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Biomedical subjects

A Eldor

Publications and source records attributed to A Eldor.

At least 37 records · Page 2Linked to original sources

Thrombophilia, thrombosis and pregnancy.

The risk of venous thromboembolism (VTE) in pregnancy is 0.05-1.8%, six times greater than in the non-pregnant state, and pulmonary embolism remains the most common cause of maternal death. Maternal age, previous history of VTE, Caesarean section and the presence of thrombophilia, significantly increase the risk of VTE. Acquired or hereditary thrombophilia occur in almost two-thirds of women presenting with recurrent miscarriages, pre-eclampsia, intrauterine growth restriction, abruptio placentae, or stillbirth, which are associated with microvascular thrombosis in placental blood vessels. Women with VTE during pregnancy and especially those with thrombophilia require individualized management, based on the type of defect, the family history and the presence of additional risk factors. These factors are important in determining the dose and duration of antithrombotic therapy during pregnancy and the puerperium, and the thromboprophylactic strategy for future pregnancies. Oral anticoagulants are now seldom used during pregnancy because of their significant side effects. Low-molecular-weight heparins (LMWHs) are increasingly replacing unfractionated heparin in the prevention and treatment of VTE during pregnancy. LMWHs have also been shown to be effective in improving the outcome of pregnancy in women with previous obstetric complications.

Female↗

[High factor VIII as a risk factor for venous thrombosis].

Several studies have shown that increased concentrations of factor VIII are associated with thrombophilia. It has been also shown that this is not an acute phase response pattern, and that these individuals have increased factor VIII concentrations due to genetic and environmental causes. Part of the thrombophilic pattern might be related to an acquired Activated Protein C resistance condition. Since individuals with venous thromboembolism and increased factor VIII concentrations present a high recurrence rate, the determination of factor VIII concentrations should be included in the laboratory thrombophilia screening work-up.

Biomarkers↗

Avian hemangioma retrovirus induces cell proliferation via the envelope (env) gene.

Several years ago, a field strain retrovirus, avian hemangioma virus (AHV), was isolated from hemangioma tumors in layer hens. Sequence analysis indicated that the AHV genome contains the three prototypic retroviral genes, gag, pol, and env, and is devoid of an oncogene. In cultured endothelial cells, however, AHV induced a significant cytopathic effect through a typical apoptotic cascade. We now demonstrate that AHV also induces cell proliferation and anchorage-independent growth of BSC-1 epithelial cells and NIH-3T3 fibroblasts. This was shown by measurements of (1) cell viability, (2) DNA synthesis, (3) flow cytometry analysis of the cell DNA content, and (4) clonogenic efficiency of the infected cells. Anchorage-independent cell growth was demonstrated by colony formation in soft agar. Moreover, the AHV env gene was cloned into a MuLV-based retroviral vector, and infection of NIH-3T3 cells with this vector induced cell proliferation as well as clonogenic growth. These results suggest that AHV, which is devoid of an oncogene, is a pleiotropic activator capable of inducing either apoptosis or cellular proliferation, depending on the infected cell type.

3T3 Cells↗

Laparoscopic splenectomies for idiopathic thrombocytopenic purpura: experience of sixty cases.

We performed a laparoscopic splenectomy (LS) in 60 patients (age 9-83, 45 females) with idiopathic thrombocytopenic purpura (ITP) who did not achieve sustained remission on steroid therapy. Using a modified procedure, the mean duration of LS was 78 min (range 25-240 min) and surgery was associated with only 5% major and 5% minor complications. Ten patients had a platelet count less than 50 x 10(9)/l during surgery despite the administration of immune globulin (0.4 g/kg x 3-5 days) or pulsed oral dexamethasone (40 mg/day x 4 days). Three patients were refractory to these therapies and underwent LS with a platelet count less than 5 x 10(9)/l. Bleeding complications during or after surgery were rare (5%). Accessory spleens were removed in eight patients. Convalescence was rapid and the mean hospital stay was 2.3 days (range 1-7 days). The patients were followed for a mean of 16 months (range 1-36 months), and 49 patients (84%) are in complete remission. Seven patients (12.5%) relapsed despite an initial good response in 6 of them. Two patients underwent laparoscopic removal of accessory spleens with excellent response. We conclude that LS for ITP is safe and effective and associated with low morbidity and fast recovery. Thus, LS may be considered earlier in the course of ITP.

Adolescent↗

Connective tissue activating peptide III expression disappears progressively with increased dysplasia in human cervical epithelium.

OBJECTIVE: The aim of this study was to explore the possible involvement of CTAP-III in the development of cervical cancer as it progresses through several cervical intraepithelial neoplasia (CIN) stages. MATERIAL AND METHODS: Twenty-four cervical specimens were obtained by direct punch biopsy, conization, or hysterectomy. Diagnosis of CIN I to CIN III was based on standard morphological criteria in 12 specimens. Tissue specimens were also obtained from 4 normal uteri and 8 cases of invasive squamous cell cervical carcinoma. RT-PCR, using CTAP-III-specific primers, was used to identify CTAP-III mRNA and polyclonal antibodies, directed against the N-terminus of CTAP-III, for immunostaining of the CTAP-III protein. RESULTS: RT-PCR yielded amplified fragments in RNA derived from normal cervical tissue, while no PCR product was detected in the invasive cervical carcinoma tissue. The PCR product corresponded to a CTAP-III plasmid PCR product. Both tissues expressed the same amounts of GAPDH mRNA as the control for the integrity and equal amounts of the isolated RNA. In each of the 16 specimens of normal cervices and of CIN tissues, epithelial cells were stained with the anti-CTAP-III antibodies. In normal epithelium, CTAP-III staining was homogeneously distributed in all epithelial layers, except in the highly active and proliferating basal cells. CTAP-III was localized at the epithelial cell membrane or between adjacent epithelial cells in a granular, chain-like pattern of staining. In the CIN specimens, CTAP-III staining was no longer seen in the deep epithelial layers, consistent with the dysplastic appearance of the cells, and remained in the seemingly normal superficial epithelial layers. Cells of invasive cervical carcinoma did not stain for CTAP-III and were detected in endothelial cells of capillary blood vessels. CONCLUSION: The specific localization of CTAP-III between adjacent epithelial cells suggests a possible role of this chemokine in maintaining the normal architecture of epithelial tissues. Its progressive disappearance in increasingly severe CIN may be applied to distinguish between specific stages in the progression of cervical carcinoma.

Amino Acid Sequence↗

Laparoscopic accessory splenectomy for recurrent idiopathic thrombocytopenic purpura and hemolytic anemia.

BACKGROUND: Laparoscopic splenectomy is an effective treatment for idiopathic thrombocytopenic purpura (ITP) and hemolytic anemia that has a remission rate of 80-90%. In some patients in whom the disease persists or recurs, a diagnosis of accessory spleen is made. The long-term efficacy of laparoscopic accessory splenectomy is unknown. METHODS: Patients who underwent laparoscopic accessory splenectomy were followed in the outpatient clinic. The perioperative course, blood counts, and need for medical therapy to maintain a normal count were recorded. RESULTS: Eight patients underwent laparoscopic accessory splenectomy. All procedures were completed laparoscopically, and all patients were discharged on the 1st postoperative day. Patients were available for a follow-up period of 15 months range, (3-27). None of the ITP patients achieved a complete remission. Two of them had a partial remission, and five ITP patients are now being treated with chronic corticosteroids to maintain a platelet count of >100,000/ml. CONCLUSION: Laparoscopic accessory splenectomy is associated with a low rate of morbidity and a short hospital stay. Despite its success in removing all residual splenic tissue, most patients will probably not enjoy a complete remission.

Adrenal Cortex Hormones↗

Severe preeclampsia and high frequency of genetic thrombophilic mutations.

OBJECTIVE: To determine whether severe preeclampsia is associated with genetic thrombophilic mutations or other types of thrombophilia. METHODS: A case-control study compared 63 consecutive women with severe preeclampsia evaluated at our institution between November 1997 and April 1999 with 126 control women matched for age and ethnicity. All of these women were tested several months after delivery for mutations of factor V Leiden, methylenetetrahydrofolate reductase, and prothrombin gene; for deficiencies of protein C, protein S, and antithrombin-III; and for the presence of anticardiolipin antibodies. RESULTS: Thirty-five study women (56%) had a thrombophilic mutation compared with 24 control women (19%), P <.001. Seven other study women (11%) had other thrombophilias, compared with one control woman (0.8%), P <.01. Within the study group, women with thrombophilia delivered at an earlier gestational age, and their neonates' birth weights were lower compared with those of women without thrombophilia. CONCLUSION: Because thrombophilia was found in 67% of women with severe preeclampsia, we suggest that women who have severe preeclampsia should be tested for thrombophilia.

Adult↗

INFLAMET: an image analyzer to display erythrocyte adhesiveness/aggregation.

Background: Due to a lack of simple, inexpensive, and real-time methodology, the state of erythrocyte adhesiveness/aggregation is not measured in daily practice by most clinicians. Methods: We measured the state of erythrocyte adhesiveness/aggregation before and following the administration of intravenous high-dose gamma globulins in 18 patients with various autoimmune diseases using a simple slide test and image analysis system (INFLAMET). Results: A significant (P=0.01) increment in the state of erythrocyte adhesiveness/aggregation (from 2+/-3 to 8+/-9 arbitrary units) was noted in the entire study group despite a significant (P=0.008) decrement (from 350+/-97 to 323+/-127 mg%) in the concentration of fibrinogen and no significant change in the erythrocyte sedimentation rate (32+/-30 mm/h before and 35+/-29 mm/h following administration of gamma globulin). Conclusions: By using a simple slide test and image analysis, we were able to provide relevant rheological information that was not available from either of the routine indirect tests, i.e. the Westergren erythrocyte sedimentation rate and the concentration of fibrinogen.

Journal Article↗

Megakaryocyte maturation is associated with expression of the CXC chemokine connective tissue-activating peptide CTAP III.

Connective tissue-activating peptide III (CTAP III), a CXC chemokine derived from the chemokine precursor platelet basic protein (PBP) by proteolytic cleavage, has been identified in platelets, activated macrophages, neutrophils and T lymphocytes. CTAP III can support stem cell-derived haematopoiesis yet inhibits the proliferation of committed megakaryocyte (MK) progenitors. This investigation was aimed at characterizing CTAP III expression in human MKs and determining it's role in MK differentiation. We report high expression of CTAP III in mature human bone marrow (BM) MKs and megakaryoblast cell lines following differentiation induction with phorbol ester 12-myristate 13-acetate (PMA). Immunostaining with anti-CTAP III antibodies demonstrated its prominent presence in platelet producing zones in the cytoplasm and intense staining around the periphery of the large BM MKs. In cultures of logarithmically growing megakaryoblast cell lines DAMI, CHRF-288 or MEG01, which contain primarily 2N cells, only 15% of the cells expressed CTAP III. The addition of PMA stimulated high levels of CTAP III after 24 h in more than 75% of the cells, being expressed in both the 2N and large polyploid MKs. Reverse transcription polymerase chain reaction (RT-PCR) revealed upregulation of CTAP III mRNA after only 1 h of exposure to PMA that was sustained for 24 h. In the bone marrow of idiopathic thrombocytopenic pupura (ITP) patients undergoing accelerated MK maturation and thrombopoiesis, 99% of large MKs and 95% of small MKs expressed high levels of CTAP III. While the biological function of this chemokine in MKs is not known, these studies demonstrate that molecular upregulation of CTAP III in MKs is associated with maturation and, as with other chemokines, may be involved in proliferation arrest and cellular interactions with extracellular matrix and platelet production.

Blood Coagulation Factors↗

Increased leukocyte aggregation induced by gamma-globulin: a clue to the presence of pseudoleukopenia.

BACKGROUND: Previous articles have reported the appearance of leukopenia after the administration of high-dose intravenous gamma-globulins. METHODS: A simple slide test was used to reveal the state of leukocyte aggregation (LA) in the peripheral blood as well as the absolute number of leukocytes in the slides. RESULTS: A significant (P < 0.00001) increment was noted in the state of LA, from 9 +/- 6% before to 25 +/- 11% after gamma-globulin administration. This was accompanied by a significant (P < 0.0004) reduction in the number of white blood cells in the peripheral blood (from 8433 +/- 3905 to 6550 +/- 3252 cells/mm3) but no significant change in the absolute number of the cells as determined by the leukocyte count per high power field in the peripheral slides. CONCLUSIONS: We raise the possibility that the leukopenia reported in some patients after the intravenous administration of high dose gamma-globulin is explained in part by the agglutination effect of the drug.

Adolescent↗

Fatal pulmonary artery thrombosis in a patient with Behçet's disease, activated protein C resistance and hyperhomocystinemia.

Behçet's disease (BD) is known for its tendency for thromboembolism, which is thought to be due to vascular injury. The important role of inherited thrombophilias is now becoming increasingly clear. However, conflicting data exist in terms of the contribution of these factors to the thrombotic risk in BD. In this case report, we describe a patient with BD who presented with severe cor pulmonale due to recurrent chronic venous thromboembolism and pulmonary artery thrombosis. The biochemical evaluation revealed that the patient was homozygotic for the factor V Leiden (R506Q) mutation and had increased levels of homocysteine. His condition deteriorated despite adequate anticoagulation treatment, and he died suddenly after 7 months of follow-up. We assume that the presence of thrombophilic risk factors augments and synergizes with the hypercoagulable state already existing in BD, leading to fatal thrombosis in this patient.

Activated Protein C Resistance↗

Activated polymorphonuclear leukocytes and monocytes in the peripheral blood of patients with ischemic heart and brain conditions correspond to the presence of multiple risk factors for atherothrombosis.

OBJECTIVE: Risk factors like hypertension, diabetes mellitus, dyslipidemia and smoking contribute to the pathogenesis of atherothrombosis. We investigated whether the multiplicity of risk factors for atherothrombosis is associated with leukocyte activation. METHODS: We examined the availability of CD11b/CD18 antigen on the surface of peripheral blood polymorphonuclear leukocytes and monocytes in patients with acute ischemic heart and brain conditions. RESULTS: There was a highly significant (p<0.00001) increment in the availability of the CD11b/CD18 antigen on the surface of the polymorphonuclear leukocytes in patients with multiple (2 or more) vascular risk factors [mean fluorescence intensity (MFI) +/- SD, 210+/-102] as opposed to individuals with none or 1 risk factor for atherothrombosis (MFI 159+/-73). Similar results were observed on the monocytes: 309+/-151 and 235+/-97, respectively (p<0. 00001). CONCLUSION: The multiplicity of risk factors for atherothrombosis is associated with the up-regulation of CD11b/CD18 antigen on the surface of peripheral blood polymorphonuclear leukocytes and monocytes, suggesting the presence of an increased inflammatory response and leukocyte activation in these individuals.

Acute Disease↗

The inflammation meter: novel technology to detect the presence of infection/inflammation in patients without leukocytosis but with increased leukocyte adhesiveness/aggregation.

OBJECTIVES: To reveal the presence of infection/inflammation in patients with relatively normal white blood cell count (WBCC) by using the leukocyte adhesiveness/aggregation test (LAAT). METHODS: The LAAT was performed by using a simple slide test and image analysis (Inflamet), the WBCC, by an electronic cell analyzer, C-reactive protein, by Laser nephelometry and CD11b/CD18 by whole blood flow cytometry. RESULTS: Forty out of a cohort of 121 patients with nonviral acute febrile illness had a WBCC within normal limits. The intensity of the inflammatory response in these individuals as judged by either C-reactive protein, or fibrinogen concentrations, erythrocyte sedimentation or polymorphonuclear leukocyte CD11b/CD18 expression was similar to that observed in patients with a leukocytic response. Our present finding that 63% out of the group with documented infection/inflammation and no leukocytosis had a significantly increased LAAT suggest that the lack of leukocytosis is in part a pseudoleukopenia, or is associated with some degree of uncompensated tissue leukostasis. CONCLUSIONS: The lack of a leukocytic response in a patient with nonviral infection/inflammation is by no means a sign of a less inflammatory response. The increased state of leukocyte adhesiveness/aggregation might help to disclose the presence of inflammation in these individuals.

Adult↗

Transient focal neurological deficits during pregnancy in carriers of inherited thrombophilia.

BACKGROUND AND PURPOSE: The aim of our study was to investigate the association of transient ischemic cerebrovascular events during pregnancy and inherited thrombophilias. METHODS: The study group comprised previously healthy pregnant women who had their first ischemic event during pregnancy (n=12). The control group included 24 healthy women matched with the study women for age, ethnicity, and smoking status. All women were evaluated for factor V Leiden mutation, methylenetetrahydrofolate reductase C677T gene mutation, the G20210A mutation in the prothrombin gene, and deficiencies of plasma proteins C and S and antithrombin III. RESULTS: Inherited thrombophilia was detected in 83% of women with transient neurological manifestations compared with 17% of the control group (P<0.001). CONCLUSIONS: Transient cerebrovascular ischemic events during pregnancy are associated with a high rate of inherited thrombophilias. Pregnant women with focal neurological symptoms should be evaluated for thrombophilia.

Adolescent↗

High prevalence of the prothrombin gene mutation in women with intrauterine growth retardation, abruptio placentae and second trimester loss.

BACKGROUND: It has been reported recently that obstetric complications are associated with thrombophilias. Our objective was to investigate the association between pregnancy complications and the guanine 20210 adenine (G20210A) mutation in prothrombin gene. METHODS: Two hundred and twenty-two women (study group) with obstetric complications were tested for the prothrombin mutation. Indications for testing were: severe preeclampsia, mild preeclampsia, intrauterine growth retardation, severe abruptio placentae, unexplained stillbirth, second trimester loss, and three or more consecutive spontaneous abortions. We also tested 156 healthy women who had at least one normal pregnancy and comprised the control group. RESULTS: Demographic data of the study and control groups were similar. Twenty-eight women of the study group (13%) were found to be heterozygous carriers of the 20210 variant of the prothrombin gene compared to five (3.2%) of the control group, p=0.001, odds ratio (OR) 2.9; 95% confidence interval (CI) 1.3-6.5. Compared to the control women, the prothrombin gene mutation was significantly more prevalent in women with IUGR, abruptio placentae, and second trimester loss but not in women with mild or severe preeclampsia, stillbirth and habitual abortion. CONCLUSIONS: Our data demonstrate that the mutation in the prothrombin gene is associated with specific pregnancy complications.

Abortion, Spontaneous↗

A comparison of enoxaparin with placebo for the prevention of venous thromboembolism in acutely ill medical patients. Prophylaxis in Medical Patients with Enoxaparin Study Group.

BACKGROUND: The efficacy and safety of thromboprophylaxis in patients with acute medical illnesses who may be at risk for venous thromboembolism have not been determined in adequately designed trials. METHODS: In a double-blind study, we randomly assigned 1102 hospitalized patients older than 40 years to receive 40 mg of enoxaparin, 20 mg of enoxaparin, or placebo subcutaneously once daily for 6 to 14 days. Most patients were not in an intensive care unit. The primary outcome was venous thromboembolism between days 1 and 14, defined as deep-vein thrombosis detected by bilateral venography (or duplex ultrasonography) between days 6 and 14 (or earlier if clinically indicated) or documented pulmonary embolism. The duration of follow-up was three months. RESULTS: The primary outcome could be assessed in 866 patients. The incidence of venous thromboembolism was significantly lower in the group that received 40 mg of enoxaparin (5.5 percent [16 of 291 patients]) than in the group that received placebo (14.9 percent [43 of 288 patients]) (relative risk, 0.37; 97.6 percent confidence interval, 0.22 to 0.63; P< 0.001). The benefit observed with 40 mg of enoxaparin was maintained at three months. There was no significant difference in the incidence of venous thromboembolism between the group that received 20 mg of enoxaparin (43 of 287 patients [15.0 percent]) and the placebo group. The incidence of adverse effects did not differ significantly between the placebo group and either enoxaparin group. By day 110, 50 patients had died in the placebo group (13.9 percent), 51 had died in the 20-mg group (14.7 percent), and 41 had died in the 40-mg group (11.4 percent); the differences were not significant. CONCLUSIONS: Prophylactic treatment with 40 mg of enoxaparin subcutaneously per day safely and effectively reduces the risk of venous thromboembolism in patients with acute medical illnesses.

Acute Disease↗