Pleural tumors as sole primary manifestation of acute promyelocytic leukemia.
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Aged↗
Biomedical subjects
M Solenthaler
Publications and source records attributed to M Solenthaler.
[Myelodysplastic syndromes--an overview for the practitioner].
Myelodysplastic syndromes (MDS) comprise a heterogeneous group of hematological diseases deriving from a clonally expanded precursor bone marrow cell. MDS are characterized by ineffective hematopoiesis, peripheral cytopenias of various degrees and increased risk for transformation into acute myeloid leukemia. The incidence is highest in elderly people. Diagnosis is based on morphology, exclusion of reactive causes of dyshematopoiesis and cytogenetics/FISH. Allogeneic stem cell transplantation, the only curative therapy so far, is not feasible for most of the patients. Other therapeutic options include supportive therapy such as blood transfusions and antibiotics, hematopoietic growth factors (rHuEPO, G-CSF), immunomodulating agents and chemotherapy. It is important to install iron chelation therapy in cases with long term transfusion dependency.
Aged↗
[Chronic myeloid leukemia--update].
Chronic myeloid leukemia (CML) is a clonal stem cells disorder and belongs to the myeloproliferative diseases. Over the past decades seminal discoveries in the field of CML research have greatly contributed to our knowledge of leukemogenesis. The hallmark of the disease is the presence of the Philadelphia chromosome, the first described acquired non-random cytogenetic abnormality in human malignancies. This chromosomal abnormality is the result of a reciprocal translocation between chromosomes 9 and 22, t(9;22). At the molecular level this involves the fusion of the ABL protooncogene on chromosome 9 with the BCR (breakpoint cluster region) gene on chromosome 22. The fusion protein has increased tyrosine kinase activity and is a key event in the malignant transformation of a given progenitor cell in the bone marrow. Diagnosis of CML is based on the peripheral blood smear, bone marrow examination, the presence of the Philadelphia chromosome and its molecular correlate, the BCR-ABL transcript. Remarkable progress has been made in the treatment options over the last years which as a result rendered the therapeutic choices more complex and challenging. The current knowledge of treatment options is reviewed with particular emphasis on the newly introduced tyrosine kinase inhibitor Imatinib which opened an as yet unexpected promising avenue in the treatment of CML.
Bone Marrow↗
Successful treatment of chemotherapy-refractory Sézary syndrome with alemtuzumab (Campath-1H).
INTRODUCTION: Sézary syndrome (SS) is a cutaneous T-cell lymphoma characterized by erythroderma, lymphadenopathy and circulating atypical T cells. Median survival after diagnosis is 10 yr, with chemotherapy resistance being a major problem in advanced disease. Alemtuzumab (Campath-1H) is a monoclonal antibody directed against the lymphocytic antigen CD52, expressed on B- and T-cells. Alemtuzumab is approved for relapsing chronic B-cell leukemia and seems to be active also in T-cell lymphomas such as T-cell prolymphocytic lymphoma, SS and mycosis fungiodes. CASE HISTORY: A 32-yr-old male patient presented with advanced stage, extensively pretreated SS with heavily itching erythroderma, peripheral lymphadenopathy, circulating Sézary cells and bone marrow infiltration. The disease had not responded to PUVA/interferon-alpha and progressed on chemotherapy with CHOP, 2-CDA, vinorelbine, etoposide and liposomal doxorubicin. Following treatment with alemtuzumab (30 mg i.v. three times per week for 10 wk), itching resolved rapidly and an almost complete remission was achieved within 3 months after starting this treatment. At 12-month follow up, no disease progression was present. CONCLUSION: In accordance with previous data, this single case underlines the potent activity of alemtuzumab in advanced, chemotherapy-refractory SS.
Adult↗
Should whole-body red cell mass be measured or calculated?
The whole-body volume of red blood cells must be known for correct diagnosis of polycythemia vera. Since the venous hematocrit may not correctly reflect the absolute amount of red blood cells, the red cell mass (RCM) is usually determined by radioisotope labeling of red blood cells according to recommendations of the International Committee for Standardization in Haematology. We examined whether the radioisotope labeling procedure can be replaced by a simple calculation of RCM from the values of venous blood hematocrit and plasma volume, using an empirical factor (Ratio f) equal to the mean ratio between whole-body and venous hematocrit. A retrospective study was performed of 264 cases in which the RCM was assayed using (51)Cr or (99m)Tc for red cell labeling, and (125)I-labeled albumin was used for estimation of plasma volume. The results showed wide scattering of Ratio f (mean value 0.911; range from 0.76 to 1.15) that was responsible for substantial differences between the measured and calculated values of RCM. We also tested whether the calculated RCM may be used as an appropriate marker for polycythemia vera according to recommendations of the International Council for Standardization in Haematology. Our data showed that 146 patients had measured RCM values more than 25% above the mean normal predicted value. Using the calculated RCM, 17 of these patients would be lost from the polycythemia vera group, whereas 29 subjects with measured RCM levels equal to or lower than 125% of predicted values would incorrectly meet the RCM criterion for polycythemia vera. Thus, a total of 46 patients would be misclassified by using the calculated RCM. We conclude that the radioisotope labeling of red blood cells remains mandatory for correct determination of the whole-body red cell volume.
Adolescent↗
[Isolated increased aPTT with anamnestic hemorrhagic diathesis--severe FXI deficiency].
A 47-year-old patient with several episodes of bleeding after tonsillectomy, after an excision of a sacral dermoid and after urinary tract surgery presented with a mechanical ileus and was admitted to the department of visceral surgery. Preoperative analysis revealed a prolonged activated partial thromboplastin time (aPTT) of 93 seconds (normal range: 40-60 seconds), whereas the prothrombin time and thrombin time were normal. A mixture of 1 volume patient plasma and 1 volume normal plasma gave a normal aPTT, both before and after incubation of the plasma mixture at 37 degrees C for 1 hour. The patient's history and the prolonged aPTT as the only abnormal clotting test indicated deficiency of either factor VIII, factor IX, factor XI or von Willebrand factor with consecutively diminished factor VIII. Laboratory analysis revealed a factor XI of 4% indicating severe factor XI deficiency. Laparotomy was successfully performed without any hemorrhagic complications under fresh frozen plasma substitution.
Diagnosis, Differential↗
[Deep venous thrombosis of the leg in acquired thrombophilia--hyperhomocysteinemia as a sequela of undetected celiac disease].
Today hyperhomocysteinemia is a well known and important risk factor for arteriosclerotic vascular and venous thromboembolic disease with a high prevalence in the general population. Elevation of plasma homocysteine levels are caused either by genetic defects in the enzymes involved in homocysteine metabolism or by nutritional deficiencies of vitamin cofactors (folate, vitamin B12, vitamin B6). A number of other factors may influence homocysteine metabolism, such as several disease states and medications. It has been demonstrated, that supplementation of folate, vitamin B12, or vitamin B6 can correct mild and moderate hyperhomocysteinemia.
Adult↗
[Severe hemorrhage, lymphocytosis and leukoerythroblastic blood picture--disseminated intravascular coagulation in metastatic prostate carcinoma and chronic lymphatic leukemia].
Hemorrhagic complications in CLL are most often related to thrombocytopenia either due to decreased megakaryopoiesis caused by diffuse lymphocytic bone marrow infiltration or to increased peripheral platelet consumption by platelet autoantibodies (immune thrombocytopenia), both being typical manifestations of the disease. Disseminated intravascular coagulation (DIC) does not belong to the spectrum of CLL-related complications. In the case here reported with DIC and newly diagnosed CLL the leukoerythroblastic blood changes hinted to bone marrow infiltration by another neoplastic process in addition to CLL. Bone marrow biopsy revealed infiltration by metastatic carcinoma of the prostate in addition to that by CLL, the former being responsible for triggering severe DIC leading to fatal intracranial bleeding.
Aged↗
[Hyperhomocysteinemia: a risk factor for arterial and venous thrombosis].
Homocysteine is a sulfur-containing amino acid intermediate involved in two metabolic pathways, in the remethylation to methionine and in the transsulfuration to cysteine. Severe hyperhomocysteinemia (> 100 mumol/l) is found in congenital homocystinuria. Moderate (15-30 mumol/l) or intermediate (> 30-100 mumol/l) hyperhomocysteinemia is caused by defects in genes encoding for enzymes of homocysteine metabolism or by inadequate intake of those vitamins that are involved in homocysteine metabolism (folic acid, cobalmin, and vitamin B6). Today, hyperhomocysteinemia should be considered an important risk factor for atherosclerotic vascular and venous thromboembolic diseases. Homocysteine-plasma levels above the 95th percentile were found to be associated with a 2 to 3-fold elevated relative risk for deep-vein thrombosis and pulmonary embolism. Moreover, mild hyperhomocysteinemia has been shown to be associated with a 2 to 4-fold increased relative risk for coronary artery disease, cerebrovascular disease, and peripheral arterial occlusive disease. Several mechanisms have been proposed by which hyperhomocysteinemia contributes to atherogenesis and thrombogenesis. Several studies have shown that hyperhomocysteinemia can be corrected by supplementation of folic acid, cobalamin and vitamin B6. Clinical trials are urgently needed which investigate the preventive effect of supplementation of these vitamins on thrombotic diseases.
Arteriosclerosis↗
Severe inclusion body beta-thalassaemia with haemolysis in a patient double heterozygous for beta(0)-thalassaemia and quadruplicated alpha-globin gene arrangement of the anti-4.2 type.
We describe a new case of an association of alpha-globin gene quadruplication of the anti-4.2 type with beta(0)-thalassaemia. The patient, a young woman of mixed Brazilian-Portuguese origin, suffered from chronic haemolytic anaemia with splenomegaly. Bone marrow supravital staining with brilliant cresyl blue and electron microscopy studies showed large inclusion bodies in about 3% of erythroblasts. Upon immunofluorescent staining these inclusions reacted with a monoclonal antibody to alpha- but not to beta-globin. Analysis of alpha-globin cluster by Southern blotting showed the presence of pathologic fragments specific for the anti-4.2 alpha-globin gene quadruplication. Alpha/beta mRNA ratio was higher than in cases combining alpha-globin triplication and beta(0)-thalassaemia or in cases of beta(0)-thalassaemia heterozygous state alone (18, 14.7 and 10.1 respectively). Our data confirmed the hypothesis that the clinically detectable haemolysis in this beta(0)-thalassaemic patient was due to an unusually high amount of precipitated alpha-globin in erythroid precursors. This considerable excess of alpha-globin chains was due partly to the beta-globin deficit caused by the presence of the beta(0)-thalassaemic gene, but also to the presence of 6 active alpha-globin genes resulting from alpha-globin gene quadruplication in one chromosome.
Anemia, Hemolytic↗
Fatal fresh frozen plasma infusion containing HPA-1a alloantibodies.
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Aged↗
A novel BCR-ABL transcript e2a2 in a chronic myelogenous leukaemia patient with a duplicated Ph-chromosome and monosomy 7.
A novel BCR-ABL transcript was detected by multiplex RT-PCR in a patient with Philadelphia chromosome (Ph) positive chronic myelogenous leukaemia (CML) in accelerated phase. Sequencing of the aberrant transcript revealed an in-frame e2a2 fusion that included a 9 basepairs insertion. Cytogenetic analysis showed t(9;22), an additional Ph chromosome and monosomy 7. The clinical course was dismal: therapy was poorly tolerated, and the patient died in blast crisis 10 months after diagnosis. These data support the association of additional Ph and monosomy 7 with poor prognosis and suggest that the novel e2a2 BCR-ABL transcript may be related to an aggressive clinical course.
Aged↗
von Willebrand factor-cleaving protease in thrombotic thrombocytopenic purpura and the hemolytic-uremic syndrome.
BACKGROUND: Thrombotic thrombocytopenic purpura and the hemolytic-uremic syndrome are severe microvascular disorders of platelet clumping with similar signs and symptoms. Unusually large multimers of von Willebrand factor, capable of agglutinating circulating platelets under high shear stress, occur in the two conditions. We investigated the prevalence of von Willebrand factor-cleaving protease deficiency in patients with familial and nonfamilial forms of these disorders. METHODS: Plasma samples were obtained from 53 patients with thrombotic thrombocytopenic purpura or hemolytic-uremic syndrome. Von Willebrand factor-cleaving protease was assayed in diluted plasma samples with purified normal von Willebrand factor as the substrate. The extent of the degradation of von Willebrand factor was assessed by electrophoresis in sodium dodecyl sulfate-agarose gels and immunoblotting. To determine whether an inhibitor of von Willebrand factor-cleaving protease was present, we measured the protease activity in normal plasma after incubation with plasma from the patients. RESULTS: We examined 30 patients with thrombotic thrombocytopenic purpura and 23 patients with the hemolytic-uremic syndrome. Of 24 patients with nonfamilial thrombotic thrombocytopenic purpura, 20 had severe and 4 had moderate protease deficiency during an acute event. An inhibitor found in 20 of these patients was shown to be IgG in five of five tested plasma samples. Of 13 patients with nonfamilial hemolytic-uremic syndrome, 11 had normal levels of activity of von Willebrand factor-cleaving protease during the acute episode, whereas in 2 patients, the activity was slightly decreased. All 6 patients with familial thrombotic thrombocytopenic purpura lacked von Willebrand factor-cleaving protease activity but had no inhibitor, whereas all 10 patients with familial hemolytic-uremic syndrome had normal protease activity. In vitro proteolytic degradation of von Willebrand factor by the protease was studied in 5 patients with familial and 7 patients with nonfamilial hemolytic-uremic syndrome and was normal in all 12 patients. CONCLUSIONS: Nonfamilial thrombotic thrombocytopenic purpura is due to an inhibitor of von Willebrand factor-cleaving protease, whereas the familial form seems to be caused by a constitutional deficiency of the protease. Patients with the hemolyticuremic syndrome do not have a deficiency of von Willebrand factor-cleaving protease or a defect in von Willebrand factor that leads to its resistance to protease.
ADAM Proteins↗
Acquired deficiency of von Willebrand factor-cleaving protease in a patient with thrombotic thrombocytopenic purpura.
Plasma of patients with thrombotic thrombocytopenic purpura (TTP) has been shown to contain unusually large von Willebrand factor (vWF) multimers that may cause platelet agglutination in vivo. Fresh frozen plasma infusions and plasma exchange represent the most efficient therapy of acute TTP. A specific protease responsible for cleavage of vWF multimers has been recently isolated from normal human plasma and was found to be deficient in four patients with chronic relapsing TTP. We examined the activity of the vWF-cleaving protease in plasma samples collected over a period of 400 days from a further patient with recurrent episodes of TTP who was treated by plasma exchange, plasma infusion, vincristine, corticosteroid therapy, and splenectomy. Complete deficiency of the vWF-cleaving protease was established during the first episode of TTP. The ensuing normalization of the platelet count was associated with the appearance of the protease activity. Three months after remission from the initial TTP event, the vWF-cleaving protease again disappeared and the platelet count gradually decreased. Relapses of severe thrombocytopenia occurred 7 and 11 months after the first acute episode of TTP. Deficient protease activity was associated with the presence in the patient plasma of an inhibitor that was found to be an IgG. Plasma exchange/infusion was followed by a temporary increase in the antibody titer, whereas treatment with vincristine led to a recovery of the platelet count without affecting the inhibitor concentration. Splenectomy and corticosteroid treatment resulted in disappearance of the autoantibody and normalization of the protease activity and of the platelet count. Our data suggest that the thrombocytopenia in this patient with TTP was associated with a lack of the vWF-cleaving protease activity depleted by an autoimmune mechanism. This case, together with our previously reported patients, leads us to conclude that acquired as well as constitutional deficiency of the vWF-cleaving protease may predispose to TTP.
ADAM Proteins↗
Deficient activity of von Willebrand factor-cleaving protease in chronic relapsing thrombotic thrombocytopenic purpura.
In patients with thrombotic thrombocytopenic purpura (TTP), excessive intravascular platelet aggregation has been associated with appearance in plasma of unusually large von Willebrand factor (vWF) multimers. These extremely adhesive vWF multimers may arise due to deficiency of a "depolymerase" cleaving vWF to smaller molecular forms, either by reducing the interdimeric disulfide bridges or by proteolytic degradation. We studied the activity of a recently described vWF-cleaving protease in four patients with chronic relapsing TTP. Diluted plasma samples of TTP patients were incubated with purified normal human vWF in the presence of a serine protease inhibitor, at low ionic strength, and in the presence of urea and barium ions. The extent of vWF degradation was assayed by electrophoresis in sodium dodecyl sulfate-agarose gels and immunoblotting. Four patients, that included two brothers, with chronic relapsing TTP displayed either substantially reduced levels or a complete absence of vWF-cleaving protease activity. In none of these patient plasmas was an inhibitor of or an antibody against the vWF-cleaving protease established. Our data suggest that the unusually large vWF multimers found in TTP patients may be caused by deficient vWF-cleaving protease activity. Deficiency of this protease may be inherited in an autosomal recessive manner and seems to predispose to chronic relapsing TTP. The assay of the vWF-cleaving protease activity may be used as a sensitive diagnostic tool for identification of subjects with a latent TTP tendency.
ADAM Proteins↗
Venous thrombosis after caesarean section in a young woman with homozygous APC resistance and type I protein S deficiency.
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Adult↗
Arrhythmogenic right ventricular dysplasia in identical twins.
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Adolescent↗
[Right ventricular dysplasia (right ventricular cardiomyopathy). Clinical aspects, diagnosis and course in 15 patients from the Zurich area].
Fifteen patients (8 men, 7 women) with right ventricular dysplasia (RVS) from the greater Zürich area are described. Two thirds of these patients were younger than 30 years at first manifestation. 12 presented with ventricular tachycardia of left bundle branch block type. Other forms of arrhythmia (supraventricular tachycardia, sinus node dysfunction) or condition disturbances were documented in 9 subjects. 6 patients had additional symptoms of congestive heart failure; in 3 of them this was the only symptom. 12-lead ECG at rest showed precordial T-negativity (1 pacemaker ECG not interpretable) in 14/15 subjects. Signal averaged ECG revealed late potentials as well as spectral turbulence in the Y or Z leads. Echocardiography yielded typical local abnormalities in the whole study cohort and all but 2 patients showed decreased right ventricular ejection fraction and right heart dilatation. Moreover, left ventricular ejection fraction was concomitantly impaired in 6 subjects. 4 of these 6 individuals suffered from further impairment of left ventricular function within a time period of 19 to 47 months. Recurrent ventricular tachycardia was documented in 11 patients. 2 subjects underwent heart transplantation because of severe progressive right heart failure. One subject died shortly after diagnosis and autopsy confirmed nearly total absence of right ventricular myocardium. This extreme form of right ventricular dysplasia corresponds to Uhl's anomaly. Thus, recurrent ventricular arrhythmias, in particular ventricular tachycardia of left bundle branch block type, together with precordial T-negativity without signs of ischemic heart disease, is highly suggestive of RVD. Echocardiography allows reliable diagnosis. Concomitant left ventricular involvement is frequent. Considering that the etiology and pathogenesis of this disease are unknown, the term right ventricular cardiomyopathy, rather than right ventricular dysplasia, seems more accurate.
Adult↗