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Biomedical subjects

R Lombardi

Publications and source records attributed to R Lombardi.

At least 55 records · Page 3Linked to original sources
PubMed1994

Regular ventricular rhythms before conversion of recent onset atrial fibrillation to sinus rhythm.

The incidence of fast atrial tachycardias with regular ventricular rhythm was assessed in a population of 243 patients with recent onset (< 72 hours) atrial fibrillation (AF), without heart failure, randomly treated with single loading oral dose of propafenone (600 mg), flecainide (300 mg), digoxin (1 mg), or placebo for acute conversion to sinus rhythm (SR). Fast atrial arrhythmias developed in 14 (6%) patients: 6/92 treated with propafenone, 3/34 treated with flecainide, 1/25 treated with digoxin, and 4/92 who received placebo (P = NS). Heart rate > 175 beats/min with 1:1 AV conduction ensued in 4 cases: 2 treated with flecainide and 2 treated with placebo; in the other cases 2:1 AV conduction was observed. Widening of QRS during regular tachycardia was observed in 4 patients; 3 who received propafenone and 1 who received flecainide. Conversion to SR within 4 hours was achieved in 55/92 (60%) patients treated with propafenone, 20/34 (59%) patients treated with flecainide, 7/25 (28%) patients treated with digoxin, and 19/92 (20%) treated with placebo (P < 0.001 propafenone vs placebo and flecainide vs placebo; P < 0.05 propafenone vs digoxin and flecainide vs digoxin). Periods of regular tachycardia are expected in recent onset AF and may not necessarily represent a proarrhythmic effect of Class 1C drugs, rather than mark the transition from AF to SR. Class 1C agents are probably responsible for widening of the QRS complex seen during these tachycardias. Propafenone and flecainide appear equally effective in converting recent onset AF.

Atrial Fibrillation↗
PubMed1993

Fine mapping of the three rRNA operons on the updated genomic map of Campylobacter jejuni TGH9011 (ATCC 43431).

The three rRNA gene loci of Campylobacter jejuni TGH9011 (ATCC 43431) were cloned. All three rRNA operons were shown to possess a contiguous 16S-23S structure and contain intercistronic tRNA(Ala) and tRNA(Ile). The three RNA operons and additional 14 genetic markers were mapped in the updated genomic map of C. jejuni TGH9011, which now has a total of 24 genetic markers.

Campylobacter jejuni↗
PubMed1993

Shear-induced platelet aggregation is potentiated by desmopressin and inhibited by ticlopidine.

Shear-induced platelet aggregation is important in physiological hemostasis and in the pathogenesis of arterial thrombosis. It requires extracellular Ca2+, platelet membrane glycoproteins Ib/IX and IIb/IIIa, von Willebrand factor (vWF), and ADP. We studied the effects of desmopressin (DDAVP), which increases plasma vWF levels and shortens the bleeding time, and of ticlopidine, which inhibits platelet responses to ADP, on shear-induced platelet aggregation. Eleven healthy volunteers were given oral ticlopidine (250 mg b.i.d.) for 7 days. The same subjects were infused intravenously with DDAVP (0.3 micrograms/kg body wt) before the first and after the last doses of ticlopidine. The degree of platelet aggregation induced by shear stress at 25, 50, 75, and 100 dyne/cm2 in a cone-and-plate viscometer, plasma vWF levels, and the bleeding time were measured before and after each DDAVP infusion. Plasma vWF levels and the extent of shear-induced platelet aggregation increased after DDAVP and were correlated. Ticlopidine partially inhibited shear-induced platelet aggregation both before and after DDAVP infusion. The bleeding time, prolonged by ticlopidine, was shortened by DDAVP. Potentiation by DDAVP of shear-induced platelet aggregation may be one mechanism by which the drug shortens the prolonged bleeding time. Since shear-induced platelet aggregation can cause thrombotic occlusions in stenotic arterial vessels, our findings may explain the therapeutic efficacy of ticlopidine in arterial thrombosis.

Adult↗
PubMed1992

Vectorial measurement of blood velocity by means of ultrasound.

The complete determination of blood velocity as a vector can be achieved using ultrasound techniques, by correlating the echo signals provided by a sector transducer. Here the general problem is approached by suggesting the processing procedure which should be adopted, so that longitudinal and transverse velocity components can be separated. After this a specific transducer layout is considered, which is suitable for in-plane measurements, and possible performances are evaluated by means of simulation. Finally, an experimental facility, set up to demonstrate the validity of the theoretical lines developed in two-dimensional geometry, is described, together with the preliminary results obtained.

Blood Flow Velocity↗
PubMed1992

Sustained correction of the bleeding time in an afibrinogenaemic patient after infusion of fresh frozen plasma.

We have evaluated the duration of the effect of replacement therapy with two different doses of fibrinogen on the prolonged bleeding time of an afibrinogenaemic patient and the relationship between changes in bleeding time and plasma and platelet fibrinogen concentrations. The infusion of 40 mg/kg fibrinogen, as fresh frozen plasma (FFP), corrected the prolonged bleeding time of the patient from longer that 30 min to 8 min. The bleeding time was still normal 9 d after infusion, at a time when the plasma and platelet fibrinogen levels were low (0.13 g/l and 27 micrograms/10(9) platelets; normal ranges 1.6-4.0 and 60-190). Two months later, the infusion of a smaller dose of fibrinogen (4 mg/kg) also corrected the bleeding time, which remained normal until the second day after infusion, despite the fact that plasma and platelet fibrinogen were very low (0.02 g/l and 3.4 micrograms/10(9) platelets). The bleeding time returned to the prolonged baseline values only by day 6 post-infusion, when plasma and platelet fibrinogen levels were 4 x 10(-4) g/l and 1.4 micrograms/10(9) platelets. Therefore, sustained correction of the prolonged bleeding time may be obtained in afibrinogenaemic patients with a single infusion of fibrinogen at lower doses than usually recommended.

Adult↗
PubMed1989

Heterogeneous phenotypes of platelet and plasma von Willebrand factor in obligatory heterozygotes for severe von Willebrand disease.

To characterize the heterogeneity of severe (type III) von Willebrand disease (vWD), plasma and platelet von Willebrand factor antigen (vWF:Ag) and ristocetin cofactor activity (Ricof) were measured in 28 obligatory heterozygotes (ie, parents or children of probands from 15 different kindreds with severe vWD). On the average, heterozygotes had low levels of vWF in both platelets and plasma. There was, however, considerable heterogeneity, with four distinct patterns. Eleven heterozygotes had concordant reduction of vWF:Ag and Ricof in both plasma and platelets; five had low levels of vWF:Ag and Ricof in plasma contrasting with normal levels in platelets; eight had a peculiar pattern, the reverse of the above (ie, low levels in platelets and normal levels in plasma); and in one, both vWF measurements were normal in plasma and platelets. These patterns were genetically determined: they were consistent in four couples of consanguineous heterozygotes and in two couples carrying the same gene deletion. Only the remaining three heterozygotes had no clearly identifiable pattern. Other findings of this study were that although most of the heterozygotes had normal bleeding times, the 7 of 28 who had prolonged bleeding times had concordantly low levels of vWF measurements in both plasma and platelets. In conclusion, this large series of obligatory heterozygotes provides evidence for phenotypic and genotypic heterogeneity of severe vWD.

Bleeding Time↗
PubMed1989

Enhanced proteolysis of plasma von Willebrand factor in thrombotic thrombocytopenic purpura and the hemolytic uremic syndrome.

To examine whether enhanced in vivo proteolysis of von Willebrand factor (vWF) would account for the reported loss of larger multimers in acute thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS), we studied eight patients with acute TTP/HUS whose blood samples were collected into an anticoagulant containing a cocktail of protease inhibitors to impede in vitro proteolysis. In all, enhanced proteolytic degradation of vWF was expressed as a relative decrease in the intact 225-Kd subunit of vWF and a relative increase in the 176-Kd fragment. However, instead of the loss of larger forms of normal multimers reported by other investigators, the plasma of all but one of our patients (whether they had TTP or HUS) contained a set of larger than normal (supranormal) multimers. Hence, although proteolytic fragmentation of vWF was enhanced during acute TTP/HUS, this phenomenon was not associated with the loss of larger multimers. In the five patients who survived the acute disease and underwent plasma exchange (three with HUS and two with chronic relapsing TTP), subunits and fragments returned to normal values, and supranormal multimers were no longer detected in plasma. In conclusion, even though vWF proteolysis is enhanced in acute TTP/HUS, it does not lead to loss of larger multimers.

Adolescent↗
PubMed1989

Supranormal von Willebrand factor multimers in scleroderma.

Platelet adhesion-aggregation reactions play an early and pivotal role in the pathogenesis of systemic sclerosis in scleroderma, but the mechanisms are incompletely understood. We determined whether or not plasma from 11 consecutive patients with scleroderma contained a subset of larger than normal ("supranormal") multimers of von Willebrand factor (vWF) that are potent inducers of platelet aggregation and adhesion. Supranormal multimers were found in all patients on at least one of two different occasions 9 to 12 months apart, whatever the duration and severity of the disease, but in none of the normal controls. Administration of low-dose aspirin (40 mg) to five of the 11 patients for ten days to inhibit the platelet release reaction slightly reduced the amounts of supranormal multimers suggesting that they might originate in part from platelets. Supranormal multimers may contribute to the pathogenesis of systemic sclerosis by inducing platelet aggregation and enhancing adhesion to subendothelium under the conditions of elevated shear stress occurring in the partially occluded vessels of the arterial microcirculation of scleroderma.

Adult↗
PubMed1989

Type II H von Willebrand disease: new structural abnormality of plasma and platelet von Willebrand factor in a patient with prolonged bleeding time and borderline levels of ristocetin cofactor activity.

In this study a new variant of type II von Willebrand disease is identified by multimeric analyses of increasing resolving power. Prior to multimeric analysis, the patient was misdiagnosed as carrying an undefined abnormality in platelet function because of his normal von Willebrand factor antigen (vWF:Ag) and low borderline ristocetin cofactor (Ricof) levels. Absence of the largest multimers from the patient's plasma and platelets was shown in a low-resolution system, but all the multimers were present in his relatives. An abnormality in the complex multimeric structure was demonstrated in both plasma and platelets with high-resolution agarose gels. The plasma of the proband and of several family members shows a broader central band with a minor, faster moving satellite band differing from the typical "triplet pattern" observed with normal plasma. Platelets show a "doublet" that runs with a mobility different from the "doublet" in normals. Therefore the proband may be either a homozygote or double heterozygote for this new abnormality. Treatment with desmopressin (DDAVP) on several occasions corrected the prolonged bleeding time of the patient only transiently. Factor VIII increased significantly, but vWF:Ag and Ricof responded poorly. We conclude that this vWF abnormality is different from those observed in the other variants (II A-G) previously described. Therefore the proposed designation for this new variant is type II H.

Adult↗
PubMed1989

[The impact of excess male mortality on sex structure. The Italian case, 1951-1981].

The purpose of this note is to analyze male excess mortality in relation to general mortality trends in a country with low levels of mortality, using Italian data for the period 1951-1981, and to examine the effect of this excess male mortality on the sex distribution of the population. Consideration is given to the apparent paradox whereby "at least during the first half of life, the sex ratio increases when excess male mortality increases. This paradox shows that the index traditionally used for measuring the disadvantage of men with regard to survival, is not the most appropriate one." (SUMMARY IN ENG AND SPA)

Demography↗
PubMed1988

Hyper-responsiveness to DDAVP for patients with type I von Willebrand's disease and normal intra-platelet von Willebrand factor.

Desmopressin (DDAVP) has gained wide acceptance as the drug of first choice in the treatment or prevention of haemorrhages in the majority of patients with von Willebrand's disease (vWd). However, data concerning the clinical effectiveness of DDAVP refer generally to mild vWd, with factor VIII and vW factor levels usually above 20% of normal. In 14 patients with type I vWd characterized by very low plasma levels of factor VIII coagulant activity (VIII:C) and vWf, measured as ristocetin cofactor activity (lower than 20% and 3% of normal respectively), but with a normal intraplatelet content of vWf, a test infusion of DDAVP (0.4 microgram/kg) elicited a very marked increase of VIII:C and vWf and normalized the bleeding time. All these patients subsequently underwent tooth extraction after DDAVP infusion. The incidence of bleeding was remarkably low, with only two minor late bleeding episodes easily stopped by repeating DDAVP infusion. Compared to the cases of type I vWd with unknown intraplatelet vWf content reported in the literature, this subgroup of patients had a more marked, albeit short-lived, increment of VIII:C and vWf.

Adolescent↗
PubMed1988

Adhesive properties of the carbohydrate-modified von Willebrand factor (CHO-vWF).

In this cooperative study, we explored the role of the carbohydrate moiety (CHO) of von Willebrand factor (vWF) in supporting platelet adhesion. Because of previous discrepant results, all purification steps and CHO modifications by various enzymes were critically evaluated. Under our conditions, CHO-modified vWF preparations contained less than 5% of the initial sialic acid ([Neu]-ase-vWF) and less than 45% ([Neu-Gal]-ase-vWF) or 21% ([Neu-Gal-eF]-ase-vWF) of the D-galactose. These preparations usually showed increased electrophoretic mobility but no significant loss of high-mol-wt multimers when proteolysis had been prevented. Some degree of proteolysis was noted in some carbohydrate-modified vWFs, but the degree of degradation observed did not correlate with the removal of D-galactose. Platelet adhesion to various matrices increased after removal of the terminal sialic acid ([Neu]-ase-vWF) and approximately 45% of the D-galactose ([Neu-Gal]-ase-vWF), but returned to normal values when greater than 70% of the total carbohydrate had been removed by endoglycosidase F [Neu-Gal-ef]-ase-vWF). These changes in reactivity were also reflected in the spontaneous aggregation in normal platelet-rich plasma (PRP) after CHO removal.

Carbohydrate Conformation↗
PubMed1988

von Willebrand disease "Vicenza" with larger-than-normal (supranormal) von Willebrand factor multimers.

When normal volunteers or patients with type I von Willebrand disease (VWD) are given desmopressin (DDAVP), a set of larger-than-normal (supranormal) von Willebrand factor (VWF) multimers, similar to those present in VWF-containing cells such as platelets megakaryocytes and endothelial cells, appear transiently in postinfusion plasma. In two kindreds with mild lifelong bleeding symptoms transmitted as an autosomal dominant trait, all ten symptomatic members (but none of the five asymptomatic members) had a supranormal multimeric structure for plasma VWF, apparently identical to that seen for postdesmopressin normal plasma. Plasma factor VIII coagulant activity (VIII:C), VWF antigen (VWF:Ag), ristocetin-induced platelet agglutination, and ristocetin cofactor (RiCof) activity were low. Platelet VWF:Ag and RiCof levels (tested for three patients only) were normal. Bleeding times were normal or slightly prolonged. The patients' platelet multimeric structure was the same as that for normal platelets. After desmopressin infusion the plasma VWF multimeric structure remained supranormal as for preinfusion plasma, with VIII:C VWF:Ag and RiCof increasing markedly over baseline values and disappearing at a normal rate. Examination of the VWF subunit composition from three of these patients indicated that proteolytic processing of their VWF did not differ from normal. This study describes the first variant of VWD with a supranormal multimeric structure.

Blood Platelets↗
PubMed1987

Effects of fenfluramine on autistic individuals residing in a state developmental center.

The effects of fenfluramine on 21 maladaptive behaviors in 20 autistic individuals were examined over a 9-month period utilizing a double-blind, cross-over, placebo-controlled design. Raters carried out time-sampled observations in the school and residence. In addition, videotaped data were collected in controlled settings and assessed by the raters at the conclusion of the study. Some individuals displayed negative side effects such as tension, agitation, insomnia, and sweating during the 16-week period they received fenfluramine. The results demonstrated that fenfluramine caused no significant reductions in maladaptive behaviors. The lack of any significant positive results from this medication and the side effects observed strongly indicate the need for caution in the use of fenfluramine with autistic persons.

Adolescent↗
PubMed1987

Maps of optical action potentials and NADH fluorescence in intact working hearts.

Voltage-sensitive dyes were used to stain intact perfused hearts and to simultaneously measure optical action potentials (APs) from 124 sites on the epicardium. Patterns of electrical depolarization (activation) and repolarization (recovery) along the surface of the heart were determined from the upstrokes and repolarization phases of optical APs. Standard surface extracellular techniques can detect electrical activation but not the recovery or the duration of APs. The optical recordings were previously shown to be equivalent to intracellular electrode measurements (Salama and Morad, Science Wash. DC 191: 485-487, 1976) and now reveal that AP durations are heterogeneous throughout the epicardium, with durations increasing from the base to the apex of the ventricles. In hearts beating under normal sinus rhythm, the direction and conduction velocity of the activation waves could be altered by electrical stimulation. The normal heterogeneities in AP durations became more pronounced in the presence of the Ca2+-entry blocker, verapamil. The local metabolic state of the tissue was also monitored optically through its intrinsic NADH fluorescence measured from 124 separate regions on the heart. The time course and extent of metabolic injury caused by general anoxia or by a local ischemia induced by a coronary ligation was monitored through maps of NADH fluorescence. The present technique makes it possible to correlate changes in the metabolic state of the muscle with detailed changes in patterns of electrical activity and thus provides a powerful new tool to study fundamental aspects of normal and abnormal cardiac rhythm.

Action Potentials↗