Biomedical subjects

R Lombardi

Publications and source records attributed to R Lombardi.

At least 73 records · Page 4Linked to original sources

PubMed1986

Conjugated estrogens for the management of bleeding associated with renal failure.

Bleeding is a major complication of uremia. Both cryoprecipitate and desmopressin effectively shorten the prolonged bleeding time and favorably influence clinical bleeding, but the former carries the risk of transmitting blood-borne infectious diseases, and both cryoprecipitate and desmopressin have a short duration of action. Preliminary evidence has suggested that estrogens may be useful, and we therefore performed a randomized, double-blind, crossover trial comparing the effect of conjugated estrogens with that of placebo on hemorrhagic tendencies and the bleeding time in six patients with uremia who were on maintenance hemodialysis. Five daily infusions of placebo or conjugated estrogens were administered at the beginning of one-month trial periods. Estrogen shortened the bleeding time in all six patients. The effect was detectable six hours after the first infusion, reached its maximum in all patients between days 5 and 7, and lasted for 14 days. By day 16 after the last infusion, the bleeding time had returned to base line in four of the six patients. No side effects were noted during or after estrogen infusion. Estrogens did not influence the circulating level of von Willebrand factor or change its multimeric structure. Moreover, the defective platelet aggregation and thromboxane formation observed in the patients were not corrected by estrogens. We conclude that conjugated estrogens are an adequate alternative to cryoprecipitate or desmopressin for the treatment of bleeding associated with renal failure, especially when a longer duration of action is needed and immediate onset of the effect is not essential. The mechanism of action of estrogens remains to be clarified.

Adult↗

PubMed1986

Electroblot and immunoperoxidase staining for rapid screening of the abnormalities of the multimeric structure of von Willebrand factor in von Willebrand's disease.

A new electrophoretic method is described for rapid screening of abnormalities of the multimeric structure of von Willebrand factor in von Willebrand's disease. The method is based on the transfer of the separated proteins from agarose gels onto nitrocellulose foils followed by immunoperoxidase staining. It has the advantage of not requiring radio-iodinated antibodies and reduces the working time for the entire procedure from 5-6 days to 3 days. Electroblotting followed by immunoperoxidase staining differentiates patients with intact multimeric structure from those without intermediate and/or large multimers. The more subtle defects of the inner structure of the smallest multimers found in patients with type II von Willebrand's disease can also be identified. A potential disadvantage of electroblotting and immunoperoxidase staining is the lesser sensitivity of this technique, which results in the detection of a smaller number of multimers (11-12 bands) than by autoradiography without transfer onto nitrocellulose (16-17 bands).

Autoradiography↗

PubMed1986

Heterogeneity in type IIB von Willebrand disease: two unrelated cases with no family history and mild abnormalities of ristocetin-induced interaction between von Willebrand factor and platelets.

Two patients from two separate families were diagnosed as having type IIB von Willebrand disease, because they had lifelong bleeding tendencies, prolonged bleeding times, no large von Willebrand factor multimers, and low levels of ristocetin cofactor in plasma with heightened ristocetin-induced platelet aggregation. There was no history of bleeding, and no laboratory abnormalities were found in the parents and sibship of either propositi, in contrast with the autosomal dominant pattern of inheritance usually observed in type IIB von Willebrand disease. Abnormalities of ristocetin-induced von Willebrand factor-platelet interactions were less severe than in a patient from a previously reported family with type IIB von Willebrand disease studied in parallel. The peculiar features of these cases provide additional evidence of the existence of heterogeneity within this variant.

Blood Platelets↗

PubMed1986

Lack of association between prodromes nausea and vomiting, and specific electrocardiographic patterns of acute myocardial infarction.

We conducted an observational study on 164 patients consecutively admitted to our coronary care unit in order to evaluate the predictive role of cardiac prodromes nausea and vomiting, in distinguishing a particular electrocardiographic pattern (Q wave versus non-Q wave and localisation) of an acute myocardial infarction. Patients with the prodromes made up 47.0% of all Q wave myocardial infarction and 59.4% in those without Q wave myocardial infarction. Furthermore, patients had nausea and vomiting in 25.0% of all Q wave myocardial infarction and in 31.2% of all non-Q wave infarction. No significant differences were found in the patients who experienced nausea and vomiting in the localisation (anterior versus inferior) of myocardial infarction. Our findings indicate that the cardiac prodromes of nausea and vomiting do not play any particular role in predicting a specific electrocardiographic pattern of acute myocardial infarction.

Electrocardiography↗

PubMed1986

A new variant of type II von Willebrand disease with aberrant multimeric structure of plasma but not platelet von Willebrand factor (type IIF).

A patient with a lifelong bleeding disorder was diagnosed as having Type II von Willebrand disease. The larger multimers of von Willebrand factor were absent from her plasma but present in platelets. A high-resolution electrophoretic technique was used to study the complex structure of individual von Willebrand factor multimers. In normal plasma, each multimer could be resolved into five bands: a more intense central one and four less intense, two moving faster and two slower than the central band. In normal platelets, each multimer could also be resolved into five bands. The central one had a mobility similar to that in plasma, whereas the four satellite bands had a mobility that differed from that of the corresponding plasma bands. In the patient, platelet von Willebrand factor antigen content and ristocetin cofactor activity were normal, and von Willebrand factor showed the same structure of individual multimers as seen in normal platelets. On the other hand, plasma von Willebrand factor antigen and ristocetin cofactor activity were decreased, and the structure of individual von Willebrand factor multimers was different from that of normal plasma and similar to that seen in normal and patient's platelets. After infusion of 1-deamino-8-D-arginine vasopressin, the largest von Willebrand factor multimers, as well as new satellite bands with a mobility similar to those in normal plasma, appeared in the patient plasma, and the levels of von Willebrand factor antigen and ristocetin cofactor activity became normal. Yet no relevant change in the prolonged bleeding time was observed. This new variant of von Willebrand disease, therefore, is characterized by the presence of a dysfunctional von Willebrand factor molecule that exhibits unique structural abnormalities in plasma but appears to be normal in platelets. The designation of Type IIF is proposed for this type of von Willebrand disease in accordance with the terminology that has been previously used.

Bleeding Time↗

PubMed1985

Multicenter comparison of von Willebrand factor multimer sizing techniques. Report of the Factor VIII and von Willebrand Factor Subcommittee.

A multicenter study of various types of von Willebrand's disease (vWD) was conducted in order to compare the different electrophoretic techniques used to evaluate von Willebrand factor multimers in plasma. Seven laboratories participated in the blind study of eight plasma samples from two healthy subjects and six vWD types and subtypes (Ia, Ib, IIA, IIB, IIC and IID). From the results of the multimeric analysis of these samples, it appears that the differential diagnosis of vWD types and subtypes should be first approached by using a low-resolution electrophoretic technique, where each vWF multimer appears as a single band. Low-resolution techniques differentiate type I from type II, subtype Ia from Ib and also subtype IIA from other type II subtypes. When type II subtypes other than IIA are identified with these techniques, samples should be rerun using high resolution techniques that resolve each of the fastest migrating multimers in at least three subbands, and permit the differentiation of subtypes IIB, IIC and IID.

Electrophoresis, Agar Gel↗

PubMed1985

Heterogeneity of type I von Willebrand disease: evidence for a subgroup with an abnormal von Willebrand factor.

Type I von Willebrand disease (vWD) is characterized by equally low plasma concentrations of von Willebrand factor antigen (vWF:Ag) and ristocetin cofactor (RiCof) and by the presence of all vWF multimers in sodium dodecyl sulfate (SDS)-agarose gel electrophoresis. For 17 patients (13 kindreds) diagnosed with these criteria, we have studied the platelet contents of vWF:Ag and RiCof and the changes of these in plasma after DDAVP infusion. Platelet vWF:Ag and RiCof were normal in four kindreds (called "platelet normal" subgroup); following 1-deamino-8-D-arginine vasopressin; plasma vWF:Ag, RiCof and the bleeding time (BT) became normal. In six kindreds, platelet vWF:Ag and RiCof were equally low (platelet low); after DDAVP, plasma vWF:Ag and RiCof remained low, and the BT was prolonged. In three additional kindreds, platelets contained normal concentrations of vWF:Ag, but RiCof was very low (platelet discordant); even though a complete set of multimers was found in plasma and platelets, there was a relatively small amount of large multimers. After DDAVP, plasma vWF:Ag became normal, but RiCof remained low and the BT was very prolonged. These findings demonstrated that there can be an abnormal vWF (RiCof less than vWF:Ag) even in type I vWD, coexisting with a complete set of vWF multimers (platelet discordant); that the abnormal vWF can be shown more clearly in platelets than in plasma or else in plasma after DDAVP infusion; and that DDAVP normalizes the BT only in those patients with normal platelet levels of both vWF:Ag and RiCof (platelet normal).

Autoradiography↗

PubMed1984

Studies of the pathophysiology of acquired von Willebrand's disease in seven patients with lymphoproliferative disorders or benign monoclonal gammopathies.

In seven patients with acquired von Willebrand's disease (AvWD) associated with lymphoproliferative disorders or benign monoclonal gammopathies, the platelet contents of von Willebrand factor antigen and ristocetin cofactor (vWF:Ag and vWF:RiCof, respectively) were normal. All the multimers of vWF:Ag could be seen in the 1.6% SDS-agarose gel electrophoresis patterns of plasma and platelet lysates. Infusion of 1-deamino-8-D-arginine vasopressin (DDAVP) augmented plasma levels of vWF:Ag and vWF:RiCof of all patients and corrected prolonged bleeding times (BT). However, compared with patients with congenital vWD type I and comparable degrees of baseline abnormalities treated in the same way, vWF:Ag and vWF:RiCof were increased less and cleared more rapidly from plasma and the BT remained normal for a shorter period of time. These studies provide evidence that these AvWD patients have qualitatively normal vWF in plasma, but at lower concentrations, that vWF in platelets is normal both qualitatively and quantitatively, and that cellular vWF can be rapidly released into plasma by DDAVP to correct the hemostatic abnormalities. However, vWF is removed rapidly from plasma, making the correction more transient than in congenital vWD type I.

Adult↗

PubMed1983

Deamino-8-D-arginine vasopressin shortens the bleeding time in uremia.

In a randomized double-blind cross-over trial we gave either 1-deamino-8-D-arginine vasopressin or placebo to 12 patients with uremia, hemorrhagic tendencies, and prolonged bleeding times. After vasopressin infusion, all patients had shortened bleeding times, with the effect lasting for at least four hours in most cases. Platelet count, platelet cyclic AMP levels, platelet retention on glass beads, plasma fibronectin, serum thromboxane B2 and residual prothrombin, hematocrit, and plasma osmolarity were unchanged after vasopressin. A consistent post-infusion increase in factor VIII coagulant activity and, to a lesser extent, in factor VIII-related antigen and ristocetin cofactor accompanied the shortening of bleeding time. In addition, vasopressin induced the appearance in plasma of larger von Willebrand-factor multimers than those present in the resting state. The compound was given to nine additional patients with acute or chronic renal failure and prolonged bleeding times, before major surgery or renal biopsy. In these patients, shortening of the bleeding time was associated with normal hemostasis. Our findings indicate that 1-deamino-8-D-arginine vasopressin can be used for temporary correction of bleeding time and may prevent surgical bleeding in patients with uremia.

Adult↗

PubMed1983

A variant of von Willebrand's disease characterized by recessive inheritance and missing triplet structure of von Willebrand factor multimers.

A 10-yr-old girl had bleeding symptoms of moderate severity; her mother and maternal aunt had milder bleeding symptoms, and other members of the kindred were asymptomatic. In the child, factor VIII coagulant activity (VIII:C) and von Willebrand factor antigen (vWF:Ag) were normal, ristocetin cofactor very low, and the bleeding time (BT) markedly prolonged. These values were normal in the rest of the kindred, but the mother and maternal aunt had prolonged BT and a high VIII:C/vWF:Ag ratio. Crossed immunoelectrophoresis (CIE) showed a vWF:Ag peak migrating more anodally in the propositus, two distinct peaks, one migrating anodally, in the father, paternal uncle, and grandmother, and normal peaks in the rest of the kindred. In the propositus, analysis of vWF multimers in plasma on 1.6% sodium dodecyl sulfate (SDS) agarose revealed that there were no larger multimers and there was a relative increase of the smallest multimer. This relative increase was also seen in her relatives with a double peak on CIE. Using gels of smaller porosity, each multimer of the propositus's plasma consisted of a single band, instead of the repeating triplet seen in normal and von Willebrand's disease varients types IIA and IIB. The abnormalities found in the propositus are tentatively interpreted as being due to double heterozygosity for two different genes. The defective gene carried by the father affects the triplet structure of vWF multimers, whereas a prolonged BT and a high VII:C/vWF:Ag ratio are the only phenotypic expressions of the defective gene of the mother. The findings of aberrant triplet structure in congenital vWD strengthen the view that this structure is an intrinsic feature of the normal vWF molecule.

Autoradiography↗

PubMed1982

Aberrant multimeric structure of von Willebrand factor in a new variant of von Willebrand's disease (type IIC).

A variant of von Willebrand's disease has been identified in which sodium dodecyl sulfate agarose electrophoresis provides evidence that the von Willebrand factor present is structurally abnormal. Rather than the repeating triplet seen in normal subjects and in patients with the IIA and IIB variants, a repeating doublet was present in the propositus. None of the bands had the same mobility as bands in normal subjects or previously described von Willebrand's disease patients. The larger multimers of von Willebrand factor were lacking both from plasma and platelets, and did not appear in the circulation after infusion of 1-deamino-[8-D-arginine]-vasopressin. There was a marked increase in the concentration of the smallest multimer in the propositus and his phenotypically normal children, indicating that this abnormality of von Willebrand factor is inherited in an autosomal-recessive manner.

Adult↗

PubMed1982

Multimeric composition of factor VIII/von Willebrand factor following administration of DDAVP: implications for pathophysiology and therapy of von Willebrand's disease subtypes.

We have studied the modifications in the multimeric composition of plasma factor VIII/von Willebrand factor and the bleeding time response following administration of 1-Deamino-[8-D-arginine]-Vasopressin (DDAVP) to patients with different subtypes of von Willebrand's disease. In type I, all multimers were present in plasma in the resting state, though they were decreased in concentration. Administration of DDAVP resulted in an increased concentration of these forms as well as the appearance of larger forms than were previously present. There was concomitant correction of the bleeding time. In type IIA, large multimers were absent in the resting state, and although DDAVP induced an average threefold increase in the plasma concentration of factor VIII/von Willebrand factor, the larger multimers did not appear and the bleeding time, although shortened, was not corrected. In contrast, the larger multimers that were also absent from type IIB plasma in the resting state rapidly appeared following DDAVP administration. However, their appearance was transitory and the bleeding time, as in IIA patients, was shortened but not corrected. The characteristic multimeric composition of platelet factor VIII/von Willebrand factor in given subtypes predicted the alteration in plasma factor VIII/von Willebrand factor induced by DDAVP. These studies provide evidence that the different subtypes of von Willebrand's disease represent distinct abnormalities of factor VIII/von Willebrand factor. They also suggest that complete hemostatic correction following DDAVP can be routinely expected only in type I von Willebrand's disease, and only if factor VIII/von Willebrand factor can be raised to normal levels.

Arginine Vasopressin↗

PubMed1982

Type IIB von Willebrand's disease: differential clearance of endogenous versus transfused large multimer von willebrand factor.

The abnormal multimeric composition of plasma von Willebrand factor in type IIB von Willebrand's disease is transiently corrected after infusion of 1-deamino-[8-D-arginine]-vasopressin. However, the larger multimers released into the circulation disappear more rapidly in these patients than in type I von Willebrand's disease or normals. We demonstrate that the larger multimers of normal von Willebrand factor transfused into a type IIB patient are cleared from the circulation more slowly than multimers of similar size endogenously released from tissue stores. The rate of disappearance of large von Willebrand factor multimers after infusion of cryoprecipitate is similar in IIB, IIA, and severe homozygous-like von Willebrand's disease. Platelets from the IIB patient exhibited normal ristocetin-induced binding of normal von Willebrand factor. However, like normal platelets, they bound IIB von Willebrand factor at lower ristocetin concentrations than required for normal von Willebrand factor. These findings provide evidence that absence of the larger multimers from IIB plasma is related to a molecular abnormality of von Willebrand factor rather than to enhanced affinity of abnormal tissue or cellular binding sites, as is the case in the recently described "pseudo" von Willebrand's disease and "platelet-type" von Willebrand's disease.

Blood Coagulation Factors↗

PubMed1981

Alterations of factor VIII von Willebrand factor in clinical conditions associated with an increase in its plasma concentration.

Factor VIII-related antigen (VIIIR:Ag) was consistently higher than factor-VIII procoagulant activity (VIII:C) in 57 patients with clinical conditions characterized by acute-phase reactions. Two different methods for measuring VIII:C (one- and two-stage assays) and VIIIR:Ag (electroimmunodiffusion and immunoradiometric assay) gave concordant results in the majority of cases. In 43% of plasma samples, crossed immunoelectrophoresis in agarose gel was characterized by the appearance of an additional, fast-moving precipitin peak which was immunologically identical with the major, slower-moving VIIIR:Ag peak. The fast-moving peak was detected in all the patients with clinical conditions typically associated with increased plasma proteolysis (DIC, acute pancreatitis, during thrombolytic therapy). It was present in a smaller proportion of cases with liver and renal failure and malignancies and in the post-operative period. The additional VIIIR:Ag peak is thought to be the result of in vivo factor VIII/von Willebrand factor fragmentation by proteolytic enzymes.

Antigens↗

PubMed1980