Antithymocyte globulin for patients with myelodysplastic syndrome

Twenty-five transfusion-dependent myelodysplastic syndrome (MDS) patients (with < 20% blasts) were treated in a phase II study with antithymocyte globulin (ATG) at 40 mg/kg/d for four doses and then followed with blood counts every 2 weeks and clinic visits every 3 months, for a median of 14 months (range 1-38 months). 11 (44%) patients responded and became transfusion-independent after ATG, including three complete responses, six partial responses, and two minimal responses. Responses were observed in 9/14 patients (64%) with refractory anaemia (RA) and 2/6 patients (33%) with refractory anaemia with excess blasts (RAEB). Median response duration was 10 months (range 3-38 months). The Kaplan-Meier estimate of overall survival was 84% at 38 months, with one early death due to pneumonia and two deaths from disease progression to leukaemia. Side-effects consisted mainly of mild serum sickness in all patients. A single course of ATG restored haemopoiesis in some patients with MDS and was well tolerated.     

Red cell folate in elderly patients with myelodysplastic syndrome

Diabetes mellitus is a lifelong condition which requires acceptance, understanding and some degree of lifestyle discipline in order to maintain glycaemic equilibrium. The situation is complicated by the fact that poor glycaemic control is not necessarily symptomatic. Routines recommended by health professionals may not always be acceptable to the recipients or may be difficult to translate into the individual's framework of daily living. Dramatic emergencies may arise from a complex interrelated multiplicity of actions or omissions, or for reasons outside the control of the patient. Most emergencies are technically preventable. An attempt should be made by Accident and Emergency (A & E) staff to determine the cause. Referral to the diabetes specialist team is usually indicated.     

Increased osteoclast-like cells formation in long-term bone marrow cultures from patients with a spinal cord injury

A simple and sensitive method for analysis of three tetracyclic antidepressants, maprotiline, mianserin, and setiptiline, in human whole blood was developed using headspace-solid-phase microextraction (SPME) and gas chromatography-mass spectrometry (GC-MS). A vial containing a blood sample, sodium hydroxide, and imipramine as an internal standard was heated at 120 degrees C. The extraction fiber of the SPME was exposed for 45 min in the headspace of the vial. The compounds absorbed on the fiber were desorbed by exposing the fiber in the injection port of a GC-MS. The calibration curves, using an internal standard method, demonstrated good linearity throughout the concentration range from 0.005 to 5.0 microg/g for mianserin and setiptiline and from 0.025 to 25 microg/g for maprotiline. No interferences were found, and the time for analysis was 60 min for one sample. In addition, this proposed method was applied to a medicolegal case in which the cause of death was suspected to be acute setiptiline poisoning. Setiptiline was detected in the left and right heart blood samples of the victim at concentrations of 1.77 and 0.78 microg/g, respectively.     

Karyotype studies of patients with a myelodysplastic syndrome]

BACKGROUND: This study examined the sources used by cancer patients to obtain helpful information regarding their treatment options and side effects and the major predictors that facilitated usage of information. METHODS: The survey was administered to a representative sample of cancer patients in Texas. The cancer treatment facilities from which the patients were sampled were part of the University of Texas M. D. Anderson Cancer Center's Texas Community Oncology Network. A total of 593 patients (65%) out of 910 contacted responded to the survey. RESULTS: The patients reported that providers such as physicians and nurses were the most helpful sources of information. White patients tended to use books and reference materials more heavily to gather additional information regarding their treatment, while black patients relied on pamphlets and television. Educational level appeared to have a major influence on the black patient's use of printed materials. CONCLUSIONS: The results document the important role that providers play in influencing patients' treatment decisions. Effective ways to communicate with cancer patients are different for patients with different racial backgrounds. Implications for the future development of patient education materials and cancer prevention initiatives targeting ethnic minorities are addressed.     

The effect of ulinastatin on CFU-C colony formation in mouse myelocyte cultures

The mixture of 5'-guanylylimidodiphosphate (Gpp(NH)p)/EDTA/NaCl has been used to delineate low-affinity conditions for agonists binding to G-protein-linked receptors. The effects of this mixture on [3H]RX821002 (2-methoxyidazoxan) binding to alpha2-adrenoceptors were evaluated in different tissues. The density of alpha2-adrenoceptors in the presence of the mixture was 11, 78 and 60% higher in human cortex (predominant alpha2A), human caudate (alpha2A + alpha2C) and rat kidney (alpha2A + alpha2B), respectively, than in its absence. In rat kidney, masking of alpha2B-adrenoceptors by ARC239 (2-[2-[4-(o-methoxyphenyl)-piperazin-1-yl]-ethyl]-4,4-dimethyl-1,3 -(2H,4H)-isoquinolindione) (50 nM) or masking of alpha2A-adrenoceptors by BRL44408 (2-[2H-(1-methyl-1,3-dihydroisoindole)methyl]-4,5-dihydroimidaz ole) (100 nM) demonstrated that the increase was in the alpha2B-adrenoceptor but not in the alpha2A-adrenoceptor subtype.     

骨髓增生异常综合征T淋巴细胞异常与克隆造血

目的 了解T淋巴细胞异常在骨髓增生异常综合征(MDS)克隆造血中的作用.方法 对76例MDS患者的染色体核型、T淋巴细胞亚群及激活状态进行分析.结果 正常核型36例,异常核型40例,异常发生率52.6%.40例异常核型中,三体8(+8)24例,占异常核型的60.0%.与健康对照组比较,MDS患者CD+3 CD-19、CD+3 CD-4 CD+8以及CD+3 HLA-DR+细胞百分率显著升高,CD-3(CD16 CD56)+细胞的百分率明显降低.将MDS患者进行核型分组,异常核型组CD+3(CD16 CD56)+细胞的百分率显著高于正常对照组.将+8核型从MDS异常核型中独立出来进行分析,CD+3 CD+4 CD-8细胞的百分率明显低于正常核型以及其他异常组,CD4/CD8的比值明显低于健康对照组.结论 MDS存在T淋巴细胞异常,异常核型MDS可能恶性克隆增殖更为优势,预后更差.+8核型MDS存在更为严重的免疫监视功能下降,导致恶性克隆过度增殖与残存造血过度受抑.     

Granulocyte-macrophage colony stimulating factor suppresses lipopolysaccharide-induced osteoclast-like cell formation in mouse bone marrow cultures

Lipopolysaccharide (LPS) is a potent bone resorbing factor. We investigated the effect of LPS on osteoclast formation in three types of cultures. LPS inhibited osteoclast formation induced by 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], in a dose-dependent manner, in cultures of whole bone marrow cells without dexamethasone. LPS increased the amount of granulocyte-macrophage colony stimulating factor (GM-CSF) in the culture supernatant, and anti-GM-CSF antiserum almost abolished the inhibition of osteoclast formation by LPS, thereby indicating that GM-CSF generated by treatment with LPS may be responsible for the inhibition of osteoclast formation. In cultures with dexamethasone, the amount of GM-CSF was decreased to one-third of that with 1,25(OH)2D3 alone and was not changed by treatment with LPS. In this culture system, LPS enhanced osteoclast formation. In the coculture system of nonadherent bone marrow cells and a stromal cell line in the presence of 1,25(OH)2D3 and dexamethasone, where no detectable GM-CSF was present in the supernatant, LPS markedly enhanced osteoclast formation, whereas exogenously added GM-CSF (100 pg/ml) almost completely inhibited osteoclast formation. LPS stimulated pit formation on dentin slices by the osteoclast-like cells formed by in vitro culture system.     

Spontaneous erythroid colony formation as the clue to an underlying myeloproliferative disorder in patients with Budd-Chiari syndrome or portal vein thrombosis

Results from this laboratory have shown that bone metabolism is directly related to extracellular pH and that high concentrations of tobramycin released from impregnated polymethylmethacryrate (PMMA) beads has pH-dependent toxic effects on bone. In the present study, beneficial effects of calcium hydroxide-impregnated PMMA were investigated regarding tobramycin toxicity and bone metabolism in chick embryo tibiae in vitro. Also using Ca(OH)2 as a pH regulator, the antibiotic efficacy of tobramycin-impregnated PMMA was evaluated with respect to inhibition of Staphylococcus aureus growth. When Ca(OH)2 was added to PMMA beads containing tobramycin, the beads released hydroxyl and calcium ions into the culture medium and released more antibiotic than beads containing only tobramycin. Bone metabolism (glycolysis, total protein synthesis, and collagen synthesis) was enhanced by Ca(OH)2-impregnated beads with or without tobramycin. Additionally, bacterial growth was inhibited more strongly when S. aureus was incubated with tobramycin- and Ca(OH)2-impregnated PMMA disks than with disks containing only tobramycin. This study demonstrates the feasibility of adding Ca(OH)2 to tobramycin-impregnated PMMA beads as a regulator of local pH and a promoter of bone metabolism for protection of bone when high concentrations of tobramycin are used to treat osteomyelitis. It also suggests that lower concentrations of antibiotic may be effective if Ca(OH)2 and tobramycin are administered simultaneously.     

The long-term follow-up of patients with Klippel-Feil syndrome and congenital scoliosis

STUDY DESIGN: This study evaluated the long-term results of Klippel-Feil syndrome in patients with congenital scoliosis. OBJECTIVES: To determine the incidence of cervical and cervical-related symptoms of patients who have Klippel-Feil syndrome associated with congenital scoliosis. SUMMARY OF BACKGROUND DATA: Many authors have described the association of Klippel-Feil syndrome and congenital scoliosis. In this population of patients, cervical lesions often are discovered incidentally. The significance of these lesions is unknown. METHODS: Thirty-two patients with congenital scoliosis and Klippel-Feil syndrome were observed for more than 10 years. They were questioned specifically about cervical and cervical-related symptoms. All patients had sequential cervical radiographs and physical examinations. RESULTS: Despite rather dramatic radiographic appearances, only seven (22%) of the 32 patients had cervical or cervical-related symptoms, with two patients requiring surgery for their cervical lesions. The extent of the deformities and the average number of cervical vertebrae fused and cervical fusion-patterns were statistically similar between the symptomatic and asymptomatic groups. Patients fused to the cervicothoracic junction for management of their deformities had a significantly increased incidence of cervical symptoms. Also, patients with congenital stenosis had a significantly greater incidence of upper extremity pain. CONCLUSIONS: Only a small number of patients with Klippel-Feil syndrome and congenital scoliosis developed cervical symptoms. No fusion pattern that placed the patient at greater risk for developing symptoms could be identified. Factors that did lead to a greater incidence of cervical symptoms were fusion to the cervicothoracic junction and congenital cervical stenosis.     

Atrioventricular conduction during long-term follow-up of patients with sick sinus syndrome

BACKGROUND: It has been claimed that patients with sick sinus syndrome have an increased risk of developing AV block, but this has never been assessed prospectively. The aim of the present study was to evaluate in a prospective trial AV conduction during the long-term follow-up of patients with sick sinus syndrome. METHODS: Two hundred twenty-five consecutive patients with sick sinus syndrome and intact AV conduction were randomized to undergo single-chamber atrial pacing (110 patients) or single-chamber ventricular pacing (115 patients). Follow-up after 3 months and then yearly included measurement of the PQ interval and, in patients with atrial pacemakers, determination of the atrial stimulus-Q intervals at pacing rates of 100 and 120 bpm. The occurrence of AV block in the atrial group was recorded. During follow-up (mean, 5.5+/-2.4 years), there was no change in PQ interval in either group and no change in atrial stimulus-Q intervals or Wenckebach block point in the atrial group. Four of 110 patients in the atrial group developed grade 2 to 3 AV block that required upgrading of the pacemaker (0.6% per year). Two of these 4 patients had right bundle-branch block at pacemaker implantation. CONCLUSIONS: AV conduction, estimated as PQ interval and atrial stimulus-Q interval at atrial pacing rates of 100 and 120 bpm and the Wenckebach block point, remains stable during long-term follow-up. Thus, treatment with single-chamber atrial pacing is safe and can be recommended to patients with sick sinus syndrome without bundle-branch block.     

Differential immunological aberrations in patients with primary and secondary Sj?gren''s syndrome

PURPOSE: To evaluate the dependence of fine particle dose charge (FPD charge) generated from powder inhalers on physico-chemical properties of the inhalation powder, inhaler type, deaggregation mechanism, dose number and/or retained powder. METHODS: Electrostatic charges were determined on micronized powders and aerosolized fine particle doses withdrawn from two, high efficiency, multidose powder inhalers, Turbohaler and prototype Dryhaler. The behavior of terbutaline sulfate, budesonide, albuterol (sulfate and base), beclomethasone dipropionate and lactose was assessed before and after aerosolization. RESULTS: Both inhalers conferred triboelectric FPD charges during aerosolization in the range -400 pC through +200 pC. Specific charges (charge/unit mass) on the fine particle doses of budesonide from Dryhaler were significantly less than those from Turbohaler (p < 0.01). Electrostatic charges on the potentially respirable cloud of terbutaline sulfate generated by Bricanyl Turbohaler were positive and/or negative and unpredictable. With Pulmicort Turbohaler, FPD charges on budesonide were always positive. Dryhaler was used to determine the chemical dependence of fine particle triboelectrification during the aerosolization of pure materials. A triboelectric series was constructed from the Dryhaler results ranking the powders from positive to negative as budesonide > lactose > albuterol sulfate > terbutaline sulfate > or = albuterol > or = beclomethasone dipropionate. CONCLUSIONS: While there was no evidence of FPD charge dependence upon dose number with either inhaler, FPD charges were dependent upon the powder under investigation, as well as the construction and deaggregation mechanism of the inhaler. The specific charge on the fine particle dose of budesonide from Turbohaler corresponded to approximately 200 electronic charges per particle, a value which is known to affect both total and regional aerosol deposition in the human lung. Electrostatic charge effects may be important determinants of aerosol behavior and should not be neglected.     

Testicular extramedullary myeloid cell tumor in a patient with myelodysplastic syndrome

We report herein a case of extramedullary myeloid tumor arising bilaterally in the testes of a 66-year-old man, who had previously been diagnosed with myelodysplastic syndrome. Light microscopy of the testicular neoplasm demonstrated a tumor composed of large, slightly polygonal cells with pale blue to weakly eosinophilic cytoplasm. The tumor cells were immunoreactive for CD45, myeloperoxidase, lysozyme, CD43, and MB2. Many of the cells also expressed chloroacetate esterase. Peripheral blood and bone marrow findings were consistent with chronic myelomonocytic leukemia (FAB-CMML), particularly in the most recent material, which showed clear cellular dysplasia and an increase in the percentage of blasts in the bone marrow (15% to 20% of all nucleated cells). This case of extramedullary myeloid tumor is unusual in view of the patient's age and the testicular location. It emphasizes the importance of including extramedullary myeloid tumor in the differential diagnosis of histologically undifferentiated large-cell tumors, as well as a need to use a broad panel of immunohistochemical stains in such cases.     

Safety and long-term durability of completion gastrectomy in 81 patients with postsurgical gastroparesis syndrome

Postsurgical gastroparesis syndrome (PGS) is characterized by postcibal nausea and vomiting and is associated with functional gastric dysmotility. Patients frequently present with marked weight loss and malnutrition requiring hospitalization and prolonged parenteral nutrition. Typically, these patients fail to respond to prokinetic agents. Gastric reoperations are frequent and usually unsuccessful. Near-completion gastrectomy (NCG) has proved useful in small series of patients, but long-term follow-up has been lacking. The purpose of this study is to assess the safety and durability of NCG in a large group of patients with PGS. Eighty-one patients with documented PGS who failed to respond to prokinetic drug therapy were treated with NCG over an 11-year period. NCG was standardized with a 55-cm Roux-en-Y reconstruction. Patients were evaluated by a retrospective chart review and a prospective phone interview that compared pre- and postoperative health status based on a standardized severity of symptoms score. There were no operative deaths or complications related to the anastomosis. Average patient follow-up was 56.1 months (range, 2-142 months). Fifteen patients died of unrelated causes, and 14 patients were lost to follow-up. The remaining 52 patients showed a significant overall decrease in severity of symptoms score largely due to reduction in gastrointestinal symptoms and to a smaller but significant reduction in systemic symptoms. Nearly 80 per cent of patients reported long-term relief of symptoms. NCG is the procedure of choice for carefully selected patients with documented. Low morbidity and durable results can be anticipated in the majority of patients.     

The effects of long-term prone positioning in patients with trauma-induced adult respiratory distress syndrome

Prone positioning improves gas exchange in some patients with adult respiratory distress syndrome (ARDS), but the effects of repeated, long-term prone positioning (20 h duration) have never been evaluated systemically. We therefore investigated 20 patients with ARDS after multiple trauma (Injury Severity Score [ISS] 27.3 +/- 10, ARDS score 2.84 +/- 0.42). Patients who fulfilled the entry criteria (bilateral diffuse infiltrates, severe hypoxemia, pulmonary artery occlusion pressure [PAOP] < 18 mm Hg, and PaO2/fraction of inspired oxygen [FIO2] < 200 mm Hg at inverse ratio ventilation with positive end-expiratory pressure [PEEP] > 8 mm Hg for more than 24 h) were turned to the prone position at noon and were turned back to the supine position at 8:00 AM on the next day. Thus only two turns per day were necessary, and the risk of disconnecting airways or medical lines was minimized. Prone positioning was repeated for another 20 h if the patients fulfilled the entry criteria. Except for FIO2, the ventilator settings remained unchanged during the study period. All patients were sedated and, if needed paralyzed to minimize patient discomfort. One hour before and after each position change, ventilator settings and pulmonary and systemic hemodynamics were recorded and blood was obtained for blood gas analysis. Derived cardiopulmonary and ventilatory variables were calculated using standard formulas. Overall mortality was 10%. Oxygenation variables improved significantly each time the patients were placed prone. Immediately after the first turn from the supine to the prone position the following changes were observed: PaO2 increased from 97 +/- 4 to 152 +/- 15 mm Hg, intrapulmonary shunt (Qva/Qt) decreased from 30.3 +/- 2.3 to 25.5 +/- 1.8, and the alveolar-arterial oxygen difference decreased from 424 +/- 24 to 339 +/- 25 mm Hg. All these changes were statistically significant. Most of these improvements were lost when the patients were turned supine, but could be reproduced when prone positioning was repeated after a short period (4 h) in the supine position. Short periods in the supine position were necessary to allow for nursing care, medical evaluation, and interventions such as placement of central lines. No position-dependent changes of systemic hemodynamic variables were observed. We conclude that, in trauma patients with ARDS undergoing long-term positioning treatment, lung function improves significantly during prone position compared to short phases of conventional supine position during which the beneficial effects are partly lost.     

Paroxysmal nocturnal haemoglobinuria clones in patients with myelodysplastic syndromes

Among acquired stem cell disorders, pathological links between myelodysplastic syndromes (MDS) and aplastic anaemia (AA), and paroxysmal nocturnal haemoglobinuria (PNH) and AA, have been often described, whereas the relationship between MDS and PNH is still unclear. We analysed blood cells of patients with MDS to determine the incidence of the PNH clone, and analysed the PIG-A gene to find mutations characteristic of the PNH clone in MDS. In four (10%) of 40 patients with MDS, flow cytometry showed affected erythrocytes and granulocytes negative for decay-accelerating factor (DAF) and CD59. The population of affected erythrocytes was smaller in MDS patients with PNH clone (MDS/PNH) than in patients with de novo PNH, and haemolysis was milder in the MDS/PNH patients. PIG-A mutations were found in granulocytes of all patients with MDS/PNH. In type and site, the PIG-A mutations were heterogeneous, similar to that observed in de novo PNH; i.e. no mutation specific to MDS/PNH was identified. Of note, three of four patients with MDS/PNH each had two PNH clones with different PIG-A mutations, suggesting that PIG-A is mutable in patients with MDS/PNH. In a MDS/PNH patient with trisomy 8, FISH detected a distinct karyotype in a portion of granulocytes with PNH phenotype, indicating that PNH and MDS partly shared affected cells. Thus, MDS predisposes to PNH by creating conditions favourable to the genesis of PNH clone. Considering the increasing prevalence and incidence of MDS, these disorders could be useful for investigating the mechanism by which PIG-A mutation is induced.     

HAG预激化疗作为诱导缓解方案治疗老年人急性髓系白血病和骨髓增生异常综合征的临床观察

目的 观察HAG预激化疗作为诱导缓解方案在治疗老年急性髓系白血病(AML)和骨髓增生异常综合征-难治性贫血伴原始细胞增多型(MDS-RAEB)患者中的疗效.方法 对应用HAG预激方案治疗的21例AML和9例MDS-RAEB患者(≥60岁)的临床资料进行回顾性总结,包括疾病完全缓解(CR)率、有效率以及不良反应.结果 21例老年AML患者中,HAG诱导缓解的有效率为66.7%(14/21),其中CR率为47.6%(10/21);9例老年MDS-RAEB患者中,CR率为55.6%(5/9):HAG预激化疗的主要不良反应为因骨髓抑制继发的感染,调整化疗方案后所有患者均能耐受.结论 HAG预激化疗作为诱导缓解方案适用于老年AML和MDS-RAEB患者.     

Cytogenetic abnormalities in primary myelodysplastic syndrome are highly predictive of outcome after allogeneic bone marrow transplantation

Allogeneic bone marrow transplantation (BMT) is the only curative therapy available for patients with myelodysplastic syndrome (MDS). In an attempt to identify prognostic factors influencing outcome, we collected data retrospectively on 60 consecutive adult patients who had undergone BMT at our center for primary MDS or acute myelogenous leukemia evolving from preexisting primary MDS (sAML). Patients were divided into subgroups according to cytogenetic abnormalities based on a recently described International MDS Workshop categorization system. The 7-year actuarial event-free survival (EFS), relapse rate, and nonrelapse mortality (NRM) for all patients were 29% (95% confidence interval [CI], 16% to 43%), 42% (CI, 24% to 67%), and 50% (CI, 37% to 64%), respectively. The EFS for the good-, intermediate-, and poor-risk cytogenetic subgroups were 51% (CI, 30% to 69%), 40% (CI, 16% to 63%), and 6% (CI, 0% to 24%), respectively (P = .003). The corresponding actuarial relapse rates were 19% (CI, 6% to 49%), 12% (CI, 2% to 61%), and 82% (CI, 48% to 99%), respectively (P = . 002) with no difference in NRM between the subgroups. Univariate analysis showed cytogenetic category, French-American-British (FAB) subtype, and graft-versus-host disease (GVHD) prophylaxis used to be predictive of relapse and EFS. In multivariate analysis, only the cytogenetic category was predictive of EFS, with the relative risk of treatment failure for the good-, intermediate-, and poor-risk cytogenetic subgroups being 1.0, 1.5, and 3.5, respectively (P = . 004). For adults with primary MDS and sAML, even after BMT, poor-risk cytogenetics are predictive of an unfavorable outcome; novel treatment strategies will be required to improve results with allogeneic BMT in this patient population.