RESUMEN
INTRODUCTION: Granular cell tumours are extremely rare on peripheral nerves, with an incidence of 0.029% of pathologic samples. In a literature review, we found only 5 cases involving the ulnar nerve, although considered the most frequently involvement nerve. CASE REPORT: A 32 year-old female from the French West Indies presented a severe arm pain with deficit of interosseous hand muscles. Imaging studies were in favour of a Schwanoma, but during surgery, we found an unremovable intra-neural tumour. Nerve biopsy revealed a granular cell tumour. Initial decision was observation only. However, within two years, tumour increased in size, along with pain aggravation and functional deficit. We performed a nerve resection (with adequate margins) with reconstruction using sural nerve graft associated with a neurotisation of the motor branch with the anterior interosseus nerve. At two years follow-up, no recurrence was observed. The scar is hypersensitive with moderate neuropathic pain. There is a sensory reinnervation of the fourth finger, with no motor recovery of the hand. We observed a slight recovery of flexor profundus tendons, which, in turn increased the claw hand. DISCUSSION: The five cases described in the literature were managed differently (biopsy only, excision, excision with reconstruction), with modest results. There is no recommended treatment. Our case is the first at arm level. We were able to perform complete resection, but functional result is poor. CONCLUSION: Granular cell tumours require treatment if symptomatic (pain, function loss), but, at the moment, there is no recommended treatment.
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Tumor de Células Granulares , Transferencia de Nervios , Adulto , Brazo , Femenino , Tumor de Células Granulares/cirugía , Humanos , Recurrencia Local de Neoplasia , Nervio CubitalRESUMEN
Some patients present at an advanced stage of their fingertip infection with an extension of the infection in anatomical spaces or into fragile structures. One hundred and twenty-five patients have been operated on for a finger infection. Forty-one patients (33%) have been treated at the "complication" stage, while 84 cases (67%) were considered "non-complicated". The delay between initial injury and the surgical treatment was 12 days in the "non-complicated" group versus 30 in the "complication" group (p < 0.001). Osteitis (39% of the complications), and flexor sheath infection (37%) were the most frequent complications. Prescribing preoperative antibiotics increases the risk of being in the "complicated" group at p = 0.09. One hundred and thirteen patients (90.4%) were cured of their infection after a single operation. Neither the cause of infection, nor the type of germ or associated diabetes increased the risk of complication in our series. A better education of the first interveners (general practitioner or emergency doctor) in hand infection care could reduce the rate of complication allowing a faster access to hand surgeons.
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Dedos , Mano , Antibacterianos/uso terapéutico , Humanos , Enfermedad Iatrogénica/epidemiologíaRESUMEN
Abdominal aortic aneurysms (AAAs) represent permanent, localized dilations of the abdominal aorta that can be life-threatening if progressing to rupture. Evaluation of risk of rupture depends on understanding the mechanical behavior of patient AAA walls. In this project, a series of patient AAA wall tissue samples have been evaluated through a combined anamnestic, mechanical, and histopathologic approach. Mechanical properties of the samples have been characterized using a novel, strain-controlled, planar biaxial testing protocol emulating the in vivo deformation of the aorta. Histologically, the tissue ultrastructure was highly disrupted. All samples showed pronounced mechanical stiffening with stretch and were notably anisotropic, with greater stiffness in the circumferential than the axial direction. However, there were significant intrapatient variations in wall stiffness and stress. In biaxial tests in which the longitudinal stretch was held constant at 1.1 as the circumferential stretch was extended to 1.1, the maximum average circumferential stress was 330 ± 70 kPa, while the maximum average axial stress was 190 ± 30 kPa. A constitutive model considering the wall as anisotropic with two preferred directions fit the measured data well. No statistically significant differences in tissue mechanical properties were found based on patient gender, age, maximum bulge diameter, height, weight, body mass index, or smoking history. Although a larger patient cohort is merited to confirm these conclusions, the project provides new insight into the relationships between patient natural history, histopathology, and mechanical behavior that may be useful in the development of accurate methods for rupture risk evaluation.
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Aneurisma de la Aorta Abdominal/patología , Fenómenos Mecánicos , Anciano , Anciano de 80 o más Años , Fenómenos Biomecánicos , Femenino , Análisis de Elementos Finitos , Humanos , Masculino , Ensayo de Materiales , Persona de Mediana Edad , Estrés MecánicoRESUMEN
Caterpillars can increase their body mass 10,000-fold in 2 weeks. It is therefore remarkable that most caterpillars appear to maintain the same locomotion kinematics throughout their entire larval stage. This study examined how the body properties of a caterpillar might change to accommodate such dramatic changes in body load. Using Manduca sexta as a model system, we measured changes in body volume, tissue density and baseline body pressure, and the dimensions of load-bearing tissues (the cuticle and muscles) over a body mass range from milligrams to several grams. All Manduca biometrics relevant to the hydrostatic skeleton scaled allometrically but close to the isometric predictions. Body density and pressure were almost constant. We next investigated the effects of scaling on the bending stiffness of the caterpillar hydrostatic skeleton. The anisotropic non-linear mechanical response of Manduca muscles and soft cuticle has previously been quantified and modeled with constitutive equations. Using biometric data and these material laws, we constructed finite element models to simulate a hydrostatic skeleton under different conditions. The results show that increasing the internal pressure leads to a non-linear increase in bending stiffness. Increasing the body size results in a decrease in the normalized bending stiffness. Muscle activation can double this stiffness in the physiological pressure range, but thickening the cuticle or increasing the muscle area reduces the structural stiffness. These non-linear effects may dictate the effectiveness of a hydrostatic skeleton at different sizes. Given the shared anatomy and size variation in Lepidoptera larvae, these mechanical scaling constraints may implicate the diverse locomotion strategies in different species.
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Locomoción , Manduca/fisiología , Animales , Conducta Animal , Fenómenos Biomecánicos , Tamaño Corporal , Peso Corporal , Epidermis/fisiología , Larva/crecimiento & desarrollo , Larva/fisiología , Manduca/crecimiento & desarrollo , Modelos Biológicos , Músculos/fisiología , Soporte de PesoRESUMEN
Screening of biomaterial and tissue systems in vitro, for guidance of performance in vivo, remains a major requirement in the field of tissue engineering. It is critical to understand how culture stimulation affects both tissue construct maturation and function, with the goal of eliminating resource-intensive trial-and-error screening and better matching specifications for various in vivo needs. In this article a multifunctional and robust bioreactor design that addresses this need is presented. The design enables a range of mechanical inputs, durations, and frequencies to be applied in coordination with noninvasive optical assessments. A variety of biomaterial systems, including micro- and nano-fiber and porous sponge biomaterials, as well as cell-laden tissue engineering constructs were used in validation studies to demonstrate the versatility and utility of this new bioreactor design. The silk-based biomaterials highlighted in these studies offered several unique optical signatures for use in label-free nondestructive imaging that allowed for sequential profiling. Both short- and long-term culture studies were conducted to evaluate several practical scenarios of usage: on a short-term basis, the authors demonstrate that construct cellularity can be monitored by usage of nonpermanent dyes; on a more long-term basis, the authors show that cell ingrowth can be monitored by green-fluorescent protein (GFP)-labeling, and construct integrity probed with concurrent load/displacement data. The ability to nondestructively track cells, biomaterials, and new matrix formation without harvesting designated samples at each time point will lead to less resource-intensive studies and should enhance our understanding and the discovery of biomaterial designs related to functional tissue engineering.
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Reactores Biológicos , Matriz Extracelular/metabolismo , Procesamiento de Imagen Asistido por Computador/métodos , Nanofibras , Ingeniería de Tejidos/instrumentación , Ingeniería de Tejidos/métodos , Animales , Línea Celular , Humanos , Ensayo de Materiales , Factores de TiempoRESUMEN
To restore physiological function through regenerative medicine, biomaterials introduced into the body must degrade at a rate that matches new tissue formation. For effective therapies, it is essential that we understand the interaction between physiological factors, such as routine mechanical loading specific to sites of implantation, and the resultant rate of material degradation. These relationships are poorly characterized at this time. We hypothesize that mechanical forces alter the rates of remodeling of biomaterials, and this impact is modulated by the concentration of enzymes and the duration of the mechanical loads encountered in situ. To test this hypothesis we subjected silk fibroin fibers to repeated cyclic loading in the presence of enzymatic degradation (either alpha-chymotrypsin or Protease XIV) and recorded the stress-strain response. Data were collected daily for a duration of 2 weeks and compared to the control cases of stretched fibers in the presence of phosphate buffered saline or non-stretched samples in the presence of enzyme alone. We observed that incubation with proteases in the absence of mechanical loads causes a reduction of the ultimate tensile strength but no change in stiffness. However, cyclic loading caused the accumulation of residual strain and softening in the material's properties. We utilize these data to formulate a mathematical model to account for residual strain and reduction of mechanical properties during silk fiber degradation. Numerical predictions are in fair agreement with experimental data. The improved understanding of the degradation phenomenon will be significant in many clinical repair cases and may be synergistic to decrease silk's mechanical properties after in vivo implantation.
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Quimotripsina/metabolismo , Fibroínas/metabolismo , Modelos Biológicos , Péptido Hidrolasas/metabolismo , Fenómenos Biomecánicos , Elasticidad , Fibroínas/químicaRESUMEN
Hydrogels have mechanical properties and structural features that are similar to load-bearing soft tissues including intervertebral disc and articular cartilage, and can be implanted for tissue restoration or for local release of therapeutic factors. To help predict their performance, mechanical characterization and mathematical modeling are the available methods for use in tissue engineering and drug delivery settings. In this study, confined compression creep tests were performed on silk hydrogels, over a range of concentrations, to examine the phenomenological behavior of the gels under a physiological loading scenario. Based on the observed behavior, we show that the time-dependent response can be explained by a consolidation mechanism, and modeled using Biot's poroelasticity theory. Two observations are in strong support of this modeling framework, namely, the excellent numerical agreement between increasing load step creep data and the linear Terzaghi theory, and the similar values obtained from numerical simulations and direct measurements of the permeability coefficient. The higher concentration gels (8% and 12% w/v) clearly show a strain-stiffening response to creep loading with increasing loads, while the lower concentration gel (4% w/v) does not. A nonlinear elastic constitutive formulation is employed to account for the stiffening. Furthermore, an empirical formulation is used to represent the deformation-dependent permeability.
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Hidrogeles/química , Seda/química , Animales , Fenómenos Biomecánicos , Bombyx , Fuerza Compresiva , Elasticidad , Hidrogeles/metabolismo , Proteínas de Insectos/química , Proteínas de Insectos/metabolismo , Cinética , Microscopía Electrónica de Rastreo , Sistema Musculoesquelético/citología , Permeabilidad , Porosidad , Presión , Seda/metabolismo , Estrés Mecánico , Ingeniería de Tejidos , Agua/química , Soporte de PesoRESUMEN
In this paper, we develop a physiologic wall stress analysis procedure by incorporating experimentally measured, non-uniform pressure loading in a patient-based finite element simulation. First, the distribution of wall pressure is measured in a patient-based lumen cast at a series of physiologically relevant steady flow rates. Then, using published equi-biaxial stress-deformation data from aneurysmal tissue samples, a nonlinear hyperelastic constitutive equation is used to describe the mechanical behavior of the aneurysm wall. The model accounts of the characteristic exponential stiffening due to the rapid engagement of nearly inextensible collagen fibers and assumes, as a first approximation, an isotropic behavior of the arterial wall. The results show a complex wall stress distribution with a localized maximum principal stress value of 660 kPa on the inner surface of the posterior surface of the aneurysm bulge, a considerably larger value than has generally been reported in calculations of wall stress under the assumption of uniform loading. This is potentially significant since the posterior wall has been suggested as a common site of rupture, and the aneurysmal tensile strength reported by other authors is of the same order of magnitude as the maximum stress value found here.
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Aorta Abdominal/fisiopatología , Aneurisma de la Aorta Abdominal/fisiopatología , Mecanotransducción Celular , Modelos Cardiovasculares , Velocidad del Flujo Sanguíneo , Presión Sanguínea , Simulación por Computador , Módulo de Elasticidad , Humanos , Resistencia al Corte , Estrés MecánicoRESUMEN
The mechanical properties of soft tissues are important for the control of motion in many invertebrates. Pressurized cylindrical animals such as worms have circumferential reinforcement of the body wall; however, no experimental characterization of comparable anisotropy has been reported for climbing larvae such as caterpillars. Using uniaxial, real-time fluorescence extensometry on millimeter scale cuticle specimens we have quantified differences in the mechanical properties of cuticle to circumferentially and longitudinally applied forces. Based on these results and the composite matrix-fiber structure of cuticle, a pseudo-elastic transversely isotropic constitutive material model was constructed with circumferential reinforcement realized as a Horgan-Saccomandi strain energy function. This model was then used numerically to describe the anisotropic material properties of Manduca cuticle. The constitutive material model will be used in a detailed finite-element analysis to improve our understanding of the mechanics of caterpillar crawling.
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Simulación por Computador , Tejido Conectivo/fisiología , Manduca/fisiología , Animales , Anisotropía , Fenómenos Biomecánicos , Técnicas In Vitro , Larva/fisiología , Modelos BiológicosRESUMEN
Experimental data on the passive mechanical properties of the ventral interior lateral muscle of the tobacco hornworm caterpillar, Manduca sexta, are reported. The stress-deformation response of the Manduca muscle is shown to be nonlinear pseudo-elastic, capable of large deformations and subject to stress softening during initial loading cycles. The muscle passive mechanical properties also depend on multiple time-dependent processes. In particular, we show new experimental data from cyclic loading tests of an unstimulated muscle with constant maximum stretch and different, constant engineering strain rates. Then, on the basis of these data a constitutive model is derived to reproduce the main characteristics of this behaviour. In formulating the constitutive model, we consider the muscle as a complex macromolecular structure with fibrous components at numerous size scales. The model uses a phenomenological approach to account for different mechanisms by which passive force changes during applied deformation and how the muscle properties recover after unloading.
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Manduca/fisiología , Modelos Teóricos , Contracción Muscular/fisiología , Músculos/fisiología , Animales , Fenómenos Biomecánicos , Simulación por ComputadorRESUMEN
In this paper, we examine the mechanical properties of muscles in a soft-bodied arthropod under both passive and stimulated conditions. In particular, we examine the ventral interior lateral muscle of the tobacco hornworm caterpillar, Manduca sexta, and show that its response is qualitatively similar to the behaviour of particle-reinforced rubber. Both materials are capable of large nonlinear elastic deformations, show a hysteretic behaviour and display stress softening during the first few cycles of repeated loading. The Manduca muscle can therefore be considered as different elastic materials during loading and unloading and is best described using the theory of pseudo-elasticity. We summarize the basic equations for transversely isotropic pseudo-elastic materials, first for general deformations and then for the appropriate uniaxial specialization. The constitutive relation proposed is in good agreement with the experimental data for both the passive and the stimulated conditions.
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Simulación por Computador , Manduca/fisiología , Modelos Biológicos , Contracción Muscular/fisiología , Goma/química , Animales , Fenómenos Biomecánicos , ElasticidadRESUMEN
OBJECTIVE: To evaluate the clinical outcome of in vitro fertilization (IVF) treatment cycles from individual oocyte donors who underwent multiple sequential donations. METHODS: We reviewed clinical outcome data from sequential anonymous oocyte donation cycles using donors who underwent multiple IVF stimulations. Donors were grouped by the interval between cycles and the cycle number (rank). The primary outcome measure was delivery rate by individual donor per retrieval from the combined derivative fresh and frozen embryo transfers. RESULTS: Duration and amount of gonadotropin therapy and the fertilization rates did not correlate significantly with the interval between cycles or cycle rank. Cumulative delivered pregnancy rates for cycles 1-6 were 51.5%, 54.6%, 50.5%, 51.5%, 51.1%, and 57.6%, respectively. Delivered pregnancy rates did not vary by interval between cycles. CONCLUSION: Young healthy presumed or proven fertile women can reliably donate oocytes for at least six cycles with the expectation of consistently high pregnancy rates.
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Fertilización In Vitro/estadística & datos numéricos , Donación de Oocito/estadística & datos numéricos , Embarazo/estadística & datos numéricos , Adolescente , Adulto , Colorado , Femenino , Humanos , Recién Nacido , Persona de Mediana Edad , Oportunidad RelativaRESUMEN
OBJECTIVE: Couples with children who have spinal muscular atrophy type I (SMA) face a 25% risk of having affected offspring with spontaneous conception. Preimplantation genetic testing (PGT) is possible for the deletions in the survival motor neuron (SMN) gene that have been identified in 98% of SMA type I cases. PGT would provide new reproductive options for families at risk for SMA. METHODS: Three couples with previously affected children confirmed by DNA testing each underwent in vitro fertilization (IVF) and PGT of the resulting embryos. One or two blastomeres were biopsied from each embryo and analyzed for deletions in exons 7 and 8 of the SMN gene. RESULTS: Nine embryos were predicted to be unaffected, three to be affected, and one embryo could not be interpreted. One of three patients receiving transfer of unaffected embryos became pregnant with twins. CONCLUSIONS: Preimplantation genetic testing provides a means for couples at risk for spinal muscular atrophy type I to reduce their chance of initiating an affected pregnancy.
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Desarrollo Embrionario , Atrofias Musculares Espinales de la Infancia/genética , Adulto , Femenino , Fertilización In Vitro , Humanos , Reacción en Cadena de la Polimerasa , EmbarazoRESUMEN
To determine whether ultrasonographic findings can predict the karyotype of spontaneous abortions, 137 pregnancies (54 spontaneous, 83 assisted ovulatory cycles) that subsequently aborted and had chromosome analysis performed on the products of conception were studied ultrasonographically. Transvaginal ultrasound was performed using an Acuson 128XP/10 with 7.5 MHz probe. The numbers of empty gestational sacs, small and normal for gestational size, embryonic poles and embryos with documented cardiac activity were calculated. The frequency of each of these findings in pregnancies with normal and abnormal karyotypes was compared. Of the 137 spontaneous abortions, 51 had normal chromosome analyses and 86 had abnormal karyotypes (68 aneuploidies and 18 polyploidies). Ultrasonographic findings in the 51 karyotypically normal pregnancies included 16 (31%) with empty gestational sacs, and 35 (69%) with embryonic poles, of which 24 (69%) were at least 1 week smaller than expected for gestational age and 11 (31%) were the expected size. Embryonic cardiac activity was documented in 22 (63%) of the 35 embryonic poles. Amongst 86 pregnancies with abnormal karyotypes, similar frequencies of ultrasound findings were found: 23 (27%) with empty gestational sacs, 42 (67%) with embryonic poles smaller than expected for gestational age, and 50 (79%) embryos lost after documentation of embryonic cardiac activity. No differences in the frequency of ultrasonographic findings of empty gestational sacs, small embryonic pole and embryonic cardiac activity were observed between karyotypically normal and abnormal spontaneous abortions. Ultrasonographic findings cannot predict the karyotype of spontaneous abortions.
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Aborto Espontáneo/diagnóstico por imagen , Aberraciones Cromosómicas/genética , Ultrasonografía Prenatal , Aborto Espontáneo/genética , Adulto , Trastornos de los Cromosomas , Femenino , Edad Gestacional , Humanos , Cariotipificación , Persona de Mediana Edad , Ploidias , Embarazo , Valores de ReferenciaRESUMEN
OBJECTIVE: To compare outcome of pregnancies after intracytoplasmic sperm injection (ICSI) with those of other assisted reproductive technologies. DESIGN: Pregnancy outcomes after ICSI were followed prospectively and compared with pregnancy outcomes after IVF with fresh and frozen ETs and donor oocyte cycles. SETTING: A private tertiary referral center for genetics and infertility in Fairfax, Virginia. PATIENTS: One hundred thirty-six couples achieving pregnancy after undergoing ICSI, 71 after IVF, 35 donor oocyte recipients, and 19 after transfer of frozen-thawed embryos. INTERVENTIONS: In vitro fertilization and/or ET for all couples. Dilatation and curettage to obtain products of conception for chromosome analysis in 28 women experiencing spontaneous abortion. MAIN OUTCOME MEASURES: Pregnancy outcomes were classified as preclinical loss, clinical loss, and ongoing pregnancy. RESULTS: The mean frequency of preclinical pregnancy loss was 26% after ICSI, 28% after IVF, 3% after ET using donor oocytes, and 11% after frozen ET. The rate of clinical loss after ICSI (21%) was compared with IVF (18%), donor oocyte cycles (11%), and frozen ETs (21%). CONCLUSIONS: Intracytoplasmic sperm injection is not associated with an increase in pregnancy losses, clinical or preclinical, compared with conventional IVF.
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Fertilización In Vitro/métodos , Resultado del Embarazo , Aborto Espontáneo , Adulto , Criopreservación , Citoplasma , Transferencia de Embrión , Femenino , Humanos , Microinyecciones , Donación de Oocito , EmbarazoRESUMEN
OBJECTIVE: To compare the frequency of chromosomal abnormalities in products of conception from women with and without a history of recurrent spontaneous abortion. DESIGN: Retrospective analysis of prospectively collected material. SETTING: Private practice at the Genetics and IVF Institute, Fairfax, Virginia and Grupo de Reproducción AGY Asociados, México City, México. PATIENTS: Women with (n = 94) and without (n = 130) a history of recurrent spontaneous abortion who had a spontaneous abortion between January 1, 1992 and November 1, 1994. INTERVENTION: Chromosomal analysis performed on products of conception using standard G-banding technique. MAIN OUTCOME MEASURE: The percentage of chromosomal abnormalities among products of conception from women with and without recurrent spontaneous abortion was compared. RESULTS: Among products of conception from women with recurrent spontaneous abortion, 57% (54/94) had abnormal and 43% (40/94) had normal chromosome analyses. Products of conception from women without recurrent spontaneous abortion had abnormal chromosome analyses in 57% (74/130) and normal results in 43% (56/130). CONCLUSIONS: No differences in frequency of abnormal karyotype were observed in products of conception from women with recurrent spontaneous abortion compared with women without recurrent spontaneous abortion.
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Aborto Habitual , Aberraciones Cromosómicas/epidemiología , Feto , Adulto , Trastornos de los Cromosomas , Femenino , Humanos , Cariotipificación , Embarazo , Estudios RetrospectivosRESUMEN
OBJECTIVE: To evaluate, in a prospective study, the fertilization and pregnancy rates after intracytoplasmic sperm injection (ICSI) in infertile couples with severe male infertility. DESIGN: Intracytoplasmic sperm injection was performed in 229 consecutive IVF cycles on 190 couples with rigorously defined severe male infertility or proven failure of fertilization in prior IVF cycles. Neither male nor female partners were chosen from a waiting list or on any other selective basis, including age, prior or anticipated ovarian response, or oocyte number or quality. There were no upper age limits, in no instance was donor sperm used for ICSI, and cycle cancellation rate was minimal. SETTING: Private genetics and fertility center in Fairfax, Virginia. MAIN OUTCOME MEASURES: Fertilization, transfer, and pregnancy rates were measured in ICSI-treated couples, and comparisons were made regarding both female age and strictly defined semen categories. RESULTS: Two hundred six cycles (90%) resulted in ETs, with initiation of 52 pregnancies (25% per transfer, 23% per cycle). Thirty-eight of 52 (18% per transfer) were clinical pregnancies with established gestational sacs or were ongoing or delivered. Pregnancies were achieved even in older women but were more readily established in younger women producing larger numbers of metaphase II oocytes. The severity of semen abnormalities had some small effect on fertilization rate, but only actual necrospermia was associated with markedly decreased frequency of embryo formation. Pregnancy per transfer was similar across groups. In some cases, pregnancy was initiated with fewer than 100 viable sperm in the ejaculate. CONCLUSIONS: Intracytoplasmic sperm injection is a very powerful new treatment for severe male infertility. Paradoxically, egg number and probably egg quality are now the main determinants of success in treating male infertility.
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Fertilización In Vitro , Infertilidad Masculina/terapia , Edad Materna , Adulto , Anciano , Citoplasma , Femenino , Humanos , Inyecciones , Masculino , Persona de Mediana Edad , Óvulo/fisiología , Embarazo , Estudios Prospectivos , EspermatozoidesRESUMEN
We prospectively studied the ability of acrosome reaction (AR) inducibility to predict fertilization success in a group of 232 infertile patients presenting sequentially for in-vitro fertilization (IVF). The median percentage of eggs fertilized for the overall patient population was 25% (interquartile range 5-58%), with one to 29 oocytes available for insemination (median, five oocytes). The median percentage of eggs fertilized at IVF increased as the percentage of spermatozoa able to undergo AR became greater: spermatozoa with a failed AR (< or = 5%) fertilized only 12% of eggs, while spermatozoa with AR values > 9% fertilized 50% of eggs. The assay had a specificity of 0.75, a sensitivity of 0.55 and an odds ratio of 2.9; thus, AR-positive patients are 2.9 times more likely to achieve fertilization than patients with a failed AR. Receiver operator characteristic (ROC) curves were constructed for AR, sperm concentration and percentage of normal forms in semen. All three parameters proved to be potentially useful in predicting the occurrence of fertilization, although AR and morphology appeared to be better than sperm concentration by ROC analysis. Patients were divided into four clearly defined subgroups according to their traditional semen characteristics, including morphology. The median percentage of eggs fertilized decreased as traditional semen characteristics deteriorated, from a median of 46% for patients with excellent sperm concentration, motility and morphology, to a median of 29% for patients with suboptimal semen quality and a median of 0% for patients with severely impaired semen.(ABSTRACT TRUNCATED AT 250 WORDS)
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Acrosoma/fisiología , Fertilización In Vitro , Adulto , Femenino , Humanos , Infertilidad/terapia , Masculino , Estudios Prospectivos , Recuento de Espermatozoides , Espermatozoides/anomalíasRESUMEN
Four cases having mosaicism for a small marker or ring [45,X/46,X,+mar or 45,X/46,X,+r] chromosome were ascertained following cytogenetic studies requested because of minor anomalies (cases 1, 3, and 4) and/or short stature (cases 2 and 4). While all 4 cases had traits typical of Ullrich-Turner syndrome (UTS), cases 1, 3, and 4 had manifestations not usually present in UTS, including unusual facial appearance, mental retardation/developmental delay (MR/DD) (cases 3 and 4), and syndactylies (case 1). The facial appearances of cases 1 and 3 were similar yet distinct from that of case 4. Using fluorescence in situ hybridization (FISH), each of the markers in these 4 cases was identified as having been derived from an X chromosome. The level of mosaicism for the mar/r(X) cell line in these cases varied from 70% (case 1) to 16% (case 4) but was not apparently correlated with the presence of MR/DD. Replication studies demonstrated a probable early replication pattern for the mar/r(X) in cases 1, 3, and 4, while the marker in case 2 was apparently late replicating. To date, 41 individuals having mosaicism for a small mar/r(X) chromosome have been described. Interestingly, most of the 14 individuals having a presumedly active mar/r(X) demonstrated clinical findings atypical of UTS, including abnormal facial changes (11) and MR/DD (13). MR was noted most frequently in those cases having at least 50% mosaicism for the marker or ring. In contrast, atypical UTS facial appearance or MR/DD was not noted in 14 of the 16 cases with UTS who carried a probable late replicating marker or ring. In conclusion, although the phenotype of 45,X/46,X,mar/r(X) individuals appears to be influenced by the genetic content and degree of mosaicism for the mar/r(X), the most significant factor associated with MR/DD appears to be the activity status of the mar/r(X) chromosome. Thus, our 4 cases provide further support for the hypothesis that a lack of inactivation of a small mar/r(X) chromosome may be a factor leading to the MR and other phenotypic abnormalities seen in this subset of individuals having atypical UTS.
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Compensación de Dosificación (Genética) , Discapacidad Intelectual/genética , Mosaicismo , Cromosomas en Anillo , Sindactilia/genética , Síndrome de Turner/genética , Cromosoma X/ultraestructura , Niño , Replicación del ADN , Cara/anomalías , Femenino , Pérdida Auditiva Conductiva/genética , Cardiopatías Congénitas/genética , Humanos , Hibridación Fluorescente in Situ , Lactante , Recién Nacido , FenotipoRESUMEN
Human X- and Y-chromosome-bearing spermatozoa were separated based on their DNA content, using modified flow cytometric cell sorting technology. The resulting separation purity of the X-bearing from Y-bearing spermatozoa was evaluated using in-situ hybridization with alpha satellite DNA probes for the X- and Y-chromosomes. In the putative X-enriched-sorted populations, an average of 82% of the spermatozoa showed a hybridization signal with the X probe. Similarly, in the Y-sorted population 75% gave a signal with the Y probe. Sorted X- and Y-bearing spermatozoa were found to maintain their viability for several hours after sorting. These results demonstrate that the human sperm sex ratio can be significantly shifted to favour the selection of female-producing (X) spermatozoa or male-producing (Y) spermatozoa when spermatozoa are flow cytometrically sorted on the basis of DNA content. We propose that flow cytometrically sorted human spermatozoa, used in conjunction with in-vitro fertilization or intra-oviductal insemination, could be used by families who are at risk for X-linked diseases to preferentially produce female offspring. Sorted spermatozoa could also be used to pre-select for male offspring if that were medically indicated.