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1.
BMC Infect Dis ; 23(1): 685, 2023 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-37833638

RESUMO

BACKGROUND: The intravenous form of fosfomycin, a bactericide antibiotic used to treat multiresistant bacterial infections is little prescribed. The most common reported adverse effects are hypokaliemia and hypernatremia. We describe a case of agranulocytosis, a rarely described side effect that may be fatal. CASE PRESENTATION: A 45 year-old woman was admitted to the intensive care unit for post-surgical meningitis following meningioma resection. Meropenem and vancomycin were first introduced. A DRESS-syndrom with meropenem was suspected. Neutropenia was diagnosed three days after the introduction of parenteral fosfomycin and agranulocytosis four days later. Eosinophilia was also observed. A bone marrow aspiration was performed showing a disappearance of the neutrophil granulocyte line and a significant eosinophilia. Meropenem was discontinued. Fosfomycin was maintained and filgrastim was added. As filgrastim had no effect, the relationship with fosfomycin was suspected, so it was then withheld. An increase of the neutrophil count was observed. Because of the complexity of the case, the unfavorable course of the illness and the urgent need for revision surgery, a rechallenge with fosfomycin was done followed by a decrease of the neutrophil count. CONCLUSION: This is the third paper reporting agranulocytosis induced by fosfomycin, and the first detailed description of a case. Based on chronological and semiological criteria and bibliographic data, the event was qualified as probable with the Naranjo adverse drug probability scale. Literature data is scarce. The summary of product characteristics mentions that only a few cases of transient neutropenia and agranulocytosis have been reported. An analysis of the FDA Adverse Event Reporting System Database highlighted a higher than expected frequency of agranulocytosis in patients treated with fosfomycin. Parenteral fosfomycin is often used in patients receiving other medications, so that it is rarely the only suspect. In our case, the results of the bone marrow aspiration, the sudden drop of the neutrophil count with concomitant eosinophilia and the absence of improvement despite the dose decrease, point towards an immuno-allergic mechanism. However, the overlap between the suspected DRESS induced by meropenem and the agranulocytosis do not allow to conclude with certainty on the causality. Awareness should be raised about this side effect.


Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Eosinofilia , Fosfomicina , Neutropenia , Feminino , Humanos , Pessoa de Meia-Idade , Fosfomicina/efeitos adversos , Filgrastim/efeitos adversos , Meropeném/efeitos adversos , Neutropenia/induzido quimicamente , Antibacterianos/efeitos adversos
2.
Indian J Med Res ; 155(1): 43-48, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-35859427

RESUMO

Background & objectives: Primary hyperparathyroidism (PHPT) is a common endocrine disorder caused by the elevated secretion of the parathormone (PTH). The aim of this study was to evaluate the haematological manifestations of PHPT in patients with normal renal functions who were treated surgically for parathyroid adenomas. Methods: In this retrospective cross-sectional study, 134 patients with normal renal functions who underwent parathyroidectomies for PHPT were included. The haematological manifestations were evaluated in the total study cohort and in the two groups of different calcium (Ca) levels (Group 1 ≤11.2 mg/dl and Group 2 >11.2 mg/dl). Results: The overall prevalence of anaemia, leucopenia and thrombocytopenia was 20.1, 6.7 and 6.0 per cent, respectively. Normocytic anaemia was present in 19 (14.2%) patients. There were no significant differences in the prevalence of anaemia, leucopenia and thrombocytopenia between the two groups. There were no correlations between the PTH levels and the leukocyte, haemoglobin or platelet values. Six to 12 months after the parathyroidectomy (PTX), 35.7 per cent of the patients with anaemia, 85.7 per cent of the patients with leucopenia and 100 per cent of the patients with thrombocytopenia had recovered. Interpretation & conclusions: In the present study, anaemia was seen with a variable frequency in PHPT, but there was no relationship between anaemia and high PTH or Ca levels. The development of anaemia can be seen regardless of the PTH levels in PHPT patients with normal renal functions. High-resolution rates after PTX indicate a possible association between PHPT and thrombocytopenia or leucopenia, although their prevalence is low in PHPT.


Assuntos
Anemia , Hiperparatireoidismo Primário , Trombocitopenia , Anemia/epidemiologia , Anemia/etiologia , Cálcio , Estudos Transversais , Humanos , Hiperparatireoidismo Primário/complicações , Hiperparatireoidismo Primário/epidemiologia , Hiperparatireoidismo Primário/cirurgia , Hormônio Paratireóideo , Paratireoidectomia , Estudos Retrospectivos , Trombocitopenia/complicações , Trombocitopenia/epidemiologia
3.
Pak J Med Sci ; 38(7): 1968-1972, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36246708

RESUMO

Objective: To determine the frequency of various hematological manifestations among newly diagnosed cases of pulmonary tuberculosis on complete blood counts. Methods: This retrospective cross-sectional study was conducted on 500 newly diagnosed patients of pulmonary tuberculosis in hematology department of Nishtar Medical University from 1st November 2020 to 30th April 2021 using consecutive sampling. Detailed history and complete general physical examination findings, complete blood picture including erythrocyte sedimentation rate were retrieved from hospital electronic medical records system. Data was collected on a specially designed Proforma, entered into SPSS version 23.0 and analyzed. Data is presented as mean±SD and frequency and percentages for numerical and categorical variables respectively using tables and figures. Results: In this study the mean age of patients was 34.36 ± 6.41 years with male to female ratio 2.52: 1. Frequency of anemia was 82.6% (n=413), leukocytosis was 46.2% (n=231) and leucopenia in 102 patients (20.4%). Thrombocytosis was detected in 131(26.2%) patients. Raised ESR was observed in 495(99%) of the patients. No association of age and gender was observed with hematological manifestations. However, thrombocytosis was significantly more common in male patients (p-value = 0. 008). Conclusion: Hematological parameters like high Erythrocyte Sedimentation Rate (ESR) and anemia were commonly detected in newly diagnosed patients with pulmonary tuberculosis. Thrombocytosis was seen more commonly in male patients of pulmonary tuberculosis.

4.
Vnitr Lek ; 68(E-7): 28-35, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36402557

RESUMO

The blood cell count is often examined in routine clinical praxis. Physiologic leucocyte count is in range 4-10 × 109 in liter of blood. Abnormal values of leukocytes and subtypes of leukocytes in differential count are often present. Changes in leukocytes counts are caused by variety of benignant or malignant conditions. It is important in clinical praxis to interpret changes in blood cell count correctly and choose adequate approach in investigation process. In general, leukocytosis and leukocytopenia may present in primary hematologic disorder or secondary/reactive states, caused by reaction of hematopoiesis to underlying condition. This article review common causes of leukocytosis or leucopenia and give basic advice how to investigate patients with changes in leukocytes count.


Assuntos
Leucocitose , Leucopenia , Humanos , Leucocitose/diagnóstico , Leucocitose/etiologia , Diagnóstico Diferencial , Leucopenia/diagnóstico , Leucopenia/complicações , Contagem de Leucócitos
5.
Rheumatology (Oxford) ; 60(11): 5185-5193, 2021 11 03.
Artigo em Inglês | MEDLINE | ID: mdl-33693676

RESUMO

OBJECTIVE: The prevalence and associations of leucopenia in SLE remain incompletely understood. We evaluated associations of disease activity and medication use with leucopenia (lymphopenia and neutropenia) in a multinational, prospectively followed SLE cohort. METHODS: Data from the Asia Pacific Lupus Collaboration cohort, in which disease activity and medications were prospectively captured from 2013 to 2018, were used. Predictors of lymphopenia (lymphocyte count <0.8 × 109/l) and neutropenia (neutrophil count <1.5 × 109/l) were examined using multiple failure, time-dependent survival analyses. RESULTS: Data from 2330 patients and 18 287 visits were analysed. One thousand and eighteen patients (43.7%) had at least one episode of leucopenia; 867 patients (37.2%) had lymphopenia, observed in 3065 (16.8%) visits, and 292 (12.5%) patients had neutropenia, in 622 (3.4%) visits. After multivariable analyses, lymphopenia was associated with overall disease activity, ESR, serology, prednisolone, AZA, MTX, tacrolimus, CYC and rituximab use. MTX and ciclosporin were negatively associated with neutropenia. Lupus low disease activity state was negatively associated with both lymphopenia and neutropenia. CONCLUSION: Both lymphopenia and neutropenia were common in SLE patients but were differentially associated with disease and treatment variables. Lymphopenia and neutropenia should be considered independently in studies in SLE.


Assuntos
Imunossupressores/efeitos adversos , Lúpus Eritematoso Sistêmico/imunologia , Linfopenia/induzido quimicamente , Neutropenia/induzido quimicamente , Adulto , Feminino , Humanos , Estudos Longitudinais , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Masculino , Pessoa de Meia-Idade
6.
Transpl Infect Dis ; 23(2): e13467, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32935909

RESUMO

BACKGROUND: Cytomegalovirus (CMV) remains an important challenge after kidney transplantation. Current Transplantation Society International Consensus Guidelines recommend antiviral prophylaxis or pre-emptive therapy for high-risk CMV-seronegative recipients with a CMV-seropositive donor (D+/R-) and moderate-risk CMV-seropositive recipients (R+). However, a split strategy according to CMV serostatus is not specifically mentioned. METHODS: We evaluated a split strategy to prevent CMV infection after kidney transplantation in which D+/R- patients received valganciclovir (VGC) prophylaxis for 200 days, and R + patients were treated pre-emptively according to CMV DNAemia. Patients were followed until 1-year post-transplant. RESULTS: Between April 2014 and March 2018, 40 D+/R- and 92 R + patients underwent kidney transplantation. Forty-six percent received antithymocyte globulin (ATG) induction, and 98% was treated with calcineurin inhibitors, mycophenolic acid (MPA), and steroids. No D+/R- patient developed CMV disease during prophylaxis (median 200 days), but 15% developed post-prophylaxis or late-onset disease. Fifty-three percent developed neutropenia during prophylaxis, including 16/40 (40%) grade 3 or 4 neutropenia requiring reduction/discontinuation of MPA (30%) and/or VGC (35%), and an occasional need for granulocyte colony-stimulating factor (5%). In the R + group, 40% received antiviral therapy for a median duration of 21 days; 5% developed early-onset CMV disease. Only 5% developed neutropenia. D+/R + status (hazard ratio (HR) 2.09,P = .004) and ATG use (HR 2.81, P < .0001) were risk factors for CMV reactivation. CONCLUSIONS: Prophylaxis leads to acceptable CMV control in high-risk patients but comes with a high risk of neutropenia. Pre-emptive therapy is effective and limits drug exposure in those at lower risk of CMV.


Assuntos
Infecções por Citomegalovirus , Transplante de Rim , Antivirais/uso terapêutico , Citomegalovirus , Infecções por Citomegalovirus/tratamento farmacológico , Ganciclovir/uso terapêutico , Humanos , Preparações Farmacêuticas , Valganciclovir/uso terapêutico
7.
J Clin Pharm Ther ; 46(1): 74-77, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32893890

RESUMO

WHAT IS KNOWN AND OBJECTIVES: Thiopurines are cornerstone drugs in the treatment of acute lymphoblastic leukaemia (ALL), but their use can be complicated by the incidence of life-threatening leucopenia. CASE DESCRIPTION: We describe a case of a 6-year-old Chinese boy with B-ALL receiving extremely low dose of 6-mercaptopurine (only 4% of recommended dose) during the ALL maintenance therapy phase. WHAT IS NEW AND CONCLUSION: Complex pharmacogenetic tests and TDM should be recommended in children with complicated ALL to highlight the large individual variability in the responses to 6-MP exposure and the associated adverse effects.


Assuntos
Mercaptopurina/uso terapêutico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Administração Oral , Criança , Relação Dose-Resposta a Droga , Humanos , Masculino , Mercaptopurina/administração & dosagem
8.
Acta Endocrinol (Buchar) ; 17(3): 383-387, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35342475

RESUMO

Hyperinsulinism/hyperammonemia (HI/HA) syndrome is caused by activating mutations in GLUD1 gene, and causes fasting as well as protein sensitive symptomatic hypoglycemia, in addition to persistently elevated plasma ammonia levels. First-line treatment is diazoxide, and most patients respond well to this agent, however side effects may be observed. The most frequent side effect of diazoxide is fluid retention and hypertrichosis, while hyperuricemia and hematologic side effects are observed less often. Herein, we report a case who had a heterozygous mutation of GLUD1 gene and who developed diazoxide related neutropenia 8 years after the start of treatment. On follow-up, leucopenia and mild neutropenia persisted and the treatment was changed to somatostatin analogues. However, she developed persistent severe symptomatic hypoglycemia and required diazoxide retreatment. A lower dose of diazoxide (6 mg/kg/day) successfully controlled hypoglycemia and cell counts increased even though they were not normalized. Neutropenia in current case presented after a long period of time of diazoxide use and this period is the longest defined in the literature. Long-term endocrine and hematologic follow-up of this patient up to 18 years old will also be presented.

9.
J Sep Sci ; 43(22): 4103-4122, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32909652

RESUMO

A selective, accurate, and efficient liquid chromatography-tandem mass spectrometry method was developed for the simultaneous determination of 13 phenolic acids. Additionally, for more comprehensively determining the chemical constituents in Sanguisorba officinalis L. extract, a previously developed method was employed for the simultaneous determination of six triterpenes. Thus, two methods were used to ensure the comprehensiveness and reliability of this study. Based on these methods, the pharmacokinetic profiles of the 13 phenolic acids and 6 triterpenes in normal and leukopenia rats after oral administration of S. officinalis L. extract were compared for the first time in the present study. Quantitative detection of the 13 phenolic acids and 6 triterpenes was performed using the multiple reaction monitoring mode with the electrospray ion source in negative and positive electrospray ionization, respectively. Chromatographic separation was performed on an Agilent Eclipse Plus C18 RRHD column (50 × 2.1 mm, 1.8 µm) using gradient elution with a mobile phase composed of methanol-0.1% aqueous formic acid. The pharmacokinetic results demonstrated that the pharmacokinetic characteristics of the 19 analytes in leukopenia rats differed significantly from those determined in normal rats, which could provide a helpful reference for the clinical application of S. officinalis L. in the prevention and treatment of leucopenia.


Assuntos
Medicamentos de Ervas Chinesas/farmacocinética , Hidroxibenzoatos/farmacocinética , Leucopenia/tratamento farmacológico , Extratos Vegetais/farmacocinética , Sanguisorba/química , Triterpenos/farmacocinética , Administração Oral , Animais , Cromatografia Líquida , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/análise , Hidroxibenzoatos/administração & dosagem , Hidroxibenzoatos/análise , Masculino , Estrutura Molecular , Extratos Vegetais/administração & dosagem , Extratos Vegetais/análise , Ratos , Ratos Sprague-Dawley , Espectrometria de Massas em Tandem , Triterpenos/administração & dosagem , Triterpenos/análise
10.
Dig Dis Sci ; 64(9): 2395-2403, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31290039

RESUMO

Thiopurines have been widely used for the maintenance of remission or steroid sparing in patients with inflammatory bowel disease. However, potential drug-related adverse events frequently interfere with their use. Indeed, drug withdrawals associated with adverse reactions have been reported in approximately 25% of patients. To balance the efficacy, safety, and tolerability of thiopurines, regular monitoring of biomarkers (complete blood cell count, liver function test, and metabolic profiles), steady dose escalation, and pretreatment thiopurine S-methyltransferase (TPMT) genotype screening have been routinely recommended. However, the complex thiopurine metabolic pathway and individual differences attributed to pharmacogenetic diversity limit the effectiveness of these strategies in the optimization of thiopurine therapy. Recently, in an effort to facilitate more accurate and personalized prediction of thiopurine response or toxicity, novel genetic markers including NUDT15 and FTO genes were discovered. These discoveries are remarkable because TPMT screening has minimal efficacy for predicting myelosuppression especially in Asian populations, despite the fact that thee populations have a higher frequency of myelosuppression than Western populations. This review focuses on the current understanding of the metabolic pathway and the pharmacogenetics of thiopurines and suggests a personalized preventive strategy against potential adverse drug reactions to optimize their therapeutic application.


Assuntos
Azatioprina/efeitos adversos , Azatioprina/metabolismo , Colite Ulcerativa/tratamento farmacológico , Doença de Crohn/tratamento farmacológico , Dioxigenase FTO Dependente de alfa-Cetoglutarato/genética , Azatioprina/administração & dosagem , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/prevenção & controle , Humanos , Mercaptopurina/administração & dosagem , Mercaptopurina/efeitos adversos , Mercaptopurina/metabolismo , Redes e Vias Metabólicas , Metiltransferases/genética , Testes Farmacogenômicos , Pirofosfatases/genética , Tioguanina/sangue
11.
J Oncol Pharm Pract ; 25(8): 1823-1830, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30537917

RESUMO

BACKGROUND: Myelosuppression remains a major toxicity in cancer patients receiving chemotherapy, and is associated with considerable morbidity, mortality and cost. OBJECTIVE: The present study aims to investigate the prevalence and incidence of myelotoxicity, anemia and neutropenia in the adult cancer population, and further to determine the factors influencing them. METHODS: This was a cross-sectional observational study conducted at National Academy of Medical Sciences, Bir Hospital, Kathmandu. A total of 170 subjects eligible for the study were enrolled for analysis. Prevalence and incidence of myelotoxicity anemia, neutropenia and myelotoxicity at enrollment and during study were investigated. Factors influencing development of myelotoxic event were determined. RESULTS: Of 170 enrolled patients, the prevalence of myelotoxicity, anemia and neutropenia at enrolment was 54 (31.8%), 20 (11.8%) and 28 (16.6%), respectively, with 27 (16%) mild and 12 (7.1%) moderate type of anemia. Incidence of myelotoxicity, anemia and neutropenia during treatment was 90 (52.94%), 44 (26%) and 53 (31.2%) respectively, with 70 (41.2%) mild, 39 (22.9%) moderate and 5 (2.9%) severe type of anemia. Age (OR: 0.49; p < 0.047), and baseline Hb (OR: 1.29; p < 0.01) were found to be independent predictors associated with anemia. Hb (OR: 2.42, CI: 1.79-3.28; p < 0.001) and smoking (OR: 0.49: p = 0.03) were found to be independent factors associated myelotoxicity. CONCLUSION: Our study confirmed a high incidence rate of myelotoxicity, neutropenia and anemia in a considerable number of Nepalese cancer patients receiving chemotherapy, and that baseline Hb, smoker and older adults are at more risk, these patients should be evaluated carefully and a prophylactic measure should be adopted accordingly so as to prevent toxicity and improve quality of life during cancer treatment.


Assuntos
Anemia/induzido quimicamente , Antineoplásicos/efeitos adversos , Neoplasias/tratamento farmacológico , Neutropenia/induzido quimicamente , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Estudos Transversais , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Nepal , Prevalência , Qualidade de Vida , Adulto Jovem
12.
Indian J Med Res ; 147(1): 73-80, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29749364

RESUMO

BACKGROUND & OBJECTIVES: Brucellosis can lead to haematological abnormalities including cytopenia confusing with haematological malignancies. The aim of this study was to compare the main characteristics of brucellosis patients without cytopenia (Group 1) and with cytopenia (Group 2). METHODS: This five-year period study which was performed in two referral hospitals in Turkey, included all adult brucellosis patients. Abnormally, low counts of leucocyte or haemoglobin or platelets in a patient were considered as cytopenia. The demographics, clinical, laboratory, treatment and outcome data were analyzed. RESULTS: A total of 484 brucellosis patients were enrolled. Among the cases, 162 (33.5%) of them had cytopenia. One hundred and four (21.5%) had anaemia, 88 (18.8%) had thrombocytopenia, 71 (14.6%) had leucopenia and 28 (5.8%) had pancytopenia. The mean age of group 2 was 35.01±16.05 yr and it was 33.31±14.39 yr in group 1. While there was no difference between the groups in terms of duration of treatment, the median length of hospital stay (LOS) was significantly longer in group 2 (9 vs 10 days; P<0.001). The most frequently applied combination therapy consisted of doxycycline plus rifampicin and doxycycline plus streptomycin regimens. No significant difference was observed in terms of duration of treatment, LOS and restoration time of cytopenia between the patients who received either of these combinations. INTERPRETATION & CONCLUSIONS: Our findings suggested that the patients with cytopenia should be investigated for brucellosis, especially if living in, or with a history of travel to, endemic areas, in view of the increase in world travel.


Assuntos
Brucelose/tratamento farmacológico , Neoplasias Hematológicas/tratamento farmacológico , Pancitopenia/tratamento farmacológico , Trombocitopenia/tratamento farmacológico , Adulto , Anemia/complicações , Anemia/tratamento farmacológico , Anemia/epidemiologia , Brucelose/complicações , Brucelose/epidemiologia , Doxiciclina/administração & dosagem , Feminino , Neoplasias Hematológicas/complicações , Neoplasias Hematológicas/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Pancitopenia/complicações , Pancitopenia/epidemiologia , Rifampina/administração & dosagem , Estreptomicina/administração & dosagem , Trombocitopenia/complicações , Trombocitopenia/epidemiologia , Turquia
13.
Transgenic Res ; 26(1): 153-163, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-27554374

RESUMO

Recent progress in genetic manipulation of pigs designated for xenotransplantation ha6s shown considerable promise on xenograft survival in primates. However, genetic modification of multiple genes in donor pigs by knock-out and knock-in technologies, aiming to enhance immunological tolerance against transplanted organs in the recipients, has not been evaluated for health issues of donor pigs. We produced transgenic Massachusetts General Hospital piglets by knocking-out the α-1,3-galactosyltransferase (GT) gene and by simultaneously knocking-in an expression cassette containing five different human genes including, DAF, CD39, TFPI, C1 inhibitor (C1-INH), and TNFAIP3 (A20) [GT-(DAF/CD39/TFPI/C1-INH/TNFAIP3)/+] that are connected by 2A peptide cleavage sequences to release individual proteins from a single translational product. All five individual protein products were successfully produced as determined by western blotting of umbilical cords from the newborn transgenic pigs. Although gross observation and histological examination revealed no significant pathological abnormality in transgenic piglets, hematological examination found that the transgenic piglets had abnormally low numbers of platelets and WBCs, including neutrophils, eosinophils, basophils, and lymphocytes. However, transgenic piglets had similar numbers of RBC and values of parameters related to RBC compared to the control littermate piglets. These data suggest that transgenic expression of those human genes in pigs impaired hematopoiesis except for erythropoiesis. In conclusion, our data suggest that transgenic expression of up to five different genes can be efficiently achieved and provide the basis for determining optimal dosages of transgene expression and combinations of the transgenes to warrant production of transgenic donor pigs without health issues.


Assuntos
Animais Geneticamente Modificados/genética , Eritropoese/genética , Galactosiltransferases/genética , Transgenes/genética , Animais , Animais Geneticamente Modificados/crescimento & desenvolvimento , Antígenos CD/genética , Apirase/genética , Proteína Inibidora do Complemento C1/genética , Regulação da Expressão Gênica , Técnicas de Inativação de Genes , Hematopoese/genética , Humanos , Leucócitos/metabolismo , Lipoproteínas/genética , Suínos , Transplante Heterólogo , Proteína 3 Induzida por Fator de Necrose Tumoral alfa/genética
14.
Immunopharmacol Immunotoxicol ; 38(2): 113-23, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26769054

RESUMO

CONTEXT: Huangqi injection (HQI), extracted from Astragali Radix, which has capability on treating the leucopenia. However, the potential metabolic mechanism is poorly understood. OBJECTIVE: To investigate the effect of HQI on cyclophosphamide (Cy)-induced leucopenia in mice, the nuclear magnetic resonance (NMR)-based metabolomic profiling technique coupled with multivariate statistical analysis was applied. MATERIALS AND METHODS: NMR analysis was used to identify the various compounds of HQI, and high-performance liquid chromatography was applied to determine the contents of major compounds. A experimental mice model of leucopenia induced by Cy and NMR-based metabolomic approach was used to evaluate the pharmacological effect of HQI and to investigate its probable acting mechanism on leucopenia. RESULTS: HQI increased body weight and elevated the white blood cell (WBC), monocytes (MO), neutrophils (NE), and lymphocyte (LY) levels of Cy-treated mice. In addition, the levels of most perturbed endogenous metabolites could be reversed after HQI treatment. Correlations between WBC, MO, NE, LY, and altered metabolite profiles in spleen were greater than that in serum, and the correlation in MO was more evident than those for WBC, NE, and LY. DISCUSSION AND CONCLUSION: HQI showed obvious efficacy on the mice model of leucopenia. And the drug action of HQI on leucopenia was probably related with regulating metabolic pathways of energy metabolism, amino acids metabolism, oxidative stress, and choline metabolism. However, various compounds were present in the HQI, and the bioactive compounds responsible for the drug actions should be further investigated.


Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Leucopenia/tratamento farmacológico , Leucopenia/metabolismo , Metaboloma/efeitos dos fármacos , Metabolômica , Animais , Astragalus propinquus , Leucopenia/patologia , Camundongos
15.
Br J Clin Pharmacol ; 79(4): 685-91, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25303309

RESUMO

AIMS: Cytarabine is a pyrimidine analogue used to treat a variety of haematological malignancies. There are few data regarding the pharmacodynamics of cytarabine. The only publications regarding this issue cite a biphasic pattern of decline in white blood cell (WBC) counts following low and intermediate doses, in patients with various malignancies, most of them non-haematological. Our purpose was to establish the pharmacodynamics of cytarabine induced leucopenia in acute myeloid leukaemia (AML) patients treated with contemporary cytarabine containing protocols. METHODS: We conducted a retrospective cohort study, including 56 patients with AML in complete remission who had received 89 cycles of intermediate or high dose cytarabine. Daily counts for WBCs and neutrophils (ANC) were collected during the first 15 days after the initiation of cytarabine administration and pharmacodynamics were analyzed. Further analysis was carried out to correlate between WBC and ANC pharmacodynamics and different cytarabine protocols [high dose cytarabine (HiDAC) vs. intermediate dose cytarabine (IDAC)]. RESULTS: Analysis of blood counts demonstrated a monophasic decline of WBCs and ANCs, unlike a previous depiction of a biphasic pattern. HiDAC was associated with a significantly sharper decline of WBCs than IDAC. CONCLUSIONS: Our data support a monophasic decline pattern of WBCs and ANCs following contemporary cytarabine protocols. The decline rate is steeper for patients receiving HiDAC than for those receiving IDAC. These results might help form evidence based guidelines regarding patient monitoring intensity, timing of prophylactic antibacterial and antifungal treatment as well as growth factors' support following cytarabine based consolidation for AML.


Assuntos
Antimetabólitos Antineoplásicos/efeitos adversos , Citarabina/efeitos adversos , Leucemia Mieloide Aguda/tratamento farmacológico , Leucopenia/induzido quimicamente , Adolescente , Adulto , Idoso , Antimetabólitos Antineoplásicos/administração & dosagem , Antimetabólitos Antineoplásicos/uso terapêutico , Estudos de Coortes , Citarabina/administração & dosagem , Citarabina/uso terapêutico , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , Humanos , Leucemia Mieloide Aguda/sangue , Contagem de Leucócitos , Leucopenia/sangue , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
17.
J Viral Hepat ; 21(9): 624-32, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24224747

RESUMO

Peginterferon-alpha (PegIFNa) frequently causes neutropenia, mainly due to bone marrow suppression. The aim of this study was to explore factors that are associated with infections during antiviral treatment. We analysed data from 275 chronic hepatitis C (CHC) patients with compensated liver disease who underwent 318 courses of PegIFNa and ribavirin. Neutropenia was defined as neutrophils <1000 cells/µL. Mean leucocytes count significantly decreased from baseline to treatment nadir (7081 ± 2182 vs 3293 ± 1331 cells/µL, P < 0.001), while neutropenia was observed in 32% during treatment. Thirty-one infections were observed. The incidence rate for infection was assessed at 1.46 infections per 100 person-months of therapy. The hazard rate for infection did not correlate with the neutrophils' nadir or the decrease in white blood cells. In multivariate Cox's regression analysis, cirrhosis was the only factor that was significantly associated with the occurrence of infection. Our data show that the development of bacterial infections during treatment with PegIFNa and ribavirin in patients with compensated CHC is not associated with reduction or the nadir of white cells or neutrophil counts. Baseline cirrhosis is the only factor related with infection during treatment. The common practice of dose adjustment or discontinuation of interferon should be revised; careful assessment of liver damage before therapy and close monitoring during therapy are essential in all patients receiving interferon-based regimes, to minimize the detrimental consequences of infections.


Assuntos
Antivirais/uso terapêutico , Infecções Bacterianas/epidemiologia , Hepatite C Crônica/complicações , Interferon-alfa/uso terapêutico , Cirrose Hepática/complicações , Neutropenia/complicações , Ribavirina/uso terapêutico , Adolescente , Adulto , Idoso , Antivirais/efeitos adversos , Feminino , Hepatite C Crônica/tratamento farmacológico , Humanos , Interferon-alfa/efeitos adversos , Masculino , Pessoa de Meia-Idade , Neutropenia/induzido quimicamente , Estudos Retrospectivos , Ribavirina/efeitos adversos , Adulto Jovem
19.
Cureus ; 16(3): e55622, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38586655

RESUMO

BACKGROUND: The dengue virus is present throughout the tropics. Thrombocytopenia is one of the severe manifestations of the dengue virus. We studied the association of thrombocytopenia with serum transaminase level, leucopenia, and nonstructural protein one antigen (Ns1Ag) level. METHODS: Data were taken retrospectively from hospital records after obtaining ethical committee approval. In the study, we included 102 patients with acute febrile illness with clinical features suggestive of dengue fever (dengue Ns1Ag positive, dengue IgM positive, or both). We excluded patients with thrombocytopenia due to other causes. Patients' demographic, clinical, and laboratory parameters were collected. We also noted episodes of bleeding or the need for a platelet transfusion. We did a statistical analysis to find out the correlation between age, sex, leucopenia, transaminitis, Ns1Ag level, and thrombocytopenia and its severity. RESULTS: Multiple regression analysis was used to find thrombocytopenia predictors among aspartate transaminase (AST), alanine transaminase (ALT), Ns1Ag level, and leucopenia. AST and ALT correlated inversely with thrombocytopenia, with p-values of 0.012 and 0.027, respectively. Ns1Ag and leucopenia were not associated with thrombocytopenia, with p-values of 0.802 and 0.532, respectively (p-values significant at 0.01<= p<=0.05). CONCLUSION: Serum AST and ALT levels correlate with thrombocytopenia in dengue fever.

20.
J Blood Med ; 15: 157-169, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38545444

RESUMO

Objective: Abnormalities in blood cells are frequently associated with thyroid hormone disorders as a result of their involvement in the proliferation and production of blood cells. This study aimed to determine the magnitude and associated factors of hematological abnormalities in patients with hypothyroidism. Methods: A cross-sectional study was conducted from January 1 to June 30, 2023, at the University of Gondar Comprehensive Specialized Hospital. The present study included a total of 300 patients with hypothyroidism prospectively using the systematic random sampling technique. The hematological parameter data were collected using data extraction sheets, whereas the associated factor data were collected using both structured questionnaires and data extraction sheets. For complete blood cell counts, 4 mL of anticoagulated venous blood was collected and analyzed. The data were entered into Epi-data version 3.1 and analyzed with Stata version 14. Both bivariate and multivariate logistic regressions were performed to identify factors associated with hematological abnormalities. A P value < 0.05 was considered to indicate statistical significance. Results: The median value of red blood cell, hemoglobin, mean cell volume, white blood cell, and platelet were 4.63 x1012/µL, 14 g/dL, 84.3fl, 5.3 x103/µL, and 228, respectively. The overall incidences of anemia, leucopoenia, and thrombocytopenia in patients with hypothyroidism were 26.3% (95% confidence interval (CI): 21-32), 15.7% (95% CI: 14.2-17.2), and 9% (95% CI: 7.5-10.5), respectively. Lymphopenia was detected in 9% (95% CI: 8.6-10.1) of the patients, and neutropenia was detected in 6% (95% CI: 4.4-7.6) of the patients. Only three factors, female sex (adjusted odds ratio (AOR) =2.1, 95% CI=1.3-3.1), alcohol consumption (AOR= 3.8, CI=1.7-8.9), and febrile illness (AOR=2.7, 95% CI=1.3-5.4), were found to be significantly associated factors for anemia. Conclusion: The present study revealed heterogeneous hematological abnormalities in patients with hypothyroidism. Thus, early diagnosis and monitoring strategies are required to minimize complications in patients.

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