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)

Decreasing of number of cases as well as incidence rate of hepatitis type B and type A, and increasing of pertussis, leptospirosis, encephalitis and some other diseases was noted in Poland in 1997. The biggest percentage of deaths was caused by tuberculosis--43.1%, sepsis--over 21.9% and hepatitis--10.6%. Introduction of ICD-10 as well as strikes of health workers in Poland in 1997 caused undernotification especially of deaths.
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PMID:[Infectious diseases in Poland in 1997]. 1040 44

Bordetella bronchiseptica rarely causes disease in man, and is an unusual pathogen in animals. It causes a pertussis-like syndrome, but pneumonia and sepsis have been described in the immunocompromised as well as in the immunocompetent. A 53-year-old man with adult-onset diabetes and healed pulmonary tuberculosis presented with lobar pneumonia and rapidly developed septic shock with adult respiratory distress syndrome. He responded well to the combination of piperacillin-tazobactam.
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PMID:[Severe pneumonia caused by Bordetella bronchiseptica]. 1095 17

The Health Council of the Netherlands (Gezondheidsraad) assessed the vaccination of infants against both group-C meningococci and pneumococci in terms of general criteria and basic principles for inclusion in the national vaccination programme. Vaccination against meningococci C in the Netherlands is expected to prevent about 300 cases of meningococcal disease (meningitis or sepsis), 22 deaths and 12 cases of severe lasting problems (neurological problems or amputations) per year. Vaccination against pneumococci may prevent about 100 cases of meningitis or sepsis, 3200 cases of pneumonia, 36,000 cases of acute otitis media, 11 deaths, 11 cases of severe permanent damage (neurological problems, deafness) per year. The Health Council advised implementing vaccination against group-C meningococci as soon as possible, through 2 injections at the ages of 5 and 6 months or through 1 injection shortly after the child's first birthday, and to carry out a catch-up programme for all children and adolescents up to and including 18 years of age. The council also advised starting a vaccination programme against pneumococci, at ages 2, 3 and 4 months, as soon as the current vaccinations against diphtheria, tetanus, pertussis and polio and against Haemophilus influenzae type b are combined into 1 injection (in 2002 or 2003). In view of the concentration of pneumococci disease in the first years of life, a catch-up programme is not indicated in this case. The Health Council emphasised the importance of microbiological and clinical monitoring of potential adverse effects and of public education programmes. The cost of vaccination against group-C meningococci is comparable to that of other accepted programmes for primary prevention. Compared to other programmes and at the current vaccine price, the cost of vaccination against pneumococci is high.
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PMID:[Universal vaccination against group-C meningococci and pneumococci; summary of the advice from the Health Counsil of the Netherlands]. 1221 5

The Lady Dufferin Fund, founded in 1885 in India, had by 1940 established 400 hospitals to alleviate diseases and mortality related to childbirth. After independence 2328 community health centers and 21254 primary health centers were created in the country. During 1974-94 more than 131,000 subcenters were set up and about 620,000 auxiliary nurse midwives (ANMs) had been trained. The Ministry of Health introduced four health prevention schemes in 1969: 1) immunization of children against diphtheria, pertussis, and tetanus; 2) immunization of pregnant women against tetanus; 3) prophylaxis of mothers and children against nutritional anemia; and 4) prophylaxis of children against blindness caused by vitamin A deficiency. As a result, infant mortality declined from 146/1000 live births to 74/1000 in 1993; but maternal mortality still stayed around 4-5/1000. In 1993 an estimated 117,356 maternal deaths occurred out of a total of 26,057,000 births, equalling 4.5 deaths per 1000 live births. The main causes of maternal deaths are hemorrhage, anemia, abortion, toxemia, and puerperal sepsis. Only about 411 first referral units in community health centers are functioning properly. Prenatal care of mothers includes the administration of tetanus toxoid and iron-folic acid tablets. However, the prenatal coverage reached only about 50% of mothers; and the coverage was only 21.4% in Bihar, 23.8% in Nagaland, 29.3% in Rajasthan, and 29.6% in Uttar Pradesh. In these areas administrative inefficiency is widespread with nonavailability of essential drugs for malaria, infections, sepsis, dysentery, and colds. During 1992-93 the rate of hospital deliveries ranged from 6.1% in Nagaland to 88.4% in Kerala, with a national average of only 25.6%. 71% of deliveries in rural areas and 30% in urban areas were conducted by untrained assistants. Although there are 450 ANM training schools in the country, the level of training has deteriorated. The major causes of infant deaths are respiratory infections and diarrhea, responsible for 13.5% and 6.9% of mortality, respectively. Severe malnutrition and inadequate vaccination are other major causes of child deaths and morbidity.
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PMID:Maternal and child health in India: a critical review. 1229 Sep 61

The objective of this study was to determine whether the serum of patients with sepsis could alter the capability of healthy human peripheral blood mononuclear cells (PBMC) to synthesize cAMP in response to beta-adrenergic stimulation and to evaluate the involvement of the inhibitory pathway (Gi) of adenylyl cyclase in the sepsis-induced alteration of beta-adrenergic signaling. First, PBMC from a healthy donor were incubated for 24 h in serum-containing medium according to three culture conditions: serum alone, serum with pertussis toxin, and serum with propranolol. Second, PBMC were stimulated with 10(-5) M isoproterenol or 10(-6) M forskolin, and measurement of cyclic adenosine monophosphate (cAMP) intracellular accumulation was performed. Serum samples were obtained from three groups of subjects: 14 patients with severe sepsis, 21 patients with septic shock, and 10 healthy control subjects. Basal and forskolin-stimulated cAMP levels were similar in PBMC cultured in control or in septic serum. Isoproterenol-stimulated accumulation was reduced in PBMC preincubated in septic serum. The lowest cAMP levels were found after exposure to serum from patients with septic shock. The addition of pertussis toxin in the incubation medium constantly increased cAMP response to isoproterenol, but more significantly in PBMC exposed to septic serum. Incubation in the presence of propranolol had no significant effect. The serum of patients with sepsis contained soluble depressant substances that inhibited adenylyl cyclase activation by beta-adrenergic agonists. Septic shock serum exhibited the most potent inhibitory effect. Hyperactivation of the Gi pathway of adenylyl cyclase was mainly responsible for the altered transmembrane beta-adrenergic signaling.
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PMID:Impairment of beta-adrenergic signaling in healthy peripheral blood mononuclear cells exposed to serum from patients with septic shock: involvement of the inhibitory pathway of adenylyl cyclase stimulation. 1257 16

FTY720, a potent immunosuppressive agent, is phosphorylated in vivo into FTY720-P, a high affinity agonist for sphingosine 1-phosphate (S1P) receptors. The effects of FTY720 on vascular cells, a major target of S1P action, have not been addressed. We now report the metabolic activation of FTY720 by sphingosine kinase-2 and potent activation of vascular endothelial cell functions in vitro and in vivo by phosphorylated FTY720 (FTY720-P). Incubation of endothelial cells with FTY720 resulted in phosphorylation by sphingosine kinase activity and formation of FTY720-P. Sphingosine kinase-2 effectively phosphorylated FTY720 in the human embryonic kidney 293T heterologous expression system. FTY720-P treatment of endothelial cells stimulated extracellular signal-activated kinase and Akt phosphorylation and adherens junction assembly and promoted cell survival. The effects of FTY720-P were inhibited by pertussis toxin, suggesting the requirement for Gi-coupled S1P receptors. Indeed, transmonolayer permeability induced by vascular endothelial cell growth factor was potently reversed by FTY720-P. Furthermore, oral FTY720 administration in mice potently blocked VEGF-induced vascular permeability in vivo. These findings suggest that FTY720 or its analogs may find utility in the therapeutic regulation of vascular permeability, an important process in angiogenesis, inflammation, and pathological conditions such as sepsis, hypoxia, and solid tumor growth.
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PMID:Phosphorylation and action of the immunomodulator FTY720 inhibits vascular endothelial cell growth factor-induced vascular permeability. 1295 48

A neonate presenting to the emergency department can present a challenge to even the most experienced clinician. This article has focused on four deceiving and potentially devastating neonatal diseases. 1. Neonatal herpes is a potentially devastating illness without pathognomonic signs or symptoms. Early recognition and therapy can reduce mortality markedly. Although no specific sign or symptom is diagnostic,the diagnosis should be strongly considered in the presence of HSV risk factors, atypical sepsis, unexplained acute hepatitis, or focal seizure activity. Acyclovir therapy should be initiated before viral dissemination or significant CNS replication occurs. 2. Pertussis is a disease in which infants are at greatest risk of death or severe complication. Neonatal pertussis often presents in an atypical manner, lacking the classic signs and symptoms such as the "whoop."More common signs and symptoms include cough, feeding difficulty,low-grade fever, emesis, increasing respiratory distress, apnea, cyanosis,and seizures. Management should include hospitalization, supportive care, and antibiotics. 3. Congenital heart defects, particularly ductal-dependent lesions, may have an initial asymptomatic period that culminates in a rapidly progressive and fatal course. A neonate with CHD presents with shock refractory to volume resuscitation or pressor support. Resuscitative efforts are ineffective unless PGE, is administered. 4. Inborn errors of metabolism often are unsuspected because of their protean and heterogeneous nature. Signs and symptoms are subtle,are nonspecific, and often mimic other, more common diseases.An elevated index of suspicion, along with application and correct interpretation of a select few laboratory tests, is the key to making a diagnosis. Therapy is relatively straightforward and focused on resuscitation followed by prevention of catabolism and correction of specifically identified abnormalities. Although these disorders are relatively uncommon, prompt diagnosis and therapy can lead to a decrease in morbidity and mortality. The key is to maintain a high index of suspicion.
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PMID:Unsuspected neonatal killers in emergency medicine. 1547 77

Adrenomedullin (ADM) acts as an autocrine or a paracrine factor in the regulation of cardiac function. The intracellular mechanisms involved in the direct effect of ADM on adult rat ventricular myocytes (ARVMs) are still to be elucidated. In ARVMs from normal rats, ADM produced an initial (< 30 min) increase in cell shortening and Ca2+ transients and a marked decrease in both on prolonged incubation (> 1 h). Both effects were sensitive to ADM antagonist ADM-(22-52). Treatment with SQ-22536, an inhibitor of adenylate cyclase, blocked the positive inotropic effect of ADM and potentiated its negative inotropic effect. The negative inotropic effect was sensitive to inhibition by pertussis toxin (PTX), an inhibitor of Gi proteins and KT-5720, an inhibitor of PKA. The observations suggest a switch from Gs-coupled to PTX-sensitive, PKA-dependent Gi coupling by ADM in ARVMs. The ADM-mediated Gi-signaling system involves cAMP-dependent pathways because SQ-22536 further increased the negative inotropic actions of ADM. Also, because ADM is overproduced by ARVMs in our rat model of septic shock, ARVMs from LPS-treated rats were subjected to treatment with ADM-(22-52) and PTX. The decrease in cell shortening and Ca2+ transients in LPS-treated ARVMs could be reversed back with ADM-(22-52) and PTX. This indicates that ADM plays a role in mediating the negative inotropic effect in LPS-treated ARVM through the activation of Gi signaling. This study delineates the intracellular pathways involved in ADM-mediated direct inotropic effects on ARVMs and also suggests a role of ADM in sepsis.
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PMID:Gs and Gi coupling of adrenomedullin in adult rat ventricular myocytes. 1632 20

We previously showed that lysozyme (Lzm-S), derived from leukocytes, caused myocardial depression in canine sepsis by binding to the endocardial endothelium to release nitric oxide (NO). NO then diffuses to adjacent myocytes to activate the cGMP pathway. In a canine right ventricular trabecular (RVT) preparation, Lzm-S also decreased the inotropic response to field stimulation (FSR) during which the sympathetic and parasympathetic nerves were simulated to measure the adrenergic response. In the present study, we determined whether the pathway by which Lzm-S decreased FSR was different from the pathway by which Lzm-S reduced steady-state (SS) contraction. Furthermore, we determined whether the decrease in FSR was due to a decrease in sympathetic stimulation or enhanced parasympathetic signaling. In the RVT preparation, we found that the inhibitory effect of Lzm-S on FSR was prevented by NO synthase (NOS) inhibitors. A cGMP inhibitor also blocked the depressant activity of Lzm-S. However, in contrast to the Lzm-S-induced decline in SS contraction, chemical removal of the endocardial endothelium by Triton X-100 to eliminate endothelial NO release did not prevent the decrease in FSR. An inhibitory G protein was involved in the effect of Lzm-S, since FSR could be restored by treatment with pertussis toxin. Atropine prevented the Lzm-S-induced decline in FSR, whereas beta(1)- and beta(2)-adrenoceptor function was not impaired by Lzm-S. These results indicate that the Lzm-S-induced decrease in FSR results from a nonendothelial release of NO. NO then acts through inhibitory G protein to enhance parasympathetic signaling.
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PMID:Lysozyme, a mediator of sepsis, impairs the cardiac neural adrenergic response by nonendothelial release of NO and inhibitory G protein signaling. 1776 78

Adrenomedullin (ADM) is upregulated in cardiac tissue under various pathophysiological conditions, particularly in septic shock. The intracellular mechanisms involved in the effect of ADM on adult rat ventricular myocytes are still to be elucidated. Ventricular myocytes were isolated from adult rats 4 h after an intraperitoneal injection of lipopolysaccharide (LPS, 10 mg/kg). Membrane potential and L-type calcium current (I(Ca,L)) were determined using whole cell patch-clamp methods. APD in LPS group was significantly shorter than control values (time to 50% repolarization: LPS, 169 +/- 2 ms; control, 257 +/- 2 ms, P < 0.05; time to 90% repolarization: LPS, 220 +/- 2 ms; control, 305 +/- 2 ms, P < 0.05). I(Ca,L) density was significantly reduced in myocytes from the LPS group (-3.2 +/- 0.8 pA/pF) compared with that of control myocytes (-6.7 +/- 0.3 pA/pF, P < 0.05). The ADM antagonist ADM-(22-52) reversed the shortened APD and abolished the reduction of I(Ca,L) in shock myocytes. In myocytes from control rats, incubating with ADM for 1 h induced a marked decrease in peak I(Ca,L) density. This effect was reversed by ADM-(22-52). The G(i) protein inhibitor, pertussis toxin (PTX), the protein kinase A (PKA) inhibitor, KT-5720, and the specific cyclooxygenase 2 (COX-2) inhibitor, nimesulide, reversed the LPS-induced reduction in peak I(Ca,L). The results suggest a COX-2-involved PKA-dependent switch from G(s) coupled to PTX-sensitive G(i) coupling by ADM in adult rat ventricular myocytes. The present study delineates the intracellular pathways involved in ADM-mediated effects on I(Ca,L) in adult rat ventricular myocytes and also suggests a role of ADM in sepsis.
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PMID:The effect of adrenomedullin on the L-type calcium current in myocytes from septic shock rats: signaling pathway. 1776 82


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