Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0243026 (sepsis)
 52,417 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Few cases of combined heart and liver transplantation (CHLT) for familial amyloidotic polyneuropathy have been reported, and the technique for the operation is far from being consolidated. Three patients with amyloidogenic transthyretin (ATTR)-related (variant Glu89Gln to ATTR Glu89Gln) cardiomyopathy underwent CHLT at our institution. Patient 1 had no serious involvement of other organs, whereas patients 2 and 3 had evident peripheral neuropathy and gastrointestinal motility alterations. Patient 3 also had high-grade orthostatic hypotension. All three patients underwent cardiac and sequential hepatic transplantation using the piggyback technique with organs procured from the same donor. Venovenous bypass (VVB) was used only in patient 1, with an uncomplicated procedure. After CHLT, his cardiac performance remained normal, and no progression of amyloidosis was observed. Patient 2 had no intraoperative complications, but experienced postoperative bleeding, renal failure, sepsis, and heart failure and eventually died of multiorgan failure 2 months after transplantation. In patient 3, right hemicolectomy was required intraoperatively because of intestinal ischemia without significant hemodynamic perturbations, whereas extracardiac symptoms of amyloidosis gradually worsened postoperatively. Two patients (no. 1 and 3) currently are alive after 38 and 18 months, respectively. CHLT for ATTR Glu89Gln can be performed successfully, even in patients with advanced disease. However, the most compromised patients are more exposed to intraoperative risks, postoperative complications, and worsening of extracardiac and extrahepatic symptoms. The need for VVB remains to be evaluated.
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PMID:Combined heart and liver transplantation for familial amyloidotic neuropathy: considerations from the hepatic point of view. 1294 63

Enhanced cardiac generation of peroxynitrite contributes to septic cardiomyopathy. Since matrix metalloproteinases (MMPs) are activated in vitro by peroxynitrite, we hypothezised that MMPs may contribute to cardiac mechanical dysfunction in sepsis. Rats were injected (i.p.) with either lipopolysaccharide (LPS, 4 mg/kg) or vehicle. MMP inhibitors, either Ro 31-9790 (20 mg/kg), doxycycline (4 mg/kg), or vehicle were administered i.p. 30 min after LPS. At 6 h, when the symptoms of endotoxemia peak, hearts were excised and perfused as working hearts with Krebs-Henseleit buffer at 37 degrees C. Cardiac work (cardiac output x peak systolic pressure product) was measured. Perfusate and ventricle samples were analyzed by gelatin zymography to quantify MMP activity. Cardiac function was significantly depressed in LPS-treated rats compared to control rats (control: 55 +/- 4, LPS: 26 +/- 6 mmHg*mL*min(-1)). LPS also caused a loss of 72 kDa MMP-2 activity in the ventricles and the perfusate. Although MMP-9 activity was not detected in the ventricles, LPS resulted in an increase in perfusate 92 kDa MMP-9 activity. The MMP inhibitors significantly improved cardiac function of LPS-treated rats (Ro 31-9790: 38 +/- 3, doxycycline: 51 +/- 3 mmHg*mL*min(-1)), had no effect on the loss of MMP-2 activity, and significantly reduced the MMP-9 activity in the perfusate. These results demonstrate, for the first time, that LPS induced cardiac dysfunction is associated with a loss in ventricular MMP-2 activity and the release of MMP-9 from the heart. MMP inhibitors can significantly preserve cardiac mechanical function during septic shock.
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PMID:Matrix metalloproteinase inhibitors attenuate endotoxemia induced cardiac dysfunction: a potential role for MMP-9. 1457 5

There are few reports of combined heart and liver transplantation (CHLT) for familial amyloidotic polyneuropathy (FAP). The technique for the operation remains to be defined. Four CHLTs were performed for amyloidogenic transthyretin-related (variant Glu89Gln-ATTR Glu89Gln) cardiomyopathy in our center. Patients 1 and 4 had no serious involvement of other organs, whereas patients 2 and 3 had evident peripheral neuropathy and gastrointestinal motility alterations. Patient 3 also had high-grade orthostatic hypotension. All four patients underwent cardiac and sequential hepatic transplantation with organs procured from the same donor. Venovenous bypass was used in patients 1 and 4 who experienced uncomplicated procedures. The amyloidotic liver of patient 4 was successfully utilized for a domino procedure to treat a patient with hepatocellular carcinoma on cirrhosis. The cardiac performance of patients 1 and 4 remains normal; there has been no progression of amyloidosis at 42 and 1 months after transplantation. Patient 2 had no intraoperative complications but experienced postoperative bleeding, renal failure, sepsis, and heart failure, and finally died of multiorgan failure 2 months after transplant. In patient 3, right hemicolectomy was required intraoperatively due to intestinal ischemia, without significant hemodynamic instability, while extracardiac symptoms of amyloidosis gradually worsened postoperatively. In conclusion, CHLT for ATTR Glu89Gln may be performed even in patients with advanced disease. However, the most compromised patients are more likely to display intraoperative risks, postoperative complications, and worsening of extracardiac, extrahepatic symptoms.
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PMID:Combined heart and liver transplantation in four adults with familial amyloidosis: experience of a single center. 1511 Jun 20

An ideal cardiac biochemical marker should have not only high sensitivity but also high specificity to myocardial infarction. The creatine kinase-MB, a relatively specific cardiac marker, could be elevated in situations other than acute myocardial infarction, such as renal failure, muscular injury, and myopathy. Although these are more specific than creatine kinase-MB, cardiac troponins have also been reported to be elevated in conditions other than acute myocardial infarction, such as chronic renal failure, acute myocarditis, cardiomyopathy, congestive heart failure, pulmonary embolism, rhabdomyolysis, sepsis, and left ventricular hypertrophy. With the ongoing research in this field, future holds hopes of finding an ideally specific marker of myocardial infarction, but until then biochemical markers should be used in conjunction with clinical assessment and electrocardiography in making the diagnosis of myocardial infarction, and the patients should not be treated merely on the basis of elevated serum levels of cardiac biochemical markers.
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PMID:Role of biochemical markers in diagnosis of myocardial infarction. 1616 23

The future perspectives of cardiovascular intensive care medicine (CVICM) are affected by an ever increasing number of elderly (> 65 years), old (> 75 years) and very old (> 85 years) patients with the incidental clinical consequences, by an increase in inpatient days due to the increasing number of patients who have to be treated despite cost pressure, and by the attempts to integrate CVICM into one interdisciplinary intensive care unit (ICU) including medical and surgical patients, although proof of equal or even superior outcome, process or structural quality is lacking presently. To overcome all the problems mentioned, CVICM must develop from a mainly consensus-oriented to a more evidence-oriented medicine; CVICM must find ways to improve the poorly validated hemodynamic monitoring concept by pulmonary artery catheter and look for additional, less invasive monitoring techniques and better monitoring parameters; CVICM must support the search for new and hopefully better pharmacotherapeutic agents and cardiovascular assist devices as presently available to support the failing heart and the impaired vascular system; and CVICM must also learn to control noncardiac processes like inflammation and multi-organ failure, which often are responsible for the fatal outcome of the ICU patient with cardiovascular disease. Real challenges for the cardiovascular intensivist are refractory shock and refractory septic cardiomyopathy, these cardiovascular disease entities being responsible for every other fatality in the wake of severe sepsis and septic shock. To handle these tremendous challenges of CVICM, training of the young cardiologists in CVICM must be intensified, and much more attention to cardiovascular topics and techniques must be paid when training our colleagues in medical intensive care medicine.
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PMID:[Future perspectives of cardiovascular intensive care medicine]. 1680 27

Despite intensive ongoing research efforts, the mortality of patients with sepsis remains unacceptably high. A significant number of clinical trials have failed to produce sufficient therapeutic strategies despite showing promising results in animal models. So far, many studies have focused on deterioration of the humoral and cellular components of the immune system, the main cause of death in septic patients being multi-organ failure. However, not much is known about the effects of the complement system on parenchymal cells of organs such as the heart. Recently, septic cardiomyopathy has been recognized as one of the major complications during sepsis, often determining the clinical outcome. In this review, we describe molecular events which are thought to be related to cardiac dysfunction during sepsis. A special emphasis will be placed on the complement system, which generates powerful anaphylatoxins (such as C5a) and which has recently been associated with septic cardiomyopathy. Together with the impact on cardiac function of various cytokines we will provide a synopsis of the current knowledge regarding the pathophysiology underlying cardiac failure during sepsis with a special emphasis on C5a and C5aR.
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PMID:Complement-related molecular events in sepsis leading to heart failure. 1687 36

The purpose of this case report is to illustrate the diagnostic difficulties of congestive heart failure in an infant. When presenting to the emergency department, these patients are often evaluated for sepsis, congenital heart disease, metabolic disorders, and myocarditis. We report a case of a 3(1/2)-month-old male who presented to the pediatric emergency department with congestive heart failure. He was found to have vitamin D deficiency rickets induced cardiomyopathy.
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PMID:An infant with tachypnea. 1711 Aug 66

In this report, we describe a brother and sister who presented at birth with short-limb skeletal dysplasia, polyhydramnios, prematurity, and generalized edema. Dysmorphic features included broad nose, thick ears, thin lips, micrognathia, inverted nipples, ulnar deviation at the wrists, spatulate fingers, fifth finger camptodactyly, nail hypoplasia, and talipes equinovarus. Other features included short stature, microcephaly, psychomotor retardation, B-cell lymphopenic hypogammaglobulinemia, sensorineural deafness, retinal detachment and blindness, intestinal malrotation with poor gastrointestinal motility, persistent hyponatremia, intermittent hypoglycemia, and thrombocytopenia. Cardiac anomalies included PDA, VSD, hypertrophic cardiomyopathy, and arrhythmias. The brother had a small penis with hypospadias, hypoplastic scrotum, and non-palpable testes. Skeletal findings included absent ossification of cervical vertebral bodies, pubic bones, knee epiphyses, and tali. Both sibs died before age 2 years, one of overwhelming sepsis and the other of cardiorespiratory failure associated with her cardiomyopathy. Metabolic studies showed a type 1 pattern of abnormal serum transferrin glycosylation. Fibroblasts synthesized truncated LLOs, primarily Man(7)GlcNAc(2), suggestive of CDG-Ig. Both sibs were compound heterozygotes for a novel 301 G > A (G101R) mutation and a previously described 437 G > A (R146Q) mutation in ALG12. Congenital disorders of glycosylation should be considered for children with undiagnosed multi-system disease including neurodevelopmental delay, skeletal dysplasia, immune deficiency, male genital hypoplasia, and cardiomyopathy.
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PMID:Expanding spectrum of congenital disorder of glycosylation Ig (CDG-Ig): sibs with a unique skeletal dysplasia, hypogammaglobulinemia, cardiomyopathy, genital malformations, and early lethality. 1750 7

The rate of infection in patients who require ventricular assist devices is estimated at more than 35%. Infections with multi-resistant organisms such as methicillin-resistant Staphylococcus aureus in ventricular assist device recipients are often difficult to treat and present a high mortality rate. Daptomycin is a new cyclic lipopeptide antibiotic, useful in gram-positive organisms resistant to standard treatment. We report a case of a 65-year-old man suffering from a dilatative cardiomyopathy and concomitant MRSA infection who received a biventricular assist device. The patient had MRSA sepsis develop resistant to conventional therapy, which was successfully treated with daptomycin.
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PMID:Daptomycin for eradication of a systemic infection with a methicillin-resistant-Staphylococcus aureus in a biventricular assist device recipient. 1758 30

Activation of leukocytes and in particular polymorphonuclear neutrophils (PMN) has emerged as a critical confounder in the pathophysiology of cardiovascular disease: Myeloperoxidase (MPO), one of the principal proteins hosted in and secreted by activated PMN, has been mechanistically linked to endothelial and left ventricular (LV) dysfunction in rodent models of sepsis and ischemic cardiomyopathy. Whether PMN activation is also overt in patients with LV dysfunction of ischemic and nonischemic origin, however, remains elusive. Prospectively, 447 consecutive, stable outpatients were included in this single-center study. In 113 patients with impaired left ventricular function (ejection fraction <50%; nonischemic cardiomyopathy, n=52; ischemic cardiomyopathy, n=61), MPO plasma levels were elevated (24.5 [IR:15.8-54.0] vs 15.5 [IR:8.9-39.2] ng/ml in controls, P<0.01) as was elastase (111.5 [IR:63.8-233.3] vs 70.5 [IR:45.0-129.0] ng/ml, P<0.01) and NT-proBNP plasma levels (747.4 [IR:216.3-1958.3] vs 264.1 [IR:82.5-671.8] ng/L, P<0.01). Elevation of circulating MPO was irrespective of the etiology of heart failure and independent of traditional confounding variables. No association was observed between MPO -463 promoter polymorphism genotype and LV dysfunction. MPO plasma levels correlated with ejection fraction (P<0.01) and left ventricular end-diastolic diameter (P<0.01), respectively. Myeloperoxidase mRNA expression levels obtained from circulating leukocytes were significantly increased in patients with LV dysfunction. Systemic leukocyte activation with increased transcription of MPO mRNA and augmented release of MPO appears to represent a so far underrecognized characteristic in LV dysfunction, which was revealed to be irrespective of the underlying pathology. Given its potent proinflammatory properties, MPO may represent an important mechanistic link to LV dysfunction and deserves to be evaluated as both marker and therapeutic target in this disease.
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PMID:Activation of polymorphonuclear neutrophils in patients with impaired left ventricular function. 1785 14


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