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1.
Hum Reprod ; 27(7): 1887-911, 2012 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-22572107

RESUMEN

The 11th report of the European Society of Human Reproduction and Embryology Preimplantation Genetic Diagnosis Consortium is presented, documenting cycles collected for the calendar year 2008 and follow-up of the pregnancies and babies born until October 2009 which resulted from these cycles. Since the beginning of the data collections, there has been a steady increase in the number of cycles, pregnancies and babies reported annually. For data collection XI, 53 centres have participated, reporting on 5641 cycles to oocyte retrieval (OR), along with details of the follow-up on 1418 pregnancies and 1169 babies born. A total of 774 OR were reported for chromosomal abnormalities, 96 OR for sexing for X-linked diseases, 1363 OR for monogenic diseases, 3401 OR for preimplantation genetic screening and 5 OR for social sexing. Data XI is compared with the cumulative data for data collections I-X.


Asunto(s)
Diagnóstico Preimplantación/métodos , Técnicas Reproductivas Asistidas/tendencias , Aberraciones Cromosómicas , Recolección de Datos , Europa (Continente) , Femenino , Enfermedades Genéticas Ligadas al Cromosoma X/diagnóstico , Heterocigoto , Humanos , Hibridación Fluorescente in Situ , Masculino , Recuperación del Oocito , Embarazo , Resultado del Embarazo , Análisis para Determinación del Sexo , Factores Sexuales , Sociedades Médicas , Resultado del Tratamiento
2.
Hum Reprod ; 26(1): 25-32, 2011 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-20966461

RESUMEN

In 2005, the European Society for Human Reproduction and Embryology (ESHRE) PGD Consortium published a set of Guidelines for Best Practice PGD to give information, support and guidance to potential, existing and fledgling PGD programmes. The subsequent years have seen the introduction of new technologies as well as evolution of current techniques. Additionally, in light of recent advice from ESHRE on how practice guidelines should be written and formulated, the Consortium believed it was timely to revise and update the PGD guidelines. Rather than one document that covers all of PGD, the new guidelines are separated into four new documents that apply to different aspects of a PGD programme, i.e. organization of a PGD centre, fluorescence in situ hybridization (FISH)-based testing, amplification-based testing and polar body and embryo biopsy for PGD/preimplantation genetic screening (PGS). Here, we have updated the sections that pertain to FISH-based PGD. PGS has become a highly controversial technique. Opinions of laboratory specialists and clinicians interested in PGD and PGS have been taken into account here. Whereas some believe that PGS does not have a place in clinical medicine, others disagree; therefore, PGS has been included. This document should assist everyone interested in PGD/PGS in developing the best laboratory and clinical practice possible. Topics covered in this guideline include inclusion/exclusion criteria for FISH-based PGD testing, referrals and genetic counselling, preclinical validation of tests, FISH-based testing methods, spreading of cells for analysis, set-up of local IVF centre and transport PGD centres, quality control/ quality assurance and diagnostic confirmation of untransferred embryos.


Asunto(s)
Trastornos de los Cromosomas/diagnóstico , Hibridación Fluorescente in Situ/métodos , Diagnóstico Preimplantación/métodos , Blastocisto , Aberraciones Cromosómicas , Humanos , Control de Calidad , Análisis para Determinación del Sexo , Manejo de Especímenes/normas
3.
Hum Reprod ; 25(11): 2685-707, 2010 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-20813804

RESUMEN

The 10th report of the European Society of Human Reproduction and Embryology (ESHRE) PGD Consortium is presented, documenting cycles collected for the calendar year 2007 and follow-up of the pregnancies and babies born until October 2008 which resulted from these cycles. Since the beginning of the data collections there has been a steady increase in the number of cycles, pregnancies and babies reported annually. For data collection X, 57 centres participated, reporting on 5887 cycles to oocyte retrieval (OR), along with details of the follow-up on 1516 pregnancies and 1206 babies born. A total of 729 OR were reported for chromosomal abnormalities, 110 OR for sexing for X-linked diseases, 1203 OR for monogenic diseases, 3753 OR for preimplantation genetic screening and 92 OR for social sexing. Data X is compared with the cumulative data for data collections I-IX.


Asunto(s)
Índice de Embarazo , Diagnóstico Preimplantación/estadística & datos numéricos , Europa (Continente) , Femenino , Genes Ligados a X , Pruebas Genéticas , Humanos , Hibridación Fluorescente in Situ , Recuperación del Oocito , Embarazo , Resultado del Embarazo , Análisis para Determinación del Sexo , Sociedades Médicas
4.
Acta Gastroenterol Belg ; 67(3): 250-4, 2004.
Artículo en Inglés | MEDLINE | ID: mdl-15587331

RESUMEN

Cancer surgery is a major challenge for patients to develop immune depression in postoperative period. Several cytokines can depress immune cell subpopulations. Increased cytokine response after surgery is assumed to arise mainly from lipooxygenase pathway acting on membrane arachidonic acid. Therefore; investigators focused their efforts to alter the membrane fatty acid profile by changing the nutritional regimen with epsilon-3 fatty acid supplementation and encouraging results were obtained after surgery. Despite the theoretical and clinical advantage of enteral nutrition many surgeons remain committed to parenteral nutrition for feeding of patients due to maintain bowel rest and fear of anastomosis leakage at the postoperative period. Several studies investigating role of the postoperative immunonutrition reported that beneficial immunological changes were associated with reduction of infectious complications. Interestingly; these findings were observed at least five days after the surgery in which the highest incidence of complications was seen. In this prospective study including 42 patients eligible for curative gastric or colon cancer surgery; we investigated the beneficial effect of enteral immunonutrition (EEN) compared to total parenteral hyperalimentation (TPN) beginning from the preoperative period. Cortisol and CRP levels as stress parameters significantly increased one day after surgery in both groups but they rapidly returned to (on POD1) preoperative baseline level in EEN group whereas these values remained high in the TPN group. Additionally a significant decrease in natural killer (NK) cells and CD8+ levels were observed in both groups. However they recovered on POD3 in EEN group and on POD6 in TPN group. CD4+ subset remained almost same as preoperative value in the TPN group whereas it increased from (%) 40.14 to 46.40, 51.29 and 54.7 on PO 6th hr, POD3 and POD6 in the EEN group. Our findings suggest that preoperative nutrition via the enteral route provided better regulation of postoperative immune system restoration than parenteral nutrition. On the basis of our findings we recommend enteral immunonutrition to be started at the preoperative period rather than postoperatively before a major operation whenever the enteral route is feasible.


Asunto(s)
Neoplasias Colorrectales/cirugía , Nutrición Enteral , Neoplasias Gastrointestinales/cirugía , Nutrición Parenteral Total , Complicaciones Posoperatorias/prevención & control , Neoplasias Colorrectales/inmunología , Femenino , Neoplasias Gastrointestinales/inmunología , Humanos , Masculino , Persona de Mediana Edad , Atención Perioperativa , Complicaciones Posoperatorias/inmunología , Estudios Prospectivos
5.
Hum Reprod ; 19(7): 1519-24, 2004 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-15178657

RESUMEN

BACKGROUND: Maintenance of ovarian homeostasis requires precise regulation of proliferation of thecal- interstitial (T-I) cells. Recent evidence indicates that oxidative stress and antioxidants modulate proliferation of various tissues under both physiological and pathological conditions. This study evaluated the effects of oxidative stress and antioxidants on T-I proliferation. METHODS: Rat T-I cells were cultured in serum-free medium and proliferation was assessed by determination of DNA synthesis using the thymidine incorporation assay, by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay and by direct counting of steroidogenically active cells and steroidogenically inactive cells. RESULTS: Antioxidants and reactive oxygen scavengers induced a dose-dependent decrease of T-I proliferation. Vitamin E succinate was inhibitory at 10-100 micro mol/l, ebselen was inhibitory at 0.3-30 micro mol/l, and superoxide dismutase was inhibitory at 300-1000 IU/ml. In contrast, oxidative stress resulted in a biphasic effect. Modest oxidative stress induced by 1 mmol/l hypoxanthine and xanthine oxidase (3-30 micro U/ml) stimulated proliferation of T-I cells, while greater oxidative stress induced by xanthine oxidase (1 mU/ml) profoundly inhibited proliferation. Direct cell counting demonstrated comparable effects on steroidogenically active and inactive cells. CONCLUSIONS: Reactive oxygen species may play a role in the regulation of growth of ovarian mesenchyme. Under pathological conditions, such as those encountered in polycystic ovary syndrome, excessive oxidative stress and depletion of antioxidants may contribute to ovarian mesenchymal hyperplasia.


Asunto(s)
Antioxidantes/farmacología , Estrés Oxidativo/fisiología , Células Tecales/citología , Vitamina E/análogos & derivados , Animales , Antioxidantes/administración & dosificación , Azoles/administración & dosificación , Azoles/farmacología , División Celular/efectos de los fármacos , División Celular/fisiología , Células Cultivadas , Relación Dosis-Respuesta a Droga , Femenino , Depuradores de Radicales Libres/administración & dosificación , Depuradores de Radicales Libres/farmacología , Isoindoles , Compuestos de Organoselenio/administración & dosificación , Compuestos de Organoselenio/farmacología , Ratas , Ratas Sprague-Dawley , Superóxido Dismutasa/administración & dosificación , Superóxido Dismutasa/farmacología , Tocoferoles , Vitamina E/administración & dosificación , Vitamina E/farmacología , Xantina Oxidasa/farmacología
6.
Reprod Biomed Online ; 6(2): 232-7, 2003 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-12676006

RESUMEN

Implantation failure (IF) is defined as three or more failed IVF attempts, and preimplantation genetic diagnosis (PGD) is being used in these patients to improve IVF outcome. PGD was performed in 49 implantation failure patients with a mean number of 4.2 +/- 1.6 previous IVF failures, and in nine fertile controls. Fluorescence in-situ hybridization (FISH) on blastomeres from biopsied day 3 embryos was performed for chromosomes 13, 16, 18, 21, 22, X and Y. There was a significantly higher rate of chromosomal abnormalities (67.4%) compared with controls (36.3%). In 57 cycles, a pregnancy rate of 34.0% and an implantation rate of 19.8% was observed in implantation failure patients compared with controls (33.3 and 24.1% respectively), with all the pregnancies in the implantation failure group coming from the transfer of at least one chromosomally normal blastocyst on day 5. It is concluded that in IVF patients, use of PGD along with blastocyst transfer improves IVF outcome.


Asunto(s)
Fertilización In Vitro/métodos , Diagnóstico Preimplantación/métodos , Adulto , Aneuploidia , Biopsia , Aberraciones Cromosómicas , Técnicas de Cocultivo , Implantación del Embrión , Transferencia de Embrión , Femenino , Humanos , Hibridación Fluorescente in Situ , Edad Materna , Embarazo , Embarazo de Alto Riesgo , Resultado del Tratamiento
7.
Hum Reprod ; 18(1): 182-8, 2003 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-12525464

RESUMEN

BACKGROUND: Chromosomal abnormalities are an important cause of spontaneous abortion and recurrent miscarriage (RM). Therefore, we have analysed the incidence of chromosomal abnormalities and embryo development in patients with RM. METHODS: Preimplantation genetic diagnosis (PGD) was performed on 71 couples with RM and 28 couples undergoing PGD for sex-linked diseases (control group). Chromosomes 13, 16, 18, 21, 22, X and Y were analysed by fluorescence in-situ hybridization. RESULTS: The implantation rate in RM patients was 28% and three patients (13%) miscarried. The percentage of abnormal embryos was significantly increased (P < 0.0001) in RM patients compared with controls (70.7 versus 45.1%). All of the embryos were abnormal in 19 cycles (22.1%) and repeated PGD cycles yielded similar rates of chromosomal abnormalities in 14 couples. Anomalies for chromosomes 16 and 22 were significantly higher (P < 0.01) in RM cases. In the RM population, euploid embryos reached the blastocyst stage more frequently than abnormal embryos (61.7 versus 24.9%; P < 0.0001). CONCLUSIONS: RM is associated with a higher incidence of chromosomally abnormal embryos, of which some are able to develop to the blastocyst stage. IVF plus PGD is an important step in the management of these couples, but the technique has to move towards a full chromosome analysis.


Asunto(s)
Aborto Habitual/genética , Aborto Habitual/fisiopatología , Aberraciones Cromosómicas , Desarrollo Embrionario y Fetal , Adulto , Aberraciones Cromosómicas/estadística & datos numéricos , Cromosomas Humanos Par 16 , Cromosomas Humanos Par 22 , Implantación del Embrión , Femenino , Feto/anomalías , Humanos , Incidencia , Diagnóstico Preimplantación , Diagnóstico Prenatal
8.
Biol Reprod ; 65(3): 704-9, 2001 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-11514331

RESUMEN

There is growing evidence that the function of ovarian theca-interstitial (T-I) cells may be modulated by paracrine actions of activin, inhibin, and follistatin. Furthermore, either dysregulation, dysfunction, or both, of these peptides may play a role in conditions associated with T-I hyperplasia, such as polycystic ovary syndrome (PCOS) and hyperthecosis. This study was designed to evaluate the role of activin, inhibin, and follistatin in the modulation of T-I cell proliferation. Interaction of these peptides with insulin-like growth factor-I (IGF-I), a known stimulator of T-I cell proliferation, was also assessed. Purified rat T-I cells were cultured for 48 h in chemically defined media and with or without activin (3-30 ng/ml), inhibin (3-30 ng/ml), follistatin (100 ng/ml), and/or IGF-I (10 nM). T-I cell proliferation was assessed using radiolabeled thymidine incorporation assay. Activin alone stimulated proliferation of T-I cells in a dose-dependent fashion (by up to 320% above control; P < 0.001), whereas inhibin alone or follistatin alone had no significant effect. Inhibin had also no effect on activin-induced proliferation. Follistatin significantly reduced the stimulatory effects of activin and decreased proliferation by up to 46% (P < 0.01) below the level attained in the presence of activin alone. IGF-I (10 nM), at a dose producing a near-maximal effect, increased proliferation by 175% above control (P < 0.001); insulin (10 nM) increased proliferation by 52% above control (P < 0.03). A combination of IGF-I (10 nM) and activin (30 ng/ml) resulted in a 1090% increase of proliferation above control (P < 0.001); this stimulatory effect was significantly greater than that achieved in the presence of either activin alone or IGF-I alone (P < 0.001). Similarly, a combination of insulin (10 nM) and activin (30 ng/ml) increased proliferation by 506% above control levels. Flow cytometry evaluation revealed that activin increased the proportion of actively dividing cells (in S or G2/M phase of the cell cycle) by 42% (P < 0.02), whereas IGF-I had no effect on the proportion of actively dividing cells. The present findings indicate that an activin-follistatin system may be involved in the regulation of the size of ovarian thecal-stromal compartment. In view of the synergy between activin and IGF-I, and the difference in the effects on the cell cycle distribution, stimulation of T-I proliferation by these agents is likely to be mediated via separate transduction pathways. Excess activin or insufficient follistatin may contribute to T-I hyperplasia.


Asunto(s)
Activinas/farmacología , División Celular/efectos de los fármacos , Ovario/citología , Células Tecales/citología , Animales , ADN/biosíntesis , Femenino , Citometría de Flujo , Hormona Folículo Estimulante/antagonistas & inhibidores , Folistatina , Sustancias de Crecimiento/farmacología , Inhibinas/farmacología , Insulina/farmacología , Factor I del Crecimiento Similar a la Insulina/farmacología , Ratas , Ratas Sprague-Dawley
9.
J Endocrinol ; 170(3): 639-45, 2001 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-11524244

RESUMEN

Ovarian development, follicular growth and atresia require mechanisms regulating proliferation and death of ovarian cells including theca-interstitial (T-I) cells. Transforming growth factors-alpha and -beta (TGF-alpha and TGF-beta) are well recognized local modulators of T-I function. This study was performed to evaluate the effects of TGF-alpha and TGF-beta on ovarian T-I cell proliferation, differentiation and apoptosis. T-I cells from immature Sprague-Dawley rats were purified and incubated in chemically defined media. Proliferation was assessed by [3H]thymidine incorporation assay and by cell counting. Steroidogenically active cells were identified histochemically by detection of 3beta-hydroxysteroid dehydrogenase (3beta-HSD) activity. DNA was extracted and apoptosis was identified by detection of internucleosomal DNA cleavage producing the characteristic 'ladder pattern' of low-molecular weight (LMW) DNA following agarose gel electrophoresis. Quantification of apoptosis was carried out with the aid of 3'-end labeling of DNA fragments with [32P]-dideoxy-ATP. TGF-alpha and TGF-beta stimulated [3H]thymidine incorporation by 2.2- to 3.1-fold and 1.7- to 3.4-fold respectively (P<0.005). A combination of TGF-alpha and TGF-beta produced a synergistic increase in DNA synthesis by 6.7-fold (at 1 ng/ml of each TGF-alpha and TGF-beta; P<0.001) and tenfold (at 10 ng/ml of each TGF-alpha and TGF-beta; P<0.001). Cell counting revealed that TGF-alpha increased the total number of cells 2.8-fold and TGF-beta 2.8-fold. The combination of TGF-alpha and TGF-beta increased the total cell count 3.2-fold, compared with control (P<0.05). The percentage of the steroidogenically active cells was 37+/-9% (mean+/-s.e.m. ) in the control cultures, 50+/-5% in the presence of TGF-alpha, 42+/-8% in the presence of TGF-beta, and 47+/-13% in the presence of both TGF-alpha and TGF-beta. TGF-alpha decreased apoptosis by 63+/-14% (P=0.02) while TGF-beta had no statistically significant effect. TGF-alpha in combination with TGF-beta produced the greatest inhibition of apoptosis by 73+/-8% (P=0.01). These findings demonstrate that TGF-alpha and -beta stimulate proliferation of both steroidogenically active and inactive T-I cells. Furthermore, TGF-alpha alone and in combination with TGF-beta protects T-I cells from apoptotic death. These effects of TGFs may be important in physiologic maintenance of ovarian mesenchymal growth and homeostasis as well as in pathophysiologic conditions associated with excessive growth of the T-I compartment, such as polycystic ovary syndrome.


Asunto(s)
Apoptosis/efectos de los fármacos , Células Tecales/efectos de los fármacos , Factor de Crecimiento Transformador alfa/farmacología , Factor de Crecimiento Transformador beta/farmacología , 3-Hidroxiesteroide Deshidrogenasas/metabolismo , Animales , Técnicas de Cultivo de Célula , División Celular/efectos de los fármacos , ADN/biosíntesis , Relación Dosis-Respuesta a Droga , Femenino , Ratas , Ratas Sprague-Dawley , Células Tecales/citología , Células Tecales/enzimología
10.
Menopause ; 8(4): 296-301, 2001.
Artículo en Inglés | MEDLINE | ID: mdl-11449089

RESUMEN

OBJECTIVE: The protective effect of estrogen against early atherosclerosis in animal models is well documented, but the mechanisms responsible for this effect are not well understood. The earliest recognizable event in the pathogenesis of atherosclerosis is an increased recruitment of macrophages into the arterial subendothelium. Macrophages first play a protective role by removing low-density lipoproteins, but when the cholesterol is in excess, macrophages are converted into foam cells and form atheromas. Recent human and animal data indicate that the recruitment of macrophages to the arterial wall is mediated by monocyte chemotactic protein-1 (MCP-1). We hypothesized that one of the mechanisms of estrogen's protective effect against atherosclerosis may be the down-regulation of MCP-1 expression in the arterial wall. DESIGN: Human coronary artery smooth muscle cells were replicated to confluence in smooth muscle cell basal medium supplemented with growth factors and 5% fetal bovine serum. Before each experiment, cells were incubated for 24 h with phenol red-free medium containing 5% charcoal-stripped calf serum, and then they were treated with various concentrations of 17beta-estradiol as well as selective estrogen receptor (ER) modulators, raloxifene and tamoxifen. MCP-1 messenger ribonucleic acid (mRNA) levels were quantified by Northern blots. MCP-1 protein was quantified using an enzyme-linked immunosorbent assay. ER expression was evaluated by reverse transcriptase-polymerase chain reaction. RESULTS: Human coronary artery smooth muscle cells expressed MCP-1 mRNA and produced MCP-1 protein. Estradiol induced up to 40% inhibition in mRNA expression at concentrations 10-9 M and higher. Raloxifene and tamoxifen also resulted in an inhibition, but the inhibition was less than when induced by estradiol. Estradiol also inhibited the MCP-1 protein production in a concentration-dependent manner (p < 0.05). Coronary smooth muscle cells expressed both ERalpha and ERbeta. CONCLUSION: Our findings suggest that one of the mechanisms by which estrogen prevents atherosclerosis is by down-regulating MCP-1 expression, thus decreasing macrophage recruitment to the arterial wall.


Asunto(s)
Arteriosclerosis/tratamiento farmacológico , Arteriosclerosis/etiología , Quimiocina CCL2/inmunología , Endotelio Vascular/efectos de los fármacos , Endotelio Vascular/inmunología , Estradiol/inmunología , Estradiol/uso terapéutico , Músculo Liso Vascular/efectos de los fármacos , Músculo Liso Vascular/inmunología , Animales , Arteriosclerosis/inmunología , Northern Blotting , Células Cultivadas/efectos de los fármacos , Quimiocina CCL2/análisis , Modelos Animales de Enfermedad , Regulación hacia Abajo/efectos de los fármacos , Evaluación Preclínica de Medicamentos , Endotelio Vascular/citología , Estradiol/farmacología , Femenino , Humanos , Músculo Liso Vascular/citología , Clorhidrato de Raloxifeno/inmunología , Clorhidrato de Raloxifeno/farmacología , Clorhidrato de Raloxifeno/uso terapéutico , Moduladores Selectivos de los Receptores de Estrógeno/inmunología , Moduladores Selectivos de los Receptores de Estrógeno/farmacología , Moduladores Selectivos de los Receptores de Estrógeno/uso terapéutico , Tamoxifeno/inmunología , Tamoxifeno/farmacología , Tamoxifeno/uso terapéutico
11.
Pediatr Int ; 43(4): 379-84, 2001 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-11472583

RESUMEN

BACKGROUND: Measles outbreaks seem to occur every 2- to 3-year intervals in Turkey. However, sero-epidemiological studies are limited. Knowing the prevalence of measles susceptibility as measured either by serologic markers of immunity or surveys of vaccination coverage is an important tool to assess the risk for measles outbreaks. METHODS: In order to determine the seroprevalence of measles antibodies among a 1 to 29-year-old population in Izmir (Turkey) and to develop the best vaccination policy for measles, a total of 600 people aged from 1 to 29 were selected for the study with cluster sampling. The information on sociodemographic characteristics, vaccination status and measles history was gathered for each participant. Measles-specific IgG antibodies were screened qualitatively by using microenzyme immune assay for 595 subjects. RESULTS: Of the 595 participants screened for the measles antibodies, 56 (9.4%) were seronegative. The proportion of the susceptible individuals in the age groups of 1-4, 5-9, 10-14, 15-19 and 20-29 was 20.0, 10.4, 6.0, 10.3 and 3.0%, respectively. The logistic regression analysis showed that none of the independent characteristics (sex, socioeconomic status, past measles history, vaccination status) with the exception of age group, was significantly associated with measles seronegativity. CONCLUSION: The optimal measles vaccination policy for Turkey may be to increase vaccination coverage above 90%, to conduct a catch-up campaign covering persons aged 1-19, regardless of previous vaccination status. Another factor to consider is to adopt a routine two-dose vaccination, giving the first dose at 12-15 months of age and the second dose at school entry.


Asunto(s)
Política de Salud , Sarampión/epidemiología , Vacunación , Adolescente , Adulto , Niño , Preescolar , Análisis por Conglomerados , Femenino , Humanos , Lactante , Masculino , Sarampión/prevención & control , Estudios Seroepidemiológicos , Factores Socioeconómicos , Turquía/epidemiología
12.
Vaccine ; 18(9-10): 947-54, 1999 Dec 10.
Artículo en Inglés | MEDLINE | ID: mdl-10580209

RESUMEN

This study was designed to assess the immunogenicity of a vaccine combining diphtheria and tetanus toxoids, acellular pertussis vaccine, and inactivated poliovirus vaccine reconstituting Haemophilus influenzae type b polysaccharide conjugated to tetanus protein (DTaP-IPV//PRP-T; Pasteur Mérieux Connaught, Lyon, France) administered simultaneously in association with hepatitis B vaccine (RECOMBIVAX (¿trade mark omitted¿) Merck, Sharp & Dohme, West Point, PA, USA) for the primary immunization of infants. The vaccines were administered at two, three and four months of age. One hundred and sixty-two healthy infants, aged 8-10 weeks, were enrolled in the study. Blood samples were taken before the first dose and 4 weeks after the third dose. The infants were observed for 15 minutes after vaccination for any immediate reaction. Adverse events requiring a medical consultation were recorded by the parents in a diary over the 7 days following vaccination. Four weeks after the third immunization, the percentages of infants fulfilling seroconversion criteria were 98.9% for pertussis toxin, 95.9% for filamentous haemagglutinin, 100.0% for tetanus, 100.0% for diphtheria, 99.3% for poliovirus type 1, 100.0% for both poliovirus types 2 and 3, 98.0% for Haemophilus influenzae type b, and 100% for hepatitis B surface antigen. No vaccine-related serious adverse event was reported. The simultaneous administration of DTaP-IPV//PRP-T and hepatitis B vaccines at two, three and four months of age yielded clinically satisfactory immune responses to all antigens compared with historical controls and gave a good safety profile.


Asunto(s)
Vacuna contra Difteria, Tétanos y Tos Ferina , Vacunas contra Haemophilus , Vacunas contra Hepatitis B , Esquemas de Inmunización , Vacuna Antipolio de Virus Inactivados , Vacunas Combinadas , Femenino , Humanos , Lactante , Masculino , Turquía , Vacunas Sintéticas , Organización Mundial de la Salud
13.
Vaccine ; 17(7-8): 875-86, 1999 Feb 26.
Artículo en Inglés | MEDLINE | ID: mdl-10067694

RESUMEN

To evaluate the priming effect, immunogenicity and safety of an Haemophilus influenzae type b (Hib) tetanus toxoid conjugate (PRP-T) and diphtheria-tetanus-acellular (two component) pertussis (DTaP) combination vaccine, a randomized, comparative study was conducted in two centers, one in Belgium and one in Turkey. A total of 410 healthy infants, 160 in Belgium and 250 in Turkey, randomly received DTaP and PRP-T vaccines in one of three fashions. One group (N = 138) received DTaP and PRP-T vaccines reconstituted immediately prior to injection at 3, 4 and 5 months of age, and are referred to as the combined, short schedule group (Co-S). A second group (N = 135) received DTaP + PRP-T simultaneously but injected at different sites according to the same schedule, and are referred to as the associated, short schedule group (As-S). The third group (N = 137) also received DTaP + PRP-T at separate sites, but at 2, 4 and 6 months, and are referred to as the associated, long schedule group (As-L). The As-L group allowed for serological bridging with a Senegalese two-component pertussis vaccine efficacy trial, using the same batch of DTaP vaccine. Children of both short-schedule groups (Co-S and As-S) received, at the age of 12-14 months, a booster dose of DTaP vaccine associated with unconjugated PRP vaccine. Mixing of the vaccines did not affect the immune response to the antigens included in the DTaP vaccine. The immune response to Hib capsular polysaccharide, however, was significantly lower after combined administration (Co-S group) than after associated (As-S group) administration (P < 0.0001), with a similar trend among both countries (GMTs, 1.78 microg/ml and 6.19 microg/ml in Belgium, and 5.02 microg/ml and 11.67 microg/ml in Turkey). Booster vaccination with the unconjugated PRP induced a vigorous and similar anamnestic response in both groups. Belgian infants showed a significantly lower immune response to all antigens than Turkish infants (P < or = 0.001 for all antigens), with a similar trend among each study group. In all groups, the incidence of adverse events was lower than that usually reported after DTwP(whole-cell) vaccine. Higher rates of systemic reactions were observed in the Belgian population, possibly due to differences in reporting practice. Our results indicate (1) that the combination vaccine, DTaP//PRP-T, represents an important improvement over the existing uncombined vaccines; (2) that immunogenicity studies should include at least one booster injection to evaluate priming effects by combined vaccines; and (3) that it is feasible and valuable to co-randomize combination vaccine studies in sufficiently different geographical areas and child populations.


Asunto(s)
Vacuna contra Difteria, Tétanos y Tos Ferina/administración & dosificación , Vacuna contra Difteria, Tétanos y Tos Ferina/inmunología , Vacunas contra Haemophilus/administración & dosificación , Vacunas contra Haemophilus/inmunología , Toxoide Tetánico/administración & dosificación , Toxoide Tetánico/inmunología , Bélgica , Vacuna contra Difteria, Tétanos y Tos Ferina/efectos adversos , Femenino , Vacunas contra Haemophilus/efectos adversos , Humanos , Esquemas de Inmunización , Inmunización Secundaria , Lactante , Masculino , Toxoide Tetánico/efectos adversos , Turquía , Vacunas Combinadas/efectos adversos , Vacunas Combinadas/inmunología , Vacunas Combinadas/uso terapéutico
14.
Am J Med Genet ; 83(3): 201-6, 1999 Mar 19.
Artículo en Inglés | MEDLINE | ID: mdl-10096597

RESUMEN

Previous studies have shown that patients with deletion of distal human chromosome arm 8p may have congenital heart disease and other physical anomalies. The gene encoding GATA-4, a zinc finger transcription factor implicated in cardiac gene expression and development, localizes to chromosome region 8p23.1. To examine whether GATA-4 deficiency is present in patients with monosomy of 8p23.1 with congenital heart disease, we performed fluorescence in situ hybridization (FISH) with a GATA4 probe on cells from a series of patients with interstitial deletion of 8p23.1. Four individuals with del(8)(p23.1) and congenital heart disease were found to be haploinsufficient at the GATA4 locus by FISH. The GATA4 gene was not deleted in a fifth patient with del(8)(p23.1) who lacked cardiac anomalies. FISH analysis on cells from 48 individuals with congenital heart disease and normal karyotypes failed to detect any submicroscopic deletions at the GATA4 locus. We conclude that haploinsufficiency at the GATA4 locus is often seen in patients with del(8)(p23.1) and congenital heart disease. Based on these findings and recent studies showing that haploinsufficiency for other cardiac transcription factor genes (e.g., TBX5, NKX2-5) causes congenital heart disease, we postulate that GATA-4 deficiency may contribute to the phenotype of patients with monosomy of 8p23.1.


Asunto(s)
Deleción Cromosómica , Cromosomas Humanos Par 8 , Proteínas de Unión al ADN/genética , Cardiopatías Congénitas/genética , Factores de Transcripción/genética , Adulto , Preescolar , Femenino , Factor de Transcripción GATA4 , Humanos , Recién Nacido , Cariotipificación , Masculino , Dedos de Zinc
15.
Acta Paediatr Jpn ; 39(6): 676-80, 1997 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-9447756

RESUMEN

Separate injections of Haemophilus influenzae type b capsular polysaccharide-tetanus conjugate (PRP-T) vaccine and diphtheria-tetanus-pertussis (DTP) reconstitution of freeze-dried PRP-T vaccine with liquid DTP vaccine have been shown to be safe and immunogenic in infants. The present study was conducted to test the safety and immunogenicity of the liquid combination vaccine administered to young infants in the dual-chamber syringe. The study was a monocenter, open clinical trial of 3 month-old infants receiving PRP-T and DTP vaccines in the dual-chamber syringe reconstituted prior to injection. Healthy infants were immunized according to a 3, 4 and 5 months-of-age schedule. The vaccine was administered in a dual-chamber syringe, ready to use with two chambers. The proximal chamber contained freeze-dried PRP-T and the distal chamber contained liquid combination-vaccine DTP. The freeze-dried PRP-T vaccine was reconstituted with the liquid DTP vaccine in the same unidose dual-chamber syringe (0.5 mL) and was injected intramuscularly into the deltoid region. Blood sampling was performed prior to vaccination at 3 months of age and after the third vaccination at 6 months. The primary end-point was the serological response to PRP-T vaccine as expressed by the percentage of infants with an antibody titer greater than or equal to 1 microgram/mL. The reactogenicity was expressed as the percentage of reported local and systemic reactions. A total of 108 infants were included in the study and received the dual-chamber syringe vaccine. After the third injection, all the infants had a PRP antibody titer greater than or equal to 0.15 microgram/mL and 94.4% of infants had a PRP antibody titer greater than or equal to 1 microgram/mL; the pertussis agglutinin titers were over the threshold 40 and 80 in all infants and 98.1% were over the threshold 320. After the third injection, all the infants had diphtheria antibody titers greater than 0.1 IU/mL and 83.3% had titers greater than 1 IU/mL; all the infants had tetanus antibody titers greater than 0.1 IU/mL and 97.2% had results over 1 IU/mL. Thirty-seven infants (34.6%) had local reactions and 64.5% had systemic reactions. The dual-chamber syringe may reduce the cost of vaccine delivery, as well as the workload, and increase the vaccine acceptability and coverage rate of vaccines.


Asunto(s)
Vacuna contra Difteria, Tétanos y Tos Ferina/administración & dosificación , Vacunas contra Haemophilus/administración & dosificación , Vacunas contra Haemophilus/inmunología , Haemophilus influenzae tipo b/inmunología , Toxoide Tetánico/administración & dosificación , Toxoide Tetánico/inmunología , Vacunas Conjugadas/administración & dosificación , Vacunas Conjugadas/inmunología , Anticuerpos Antivirales/sangre , Humanos , Lactante , Seguridad , Jeringas
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