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1.
Pediatr Nephrol ; 39(7): 2091-2097, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38270601

RESUMEN

BACKGROUND: Plasma exchanges (PEX) and immunosuppression are the cornerstone of management of anti-factor H (FH) antibody-associated atypical hemolytic uremic syndrome (aHUS), particularly if access to eculizumab is limited. The duration of therapy with PEX for anti-FH aHUS is empirical. METHODS: We compared the efficacy of abbreviated PEX protocol (10-12 sessions) in a prospective cohort of patients diagnosed with anti-FH aHUS (2020-2022), to standard PEX protocol (20-22 sessions) in a historical cohort (2016-2019; n = 65). Efficacy was defined as 70% decline in anti-FH titers or fall to ≤ 1300 AU/ml at 4 weeks. Patients in both cohorts received similar immunosuppression with oral prednisolone, IV cyclophosphamide (5 doses) and mycophenolate mofetil. Outcomes included efficacy, rates of hematological remission and adverse kidney outcomes at 1, 3 and 6 months. RESULTS: Of 23 patients, 8.2 ± 2.1 years old enrolled prospectively, two were excluded for significant protocol deviation. PEX was abbreviated in 18/21 (86%) patients to 11.5 ± 3.3 sessions. Abbreviation failed for lack of hematological remission by day 14 (n = 2) and persistent neurological manifestations (n = 1). All patients in whom PEX was abbreviated achieved > 70% reduction in anti-FH titers at day 28. The percentage fall in anti-FH titers was similar for the abbreviated vs. standard PEX protocols at 1, 3 and 6 months. At last follow-up, at median 50 months and 25 months for standard and abbreviated cohorts, the estimated GFR was similar at 104.8 ± 29.1 vs. 93.7 ± 53.4, respectively (P = 0.42). CONCLUSION: Abbreviation of the duration of PEX is feasible and efficacious in reducing anti-FH titers. Short-term outcomes were comparable in patients managed by abbreviated and standard PEX protocols.


Asunto(s)
Síndrome Hemolítico Urémico Atípico , Factor H de Complemento , Intercambio Plasmático , Niño , Preescolar , Humanos , Masculino , Anticuerpos Monoclonales Humanizados/uso terapéutico , Síndrome Hemolítico Urémico Atípico/terapia , Síndrome Hemolítico Urémico Atípico/inmunología , Síndrome Hemolítico Urémico Atípico/sangre , Autoanticuerpos/sangre , Autoanticuerpos/inmunología , Factor H de Complemento/inmunología , Inmunosupresores/uso terapéutico , Ácido Micofenólico/uso terapéutico , Ácido Micofenólico/administración & dosificación , Intercambio Plasmático/métodos , Estudios Prospectivos , Resultado del Tratamiento
2.
Pediatr Nephrol ; 39(6): 1909-1916, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38252289

RESUMEN

BACKGROUND: The etiology of atypical hemolytic uremic syndrome (aHUS) is unknown in 30-40% of patients. Anti-factor B (FB) antibodies are reported in C3 glomerulopathy (C3G) and immune-complex membranoproliferative glomerulonephritis (IC-MPGN), though not in aHUS. METHODS: We screened patients < 18-year-old from cohorts of aHUS and C3G/idiopathic IC-MPGN. Anti-FB IgG antibodies were measured by ELISA and confirmed by Western blot. Normative levels were based on antibody levels in 103 healthy blood donors. RESULTS: Prevalence of anti-FB antibodies was 9.7% (95% CI 6.1-14.5%; n = 21) in 216 patients with aHUS, including 11.5% (95% CI 6.4-18.5%; n = 14) in anti-FH associated aHUS and 11.8% (95% CI 4.4-23.9%; n = 6) in patients without a definitive genetic or autoimmune etiology. Patients with significant genetic variants did not show anti-FB antibodies. In patients with concomitant anti-FB and anti-FH antibodies, median anti-FH titers were higher (11,312 AU/mL vs. 4920 AU/mL; P = 0.04). Anti-FB antibody titer correlated with disease severity (hemoglobin and platelets; P < 0.05), declined following plasma exchange and increased during relapse. While 4/64 patients with C3G (6.3%) and 1/17 with IC-MPGN showed anti-FB antibodies, titers were higher in aHUS (544.8 AU/mL vs. 1028.8 AU/mL; P = 0.003). CONCLUSION: Anti-FB antibodies are present in 6-10% of patients with aHUS and C3G/IC-MPGN, with higher titers in the former. The diagnostic and therapeutic implication of anti-FB antibodies in aHUS needs confirmation and further studies. The study shows propensity for autoantibody generation and co-existence of multiple risk factors for aHUS in Indian children.


Asunto(s)
Síndrome Hemolítico Urémico Atípico , Glomerulonefritis Membranoproliferativa , Glomerulonefritis , Niño , Humanos , Adolescente , Síndrome Hemolítico Urémico Atípico/genética , Glomerulonefritis Membranoproliferativa/tratamiento farmacológico , Autoanticuerpos , Inmunoglobulina G , Suero Antilinfocítico/uso terapéutico , Factor H de Complemento/genética
3.
J Clin Apher ; 38(4): 376-389, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-36408827

RESUMEN

BACKGROUND: Acute-on-chronic liver failure (ACLF) is associated with a high short-term mortality rate in the absence of liver transplantation. The role of therapeutic plasma exchange (TPE) in improving the outcomes of ACLF and acute decompensation (AD) is unclear. In this retrospective analysis, we aimed to determine the impact of TPE on mortality in patients with ACLF. METHODS: ACLF patients receiving TPE with standard medical treatment (SMT) were propensity score matched (PSM) with those receiving SMT alone (1:1) for sex, grades of ACLF, CLIF C ACLF scores, and the presence of hepatic encephalopathy. The primary outcomes assessed were mortality at 30 and 90 days. Survival analysis was performed using Kaplan Meier survival curves. RESULTS: A total of 1151 patients (ACLF n = 864 [75%], AD [without organ failure] n = 287 [25%]) were included. Of the patients with ACLF (n = 864), grade 1, 2, and 3 ACLF was present in 167 (19.3%), 325 (37.6%), and 372 (43.0%) patients, respectively. Thirty-nine patients received TPE and SMT, and 1112 patients received only SMT. On PSM analysis, there were 38 patients in each group (SMT plus TPE vs SMT alone). In the matched cohort, the 30-days mortality was lower in the TPE arm compared to SMT (21% vs 50%, P = .008), however, the 90-day mortality was not significantly different between the two groups (36.8% vs 52.6%, P = .166); HR, 0.82 (0.44-1.52), P = .549. CONCLUSION: TPE improves short-term survival in patients with ACLF, but has no significant impact on long-term outcomes. Randomized control trials are needed to obtain a robust conclusion in this regard.


Asunto(s)
Insuficiencia Hepática Crónica Agudizada , Femenino , Humanos , Masculino , Insuficiencia Hepática Crónica Agudizada/complicaciones , Intercambio Plasmático , Puntaje de Propensión , Estudios Retrospectivos
4.
Transfus Apher Sci ; 61(2): 103318, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-34782243

RESUMEN

BACKGROUND: The introduction of chemiluminescent immunoassay (CLIA) in blood donor screening has led to a gradual replacement of enzyme-linked-immunosorbent assay (ELISA) as the former offers automation, higher sensitivity and lower turn-around-time. However, only a few CLIA platforms are used for blood donor screening in India. The present study evaluated one such newer platform viz., Adiva Centaur XP CLIA for screening of HBV, HCV, HIV and syphilis. MATERIAL AND METHODS: Prospective comparative study wherein 4843 whole blood donors were screened for HBsAg, Anti-HCV, HIV Ag-Ab and Anti-treponemal antibodies in both Advia Centaur XP and Architect i2000SR platforms. Additional tests were performed in samples which were reactive in only one of the platforms. The sensitivity, specificity, positive predictive value, negative predictive value, accuracy, false positive rate and false negative rate of both the platforms were compared. Kappa coefficient was calculated to determine the agreement between the testing platforms. RESULTS: The sensitivity of Advia Centaur platform for HBV, HCV, HIV and syphilis detection were 94.9 %, 100 %, 100 % and 100 % respectively as compared to 96.6 %, 100 %, 100 % and 100 % in Architect i2000SR platform. The specificity of both the platforms were 99.8-99.9 % for all the four tests. The agreement between the two platforms was almost perfect for HBV, HCV and syphilis testing; and fair for HIV testing. CONCLUSION: The Advia Centaur CLIA platform was found to be comparable with the Architect CLIA platform for blood donor screening. Unexpected finding was the occurrence of HBV false negatives in both the platforms, possibly due to HBsAg mutations.


Asunto(s)
Infecciones por VIH , Hepatitis C , Sífilis , Donantes de Sangre , Infecciones por VIH/diagnóstico , Antígenos de Superficie de la Hepatitis B , Virus de la Hepatitis B , Hepatitis C/diagnóstico , Humanos , Inmunoensayo , Luminiscencia , Estudios Prospectivos , Sífilis/diagnóstico
5.
Vox Sang ; 116(5): 497-503, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33103772

RESUMEN

INTRODUCTION: Numerous concerns regarding maintenance of blood inventory have been raised after SARS-CoV-2 pandemic outbreak. These concerns were based on the experience of blood centres in previous pandemics where shortage of blood components was reported. The present study had tried to understand the impact of SARS-CoV-2 pandemic on blood collection and demand as well as the impact of disaster planning in maintaining an adequate inventory. METHODS: Data related to blood supply and demand were collected retrospectively using blood bank management software for pre-COVID-19 and COVID-19 time period and compared. Strategies adopted and effects of changes in existing disaster plans to maintain an adequate inventory were studied. RESULTS: A drastic fall in the red cell inventory was observed as compared to pre-COVID-19 time period was observed due to disproportionate decrease in blood collection (1/6 to 1/9 of the previous collection) and demand (1/2 of the previous demand). The buffer stock fell gradually over a period of three weeks with cancellation of planned blood donation drives. A buffer stock equivalent to 2-week inventory led to adequate inventory in the initial lockdown periods. Similar fall was observed in the platelet inventory with reduction in the blood collection but almost a proportionate reduction in the platelet demand led to adequate inventory. No increase in wastage was observed for both red cells and platelets during this period. DISCUSSION: A buffer stock of blood and blood components, strict adherence to the transfusion triggers, good coordination with the clinical staff and a prospective review of blood transfusion requests to ensure rational blood transfusion were some of the steps which helped us to successfully maintain transfusion requirements in the initial phases of the COVID-19 pandemic. Use of first-in-first-out policy prevented any wastage due to outdating of blood.


Asunto(s)
Bancos de Sangre/organización & administración , Seguridad de la Sangre/normas , COVID-19/epidemiología , Bancos de Sangre/normas , Donantes de Sangre/provisión & distribución , Seguridad de la Sangre/métodos , Hospitales/normas , Humanos
6.
Transfus Apher Sci ; 60(3): 103118, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-33752991

RESUMEN

INTRODUCTION: SARS-Coronavirus-2 pandemic has adversely affected blood supply as potential blood donors were afraid of acquiring infection in hospital settings. We aimed to compare COVID-19 seroprevalence among asymptomatic blood donors from healthcare and non-healthcare setting to analyse the difference in exposure level of each group as well as the risk of acquiring infection during the process of blood donation. MATERIAL AND METHODS: Analysis of whole blood donors tested for SARS-CoV-2 IgG antibodies was carried out after categorizing them into healthcare workers (HCW) and non-healthcare workers (NHCW). NHCW were further categorized into residents of containment and non-containment zones and seroprevalence analyzed. Seroprevalence among different ABO blood groups was also analyzed. RESULTS: 1191 blood donors were tested for SARS-CoV-2 antibodies with 9.5 % seropositivity. Significantly lower seropositivity of 3.2 % (p < 0.001) was observed among HCW as compared to 10.9 % seropositivity in NHCW. Among NHCW no difference in seropositivity was observed based on residence in containment or non-containment zone. Significantly higher (p = 0.012) seroprevalence was observed among A blood group donors (12.5 %) as compared to O blood group donors (6.8 %). CONCLUSION: Results suggests that a blood donor, in a hospital setting is less likely to be exposed to COVID-19 disease than when participating in activities of daily living. It is postulated that the lower seroprevalence among HCW as compared to NHCW reflects differences in knowledge and practice of preventive measures among these groups. The findings should instil confidence among blood donors and motivate them to donate blood without fear.


Asunto(s)
Donantes de Sangre/estadística & datos numéricos , COVID-19/epidemiología , Pruebas Diagnósticas de Rutina/métodos , Personal de Salud , SARS-CoV-2/aislamiento & purificación , Adolescente , Adulto , Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/inmunología , COVID-19/sangre , Humanos , India/epidemiología , Persona de Mediana Edad , Pandemias , Estudios Seroepidemiológicos , Adulto Joven
7.
Transfus Apher Sci ; 60(2): 103025, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33353804

RESUMEN

The Coronavirus disease-19 (COVID-19) pandemic has in multiple ways affected healthcare delivery to non-COVID patients throughout the world. Adequate transfusion services are fundamental in ongoing therapy of patients with hematological ailments. We present the transfusion services in the hematology daycare under the department of Hematology and supported by the Blood Bank at our institution for the period 12th April 2020-30th June 2020, which saw the stringent lockdown and unlocking Phase I in India, declared in lieu of the pandemic. A 56 % reduction in total transfusion sessions was observed in 2020 (588 sessions given to 176 patients) compared to 1336 sessions in 516 patients over the same period in 2019. The reductions were seen across the different blood components (packed red blood cells [PRBC]: 585 vs. 1840, platelet rich plasma: 372 vs. 1313, single donor platelet 18 vs. 16), with a significant reduction in the mean PRBC transfused per PRBC transfusion session (1.11 vs 1.99, p<0.001) in 2020, compared to 2019. There were however no major differences in the transfusion practices across the different phases of the lockdown. Our study highlights the detrimental reduction in transfusion services due to the COVID-19 pandemic and related lockdown and showcases the remedial strategies taken to maximize transfusion support to patients during this period. Our observations might help to provide insights to adequately combat possible similar adverse situations in the future.


Asunto(s)
Transfusión de Componentes Sanguíneos , COVID-19 , Pandemias , Plasma Rico en Plaquetas , SARS-CoV-2 , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , COVID-19/epidemiología , COVID-19/terapia , Niño , Preescolar , Femenino , Hematología , Humanos , India/epidemiología , Lactante , Masculino , Persona de Mediana Edad , Estudios Retrospectivos
8.
Transfus Med ; 31(3): 149-154, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-33749020

RESUMEN

INTRODUCTION: Recruitment of Covid-19 convalescent plasma (CCP) donors may present as a challenge due to inexperience and differences in donor profile as compared to whole blood donation. Present study highlights the deterrents to recruiting CCP donors at a hospital based blood centre. MATERIALS AND METHODS: Potential CCP donors were contacted individually by telephone and a group approach through camp organisers from May to July 2020. Recruitment challenges were noted and deferrals of these recruited donors during screening and medical examination was obtained and analysed. RESULTS: Total 1165 potential CCP donors were contacted. Around 47% donors were lost due to challenges related to information storage and retrieval. Fear of health, family pressure, and fear of a new procedure were major reason (27.2%) for unwillingness to donate. The main reasons for deferral among potential donors were multiparity (38%) and being overage/underage (31.6%). Finally, 468 donors were recruited including 408 by individual approach and 60 by a group approach. From these absence of detectable COVID-19 antibodies were found in 15.4%. Few donors (9.0%) were deferred as they had not completed 28 days post recovery. CONCLUSION: The process of CCP donor recruitment differs from that of whole blood donation and requires an individualised approach with involvement of clinicians in the initial phases of the pandemic. A group approach targeting specific organisations could be adopted for a successful CCP collection program. There is a need to relook into some aspects of donor selection such as consideration of multiparous female donors and overage/underage donors after reviewing scientific evidence.


Asunto(s)
Donantes de Sangre/psicología , COVID-19/terapia , Selección de Donante/estadística & datos numéricos , Plasma , SARS-CoV-2 , Adulto , Factores de Edad , Bancos de Sangre , Donantes de Sangre/estadística & datos numéricos , Selección de Donante/métodos , Miedo , Femenino , Hospitales , Humanos , Inmunización Pasiva/estadística & datos numéricos , India , Masculino , Persona de Mediana Edad , Paridad , Embarazo , Estudios Retrospectivos , Sueroterapia para COVID-19
9.
J Clin Apher ; 36(1): 41-47, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-32894894

RESUMEN

BACKGROUND: Single donor apheresis platelets are superior in quality, but their usage is limited in a developing country due to cost and time constraints. Hence the product obtained must exceed in terms of yield, donor safety and technical convenience. Previous literature available on cell separators is on older versions. AIMS: Prospective comparison of 5 latest cell separators (AmiCORE, COM.TEC, Haemonetics MCS+, SpectraOptia and TrimaAccel) for product yield, performance variables and donor adverse effects. MATERIAL & METHODS: From October 2019 - March 2020, 1108 donors were randomly allotted to a cell separator. Post-donation sample was taken from the donor 15-20 minutes after procedure completion. The platelet yield from the product collected was measured twice (day 0 and day 1). Donor demography, pre-and post-procedural donor peripheral blood values, performance and product variables were statistically analyzed. RESULTS: AmiCORE had an optimal collection efficacy (44.6%) and collection rate (0.037 x 1011/minute). Haemonetics MCS+ had a better collection efficacy (48.4%) and rate (0.038 x 1011/minute). Spectra Optia achieved least procedural time (59.5 minutes), donor adverse effects (6.3%); highest collection efficacy (52.8%) and rate (0.056 x 1011/minute). Trima Accel achieved highest collection rate (0.056 x 1011/minute) and the least product volume (228 ml). CONCLUSION: Highest collection efficacy was achieved by Trima Accel, highest collection rate by Trima Accel and Spectra Optia, lowest donor adverse effects by Spectra Optia and least number of procedural troubleshooting by COM.TEC. Apart from this, fiscal factors and service availability also need to be considered before choosing a cell separator.


Asunto(s)
Plaquetoferesis/instrumentación , Adulto , Donantes de Sangre , Femenino , Humanos , Masculino , Estudios Prospectivos , Centros de Atención Terciaria , Adulto Joven
10.
Transfus Apher Sci ; 59(4): 102814, 2020 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-32444281

RESUMEN

BACKGROUND AND OBJECTIVES: Treponemal tests provide advantage of better detection during early, late and latent stages of syphilis with equal or higher sensitivity & specificity in comparison to non-treponemal tests. The objective of the present study was to analyse the level of concordance between treponemal and non-treponemal tests for donor screening and to correlate them with donor history. MATERIALS AND METHODS: Retrospective analysis of syphilis screening by treponemal (Chemiluminescence & TPHA) and non-treponemal tests (RPR) was done and donor history for high-risk behaviour and factors associated with false positivity were collected from post-donation counselling and collected data was coded and analysed. RESULTS: Amongst the 12,000 donors screened, reactivity rate by RPR, TPHA and Chemiluminescence was 0.45%, 0.8% and 1.17% respectively. There was discordance of 62% and 32% for reactive results by RPR and TPHA respectively when compared with Chemiluminescence. History of high-risk behaviour was present in ∼ 50% and 15% of donors with discordant results by RPR and TPHA respectively. Of 34 donors who were reactive only by Chemiluminescence and were followed up, 15% had history of high-risk behaviour and 56% had factors associated with false reactivity. CONCLUSION: Treponemal tests showed high syphilis reactivity amongst blood donors as compared to non-treponemal tests most likely due to their ability to detect early, late and latent syphilis cases. This may confer added transfusion safety in centres dependent on replacement donors without NAT testing by identifying donors with high-risk history with negligible increase in discard rate due to false reactivity.


Asunto(s)
Donantes de Sangre/estadística & datos numéricos , Selección de Donante/métodos , Sífilis/terapia , Humanos , Estudios Retrospectivos , Sífilis/sangre , Atención Terciaria de Salud
11.
J Clin Immunol ; 39(3): 336-345, 2019 04.
Artículo en Inglés | MEDLINE | ID: mdl-30945073

RESUMEN

A homozygous 83-kb deletion encompassing the genes for complement factor-H-related proteins 1 and 3 (FHR 1, FHR3) is known as a risk factor for some immune inflammatory disorders. However, the functional relevance of this FHR1/3 deletion is relatively unexplored. Globally, healthy populations of all ethnic groups tested show an 8-10% prevalence of homozygosity for this deletion polymorphism. We have begun to compare the peripheral leucocyte phenotype and functionality between FHR1/3-/- and FHR1/3+/+ healthy adult individuals. We report that the two groups show significant differences in their peripheral blood innate leucocyte subset composition, although the adaptive immune subsets are similar between them. Specifically, FHR1/3-/- individuals show higher frequencies of patrolling monocytes and lower frequencies of classical monocytes than FHR1/3+/+ individuals. Similarly, FHR1/3-/- individuals show higher frequencies of plasmacytoid dendritic cells (pDCs) and lower frequencies of myeloid DCs (mDCs) than FHR1/3+/+ individuals. Notably, classical monocytes specifically showed cell-surface-associated factor H (FH), and cells from the FHR1/3-/- group had somewhat higher surface-associated FH levels than those from FHR1/3+/+ individuals. FHR1/3-/- monocytes also showed elevated secretion of TNF-α, IL-1ß, and IL-10 in response to TLR7/8 or TLR4 ligands. Similarly, FHR1/3-/- mDCs and pDCs showed modest but evident hyper-responsiveness to TLR ligands. Our findings, that the FHR1/3-/- genotype is associated with significant alterations of both the relative prominence and the functioning of monocyte and DC subsets, may be relevant in understanding the mechanism underlying the association of the genotype with immune inflammatory disorders.


Asunto(s)
Proteínas Sanguíneas/genética , Proteínas Inactivadoras del Complemento C3b/genética , Genotipo , Enfermedades del Sistema Inmune/genética , Inflamación/genética , Leucocitos Mononucleares/fisiología , Eliminación de Secuencia/genética , Adulto , Células Cultivadas , Citocinas , Femenino , Homocigoto , Humanos , Inmunidad Celular , Masculino , Persona de Mediana Edad , Fenotipo , Adulto Joven
12.
Indian J Med Res ; 150(5): 468-476, 2019 11.
Artículo en Inglés | MEDLINE | ID: mdl-31939390

RESUMEN

Background & objectives: The well-being of donors undergoing frequent plateletpheresis has been a matter of concern. The aim of this study was to analyze the effect of frequent plateletpheresis on the haematological parameters (HP) of repeat donors. Methods: The study was conducted during February 2016 to March 2017 on all the repeat plateletpheresis donors undergoing the 2nd plateletpheresis within a month of the first in a tertiary care centre. Donors repeating plateletpheresis 3rd and 4th times were also studied. The values of the HP observed on follow up after plateletpheresis done on three different separators were compared. Results: HPs of the 98 donors were similar at follow up except mean platelet volume (P <0.05). Of the 98 donors, 35 were followed up within a week and 63 were followed up within 8-30 days. No significant alteration was found in the HPs except a significant difference in the variation of platelet counts of the two groups (P=0.025). In 34 donors who presented 3rd time for plateletpheresis (mean gap between 1st and 3rd plateletpheresis=31 days), no significant differences in the HPs were found except the platelet distribution width (P <0.05). Minimal difference in the HP was found in the baseline and the follow up of 3rd plateletpheresis i.e., at 4th plateletpheresis donation. Plateletpheresis through all the three cell separators used had similar effects on the follow up HPs. Interpretation & conclusions: Repeated plateletpheresis can be done without any detrimental effects on the cell counts of the plateletpheresis donors. The three cell separators yielded similar post-donation follow up haematological parameters.


Asunto(s)
Donantes de Sangre , Plaquetas/metabolismo , Plaquetoferesis/efectos adversos , Adolescente , Adulto , Recuento de Células , Femenino , Humanos , Masculino , Persona de Mediana Edad , Recuento de Plaquetas , Plaquetoferesis/métodos , Factores de Tiempo , Adulto Joven
13.
Cell Biol Int ; 41(5): 570-576, 2017 May.
Artículo en Inglés | MEDLINE | ID: mdl-28198586

RESUMEN

The Pregnane and Xenobiotic Receptor (PXR; NR1I2) is a ligand-modulated transcription factor that belongs to the nuclear receptor superfamily. It is expressed at higher levels primarily in liver and intestine as compared to the levels in several other organs. It is activated by a broad spectrum of xenobiotics and endobiotics. The primary function of PXR is to regulate the expression of drug metabolizing enzymes and transporters and prevent the accumulation of toxic chemicals in the body, thereby maintaining body's homeostasis. In this study, we identified a C/T single nucleotide polymorphism at position -831 from the transcriptional start site of the PXR gene promoter and examined the functional significance of this variant using both the luciferase reporter gene assays and electrophoretic mobility shift assays (EMSA). Transient transfection experiments showed that the T-allele was associated with significantly greater transcriptional activity than the C-allele of SNP rs3814055. These results indicate that the -831C/T polymorphism has a direct effect on transcriptional regulation of PXR gene. This allelic variation may be a potential genetic marker that can help identify individuals at higher risk for Inflammatory Bowel Disease (IBD).


Asunto(s)
Polimorfismo de Nucleótido Simple/genética , Regiones Promotoras Genéticas , Receptores de Esteroides/genética , Alelos , Extractos Celulares , Hepatocitos/metabolismo , Humanos , Proteínas Nucleares/metabolismo , Receptor X de Pregnano , Unión Proteica
14.
J Clin Monit Comput ; 31(4): 739-746, 2017 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-27484693

RESUMEN

Non-hypotensive hypovolemia, observed during mild haemorrhage or blood donation leads to reflex readjustment of the cardiac autonomic tone. In the present study, the cardiac autonomic tone was quantified using heart rate and blood pressure variability during and after non-hypotensive hypovolemia of blood donation. 86 voluntary healthy male blood donors were recruited for the study (age 35 ± 9 years; weight 78 ± 12 kg; height 174 ± 6 cms). Continuous lead II ECG and beat-to-beat blood pressure was recorded before, during and after blood donation followed by offline time and frequency domain analysis of HRV and BPV. The overall heart rate variability (SDNN and total power) did not change during or after blood donation. However, there was a decrease in indices that represent the parasympathetic component (pNN50 %, SDSD and HF) while an increase was observed in sympathetic component (LF) along with an increase in sympathovagal balance (LF:HF ratio) during blood donation. These changes were sustained for the period immediately following blood donation. No fall of blood pressure was observed during the period of study. The blood pressure variability showed an increase in the SDNN, CoV and RMSSD time domain measures in the post donation period. These results suggest that mild hypovolemia produced by blood donation is non-hypotensive but is associated with significant changes in the autonomic tone. The increased blood pressure variability and heart rate changes that are seen only in the later part of donation period could be because of the progressive hypovolemia associated parasympathetic withdrawal and sympathetic activation that manifest during the course of blood donation.


Asunto(s)
Sistema Nervioso Autónomo/fisiopatología , Frecuencia Cardíaca/fisiología , Hipovolemia/fisiopatología , Adulto , Arterias/fisiopatología , Donantes de Sangre , Presión Sanguínea/fisiología , Determinación de la Presión Sanguínea , Electrocardiografía , Corazón/fisiopatología , Hemorragia/fisiopatología , Humanos , Hipotensión , Masculino , Monitoreo Fisiológico , Sistema Nervioso Parasimpático/fisiología , Presorreceptores/fisiopatología , Procesamiento de Señales Asistido por Computador , Sistema Nervioso Simpático/fisiología
15.
STAR Protoc ; 5(2): 103119, 2024 Jun 21.
Artículo en Inglés | MEDLINE | ID: mdl-38850540

RESUMEN

The B cell "help" function of CD4+ T cells is critical in establishing the humoral arm of adaptive immunity. Here, we present a protocol to measure the "help" function of antigen-specific memory T cells using an autologous T-B coculture supplemented with monocytes. We describe steps for cell preparation, human cell sorting, coculture, and a flow cytometry-based assessment of B cell outputs. This protocol demonstrates enhanced sensitivity and proves useful in evaluating T-B collaboration in various contexts of health and disease. For complete details on the use and execution of this protocol, please refer to Ansari et al.1.


Asunto(s)
Linfocitos B , Linfocitos T CD4-Positivos , Técnicas de Cocultivo , Citometría de Flujo , Humanos , Técnicas de Cocultivo/métodos , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD4-Positivos/citología , Linfocitos B/inmunología , Linfocitos B/citología , Citometría de Flujo/métodos , Células T de Memoria/inmunología , Células T de Memoria/citología , Memoria Inmunológica/inmunología
16.
Indian Pediatr ; 61(6): 564-570, 2024 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-38872290

RESUMEN

OBJECTIVE: To report the outcomes of pediatric patients who underwent allogeneic hematopoietic stem cell transplant (HSCT) in single rooms without high-efficiency particulate air (HEPA) filters, laminar air flow or positive pressure at our centre and discuss the adaptations of a high-volume government centre. METHODS: Data of the first 20 children who underwent allogeneic HSCT between May 2019 and July 2023 in adaptive settings were reviewed retrospectively. All patients were managed in in single rooms without HEPA filters, positive pressure or laminar air flow. Supportive care in the form of antimicrobial prophylaxis, veno-occlusive disease prophylaxis, anti-epileptics (with busulfan) and irradiated blood products were provided. Trained manpower including multi-specialty consultations were readily available. All complications including infections were managed as per standard guidelines. RESULTS: The median (range) of children included was 6 (1-20) years. For eight patients we used alternate donors. The mean (SD) time to neutrophil and platelet engraftment were 17.0 (8.07) days and 18.8 (10.1) days, respectively. The mean (SD) time to discharge from the hospital was 30.9 (10.04) days. There were no deaths within 30 days. Six children each developed acute and chronic graft-versus-host disease (GVHD). The overall survival at a median follow-up of 292 days was 70% (n = 14). CONCLUSION: With certain adaptations in the existing infrastructure in resource-limited settings, allogeneic HSCT can be performed with good outcomes, provided experienced, dedicated and adequate personnel, comprehensive supportive care, multidisciplinary consultative support and isolation are provided.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Humanos , Trasplante de Células Madre Hematopoyéticas/métodos , Niño , India , Adolescente , Femenino , Masculino , Preescolar , Estudios Retrospectivos , Lactante , Adulto Joven , Hermanos , Trasplante Homólogo/métodos , Atención Terciaria de Salud , Enfermedad Injerto contra Huésped/prevención & control , Donantes de Tejidos/estadística & datos numéricos
17.
Blood Cell Ther ; 7(1): 25-32, 2024 Feb 25.
Artículo en Inglés | MEDLINE | ID: mdl-38486828

RESUMEN

Autologous stem cell transplantation (ASCT) is the standard treatment for many high-risk solid tumors. Patients undergoing ASCT should be managed in a dedicated hematopoietic stem cell transplantation (HSCT) unit with isolation rooms, high-efficiency particulate air (HEPA) filters, and positive pressure. We report the outcomes of the first 20 pediatric patients who underwent ASCT in isolation rooms with no HEPA filters or positive pressure. Moreover, the isolation rooms were not part of a dedicated HSCT unit. Data from 20 patients were analyzed. All patients included in the study underwent ASCT after harvest and cryopreservation of the hematopoietic stem cells (HSC). Furthermore, all patients also underwent myeloablative conditioning. The most common indications for ASCT included high-risk neuroblastoma (HR-NB) (n=9) and refractory/relapsed Hodgkin's lymphoma (HL) (n=6). The median CD-34 positive HSC administered was 4.5 (0.8-21.9) million per kg. The median time to neutrophil and platelet engraftment was 16.5 (10-35) and 19 (10-87) days, respectively. Additionally, only one transplant-related mortality was observed and the mean time to discharge from the hospital was 27.6+8.3 days. The overall survival for all our patients was 75% at a median follow-up of 33.2 months (15 out of 20 patients survived), and the disease-free survival was 60% (median follow-up, 28.4 months). The overall survival for the patients with HL was 85.7% at a median of 45.3 months and for the HR-NB was 66.7% at a median of 34.9 months. This study provides evidence that ASCT can be safely performed in isolation rooms without HEPA filters and positive pressure if expertise and supportive care are available. In settings with limited resources, such a model could help establish low-cost HSCT units.

18.
Blood Cell Ther ; 6(3): 72-76, 2023 Aug 25.
Artículo en Inglés | MEDLINE | ID: mdl-38146356

RESUMEN

Plerixafor for peripheral blood hematopoietic stem cell (PB HSC) mobilization in children undergoing autologous hematopoietic stem cell transplantation is primarily used following failure of the initial mobilization attempt. Data on plerixafor use in pediatric patients are limited. This retrospective study conducted at a single tertiary care center in India, details the efficacy and safety of plerixafor for 10 children with relapsed/refractory solid tumors or lymphomas. High risk neuroblastomas (HR NB) underwent autologous HSCT as part of consolidation. Plerixafor was administered at a dose of 240 µg/kg body weight of the recipient, subcutaneously, approximately 11-12 h prior to harvest. Ten patients (eight males, two females), with a median age of 8 years (range 2-18 years), received plerixafor prior to PB HSC harvest. All patients were administered granulocyte colony stimulating factor (GCSF) before the administration of plerixafor. The median CD 34 count for all patients pre-plerixafor was 29/µL, nine patients exhibited higher CD 34 post plerixafor (median of 148/µL). In nine patients, the values of the CD 34 count and total leukocyte count (TLC) of the harvested product were available, and in all cases, we achieved a good yield. All patients in this study were heavily chemotherapy pre-treated, and the use of plerixafor resulted in a satisfactory yield of peripheral blood stem cells. No side effects were observed.

19.
Asian J Transfus Sci ; 17(2): 182-188, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38274978

RESUMEN

BACKGROUND: Asymptomatic/presymptomatic COVID-19 affected individuals who may appear healthy during blood donor screening can donate blood despite being infective. Most blood donors in India are relatives/friends/acquaintances of patients, who under peer pressure overlook the donor selection process, which can significantly impact the transfusion safety. AIMS: The prevalence of severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) antibodies among blood donors was assessed, along with the possible transmissibility of SARS-CoV-2 virus in transfusion recipients of blood components prepared from sero-reactive blood donors. SETTINGS AND DESIGN: A prospective cross-sectional study was conducted among eligible blood donors from November-2020 to April 2021. METHODS: 1500 blood donors were tested for SARS-CoV-2 IgG antibodies. Sero-reactive donors were followed-up telephonically to inquire about risk factors prior to donation or appearance of COVID-19 related symptoms postdonation. Patients transfused with blood components from seroreactive donors were also followed up for posttransfusion symptoms suggestive for COVID-19. Descriptive analysis was done for the donor and patient follow-up data. RESULTS: A total of 452 (30.1%) donor were reactive, with median S/CO ratio of 2.8 (interquartile range 1.5-5.5). Risk factors such as travel, contact, or quarantine were significantly higher among reactive donors. History of diabetes and/or hypertension was associated with seroreactivity. Total 516 patients were transfused with blood components from these seroreactive donors. Three patients developed fever after transfusion, one of which was found to be PCR positive after 4 days of transfusion. CONCLUSION: Sero-reactivity rate among blood donors was lower than the general population. Optimum blood donor screening strategies can help decrease the possibility of blood collection from infected blood donors.

20.
Am J Blood Res ; 13(5): 152-161, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38023414

RESUMEN

BACKGROUND: Transfusion of granulocytes obtained by apheresis is beneficial in febrile neutropenia (FN) but expensive and time-consuming. Buffy-coat-derived granulocytes could be an alternative. We studied the efficacy and safety of the administration of irradiated buffy-coat-derived granulocytes along with the standard of care in pediatric high-risk (HR) FN. METHODS: Sixty children ≤18 years with malignancy and chemotherapy-induced HR FN were randomized to either the granulocyte transfusion (GT) arm which received irradiated buffy-coat derived granulocyte transfusion along with the standard treatment or the standard treatment (ST) arm. RESULTS: Baseline characteristics, day-to-defervescence, antibiotic duration, hospital stay, and mortality were comparable between the groups. A significant difference was seen in days to achieve absolute neutrophil count (ANC) >500/mm3 in the 2 groups: 4.5 days (3-6.5) in the GT arm v/s 8 days (4-11) in the ST arm (P=0.01). CONCLUSION: Buffy-coat-derived granulocyte transfusion was safe and led to early hematological recovery but was not associated with survival benefits. Future studies with earlier initiation in the intended dose could be undertaken to generate more evidence.

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