RESUMO
The effects of statin use on conventional semen parameters in humans are largely unknown and have not been previously studied in subfertile men. We retrospectively reviewed data from 10,140 patients seen at our fertility clinic between 2002 and 2013 to assess the effects of statin use on semen parameters. Men who used any statins for >3 months before semen sample collection were included as cases. Data were gathered on patient age, medication use and conventional semen parameters. A total of 118 patients (126 samples) used statins for at least 3 months before semen sample collection. Data from 7698 patients (8,760 samples), who were not using any medications, were used as controls. In age-adjusted regression models, statin use was not associated with statistically significant changes in semen parameters. When used in combination with other nonspermatotoxic medications, it was associated with 0.3 ml decrease in semen volume (95% confidence interval: 0.02 to 0.58 ml, p-value = .04). In conclusion, statin use was not adversely associated with semen parameters other than semen volume in subfertile patients. These findings from our large-scale retrospective study suggest that there are no clinically relevant deleterious effects from statin use on conventional semen parameters.
Assuntos
Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Hipercolesterolemia/tratamento farmacológico , Infertilidade Masculina/complicações , Sêmen/efeitos dos fármacos , Motilidade dos Espermatozoides/efeitos dos fármacos , Adulto , Feminino , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hipercolesterolemia/complicações , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Análise do Sêmen , Contagem de EspermatozoidesRESUMO
The alkaline Comet assay has shown high diagnostic value to determine male reproductive health and prognostic ability to predict ART success. Here, spermatozoon was analysed in 47 fertile donors and 238 patients, including 132 couples undergoing ART [semen was collected: Group I - within 3 months of their treatment (n = 79); and Group II - 3 months prior to their treatment (n = 53)]. We introduce four Comet distribution plots (A, B1, B2 and C) by plotting the level of DNA damage (x-axis) and percentage of comets (y-axis). Fertile donors had low mean DNA damage, olive tail moment and per cent of spermatozoa with damage and increased type A plots. Comet parameters were associated with clinical pregnancies in Group I. About 66% of couples with type A distribution plot were successful after ART, whereas couples with type B1, B2 and C distribution plots achieved 56%, 44% and 33% pregnancies respectively. The efficiency of the Comet assay was due to complete decondensation process, where the compact sperm nuclear DNA (28.2 ± 0.2 µm3 ) is decondensed to ~63 µm3 (before lysis) and ~1018 µm3 (after lysis). A combinational analysis of all the Comet output parameters may provide a comprehensive evaluation of patient's reproductive health as these parameters measure different aspects of DNA damage within the spermatozoa.
Assuntos
Ensaio Cometa , Dano ao DNA , Infertilidade Masculina/diagnóstico , Espermatozoides/metabolismo , Humanos , Infertilidade Masculina/genética , Masculino , Valor Preditivo dos Testes , Técnicas de Reprodução Assistida , Análise do Sêmen , Doadores de TecidosRESUMO
Spermatogenesis is a complex process in which >2300 genes are temporally and spatially regulated to form a terminally differentiated sperm cell that must maintain the ability to contribute to a totipotent embryo which can successfully differentiate into a healthy individual. This process is dependent on fidelity of the genome, epigenome, transcriptome, and proteome of the spermatogonia, supporting cells, and the resulting sperm cell. Infertility and/or disease risk may increase in the offspring if abnormalities are present. This review highlights the recent advances in our understanding of these processes in light of the "omics revolution". We briefly review each of these areas, as well as highlight areas of future study and needs to advance further.
Assuntos
Genômica/métodos , Infertilidade Masculina/genética , Espermatozoides/metabolismo , Espermatozoides/patologia , Metilação de DNA , Epigênese Genética , Humanos , Infertilidade Masculina/metabolismo , Infertilidade Masculina/patologia , Masculino , Polimorfismo Genético , Espermatogênese , Espermatozoides/citologia , Biologia de Sistemas/métodosRESUMO
A Gram-negative, aerobic, motile, spiral-shaped bacterium, strain H5569(T), was isolated from a human blood sample. Phenotypic and molecular characteristics of the isolate were investigated. Optimal growth was found to occur at 35 °C under aerobic conditions on Heart Infusion Agar supplemented with 5 % rabbit blood. The major fatty acids present in the cells were identified as C16:0, C16:1ω7c and C18:1ω7c. The predominant respiratory quinone was found to be ubiquinone-Q10. The G+C content of genomic DNA for strain H5569(T) was found to be 49.9 %. Based on 16S rRNA gene sequence analysis results, 13 additional isolates were also analysed in this study. Phylogenetic analysis based on 16S rRNA gene sequences revealed that the organism, represented by strain H5569(T), forms a distinct lineage within the family Rhodospirillaceae, closely related to two Novispirillum itersonii subspecies (93.9-94.1 %) and two Caenispirillum sp. (91.2-91.6 %). Based on these results, the isolate H5569(T) is concluded to represent a new genus and species for which the name Haematospirillum jordaniae gen. nov., sp. nov. is proposed. The type strain is H5569(T) (=DSM(T) 28903 = CCUG 66838(T)).
Assuntos
Sangue/microbiologia , Infecções por Bactérias Gram-Negativas/sangue , Infecções por Bactérias Gram-Negativas/microbiologia , Rhodospirillaceae/isolamento & purificação , Adulto , Idoso , Composição de Bases , Sequência de Bases , Células Cultivadas , DNA Bacteriano/genética , Humanos , Masculino , Pessoa de Meia-Idade , Filogenia , RNA Ribossômico 16S/genética , Rhodospirillaceae/classificação , Rhodospirillaceae/genética , Análise de Sequência de DNARESUMO
Male infertility is often associated with a decreased sperm count. The Pygo2 gene is expressed in the elongating spermatid during chromatin remodeling; thus impairment in PYGO2 function might lead to spermatogenic arrest, sperm count reduction, and subsequent infertility. The aim of this study was to identify mutations in Pygo2 that might lead to idiopathic oligospermia and azoospermia. DNA was isolated from venous blood from 77 men with normal fertility and 195 men with idiopathic oligospermia or azoospermia. Polymerase chain reaction-sequencing analysis was performed for the three Pygo2 coding regions. Non-synonymous single nucleotide polymorphisms (SNPs) were detected and analyzed using SIFT, Polyphen-2, and Mutation Taster softwares to identify possible changes in protein structure that could affect phenotype. Pygo2 sequencing was successful for 178 patients (30 with mild or moderate oligospermia, 57 with severe oligospermia, and 91 with azoospermia). Three previously reported non-synonymous SNPs were identified in patients with azoospermia or severe oligospermic but not in those with mild or moderate oligozoopermia or normozoospermia. SNPs rs61758740 (M141I) and rs141722381 (N240I) cause the replacement of one hydrophobic or hydrophilic amino acid, respectively, with another, and SNP rs61758741 (K261E) causes the replacement of a basic amino acid with an acidic one. The software predictions demonstrated that SNP rsl41722381 would likely result in disrupted tertiary protein structure and thus could be involved in disease pathogenesis. Overall, this study demonstrated that SNPs in the coding region of Pygo2 might be one of the causative factors in idiopathic oligospermia and azoospermia, resulting in male infertility.
Assuntos
Azoospermia/genética , Estudos de Associação Genética , Infertilidade Masculina/genética , Peptídeos e Proteínas de Sinalização Intracelular/genética , Oligospermia/genética , Adulto , Azoospermia/congênito , Azoospermia/patologia , Humanos , Infertilidade Masculina/patologia , Masculino , Mutação , Oligospermia/patologia , Polimorfismo de Nucleotídeo ÚnicoRESUMO
STUDY QUESTION: Does sperm DNA damage affect early embryonic development? SUMMARY ANSWER: Increased sperm DNA damage adversely affects embryo quality starting at Day 2 of early embryonic development and continuing after embryo transfer, resulting in reduced implantation rates and pregnancy outcomes. WHAT IS KNOWN ALREADY: Abnormalities in the sperm DNA in the form of single and double strand breaks can be assessed by an alkaline Comet assay. Some prior studies have shown a strong paternal effect of sperm DNA damage on IVF outcome, including reduced fertilization, reduced embryo quality and cleavage rates, reduced numbers of embryos developing into blastocysts, increased percentage of embryos undergoing developmental arrest, and reduced implantation and pregnancy rates. STUDY DESIGN, SIZE, DURATION: A cross-sectional study of 215 men from infertile couples undergoing assisted reproduction techniques at the University of Utah Center for Reproductive Medicine. PARTICIPANTS/MATERIALS, SETTING, METHODS: Sperm from men undergoing ART were analyzed for DNA damage using an alkaline Comet assay and classified into three groups: 'low damage' (0-30%), 'intermediate damage' (31-70%) and 'high damage' (71-100%). The cause of couples' infertility was categorized into one of the three types (male, female or unexplained). Each embryo was categorized as 'good', 'fair' or 'poor' quality, based on the number and grade of blastomeres. The influence of sperm DNA damage on early embryonic development was observed and classified into four stages: peri-fertilization effect (fertilization rate), early paternal effect (embryonic days 1-2), late paternal effect (embryonic days 3-5) and implantation stage effect. MAIN RESULTS AND THE ROLE OF CHANCE: The paternal effect of sperm DNA damage was observed at each stage of early embryonic development. The peri-fertilization effect was higher in oocytes from patients with female infertility (20.85%) compared with male (8.22%; P < 0.001) and unexplained (7.30%; P < 0.001) infertility factors. In both the early and late paternal effect stages, the low DNA damage group had a higher percentage of good quality embryos (P < 0.05) and lower percentage of poor quality embryos (P < 0.05) compared with the high DNA damage group. Implantation was lower in the high DNA damage (33.33%) compared with intermediate DNA damage (55.26%; P < 0.001) and low DNA damage (65.00%; P < 0.001) groups. The implantation rate was higher following blastocyst transfer (58.33%), when compared with early stage blastocyst (53.85%; P = 0.554) and cavitating morula transfers (34.40%; P < 0.001). Implantation was higher when the female partner age was ≤35 years when compared with >35 year age group (52.75 versus 35.44%; P = 0.008). LIMITATIONS, REASONS FOR CAUTION: A potential limitation of this study is that it is cross-sectional. Generally in such studies more than one variable could affect the outcome. Analyzing sperm is one part of the equation but a number of environmental and female factors also have the potential to influence embryo development and implantation. Furthermore, the selection of morphologically normal and physiologically motile sperm may result in isolation of sperm with reduced DNA damage. Therefore, selecting the best available sperm for ICSI may lead to experimental bias, as the selected sperm do not represent the overall sperm population in which the DNA damage is measured. Similar studies on selected sperm and with a larger sample size are now required. WIDER IMPLICATIONS OF THE FINDINGS: The paternal influence of damaged chromatin is more prominent after zygotic transcriptional activation. A prolonged paternal effect on the developing embryo may be due to the active repair mechanism present in oocytes that tends to overcome the damaged paternal chromatin. The probability of eliminating an embryo fertilized by a sperm with damaged DNA is higher at the blastocyst stage than the cleavage stage; therefore blastocyst transfer could be recommended for better implantation success. Finally, we recommend ICSI treatment for patients with a higher percentage of sperm with DNA damage as well as additional studies with a larger sample size aimed at assessing DNA damage analysis as a diagnostic tool for IVF. STUDY FUNDING/COMPETING INTERESTS: This work was supported by the University of Utah internal funds. The authors declare no competing interests. TRIAL REGISTRATION NUMBER: N/A.
Assuntos
Dano ao DNA , Implantação do Embrião/genética , Desenvolvimento Embrionário/genética , Infertilidade/genética , Espermatozoides/metabolismo , Adulto , Estudos Transversais , Transferência Embrionária/métodos , Feminino , Fertilização in vitro , Humanos , Infertilidade/metabolismo , Masculino , Gravidez , Resultado da Gravidez , Taxa de GravidezRESUMO
STUDY QUESTION: Is there an association between sperm DNA damage, measured by three different assays, sperm nuclear protein content and clinical outcomes in assisted reproduction treatment (ART)? SUMMARY ANSWER: Sperm DNA damage measured by terminal deoxynucleotidyltransferase-mediated dUTP nick-end labelling (TUNEL) and the Comet assay were significantly associated with ART outcomes in our single institution study. WHAT IS KNOWN ALREADY: Abnormal protamine expression is known to be associated with sperm DNA damage and male infertility. A number of studies have shown a significant relationship between sperm DNA damage and ART outcomes. To date, there are no large studies providing direct comparisons of DNA damage tests within the same study population. Thus, the prognostic value for each method remains unknown. STUDY DESIGN, SIZE, DURATION: Cross-sectional study of 238 men from infertile couples undergoing ART at the University Center for Reproductive Medicine, Utah, USA, between April 2011 and March 2013. PARTICIPANTS/MATERIALS, SETTING, METHODS: Sperm from men undergoing ART were tested for DNA damage using the alkaline Comet assay, TUNEL and flow cytometric chromatin evaluation (FCCE) assays. Histone retention was analysed using the aniline blue staining method, whereas protamine content (proteins P1 and P2) and ratio were analysed using acid urea gel electrophoresis. The prognostic value of each sperm DNA test to predict clinical pregnancy was calculated. MAIN RESULTS AND THE ROLE OF CHANCE: Histone retention was associated with sperm DNA damage (P < 0.001), reduced embryo quality (P = 0.005) and clinical pregnancies (P < 0.001). The mean percentage of sperm with DNA damage was significantly higher in sperm from non-pregnant couples compared with that from pregnant couples, as measured by TUNEL assay (15.04 ± 1.16% versus 8.79 ± 0.56%; P < 0.001) and alkaline Comet assay (72.79 ± 2.49% versus 55.86 ± 2.29%; P < 0.001). There was no association between clinical pregnancies and DNA fragmentation index measured by FCCE (12.97 ± 1.46 versus 14.93 ± 1.65; P = 0.379). Of the protamine parameters analysed, only the P1/P2 ratio was associated with sperm count (P = 0.013), men's age (P = 0.037), maturity (P = 0.049) and blastocyst quality (P = 0.012). Histone retention and sperm DNA damage measured by Comet and TUNEL assays were associated with fertilization rate (P < 0.05), embryo quality (P < 0.05) and implantation rate (P < 0.05). LIMITATIONS, REASONS FOR CAUTION: A potential drawback of this study is that it is cross-sectional. Generally in such studies there is more than one variable that could cause the effect. Analysing sperm is one part of the equation; there are also a number of female factors that have the potential to influence ART outcomes. Therefore, given the large and well-established role of female factors in infertility, normal sperm DNA integrity and protamination do not necessarily ensure clinical pregnancy in ART. Thus, female factors can reduce the prognostic value of sperm DNA tests. Further, our use of native semen instead of prepared sperm may have iatrogenically increased the DNA damage. WIDER IMPLICATIONS OF THE FINDINGS: Alteration in sperm nuclear protein affects sperm DNA integrity. Further, with the current dataset, TUNEL and Comet assays appeared more predictive of ART success than FCCE. STUDY FUNDING/COMPETING INTEREST(S): No personal or direct financial support has been received for any of this work. The authors declare no competing interests. TRIAL REGISTRATION NUMBER: N/A.
Assuntos
Ensaio Cometa/métodos , Dano ao DNA , Citometria de Fluxo/métodos , Marcação In Situ das Extremidades Cortadas/métodos , Infertilidade Masculina/genética , Análise do Sêmen/métodos , Cromatina/metabolismo , Estudos Transversais , Fragmentação do DNA , Feminino , Fertilização in vitro , Humanos , Masculino , Gravidez , Taxa de Gravidez , Injeções de Esperma IntracitoplásmicasRESUMO
Dichotic listening (DL) techniques have been used extensively as a non-invasive procedure to assess language lateralization among children with and without learning disabilities (LD), and with individuals who have other auditory system related brain disorders. Results of studies using DL have indicated that language is lateralized in children with LD and that the lateralized language asymmetries do not develop after age 6 nor are they affected by gender. Observed differences in lateralized language processes between control children and those with LD were found not due to delayed cerebral dominance, but rather to deficits in selective attention. In addition, attention factors have a greater influence on auditory processing of verbal than nonverbal stimuli for children with LD, and children with LD exhibit a general processing bias to the same hemisphere unlike control children. Furthermore, employing directed attention conditions in DL experiments has played an important role in explaining learning disabled children's performance on DL tasks. We conclude that auditory perceptual asymmetries as assessed by DL with children who experience LD are the result of the interaction of hemispheric capability and attention factors.
Assuntos
Percepção Auditiva/fisiologia , Lateralidade Funcional/fisiologia , Transtornos da Linguagem/fisiopatologia , Deficiências da Aprendizagem/fisiopatologia , Atenção/fisiologia , Criança , Testes com Listas de Dissílabos , Humanos , IdiomaRESUMO
We have previously demonstrated that thyromimetics stimulate oligodendrocyte precursor cell differentiation and promote remyelination in murine demyelination models. We investigated whether a thyroid receptor-beta selective thyromimetic, sobetirome (Sob), and its CNS-targeted prodrug, Sob-AM2, could prevent myelin and axonal degeneration in experimental autoimmune encephalomyelitis (EAE). Compared to controls, EAE mice receiving triiodothyronine (T3, 0.4 mg/kg), Sob (5 mg/kg) or Sob-AM2 (5 mg/kg) had reduced clinical disease and, within the spinal cord, less tissue damage, more normally myelinated axons, fewer degenerating axons and more oligodendrocytes. T3 and Sob also protected cultured oligodendrocytes against cell death. Thyromimetics thus might protect against oligodendrocyte death, demyelination and axonal degeneration as well as stimulate remyelination in multiple sclerosis.
Assuntos
Acetatos/farmacologia , Encefalomielite Autoimune Experimental/patologia , Bainha de Mielina/efeitos dos fármacos , Oligodendroglia/efeitos dos fármacos , Fenóis/farmacologia , Tri-Iodotironina/farmacologia , Animais , Doenças Desmielinizantes/patologia , Feminino , Camundongos , Camundongos Endogâmicos C57BL , Degeneração Neural/patologia , Pró-Fármacos/farmacologiaRESUMO
Multiple sclerosis is an autoimmune disease of the CNS that results in the death of oligodendrocytes, the myelinating cells of the CNS. Previous studies have indicated that the cytokine leukemia inhibitory factor prevents the cytotoxic effects of interferon-gamma on oligodendrocytes in vitro, and the death of oligodendrocytes in an animal model of multiple sclerosis. Members of a recently characterized family of proteins, the suppressors of cytokine signaling, have been demonstrated to mediate negative cross-talk between cytokines, with induction of suppressors of cytokine signaling proteins by one cytokine inhibiting the activity of a second. Here, we assess whether induction of members of the suppressors of cytokine signaling family could explain the antagonistic biological effects of leukemia inhibitory factor and interferon-gamma upon oligodendrocytes. It is found that leukemia inhibitory factor rapidly and strongly induces the expression of suppressors of cytokine signaling-3 in cultured rat oligodendrocytes, whereas interferon-gamma weakly induces the expression of both suppressor of cytokine signaling-1 and 3. Pre-treatment of oligodendrocytes with leukemia inhibitory factor does not prevent the subsequent phosphorylation of signal transducer and activator of transcription-1 by interferon-gamma indicating that the leukemia inhibitory factor inhibition of interferon-gamma toxicity in oligodendrocytes is mediated by a suppressor of cytokine signaling-3 independent mechanism.
Assuntos
Interferon gama/toxicidade , Interleucina-6/farmacologia , Oligodendroglia/imunologia , Fator de Transcrição STAT1/metabolismo , Proteínas Supressoras da Sinalização de Citocina/metabolismo , Animais , Animais Recém-Nascidos , Morte Celular/efeitos dos fármacos , Morte Celular/imunologia , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/imunologia , Células Cultivadas , Modelos Animais de Doenças , Interações Medicamentosas/imunologia , Retroalimentação Fisiológica/fisiologia , Feminino , Peptídeos e Proteínas de Sinalização Intracelular/genética , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Fator Inibidor de Leucemia , Masculino , Camundongos , Esclerose Múltipla/imunologia , Esclerose Múltipla/fisiopatologia , Oligodendroglia/efeitos dos fármacos , Oligodendroglia/metabolismo , Fosforilação/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismo , Fator de Transcrição STAT1/genética , Proteína 1 Supressora da Sinalização de Citocina , Proteína 3 Supressora da Sinalização de Citocinas , Proteínas Supressoras da Sinalização de Citocina/genética , Regulação para Cima/efeitos dos fármacos , Regulação para Cima/fisiologiaRESUMO
Over recent years the secreted guidance cue, netrin-1, and its receptor, DCC, have been shown to be an essential guidance system driving axon pathfinding within the developing vertebrate central nervous system (CNS). Mice lacking DCC exhibit severe defects in commissural axon extension towards the floor plate demonstrating that the DCC-netrin guidance system is largely responsible for directing axonal projections toward the ventral midline in the developing spinal cord (Fazeli et al., Nature 386 (1997) 796). In addition, these mutants lack several major commissures within the forebrain, including the corpus callosum and the hippocampal commissure. In contrast to the CNS, the role of the DCC guidance receptor in the development of the mammalian peripheral and enteric nervous systems (PNS and ENS) has not been investigated. Here we demonstrate using immunohistochemical analysis that the DCC receptor is present in the developing mouse PNS where it is found on spinal, segmental, and sciatic nerves, and in developing sensory ganglia and their associated axonal projections. In addition, DCC is present in the ENS throughout the early developmental phase.
Assuntos
Moléculas de Adesão Celular/metabolismo , Fatores de Crescimento Neural/metabolismo , Sistema Nervoso Periférico/embriologia , Estômago/embriologia , Estômago/inervação , Proteínas Supressoras de Tumor , Animais , Corpo Caloso/embriologia , Receptor DCC , Hipocampo/embriologia , Imuno-Histoquímica , Camundongos , Netrina-1 , Receptores de Superfície Celular , Medula Espinal/embriologia , Fatores de Tempo , Distribuição TecidualRESUMO
BACKGROUND: In vitro maturation of mammalian oocytes is an area of great interest due to its potential application in the treatment of infertility. The morphological and physiological changes that occur during oocyte development are poorly understood, and further studies are needed investigating the physiological changes associated with oocyte maturation. In this study we evaluated the membrane potential and the sodium/potassium permeability ratio of oocytes acutely isolated, and cumulus-oocyte complexes in metaphase II and preantral follicle stages. RESULTS: Intracellular electrical recordings revealed that cumulus-enclosed oocytes have a membrane potential significantly more negative at the preantral follicle stage than at metaphase II stage (-38.4 versus -19.7 mV, p < 0.0005). The membrane potential of the cumulus-free oocytes was not different between the preantral and metaphase II stages. The membrane potential of the cumulus cells forming preantral stage follicles was shown to be significantly different from that of the oocyte within the follicle (-28.6 versus -38.4 mV, p < 0.05). The sodium/potassium permeability measured in cumulus-enclosed oocytes at the preantral stage equaled a mean value of 0.33. The ratio was significantly lower when measured in oocytes denuded of cumulus cells or cumulus-enclosed metaphase II oocytes, 0.76, 0.79, 0.77 respectively (p < 0.001). CONCLUSIONS: These data show a change in the membrane potential and Na+/K+ permeability ratio during ooycte development from the preantral stage oocyte to the metaphase II stage. We have also demonstrated a change in the preantral oocyte membrane potential when surrounding cumulus cells are removed; either due to membrane changes or loss of cumulus cells.
Assuntos
Permeabilidade da Membrana Celular/fisiologia , Potenciais da Membrana/fisiologia , Oócitos/crescimento & desenvolvimento , Oócitos/fisiologia , Folículo Ovariano/embriologia , Folículo Ovariano/metabolismo , Potássio/metabolismo , Sódio/metabolismo , Animais , Cricetinae , Feminino , MesocricetusRESUMO
A guinea pig model of nasal secretory responses was developed to assess the contributions of vascular permeability and glandular secretion responsible for the production of cholinergically stimulated nasal secretions. The nasal secretory responses to provocation with saline, methacholine, and atropine on the ipsilateral (challenged) side and contralateral (reflex) side were analyzed by measurement of total protein (Lowry method), guinea pig albumin (enzyme-linked immunosorbent assay), 125I-labeled bovine serum albumin after intravenous injection, and alkaline phosphatase enzyme activity in nasal fluid. Alkaline phosphatase was found to be localized to submucosal glands by zymography. Topical methacholine challenge increased the secretion of total protein, alkaline phosphatase activity, and albumin on the ipsilateral challenged side, whereas the percentage of total protein represented by albumin was not increased. This response was totally prevented by atropine pretreatment. Serial provocation with methacholine resulted in progressively reduced amounts of both the total protein and alkaline phosphatase in secretions. The observation that repeated challenges produced progressively smaller responses was also examined employing human nasal provocation. Repeating methacholine (25 mg) challenges four times at 10-min intervals in six human volunteers revealed that the initial challenge produced the largest response as reflected in total protein, albumin, lysozyme, lactoferrin, immunoglobulin (Ig) G, IgA, and secretory IgA secretion. When the constituents in secretions were analyzed in relationship to the total protein, the two vascular proteins, IgG and albumin, demonstrated the greatest decrements with repeated methacholine challenges. The glandular proteins, lactoferrin, lysozyme, and secretory IgA, either remained constant or increased in their relative proportion to total protein. Thus, cholinergic stimulation causes glandular secretion from both the guinea pig and human nasal mucosa.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Atropina/farmacologia , Cloreto de Metacolina/farmacologia , Mucosa Nasal/efeitos dos fármacos , Mucosa Nasal/metabolismo , Adolescente , Adulto , Albuminas/metabolismo , Fosfatase Alcalina/metabolismo , Animais , Cobaias , Humanos , Imunoglobulinas/metabolismo , Masculino , Pessoa de Meia-Idade , Mucosa Nasal/enzimologia , Proteínas/metabolismoRESUMO
OBJECTIVE: To characterize and contrast protamine levels, chromatin decondensation, chromosome aneuploidy rates, and functional ability of round-headed sperm from two brothers with round-headed sperm syndrome. DESIGN: Analysis of semen samples from siblings with round-headed sperm syndrome and comparison with semen of fertile donors. SETTING: University school of medicine and laboratories. PATIENT(S): Two infertile siblings. MAIN OUTCOME MEASURE(S): Sperm aneuploidy rates of chromosomes X, Y, 13, 18, and 21, protamine 1 and 2 (P1-P2) ratios, Western blot evaluation of protamines, and chromatin decondensation rates. Additional measures include standard semen quality parameters, electron microscopy ultrastructure evaluation, analysis of acrosome morphology, and sperm penetration rates. RESULT(S): Aneuploidy rates were significantly increased in sibling no. 1 but not in sibling no. 2. The levels of P1 and P2 were decreased in sibling no. 1, and an unusual level of protamine precursors was present. Ultrastructural differences also were observed between the siblings. CONCLUSION(S): These data indicate profound differences in sperm from two siblings with complete round-headed sperm syndrome. Multigenic defects and/or variable expression of the syndrome may be responsible for the syndrome and necessitate individual screening of affected individuals because the pattern of expression appears highly variable.
Assuntos
Aneuploidia , Fertilização in vitro/métodos , Infertilidade Masculina/genética , Protaminas/metabolismo , Interações Espermatozoide-Óvulo , Espermatozoides/metabolismo , Espermatozoides/ultraestrutura , Acrossomo , Adulto , Cromatina/ultraestrutura , Cromossomos Humanos Par 18 , Cromossomos Humanos Par 21 , Feminino , Humanos , Masculino , Microinjeções , Síndrome , Cromossomo X , Cromossomo YRESUMO
This study investigated current uses of the Children's Depression Inventory (CDI), a frequently cited self-report measure for children's depressive symptomatology. Recently published studies of "childhood depression" were reviewed: Half of them used the CDI. Of these studies, 68% did not use a clinical or structured interview to determine diagnostic status. When the CDI was used alone to assess depressive symptoms, 44% of studies referred to high CDI scorers as "depressed" without providing a clear cautionary statement (i.e., either stating that the CDI cannot be used to diagnose depression or clarifying limitations regarding generalization of findings from a nonclinical to a clinical sample). These results are similar to those previously published regarding the Beck Depression Inventory, and they suggest a need for caution in the administration and interpretation of results from self-report inventories for children's depressive symptoms.
Assuntos
Psiquiatria Infantil/normas , Depressão/diagnóstico , Escalas de Graduação Psiquiátrica/normas , Projetos de Pesquisa/normas , Distribuição de Qui-Quadrado , Criança , Psiquiatria Infantil/métodos , HumanosRESUMO
OBJECTIVE/HYPOTHESIS: Current options for the treatment of snoring have limited acceptance because of intolerance, expense, pain, or need for general anesthesia. A clinical trial using a new application of a previously known technology-radiofrequency energy-was investigated to determine its efficacy in the treatment of snoring. Effects of treatment on speech, swallowing, pain, snoring, and degree of sleepiness were evaluated. These effects were evaluated by post-treatment questionnaires. METHODS: Prospective nonrandomized study. All included subjects snored at a level considered bothersome to their bed partner. A total of 43 patients were enrolled at the University of Maryland (UM) and the Georgia Ear Institute (GEI). Polysomnography was performed before treatment to eliminate patients with significant sleep apnea who had respiratory disturbance indices (RDIs) greater than 15 or nadir desaturations less than 80%. The mean pretreatment RDI for all patients who entered the protocol at UM was 6.7 +/- 4.7. Nine patients completed the study in this group in all other aspects, but did not return for their scheduled post-treatment polysomnogram. At GEI, pretreatment polysomnograms revealed a mean RDI of 8.9 +/- 3.8. Eleven patients at GEI completed the study in all other aspects but did not return for their scheduled post-treatment polysomnogram. Radiofrequency energy was delivered to the soft palate either in the midline (19 patients) at a mean of 698 +/- 52 J per treatment at UM or in the midline and lateral soft palate (24 patients) at a mean of 1,254 +/- 191 J per treatment at GEI. At UM the mean age was 44.3 +/- 8.4 years, with a range from 29 to 59 years. Eighty-four percent of the patients were men. The mean body mass index (BMI) was 28.5 +/- 3.2. Twenty-four patients were enrolled at GEI. The mean age was 44.0 +/- 10.9 years, with a range from 23 to 63 years. Seventy-four percent of patients were men. The mean BMI was 27.7 +/- 3.8. Snoring, pain, swallowing, and speech were assessed after each treatment at post-treatment day 1, 2, or 3; week 1; week 4; and week 7. Daytime sleepiness was assessed by the Epworth Sleepiness Scores (ESS) obtained at the same intervals. RESULTS: Snoring was improved in 77% of patients after three treatments or less. Seventy-nine percent of patients treated with the midline technique at UM and 96% of patients treated with the midline and left and right lateral palate technique at GEI achieved an improvement in their snoring to a level that was no longer bothersome to their bed partner. No persistent negative impact was noted concerning speech or swallowing. Improvements in degree of sleepiness were observed by comparing pretreatment and post-treatment ESS. ESS was significantly reduced (P < .005) after treatment from 10.2 +/- 6.1 to 6.1 +/- 4.7 at UM, and at the GEI, from 8.75 +/- 4.4 to 5.3 +/- 3.2. After a treatment, 27% of the patients at UM and 29% at GEI required analgesics. CONCLUSIONS: This clinical trial demonstrates the efficacy, safety, and lack of pain encountered when using radiofrequency energy delivered to the palate for the treatment of snoring. The tolerability, lack of pain, and ability to perform the procedure with the patient under local anesthesia in the office make the use of this technology an excellent option for the treatment of snoring.
Assuntos
Palato Mole/anatomia & histologia , Ronco/terapia , Adulto , Idoso , Diagnóstico por Computador , Distúrbios do Sono por Sonolência Excessiva/diagnóstico , Distúrbios do Sono por Sonolência Excessiva/etiologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Polissonografia , Estudos Prospectivos , Índice de Gravidade de Doença , Apneia Obstrutiva do Sono/complicações , Apneia Obstrutiva do Sono/diagnóstico , Ronco/diagnóstico , Ronco/etiologia , Inquéritos e Questionários , Resultado do TratamentoRESUMO
OBJECTIVE: To determine whether perioperative steroids affect the outcome of patients who undergo palatoplasty. DESIGN: A prospective, double-blind, randomized study. SETTING: A university medical center. PATIENTS: Twenty patients undergoing primary repair of a cleft palate. INTERVENTION: A prospective double-blind technique was used to randomly assign patients to receive a placebo or dexamethasone sodium phosphate perioperatively. MAIN OUTCOME MEASURE: Patients were monitored for postoperative airway distress, fever, oral fluid intake, days of hospitalization, and wound healing. RESULTS: The use of perioperative steroids was associated with shorter hospitalizations. No adverse sequelae from the administration of steroids were identified. CONCLUSIONS: In our current managed care environment, the use of perioperative steroids may play an important role in reducing health care costs.
Assuntos
Anti-Inflamatórios não Esteroides/administração & dosagem , Fissura Palatina/cirurgia , Dexametasona/análogos & derivados , Dexametasona/administração & dosagem , Método Duplo-Cego , Feminino , Custos de Cuidados de Saúde , Humanos , Lactente , Injeções Intravenosas , Tempo de Internação , Masculino , Cuidados Pós-Operatórios , Cuidados Pré-Operatórios , Estudos ProspectivosRESUMO
OBJECTIVE: To validate the use of temperature-controlled radiofrequency energy applied to the soft palate in a multicenter setting for reduction of snoring in a minimally morbid manner. METHODS: Prospective, nonrandomized multicenter study of 113 patients who had a respiratory disturbance index less than 15 and minimum oxygen saturation not less than 85% and who were seeking treatment for habitual disruptive snoring. Patients were given either single or multiple lesions to the soft palate during each treatment session. RESULTS: Patients received 1978 J on average with an overall average of 2.4 treatments. Snoring scores went from an average of 7.8 (visual analog scale (VAS), 0-10) pretreatment to 3.2 posttreatment. Pain was minimal, averaging 1.7 (VAS 0-10) on days 1 to 6. Complications were few and transient, and mild. CONCLUSIONS: The multiple lesion protocol was the most successful; reducing snoring from 7.6 to 2.7, on a VAS with an average of 1232 J delivered over 1.6 treatments. Temperature-controlled radiofrequency was found to be a minimally invasive, well-tolerated procedure that was safe and efficacious in this study group.
Assuntos
Eletrocirurgia/métodos , Palato Mole/cirurgia , Ronco/cirurgia , Adulto , Idoso , Feminino , Temperatura Alta , Humanos , Masculino , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
In this retrospective study we reviewed the charts of 169 consecutive admissions to the Palliative Care Unit, Edmonton General Hospital. Demographic and social characteristics of patients were assessed in order to determine the likelihood that the patients could be managed at home according to currently available services. The mean age of the population was 65 +/- 12 years, 97 (57%) were women, they had a variety of cancers with major prevalence of the most frequent adult tumors, and 72% of patients were coming from acute care hospitals. Each patient had an average of 2.7 +/- 1.8 children (median = 3), a mean of 0.18 +/- 0.6 dependents (median = 0), a mean of 1 +/- 0.9 support persons at home (median = 1), and a mean of 2.6 +/- 1 support persons outside the household (median = 2). Of a total of 119 main caregivers who lived in the same household as the patient, 69 (58%) were not able to take care of the patient. Only 27 patients (16%) considered that there were major financial problems, and all 169 patients had universal health care available (95 patients had additional private health care coverage). Of 125 patients who were asked where they preferred to die, 112 (90%) stated that they did not want to die at home. Our data suggest that the lack of family support and lack of intensive home care services are the main obstacles to home care of terminally ill cancer patients in our province. Home care services as currently available are not able to care for a large number of patients with terminal cancer. More prospective research into this subject is badly needed.