Search PubMed⌕ Search

Biomedical subjects

E Melissari

Publications and source records attributed to E Melissari.

At least 37 records · Page 2Linked to original sources
PubMed1992

Long term effects of tamoxifen. Biological effects of Tamoxifen Working Party.

A total of 153 breast cancer patients who participated in two trials of adjuvant tamoxifen and who had not recurred were recruited into a study of the long term effects of tamoxifen. There were 60 controls (no tamoxifen), 73 ex-users (mostly for 2 years) and 20 current users (median treatment duration 72 months) and the median follow-up time was 7 years. A wide ranging study of lipids, hormones, bone density and haemostasis was undertaken. When compared with controls, current users had lower cholesterol levels (especially low density cholesterol), and increased triglyceride levels. Thyroid hormones were higher and sex hormone binding globulin was almost doubled. Bone density was non-significantly higher, clotting times were slightly shorter and fibrinogen and antithrombin III levels were reduced. However few of these changes persisted in ex-users, suggesting that most of the biological effects of treatment are reversible on cessation of treatment. This is reassuring for potentially negative side-effects, but also indicates that potentially positive 'side-effects' such as cholesterol lowering only occur while on active treatment.

Bone Density↗
PubMed1992

Congenital thrombophilia among patients with venous thromboembolism.

During a 3-year period we studied 393 adult patients (382 of whom were unrelated) with a history of acute venous thromboembolism. A congenital deficiency state known to predispose to thrombosis was found in 27.2%. Of these, most were due to deficiencies of protein C (9.2%), protein S (7.6%), antithrombin III (5%) or to increased plasma PAI-1 concentration (3.1%) which, in the absence of any known factor that predisposes towards thrombosis, results in a diminished fibrinolytic activity. There was a characteristic pattern between the age of onset (mean 34 years) of thrombosis and individual protein deficiency. Thrombosis appeared spontaneously in 73% of cases with recurrence in 80%. In contrast, in the remaining unrelated patients, 138 (35.1%) in whom venous thromboembolism was secondary and occurred at a mean age of 43 years, and in the other 140 (35.6%) who suffered thromboembolism spontaneously at a later age (mean age 55), there was no permanent protein deficiency state or alteration in fibrinolytic activity and thrombosis recurrence was lower (53.6% and 20.7% respectively). Of the 393 patients, deep vein thrombosis was the most common manifestation; however, in congenital thrombophilia, thrombosis of visceral vessels and Raynaud's syndrome (6%) were also detected.

Acute Disease↗
PubMed1991

Recurrent deletion in the human antithrombin III gene.

Eight unrelated patients with recurrent thromboembolism, a family history of thrombosis, and plasma antithrombin III (ATIII) activity/antigen levels consistent with a diagnosis of heterozygous type I ATIII deficiency were studied by polymerase chain reaction/direct sequencing of ATIII gene exon-coding regions. Frameshift mutations of one base and two bases, respectively, were found to have occurred in two unrelated patients at the same GAG codon (Glu 245) within exon 4 of the ATIII gene. A literature search showed six further hitherto unrecognized deletion "hotspots" in four other human genes. These deletion-prone sites exhibited sufficient sequence homology with each other to derive a consensus sequence (T G A/G A/G G A/C), suggesting that deletion in human genes may not only be non-random but also sequence-directed.

Antithrombin III↗
PubMed1991

Intra-operative antithrombotic therapy with low molecular weight heparin in aortic surgery. How should heparin be administered?

This prospective study evaluates, for the first time, the efficacy of heparinisation with low molecular weight heparin (LMWH) in aortic surgery and identifies the most effective route of administration for heparin. Sixteen patients undergoing abdominal aortic grafting for aneurysmal and occlusive disease were studied. They were randomised to receive 10,000 anti Xa units of LMWH either intravenously or directly into the aorta before or after aortic cross-clamping. Serial venous blood samples and a paired arterial sample from the superficial femoral artery were taken for the estimation of systemic and lower limb heparin activity. All three methods of administration gave therapeutic levels of heparin in the systemic and lower limb circulation. Intravenous and aortic administration before clamping resulted in significantly higher systemic levels when compared with aortic injection after clamping (p less than 0.05 Mann-Whitney U test). Intra-aortic administration resulted in a significantly higher heparin activity in the lower limb when compared with the intravenous route (p less than 0.05). No patient developed distal thrombosis. This study demonstrates that the most effective way of giving heparin in aortic surgery is by direct injection into the aorta. Administration of LMWH after cross-clamping results in less systemic activity which may help to reduce any haemorrhagic side effects.

Aged↗
PubMed1991

The influence of venous occlusion on the status of protein S.

In the present study the effect of perturbation of the vessel wall by venous occlusion on protein S release, was evaluated in 10 healthy male volunteers. A 9% (P less than 0.01) increase in free protein S and a 7% (NS) in total protein S over the baseline were observed 7 min after venous occlusion, whereas von Willebrand factor antigen (vWF:Ag)--a known release product of vascular endothelium--increased by 11% (P less than 0.01). In addition, the possibility of free protein S release from unstimulated platelets was investigated in pre- and post-occlusion samples incubated at room temperature for 24 h as whole blood or platelet-rich plasma. An increase in the mean free protein S was observed in the pre-occlusion samples which peaked after 4 h of incubation--121% at time 0 to 130% (P less than 0.05) of the normal pooled plasma whereas total protein S increased by only 4% (NS). In the post-occlusion samples, a similar peak in mean free protein S levels was observed after 12 h of incubation--132% at time 0 increased to 142% (P less than 0.01) of the normal human plasma pooled and the total protein S was increased by 8.55 (P less than 0.05). Small but significant increases in vWF:Ag levels were observed at 2 h and 6 h for the pre- and post-occlusion samples, respectively. No changes in C4b-binding protein were observed throughout the study. We conclude that, firstly, venous occlusion causes release of protein S in addition to vWF:Ag and, secondly, unstimulated platelets release protein S in addition to vWF:Ag.

Adolescent↗
PubMed1989

Influence of whole blood on standard curve for heparin measurement--possible heparin binding by red cells.

Measurement of heparin ex vivo is usually with reference to standard curve prepared with a "spiked" normal human plasma pool (NHP). When the calibration curve was prepared by addition of heparin to whole blood before plasma separation, although the linear relationship was maintained the slope was increased in comparison to the classical standard calibration curve. It is concluded that the preparation of the calibration curve by addition of heparin to NHP may give erroneously high heparin levels in treated patients' plasma, leading perhaps to inappropriate dosage. It was also observed that when heparin was added to blood of different haematocrit (prepared by addition of washed RBC to plasma) and plasma prepared, the subsequent APTT was decreased with the fall in haematocrit; suggesting that the laboratory monitoring of heparin treatment should take into account the patient's haematocrit.

Calibration↗
PubMed1989

The effect of a bolus injection of unfractionated or low molecular weight heparin during aortobifemoral bypass grafting.

Eighteen patients undergoing aortobifemoral graft surgery for severe aortoiliac atherosclerotic disease received a bolus injection of 10,000 anti-Xa units of either unfractionated heparin (UFH) or low molecular weight heparin (LMWH) into the distal aorta as prophylaxis against thromboembolic complications related to clamping. Heparin activity was measured by factor Xa inhibition and by prolongation of the APTT. In both groups there was a delay before peak levels of heparin were observed. In the LMWH group, this amounted to 30 min. In the UFH group, APTT was prolonged by 46 s, 7 min after injection but only by 5 s at the end of the operation. In contrast, in the LMWH group, the prolongation in APTT 7 min after injection was less (34 s) but more sustained since a 12.5 s prolongation was still present at the end of the operation. During surgery, heparin activity exceeded 0.7 U/ml in the LMWH group, compared to significantly lower levels in the UFH group (less than or equal to 0.20 U/ml). By the end of the operation no heparin activity was detectable in the UFH group. Protein C antigen decreased after heparin injection and this fall was more pronounced in the UFH group. The level of C1q (a subcomponent of the first component of the complement system) was decreased in the UFH group (P less than 0.04), whereas in the LMWH group C1q levels increased. Platelet aggregation with collagen was inhibited to a significantly greater degree in the LMWH group than the UFH group (54% compared with 23%) (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1989

Congenital severe protein C deficiency in adults.

Two unrelated families are described, of which four adult members were found to be suffering from severe protein C deficiency (less than or equal to 5% of normal plasma level). Newborn deaths were reported in the first family but the second family had no history of neonatal purpura fulminans and infant death. Thrombotic symptoms developed mainly in their early twenties, consisting chiefly of recurrent superficial and deep iliofemoral vein thromboses and pulmonary emboli. Other clinical features included generalized peritonitis due to massive mesenteric vein thrombosis, thrombosis of the cavernus sinus, renal vein thrombosis and priapism. In the second family, five members (all aged approximately 40 years) died of intravascular abdominal thrombosis. Massive thromboembolic episodes were associated with a compensated disseminated intravascular coagulation syndrome as evidenced by high concentrations of D-dimer (mean levels 5000 ng/ml plasma) and by a moderate reduction in platelet count and fibrinogen concentrations. D-dimer levels in noncrisis periods were also raised above normal (mean levels 400 ng/ml). The thrombotic problems of these patients were controlled satisfactorily by long-term administration of low molecular weight heparin alone or in combination with low dose warfarin.

Adolescent↗
PubMed1988

The effects of oestrogen administration on the plasma free protein S and C4b-binding protein.

This study was undertaken to evaluate the effects of oestrogen administration (low dose as an oral contraceptive or higher dose as a hormone replacement therapy) on the levels of plasma free protein S and C4b-binding protein. The participants were 59 women aged 18-49 years, divided into 2 groups: A and B. Group A was composed of 22 post-menopausal women on a hormonal replacement therapy programme (HRT) consisting of 2 mgs daily oestradiol valerate for 21 days. Group B was divided into subgroup B1: 18 women who had been on oral contraceptive for at least one year and subgroup B2 (control): 17 women who were not pregnant and not taking any oral contraceptive. In this study were also included two young women who both suffered from severe thromboembolic disease a few months after initiation of oral contraceptive. The first was 25 years old, with congenital moderately decreased prekallikrein (activity and antigen 40% and 45% respectively) and the second was a 21 year-old woman with congenital moderately decreased plasminogen activity and antigen 45%). In both cases, family members with similarly reduced levels of prekallikrein (PK) and plasminogen (PLG) respectively were free from any thromboembolic disease and had normal protein S levels. In Group A, 22 women at the end of the first cycle of treatment, had lower levels of free protein S (p less than 0.001) than before the initiation of HRT. In subgroup B1, the levels of free protein S were found to be significantly lower than in subgroup B2 (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1988

Protein S and C4b-binding protein in fetal and neonatal blood.

The levels of protein C, free protein S, C4b-binding protein and the distribution of total protein S between a free form and a conjugated form with C4b-binding protein, were measured in fetuses between 15 and 35 weeks of gestation, in newborns and in maternal blood throughout pregnancy. Fetal and newborn umbilical blood samples were obtained by cordocentesis; in the case of newborns, immediately after delivery. C4b-binding protein was detected in five out of seven newborns and in only three out of 20 fetuses. The fetuses (21, 24, 29 weeks, respectively) whose blood contained C4b-binding protein (10%, 29%, 12% of adult level, respectively), did not survive: the possible cause of death for one was given as viral infection; all three were severely deformed. Only free protein S was detected in fetal blood and the mean value was 40%. By contrast, the mean levels of protein C in the fetuses increased from 11% to 15.5% of adult levels with advancing gestation. We conclude that the relatively high levels of free protein S in fetal blood may contribute to its non-coagulability and compensate for the low protein C levels.

Carrier Proteins↗
PubMed1986

The influence of DDAVP infusion on the coagulation and fibrinolytic response to surgery.

The response of components of the coagulation and fibrinolysis systems to infusion of DDAVP has been examined in patients undergoing elective surgery. In the DDAVP treated group there was a significant increase, compared to control, in plasminogen activator (by fibrin plates p less than 0.005, ECLT p less than 0.0125, by Student's t test) before operation. No difference between groups was seen by either methods in the activator levels in samples 24 h postoperation, whereas a significant drop (p less than 0.002) in protein C concentration was observed at this stage in the treated group. Levels of factor VIII components were significantly higher (p less than 0.005) than control at all stages of operation and a significant shortening (5 sec p less than 0.05) of the APTT was seen at all stages (apart from 24 h samples). DDAVP infusion therefore may exacerbate the hypercoagulable state observed in surgical patients without preventing the (post-operatively) fibrinolytic shutdown. Instead, infusion tends to produce fibrinolytic depletion at the key mid-operative stage.

Adult↗
PubMed1985

The influence of LMW heparin on the coagulation and fibrinolytic response to surgery.

The response of components of the coagulation and fibrinolytic systems has been examined in patients undergoing minor and major elective surgery and receiving or not receiving subcutaneously administered prophylactic low molecular weight (LMW) heparin. Blood samples were withdrawn pre-operation (PO), post-anaesthesia (PA), during operation (DO) and 24 hours post-operation. Release of plasminogen activator occurred post anaesthesia at a time when factor VIII components were unchanged or decreased. Induction of anaesthesia decreased plasminogen (p less than 0.005) fibrinogen (p less than 0.02) ATIII (p less than 0.002) and fast a2-antiplasmin (p less than 0.005). During operation plasminogen activator release reached a peak in association with a moderate increase in factor VIII components. Heparin treatment produced a prolongation of APTT at DO (p less than 0.05) and at 24hr (p less than 0.002) stages, this prolongation being apparently unrelated to its concentration but did not prevent the rise of factor VIII components observed at 24 hr (p less than 0.02). Prekallikrein (p less than 0.05) and antithrombin III levels (p less than 0.05) were significantly higher whereas fast a2-antiplasmin (p less than 0.002) was significantly lower at 24 hours in patients undergoing major operation and treated with heparin. Protein C levels fell significantly at 24 hours in the untreated patient (p less than 0.014) and in the heparin treated group the fall was greater than the control group (p less than 0.007). At 24 hours other haemostatic and fibrinolytic components were unaffected by heparin treatment.

Adult↗