摘要:

AbstractIn a 10‐year interval, a total of 12 cases of familial hairy cell leukemia have been published. They were noted in first degree relatives, mostly in men. In some instances, when the HLA type was performed, a specific HLA type was found in the studied family, but a different haplotype was seen in other families. It appeared that familial cases of hairy cell leukemia were not associated with a “specific HLA antigen” and other factor(s) such as environmental, or some kind of occupational exposure, were suggested to play a role in the familial occurrence of hairy cell leukemia.We add three more familial hairy cell leukemia cases which are different from other published cases, showing a female predominance. The HLA typing revealed interesting findings. The HLA type shared by case 1 and 3 was A2, A30/31(19), B27, Bw4, Bw6. From these, HLA A2, Bw4, and Bw6 were previously reported (Ward FT, Baker J, Krishnan J, Dow N, Kjobech CH:Cancer65:319–321, 1990). Case 2, shared with the other two the antigen Bw6. Its specific HLA type was A3 and B7, the type previously reported in a family (Begley CG, Tait B, Crapper RM, Briggs RG, Brodie GN, Mackay IR:Leuk Res11:1027–1028, 1987). Based on these observations, we may conclude that a “specific HLA type,” A2, Bw4, Bw6 and A3, B7 might have a role in the genetic predisposition for hairy cell leukemia. © 1993 W

ISSN:0361-8609    

DOI:10.1002/ajh.2830420402

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

年代:1993

数据来源: WILEY

摘要:

AbstractThe prospect of selecting oral α‐ketohydroxypyridine chelators intended for clinical use in iron overload has been examined using several animal models of efficacy and toxicity. Studies using iron dextran‐loaded mice labelled with59Fe have shown that only the 1‐substituted methyl, ethyl, (n)propyl, allyl, cyclopropyl, 2′‐methoxyethyl, 3′‐ethoxypropyl, or 2‐methyl‐ or 2‐ethyl‐ 3‐hydroxypyrid‐4‐one chelators were orally effective in increasing iron (59Fe) excretion by comparison to intraperitoneally administered desferrioxamine at the same dose (250 mg/kg). In contrast, chelators containing ‐H, mono‐ or dihydroxyalkyl and diethoxyethyl 1‐substituents caused very little or no increase in iron (59Fe) excretion by the oral or intraperitoneal routes. In vitro studies using ferritin and haemosiderin have shown that equivalent iron release took place with both groups of chelators irrespective of their in vivo effects. In most cases there was no correlation between the n‐octanol/water partition coefficient (Kpar) and iron removal efficacy but positive correlation between the lipophilicity and acute or subacute toxicity of these chelators in rats. The most toxic chelator in the chronic toxicity studies in rats was the lipophilic 1, 2‐diethyl‐3‐hydroxypyrid‐4‐one (EL1NEt). The most effective chelator in increasing iron excretion in mice and rabbits was 1‐allyl‐2‐methyl‐3‐hydroxypyrid‐4‐one (L1NAll), and the chelator with the highest safety margin in mice and rats was 1, 2‐dimethyl‐3‐hydroxypyrid‐4‐one (L1). Overall the oral effectiveness in increasing iron excretion by these chelators in animals does not appear to be related to their lipophilicity or their ability to mobilise polynuclear iron in vitro but rather to other properties possibly related to

ISSN:0361-8609    

DOI:10.1002/ajh.2830420403

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

年代:1993

数据来源: WILEY

摘要:

AbstractWe report on the use of leuprolide to prevent heavy menstrual bleeding that often occurs before platelet engraftment in premenopausal women undergoing bone marrow transplantation (BMT). Leuprolide, a synthetic analog of gonadotropin‐releasing hormone (Gn‐RH‐a), was given to 34 patients by intravenous bolus injection, 1 mg daily, until platelet recovery. The median duration of therapy was 50 days (range 16–170). When necessary, patients self‐administered the drug after discharge from the hospital. No adverse effects could be related directly to the use of leuprolide. Leuprolide effectively prevented menstruation in 25 patients (73%), failed in seven (21%), and two patients were not evaluable. The success of leuprolide therapy was related to the time of onset of treatment, as anticipated from the gradual effect of Gn‐RH‐a on the menstrual cycle. The failure rate was only 6% (one of 16 patients) when leuprolide was started at least 2 weeks prior to the development of thrombocytopenia, compared to a failure rate of 33% (six of 18 patients) when leuprolide was started at a later time. We conclude that leuprolide as a single agent is a safe and effective method to prevent menstrual bleeding during BMT. Additional studies are needed to determine the best timing for the onset of therapy and the relative benefit of leuprolide compared to other prophylactic approaches in patients with lengthy thrombocytopenia. © 1993 W

ISSN:0361-8609    

DOI:10.1002/ajh.2830420404

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

年代:1993

数据来源: WILEY

摘要:

AbstractWe have recognized a rapidly progressive, often fatal shock syndrome associated with viridans streptococcal sepsis following bone marrow transplantation (BMT). Of 832 patients receiving a marrow transplant at the University of Minnesota between 1976 and 1988, including 123 with viridans streptococcal bacteremia, 10 patients (8%) developed clinical shock within an average of 2 days (range 0–4 days) of their first positive blood culture. Viridans streptococcal shock occurred in patients early in the transplantation course, between 1 and 28 (median 6) days following BMT when all 10 patients were neutropenic. Six of the 10 patients died as a consequence of their shock or from subsequent complications. The most frequent (6 of 10 patients) viridans streptococcal species isolated in the shock patients wasStreptococcus mitis.Of multiple factors analyzed for increased risk of developing viridans streptococcal shock, only younger patient age was significantly associated with the development of shock. Although 58% of BMT recipients with viridans streptococcal bacteremia were younger than 15 years, all 10 patients comprising the shock population were<15 years of age (P<0.02). We speculate that certain streptococcal strains may trigger fulminant shock in the immunocompromised BMT patient. © 1993 Wiley‐Liss,

ISSN:0361-8609    

DOI:10.1002/ajh.2830420405

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

年代:1993

数据来源: WILEY

摘要:

AbstractA pilot study was conducted of the biological characteristics of the leukemia cells of newly diagnosed patients with poor prognosis acute myelogenous leukemia (AML). This study included measurements of the pretherapy proliferative rate of the leukemia cells in vivo, assessment of differentiation in vivo during remission induction therapy, and the level of expression of the fms, myc, and IL1β genes in pretherapy leukemia cells. Short cell cycle times were characteristic of the best prognostic category and were associated with a rapid reduction in marrow leukemia cells in cytosine arabinoside (araC)‐sensitive patients. Expression of c‐fms was associated with rapid reduction in marrow leukemia cells during araC therapy and with a successful treatment outcome. Expression of the IL1β gene was associated with short remissions. These studies suggest that when compared to newly diagnosed standard prognosis AML, the leukemia of poor prognosis patients is more likely to exhibit long cell cycle times, low levels of fms expression, and is less likely to be associated with myeloid differentiation during remission induction therapy. © 1993 Wiley‐L

ISSN:0361-8609    

DOI:10.1002/ajh.2830420406

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

年代:1993

数据来源: WILEY

摘要:

AbstractHb Questembert [α131(H14) Ser→Pro] was found in several members of a French family suffering from congenital Heinz body anemia. The unstable hemoglobin was expressed in the peripheral red blood cells at a very low level. Globin biosynthetic studies revealed a high specific activity of the abnormal chain and an α‐/β‐labeling ratio similar to that of β‐thalassemia trait. Hb Caen [α132(H15) Val→Gly]is another unstable variant with the same globin biosynthesis abnormality. In both cases the structural modification is localized at the end of the H helix, a region encoded by the third exon. The mechanism for the unbalanced globin synthesis is not yet clear. It may be related 1) to a defect in chain assembly, 2) to an increased rate of degradation of the variant chain followed by the release of unlabeled β‐chains from the abnormal hemoglobin, thus leading to an apparent suppression of β‐chain synthesis, or 3) to a modified stability of the abnormal α‐globin mRNA.

ISSN:0361-8609    

DOI:10.1002/ajh.2830420407

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

年代:1993

数据来源: WILEY

摘要:

AbstractTo evaluate the effects of human immunodeficiency virus type 1 (HIV‐1) infection on the loss of factor VIII alloantibodies, we identified 77 patients with a history of inhibitors from among a large cohort of HIV‐1‐infected participants enrolled in a natural history study of HIV‐1 infection in hemophilia. Fifty‐six patients were high responders with inhibitors titers greater than 5 Bethesda Units (BU) measured on at least one occasion. From May 1985 to December 1989, 13 of the high‐responder patients were rechallenged with factor VIII concentrates after several years of treatment with other plasma products. All exhibited excellent hemostasis upon reinstitution of factor VIII. Seven of the 13 patients (11.3–46.3 years of age) were in the advanced stages of HIV‐1 infection at the time of rechallenge. Inhibitor titers measured subsequent to the reinstitution of factor VIII were consistently less than 1 BU in five of these seven patients. The remaining six patients (6.1–57.5 years of age) had mild to moderate CD4+ lymphocyte depletion (absolute CD4+ cells: 262–935/ mm3) at the time of factor VIII rechallenge. Follow‐up inhibitor titers were negative 7–42 months after consistent factor VIII use in these six patients. The lack of anamnestic response to factor VIII in all 13 patients who were rechallenged indicates that HIV‐1‐infected patients who have a history of high‐responder inhibitors frequently benefit from the reintroduction of factor VIII use for the control of bleeding, regardless of their stage of HIV‐1

ISSN:0361-8609    

DOI:10.1002/ajh.2830420408

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

年代:1993

数据来源: WILEY

摘要:

AbstractAntiphospholipid antibody formation can be induced in mice by phospholipid in a hexagonal II phase but not by phospholipid in a bilayer phase. Since sickle red cell membranes have increased hexagonal II phase content, we have measured serum antiphospholipid antibody levels in 25 patients with sickle cell disease to determine whether anti‐phospho‐lipid antibody may similarly be induced in these patients. Seventeen of the 25 patients (68%) had increased levels of antiphospholipid antibodies. Eleven patients (65%) had IgG and six each (35%) had IgM and IgA isotypes. Antiphosphatidylethanolamine, antiphos‐phatidylserine, antiphosphatidylinositol, and antiphosphatidic acid were the most frequently increased antibodies. The finding of increased antiphospholipid antibodies in these patients is compatible with the concept that antiphospholipid antibody formation is associated with structural changes in the red cell membrane and that such structural changes occur in the red cells of patients with sickle cell disease. © 1993 Wiley‐L

ISSN:0361-8609    

DOI:10.1002/ajh.2830420409

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

年代:1993

数据来源: WILEY

摘要:

AbstractA 68‐year‐old previously well woman developed sudden onset of limb gangrene in association with liver dysfunction. An immediately acting inhibitor to factor V with some of the features of lupus anticoagulant was demonstrated. The patient required limb amputation within 2 weeks and activity of the anticoagulant seemed to be on the decline 6 months later. © 1993 Wiley‐Lis

ISSN:0361-8609    

DOI:10.1002/ajh.2830420410

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

年代:1993

数据来源: WILEY

摘要:

AbstractThe activity of chloroquine and quinine, alone and in combination with desferrioxamine (7 μmol/liter), was evaluated in vitro against susceptible and resistant clones ofPlasmodium falciparumby a semimicroassay system. The addition of desferrioxamine had no effect on the activity of chloroquine against both clones. Desferrioxamine had no effect on the activity of quinine against the susceptible clone but had slightly enhanced quinine action against the resistant clone. Further development of desferrioxamine as an antimalarial drug may be of limited interest. © 1993 Wiley‐Liss,

ISSN:0361-8609    

DOI:10.1002/ajh.2830420411

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

年代:1993

数据来源: WILEY