The effect of motilin on the rectum in healthy volunteers.

AIMS: The role of motilin in the regulation of upper gastrointestinal (GI) motility is well defined. However, little is known about the effects on the distal GI tract. To investigate the effect of exogenous motilin on rectal function, barostat measurements in the rectum were performed and lower abdominal symptoms were scored. METHODS: Eight fasted, healthy volunteers were infused intravenously with synthetic motilin or placebo over 90 min in a double-blind, randomized, cross-over design. Rectum volume was measured with a barostat device during constant pressure and during isobaric distensions. Lower abdominal symptoms were scored by visual analogue scales. Plasma motilin concentrations were measured by radioimmunoassay. RESULTS: Baseline rectum volumes were similar between treatments: 185 +/- 62 mL (motilin) and 136 +/- 41 mL (placebo). During the constant pressure procedure, motilin increased rectum volume [area under the effect curve (AUEC)] by 6%[95% confidence interval (CI) -3, 16] of baseline, compared with placebo. During isobaric distensions motilin increased rectum volume (AUEC) by 43 mL (95% CI 0.4, 85; P < 0.05) and compliance by 10 mL mmHg-1 (95% CI 0.3, 20; P < 0.05) relative to placebo. Motilin did not induce changes in the sensation of rectal feelings. CONCLUSION: Exogenous motilin increased rectal compliance in healthy volunteers, without affecting rectal sensations.

Perflubron emulsion delays blood transfusions in orthopedic surgery. European Perflubron Emulsion Study Group.

BACKGROUND: Fluorocarbon emulsions have been proposed as temporary artificial oxygen carriers. The aim of the present study is to compare the effectiveness of perflubron emulsion with the effectiveness of autologous blood or colloid infusion for reversal of physiologic transfusion triggers. METHODS: A multinational, multicenter, randomized, controlled, single-blind, parallel group study was performed in 147 orthopedic patients. Patients underwent acute normovolemic hemodilution with colloid to a target hemoglobin of 9 g/dl with an inspiratory oxygen fraction (FIO2) of 0.40. Patients were then randomized into one of four treatment groups after having reached any of the protocol-defined transfusion triggers including tachycardia (heart rate > 125% of posthemodilution rate or > 110 bpm), hypotension (mean arterial pressure < 75% of posthemodilution level or < or = 60 mmHg), elevated cardiac output (> 150% of posthemodilution level) or decreased mixed venous oxygen partial pressure (PVO2; < 38 mmHg). Treatments in the four groups were 450 ml autologous blood harvested during acute normovolemic hemodilution given at FO2 = 0.40; 450 ml colloid at FIO2 = 1.0; 0.9 g/kg perflubron emulsion with colloid (total = 450 ml) at FIO2 = 1.0; and 1.8 g/kg perflubron emulsion with colloid (total = 450 ml) at FIO2 = 1.0. The primary endpoint was duration of transfusion-trigger reversal. A secondary end-point was percentage of transfusion-trigger reversal. RESULTS: Perflubron emulsion was well tolerated with no serious adverse event attributed to drug treatment. Duration of reversal was longest in the 1.8 g/kg perflubron group (median, 80 min; 95% confidence interval, 60-100 min; P = 0.014 vs. autologous blood, P < 0.001 vs. colloid) followed by the 0.9 g/kg perflubron group (median, 59 min; 95% confidence interval, 40-90 min), the autologous blood group (median, 55 min; 95% confidence interval, 30-70 min) and the colloid group (median, 30 min; 95% confidence interval, 27-60 min). Percentage of reversal was also highest in the 1.8 g/kg perflubron group (97%; P < 0.001 vs. autologous blood; P = 0.014 vs. colloid), followed by 0.9 g/kg perflubron (82%), colloid (76%), and autologous blood (60%). CONCLUSIONS: Perflubron emulsion (1.8 g/kg) combined with 100% oxygen ventilation is more effective than autologous blood or colloid infusion in reversing physiologic transfusion triggers.

Genetic and transcriptional analysis of flgB flagellar operon constituents in the oral spirochete Treponema denticola and their heterologous expression in enteric bacteria.

Oral spirochetes possess many potential virulence factors, including the capacity for tissue invasion and persistence despite a vigorous host immune response. In an attempt to identify treponemal immunoreactive components, sera derived from individuals with advanced periodontal disease were used as a reagent to isolate recombinant bacteriophage lambda clones expressing antigens of the oral spirochete Treponema denticola ATCC 35405. Nucleotide sequence analysis of a clone expressing three immunoreactive products has revealed seven T. denticola genes which appear to encode homologs of flagellar basal body constituents, FlgB, FlgC, FliE, and FliF, a flagellar switch component, FliG, and the putative flagellar export proteins, FliH and FliI, initially characterized in Salmonella typhimurium. Also identified was a gene resembling fliJ. Primer extension analysis identified a transcriptional start site 5' to the treponemal flgB gene. Appropriately spaced with respect to this start site was a sigma28 binding motif. The absence of additional identifiable sigma factor binding motifs within the treponemal sequence and the proximity of adjacent genes suggested operonic arrangement, and reverse transcriptase PCR provided evidence of cotranscription. Supporting the identification of these genes as flagellar components, heterologous expression in enteric bacteria of the putative switch basal body genes from T. denticola interfered with motility. Specifically, the presence of a plasmid expressing treponemal fliG reduced swarming motility in S. typhimurium, while in Escherichia coli, this plasmid conferred a nonmotile phenotype and a reduction in flagellar number. Thus, while spirochetal flagella are subject to unique synthetic and functional constraints, the organization of flagellar genes and the presence of sigma28-like elements are reminiscent of the flagellar systems of other bacteria, and there appears to be sufficient conservation of constituent proteins to allow interaction between T. denticola switch-basal body proteins and the flagellar machinery of gram-negative bacteria.

Identification of a fliG homologue in Treponema denticola.

Using a bacteriophage lambda library of Treponema denticola (Td) ATCC 35405 DNA, and, as a reagent, sera derived from individuals with advanced adult periodontal disease, a variety of recombinant clones producing antigens of this oral spirochete have been isolated. Nucleotide sequence analysis of a clone expressing three immunoreactive antigens has revealed the presence of an open reading frame highly homologous to the flagellar switch/motor protein, FliG, which is known to be essential for flagellar assembly and rotation, and chemotaxis in enteric bacteria. The deduced amino-acid sequence of the treponemal FliG protein had 73% similarity (55% identity) to the Bacillus subtilis FliG protein, and showed significant, but lesser homologies to Gram- FliG proteins. Sequence analysis of regions flanking fliG indicated that this gene is immediately preceded by a fliF homologue, further supporting that the cloned DNA encodes FliG of Td. The findings imply that although the signals for control of chemotaxis may be distinctly different in spirochetes, at least some of the molecules involved in torque generation, control of flagellar rotation and signal transduction are highly conserved with other bacteria. The stronger homology of the spirochete FliG with those of Gram+ bacteria is also consistent with recent analyses of other spirochetal genes.