Subunit composition of plasma von Willebrand factor (vWF) in two uremic patients with acquired vWF abnormalities.
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Humans↗
Biomedical subjects
A Lattuada
Publications and source records attributed to A Lattuada.
Platelet von Willebrand factor assay: results using two methods for platelet lysis.
Two different methods (using Triton X-100 and glycerol) for lysing platelets to measure platelet vWF concentrations were compared directly. The platelet concentration of von Willebrand factor antigen (vWF:Ag) was similar for both methods, whereas ristocetin cofactor activity (Ricof) was higher with Triton than with glycerol. After storing platelet lysates for two months at -80 degrees C vWF:Ag and Ricof concentrations decreased with both methods of lysis. Larger than normal (supranormal) vWF multimeric forms could be visualized in platelet lysates obtained using both methods, with no change of the multimeric pattern during storage. Triton can be recommended as the agent of choice to lyse platelets for measurement of their vWF concentration, but the samples must be assayed within two weeks to avoid decay of Ricof activity.
Blood Platelets↗
Total body irradiation and high-dose melphalan with bone marrow transplantation at Istituto Nazionale Tumori, Milan, Italy.
The technique of total body irradiation (TBI) developed at Istituto Nazionale Tumori, Milan, Italy, is described. This technique consists of i) administration of 12.5 Gy and 14.85 Gy TBI for autologous and allogeneic bone marrow transplantation respectively; ii) in all cases in vivo dosimetry of absorbed TBI dose; and iii) radiation doses to lungs higher than previously described. As of June 1988, seventeen patients with Hodgkin's disease and four with lymphoblastic lymphoma received TBI and 120-180 mg/m2 melphalan. Respiratory function was prospectively evaluated demonstrating moderate and transient reduction of pulmonary function.
Adolescent↗
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↗
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↗
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↗
Subcutaneous desmopressin (DDAVP) shortens the bleeding time in uremia.
The intravenous infusion of 1-deamino-8-D-arginine vasopressin (DDAVP) is used as a nontransfusional form of treatment in patients with congenital and acquired bleeding disorders, including patients with uremia associated with prolonged bleeding times. Since uremic patients experience minor bleeding episodes that might be self-managed at home (particularly epistaxis, gingival bleeding, and menorrhagia), we carried out a double-blind, placebo-controlled crossover study in nine uremics to evaluate whether the prolonged bleeding times could be shortened by subcutaneous injections of DDAVP. One hour after administration, the bleeding time was significantly shortened (P less than .01) and became normal in seven of nine patients. After 4 hr, the bleeding time was still shorter than baseline (P less than .01), but in only three patients was it still normal. There was no significant bleeding time change after placebo. When the same patients were treated with the same dose of DDAVP infused intravenously, the bleeding times were not significantly different from those measured after subcutaneous administration. Hence, subcutaneous DDAVP is an alternative method for short-term shortening of the bleeding time in uremia, at least as effective as intravenous DDAVP but with the possibility of self-administration by the patients at home.
Adult↗
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↗
Advanced neuroblastoma: results of two treatment programs including sequential hemibody irradiation.
Results of two consecutive treatment programs for advanced neuroblastoma, including sequential hemibody irradiation, are analyzed and compared. The first treatment program (I-TP) included one single-fraction (7 Gy) irradiation to the upper and lower halves of the body as consolidation of remission achieved by previous chemotherapy with CDDP and VP16. A fractionated technique (2 Gy daily for 4 consecutive days to each hemibody) was used in the second treatment program (II-TP) for children in remission following a combination of CDDP + VP16 and ADM + VCR + CTX. In both treatment programs, chemotherapy was continued according to the same pre-radiation regimen following the two sessions of hemibody irradiation. Overall response rate to pre-radiation chemotherapy was 84% and 60% for I-TP and II-TP, respectively. Thirty-month overall progression-free survival was 0 for I-TP and 20% for II-TP. No treatment-related fatalities occurred. In the subsets of patients who reached complete or good partial remission during the pre-radiation chemotherapeutic phase, 30-month progression-free survival in I-TP and II-TP was 0 and 33%, respectively. The role of fractionated hemibody irradiation in prolonging the progression-free survival can be inferred.
Adolescent↗
[Treatment technic and clinical dosimetry in whole-body irradiation].
At the Istituto Nazionale Tumori, Milan, total-body irradiation (TBI) is delivered by a 15 MV linear accelerator, with two lateral opposed beams. Maximum build-up at the skin is achieved by lateral slabs of perspex 3 cm thick. Attenuation filters or bolus are used for dose compensation, or reduction, to the head and lungs. The dose delivered to clinically relevant anatomic regions is determined by "in vivo" dosimetry. For this purpose, calibrated diodes are employed, which are positioned at the entrance and at the exit of the beams. "In vivo" dosimetry data show our TBI technique to allow an homogeneous irradiation of all body areas, with maximum deviation of the mean dose value from reference point dose of -11% in the posterior abdomen, at the spinal cord shielded by arms.
Humans↗
[The prognostic significance of anaplastic variants in patients with testicular seminoma subjected to exclusive radiotherapy].
Three-hundred and sixty-six patients affected with seminoma testis (234 stage I, 85 stage II low, 47 advanced diseases) were treated between January 1968 and December 1985. Overall incidence of anaplastic lesions (43 patients) was 12%, progressively increasing with stage of the disease (9% stage I, 13% stage II low, 21% advanced disease). Only 343 patients submitted to exclusive curative/prophylactic radiotherapy were studied: 35 of them were anaplastic (22 stage I, 11 stage II low, 2 advanced disease). Radiation therapy was always performed regardless of the histologic subtype. Recurrences occurred in 14% of anaplastic tumors (5/35) and in 7.5% of classical seminomas (23/308). There was no statistically-significant difference between global and stage-by-stage failures. After literature review and complete analysis of the patterns of recurrence, the authors stress the lack of evidence suggesting a different radioresponsiveness of anaplastic versus classical seminomas; nonetheless, a more accurate staging is recommended for anaplastic variants, since they tend to appear in the advanced stages of the disease.
Adult↗
Combined modality treatment for stage I-II non-Hodgkin's lymphomas: CVP versus BACOP chemotherapy.
This paper reports the 5-year results of a prospective randomized study beginning in 1976 on 177 evaluable patients with pathologic Stage I-IE and II-IIE non-Hodgkin's lymphomas with diffuse histology according to the Rappaport classification. Treatment consisted of either CVP or BACOP chemotherapy (3 cycles) followed by regional radiotherapy (40 to 50 Gy) and further cycles of either combination. In both arms, complete remission at the end of combined treatment was high (CVP 93%, BACOP 98%) regardless of age, stage or bulky disease. At 5 years, the comparative freedom from first progression was 62% for CVP vs 78% for BACOP (p = 0.02), respectively. Clinically relevant differences favoring BACOP chemotherapy were essentially documented in patients with large cell lymphomas (International Working Formulation), those with Stage II having more than three involved anatomical sites, bulky disease and age over 60 years. Recurrence within radiation fields was documented in only 5% of complete responders. Combined treatment was, in general, well tolerated particularly when BACOP was used. In only 2 patients given CVP post radiation cutaneous fibrosis was documented. Second solid tumors were detected in 4 patients. One patient started on CVP died because of brain stem necrosis after 45 Gy. We conclude that in Stage I-II patients with nodal and extranodal diffuse non-Hodgkin's lymphomas, particularly large cell lymphomas, combined modality approach with primary Adriamycin and bleomycin containing regimen, such as BACOP, followed by adjuvant radiotherapy offers high chances of cure with minimal toxicity.
Antineoplastic Combined Chemotherapy Protocols↗
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↗
[Radiotherapy of low-stages seminoma. Results and controversies].
From January 1968 to December 1983, 297 low-stage testicular seminoma patients (209 stage I, 80 stage II A-B, and 8 Nx) were treated by means of prophylactic and/or curative radiotherapy. Overall 10-year relapse-free survival rate is 94% (97.3% stage I, 85.8% stage II A-B). Global survival-rate: 95.8% (100% stage I). Saving treatment was always effective in five relapses at stage I (2 lymphnodal recurrences in untreated areas, and 3 distant metastases). Out of twelve relapses at stage II A-B and Nx patients (4 lymphnodal recurrences in treated areas, 2 in untreated areas, and 6 distant metastases) saving treatment was effective in 3 patients, one of whom died for radiation late effect. Nine radiation sequelae were observed, three of which were neoplastic diseases. Referring to analysis of the results, failures and possible options in the management of seminomas, the authors confirm the effectiveness of current treatment schedule.
Dysgerminoma↗
Germ cell tumors of the ovary: the experience of the National Cancer Institute of Milan. I. Dysgerminoma.
The experience of the Istituto Nazionale Tumori of Milan on dysgerminoma is presented. Between 1970 and December of 1982, 25 patients were treated with a unique protocol which considered surgery and radiotherapy with different schedules according to the extension of the disease. With this treatment protocol all 13 patients at Stage I were alive and free of disease with a median follow-up of 77 months. Of 12 patients at Stage III (10 retroperitoneal and 2 retroperitoneal and peritoneal) 4 relapsed. The 5-year relapse-free survival of Stage III patients was 61.4% and the overall survival 89.5%. Amenorrhea due to radiation dose absorbed by the contralateral shielded ovary was found in 7.7%. The excellent results in Stage I patients were balanced by the unsatisfactory results in Stage III patients. A more aggressive treatment and the knowledge of other prognostic factors seem necessary.
Adolescent↗
Adjuvant irradiation after radical surgery of cancer of the rectum and rectosigmoid.
From January 1975 through December 1983, 74 consecutive patients were given adjuvant radiotherapy on the whole pelvis after radical surgery for locally advanced rectal (44 cases) and rectosigmoidal (30 cases) cancer. Most patients received 45 Gy to the whole pelvis in 5-7 weeks through AP, PA opposed fields. Fourteen patients were also given adjuvant chemotherapy. Minimum follow-up time of the series is 24 months and median follow-up is 36 months. First relapse was evaluated. Pelvic failures occurred in 17.5% of patients, while distant metastases rate was 32%; median time to relapse was 18 and 10 months respectively. Thirty patients (40.5%) never relapsed and are alive and well, while five additional patients are alive with disease. Four patients died of treatment toxicity. Thirty-one patients died of cancer (41.9%); 8 of them from pelvic failure only. Actuarial relapse-free survival at 3 and 5 years was 51.7% and 46.8%, while actuarial overall survival was 63% and 49%.
Adult↗
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↗
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↗