The spectrum of septic encephalopathy. Definitions, etiologies, and mortalities.

OBJECTIVE: To determine whether the severity of septic encephalopathy is correlated with gram-negative bacteremia and mortality and whether there exists a single or combination of metabolic derangements(s) that cause septic encephalopathy. DESIGN AND SETTING: Prospective case series in an academic medical center. PATIENTS: Fifty patients selected according to clinical and laboratory criteria for severe sepsis. The criteria included temperature, heart rate, respiratory rate, and hypotension and/or signs of systemic hypoperfusion. MAIN OUTCOME MEASURES: A single or combination of metabolic and laboratory derangements and organ failures, three different methods to grade the severity of septic encephalopathy, Acute Physiology and Chronic Health Evaluation II (APACHE II) scores, gram-negative bacteremia and infection, and mortality. RESULTS: Encephalopathy was associated with an increase in mortality when graded by the Glasgow Coma Score; a score of 15 had 16% mortality, 13 to 14 had 20%, 9 to 12 had 50%, and 3 to 8 had 63% mortality (P < .05). Bacteremia was associated with encephalopathy; 13% of septic patients without encephalopathy vs 59% of patients with encephalopathy had bacteremia (P < .001) when graded by altered mental status. Septic encephalopathic patients had elevated serum urea nitrogen and bilirubin levels, increased APACHE II scores, and a higher incidence of renal failure. CONCLUSIONS: The severity of septic encephalopathy correlated with mortality, bacteremia, and renal and hepatic dysfunction. The Glasgow Coma Score is a useful tool for characterizing septic encephalopathy. Considerable variations can be found according to different criteria used to classify septic encephalopathy.

Pulmonary embolism as the presenting feature of hepatocellular carcinoma.

Primary hepatocellular carcinoma can be revealed by recurrent pulmonary embolism as observed in this case of a 63-year-old woman initially hospitalized for abdominal pain and shortness of breath. The clinical diagnosis was confirmed by laboratory findings, a ventilation perfusion scan and pulmonary angiography which demonstrated peripheral basal artery cut-off and slow filling with delayed washout. The patient was treated with heparin then with nicoumarol and responded well. One month after discharge the patient again complained of shortness of breath and was readmitted. Anticoagulation was adequate as evidenced by a prothrombin time of 1.39 INR and the physical examination and laboratory tests again suggested pulmonary emboli, confirmed by a ventilation perfusion scan. Computed tomography of the chest and abdomen revealed multiple hypodense masses filling half of the liver volume and needle biopsy led to the diagnosis of hepatocellular carcinoma. Hypercoagulability in malignancy is well-known although cases of migratory thrombophlebitis are extremely rare. Pulmonary embolism has not been described as a presenting feature of hepatocellular carcinoma. In this case, there was no evidence of hepatic dysfunction and the pulmonary embolism occurred despite adequate anticoagulation. Clinicians should include occult carcinoma among the possible causes of recurrent pulmonary embolism and when searching for malignancy can include hepatocellular carcinoma among the causes of hypercoagulation.

Ubiquitin in avian leukosis virus particles.

We have identified unconjugated ubiquitin as a component of avian leukosis virus (ALV). Quantitation both by immunoblotting and by protein staining showed that ubiquitin makes up about 0.5% of total viral protein, corresponding to 100 molecules per virion. This level is about fivefold higher than the level of unconjugated ubiquitin in the cytosol, when expressed as a fraction of total protein. Other abundant low molecular weight proteins in the cytosol were not detected in virions, indicating that packaging occurs in a specific manner. A naturally occurring ALV mutant that lacks the env gene was found to package normal levels of ubiquitin, ruling out involvement of the viral glycoproteins as carriers of ubiquitin. We examined disrupted virus particles as well as lysates of infected cells for the presence of gag protein-ubiquitin conjugates. No conjugates could be detected, suggesting that ubiquitin does not enter virions linked to gag protein.

Nucleotide sequence of the genome of Pf3, an IncP-1 plasmid-specific filamentous bacteriophage of Pseudomonas aeruginosa.

The circular, single-stranded DNA genome of the Pf3 bacteriophage was sequenced in its entirety by each of two methods, the M13-dideoxy chain termination method and the chemical degradation method. It consists of 5,833 nucleotides. With respect to both the DNA and the protein sequences, there is virtually no homology between Pf3 and the phages Ff (M13, f1, and fd) and IKe. However, similarities between these phages were noted with respect to their overall genome organizations. The gene for the single-stranded DNA-binding protein is followed by the gene for the major coat protein and then by a transcription termination signal. Open reading frames for seven other proteins were predicted, and their sizes and order show a fair correspondence to the sizes and order of the genes of the Ff phages and IKe. In addition, several regions have the potential to form stem and loop structures similar to those in the intergenic region of the Ff phage genome, but in Pf3 some are within open reading frames. Evolutionary relationships between Pf3 and the Ff phages and IKe are thus apparent through the correspondence of overall gene order rather than through primary sequence homologies.

Major coat protein and single-stranded DNA-binding protein of filamentous virus Pf3.

The region of the Pf3 virus genome encoding its major coat protein and its single-stranded DNA-binding protein is organized somewhat like the corresponding region of the fd (M13, f1) genome. Nevertheless, the major coat protein is unique among the major coat proteins of fd and the other filamentous phages studied in that it lacks a signal sequence and appears to be a direct translation product and in that it has fewer basic amino acid residues than its equivalent of DNA phosphates in the virion. These features are relevant to considerations of both protein insertion into membranes and DNA structure in filamentous viruses. The single-stranded DNA-binding protein also has a sequence that is different from the sequences of single-stranded DNA-binding proteins from other filamentous viruses.

Cloning of Pf3, a filamentous bacteriophage of Pseudomonas aeruginosa, into the pBD214 vector of Bacillus subtilis.

The genome of Pf3, a filamentous single-stranded DNA bacteriophage of Pseudomonas aeruginosa (a gram-negative organism) was cloned into pBD214, a plasmid cloning vector of Bacillus subtilis (a gram-positive organism). Cloning in the gram-positive organism was done to avoid anticipated lethal effects. The entire Pf3 genome was inserted in each orientation at a unique Bc/I site within a thymidylate synthetase gene (from B. subtilis phage beta 22) on the plasmid. Additional clones were made by inserting EcoRI fragments of Pf3 DNA into a unique EcoRI site within this gene.