RESUMO
OBJECTIVES: Previous systematic reviews and meta-analyses of treatments in relapsing-remitting multiple sclerosis (RRMS) derived their findings from either placebo-controlled studies only or separately from head-to-head and comparative studies. The purpose of this study is to compare annualized relapse rates (ARR) of fingolimod versus all of the commonly used first-line treatments in RRMS using evidence from both placebo-controlled and head-to-head studies. In absence of the head-to-head data between fingolimod and the other treatments, these comparisons were formed using meta-analysis techniques for indirect treatment comparisons. METHODS: A systematic literature review was conducted by searching MEDLINE, EMBASE, and the Cochrane Library with no limitations applied on publication language or dates. Included studies were randomized controlled trials evaluating one or more of fingolimod, interferon beta-1a, interferon beta-1b, or glatiramer acetate in RRMS populations. Primary outcome was ARR. Data extraction included author, year, treatment, dosage, mean age, percentage females, duration of disease, Expanded Disability Status Scale (EDSS) score at baseline, relapses in 2 years prior to baseline, trial duration, relapse-related outcome, and definition of relapse. The indirect treatment comparisons were performed using a mixed-treatment comparison framework. ARR was analyzed as a Poisson outcome. RESULTS: The relative ARRs, for each treatment versus fingolimod, estimated from our meta-analyses were 1.43 (glatiramer acetate 20 mg), 1.51 (interferon beta-1b 250 mcg), 1.55 (interferon beta-1a 44 mcg), 1.67 (interferon beta-1a 22 mcg), 1.93 (interferon beta-1a 30 mcg), and 2.32 (placebo). None of the 95% confidence intervals for these estimates overlapped unity, implying statistical significance of these findings. LIMITATIONS: The key limitations of this study are the persisting heterogeneity even after adjusting for covariates and the variability in outcome definition across the included trials. CONCLUSIONS: Our study demonstrated that fingolimod significantly reduces relapse frequency in patients with RRMS compared with current first-line disease-modifying therapies.
Assuntos
Interferon beta/uso terapêutico , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Propilenoglicóis/uso terapêutico , Esfingosina/análogos & derivados , Adulto , Feminino , Cloridrato de Fingolimode , Acetato de Glatiramer , Humanos , Interferon beta-1a , Interferon beta-1b , Masculino , Esclerose Múltipla/tratamento farmacológico , Peptídeos/uso terapêutico , Distribuição de Poisson , Recidiva , Esfingosina/uso terapêutico , Fatores de TempoRESUMO
BACKGROUND: We used the PCR technique based on the abovementioned primer pair and sequencing to demonstrate the Theileria infection in the sheep samples collected from Sultanate of Oman. METHODS: According to the frame work of "integrated control of ticks and tick borne diseases in globalized world managed by EU-ICTTD-3 project, the samples from blood, liver, spleen, lymph node and lung were sent to the laboratory of Iranian Research Center for Ticks and Tick-borne Diseases (IRCTTD). Samples from blood smear and impression smears from liver, spleen, lymph node, and lung were analyzed by Geimsa staining. The DNA was extracted from the abovementioned samples and analyzed by PCR technique using specific primers derived from the nucleotide sequences of 18S rRNA gene of T. lestoquardi, which can amplify the common region in other Theileria and Babesia spp. Subsequently the amplified DNA was sequenced. RESULTS: The analysis of blood smears of the sheep was negative for piroplasmosis performed through the Giemsa staining. The impression smears prepared from liver, spleen, lymph node, and lung showed suspicious structures mimicking Theileria schizonts in some cells. The results showed an expected PCR product of 428 bp in length, which is specific for Theileria spp. The PCR products were subsequently sequenced. The corresponding nucleotide sequence is registered under accession number JF309152 in GenBank. The sequence alignment in GenBank showed that the PCR products had 99% homology to the known T. lestoquardi registered under accession number AF081135 in the GenBank. CONCLUSION: Oman sheep are highly susceptible for Theileria infection and the infected sheep mostly die before the microschizonts or erythrocytic form of Theileria appears in the nucleated or erytrocytic cells respectively.
RESUMO
In this pediatric case of vanishing white matter disease with early onset, rapidly progressive course, and fatal outcome, the white matter vanishing process in patient was for the first time documented morphologically in detail: An initial magnetic resonance imaging documented a normal appearing brain maturation. Rapid progressive brain lesions initiated morphologically DE NOVO in the former well myelinated deep white matter were observed six months later after disease onset, including concentric ongoing signs of restricted proton diffusion cytotoxic edema on diffusion weighted imaging. Cyst-like defects at the lesion center of the deep white matter were detected more clearly on MRI ten months later. A pathomechanism like tumor necrosis factor induced oligodendrocyte apoptosis and primary demyelination was postulated. The case demonstrates that in the presence of clinically progressive symptoms, the development of VWM is possible even if first MRI findings are negative.
Assuntos
Encefalopatias/patologia , Imageamento por Ressonância Magnética/métodos , Atrofia/patologia , Pré-Escolar , Progressão da Doença , Feminino , HumanosRESUMO
POEMS/Crow-Fukase syndrome is a rare multisystem disorder associated with elevated vascular endothelial growth factor (VEGF), which clinically presents with polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes. We report a case of POEMS syndrome due to a gammopathy of undetermined significance with thrombocytosis, vitamin B(12) deficiency, highly elevated VEGF and in addition to glomeruloid angiomas two previously undescribed proliferative vascular lesions: a spinal arteriovenous fistula and a plexogenic pulmonary arteriopathy, which ultimately resulted in lethal pulmonary hypertension. We assume that the high VEGF levels caused the vascular abnormalities observed in our patient.
Assuntos
Síndrome POEMS/complicações , Trombocitose/complicações , Doenças Vasculares/complicações , Deficiência de Vitamina B 12/complicações , Adulto , Fístula Arteriovenosa/complicações , Feminino , Humanos , Pulmão/irrigação sanguínea , Pulmão/patologia , Pneumopatias/complicações , Pneumopatias/patologia , Síndrome POEMS/sangue , Síndrome POEMS/patologia , Síndrome POEMS/fisiopatologia , Paraproteinemias/complicações , Paraproteinemias/fisiopatologia , Medula Espinal/irrigação sanguínea , Medula Espinal/patologia , Doenças da Medula Espinal/complicações , Doenças da Medula Espinal/patologia , Doenças Vasculares/patologia , Fator A de Crescimento do Endotélio Vascular/sangueRESUMO
Endovascular treatment of ruptured vertebrobasilar artery aneurysms with Gugliemi detachable coils (GDC) has become an alternative to surgery. Mid-term angiographic follow-up can now be reported. Of 111 vertebrobasilar aneurysms in 110 patients we treated with GDC since 1992, 53 underwent angiography within 1 year and 59 after more than 18 months. We did not achieve complete occlusion on initial treatment of 23 aneurysms (21%). Complications were observed in 19 patients (17%), leading to permanent clinical disability in eight. Enlargement of the neck or reopening was seen in 12 (23%) of 53 aneurysms followed by angiography within 12 months. Documented recanalisation was treated in four (8%). Angiography was performed after 18-78 months in 59 patients, of whom nine, including three with initially incomplete occlusions, were retreated with GDC. Within the entire second observation period, three (5%) of the 59 patients had a further haemorrhage and were retreated with GDC. Rebleeding proved to be the only factor influencing the clinical outcome of retreated patients.
Assuntos
Angiografia Cerebral/métodos , Embolização Terapêutica , Aneurisma Intracraniano/terapia , Angiografia Digital/métodos , Transtornos Cerebrovasculares/complicações , Transtornos Cerebrovasculares/terapia , Feminino , Seguimentos , Escala de Resultado de Glasgow/estatística & dados numéricos , Humanos , Aneurisma Intracraniano/complicações , Masculino , Retratamento , Estudos Retrospectivos , Hemorragia Subaracnóidea/fisiopatologia , Fatores de Tempo , Resultado do TratamentoRESUMO
PURPOSE: Technical essentials and therapeutic results of carotid stenting without cerebral protection are presented. MATERIALS AND METHODS: In 161 patients, 167 high grade carotid stenoses were stented, followed by percutaneous transluminal angioplasty, with subsequent evaluation of the clinical and angiographic results. Diffusion-weighted MRI was carried out in 108 patients to detect cerebral sequelae. RESULTS: Endovascular therapy was successful (residual stenosis < 25 %) in 166 stenoses (99.4 %). Twelve patients (7.5 %) had cerebrovascular complications within the 30-day perioperative period, seven of which occurred during the procedure. After treatment, diffusion-weighted MRI disclosed at least one new cerebral lesion in 40 patients (37 %), which were symptomatic in six patients. CONCLUSION: Even without cerebral protection, high grade carotid stenosis can be safely treated with stent-protected percutaneous angioplasty. Microemboli detected by postoperative MRI are infrequently symptomatic.
Assuntos
Angioplastia com Balão , Estenose das Carótidas/terapia , Stents , Adulto , Idoso , Idoso de 80 Anos ou mais , Angiografia Digital , Estenose das Carótidas/diagnóstico por imagem , Embolia/diagnóstico , Endarterectomia das Carótidas , Feminino , Seguimentos , Humanos , Ataque Isquêmico Transitório/diagnóstico , Ataque Isquêmico Transitório/etiologia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Minimamente Invasivos , Complicações Pós-Operatórias/diagnóstico , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/etiologia , Fatores de Tempo , Tomografia Computadorizada por Raios X , Ultrassonografia Doppler DuplaRESUMO
A new group of nitrogen-fixing Azospirillum sp. bacteria was isolated from the roots of the C4-gramineous plant Miscanthus. Polyphasic taxonomy was performed, including auxanography using API galleries, physiological tests and 16S rRNA sequence comparison. The ability of the isolates to fix dinitrogen was evaluated by amplification of the nifD gene, immunodetection of the dinitrogenase reductase and acetylene-reduction assay. On the basis of these results, the nitrogen-fixing isolates represent a new species within the genus Azospirillum. Its closest phylogenetic neighbours, as deduced by 16S rDNA-based analysis, are Azospirillum lipoferum, Azospirillum largimobile and Azospirillum brasilense with 96.6, 96.6 and 95.9% sequence similarity, respectively. Two 16S rRNA-targeting oligonucleotide probes were developed which differentiate the new species from the other Azospirillum species by whole-cell fluorescence hybridization. Strains of the new species are curved rods or S-shaped, 1.0-1.5 microm in width and 2,0-3.0 microm in length, Gram-negative and motile with a single polar flagellum. Optimum growth occurs at 30 degrees C and at pH values between 6.0 and 7.0. No growth takes place at 37 degrees C. They have a respiratory type of metabolism, grow well on arabinose, D-fructose, gluconate, glucose, glycerol, malate, mannitol and sorbitol. They differ from A. largimobile and A. lipoferum by their inability to use N-acetylglucosamine and D-ribose, from A. lipoferum by their ability to grow without biotin supplementation and from A. brasilense by their growth with D-mannitol and D-sorbitol as sole carbon sources. Nitrogen fixation occurs in microaerobic nitrogen-limited conditions. For this species, the name Azospirillum doebereinerae sp. nov. is suggested, with strain GSF71T as the type strain (= DSM 13131T; reference strain Ma4 = DSM 13400). Its G+C content is 70.7 mol%.
Assuntos
Azospirillum/classificação , Fixação de Nitrogênio , Poaceae/microbiologia , Azospirillum/genética , Azospirillum/isolamento & purificação , Azospirillum/fisiologia , Composição de Bases , DNA Bacteriano/química , DNA Bacteriano/genética , DNA Ribossômico/química , DNA Ribossômico/genética , Hibridização in Situ Fluorescente , Dados de Sequência Molecular , Fixação de Nitrogênio/genética , Sondas de Oligonucleotídeos , Fenótipo , Filogenia , Raízes de Plantas/microbiologia , RNA Ribossômico 16S/genética , Análise de Sequência de DNARESUMO
BACKGROUND: Keratins are members of a diverse group of tissue-specific cytoskeletal components known as intermediate filaments. Regulation of the structure and intracellular distribution of intermediate filaments is known to be related to the phosphorylation state of their structural subunits. It also is known that disruption of the keratin filaments of hepatocytes in response to chronic ethanol ingestion is characteristic of alcoholic liver disease. METHODS: To characterize the mechanism of ethanol-induced keratin filament reorganization and dephosphorylation, cells were grown in culture with and without ethanol, and then were treated at the end of the incubation period for 1 hr with either 8-bromo-adenosine 3':5'-cyclic monophosphate (8Br), water-soluble forskolin (ws-forskolin), H-89 diHCL, or okadaic acid. Morphology of the cells was examined by immunofluorescence microscopy, and keratin phosphorylation levels were determined by analysis of 32p labeling. RESULTS: We found that treatment of hepatoma cells with 300 mM ethanol results in disruption and aggregation of the keratin network in the vicinity of the nucleus as well as a hypophosphorylation of keratin subunits from ethanol-treated cells compared with non-ethanol-treated controls. 8Br and ws-forskolin treatment of ethanol groups restored keratin phosphorylation to control levels and reversed the ethanol-induced aggregation of keratin filaments. When H-89, an inhibitor of A-kinase, was added to control cells, keratin filament disorganization and dephosphorylation was observed. H-89 produced only a slight additional decrease in keratin phosphorylation in ethanol-treated cells, with no change in keratin distribution. Okadaic acid treatment of control cells produced hyperphosphorylation and filament network disruption, whereas in ethanol groups a reversal of the ethanol-mediated hypophosphorylation was observed but without reversal of the keratin filament aggregation. CONCLUSIONS: These results suggest that site-specific phosphorylation of keratin filaments is important in maintaining their integrity and that activation of the A-kinase system can antagonize the effects of ethanol, whereas its inhibition results in filament dephosphorylation and reorganization, mimicking effects of ethanol treatment.
Assuntos
Depressores do Sistema Nervoso Central/farmacologia , Proteínas Quinases Dependentes de AMP Cíclico/efeitos dos fármacos , Etanol/farmacologia , Filamentos Intermediários/efeitos dos fármacos , Queratinas/efeitos dos fármacos , Sulfonamidas , Animais , Carcinoma Hepatocelular/ultraestrutura , Inibidores Enzimáticos/farmacologia , Hepatócitos/efeitos dos fármacos , Hepatócitos/ultraestrutura , Filamentos Intermediários/ultraestrutura , Isoquinolinas/farmacologia , Queratinas/ultraestrutura , Fosforilação/efeitos dos fármacos , Ratos , Células Tumorais Cultivadas/efeitos dos fármacosAssuntos
Córtex Cerebral/patologia , Córtex Cerebral/fisiopatologia , Doenças Desmielinizantes/etiologia , Doenças Desmielinizantes/patologia , Encefalomielite/etiologia , Encefalomielite/patologia , Histiocitose de Células não Langerhans/complicações , Histiocitose de Células não Langerhans/patologia , Adulto , Córtex Cerebral/efeitos dos fármacos , Doenças Desmielinizantes/tratamento farmacológico , Progressão da Doença , Encefalomielite/tratamento farmacológico , Feminino , Histiocitose de Células não Langerhans/tratamento farmacológico , Humanos , Esclerose Múltipla/tratamento farmacológico , Esclerose Múltipla/etiologia , Esclerose Múltipla/patologia , Resultado do TratamentoRESUMO
Hypoglycaemia is presumed to be the cause of death in about 3% of insulin-treated diabetic patients. Some of these patients suffer from hypoglycaemic brain damage, but the majority have no evident brain damage and are supposed to have died from other causes such as a cardiac arrhythmia. The putative mechanism is a hypoglycaemia-induced prolongation of the QT interval which increases the risk of malignant ventricular tachycardia. The aim of the present study was to examine the electrocardiogram during and after hypoglycaemia in healthy men. To that end, hypoglycaemia was induced by an intravenous infusion of insulin (2.5 mU kg-1 min-1) in 10 healthy men to reach a venous blood glucose level of 2.1 +/- 0.3 mmol l-1 for 65 +/- 9 min. Before hypoglycaemia, after 20 and 50 min of hypoglycaemia and 20 and 45 min after normalization of the blood glucose, the QT interval was measured by a ruler and corrected for the heart rate. Results are given as mean +/- SD and comparisons were made with an ANOVA, except for symptom scores and plasma adrenaline where non-parametric tests were used. When this indicated significance, further analysis was performed with a two-tailed t-test. During hypoglycaemia the corrected QT interval increased from 380 +/- 20 ms1/2 to 440 +/- 30 ms1/2 (P < 0.001), and the amplitude of the T wave decreased (P = 0.002). The serum potassium level decreased from 4.3 +/- 0.3 mmol l-1 to 3.5 +/- 0.2 mmol l-1 (P < 0.001) and the plasma adrenaline concentration increased from 0.20 +/- 0.04 nmol l-1 to 2.46 +/- 2.58 nmol l-1 (P < 0.01). The results of this study confirm that a prolongation of the QT interval occurs during hypoglycaemia, but the significance of this finding still has to be proven.
Assuntos
Eletrocardiografia , Hipoglicemia/fisiopatologia , Contração Miocárdica/fisiologia , Adulto , Gasometria , Glicemia/análise , Cálcio/sangue , Epinefrina/sangue , Glucose/administração & dosagem , Frequência Cardíaca/fisiologia , Humanos , Concentração de Íons de Hidrogênio , Hipoglicemia/induzido quimicamente , Infusões Intravenosas , Insulina/administração & dosagem , Masculino , Potássio/sangueRESUMO
PURPOSE: Our objective was to evaluate the sensitivity of transcranial Doppler (TCD) sonographic monitoring during permanent balloon occlusion of the internal carotid artery (ICA) in predicting hemodynamic ischemia. METHODS: Thirty-two consecutive patients underwent controlled therapeutic balloon occlusion of the ICA. Selection criteria included assessment of the circle of Willis by compression angiography, clinical tolerance during a 20-minute test occlusion, and TCD monitoring of the ipsilateral middle cerebral artery. The mean blood flow velocity (MBFV) (n = 32) and pulsatility index (PI) (n = 28) were recorded. In 25 patients, MBFV changes upon motor stimulation were recorded before and after ICA occlusion. RESULTS: Twenty-eight (88%) of the patients had no complications. Three patients suffered delayed symptoms 30 minutes to 20 hours after balloon detachment. Two of these patients recovered spontaneously within 1 day, the other improved after extracranial/intracranial (EC/IC) bypass surgery. One patient, who did not tolerate the test occlusion, suffered a hemodynamic stroke despite EC/IC bypass before permanent balloon occlusion. No embolic complications occurred. The mean MBFV reduction was 20% (range, 0% to 55%); the mean PI reduction was 20% (range, 0% to 56%). No complications occurred in patients who had mild MBFV and PI reduction (30% or less, n = 21). All three patients with severe MBFV or PI reduction (> 50%) had neurologic symptoms. Among those with moderate MBFV or PI reduction (30% to 50%, n = 8), symptoms developed in only one patient who had moderate reduction of both MBFV (33%) and PI (38%). Motor vasoreactivity showed wide variation and was markedly reduced in two symptomatic patients. CONCLUSION: TCD monitoring reflects changes in cerebral hemodynamics after therapeutic balloon occlusion of the ICA. MBFV and PI reductions under 30% are highly predictive of clinical tolerance. A reduction of more than 50% may be a critical threshold for the occurrence of symptoms; in such cases, EC/IC bypass should be considered before proceeding with permanent balloon occlusion.
Assuntos
Isquemia Encefálica/diagnóstico por imagem , Isquemia Encefálica/etiologia , Doenças das Artérias Carótidas/terapia , Cateterismo/efeitos adversos , Embolização Terapêutica/efeitos adversos , Monitorização Fisiológica/métodos , Ultrassonografia Doppler Transcraniana , Adolescente , Adulto , Idoso , Artéria Carótida Interna , Circulação Cerebrovascular/fisiologia , Criança , Embolização Terapêutica/métodos , Feminino , Previsões , Hemodinâmica , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
In a 71-year-old woman with macroglossia and heart failure, a monoclonal protein (kappa-light chains) was found in the serum. Congestive heart failure was diagnosed on the basis of heart catheterization and echocardiography. The tongue biopsy showed numerous amyloid fibrils, and plasmacytosis was present in the bone marrow. All these findings indicated a restrictive cardiomyopathy as part of a primary systemic amyloidosis.
Assuntos
Amiloide/sangue , Amiloidose/diagnóstico , Cardiomiopatia Restritiva/diagnóstico , Idoso , Amiloidose/patologia , Biópsia , Cardiomiopatia Restritiva/patologia , Ecocardiografia , Feminino , Humanos , Cadeias Leves de Imunoglobulina/sangue , Cadeias kappa de Imunoglobulina/sangue , Miocárdio/patologia , Glândula Submandibular/patologia , Língua/patologiaRESUMO
In pancreatic beta-cells, calcium is required for insulin secretion, but can also stimulate gene transcription. High potassium-induced membrane depolarization and calcium influx have previously been shown to activate kinases that phosphorylate and thereby activate the transcription factor cAMP response element (CRE-binding protein (CREB) binding to CREs. It is unknown, however, whether hormones and neurotransmitters can activate this mechanism. Arginine vasopressin (AVP), bombesin, and acetylcholine potentiate glucose-induced insulin secretion and are known to raise cytosolic calcium levels through binding to cell surface receptors that activate phospholipase C. The effect of AVP on CRE-directed transcription was examined in the beta-cell line HIT. AVP (0.1-100 nM) stimulated gene transcription after transient transfection of a reporter gene that was placed under the transcriptional control of a CRE. This effect was inhibited by a vasopressin V1 receptor antagonist and depended on calcium influx and calcineurin phosphatase activity. By immunoblots with antiphospho-CREB antibodies and by using a Gal4-CREB fusion protein, it was shown that AVP induces the phosphorylation and activation of CREB. Like AVP, bombesin (100 nM) and the muscarinic agonist carbachol (200 microM) stimulated CRE-mediated transcription. These results show that calcium-mediating insulin secretagogues can activate CREB/CRE-directed transcription in HIT cells, offering a mechanism by which these secretagogues could produce long term effects on beta-cell function, changing the pattern of gene expression.
Assuntos
Cálcio/metabolismo , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/fisiologia , Insulina/metabolismo , Ilhotas Pancreáticas/fisiologia , Transcrição Gênica , Animais , Arginina Vasopressina/farmacologia , Transporte Biológico , Cálcio/fisiologia , Linhagem Celular , Cricetinae , Ciclosporina/farmacologia , Secreção de Insulina , Ilhotas Pancreáticas/citologia , Fosforilação/efeitos dos fármacos , Tacrolimo/farmacologia , Transcrição Gênica/efeitos dos fármacosRESUMO
Gliomas (n = 44) and meningiomas (n = 24) of different grades of malignancy were analysed for allele losses at loci on chromosomes 10, 13, 17 and 22. Deletions of genetic material on these chromosomes occurred in gliomas without being restricted to any histological entity. The frequency of chromosome-10-specific allele losses increased significantly with the age of the patients and with the grade of malignancy of the tumours. Deletions of chromosome 10 material were associated with a poor prognosis. The glioblastomas of patients aged over 70 years lacked the loss of the entire chromosome 10, even in tumours with EGFR gene amplification. Deletions at loci of chromosomes 13, 17 and 22 were observed in 18-32% of all gliomas, independent of grade of malignancy, patients' age, EGFR gene amplification and clinical course. Only chromosome-22-specific allele losses were found preferentially in gliomas of female patients. Loss of chromosome 22 alleles in 44% was the only mutation detected in meningiomas. This occurred independently of grade of malignancy and biological factors.
Assuntos
Neoplasias Encefálicas/genética , Cromossomos Humanos Par 10 , Cromossomos Humanos Par 9 , Glioma/genética , Neoplasias Meníngeas/genética , Meningioma/genética , Adolescente , Adulto , Idoso , Alelos , Sequência de Bases , Neoplasias Encefálicas/fisiopatologia , Criança , Pré-Escolar , Deleção Cromossômica , Receptores ErbB/genética , Feminino , Glioma/fisiopatologia , Humanos , Masculino , Neoplasias Meníngeas/fisiopatologia , Meningioma/fisiopatologia , Pessoa de Meia-Idade , Dados de Sequência Molecular , MutaçãoRESUMO
The cAMP response element (CRE)-binding transcription factor CREB can mediate induction of gene transcription in response to calcium as well as to cAMP. Since the rat insulin I gene 5'-flanking region contains a CRE with an octamer-like motif (TGACGTCC), CREB binding and cAMP/calcium responsiveness of the insulin CRE were investigated. In an electrophoretic mobility shift assay and in Southwestern blot experiments, bacterially expressed recombinant CREB bound to the insulin CRE as it did to the rat glucagon and rat somatostatin gene CREs. However, in nuclear extracts of the pancreatic islet cell line HIT, protein complexes binding to the insulin CRE did not contain proteins with CREB-like immunoreactivity, although these bound to the glucagon and somatostatin CREs. When reporter fusion genes were transfected into HIT cells, the isolated insulin CRE increased basal activity and mediated transcriptional activation by cAMP. However, cAMP stimulation of transcription through the insulin CRE was weak when compared with the response through the glucagon and somatostatin CREs. Furthermore, the insulin CRE did not confer responsiveness to membrane depolarization and calcium influx, in contrast to the glucagon and somatostatin CREs. These results demonstrate that the functional properties of the rat insulin I gene CRE are different from those of the rat glucagon and somatostatin CREs which may be explained by a distinct pattern of nuclear protein binding and suggest the existence of post-translational mechanisms that decrease the binding of cellular CREB to the insulin CRE.
Assuntos
AMP Cíclico/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Insulina/genética , Ilhotas Pancreáticas/metabolismo , Ratos/genética , Sequências Reguladoras de Ácido Nucleico , Animais , Southern Blotting , Western Blotting , Cálcio/metabolismo , Núcleo Celular/metabolismo , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/genética , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Glucagon/metabolismo , Potenciais da Membrana , Ligação Proteica , Transdução de Sinais , Somatostatina/metabolismo , Frações Subcelulares/metabolismo , Transcrição GênicaRESUMO
Continuous transcranial Doppler ultrasound (TCD) monitoring of the middle cerebral artery (ACM) is a potent new technique in detecting thromboembolic and haemodynamic complications in interventional neuroradiology. An illustrative case is reported of a 6-year-old boy suffering from right-sided rhabdomyosarcoma of the neck in which permanent balloon occlusion of the right ACI was attempted. During the procedure, repeated severe thromboembolic events with temporary occlusion of the M1 segment of the ACM could be detected by TCD monitoring. Complications could then be avoided by cessation of the undertaking and lysis therapy with urokinase. The report concludes that TCD monitoring during endovascular treatment provides important insight into the thromboembolic pathophysiology, guides management strategies, helps in the avoidance of devastating events and should be performed during all interventional procedures, as well as during balloon occlusion of the ACI.
Assuntos
Doenças Arteriais Cerebrais/diagnóstico por imagem , Embolia e Trombose Intracraniana/diagnóstico por imagem , Ultrassonografia Doppler Transcraniana , Criança , Embolização Terapêutica , Humanos , Masculino , Neoplasias Mandibulares/terapia , Monitorização Fisiológica/métodos , Doenças Musculares/terapia , Músculos Pterigoides , Rabdomiossarcoma/terapia , Neoplasias de Tecidos Moles/terapiaRESUMO
The authors review the therapeutic results of 20 patients (aged 12 months to 30 years, mean age 9 years) with benign pilocytic astrocytoma of the chiasmatic/hypothalamic region, seen at the University Hospital Hamburg-Eppendorf between February 1980 and April 1993. Six patients suffered from neurofibromatosis 1 (NF-1). The patients were divided into two subgroups relative to tumour extension and growth patterns, as revealed by CT scans and/or MR imaging. Fourteen patients revealed a large globular suprasellar tumour extending into the hypothalamus and/or the anterior third ventricle (group A). A suprasellar tumour with optic tract involvement could be identified in six cases (group B). Subtotal (70-90%) resection was achieved in ten tumours (50%), the majority of which were of the large globular type. There were no deaths. Postoperative morbidity was comprised of visual and endocrine impairment in four patients and right hemiparesis and dysphasia in one patient. Radiation therapy was given in nine cases (45%). Three tumours (38%) were reduced in size by irradiation. Tumour progression was seen in seven patients (35%). The presence of young age and NF-1 were predictors of progressive disease in our series. Growth capacity was not related to the extent of cytoreductive surgery.
Assuntos
Astrocitoma/cirurgia , Neoplasias dos Nervos Cranianos/cirurgia , Neoplasias Hipotalâmicas/cirurgia , Quiasma Óptico/cirurgia , Complicações Pós-Operatórias/etiologia , Adolescente , Adulto , Astrocitoma/patologia , Astrocitoma/radioterapia , Biomarcadores Tumorais/análise , Biópsia , Criança , Pré-Escolar , Terapia Combinada , Neoplasias dos Nervos Cranianos/patologia , Neoplasias dos Nervos Cranianos/radioterapia , Feminino , Seguimentos , Humanos , Neoplasias Hipotalâmicas/patologia , Neoplasias Hipotalâmicas/radioterapia , Lactente , Imageamento por Ressonância Magnética , Masculino , Estadiamento de Neoplasias , Neurofibromina 1 , Quiasma Óptico/patologia , Quiasma Óptico/efeitos da radiação , Proteínas/análise , Tomografia Computadorizada por Raios XRESUMO
Because of the generally accepted operability of patients without any age limit nowadays, more information is needed about functional disorders of organs, for example of the lung in old age. The preoperative PaO2 value at rest in 120 patients due to undergo urological operations (average age 77.7 +/- 4.6 years) was determined as 81.81 +/- 8.63 mmHg. The PaO2 values corresponding to age were significantly higher than the reference values in literature. During cholecystectomy the respiratory volume per minute at an FECO2 of 4.5 vol.% was measured as 6.6 +/- 1.41 l/min in 54 patients with an average age of 68.7 +/- 5.8 years. There was no correlation with any anthropometrical data. Considerable fluctuations in the respiratory volume per minute make the measure of FECO2 and PaCO2 necessary. In old age the cerebral blood flow rate depends on PaCO2, so that a normocapnia is of particular importance. Similar results were found in 20 traumatologic patients aged over 80, i.e. there were considerable differences between tabular values and capnometrically controlled respiratory volume per minute. The blood gas values were measured in 50 patients over 65 years old in the immediate postoperative phase of cholecystectomy. Compared with initial values, there was a significant decrease in PaO2 at 5, 15 and 25 minutes after the operation with values at 8.22 +/- 1.83 kPa, 8.24 +/- 1.83 kPa and 8.15 +/- 1.75 kPa. These values were 27% under the preoperative values. No clinically discernible hypoxia occurred. The results support the demand that geriatric patients be given suitable attention and adequate monitoring to avoid complications due to the restricted compensationability of the organs and lungs.
Assuntos
Dióxido de Carbono/fisiologia , Avaliação Geriátrica , Oxigênio/fisiologia , Procedimentos Cirúrgicos Operatórios , Idoso , Idoso de 80 Anos ou mais , Humanos , Pessoa de Meia-Idade , Pressão ParcialRESUMO
Pulmonary emphysema is likely to be the result of elastic tissue digestion by unrestrained elastase activity in the lung. Elastin breakdown by elastases results in the release of soluble elastin fragments (EDP), which may be measured in plasma by an ELISA. Plasma EDP levels measured using an ELISA were determined in the following groups: disease-free children (n = 24), 0.162 +/- 0.082 ng/ml; disease-free adult nonsmokers (n = 114), 1.74 +/- 0.8 ng/ml; smokers (n = 68), 2.76 +/- 4.59 ng/ml; reformed smokers (n = 43), 1.91 +/- 1.14 ng/ml. Adults with established pulmonary emphysema (n = 50), as defined by bullous formation on the chest radiograph, had levels of 50.83 +/- 24.8 ng/ml, significantly higher than the disease-free groups at p < 0.01. Pulmonary emphysema can be reflected by pulmonary function tests, especially those that measure the pulmonary elastic properties, and by computed tomographic (CT) scan percent emphysema score. We therefore examined the relationship of plasma EDP to these other indicators of pulmonary emphysema in a separate group of 26 subjects using elastic recoil measurements (K), and a further group of 30 subjects with CT scan percent emphysema score. A significant correlation of p < 0.001 was shown for plasma EDP and K and a significant correlation of p < 0.01 was shown for plasma EDP and CT scan percent emphysema score, these correlations suggesting that plasma EDP levels are indicators of the loss of pulmonary distensibility and of mild to moderate pulmonary emphysema. These findings suggest that pulmonary emphysema is characterized by active elastin breakdown.
Assuntos
Elastina/metabolismo , Ensaio de Imunoadsorção Enzimática/normas , Fragmentos de Peptídeos/sangue , Enfisema Pulmonar/diagnóstico , Adulto , Idoso , Criança , Pré-Escolar , Estudos de Avaliação como Assunto , Feminino , Humanos , Complacência Pulmonar , Masculino , Pessoa de Meia-Idade , Enfisema Pulmonar/enzimologia , Enfisema Pulmonar/epidemiologia , Valores de Referência , Testes de Função Respiratória/normas , Sensibilidade e Especificidade , Fumar/sangue , Tomografia Computadorizada por Raios X/normasRESUMO
In the differential diagnosis of endocrine symptoms, the autosomal dominant multiple endocrine neoplasia (MEN) syndromes are rare but important. We found seven index cases of MEN-I in 176 patients with adenomas of the anterior pituitary and 26 patients with primary hyperparathyroidism. Of 23 cases of medullary thyroid carcinoma and eight cases of pheochromocytoma, 14 patients are classified as MEN-IIa and one as MEN-IIb. Family screening identified six MEN-I and seven MEN-II cases among 32 individuals examined. Because of autosomal dominant inheritance and sometimes-delayed manifestation of the complete syndrome, screening of healthy and affected family members should be repeated at least every other year.