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

Twenty critically ill patients with a diagnosis of possible or documented Gram-negative sepsis received gentamicin sulphate by i.v. short infusion (30 min). The same daily dose was administered in a variable frequency regimen (ten were treated by an 8 h frequency regimen and ten by a 12 h frequency regimen). Repeated measurements of gentamicin plasma levels and of serum creatinine, albumin, total proteins and haematocrit were performed simultaneously, with measurements of tubular casts, alkaline phosphatase, leucine aminopeptidase and gamma-glutamyl-transpeptidase activity in urine. There was a considerable variation in plasma gentamicin concentrations among individuals patients and in the same patient from day to day with each dosage regimen. Despite the daily administration of at least 5 mg/kg/day of gentamicin, nephrotoxicity occurred in only one patient. The mean duration of therapy was about ten days. Although the series of patients was small, no significant difference was reported in either the 8 or 12 h dosage regimen in respect to favourable response to treatment among the patients. Probably a high peak concentration greatly exceeding the minimal inhibitory concentration (MIC) for a short duration, kills Gram-negative bacteria as effectively as a long concentration exceeding the MIC for a longer period of time. The reported half-lives and area under curve values for gentamicin in our patients varied widely even in the same patient.
 ...
PMID:Dosing problems of gentamicin in critically ill patients. 378 98

Liver injury is a common complication in allogeneic hematopoietic stem cell transplantation. Its major causes comprise graft-versus-host disease (GVHD), infection, and toxicities of preparative regimens and immunosuppressants; however, we have little information on liver injuries after reduced intensity cord blood transplantation (RICBT). We reviewed medical records of 104 recipients who underwent RICBT between March 2002 and May 2004 at Toranomon Hospital. Preparative regimen and GVHD prophylaxis comprised fludarabine/melphalan/total body irradiation and cyclosporine or tacrolimus. We assessed the etiology of liver injuries based on the clinical presentation, laboratory results, comorbid events, and imaging studies in 85 patients who achieved primary engraftment. The severity of liver dysfunction was assessed according to the National Cancer Institute Common Toxicity Criteria version 2.0. Hyperbilirubinemia was graded according to a report by Hogan et al (Blood. 2004;103:78-84). Moderate to very severe liver injuries were observed in 36 patients. Their causes included cholestatic liver disease (CLD) related to GVHD or sepsis (n = 15), GVHD (n = 7), cholangitis lenta (n = 5), and others (n = 9). Median onsets of CLD, GVHD, and cholangitis lenta were days 37, 40, and 22, respectively. Frequencies of grade 3-4 alanine aminotransferase elevation were comparable across the 3 types of hepatic injuries. Serum gamma-glutamil transpeptidase was not elevated in any patients with cholangitis lenta, whereas 27% and 40% of patients with CLD and GVHD, respectively, developed grade 3-4 gamma-glutamil transpeptidase elevation. Multivariate analysis identified 2 risk factors for hyperbilirubinemia; grade II-IV acute GVHD (relative risk, 2.23; 95% confidential interval, 1.11-4.47; P = .024) and blood stream infection (relative risk, 3.77; 95% confidential interval, 1.91-7.44; P = .00013). In conclusion, the present study has demonstrated that the hepatic injuries are significant problems after RICBT, and that GVHD and blood stream infection contribute to their pathogenesis.
 ...
PMID:Hepatic injury following reduced intensity unrelated cord blood transplantation for adult patients with hematological diseases. 1716 12

Methicillin-resistant Staphylococcus aureus (MRSA) is the most frequent cause of hospital-acquired infection, which manifests as surgical site infections, bacteremia, and sepsis. Due to drug-resistance, prophylaxis of MRSA infection with antibiotics frequently fails or incites nosocomial diseases such as Clostridium difficile infection. Sortase A is a transpeptidase that anchors surface proteins in the envelope of S. aureus, and sortase mutants are unable to cause bacteremia or sepsis in mice. Here we used virtual screening and optimization of inhibitor structure to identify 3-(4-pyridinyl)-6-(2-sodiumsulfonatephenyl)[1,2,4]triazolo[3,4-b][1,3,4]thiadiazole and related compounds, which block sortase activity in vitro and in vivo. Sortase inhibitors do not affect in vitro staphylococcal growth yet protect mice against lethal S. aureus bacteremia. Thus, sortase inhibitors may be useful as antiinfective therapy to prevent hospital-acquired S. aureus infection in high-risk patients without the side effects of antibiotics.
...
PMID:Antiinfective therapy with a small molecule inhibitor of Staphylococcus aureus sortase. 2519 57