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1.
ACS Omega ; 6(11): 7711-7718, 2021 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-33778281

RESUMO

MicroRNA miR-486-5p has been reported as a potential biomarker for diagnosis, prognosis, and as a therapeutic target in various cancers. In this study, we analyzed alterations in the expression of miR-486-5p in chronic Myeloid Leukemia (CML) patients. Initially, the expression of miR-486-5p was studied in the BCR-ABL1+ve CML K562 cell line by quantitative real-time polymerase chain reaction (qRT-PCR). The results indicated that the miR-486-5p expression was significantly upregulated in K562 cells after imatinib exposure, as compared to untreated K562 cells (p-value = 0.047). These observations were corroborated by a hospital-based study of the miR-486-5p expression in peripheral blood leucocytes of 36 CML patients in the chronic phase (CP) and compared with age and sex-matched healthy volunteers as control subjects. qRT-PCR-based quantification revealed significant downregulation of the miR-486-5p expression in newly diagnosed untreated CP-CML patients' samples (2-ΔCt = 13.19 ± 14.41) as compared to control samples (2-ΔCt = 254.5 ± 274.8) (p-value < 0.0001). Levels of miR-486-5p were found to be distinctly elevated in the post-imatinib treatment samples of CML patients (2-ΔCt = 469.7 ± 312.9) as compared to pre-treatment samples (p-value < 0.0001). CML patients' clinical and hematological responses to imatinib therapy (oral dose of 400 mg OD) were monitored for 12 months. The correlation of pre-treatment miR-486-5p levels with Sokal score indicated that patients with a higher expression of miR-486-5p had better prognoses. Patients with higher pre-imatinib miR-486-5p levels also showed a major hematologic response to imatinib in a shorter time and vice versa. To the best of our knowledge, this is the first report of alterations in the miR-486-5p expression in peripheral blood leucocytes of CML patients. Our observations support a tumor suppressor role of miR-486-5p in CML. The downregulation of the miR-486-5p expression may be critically important in the disease progression of CML patients. The upregulation of the miR-486-5p expression in post-imatinib exposure K562 cells and CML patients after 12 months of imatinib treatment suggests an onco-suppressor effector role of miR-486-5p in the BCR-ABL downstream signaling pathway. miR-486-5p can be explored as a novel biomarker for the early detection of CML.

2.
Indian J Surg Oncol ; 11(3): 378-386, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33013114

RESUMO

The optimal duration of prophylactic antimicrobial usage in clean-contaminated elective oncological surgeries is not clear. This single-center randomized trial evaluated the effectiveness of single-dose antimicrobial prophylaxis in clean-contaminated surgeries for the reduction of surgical site infection (SSI). Between April 2018 and January 2019, 315 patients undergoing major oncological clean-contaminated surgeries where the gastrointestinal or genital tract was opened under controlled conditions were randomized into 2 groups i.e., single dose versus extended dose groups. The single dose group received a 1.5 g dose of cefuroxime immediately before surgery while the extended group received the same dose of cefuroxime thrice daily for 4 days from the day of surgery till postoperative day 3. In addition, patients undergoing esophageal and colorectal surgeries received metronidazole. The overall SSI rate of the single dose group was not significantly different from that of the extended group (11.3% vs. 14.7%, respectively, p 0.40), with absolute difference of 3.4% and relative risk of 0.85 (95% C.I, 0.59 to 1.22). The rate of remote site infection was also not different between the two groups (14.4% vs 10.2%, p 0.31) with absolute difference of 4.2% and relative risk 1.19 (95% C.I, 0.89 to 1.59). In univariate analysis, parameters like nodal dissection, colorectal surgery, smoking, and hospital stay were significantly associated with SSI. In multivariate analysis, age, smoking, nodal dissection, and hospital stay retained significance. Single-dose antimicrobial prophylaxis is as effective as extended usage for 4 days in the prevention of postoperative SSI in patients undergoing clean-contaminated major oncological surgeries. Trial was registered with the clinical trial registry of India (CTRI/2018/06/014344).

3.
J Coll Physicians Surg Pak ; 29(1): 78-80, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30630577

RESUMO

Chronic myeloid leukemia (CML) is a chronic myeloproliferative disorder that usually presents with high white blood cell counts and massive splenomegaly. Priapism is a rare manifestation of CML and is mostly due to hyperleukocytosis. Its debut appearance as a sign of hematological dyscrasia is a rare event. Priapism occurring in a setting of any leukemia is both a medical and a urological emergency that requires immediate local therapy, symptomatic treatment, cytoreductive therapy and early initiation of targeted therapy. This case report describes priapism as an unusual presentation of CML and its importance in the work-up and management of patients presenting with priapism.


Assuntos
Leucemia Mielogênica Crônica BCR-ABL Positiva/complicações , Priapismo/etiologia , Antineoplásicos/uso terapêutico , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Priapismo/cirurgia , Resultado do Tratamento
4.
Tumour Biol ; 39(10): 1010428317713857, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29019285

RESUMO

Platelet-derived growth factor receptor has been implicated in many malignant and non-malignant diseases. Platelet-derived growth factor receptor-α is a tyrosine kinase and a side target for imatinib, a revolutionary drug for the treatment of chronic myeloid leukemia that has dramatically improved the survival of chronic myeloid leukemia patients. Given the importance of platelet-derived growth factor receptor in platelet development and its inhibition by imatinib, it was intriguing to analyze the role of platelet-derived growth factor receptor-α in relation to imatinib treatment in the development of imatinib-induced thrombocytopenia in chronic myeloid leukemia patients. We hypothesized that two known functional polymorphisms, +68GA insertion/deletion and -909C/A, in the promoter region of the platelet-derived growth factor receptor-α gene may affect the susceptibility of chronic myeloid leukemia patients receiving imatinib treatment to the development of thrombocytopenia. A case-control study was conducted among a cohort of chronic myeloid leukemia patients admitted to the Lok Nayak Hospital, New Delhi, India. A set of 100 patients of chronic myeloid leukemia in chronic phase and 100 age- and sex-matched healthy controls were studied. After initiation of imatinib treatment, the hematological response of chronic myeloid leukemia patients was monitored regularly for 2 years, in which the development of thrombocytopenia was the primary end point. Platelet-derived growth factor receptor-α promoter polymorphisms +68GA ins/del and -909C/A were studied by allele-specific polymerase chain reaction. Platelet-derived growth factor receptor-α messenger RNA expression was evaluated by quantitative real-time polymerase chain reaction. The messenger RNA expression results were expressed as 2-Δct ± standard deviation. The distribution of +68GA ins/del promoter polymorphism genotypes differed significantly between the thrombocytopenic and non-thrombocytopenic chronic myeloid leukemia patient groups (p < 0.0001). Moreover, +68GA del/del and ins/del genotypes in imatinib-treated chronic myeloid leukemia patients were associated with an increased risk of developing thrombocytopenia, with odds ratios 6.5 (95% confidence interval = 2.02-0.89, p = 0.001) and 6.0 (95% confidence interval = 2.26-15.91, p = 0.0002), respectively. Similarly, -909C/A promoter polymorphism genotype distribution also differed significantly between thrombocytopenic and non-thrombocytopenic chronic myeloid leukemia patient groups (p = 0.02), and a significantly increased risk of imatinib-induced thrombocytopenia was associated with -909C/A polymorphism mutant homozygous (AA) genotypes the odds ratio being 7.7 (95% confidence interval 1.50 to 39.91, p = 0.009). However, no significant risk of imatinib-induced thrombocytopenia was found to be associated with heterozygous genotype (-909C/A) with odds ratio 1.9 (95% confidence interval = 0.86-4.56, p = 1.14). Platelet-derived growth factor receptor-α messenger RNA expression was significantly higher in chronic myeloid leukemia patients compared to controls (p = 0.008). Moreover, patients with imatinib-induced thrombocytopenia had a significantly lower platelet-derived growth factor receptor-α messenger RNA expression, compared to patients without thrombocytopenia (p = 0.01). A differential expression of platelet-derived growth factor receptor-α messenger RNA was observed with respect to different +68 GA ins/del and -909C/A polymorphism genotypes. The +68GA deletion allele and -909A allele were significantly associated with lower expression of platelet-derived growth factor receptor-α messenger RNA. The platelet-derived growth factor receptor-α +68GA del/del, +68GA ins/del, and -909AA genotypes are associated with an increased risk of developing thrombocytopenia in imatinib-treated chronic myeloid leukemia patients. A significantly lower platelet-derived growth factor receptor-α messenger RNA expression accompanies the +68GA deletion allele in an allele dose-dependent manner. Platelet-derived growth factor receptor-α -909AA genotype is also associated with lower expression of platelet-derived growth factor receptor-α. The downregulation of platelet-derived growth factor receptor-α expression may play a causative role in imatinib-induced thrombocytopenia, a common side effect, in the subset of chronic myeloid leukemia patients with platelet-derived growth factor receptor-α +68 GA ins/del, +68 GA del/del, and -909C/A genotypes.


Assuntos
Antineoplásicos/efeitos adversos , Predisposição Genética para Doença/genética , Mesilato de Imatinib/efeitos adversos , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Receptor alfa de Fator de Crescimento Derivado de Plaquetas/genética , Trombocitopenia/genética , Adulto , Estudos de Casos e Controles , Feminino , Genótipo , Humanos , Índia , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Polimorfismo de Nucleotídeo Único , Regiões Promotoras Genéticas/genética , Fatores de Risco , Trombocitopenia/induzido quimicamente
6.
JAMA ; 317(14): 1443-1450, 2017 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-28399252

RESUMO

IMPORTANCE: Midlife vascular risk factors have been associated with late-life dementia. Whether these risk factors directly contribute to brain amyloid deposition is less well understood. OBJECTIVE: To determine if midlife vascular risk factors are associated with late-life brain amyloid deposition, measured using florbetapir positron emission tomography (PET). DESIGN, SETTING, AND PARTICIPANTS: The Atherosclerosis Risk in Communities (ARIC)-PET Amyloid Imaging Study, a prospective cohort study among 346 participants without dementia in 3 US communities (Washington County, Maryland; Forsyth County, North Carolina; and Jackson, Mississippi) who have been evaluated for vascular risk factors and markers since 1987-1989 with florbetapir PET scans in 2011-2013. Positron emission tomography image analysis was completed in 2015. EXPOSURES: Vascular risk factors at ARIC baseline (age 45-64 years; risk factors included body mass index ≥30, current smoking, hypertension, diabetes, and total cholesterol ≥200 mg/dL) were evaluated in multivariable models including age, sex, race, APOE genotype, and educational level. MAIN OUTCOMES AND MEASURES: Standardized uptake value ratios (SUVRs) were calculated from PET scans and a mean global cortical SUVR was calculated. Elevated florbetapir (defined as a SUVR >1.2) was the dependent variable. RESULTS: Among 322 participants without dementia and with nonmissing midlife vascular risk factors at baseline (mean age, 52 years; 58% female; 43% black), the SUVR (elevated in 164 [50.9%] participants) was measured more than 20 years later (median follow-up, 23.5 years; interquartile range, 23.0-24.3 years) when participants were between 67 and 88 (mean, 76) years old. Elevated body mass index in midlife was associated with elevated SUVR (odds ratio [OR], 2.06; 95% CI, 1.16-3.65). At baseline, 65 participants had no vascular risk factors, 123 had 1, and 134 had 2 or more; a higher number of midlife risk factors was associated with elevated amyloid SUVR at follow-up (30.8% [n = 20], 50.4% [n = 62], and 61.2% [n = 82], respectively). In adjusted models, compared with 0 midlife vascular risk factors, the OR for elevated SUVR associated with 1 vascular risk factor was 1.88 (95% CI, 0.95-3.72) and for 2 or more vascular risk factors was 2.88 (95% CI, 1.46-5.69). No significant race × risk factor interactions were found. Late-life vascular risk factors were not associated with late-life brain amyloid deposition (for ≥2 late-life vascular risk factors vs 0: OR, 1.66; 95% CI, 0.75-3.69). CONCLUSIONS AND RELEVANCE: An increasing number of midlife vascular risk factors was significantly associated with elevated amyloid SUVR; this association was not significant for late-life risk factors. These findings are consistent with a role of vascular disease in the development of Alzheimer disease.


Assuntos
Fatores Etários , Amiloide/metabolismo , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Idoso , Idoso de 80 Anos ou mais , Alelos , Doença de Alzheimer/genética , Compostos de Anilina/farmacocinética , Apolipoproteínas E/genética , População Negra , Índice de Massa Corporal , Demência/etiologia , Complicações do Diabetes , Etilenoglicóis/farmacocinética , Feminino , Radioisótopos de Flúor/farmacocinética , Seguimentos , Humanos , Hipercolesterolemia/complicações , Hipertensão/complicações , Masculino , Pessoa de Meia-Idade , Razão de Chances , Tomografia por Emissão de Pósitrons/métodos , Estudos Prospectivos , Fatores de Risco , Fumar/efeitos adversos , Fatores de Tempo , População Branca
7.
Leuk Lymphoma ; 58(7): 1694-1701, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-27830966

RESUMO

RIZ1 encodes a retinoblastoma (Rb)-interacting zinc finger protein, is commonly lost or expressed at reduced levels in cancer cells. The RIZ1 gene locus commonly undergoes LOH in many cancers. Here, we analyzed Proline insertion-deletion polymorphism at amino acid position 704 in the RIZ1 gene and its association with CML. The RIZ1 pro-704 LOH genotypes were determined by AS-PCR in 100 CML patients among which 50 were in CP-CML, 25 in AP-CML, and 25 in BC-CML. Pro704 ins/del polymorphism (LOH) was detected in 27% CML patients. Proline ins-ins homozygosity, del-del homozygosity and ins-del heterozygosity was detected in 9%, 18%, and 73% CML patients compared with 3%, 3%, and 94% in healthy controls, respectively (p < .0003). A four-fold increased risk was found to be associated del-del genotype. We found a statistically significant association between RIZ1 LOH and stage (p > .01) and hematological resistance (p > .001). However, there were no correlations found with other clinical parameters like age, gender, thrombocytopia, type of BCR-ABL, and molecular response. Our findings suggest that proline 704 del-del homozygosity phenotype can play an important role in progression of CML.


Assuntos
Proteínas de Ligação a DNA/genética , Histona-Lisina N-Metiltransferase/genética , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Proteínas Nucleares/genética , Polimorfismo Genético , Deleção de Sequência , Fatores de Transcrição/genética , Adulto , Idoso , Alelos , Estudos de Casos e Controles , Progressão da Doença , Feminino , Proteínas de Fusão bcr-abl/genética , Genótipo , Humanos , Mutação INDEL , Mesilato de Imatinib/administração & dosagem , Mesilato de Imatinib/efeitos adversos , Mesilato de Imatinib/uso terapêutico , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Translocação Genética , Resultado do Tratamento
8.
Indian J Med Res ; 143(Supplement): S17-S22, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-27748273

RESUMO

BACKGROUND & OBJECTIVES: Flow cytometry is an important tool to diagnose acute leukaemia. Attempts are being made to find the minimal number of antibodies for correctly diagnosing acute leukaemia subtypes. The present study was designed to evaluate the analysis of side scatter (SSC) versus CD45 flow dot plot to distinguish acute myeloid leukaemia (AML) from acute lymphoblastic leukaemia (ALL), with minimal immunological markers. METHODS: One hundred consecutive cases of acute leukaemia were evaluated for blast cluster on SSC versus CD45 plots. The parameters studied included visual shape, CD45 and side scatter expression, continuity with residual granulocytes/lymphocytes/monocytes and ratio of maximum width to maximum height (w/h). The final diagnosis of ALL and AML and their subtypes was made by morphology, cytochemistry and immunophenotyping. Two sample Wilcoxon rank-sum (Mann Whitney) test and Kruskal-Wallis equality-of-populations rank tests were applied to elucidate the significance of the above ratios of blast cluster for diagnosis of ALL, AML and their subtypes. Receiver operating characteristic (ROC) curves were generated and the optimal cut-offs of the w/h ratio to distinguish between ALL and AML determined. RESULTS: Of the 100 cases, 57 of ALL and 43 cases of AML were diagnosed. The median w/h ratio of blast population was 3.8 for ALL and 1 for AML (P<0.001). ROC had area under curve of 0.9772.The optimal cut-off of the w/h ratio for distinction of ALL from AML was found to be 1.6. INTERPRETATION & CONCLUSIONS: Our findings suggest that if w/h ratio on SSC versus CD45 plot is less than 1.6, AML may be considered, and if it is more than 1.6, ALL may be diagnosed. Using morphometric analysis of the blast cluster on SSC versus CD45, it was possible to distinguish between ALL and AML, and their subtypes.


Assuntos
Diagnóstico Diferencial , Leucemia Mieloide Aguda/diagnóstico , Antígenos Comuns de Leucócito/biossíntese , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Adolescente , Adulto , Anticorpos/genética , Criança , Pré-Escolar , Feminino , Citometria de Fluxo , Regulação Neoplásica da Expressão Gênica , Humanos , Imunofenotipagem/métodos , Leucemia Mieloide Aguda/classificação , Leucemia Mieloide Aguda/genética , Antígenos Comuns de Leucócito/genética , Masculino , Pessoa de Meia-Idade , Patologia Molecular , Leucemia-Linfoma Linfoblástico de Células Precursoras/classificação , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética
9.
J Clin Diagn Res ; 10(7): OC19-23, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27630882

RESUMO

INTRODUCTION: Chronic Myeloid Leukaemia (CML) is characterized by derangement of various components of the haemostatic system resulting in thrombo-haemorrhagic complications. Although less common than other myeloproliferative neoplasms, derangement of various components of the haemostatic system is observed in CML. Haemostatic abnormalities have been described in relation to hyperleucostasis and drugs used to treat CML. However, the correlation between haemostatic derangements and phase of CML is unclear in the literature. AIM: The purpose of this cross-sectional study was to assay various haemostatic parameters in patients of CML receiving Imatinib and to determine any correlation between them and phases of disease as well as the status of remission. MATERIALS AND METHODS: The study included 30 patients with CML (17 males, 13 females, mean age of 35.53 ± 8.92 years) receiving imatinib mesylate. Haemostatic parameters including platelet counts, Prothrombin Time (PT), activated Partial Thromboplastin Time (APTT), fibrinogen, D-dimers and Factor VIII levels were assayed for all patients using standard methods. Bcr-abl gene product (quantitative) was determined on the peripheral blood by reverse transcriptase polymerase chain reaction (RT-PCR). Patients were grouped into phases of disease (chronic, accelerated and blast) and their response to imatinib was determined in the form of remission (clinical, haematological and molecular). Correlations were drawn between them using spearman's coefficient. RESULTS: A significant positive correlation was found between PT (p=0.002), fibrinogen (p=0.011), D-dimers (p=0.050), Factor VIII levels (p=0.006) with the phase of CML and a significant negative correlation was observed between PT (p=0.003, 0.006), fibrinogen (p=0.010, 0.005), D-dimers (p=0.035, 0.017), Factor VIII levels (p=0.005, 0.001) and clinical and haematological remission respectively. No significant correlation of platelet counts and APTT was seen with the phase of CML or remission status. CONCLUSION: Haemostatic system is significantly disturbed in CML and correlate positively with the progression of the disease. Imatinib treatment leads to improvement in some of these parameters.

10.
J Clin Diagn Res ; 10(6): XE07-XE10, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27504392

RESUMO

Sternal masses present a unique diagnostic challenge in clinical practice. A wide array of differential diagnosis of a sternal mass includes osteomyelitis, tuberculosis, eosinophilic granuloma, sarcoma and lymphoma (usually Non-Hodgkin's) amongst others. Sternum is a rare site of Hodgkin's lymphoma and is usually misdiagnosed as tuberculosis or eosinophilic granuloma on routine histopathology. This delayed diagnosis culminates in death of patients. We report a 30-year-old lady who presented with swelling in upper part of chest wall since 1 month. Past history was significant for a similar swelling 2 years back, which was diagnosed as hodgkin's lymphoma and treated with 4 cycles of chemotherapy at another centre (which led to resolution of the swelling). Examination revealed a 6x6.5cm firm swelling originating from the upper part of sternum. There was no lymphadenopathy or organomegaly. Histopathological examination (with immunohistochemistry) of the trucut biopsy from the swelling confirmed the diagnosis of Hodgkin's lymphoma (nodular sclerosis). Patient was diagnosed as a late relapse of primary sternal Hodgkin's lymphoma (stage IBE) and was administered 4 cycles of ABVD followed by local radiotherapy to the involved site which led to complete resolution of the disease as assessed by PET scan. We present this unusual case of primary sternal Hodgkin's lymphoma. Rarity of this entity, with diagnostic challenges encountered and treatment options available are highlighted in the current report. A pubmed search revealed 18 cases of sternal involvement in Hodgkin's lymphoma which have been tabulated.

11.
Thromb Haemost ; 116(1): 1-8, 2016 07 04.
Artigo em Inglês | MEDLINE | ID: mdl-26962852

RESUMO

The Phase 3 A-LONG and Kids A-LONG studies demonstrated the prolonged half-life of rFVIIIFc compared with rFVIII, and the safety and efficacy of rFVIIIFc in subjects with severe haemophilia A. Eligible subjects from A-LONG and Kids A-LONG continued rFVIIIFc treatment by enrolling in ASPIRE, an ongoing extension study. Based on combined data from the primary studies and ASPIRE interim data, the safety and efficacy of rFVIIIFc in subjects requiring surgery were evaluated. Perioperative dosing regimens were determined by investigators with guidance based on pharmacokinetic data and recommendations from a clinical dosing committee. In addition to dosing frequency, factor consumption, blood loss, transfusions, bleeding episodes, and haemostatic response were assessed. Across studies, 21 subjects underwent 23 evaluable major surgeries, including 19 orthopaedic surgeries; 41 subjects underwent 52 minor surgeries, including 30 dental procedures. No major and 10 minor surgeries were performed in paediatric subjects. Of the major (n = 22) and minor (n = 32) surgeries assessed for haemostatic response, all were rated as excellent or good by the investigator/surgeon. During most major surgeries (95.7 %), haemostasis was maintained with one rFVIIIFc infusion. Blood loss in major surgeries was consistent with similar surgeries in subjects without haemophilia. Across studies, rFVIIIFc was well tolerated; no subject developed an inhibitor.


Assuntos
Fator VIII/uso terapêutico , Hemofilia A/cirurgia , Hemofilia A/terapia , Hemostasia Cirúrgica/métodos , Fragmentos Fc das Imunoglobulinas/uso terapêutico , Proteínas Recombinantes de Fusão/uso terapêutico , Adolescente , Adulto , Perda Sanguínea Cirúrgica/prevenção & controle , Transfusão de Sangue , Criança , Pré-Escolar , Fator VIII/administração & dosagem , Fator VIII/farmacocinética , Meia-Vida , Hemofilia A/sangue , Hemostáticos/administração & dosagem , Hemostáticos/farmacocinética , Hemostáticos/uso terapêutico , Humanos , Fragmentos Fc das Imunoglobulinas/administração & dosagem , Masculino , Pessoa de Meia-Idade , Proteínas Recombinantes de Fusão/administração & dosagem , Proteínas Recombinantes de Fusão/farmacocinética , Resultado do Tratamento , Adulto Jovem
12.
J Clin Diagn Res ; 10(1): OE01-5, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26894118

RESUMO

Extramedullary blast crises of Chronic Myeloid Leukaemia (CML) involving CNS is rare and usually accompanies systemic relapse. Isolated CNS blast relapse is an extremely uncommon event. A 35-year-old male was diagnosed with chronic phase (CP) CML two years back at our hospital and was started on imatinib 400 mg daily. Patient achieved haematological and cytogenetic remission at three and 12 months respectively but was non-compliant with medications thereafter. He presented to our emergency with headache and bilateral visual loss. CNS examination revealed neck rigidity and fundoscopy revealed disc edema with retinal vein dilatation and haemorrhages. Cerebrospinal fluid (CSF) analysis revealed lymphocytic pleocytosis and a positive cytospin for myeloid blasts. MRI brain suggested pachymeningeal enhancement involving falx cerebri and tentorium along with bilateral optic nerve thickening. Patient maintained cytogenetic remission at current presentation. A diagnosis of isolated CNS blast crises with pachymeningitis and bilateral optic nerve involvement was made and two doses of intrathecal chemotherapy were administered. However, patient died due to a rapidly downhill course. A previously unreported finding of pachymeningitis with bilateral optic neuritis has been highlighted in this case, along with a brief review of this rare condition.

13.
Mycopathologia ; 180(3-4): 223-7, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25894510

RESUMO

We present the case of an 18-year-old male patient admitted with complaints of fever and rapid weight loss since 3 months. Patient had multiple umbilicated papular to nodular lesions over chin and forehead region. Complete blood count revealed bicytopenia. An excisional biopsy of the skin lesions had revealed cutaneous histoplasmosis. On further investigations for bicytopenia, histoplasmosis had been diagnosed on bone marrow trephine biopsy. For the immune status, patient's serology against HIV was negative and his CD4 lymphocyte counts were low at 161. Patient received antifungal therapy including amphotericin B and itraconazole. He showed remarkable improvement in his general condition and blood counts. A repeat CD4 count showed normal counts, and idiopathic CD4 lymphocytopenia was excluded. Disseminated histoplasmosis presenting as cutaneous lesions in an immunocompetent host is very rare, and we are not aware of any case report in the literature where there is reversible depletion of CD4 counts following antifungal treatment in an immunocompetent host of nonendemic area.


Assuntos
Antifúngicos/administração & dosagem , Linfócitos T CD4-Positivos/imunologia , Histoplasmose/diagnóstico , Histoplasmose/patologia , Depleção Linfocítica , Dermatopatias/diagnóstico , Dermatopatias/patologia , Adolescente , Anfotericina B/administração & dosagem , Histoplasmose/tratamento farmacológico , Histoplasmose/imunologia , Humanos , Itraconazol/administração & dosagem , Masculino , Dermatopatias/tratamento farmacológico , Dermatopatias/imunologia , Resultado do Tratamento
14.
World J Oncol ; 6(2): 321-328, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29147425

RESUMO

BACKGROUND: Mammalian cells contain three functional RAS proto-oncogenes, known as H-RAS, K-RAS, and N-RAS, which encode small GTP-binding proteins in terms of p21rass. RAS genes have been elucidated as major participants in the development and progression of cancer. A single nucleotide polymorphism (SNP) at H-RAS cDNA position 81 T→C (rs12628) has been found to be associated with the risk of many human cancers like gastrointestinal, oral, colon, bladder and thyroid carcinomas. Therefore, we hypothesized that this polymorphisms in H-RAS could influence susceptibility to chronic myeloid leukemia as well, and we conducted this study to test the hypothesis in Indian population. METHOD: H-RAS polymorphism was studied in 100 chronic myeloid leukemia (CML) patients and 100 healthy controls by restriction fragmentation length polymorphism (RFLP-PCR). Associations between polymorphism and clinicopathological features of CML patients were investigated. RESULTS: In CML patients, the TT, TC and CC genotype frequency was 38%, 61% and 1% respectively, compared to 92%, 8% and 0% in healthy controls respectively. Compared to TT genotype, CT was significantly associated with increased risk of CML (odds ratio (OR): 8.4, P < 0.00001). There was a statistically significant correlation of H-RAS polymorphism with phases (P < 0.0003), molecular response (P < 0.0001), hematological response (P < 0.04) and thrombocytopenia (P < 0.003). However, there was no correlation of this polymorphism found with other clinical parameters. CONCLUSION: H-RAS T81C polymorphism was found to be associated with CML risk and prognosis of CML. These results suggest that C heterozygosis may be considered a potential risk factor for CML development in the North Indian population.

15.
Artigo em Inglês | MEDLINE | ID: mdl-24653651

RESUMO

We present the case of a 65-year-old female who presented to our hospital with nodular swelling in her breast that first appeared in the right upper quadrant 10 months earlier, followed by involvement of the left upper quadrant along with nodular swelling in the right inguinal region for the past six months. She was also complaining of breathlessness on exertion and right-sided pleuritic chest pain for the past one year. Her chest X-ray showed well defined consolidation in the right lower lobe of the lung with pleural effusion. Further pleural tap showed malignant cells with squamous differentiation. Fine needle aspiration cytology (FNAC) from breast lumps was suggestive of malignant cells with morphology of cells likely to be squamous. CT-guided biopsy of the lung mass showed moderately differentiated squamous cell carcinoma of the lung. She succumbed to her illness following severe respiratory distress. Breast lump secondary to lung malignancy is very rare. Squamous cell carcinoma presenting as breast metastasis is a very rare presentation and reported in few cases. No previous case reporting bilateral breast lumps as a presentation of squamous cell carcinoma of the lung could be found in the literature.

17.
J Clin Diagn Res ; 8(11): MD08-10, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25584257

RESUMO

Inflammatory pseudotumor of liver although a rare entity is an important differential diagnosis of hepatic space occupying lesions as well as an important cause of portal hypertension, commonly mimicking malignant tumors on imaging and histology. We report a case of a 25-year-old postpartum female who presented to our emergency with seizures and altered sensorium and was found to be having uncontrolled hyperglycemia and metabolic encephalopathy. She had a 2 month history of low grade fever and pain in right hypochondrium. Examination revealed an enlarged, tender, left lobe of the liver, splenomegaly and ascites. CT scan of the abdomen revealed an ill-defined mass lesion in left lobe of the liver with dilated intrahepatic biliary radicles along with dorsal pancreatic agenesis and evidence of portal hypertension in the form of ascites and splenomegaly. Histopathology confirmed the presence of inflammatory pseudotumor in left lobe of the liver. Conservative management of the patient resulted in reduction of the tumor size and regression of splenomegaly and ascites in 1 month. Present case highlights inflammatory pseudotumor of liver as a rare entity, it's resemblance to malignant conditions, pancreatic agenesis as a previously unreported association as well as a potentially reversible cause of portal hypertension by conservative treatment only.

18.
BMJ Case Rep ; 20132013 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-24234432

RESUMO

We present the case of a 57-year-old male patient diagnosed with chronic lymphoid leukaemia (CLL) B-cell type along with moderate anaemia. On follow-up investigations the aetiology of anaemia turned out to be pure red cell aplasia (PRCA) on trephine bone biopsy with an elevated serum erythropoietin level. The patient received blood transfusion support. He showed remarkable improvement on oral corticosteroids (prednisolone 60 mg/daily dose) with no further requirement of blood transfusion over next 3 months. However, when the dose of steroid was tapered down to 10 mg/day, the anaemia reappeared. An increase in the dose of steroid brought the haemoglobin level back to normal. Anaemia in CLL can be due to many reasons, of which PRCA is an uncommon association occurring in only around 1% of patients with CLL and usually refractory to the conventional treatment with steroids. This PRCA secondary to CLL is considered to be immune in origin and a response to combination of immunosuppressive therapy such as steroids, cyclosporine, rituximab is anticipated. Our case responded completely to oral steroids alone.


Assuntos
Corticosteroides/uso terapêutico , Leucemia Linfocítica Crônica de Células B/complicações , Prednisolona/uso terapêutico , Aplasia Pura de Série Vermelha/etiologia , Administração Oral , Corticosteroides/administração & dosagem , Medula Óssea/patologia , Diagnóstico Diferencial , Humanos , Leucemia Linfocítica Crônica de Células B/diagnóstico , Masculino , Pessoa de Meia-Idade , Prednisolona/administração & dosagem , Aplasia Pura de Série Vermelha/diagnóstico , Aplasia Pura de Série Vermelha/tratamento farmacológico
19.
J Commun Dis ; 45(1-2): 25-32, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-25141551

RESUMO

This study was carried out in a Anti-Retroviral Therapy Clinic and TB center of a tertiary level hospital to find out socio-demographic correlates of HIV/TB individuals and risk factors of HIV/TB co-infection in Indian context. It is a case-control study comprising 420 subjects, 3 groups of 140 each. For a case group of HIV-TB co-infected subjects, two control groups, one comprising HIV patients (not having TB), and the other TB patients (not having HIV). Majority 267 (63.6%) males, 100 (71.4%) in case group (HIV/ TB), 74 (52.9%) in control group 1 (TB) and 93 (66.4%) in control group 2 (HIV). Mean (+/-SD) age of case-group was 34.91 (+/- 8.57) years. New TB cases were 213 (76.1%), more among control-group 1, compared to case-group. Multivariate analysis showed that risk of co-infection was 1.94 times higher among individuals aged >35 years. Difference statistically significant amongst those who were not on ART than who were on ART (p < 0.001). Those with CD4 counts <200 had 1.85 times risk of TB. Smokers had 1.92 times risk of TB. Co-infection higher in males, in age group 35-44 years, urban area, lower educational status and lower socioeconomic class. Current history of smoking significantly associated with co-infection. HIV status during TB infection was detected in 1/4th of study subjects. History of TB symptoms in family significantly associated with co-infection.


Assuntos
Infecções por HIV/complicações , Tuberculose/complicações , Adolescente , Adulto , Estudos de Casos e Controles , Feminino , Infecções por HIV/epidemiologia , Humanos , Índia/epidemiologia , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Tuberculose/epidemiologia , Adulto Jovem
20.
Environ Toxicol Pharmacol ; 34(3): 941-8, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22986104

RESUMO

C-Phycocyanin (C-PC), a biliprotein from the sea weed, has been shown to have the beneficial effects like antioxidant, anti-inflammatory, neuroprotective, and hepatoprotective properties and is used as food supplement. We are showing the effect of C-Phycocyanin on the early events altered by tumor promoter. TPA induced the expression of critical events of tumorigenesis like ornithine decarboxylase, cyclooxygenase-2, interleukin-6 and pSTAT3 in mouse skin after 5h of application, whereas expression of transglutaminase2 was decreased at this time point. This TPA-caused altered expression of genes was prevented in presence of C-Phycocyanin. This prevention by C-Phycocyanin appeared to be dependent on the dose of C-Phycocyanin used. The results are useful for the detailed study on the preventive effect of C-Phycocyanin on TPA induced tumor promotion.


Assuntos
Carcinógenos/toxicidade , Neoplasias Cutâneas/metabolismo , Pele/metabolismo , Acetato de Tetradecanoilforbol/toxicidade , Animais , Ciclo-Oxigenase 2/genética , Ciclo-Oxigenase 2/metabolismo , Feminino , Expressão Gênica , Interleucina-6/genética , Interleucina-6/metabolismo , Camundongos , Ornitina Descarboxilase/genética , Ornitina Descarboxilase/metabolismo , Ficocianina/genética , Ficocianina/metabolismo , Pele/patologia , Neoplasias Cutâneas/genética
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