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[Steroidal leukocytosis and immediate results of treatment in patients with sarcoidosis].

The occurrence of steroidal leukocytosis at early stages of an observation may, to a certain extent, serve an objective criterion for predicting the pronounced immediate results of treatment in first detected patients with sarcoidosis (that of intrathoracic lymph nodes and the lung in particular) and thus makes it possible to judge the adequacy of therapy in the inpatient setting. When steroidal leukocytosis is absent, it is necessary to differentiately decide whether it is expedient to correct a hormonal therapy regimen in order to achieve the optimal results of its efficiency.

Adolescent↗

Effects of arsenic trioxide administration styles on leukocytosis.

OBJECTIVE: To study the effects of constantly slow intravenous arsenic trioxide (As2O3) infusion regimen on decreasing leukocytosis in vivo and in vitro. METHODS: Three kinds of leukemia cells, NB4, K562, and acute promyelocytic leukemia (APL) cells, were cultured in the media with constant concentration and varying concentrations of As2O3 respectively for 24 hours. Seventy-five patients were enrolled in two groups randomly. In trial group, 37 patients received continuously slow intravenous As2O3 infusion regimen for 24 hours with an infusion rate of 8 drips per minute and total infusion duration of about 18-21 hours daily. In control group, 38 patients received routine regimen with an infusion rate of 45-55 drips per minute and total infusion duration of about 2-3 hours daily for 24 hours. The daily As2O3 dosage was 0. 16 mg/kg. The intracellular arsenic concentration was measured by atomic fluorescence assay. The apoptosis rate of cells, CD33- CD11b+ cells, and CD33+ CD11b- cells were monitored by flow cytometry. RESULTS: The apoptosis rates of NB4, K562, and APL leukemia cells in the media with constant As2O3 concentration were 56.6% +/- 2.4%, 27.6% +/- 3.1%, and 52.2% +/- 2.8%, respectively, which were significantly higher than those with changing As2O3 concentration (23.2% +/- 2.1%, 11.0% +/- 2.5%, and 21.0% +/- 2.5%, respectively, P < 0.01). The apoptosis rates of APL, M2 type acute myeloid leukemia (AML-M2), and chronic myeloid leukemia (CML) patients in the trial group (28.5% +/- 1.9%, 9.5% +/- 0.6%, and 12.5% +/- 1.8%) were also significantly higher than those in control group (8.5% +/- 2.2%, 2. 9% +/- 0.8%, and 4.5% +/- 1.2%; P < 0.05). The ratios of CD33 CD11b- and CD33- CD11b+ cells in control group were significantly higher than those in trial group. CONCLUSION: The continuously slow intravenous As2O3 infusion regimen can obtain high efficiency of apoptosis and low differentiation proportion, relieve leukocytosis, and gain maximal therapeutic benefit.

Antineoplastic Agents↗

[Isolation and purification of a preparation possessing leukocytosis-stimulating properties from pertussis bacteria].

A homogeneous protein LSF-2 preparation was extracted from the cultural fluid of Bordetella pertussis strains of the 1.0.3 serological type by means of precipitation with ammonium sulphate and electrofocussing; this preparation proved to produce a marked leukocytosis-stimulating and a weak toxic action of delayed type in experiments on animals. Intraperitoneal administration of 5 mug of the LSF-2 preparation caused a rise of leukocytosis in mice to 100,000 cells per 1 mm3, a delay in the gain in weight beginning from the 3rd day of the administration and a late death of the animals in 5% of cases. The LSF-2 preparation protected the mice in infection with a virulent pertussis strain No. 18323 in the amount of from 12 to 91%, depending on the immunizing dose; its ImD50 was equal to 2.0 -2.4 mug of protein. The results of investigations carried out permitted to assess the role of this substance in the formation of specific immunity in pertussis infection.

Animals↗

Asymptomatic cervicovaginal leukocytosis in infertile women.

Cervicovaginal cells were obtained from 114 women undergoing intrauterine insemination and 21 women undergoing donor insemination. Monoclonal antibodies were used to identify leukocyte subpopulations in women with nonepithelial cell counts greater than 2 X 10(5) (termed asymptomatic cervicovaginal leukocytosis). Leukocyte counts exceeding this number were not found in any of the women undergoing donor insemination; however, greater than 2 X 10(5) leukocytes were detected in 22% of the infertile women. Granulocytes predominated; lymphocytes and macrophages were detected in only 8 of 114 samples. Women with cervical factor infertility had a significantly higher incidence of asymptomatic cervicovaginal leukocytosis than women with either male factor or unexplained infertility. These data suggest that cervicovaginal leukocytes may play a role in cervical factor infertility since soluble products of activated leukocytes are known to adversely affect reproduction.

Cervix Uteri↗

Paraneoplastic syndrome of hypercalcemia and leukocytosis caused by squamous carcinoma cells (T3M-1) producing parathyroid hormone-related protein, interleukin 1 alpha, and granulocyte colony-stimulating factor.

Previously we reported that a clonal squamous cell carcinoma cell line (T3M-1) derived from a lower jaw cancer of a patient with marked leukocytosis and hypercalcemia produced factors containing a potent bone-resorbing activity (BRA) (Mr 15,000-20,000) and a colony-stimulating activity. To elucidate the pathogenesis of this humoral hypercalcemia, BRA and colony-stimulating activity in both the conditioned medium and cells were characterized. The conditioned medium, when eluted at neutral pH, contained colony-stimulating activity and thymocyte proliferation-stimulating activity, the latter of which comigrated with BRA. Upon elution with acetic acid (pH 2.0), the conditioned medium contained no interleukin 1-like activity but potent parathyroid hormone-like activity, which comigrated with BRA. Northern blot hydridization analysis revealed that T3M-1 cells produced constitutively mRNA for parathyroid hormone-related protein and granulocyte colony-stimulating factor. Furthermore, primer extension analysis revealed that the cells also produced mRNA for interleukin 1 alpha (IL-1 alpha). Since parathyroid hormone-related protein and IL-1 alpha (osteoclast-activating factor) synergistically increase the concentration of serum calcium, and since IL-1 alpha (hemopoietin 1) potentiates granulocyte colony-stimulating factor-induced granulocytopoiesis, we speculate that parathyroid hormone-related protein, granulocyte colony-stimulating factor, and IL-1 alpha are synergistically involved in a paraneoplastic syndrome of hypercalcemia and leukocytosis, at least in some patients with solid tumors.

Animals↗

[An autopsy case of colonic carcinoid with marked leukocytosis].

A 45-year-old man with right hypochondralgia and marked leukocytosis was found to have Borrmann type II carcinoma of the sigmoid colon and its metastasis to the liver. The peripheral leukocyte count gradually increased up to 150 X 10(3)/mm3 according to the tumor enlargement. The patient died of hepatic insufficiency, and autopsy revealed carcinoid of the colon and its metastasis to the liver. Leukemoid reaction has been reported in various kinds of malignancies. However, the present case seems to be of particular interest because of the rare association with carcinoid and marked leukocytosis of more than 100 X 10(3)/mm3 without any evidence of infection.

Carcinoid Tumor↗

[Leukocytosis, the leftward shift of the white blood picture and leukemoid reactions in the internal medicine clinic].

The white blood count of 6549 patients with various internal diseases of respiratory, cardiovascular, gastrointestinal, excretory and endocrine systems was studied as well as in neoplasms, collagenosis, etc. with the exception of malignant hemopathies. Leukocytosis was established in 21.8% of them. In almost half of the cases, leukocytosis is low, in 44.6% it ranges from 12-20 X 10(9)/l and in 10.2%--it is high--from 20 to 40 X 10(9)/l. Immature cells in the peripheral blood were established corresponding to stab neutrophils over 0.06-0.10, metamyelocytes, myelocytes reaching myeloblasts in the cases with leukemoid reactions. The leukemoid reactions have, with no exceptions, been of myeloid type and developed in various diseases.

Adolescent↗

Primary squamous cell carcinoma of the thyroid associated with leukocytosis and hypercalcemia.

Primary squamous cell carcinoma of the thyroid is an extremely rare, aggressive neoplasm with a uniformly poor prognosis. Described herein is a case of a 66-year-old man with primary squamous cell carcinoma of the thyroid associated with hypercalcemia (13 mg/dL [3.24 mmol/L]) and unexplained leukocytosis (28,400/mm3 [28.4 X 10(9)/L]). The histogenesis of squamous cell carcinoma of the thyroid remains controversial. The associated hypercalcemia and leukocytosis most likely represent a form of paraneoplastic syndrome; possible mechanisms will be discussed in the light of recent studies on tumor-derived mediators.

Aged↗

Lithium carbonate and leukocytosis.

White blood cell (WBC) counts of 37 hospitalized adult psychiatric patients were examined for changes during treatment with lithium carbonate. Group 1 (n = 19) patients had WBC counts taken before and after lithium therapy. Group 2 (n = 16) patients had WBC counts taken only after lithium therapy. The remaining two patients had infections and were considered separately. In Group 1, a significant leukocytosis was observed over baseline values (p less than 0.001). The mean increase in WBC count was 2,237 cells/cu mm. For Group 2 patients, the mean WBC count observed was 11,950 +/- 4,028 cells/cu mm, which is higher than the normal leukocyte count in peripheral blood. An increase in circulating leukocytes was observed in the majority of these patients. The data indicate that the leukocytosis was drug related, but the increase did not appear to be dose related or dependent on the concentration of lithium in the blood.

Adult↗

Explanation for apparent hypoxemia associated with extreme leukocytosis: leukocytic oxygen consumption.

We investigated the hypoxemia associated with extreme leukocytosis in leukemic patients. In vitro experiments showed that the rate of decrease in the partial pressure of oxygen in the blood samples from such patients was proportional to the white cell count. In the presence of normal white cell count no drop in PO2 was observed. We conclude that a low arterial oxygen tension in the presence of extreme leukocytosis reflects oxygen consumption by leukocytes rather than true hypoxemia. Both normal as well as leukemic leukocytes appear to exhibit this phenomenon.

Blood Gas Analysis↗

[A case of leukocytosis after massive blood transfusion for postpartum hemorrhagic shock].

We experienced the perioperative management of a hemorrhagic shock associated with postpartum uterine rupture. After the emergency abdominal total hysterectomy, massive blood transfusion was required to maintain the hemodynamics and the laparotomy for hemostasis was performed on the 1st, 2nd and 7th ICU day. Total amount of transfused blood products was 37,000 ml during one week. The patient immediately developed DIC and acute renal failure. Laboratory data showed increased leukocyte count (the peak value was 56,100 microliters-1 on the 12th ICU day), and neutrophilic fraction was more than 90% of leucocyte. After the decrease in CRP, the decrease in total bilirubin concentration was delayed. There were no other signs of infection and no remarkable change in MOF score. There was a discrepancy between this leukocytosis and the severity of organ dysfunction, and the cause of the leukocytosis was unknown.

Female↗

[Etiopathogenesis of acute myocardial infarction: role of early leukocytosis].

It has recently been suggested that inflammation may play an important role in the pathogenesis of acute ischemic syndromes. It may therefore be important to relate their clinical features with plasma indexes of inflammation. We have studied leukocyte, platelet and fibrinogen blood levels in 57 consecutive patients with acute myocardial infarction admitted to our Intensive Care Unit within 90 min after the onset of chest pain and treated with primary coronary angioplasty. Patients were divided into two groups on the basis of blood leukocyte levels: Group A, 24 patients, 17 males, mean age 54.2 +/- 13.7 years, with high blood leukocytes and Group B, 33 patients, 28 males, mean age 60.9 +/- 10.3 years, with normal blood leukocytes. Group A patients also had higher serum fibrinogen (p = 0.05) and blood platelet levels (p < 0.05). The stenosis observed after guidewire advancement was significant (> 75%) in 33% of the patients with leukocytosis vs 94% of the others (p < 0.01). No difference between the two groups was observed in the success rate of coronary angioplasty and prevalence of stent placement (100 vs 97%, and 43 vs 42% of the patients of Group A and B, respectively). In contrast, a tendency to rethrombosis requiring Rheopro administration was observed in 62% Group A patients vs 21% Group B patients (p < 0.01). In conclusion, the finding of leukocytosis in the acute phase of myocardial infarction suggests that coronary occlusion is mainly caused by a coronary thrombus occurring at the site of a non significant stenosis. In contrast, when blood leukocytes are normal, the underlying coronary stenosis is more often critical and the thrombotic process is less important. The high blood leukocytes, platelet and fibrinogen levels of Group A patients are consistent with a significant role of inflammation in the pathogenesis of the thrombotic process while hemodynamic and local mechanical factors are probably more important in patients with normal blood leukocytes.

Adult↗

Production and expression of granulocyte- and macrophage-colony-stimulating factors in newborns: their roles in leukocytosis at birth.

We analyzed the production and expression of three colony-stimulating factors (CSFs) in neonates to clarify the mechanism of leukocytosis at birth. Serial blood samples (n = 23) were collected from mothers, cord blood, and from newborn infants on days 1, 5, and 30 after birth. The serum levels of granulocyte-CSF (G-CSF), granulocyte/macrophage/CSF (GM-CSF) and macrophage-CSF (M-CSF) were measured by ELISA. The G-CSF levels on day 1 after birth were significantly higher than those thereafter, and they were also higher in the mothers than those on days 5 and 30 after birth. The GM-CSF levels did not change significantly during the neonatal period. The serum M-CSF levels were higher on postnatal day 1 than at other times, and gradually decreased thereafter. To confirm the production sites of G-CSF and M-CSF, the mRNA for these CSFs in peripheral mononuclear cells (MNCs) from healthy adults, mothers, and cord blood were analyzed by PCR. The expression of G-CSF and GM-CSF mRNA was undetectable in MNCs from adults, mothers, and cord blood, while these cells expressed low levels of M-CSF mRNA. After stimulation with lipopolysaccharide or phorbol myristate acetate, the MNCs expressed high levels of G-CSF and GM-CSF mRNA. The levels of G-CSF PCR products in cord MNCs were lower than those in adult and maternal MNCs. The expression of M-CSF mRNA was virtually unchanged by stimulation. To detect the localization of G-CSF and M-CSF in the placenta and umbilical cord, these tissues were immunocytochemically stained with anti-G-CSF and anti-M-CSF antibodies, G-CSF and M-CSF were expressed in trophoblasts and decidual stromal cells, whereas the umbilical cord did not express these CSFs. Moreover, large amounts of G-CSF and M-CSF were detected in the supernatant of cultured trophoblasts and decidual stromal cells. The expression of G-CSF and M-CSF in these cells was confirmed by PCR. These findings suggested that G-CSF and M-CSF produced in the placenta (trophoblasts and decidual stromal cells) are the major factors that induce leukocytosis in newborn infants at birth.

Base Sequence↗

Fat droplets and synovial fluid leukocytosis in traumatic arthritis.

The presence of fat droplets in synovial fluid signifies major or minor joint trauma with damage to the bones or adjacent supporting structures. Synovial fluids aspirated after traumatic hemorrhage usually have a low white blood cell count. In this report 2 patients with hemorrhagic effusions had synovial fluid leukocytosis, presumably secondary to lipid droplet phagocytosis. Lipid globules intra- and extracellulalary in the synovial fluid and a top fatty layer in the hematocrit spin of the hemorrhagic synovial fluid are indications of the traumatic etiology of this inflammatory arthritis.

Adult↗

Catecholamine-induced leukocytosis: early observations, current research, and future directions.

Recent studies demonstrate that acute psychological stress in man affects lymphocyte circulation. It has been suggested that catecholamines are responsible for these changes. The present review summarizes findings regarding catecholamine-induced lympho- and leukocytosis, starting with observations dating back to the beginning of this century. Particular attention is given to the mechanisms of this phenomenon and the potential site of origin of newly appearing leukocytes. Characteristically, two phases are recognized after catecholamine administration: a quick (<30 min) mobilization of lymphocytes, followed by an increase in granulocyte numbers with decreasing lymphocyte numbers. Many studies have shown that catecholamines predominantly affect natural killer (NK) cell and granulocyte circulation, whereas T- and B-cell numbers remain relatively unaffected. The changes in lymphocyte circulation seem to be mainly mediated via activation of beta2-adrenoceptors, whereas granulocyte increases involve alpha-adrenoceptor stimulation. Results further indicate that the marginal pool and the spleen are the major sources for freshly recruited lymphocytes, whereas granulocytes are predominantly released from the marginal pool and the lung. Results from acute psychological stress or physical exercise models corroborate the results obtained with catecholamine administration. Together, the data demonstrate that components of the innate immune system participate in the classical fight/flight response.

Acute Disease↗

Inhibition of calcium-dependent nitric oxide synthase causes ileitis and leukocytosis in guinea pigs.

As nitric oxide reduces gut epithelial permeability, we designed a study to determine if chronic nitric oxide synthase inhibition predisposes the gut to inflammation. Nitric oxide synthase (NOS) inhibitors were administered in the drinking water ad libitum, for seven days: aminoguanidine (10 micrograms/ml), a selective inhibitor of the inducible form of nitric oxide synthase; and NG-nitro-L-arginine methyl ester (L-NAME, 1, 10, and 100 micrograms/ml), which inhibits both the constitutive and inducible forms. Control animals drank tap water only or water with D-NAME, the inactive enantiomer. After one week, circulating leukocyte count and tissue myeloperoxidase activity were measured. L-NAME (100 micrograms/ml), but not D-NAME or aminoguanidine, caused a twofold increase in a circulating leukocyte numbers. This increase in leukocyte numbers was time- and dose-dependent, but the differential count was unaltered. Tissue myeloperoxidase (MPO) activity as an index of granulocyte infiltration was comparable in all groups in the stomach, jejunum, colon, liver, lung, kidney, heart, and skeletal muscle. However, ileal MPO activity was elevated threefold in the L-NAME-(100 micrograms/ml) treated group (P < 0.05). Results in the D-NAME and aminoguanidine groups were similar to controls. L-NAME administration resulted in a reduction in NOS activity ([14C]citrulline formation) in the ileum but not jejunum, whereas cGMP levels were elevated in both ileum and jejunum. We conclude that chronic inhibition of the constitutive form of nitric oxide synthase predisposes the ileum to inflammation and leads to a progressive leukocytosis.

Amino Acid Oxidoreductases↗

Prognostic significance of marked leukocytosis in hospitalized patients.

STUDY OBJECTIVE: To identify the prognostic significance of marked neutrophilic leukocytosis (MNL), defined as white blood cell (WBC) count of greater than or equal to 25,000/microL and greater than or equal to 80% mature neutrophils by differential count, in hospitalized patients. DESIGN: A central laboratory computer identified all consecutive patients with MNL in a one-month period. After exclusion of outpatients, neonates, and patients with hematologic malignancies or incomplete records, the remaining patients were studied and followed until discharge or death. SETTING: Inpatient services of a 988-bed tertiary care teaching hospital. PATIENTS: 72 inpatients with MNL. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Associated conditions and hospital mortality were recorded. Potentially confounding or contributing variables, including age, sex, intensive care unit stay, infection, acidosis, uremia, malignancy, hemorrhage, surgery or invasive procedure, peak WBC count, and duration of MNL, were examined by multivariate analysis with mortality as the outcome variable. Overall hospital mortality was 29% in study patients. A higher peak WBC count (p = 0.0046), increasing age (p = 0.0058), MNL duration of greater than one day (p = 0.025), and lack of associated invasive procedures (p = 0.04) were jointly significant in the prediction of mortality in MNL patients. CONCLUSIONS: The results confirm the impression of poor outcome associated with MNL and validate the use of MNL data in indices of severity of illness and as a prognostic marker for hospitalized patients regardless of underlying disease.

Adolescent↗

Spurious hyperkalaemia associated with severe thrombocytosis and leukocytosis.

A patient with marked thrombocytosis and leukocytosis associated with myelofibrosis was found to have spurious hyperkalaemia caused by in vitro cell lysis. Initial failure to recognize the cause of the hyperkalaemia led to an inappropriate and potentially harmful intervention in an effort to optimize the patient's preoperative status.

Aged↗