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Biomedical subjects

A Elias

Publications and source records attributed to A Elias.

At least 109 records · Page 6Linked to original sources
PubMed1989

[Exploratory strategy in venous thromboembolic disease].

It is currently accepted that the clinical signs are not very reliable in the diagnosis of deep venous thromboses (DVT). For this reason, various methods, more objective, are used in daily practice. Anatomical methods permitting direct visualization of the thrombus: one is invasive: phebography, the other is non-invasive: ultrasonography, which is quite competitive with the previous one and presents the advantage of evaluating the surrounding structures and providing functional informations when associated with a Doppler test. Haemodynamic functional methods, less reliable, permitting an indirect evaluation of the venous return: the Doppler analyzes the blood velocity, qualitatively and subjectively, plethysmography, more objective, studies the variations of the blood volume, artificially created by venous obstruction. Isotopic methods, using radioactive materials incorporated in the coagulation factors resulting in the formation of a thrombus, such as iodine 125 labelled fibrinogen. Biological methods, reflecting the formation and dissolving of a thrombus: it consists in the plasma titration of D-Dimer, specific disintegration product of fibrin. The advantages, limitations and indications of each technique are discussed. Selection of the exploration method must take into consideration the prevalence of DVTs and the value of the tests according to various clinical situations: presence or not of thrombogenic circumstances (ambulatory patient, hospitalized patient), presence or not of clinical manifestations (high-risk asymptomatic patient, symptomatic patient). Haemodynamic and isotopic tests have been substituted for phlebography. The current tendency leans toward Ultrasonography-Doppler, a very reliable method in symptomatic patients, but its value still has not been properly determined under other circumstances.

Doppler Effect↗
PubMed1988

Cyclophosphamide and thiotepa with autologous bone marrow transplantation in patients with solid tumors.

Autologous bone marrow transplantation to avoid dose-limiting myelosuppression may allow significant drug dose escalations and exploitation of the linear-log correlation between chemotherapy and tumor cytotoxicity. In a phase I trial of cyclophosphamide and thiotepa (with subsequent addition of melphalan), 23 patients were entered; there were two deaths due to toxic effects. The maximum tolerated dose was 6 g of cyclophosphamide/m2 and 720 mg of thiotepa/m2. No significant dose of melphalan could be added. Stomatitis was dose limiting. Eleven of 20 patients who were able to be evaluated responded. Plasma thiotepa concentrations correlated more closely with toxicity and response than with drug dose level. Continuous infusion cyclophosphamide and thiotepa is an active core regimen for the further design of high-dose combination chemotherapy regimens.

Adult↗
PubMed1988

Effect of recombinant human granulocyte-macrophage colony-stimulating factor on chemotherapy-induced myelosuppression.

An increase in the dose of chemotherapy enhances the response of many experimental and clinical cancers, but the extent of dose escalation is often limited by myelosuppression. In preliminary trials, recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) has augmented leukocyte numbers and function, but the optimal dose is not established. We treated 16 adults who had inoperable or metastatic sarcomas with escalating doses of rhGM-CSF before and immediately after a first cycle of chemotherapy (cycle 1) to assess hematologic response and toxicity. A second cycle of chemotherapy (cycle 2) was given without rhGM-CSF. RhGM-CSF was tolerated well at doses of 4 to 32 micrograms per kilogram of body weight per day. At 64 micrograms per kilogram per day, edema and thrombi around a central venous catheter developed in two of four patients. Leukocyte and granulocyte counts increased significantly during the rhGM-CSF infusion. Neutropenia after cycle 1 was significantly less severe and shorter in duration than after cycle 2 (P less than 0.01). Mean total leukocyte and platelet nadirs were 1.0 and 101 x 10(9) per liter for cycle 1 and 0.45 and 44 x 10(9) per liter for cycle 2 (P less than 0.01), and the median intervals from day 1 of chemotherapy to neutrophil recovery (greater than 0.500 x 10(9) per liter) were 15 and 19 days, respectively (P less than 0.01). The duration of neutropenia was 3.5 days with cycle 1 and 7.4 days with cycle 2 (P less than 0.01). We conclude that rhGM-CSF is tolerated well at doses up to 32 micrograms per kilogram per day and is biologically active in leukopenic patients. It merits further evaluation for the prevention of morbidity from chemotherapy.

Adolescent↗
PubMed1988

Granulocyte-macrophage colony stimulating factor expands the circulating haemopoietic progenitor cell compartment in man.

The effect of granulocyte-macrophage colony-stimulating factor (GM-CSF) on bone-marrow and peripheral-blood progenitor cells was investigated in a three-phase study in 13 patients with sarcoma. In the first phase patients were given GM-CSF alone. In phase II, which started a week after completion of phase I, patients received a course of cytotoxic chemotherapy, then a course of GM-CSF. Phase III consisted only of cytotoxic chemotherapy. GM-CSF (phase I) alone produced an 18-fold increase in peripheral blood granulocyte-macrophage colony-forming units (CFU-GM) and an 8-fold increase in erythroid burst-forming units (BFU-E) in the peripheral blood. GM-CSF had no effect on bone-marrow CFU-GM and BFU-E in the group as a whole. Three patients were investigated after phases II and III. GM-CSF increased the absolute number of peripheral blood CFU-GM by approximately 60-fold compared with the pretreatment baseline. These effects of GM-CSF may be of clinical importance with regard to facilitating the harvest of peripheral blood progenitor cells for autotransplantation.

Adolescent↗
PubMed1988

Malignant melanoma. Treatment with high-dose combination alkylating agent chemotherapy and autologous bone marrow support.

Nineteen patients with metastatic malignant melanoma were treated with 20 courses of high-dose combination alkylating agent chemotherapy and autologous bone marrow support. All 20 treatment courses were evaluable for toxic reactions and 17 of 20 courses were assessable for response. Twelve of the 20 courses were given at the phase 2 dose per square meter of cyclophosphamide (5.625 g), cisplatin (165 mg), and carmustine (600 mg). Marrow reconstitution occurred with a median time to recovery of 21 and 24 days for more than 500 neutrophils and more than 20,000 platelets, respectively. The overall response rate was 65%, with one patient achieving a complete response with chemotherapy alone. Ten additional patients achieved partial responses following chemotherapy, of which three were subsequently rendered disease free by surgical resection of single areas of residual tumor. Two of these patients are alive and disease free more than 22 months following chemotherapy and one remains relapse free. The median survival for responding patients was 15.2 months and 8.6 months for the entire group.

Adult↗
PubMed1988

Indium-111 platelet scintigraphy in carotid disease.

Forty-five patients (35 men, 10 women) undergoing carotid surgery had Indium-111 platelet scintigraphy as part of their preoperative work-up. Imaging was performed within three hours after injection of the Indium-111. A second series of views was obtained 24 hours later and repeated at 24 hour intervals for two days. Of 54 scintigrams, 22 were positive and 32 negative. Positive results were defined as a twofold or more increase in local activity on a visualized carotid after 24 hours. The sensitivity of the method was 41%, intraoperatively, and the specificity, 100%. The low sensitivity places this method behind sonography and duplex-scanning for screening patients for surgery. We believe that indications for platelet scintigraphy are limited to: 1. Repeated transient ischemic attacks in the same territory with minimal lesions on arteriography and non-homogeneous plaque on duplex scan; 2. Symptomatic patients being treated medically as a possible argument for surgery; 3. Determining therapeutic policy for patients having experienced a transient ischemic attack with a coexisting intracardiac thrombus.

Aged↗
PubMed1988

[The significance of the levels of D-dimer in thrombotic conditions].

A D Dimer ELISA test (Asserachrom D Di Stago) was used to quantify the modification of plasmatic D Dimer levels in two kinds of thrombotic diseases: DIC and deep venous thrombosis. Very high values were obtained in these two situations (m +/- sd): DIC (n = 22): 15.2 +/- 18.5 micrograms/ml. (Normal values were defined in 20 healthy subjects: 0.15 +/- 0.04 micrograms/ml). In DIC highest values were a bad prognosis, they were found in patients who died during the ten days following the diagnosis. In deep venous thrombosis the increase was not related to the size of the clot but to the endogenous fibrinolysis. An elevated concentration of D Dimer was often related to a good phlebographic evolution. During heparin therapy with standard heparin or low molecular weight heparin (LMWH) a greater decrease of D Dimer level was observed in patients with a good phlebographic evolution. Results expressed in percentage of decrease were (successful group against the failure group): J3/J10: 46.4 +/- 29.2 p. cent/13.4 +/- 11.0 p. cent (p less than 0.05); J7/J10: 52.3 +/- 31.5 p. cent/24.2 +/- 26.3 p. cent (p less than 0.05). The intensity of the decrease may have an indicative value for in vivo thrombolysis. This could be explained by a smaller clot mass to be lysed in successful group. During streptokinase treatment the D Dimer levels were very high (greater than 50 micrograms/ml). A problem of specificity could be evoked in presence of a massive quantity of fibrinogen degradation products levels.

Adult↗
PubMed1988

Granulocyte-macrophage colony-stimulating factor induces the expression of the CD11b surface adhesion molecule on human granulocytes in vivo.

The CD11b (Mol) molecule is a member of a family of surface glycoproteins that are essential for adhesion-dependent granulocyte functions. Brief exposure of granulocytes to human granulocyte-macrophage colony-stimulating factor (GM-CSF) in vitro increases the surface expression of CD11b and increases granulocyte adhesiveness. To assess the possible in vivo significance of these observations we studied the effect of GM-CSF on CD11b, CD11a (LFA-1), and CD11c (gp 150, 95) expression on granulocytes from nine adult patients with sarcoma who were receiving GM-CSF as part of a phase I trial. GM-CSF was administered as a continuous infusion at a dose of 32 or 64 micrograms/kg/d. Granulocyte CD11b, CD11a, and CD11c expression was determined by indirect immunofluorescence staining of whole blood, thereby minimizing in vitro manipulation. A transient leukopenia developed within 15 minutes of initiation of GM-CSF treatment that was associated with a marked increase in the surface antigen density of CD11b. A mean 1.7-fold increase (P = .001) in the percentage of CD11b-positive granulocytes and a mean 2.1-fold increase (P = .002) in CD11b surface antigen density was noted after 12 hours of treatment. No change in CD11a or CD11c expression was observed over the first 12 hours. The level of CD11b expression was followed in six patients for up to 5 days of treatment with GM-CSF. Compared with the 12-hour value, three of six patients showed a subsequent decrease in CD11b expression, two remained constant, and one showed a continued increase in CD11b surface density. Fluorescence-activated cell sorting of granulocytes into high- and low-density CD11b-positive groups revealed a preponderance of immature myeloid forms in the low-density CD11b fraction, which suggests that the late decrease in CD11b expression in some patients may be related to a greater proportion of circulating immature myeloid forms in the peripheral blood. This study suggests that GM-CSF administered as a continuous infusion rapidly upregulates the expression of granulocyte CD11b in vivo. The influence of this phenomenon on in vivo granulocyte aggregation may be clinically relevant with regard to the toxicity of GM-CSF and deserves further investigation.

Antigens, Differentiation↗
PubMed1988

Thrombolytic treatment of pulmonary embolism with APSAC.

BRL 26921 (Eminase registered trade mark in Belgium, Germany and The Netherlands) is the p-anisoyl derivative of the primary (human) lys plasminogen-streptokinase activator complex (APSAC). The acyl-enzyme has the theoretical advantage of causing fibrinolysis in situ in the presence of fibrin clotbound plasminogen. It was administered to 34 patients with severe pulmonary embolism (PE) in an open multicentre study. PE was suspected on clinical, blood gas, ECG, and radiographic data. Pulmonary angiograms performed pre- and post-treatment confirmed the diagnosis and were assessed using the Miller Index (MI). Fibrinogen, plasminogen, alpha-2-antiplasmin, fibrinogen degradation products (FDP), activated partial thromboplastin time (APTT), partial thromboplastin time (PTT) were closely monitored before and after each administration of APSAC. Median angiographic improvement was 50% (range 0-94%). The following adverse events were reported: bleeding at puncture sites (n = 12), haematuria (n = 1), epistaxis (n = 3), fever (n = 2). A blood transfusion was given in one patient with an inguinal haematoma. Systemic fibrinogenolysis occurred in 20/28 patients.

Adult↗
PubMed1987

Pharmacokinetics of continuous-infusion high-dose thiotepa.

The pharmacokinetics of thiotepa administered as a continuous infusion over 4 days have been studied in 18 patients receiving high-dose thiotepa, cyclophosphamide, and autologous bone marrow reinfusion as treatment for advanced neoplasms. Patients received cyclophosphamide at a total dose of 6 g/m2 and thiotepa at a total dose of 180-900 mg/m2 over the 4-day infusion. Samples of plasma were obtained during and following infusion, and the plasma concentration of thiotepa was determined by the method of Egorin et al. For many patients (72%), peak concentrations of plasma thiotepa were achieved during the initial 24 hours of infusion and then declined an average of 29% by the end of the 96-hour infusion. The average total systemic clearance of thiotepa was 16.7 +/- 7.4 (SD) L/m2/hour [or 420 +/- 162 (SD) ml/kg/hr]. An inverse correlation between the average total systemic clearance and the dose of thiotepa was observed (P less than 0.01).

Adult↗
PubMed1987

[Detection by echocardiography of a thrombus of the right cavities in acute pulmonary embolism].

Echocardiography evaluates the severity of acute pulmonary embolism from its repercussions on haemodynamics. However, many authors have reported the discovery of thrombosis in the right heart cavities of patients with acute pulmonary embolism. In order to assess the frequency of intracavitary thrombosis and to evaluate the practical problems it raises, we have systematically examined by echocardiography 84 patients hospitalized for severe, acute pulmonary embolism (mean Miller's score: 21). In this series of 39 men and 45 women (mean age 62 years), 9 thrombi were detected, i.e. an incidence of 11%. Depending on the ultrasonographic images they presented, these patients were divided into two groups: 1. Six patients with low mobility thrombi attached to the cardiac wall. All benefited from a medical treatment consisting of heparin in 4 cases and a thrombolytic drug in 2 cases. There was no clinical evidence of recurrent embolism. Echocardiography showed complete disappearance of the thrombi in 5 of these 6 patients and partial regression under heparin therapy in one. 2. Three patients with a large and mobile thrombus threatening to prolapse through the tricuspid valve during atrial systole. It seemed rational to regard such thrombi as carrying a high risk of embolism with recurrences, especially since they had formed in patients already with severe pulmonary embolism. This view was confirmed by a search in the literature which yielded a 40% death rate figure when these thrombi were associated with pulmonary embolism. This high mortality, however, can be reduced by diagnostic and therapeutic measures.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1987

[Value and place of real-time ultrasonic diagnosis combined with continuous-wave Doppler in the diagnosis and follow-up of thromboembolic disease].

The authors compared the results of real time ultrasound imaging and continuous wave Doppler (Echography-Doppler with bilateral venography and ilio-cavography in the diagnosis and the follow-up of deep venous thrombosis (D.V.T.). Diagnosis of D.V.T. The value of echography-Doppler (ED) compared to venography is studied on 297 patients (590 legs) suspected of D.V.T. (221) or pulmonary emboli (76). The two methods give concording results in 95% (563/590). Discrepancies (27) are more often located in distal veins. If we refer to venography as the gold standard, sensitivity of ED is 98% (236/242) and specificity is 95% (327/344). Other diagnosis are possible: hematoma (9), extrinsic compression (15), Baker's cyst (4), muscular problems (3)... Topographic value Sensitivity in isolated calf vein thrombosis is 90% (54/60 are detected, 22 are bilateral). 4/6 false negatives are located in the presumable healthy legs. Sensitivity in proximal D.V.T. is excellent 100% (182 D.V.T. with 28 bilateral). The upper extremity of the thrombus is located exactly by ED whatever the topography (35 in the inferior vena cava, three of them beyond the renal veins), the degree of obstruction (partially occluded veins: 32), and even if it's extended or not (27). Follow-up of D.V.T. Assessment of the results in 80 patients under treatment is identical with the two methods, whatever the topography, the degree of obstruction and the evolution of thrombosis. E.D. predictive value in therapeutic efficiency is discussed according to the evolution data in 260 patients. Screening of D.V.T. ED is compared to venography (13) and/or Fibrinogen test (15), in 23 patients (46 legs) with high risk of thrombosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Follow-Up Studies↗
PubMed1987

High-dose combination alkylating agent preparative regimen with autologous bone marrow support: the Dana-Farber Cancer Institute/Beth Israel Hospital experience.

Fifty-nine patients received 61 courses of cyclophosphamide, cisplatin, and carmustine combined. The phase I study consisted of seven dose escalations. Dose levels 5 and 6 also included the attempted addition of melphalan at 40 and 80 mg/m2. The maximum tolerated dose for the three-drug combination was 5620 mg/m2 of cyclophosphamide, 165 mg/m2 of cisplatin, and 600 mg/m2 of carmustine. The dose-limiting toxic effect was fatal veno-occlusive disease of the liver in two of five patients treated at the highest dose level. Veno-occlusive disease of the liver was fatal in two of 40 patients treated at Dose level 4, the maximum tolerated dose. The median time to recovery of polymorphonuclear leukocyte counts to greater than 500/microliters and platelet counts to transfusion independence greater than 20,000/microliters was 19 and 22 days, respectively, after marrow reinfusion. Other toxic effects observed included postdischarge pulmonary toxicity, which appeared to respond to prednisone therapy. Thus, this combination of alkylating agents can be combined at close to the transplant dose of each individual agent. The response rate was high despite considerable prior treatment in most patients. Of 16 evaluable patients with breast cancer, 15 responded (six complete responses). Of six evaluable patients with sarcoma, six responded (one complete response). While patients with melanoma had had no prior treatment, 11 of 17 patients responded (65%). There are currently three patients who are disease-free. Two patients with melanoma were rendered disease-free by excisional biopsy of the only remaining nodule after good partial response, and a patient with metastatic breast cancer remains disease-free after a complete response at 36+ months.

Adult↗