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1.
Pediatr Obes ; 11(2): 151-7, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25955285

RESUMO

BACKGROUND: Indian newborns have been described as 'thin-fat' compared with European babies, but little is known about how this phenotype relates to the foetal growth factor IGF-I (insulin-like growth factor I) or its binding protein IGFBP-3. OBJECTIVE: To assess cord IGF-I and IGFBP-3 concentrations in a sample of Indian newborns and evaluate their associations with neonatal adiposity and maternal factors. METHODS: A prospective cohort study of 146 pregnant mothers with dietary, anthropometric and biochemical measurements at 28 and 34 weeks gestation. Neonatal weight, length, skin-folds, circumferences, and cord blood IGF-I and IGFBP-3 concentrations were measured at birth. RESULTS: Average cord IGF-I and IGFBP-3 concentrations were 46.6 (2.2) and 1269.4 (41) ng mL(-1) , respectively. Girls had higher mean IGF-I than boys (51.4 ng mL(-1) vs. 42.9 ng mL(-1) ; P < 0.03), but IGFBP-3 did not differ. Cord IGF-I was positively correlated with all birth size measures except length, and most strongly with neonatal sum-of-skin-folds (r = 0.50, P < 0.001). IGFBP-3 was positively correlated with ponderal index, sum-of-skin-folds and placenta weight (r = 0.21, 0.19, 0.16, respectively; P < 0.05). Of maternal demographic and anthropometric characteristics, only parity was correlated with cord IGF-I (r = 0.27, P < 0.001). Among dietary behaviours, maternal daily milk intake at 34 weeks gestation predicted higher cord IGF-I compared to no-milk intake (51.8 ng mL(-1) vs. 36.5 ng mL(-1) , P < 0.01) after controlling for maternal characteristics, placental weight, and newborn gestational age, sex, weight and sum-of-skin-folds. Sum-of-skin-folds were positively associated with cord IGF-I in this multivariate model (57.3 ng mL(-1) vs. 35.1 ng mL(-1) for highest and lowest sum-of skin-fold quartile, P < 0.001). IGFBP-3 did not show significant relationships with these covariates. CONCLUSION: In this Indian study, cord IGF-I concentration was associated with greater adiposity among newborns. Maternal milk intake may play a role in this relationship.


Assuntos
Composição Corporal , Aleitamento Materno , Comportamento Alimentar , Sangue Fetal/metabolismo , Recém-Nascido/sangue , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/sangue , Fator de Crescimento Insulin-Like I/metabolismo , Leite , Mães , Animais , Peso ao Nascer , Índice de Massa Corporal , Feminino , Desenvolvimento Fetal , Idade Gestacional , Humanos , Índia , Lactente , Masculino , Paridade , Gravidez , Estudos Prospectivos , Fatores de Risco
2.
J Dev Orig Health Dis ; 3(1): 32-8, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25101809

RESUMO

Longitudinal studies investigating vitamin B12 and folate status of mothers and their offspring will provide a better understanding of intergenerational nutrition. During pregnancy and 2 years (2y) after delivery, we measured plasma vitamin B12 and folate concentrations in 118 women [aged (mean ± s.d.) 22.9 ± 3.9y] who attended a rural (n = 68) or an urban (n = 50) antenatal clinic in Pune, India. Cord blood vitamin B12 and folate were measured, and when the child was 2y total homocysteine (tHcy) was also measured. Demographic and diet measurements were recorded using standard methods. Pregnancy plasma vitamin B12 concentration at 34 weeks was low [median (25th, 75th), 115 (95, 147) pm]; 75% had low status (<150 pm). Plasma folate was high (mean ± s.d., 33 ± 21 nm); one had a folate concentration <7 pm. Cord plasma vitamin B12 and folate concentrations were higher than and positively associated with maternal concentrations. In stepwise regression, higher child vitamin B12 at 2y was predicted (total R 2 15.7%) by pregnancy vitamin B12 (std ß 0.201, R 2 7.7%), current consumption of cow's milk (std ß 0.194, R 2 3.3%) and whether breast feeding was stopped before 2y (std ß -0.234 R 2 7.2%). Child's 2y tHcy concentration was high (11.4 ± 3.6 µm) and predicted by lower pregnancy vitamin B12 (std ß -0.206, R 2 4.1%), lack of vitamin supplementation (std ß -0.256, R 2 5.6%) in pregnancy and whether currently breastfed (std ß 0.268, R 2 8.4%). Low maternal vitamin B12 status in pregnancy and prolonged breast-feeding results in disturbed one-carbon metabolism in offspring at 2y. Supplementation of women of child-bearing age, particularly during pregnancy and lactation, may improve the homocysteine status of these children.

3.
J Dev Orig Health Dis ; 3(2): 123-30, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25101923

RESUMO

Insufficiency of vitamin B12 (B12) and folate during pregnancy can result in low concentrations in the fetus and have adverse effects on brain development. We investigated the relationship between maternal B12 and folate nutrition during pregnancy and offspring motor, mental and social development at two years of age (2 y). Mothers (n = 123) and their offspring (62 girls, 61 boys) from rural and middle-class urban communities in and around Pune city were followed through pregnancy up to 2 y. Maternal B12 and folate concentrations were measured at 28 and 34 weeks of gestation. At 2 y, the Developmental Assessment Scale for Indian Infants was used to determine motor and mental developmental quotients and the Vineland Social Maturity Scale for the social developmental quotient. Overall, 62% of the mothers had low B12 levels (<150 pmol/l) and one mother was folate deficient during pregnancy. Maternal B12 at 28 and 34 weeks of gestation was associated with offspring B12 at 2 y (r = 0.29, r = 0.32, P < 0.001), but folate was not associated with offspring folate. At 2 y, motor development was associated with maternal folate at 28 and 34 weeks of gestation. Mental and social development quotients were associated positively with head circumference and negatively with birth weight. In addition, pregnancy B12 and folate were positively associated with mental and social development quotients. Maternal B12 and folate during intrauterine life may favorably influence brain development and function. Pregnancy provides a window of opportunity to enhance fetal psychomotor (motor and mental) development.

4.
Br J Neurosurg ; 23(3): 318-20, 2009 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-19533467

RESUMO

Intracranial endodermal cysts are most commonly located in the posterior cranial fossa anterior to the brainstem. We report a rare case of an endodermal cyst of the posterior fossa located dorsal to the brainstem and is to our knowledge the only other such case reported in the literature.


Assuntos
Cistos do Sistema Nervoso Central/cirurgia , Fossa Craniana Posterior/cirurgia , Neoplasias da Base do Crânio/cirurgia , Cistos do Sistema Nervoso Central/diagnóstico , Cistos do Sistema Nervoso Central/patologia , Ataxia Cerebelar/etiologia , Fossa Craniana Posterior/patologia , Diagnóstico Diferencial , Feminino , Humanos , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Neoplasias da Base do Crânio/diagnóstico , Neoplasias da Base do Crânio/patologia
5.
Br J Neurosurg ; 23(1): 30-2, 2009 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19234906

RESUMO

Giant pituitary adenomas causing hydrocephalus are rare (Scarone P, Losa M, Mortini P, Giovanelli M. J Neurooncol 2006;76:51-4; Zikel OM, Atkinson JL, Hurley DL. Mayo Clinical Proc 1999;74:475-7). Guidelines for management of this rare condition are missing. Here we present a five-case series collected over 22 years. We suggest that where the two conditions coexist, the safest option is to insert an external ventricular drain prior to any definitive surgical intervention.


Assuntos
Adenoma/cirurgia , Hidrocefalia/cirurgia , Procedimentos Neurocirúrgicos/métodos , Neoplasias Hipofisárias/cirurgia , Adenoma/complicações , Adenoma/patologia , Adulto , Idoso , Feminino , Humanos , Hidrocefalia/etiologia , Hidrocefalia/patologia , Masculino , Neoplasias Hipofisárias/complicações , Neoplasias Hipofisárias/patologia , Tomografia Computadorizada por Raios X , Resultado do Tratamento
6.
J Trop Pediatr ; 55(2): 97-102, 2009 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-18782858

RESUMO

The study aims to evaluate the efficacy of technetium-99m diethylenetriaminepentaacetic acid ((99m)Tc-DTPA) lung clearance test in the diagnosis of pneumocystis carinii pneumonia (PCP) in HIV-positive paediatric patients. Twenty HIV-negative patients with no chest symptoms constituted Group A, 25 HIV antibody positive asymptomatic children formed Group B, while 45 HIV antibody positive children with respiratory infections comprised Group C. Group C was subdivided into C(1) (n = 20, documented PCP on microbiology), C(2) (n = 10, tuberculosis) and C(3) (n = 15, bacterial pneumonias). The mean age group of patients in Group A, Group B and Group C was 4.7 +/- 1.9, 4.2 +/- 1.5 and 4.8 +/- 1.7 years, respectively. All patients were subjected to complete blood count, blood culture, chest radiographs, microscopic staining of sputum (PCP stains, Ziehl-Nielsen staining, Gram staining), ABG and Mantoux test. All these patients underwent dynamic lung scans using (99m)Tc-DTPA aerosols and lung clearance was calculated in terms of half-time transfer value (T(1/2)) value. T(1/2) was compared between different groups and lung scan findings were correlated with radiological and microbiological results. Patients with PCP had T(1/2) in the range of 9.02 +/- 1.35, TB 28.2 +/- 3.03 min and other bacterial pneumonias in the range of 20.5 +/- 3.1 min (range for normal individuals was 49.8 +/- 6.13 min). T(1/2) in patients with PCP was found to be significantly lower when compared with T(1/2) in other groups. Patients with PCP had characteristic biphasic curves while the rest had monophasic curves. Some patients with PCP had low T(1/2) values even when chest radiographs and arterial blood gases were normal. (99m)Tc-DTPA lung clearance test is a sensitive, safe and non-invasive diagnostic tool for the early detection of PCP in HIV-positive paediatric patients.


Assuntos
Soropositividade para HIV/complicações , Pulmão/diagnóstico por imagem , Pneumonia por Pneumocystis/diagnóstico por imagem , Compostos Radiofarmacêuticos , Pentetato de Tecnécio Tc 99m , Infecções Oportunistas Relacionadas com a AIDS/complicações , Infecções Oportunistas Relacionadas com a AIDS/tratamento farmacológico , Administração por Inalação , Aerossóis , Criança , Pré-Escolar , Feminino , HIV-1 , Humanos , Masculino , Pneumonia por Pneumocystis/complicações , Pneumonia por Pneumocystis/tratamento farmacológico , Estudos Prospectivos , Cintilografia , Combinação Trimetoprima e Sulfametoxazol/uso terapêutico
7.
J Laryngol Otol ; 123(8): 925-7, 2009 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-18796183

RESUMO

OBJECTIVE: We report an adult case of nasopharyngeal carcinoma treated with radical chemo-radiotherapy, with subsequent development of a histologically proved temporal cavernous haemangioma within the radiation field. METHOD: Case report and review of the current literature concerning radiation-induced, secondary, space-occupying lesions. CONCLUSION: The increasing role of radiotherapy in nasopharyngeal carcinoma treatment, together with improved patient survival, is likely to lead to radiation-induced, secondary, space-occupying lesions being encountered more frequently. We emphasise the need to be vigilant for this important but relatively rare complication, which has significant associated morbidity.


Assuntos
Hemangioma Cavernoso/etiologia , Neoplasias Nasofaríngeas , Neoplasias Induzidas por Radiação/etiologia , Quimioterapia Adjuvante/efeitos adversos , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias Nasofaríngeas/tratamento farmacológico , Neoplasias Nasofaríngeas/radioterapia , Dosagem Radioterapêutica , Fatores de Risco , Tomografia Computadorizada por Raios X , Resultado do Tratamento
8.
J Acoust Soc Am ; 124(3): EL157-62, 2008 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-19045559

RESUMO

On the New Jersey continental shelf ambient sound levels were recorded during tropical storm Ernesto that produced wind speeds up to 40 knots in early September 2006. The seabed at the position of the acoustic measurements can be approximately described as coarse sand. Differences between the ambient noise levels for the New Jersey shelf measurements and deep water reference measurements are modeled using both normal mode and ray methods. The analysis is consistent with a nonlinear frequency dependent seabed attenuation for the New Jersey site.


Assuntos
Acústica , Tempestades Ciclônicas , Sedimentos Geológicos , Ruído , Dióxido de Silício , Vento , Oceano Atlântico , Modelos Teóricos , New Jersey , Dinâmica não Linear , Oceanos e Mares , Oceano Pacífico , Espectrografia do Som
9.
Br J Neurosurg ; 21(4): 399-402, 2007 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-17676462

RESUMO

Pituitary tumours usually present with visual field defects; extraocular palsy is usually a sign of cavernous sinus extension and is a sign of advanced disease. We report a case of a pituitary adenoma presenting with complete, bilateral oculomotor nerve palsies, but minimal loss of visual fields, and intact abducens and trochlear nerves.


Assuntos
Síndromes de Compressão Nervosa/etiologia , Nervo Oculomotor/cirurgia , Oftalmoplegia/etiologia , Apoplexia Hipofisária/etiologia , Neoplasias Hipofisárias/complicações , Idoso , Feminino , Humanos , Síndromes de Compressão Nervosa/diagnóstico , Oftalmoplegia/diagnóstico , Apoplexia Hipofisária/diagnóstico , Neoplasias Hipofisárias/diagnóstico , Resultado do Tratamento
12.
Emerg Med J ; 22(12): 909-10, 2005 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-16299213

RESUMO

Colloid cyst of the third ventricle is a rare benign intracranial lesion, and familial cases are rarer still. They may be asymptomatic or present with symptoms of raised intracranial pressure, including sudden death. Surgical excision is curative. We report a 24 year old pregnant woman with familial colloid cyst, who presented with headaches and suffered a cardiorespiratory arrest. Early computed tomography scan of the brain is advised in patients with a family history of third ventricular colloid cyst presenting to the accident and emergency department with headache.


Assuntos
Encefalopatias/diagnóstico por imagem , Cistos/diagnóstico por imagem , Complicações na Gravidez/diagnóstico por imagem , Terceiro Ventrículo , Adulto , Encefalopatias/complicações , Encefalopatias/genética , Ventriculografia Cerebral , Cistos/complicações , Cistos/genética , Morte Súbita/etiologia , Evolução Fatal , Feminino , Cefaleia/etiologia , Humanos , Gravidez , Tomografia Computadorizada por Raios X
13.
Br J Neurosurg ; 17(2): 160-3, 2003 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-12820759

RESUMO

The objective of the study was to highlight the diagnostic challenge of this elusive rare disease. A retrospective study of non-tuberculous spinal epidural abscesses (SEA) was carried out in Southern General Hospital, Glasgow, University Hospital of Wales, Cardiff, and Morriston Hospital, Swansea, from 1990 to 2000. Thirty-nine patients, consisting of 20 females and 19 males, with an age range from 20 to 85 years (mean: 61.1) were identified. Thirty-eight had localized back/neck pain. Eighteen were apyrexial. Twenty-nine demonstrated neurological deficit. All patients had raised inflammatory markers and gadolinium-enhanced magnetic resonance imaging (MRI) was diagnostic in 34. The most commonly identified organism was Staphylococcus aureus. All underwent surgical decompression, of which 13 required stabilization. Three died, seven lacked sphincter control and nine had motor deficit at the end of 1 year. It was concluded that fever is not mandatory for the diagnosis of SEA. Patients with localized back/neck pain and raised inflammatory markers need urgent MRI.


Assuntos
Abscesso Epidural/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Abscesso Epidural/microbiologia , Abscesso Epidural/terapia , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Infecções Estafilocócicas/diagnóstico , Staphylococcus aureus , Resultado do Tratamento
15.
J Virol ; 75(6): 2753-64, 2001 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-11222698

RESUMO

Purified retrovirus Gag proteins or Gag protein fragments are able to assemble into virus-like particles (VLPs) in vitro in the presence of RNA. We have examined the role of nucleic acid and of the NC domain in assembly of VLPs from a Rous sarcoma virus (RSV) Gag protein and have characterized these VLPs using transmission electron microscopy (TEM), scanning TEM (STEM), and cryoelectron microscopy (cryo-EM). RNAs of diverse sizes, single-stranded DNA oligonucleotides as small as 22 nucleotides, double-stranded DNA, and heparin all promoted efficient assembly. The percentages of nucleic acid by mass, in the VLPs varied from 5 to 8%. The mean mass of VLPs, as determined by STEM, was 6.5 x 10(7) Da for both RNA-containing and DNA oligonucleotide-containing particles, corresponding to a stoichiometry of about 1,200 protein molecules per VLP, slightly lower than the 1,500 Gag molecules estimated previously for infectious RSV. By cryo-EM, the VLPs showed the characteristic morphology of immature retroviruses, with discernible regions of high density corresponding to the two domains of the CA protein. In spherically averaged density distributions, the mean radial distance to the density corresponding to the C-terminal domain of CA was 33 nm, considerably smaller than that of equivalent human immunodeficiency virus type 1 particles. Deletions of the distal portion of NC, including the second Zn-binding motif, had little effect on assembly, but deletions including the charged residues between the two Zn-binding motifs abrogated assembly. Mutation of the cysteine and histidine residues in the first Zn-binding motif to alanine did not affect assembly, but mutation of the basic residues between the two Zn-binding motifs, or of the basic residues in the N-terminal portion of NC, abrogated assembly. Together, these findings establish VLPs as a good model for immature virions and establish a foundation for dissection of the interactions that lead to assembly.


Assuntos
Vírus do Sarcoma Aviário/metabolismo , Produtos do Gene gag/química , Produtos do Gene gag/metabolismo , Vírion/metabolismo , Vírus do Sarcoma Aviário/química , Vírus do Sarcoma Aviário/genética , Vírus do Sarcoma Aviário/ultraestrutura , Escherichia coli , Produtos do Gene gag/genética , Microscopia Eletrônica/métodos , RNA Viral/química , RNA Viral/genética , RNA Viral/metabolismo , Proteínas Virais/genética , Proteínas Virais/metabolismo , Vírion/ultraestrutura , Montagem de Vírus
16.
Indian J Dent Res ; 12(4): 222-8, 2001.
Artigo em Inglês | MEDLINE | ID: mdl-11987661

RESUMO

Finishing and Polishing constitutes an essential requisite after the fabrication of removable partial dentures. Improper finishing and polishing of cast framework will adversely affect the quality of functional units of partial dentures due to reduced dimensions. In this study the polished surface characteristic and loss of weight of the casting were evaluated and compared following different finishing and polishing techniques. A total number of thirty test specimens were cast and each surface finishing and polishing technique was carried out with a high speed polishing motor and an electropolishing unit under standardised conditions. Surface roughness was evaluated by means of a surface roughness analyzing instrument, Perthometer. The loss of weight due to the metal lost was observed on a sensitive electronic balance. The results of polishing technique employed with G3 group revealed better surface characteristic. It may be understood that sandblasting causes initial roughness and the sequence of coarse cylindrical abrasive, Black hard rubber polisher (coarse grit-Dentauram), Grey hard rubber polisher (Med-grit-Dentauram), Green hard rubber polisher (Fine-grit-Dentauram), Grey flexible rubber polisher (Fine grit-Renfert), felt buff with pumice slurry and felt buff with green polishing compound (Degussa) produced improved surface in this case. The loss of weight due to metal lost show concern with technique groups G4, G5, G6. It can be avoided by judicious sandblasting and application of proper grit of abrasive agents.


Assuntos
Ligas de Cromo , Polimento Dentário/métodos , Prótese Parcial Removível , Análise de Variância , Cobalto , Técnica de Fundição Odontológica , Planejamento de Dentadura , Estatísticas não Paramétricas , Propriedades de Superfície
17.
J Virol ; 74(21): 10260-8, 2000 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-11024160

RESUMO

Purified retrovirus Gag proteins can assemble in vitro into virus-like particles (VLPs) in the presence of RNA. It was shown previously that a Rous sarcoma virus Gag protein missing only the protease domain forms spherical particles resembling immature virions lacking a membrane but that a similar protein missing the p10 domain forms tubular particles. Thus, p10 plays a role in spherical particle formation. To further study this shape-determining function, we dissected the p10 domain by mutagenesis and examined VLPs assembled within Escherichia coli or assembled in vitro from purified proteins. The results identified a minimal contiguous segment of 25 amino acid residues at the C terminus of p10 that is sufficient to restore efficient spherical assembly to a p10 deletion mutant. Random and site-directed mutations were introduced into this segment of polypeptide, and the shapes of particles formed in E. coli were examined in crude extracts by electron microscopy. Three phenotypes were observed: tubular morphology, spherical morphology, or no regular structure. While the particle morphology visualized in crude extracts generally was the same as that visualized for purified proteins, some tubular mutants scored as spherical when tested as purified proteins, suggesting that a cellular factor may also play a role in shape determination. We also examined the assembly properties of smaller Gag proteins consisting of the capsid protein-nucleocapsid protein (CA-NC) domains with short N-terminal extensions or deletions. Addition of one or three residues allowed CA-NC to form spheres instead of tubes in vitro, but the efficiency of assembly was extremely low. Deletion of the N-terminal residue(s) abrogated assembly. Taken together, these results imply that the N terminus of CA and the adjacent upstream 25 residues play an important role in the polymerization of the Gag protein.


Assuntos
Vírus do Sarcoma Aviário/química , Produtos do Gene gag/química , Produtos do Gene gag/metabolismo , Proteínas Virais/metabolismo , Vírion/ultraestrutura , Sequência de Aminoácidos , Vírus do Sarcoma Aviário/genética , Escherichia coli , Produtos do Gene gag/genética , Microscopia Eletrônica , Dados de Sequência Molecular , Mutagênese Sítio-Dirigida , Conformação Proteica , Estrutura Terciária de Proteína , Proteínas Virais/química , Proteínas Virais/genética , Vírion/metabolismo , Montagem de Vírus
19.
Br J Neurosurg ; 12(4): 325-8, 1998 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-10070424

RESUMO

A retrospective study of 57 surgically-managed brain abscesses at the Neurosurgical Unit, Bir Hospital during a 6-year period from October 1990 is presented. Detailed hospital case notes could be traced in only 37 cases, consisting of 25 males and 12 females with age range from 5 months to 60 years. Cryptogenic abscess was the commonest category followed by abscess caused by chronic ear infection. The diagnosis was made with enhanced computed tomography (CT) in all the cases. Positive bacteriology was found in only nine cases. The treatment consisted of 6 weeks of intensive intravenous antibiotics and emergency surgical drainage of the abscess. Five out of the total cases died (13.5%). These patients were all in an extremely poor condition at the time of presentation. All the survivors made a good recovery. With timely CT diagnosis, surgical drainage and antibiotics, good results can be achieved even in a developing country.


Assuntos
Abscesso Encefálico/cirurgia , Otopatias/microbiologia , Infecções por Bactérias Gram-Positivas/complicações , Infecções por Proteus/complicações , Adolescente , Adulto , Antibacterianos/uso terapêutico , Abscesso Encefálico/tratamento farmacológico , Abscesso Encefálico/microbiologia , Criança , Pré-Escolar , Países em Desenvolvimento , Feminino , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Nepal , Infecções por Proteus/tratamento farmacológico , Estudos Retrospectivos , Infecções Estafilocócicas/complicações , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estreptocócicas/complicações , Infecções Estreptocócicas/tratamento farmacológico , Resultado do Tratamento
20.
J Hematother ; 6(5): 441-6, 1997 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-9368180

RESUMO

Effective ex vivo purging techniques can decrease the likelihood of infusing bone marrow contaminated with leukemic cells during autologous transplantation. In preliminary studies, OL(1)p53, a 20-mer phosphorothioate oligonucleotide directed against p53 mRNA, decreased the number of acute myelogenous leukemia (AML) cells in vitro, suggesting a possible role for OL(1)p53 in purging bone marrow harvests of leukemia cells. To demonstrate that OL(1)p53 was nontoxic to hematopoietic progenitor cells, normal bone marrow cells were incubated with 10 microM OL(1)p53 for 36 h, and hematopoietic progenitor cell survival was determined by in vitro colony assays. OL(1)p53 had no toxic effect on the growth of either myeloid (CFU-GM) or erythroid (BFU-E) progenitor cells. OL(1)p53 was then used to ex vivo purge bone marrow harvests from nine patients with either AML or myelodysplastic syndrome (MDS). Bone marrow cells were incubated with 10 microM OL(1)p53 for 36 h before transplantation. The median times posttransplantation for the patient to recover an absolute neutrophil count greater than 0.5 x 10(9)/L and a platelet transfusion independence were 30 days and 56 days, respectively. Incubation of bone marrow cells with OL(1)p53 had no detrimental effect on the growth of hematopoietic progenitor cells, and transplantation of autologous bone marrow cells treated with the phosphorothioate oligonucleotide, OL(1)p53, resulted in successful recovery of circulating neutrophils following high-dose therapy in patients with AML or MDS. The data show that OL(1)p53 can be used safely to purge autologous bone marrow harvests from patients with leukemia.


Assuntos
Purging da Medula Óssea , Transplante de Medula Óssea , Leucemia Mieloide Aguda/terapia , Síndromes Mielodisplásicas/terapia , Oligodesoxirribonucleotídeos Antissenso , Oligonucleotídeos Antissenso , Tionucleotídeos , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Transplante Autólogo
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