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The purpose of this study is to examine associations between maternal lipid profiles in pregnancy and offspring growth trajectories in a largely macrosomic cohort. This is a secondary analysis of the ROLO birth cohort (n = 293), which took place in the National Maternity Hospital, Dublin, Ireland. Infants were mostly macrosomic, with 55% having a birthweight > 4 kg. Maternal mean age was 32.4 years (SD 3.9 years), mean BMI was 26.1 kg/m2 (SD 4.4 kg/m2) and 48% of children born were males. Total cholesterol, high density lipoprotein cholesterol (HDL-cholesterol), low density lipoprotein cholesterol (LDL-cholesterol) and triglycerides were measured from fasting blood samples of mothers at 14 and 28 week gestation. The change in maternal lipid levels from early to late pregnancy was also examined. Offspring abdominal circumference and weight were measured at 20- and 34-week gestation, birth, 6 months, 2 years and 5 years postnatal. Linear spline multilevel models examined associations between maternal blood lipid profiles and offspring growth. We found some weak, significant associations between maternal blood lipids and trajectories of offspring growth. Significant findings were close to the null, providing limited evidence. For instance, 1 mmol/L increase in maternal triglycerides was associated with faster infant weight growth from 20- to 34-week gestation (0.01 kg/week, 95% CI - 0.02, - 0.001) and slower abdominal circumference from 2 to 5 years (0.01 cm/week, 95% CI - 0.02, - 0.001). These findings do not provide evidence of a clinically meaningful effect. Conclusion: These findings raise questions about the efficacy of interventions targeting maternal blood lipid profiles in pregnancies at risk of macrosomia. New studies on this topic are needed. What is Known: ⢠Maternal fat accumulation during early pregnancy may potentially support fetal growth in the third trimester by providing a reserve of lipids that are broken down and transferred to the infant across the placental barrier. ⢠There are limited studies exploring the impact of maternal lipid profiles on infant and child health using growth trajectories spanning prenatal to postnatal life. What is New: ⢠Maternal blood lipid profiles were not associated with offspring growth trajectories of weight and abdominal circumference during pregnancy up to 5 years of age in a largely macrosomic cohort, as significant findings were close to the null, providing limited evidence for a clinically meaningful relationship. ⢠Strengths of this work include the use of infant growth trajectories that span prenatal to postnatal life and inclusion of analyses of the change of maternal lipid levels from early to late pregnancy and their associations with offspring growth trajectories from 20-week gestation to 5 years of age.
Assuntos
Lipídeos , Placenta , Masculino , Lactente , Criança , Gravidez , Feminino , Humanos , Adulto , Estudos de Coortes , Peso ao Nascer , Triglicerídeos , HDL-ColesterolRESUMO
Although confined to fresh water, non-parasitic species of lampreys and the landlocked parasitic sea lamprey, all of which were derived relatively recently from an adromous ancestors, still develop chloride cells, whose function in their ancestors was for osmoregulation in marine waters during the adult parasitic phase. In contrast, such cells are not developed by the non-parasitic least brook lamprey Lampetra aepyptera, which has been separated from its ancestor for >2 million years, nor by the freshwater parasitic species of the genus Ichthyomyzon. The length of time that a non-parasitic species or landlocked parasitic form or species has spent in fresh water is thus considered the overriding factor determining whether chloride cells are developed by those lampreys.
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Evolução Biológica , Brânquias/citologia , Lampreias/anatomia & histologia , Metamorfose Biológica , Osmorregulação , Animais , Água Doce , Lampreias/fisiologiaRESUMO
Incarcerated gravid uterus (IGU) is a rare and serious obstetric complication. IGU is defined as the entrapment of the gravid uterus between the pubic symphysis and the sacral promontory. The incidence of IGU is 1 in 3000-10 000 cases. IGU is associated with significant obstetric complications, including preterm labor, intrauterine fetal death, growth restriction, renal failure, uterine ischemia/rupture and thrombosis. Here, we present the case of a primigravida with urinary retention at 14 weeks. On transabdominal ultrasound at 19+5/7 weeks the cervix was difficult to visualize, and the anterior uterine wall appeared thickened. The bladder was elongated superior to the uterus and the placenta was low-lying. Initially the patient was managed with intermittent self-catheterization, and subsequently indwelling catheterization was required from 22 weeks. At 30 weeks, the patient was transferred to a tertiary center and magnetic resonance imaging (MRI) was preformed due to challenging visualization of the cervix on ultrasound and the patient's continued symptoms of constipation and recurrent urinary infections. The MRI found a retroflexed gravid uterus, with vagina and endocervix displaced anteriorly and compressed by the gravid uterus. The findings were consistent with an incarcerated uterus. The patient subsequently had positive urinary cultures for Pseudomonas and rising creatinine. Given the obstructive uropathy and associated morbidity and mortality, a plan for elective pre-term delivery at 33+6/7 weeks was made. Delivery was by midline laparotomy, normal anatomy was restored after manual evacuation of the fundus from below the sacral promontory, and an uncomplicated lower segment transverse uterine cesarean section was performed.
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Papillary urothelial neoplasia of low malignant potential (PUNLMP) recurs in approximately 35% of patients. Conventional histopathological assessment does not distinguish non-recurrent from recurrent PUNLMP. The aim of this study is to explore the differences in global histone acetylation and global DNA methylation between non-recurrent and recurrent PUNLMP. Acetylated histone H3 lysine 9 (AcH3K9) and 5-methylcytosine (5MeC) were investigated by immunohistochemistry (IHC) in 20 PUNLMP cases (10 non-recurrent and 10 recurrent), in 5 cases of normal urothelium (NU) and in 5 cases of muscle invasive pT2 urothelial carcinoma (UC). The total optical density of the nuclear staining was measured photometrically in at least 40 nuclei separately for the basal, intermediate and luminal positions in each case. Concerning the total optical density values for both acetylation and methylation, a decrease in staining is observed from non-recurrent PUNLMP to recurrent PUNLMP, at all nuclear locations. For acetylation the mean value in non-recurrent PUNLMP, intermediate between NU and UC, is closer to the former than to latter. The mean value in recurrent PUNLMP is closer to UC than to NU. In NU, non-recurrent and recurrent PUNLMP, the acetylation to methylation ratio decreased from the nuclei in basal position to those in the surface, the average for the above groups being 1.491, 1.611 and 1.746, respectively. Setting the observed values for NU at each sampling location to unity, acetylation shows a steady decrease, the percentages of changes in this nuclear location compared to NU being -5% in non-recurrent PUNLMP, -15% in recurrent PUNLMP and -24% in UC. Concerning methylation, there is a slight increase in non-recurrent PUNLMP (+5%), a decrease in recurrent PUNLMP (-19%) followed by a sharp rise for the UC (+61%). In conclusion, there are differences in global histone acetylation and DNA methylation patterns between non-recurrent and recurrent PUNLMP. Further studies are needed to elucidate the complex interplay between chromatin structure, its modifications and recurrence of PUNLMP.
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5-Metilcitosina/análise , Carcinoma Papilar/química , Metilação de DNA , Histonas/análise , Recidiva Local de Neoplasia , Processamento de Proteína Pós-Traducional , Neoplasias Urológicas/química , Acetilação , Carcinoma Papilar/genética , Carcinoma Papilar/patologia , Carcinoma Papilar/terapia , Diagnóstico Diferencial , Estudos de Viabilidade , Regulação Neoplásica da Expressão Gênica , Humanos , Imuno-Histoquímica , Lisina , Invasividade Neoplásica , Valor Preditivo dos Testes , Prognóstico , Neoplasias Urológicas/genética , Neoplasias Urológicas/patologia , Neoplasias Urológicas/terapia , Urotélio/química , Urotélio/patologiaRESUMO
BACKGROUND: The growth of the fetus is a complex process influenced by multiple factors. Studies have highlighted the important role of biochemical growth markers such as leptin and adiponectin on fetal growth. OBJECTIVE: To compare fetal growth trajectories with biochemical growth markers from maternal blood samples at 28 weeks' gestation, cord blood samples at birth, and in child blood samples at 5 years of age from mother-infant pairs who were part of the longitudinal ROLO study. METHODS: 781 mother-infant pairs from the ROLO and ROLO Kids study were included. Ultrasound measurements and birth weight were used to develop fetal growth trajectory groups for estimated abdominal circumference and estimated weight. Blood serum levels of leptin, adiponectin, insulin, TNF-alpha, and IL-6 from maternal, cord, and 5-year child samples were recorded. ANOVA and chi-square tests were applied to test the associations between fetal growth trajectory membership and maternal and child biochemical growth indicators. The influence of child sex was also investigated. RESULTS: Male sex was associated with a faster weight trajectory compared to females (p=0.001). At 28 weeks' gestation, maternal leptin levels were significantly higher in mothers with a fetus on a slower estimated abdominal circumference trajectory compared to fast (25616 [IQR: 11656.0 to 35341.0] vs. 14753.8 [IQR: 8565.4 to 24308.1], p < 0.001) and maternal adiponectin levels were lower in fetuses on a slower estimated abdominal circumference trajectory compared to a fast trajectory (22.4 [IQR: 13.6 to 35.9] vs. 27.6 [IQR: 17.6 to 46.3], p=0.027). No associations were noted with inflammatory markers. No associations were identified between fetal growth trajectories and growth markers at 5 years of age. CONCLUSIONS: This study shows that male sex is associated with an accelerated estimated weight trajectory. Furthermore, high leptin and low adiponectin in maternal serum in late gestation are associated with a slower fetal growth trajectory. No associations were identified with blood growth markers after pregnancy.
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BACKGROUND: Therapeutic strategies for cervical oesophageal squamous cell carcinoma (SCC) are controversial. Treatment options range from definitive radiotherapy to multimodal treatment. Outcome after limited resection and reconstruction with a free jejunal graft interposition was evaluated retrospectively. METHODS: Patients with clinical T1-4 Nx M0 tumours treated between 1986 and 2006 were included. RESULTS: Of 109 patients, 94 underwent preoperative chemoradiotherapy and 15 had a primary resection. Complete or partial preservation of the larynx was achieved in 93 patients (85.3 per cent). Minor and major complications occurred in 74.3 per cent, with 44.0 per cent of all patients having more than one complication. Reoperation was necessary in 29.4 per cent. The 30-day mortality rate was 1.8 per cent, and the in-hospital mortality rate 2.8 per cent. The complete R0 resection rate was 72.5 per cent. Median overall survival was 34.3 months; 1-, 3- and 5-year survival rates were 83.8, 47.0 and 47.0 per cent respectively. Survival was not influenced by complications (P = 0.401) or reoperation (P = 0.428). CONCLUSION: Despite high complication and reoperation rates, the mortality rate was low, even after preoperative chemoradiation. This complex surgical strategy is a treatment option for cervical SCC in oncological centres with an infrastructure providing multidisciplinary management.
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Carcinoma de Células Escamosas/cirurgia , Neoplasias Esofágicas/cirurgia , Esôfago/cirurgia , Jejuno/transplante , Complicações Pós-Operatórias/etiologia , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/radioterapia , Quimioterapia Adjuvante , Intervalo Livre de Doença , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/radioterapia , Feminino , Humanos , Laringectomia/métodos , Masculino , Pessoa de Meia-Idade , Reoperação , Retalhos Cirúrgicos , Resultado do TratamentoRESUMO
OBJECTIVE: Evaluating the effect of anxiety and depression on clinical measures of general health, tinnitus-specific quality of life, and coping abilities. DESIGN: Two hundred sixty-five chronic, subjective tinnitus sufferers were divided into four psychological symptom groups according to cut-off scores on anxiety and depression subscales of the Hospital Anxiety and Depression Scale: (1) no-symptoms, (2) anxiety-only, (3) depression-only, and (4) anxiety-plus-depression. General health-related quality of life (SF-36), tinnitus-specific quality of life (tinnitus reaction questionnaire and tinnitus handicap inventory), and coping abilities (tinnitus coping style questionnaire) were assessed and analyzed across these four psychological symptom groups, which did not differ on age, gender, marital, and working status. RESULTS: Statistically significant and clinically relevant differences on general health-related and tinnitus-specific quality of life and coping abilities were identified when comparing anxiety-plus-depression subgroup with the subgroups anxiety-only, depression-only, or no-symptoms. Highest associations were seen between the anxiety-plus-depression subgroup and impaired quality of life and maladaptive coping. CONCLUSIONS: Our results demonstrate the additive effect of both anxiety and depression in impairing general health-related and tinnitus-specific quality of life and application of coping strategies, and reiterate the need for investigating both symptoms in the clinical evaluation of tinnitus patients.
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Adaptação Psicológica , Ansiedade/complicações , Depressão/complicações , Zumbido/complicações , Zumbido/psicologia , Adulto , Sintomas Afetivos , Idoso , Feminino , Nível de Saúde , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Qualidade de Vida , Inquéritos e QuestionáriosRESUMO
CONCLUSIONS: This article shows that the inferior colliculus plays a key role in unilateral subjective tinnitus. OBJECTIVES: The major aim of this study was to determine tinnitus-related neural activity in the central auditory system of unilateral tinnitus subjects and compare this to control subjects without tinnitus. SUBJECTS AND METHODS: Functional MRI (fMRI) was performed in 10 patients (5 males) with unilateral tinnitus (5 left-sided, 5 right-sided) and 12 healthy subjects (6 males); both groups had normal hearing or mild hearing loss. fMRI experiments were performed using a 3T Philips Intera Scanner. Auditory stimuli were presented left or right and consisted of dynamically rippled broadband noise with a sound pressure level of 40 or 70 dB SPL. The responses of the inferior colliculus and the auditory cortex to the stimuli were measured. RESULTS: The response to sound in the inferior colliculus was elevated in tinnitus patients compared with controls without tinnitus.
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Córtex Auditivo/fisiopatologia , Audição/fisiologia , Colículos Inferiores/fisiopatologia , Imageamento por Ressonância Magnética/métodos , Zumbido/diagnóstico , Estimulação Acústica/métodos , Adulto , Idoso , Audiometria de Tons Puros , Córtex Auditivo/patologia , Feminino , Seguimentos , Humanos , Colículos Inferiores/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Análise de Regressão , Índice de Gravidade de Doença , Zumbido/fisiopatologiaRESUMO
Mediastinitis caused by anastomotic leaks is the most severe complication after esophagectomy and the major source of morbidity and mortality. It is characterized by local intrathoracic reactions (mediastinitis) and systemic extrathoracic reactions (sepsis). Consequently the therapeutic concepts are clearly defined. To achieve successful management, early diagnostic work-up is mandatory in every disturbance of the normal postoperative course. This includes direct endoscopic inspection of the anastomosis to evaluate the vitality of the anastomosed organs and the size of the leak. According to location and clinical classifications of the leak, the spectrum of therapeutic options ranges from simple drainage procedures, endoscopic interventions, and stent implantation to reoperation or discontinuity resection. In any case the treatment goals must be immediate and sufficient drainage of the leakage and hindrance of further contamination across the leakage by gastrointestinal content. Also mandatory is the early initiation of supportive systemic strategies according to pathophysiologic principles of sepsis. The fundamental requirements for successful management are therefore aggressive local intervention and application of new concepts in sepsis therapy.
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Neoplasias Esofágicas/cirurgia , Esofagectomia/efeitos adversos , Mediastinite/cirurgia , Anastomose Cirúrgica , Drenagem , Endoscopia , Humanos , Mediastinite/etiologia , Complicações Pós-Operatórias , Estudos Prospectivos , Reoperação , Sepse/etiologia , Sepse/terapia , StentsRESUMO
AIM: This study aimed to explore the molecular mechanisms for the parietal cell loss and fundic hyperplasia observed in gastric mucosa of mice lacking the carbonic anhydrase 9 (CAIX). METHODS: We assessed the ability of CAIX-knockout and WT gastric surface epithelial cells to withstand a luminal acid load by measuring the pHi of exteriorized gastric mucosa in vivo using two-photon confocal laser scanning microscopy. Cytokines and claudin-18A2 expression was analysed by RT-PCR. RESULTS: CAIX-knockout gastric surface epithelial cells showed significantly faster pHi decline after luminal acid load compared to WT. Increased gastric mucosal IL-1ß and iNOS, but decreased claudin-18A2 expression (which confer acid resistance) was observed shortly after weaning, prior to the loss of parietal and chief cells. At birth, neither inflammatory cytokines nor claudin-18 expression were altered between CAIX and WT gastric mucosa. The gradual loss of acid secretory capacity was paralleled by an increase in serum gastrin, IL-11 and foveolar hyperplasia. Mild chronic proton pump inhibition from the time of weaning did not prevent the claudin-18 decrease nor the increase in inflammatory markers at 1 month of age, except for IL-1ß. However, the treatment reduced the parietal cell loss in CAIX-KO mice in the subsequent months. CONCLUSIONS: We propose that CAIX converts protons that either backflux or are extruded from the cells rapidly to CO2 and H2 O, contributing to tight junction protection and gastric epithelial pHi regulation. Lack of CAIX results in persistent acid backflux via claudin-18 downregulation, causing loss of parietal cells, hypergastrinaemia and foveolar hyperplasia.
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Anidrase Carbônica IX/metabolismo , Claudinas/metabolismo , Ácido Gástrico/metabolismo , Mucosa Gástrica/metabolismo , Células Parietais Gástricas/metabolismo , Animais , Regulação para Baixo , Concentração de Íons de Hidrogênio , Camundongos , Camundongos Endogâmicos C57BL , Camundongos KnockoutRESUMO
The young pigeon disease syndrome (YPDS) affects mainly young pigeons of less than one year of age and leads to crop stasis, vomitus, diarrhea, anorexia and occasionally death. This disease is internationally a major health problem because of its seasonal appearance during competitions such as homing pigeon races or exhibitions of ornamental birds. While the etiology of YPDS is still unclear, adenoviruses are frequently discussed as potential causative agents. Electron microscopy of feces from a YPDS outbreak revealed massive shedding of adenovirus-like particles. Whole genome sequencing of this sample identified a novel adenovirus tentatively named pigeon adenovirus 2 (PiAdV-2). Phylogenetic and comparative genome analysis suggest PiAdV-2 to belong to a new species within the genus Aviadenovirus, for which we propose the name Pigeon aviadenovirus B. The PiAdV-2 genome shares 54.9% nucleotide sequence identity with pigeon adenovirus 1 (PiAdV-1). In a screening of further YPDS-affected flocks two variants of PiAdV-2 (variant A and B) were detected which shared 97.6% nucleotide identity of partial polymerase sequences, but only 79.7% nucleotide identity of partial hexon sequences. The distribution of both PiAdV-2 variants was further investigated in fecal samples collected between 2008 and 2015 from healthy or YPDS-affected racing pigeons of different lofts. Independent of their health status, approximately 20% of young and 13% of adult pigeon flocks harbored PiAdV-2 variants. Birds were free of PiAdV-1 or other aviadenoviruses as determined by PCRs targeting the aviadenovirus polymerase or the PiAdV-1 fiber gene, respectively. In conclusion, there is no indication of a correlation between YPDS outbreaks and the presence of PiAdV-2 or other aviadenoviruses, arguing against an causative role in this disease complex.
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Aviadenovirus/classificação , Aviadenovirus/genética , Columbidae/virologia , Animais , Animais Domésticos , Aviadenovirus/ultraestrutura , Sequência de Bases , Doenças das Aves/epidemiologia , Doenças das Aves/virologia , Biologia Computacional/métodos , Ordem dos Genes , Genes Virais , Genoma Viral , Genômica/métodos , Alemanha , Sequenciamento de Nucleotídeos em Larga Escala , Filogenia , Reação em Cadeia da PolimeraseRESUMO
BACKGROUND: The aim of this study was to develop a simple method for closure of a perforated peptic ulcer, making it more accessible for laparoscopic surgery. METHODS: An experimental pilot study was performed using five male Wistar rats. The perforation was closed by a bioabsorbable patch made of lactide-glycolid-caprolactone fixed with glue onto the outside of the stomach. RESULTS: Postoperatively, there were no signs of leakage or other complications. Histologically, there were no signs of inflammation on the inside of the stomach, and there was a 50% reduction of the perforation each successive postoperative week. No adverse reactions because of the degradable material or glue were observed. CONCLUSIONS: Treatment of a perforated peptic ulcer by placing a patch of biodegradable material like a "stamp" on the outside of the stomach is a feasible option.
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Implantes Absorvíveis , Úlcera Péptica Perfurada/cirurgia , Animais , Laparotomia , Masculino , Úlcera Péptica Perfurada/patologia , Poliésteres , Ratos , Ratos Wistar , Reoperação , Fatores de TempoRESUMO
PURPOSE: The aim of this study was to evaluate the significance of cytogenetic findings for the clinical outcome of patients with Angioimmunoblastic Lymphadenopathy (AILD)-Type T-cell lymphoma. MATERIALS AND METHODS: In a retrospective analysis, the cytogenetic findings of 50 patients with AILD-type T-cell lymphoma were correlated with the frequency of spontaneous and therapy-induced remissions and with survival using the statistical methods of Kaplan and Meier and the model of Cox for multivariate analysis. Treatment was not uniform because the patients were treated in different hospitals during a period of 8 years and because a standard therapy has not yet been established. RESULTS: The following cytogenetic findings were associated with a significantly lower incidence of therapy-induced remissions and a significantly shorter survival duration: presence of aberrant metaphases in unstimulated cultures (P = .04 for both parameters); clones with an additional X chromosome (P = .0001 and P = .03, respectively); structural aberrations of the short arm of chromosome 1, preferentially involving 1p31-32 (P < .001 and P = .04, respectively); and complex aberrant clones with more than four aberrations (P = .0003 and P = .005, respectively). Multivariate analysis showed that these cytogenetic findings had a significant influence on survival, but therapy modalities did not. Only the presence of complex aberrant clones was an independent prognostic factor. Trisomy 3 had no effect on survival, but patients without trisomy 5 (P = .08) tended to live longer. CONCLUSION: This is the first study that seems to indicate that cytogenetic findings have prognostic significance in AILD-type T-cell lymphoma. These results must be proven in prospective studies of homogeneously treated patients.
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Aberrações Cromossômicas , Linfadenopatia Imunoblástica/genética , Linfoma de Células T/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Linfadenopatia Imunoblástica/mortalidade , Linfadenopatia Imunoblástica/terapia , Linfoma de Células T/mortalidade , Linfoma de Células T/terapia , Masculino , Pessoa de Meia-Idade , Prognóstico , Indução de Remissão , Remissão Espontânea , Estudos RetrospectivosRESUMO
PURPOSE: To determine the appropriate irradiation dose after four cycles of modern combination chemotherapy in nonbulky involved field (IF/BF) and noninvolved extended-field (EF/IF) sites in patients with intermediate-stage Hodgkin's disease (HD). MATERIALS AND METHODS: HD patients in stage I to IIIA with a large mediastinal mass, E stage, or massive spleen involvement were treated with two double cycles of alternating cyclophosphamide, vincristine, procarbazine, and prednisone (COPP) plus doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) followed by EF irradiation in two successive trials (HD1 and HD5). In the HD1 trial (1983 to 1988), 146 patients who responded to chemotherapy were randomized to receive 20 Gy (70 patients) or 40 Gy (76 patients) of EF irradiation in all fields outside bulky disease sites. A cohort of 111 patients who fulfilled the same inclusion criteria in the subsequent trial HD5 (1988 to 1993) were treated with 30 Gy. Bulky disease always received 40 Gy. RESULTS: Freedom-from-treatment-failure (FFTF) and survival (SV) curves showed no differences between the 20-, 30-, and 40-Gy groups. However, acute toxicities were more frequent in the 40-Gy arm. Analysis of relapse patterns showed that 18 of 26 relapsing patients either failed to respond in initial bulky sites (n = 5) or had an extranodal relapse (n = 9) or both (n = 4). After 5 years, the cumulative risk for relapse in bulky sites is 10%, despite 40 Gy of radiation. CONCLUSION: Our results strongly suggest that there is no relevant radiotherapy dose effect in the range between 20 Gy and 40 Gy in IF/BF and EF/IF after 4 months of modern polychemotherapy in patients with intermediate-stage HD. Relapse patterns indicate that patients destined to relapse need more systemic, rather than local, treatment. Based on our data, we conclude that 20 Gy is sufficient in EF/IF of intermediate-stage HD following four cycles of modern polychemotherapy.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Doença de Hodgkin/tratamento farmacológico , Doença de Hodgkin/radioterapia , Adolescente , Adulto , Bleomicina/administração & dosagem , Terapia Combinada , Ciclofosfamida/administração & dosagem , Dacarbazina/administração & dosagem , Relação Dose-Resposta à Radiação , Doxorrubicina/administração & dosagem , Feminino , Doença de Hodgkin/mortalidade , Doença de Hodgkin/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prednisona/administração & dosagem , Procarbazina/administração & dosagem , Modelos de Riscos Proporcionais , Recidiva , Análise de Sobrevida , Resultado do Tratamento , Vimblastina/administração & dosagem , Vincristina/administração & dosagemRESUMO
The ideal chemopreventive agent targets pre-neoplastic changes and intraepithelial neoplasia, preventing progression over time without notable side effects. Assessment of success of chemopreventive intervention in the short and medium term remains a challenge, and in this review the suggestion is investigated that karyometric measurements constitute suitable markers of chemopreventive efficacy. Karyometry provides the sensitivity required to detect small differences amidst relatively high biological variability. It can help establish progression curves of intraepithelial neoplasia (IEN) to invasive cancer, and thus detect chemopreventive effects. Such effects can be observed in two ways, at the group level (intervention vs. placebo), and at the case (or patient) level. The latter is more difficult to establish, necessitating the development of specialised statistical methods. Analysis of between-case and within-case heterogeneity can reveal useful information about cancer progression and prevention. We suggest that karyometry can objectively quantify IEN progression, providing a framework for statistically securing chemopreventive effects. It can act as an integrating biomarker by detecting chemopreventive activity even when the mechanism for a given progression pathway is unknown, or when multiple pathways exist. The sensitivity of karyometric detection can help optimise the design of clinical trials of novel chemopreventive agents by decreasing trial duration and/or sample size.
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Carcinoma/prevenção & controle , Neoplasias/prevenção & controle , Lesões Pré-Cancerosas/prevenção & controle , Antineoplásicos/uso terapêutico , Neoplasias da Mama/patologia , Carcinoma/patologia , Carcinoma Ductal de Mama/patologia , Progressão da Doença , Diagnóstico Precoce , Eflornitina/uso terapêutico , Humanos , Cariometria/métodos , Cariometria/normas , Masculino , Neoplasias/patologia , Lesões Pré-Cancerosas/patologia , Neoplasia Prostática Intraepitelial/patologia , Neoplasias da Próstata/patologia , Sensibilidade e EspecificidadeRESUMO
An improved form of crystals of large (50 S) ribosomal subunits from Haloarcula marismortui, formally named Halobacterium marismortui, diffracting to 3 A resolution, has been obtained by the addition of 1 mM-Cd2+ to the crystallization medium, which contained more than 1.9 M of other salts. The improved crystals, grown from functionally active particles to an average size of 0.3 mm x 0.3 mm x 0.08 mm, are isomorphous with the previously reported ones, which diffracted to 4.5 A. They are of space group C222(1), cell dimensions a = 210 A, b = 300 A, c = 581 A, and contain one particle in the asymmetric unit. Their superior internal order is reflected not only in their high resolution, but also in their reasonable mosaicity (less than 0.3 degrees). In contrast to the previously grown crystals, the new ones are of adequate mechanical strength and survive well the shock-cooling treatment. Due to their weak diffracting power, all crystallographic studies have been performed with synchrotron radiation. At cryotemperature, these crystals showed no measurable decay for a few days of irradiation and a complete diffraction data set could be collected from a single crystal. Efforts for initial phasing by specific and quantitative derivatization with super-dense heavy-atom clusters are in progress.
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Halobacterium/ultraestrutura , Proteínas Ribossômicas/química , Cristalização , Difração de Raios XRESUMO
Cytogenetic studies were performed in 21 cases of Hodgkin's disease. Fourteen cases revealed chromosomally aberrant clones which could be fully described in 12 cases. Two cases showed different unrelated clones and five cases only single cell aberrations. Recurrent breakpoints were 1p13/21 (six cases), 7q32/34 (five cases), 2p16/21 and 19p13 (four cases each), 4q25/28, 6q15/21 and 12q22/23 (three cases each). In two cases, a translocation between band 19q13 and band 14q11 or 14q32 was found. This finding may indicate that an unknown oncogene in 19p13 is activated by juxtaposition next to a T-cell receptor or immunoglobulin gene in 14q11 or 14q32, respectively. In eight cases each, total or partial monosomy 4 or 6 was present suggesting that tumor suppressor genes in 4q or 6q play a role in tumor development in Hodgkin's disease. Moreover, the aberrant clones lacked the Y-chromosome in men and the second X-chromosome in women in eight out of nine and in two out of three cases, respectively. Although different cell populations, especially T cells, showed mitotic activity in unstimulated short term culture, combined immunophenotyping and karyotyping unequivocally demonstrated that CD30 and CD15 positive Hodgkin and Sternberg-Reed cells represented the chromosomally aberrant clones.
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Doença de Hodgkin/genética , Adulto , Idoso , Feminino , Doença de Hodgkin/imunologia , Humanos , Imunofenotipagem , Cariotipagem , Masculino , Pessoa de Meia-IdadeRESUMO
Tracheostomy has become the method of choice in managing patients requiring long-term mechanical ventilation. At present, there are several alternatives to conventional surgical tracheostomy such as percutaneous dilatational techniques according to Ciaglia, Frova, and Fantoni. The basic principle of these new techniques is percutaneous puncture of the trachea and subsequent dilatation of the puncture channel until the tracheal cannula can be inserted. The advantages are "bedside" performance in the intensive care unit and the use of minimal technical equipment. Nevertheless, dilatation tracheostomy is not always technically feasible and safe. Some significant complications and contraindications have been recognized recently. This should be taken into account when planning tracheostomy in long-term ventilated patients. Compared to conventional surgical tracheostomy, this new procedure retains its value and benefit only if these contraindications are carefully observed.
Assuntos
Traqueostomia/métodos , Traqueotomia/métodos , Adulto , Broncoscopia , Criança , Contraindicações , Cuidados Críticos , Dilatação , Humanos , Assistência de Longa Duração , Avaliação de Resultados em Cuidados de Saúde , Complicações Pós-Operatórias/etiologia , Punções , Respiração ArtificialRESUMO
The modified technique of abdomino-right-thoracic esophagectomy (the Lewis-Tanner approach) is increasingly being favoured as the surgical procedure of choice in patients with resectable adenocarcinoma of the distal esophagus, so-called Barrett's cancer. The technical details of this procedure and the reconstruction of gastrointestinal continuity using a gastric tube with high intrathoracic anastomosis are illustrated, as they have proved useful in our own practice during recent years.