Background: Glucocorticoids (GCs) may cause leukocytosis via several mechanisms. This study was conducted to examine the impact of a single dose of systemic GCs on total white blood cell count (WBC), absolute neutrophilic count (ANC), and absolute lymphocytic count (ALC) in hospitalized adults without bacterial infections. Methods: This retrospective cohort study was carried out in a university hospital. Hospitalized patients 18 years of age or older who received a single dose of a systemic GC were included. Baseline blood cell counts prior to GC administration were required for subjects to be included in the study. Glucocorticoids included in this study were oral or intravenous methylprednisolone and hydrocortisone and oral prednisone. Results: A total of 99 patients were included in the study. After the administration of a single GC dose, ALC began to drop significantly as early as the interval of 0 - <6 hours [median (IQR), 0.90 (0.60-1.10), P=0.011]. ANC increased significantly as early as the interval of 6 - <12 hours [median (IQR), 6.22 (4.45-7.33), P=0.049] and continued to be significantly increased from baseline up to 42 hours from GC administration. Total WBC counts significantly decreased in the 6 - <12 hours interval [median(IQR), 6.90 (5.15-8.85) P=0.03] and then increased significantly in the12 - <18 hours interval [median(IQR), 8.80 (6.50-11.95), P= 0.002]. This effect on total WBC count continued to be significant until the 36 - <42 hours interval [median (IQR), 10.55 (7.23-13.03), P<0.001] Conclusion: ANC, followed by WBC count increase significantly after a single dose administration of GC in hospitalized patients within 12 hours of a single GC dose. Variability in timing and extent of leukocyte and ANC elevation was seen. A decrease in WBC and ALC was seen within the first few hours of GC dose. High doses of GC and autoimmune disease were associated with greater elevation in WBC counts.

Thesis (M.S.)--Case Western Reserve University, 2008. / [School of Medicine] Department of Clinical Research. Includes bibliographical references.

Background and objecttives: The aims of this study were to determine whether: i) diseases in hospitalised South African dogs with leukocyte counts ≥35x109/l were different from, ii) hospitalisation time longer than and mortality rate higher than control dogs; iii) glucocorticoid treatment contributed to significant leukocytosis; iv) hypoalbuminaemia and thrombocytopaenia added prognostic value, v) high leukocyte counts predict complicated babesiosis. Methods: Records were examined from 182 hospitalized dogs with a WBC ≥35Χ109/l (LCG) and 179 hospitalized dogs with 3.0 ≤ WBC ≤30Χ109/l and immature neutrophil count ≤0.5Χ109/l (CG). Diagnoses were assigned to groups Infection, Immune-mediated; Necrosis; Neoplasia; Babesiosis; Other. Results: WBC, neutrophil count, lymphocyte count and monocyte count were higher in LCG than CG (p<0.0001) while eosinophil count was lower in LCG than CG (p<0.0001). Hct, platelet count, and serum albumin concentration were lower in LCG than CG (p<0.0001). There was no difference in neutrophil count, lymphocyte or monocyte count between glucocorticoid-treated and non-glucocorticoid-treated dogs in LCG. Disease frequencies differed significantly (LCG > CG) in Infection, Necrosis, Babesiosis and immune mediated haematological disease groups. The frequency of complicated babesiosis cases was higher in LCG in than in CG (p < 0.0001). Time of hospitalization was significantly (p<0.0001) longer for LCG than for CG. There was a significant relationship between total and immature neutrophil count and survival (p=0.01) Conclusions: Leukocytosis is more likely to indicate infection, complicated babesiosis, immune mediated hematological disease or necrosis in the population of dogs examined. Hypoalbuminaemia and thrombocytopaenia in an animal with significant leukocytosis is not prognostically useful, while the combination of total and immature neutrophil count is. In hospitalized animals with severe leukocytosis, glucocorticoid treatment does not increase the leukocyte count. / Dissertation (MMedVet)--University of Pretoria, 2007. / Companion Animal Clinical Studies / unrestricted

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Made available in DSpace on 2014-06-11T19:27:56Z (GMT). No. of bitstreams: 0 Previous issue date: 2009-02-27Bitstream added on 2014-06-13T19:15:38Z : No. of bitstreams: 1 moreto_f_me_botfm.pdf: 265961 bytes, checksum: 5fc3e5d57d7b4103b09769cd9aee78a0 (MD5) / Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) / A proteína C-reativa (PCR) é um marcador muito utilizado na caracterização do estresse inflamatório, uma co-morbidade frequentemente associada à presença de síndrome metabólica (SM) e seus componentes diagnóstico. Verificar os determinantes do estresse inflamatório associado à presença de SM e caracterizar suas causas. Participaram do estudo 435 indivíduos adultos acima de 40 anos de idade triados clinicamente para programa de mudança de estilo de vida. Foram submetidos a avaliações nutricionais, médica, de aptidão física e laboratorial e classificados como portadores ou não de SM conforme os critérios da NCEP-ATPIII modificado para valores de glicemia maiores que 100mg/dL. Os valores de PCR foram distribuídos em quartis, compondo três grupos (G1 <p25; G2 p25-p75; G3 >p75). Os testes estatísticos utilizados para processamento dos dados foram a descritiva, teste t de Student, ANOVA one-way, correlações de Pearson e razão de chance (Odds ratio - OR) com significância para p<0,05. Resultados: entre os indivíduos com as maiores concentrações de PCR (G3>p75) a prevalência de SM foi maior. Dentre os componentes da SM, as maiores concentrações de PCR foram observadas para circunferência abdominal (CA) e glicemia (Glic) com razão de chance (OR) para predizer o risco para elevação das concentrações de PCR de OR= 3,16 (IC=1,70 – 5,88) e OR=2,43 (IC=1,42 – 4,18) respectivamente. A contagem de leucócitos e a atividade da enzima hepática γ-glutamil transferase (Gama-GT) também apresentaram OR significante. Os valores de consumo máximo de oxigênio (VO2max) foram menores nos indivíduos com maiores concentrações de PCR. A SM cursa com estado pró-inflamatório induzido principalmente pelo acúmulo adiposo central e elevação da glicemia com participação importante do sedentarismo. / C-reactive protein (CRP) is a useful biomarker to characterize inflammatory stress, a pathological process associated with metabolic syndrome (MS) and its diagnosis components. To verify the determinants of the inflammatory stress associated with metabolic syndrome and characterize their causes. 435 adults subjects, ≥ 40 years old, were accessed to a life-stile change program. They were assessed nutritional, medical, physical and laboratorial and then classified with or without MS following the NCEP-ATPIII criteria, with glycemic abnormal values ≥ 100mg/dL. CRP values were distributed into groups: G1 (<p25), G2 (p25-p75) and G3 (>p75). Statistical tests used were descriptive, ANOVA one-way, Pearson’s correlation and Odds Ratio (OR), with statistical significance to p<0,05. Prevalence of MS was higher in those subjects with elevated CRP levels. Waist circumference and glucose were associated with higher CRP levels, with OR 3,16 (IC=1,70 – 5,88) and 2,43 (IC=1,42 – 4,18), respectively. Leukocytes counts and γ-glutamil transferase also presented significant OR. Cardiorespiratory fitness was lower in those subjects with higher CRP levels. The major determinants of inflammatory stress associated with MS were elevated adipose tissue deposition and hyperglycemia, with participation of the sedentarism.

Orientador: Roberto Carlos Burini / Banca: Wilson Luvizotto Medina / Banca: Kátia Cristina Portero McLellan / Resumo: A proteína C-reativa (PCR) é um marcador muito utilizado na caracterização do estresse inflamatório, uma co-morbidade frequentemente associada à presença de síndrome metabólica (SM) e seus componentes diagnóstico. Verificar os determinantes do estresse inflamatório associado à presença de SM e caracterizar suas causas. Participaram do estudo 435 indivíduos adultos acima de 40 anos de idade triados clinicamente para programa de mudança de estilo de vida. Foram submetidos a avaliações nutricionais, médica, de aptidão física e laboratorial e classificados como portadores ou não de SM conforme os critérios da NCEP-ATPIII modificado para valores de glicemia maiores que 100mg/dL. Os valores de PCR foram distribuídos em quartis, compondo três grupos (G1 <p25; G2 p25-p75; G3 >p75). Os testes estatísticos utilizados para processamento dos dados foram a descritiva, teste t de Student, ANOVA one-way, correlações de Pearson e razão de chance (Odds ratio - OR) com significância para p<0,05. Resultados: entre os indivíduos com as maiores concentrações de PCR (G3>p75) a prevalência de SM foi maior. Dentre os componentes da SM, as maiores concentrações de PCR foram observadas para circunferência abdominal (CA) e glicemia (Glic) com razão de chance (OR) para predizer o risco para elevação das concentrações de PCR de OR= 3,16 (IC=1,70 - 5,88) e OR=2,43 (IC=1,42 - 4,18) respectivamente. A contagem de leucócitos e a atividade da enzima hepática γ-glutamil transferase (Gama-GT) também apresentaram OR significante. Os valores de consumo máximo de oxigênio (VO2max) foram menores nos indivíduos com maiores concentrações de PCR. A SM cursa com estado pró-inflamatório induzido principalmente pelo acúmulo adiposo central e elevação da glicemia com participação importante do sedentarismo. / Abstract: C-reactive protein (CRP) is a useful biomarker to characterize inflammatory stress, a pathological process associated with metabolic syndrome (MS) and its diagnosis components. To verify the determinants of the inflammatory stress associated with metabolic syndrome and characterize their causes. 435 adults subjects, ≥ 40 years old, were accessed to a life-stile change program. They were assessed nutritional, medical, physical and laboratorial and then classified with or without MS following the NCEP-ATPIII criteria, with glycemic abnormal values ≥ 100mg/dL. CRP values were distributed into groups: G1 (<p25), G2 (p25-p75) and G3 (>p75). Statistical tests used were descriptive, ANOVA one-way, Pearson's correlation and Odds Ratio (OR), with statistical significance to p<0,05. Prevalence of MS was higher in those subjects with elevated CRP levels. Waist circumference and glucose were associated with higher CRP levels, with OR 3,16 (IC=1,70 - 5,88) and 2,43 (IC=1,42 - 4,18), respectively. Leukocytes counts and γ-glutamil transferase also presented significant OR. Cardiorespiratory fitness was lower in those subjects with higher CRP levels. The major determinants of inflammatory stress associated with MS were elevated adipose tissue deposition and hyperglycemia, with participation of the sedentarism. / Mestre

IntroduÃÃo: Diversos mecanismos tÃm sido propostos para explicar a Osteonecrose dos Maxilares induzida por Bisfosfonatos (OMB), mas nÃo hà consenso acerca do desenvolvimento fisiopatolÃgico dessa condiÃÃo. Objetivo: Avaliar o efeito de alteraÃÃes sistÃmicas e hematolÃgicas que possam interferir no desenvolvimento de OMB. MÃtodos: ApÃs trÃs infusÃes venosas semanais consecutivas de Ãcido ZoledrÃnico (AZ) (0,04, 0,20, 1,00mg/kg) ou salina (controle), ratos Wistar machos (n=6-7) tiveram seus primeiros molares inferiores esquerdos extraÃdos quatro semanas apÃs a Ãltima administraÃÃo. Uma semana apÃs exodontia foi realizada infusÃo extra de AZ ou salina (controle), sendo os animais sacrificados 28 dias apÃs a exodontia. Os animais foram pesados e foi coletado sangue semanalmente (anÃlise de variaÃÃo de peso corpÃreo e anÃlise hematolÃgica, respectivamente), alÃm disso, mandÃbulas, fÃgado, baÃo, rins e estÃmago foram removidos e analisados microscopicamente. Resultados: Obervou0se necrose Ãssea nos animais tratados com 0,20 e 1,00 mg/kg de AZ sob os aspectos radiogrÃficos e histolÃgicos (p<0.0001). Nesses dois grupos houve aumento significativo do nÃmero de leucÃcitos circulantes (p<0.0001) em relaÃÃo ao grupo controle e os Ãndices de anemia (p<0.0001) tambÃm se mostraram superiores. NÃo houve toxicidade hepÃtica e renal, no entanto o baÃo apresentou nÃmero aumentado de deposiÃÃo de pigmentos de hemossiderina nos dois grupos experimentais (p=0.0004), os quais apresentaram tambÃm significante alteraÃÃo inflamatÃria gÃstrica (p=0.0168). ConclusÃo: a OMB està diretamente associada a leucocitose, anemia e provÃvel toxicidade sistÃmica (hematolÃgica e ÃrgÃo-especÃfica). / Introduction: Several mechanisms have been proposed to explain the induced Osteonecrosis of the Jaw Bisphosphonates (OMB), but there is no consensus about the pathophysiological development of this condition. Objective: To evaluate the effect of systemic and hematologic changes that may interfere with the development of OMB. Methods: After three consecutive weekly venous infusions of zoledronic acid (AZ) (0.04, 0.20, 1,00mg / kg) or saline (control), male Wistar rats (n = 6-7) had their first molars left extracted four weeks after the last administration. A week after extraction extra infusion of AZ or saline (control) was performed, and the animals were sacrificed 28 days after the extraction. The animals were weighed and blood was collected weekly (analysis of variance in body weight and hematologic analysis, respectively) furthermore jaws, liver, spleen, kidney and stomach were removed and examined microscopically. Results: Obervou0se bone necrosis in animals treated with 0.20 and 1.00 mg / kg of AZ under the radiographic and histological aspects (p <0.0001). In both groups there was a significant increase in the number of circulating leukocytes (p <0.0001) compared to the control group and the rates of anemia (p <0.0001) were also higher. There was no liver and kidney toxicity, however the spleen showed increased numbers of hemosiderin pigment deposition in both experimental groups (p = 0.0004), which also showed a significant gastric inflammatory changes (p = 0.0168). Conclusion: The OMB is directly associated with leukocytosis, anemia and probable (hematologic and organ-specific) systemic toxicity.

Background: Non-small cell lung cancer (NSCLC) is the cancer disease with the highest mortality globally. About 75% of NSCLC patients are diagnosed in an advanced stage where surgical treatment is not possible. For patients with locally advanced disease without distant metastases, the treatment of choice is curatively intended radiotherapy. However, this treatment has considerable side effects and many patients relapse. To individualize the treatment strategy for these patients, it is essential to have as much prognostic information as possible. The aim of this thesis was to investigate the prognostic significance of histology and pre-treatment hematopoietic blood parameters. Material and Methods: Data were collected retrospectively for NSCLC patients treated between 1990 and 2000 with curatively intended radiotherapy. The data were obtained by manually searching patient records from all radiation oncology departments in Sweden. The prognostic significance of histology, and pre-treatment levels of hemoglobin (Hgb), white blood cells (WBC) and platelets (Plt) were analyzed in relation to overall survival using univariate and multivariate statistical methods. These prognostic factors were further analyzed in a chemoradiation patient cohort and in a cohort of patients with recurrent NSCLC treated with palliative docetaxel, or the insulin-like growth factor 1 receptor (IGF-1R) modulator AXL1717. Results: In the cohort of NSCLC patients treated between 1990 and 2000, squamous cell carcinoma (SCC) histology and pre-treatment anemia (Hgb &lt;110 g/L), leukocytosis (WBC &gt; 9.0 x109/L), and thrombocytosis (Plt &gt;350 x109/L) were independent prognostic factors for shorter overall survival. However, in the chemoradiation cohort only thrombocytosis retained independent prognostic significance in a multivariate analysis. In the cohort of patients with recurrent disease treated with palliative systemic therapy, only leukocytosis was significantly associated with worse survival. Conclusions: Routine pre-treatment hematopoietic blood parameters—together with other prognostic factors such as disease stage and performance status—can provide decision-making support when individualizing treatment of NSCLC. The prognostic role of histology is unclear and further research is warranted to determine its significance.

Primär myelofibros (PMF) är en typ av myeloproliferativ neoplasm (MPN) som leder till en progressiv och irreversibel benmärgsfibros. En somatisk mutation, Jak2V617F, har hittats hos 50 % av patienterna med MPN i hematopoetiska stamceller. Nyligen har man upptäckt grupp 2 av medfödda lymfoida celler (ILC2) som tillhör det medfödda systemet. De är T-cellernas motsvarighet men saknar TCR-receptorn. ILC2 reagerar på IL-33 och producerar Il-13. Under de senaste åren har man upptäckt att dessa två cytokiner är inblandade i PMF. För att undersöka ILC2:s roll i utvecklingen av benmärgsfibros in vivo producerade vi retrovirus som uttrycker Jak2 vildtyp (JAK2_WT) eller Jak2V617F (JAK2_V617F) och transducerade benmärg vildtyp (BM_WT) eller benmärg ILC2KO (BM_ILC2KO). Benmärgen transplanterades till subletalt bestrålade immunbristande möss (NOG). Klinikopatologiska drag som är karakteristiska för sjukdomens första stadier, som förhöjda hemoglobinnivåer, megakaryocythyperplasi och betydande trombocytos, uppstod inte under studieperioden. Ökade vita blodkroppar uppstod dock på grund av avsaknaden av ILC2 i JAK2_V617F-expressiva möss. Flödescytometeranalys visade ursprunget till den markerade leukocytosen som ett resultat av expansionen från lymfocytlinjen, mer specifikt B-celler, men resultaten är inte entydiga eftersom de förhöjda nivåerna av B-celler kan vara en följd av ILC2 knock-out fenotypen som förvärras av närvaron av mutationen. Granulocytnivåerna från de inympade cellerna hölls låga till följd av att stamcellerna i värdens benmärg var inblandade på grund av subletal bestrålning. Vi drar slutsatsen att frånvaron av ILC2 i JAK2_V617F-uttryckta benmärgsprogenitorer har en tendens att förvärra den myeloproliferativa fenotypen i sjukdomens tidiga skeden, vilket tyder på en möjlig skyddande roll för ILC2 vid utvecklingen av MPN. / Primary myelofibrosis (PMF) is one type of myeloproliferative neoplasm (MPN) that leads to a progressive and irreversible bone marrow fibrosis. A somatic mutation, Jak2V617F has been found in 50% of patients with MPN in hematopoietic stem cells. Group 2 innate lymphoid cells (ILC2) belonging to the innate system has been recently discovered. They are the counter part of T cells but lacking the TCR receptor. ILC2 response to IL-33 producing Il-13. In recent years, the involvement of these two cytokines in the PMF has been uncovered. To investigate the role of ILC2 in the progression of bone marrow fibrosis in vivo we produced retrovirus expressing Jak2 wild-type (JAK2_WT) or Jak2V617F (JAK2_V617F) and transduced bone marrow wild type (BM_WT) or bone marrow ILC2KO (BM_ILC2KO). The bone marrow was transplanted into sub-lethally irradiated immunodeficient mice (NOG). Clinicopathologic features characteristic from the first stages of the disease, as elevated hemoglobin levels, megakaryocyte hyperplasia and significant thrombocytosis did not emerge during the study period. However, increased in white blood cells arise from the absence of ILC2 in JAK2_V617F expressing mice. Flow cytometer analysis revealed the origin of the marked leukocytosis as a result of the expansion from the lymphocyte lineage, more specifically B cells, but the results are inconclusive as the elevated levels of B-cells could be a consequence of the ILC2 knock-out phenotype aggravated by the presence of the mutation. Granulocyte levels from engrafted cells were kept low because of the involvement of host bone marrow stem cells due to sublethal irradiation. We conclude that the absence of ILC2 in JAK2_V617F-express bone marrow progenitors has a tendency to aggravate the myeloproliferative phenotype in the early stages of the disease, indicating a possible protective role of ILC2 in the development of MPNs.

No description available.