Validation and characterization of a human volunteer challenge model for cholera by using frozen bacteria of the new Vibrio cholerae epidemic serotype, O139.

Until recently, all epidemic strains of Vibrio cholerae were of the O1 serotype. Current epidemics have also been caused by a new serotype, Vibrio cholerae O139. Although the pathogenesis and clinical features of O139 cholera are similar to those of O1 cholera, immunity to serotype O1 does not confer immunity to serotype O139. Therefore, prior to beginning vaccine efficacy studies, we sought to validate the use of a large standardized frozen inoculum of virulent V. cholerae O139 4260B for use in a human volunteer challenge model. Healthy volunteers (n = 25) were recruited for an Internal Review Board-approved inpatient dose-escalation challenge. Our goal was to identify a dose at which the cholera attack rate and the geometric mean purge were sufficient for determining vaccine efficacy against moderate and severe disease. At a dose of 10(5) CFU, 8 of 10 volunteers experienced purging and had a positive stool culture for V. cholerae. However, at this dose, the geometric mean stool volume of 2,175 g was insufficient by study criteria. At a dose of 10(6) CFU, 14 of 15 volunteers experienced purging, with a geometric mean stool volume of 5,621 g. Disease severity was significantly greater in volunteers with blood group O than those with non-O blood types (10,353 g versus 3,555 g, P < 0.001). Following challenge, all volunteers demonstrated a significant rise in antitoxin antibodies but the serum vibriocidal titer was attenuated compared to that seen after challenge with an O1 strain. This model provides a reproducible illness of sufficient severity for testing the efficacies of new O139 or combined O1-O139 vaccines.

Trimethaphan versus sodium nitroprusside for the control of proximal hypertension during thoracic aortic cross-clamping: the effects on spinal cord ischemia.

Sodium nitroprusside (SNP) has been used to control the proximal hypertension associated with thoracic aortic cross-clamping (TACC) during thoracic aortic surgery. It worsens neurologic outcome, presumably by further decreasing distal arterial pressure and increasing cerebrospinal fluid (CSF) pressure, thereby worsening the spinal cord perfusion pressure (SCPP). Trimethaphan does not increase CSF pressure. Therefore, the present study investigates the effect of trimethaphan versus SNP to control proximal hypertension during TACC on neurologic outcome. Two groups, each with eight mongrel dogs, were studied. All animals underwent descending TACC for 45 min. The mean proximal aortic blood pressure was maintained at 95-100 mm Hg by the use of SNP or trimethaphan. Distal aortic pressure was allowed to vary. The dogs were neurologically evaluated 24 and 48 h later by a blinded observer. During cross-clamping, there was no difference in mean proximal aortic pressure between groups. After 10 min of cross-clamping, distal aortic pressure was higher (P < 0.01), CSF pressure was lower (P < 0.01), and SCPP was higher (P < 0.005) in the trimethaphan group as compared with the SNP group (group effect). Neurologic outcome as assessed by Tarlov's score was better at 24 and 48 h in the trimethaphan group (P < 0.05). Histopathologic injury trended with worsened neurologic outcome. We conclude that 1) trimethaphan produced higher SCPP than SNP, and 2) neurologic outcome was better in the trimethaphan group.

Effect of nitroglycerin on spinal cord ischemia after thoracic aortic cross-clamping.

BACKGROUND: Thoracic aortic cross-clamping with the use of sodium nitroprusside (SNP) has been shown to cause a decrease in spinal cord perfusion pressure and an increased incidence of paraplegia. Nitroglycerin is frequently used in this setting. This study investigated the effects of nitroglycerin and SNP on spinal cord ischemia. METHODS: Three-groups of 8 mongrel dogs underwent thoracic aortic cross-clamping for 45 minutes. Proximal pressure was maintained between 95 and 100 mm Hg with SNP, nitroglycerin, or phlebotomy. All animals were neurologically evaluated 24 hours later by a blinded observer, and the findings were confirmed by histopathologic study. Statistical analysis (p value of less than 0.05) of measured hemodynamic data was by analysis of variance and of Tarlov scores, the Mann-Whitney U test. RESULTS: Distal aortic pressures (p < 0.001), Tarlov scores, and spinal cord perfusion pressures (p < 0.01 and p < 0.05 for SNP group and nitroglycerin group, respectively) were significantly higher in the phlebotomy group compared with the SNP and NTG groups. Cerebrospinal fluid pressures were significantly lower in the phlebotomy group compared with the SNP group (p < 0.001). CONCLUSIONS: The use of either NTG or SNP was associated with a high incidence of paraplegia. Nitroglycerin appears to be no safer than SNP when used during thoracic aortic cross-clamping.

Isoflurane versus sodium nitroprusside for the control of proximal hypertension during thoracic aortic cross-clamping: effects on spinal cord ischemia.

OBJECTIVE: This study was designed to compare the effects of isoflurane and nitroprusside on spinal cord ischemia when they are used to control proximal hypertension during thoracic aortic cross-clamping (TACC). DESIGN: Prospective, randomized, blinded experimental study. SETTING: Laboratory and animal research facility. PARTICIPANTS: Adult mongrel dogs. INTERVENTIONS: Two groups of eight dogs had TACC for 45 minutes. Proximal aortic, distal aortic, and cerebrospinal pressure was calculated as the distal mean pressure minus the CSF pressure. Group 1 received nitroprusside and group 2 received isoflurane to control proximal hypertension during cross-clamping. The dogs were neurologically evaluated 24 and 48 hours later by an observer blinded as to the study group. Spinal cord segments were obtained for histopathologic examination. MEASUREMENTS AND MAIN RESULTS: Distal perfusion pressure and spinal cord perfusion pressure were significantly higher in the isoflurane group (p < .005). At 24 hours, seven of eight dogs in group 1 had severe neurologic injury (ie, paraplegia), with the eight having mild neurologic injury. This is in contrast to group 2, where 6 of 8 dogs had either minimal or no injury, one had mild injury, and one had severe injury. Similar results were observed at 48 hours (p < .005). CONCLUSIONS: Isoflurane, when used to control proximal hypertension during TACC, produces a higher spinal cord perfusion pressure and is associated with a lower incidence of neurologic injury than nitroprusside in this canine model.

Intrathecal magnesium sulfate protects the spinal cord from ischemic injury during thoracic aortic cross-clamping.

BACKGROUND: Paraplegia is a known complication after surgery on the descending thoracic aorta. Thoracic aortic cross-clamping causes an increase in proximal aortic and cerebrospinal fluid pressures. Sodium nitroprusside, though effectively decreasing proximal aortic pressure, has been implicated in worsening the incidence of paraplegia by further increasing cerebrospinal fluid pressure and decreasing distal blood pressure, thereby reducing spinal cord perfusion pressure. Intravenous administration of magnesium sulfate has been shown to offer some spinal cord protection when used with mild hypothermia. This study investigated the effect of intrathecal magnesium on the prevention of paraplegia when sodium nitroprusside is used to control proximal hypertension during thoracic aortic cross-clamping in a dog model of spinal cord ischemia. METHODS: Two groups of eight dogs underwent thoracic aortic cross-clamping via a small thoracotomy incision for 45 min. Proximal, distal, and central venous pressures and cerebrospinal fluid pressures were monitored. Temperature was maintained at 36 degrees C. Sodium nitroprusside was used to control proximal hypertension. The control group received no magnesium sulfate, and a second group received 3 mg/kg intrathecal magnesium sulfate before thoracic aortic cross-clamping. The dogs were neurologically evaluated 24 h later by an observer blinded to the dogs' group. Spinal cord segments were obtained for histologic examination. RESULTS: Proximal mean arterial pressure, cerebrospinal fluid pressure, spinal cord perfusion pressure, and central venous pressure were not statistically different between the two groups. Neurologic outcome, however, was statistically different between the groups. None of the eight dogs in the magnesium group had any measurable neurologic injury, in contrast to the control group, in which seven of the eight dogs had severe neurologic injury (P < 0.005). Post mortem histologic data supported these findings. CONCLUSIONS: Intrathecal magnesium can prevent spinal cord injury despite markedly negative spinal cord perfusion pressure during thoracic aortic cross-clamping in a canine model of spinal cord ischemia.

The oxygen and nitrous oxide indices of flammability of endotracheal tubes determined by laser ignition.

This study determines the flammability of polyvinylchloride (PVC), red rubber (RR), and silicone (Si) endotracheal tubes in oxygen- and nitrous-oxide-enriched atmospheres. Flammability is measured by using the oxygen and nitrous oxide indices of flammability with laser ignition. The laser-ignited oxygen (O2) index of flammability of the endotracheal tubes is: PVC, 0.25; RR, 0.19; Si, 0.20. The laser-ignited nitrous oxide (N2O) index of flammability of the endotracheal tubes is: PVC, 0.45; RR, 0.37; and Si, 0.41. These results are similar to the previously reported O2 and N2O indices of flammability with propane-torch ignition. This study validates the concept that the indices of flammability are useful measures of endotracheal tube flammability and are independent of the ignition source.

The effect of helium on endotracheal tube flammability.

The effect on endotracheal tube flammability of helium (He)-diluted oxygen and He-diluted nitrous oxide was determined with the oxidant O2 (He) and oxidant N2O (He) indices of flammability. These values then were compared with the corresponding values for nitrogen dilution, i.e., oxidant O2 (N2) and oxidant N2O (N2) indices of flammability. Four different types of endotracheal tubes were studied: polyvinylchloride (PVC), red rubber (RR), silicone (Si), and the Xomed (Xo) Lasershield tube. The oxidant O2 (He) indices are: PVC 0.274 +/- 0.0055, RR 0.194 +/- 0.0089, Si 0.194 +/- 0.0055, and Xo 0.256 +/- 0.0055. The oxidant N2O (He) indices are: PVC 0.526 +/- 0.0055, RR 0.434 +/- 0.0114, Si 0.416 +/- 0.0055, and Xo 0.456 +/- 0.0154. The oxidant O2 (N2) indices are: PVC 0.254 +/- 0.0055, RR 0.182 +/- 0.0045, Si 0.200 +/- 0, and Xo 0.230 +/- 0. The oxidant N2O (N2) indices are: PVC 0.472 +/- 0.0084, RR 0.356 +/- 0.0055, Si 0.392 +/- 0.0045, and Xo 0.444 +/- 0.0114. These differences, although statistically significant, are modest and demonstrate only a small, and probably clinically not significant, preference of He over N2 in decreasing flammability.