White Blood Cells Of Patients Research Articles

Leukopenia Associated with Paroxetine Use

Objective: To report a case of leukopenia associated with paroxetine treatment. Case Summary: A 44-year-old white female with a history of anemia secondary to heavy menses, anxiety, depression, and current tobacco dependence presented with general symptoms of fatigue and blurred vision. The patient's medications at the time of the initial visit were ferrous sulfate 325 mg twice a day and paroxetine 20 mg/day. Three years prior to the initiation of paroxetine, the patient's documented white blood cell (WBC) count was 7.4 × 103/ μL with normal differential and hemoglobin was 10.5 g/dL; on presentation, laboratory test results were WBC count 1.3 × 103/ μL, red blood cell count 1.78 × 106/ μL, hemoglobin 4.5 g/dL, hematocrit 15.1%, and platelets 248 × 103/ μL. Three months after discontinuation of paroxetine, the patient's WBC count was 4.4 × 103/ μL. Discussion: Paroxetine and other antidepressants have not been known to cause adverse hematologic effects that can be seen with other antipsychotics, namely, clozapine. The use of the Naranjo probability scale indicated a probable relationship between leukopenia and paroxetine therapy in this patient. Based on a MEDLINE search (February 12, 2007), there are limited data on leukopenia as an adverse event of paroxetine. We found this to be a unique case of leukopenia suspected to be secondary to extended use of low-dose paroxetine. Conclusions: Although leukopenia caused by paroxetine and other medications with serotonergic effects appears to be uncommon, physicians and pharmacists should be aware of this rare but potentially serious adverse event.

A case of maxillary gingival squamous cell carcinoma producing granulocyte colony-stimulating factor (G-CSF)

A case of gingival squamous cell carcinoma producing G-CSF is reported.A 78-year-old man presented with a granulated mass in the right upper gingiva. Pathological examination of a biopsy specimen revealed a welldifferentiated squamous cell carcinoma. Laboratory ndings on admission showed marked leukocytosis (12.3×103/μl).We had planned a partial resection of the maxilla under general anesthesia. However, the operation was canceled on the originally scheduled day, because of fever and leukocytosis (13.6×103/μl).After 10 days, tumor resection was performed under general anesthesia, despite fever and leukocytosis (18.3×103/μl). Postoperatively, the patient's white blood cell count soon decreased, and the fever disappeared.Immunohistochemically staining with monoclonal anti-G-CSF antibody was positive. The serum G-CSF concentration reached an abnormally high level preoperatively, which soon decreased to the normal range postoperatively.We diagnosed the disease as gingival squamous cell carcinoma producing G-CSF.

Acute Respiratory Failure Associated with Cryptococcal Pneumonia and Disseminated Cryptococcosis in an AIDS Patient

A 36-year-old homosexual Mexican man was admitted to our hospital, with a 30-day history of fever and headache. Upon cerebrospinal fluid examination, the patient's white blood cell count was 1,580/L, total protein was 26 mg/dL, sugar was 17 mg/dL, and his intracranial pressure was 23 cmH2O. The patient was diagnosed with HIV (Human Immunodeficiency Virus) infection by serum Western blotting. Cryptococcus neoformans was isolated in cultures of the patient's blood and cerebrospinal fluids. Chest computerized tomography revealed diffuse reticulonodular infiltration and a ground-glass appearance in both perihilar regions, suggestive of either Pneumocystis carinii pneumonia or cryptococcal pneumonia. On the patient's 6th day in our hospital, bronchoalveolar lavage and transbronchial lung biopsy were conducted via bronchoscopy, and a pathologic examination of lung biopsy specimens revealed signs of cryptococcal pneumonia.This patient died on his 14th day in our hospital, as the result of acute respiratory failure, associated with cryptococcal pneumonia and disseminated cryptococcosis.

Evaluation of Progenitor Cells (CFU-GM, CFU-GEMM, BFU-E, CD34+ Cells) and White Blood Cells in Patients with Newly Diagnosed Diffuse Large B-Cell Lymphoma Treated with Rituximab-CHOP-14 and Supported with Pegfilgrastim.

Purpose: To investigate the behavior of CFU-GM, CFU-GEMM, BFU-E, CD34+ cells and white blood cells before and during six courses of dose-dense immune-chemotherapy (R-CHOP-14) supported by pegfilgrastim in eight patients affected with newly diagnosed diffuse large B cell lymphoma (3 men, 5 women, aged 18–51).Patients and Methods: The standard-dose CHOP chemotherapy was delivered every 14 days, preceded on day 1 by rituximab (375 mg/m2) and followed on day 3 by pegfilgrastim (6 mg per cycle). In each course of therapy, the evaluation was performed before treatment (day 1) and on days +3, +6, +8, +10 and +13. Hemopoietic progenitors were assayed in a complete StemCell medium (MethoCultTM GF H4434 StemCell, Canada) and counted with an inverted microscope after 14-day incubation at 37°C, in 5% CO2. CD34+ cells were evaluated with flow cytometry (EPICS XL, Beckman Coulter); WBC were evaluated with an automatic counter (ADVIA 120 Bayer).Results: The peak of CFU-GM, CFU-GEMM, BFU-E colonies and of CD34+ cells was invariably reached on day +13 and the highest absolute values were detected after the first cycle of therapy: CFU-GM/ml 3704±738; CFU-GEMM/ml 199±62; BFU-E/ml 8848±3499; CD34+cells/μL 33±3. In the subsequent courses, the number of both hematopoietic colonies and of CD34+ cells progressively lowered; however, the median value of CD34+ cells was still over 20/μL (range 20–35/μL) before the start of the fourth cycle of R-CHOP-14. A significant direct correlation was found between the number of CFU-GM, CFU-GEMM and BFU-E colonies and that of CD34+ cells (p<0.05). The WBC peak was constantly reached on day +6, with a mean value, all cycles considered, of 32±14 x 109/l.Comments: Hemopoietic progenitor cells kynetic showed that colonies and CD34+ cells started to increase at the WBC nadir. Most important, the level of circulating CD34+ cells at day 13 of the first three cycles of therapy was above 20/μL which we consider permissive for a productive leukaferesis; this observation adds further evidence of the pegfilgrastim progenitor cells mobilizing capacity.

Differences in the nitric oxide metabolism in streptozotocin-treated rats and children suffering from Type 1 diabetes

The relationship between diabetes mellitus Type 1 and nitric oxide (NO) synthesis was studied in multiple low-dose streptozotocin (STZ)-treated rats and diabetic children. The aim of our experimental work was to test the effect of hyperglycemic state on the level of urinary stable NO end products and on the expression of inducible nitric oxide synthase (NOS II) in white blood cells (WBC). It was also studied whether the measurements of these parameters were suitable to predict the presence of early diabetes before its onset. The occurrence of insulitis in streptozotocin-treated rats could not be clearly demonstrated. Urinary nitrite plus nitrate level significantly increased both in diabetic rats and in children compared to controls. However, the increase of the activity and the expression of inducible NOS II were only observed in rat white blood cells and this effect was prevented by insulin treatment. In human samples, less than 25% of children showed elevated NOS II expression in white blood cells without any correlation to the level of urinary NO end products and glycated hemoglobin in blood. Correlation was found only between the activity and expression of NOS II in white blood cells of patients whose white blood cells were positive for the presence of NOS II. Measurement of urinary nitrite plus nitrate content as well as the determination of NOS II expression of white blood cells in an early phase of diabetes are not suitable predictors in humans probably due to the basic differences in the mechanism of streptozotocin-induced rat and spontaneous human Type 1 diabetes.

Ochrobactrum anthropi and Delftia acidovorans to Bacteremia in a Patient With a Gunshot Wound

We describe a case of bacteremia involving Ochrobactrum anthropi and Delftia acidovorans in a patient who suffered a thoracoabdominal gunshot wound. Human infections with each of these organisms are reviewed, including microbiologic characteristics for identification and proper antimicrobial treatment. The possible sources of infection in this particular patient are discussed.

QSAR modeling and transmission electron microscopy stereology of altered mitochondrial ultrastructure of white blood cells in patients diagnosed as schizophrenic and treated with antipsychotic drugs.

Treatment of patients diagnosed as schizophrenic with antipsychotic drugs (neuroleptics) is known to cause occasional unexplained depletion of white blood cells, especially neutrophil granulocytes. It has been known for many years that neuroleptics can interfere with the mitochondrial respiratory chain in vitro. Because there has been a growing interest recently in mitochondrial targeting of drugs, and since a quantitative structure-activity relationship (QSAR) model that predicts mitochondrial accumulation of neuroleptics has been published, we investigated the effects of neuroleptics on white blood cell mitochondria. Venous blood samples were collected from both patients undergoing treatment with neuroleptics and healthy volunteers. The samples were processed for transmission electron microscopy. The resulting images of white blood cells were analyzed using stereology to compare quantitatively mitochondrial morphology in the patient and control groups. We found that in patients, but not in controls, there was swelling of mitochondria and fragmentation of the mitochondrial cristae. There also were fewer mitochondria in patients than in controls, although due to the swelling of the organelles, the volume density of mitochondria in the two groups was not significantly different. Such changes are typical of a toxic insult. Consequently, it seems plausible that, since schizophrenia is not a disease considered to affect white blood cells per se, these changes probably are due to the medication.

The Effect of Perioperative Analgesic Methods on the Postoperative Changes of White Blood Cells in Patients Undergoing Knee Replacement Surgery

Background: Postoperative pain is a major contributing factor to immune dysfunction related to changes of peripheral neutrophils, lymphocytes and monocytes. The aim of this study is to compare alterations in peripheral white blood cells perioperatively in patients under intravenous patient controlled analgesia (IVPCA) with intra-articular patient controlled analgesia (IAPCA) after general or spinal anesthesia, or epidural patient controlled analgesia (EPCA) after combined spinal epidural anesthesia for knee replacement surgery. Methods: Thirty-three patients with IVPCA and IAPCA after general anesthesia (group 1), 33 patients with IVPCA and IAPCA after spinal anesthesia (group 2), and 34 patients with EPCA after combined spinal epidural anesthesia (group 3) were reviewed. The number of peripheral neutrophils, lymphocytes and monocytes were counted preoperatively, immediate postoperatively, on the first, third and fifth postoperative day. Results: There were significant increases in neutrophils, decreases in lymphocytes, and increases in monocytes postoperatively in all the groups. However, there were no differences among the groups in three subtypes of white blood cells, except significantly low value of monocytes in the group 1 compared to that of group 2 immediate postoperatively.

Expression of apolipoprotein AI mRNA in peripheral white blood cells of patients with alcoholic liver disease

Because (i) changes in plasma and liver mRNA of apolipoprotein (apo) AI have been observed in patients with alcoholic liver disease, (ii) apo AI mRNA can be induced in non-hepatic tissues, and (iii) apolipoproteins expression is influenced by plasma colloid osmotic pressure (P(CO)) and viscosity (eta), we analyzed the Apo AI mRNA expression in the peripheral white blood cells (PWBC), P(CO), and eta in control volunteers (C), patients with liver cirrhosis (LC), and cirrhotic patients with superimposed alcoholic hepatitis (LC+AH). We found that apo AI mRNA is expressed in the PWBC in 20% of C and it is induced 1.5 fold in 66.6% of LC and 1.95 fold in 85% of LC+AH. A significant decrease of P(CO) in LC and LC + AH (14.8 +/- 2.4 and 16.2 +/- 2.4 mm Hg, respectively) compared to C (27.9 +/- 2 mm Hg) was observed. By contrast, eta was mildly increased from 1.7389 +/- 0.07 in C to 1.8022 +/- 0.154 in LC and 1.9030 +/- 0.177 in LC+AH. No significant correlation was found between P(CO) and eta with apo AI mRNA but with lipid profile. In conclusion, apo AI mRNA expression in PWBC is associated to liver disease severity and could be an indirect indicator of alcoholic liver damage.

An In-Frame Deletion of Six Amino Acids and a Point Mutation in the Disintegrin Domain of ADAMTS-13 Associates with a Case of Congenital Thrombotic Thromocytopenic Purpura.

Thrombotic thrombocytopenic purpura (TTP) is characterized by severe thrombocytopenia, hemolytic anemia, and diffuse and non-focal neurological findings. Microthrombi found in these patients are predominantly composed of platelets and von Willebrand factor (VWF). Recent studies suggest that the systemic thrombosis in TTP is mostly due to the congenital or acquired deficiency of the VWF-cleaving metalloprotease ADAMTS-13, which cleaves the ultra-large and hyperreactive VWF to smaller and less active form found in plasma. Most congenital cases of TTP have so far been identified in children. Here, we report a 60-year-old Caucasian man with a history of chronic relapsing TTP over thirty years, requiring plasma transfusion every 24 days in recent years. Repeat assays showed no ADAMTS13 activity in patient's plasma under both static and flow conditions without inhibitors being detected. We therefore examined the possible genetic defects in the ADAMTS-13 gene of this patient. Genomic DNA was extracted from patient's white blood cells and exons of ADAMTS-13 gene were amplified by polymerase chain reaction. The amplified DNA fragments were then screened for mutations by direct DNA sequencing. We identified a deletion of 18 base pairs from G1095 to G1112 (GTGCTCCAAGGGTCGCTG) in the exon10 of ADAMTS-13 gene, resulting in a deletion of six amino acids (C366 to C371) in the disintegrin domain of the metalloprotease. A point mutation (W365C) occurred immediately before the deletion due to a nucleotide realignment. The patient is heterozygote for the deletion. This is the first report of a deletion mutant (without frame shift and truncations) in the disintegrin region that has previously been demonstrated as critical for the ADAMTS-13 function by in vitro mutagenesis, epitope mapping of autoantibody to the metalloprotease in patients with adult acquired TTP, and identification of natural occurring mutations in patients with congenital TTP. Our ongoing studies are to determine the impact of these two mutations on the synthesis, release, and cleavage of ADAMTS-13.

Ultratrace voltammetric determination of DNA-bound platinum in patients after administration of oxaliplatin.

Oxaliplatin, a novel diaminocyclohexane-platinum complex, is used for the treatment of metastatic colorectal cancer. The amount of DNA-adduct formation of this drug in white blood cells of patients is determined after isolation of the DNA by density gradient centrifugation and a four-step solid phase extraction procedure. DNA is quantified by UV spectrometry, and platinum is determined after mineralization of the DNA sample by adsorptive stripping voltammetry (formazone method). It is possible to determine Pt-nucleotide ratios in clinical samples down to five Pt atoms in 10(8) nucleotides, and the dynamic range of the method covers three orders of magnitude. An absolute amount of 25 microg of DNA is sufficient for such measurements. With the method described, the time-dependent formation of oxaliplatin DNA adducts can be monitored in clinical studies, which may help us to understand inter-individual differences in the responses of patients to oxaliplatin-based therapy.

Systemic inflammation, Chlamydia pneumoniae DNA in circulating leukocytes and coronary atherosclerosis

Objective — Earlier studies have suggested that C. pneumoniae may be involved in the progression of atherosclerosis by contributing to the pathogenesis of inflammation in the vessel wall.The aim of the present study was to determine the prevalence of C. pneumoniae DNA in circulating white blood cells of patients with ischaemic heart disease and to correlate these findings with the extent of coronary atherosclerosis and serum markers of inflammation.Methods and results — In 203 consecutive patients undergoing diagnostic coronary angiography for different coronary syndromes, presence of C. pneumoniae DNA in circulating leukocytes could not be demonstrated by the polymerase chain reaction. Serum concentrations of CRP were significantly higher in patients with significant coronary artery disease compared to those with normal coronary arteries. In addition, patients with a three-vessel disease had significantly higher serum CRP compared to patients with diffuse, non-critical coronary atherosclerosis. A positive correlation was found between serum fibrinogen and serum CRP.Conclusion — In spite of a significant relation between serum CRP and the extent of atherosclerotic coronary artery disease, we were unable to detect C. pneumoniae DNA in circulating white blood cells. This observation suggests that there is no relation between circulating C. pneumoniae, systemic inflammation and extent of coronary atherosclerosis.

Molecular markers of liver regeneration in white blood cells of patients with orthotopic liver transplantation

Molecular markers of liver regeneration in white blood cells of patients with orthotopic liver transplantation

Topoisomerase I levels in white blood cells of patients with ovarian cancer treated with paclitaxel-cisplatin-topotecan in a phase I study.

Topotecan stabilizes the topoisomerase I (Topo I) cleavable complex. We measured Topo I levels in white blood cells of patients with ovarian cancer treated with topotecan. Topotecan was given i.v. daily x 5 q 3 weeks in combination with paclitaxel (1 day before topotecan) and cisplatin (just prior topotecan). Our aim was to correlate Topo I levels to pharmacokinetics and toxicity. Topo I levels were determined using Western blotting and were expressed relative to the Topo I level present in 10 microg cell lysate of the human IGROV1 ovarian cancer cell line. We found no correlation between Topo I levels and (non-)hematological toxicity. Topo I levels after the fifth topotecan infusion were significantly negatively correlated with the AUC of topotecan (R = -0.64, p = 0.026), in contrast with Topo I levels prior to (R = -0.25, p = 0.4) and after (R = -0.30, p = 0.3) the first topotecan infusion. Topo I levels after the fifth topotecan infusion (48 +/- 27%, mean +/- SD) were higher than Topo I levels prior to and after the first topotecan infusion (3.0 +/- 4.7 and 2.7 +/- 3.6%, respectively) (p = 0.001). In conclusion, we detected a significant inverse correlation between Topo I level and topotecan AUC at day 5, and we found increasing Topo I levels during a daily x 5 schedule of treatment with topotecan.

Orientia tsutsugamushi in peripheral white blood cells of patients with acute scrub typhus.

Scrub typhus, caused by Orientia tsutsugamushi, is an acute illness that occurs in many parts of Asia. Clinical manifestations range from inapparent to organ failure. Organisms disseminate from the skin to target organs, suggesting that they may enter the peripheral circulation. Here, peripheral blood cell smears from patients with acute scrub typhus were obtained before treatment and for 2 days after treatment and reacted with antibodies specific for O. tsutsugamushi. White blood cells from 3 of 7 patients with acute scrub typhus stained positively for O. tsutsugamushi. Cells containing O. tsutsugamushi were mononuclear and were detected on each day of sampling. The presence of O. tsutsugamushi in peripheral white blood cells of patients with acute scrub typhus is a new finding with clinical and pathogenic implications.

Allogeneic Marrow Engraftment Following Whole Body Irradiation in a Patient with Leukemia

A 46-year-old man with blastic crisis of chronic myelogenous leukemia was given 950 rads whole-body irradiation followed immediately by 17.6 x 109 marrow cells. The marrow donor was the patient's sister who matched the patient in 11 of 12 HL-A groups and whose leukocytes reacted to the patient's leukemic cells in mixed leukocyte culture. The patient's white blood cell count began to go up on the 13th day and marrow engraftment was confirmed by repeated cytogenetic analyses. Secondary disease with skin rash and diarrhea was evident by the end of the second week but appeared to be controlled by methotrexate. The patient then developed fever, recurrent diarrhea and pneumonitis and died 56 days after irradiation. Autopsy showed inclusion bodies typical of cytomegalovirus. There was no histological evidence of acute secondary disease nor of leukemia.

EFFECT OF SHORT-COURSE, HIGH-DOSE STEROID THERAPY IN A CHILD WITH MYELODYSPLASTIC SYNDROME

High-dose methylprednisolone (HDMP) has been shown to induce differentiation of myeloid leukemic cells with a remarkable antileukemic effect in children with various subtypes of acute myeloblastic leukemia (AML). Here the beneficial effect of short-course HDMP therapy in a child with myelodysplastic syndrome (MDS) is reported. Oral methylprednisolone sodium succinate (Prednol-L) was administered at a single daily dose of 30 mg/kg for 5 days to a 4-year-old girl with refractory anemia with excess of blasts and hypocellular bone marrow before the initiation of chemotherapy. In addition to dramatic clinical improvement, the patient's white blood cell count increased from 2.3 2 10 9 /L to 5.0 2 10 9 /L, and peripheral blood blast cells disappeared 4 days after HDMP treatment. Repeated bone marrow aspirate 1 week after the initiation of HDMP disclosed increased cellularity with no blasts. Furthermore, short-course HDMP treatment stimulated the increase in the number of peripheral blood lymphocytes and CD3 + , CD4 + , CD8 + , CD19 + , CD34 + , and NK cells. Results obtained with HDMP from the previous studies and the present case suggest that high-dose methylprednisoloneis a promising agent in the treatment of MDS and it is recommended as an initial treatment especially for MDS children with hypocellular bone marrow at presentation.

Effects of metal ions on white blood cells of patients with failed total joint arthroplasties.

In this study twenty-two patients who had revision surgery for aseptic loosening of joint prostheses were examined. The concentration in serum of soluble products of corrosion from the implant, that is, chromium (Cr), cobalt (Co), and nickel (Ni) ions, and the number of white blood cells (leucocytes, myeloid cells, lymphocyte subpopulations) were measured. Twenty patients with no implants were used as controls. The patients who had revision surgery showed normal Ni concentration whereas by statistical analysis that same patient group was shown to have serum Cr and Co levels significantly higher than those of the control. By flow cytometry, a significant decrease of leucocytes, myeloid cells, lymphocytes, and CD16 populations as found in patients versus controls whereas CD3, CD4, CD8, and CD20 positive cells were decreased, but not significantly. In the arthroplasty patients the Cr concentrations were inversely correlated with some of the immunologic parameters while no significant correlation was found between Co levels and decreased lymphocyte subpopulations. Only in revision surgery patients with high Cr concentrations did we find a significant decrease of lymphocytes, namely of CD4 and CD16 positive cells; revision surgery patients with normal Cr concentrations did not show a significant decrease of lymphocyte subpopulations. These data suggest that the presence of metal ions, especially chromium, released from prosthesis components could be associated with changes of lymphocyte subpopulations in patients with loosening of joint prostheses.

Increased expression of the CD11b/CD18 antigen on the surface of peripheral white blood cells in patients with ischemic heart disease: Further evidence for smoldering inflammation in patients with atherosclerosis

Background This study examined the availability of the CD11b/CD18 and CD62L antigens on the surface of peripheral blood leukocytes in patients with ischemic heart disease. Methods and Results The study population included 45 patients with angiographically documented ischemic heart disease admitted to our department of internal medicine and the cardiology department during 1 month (December 1997). Sixty-six healthy members of the hospital medical staff served as control subjects. Another 39 post-trauma patients who were admitted to the emergency room were also evaluated. Patients with ischemic heart disease had significantly ( P < .002) higher concentrations of CD11b/CD18 antigen on the surface of their polymorphonuclear leukocytes and monocytes (mean fluorescence intensity of 203 ± 81 and 261 ± 75, respectively) compared with the control group (mean fluorescence intensity 158 ± 68 and 211 ± 74, respectively) and to the group of patients with acute stress (mean fluorescence intensity of 146 ± 70 and 200 ± 22, respectively). Conclusions The presence of increased concentration of CD11b/CD18 suggests that circulating leukocytes are activated in patients with ischemic heart disease. This activation probably reflects the presence of an inflammatory response involving the atherosclerotic lesion and is not merely a result of acute stress. (Am Heart J 1999;138:555-9.)

The usefulness of in vivo gene expression investigations from peripheral white blood cells: a preliminary study.

Alterations of onco/tumour suppressor genes are involved in the formation of human hematological malignancies. Previously, in animal models, we demonstrated the applicability of in vivo gene expression investigations to monitor the effects of certain carcinogenic chemicals. In our present study we determined the expression of onco/suppressor genes from isolated peripheral white blood cells of patients with chronic myeloid leukaemia (CLL) and non-Hodgkin lymphoma (NHL). Gene expressions were determined by isolation of total RNA and slot blot hybridization with chemiluminescently labeled gene probes (Ha-ras, c-myc and p53) Expression levels were compared before and after treatment with a combined cytostatic protocol, containing cyclophosphamide, doxorubicin, vincristine and prednisolone (CHOP). Both the CLL and NHL group of patients exhibited significantly higher expression of the investigated genes than healthy controls. One month after the cytostatic treatment, we found considerably fewer individuals with overexpressed oncogenes than before the treatment. Our study proved that onco/tumour suppressor gene expressions could be used as biomarkers of certain hematological malignancies, and to monitor the therapeutical effect of cytostatic drugs.