RESUMO
INTRODUCTION: Metformin-associated lactic acidosis (MALA) is a rare but life-threatening condition. Here, we report the outcome of a patient with MALA complicated by acute coronary syndrome. CASE PRESENTATION: A 47-year-old obese woman of Caucasian ethnicity was admitted for syncope and tachypnea with Kussmaul breathing. She had a type-2 diabetes and was on oral antidiabetic therapy. Hemoglobin A1c was 6.6%. On admission, a severe acute kidney injury (serum creatinine: 1251 µmol/L) with hyperkalemia (7.5 mmol/L) and severe lactic acidosis (ph:7.042, bicarbonate: 9.9 mmol/L, partial pressure of carbon dioxide: 21.8 mmHg, lactate: 20.0 mmol/L) was found. Despite bicarbonate therapy, ph further decreased. Within 2.5 h of admission, a temporary hemodialysis catheter was placed, and one session of a high-efficiency hemodialysis was performed. 8 h after admission, a continuous venovenous hemodiafiltration was initiated and maintained for 2 days. The metformin therapy was stopped. Supplemental oxygen, intravenous catecholamines (4 days) and antibiotic therapy (7 days) were applied. During this therapy of lactic acidosis, an acute coronary syndrome evolved by day 2 after admission and resolved by day 5 in hospital. After recovery, the patient was transferred to a general ward on day 7 and left the hospital on day 11. By discharge, both the acute kidney injury and the acute coronary syndrome were reversible. CONCLUSION: In the patient with MALA complicated by acute coronary syndrome, the combination of a high-efficiency hemodialysis and, consecutively, continuous venovenous hemodiafiltration led to a favorable outcome.
Assuntos
Acidose Láctica , Síndrome Coronariana Aguda , Injúria Renal Aguda , Diabetes Mellitus Tipo 2 , Metformina , Acidose Láctica/induzido quimicamente , Acidose Láctica/terapia , Síndrome Coronariana Aguda/complicações , Síndrome Coronariana Aguda/terapia , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/terapia , Bicarbonatos , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Feminino , Humanos , Hipoglicemiantes/efeitos adversos , Masculino , Metformina/efeitos adversos , Pessoa de Meia-IdadeAssuntos
Candidíase Bucal/tratamento farmacológico , Candidíase Bucal/microbiologia , Candidíase Vulvovaginal/tratamento farmacológico , Candidíase Vulvovaginal/microbiologia , Administração Oral , Angioedema/induzido quimicamente , Angioedema/diagnóstico , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/uso terapêutico , Antifúngicos/administração & dosagem , Antifúngicos/uso terapêutico , Compostos Benzidrílicos/efeitos adversos , Compostos Benzidrílicos/uso terapêutico , Candida albicans/isolamento & purificação , Candidíase Bucal/patologia , Candidíase Vulvovaginal/patologia , Feminino , Fluconazol/administração & dosagem , Fluconazol/uso terapêutico , Prepúcio do Pênis/patologia , Glucosídeos/efeitos adversos , Glucosídeos/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Diagnóstico Ausente , Pênis/patologia , Inibidores do Transportador 2 de Sódio-Glicose/administração & dosagem , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Resultado do TratamentoRESUMO
Pneumocystis jirovecii pneumonia (PCP) and cytomegalovirus (CMV) infection represent possible complications of medical immunosuppression. Between 2005 and 2010, non-human immunodeficiency virus (HIV) PCP patients admitted to a nephrology unit were analyzed for outcome, CMV comorbidity, and patient-to-patient contacts prior to PCP. In contrast to 2002-2004 (no cases) and 2008-2010 (10 cases), a PCP outbreak of 29 kidney-transplant recipients and one patient with anti-glomerular basement membrane disease occurred between 2005 and 2007. None of the patients were on PCP chemoprophylaxis. In four PCP patients, the genotyping data of bronchoalveolar lavage specimen showed an identical Pneumocystis strain. PCP cases had a higher incidence of CMV infection (12 of 30 PCP patients) and CMV disease (four patients) when compared to matched PCP-free controls (p < 0.05). Cotrimoxazole and, if applicable, ganciclovir were started 2.0 ± 4.0 days following admission, and immunosuppressive medication was reduced. In-hospital mortality was 10% and the three-year mortality was 20%. CMV co-infection did not affect mortality. CMV co-infection more frequently occurred during a cluster outbreak of non-HIV PCP in comparison to PCP-free controls. Here, CMV awareness and specific therapy of both CMV infection and PCP led to a comparatively favorable patient outcome. The role of patient isolation should be further investigated in incident non-HIV PCP.
Assuntos
Coinfecção/epidemiologia , Infecção Hospitalar/epidemiologia , Infecções por Citomegalovirus/epidemiologia , Surtos de Doenças , Pneumocystis carinii/isolamento & purificação , Pneumonia por Pneumocystis/epidemiologia , Adulto , Idoso , Antifúngicos/administração & dosagem , Antivirais/administração & dosagem , Estudos de Casos e Controles , Infecção Hospitalar/complicações , Infecção Hospitalar/microbiologia , Citomegalovirus/patogenicidade , Infecções por Citomegalovirus/complicações , Feminino , Ganciclovir/administração & dosagem , Genótipo , Humanos , Hospedeiro Imunocomprometido , Transplante de Rim/efeitos adversos , Masculino , Pessoa de Meia-Idade , Tipagem Molecular , Técnicas de Tipagem Micológica , Pneumocystis carinii/classificação , Pneumocystis carinii/genética , Pneumonia por Pneumocystis/complicações , Pneumonia por Pneumocystis/microbiologia , Combinação Trimetoprima e Sulfametoxazol/administração & dosagemRESUMO
The risk of cytomegalovirus (CMV) reactivation among hemodialysis (HD) patients is unknown. In 52 HD patients from a single center, CMV serology and quantitative PCR were performed. The detection limit of PCR was 20 copies/ml. Here, PCR ruled out CMV viremia, despite CMV-IgM seropositivity in 15.4% patients.
Assuntos
Infecções por Citomegalovirus/epidemiologia , Infecções por Citomegalovirus/virologia , Citomegalovirus/isolamento & purificação , Diálise Renal/efeitos adversos , Diálise Renal/métodos , Ativação Viral , Citomegalovirus/genética , Citomegalovirus/imunologia , Humanos , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Testes Sorológicos , Viremia/diagnósticoRESUMO
Neurohumoral stimulation comprising both autonomic-nervous-system dysfunction and activation of hormonal systems including the renin-angiotensin-aldosterone system (RAAS) was found to be associated with Type-2-diabetes (T2D). Therapeutic strategies such as RAAS interference proved to be beneficial in both T2D treatment and prevention. In addition to an activated RAAS, hyperleptinemia in obesity, hyperinsulinemia in conditions of peripheral insulin resistance and overall oxidative stress in T2D represent known activators of the sympathetic component of the autonomic nervous system. Here, we hypothesize that sympathetic activation may cause peripheral insulin resistance defined as partial blocking of insulin effects on glucose uptake. Resulting hyperinsulinemia or hyperglycemia-related oxidative stress may further aggravate sympatho-excitation. This notion leads to a secondary hypothesis: sympathetic activation worsens from obesity towards insulin resistance, and further towards T2D. In this review, existing evidence relating to neurohumoral stimulation in T2D and consequences thereof, such as oxidative stress and inflammation, are discussed. The aim of this review is to provide a rationale for therapies, which are able to intercept neuroendocrine pathways in T2D and precursor states such as obesity.
RESUMO
Sympatho-excitation is a hallmark of the chronic heart failure (CHF) state. It has long been assumed that this sympatho-excitation is mediated by a reduction in sensory input from cardiopulmonary and arterial baroreceptors. However, recent data suggest that these reflexes may only be important in the initiation of the sympatho-excitatory state and may not be necessary for the sustained increase in sympathetic nerve activity (SNA) in CHF. Two humoral factors that can influence SNA are nitric oxide (NO) and angiotensin II (AngII). Animals with CHF exhibit a downregulation in central gene expression for the neuronal isoform of nitric oxide synthase (nNOS). In addition, blockade of AngII receptors in combination with NO donation reduces SNA in animals with CHF, while NO donation alone has no effect on SNA. Chronic exercise training (EX) reduces both plasma AngII and SNA in rabbits with CHF while improving baroreflex function. Blockade of AT1 receptors enhances baroreflex function in non-EX CHF rabbits, but has little effect in EX CHF rabbits. These data suggest that the sympatho-excitatory state that is typical of CHF is, in part, due to changes in AngII and NO. Depressed baroreflex function and the elevated SNA can be improved by EX in animals with CHF.
Assuntos
Angiotensina II/fisiologia , Baixo Débito Cardíaco/fisiopatologia , Óxido Nítrico/fisiologia , Condicionamento Físico Animal/fisiologia , Sistema Nervoso Simpático/fisiopatologia , Animais , Doença Crônica , Endotelina-1/fisiologiaRESUMO
The reflex regulation of sympathetic nerve activity has been demonstrated to be impaired in the chronic heart failure (CHF) state compared with the normal condition (Liu JL, Murakami H, and Zucker IH. Circ Res 82: 496-502, 1998). Exercise training (Ex) appears to be beneficial to patients with CHF and has been shown to reduce sympathetic outflow in this disease state (Hambrecht R, Hilbrich L, Erbs S, Gielen S, Fiehn E, Schoene N, and Schuler G. J Am Coll Cardiol 35: 706-713, 2000). We tested the hypothesis that Ex corrects the reduced cardiopulmonary (CP) reflex response to volume expansion in the CHF state. Normal, normal with Ex, CHF, and CHF with Ex (CHF-Ex) groups (n = 10-21) of male New Zealand White rabbits were studied. CHF was induced by chronic ventricular pacing. Rabbits were instrumented to record left ventricular end-diastolic pressure (LVEDP), left ventricular end-diastolic diameter (LVEDD), and renal sympathetic nerve activity (RSNA). Experiments were carried out with the animals in the conscious state. Volume expansion was performed with 6% dextran in normal saline at a rate of 5 ml/min to approximately 20% of estimated plasma volume without any significant effect on mean arterial pressure being exhibited. The relationships between RSNA and LVEDP and between RSNA and LVEDD were determined by linear regression; the slopes served as an index of CP reflex sensitivity. Normal rabbits exhibited a CP reflex sensitivity of -8.4 +/- 1.5%delta RSNA/mmHg. This value fell to 0.0 +/- 1.3%delta RSNA/mmHg in CHF rabbits (P < 0.001). Ex increased CP reflex sensitivity to -5.0 +/- 0.7%delta RSNA/mmHg in CHF-Ex rabbits (P < 0.05 compared with CHF). A similar trend was seen when related to the change in LVEDD. Furthermore, resting RSNA expressed as a percentage of maximum RSNA in response to cigarette smoke was also normalized by Ex in rabbits with CHF. Ex had no effect on these parameters in normal rabbits. These data confirm an impairment of CP reflex sensitivity and sympathoexcitation in CHF vs. normal animals. Ex substantially restored both CP reflex sensitivity and baseline RSNA in CHF animals. Thus Ex beneficially affects reflex regulation in CHF, thereby lowering resting sympathetic nerve activity.
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Insuficiência Cardíaca/fisiopatologia , Condicionamento Físico Animal/fisiologia , Reflexo/fisiologia , Sistema Nervoso Simpático/fisiologia , Animais , Pressão Sanguínea/fisiologia , Catecolaminas/sangue , Frequência Cardíaca/fisiologia , Rim/inervação , Rim/fisiologia , Pulmão/fisiologia , Masculino , Coelhos , Pressão Ventricular/fisiologiaAssuntos
Antineoplásicos Hormonais/efeitos adversos , Antineoplásicos Hormonais/uso terapêutico , Síndrome do QT Longo/induzido quimicamente , Mitotano/efeitos adversos , Mitotano/uso terapêutico , Feminino , Humanos , Síndrome do QT Longo/diagnóstico , Síndrome do QT Longo/fisiopatologia , Pessoa de Meia-IdadeRESUMO
Appetite and satiety are subject to complex regulation, with neuroendocrine mechanisms playing an important role. The central nervous system is attracting increasing attention as a target tissue for many hormones such as leptin, PYY3-36, ghrelin, glucagon-like-peptide 1 and many others. Among its many well-known functions, insulin is also a potent anorexigenic hormone, and insulin receptors are widely distributed throughout the central nervous system. One way to advance our understanding of central nervous regulation of hunger and satiety in humans is to develop suitable neuroimaging techniques for use in various clinical and experimental conditions. Several studies have been performed using functional magnetic resonance imaging and positron emission tomography to identify areas of the brain that are differentially activated by alteration of the feeding state. These preliminary data are taking shape as a complex neuronal network involving the hypothalamus, thalamus, limbic and paralimbic areas including the insular cortex and the anterior cingulate gyrus and the orbitofrontal cortex. Continuous efforts to understand hormonal effects on these pathways may advance our understanding of human obesity.
Assuntos
Regulação do Apetite/fisiologia , Sistema Nervoso Central/fisiologia , Insulina/metabolismo , Animais , Humanos , Imageamento por Ressonância Magnética , Obesidade/metabolismoRESUMO
Endothelin-1 (ET-1) is elevated in chronic heart failure (CHF). In this study, we determined the effects of chronic ET-1 blockade on renal sympathetic nerve activity (RSNA) in conscious rabbits with pacing-induced CHF. Rabbits were chronically paced at 320--340 beats/min for 3--4 wk until clinical and hemodynamic signs of CHF were present. Resting RSNA and arterial baroreflex control of RSNA were determined. Responses were determined before and after the ET-1 antagonist L-754,142 (a combined ET(A) and ET(B) receptor antagonist, n = 5) was administered by osmotic minipump infusion (0.5 mg. kg(-1) x h(-1) for 48 h). In addition, five rabbits with CHF were treated with the specific ET(A) receptor antagonist BQ-123. Baseline RSNA (expressed as a percentage of the maximum nerve activity during sodium nitroprusside infusion) was significantly higher (58.3 +/- 4.9 vs. 27.0 +/- 1.0, P < 0.001), whereas baroreflex sensitivity was significantly lower in rabbits with CHF compared with control (3.09 +/- 0.19 vs. 6.04 +/- 0.73, P < 0.001). L-754,142 caused a time-dependent reduction in arterial pressure and RSNA in rabbits with CHF. In addition, BQ-123 caused a reduction in resting RSNA. For both compounds, RSNA returned to near control levels 24 h after removal of the minipump. These data suggest that ET-1 contributes to sympathoexcitation in the CHF state. Enhancement of arterial baroreflex sensitivity may further contribute to sympathoinhibition after ET-1 blockade in heart failure.