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The modified leukocytosis promoting factor (LPF)-test: a valuable supplement to the mouse weight gain (MWG)-test in toxicity control of whole cell pertussis vaccine.

For the safety testing of pertussis vaccine, many in vivo assays have been developed, but none of these assays, except the Mouse Weight Gain (MWG)-test, are obligatory. Leukocytosis Promoting Factor (LPF) test, performed in mice, is one of the tests to examine the toxicity. However, due to lack of standardization, this test has not been implemented in the regular safety testing of the vaccine. Our investigations demonstrate that the LPF-test becomes more reproducible and sensitive if preparations are administered subcutaneously on day 0 and and counting of the leukocytes are done on day 6. Therefore, it is suggested to include the revised LPF-test in the quality control panel for the assessment of the toxicity of whole-cell pertussis vaccine.

Animals↗

Leukocytosis is a poor indicator of acute osteomyelitis of the foot in diabetes mellitus.

The purpose of this article is to describe the frequency of leukocytosis and elevated erythrocyte sedimentation rate in a series of diabetics with acute foot infections and osteomyelitis due to neuropathic foot ulcerations. The authors reviewed the admission records of 28 type II diabetic patients admitted to University Hospital in San Antonio, Texas between January 1, 1990 and December 30, 1992 with acute osteomyelitis of the foot secondary to neuropathic ulceration. The mean white blood cell count on admission for all subjects studied was calculated at 11.9 +/- 5.4 x 10(3) cells/mm3. Of all white blood cell counts collected for patients admitted with acute osteomyelitis of the foot, 54% were within normal limits. Erythrocyte sedimentation rate was elevated in 96% of patients. Oral temperature was normal in 82% of patients. The authors conclude that a normal white cell count should not deter one from taking appropriate action to mitigate the propagation of a potentially limb-threatening foot infection.

Acute Disease↗

Impact of solid organ transplantation and immunosuppression on fever, leukocytosis, and physiologic response during bacterial and fungal infections.

Immunosuppressed solid organ transplant patients may exhibit a blunted response to infection compared to non-transplant patients. To test this hypothesis, we prospectively identified all episodes of bacterial and fungal infection on the in-patient abdominal organ transplant service in our hospital, in 1997, and compared them to infected general surgery and trauma admissions treated simultaneously on the same wards. Eighty-two infections occurred in transplant patients versus 463 in non-transplant patients. Transplant patients demonstrated an overall greater physiologic response [Acute Physiology and Chronic Health Evaluation (APACHE II) and Acute Physiology Scores (APS) at the time of infection of 17.0+/-0.7 and 10.3+/-0.6, respectively, vs. 12.2+/-0.4 and 8.0+/-0.3 for non-transplant patients, p < 0.003], with a similar maximum temperature (38.0+/-0.1 vs. 38.2+/-0.1 degrees C, p = 0.2) and white blood cell (WBC) count (12.1+/-1.0 vs. 13.9+/-0.4 k/mL, p = 0.08). Upon further analysis of subgroups, patients receiving mycophenolate or azathioprine had significantly lower maximum temperatures (37.9+/-0.2 degrees C) and WBC counts (11.0+/-0.9 k/mL) when compared to non-transplant patients, while steroids appeared to have little effect on the systemic inflammatory response. Overall mortality was similar between groups. In general, solid organ transplant recipients exhibit a physiologic response to bacterial or fungal infection (as measured by the APS) at least as great as that seen in non-transplant surgical patients, although mycophenolate and azathioprine appear to slightly depress the ability to respond with fever and leukocytosis. None of these differences appeared to affect overall mortality.

APACHE↗

High concentration of leptin stimulates myeloid differentiation from human bone marrow CD34+ progenitors: potential involvement in leukocytosis of obese subjects.

OBJECTIVE AND DESIGN: As well as its involvement in control of adipose mass and body energy balance, several reports suggest a link between leptin and hemopoiesis. To test its putative role in human hemopoiesis, we developed a homologous system, ie recombinant human leptin treatment of purified CD34+ progenitors from adult human bone marrow. RESULTS: Leptin (50-100 ng/ml) significantly stimulated the appearance of granulocyte-macrophage colonies in the presence or absence of erythropoietin. The concentration of leptin required for this effect was rather high but within the range of plasma leptin levels observed in obesity. Two results further support the hypothesis that leptin may be involved in the leukocytosis associated with obesity: (i) leptin concentrations in bone marrow and plasma of subjects studied were highly correlated; (ii) leptin and leukocyte count were correlated only in obese subjects. Paracrine effects of locally released leptin from bone marrow adipocytes could also be involved in the regulation of hemopoiesis, a hypothesis supported by marrow immunocytochemistry revealing the close association of CD34+ cells with adipocytes and by previous demonstration that leptin is secreted at a high level by these cells. CONCLUSION: These results indicate that leptin acts on human multilineage CD34+ cells and that high plasma leptin levels associated with obesity could participate in the differentiation of granulocytes from hemopoietic progenitors.

Adult↗

Studies on the leukocytosis and lymphocytosis induced by Bordetella pertussis. I. Radioautographic analysis of the circulating cells in mice undergoing pertussis-induced hyperleukocytosis.

By the use of radioautographic techniques it was shown that the lymphocytosis induced by Bordetella pertussis in mice was not caused by an increased production of lymphocytes but was primarily due to the entry into the circulation of mature cells from tissue pools. The accompanying polymorphonuclear leukocytosis was due to both proliferation of myeloid elements and entry of mature cells from tissue reserves, with the former the predominant mechanism.

Animals↗

Cytokine profiles in cerebrospinal fluid of human immunodeficiency virus-infected patients with cryptococcal meningitis: no leukocytosis despite high interleukin-8 levels. University of Zimbabwe Meningitis Group.

Cytokine levels were studied in the cerebrospinal fluid (CSF) of 16 adults with cryptococcal meningitis (CM). Low levels of tumor necrosis factor (TNF)-alpha and interferon-gamma, high levels of interleukin (IL)-1beta, IL-6, and IL-8, and the presence of IL-10 were documented. There were no significant differences in levels of TNF-alpha and interferon-gamma for CM and control patients. Mean CSF levels of IL-1beta (139.5 pg/mL), IL-6 (346 pg/mL), IL-8 (1160 pg/mL), and IL-10 (9.27 pg/mL) were significantly (P < .01) elevated in CM patients compared with levels in control patients. Despite the high CSF levels of IL-8, minimal leukocytosis was seen. Significant correlations between cryptococcal antigen titers and IL-10 levels (r = .8, P < .05), protein and cryptococcal antigen titer (r = .9, P < .05), and protein and IL-10 levels (r = .8, P < .05) were found.

AIDS-Related Opportunistic Infections↗

Lipid deficiencies, leukocytosis, brittle skin--a lethal syndrome caused by a recessive mutation, edematous (oed), in the mouse.

A new neonatal lethal mutation in the mouse with pleiotropic effects, edematous (oed), arose spontaneoutosomal recessive mode of inheritance. The external phenotypic characteristics include a generally bloated appearance, shiny celophane-like skin, and distal hematomata of the extremities. Internally, no gross or histological abnormalities could be identified, with the exception of a striking leukocytosis. Biochemical analysis revealed a severe disturbance of lipid metabolism. Deficiencies in the VLDL, LDL, and the HDL lipoprotein fractions have been found in the mutant plasma. In addition, all serum lipids are markedly decreased. However, in the mutant liver, only triglycerides are significantly decreased; total liver cholesterol and phospholipid values are within normal limits. The primary biochemical defect as well as the causal relationship between the striking abnormalities of lipid metabolism and those of skin and blood are unknown at this time.

Animals↗

Leukocytosis in children with Escherichia coli O157:H7 enteritis developing the hemolytic-uremic syndrome.

BACKGROUND: Fewer than 10% of children with Escherichia coli O157:H7 enteritis develop hemolytic-uremic syndrome (HUS). OBJECTIVE: To determine whether circulating leukocytes are independent risk markers of developing HUS during E. coli O157:H7 enteritis. METHODS: We reviewed the charts of all children with culture-proved E. coli O157:H7 infections seen at Sainte-Justine Hospital between 1987 and 1997. Epidemiologic data, laboratory indices and circulating leukocytes counts were noted. HUS diagnosis was validated with independent HUS patient lists from the pediatric nephrology services of tertiary care hospitals in the Montreal metropolitan area. The date of onset of enteritis was determined by two independent observers. Leukocyte counts were compared among the following independent groups: (1) uncomplicated O157:H7 enteritis (Group 1); (2) O157:H7 enteritis with the subsequent development of HUS (Group 2); (3) HUS already present at the time of medical consultation (Group 3). RESULTS: There were 369 children with E. coli O157:H7 infection. A complete blood count was not performed in 114 (31%) patients. Observers disagreed on the date of onset of gastroenteritis in 34 (9%) children only (kappa 0.92). The study population thus included 221 patients: Group 1, n = 161; Group 2, n = 27; and Group 3, n = 33. Patients developing HUS (Group 2) presented greater total leukocyte (P < 0.008), polymorphonuclear (P < 0.008) and monocyte (P < 0.07) counts than those with an uncomplicated course (Group 1). Logistic regression analysis showed that young age [odds ratio (OR), 0.98; 95% confidence interval (CI), 0.96 to 0.99], duration of enteric prodrome < or =3 days (OR 4.8, 95% CI 1.13 to 20.7) and initial leukocytosis (OR 1.22, 95% CI, 1.11 to 1.35) were independent predictors of HUS. CONCLUSIONS: Based on the variables identified above, further studies are needed to determine whether the inflammatory response of the host represents only a marker of the severity of gastrointestinal infection or whether, alternatively, it is a pathophysiologic factor that leads to HUS.

Biomarkers↗

Fever and leukocytosis related to terconazole vaginal suppository.

We describe a 22-year-old woman who developed fever, shaking chills, and leukocytosis after insertion of a terconazole (80 mg) vaginal suppository for mild vaginal candidiasis. The patient became afebrile and asymptomatic 24 hours after hospital admission without antibiotic therapy. More experience with terconazole is needed before it can be considered as safe as other imidazole derivatives that have been available for more than 15 years.

Administration, Intravaginal↗

CD2+ acute promyelocytic leukemia is associated with leukocytosis, variant morphology and poorer prognosis.

The T cell-lineage marker CD2 is sometimes expressed in acute promyelocytic leukemia (APL), and CD2 expression is reported to correlate with some clinical characteristics. However, the significance of CD2 expression in APL has not been fully elucidated. We evaluated CD2 expression in APL treated by the same treatment strategy in a single institute, and whether it had any special characteristics. Among 29 APL, 6 were positive for CD2. Patients with CD2+ APL tended to have a higher leukocyte count than CD2- APL (34.5 +/- 13.1/l vs. 6.8 +/- 2.1/l), morphological characteristics as variant-APL (50 vs. 0%). They also showed poor clinical prognosis. The CR rate of CD2- APL was 87.0% while that of CD2+ APL was 50 %. The mortality was 13.0 and 66.7%, respectively, and the survival rate was significantly lower in CD2+ APL. CD2 expression was proven to be a risk factor associated with death in addition to the morphological characteristics of variant-APL and leukocytosis. These results indicated that CD2 expression might have a significant impact on the prognosis of APL. Whether CD2+ APL should be characterized as a special clinical entity should be discussed in a larger patient population.

Adult↗

LPS-induced microvascular leukocytosis can be assessed by blue-field entoptic phenomenon.

Administration of low doses of Escherichia coli endotoxin [a lipopolysaccharide (LPS)] to humans enables the study of inflammatory mechanisms. The purpose of the present study was to investigate whether the blue-field entoptic technique may be used to quantify the increase in circulating leukocytes in the ocular microvasculature after LPS infusion. In addition, combined laser Doppler velocimetry and retinal vessel size measurement were used to study red blood cell movement. Twelve healthy male volunteers received 20 IU/kg iv LPS as a bolus infusion. Outcome parameters were measured at baseline and 4 h after LPS administration. In the first protocol (n = 6 subjects), ocular hemodynamic effects were assessed with the blue-field entoptic technique, the retinal vessel analyzer, and laser Doppler velocimetry. In the second protocol (n = 6 subjects), white blood cell (WBC) counts from peripheral blood samples and blue-field entoptic technique measurements were performed. LPS caused peripheral blood leukocytosis and increased WBC density in ocular microvessels (by 49%; P = 0.036) but did not change WBC velocity. In addition, retinal venous diameter was increased (by 9%; P = 0.008), but red blood cell velocity remained unchanged. The LPS-induced changes in retinal WBC density and leukocyte counts were significantly correlated (r = 0.87). The present study indicates that the blue-field entoptic technique can be used to assess microvascular leukocyte recruitment in vivo. In addition, our data indicate retinal venous dilation in response to endotoxin.

Adult↗

Leukocytosis of exercise: role of cardiac output and catecholamines.

The effect of propranolol (5 mg iv) on the leukocytosis of exercise was studied in seven normal young males. Leukocyte counts, plasma norepinephrine (NE), epinephrine (E), and cardiac output were measured at rest and in the steady state of several submaximal work loads when subjects exercised on a cycle ergometer. The results in control experiments were compared with those obtained on a different day with propranolol. Propranolol decreased heart rate at all work loads (P less than 0.001) but had no effect on the increase in cardiac output at increasing work loads. Plasma NE and E levels were similar at rest and in exercise in control and propranolol studies. There was no effect of propranolol on the increase in leukocyte counts with increasing work loads. Although propranolol did not affect the increase in total leukocyte count, the increase in lymphocyte count at higher work loads was less with propranolol. We conclude that the demargination of leukocytes from the pulmonary circulation in exercise is probably a mechanical effect of the increase in cardiac output. However, we have not excluded a contribution from a humoral event that would decrease the adherence of leukocytes to endothelium during exercise. The smaller increase in lymphocytes at higher work loads in the presence of propranolol suggests that catecholamines affect the lymphocyte count over and above their effect on cardiac output.

Adult↗

Hypocomplementemia and leukocytosis in diarrhea-associated hemolytic uremic syndrome.

Sixty-eight children with diarrhea-associated hemolytic uremic syndrome (D+HUS) were retrospectively examined to assess clinical variables associated with the combination of leukocytosis and hypocomplementemia. There was a statistically significant association between the white blood cell count (WBC) and the level of the third component of the complement system (C3). Children with both a low C3 and a high WBC were significantly younger and required hospitalization for a significantly longer period of time. Although there were also trends to increases in the presence of anuria and central nervous system complications and in the duration of anuria, elevated WBC, thrombocytopenia, dialysis, and hemorrhagic colitis in children with both an elevated WBC and a low C3, these changes did not achieve statistical significance. The presence of a low C3 and an elevated WBC may indicate a subset of children with D+HUS with a more severe episode.

Age Factors↗

Spontaneous remission with cyclic leukocytosis in chronic myelogenous leukemia.

A 41-year-old female with Philadelphia chromosome (Ph1)-positive chronic myelogenous leukemia was observed for 7 years. Cytotoxic therapy was not instituted until blastic crisis developed in the last 4 months. Successive hematologic measurements revealed cyclic fluctuations in blood leukocyte and platelet counts. These cycles had an average duration of 71 days during the 43 months observed. The oscillation amplitude decreased gradually over time, followed by hematologic remission until the last 4 months. The possible relationship between long-term survival and cyclic leukocytosis is discussed.

Adult↗

Cyclic leukocytosis and long survival in chronic myeloid leukemia.

A patient with an unusually prolonged course of Ph' positive chronic myeloid leukemia is presented. His disease was marked by cyclic leukocytosis, various chromosomal aberrations and secondary thrombasthenia. In vitro culture studies and granulocyte-macrophage colony stimulating factor (GM-CSF) production were consistent with responsiveness of the leukemic clone to GM-CSF. The possible relationship between the long survival and the feedback regulation of leukopoiesis is raised.

Blood Platelets↗

Chronic myelogenous leukemia with elevated leukocyte alkaline phosphatase, positive indirect Coombs' test, neutrophilic leukocytosis and unusual cytogenetical findings.

An unusual case of chronic myelogeous leukemia (CML) is reported which was characterized by leukocytosis without a shift to the left, elevated leukocyte alkaline phosphatase, positive indirect Coombs' test, anemia and thrombocytosis, as well as the absence of hepatosplenomegaly. The diagnosis of CML was ascertained by the presence of Philadelphia chromosome with translocation of its deleted arms on the short arms on the short arms of a chromosome No. 6. The possible relationship between the chromosomal aberration and the unusual hematological and clinical features of this case is discussed.

Adult↗

Chinese hamster ovarian cells transfected with the murine interleukin-6 gene cause hypercalcemia as well as cachexia, leukocytosis and thrombocytosis in tumor-bearing nude mice.

The effects of interleukin-6 (IL-6) in vivo were assessed by inoculating Chinese hamster ovarian (CHO) cells which were transfected with the murine IL-6 gene in nude mice. Nude mice bearing CHO cells expressing IL-6 developed hypercalcemia. Tumor-bearing mice also showed increases in white cell count, platelet count, and decreases in body weight. In nude mice carrying CHO tumors which had not been transfected with the IL-6 gene, there were no changes in these parameters. These results suggest that increased circulating concentrations of IL-6 in patients with malignant disease may contribute to a number of paraneoplastic syndromes including hypercalcemia, cachexia, leukocytosis and thrombocytosis.

Animals↗

Leukocytosis might precede in-hospital eclampsia in preeclamptic women who do not receive magnesium sulfate.

In an effort to better define preeclamptic women at risk of eclampsia, we examined the predictive value of maternal demographic characteristics and admission maternal laboratory values for the risk of subsequent development of eclampsia in preeclamptic women, who were not receiving magnesium sulfate during hospitalization. The decision to use magnesium sulfate prophylaxis was at the discretion of the treating physician. Preeclamptic women admitted throughout a 3-year period and treated with a protocol exempting magnesium sulfate therapy were retrospectively included (n=497). Maternal data at admission were recorded and analyzed. Eight women developed an eclamptic seizure during subsequent hospital follow-up. Logistic regression models were used to assess the independent predictive role of each variable on the development of eclampsia. Lower serum fibrinogen values, increased leukocyte counts, and increased diastolic blood pressure at admission were independent predictors of a subsequent in-hospital eclamptic seizure. An initial diastolic blood pressure >or=120 mm Hg, blood leukocyte count >16,000/microL, and serum fibrinogen value <450 mg/dL were associated with a 25.4-, 7.1-, and 26.6-fold increased risk of eclampsia, respectively. We conclude that marked leukocytosis and diastolic blood pressure increment might precede the development of eclampsia. Serum fibrinogen concentrations >450 mg/dL seem to be protective for eclampsia. The association between inflammation and eclampsia merits further investigation.

Adult↗