RESUMO
It was recently reported that 4-substituted picolinohydrazonamides carrying hydrophilic cyclic amines, such as morpholine and pyrrolidine, at the end of their thiosemicarbazide chain have potent antimycobacterial activity in vitro at concentrations below 1 µg/ml. Here, two selected compounds, 2,4-disubstituted pyridine derivatives 11 and 15, revealed significant bactericidal activity against Mycobacterium tuberculosis localized intracellularly within human macrophages, as well as against biofilm-forming tubercle bacilli. Mutants were selected that were resistant to the investigated compounds at an efficiency similar to that identified in the presence of the first line antituberculosis drug rifampicin. The resistant mutants were viable in the presence of the tested compounds exclusively on solid media. Genome-wide sequencing of the mutants selected in the presence of compound 11 revealed the accumulation of nonsynonymous mutations in the mmpR5 gene encoding a transcriptional repressor of the MmpS5-MmpL5 efflux pump, whose upregulation has been associated with bedaquiline resistance. The depletion of MmpR5 in wild-type M. tuberculosis using CRISPR-Cas9 technology increased the resistance of this strain to compound 11. Mass spectrometry-based proteomics (LC-MS/MS) of wild-type tubercle bacilli growing in subinhibitory concentrations of compounds 11 or 15 revealed 15 overproduced proteins not detectable in the control cells, including virulence-related proteins.
RESUMO
About 75-80% chronic subdural hematomas give positive results in a brain scan. The typical scintigraphic finding of chronic subdural hematoma is a diffuse widening and increase of the peripheral activity on the anterior view. In the flow studies subdural hematomas lead occasionally to peripheral activity defects. In two cases of chronic subdural hematoma without typical patterns in a perfusion study as well as in static images, we found a displacement of the anterior cerebral vessels as an indircet sign of space occupation.
Assuntos
Hematoma Subdural/diagnóstico , Cintilografia , Astrocitoma/diagnóstico , Encefalopatias/diagnóstico , Neoplasias Encefálicas/diagnóstico , Circulação Cerebrovascular , Cistos/diagnóstico , Diagnóstico Diferencial , Humanos , Masculino , Pessoa de Meia-Idade , TecnécioRESUMO
Although several reports on the clinical usefulness of N-isopropyl-[123]p-iodoamphetamine (IMP) in the diagnosis of cerebral disease have appeared in the literature, quantitative, noninvasive measurements of regional cerebral blood flow with this method pose difficulties because cerebral IMP uptake not only depends on cerebral perfusion but also on cerebral function. Rather than trying to develop a method to measure cerebral perfusion with IMP, we have chosen to test a method to quantitatively evaluate planar and emission computed tomographic (ECT) studies by comparing the data obtained in patients with established pathology (n = 51, number of scans = 54) with the data obtained in a group of normal individuals (n = 10, number of scans = 11). Using this method, absolute cerebral IMP uptake (counts/pixel/mCi/min) and planar anterior right-left ratios were obtained. Also measured were right-left ratios obtained from 12 paired regions in three ECT slices. In the control group, we found an IMP uptake of 35.6 +/- 4.3 cts/pixel/mCi/min and right-left ratios around 1.00 (s.d. less than 2%). The evaluation of the patients cerebral IMP uptake asymmetries relative to the normal standard values is a useful adjunct to qualitative image analysis in assessing the presence and severity of disease, as qualitative analysis is prone to false-positive and negative results. Cerebral IMP uptake as measured in cts/pixel/mCi/min is abnormal only in severe cerebral disease and therefore generally a less helpful parameter.
Assuntos
Anfetaminas , Encéfalo/diagnóstico por imagem , Circulação Cerebrovascular , Transtornos Cerebrovasculares/diagnóstico por imagem , Radioisótopos do Iodo , Neoplasias Encefálicas/diagnóstico por imagem , Transtornos Cerebrovasculares/fisiopatologia , Diagnóstico Diferencial , Erros de Diagnóstico , Epilepsia/diagnóstico por imagem , Humanos , Iofetamina , Esclerose Múltipla/diagnóstico por imagem , CintilografiaRESUMO
[123I]SCH 23982, a dopamine D1 ligand, was labelled in a large scale process and then tested in vitro for binding to rat brain sections and membranes. Because of the promising values of KD = 1.5 x 10(-10) M and Bmax = 0.7 x 10(-11) mol/g, in vivo evaluation was performed on rats and normal volunteers to test its possible usefulness for SPET imaging. In competition experiments, a higher binding in the presence of sulpiride was found while ketanserin displaced [123I]SCH 23982 only at a 10,000-fold excess. Differences between rats and men were seen with respect to their metabolism. SPET investigations failed because the washout of [123I]SCH 23982 was too rapid.
Assuntos
Benzazepinas/análogos & derivados , Receptores de Dopamina D1/antagonistas & inibidores , Tomografia Computadorizada de Emissão de Fóton Único/métodos , Idoso , Animais , Benzazepinas/metabolismo , Benzazepinas/farmacocinética , Feminino , Humanos , Técnicas In Vitro , Radioisótopos do Iodo , Masculino , Pessoa de Meia-Idade , Ratos , Ratos Wistar , Distribuição TecidualRESUMO
In 156 patients the dynamic liver perfusion study with 99mTc-sulfur colloid and the scintillation camera was performed. Out of the 81 cases with confirmed diagnosis, the rapid sequential liver study was only in one case to provide an additional information of clinical importance, which could not be demonstrated by static liver imaging. Except for 2 patients with carcinoid metastases of the liver and 3 cases of acute hepatitis, we did not find any significant difference in the activity appearance in the liver between normal subjects and patients with liver metastases and diffuse liver diseases.
Assuntos
Hepatopatias/diagnóstico , Cintilografia , Tecnécio , Adolescente , Adulto , Idoso , Aorta Abdominal , Neoplasias da Mama , Coloides , Feminino , Humanos , Fígado/metabolismo , Neoplasias Hepáticas/diagnóstico , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Fluxo Sanguíneo Regional , Enxofre , Tecnécio/metabolismo , Fatores de TempoRESUMO
A 28 year old patient complained of sensory disturbances and pain in the right upper arm during pregnancy. During the 32nd week of her pregnancy, a large painful mass developed in the flexor muscles which, radiographically, showed some calcification. A diagnosis of a parosseous sarcoma was made; biopsy, however, indicated a diagnosis of non-traumatic myositis ossificans. Since the histological appearances of active myositis may be vary difficult to distinguish from a juxtacortical sarcoma, a right brachial angiogram and scintiscan were obtained. The angiographic and scintigraphic findings were erroneously considered to suggest malignancy. Following delivery, the tumour was removed. Futher histology confirmed the diagnosis of localised, non-traumatic myositis ossificans. The value of radiology, biopsy, angiography and scintigraphy are discussed with reference to our experience.
Assuntos
Miosite Ossificante/diagnóstico , Complicações na Gravidez/diagnóstico , Adulto , Neoplasias Ósseas/diagnóstico , Artéria Braquial/diagnóstico por imagem , Diagnóstico Diferencial , Erros de Diagnóstico , Feminino , Humanos , Úmero , Miosite Ossificante/patologia , Gravidez , Radiografia , Cintilografia , Ombro/diagnóstico por imagem , TecnécioRESUMO
Between 1971 and 1975 we performed 1580 dynamic perfusion studies in 1411 patients. The patients were admitted to the nuclear medicine department for brain scanning from the medical, neurological and neurosurgical departments as well as directly by private family physicians. For dynamic brain studies we used the scintillation camera (Searle Radiographics) and a bolus of 99mTc-pertechnetate intravenously injected. The polaroid frames were exposed at 4 second intervals The results of the dynamic brain study were divided into five categories: normal, moderately diminished perfusion of one hemisphere, severe perfusion defect of one hemisphere, focal or multifocal hypervascular areas ("hot areas") and stenosis or occlusion of the carotid artery. In 1009 cases we found a normal perfusion of the tracer material without any side difference between the brain hemispheres. In 68 patients with motoric hemisyndrome of the right side and in 89 patients with hemisyndrome of the left side we were able to demonstrate a diminished perfusion of the contralateral hemisphere. In 65 patients with confirmed primary or metastatic brain tumors we observed a perfusion deficiency in 39 cases and focal "hot" areas in 26 cases. In 24 epileptic patients we found asymmetrical perfusion of the brain. In 109 patients without any neurological signs or symptoms we registered a "false positive" dynamic perfusion study with an asymmetrical initial transition of the injected tracer material. The left hemisphere showed a diminished perfusion in 86 cases, the right in 23 cases. The asymmetrical brain perfusion was not observed in patients under the age of twenty years. The incidence of "false positive" dynamic brain studies was found to be dependent on the age of the investigeted patients with a maximum of asymmetrical brain perfusion scans in the age group between 61 and 70 years. At present time we are not able to explain the reason of the "false positive" results. Because of this reason the investigation will be continued together with the neurologists and radiologists to find out a possible correlation between our study, the EEG-curves and results of the morphological brain investigations such as pneumoencephalography or ACT-scans.
Assuntos
Envelhecimento , Circulação Cerebrovascular , Adolescente , Adulto , Idoso , Encefalopatias/diagnóstico , Criança , Pré-Escolar , Reações Falso-Positivas , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Cintilografia , TecnécioRESUMO
In order to check a new rebreathing unit for ventilation investigations of the lungs with radioactive gases, a 133Xe lung ventilation study was performed in a 56-year old healthy volunteer. The contamination check on the following day triggered a radiation warning caused by the retained xenon activity in the body. The whole-body scan performed 18 h after the inhalation showed clearly a faint delineation of the xenon activity, corresponding to the subcutaneous fatty tissue of the individual studied.
Assuntos
Tecido Adiposo/metabolismo , Pulmão/diagnóstico por imagem , Testes de Função Respiratória , Radioisótopos de Xenônio/farmacocinética , Tecido Adiposo/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , CintilografiaRESUMO
1971 Sorbie et al. described a simple 57Co-excretion test (16) as an aid in the diagnosis of iron deficiency anemia. The authors found that renal excretion of a tracer dosis of 0,5 muCi 57CoCl2 was significantly elevated in patients with iron deficiency anemia (31% of the administered dose in 24 hours' urine) as compared with the controls (18%). Between 1972-1974 we performed the 57Co-excretion test in 29 patients with different kind of anemia and in 10 healthy volunteers. The test was modified by measurement of the serum activity 1, 2, 3, 7, 11 and 24 hours after the oral administration of the test dosis. In all anemias as well as in the control group we found the maximum of serum activity three hours after the oral administration of the tracer. The three hours serum activity was elevated only in patients with iron deficiency anemia (5,53%/1 serum) as compared with the control group (1,92%/1) and renal, tumor and infectious anemia (1,20%/1). p less than 0,001. The 57Co excretion was moderately elevated in most of the patients with iron dificiency anemia (average 31,5% 57Co-activity in 24 hours' urine) in comparison to the healthy controls (average 25,30%). Contrary to the results obtained by Sorbie et al. we found a wide range of fluctuation of the Co-excretion test in each group of patients with a poor statistical significance of p greater than 0,005.
Assuntos
Anemia Hipocrômica/diagnóstico , Radioisótopos de Cobalto , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Técnica de Diluição de RadioisótoposRESUMO
Between June 1983 and March 1985 197 patients were examined with 123I-IMP brain scintigraphy and ECT. They had various neurological diseases, the majority suffered from cerebrovascular affections. The reference for pathological findings was a group of 14 healthy volunteers. A visual interpretation of the ECT-slices alone is not reliable enough. A semiquantitative assessment of perfusion abnormalities seems to be very important, especially in diffuse or bilateral alterations. The proposed semiquantitative evaluation makes use of the total cerebral accumulation in the control group (35.6 +/- 4.3 cts/pixel/mCi/min) and right-left ratios of 14 paired and fixed regions of interest (ROI) in three ECT slices. The ROIs are related to the anatomical flow supply areas in the brain. The right-left ratios are around 1.0 with a physiological asymmetry of +/- less than 2% (standard deviation). The asymmetry is an important parameter in assessing presence and severity of disease. If pathological findings are diffuse or symmetric, the visual interpretation of scintigrams or the calculation of right-left ratios are often unsuccessful. Thus, the same ROI-data were separated for the right and left hemisphere and drawn as cts/ROI/pixel/mCi in diagrams as profile. The diagram demonstrates perfusion abnormalities semiquantitatively without using calculation of asymmetry, since asymmetry alone cannot differentiate between hypoperfusion of one and hyperperfusion of the contralateral side.
Assuntos
Anfetaminas , Encefalopatias/diagnóstico por imagem , Circulação Cerebrovascular , Tomografia Computadorizada de Emissão , Adulto , Idoso , Encefalopatias/fisiopatologia , Transtornos Cerebrovasculares/diagnóstico por imagem , Transtornos Cerebrovasculares/fisiopatologia , Feminino , Humanos , Radioisótopos do Iodo , Iofetamina , Masculino , Pessoa de Meia-IdadeRESUMO
The tracer 123I-SCH 23982 was tested with regard to its ability to image dopamine D1 receptor in the human brain in vivo with single photon emission computed tomography (SPECT). The tracer did not reach equilibrium with regard to its binding to dopamine D1 receptors, presumably owing to fast metabolism to hydrophilic products and deiodination. It is concluded that 123I-SCH 23982 is not suitable for dopamine D1 receptor imaging with SPECT in the human brain.
Assuntos
Benzazepinas/análogos & derivados , Encéfalo/diagnóstico por imagem , Receptores de Dopamina D1/análise , Adulto , Idoso , Química Encefálica , Contraindicações , Antagonistas de Dopamina , Feminino , Humanos , Radioisótopos do Iodo , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada de Emissão de Fóton ÚnicoRESUMO
After showing in an earlier publication that Iomazenil is a potent benzodiazepine receptor antagonist, the substance has been distributed to 11 clinical centres in Europe for further tests. The protocol asked for volunteers, epileptic cases and patients with Alzheimer's disease. Prior to the Iomazenil examination, flow images by perfusamine or HMPAO were required, and as comparative methods EEG, computed tomography (CT) and magnetic resonance imaging (MRI) were performed. The results allowed first the determination of the normal distribution of the benzodiazepine receptors in the human brain. The highest uptake was found in medial occipital cortex. Second, the evaluation of the epileptic cases shows a 100% positive prediction value for Iomazenil compared to 92% for flow images. Negative prediction values were calculated as 81% for Iomazenil and 54% for flow images. Furthermore, one group reported the successful diagnosis of Alzheimer's disease at an early stage. The visual image examination was tentatively compared to a more objective semiquantitative one based on quotients of corresponding left/right regions of interest. This semiquantitative method has not proved successful yet, but the problems have been identified. A more precise protocol for further studies is therefore proposed.
Assuntos
Doença de Alzheimer/diagnóstico por imagem , Epilepsias Parciais/diagnóstico por imagem , Flumazenil/análogos & derivados , Adulto , Química Encefálica , Estudos de Avaliação como Assunto , Feminino , Humanos , Radioisótopos do Iodo , Masculino , Pessoa de Meia-Idade , Receptores de GABA-A/análise , Tomografia Computadorizada de Emissão de Fóton ÚnicoRESUMO
We studied a 57-year old woman with severe myasthenic syndrome predominantly proximal. There was no therapeutic effect using cholinesterase inhibitors. Clinical findings, electromyography, whole body scanning and biopsy revealed polymyositis. Thirteen years before the patient was operated of a benign thymoma. The history of the patient showed numerous life threatening episodes of viral and fungal infections. Autoimmune anemia was diagnosed. Investigations of the immune system in vivo and in vitro revealed severe qualitative and quantitative defects in the lymphocyte population spontaneously forming rosettes with sheep red blood cells (SRBC). Thymoma, autoimmune disorder, such as polymyositis and myasthenia gravis, unspecifically elevated antibody titers, multiple severe viral and fungal infections and the defect of the cell-mediated immunity suggest a T-lymphocyte effector- and regulatory dysfunction in this patient.
Assuntos
Doenças Autoimunes/imunologia , Imunidade Celular , Miastenia Gravis/imunologia , Miosite/imunologia , Timoma/imunologia , Neoplasias do Timo/imunologia , Feminino , Humanos , Pessoa de Meia-Idade , Linfócitos T/metabolismoRESUMO
Due to the rapid growth of basic knowledge in recent decades, a tremendous amount of superspecial scientific information is confronting us today. This overflow of new and often short-lived data is influencing in a considerable way the view and the management of all life sciences. On the basis of the change of paradigm in modern economic systems, also influencing management, we try to compare the particular components of these changes that occur in medical sciences, e.g. in pathophysiology, diagnostic investigations and therapy. Most of the paradigm components can be used for an analysis of the consequences of the rapid changes in the medical way of thinking. For this contemplation, selected cases of thyroid disorders have been chosen.