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)

A new treatment program was developed in an attempt to increase the complete remission rate and survival of previously untreated patients with advanced stages of diffuse aggressive lymphomas. A flexible number of cycles of ProMACE chemotherapy (prednisone, methotrexate, doxorubicin, cyclophosphamide, and epipodophyllotoxin VP-16) was alternated with a flexible number of cycles of MOPP chemotherapy (mechlorethamine, vincristine sulfate, procarbazine, and prednisone), and finally late intensification with ProMACE therapy was given. The duration of each phase of treatment was determined by the patient's rate of tumor response. Complete remissions were achieved in 55 of 74 patients (74%) with a median duration of follow-up exceeding 2 1/2 years. Only ten of the complete responders (18%) have had relapse. The dose-limiting toxicity is myelosuppression, and eight patients (10%) died from sepsis. Median survival for all patients has not been reached but is predicted to exceed 4 years with 65% of patients alive at 4 years. Previously we achieved a 46% complete remission rate with 38% of all patients alive at 4 years; relapse-free survival beyond 2 years was tantamount to cure. Therefore, ProMACE-MOPP chemotherapy represents a substantial improvement in treating patients with diffuse aggressive lymphomas.
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PMID:Diffuse aggressive lymphomas: increased survival after alternating flexible sequences of proMACE and MOPP chemotherapy. 660 Sep 2

This study was designed to determine whether intravenously administered gentamicin sulfate and tobramycin sulfate penetrate into the eschar of patients with severe burns. In addition, each antibiotic's pharmacokinetics in serum and the effect on eschar microbiology were determined. Twenty patients with suspected burn wound sepsis received either gentamicin or tobramycin. The microbiology of the baseline eschar was determined and repeated on days 2, 4, and 7. All patients had measurable aminoglycoside tissue concentrations, and elimination from serum was not unusually rapid. Thirteen patients had baseline eschar cultures positive for Pseudomonas aeruginosa or Serratia marcescens; eight patients were initially bacteremic. Pseudomonas aeruginosa strains were sensitive to both antibiotics and usually declined in concentration with time or were eliminated; the more drug-resistant isolates of S marcescens persisted or caused super-infection and bacteremia. Aminoglycoside antibiotics penetrate into burn eschar and appear to have a substantial effect on eschar microbiology.
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PMID:Gentamicin and tobramycin penetration into burn eschar. Pharmacokinetics and microbiological effects. 682 30

Twelve dogs with lymphosarcoma and hypercalcemia were treated over a period of 36 months. Signs and laboratory findings were referable to hypercalcemia and azotemia. All dogs were staged, classified histologically, and given cytoreductive chemotherapy, using 5 drugs (vincristine sulfate, cytosine arabinoside, cyclophosphamide, L-asparaginase and prednisone). For azotemia, symptomatic therapy (0.9% NaCl solution and furosemide) was given. Seven dogs responded completely, with marked reduction of lymphadenopathy and return of serum calcium concentration to normal. Median duration of remission in this group was 48 days (range, 14 to 93), and median survival time was 112 days (range, 85 to 153). Five nonresponding dogs had less than 50% reduction in measurable tumor mass, although serum calcium concentration returned to normal. The median survival time for this group was 34 days (range, 23 to 68). Two of the nonresponders died from sepsis and another from disseminated intravascular coagulation. Response to therapy did not appear to be influenced by age, breed, sex, initial calcium concentration, degree of azotemia, or histologic classification.
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PMID:Chemotherapeutic responses in dogs with lymphosarcoma and hypercalcemia. 689 39

The techniques of biotype determination and sodium dodecyl sulfate-polyacrylamide gel electrophoresis of outer membrane protein preparations were applied to 35 epidemiologically unrelated isolates of pathogenic nontypable Haemophilus influenzae. Three of five isolates obtained from the blood of unrelated newborns with sepsis had concordant major outer membrane from the blood of unrelated older children or adults with bacteremia had concordant major outer membrane protein profiles, distinct from the common profile of neonatal strains, and were biotype II. The outer membrane protein profiles of the remaining 5 isolates from blood, 2 isolated from cerebrospinal fluid, and 23 isolated from middle ear aspirates of children with otitis media were unique, although each isolate had peptides with apparent molecular weights of 16,000 and 31,500. These results suggest that a subset of nontypable isolates associated with bacteremia has distinctive strain markers. Their pathogenicity may relate to a prediction for colonizing the female genital tract in the case of the common neonatal strain or an increased ability to evade host defenses.
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PMID:Outer membrane protein and biotype analysis of pathogenic nontypable Haemophilus influenzae. 697 11

Eleven premature neonates received gentamicin sulfate for treatment of suspected gram-negative sepsis with accompanying respiratory distress syndrome. Serum gentamicin concentrations were measured during and after treatment to monitor therapy and to determine the two-compartment distribution and elimination characteristics of the drug. The measured pharmacolinetic parameters were compared to those of 14 adult patients with similar glomerular filtration rates. Neonates, like adults and children, had a prolonged persistence of gentamicin in the serum after treatment was stopped. Although there were marked differences between neonates and adults in administered dose, clearance, and distribution volume when the data were expressed on the basis of body weight, these differences were no longer apparent when the data were expressed relative to body surface area. Differences in gentamicin disposition cannot explain the apparent lack of aminoglycoside nephrotoxicity among premature neonates.
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PMID:Two-compartment gentamicin pharmacokinetics in premature neonates: a comparison to adults with decreased glomerular filtration rates. 735 7

Streptococcus suis causes meningitis, sepsis, and other serious infections in newborn and young pigs and in adult humans. The Gal alpha 1-4Gal-binding adhesin of S. suis was purified to homogeneity by ultrasonic treatment, fractional ammonium sulfate precipitation, and preparative polyacrylamide gel electrophoresis. Pigeon ovomucoid, a glycoprotein with Gal alpha 1-4Gal terminals, was used to detect the adhesin by blotting. The purified adhesin appeared as single band of an apparent size of 18 kDa and of a pI of 6.4; no disulfide bridges were present. The amount of adhesin as revealed by pigeon ovomucoid binding correlated with the hemagglutination activity of different S. suis strains. The purified adhesin bound to latex particles induced hemagglutination which was specifically inhibited with the same inhibitors as hemagglutination by the intact bacteria, thus demonstrating that the purified protein was the Gal alpha 1-4Gal-recognizing adhesin of S. suis. Two adhesin variants (PN and PO) with differing Gal alpha 1-4Gal binding specificity had the similar electrophoretic mobilities and the same N-terminal peptide sequences, indicating that they were closely related. This represents the first isolation of an adhesin with well-defined cell surface carbohydrate binding activity from Gram-positive bacteria associated with meningitis.
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PMID:Purification of a galactosyl-alpha 1-4-galactose-binding adhesin from the gram-positive meningitis-associated bacterium Streptococcus suis. 749 14

Vascular endothelial injury observed in overwhelming sepsis may be caused by neutrophil-derived enzymes. Adherence to the endothelium, a prerequisite for this process, is mediated sequentially by the neutrophil adhesion molecules L-selectin and the beta 2 integrins including CD11b/CD18. The relationship between expression of these molecules, neutrophil adherence, endothelial activation, and consequent endothelial injury was assessed by changes in heparan sulfate and fibronectin matrices. Endothelial prestimulation with lipopolysaccharide caused both an increase in adherence and a generalized reduction in heparan sulfate; disruption of the fibronectin matrix occurred only on the further addition of FMLP. Although maximal disruption of these matrices was associated with elevation of neutrophil CD11b/CD18 and reduction in L-selectin expression, these changes did not determine either the nature or extent of endothelial damage. This model may provide further insights into the interrelationship between neutrophil activation and endothelial damage in gram-negative sepsis.
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PMID:Degradation of glycosaminoglycans and fibronectin on endotoxin-stimulated endothelium by adherent neutrophils: relationship to CD11b/CD18 and L-selectin expression. 768 Jul

Sepsis induces a net catabolic state in gastrocnemius by increasing protein degradation and decreasing protein synthesis. To determine whether or not sepsis induces a preferential effect on the expression of individual proteins, proteins from gastrocnemius muscle of control and septic rats were separated by two-dimensional isoelectric focusing/sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Laser densitometry of proteins stained with silver provided evidence that the relative abundance of thirty-five proteins was significantly (p < .05) and reproducibly increased during sepsis compared to control. No individual protein underwent significant down-regulation in their relative abundance during sepsis. Twenty-three of the 35 proteins identified in two-dimensional gels of the gastrocnemius were also present in the plasma of septic rats. The remaining 12 proteins, therefore, were taken to represent skeletal muscle proteins. One of the 12 proteins was identified by immunoblot analysis to be carbonic anhydrase III. Another of the proteins was identified as triosephosphate isomerase based upon microsequencing of the N terminus.
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PMID:Altered expression of skeletal muscle proteins during sepsis. 774 46

The effect of heparan sulfate (HS) on survival rate, bacterial translocation, and host defense was studied in a model of gut-derived sepsis that included transfusion-induced immunosuppression. Balb/c mice were treated pre- and postburn injury and bacterial challenge with HS, 5 mg/kg/day, or sterile phosphate-buffered saline. The HS pre- and postburn treated animals showed a significant improvement in survival compared to control animals (80 vs. 30%, p = .004, and 60 vs. 20%, p = .02, respectively). A lower amount of translocation was observed in the spleen (p < or = .001) of the HS group compared to control group. Quantitative colony counts and the calculated percentage of viable bacteria showed that the ability to kill translocated organisms was enhanced in all tissues of the animals receiving HS. These data suggest that treatment with HS positively affects the outcome in gut-derived sepsis. The beneficial effect was related both to an improved gut barrier function and to an enhanced host defense.
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PMID:Heparan sulfate increases survival during gut-derived sepsis by decreasing bacterial translocation and enhancing host defense. 775 15

We investigated whether hypermagnesemia alleviates hypoxic or group B streptococcal (GBS) pulmonary hypertension (PH). Hypoxic PH was induced and maintained in 14 lambs by continuous ventilation with 12% oxygen. GBS PH was induced and maintained in 16 lambs by the continuous infusion of 5-10 x 10(8) colony-forming units.kg-1.h-1 of GBS. After the onset of PH, lambs were randomized to receive either magnesium sulfate (MgSO4, intermittent boluses of 0.38 mmol/kg, with a continuous infusion of 0.15 mmol.kg-1.h-1) or a similar volume of normal saline. Hypermagnesemia lowered pulmonary arterial pressure (PAP) and delayed the fall in systemic arterial pressure and stroke volume index seen in the control animals (each P < 0.05). At a serum magnesium concentration ([Mg]) of 2.75 +/- 0.25 mmol/l, PAP was 27 +/- 3 compared with 40 +/- 4 Torr in the control animals ([Mg] = 0.87 +/- 0.06 mmol/l; P < 0.05). In the GBS PH trial, hypermagnesemia prevented the continued increase in PAP seen in the control animals. At [Mg] = 2.15 +/- 0.07 mmol/l, PAP fell 2 +/- 1 Torr from prerandomization values, whereas it rose 4 +/- 2 Torr in the control animals ([Mg] = 0.59 +/- 0.07 mmol/l; P < 0.05). However, during the same time the systemic arterial pressure fell further in the magnesium-treated animals (-19 +/- 1 vs. -2 +/- 5 Torr). MgSO4 attenuates PH in both models but may cause systemic hypotension in sepsis.
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PMID:Magnesium attenuates pulmonary hypertension due to hypoxia and group B streptococci. 800 24


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