摘要:

AbstractIn five patients with idiopathic osteonecrosis (ON) of the hip, four having hypofibrinolysis mediated by high plasminogen activator inhibitor (PAI‐Fx), and one with high Lp(a), our specific aim was to determine whether therapy (Rx) with the anabolic‐androgenic steroid, Stanozolol(6 mg/day), would normalize PAI‐Fx and Lp(a) and thus potentially ameliorate ON. Prior to Rx, none of the four patients with high PAI‐Fx could normally elevate tissue plasminogen activator (tPA‐Fx) after 10 min venous occlusion at 100 mm Hg. After 12‐18 weeks on Rx, PAI‐Fx and stimulated tPA‐Fx normalized in all four patients. Prior to Rx, mean (SD) stimulated tPA‐Fx was low, 0.4 ± 0.3 IU/ml (lower limit of normal 2.28 IU/ml). On Rx, stimulated tPA‐Fx normalized, rising to 2.83 ± 1.9 IU/ml,P= 0.004. Prior to Rx, mean (SD) basal PAI‐Fx was high, 99 ± 68 (upper limit of normal 26.9 U/ml), and fell on Rx to 22.5 ± 22,P= 0.004. In two of the five patients normalization of hypofibrinolysis or high Lp(a) was accompanied by major symptomatic improvement. Prior to Rx, and 2 years after onset of unilateral hip pain, one of the four patients with high PAI‐Fx and low stimulated tPA‐Fx could walk only one block painfully. After 8 weeks on Stanozolol Rx, and continuing through 54 weeks on Rx, he walked 2 miles per day without pain, despite radiographic progression of ON. In three of the four patients with high PAI and with osteonecrosis present 0.3, 2, and 6 years prior to Stanozolol Rx, there was no clinical improvement after 14‐156 weeks of Rx despite normalization of stimulated tPA‐Fx and PAI‐Fx. The fifth patient, 1 month after onset of disabling hip pain, had normal PAI‐Fx but high Lp(a) (27 mg/dl), and MRI evidence of bone marrow edema (“transient osteoporosis”). After 3 weeks on Rx, Lp(a) normalized (14 mg/dl) and there was marked amelioration of symptoms. For the subsequent 11 weeks on Rx, this patient's Lp(a) was 5 mg/dl, and he became totally asymptomatic and remains asymptomatic 14 months later. We speculate that when ON is diagnosed prior to segmental collapse of the femoral head, it may be possible to reverse hypofibrinolysis, and/or to arrest the progression of ON. We postulate that high PAI or high Lp(a) lead to inadequate lysis of venous thrombi in bone, impaired bone venous circulation, venous hypertension of bone, and subsequent, potentially reversible

ISSN:0361-8609    

DOI:10.1002/ajh.2830480402

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

年代:1995

数据来源: WILEY

摘要:

AbstractThe objective of this study was to design and validate a bedside decision instrument to be used by patients with chronic myeloid leukemia and their physicians in deciding between the therapeutic alternatives of bone marrow transplantation and conservative management during the early phase of disease.A decision board was constructed containing detailed scenarios associated with the treatment alternatives, together with estimates of survival probabilities at various periods of followup. The instrument was tested on 42 healthy hospital personnel and validated by measuring the extent to which systematic alterations in the scenarios with respect to toxicities and survival probabilities produced predicted shifts in treatment preferences. A subgroup of respondents was randomized to receive information through the decision board alone or a shorter and less informative version of the instrument, followed by the decision board. The direction and strength of stated preferences were compared, together with satisfaction for these preferences.The direction and strength of preferences between bone marrow transplantation or conservative chemotherapy were influenced in a predictable way by changes in the toxicity and survival descriptions in the scenarios. Using the test‐retest method in 16 subjects, the stated preferences were found to be highly reliable (intraclass correlation coefficient, 0.87). The mean level of satisfaction with the stated preference, on a scale from not at all satisfied = 1 to very satisfied = 5, was higher for those exposed to the decision board (3.7, SD 1.06) compared with those presented with the short version (2.95, SD 0.67) (p<0.01).The results demonstrate the feasibility and acceptability of the instrument in healthy individuals. The preferences elicited by the instrument appear to be reliable and valid according to prespecified constructs of the relation between the information provided and the preferences predicted. These results support further testing of this approach in actual patients. © 1995 Wiley‐Liss,

ISSN:0361-8609    

DOI:10.1002/ajh.2830480403

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

年代:1995

数据来源: WILEY

摘要:

AbstractAcute myelogenous leukemia (AML) in the elderly continues to have a poor prognosis and new treatment approaches are needed. This Phase II trial was undertaken to evaluate the complete remission rate and toxicity of a chemotherapeutic regimen including etoposide and 6‐thioguanine, combined with reduced doses of cytosine arabinoside and daunorubicin (V‐TAD) in individuals greater than 50 years of age with AML.Thirty‐five patients, ranging in age from 51 to 80 years (median, 66 years), were registered onto the study. Twenty‐nine patients were entered at the first dose level (daunomycin 20 mg/m2days 1 and 2, ara‐C 75 mg/m2days 1‐5, 6‐thioguanine 75 mg/m2every 12 hr days 1‐5, and etoposide 50 mg/m2days 1, 2, and 3) and six patients underwent therapy at the second dose level (ara‐C 75 mg/m2days 1‐7 with the remainder of the regimen unchanged). After achieving a complete remission, patients underwent two to three consolidation cycles of chemotherapy.Thirty‐one patients were evaluable for response. Thirteen patients (ten of twenty‐five at the first dose level and three of six at the second dose level) achieved a complete remission (42%). Median remission duration was 6 months (range 1‐21 months).The current regimen, while tolerated, did not result in improved survival compared with prior treatment regimens because of a high incidence of resistant and recurrent leukemi

ISSN:0361-8609    

DOI:10.1002/ajh.2830480404

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

年代:1995

数据来源: WILEY

摘要:

AbstractWe prospectively treated 46 patients with favorable myelodysplastic syndrome classified as refractory anemia (RA), refractory cytopenia (RC), or refractory anemia with ringed sideroblasts (RARS). These patients received one of two schedules of 13‐Cis‐Retinoic Acid (low dose 80 mg daily for 6 months vs. high dose 200 mg po daily for 3 months), or Danazol (800 mg po daily for 3 months), and were crossed over to the alternative drug in the absence of response or at progression.Using strict criteria of response we found little objective evidence of activity for either compound. Only two minor responses were seen among 22 patients treated with low dose 13‐CRA, 1 response among 20 cases that received high dose 13‐CRA, and 1 partial response and 1 minor response to Danazol among 34 cases.Neither 13‐Cis‐Retinoic Acid nor Danazol appear active enough in patients with favorable myelodysplastic syndrome to justify their use. © 1995 Wil

ISSN:0361-8609    

DOI:10.1002/ajh.2830480405

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

年代:1995

数据来源: WILEY

摘要:

AbstractA written survey of all licensed medical laboratories in Canada performing coagulation testing was performed to investigate the level of knowledge and overall usage of the INR system for reporting prothrombin time results in medical laboratories. There was an overall response rate of 857 of 1,228 laboratories surveyed. Fifty‐seven percent of responding laboratories utilized some format of INR reporting. The ISi of the individual thromboplastin utilized was known by 89% of laboratories. The IS1 of the thromboplastin utilized was known to be specific for the particular reagent/Instrument combination in 44% of cases. Fifty‐five percent of client physicians preferred PT results to be reported in seconds while 42% desired an INR format. The situation in Canada is similar to the United States in that further education regarding the INR system for PT reporting is required by both medical laboratories and physicians. © 1995 Wiley‐Lis

ISSN:0361-8609    

DOI:10.1002/ajh.2830480406

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

年代:1995

数据来源: WILEY

摘要:

AbstractNineteen children who presented with thromboses over a 7‐year period were found to have a lupus anticoagulant (LA). The initial thrombosis was proximal deep vein thrombosis (DVT) in six children, central nervous system (CNS) in five, primary pulmonary in four, distal DVT in two, central venous in one, and proximal arterial in one. Five children were diagnosed with systemic lupus erythematosus (SLE), including two children for whom thrombosis was the presenting sign of SLE. The remaining 14 children were diagnosed with the antiphospholipid antibody (APA) syndrome. The APA syndrome was manifest by venous or arterial thrombosis in association with a positive LA; positive anticardiolipin antibodies and a fine, speckled antinuclear antibody (ANA) pattern were additionally found in the majority of children. Approximately one‐half of the children with SLE or the APA syndrome had a pulmonary embolus, and one‐half developed recurrent thrombosis. Oral anticoagulation with coumadin to achieve an INR of>2.0 prevented thrombosis recurrence. The recognition of a LA in children with thrombosis necessitates evaluation for SLE, APA, and other autoantibodies. © 1995 Wiley‐L

ISSN:0361-8609    

DOI:10.1002/ajh.2830480407

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

年代:1995

数据来源: WILEY

摘要:

AbstractThe 20 × 109/L (20,000/μl) threshold for prophylactic platelet transfusion may be unnecessarily high. The widespread use of this threshold may reflect lack of confidence in the reliability of low platelet counts. We evaluated the performance of automated platelet counts and their relation to clinical bleeding. First, we prepared serial blood dilutions with “target” platelet counts from 2 to 40 × 109/L For the 48 measurements on 2 × 109/L “target” dilutions, values of 1 or 2 × 109/L were obtained with the Sysmex NE‐8000 analyzer (mean 1.44 × 109/L; SD 0.31 × 109/L). Similarly, for 5 × 109/L “target” counts, automated counts were 3‐6 × 109/L (mean 4.42 × 109/L; SD 0.18 × 109/L). Similar results were observed with all other “target” levels, with coefficients of variation (CV) from 6.39% to 7.71% with 10‐40 × 109/L “target” values. Secondly, we compared triplicate automated and manual platelet counts on thrombocytopenic patients with platelet counts from 4–30 × 109/L. The triplicate automated platelet counts differed by no more than 5 × 109/L among themselves, whereas the manual counts varied by as much as 30 × 109/L. Mean platelet counts: automated, 14.40 × 109/L (CV 10.12%); manual, 16.48 × 109/L (CV 30.39%) (P= 0.038 for counts;P<0.001 for CV). Finally, we prospectively evaluated bleeding in thrombocytopenic patients (1,809 patient‐days of observation). Univariate and multivariate logistic regression analysis revealed highly significant correlations between the automated platelet count and major and minor bleeding manifestations. Thus, automated platelet counts are highly reliable and accurately predict clinical bleeding. The use of automated analyzers should facilitate improv

ISSN:0361-8609    

DOI:10.1002/ajh.2830480408

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

年代:1995

数据来源: WILEY

摘要:

AbstractTo determine the significance of the commonly observed fall in serum vitamin B12levels during pregnancy, serum levels of the B12metabolites methylmalonic acid (MMA) and homocysteine (Hcy) were measured in a group of 50 pregnant patients with subnormal serum B12(range 45‐199 pg/ml) and the results compared with those of 25 pregnant controls (serum B12208‐580 pg/ml). Mean values for serum MMA and total Hcy in the subnormal B12group were 445.4 nmol/L and 7.03 μmol/L, respectively, which were not significantly different from the mean MMA of 440.5 nmol/L and Hcy of 6.88 nmol/L in the controls. For the total group of patients, neither serum MMA nor serum Hcy levels correlated with serum B12. One‐third of pregnant patients showed elevated serum MMA values, independent of B12status. Significant elevation of serum Hcy was detected in only two patients, both with subnormal serum B12and hematological evidence of B12deficiency. We conclude that the usual fall in serum B12concentration in pregnancy does not reflect B12deficiency at the biochemical level. In establishing true B12deficiency in pregnancy, the serum Hcy level (in the absence of folate deficiency) but not serum MMA, is of value. © 1995 Wiley‐

ISSN:0361-8609    

DOI:10.1002/ajh.2830480409

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

年代:1995

数据来源: WILEY

摘要:

AbstractBone marrow transplantation (BMT) is the only curative therapy available for hemoglobinopathies. BMT was performed on a young child with sickle cell anemia (SCA) after approximately 9 months of transfuslon therapy following her initial stroke. The patient received a matched sibling donor (sickle trait) BMT. The conditioning regimen consisted of busulfan 4 mg/kg/day × 4, cyclophosphamide 50 mg/kg/day × 4. Graft vs. host disease prophylaxis was daily cyclosporine for 6 months. There were no significant complications during BMT. Engraftment occurred on day + 17 and the patient was transfusion independent since day +45. Pre‐BMT cerebral arteriography showed multiple stenotic cerebral vessels and a moya‐moya pattern. Perfusion MRI demonstrated reduced capillary perfusion. Approximately 170 days after BMT the patient experienced episodes of transient left‐sided weakness and speech problems. Neuroimaging revealed progression of large vessel pathology by angiography despite significant improvement in cortical perfusion (MR perfusion scan). Molecular analysis by PCR and DNA fingerprinting confirmed absence of mixed mosaicism. Rheologic evaluation showed normal corrected bulk viscosity. It is possible that progression of large vessel pathology and return of clinical symptoms in the face of normal rheologic parameters may be due to worsening of the already damaged cerebral vessels by the BMT conditioning regimen. Further evaluations of patients with SCA undergoing BMT after a stroke are needed to answer this question. © 1995 Wiley

ISSN:0361-8609    

DOI:10.1002/ajh.2830480410

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

年代:1995

数据来源: WILEY

摘要:

AbstractTwo patients with macroglobulinemia (monoclonal lgM in the serum) and massive splenomegaly were incapacitated by progressive disease refractory to standard chemotherapy. In each case, palliative splenectomy was followed by a prompt, complete, and unexpected clinical remission with disappearance from the serum of the monoclonal IgM component. One patient remains free of disease 12 years after splenectomy. The other patient remained free of detectable macroglobulinemia for 13 years after splenectomy. A review of the literature revealed other cases of remission of macroglobulinemia attributable to splenectomy alone. Data in humans and animals suggest that the spleen may facilitate IgM secretion by normal and malignant B lymphocytes. Splenectomy should be considered a possible treatment option for patients with massive splenomegaly and macroglobulinemia who progress on chemotherapy. © 1995 Wiley‐Liss, I

ISSN:0361-8609    

DOI:10.1002/ajh.2830480411

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

年代:1995

数据来源: WILEY