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PubMed1995

[Simultaneous production of parathyroid hormone-related protein (PTHrP) and granulocyte colony-stimulating factor (G-CSF) in lung cancer patients with hypercalcemia and leukocytosis].

Hypercalcemia and leukocytosis are often associated with primary lung cancer as a paraneoplastic syndrome. Recently, parathyroid hormone-related protein (PTHrP) and granulocyte colony stimulating factor (G-CSF) have been identified as major causative peptides for hypercalcemia and leukocytosis, respectively. We studied four men with advanced primary lung cancer (stages from IIIA to IV) who presented with hypercalcemia (corrected serum calcium levels: 10.5 mg/dl) and leukocytosis (WBC > 10,000 per mm3). The age of the patients ranged from 59 to 79 years old. The pathological subtypes were squamous cell carcinoma in three and adenocarcinoma in one. The mean serum calcium levels and leukocyte counts were 15.8 +/- 1.4 mg/dl (mean +/- SE) and 24,800 +/- 3,253 cells/mm3 (mean +/- SE), respectively. Abnormally high serum levels of PTHrP and G-CSF were found in three patients (mean +/- SE: 137 +/- 68 pg/ml; normal range in human serum, < 16 pg/ml), and in all four (mean +/- SE: 72 +/- 7.7 pg/ml; normal range in human serum, < 20 pg/ml), respectively. Immuno-histochemical examination of cancerous tissue obtained from these patients showed positive staining for both PTHrP and G-CSF within the cytoplasm of all the cancerous tissue. These results suggest that the association of hypercalcemia and leukocytosis in patients with advanced primary lung cancer is caused by production of both PTHrP and G-CSF by cancerous tissue.

Aged↗
PubMed2006

Dedifferentiated chondrosarcoma with leukocytosis and elevation of serum G-CSF. A case report.

BACKGROUND: G-CSF is known to function as a hematopoietic growth factor and it is known to be responsible for leukocytosis. G-CSF-producing tumors associated with leukocytosis include various types of malignancies. CASE PRESENTATION: We report the case of a 72-year-old man with dedifferentiated chondrosarcoma characterized by dedifferentiated components of malignant fibrous histiocytoma- or osteosarcoma-like features in addition to conventional chondrosarcoma, arising from his pelvic bone. After hemipelvectomy, when local recurrence and metastasis were identified, leukocytosis appeared and an elevated level of serum granulocyte-colony-stimulating factor (G-CSF) was also recognized. The patient died of multiple organ failure 2 months after surgery. Autopsy specimens showed that the histological specimens of the recurrence and metastasis were dedifferentiated components, without any conventional chondrosarcoma components. G-CSF was expressed only in the dedifferentiated components, not in the chondrosarcoma components, immunohistochemically. CONCLUSION: This is the first report of chondrosarcoma, or any other primary bone tumor, with leukocytosis, probably stimulated by tumor-produced G-CSF from the dedifferentiated components.

Journal Article↗
PubMed1996

Blood transfusion for haemolytic disease as a cause of leukocytosis in the fetus.

We evaluated the effect of fetal intravascular transfusion (IVT) of leukocyte-poor red blood cells to correct fetal anaemia due to haemolytic disease on the fetal leukocyte count in 153 patients. Initial, mid-transfusion, and closing haematological studies were obtained when possible. The effect on leukocyte subsets was evaluated by the manual differential count. Fetal leukocyte count increased an average of 18.0 per cent during all IVTs (P < 0.01), despite the dilutional effect of the transfusion. The degree of leukocytosis increased with subsequent transfusions. The smallest (10.1 per cent) change occurred during the initial transfusion. A 41.8 per cent increase was noted during the sixth procedure. There was no relation between leukocytosis and gestational age, volume of transfusion, changes in umbilical vein pressure, or hydrops. Forty-two per cent of the increase was due to expansion of the neutrophil pool and 22 per cent was due to expansion of the monocyte pool. The neutrophil count increased 29 per cent (P < 0.01) and monocytes increased 64.7 per cent (P < 0.001). There was no change in eosinophil and lymphocyte counts. Both an immune aetiology and an effect of inflammatory agents may contribute to this leukocytosis.

Blood Transfusion, Intrauterine↗
PubMed1987

Leukocytosis and large cell lung cancer. A frequent association.

In a retrospective study of 105 patients with non-small cell lung cancer during a 5-year period, 43 had leukocytosis. In 19 of the 43 patients, no clear cut etiology for the leukocytosis was apparent and it was attributed to the tumor itself. In these 19 patients, absolute neutrophilia was detected in 13, eosinophilia was present in three, and eleven exhibited concomitant thrombocytosis. Tumor-associated leukocytosis occurred predominantly, and eosinophilia exclusively, in patients with large cell pulmonary neoplasms. These results suggest an unusual myeloproliferative stimulus in this type of cancer. It may result from tumor cell production of hemopoietic growth factors such as granulocyte-macrophage colony-stimulating activity; however, additional studies are needed to elucidate the underlying mechanism(s), and to determine whether this is a peculiar characteristic of the cells that comprise large cell undifferentiated carcinoma of the lung.

Adenocarcinoma↗
PubMed2001

Tumor-related leukocytosis is linked with poor prognosis in patients with lung carcinoma.

BACKGROUND: Tumor-related leukocytosis is a paraneoplastic syndrome that is encountered occasionally in the clinical course of patients with lung carcinoma. Recently, autonomous production of hematopoietic cytokines (granulocyte-colony stimulating factor [G-CSF], granulocyte-macrophage-colony stimulating factor [GM-CSF], and interleukin-6 [IL-6]) were identified in some of these patients. However, the incidence and clinical characterization of this phenomenon have not been clarified. METHODS: During a 7-year period, 227 patients with carcinoma of the lung were investigated, and 33 patients were diagnosed with tumor-related leukocytosis. Except for one patient with small cell lung carcinoma, the other 32 patients had nonsmall cell lung carcinoma, and the highest incidence is recognized in large cell carcinoma. These 33 patients were examined for serum G-CSF, GM-CSF, and IL-6 levels using enzyme immunoassays and enzyme-linked immunosorbent assays. Tumor specimens were stained for antihuman cytokine (G-CSF, GM-CSF, and IL-6) monoclonal antibodies. RESULTS: Sixteen patients showed high serum G-CSF levels, 4 patients showed high serum GM-CSF levels, and 18 patients showed high serum IL-6 levels. Twelve specimens stained positively against anti-G-CSF antibody. Two specimens stained positively against anti-GM-CSF antibody, and three specimens were stained positively against anti-IL-6 antibody, including one double positive specimen for both G-CSF and IL-6. All specimens that were positive for monoclonal antibodies were from patients with nonsmall cell lung carcinoma. These patients had a poor outcome compared with the other patients. CONCLUSIONS: Tumor-related leukocytosis and cytokine production frequently occur in the clinical course of lung carcinoma, and this phenomenon is related mainly to nonsmall cell lung carcinoma. Its occurrence appears to be an ominous prognostic sign in patients with lung carcinoma.

Adult↗
PubMed1986

Effect of chronic beta-adrenergic blockade on exercise-induced leukocytosis.

Chronic beta-receptor blockade on exercise-induced leukocytosis was studied in 11 hypertensive males. Blood samples for determinating leukocytes were taken before and during the 6th min and the 30th min of submaximal exercise, at maximal exercise, and 5 and 15 min after work. Lymphocytosis and granulocytosis were found to be dependent on the intensity and duration of the exercise. Leukocytosis during short-term and long-term exercise was due to both a lymphocytosis and granulocytosis. Under resting conditions, the chronic beta-receptor blockade caused a significant decrease of neutrophil granulocytes. Both the patients and the controls showed the same percent increase in leukocytes compared with the untreated control study. This suggests that the adrenergic system does not play the primary role in exercise-induced leukocytosis.

Acebutolol↗
PubMed1990

Number and types of hemocytes in Sunetta scripta and Villorita cyprinoides var. cochinensis (Bivalvia), and leukocytosis subsequent to bacterial challenge.

The number and types of hemocytes in four size groups of the clam species Sunetta scripta and Villorita cyprinoides var. cochinensis, and leukocytosis in the 38- to 40-mm-size-group clams of both species subsequent to challenge with Vibrio alginolyticus at a concentration of 1 x 10(8) cells/0.02 ml of sterile 2% saline was investigated. In S. scripta, the mean total hemocyte count in the 42- to 44-mm size group was significantly lower than that of the three other size groups but there was no significant variation in total cell counts in the four size groups of V. cyprinoides var. cochinensis. Only two types of hemocytes, granulocytes and agranulocytes, occur and the percentage of agranulocytes was roughly half of that of granulocytes. The data on the effects of sham injection and Vibrio injection suggest that there is significant leukocytosis early in both clam species as a result of sham injection; the bacterial challenge produces significant leukocytosis in V. cyprinoides var. cochinensis both early (6 and 12 hr) and later (48,96 and 120 hr), but only at 48 hr in S. scripta; and in both clam species there is significant increase in total cell counts in Vibrio-injected ones than in untampered controls at various time intervals.

Animals↗
PubMed2005

Leukocytosis and blood eosinophilia in a polyparasitised population in north-eastern Brazil.

It has long been known that leukocytosis and blood eosinophilia are common in the tropical environment, but data derived from population-based studies are scarce. A study was undertaken in a fishing village in north-east Brazil where both intestinal helminthiases and parasitic skin diseases are common. Of 409 individuals studied, 128 (31.3%) were infected with one intestinal helminth or ectoparasite species, 93 (22.7%) with two, 61 (14.9%) with three, 25 (6.1%) with four and 11 (2.7%) with more than four species; no parasites were found in 91 (22.2%) individuals. Leukocyte counts ranged between 3,300 cells/microl and 16,100 cells/microl (median, 7,200 cells/microl) and eosinophil counts between 40 cells/microl and 5,460 cells/microl (median, 455 cells/microl). Eosinophilia (>500/microl) was detected in 44.7% of the individuals, and hypereosinophilia (>1,000/microl) in 12.9%. Thirty-six (8.8%) individuals showed leukocytosis. While 75% of individuals with normal eosinophil counts were considered parasite-free, only 14% with eosinophilia and 11% with hypereosinophilia did not have enteroparasites or ectoparasites. Multivariate regression showed that the probability of eosinophilia and hypereosinophilia, but not of leukocytosis, increased with the number of parasite species present. The data show that eosinophilia occurs in almost one-half of the individuals from a resource-poor setting and that it is significantly associated with the presence of intestinal helminths, but not with the presence of ectoparasites.

Adolescent↗
PubMed1996

Leukocytosis, hyperglycemia, vomiting, and positive X-rays are not indicators of severity of iron overdose in adults.

To determine whether leukocytosis, hyperglycemia, vomiting, and opacities in abdominal radiographs are indicators of a serum iron concentration of > 300 micrograms/dL in adult iron overdose patients, a retrospective medical record review was undertaken at a university medical center of all patients older than 12 years of age for whom clinical data were collected before deferoxamine therapy and within 6 hours of iron ingestion. Forty-three patients met the inclusion criteria; 37 were female. The mean and range serum iron concentrations were 382 micrograms/dL and 58 to 710 micrograms/dL, with 34 patients having values of > 300 micrograms/dL. There were no statistically significant relationships between iron concentration of > 300 microgram/dL and leukocytosis, hyperglycemia, vomiting, and opacities in abdominal radiographs (P > .05). Sensitivities, specificities, and positive and negative predictive values indicate poor performance of these parameters as clinical predictors of serum iron concentration of > 300 micrograms/dL. Leukocytosis, hyperglycemia, vomiting, or the presence of opacities in abdominal X-rays are not indicators of a serum iron concentration of > 300 micrograms/dL in adults. These parameters should not be used to assess the severity of iron overdose or to guide its management.

Adolescent↗
PubMed2001

Murine gammaherpesvirus-68-induced interleukin-10 increases viral burden, but limits virus-induced splenomegaly and leukocytosis.

Based on its genomic sequence and its pathogenesis, murine gammaherpesvirus-68 (gammaHV-68) has been established as a tractable model for the study of viral infections caused by the human gammaherpesviruses, Epstein-Barr virus or human herpesvirus-8. Despite significant advances, the mechanisms responsible for gammaHV-68-induced alterations in the protective host response, and the accompanying virus-induced leukocytosis, are not clear. In the present study, we questioned whether viral infection resulted in endogenous interleukin-10 (IL-10) production that might alter the host response. Infection of C57BL/6 mice resulted in increased IL-10 expression, demonstrating that gammaHV-68 could induce endogenous production of this cytokine. Infected C57BL/6 mice demonstrated the characteristic splenomegaly associated with this viral infection, however, we were surprised to discover that the splenomegaly was greater in syngeneic mice genetically deficient in IL-10 (IL-10-/-). These results strongly suggested that endogenously produced IL-10 might serve to limit leukocytosis in wild-type mice. Quantification of viral burden demonstrated a significant elevation in C57BL/6 versus IL-10-/- mice, with increases in virus being observed in both the macrophage and B-lymphocyte populations. The decreased viral load in syngeneic IL-10-/- mice correlated with an increased expression of endogenous IL-12, suggesting a mechanism of protection that was IL-12 dependent. Taken together, these studies demonstrate a surprising dichotomy for endogenous IL-10 production during gammaHV-68 infection. While the lack of IL-10 results in increased IL-12 expression and a lower viral burden, IL-10-/- mice also experience an increased leukocytosis.

Animals↗
PubMed1983

Amphetamines and leukocytosis. A possible association.

An increased incidence of leukocytosis and statistically significant elevations of both median and mean white blood cell counts were found in a small series of patients who presented to an emergency department with nonspecific complaints after amphetamine use. These findings suggest the possibility of an association between amphetamines and increased leukocyte counts, which would most likely be due to a mechanism the same as or similar to that responsible for stress leukocytosis, which can be seen with epinephrine administration or stress in general. Before such an association can be considered in any patient, other causes of leukocytosis, especially infection, must be carefully excluded.

Administration, Oral↗
PubMed1975

Characterization of R-type vitamin B12-binding proteins by isoelectric focusing. III. Cobalophilin (R protein) in myeloproliferative states and leukocytosis.

The R-type vitamin B12-binding protein (cobalophilin) in plasma and serum of patients with myeloproliferative diseases and leukocytosis was studied by gel filtration and isoelectric focusing. The isoproteins composing the cobalophilin were mainly the same in these disorders as in plasma of health subjects. In half the patients with chronic myelogenous leukaemia and a few of those with leukocytosis some of the isoproteins were more acid than those found in healthy subjects. In chronic myelogenous leukaemia the high unsaturated vitamin B12-binding capacity of plasma was due to an increase in the fairly acid isoproteins, whereas in polycythaemia vera and in most cases of leukocytosis there was an increase in the least acid isoproteins.

Blood Proteins↗
PubMed1976

Isolation and properties of the leukocytosis- and lymphocytosis-promoting factor of Bordetella pertussis.

The leukocytosis- and lymphocytosis-promoting factor (LPF) of Bordetella pertussis has been isolated to near homogeneity by physical, chemical, and electron microscopical criteria. LPF contains 14.5% nitrogen and is lipid and carbohydrate free. It is apparently composed of four polypeptide subunits. LPF caused leukocytosis and lymphocytosis in "nude" as well as in normal mice. In addition, purified LPF also induced histamine sensitization and hypoglycemia and refractoriness to the hyperglycemic effect of epinephrine. A monospecific LPF antiserum blocked these reactions as well as leukocytosis and lymphocytosis. LPF is clearly distinct from the hemagglutinating pili of B. pertussis.

Amino Acids↗
PubMed1996

Leukocytosis: a new look at an old marker for acute myocardial infarction.

OBJECTIVE: To determine the test performance of leukocytosis for identifying acute myocardial infarction (AMI) in patients with nondiagnostic ECGs, admitted to rule out AMI. METHODS: A retrospective, comparative test performance study was conducted using patients admitted to a university teaching hospital to rule out AMI. Clinical and laboratory information was reviewed and hospital laboratory ranges were used to define threshold elevations: total creatine kinase (CK), 275 U/L; CK-MB, 7.5 micrograms/L ; white blood cell (WBC) count, 11.5 x 10(9)/L; and absolute neutrophil count (ANC), 8.0 x 10(9). Sensitivity, specificity, and predictive values of the total CK, CK-MB, WBC count, and ANC were calculated, and receiver operating characteristic (ROC) curves constructed. Test performances of marker combinations also were determined. RESULTS: The initial WBC count was significantly higher for the subjects who had AMI (11.1 vs 8.8 x 10(9)/L, p < 0.001). For the 688 subjects who had nondiagnostic ECGs, sensitivities for the initial total CK, CK-MB, WBC, and ANC were 39%, 73%, 35%, and 36%, respectively, while the corresponding specificities were 94%, 93%, 85%, and 86%. Logistic regression analysis confirmed leukocytosis as an independent predictor of AMI (adjusted odds ratio 4.08, 95% CI 1.73-9.63). While CK-MB alone was 73% sensitive for AMI, the decision rule of either an elevated CK-MB or an elevated WBC count increased this sensitivity to 88% (corresponding specificity 79%). Similarly, while CK-MB alone was 93% specific for AMI, the combination of an elevated CK-MB and an elevated WBC count increased this specificity to 99% (corresponding sensitivity 20%). CONCLUSIONS: Leukocytosis is significantly associated with AMI, and is a weak but independent laboratory predictor of this condition. In this preliminary study of admitted patients suspected of AMI, the combination of the WBC and the CK-MB may have additional diagnostic value over an isolated CK-MB result. Neither parameter in isolation was satisfactorily sensitive for AMI. Prognostic assessment of the role of the WBC count in clinical decision making should address its complementary role to that of other clinical and ancillary test parameters.

Acute Disease↗
PubMedDate not supplied

Production of granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor by carcinomas in a dog and a cat with paraneoplastic leukocytosis.

A dog with a pulmonary papillary carcinoma and a cat with a dermal tubular adenocarcinoma had profound paraneoplastic neutrophilic leukocytosis with no clinically detectable inflammatory foci. To investigate the mechanism of the leukocytosis, oligonucleotide primers were designed from the cDNA sequences of granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) of dogs. Reverse transcription polymerase chain reaction was performed on tumor tissues, and specific amplification of G-CSF and GM-CSF was obtained with the tumor RNA in the dog. The tumor RNA in the cat demonstrated specific amplification of G-CSF but not GM-CSF. These findings are consistent with the production of G-CSF and/or GM-CSF by neoplasms as a mechanism for paraneoplastic leukocytosis in small animals.

Adenoma↗
PubMed1973

Leukocytosis-promoting factor of Bordetella pertussis. II. Biological properties.

The leukocytosis-promoting factor (LPF), purified from materials extracted from agar in which Bordetella pertussis was grown, caused leukocytosis and an increased sensitivity to histamine when as little as 0.04 mug of protein was given intravenously to mice. LPF was adsorbed onto erythrocytes, causing hemagglutination. As little as 0.03 mug of LPF protein agglutinated chicken erythrocytes in 0.05 ml of a 0.5% suspension. The physicochemical, biological, and immunological properties indicated that leukocytosis, increased sensitivity to histamine in mice, and agglutination of erythrocytes are functions of a single substance.

Animals↗
PubMed2001

Rapidly relapsing squamous cell carcinoma of the renal pelvis associated with paraneoplastic syndromes of leukocytosis, thrombocytosis and hypercalcemia.

A case history is reported here in which leukocytosis, thrombocytosis and hypercalcemia associated with rapidly relapsing squamous cell carcinoma (SCC) of the renal pelvis were observed. In a 58-year-old man, SCC of the renal pelvis was documented during nephrolithotomy, and right nephrectomy was performed. Local relapse of the tumor occurred rapidly in 2 months' time and hypercalcemia, leukocytosis and thrombocytosis worsened in accordance with tumor volume. Cranial computerized tomography (CT), thorax CT and bone scintigraphy were negative for metastasis. The serum parathyroid hormone level was 28 pg/ml (normal 9- 55 pg/ml). To disclose leukocytosis and thrombocytosis, peripheral smear and bone marrow aspiration were performed and no pathologic finding regarding any hematologic disorder was found; the samples were also BCR-ABL negative and Philadelphia chromosome negative. Production of several factors by tumor cells may be responsible for this paraneoplastic syndrome. The association of SCC of the renal pelvis with this triple paraneoplastic syndrome is an extremely rare occurrence.

Carcinoma, Squamous Cell↗
PubMed1986

Squamous cell carcinoma with hypercalcemia and leukocytosis.

Squamous cell carcinoma with hypercalcemia and leukocytosis arising from burn scars in a 45-year-old man is reported. Hypercalcemia and leukocytosis improved with pepleomycin treatment and worsened with recurrence of the tumor. Serum levels of parathyroid hormone, prostaglandin E and 25-OH-Vitamin D were within normal limits. Autopsy did not disclose any bone metastases or abnormalities of the parathyroid glands. It is suggested that hypercalcemia and leukocytosis were due to factors produced by the squamous cell carcinoma. This is the fifth reported case of cutaneous squamous cell carcinoma associated with hypercalcemia in the absence of bone metastasis or parathyroid gland abnormalities.

Bleomycin↗