Results: SLAC markedly reduced (approximately 60%) septal-lateral annular diameter at both end-diastole (ED) (2.5+/-0.3 to 1.0+/-0.3 cm, p=0.001) and end-systole (ES) (2.4+/-0.4 to 1.0+/-0.3 cm, p=0.001). In the LV wall remote from the mitral annulus, transmural systolic strains did not change. In the anterobasal region adjacent to the mitral annulus, ED wall thickness increased (p=0.01) and systolic wall thickening was less in the epicardial (0.28+/-0.12 vs 0.20+/-0.06, p=0.05) and midwall (0.36+/-0.24 vs 0.19+/-0.11, p=0.04) LV layers. This impaired wall thickening was due to decreased systolic sheet thickening (0.20+/-0.8 to 0.12+/-0.07, p=0.01) and sheet shear (-0.15+/-0.07 to -0.11+/-0.04, p=0.02) in the epicardium and sheet extension (0.21+/-0.11 to 0.10+/-0.04, p=0.03) in the midwall. Transmural systolic and remodeling strains in the lateral midwall (remote from the annulus) were unaffected. CONCLUSIONS: Although SLAC is an alluring concept to correct ischemic mitral regurgitation, these data suggest that extreme SLAC adversely effects systolic wall thickening adjacent to the mitral annulus by inhibiting systolic sheet thickening, sheet shear, and sheet extension. Such alterations in LV strains could result in unanticipated deleterious remodeling and warrant further investigation.     

Effect of tray space on the accuracy of monophasic polyvinylsiloxane impressions.

The effect of tray space on the dimensional accuracy and stability of impressions made from four brands of monophasic polyvinyl siloxane material was assessed on the recovered stone casts by quantitative and qualitative methods. In general, both evaluation methods agreed that tray space and repeat pour did not affect the accuracy of the dies for individual castings. But disagreement was observed in the findings for fixed partial dentures (FPDs). Quantitative measurement of the interpreparation (IP) dimensions did suggest the possibility of a potential problem when a FPD is cast in one piece because of a significantly reduced distance between the two abutments. However, from the findings of this study it can be concluded that a rigid stock tray can be used with a monophasic polyvinyl siloxane impression material.     

Mammalian wound repair environment does not permit skeletal muscle regeneration

Repair and regeneration are mutually exclusive responses to injury. Previous studies have shown that wound fluids promote proliferation, but not differentiation, of myoblasts in vitro. This study explored the ability of the repair environment within polyvinyl alcohol sponges to support cellular events of skeletal muscle regeneration in vivo. Neonatal rat L8 myoblasts were modified to express beta-galactosidase then inoculated into plain sponges or sponges containing minced muscle. Labeled myoblasts were found in myotubes within minced muscle. In contrast, myoblasts inoculated into sponges lacking muscle remained mononucleate. Occurrence of labeled myoblasts within myotubes, which required fusion, represents differentiation of inoculated myoblasts to participate in regeneration. Failure of myoblasts to form myotubes in sponges lacking muscle suggests that this wound repair environment cannot support morphologic differentiation of myoblasts. Although this repair environment can support the survival of myoblasts, it did not support myogenesis, an event necessary to complete skeletal muscle regeneration. Data from this study reinforce earlier studies in vitro and suggest that the properties attributed to wound fluids are inherent in the wound environment. Whether the inability of this environment to support myogenesis is the consequence of the absence of essential factors or the presence of inhibitors remains to be determined.     

Effect of photodynamic therapy on blood flow in normal and tumor vessels

The aim of this series of experiments was to determine the dynamic blood flow changes that occur in normal and neoplastic tissues during photodynamic therapy. Mice bearing SMT-F tumors and rats with transplanted chondrosarcomas were injected with graded doses of dihematoporphyrin ether. Studies of changes in single-vessel and whole-tumor blood flow were carried out with 630 nm light activation. A helium neon laser Doppler velocimeter was used to stimulate dihematoporphyrin ether, as well as to measure changes in flow velocity in both single-vessel and whole-tumor models. There was a reduction of flow velocity in all vessels and tumors in animals injected with 1 to 40 mg/kg dihematoporphyrin ether intraperitoneally. The extent of flow reduction was related to drug dose administered. Decreases in blood flow began within 10 seconds of light stimulation and were maximal within 5 minutes. Both normal and tumor vessels responded similarly. We conclude that photodynamic therapy leads to significant microcirculatory changes that may be pertinent to the mechanism of tumor necrosis.     

Rapid evaluation of tetanus immunity by a haemagglutination test in the injured at a hospital emergency unit

A turkey red blood cell haemagglutination assay (TRBC HA) allowing rapid measurement of the antibodies against tetanus has been set recently. Its feasibility was evaluated in injured patients admitted into an emergency unit during summer 1987. TRBC HA was performed by the same physician who questioned the patient on his/her previous vaccinations and evaluated his/her immunization status. The rapid HA test practiced in emergency was controlled by TRBC HA and ELISA measurement of antibodies carried out in the laboratory. Each method was compared to the others: the results were fitted and no significant difference was found. The preventive procedures which would have followed the antibody measurement by immediate TRBC HA were compared to the decision resulting from clinical evaluation. The immunoprophylactic attitude would have been the same in 82% of cases. TRBC HA is a reliable test, and feasible in an emergency: it could help in making the appropriate decision for immunoprophylaxis to be applied to the injured and other patients at risk of tetanus.     

Transsynaptic degeneration of motoneurones caudal to spinal cord lesions

We studied the effects of complete transversal section of the spinal cord, at T8-10, in adult rats, upon the number and morphology of identified motoneurones in lumbar segments L4 and L5. In observations by light and electron microscopy many lumbar motoneurones had structural abnormalities when the interval between surgery and perfusion ranged between a few hours and one week. We found also that as many as 25% of the motoneurones distal to a cord transection disappeared as a consequence of the lesions. We did not find comparable changes in the spinal cord at C6 after transection at T8-10. Complete removal of the cerebellum did not reduce the lumbar motoneurone counts. Bilateral ablation of the "motor" cortex did cause a reduction of motoneurone counts at L4-5; these animals showed normal or near normal spontaneous locomotor activity beginning a few days after the lesion was placed. Motoneurone counts were significantly reduced after partial cord lesions that spared the dorsal funiculi (where the corticospinal tract travels in the rat), but in this case the rats were paraplegic as a result of the lesion. Cord transection at 7 days of postnatal age resulted in reduced motoneurone counts when the rats reached adulthood. Intraspinal or subarachnoid administration of colchicine led to reduced motoneurone counts. Prolonged infusion of a GABA agonist, muscimol, into the lumbar CSF did not prevent the loss of motoneurones produced by cord transection. Pretreatment of animals with a Ca2+ channel blocker (nimodipine) did not prevent the effects of cord transection.(ABSTRACT TRUNCATED AT 250 WORDS)