Purging of acute myeloid leukemic cells by ether lipids and hyperthermia

Ether lipids (EL) and hyperthermia have been shown to possess a relatively selective cytotoxicity to leukemic cells. In this study, the combined effects of EL (ET-18-OCH3, ET-16-NHCOCH3, or BM 41.440) and hyperthermia on the growth of hematopoietic progenitors, myeloid leukemic cell lines, and leukemic cells obtained from patients with acute myeloid leukemia (AML) were examined to determine if this combination resulted in a greater selective killing of leukemic cells than that achieved by either EL or heat alone. When the cells were treated simultaneously with EL (50 micrograms/mL) and hyperthermia (42 degrees C) for one hour, the killing of leukemic cell line cells was enhanced considerably. Among the three EL, however, the combination of ET-18-OCH3 and heat seemed to be the most cytotoxic to leukemic cell line cells with no effect on the growth of hematopoietic progenitors. An increase in the duration of treatment with ET-18-OCH3 to four hours with heat added during the last hour resulted in a further reduction of leukemic cell line cells while sparing 50% of hematopoietic progenitors after cryopreservation. The combined treatment with ET-18-OCH3 and heat also inhibited the growth of leukemic progenitors obtained from AML patients by 97% to 100%. These data indicate that the combined treatment with EL and hyperthermia might offer an efficient means to eliminate myeloid leukemic cells in vitro.     

Injury to major abdominal vessels during posterior lumbar interbody fusion. A case report and review of the literature

Background contextNumerous cases of injury to major abdominal vessels during the excision of a lumbar herniated disc have been reported, but no cases of injury during interbody fusion by a posterior approach have been described.PurposeTo report on an injury to common iliac vessels during a posterior lumbar interbody fusion (PLIF) and discuss the causes and possible preventive measures.Study designA unique case report and a review of the literature.MethodsThe hospital chart and autopsy report of a single patient were analyzed.ResultsA 52-year-old woman with L4–L5 disc degeneration underwent PLIF. During scraping of the vertebral end plates, there was a sudden increase in blood flow from the disc space, however not copious, with no changes of vital parameters. When the patient was placed supine, severe hypotension and abdominal distension led to strongly suspect a lesion to abdominal vessels. At laparotomy, carried out by a vascular surgeon, a vast retroperitoneal hematoma was evacuated and the vascular lesions were repaired. Postoperatively, the patient continued to lose blood from the abdominal drains and after 4 hours, she was reoperated by another vascular surgeon, who found a diffuse hemorrhage from the small vessels in the surgical field. Soon after the surgery the patient died.ConclusionsThe lesions were produced by a shaver used for scraping the vertebral end plates. The absence of abundant bleeding from the disc space was possibly because of the compression of the iliac vessels by the pads of the frame on which the patient was lying. The causes of the lesions and possible prevention of similar injuries are analyzed.     

Does ergometric stress test induce a procoagulative condition in patients with previous myocardial infarction?

A regularly scheduled physical training program seems to have antithrombotic effects. Moreover, the hemostatic changes occurring in patients with coronary artery disease during acute exercise have not been clearly elucidated. Since stress testing is routinely performed in clinical cardiology, it would be helpful to assess whether patients with coronary artery disease are exposed to acute coronary thrombosis during or soon after sustained physical exercise. This study was designed to evaluate the effect of acute physical exercise (stress test by bicycle ergometer) on blood coagulation in a group of patients with previous myocardial infarction, and to determine whether the antithrombotic therapy commonly administered favorably influences hemostatic equilibrium. Our results suggest that exercise testing is not harmful to patients with previous myocardial infarction in regard to hemostasis and fibrinolysis and that antithrombotic therapy reduces postexercise increase in platelets.     

An inhibitory monoclonal antibody to factor X that blocks prothrombin activation but not prothrombinase enzyme assembly

A monoclonal antibody (designated alpha BFX-2b) prepared against bovine factor X inhibited factor X activity in human, bovine, porcine, rabbit, and canine plasma. In assays using purified prothrombinase components, factor Xa, factor Va, phospholipid vesicles, and calcium ion with the fluorescent active site thrombin inhibitor dansylarginyl-N-(3-ethyl-1,5- pentanediyl)amide, the antibody inhibited the conversion of prothrombin to thrombin. Antibody alpha BFX-2b also blocked prothrombinase cleavage of the macromolecular substrates prethrombin 1 and prethrombin 2 but did not inhibit factor Xa hydrolysis of the synthetic substrate benzoyl- Ile-Glu-Gly-Arg-p-nitroanilide. The antibody also prevented the inactivation of factor Xa by antithrombin III but did not prevent the inactivation by soybean trypsin inhibitor. Antibody alpha BFX-2b bound factor Xa with a stoichiometry of 1:1 and an apparent dissociation constant of 9.0 x 10(-11) mol/L as estimated from its inhibition of prothrombinase activity. Antibody alpha BFX-2b did not prevent binding of factor Xa to factor Va-phospholipid as measured by using fluorescence polarization or high-pressure liquid gel chromatography with the fluorescent Factor Xa analogue dansyl-glutamyl-glycyl-arginyl- Xa. Immunoblotting of factor X following electrophoresis on sodium dodecyl sulphate-polyacrylamide gels and transfer to nitrocellulose indicated that the antigenic determinant recognized by antibody alpha BFX-2b was found on the heavy chain of factors X and Xa. From these observations it can be concluded that antibody alpha BFX-2b recognizes a highly conserved epitope on the factor X heavy chain that is remote from the topographic sites required for prothrombinase complex assembly and substrate hydrolysis but may be located at or near a portion of the macromolecular substrate binding site.     

Platelet-collagen interaction: inhibition by ristocetin and enhancement by von Willebrand factor-platelet binding

The contribution of von Willebrand factor (vWF)-platelet binding to platelet-collagen interaction was examined in vitro. The binding of vWF to platelets was mediated and regulated by ristocetin. Subthreshold concentrations of ristocetin (less than or equal to 1 mg/mL), insufficient to cause ristocetin-induced platelet aggregation (RIPA), were added to platelet-rich plasma (PRP) prior to the addition of collagen. The collagen-induced platelet aggregation (CIPA) was modified by ristocetin and the degree of alteration was dependent on the ristocetin concentration. Response as a function of ristocetin concentration was designated the Collagen-Platelet Aggregation Response (CoI-PAR). In normal PRP the CoI-PAR was a progressive inhibition followed by decreasing inhibition and then an enhanced response. The enhanced response occurred over a narrow range of ristocetin concentrations (0.8 to 1.0 mg/mL). In the absence of vWF (severe von Willebrand's disease, Type I, vWF less than 1%) the CoI-PAR was a progressive, eventually complete inhibition with no enhanced response (with ristocetin concentrations up to 3.0 mg/mL). With addition of vWF to this PRP an enhanced response was observed at a ristocetin concentration inversely proportional to the vWF level. PRP from a patient with severe Hemophilia A showed a response within the normal range. Subthreshold ristocetin did not cause plasma protein precipitation or platelet release of 3H-serotonin, nor induce micro platelet aggregate formation. Digestion of platelet membrane glycoproteins (GP(s] with chymotrypsin demonstrated that upon removal of GPI, RIPA was absent, CIPA retained and the CoI-PAR was progressive inhibition, with no enhancement. With removal of GPs I, II, and III, RIPA, CIPA, and the CoI-PAR were absent. A dose-response 125I-vWF- platelet binding occurred with increasing ristocetin concentrations which was unchanged by the addition of collagen. These results demonstrated that ristocetin-platelet association inhibited CIPA, and vWF-platelet binding enhanced platelet-collagen adhesion and platelet aggregation. The in vitro-enhanced CIPA represents a vWF-dependent aggregation of sufficient magnitude to overcome the inhibitory effect of ristocetin. These studies demonstrate an influential interaction of ristocetin, vWF, and collagen with the platelet membrane and imply an important hemostatic contribution of vWF-platelet binding in platelet- collagen interaction.     

Radial head,radiocapitellar and total elbow arthroplasties: A review of recent literature

The outcome of prosthetic elbow surgery is continually evolving. We thoroughly reviewed the literature on this issue to analyse the indications, outcomes and complications of the numerous types of implants currently in use. Radial head replacement is recommended in comminuted fractures of the radial head and in post-traumatic conditions. Medium- and long-term results prove to be satisfactory in the majority of cases, with no evidence to indicate that some prostheses (monopolar vs. bipolar; cemented vs. press-fit) are more effective than others; nonetheless, the bipolar-cemented implant was found to be associated with a lower revision rate than other prostheses. Unicompartmental arthroplasty has recently been used for the treatment of osteoarthritis and rheumatoid arthritis when the lateral compartment is prevalently involved; the results reported to date have been encouraging, although further studies are warranted to confirm the validity of these implants. Total elbow arthroplasty is performed in a range of conditions, including distal humerus fractures in the elderly and elbow arthritis. In the former condition, linked elbow replacement yields excellent results with few complications and a low revision rate. In elbow arthritis, total elbow arthroplasty is indicated when patients suffer from disabling pain, stiffness and/or instability that prevent them from performing daily activities. Unlinked elbow arthroplasty, which is used above all in rheumatoid arthritis, also yields satisfactory results, although the risk of instability persists. The use of linked elbow arthroplasty, which yields similar results but lower revision rates, has consequently increased. Lastly, the results yielded by linked elbow prosthesis in post-traumatic conditions are good, although not quite as good as those obtained in rheumatoid arthritis. Early mechanical failure may occur in younger and more active patients after elbow arthroplasty. However, the careful selection of patients who are prepared to accept functional limitations imposed by elbow implants will enable indications for elbow arthroplasty to be extended to young subjects, particularly when no other therapeutic options are available.     

Contralateral recurrent lumbar disc herniation. Results of discectomy compared with those in primary herniation

STUDY DESIGN: The surgical outcomes of patients who underwent discectomy for contralateral recurrent herniation and primary herniation were evaluated. OBJECTIVE: To assess whether the clinical results in patients undergoing surgery for contralateral recurrent disc herniation may be as good as those reported after primary discectomy. SUMMARY OF BACKGROUND DATA: No retrospective or prospective investigation has been conducted on the surgical treatment of contralateral recurrent lumbar disc herniation. METHODS: Sixteen patients who underwent surgery for recurrent disc herniation at the same level as primary disc excision, but on the opposite side, were analyzed prospectively from the recurrence of contralateral radicular pain (Group 1). All patients had reported a satisfactory results after primary discectomy. Fifty consecutive patients who underwent disc excision during the study period, who did not report recurrent radicular pain, were analyzed for comparison (Group 2). Overall patient satisfaction, pain severity, functional outcome, and work status were evaluated. RESULTS: At the 2-year follow-up, the clinical outcome was rated as satisfactory in 14 of 16 patients in Group 1 and in 45 of 50 in Group 2 (P > 0.05). Twelve patients in Group 1 and 42 in Group 2 had resumed their work or daily activities at the same level as before the operation (P > 0.05). Radicular pain was significantly improved in both groups at the 6-month and 2-year follow-ups. At the 6-month follow-up, low back pain was significantly improved only in the patients in Group 2; however, at the 2-year follow-up, low back pain was significantly improved in both groups. CONCLUSIONS: Clinical results in patients reoperated on for contralateral recurrent lumbar disc herniation compare favorably with those reported after primary discectomy. The improvement of pain in the low back and lower limbs reported by the majority of patients 2 years after reoperation suggests that fusion is not needed in this patient population.     

18F FDG PET-Applications in Oncology

In the first part our intention was, essentially, to present the particularities of glucose tumoral cells metabolism, PET components, the synthesis of 18F FDG and the detection of unknown cancers. This second part makes reference about mainly types of tumors who benefit by FDG-PET indications. Clinical PET has a rapid growth because of its use in cancer diagnosis and management. According with published studies all over the world, the sensibility and specificity of FDG-PET, noninvasive method, is higher than that of the conventional methods like CT, IRM, ultrasonography. PET is en excellent detection method of most of common cancer types and depends not on the histological neoplasm type; the more aggressive is the tumor, more it will uptake the radiotracer. The cost is significant, so the indications must be very precise: evaluating the malignity of solitary pulmonary nodules, evaluating the recurrences of melanoma, colon cancer diagnosis, differentiation between recurrent brain tumor and radiation injury, differential diagnosis of the benign lymph and malign lymph nodes, staging of Hodgkin's and non-Hodgkin's lymphoma, evaluation the response to therapy. Because the PET images are difficult to interpret, appears the necessity of correlation with anatomic images: this was the fusion images beginnings (the PET and CT images combination); now the physiologic information has precise anatomic localization. The growing of this method is very probably, both using 18F FDG -thanks to its highly favorable physical characteristics- and other new radiopharmaceuticals. The clinical cases that illustrate the applications are investigated at CERMEP, Lyon, France.