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1.
Nature ; 543(7645): 397-401, 2017 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-28300118

RESUMO

In the cold dark matter cosmology, the baryonic components of galaxies-stars and gas-are thought to be mixed with and embedded in non-baryonic and non-relativistic dark matter, which dominates the total mass of the galaxy and its dark-matter halo. In the local (low-redshift) Universe, the mass of dark matter within a galactic disk increases with disk radius, becoming appreciable and then dominant in the outer, baryonic regions of the disks of star-forming galaxies. This results in rotation velocities of the visible matter within the disk that are constant or increasing with disk radius-a hallmark of the dark-matter model. Comparisons between the dynamical mass, inferred from these velocities in rotational equilibrium, and the sum of the stellar and cold-gas mass at the peak epoch of galaxy formation ten billion years ago, inferred from ancillary data, suggest high baryon fractions in the inner, star-forming regions of the disks. Although this implied baryon fraction may be larger than in the local Universe, the systematic uncertainties (owing to the chosen stellar initial-mass function and the calibration of gas masses) render such comparisons inconclusive in terms of the mass of dark matter. Here we report rotation curves (showing rotation velocity as a function of disk radius) for the outer disks of six massive star-forming galaxies, and find that the rotation velocities are not constant, but decrease with radius. We propose that this trend arises because of a combination of two main factors: first, a large fraction of the massive high-redshift galaxy population was strongly baryon-dominated, with dark matter playing a smaller part than in the local Universe; and second, the large velocity dispersion in high-redshift disks introduces a substantial pressure term that leads to a decrease in rotation velocity with increasing radius. The effect of both factors appears to increase with redshift. Qualitatively, the observations suggest that baryons in the early (high-redshift) Universe efficiently condensed at the centres of dark-matter haloes when gas fractions were high and dark matter was less concentrated.

2.
Histochem Cell Biol ; 155(5): 581-591, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33502623

RESUMO

In human glandular endometrial epithelial cells, desmosomal and adherens junction proteins have been shown to extend from a subapically restricted lateral position to the entire lateral membrane during the implantation window of the menstrual cycle. Similarly, a menstrual cycle stage-dependent redistribution of the extracellular matrix adhesion protein α6-integrin has been reported. These changes are believed to be important for endometrial receptiveness and successful embryo implantation. To prove the hypothesis that steroid hormones and human choriogonadotropin can induce the redistribution of these adhesion molecules, we used the human endometrial cell line Ishikawa in a 3D culture system. Gland-like spheroids were grown in reconstituted basement membrane (Matrigel™). The lumen-bearing spheroids were treated for 2 or 4 days with ovarian steroids or human choriogonadotropin and then assessed by immunofluorescence microscopy. In addition, human endometrial biopsies were obtained from patients, who were in therapy for assisted reproductive technology, and were examined in parallel. Lateral redistribution of the desmosomal plaque protein desmoplakin 1 was observed in the spheroids treated either with progesterone, medroxyprogesterone acetate or human choriogonadotropin. Furthermore, the extracellular matrix adhesion protein α6-integrin showed an increased lateral membrane localization upon gestagen stimulation in the 3D culture system. The results of this study demonstrate that the 3D endometrial Ishikawa cell culture might be suited as an experimental model system to prove the effect of hormonal changes like those occurring during the window of implantation.


Assuntos
Gonadotropina Coriônica/metabolismo , Desmoplaquinas/metabolismo , Endométrio/metabolismo , Hormônios Esteroides Gonadais/metabolismo , Integrina alfa6/metabolismo , Esferoides Celulares/metabolismo , Células Cultivadas , Desmoplaquinas/análise , Feminino , Humanos , Integrina alfa6/análise
3.
Radiologe ; 60(11): 1069-1076, 2020 Nov.
Artigo em Alemão | MEDLINE | ID: mdl-32468123

RESUMO

OBJECTIVE: The goal of this article is the radiological visualization of the often very difficult pathoanatomical changes associated with calcifying tendinitis, which in rare cases may erode and ultimately invade the bone. MATERIALS AND METHODS: We investigated the diagnostic reliability of radiographs, magnetic resonance imaging (MRI) and computed tomography (CT) in 11 patients with calcifying tendinitis. Eight lesions were located in the upper (4 supraspinatus tendon, 2 deltoideus tendon, 1 pectoralis tendon, 1 biceps tendon) and 3 in the lower extremity (2 gluteus tendon, 1 adductor magnus tendon). The average age was 58 years (8 women, 3 men). CASE STUDIES AND DISCUSSION: Calcifying tendinitis is the consequence of overuse of an enthesis with consecutive necrosis and calcification. However, in rare cases, erosion of the underlying bone with bone invasion, which is associated with sudden escalation of long-term pain, is observed. The detection of the pathoanatomical changes using MRI is problematic because with this method calcifications and ossifications are only indirectly visualized and, thus, can only be interpreted with uncertainty. The method of choice is CT, which can be used to demonstrate the three key elements of calcifying tendinitis, i.e., the calcified/ossified part of the tendon in the insertion area, a defect in the cortex, and calcification in the medullary space.


Assuntos
Calcinose , Tendinopatia , Calcinose/diagnóstico por imagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Manguito Rotador , Tendinopatia/diagnóstico por imagem , Tendões
4.
N Engl J Med ; 374(19): 1842-1852, 2016 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-27168434

RESUMO

BACKGROUND: Tracking longitudinal measurements of growth and decline in lung function in patients with persistent childhood asthma may reveal links between asthma and subsequent chronic airflow obstruction. METHODS: We classified children with asthma according to four characteristic patterns of lung-function growth and decline on the basis of graphs showing forced expiratory volume in 1 second (FEV1), representing spirometric measurements performed from childhood into adulthood. Risk factors associated with abnormal patterns were also examined. To define normal values, we used FEV1 values from participants in the National Health and Nutrition Examination Survey who did not have asthma. RESULTS: Of the 684 study participants, 170 (25%) had a normal pattern of lung-function growth without early decline, and 514 (75%) had abnormal patterns: 176 (26%) had reduced growth and an early decline, 160 (23%) had reduced growth only, and 178 (26%) had normal growth and an early decline. Lower baseline values for FEV1, smaller bronchodilator response, airway hyperresponsiveness at baseline, and male sex were associated with reduced growth (P<0.001 for all comparisons). At the last spirometric measurement (mean [±SD] age, 26.0±1.8 years), 73 participants (11%) met Global Initiative for Chronic Obstructive Lung Disease spirometric criteria for lung-function impairment that was consistent with chronic obstructive pulmonary disease (COPD); these participants were more likely to have a reduced pattern of growth than a normal pattern (18% vs. 3%, P<0.001). CONCLUSIONS: Childhood impairment of lung function and male sex were the most significant predictors of abnormal longitudinal patterns of lung-function growth and decline. Children with persistent asthma and reduced growth of lung function are at increased risk for fixed airflow obstruction and possibly COPD in early adulthood. (Funded by the Parker B. Francis Foundation and others; ClinicalTrials.gov number, NCT00000575.).


Assuntos
Anti-Inflamatórios/uso terapêutico , Asma/fisiopatologia , Pulmão/fisiologia , Administração por Inalação , Adolescente , Asma/tratamento farmacológico , Broncodilatadores/uso terapêutico , Budesonida/uso terapêutico , Criança , Pré-Escolar , Feminino , Volume Expiratório Forçado , Humanos , Estimativa de Kaplan-Meier , Estudos Longitudinais , Pulmão/crescimento & desenvolvimento , Masculino , Nedocromil/uso terapêutico , Fatores de Risco , Fatores Sexuais , Espirometria , Adulto Jovem
5.
Phys Rev Lett ; 122(10): 101102, 2019 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-30932663

RESUMO

During its orbit around the four million solar mass black hole Sagittarius A* the star S2 experiences significant changes in gravitational potential. We use this change of potential to test one part of the Einstein equivalence principle: the local position invariance (LPI). We study the dependency of different atomic transitions on the gravitational potential to give an upper limit on violations of the LPI. This is done by separately measuring the redshift from hydrogen and helium absorption lines in the stellar spectrum during its closest approach to the black hole. For this measurement we use radial velocity data from 2015 to 2018 and combine it with the gravitational potential at the position of S2, which is calculated from the precisely known orbit of S2 around the black hole. This results in a limit on a violation of the LPI of |ß_{He}-ß_{H}|=(2.4±5.1)×10^{-2}. The variation in potential that we probe with this measurement is six magnitudes larger than possible for measurements on Earth, and a factor of 10 larger than in experiments using white dwarfs. We are therefore testing the LPI in a regime where it has not been tested before.

6.
Nature ; 463(7282): 781-4, 2010 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-20148033

RESUMO

Stars form from cold molecular interstellar gas. As this is relatively rare in the local Universe, galaxies like the Milky Way form only a few new stars per year. Typical massive galaxies in the distant Universe formed stars an order of magnitude more rapidly. Unless star formation was significantly more efficient, this difference suggests that young galaxies were much more molecular-gas rich. Molecular gas observations in the distant Universe have so far largely been restricted to very luminous, rare objects, including mergers and quasars, and accordingly we do not yet have a clear idea about the gas content of more normal (albeit massive) galaxies. Here we report the results of a survey of molecular gas in samples of typical massive-star-forming galaxies at mean redshifts of about 1.2 and 2.3, when the Universe was respectively 40% and 24% of its current age. Our measurements reveal that distant star forming galaxies were indeed gas rich, and that the star formation efficiency is not strongly dependent on cosmic epoch. The average fraction of cold gas relative to total galaxy baryonic mass at z = 2.3 and z = 1.2 is respectively about 44% and 34%, three to ten times higher than in today's massive spiral galaxies. The slow decrease between z approximately 2 and z approximately 1 probably requires a mechanism of semi-continuous replenishment of fresh gas to the young galaxies.

7.
Nature ; 442(7104): 786-9, 2006 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-16915282

RESUMO

Observations and theoretical simulations have established a framework for galaxy formation and evolution in the young Universe. Galaxies formed as baryonic gas cooled at the centres of collapsing dark-matter haloes; mergers of haloes and galaxies then led to the hierarchical build-up of galaxy mass. It remains unclear, however, over what timescales galaxies were assembled and when and how bulges and disks--the primary components of present-day galaxies--were formed. It is also puzzling that the most massive galaxies were more abundant and were forming stars more rapidly at early epochs than expected from models. Here we report high-angular-resolution observations of a representative luminous star-forming galaxy when the Universe was only 20% of its current age. A large and massive rotating protodisk is channelling gas towards a growing central stellar bulge hosting an accreting massive black hole. The high surface densities of gas, the high rate of star formation and the moderately young stellar ages suggest rapid assembly, fragmentation and conversion to stars of an initially very gas-rich protodisk, with no obvious evidence for a major merger.

8.
Eur Respir J ; 35(5): 1048-56, 2010 May.
Artigo em Inglês | MEDLINE | ID: mdl-19926748

RESUMO

Chronic obstructive pulmonary disease (COPD) exhibits airflow obstruction that is not fully reversible. The importance of bronchoreversibility remains controversial. We hypothesised that an emphysematous phenotype of COPD would be associated with decreased bronchoreversibility. 544 patients randomised to the medical arm of the National Emphysema Treatment Trial formed the study group. Participants underwent multiple measurements of bronchoreversibility on a mean of four sessions over 1.91 yrs. They were also characterised by measures of symptoms, quality of life and quantitative measures of emphysema by computed tomography. Mean baseline forced expiratory volume in 1 s (FEV(1)) in this patient population is 24% predicted. 22.2% of patients demonstrated bronchoreversibility on one or more occasions using American Thoracic Society/European Respiratory Society criteria. Few patients (0.37%) had bronchoreversibility on all completed tests. Patients who demonstrated bronchoreversibility were more likely to be male, and have better lung function and less emphysema. 64% of patients demonstrated large (> or =400 mL) changes in forced vital capacity (FVC). In a severe emphysema population, bronchoreversibility as defined by change in FEV(1) is infrequent, varies over time, and is more common in males and those with less severe emphysema. Improvements in FVC, however, were demonstrated in the majority of patients.


Assuntos
Albuterol/uso terapêutico , Broncodilatadores/uso terapêutico , Enfisema/tratamento farmacológico , Idoso , Albuterol/administração & dosagem , Broncodilatadores/administração & dosagem , Enfisema/diagnóstico , Enfisema/diagnóstico por imagem , Enfisema/fisiopatologia , Feminino , Humanos , Modelos Logísticos , Masculino , Nebulizadores e Vaporizadores , Fenótipo , Estudos Prospectivos , Qualidade de Vida , Testes de Função Respiratória , Índice de Gravidade de Doença , Tomografia Computadorizada por Raios X
9.
J Clin Pathol ; 59(2): 207-10, 2006 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-16443740

RESUMO

BACKGROUND: Venous invasion (VI) is an important prognosis predictor after colorectal carcinoma (CRC) resection, enabling more accurate staging and influencing postoperative management. AIMS: To assess/compare various tissue block types (perpendicular, tangential, across mesentery (AM), from major vessels or lymph nodes (LNs)) for VI detection in CRC. METHODS: Fifty two CRCs (51 colectomies, one polypectomy) were studied. Tumours were measured, surface area calculated, and colorectum and bowel wall sites recorded. Weigert's staining for elastin facilitated VI detection. VI sites, type, and amount were recorded. Ratios of relative yield of tissue block types to their frequency were calculated. RESULTS: Average numbers of tissue blocks/colectomy specimen were: perpendicular, 10.2; tangential, 9.1; AM, 3.3; from major vessels, 2.1. Average number of LNs examined was 16.47. VI was detected in 22 tumours. Overall, VI was detected in 16 perpendicular, seven tangential, five AM, and two LN blocks. VI was detected in eight, two, one, and three tumours in perpendicular, tangential, LN, and AM blocks alone, respectively. In seven tumours, VI was identified in multiple tissue block types. The average number of blocks obtained was 39.7, 42.1, and 38 from all tumours, VI positive, and VI negative tumours, respectively (p = 0.0497). Efficacy to detect VI was 2.151, 2.088, 1.092, 0.172, and 0 for AM, perpendicular, tangential, LN, and mesenteric vessel blocks, respectively. CONCLUSIONS: VI was identified most frequently and in eight cases only in perpendicular blocks. However, extramural VI was detected in six tumours only in blocks cut tangentially, AM, or from harvested LNs. Hence, all these types of blocks should be submitted routinely and scanned for VI.


Assuntos
Vasos Sanguíneos/patologia , Neoplasias Colorretais/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Colectomia , Colo/irrigação sanguínea , Neoplasias Colorretais/cirurgia , Feminino , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Prognóstico , Reto/irrigação sanguínea , Manejo de Espécimes/métodos
10.
Eur J Clin Nutr ; 59(10): 1136-41, 2005 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-16015258

RESUMO

OBJECTIVE: The primary aims of this trial were to evaluate the reproducibility of a portable handheld calorimeter (Medgem) in a clinical population, and to compare its measures with a calorimeter in typical use with these patients. DESIGN: Cross-sectional clinical validation study. SETTING: Outpatient Clinical Research Center. SUBJECTS: A total of 24 stable home nutrition support patients. INTERVENTIONS: In random order three measures of resting metabolic rate (RMR) were taken after a 4-h fast, 15 min rest and 2-h abstention from exercise. Two measures were taken with the same Medgem (MG) and one with the traditional calorimeter (Deltatrac). Reproducibility of MG measures and their comparability to a Deltatrac measure were assessed by Bland-Altman analysis, with >+/-250 kcal/day established a priori as a clinically unacceptable error. In addition, disagreement between the two types of measures was defined as greater than 10% difference. RESULTS: The mean difference between two MG measures was -6.8 kcal/day, with limits of agreement between 233 and -247 kcal/day and clinically acceptable. The mean difference between the Deltatrac and mean of two MG measures was -162 kcal/day, with limits of agreement between 577 and -253 kcal/day and clinically unacceptable. In all, 80% of the repeated MG RMR measures agreed within 10%, and the mean MG reading agreed with the Deltatrac in 60% of cases. CONCLUSIONS: RMR obtained using the MG calorimeter has an acceptable degree of reproducibility, and is acceptable to patients. The MG measures, however, are frequently lower than traditional measures and require further validation prior to application to practice in this vulnerable patient group.


Assuntos
Metabolismo Basal/fisiologia , Calorimetria Indireta/normas , Síndromes de Malabsorção/metabolismo , Consumo de Oxigênio/fisiologia , Nutrição Parenteral no Domicílio , Adolescente , Adulto , Idoso , Calorimetria Indireta/instrumentação , Calorimetria Indireta/métodos , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
11.
J Clin Pathol ; 55(1): 17-21, 2002 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-11825918

RESUMO

AIMS: Venous invasion is an established predictor of prognosis in colorectal cancer (CRC). The reported incidence of venous invasion in CRC specimens varies between 10% and 89.5%, mainly as a result of interobserver variability and differences in specimen processing (for example, staining with haematoxylin and eosin (H+E) alone versus the addition of an elastic fibre stain). This study was performed with three purposes in mind, namely: (1) To assess and compare the incidence of venous invasion diagnosed on H+E stained tissue versus tissue stained with both H+E and an elastic fibre stain. (2) To estimate the inherent false negative rate associated with the diagnosis of venous invasion by histopathological evaluation of resected CRC specimens. (3) To compare the resulting data regarding incidence, quantity, site, and type of venous invasion to the pertinent literature. METHODS: Venous invasion was assessed on sections from 81 CRCs resected from patients with synchronous distant metastases (hepatic and non-hepatic). Only stage IV tumours were studied for the following reasons: (1) it can be assumed that in all patients with distant haematogenous metastases venous invasion had occurred, thus enabling the false negative rate to be calculated; (2) there can be no dispute about the clinical relevance of the various characteristics of venous invasion identified in the tumours of patients with synchronous distant haematogenous metastases; and (3) to eliminate the effect of variance in tumour stage on the incidence of venous invasion. Initially, H+E stained sections were studied for venous invasion. Sections that were negative or questionable with regard to venous invasion were then stained with an elastic fibre stain, and a second search for venous invasion was carried out. Venous invasion was characterised by incidence, quantity, type, and site. The chi(2) test for independence was used to compare the incidence of venous invasion in colonic versus rectal and rectosigmoid primary tumours, and in patients with hepatic versus non-hepatic metastases. RESULTS: Venous invasion was identified in 42 (51.9%) (of the 81 specimens on H+E stained sections. The addition of the elastic fibre stain enabled the diagnosis of venous invasion in 15 (38.5%) of the remaining 39 specimens, increasing the overall incidence to 57 of 81 cases (70.4%). Of the 57 positive specimens, venous invasion was minimal in 27 (47.4%), intermediate in five, (8.8%) and massive in 25 (43.9%). Only intramural veins were involved in 18 (31.6%), only extramural veins in 26 (45.6%), and both intramural and extramural veins in 13 (22.8%) of the 57 positive specimens. The filling type of venous invasion was found in 41 (71.9%), the floating type in 28 (49.1%), and the infiltrating type in six (10.5%) of the 57 positive specimens. There was no significant difference between the incidence of venous invasion in the colon (42 of 60; 70%) versus rectal and rectosigmoid tumours (15 of 21; 71.4%; p = 0.8539), nor in the incidence of venous invasion in patients with hepatic (49 of 70; 70%) versus non-hepatic (eight of 11; 72.7%) metastases (p = 0.9018). CONCLUSIONS: The addition of an elastic fibre stain enables the identification of venous invasion in a considerable proportion of sections from CRC tumours that are falsely negative for venous invasion on H+E stain alone. The inherent chance of missing venous invasion on histopathological evaluation of CRC tumours stained with H+E and elastic fibre stains is at least 10.5%, and may be as high as 29.6%. In a large proportion of stage IV CRCs, despite the presence of synchronous distant metastases, only a minimal extent of venous invasion (that is, one to two involved veins) is demonstrable in the primary tumour. This suggests that only minimal venous invasion is required for the seeding of clinically relevant haematogenous metastases, and emphasises the careful, dedicated search for venous invasion that is required from the pathologist. Although extramural venous invasion was predominant in stage IV CRCs, in a considerable proportion of tumours (about a third) only intramural venous invasion was found. This suggests that intramural venous invasion may also seed clinically relevant haematogenous metastases, and should therefore also be considered as an indicator of poor prognosis.


Assuntos
Adenocarcinoma/patologia , Neoplasias Colorretais/patologia , Neoplasias Vasculares/patologia , Adenocarcinoma/secundário , Colo/irrigação sanguínea , Feminino , Humanos , Neoplasias Hepáticas/secundário , Mesocolo/irrigação sanguínea , Invasividade Neoplásica/diagnóstico , Invasividade Neoplásica/patologia , Estadiamento de Neoplasias , Reto/irrigação sanguínea , Manejo de Espécimes/métodos , Coloração e Rotulagem/métodos , Veias/patologia
12.
Cancer Genet Cytogenet ; 31(1): 113-8, 1988 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-3345500

RESUMO

A familial fragile 8q22 and an interferon-induced fragile 16q22 were found in two sisters. Eight years previously, both sisters developed an endometrial adenocarcinoma and now one of them presented with an adenocarcinoma of the colon. An 8q22 deletion was found in all the cells of the colonic tumor and seemed to be the primary initiating change. Other nonrandom and possibly promoting aberrations were also present, among others, a 16q22 deletion. The possibility exists that a familial fragile 8q22 may predispose to cancer and a fragile 16q22 may have promoting capacities.


Assuntos
Adenocarcinoma/genética , Fragilidade Cromossômica , Cromossomos Humanos Par 8 , Síndromes Neoplásicas Hereditárias , Neoplasias do Colo Sigmoide/genética , Bandeamento Cromossômico , Suscetibilidade a Doenças , Feminino , Humanos , Cariotipagem , Pessoa de Meia-Idade , Neoplasias Uterinas/genética
13.
Cancer Genet Cytogenet ; 27(1): 171-5, 1987 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-3472645

RESUMO

We report on the cytogenetic findings in direct preparations of two tumors of the sigmoid colon. Respectively, they had a near-triploid and a near-tetraploid constitution and relative numerical and other inconstant chromosomal imbalances. The only constant chromosomal structural anomaly apparently was inversion of chromosome #16, inv(16)(p13q22), which was found in all the cells examined. This rearrangement has been found to be associated with a type of acute myelomonocytic leukemia type M4. We suggest that an etiologic clastogenic (and oncogenic) agent responsible for this rearrangement may eventually be the cause of various kinds of malignancy.


Assuntos
Adenocarcinoma/genética , Inversão Cromossômica , Cromossomos Humanos Par 16 , Neoplasias do Colo Sigmoide/genética , Adulto , Idoso , Bandeamento Cromossômico , Fragilidade Cromossômica , Feminino , Marcadores Genéticos , Humanos , Cariotipagem
14.
Cancer Genet Cytogenet ; 38(1): 43-8, 1989 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-2713813

RESUMO

The relatively simple cytogenetic findings in an aggressive metastatic Merkel cell carcinoma are reported. Deletion 2p was found in 100% of the cells. Nevertheless, this was considered a secondary (metastatic?) change because the same aberration has been found in several other kinds of malignancy. The involvement of chromosome 22 [del(22q) and -22] in 85% of the cells seemed more intriguing, considering the fact that the Merkel cell carcinoma followed a previous meningioma.


Assuntos
Carcinoma de Célula de Merkel/genética , Aberrações Cromossômicas , Cromossomos Humanos Par 22 , Neoplasias Meníngeas/genética , Meningioma/genética , Humanos , Masculino , Pessoa de Meia-Idade
15.
Cancer Chemother Pharmacol ; 13(3): 218-22, 1984.
Artigo em Inglês | MEDLINE | ID: mdl-6488442

RESUMO

Concurrent administration of thymidine (TdR) has been shown to increase the antitumor activity of 5-fluorouracil (5-FU) in various experimental models. The clinical response rate, side-effects, and toxicity of 5-FU and TdR were evaluated in 27 patients with advanced colorectal carcinomas. Each 6-day treatment course consisted of an IV loading dose of TdR (405 mg/kg, over 30 min), followed by continuous IV infusions of 5-FU (7.5 mg/kg per day for 5 days), and TdR (216 mg/kg per day for 6 days); courses were repeated every 4 weeks. The overall partial response rate was 4.5%, or 16.7% in patients with no prior 5-FU chemotherapy. Short-lived stable disease was seen at an overall rate of 27.3%, half of these patients with prior 5-FU chemotherapy. Myelotoxicity occurred in 64% of the patients, but this was dose-limiting in only 20%. Gastrointestinal and neurological symptoms were mild and infrequent. There was one case of treatment-related death due to sepsis secondary to leukopenia. It is concluded that the concurrent IV administration of 5-FU and TdR does not improve the response rate over that obtained with 5-FU alone.


Assuntos
Medula Óssea/efeitos dos fármacos , Neoplasias do Colo/tratamento farmacológico , Fluoruracila/administração & dosagem , Neoplasias Retais/tratamento farmacológico , Timidina/administração & dosagem , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica , Sinergismo Farmacológico , Feminino , Fluoruracila/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Timidina/efeitos adversos
16.
Am J Ophthalmol ; 126(4): 607-9, 1998 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-9780114

RESUMO

PURPOSE: To report the cyclosporine-induced complications of optic neuropathy, partial external ophthalmoplegia, and other neurologic abnormalities. METHODS: Case report. A 22-year-old man with severe active Crohn disease developed bilateral optic neuropathy, nystagmus, external ophthalmoplegia, and ataxia on the fifth day of cyclosporine A (CyA) parenteral therapy. RESULTS: Cyclosporine therapy was discontinued as soon as toxic clinical manifestations appeared. Cyclosporine blood level detected then was 1,290 ng/ml (therapeutic level: 150 to 300 ng/ml). Partial external ophthalmoplegia improved dramatically; however, the patient's optic neuropathy progressed to optic atrophy, leaving the patient visually impaired. Various possible mechanisms for cyclosporine-induced neurotoxicity are discussed. CONCLUSION: It is important to closely monitor neuro-ophthalmologic and neurologic signs of patients treated with cyclosporine.


Assuntos
Doença de Crohn/tratamento farmacológico , Ciclosporina/efeitos adversos , Imunossupressores/efeitos adversos , Nistagmo Patológico/induzido quimicamente , Oftalmoplegia/induzido quimicamente , Atrofia Óptica/induzido quimicamente , Adulto , Humanos , Masculino , Oftalmoplegia/fisiopatologia , Atrofia Óptica/patologia , Acuidade Visual
17.
J Neural Transm Suppl ; 33: 149-55, 1991.
Artigo em Inglês | MEDLINE | ID: mdl-1753245

RESUMO

A planned prospective documentation of the course of rehabilitation of 303 stroke patients was undertaken using the Bathel-Index as a measure of basic everyday functions and the Guttman-Scale as a measure of complex activities of daily living. These were determined at the beginning of rehabilitation, after an average of 7 weeks of in-patient treatment and one year following the stroke. Four patterns in the course of rehabilitation could be differentiated. The causes of the differing functional results were investigated. Besides a positive spontaneous progress of the underlaying disease with an early reparation of the neurological deficits it is the premorbid status, the overprotection of the physically disabled and the determinative cognitive and mental functions that decide the long term fate of stroke patients.


Assuntos
Transtornos Cerebrovasculares/reabilitação , Atividades Cotidianas , Adulto , Idoso , Idoso de 80 Anos ou mais , Humanos , Pessoa de Meia-Idade , Testes Neuropsicológicos , Estudos Prospectivos , Fatores de Tempo
18.
J Neural Transm Suppl ; 33: 157-61, 1991.
Artigo em Inglês | MEDLINE | ID: mdl-1753246

RESUMO

To evaluate the medical educational and functional determinants of employment after stroke a total of 204 Patients were assessed for functional changes during rehabilitation and after one year. Additionally the educational and social background of each patient was documented. One year after discharge from the rehabilitation unit 11.3% of the patients worked full-time and 2.7% part time. Another 14.7% had the decision pension versus employment still pending and 0.5% were classified as unemployed. 70.8% received regular retirement plan payments or disability pensions. Generally a similar level of functional capabilities can be observed after one year for working and non-working patients except for manual dexterity. Early admission to rehabilitation (within the first 12 weeks) favours return to work. A high school degree qualifying for university entrance and a well paid and better qualified profession as well are correlated with a higher percentage of patients regaining their employment. An other determining factor of employment after CVA is the physical requirement of the former work. Most of the working patients (92%) had been either transferred onto a job suited for an handicapped people or their work plan had been restructured accordingly.


Assuntos
Transtornos Cerebrovasculares/reabilitação , Emprego/psicologia , Desempenho Psicomotor/fisiologia , Transtornos Cerebrovasculares/psicologia , Escolaridade , Humanos , Pessoa de Meia-Idade
19.
Respir Med ; 92(8): 1071-5, 1998 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-9893778

RESUMO

Exercise-induced bronchoconstriction (EIB) occurs in the majority of patients with asthma. The relationship between asthma and gastro-oesophageal reflux (GER) is well defined, and the reports of exertional gastro-oesophageal acid reflux in healthy subjects, prompted us to study the relationship between EIB and GER. Following an overnight fast and medication withholding, 15 asthmatics and 15 normal subjects were placed on continuous monitoring of oesophageal pH and ECG. After baseline monitoring of oesophageal pH, at rest, for 30 min, spirometry was performed. Thereafter, the subjects underwent rigorous treadmill exercise for 8 min followed by spirometry, 10 min after running. Twelve out of 15 asthmatics and none in the control group demonstrated significant fall in FEV1 in response to exercise. However, only six out of 15 normal subjects and three in the asthmatic group had evidence of GER during or following exercise. We concluded that there is no significant correlation between EIB and GER in patients with asthma.


Assuntos
Asma Induzida por Exercício/complicações , Refluxo Gastroesofágico/complicações , Adolescente , Adulto , Asma Induzida por Exercício/fisiopatologia , Exercício Físico/fisiologia , Teste de Esforço , Feminino , Volume Expiratório Forçado , Humanos , Concentração de Íons de Hidrogênio , Masculino , Pessoa de Meia-Idade , Espirometria
20.
Dig Liver Dis ; 33(4): 322-5, 2001 May.
Artigo em Inglês | MEDLINE | ID: mdl-11432509

RESUMO

BACKGROUND/AIMS: The incidence of adenocarcinoma of the oesophagus has increased. Its major risk factor is Barrett's epithelium of which the sine qua non is microscopically diagnosed intestinal metaplasia. Short segment Barrett's epithelium may often be overlooked during routine endoscopy. In routine biopsies taken from normal-appearing mucosa of the distal oesophagus, the reported rates of short segment Barrett's epithelium in the distal oesophagus reached 36%. We compared these rates with the results obtained in a community hospital in Israel. METHODS: Consecutive patients undergoing oesophagogastroduodenoscopy were enrolled. Biopsy specimens taken from cardia, oesophagogastric junction and 2 cm above the oesophagogastric junction were stained with haematoxylin & eosin and Alcian blue. RESULTS: There were 112 study patients (mean age +/- SD 48. 9+/-18.3 years, 51.8% males). Nine (8.04%) patients had intestinal metaplasia (according to specimen from 2 cm above oesophagogastric junction), and symptoms of gastro-oesophageal reflux were found in only four (44.4%) of them. Of these nine patients, six (6.66%) had normal-appearing mucosa and three (3.33%) had macroscopic Barrett's epithelium. Alcian blue staining revealed two patients with intestinal metaplasia that haematoxylin & eosin staining had missed. CONCLUSION: We found an 8% prevalence of intestinal metaplasia compared to 18-36% reported in the literature. We also determined that the added advantage of routine biopsy was 5.4%.


Assuntos
Esôfago de Barrett/epidemiologia , Adenocarcinoma/epidemiologia , Esôfago de Barrett/patologia , Endoscopia do Sistema Digestório , Neoplasias Esofágicas/epidemiologia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco
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