RESUMO
AIMS/HYPOTHESIS: The carcino-embryonic antigen-related cell adhesion molecule (CEACAM)2 is produced in many feeding control centres in the brain, but not in peripheral insulin-targeted tissues. Global Ceacam2 null mutation causes insulin resistance and obesity resulting from hyperphagia and hypometabolism in female Ceacam2 homozygous null mutant mice (Cc2 [also known as Ceacam2](-/-)) mice. Because male mice are not obese, the current study examined their metabolic phenotype. METHODS: The phenotype of male Cc2(-/-) mice was characterised by body fat composition, indirect calorimetry, hyperinsulinaemic-euglycaemic clamp analysis and direct recording of sympathetic nerve activity. RESULTS: Despite hyperphagia, total fat mass was reduced, owing to the hypermetabolic state in male Cc2(-/-) mice. In contrast to females, male mice also exhibited insulin sensitivity with elevated ß-oxidation in skeletal muscle, which is likely to offset the effects of increased food intake. Males and females had increased brown adipogenesis. However, only males had increased activation of sympathetic tone regulation of adipose tissue and increased spontaneous activity. The mechanisms underlying sexual dimorphism in energy balance with the loss of Ceacam2 remain unknown. CONCLUSIONS/INTERPRETATION: These studies identified a novel role for CEACAM2 in the regulation of metabolic rate and insulin sensitivity via effects on brown adipogenesis, sympathetic nervous outflow to brown adipose tissue, spontaneous activity and energy expenditure in skeletal muscle.
Assuntos
Tecido Adiposo Marrom/metabolismo , Metabolismo Energético , Glicoproteínas/metabolismo , Hiperfagia/metabolismo , Resistência à Insulina , Músculo Esquelético/metabolismo , Adipogenia , Tecido Adiposo Marrom/inervação , Tecido Adiposo Marrom/patologia , Adiposidade , Animais , Moléculas de Adesão Celular , Feminino , Glicoproteínas/genética , Hiperfagia/genética , Hiperfagia/patologia , Hiperfagia/fisiopatologia , Hipotálamo/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Mutantes , RNA Mensageiro/metabolismo , Caracteres Sexuais , Sistema Nervoso Simpático/fisiopatologia , Transmissão SinápticaRESUMO
BACKGROUND AND PURPOSE: Coronavirus disease 2019 (COVID-19) appears to be an independent risk factor for stroke. We hypothesize that patients who develop stroke while hospitalized for severe COVID-19 will have higher inflammatory markers and distinct stroke imaging patterns compared with patients positive for COVID-19 with out-of-hospital stroke onset and milder or no COVID-19 symptoms. MATERIALS AND METHODS: This is a retrospective case series of patients positive for COVID-19 on polymerase chain reaction testing with imaging-confirmed stroke treated within a large health care network in New York City and Long Island between March 14 and April 26, 2020. Clinical and laboratory data collected retrospectively included complete blood counts and creatinine, alanine aminotransferase, lactate dehydrogenase, C-reactive protein, ferritin, and D-dimer levels. All CT and MR imaging studies were independently reviewed by 2 neuroradiologists who recorded stroke subtype and patterns of infarction and intracranial hemorrhage. RESULTS: Compared with patients with COVID-19 with outside-of-hospital stroke onset and milder or no COVID-19 symptoms (n = 45, 52.3%), patients with stroke already hospitalized for severe COVID-19 (n = 41, 47.7%) had significantly more frequent infarctions (95.1% versus 73.3%, P = .006), with multivascular distributions (56.4% versus 33.3%, P = .022) and associated hemorrhage (31.7% versus 4.4%, P = .001). Patients with stroke admitted with more severe COVID-19 had significantly higher C-reactive protein and ferritin levels, elevated D-dimer levels, and more frequent lymphopenia and renal and hepatic injury (all, P < .003). CONCLUSIONS: Patients with stroke hospitalized with severe COVID-19 are characterized by higher inflammatory, coagulopathy, and tissue-damage biomarkers, supporting proposed pathogenic mechanisms of hyperinflammation activating a prothrombotic state. Cautious balancing of thrombosis and the risk of hemorrhagic transformation is warranted when considering anticoagulation.
Assuntos
Biomarcadores , COVID-19/complicações , Acidente Vascular Cerebral/complicações , Adulto , Idoso , Idoso de 80 Anos ou mais , Transtornos da Coagulação Sanguínea/etiologia , COVID-19/diagnóstico por imagem , Infarto Cerebral/complicações , Infarto Cerebral/diagnóstico por imagem , Feminino , Hospitalização , Humanos , Hepatopatias/etiologia , Linfopenia/sangue , Linfopenia/etiologia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Estudos Retrospectivos , Acidente Vascular Cerebral/diagnóstico por imagem , Trombose/complicações , Tomografia Computadorizada por Raios XRESUMO
AIM: We investigated the gender-specific control of cardiovascular (CV) risk factors and subclinical vascular lesions in a founder population in Italy. METHODS AND RESULTS: 6148 subjects were enrolled (aged 14-102 years) from four towns. Hypertension (HT), diabetes mellitus (DM) and dyslipidemia (LIP) were defined in accordance with guidelines. A self-reported diagnosis defined awareness of these conditions, and the current use of specific medications as treatment. Prevalence was HT 29.2%, DM 4.8%, LIP 44.1% and was higher in men than in women. Disease prevalence increased with age for every CV risk factor. Men were less likely than women to take anti-HT drugs and to reach BP control (9.9% vs. 16%). Only 17.6% of HT > 65 years had a BP < or =140/90 mmHg, though 48.5% were treated. The use of statins was very low (<1/3 of eligible subjects > 65 years, those with the highest treatment rate). The ratio of control-to-treated HT was lower in subjects with, than in those without, thicker carotid arteries (31.5% vs. 38.8%, p < 0.05) or stiffer aortas (26.0% vs. 40.0%, p < 0.05) or carotid plaques (26.3% vs. 41.1%, p<0.05). CONCLUSION: A large number of subjects at high CV risk are not treated and the management of subclinical vascular lesions is far from optimal.
Assuntos
Conscientização , Doenças Cardiovasculares/prevenção & controle , Diabetes Mellitus/tratamento farmacológico , Dislipidemias/tratamento farmacológico , Conhecimentos, Atitudes e Prática em Saúde , Hipertensão/tratamento farmacológico , Síndrome Metabólica/tratamento farmacológico , Obesidade/tratamento farmacológico , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Anti-Hipertensivos/uso terapêutico , Aterosclerose/complicações , Aterosclerose/tratamento farmacológico , Aterosclerose/epidemiologia , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Diabetes Mellitus/epidemiologia , Uso de Medicamentos , Dislipidemias/complicações , Dislipidemias/epidemiologia , Feminino , Efeito Fundador , Fidelidade a Diretrizes , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hipertensão/complicações , Hipertensão/epidemiologia , Hipoglicemiantes/uso terapêutico , Itália/epidemiologia , Masculino , Síndrome Metabólica/complicações , Síndrome Metabólica/epidemiologia , Pessoa de Meia-Idade , Obesidade/complicações , Obesidade/epidemiologia , Guias de Prática Clínica como Assunto , Padrões de Prática Médica , Prevalência , Medição de Risco , Fatores de Risco , Fatores Sexuais , Adulto JovemRESUMO
OBJECTIVE: To determine the respective roles of socio-economic status (SES) and ethnicity in the risk of incident metabolic syndrome in middle-aged women. DESIGN AND PARTICIPANTS: A total of 3302 pre- and peri-menopausal women, not receiving hormone therapy at baseline, took part in the Study of Women's Health Across the Nation, a multi-site, community-based, longitudinal study of the menopausal transition. The main outcome measures were to ascertain the prevalence of the metabolic syndrome and the incidence of the metabolic syndrome over 5 years of follow-up. RESULTS: At baseline, the prevalence of the metabolic syndrome was 21% (n = 673). Among 2512 women without metabolic syndrome at baseline, 12.8% (n = 321) developed the metabolic syndrome during 5 years of follow-up. Both ethnicity and SES were significant univariate predictors of incident metabolic syndrome. In multivariate logistic regression models that included age at baseline, menopausal status and site, baseline smoking and alcohol consumption at follow-up visit 1, as well as baseline values of each of the components of the metabolic syndrome, only education was an independent predictor of incident metabolic syndrome. CONCLUSION: Approximately 13% of peri-menopausal women developed the metabolic syndrome during the 5-year follow-up period. Education, but not ethnicity, was an independent predictor of incident metabolic syndrome risk.
Assuntos
Menopausa/etnologia , Síndrome Metabólica/etnologia , Grupos Raciais/etnologia , Saúde da Mulher/etnologia , Adulto , Doenças Cardiovasculares/etnologia , Feminino , Humanos , Pessoa de Meia-Idade , Prevalência , Classe Social , Estados Unidos/epidemiologiaRESUMO
Forensic investigation performed on people suspected to be drug abusers covering all Tunisian cities was conducted by monitoring an epidemiological study of human urine samples surveying positive rates of consumption for drugs of abuse. The forensic investigations were conducted on a total of 28,298 arrested individuals suspected to be drug addicts during five years (January 2010-December 2015). An immunoassay screening tests to detect elevated levels of drugs classes in urine samples was performed. These screening assays provide a preliminary qualitative test result. Only positives urine specimens were analyzed with GC-MS for confirmation. Except for cannabis, the results showed insignificant number of positive cases for cocaine, ecstasy (MDMA) and amphetamine consumptions (<1%).
Assuntos
Drogas Ilícitas/urina , Detecção do Abuso de Substâncias/métodos , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Adolescente , Adulto , Distribuição por Idade , Idoso , Feminino , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Imunoensaio , Masculino , Estado Civil/estatística & dados numéricos , Pessoa de Meia-Idade , Distribuição por Sexo , Transtornos Relacionados ao Uso de Substâncias/diagnóstico , Transtornos Relacionados ao Uso de Substâncias/urina , Tunísia/epidemiologia , Adulto JovemRESUMO
IL-2 gene transcription is affected by several nuclear proteins. We asked whether dexamethasone (Dex) and cyclosporin A (CsA) inhibit IL-2 gene transcription by interfering with the activity of nuclear proteins that bind to the IL-2 promoter. Nuclear extracts from primary human T lymphocytes were analyzed by electrophoretic DNA mobility shift assays. Both Dex and CsA inhibited the binding of transcription factors AP-1 and NF-AT, but not of NF-kB and OCT-1/OAF, to their corresponding sites on the IL-2 gene promoter. To correlate changes in nuclear factor binding in vitro with transcriptional activity in vivo and define the structural requirements for IL-2 promoter repression, we used transient DNA transfections. Jurkat cells were transfected with plasmids containing either the intact IL-2 promoter or its AP-1, NF-AT, and NF-kB motifs. Dex inhibited the IL-2 promoter and the AP-1, but not the NF-AT and NF-kB plasmids. In contrast, CsA inhibited the IL-2 promoter and the NF-AT, but not the AP-1 and NF-kB plasmids. These results suggest that in human T lymphocytes both Dex and CsA inhibited IL-2 gene transcription through interference with transcription factors AP-1 and NF-AT. We propose that, while maximum inhibition may involve interaction with both transcription factors, AP-1 is the primary target of Dex.
Assuntos
Proteínas de Ligação a DNA/farmacologia , Glucocorticoides/farmacologia , Interleucina-2/genética , Proteínas Nucleares , Proteínas Proto-Oncogênicas c-jun/farmacologia , Fatores de Transcrição/farmacologia , Ciclosporina/farmacologia , Proteínas de Ligação a DNA/efeitos dos fármacos , Dexametasona/farmacologia , Humanos , Fatores de Transcrição NFATC , Regiões Promotoras Genéticas/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-jun/efeitos dos fármacos , Linfócitos T/fisiologia , Fatores de Transcrição/efeitos dos fármacos , Transcrição Gênica/efeitos dos fármacosRESUMO
OBJECTIVE: To identify risk factors for subclinical hypothyroidism (SCH) (thyroid-stimulating hormone levels >5 mIU/mL) in patients receiving valproate (VPA) therapy. STUDY DESIGN: During a period of 2 years, consecutive patients with epilepsy receiving VPA and a control group of patients with diseases other than epilepsy attending a tertiary care neurology clinic were screened for SCH. The 2 groups were compared. The association between SCH and specific risk factors was investigated with bivariate and multivariate analyses. RESULTS: Thirty-six of 143 patients receiving VPA (25.2%, mean age +/- SD: 8.5 +/- 6.6 years) and none of the 35 control subjects had SCH (P < .001). Predictors of SCH were younger age (OR: 1.15, cutoff age 3.9 years); duration of treatment between 6 and 24 months versus <6 months (OR: 2.98) and >24 months (OR: 2.66); VPA polytherapy with enzyme-inducing agents (OR: 6.08), or polytherapy with non-enzyme-inducing agents (OR: 3.34) compared with VPA monotherapy. Most (88.2%) patients with duration of therapy >2 years were older than 3.9 years. CONCLUSION: Risk factors for SCH were young age, co-medication with antiepileptic drugs, and duration of therapy between 6 and 24 months. Screening patients with these risk factors may be warranted.
Assuntos
Hipotireoidismo/induzido quimicamente , Hipotireoidismo/epidemiologia , Tireotropina/sangue , Ácido Valproico/efeitos adversos , Adolescente , Distribuição por Idade , Estudos de Casos e Controles , Criança , Pré-Escolar , Estudos de Coortes , Relação Dose-Resposta a Droga , Epilepsia/diagnóstico , Epilepsia/tratamento farmacológico , Feminino , Seguimentos , Humanos , Hipotireoidismo/diagnóstico , Incidência , Modelos Logísticos , Masculino , Análise Multivariada , Probabilidade , Valores de Referência , Fatores de Risco , Índice de Gravidade de Doença , Distribuição por Sexo , Testes de Função Tireóidea , Ácido Valproico/uso terapêuticoRESUMO
pp120 (Ceacam 1) undergoes ligand-stimulated phosphorylation by the insulin receptor, but not by the insulin-like growth factor 1 receptor (IGF-1R). This differential phosphorylation is regulated by the C terminus of the beta-subunit of the insulin receptor, the least conserved domain of the two receptors. In the present studies, deletion and site-directed mutagenesis in stably transfected hepatocytes derived from insulin receptor knockout mice (IR(-/-)) revealed that Tyr(1316), which is replaced by the nonphosphorylatable phenylalanine in IGF-1R, regulated the differential phosphorylation of pp120 by the insulin receptor. Similarly, the nonconserved Tyr(1316) residue also regulated the differential effect of pp120 on IGF-1 and insulin mitogenesis, with pp120 downregulating the growth-promoting action of insulin, but not that of IGF-1. Thus, it appears that pp120 phosphorylation by the insulin receptor is required and sufficient to mediate its downregulatory effect on the mitogenic action of insulin. Furthermore, the current studies revealed that the C terminus of the beta-subunit of the insulin receptor contains elements that suppress the mitogenic action of insulin. Because IR(-/-) hepatocytes are derived from liver, an insulin-targeted tissue, our observations have finally resolved the controversy about the role of the least-conserved domain of insulin and IGF-1Rs in mediating the difference in the mitogenic action of their ligands, with IGF-1 being more mitogenic than insulin.
Assuntos
Fator de Crescimento Insulin-Like I/metabolismo , Insulina/metabolismo , Mitógenos/metabolismo , Proteínas Tirosina Quinases/metabolismo , Receptor de Insulina/metabolismo , Tirosina/metabolismo , Animais , Divisão Celular , Linhagem Celular Transformada , Quinase 1 de Adesão Focal , Proteína-Tirosina Quinases de Adesão Focal , Humanos , Insulina/farmacologia , Fator de Crescimento Insulin-Like I/farmacologia , Camundongos , Camundongos Knockout , Mitógenos/farmacologia , Mutagênese Sítio-Dirigida , Fosforilação , Proteínas Tirosina Quinases/genética , Receptor IGF Tipo 1/genética , Receptor IGF Tipo 1/metabolismo , Receptor de Insulina/genética , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/metabolismo , Tirosina/genéticaRESUMO
OBJECTIVES: To assess the bio-equivalence of two citalopram 40 mg tablet formulations (Lecital of the Jordan Sweden Medical and Sterilization Co. (JOSWE) as a test product, and Cipramil of Lundbeck (Denmark) as a reference product), and to develop a new high-performance liquid chromatography (HPLC) method using liquid-liquid extraction followed by addition of acid for the quantification of citalopram in human plasma. METHODS: A single-blind, randomized, single-dose, 2-treatment, 2-period, 2-sequence, crossover bioequivalence study with a 20-day washout period in 24 healthy volunteers. The drug was administered with 240 ml of water after 10-h overnight fasting. After dosing, serial blood samples were collected for a period of 192 h. Plasma harvested from blood was analyzed for citalopram by a novel method using HPLC coupled with an electrochemical detector. The limit of quantitation of citalopram was 1.493 ng/ml. Matrix-based calibration curves were linear over the range 1.493 - 80.640 ng/ml for citalopram. RESULTS: The average bioavailability and pharmacokinetic parameters of the two citalopram tablets were as follows: peak plasma concentration Cmax was 35.0 +/- 10.04 ng/ml and 33.4 +/-7.80 ng/ml for Lecital and Cipramil, respectively. The time to peak plasma concentrations tmax were 3.81 +/- 1.18 and 4.08 +/- 1.54 h, while the plasma half-life (t1/2) values were 54.0 +/- 7.50 and 54.7 +/- 10.6 h. The area under the plasma concentration-time profiles AUCo-t were 1,820 +/- 582 ng x h/ml and 1,660 +/- 510 ng x h/ml, whereas the AUC0-infinity were 2,010 +/- 663 ng x h/ml and 1,850 +/- 577 ng x h/ml for Lecital and Cipramil, respectively. The 90% confidence intervals for test/reference ratio were found within the acceptable limits of 80 - 125%, consequently no significant difference was found between the test and reference. CONCLUSION: Based on the pharmacokinetic and statistical results, it was concluded that Lecital 40 mg tablets of JOSWE is bioequivalent to Cipramil 40 mg tablets of Lundbeck (Denmark).
Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Citalopram/farmacocinética , Inibidores Seletivos de Recaptação de Serotonina/farmacocinética , Administração Oral , Adulto , Análise de Variância , Área Sob a Curva , Disponibilidade Biológica , Citalopram/administração & dosagem , Intervalos de Confiança , Estudos Cross-Over , Estabilidade de Medicamentos , Meia-Vida , Humanos , Masculino , Sensibilidade e Especificidade , Inibidores Seletivos de Recaptação de Serotonina/administração & dosagem , Comprimidos , Equivalência TerapêuticaRESUMO
We have optimized a liposome-based transfection method that mediated highly efficient stable expression of foreign genes in hepatocytes. Moreover, we have observed that the metallothionein 1 promoter in the bovine papilloma virus-based expression vector drove the highest expression of foreign genes in hepatocytes as compared with the cytomegalovirus and the human polypeptide chain elongation factor 1alpha (EF-1alpha) promoters in the pcDNA 3-based expression vector. The cytomegalovirus promoter failed to yield significant expression in these cells. Furthermore, expression of foreign genes persisted up to at least 15 passages when expression was under the control of either the EF-1alpha or the metallothionein 1 promoter. Thus, these two promoters led to comparable stability of foreign genes in hepatocytes, with the metallothionein 1 promoter yielding a higher level of expression of foreign genes in these cells.
Assuntos
Expressão Gênica/genética , Vetores Genéticos/genética , Hidroxiesteroide Desidrogenases , Fígado/metabolismo , Glicoproteínas de Membrana , Transfecção/métodos , Animais , Papillomavirus Bovino 1/genética , Proteínas de Transporte/genética , Proteínas de Transporte/metabolismo , Células Cultivadas , Células Clonais/metabolismo , Citomegalovirus/genética , Lipossomos/metabolismo , Metalotioneína/genética , Camundongos , Camundongos Knockout , Proteínas Nucleares/genética , Regiões Promotoras Genéticas , Vírus 40 dos Símios/genética , Fatores de Transcrição/genéticaRESUMO
The existence and specificity of a characteristic behavioral syndrome among patients with temporal lobe epilepsy (TLE) remains controversial. The behavioral pattern of many epilepsy patients differs from that of age-, sex-, and socioeconomic-matched control subjects. Patients with TLE and other forms of epilepsy can experience changes in cognitive function, personality, affect, and drive-related behavior (e.g., libido, aggression). Biologic factors (e.g., underlying brain pathology, epileptogenic process, localization and lateralization, recurrent seizures, family history), antiepileptic drugs, and psychosocial factors interact pathogenically. Their roles vary among patients and among different neurobehavioral disorders. Behavioral changes occur in some epilepsy patients. However, the question of whether specific behavioral changes occur with different seizure types or epilepsy syndromes remains unanswered. For example, behavioral changes can occur in patients with absence epilepsy, juvenile myoclonic epilepsy, frontal lobe epilepsy, and tonic-clonic seizures. Many of these behavioral changes overlap with features of the purported TLE syndrome. We lack a clear delineation of the spectrum, frequency, and severity of changes in well-characterized partial and primary generalized epilepsy syndromes. Furthermore, the relative roles and the interplay among pathogenic factors remain poorly defined.
Assuntos
Epilepsia do Lobo Temporal/psicologia , Transtornos da Personalidade/psicologia , Epilepsia do Lobo Temporal/complicações , Humanos , Transtornos da Personalidade/complicações , SíndromeRESUMO
The synthesis of fully deuterated amphetamine (phenyl-2-aminopropane-d11) in which 11 deuterium atoms are bonded to carbons and two other highly deuterated analogues is described. Their toxicities and in vivo spontaneous locomotor activities in mice were examined and compared with that of the parent protioamphetamine. A significant reduction in toxicities and a decrease in spontaneous locomotor activity were observed for these highly enriched deuterated analogues, as compared to protioamphetamine.
Assuntos
Anfetamina/farmacologia , Deutério , Atividade Motora/efeitos dos fármacos , Anfetamina/síntese química , Anfetamina/toxicidade , Animais , Marcação por Isótopo , Dose Letal Mediana , Masculino , CamundongosRESUMO
Previous studies have established that the cell-cell adhesion molecule-1 (CEACAM1, previously known as C-CAM1) functions as a tumor suppressor in prostate cancer and is involved in the regulation of prostate growth and differentiation. However, the molecular mechanism that modulates CEACAM1 expression in the prostate is not well defined. Since the growth of prostate epithelial cells is androgen-regulated, we investigated the effects of androgen and the androgen receptor (AR) on CEACAM1 expression. Transient transfection experiments showed that the AR can enhance the Ceacam1 promoter activity in a ligand-dependent manner and that the regulatory element resides within a relatively short (-249 to -194 bp) segment of the 5'-flanking region of the Ceacam1 gene. This androgen regulation is likely through direct AR-promoter binding because a mutant AR defective in DNA binding failed to upregulate reporter gene expression. Furthermore, electrophoretic mobility shift assays demonstrated that the AR specifically binds to this sequence, and mutation analysis of the potential ARE sequences revealed a region within the sequence that was required for the AR to activate the Ceacam1 gene. Therefore, the regulation of Ceacam1 gene expression by androgen may be one of the mechanisms by which androgen regulates prostatic function.
Assuntos
Androgênios/fisiologia , Antígenos CD/genética , Antígenos de Diferenciação/genética , Regulação da Expressão Gênica/efeitos dos fármacos , Animais , Antígenos CD/efeitos dos fármacos , Antígenos de Diferenciação/efeitos dos fármacos , Sítios de Ligação/genética , Moléculas de Adesão Celular , Proteínas de Ligação a DNA/fisiologia , Células HeLa , Humanos , Mutagênese Sítio-Dirigida , Regiões Promotoras Genéticas/efeitos dos fármacos , Ratos , Receptores Androgênicos/genética , Receptores Androgênicos/metabolismo , Receptores Androgênicos/fisiologia , TransfecçãoRESUMO
We report on a 12-year-old girl who presented with generalized enamel hypoplasia, cataracts, and enlargement of the cerebral ventricles secondary to aqueductal stenosis. Previously described syndromes of enamel defects with or without cataracts were excluded on the basis of clinical criteria and appearance of the dentition. Metabolic conditions which could have caused cataracts were excluded clinically and by biochemical tests. The combination of signs in this patient may represent a new syndrome.
Assuntos
Catarata/etiologia , Aqueduto do Mesencéfalo/anormalidades , Hipoplasia do Esmalte Dentário/etiologia , Anormalidades Múltiplas , Ventrículos Cerebrais/anormalidades , Criança , Constrição Patológica/embriologia , Feminino , Humanos , Síndrome , Dente Impactado/etiologiaRESUMO
Four sibs, three males and one female, had microcephaly, hypergonadotropic hypogonadism, short stature, and multiple congenital anomalies. They had five normal sibs and consanguineous parents. Findings in the affected sibs also included a narrow forehead, synophrys, micrognathia, abnormally folded pinnae, early loss of teeth in three, cubitus valgus in two, genu valgum, gynecomastia, and undescended testes in one. All sibs had normal chromosomes. Results of tests for growth hormone release and adrenocortical function were normal. Luteinizing hormone releasing hormone (LHRH) and human chorionic gonadotropin (hCG) stimulation tests were consistent with primary gonadal failure. Testicular biopsy, performed on two affected males, was normal in one and showed focal atrophy with decreased spermatogenesis in the other. The patients manifest a phenotype different from all other known types of hypergonadotropic hypogonadism and appear to represent a new MCA/MR syndrome.
Assuntos
Transtornos do Crescimento/complicações , Hipogonadismo/complicações , Microcefalia/complicações , Hormônio Adrenocorticotrópico , Adulto , Pré-Escolar , Gonadotropina Coriônica , Feminino , Genes Recessivos , Hormônio Liberador de Gonadotropina , Transtornos do Crescimento/genética , Hormônio do Crescimento , Humanos , Hipogonadismo/genética , Deficiência Intelectual/complicações , Deficiência Intelectual/genética , Masculino , Microcefalia/genética , Linhagem , Síndrome , Hormônio Liberador de TireotropinaRESUMO
Syncope due to atrioventricular block may occur as a result of a cardiac vasodepressor reflex. This article reports a case of syncope in a 58-year-old man with high-grade atrioventricular block documented by ambulatory ECG monitoring at home. What makes this case unusual is that the patient's principal diagnosis was noncardiac.
Assuntos
Bloqueio Cardíaco/diagnóstico , Síncope Vasovagal/diagnóstico , Diagnóstico Diferencial , Eletrocardiografia Ambulatorial , Humanos , Masculino , Pessoa de Meia-Idade , Embolia Pulmonar/diagnósticoRESUMO
The electrocardiographic effects isometric (handgrip) and combined isometric-dynamic (treadmill-plus-brief-case) exercise were evaluated and compared to a submaximal treadmill stress test in 140 patients with known or suspected coronary artery disease. Only 3 of 90 patients developed ischemic ST changes during handgrip, as opposed to 25 positive treadmill tests (p less than 0.01). Of 19 of 50 patients who were positive during the standard treadmill test, only 17 showed positive findings during the combined treadmill-briefcase test. Analysis of hemodynamic responses showed significant (p less than 0.01) differences between the handgrip and treadmill tests in terms of heart rate response (control 83 plus or minus beats/minute, handgrip 105 plus or minus 4, treadmill 151 plus or minus 6), diastolic blood pressure (control 80 plus or minus 2 mm Hg, isometric 93 plus or minus 3, treadmill 81 plus or minus 3) and heart rate-systolic pressure product (control 9940 plus or minus 564 units, handgrip 15022 plus or minus 779, treadmill 22270 plus or minus 1147). In comparing treadmill and combined treadmill-briefcase tests, significant differences were seen in systolic blood pressure (control 114 plus or minus 2 mm Hg, treadmill 143 plus or minus 3, briefcase 155 plus or minus 3), diastolic blood pressure (control 83 plus or minus 2 mm Hg, treadmill 82 plus or minus 2, briefcase 89 plus or minus 2) and rate-pressure product (control 10134 plus or minus 373, treadmill 19624 plus or minus 777, briefcase 21201 plus or minus 798). Isometric exercise alone is much less likely to produce myocardial ischemia than vigorous dynamic exercise. Higher arterial diastolic (coronary perfusion) pressure may retard the development of myocardial ischemia during isometric or combined isometricdynamic exercise in coronary patients.
Assuntos
Circulação Coronária , Doença das Coronárias/fisiopatologia , Teste de Esforço , Hemodinâmica , Esforço Físico , Angina Pectoris/diagnóstico , Arritmias Cardíacas/diagnóstico , Pressão Sanguínea , Débito Cardíaco , Angiografia Coronária , Eletrocardiografia , Mãos , Frequência Cardíaca , Humanos , Masculino , Pessoa de Meia-Idade , Contração Muscular , Estatística como AssuntoRESUMO
Amino-oligopeptidase (AOP, aminopeptidase N), a major glycoprotein hydrolase in intestinal and kidney brush border membranes, plays a crucial role in digesting peptide nutrients and salvaging filtered peptides. The molecular structure of rat intestinal and kidney AOP was compared for normal Wistar and congenitally diabetic BB Wistar (BBd) rats. Brush border membranes were isolated, solubilized with Triton X-100, and the AOP specifically immunoprecipitated with polyvalent rabbit antiserum and analyzed on 7% sodium dodecyl sulfate (SDS)-acrylamide electrophoresis. While the specific hydrolytic activity was maintained, BBd rats displayed an altered migration of AOP on SDS gels. Intestinal AOP migrated as a smaller species (130 kd) in the BBd than in the normal Wistar (135 to 140 kd). In some BBd rats, additional intestinal AOP species were observed (a 130- to 135-kd doublet or a 125-, 130-, or 135-kd triplet). Kidney AOP migrated as a broader band (125 to 140 kd) than intestine for all rat groups, probably due to carbohydrate chain heterogeneity, and was approximately 5 kd smaller in the BBd rat than in the normal Wistar. In contrast, no mass change was found in diabetes induced by streptozotocin (STZ). The altered intestinal AOP in the BBd rat was present when first inserted into the brush border membrane (6 hours after intraperitoneal [35S]methionine labeling), and hence was not due to nonenzymatic glycosylation (NEG). Abnormal intestinal and kidney AOP structure appeared in early diabetes, irrespective of high plasma glucose levels or ketoacidosis, and was reversed following evolution of the diabetes under prolonged (21 to 120 days) insulin treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Acidose/metabolismo , Aminopeptidases/análise , Antígenos CD13 , Diabetes Mellitus/enzimologia , Intestinos/enzimologia , Rim/enzimologia , Aminopeptidases/química , Animais , Glicemia/análise , Carboidratos/química , Eletroforese , Insulina/farmacologia , Microvilosidades/enzimologia , Ratos , Ratos EndogâmicosRESUMO
OBJECTIVE AND IMPORTANCE: Surgical intervention can reduce the burden of seizures in selected patients with tuberous sclerosis and medically refractory epilepsy. CLINICAL PRESENTATION: A child presented with tuberous sclerosis and severe epilepsy beginning in the first month of life and delayed development before 1 year of age. Video-electroencephalographic monitoring at the age of 1 year revealed a left temporal seizure focus. Repeat videoelectroencephalography at 2 years of age revealed a right posterior quadrant seizure focus. Bilateral subdural electrodes were placed, confirming independent seizure onsets from the right parietal area (overlying a tuber) and prominent interictal activity over the left superior temporal region. INTERVENTION: The right parietal focus was resected, and electrodes were maintained over the left temporal focus. After right parietal resection, ictal discharges were recorded over the left temporal region; a corticectomy was performed 2 days later. No tonicoclonic or complex partial seizures have occurred during a follow-up period of more than 24 months. Simple partial motor seizures involving the right foot have been reduced by more than 80%, and other simple partial seizures have been eliminated. Postoperatively, there has been marked improvement in the patient's cognitive and motor developmental status. CONCLUSION: In selected patients with bilateral seizure foci involving separate lobes, aggressive bilateral surgery can be safe and effective.
Assuntos
Epilepsias Parciais/etiologia , Epilepsias Parciais/cirurgia , Esclerose Tuberosa/complicações , Transtornos Cognitivos/diagnóstico , Transtornos Cognitivos/etiologia , Eletroencefalografia , Epilepsias Parciais/fisiopatologia , Humanos , Lactente , Transtornos da Linguagem/diagnóstico , Transtornos da Linguagem/etiologia , Imageamento por Ressonância Magnética , Masculino , Procedimentos Neurocirúrgicos/métodos , Lobo Parietal/patologia , Lobo Parietal/fisiopatologia , Lobo Temporal/patologia , Lobo Temporal/fisiopatologia , Esclerose Tuberosa/diagnóstico , Esclerose Tuberosa/fisiopatologia , Gravação de VideoteipeRESUMO
The screening of newborn babies for congenital hypothyroidism has changed the natural history of this abnormality. We describe here a case of a female patient with congenital hypothyroidism that was missed by primary neonatal thyroid screening (using thyroid-stimulating hormone) at two days of age; it was detected only after the development and persistence of jaundice during the first three weeks of life. A normal neonatal screening result does not preclude the development of hypothyroidism later in infancy. Clinical vigilance must be maintained by practitioners. A second screening between two and six weeks of age may be useful in order to detect the few cases missed at first screening.