Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036690 (sepsis)
 59,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pertussis toxin, and also cholera toxin are capable of inhibiting the effects of LPS in the elicitation of the generalized Schwartzman reaction. This is a potentially lethal generalized thrombo-haemorrhagic hypersensitivity and inflammatory-type response that occurs after two consecutive injections of LPS. The two exotoxins furnish significant protection against the lethal outcome of this reaction. It is known that the acute haematological and haemodynamic changes are accompanied by alterations in the levels of various endogenous mediators: glucocorticoid hormones, prostaglandins, arachidonic acid metabolites, cytokines and proteases. In vitro effects of LPS on murine leukocyte cell lines can be antagonized by pertussis toxin, implicating a Gi-like regulatory protein in the mediation of these effects. Experiments designed to study the involvement of particular second messenger systems (cAMP and phosphatidylinositol) used by LPS in vivo, revealed that the protective effects conferred by these exotoxins are associated with the antagonization of alterations caused by LPS. No correlation was found between the levels of IL-6 and the mortality rate in this experimental mouse model. The results indicate that G proteins play a role in the generation of the Schwartzman reaction and open a new approach for pharmacological intervention in endotoxemia and in clinical settings with Gram-negative sepsis.
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PMID:Cholera and pertussis exotoxins protect mice against the lethal Schwartzman reaction and antagonize the effects of lipopolysaccharide on second messenger systems. 216 28

Despite numerous reports, the role of tumor necrosis factor (TNF) in polymorphonuclear leukocyte (PMN) function remains controversial. We found TNF to be a potent, pertussis toxin-independent stimulator of PMN adhesion (ED50 2.6 pM). TNF-stimulated PMN under adherent conditions released up to 65% of their transcobalamine content (ED50 3.9 pM) and increased their burst activity 10-fold (ED50 3.2 pM) as measured by the hexose monophosphate shunt, whereas PMN held in suspension hardly degranulated at all and only little burst activity was demonstrable. However, preincubation of PMN with TNF in suspension led to a decrease in cellular adhesiveness, degranulation, and burst activity in response to a secondary stimulus of TNF under adherent conditions, although cells remained fully responsive toward phorbol myristate acetate. A concomitant dose-dependent decline of TNF receptor numbers that correlated well with the inhibition of PMN function (r = 0.91) suggests receptor down-regulation as the mechanism of functional PMN deactivation. Remarkably, preincubation with other PMN stimuli such as N-formyl-methionyl-leucyl-phenylalanine, platelet-activating factor, leukotriene B4, complement component fragment 5a (C5a)/C5a (desarginated), and endotoxin also led to a reduction of TNF-specific PMN responses (cross-deactivation) from 35% (LTB4) to 90% (endotoxin), corresponding with the down-regulation of TNF receptors. Deactivation and receptor down-regulation are independent of pertussis toxin-sensitive G proteins and protein kinase C but seemed to depend on changes in calcium metabolism. Granulocyte hyporesponsiveness towards TNF in sepsis (with elevated blood levels of endotoxin and TNF) might be a mechanism of self-protection or, to the contrary, might impair a possibly central mode of host defense.
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PMID:The tumor necrosis factor receptor and human neutrophil function. Deactivation and cross-deactivation of tumor necrosis factor-induced neutrophil responses by receptor down-regulation. 216 42

Endothelium is an important target of tumor necrosis factor/cachectin (TNF), a central mediator of the host response in endotoxemia and Gram-negative sepsis. In this report, TNF is shown to increase the permeability of endothelial cell monolayers to macromolecules and lower molecular weight solutes by a mechanism involving a pertussis toxin-sensitive regulatory G protein. Within 1-3 h of exposure to TNF (5 nM), changes in cell shape/cytoskeleton occurred that led to disruption of monolayer continuity with the formation of intercellular gaps. Correlated with these structural changes was an increase in endothelial permeability to macromolecular and lower molecular weight tracers; time-dependent, reversible increases in passage of these tracers, evident by 1-3 h, were observed after addition of TNF to cultures. Perturbation of barrier function by TNF also depended on the dose of TNF added being half-maximal by approximately 0.4 nM. Only a brief exposure (15 min) of TNF to endothelium was required to induce an increase in permeability, and this was not prevented by the presence of cycloheximide or actinomycin D. Preincubation of monolayers with pertussis toxin blocked in parallel TNF-induced increased passage of solutes and cell shape/cytoskeletal perturbation, indicating the close correlation between these changes in endothelial cell function. In contrast, pertussis toxin did not alter TNF-induced modulation of two endothelial cell coagulant properties. These data provide evidence for two intracellular pathways of TNF action that are distinguishable by pertussis toxin and provide insight into a mechanism underlying loss of solute from the intravascular space mediated by TNF: alteration in endothelial cell barrier function.
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PMID:Tumor necrosis factor/cachectin increases permeability of endothelial cell monolayers by a mechanism involving regulatory G proteins. 249 53

To focus attention on the problem of infant mortality in Lebanon, data were compiled on infant mortality from 1978 to 1986 at the American University of Beirut Medical Center. Causes of death are analyzed for 602 males and 398 females. 54.9% deaths occurred at 1 month of age and 77.4% died within the 1st year. Autopsies were performed on .7%. 37.7% of all neonatal deaths were due to neonatal diseases such as hyaline membrane disease, asphyxia neonatorum, immaturity, necrotizing enterocolitis, hemorrhage, hemolysis, meconium aspiration, and kernicterus. Better prenatal care would reduce this group, or the administration of corticosteroids to the mother 24-48 hours prior to delivery, as well as rapid resuscitation at birth and prevention of the 5 curses: hypoxemia, hypoglycemia, hypothermia, hypotension, and acidosis. Although unavailable in Lebanon, administration of surfactants through an endotracheal tube would also help. Infections constitute 25.1% of deaths; many are preventable through adequate public health measures and strict personal hygiene, i.e., diseases such as sepsis, pneumonia, meningitis, gastroenteritis, hepatitis, encephalitis, and 1-2 cases of the following: diphtheria, measles, peritonitis, tetanus, tuberculosis, cytomegalis inclusion, herpes, parathyphoid, pertussis, poliomyelitis, and shigellosis. Congenital diseases were 21.6%. In utero diagnosis could prevent some diseases and in utero treatment is possible for hydrocephalus and hydronephrosis. Screening programs postnatally could lead to treatment. 5.9% were malignancies such as leukemia, lymphoma, brain tumors, histocytosis, Wilm's tumor, Ewing sarcoma, and Hodgkin's disease. Early diagnosis is critical if mortality is to be reduced in this group, but medical advances are still needed. 2.9% are miscellaneous diseases such as poisoning, rheumatic diseases, marasmus, Reye's syndrome, nephrosis, rickets, and epilepsy. Most of these diseases are preventable, except for rheumatic inflammation of the heart. Recommended necessary steps to reduce infant mortality are: prenatal care, diagnosis and screening, intrauterine surgery; resuscitation and intensive care centers with modern equipment and trained personnel; national vaccination and screening programs; adequate public health measures and hygiene; parental education; and well-equipped hospitals to serve all regardless of income level.
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PMID:Pediatric mortality: an avoidable tragedy. 251 28

Infant mortality rate (IMR) and its relation to the utilization of health services was studied in twelve villages of ICDS block Rajsamand, Rajasthan from 1st April, 1985 to 31st March, 1986. The total number of births and infant deaths were 386 and 74, respectively during one year, computing 37.44 as birth rate and 191.70 as IMR. Neonatal deaths contributed 51.4%, the most common causes of which were septicemia (28.9%), birth asphyxia (23.6%), extreme prematurity (18.4%) and tetanus neonatorum (13.1%). The common causes of deaths in post-neonatal period were pneumonia (36.1%), diarrhea (25.0%), complications of measles (16.7%) and that of pertussis (8.3%). Extreme under utilization of preventive, promotive and curative MCH services was found to be one of the major factors for very high IMR prevailing in the region.
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PMID:Under utilization of MCH services--the major factor for very high IMR in rural Rajasthan. 275 49

A double blind placebo-controlled efficacy trial of two acellular pertussis vaccines was conducted in 3801 6- to 11-month-old children. Four vaccinated children died during 7 to 9 months follow-up as a result of Haemophilus influenzae type b meningitis, heroin intoxication with concomitant pneumonia, suspected septicemia, and Neisseria meningitidis Group B septicemia. From the actual death rate in children belonging to the same birth cohort in Sweden that could have been eligible for the trial, one death was expected among vaccinated children. Several investigations were carried out to examine the possibility that the deaths could be causally related to the vaccination. The relative risk for hospitalization due to systemic or respiratory infections was 1.07 (95% confidence interval, 0.95 to 1.20) and 0.83 (95% confidence interval, 0.64 to 1.08) in the vaccine groups as compared with the placebo group. Subsets of the population were studied for signs of immunosuppression. There was no indication of immunoglobulin deficiency or any sign of clinically significant leukopenia or lymphocytosis in vaccine recipients. The results of this analysis provide no evidence for a causal relation between vaccination with the studied acellular pertussis vaccines and altered resistance to invasive disease caused by encapsulated bacteria. The hypothesis that the two variables are related, however, cannot be refuted from these data.
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PMID:Mortality and morbidity from invasive bacterial infections during a clinical trial of acellular pertussis vaccines in Sweden. 305 Aug 58

Ceftazidime (CAZ) intravenous injection was evaluated from fundamental and clinical aspects in neonates, and the results obtained are summarized below. Following a 60-minute intravenous drip infusion of CAZ at 10 mg/kg, the peak serum level was 19.8 micrograms/ml at 30 minutes after the completion of the infusion(half-life: 2.75 hours). Following 30 to 60-minute intravenous drip infusions of CAZ at 20 mg/kg, the mean peak serum levels of CAZ were 33.1-33.0 micrograms/ml. Mean levels at 6 hours were 5.2-6.7 micrograms/ml (half-life: 1.6-4.1 hours). Following 30 to 60-minute intravenous drip infusions of CAZ at 25-30 mg/kg, peak serum levels were 51.7-64.6 micrograms/ml (half-life: 1.6-2.05 hours). Dose response relationship was clearly observed in peak serum levels after intravenous drip infusion, and half-lives of serum CAZ levels in neonates aged 0-10 days tended to be longer than those in infants. Following intravenous administration of CAZ at 20-30 mg/kg, urinary excretion rates during the first 6 hours were 18.7-66.5%, and the rates were low in neonates compared to those in infants and children. Following a 60-minute intravenous drip infusion of CAZ at 28.7 mg/kg, the cerebrospinal fluid level was 5.0 micrograms/ml at 3 hours, the ratio of cerebrospinal fluid level to serum level was 22.5%. Eleven neonates were subjected to the present study. Clinical efficacy of CAZ was excellent in sepsis caused by A. anitratus, which showed higher sensitivity to CAZ compared with other cephem antibiotics of the third generation. In all of the other cases, including those of pertussis and acute urinary tract infections and in the prophylaxis of amniotic infection, clinical efficacy of CAZ was excellent or good. S. epidermidis, E. coli and A. anitratus, identified from cultures of pharynx, urine or blood, were rapidly eliminated during the CAZ treatment. Doses of CAZ used in the present study were 29-133 mg/kg/day, mostly in the range of 40-60 mg/kg/day. Durations of treatment ranged from 3 to 10 days. Neither systemic nor local adverse effect was observed, nor was any abnormality observed in laboratory findings.
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PMID:[Fundamental and clinical evaluations of ceftazidime in neonates]. 354 Mar 44

Studies on T-1982 (cefbuperazone), a new cephamycin antibiotic, were carried out in the field of pediatrics, and the following results were obtained. 1. Peak MIC of T-1982 against S. pyogenes (group A) lately isolated was 0.39 micrograms/ml, and the drug was active even against highly resistant strains of macrolides, lincomycin, tetracycline and chloramphenicol. 2. Peak MICs of T-1982 were 0.78 microgram/ml against B. pertussis, 0.2 microgram/ml against E. coli and less than or equal to 0.05 microgram/ml against K. oxytoca, and the drug was also active against ampicillin-resistant bacteria. 3. Serum levels and urinary excretions of T-1982 were investigated in 6 cases. When given at a dose of 20-28 mg/kg by 1 hour intravenous drip infusion, serum concentrations of T-1982 attained the peak level of 63.5-75.9 micrograms/ml at the end of administration and sustained the level of 0.9-2.6 micrograms/ml at 6 hours, the serum half-life (T 1/2) ranging 70-82 minutes. Approximately 20-72% of the dose were excreted in the active form into urine within 6 hours. 4. Twenty-seven cases of acute pediatric infections were treated with T-1982 mainly by intravenous drip infusion, and satisfactory clinical results were obtained in all the cases of angina lacunaris, bronchitis, bronchopneumonia, pertussis, sepsis caused by Serratia and acute urinary tract infections caused by ampicillin-resistant E. coli. The efficacy rate was 96.3%. In this study the drug was administered chiefly at a daily dose of 50-70 mg/kg 2-3 times a day for 2-12 days. 5. Gram-positive cocci (S. aureus, S. pneumoniae, S. pyogenes) and Gram-negative rods (H. influenzae, H. parainfluenzae P. vulgaris, B. pertussis, S. marcescens, E. coli) were eradicated by the treatment with T-1982. 6. No noticeable side effects were observed, except for temporary increase of eosinophil in 2 cases and slight elevation of GOT in 1 case.
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PMID:[Fundamental and clinical studies on T-1982 (cefbuperzone), a new cephamycin antibiotic, in the field of pediatrics]. 630 96

Cefoperazone (CPZ) was given intravenously to 23 children with the following acute bacterial infections; 10 cases of pneumonia, 4 cases of urinary tract infection, 2 cases of purulent cervical lymphadenitis, 2 cases of pertussis pneumonia, 2 cases of septicemia, 1 case of osteomyelitis, 1 case of perforative peritonitis and 1 case of bacterial meningitis. Clinical effectiveness was obtained in 20 cases out of 23 cases and bacteriological effectiveness in 14 cases out of 17 cases. With CPZ, the following side effects developed; transient diarrhea in 1 case, asymptomatic eosinophilia in 2 cases. From the above clinical results, it is apparent that CPZ is a useful antibiotic for treating pediatric patients with various kinds of bacterial infections.
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PMID:[Clinical experience with cefoperazone in the pediatric field (author's transl)]. 645 40

A new semisynthetic 1-oxa-beta-lactam derivative, 6059-S, was evaluated for its safety and efficacy in children. Twenty-five patients were treated with 10 to 274 mg/kg per day of 6059-S by intravenous administrations. The diagnosis of the patients were acute pharyngitis (2), acute bronchitis (2), pneumonia (4), pertussis (4), acute enterocolitis (2), recurrent urinary tract infection (2), suspected septicemia (3), and acute purulent meningitis (1); and the remaining 5 patients were considered to have nonbacterial infections. The pathogens recovered were Streptococcus pneumoniae (1), Haemophilus influenzae (4), Haemophilus parainfluenzae (1), Enterobacter cloacae (1), Enterobacter aerogenes (1), Proteus morganii (1), Psuedomonas aeruginosa (2) and Salmonella typhimurium (1). All the patients of bacterial infections were cured after the 6059-S therapy. However, Pseudomonas aeruginosa and Salmonella typhimurium were not eradicated after the 6059-S therapy, and the rate of bacterial disappearance was 75%. Diarrhea (3), precordial pain (2, only in cases with high-dose therapy), transient elevation of GOT and GPT (2), and transient eosinophilia (2) were found to be associated with the 6059-S therapy. However, no severe adverse reactions were encountered. Half life of the serum 6059-S level was 1.34 +/- 0.16 hours. CSF concentrations in a case with Haemophilus influenzae meningitis ranged 4.0 to 9.7 mcg/ml after an intravenous injection of 34.3 to 75 mg/kg of 6059-S. From the present study, 6059-S appears to be a safe and effective antibiotic when used in children with susceptible bacterial infections. It remains to be further determined whether 6059-S is superior to ABPC in the treatment of Haemophilus influenzae meningitis.
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PMID:[Clinical evaluation of 6059-S therapy in children (author's transl)]. 645 68


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