摘要:

AbstractA 38‐year‐old male patient with a life‐long history of easy bruising and mild bleeding had a prolonged activated partial thromboplastin time (APTT), prothrombin time (PT), and thrombin time (TT). Reptilase (Bathrops atrox) clotting time was normal. His undiluted and diluted plasma prolonged the APTT, PT, and TT of normal plasma. Fibrin produced from patient plasma was insoluble in 5 M urea. Plasma fibrinogen level was increased when measured as clottable protein and by Laurell electroimmunoassay. Specific assays of plasma factors II, V, VII, X, VIII, IX, XI, and XII were normal. A circulating antithrombin in patient plasma was excluded by demonstrating normal thrombin‐induced platelet aggregation of gel‐separated platelets in the presence of patient plasma. Purified patient fibrinogen reproduced the anticoagulant effect of patient plasma. Patient fibrinogen antigen was similar to normal fibrinogen antigen by immunodiffusion, immunoelectrophoresis (pH 5.2 and 8.6), and crossed immunoelectrophoresis. His unreduced purified fibrinogen had normal migration on polyacrylamide slab gels. Also, the migration in gel slabs of Aα, Bβ and γ‐polypeptide chains, produced by mercaptoethanol reduction of purified patient fibrinogen, was similar to reduced normal fibrinogen. Thrombin‐induced total fibrinopeptide release was normal. However, fibrin monomers produced from patient fibrinogen by thrombin (devoid of fibrinopeptides A and B) reaggregated abnormally; fibrin monomers produced by reptilase (devoid of only fibrinopeptides A) reaggregated normally. Fibrin generated from patient plasma in the presence of factor XIII and calcium, was defective in the formation of covalently bonded α‐α polymers and demonstrated an increased susceptibility to the lytic effects of plasmin (generated in vitro by the additi

ISSN:0361-8609    

DOI:10.1002/ajh.2830090302

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1980

数据来源: WILEY

摘要:

AbstractThe object of this work was to define a model using hypotonically loaded erythrocytes as a vehicle to target drugs to the reticuloendothelial system (RES). The optimum hemolytic event was found to occur at 100 mOsm/kg using a 0.5‐min exposure at 0°C. Approximately one third of the total volume of the cells could be replaced with hypotonic drug solutions under these conditions. Although cytosine‐β‐D‐arabinofuranoside, ara C, is membrane permeable and could not be entrapped in the erythrocytes, phosphorylation of this nucleoside antimetabolite enabled it to be loaded efficiently. Actinomycin D could be loaded and retained within the cells at 0°C, but 90% of this loaded drug leaked out of the erythrocytes in 1 min at 37°C. Actinomycin D‐DNA complexes, however, could be loaded and retained for longer periods. In this case, 50% of the DNA‐bound drug was retained in the cells for one hour at 37°C. It was found that the glycopeptide antitumor antibiotic, bleomycin, could be entrapped and retained in the cells without appreciable leakage. It was possible to load a human therapeutic dose of this drug in 1–2 ml of packed cells. Furthermore, it was demonstrated that bleomycin entrapped in erythrocytes was significantly more effective than the same dose of free drug in suppressing the phagocytic function of the RES in Balb/C and C3H mice. The rationale is discussed for the possible use of these drugs, entrapped in erythrocytes, for the production of RES blockade in the treatment o

ISSN:0361-8609    

DOI:10.1002/ajh.2830090303

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1980

数据来源: WILEY

摘要:

AbstractSix patients and their parents from five different families with Hb H have been evaluated clinically and hematologically. Previous studies using restriction endo‐nuclease mapping technique indicated that α‐thalassemia determinants in these cases are heterogeneous. Only one of the five cases have the usual genotype for Hb H, which is characterized by an α‐DNA‐specific fragment of 20 kb long by Eco RI digestion.Three cases from two different families have Hb H disease with α‐specific DNA fragments of 22.5 kb/2.6 kb long; and the other two have α‐specific DNA fragments of 20 kb/2.6 kb long, in Eco RI digestion of the cellular DNA. The hematological examination of the parents suggests that the α‐thalassemia condition associated with the Eco RI fragment of α‐specific cellular DNA of approximately 22.5 kb long produces an α‐thal‐2‐like clinical condition, while the other α‐thalassemia determinant associated with a fragment 2.6 kb long results in an α‐thal‐1‐like clinical condition. The clinical and hematological findings of the cases with 22.5 kb/2.6 kb fragment patterns were more severe than the case with the 20 kb/2.6 kb combination. This study suggests that variation in the clinical and hematological findings among patients with Hb H disease may well reflect a hete

ISSN:0361-8609    

DOI:10.1002/ajh.2830090304

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1980

数据来源: WILEY

摘要:

AbstractTwo patients with Wilson disease who presented with severe hemolytic anemia are described. One was noted to have unusually high serum copper levels (369 μg/100 ml). A review of similar such patients in the literature suggests that, rather than having a low serum copper, patients with hemolysis accompanying Wilson disease have very high serum copper levels. For this reason, in vitro studies of the toxic effects of copper on erythrocytes were undertaken. It was found that, although copper does not have a major direct inhibitory effect on glycolytic enzymes such as hexokinase, the metal does inhibit hexokinase as a consequence of its interaction with oxyhemoglobin. However, such inhibition does not appear to be a major factor in copper‐induced hemolysis. On the other hand, the addition of the lipid antioxidant butylated hydroxyanisole (BHA) suppresses hemolysis in copper‐treated cells. These experiments suggest that the primary toxic effect of copper is mediated through its oxidant actions on membrane phospholipids rather than through its potential inhibitory effects on intracellular enz

ISSN:0361-8609    

DOI:10.1002/ajh.2830090305

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1980

数据来源: WILEY

摘要:

AbstractIn Pennsylvania, the prevalence of hemophilia is one per 10,000 males. Factor VIII deficiency is five times more frequent than Factor IX deficiency, and 34% of the patients have no relatives affected with the disease. The mean age is 23 years old, and 50% of the patients are less than 20 years old. Approximately one‐third of the patients with Factor VIII deficiency and one fourth of the patients with Factor IX deficiency have levels of<0.01 μ/ml. By clinical criteria, 55% of those with Factor VIII deficiency are severe compared to 45% of those with Factor IX deficiency. Factor VIII‐deficient patients are treated an average of 18 times per year compared to ten times per year for patients with Factor IX deficiency. Hemarthroses account for 70% of the hemorrhages treated and for 40% of the concentrate usage. Home therapy patients use an average of 45,950 Factor VIII units per year at a cost of $4,170 per patient and their use accounts for 60% of the total Factor VIII usage of 1.7 million units. Less than five days per patient per year are lost from school or work because of bleeding, and patients are hospitalized for bleeding an average of only two to three days per patient per year. Adverse immediate reactions to therapy are infrequent. Five percent of patients have persistence of the hepatitis B virus, and 7.5% have inhibitors. The mortality rate is 0.04% per year, with half of the deaths being hemophilia‐r

ISSN:0361-8609    

DOI:10.1002/ajh.2830090306

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1980

数据来源: WILEY

摘要:

AbstractTerminal deoxynucleotidyl transferase (TdT) activity was assayed in leukemic cells of 34 patients in blastic phase of Philadelphia‐positive chronic myelogenous leukemia (CML). The TdT levels were correlated with the response to vincristine and prednisone therapy. None of 20 TdT‐negative patients, but 10 of 14 TdT‐positive patients responded to vincristine and prednisone. There was poor correlation between blast cell morphology and response to this therapy. This study confirms that TdT levels in the majority of patients predict effectiveness of vincristine and prednisone therapy in blastic phase o

ISSN:0361-8609    

DOI:10.1002/ajh.2830090307

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1980

数据来源: WILEY

摘要:

AbstractSince 1952 we have seen nine patients with priapism leading to a diagnosis of chronic granulocytic leukemia (CGL) and a tenth patient who gave a history of priapism when CGL was diagnosed as a result of other symptoms. Seven patients had had one or more transient episodes of prolonged erection before the diagnosis of CGL was established. All ten had high blood leukocyte counts (mean 380 × 109/liter, range 186‐782) in comparison with other newly diagnosed patients. We estimate the incidence of this complication at 1%–2% of all male patients presenting with CGL. Treatment of patients in this series varied greatly. Five patients were treated mainly by local measures with or without cytotoxic drugs at conventional dosage, three were treated by sapheno‐cavernous bypass operations and leukapheresis followed by cytotoxic drugs at high dosage, and two were treated initially by leukapheresis alone. In general, the prompt initiation of measures designed to reduce the leukocyte count seemed more valuable than the surgical procedures employed in these pa

ISSN:0361-8609    

DOI:10.1002/ajh.2830090308

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1980

数据来源: WILEY

摘要:

AbstractWith a new method, sequential immunological, cytochemical and cytokinetic studies were done on lymphoid cells in the peripheral blood of 12 healthy adults. Every single lymphoid cell could therefore be characterized by the following markers: surface immunoglobulins (sIg); rosetting with sheep red blood cells (E); unspecific acid alpha‐naphthyl acetate esterase (ANAE); and3HdT incorporation. Significantly more E+sIg−cells were ANAE+than E−sIg+cells (70% vs. 11%). About half of the E+sIg−cells were ANAE+. By combining esterase and surface marker analyses eight subpopulations of lymphoid cells could be distinguished. The most common subpopulations were E+sIg−ANAE+and E+sIg−ANAE−cells (51% and 22% of all lymphoid cells, respectively). Of all ANAE+cells 90% were E+, but 64% of all ANAE−cells were also E+. In all individuals a subpopulation of E+sIg+cells was found. The esterase pattern of these cells was similar to that of E−sIg+cells. The overall labeling index of the lymphoid cells ex

ISSN:0361-8609    

DOI:10.1002/ajh.2830090309

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1980

数据来源: WILEY

摘要:

AbstractIsoelectric focusing (IEF) with suitable „spacers”︁ can be used to distinguish glycosylated hemoglobins from HbA and HbF in adults and infants, respectively. Using this technique we have shown that there is a good correlation between glycosylated hemoglobins measured by IEF and column chromatography (r = 0.778, P<0.001). There was no significant difference in the rate of glycosylation between adult and cord blood hemolysates following incubation with glucose in vitro: In both instances there was an increase from the normal levels of about 5% to 26% through 31% after 18 hours of incubation. The levels of glycosylated hemoglobins in infants of varying gestation, neonates, and normal adults was remarkably constant, varying from 4.7 ± 1.1% to 6.1 ± 1.6%.These results show that IEF can be useful in the quantitation of glycosylated hemoglobins, particularly in the presence of hemoglobins (eg, HbF) where standard chromatographic techniques cannot be used. IEF has the added advantage of using small quantities of blood, and allows a number of samples to be tested at the same time, thus facilitating the identification of abnormal hemo

ISSN:0361-8609    

DOI:10.1002/ajh.2830090310

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1980

数据来源: WILEY

摘要:

AbstractCells isolated from four patients with prolymphocytic leukemia were evaluated by surface markers, cytogenetics, and flow microfluorometric analysis of cell size and DNA content. All four patients had B‐cell markers with a high density of IgM, kappa type, and Ia‐like antigen. Less intense staining for surface IgD was also observed. In each patient studied, chromosomal modes were in the hypodiploid or near‐diploid range. Despite the karyotypic abnormalities, the cellular DNA content, as determined by flow microfluorometry, was within normal limits in all cases. This suggests that the variability in chromosome numbers seen in these patients may reflect an abnormality in DNA packaging rather than differences in total DNA content. The modal electronic cell size of the prolymphocytes, determined by light scatter, was readily distinguishable from that of normal peripheral blood lymphocytes and the lymphocytes of chronic lymphocytic leukemia. Fewer than 4% of the peripheral prolymphocytes had S‐phase DNA content, a finding consistent with the chronic nature of this l

ISSN:0361-8609    

DOI:10.1002/ajh.2830090311

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1980

数据来源: WILEY