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Biomedical subjects

G Cella

Publications and source records attributed to G Cella.

At least 19 recordsLinked to original sources
PubMed1995

[Symptomatic relief of carcinoid syndrome by ketanserin. A case].

The carcinoid syndrome is a rare clinical entity mainly characterized by flushing and diarrhoea. It is due to different biological mediators produced by tumours that arise from enterochromaffin cells. Such tumours are typically located in the ileum, have a long course and become symptomatic only in the presence of overt liver metastases. Among the involved mediators, the role of serotonin (5-hydroxytryptamine, 5-HT) has been ascertained in the pathogenesis of diarrhoea, while it remains controversial in that of flushing. Ketanserin is a 5HT-2 antagonist with no mixed receptor agonist-antagonist activity. We report the case of a severely distressing carcinoid syndrome fully dominated by ketanserin. The patient was a 75-year-old man, who came to our attention because of marked weight loss, impossibility to feed and almost continuous diarrhoea due to liver colonization of a mid ileum carcinoid tumour, previously resected at the age of 65. Sustained facial and trunk flushing also presented several times daily. Ketanserin, 20 mg twice a day orally, was administered and then increased up to 40 mg daily with no side effects and progressive complete control of both diarrhoea and flushing. It is suggested that ketanserin, due to its availability and tolerability, should first be considered for palliative relief of carcinoid syndrome. The literature on this subject is extensively reviewed.

Aged↗
PubMed1992

Neutralization of the antiheparin activity of platelet factor 4 by a monoclonal antibody.

We have produced a panel of monoclonal antibodies (mAbs) against rabbit platelet factor 4 (PF4). Two of these mAbs have been characterized in this study. In particular the antibody called 10B2, which also recognizes the human molecule, is able to block PF4's ability to neutralize heparin in a modified Heparin-Factor Xa chromogenic assay. The inhibition appears to be more than 95% at 1:1 mAb/PF4 molar ratio both for purified rabbit and human PF4. Similar results were obtained using supernatants from stimulated human platelets (90% of inhibition at 1:1 mAb/PF4 molar ratio) or using Fab fragments from 10B2. Studies to determine the antigenic determinant against which 10B2 is directed, show that this is an assembled epitope which involves disulfide bonds of the PF4.

Amino Acid Sequence↗
PubMed1992

Interaction between histidine-rich glycoprotein and platelet factor 4 with dermatan sulfate and low-molecular-weight dermatan sulfate.

There is a controversy about whether or not histidine-rich glycoprotein (HRG), the most abundant plasma protein with glycosaminoglycans-neutralizing capacity, is able to prevent the inhibition of human thrombin by heparin cofactor II (HC II) in the presence of dermatan sulfate (DS). The authors studied the interaction of DS and low molecular weight DS, in a purified system with HRG, platelet factor 4 (PF 4), and with HC II. Their results show that HRG, like PF 4, has an affinity, not only for heparin, but also for DS. However, this affinity seems very weak. In fact, HRG is 10 times less effective than PF 4 in neutralizing the 50% antithrombin activity of HC II in the presence of DS.

Blood Proteins↗
PubMed1991

Effect of buflomedil, dipyridamole and indobufene on hemorrheologic and blood coagulation parameters in patients who underwent vascular surgery for severe atherosclerosis.

We studied 30 patients (age range 58 to 64 years) who underwent vascular surgery for peripheral vascular disease (24 patients) and for carotid stenosis (6 patients). At the time of the study, all subjects have been taking antiplatelet agents for at least three months. They were divided into three groups of ten patients each: the first group received buflomedil (BUF), the second dipyridamole (DIP) and the third indobufene (IND), as treatment before vascular surgery. We investigated the influence of these drugs on hemorrheologic (hematocrit, whole blood and plasma viscosity) and blood coagulation (partial thromboplastin time, prothrombin time and bleeding time) parameters in all patients. In our experience, none of the three drugs influenced any tested parameters, which were within normal limits: among them we noted only a statistically significant difference in bleeding time between patients treated with BUF and IND.

Arteriosclerosis↗
PubMed1990

Effect of cellulose acetate 0.2 micron filter on platelet specific proteins plasma levels.

We are reporting the effect of a cellulose acetate 0.20 micron filter (Flow Pore D26) on preparation of platelet poor plasma (PPP) for subsequent assay of platelet specific proteins. PPP was obtained using the Edinburgh anticoagulant mixture and a centrifugation at 2,300 g for 20 minutes. The mean levels of platelet factor 4 (PF4) and beta-thromboglobulin (beta TG) before filtration were: PF4 15.7 ng/ml (1.5-42.8 ng/ml); beta TG 62.0 ng/ml (25-140 ng/ml). After filtration we obtained: PF4 4.8 ng/ml (1.0-8.9 ng/ml), beta TG 28.4 ng/ml (8.5-51.1 ng/ml). Thus difference for both the platelet specific proteins was statistically significant (p less than 0.005). The contamination by platelet-like material was also greatly affected by the filter (before filtration 4.3 x 10(6)/ml), (2-15 x 10(6)/ml), after filtration 2.0 x 10(6)/ml (1-5 x 10(6)/ml), p less than 0.005). If a high speed centrifuge is not available, the use of this simple filter method could avoid falsely elevated values of platelet specific proteins.

Adult↗
PubMed1989

Improved method for purification of human platelet factor 4 by affinity and ion-exchange chromatography.

A simple method for the reproducible purification of human platelet factor 4 (PF4) is described. PF4 is obtained in a highly purified form from platelet concentrate by utilizing a combination of affinity and FPLC ion-exchange chromatography. In every instance, after elution from heparin affinity and cation exchange chromatography, SDS gel electrophoresis reveals a single band attributable to PF4. Moreover, the amino acid composition of PF4 isolated by this method is compatible with that described for a PF4 cDNA clone and with other reported PF4 analysis. The purified protein is used to study in vitro the affinity of PF4 for several glycosaminoglycans (GAGs), by measuring the fluorescence of each PF4-GAG complex bound to fluorescamine. PF4 affinity for GAGs is as follows: heparin greater than heparan sulphate much greater than dermatan sulphate.

Amino Acids↗
PubMed1989

Effects of glycosaminoglycans and protamine chloridrate on platelet aggregation induced by collagen and thrombin.

The effects of heparin (HE), dermatan sulfate (DS), heparan sulfate (HS) and protamine chloridrate (PC) on platelet aggregation were studied. Both PC and the three glycosaminoglycans (GAGs) did not influence collagen-induced platelet aggregation. In contrast, all the tested GAGs blocked thrombin-induced platelet aggregation. HE and HS were equivalent and very effective, while DS was also but to a lesser extent. This could be because HE and HS act via both antithrombin III and heparin-cofactor II, whereas DS exerts its action on the latter only. PC, too, inhibited, in a dose-dependent fashion, thrombin-induced platelet aggregation, probably by competing with the thrombin affinity binding sites on the platelet surface. When the GAGs were tested together with PC, HE was shown to be the most effective: on a weight-for-weight basis, an identical amount of PC was unable to counteract the inhibitory effect of HE, while it partially reversed those of DS and HS. A full reversal of the inhibitory effect of DS and HS was never observed, in spite of adding increasing amounts of PC. It seems likely that plasma components may preserve the bindings of such GAGs with their cofactors.

Collagen↗
PubMed1989

Prospective study of a standardized questionnaire to improve clinical estimate of pulmonary embolism.

A standardized questionnaire was administered to 100 patients suspected of having pulmonary embolism to investigate whether clinical data may be reliably used in the decision-making process of such patients. Questionnaire data were compared with lung scintigraphy outcome and 16 variables were selected as significantly associated with the scintigraphic diagnosis. Based on these variables, patients with abnormal scintigraphy compatible with pulmonary embolism and patients with scintigraphy not compatible with embolism were classified in accordance with the scintigraphic diagnosis. When these 16 variables were tested in an additional validation group, clinical and scintigraphic diagnosis matched in most cases. These results show that clinical data can be used to predict the outcome of lung perfusion scintigraphy in patients suspected of pulmonary embolism. Use of a standardized questionnaire can improve the accuracy of pretest assessment of such patients and positively influence the decisions to start heparin coverage or obtain pulmonary angiography.

Electrocardiography↗
PubMed1988

Serial determinations of PF4 and beta TG: comparisons between multiple venipunctures vs a catheter infusion system.

Platelet factor 4 (PF4) and beta thromboglobulin (beta TG) are platelet-specific proteins which are released upon platelet aggregation and which can be accurately measured by radioimmunoassay. We devised a catheter-infusion system that enables serial determinations of these proteins. In 20 subjects (10 healthy volunteers and 10 patients with stable coronary artery disease), we compared samples collected by individual venipunctures with those simultaneously obtained by means of a simple catheter-infusion system. At least 5 samples were obtained over a period of time which was as long as 60 min, and at least 30 min. Subjects with stable coronary artery disease were selected so that they would be expected to have stable and normal PF4 and beta TG levels. Thus, elevations of either PF4 or beta TG would represent artifacts secondary to sampling technique. Analysis of the results demonstrated that the catheter-infusion system was equivalent to individual venipunctures for determination of PF4 and beta TG. 16.8% of samples obtained via the catheter and 17.2% of those obtained by individual venipunctures were spuriously elevated. A second series of studies were performed to refine the technique further by examining the impact of infusion rate and the addition of citrate phosphate dextrose (CPD) to the infusate. Ten additional subjects had catheter systems utilized in both arms simultaneously. The addition of CPD resulted in significantly less abnormal values at slower infusion rates (1 and 2.5 cc/min). At 5 cc/min D5/w or saline alone are suitable. These investigations confirm that this simple catheter system is equivalent to individual venipunctures for determination of PF4 and beta TG while avoiding patient discomfort.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1987

Human platelet factor 4 and protamine sulphate interaction with glycosaminoglycans in the rabbit.

We studied the action of protamine sulphate on human platelet factor 4 (PF4) kinetics in rabbits in the presence of various glycosaminoglycans (CAGs). The animals pretreated with heparin showed high initial PF4 levels with a subsequent slow monoexponential clearance. The PF4 kinetics, in the presence of heparan and dermatan sulphate, reflected the different affinities that PF4 has for these GAGs. Protamine, at dosages that totally neutralized 1000 USP units of heparin pretreatment, caused an immediate disappearance in the circulating PF4. However, a second heparin injection 10 min after protamine, induced a PF4 peak release. It is possible that protamine displaced the PF4 from the binding sites of heparin, releasing it for storage in the body 'pool', from where it can be harvested again. The action of protamine on PF4 kinetics in the rabbits pretreated with 30 mg heparan sulphate was similar to that obtained with heparin pretreatment; however, a higher dose of protamine was required to obtain the optimal effect. After a 20 mg dose of protamine, unexpectedly, a bolus of heparin did not produce any peak release of PF4 in the rabbits pretreated with 30 mg of dermatan sulphate. Although part of the protamine will displace PF4 from the binding sites of the dermatan sulphate molecule, the remaining part of protamine could probably be bound to this GAG without losing its activity so that, upon subsequent heparin injection, it is immediately neutralized, rendering it unavailable for further PF4 harvesting.

Animals↗