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PubMed1995

Postsurgical gout.

Although catabolic events are known to precipitate gout, postsurgical gout has rarely been reported. We identified the charts of 302 patients treated over a 10-year period in a university center who carried the diagnosis of gout and who also had a surgical procedure. Fifty-two patients (42 male, 10 female) were found to have had a postsurgical episode of gouty arthritis. Ages ranged from 20 to 82 years (mean 60.1 +/- 2.1). Forty-five patients had a history of gout, 22 of whom were receiving medication and 23 who were not receiving chronic therapy. In seven patients the postsurgical event was their first attack. Attacks occurred 1-17 days (mean 4.2 +/- 0.5 [SE]) after surgical admission. Most attacks were in the lower extremity, but classic podagra was uncommon. Essentially all patients were febrile (100.7 +/- 0.2 degrees F) compared with admission (99.0 +/- 0.1 degree) (P < 0.001). There was a trend toward leukocytosis in the group as a whole, but the relationship of leukocytosis to the gout attack was most clearly seen in patients admitted for noninflammatory conditions (9.4 +/- 0.7 versus 12.8 +/- 0.8 x 1000 WBC/mm3, P < 0.001). Uric acid levels were elevated but did not follow the course of the attack. Most patients underwent a variety of tests and consultative evaluations because of their undiagnosed febrile episode. Once the diagnosis was established, all patients responded quickly to nonsteroidal anti-inflammatory drugs or colchicine. Despite evidence of a significant inflammatory response, no patient proved to have a suppurative focus as the source of their febrile episode.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1994

Clozapine-induced transient white blood count disorders.

BACKGROUND: The aim of the study was to shed more light on the incidence and course of clozapine-induced transient white blood count (WBC) disorders. METHOD: In an analysis of our clozapine drug monitoring program, we evaluated the data of 68 patients receiving clozapine for the first time. Incidence rates were calculated by actuarial life table analysis. The potential influence of sex, age, dose, and plasma level was evaluated using discriminant analysis. RESULTS: Two patients developed progressive neutropenia, leading to agranulocytosis in one case. We also found the following transient hematologic dysfunctions: neutropenia (22.0%), eosinophilia (61.7%), and leukocytosis (40.9%). One patient showed chronic leukocytosis. Additionally, minor changes in the number of lymphocytes, monocytes, and basophilic granulocytes were detected in the study population. CONCLUSION: Hematologic side effects are frequently induced by the atypical antipsychotic clozapine. Next to agranulocytosis, a progressive and potentially lethal hematologic adverse effect, most of the WBC disorders are transient and appear to be harmless.

Actuarial Analysis↗
PubMed1994

[The interrelation of serum lysozyme level and cytoplasmic lysozyme level].

By means of the immunocytochemical method, the level of cytoplasmic lysozyme in leukocytes from healthy volunteers (n = 50) and from patients with uremia (n = 50), leukocytosis (n = 50), various forms of leukemia (n = 36) and myelodysplastic syndrome (MDS) (n = 7) were analysed, and compared with that of simultaneously assayed serum lysozyme. Both the cytoplasmic and serum levels of lysozyme in uremia and leukocytosis were significantly higher than normal subjects (p < 0.001). No correlation, however, was found between their cytoplasmic and serum levels of lysozyme. Morphological analysis for various kinds of leukemia and MDS indicated that myelocytic and monocytic cells became highly positive for lysozyme staining with maturation, and that lymphocytes, leukemic myeloblasts and monoblasts were negative. The cytoplasmic and serum lysozyme levels of leukemias or MDS having a number of lysozyme-positive cells were elevated as compared with those of normal individuals. Among them acute myelocytic leukemia (FAB M4) revealed an excellent correlation between the lysozyme levels in cytoplasm and in serum. The rest whose serum lysozyme level tend to be lower than the cytoplasmic one gave poor correlation. Thus, serum lysozyme level is not fully reflected by the cytoplasmic level. The dual determination of cytoplasmic and serum lysozyme is suggested to be helpful on estimating leukemia types, the degree of cellular maturation and total cell mass, and might also provide a valuable tool for prediction of prognosis for these disorders.

Cytoplasm↗
PubMed1993

[Properties of an acellular preparation of Bordetella pertussis and its analysis after centrifugation in saccharose gradient].

Acellular preparations were studied which were obtained by a method of acidic extraction from culture of strain Tohama of Bordetella pertussis. Obtained preparations EM I and EM II were exhibiting property of leukocytosis stimulation and were respectively of following values: 43.5 and 19 u LPF/mg of protein. They also caused hemagglutination (150 and 19 u HA/mg of protein). Both preparations were exhibiting protective effect in intracerebral test performed on mice. After differentiation of EM I preparation by preparative centrifugation in saccharose gradient two fractions were obtained, of which lighter was exhibiting high hemagglutinating activity and leukocytosis stimulation (198 u LPF/mg of protein). Heaver fraction contained mainly endotoxin. Applied method permitted for partial purification of acellular preparation of B. pertussis; mainly decrease in its content of endotoxin responsible for high reactogenicity of pertussis vaccines.

Animals↗
PubMed1993

[Two cases of re-expansion pulmonary edema].

A 62-year-old man and 26-year-old man with re-expansion pulmonary edema (RPE) after thoracic drainage as a treatment for pneumothorax are presented. Blood cell counting and biochemical serum analysis were performed throughout their treatment in both patients, and biochemical sputum analysis was in one patient. The results showed transient marked leukocytosis just after RPE. Total protein and albumin concentrations of sputum approximated to those of serum. The above results suggested that RPE is based on pulmonary microvascular injury, which may introduce leukocytosis.

Adult↗
PubMed1993

Selected white cell disorders.

The emergency physician frequently is confronted with an abnormal white blood cell count when evaluating patients. Leukocytosis may be caused by malignancy, infection, or a variety of other reasons. Leukopenia is an increasingly common finding as the population of immunocompromised patients continues to expand. This article reviews the differential diagnosis of leukocytosis and leukopenia. The management of the neutropenic patient with and without fever is also reviewed and includes currently recommended empiric antibiotic regimens.

Blood Cell Count↗
PubMed1996

Chronic myeloid leukemia of thrombocythemic onset: a CML subtype with distinct hematological and molecular features?

Among 84 consecutive patients with chronic phase Ph-positive chronic myeloid leukemia (CML) who were investigated for the hybrid BCR/ABL mRNA, in six cases (7%) the disease mimicked essential thrombocythemia (ET) at presentation, because of marked thrombocytosis (platelet counts ranging from 1003 x 10(9)/l to 2800 x 10(9)/l) and moderate leukocytosis (WBC counts from 10 x 10(9)/l to 19 x 10(9)/l). At initial examination, four of the six patients showed a few (4-9%) immature myeloid cells in the peripheral blood, and two had blood basophilia. All six patients later developed increasing leukocytosis, and two subsequently died from blast crisis and accelerated CML, respectively. In the overall series, 38 patients (45%) expressed the b2a2 type of BCR/ABL mRNA, and 46 (55%) either the b3a2 or both mRNAs. By contrast, only one of the six patients with CML of thrombocythemic onset expressed the b2a2 mRNA vs five with either b3a2 (n = 4) or both mRNA types (n = 1). The above results, in conjunction with similar data from a few previously published cases, suggest an association between the above form of CML and b3a2 type of BCR/ABL transcript.

Adolescent↗
PubMedDate not supplied

[The risk factors for the development of the multiple organ failure syndrome in destructive pancreatitis].

The role of neutrophil leukocytes in the development of the polyorgan failure syndrome during an unfavorable course of destructive pancreatitis is discussed. The examinations of 52 patients demonstrated a high correlation of neutrophil functional activity tests (nitroblue tetrazolium reduction test and leukocyte-platelet aggregation) and disorders of microcirculation and hepatorenal involvement (detected clinically and by laboratory tests). The "critical mass" of leukocytosis has been estimated: at least 18 . 10(9)/liter, at which the risk of polyorgan failure appreciably increases. The authors discuss the advisability of selective cytopheresis in a complex of intensive care for critical states involving endogenous poisoning and leukocytosis.

Acute Disease↗
PubMed1997

[Effect of patients' gender on the course of chronic myeloid leukemia].

Chronic myeloid leukemia course was evaluated versus sex in 271 patients. Chronic stage involved more pronounced leukocytosis, thrombocytosis and splenomegaly in females, the latter showing higher susceptibility to anemia. As a result, treatment has to deal with a greater mass of tumor. A relatively longer survival time in males (44 and 42 months, respectively) suggest a higher effectiveness of therapy in such patients. When diagnosed, leukocytosis, thrombocytosis, enhanced splenomegaly and anemia should be regarded as factors of unfavorable prognosis.

Adolescent↗
PubMed1998

[Hypercalcemia associated with hyperleukocytosis, a new paraneoplastic syndrome].

BACKGROUND: The association of hypercalcemia and leukocytosis constitutes a novel paraneoplastic syndrome rarely reported in the course of head and neck and lung squamous cell carcinoma. We report 7 new cases. CASE REPORTS: In 5 cases the diagnosis was well-differentiated squamous cell carcinoma, in 1 differentiated non-small-cell carcinoma and in 1 adenocarcinoma of unknown origin. There was no argument favoring hyperparathyroidism in any of the cases. Microbiology tests were negative and large spectrum antibiotics were unsuccessful, eliminating an associated infection as cause of the leukocytosis. DISCUSSION: This association probably involves the secretion of hematopoietic growth factors such as G-CSF or GM-CSF by the tumor, acting simultaneously on osteoclasts and granulomonocytic cells which have common precursers.

Aged↗
PubMed1999

The role of transthoracic echocardiography in the diagnosis of infective endocarditis in children.

BACKGROUND: Infective endocarditis (IE) is frequently suspected but infrequently diagnosed in children. Clinicians often order echocardiograms to "rule out" IE. In an era of cost constraint, clinically efficient strategies must be developed to eliminate unnecessary tests. We hypothesized that transthoracic echocardiography (TTE) is only useful in children in whom there is a high clinical suspicion of IE based on history, physical examination, and persistently positive blood cultures. OBJECTIVE: To determine the role of TTE as a screening test for suspected IE in children. METHODS: Echocardiographic reports and medical records were reviewed retrospectively for 173 consecutive patients who underwent TTE to rule out IE from January 1993 to August 1996. RESULTS: Persistent fever was the predominant symptom leading to a suspicion of IE (120 patients [69.4%]). Fifty-seven (32.9%) of the 173 patients had congenital heart disease and 95 patients (54.9%) had indwelling venous catheters. Twenty-six patients (15.0%) were diagnosed and treated for IE. Twelve (46.2%) of these 26 patients had vegetations seen on TTE. The conditions of the remaining 14 patients were diagnosed clinically and these patients had persistently positive blood cultures. By univariate analysis, the risk factors associated with the diagnosis of IE were malaise, congestive heart failure, new or changing heart murmur, leukocytosis, hematuria, and the presence of 2 or more positive blood cultures for the same organism. The risk factors associated with positive TTE were malaise, congestive heart failure, new or changing heart murmur, leukocytosis, hematuria, and 2 or more positive blood cultures. The presence of an indwelling catheter or immunocompromised status were not predictive of vegetation or IE. CONCLUSIONS: Transthoracic echocardiography has poor sensitivity as a screening test for IE in patients with low clinical probability of the disease. A diagnostic algorithm for IE is suggested based on these data.

Adolescent↗
PubMed2001

Computed tomography and ultrasonography do not improve and may delay the diagnosis and treatment of acute appendicitis.

HYPOTHESIS: Computed tomography (CT) and ultrasonography (US) do not improve the overall diagnostic accuracy for acute appendicitis. DESIGN: Retrospective review. SETTING: University tertiary care center. PATIENTS: Seven hundred sixty-six consecutive patients undergoing appendectomy for suspected appendicitis from January 1, 1995, to December 31, 1999. MAIN OUTCOME MEASURES: Epidemiology of acute appendicitis and the roles of clinical assessment, CT, US, and laparoscopy. RESULTS: The negative appendectomy rate was 15.7%, and the incidence of perforated appendicitis was 14.6%. A history of migratory pain had the highest positive predictive value (91%), followed by leukocytosis greater than 12 x 10(9)/L (90.1%), CT (83.8%), and US (81.3%). The false-negative rates were 60% for CT and 76.1% for US. Emergency department evaluation took a mean +/- SD of 5.2 +/- 5.4 hours and was prolonged by US or CT (6.4 +/- 7.4 h and 7.8 +/- 10.8 h, respectively). The duration of emergency department evaluation did not affect the perforation rate, but patients with postoperative complications had longer evaluations (mean +/- SD, 8.0 +/- 12.7 h) than did those without (4.8 +/- 3.3 h) (P =.04). Morbidity was 9.1%, 6.4% for nonperforated cases and 19.8% for perforated cases. Seventy-six patients had laparoscopic appendectomy, with a negative appendectomy rate of 42.1%, compared with 15.4% for open appendectomy (P<.001). Laparoscopy, however, had minimal morbidity (1.3%) and correctly identified the abnormality in 91.6% of patients who had a normal-appearing appendix. CONCLUSIONS: Migratory pain, physical examination, and initial leukocytosis remain reliable and accurate in diagnosing acute appendicitis. Neither CT nor US improves the diagnostic accuracy or the negative appendectomy rate; in fact, they may delay surgical consultation and appendectomy. In atypical cases, one should consider the selective use of diagnostic laparoscopy instead.

Acute Disease↗
PubMed2005

Every case of essential thrombocythemia should be tested for the Philadelphia chromosome.

Essential thrombocythemia (ET) and chronic myelogenous leukemia (CML) usually present with distinctive features. Citing experience with cases that overlap, the Polycythemia Vera Study Group recommends that negative tests for the Philadelphia chromosome be obtained before diagnosing ET. We describe two young women presenting with features absolutely typical for ET, including extreme thrombocytosis, no leukocytosis, no basophilia, no peripheral immature cells, and no splenomegaly. Severe thrombotic complications ensued: multiple cerebrovascular thromboemboli, pulmonary emboli, and miscarriage in one and myocardial infarction in the other. By 4 years, both developed leukocytosis, extreme basophilia, and circulating blasts, typical of accelerated CML. Cytogenetic studies were then performed, revealing the Philadelphia chromosome. Imatinib produced rapid clearing of blasts and basophils, but one woman later succumbed after allogeneic bone marrow transplant and the other has not achieved a major cytogenetic response. We conclude that CML can present in identical fashion as ET. The mandate for routine Philadelphia chromosome testing is magnified by the availability of targeted therapy and its greater efficacy in early stage disease.

Adult↗
PubMed2005

Primary plasma cell leukemia: report of 17 new cases treated with autologous or allogeneic stem-cell transplantation and review of the literature.

Primary plasma cell leukemia (PPCL) is a rare hematologic malignancy characterized by the proliferation of plasma cells in blood, bone marrow, and other organs in the absence of established multiple myeloma. PPCL has a poor prognosis when treated with conventional therapy for multiple myeloma. We describe here 17 new cases of PPCL who underwent stem-cell transplantation (SCT) (2 cases observed by the authors and 15 cases from the International Bone Marrow Transplant Registry [IBMTR]). The first case was diagnosed in a 21-year-old male who presented with leukocytosis and acute renal failure. He was treated with hyper-CVAD, entered complete remission, and then proceeded to high-dose chemotherapy with peripheral stem-cell support. He is currently in complete remission 23 months after initial diagnosis and 19 months after autologous SCT. The second case was observed in a 31-year-old male who presented with leukocytosis and hepatic infiltration with plasma cells. He was treated with VAD chemotherapy and underwent allogeneic bone marrow transplantation from his HLA-identical sister. He remained in complete remission for 3 years and then developed progressive refractory disease, dying 7 years after the initial diagnosis. In addition to these 2 cases, 15 further unpublished cases of PPCL from the IBMTR are reported here (treated between 1993 and 2001, 6 by autologous and 9 by allogeneic transplantation). Finally, the features of PPCL, the outcome, published data of SCT for PPCL, and indications for treatment are discussed.

Adult↗
PubMed2006

Transcriptosome and serum cytokine profiling of an atypical case of myelodysplastic syndrome with progression to acute myelogenous leukemia.

A Native American-Indian female presenting with anemia and thrombocytosis was diagnosed with myelodysplastic syndrome (MDS, refractory anemia). Over the course of 5 years she developed cytopenias and periods of leukocytosis with normal bone marrow (BM) blast counts, features of an unclassifiable MDS/MPS syndrome. The patient ultimately progressed to acute myelogenous leukemia (AML, FAB M2) and had a normal karyotype throughout her course. The episodes of leukocytosis were associated with infectious complications. Transformation to AML was characterized by a BM blast percentage of 49%. Peripheral blood and BM samples were obtained for serum protein analysis and gene expression profiling (GEP) to elucidate her disease process. An ELISA assay of the serum analyzed approximately 80 cytokines, which demonstrated that hepatocyte growth factor/scatter factor and insulin-like growth factor binding protein 1 were markedly elevated compared to normal. GEP demonstrated a unique "tumor molecular profile," which included overexpression of oncogenes (HOXA9, N-MYC, KOC1), proliferative genes (PAWR, DLG5, AKR1C3), invasion/metastatic genes (FN1, N-CAM-1, ITGB5), pro-angiogenesis genes (c-Kit), and down regulation of tumor suppressor genes (SUI1, BARD1) and anti-apoptotic genes (PGLYRP, SERPINB2, MPO). Hence, a biomics approach has provided insight into elucidating disease mechanisms, molecular prognostic factors, and discovery of novel targets for therapeutic intervention.

Aged↗
PubMed2007

Reversible posterior leukoencephalopathy syndrome after repeat intermediate-dose cytarabine chemotherapy in a patient with acute myeloid leukemia.

A 56-year-old man was admitted to our hospital with leukocytosis, anemia, and thrombocytopenia. Acute monoblastic leukemia was diagnosed. Two subsequent courses of consolidation chemotherapy consisted of conventional doses of cytarabine and intermediate-dose cytarabine. Intermediate-dose cytarabine was infused intravenously every 12 hr for 6 days. On day 15 after the final infusion of cytarabine, the patient suffered headache, and on day 21, he experienced a decrease in sensation on the sole of his left foot. Magnetic resonance imaging (MRI) of the brain revealed widespread areas of white matter edema. Cerebrospinal fluid (CSF) examination revealed an increase in the number of cells to 31 mm(-3); the majority were lymphocytes. No infiltration of leukemia cells was seen. After 2 months, brain MRI findings were normal. The clinicoradiologic features of the case were consistent with reversible posterior leukoencephalopathy syndrome (RPLS). RPLS in the present case was unlikely to have been caused by direct neurotoxicity because (1) the doses of cytarabine (500 mg/m(2); total dose 9.2 g) were much smaller than those in reported cases and were repeatedly infused until RPLS developed; (2) the RPLS developed 21 days after the final infusion of cytarabine, a much longer period than previously reported; (3) the slight leukocytosis in the CSF observed on day 33 might also have been related to the cellular immune responses evoked by the infused cytarabine. These details suggest not only that direct cerebral neurotoxicity of cytarabine but also that some type of allergic response may have been involved in the development of RPLS.

Antimetabolites, Antineoplastic↗
PubMed2004

Analysis of gene expression profiles in human HL-60 cell exposed to cantharidin using cDNA microarray.

Cantharidin is a natural toxin that has antitumor properties and causes leukocytosis as well as increasing sensitivity of tumor cells resistant to other chemotherapeutic agents. There is limited information, however, on the molecular pharmacological mechanisms of cantharidin on human cancer cells. We have used cDNA microarrays to identify gene expression changes in HL-60 promyeloid leukemia cells exposed to cantharidin. Cantharidin-treated cells not only decreased expression of genes coding for proteins involved in DNA replication (e.g., DNA polymerase delta), DNA repair (e.g., FANCG, ERCC), energy metabolism (e.g., isocitrate dehydrogenase alpha, ADP/ATP translocase), but also decreased expression of genes coding for proteins that have oncogenic activity (e.g., c-myc, GTPase) or show tumor-specific expression (e.g., phosphatidylinositol 3-kinase). In contrast, these treated cells overexpressed several genes that encode intracellular and secreted growth-inhibitory proteins (e.g., BTG2, MCP-3) as well as proapoptotic genes (e.g., ATL-derived PMA-responsive peptide). Our findings suggest that alterations in specific genes functionally related to cell proliferation or apoptosis may be responsible for cantharidin-mediated cytotoxicity. We also found that exposure of HL-60 cells to cantharidin resulted in the decreased expression of multidrug resistance-associated protein genes (e.g., ABCA3, MOAT-B), suggesting that cantharidin may be used as an oncotherapy sensitizer, and the increased expression of genes in modulating cytokine production and inflammatory response (e.g., NFIL-3, N-formylpeptide receptor), which may partly explain the stimulating effects on leukocytosis. Our data provide new insight into the molecular mechanisms of cantharidin.

Cantharidin↗
PubMed2004

Reduction of tumor progression and paraneoplastic syndrome development in murine lung adenocarcinoma by nonsteroidal antiinflammatory drugs.

Mice bearing LP07 lung adenocarcinoma show some characteristics that are similar to those present in patients with NSCLC. LP07 tumor-bearing mice develop the paraneoplastic syndromes of cachexia, leukocytosis and hypercalcemia. These symptoms may be partly due to a systemic inflammatory response. Our aim was to determine if treatment with NSAIDs would lower tumor and metastasis growth and their accompanying syndromes. The nonselective COX inhibitor indomethacin and the selective COX-2 inhibitor celecoxib reduced tumor growth and metastasis outcome in s.c. LP07 tumor-bearing mice. Both drugs also inhibited the development of leukocytosis and the weight loss associated with LP07 progression. Serum levels of the inflammatory cytokines IL-1beta and IL-6, mediators of cachexia, were modulated by NSAIDs. Inhibition of in vitro migration and invasion and reduction in angiogenesis were attained when cells were treated with either indomethacin or celecoxib. MMP-9 activity was also reduced in conditioned media from LP07 cells treated with celecoxib. These data suggest that several processes implicated in tumor progression can be modulated with NSAID treatment. Improvement in performance status through modulation of cachexia may offer a possibility for combining anti-inflammatory treatments with more aggressive therapies.

Adenocarcinoma↗