Leukemoid reactions complicating colitis due to Clostridium difficile

BACKGROUND: We sought to describe the characteristics of patients who had Clostridium difficile colitis complicated by leukemoid reactions (total leukocyte count greater than 35 x 10(9)/L) and to determine whether this complication is associated with higher morbidity or mortality than C difficile colitis without leukemoid reactions. METHODS: We performed a retrospective case series analysis of patients with a positive fecal assay for C difficile toxin and a peak leukocyte count greater than 35 x 10(9)/L during 1998 and 1999. Twenty cases that met these criteria were compared with 65 randomly selected control patients (patients with a positive C difficile toxin and a peak leukocyte count less than 35 x 10(9)/L). Results: The mean peak leukocyte count was 52 +/- 18.2 x 10(9)/L (+/- SD) in the case group and 14.9 +/- 6.5 x 10(9)/L in the control group. Patients with a leukemoid reaction had a lower temperature, a lower serum albumin level, and a higher hematocrit value. Multivariable logistic regression showed respiratory tract infection and lower temperature to be independent predictors of a leukemoid reaction. There were 10 deaths (50%) in the leukemoid reaction group and 5 deaths (7.7%) in the control group. All seven patients with a peak leukocyte count greater than 50 x 10(9)/L died, compared with eight deaths (10.3%) among the remaining 78 patients whose peak leukocyte count was less than 50 X 10(9)/L. CONCLUSION: Patients with C difficile colitis and a leukocyte count greater than 35 x 10(9)/L have a poor prognosis with a much higher mortality rate than patients who have C difficile colitis without a leukemoid reaction.     

Agranulocytosis associated with initiation of famotidine therapy

OBJECTIVE: To report a case of agranulocytosis associated with initiation of famotidine. CASE SUMMARY: An 87-year-old white man was admitted to the internal medicine department of an acute care hospital because of fever and agranulocytosis (granulocyte count 0). Eight days prior to admission, famotidine therapy had been initiated. Famotidine was discontinued and granulocyte-macrophage colony stimulating factor was administered, with concomitant recovery of the granulocyte count and subsequent development of a leukemoid reaction. DISCUSSION: According to the Naranjo probability scale, famotidine was the probable cause of agranulocytosis. This is a rare adverse effect of this medication; only a few other cases have been reported. CONCLUSIONS: Although agranulocytosis is a rare adverse effect of famotidine, the pharmacist and physician should be aware of this potentially fatal event. If any patient treated with famotidine develops fever, the clinician should consider, among other things, performing a white blood cell count.     

Serum eosinophil cationic protein in active and quiescent ulcerative colitis.

Inflammatory bowel disorders are characterized by an accumulation of eosinophilic granulocytes, mast cells, lymphocytes and neutrophilic granulocytes in the intestinal mucosa. The aim of this study was to examine the concentration of eosinophilic granulocytes in the blood of patients during active ulcerative colitis in comparison with patients during remission and apparently healthy control subjects. Besides counting, the activity grade of eosinophilic granulocytes has been studied by estimation of their degranulation product eosinophil cationic protein. Subjects with active ulcerative colitis could be distinguished from patients with quiescent ulcerative colitis by establishment of the eosinophil cationic protein concentration, neutrophilic granulocyte count, erythrocyte sedimentation rate, C-reactive protein and albumin concentration. After two weeks of corticosteroid treatment, serum eosinophil cationic protein concentrations and eosinophil counts in blood were significantly decreased. A decrease in blood eosinophil count was accompanied by a decrease in eosinophil cationic protein concentrations in serum in most subjects with ulcerative colitis. After twelve weeks of corticosteroid administration, serum albumin concentrations were significantly increased, whereas serum concentrations of C-reactive protein were significantly decreased. During treatment with corticosteroids, serum eosinophil cationic protein concentrations and blood eosinophil counts are appropriate laboratory markers to detect the effect of medication in the course of ulcerative colitis.     

Hematological masks of malignant neoplasms of the internal organs

Hematological "masks" of malignant tumors of the internal organs are not infrequent in clinical practice. A total of 45 patients with malignant tumors of the internal organs (stomach-12, colon-9, liver-3, lungs-9, kidneys-6, pancreas-2, thyroid-2, bladder-1, prostate-1) were under observation. Hematological signs of bone marrow metastatic involvement were as follows: anemia (mainly hypochromic), leukemoid neutrophilic reaction, leukemoid reaction of myeloid type, erythrocytosis, thrombocytosis, plasmocyte bone marrow reaction. Early cancer diagnosis, especially in obscure peripheral blood changes, requires a complete all-round investigation of a patient including an analysis of clinico-anamnestic data, the use of radiographic and endoscopic methods, sternal puncture and trephine biopsy.     

恶性肿瘤类白血病反应的中毒性中性粒细胞的MAXM血液分析仪分析

目的探讨恶性肿瘤伴类白血病反应患者的中毒中性粒细胞是否被MAXM血细胞分析仪误认为嗜碱性粒细胞。方法MAXM血细胞分析仪进行白细胞计数和分类;瑞氏染色镜检白细胞分类;过氧化物酶染色区分中性粒细胞和嗜碱性粒细胞;碱性磷酸酶染色区分类白血病反应。结果26例恶性肿瘤患者用MAXM血细胞分析仪进行白细胞计数为:(28.6±5.7)×109/L;分类为:中性粒细胞49.9%±10.6%,淋巴细胞15.2%±4.3%,单核细胞2.2%±1.2%,嗜酸性粒细胞0.4%±0.3%,嗜碱性粒细胞32.3%±10.2%。镜检分类为:中性粒细胞85.6%±11.8%,淋巴细胞12.9%±5.1%,单核细胞1.5%±1.4%,嗜酸性粒细胞0%,嗜碱性粒细胞0%,其中中毒中性粒细胞为36.5%±7.6%。过氧化物酶染色阳性率为:89.6%±12.3%。中性粒细胞碱性磷酸酶阳性率为83.1%±12.5%,积分395±63。结论MAXM血细胞分析仪把类白血病中毒中性粒细胞误认为嗜碱性粒细胞。     

Leukemoid reaction due to Clostridium dificile infection in acquired immunodeficiency syndrome: two case reports and a review of the literature

The clinical presentation of colitis associated with Clostridium difficile infection in immunosuppressed patients with acquired immunodeficiency syndrome (AIDS) has not been completely characterized. Previous reports suggest that these patients present with low blood leukocyte counts, consistent with the impaired myelopoiesis that can occur with human immunodeficiency virus (HIV) infection. In contrast, we describe the cases of two patients with colitis associated with C difficile infection who developed intense leukemoid reactions despite being in advanced stages of AIDS. To the best of our knowledge, these are the first described cases of leukemoid reaction associated with C difficile or other bacterial infection in AIDS patients. We review the literature on C difficile colitis in patients infected with HIV and suggest that severe C difficile infection should be considered in such patients presenting with leukemoid reaction and diarrhea.     

436例关节液检查白细胞分类结果分析及临床意义

目的关节液中白细胞分类结果检查可协助临床诊断、治疗骨关节病。方法将关节液离心、沉淀、涂片、染色,油镜下作白细胞分类计数。结果化脓性关节炎中性粒细胞值为72%-97%;类风湿性关节炎中性粒细胞值为20%~81%;痛风性关节炎中性粒细胞为55%-82%;结核性关节炎中性粒细胞为20%-71%;骨性关节炎中性粒细胞为19%-50%;强直性脊柱炎中性粒细胞为13%-18%;假痛风中性粒细胞为25%-55%;创伤性骨关节病中性粒细胞为35%-45%;骨关节肿瘤中性粒细胞为20%-30%;其他病因不明的骨关节病中性粒细胞为11%-63%之间,淋巴细胞为20%-69%。结论关节液的中性粒细胞分类是区分炎性或非炎性关节液的重要指标,化脓性关节炎中性粒细胞分类很高,在72%-97%之间,最高可达到97%以上,平均为93%。当中性粒细胞分类介于50%-72%时,一般来说是非化脓性的炎性感染。     

The migration capability of neutrophilic granulocytes in disseminated tuberculosis and sarcoidosis of the lungs]

A method for estimation of neutrophilic granulocyte spontaneous migration in capillaries is suggested. Twenty-one patients with disseminated pulmonary tuberculosis, 19 ones with active pulmonary sarcoidosis, and 30 normal subjects were examined. The findings evidence a higher migration activity of neutrophilic granulocytes in the patients, 66.4 +/- 8.5 in tuberculosis and 65.1 +/- 7.7 in sarcoidosis as against that in health (32.4 +/- 4.0). Tuberculin was found to stimulate cell migration in tuberculosis patient; the migration index made up 1.3 +/- 0.07 in this case. This agent had no apparent effect on the phagocytes of sarcoidosis patients and normal subjects, and their migration index did not exceed 1.0. Neutrophilic granulocyte reaction to tuberculin may be used in the differential diagnosis between pulmonary tuberculosis and sarcoidosis.     

Correlation between blood granulocyte progenitor cells and polymorphonuclear leukocytes. A tentative pathophysiological subgrouping of neutropenic and neutrophilic patients

Blood granulocyte-macrophage progenitors (CFU-GM) were studied in 116 normal, 32 neutropenic and 22 neutrophilic subjects through a double layer agar culture system. The neutropenic group showed significantly lower than normal mean value of CFU-GM per ml of blood, the blood concentration of CFU-GM being within normal limits in 25/32 subjects (78.1%). The neutrophilic group showed significantly higher than normal mean value of blood CFU-GM, and a normal blood concentration of CFU-GM was found in 17/22 patients (77.3%). Within the neutropenic group the concentration of blood CFU-GM was lower than normal in 5/11 (45.4%) patients with less than 1.1 x 10(9) polymorphonuclear leukocytes (PMN) and only in 2/21 (9.5%) patients with more than 1.1 x 10(9)/1 PMN. Within the neutrophilic group the concentration of blood CFU-GM was normal in all 12 subjects having less than 10.5 x 10(9)/1 PMN, while 5/10 (50%) patients with more than 10.5 x 10(9)/1 PMN had higher than normal blood concentration of CFU-GM. The mean leukocyte CSA of the normal, neutropenic and neutrophilic groups did not differ significantly. Within the neutropenic group the CSA was lower than normal in 3/11 (27%) patients with less than 1.1 x 10(9)/1 PMN and in 2/20 (10%) patients with more than 1.1 x 10(9)/1 PMN. Within the neutrophilic group the CSA was normal in all patients with less than 10.5 x 10(9)/1 PMN and it was higher than normal in 2/10 (20%) patients with more than 10.5 x 10(9)/1 PMN. A pathophysiological approach to both neutropenia and neutrophilia, according to PMN and CFU-GM blood concentration, is discussed.     

成人脓毒症患者骨髓细胞学特征的研究

目的探讨脓毒症患者骨髓细胞学特征及其临床意义。 方法回顾性分析2015年1月至2020年10月在中山大学孙逸仙纪念医院重症医学科和全科医学科住院,诊断为脓毒症并行骨髓细胞学检查的57例患者的骨髓象特征,分析其与外周血血象、感染指标、临床转归和预后的相关性。 结果脓毒症患者外周血血象表现多样,白细胞计数从极度降低到明显升高不等,多表现为中度贫血、血小板减少、淋巴细胞减少;骨髓象以有核细胞增生活跃或明显活跃为主,占82.5%（47/57）,少数患者增生减低;粒红比例升高,多表现为中性杆状粒比例下降,中性分叶粒比例升高,伴部分中性粒胞浆颗粒增粗、增多或可见空泡,部分可见过分叶现象;部分伴有网状吞噬细胞增多,可见噬血现象;多数外周血涂片中性粒细胞碱性磷酸酶（NAP）染色阳性率和积分升高。脓毒症患者骨髓粒系增生情况与外周血粒细胞计数、骨髓巨核细胞计数与外周血血小板计数均存在正相关（r = 0.324、0.574,P均< 0.05）;大肠杆菌感染与脓毒症患者的骨髓增生情况密切相关（χ² = 13.434,P < 0.001）。 结论脓毒症患者多为感染较重阶段,感染发展至脓毒症,骨髓功能在一定程度上呈耗竭状态,部分增生明显低下,其与外周血象、感染具有一定相关性。脓毒症患者血小板减少与骨髓巨核细胞功能直接相关,脓毒症骨髓巨核细胞减少或成熟障碍为脓毒症血小板减少症发病机制之一。此外,大肠杆菌感染的脓毒症患者多表现为骨髓增生减低。     

High mortality among patients with the leukemoid reaction and alcoholic hepatitis

We describe a patient with severe alcoholic hepatitis, markedly elevated white blood cell count, and high fever. After review of the English literature, we discovered reports of other cases similar to our case. The striking feature in all of these cases was a high short-term mortality rate, despite predictions of a favorable outcome. We therefore believe these patients represent a subgroup of patients with alcoholic hepatitis and that the leukemoid reaction is a poor prognostic sign in this disease.     

Leukemoid reaction associated with severe diabetic ketoacidosis

A 30-year-old man had severe diabetic ketoacidosis and a leukemoid reaction, which promptly resolved after therapy with intravenous fluids and insulin. There was no evidence of an underlying malignancy or infection. Although a mild leukocytosis may accompany DKA, a leukemoid reaction has not been previously reported to occur with uncomplicated diabetic ketoacidosis.     

Endothelial cells suppress granulocyte clusters and stimulate large granulocyte colonies in culture

Endothelial cells have been shown to produce granulopoietic colony stimulating activity (CSA) under the regulatory control of a humoral factor, MRA produced by blood monocytes. An endothelial cell-derived granulopoietic inhibitory factor has also been described. To further define these apparently paradoxical observations, human bone marrow mononuclear cells were co-cultured with umbilical cord derived endothelial cells in a plasma clot system in vitro. To enhance the sensitivity of the assay for growth effects attributable to the endothelial cells (or their products) alone, an exogenous source of CSA (e.g. a peripheral blood leukocyte feeder layer) was not used. On day ten of culture, less than or equal to 1% endothelial cells markedly stimulated the growth of early granulocyte progenitors (large diaminofluorine positive (DAF+) GM-CFUc) (p less than .01) and a linear dose response relationship was confirmed (p less than .001). Late granulocyte progenitors (DAF+ clusters) were coincidently suppressed by less than or equal to 2% endothelial cells (p less than .01). No effect of endothelial cells on intermediate progenitors (small GM-CFUc) was demonstrated at any concentration. Similar effects were observed with the addition of 5% to 30% endothelial conditioned medium (ECM) (p less than .01). When cohort cultures were evaluated serially, suppression of clusters was observed by day four and stimulation of large GM-CFUcs by day six. These varied effects on different stages of granulocyte differentiation suggest that endothelial cell derived CSA(S) may be of biological relevance in the regulation of granulopoiesis.     

自动血细胞形态预分类系统的性能验证方法的探索

目的：按ICSH 2014年版血细胞分析仪评价指南,对Celldiff BCM-2自动血细胞形态分析系统的白细胞分类计数进行验证及临床应用评估。方法 Celldiff分析仪对401例需显微镜复检的住院患者血涂片、101例健康体检者血涂片进行白细胞分类。（1）通过对Celldiff预分类结果与人工纠正后结果符合性分析。（2）人工纠正后结果与人工镜检结果相关性分析。结果住院患者标本,绝对偏差从低到高分别为中性中幼粒细胞（3．3％）、中性分叶核粒细胞（11．8％）,单核细胞（20．5％）、嗜酸性粒细胞（28．4％）、中性杆状核粒细胞（31．6％）、淋巴细胞（42．0％）、中性晚幼粒细胞（68．0％）、嗜碱性粒细胞（77．1％）、异型淋巴细胞（100．0％）、幼稚淋巴细胞（100．0％）、原始细胞（236．5％）、涂抹细胞（306．7％）、早幼粒细胞（413．3％）和有核红细胞（1321．2％）。健康体检者标本,绝对偏差从低到高分别为单核细胞（0．4％）、中性分叶核粒细胞（2．1％）、中性杆状核粒细胞（14．1％）、淋巴细胞（15．5％）、嗜酸性粒细胞（21．8％）、嗜碱性粒细胞（69．2％）和涂抹细胞（728．6％）。镜检分类与人工纠正后的相关性除了嗜碱性粒细胞的线性有明显偏差（P＜0．01）,其余中性杆状核粒细胞、中性分叶核粒细胞、淋巴细胞、单核细胞、嗜酸性粒细胞及幼稚粒细胞的线性均无明显偏差。结论 Celldiff虽然预分类的结果不是非常理想,但经过人工审核后同人工镜检结果的相关性较好还是具有较好的临床应用以及教学的价值,再结合全自动外周血制片机利于实现白细胞分类的自动化与标准化。     

436例关节液检查白细胞分类结果分析及临床意义

目的关节液中白细胞分类结果检查可协助临床诊断、治疗骨关节病。方法将关节液离心、沉淀、涂片、染色,油镜下作白细胞分类计数。结果化脓性关节炎中性粒细胞值为72%~97%;类风湿性关节炎中性粒细胞值为20%~81%;痛风性关节炎中性粒细胞为55%~82%;结核性关节炎中性粒细胞为20%~71%;骨性关节炎中性粒细胞为19%~50%;强直性脊柱炎中性粒细胞为13%~18%;假痛风中性粒细胞为25%~55%;创伤性骨关节病中性粒细胞为35%~45%;骨关节肿瘤中性粒细胞为20%~30%;其他病因不明的骨关节病中性粒细胞为11%~63%之间,淋巴细胞为20%~69%。结论关节液的中性粒细胞分类是区分炎性或非炎性关节液的重要指标,化脓性关节炎中性粒细胞分类很高,在72%~97%之间,最高可达到97%以上,平均为93%。当中性粒细胞分类介于50%~72%时,一般来说是非化脓性的炎性感染。     

The effect of pentamidine salts on the in-vitro responses of neutrophilic granulocytes

Therapeutic concentrations (0.3-1.5 mg/l) of pentamidine isethionate and pentamidine mesylate, obtained after parenteral administration of the drugs, did not influence neutrophilic granulocyte adherence, random and chemotactic migration or phagocytosis of Candida albicans spores in vitro. At concentrations of 0.7, 1.1 and 1.5 mg/l, the ability of neutrophilic granulocytes to kill C. albicans spores was depressed (P less than 0.001); at all concentrations used, their ability to reduce nitroblue tetrazolium was decreased (P less than 0.001). There was no significant difference between the drugs with regard to these impairments in neutrophilic granulocyte function. It is likely that pentamidine salts inhibit superoxide radical formation in the stimulated neutrophilic granulocyte and that this dysfunction leads to depressed intracellular killing of C. albicans spores.     

Quantification of deposition of neutrophilic granulocytes on vascular grafts in dogs with 111In-labeled granulocytes

A new radioisotopic technique has been developed for quantification of deposition of neutrophilic granulocytes on vascular grafts. Nine healthy mongrel dogs underwent bilateral femoral artery resection and reconstruction with grafts of femoral vein and Gore-Tex. Pure granulocytes that had been separated from whole blood by centrifugal elutriation were labeled with 111In-tropolone in plasma. The granulocyte harvesting efficiency was 25 +/- 12%, and the labeling efficiency was 87 +/- 7%. Three hours after injection of labeled granulocytes and 2 hours after reperfusion, the grafts were harvested and cut into several segments for study of areas of anastomoses and midsections. On the basis of the radioactivity in the blood and in anastomotic and graft sections, the area of graft sections, and the neutrophilic granulocyte and differential leukocyte counts, the number of neutrophilic granulocytes adherent to a unit area and the total number of neutrophilic granulocytes on graft sections were calculated. These quantifications of the deposition of neutrophilic granulocytes indicated that the midsections of Gore-Tex grafts retained more neutrophilic granulocytes than did the midsections of vein grafts. Although the anastomotic areas retained more neutrophilic granulocytes than did the midsections of vein grafts, the opposite finding prevailed for the Gore-Tex grafts. A major fraction of neutrophilic granulocytes on Gore-Tex grafts was incorporated into thrombus. Semiquantitative information obtained by scintigraphy of the deposition of neutrophilic granulocytes on vascular grafts also confirmed this observation.     

采用多功能流式细胞术分析分选造血干细胞和髓系定向分化祖细胞

目的 探讨富集纯化造血干细胞(HSC)和髓系定向分化祖细胞的新实验方案.方法 根据造血干细胞和定向分化祖细胞在发育过程中表达某些特异性分化抗原的特性,通过免疫磁珠分选技术结合四色和六色流式细胞术分析14只健康小鼠的骨髓造血干细胞、造血祖细胞及定向分化祖细胞系列的表达,并对其进行分选,以进一步通过集落细胞培养和传代试验对分选后细胞的活性进行检测.结果 经上述实验方案分析,14只健康小鼠骨髓造血祖细胞(HPC)的表达率约为HSC的10倍;但其牛成活性远不如造血干细胞,共同髓系祖细胞(CMP)的传代能力仅为HSC的1/2,且次级分化的粒系单核系祖细胞(GMP)和红系巨核系祖细胞(MEP)的生成活性更弱,其传代次数为零.结论 通过多色流式细胞术实验方案可以分析纯化HSC和髓系定向分化祖细胞的表达,并精确计数HSC和祖细胞.     

Abnormal responses of myeloid progenitor cells to granulocyte-macrophage colony-stimulating factor in human cyclic neutropenia.

Granulocyte-macrophage progenitors (CFU-GM) from four patients with childhood onset cyclic neutropenia demonstrated abnormal in vitro proliferative responses to purified, recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) when examined in detailed dose-response studies. Marrow aspirate specimens were obtained for these studies from cyclic neutropenia patients (both during neutropenic nadirs and during recovery phases of cycles), from leukemia patients in remission who had received myelosuppressive chemotherapy, and from healthy normal volunteers. Nucleated marrow cells were then isolated by density-gradient centrifugation and cryopreserved to permit studies of CFU-GM from patients and controls to be carried out at the same time and in replicate. Maximum clonal growth of CFU-GM from normal subjects and from individuals recovering from drug-induced myelosuppression was elicited by 20-100 pmol/liter rhGM-CSF, and the CSF concentrations that induced half-maximal responses (ED50) were between 1.0 and 3.0 pmol/liter. In contrast, maximum growth of CFU-GM from the cyclic neutropenia patients required greater than or equal to 1.0 nmol/liter rhGM-CSF and ED50's were greater than 30.0 pmol/liter. These abnormalities in the GM-CSF responsive growth of myeloid progenitors were independent of cycle time and were most apparent with the predominantly neutrophilic 7-d CFU-GM. Moreover, differences in the growth of 14-d CFU-GM could be attributed mostly if not entirely to differences in the generation of neutrophilic colonies. These findings indicate that childhood onset cyclic neutropenia is associated with an underlying disturbance in the GM-CSF responsive growth of myeloid progenitors committed to neutrophilic differentiation.     

β地中海贫血伴髓外造血组织瘤样增生的探讨

为了研究β地中海贫血伴髓外造血组织瘤样增生细胞形态特点其及诊断，对纵隔髓外造血组织瘤样增生用细针抽吸活组织行细胞学检测（FNAC），并与骨髓片进行比较分析。结果表明：纵隔肿块的细针抽吸活组织的细胞学涂片显示粒系细胞中可见中性中幼粒细胞、中性晚幼粒细胞、中性杆状粒细胞、中性分叶核粒细胞；红系细胞中可见早幼红细胞、中幼红细胞、晚幼红细胞；并可见颗粒巨核细胞、产血小板的巨核细胞、散在血小板及成熟淋巴细胞；细胞形态及各期细胞分布与骨髓片相似，为髓外造血组织。结论：β地中海贫血伴髓外造血组织瘤样增生为罕见病，细针穿刺活检方法为一种快速、方便、有效诊断该病的方法。