Sustained venoconstriction in man supplemented with CO2 at high altitude.

Venoconstriction occurs at high altitude. This study sought to determine whether hypoxia or hypocapnia is the cause of the venoconstriction. Five male subjects were exposed to 4,000-4,400 m (PB 440-465 mmHg) with supplemental 3.77 +/- 0.02% CO2 in a hypobaric chamber for 4 days. Similar alveolar O2 tensions were obtained in four control subjects exposed to 3,500-4,100 m (PB 455-492 mmHg) without CO2. A water-filled plethysmograph was used to determine forearm flow and venous compliance. Systemic blood pressure was measured with the cuff procedure. Catecholamines were measured in 24-h urine collections. Venous compliance fell at high altitude in both groups and was less (P less than 0.01) than control values. Forearm flow and resistance were unaltered at altitude in the group with CO2 supplementation while forearm flow decreased and resistance increased in the hypocapnic group at 72 h of exposure. Urinary catecholamines increased in the group with CO2 and remained unaltered in the hypocapnic group. It is concluded that hypoxia is responsible for decreasing venous compliance, and hypocapnia for increasing resistance and decreasing flow. Group differences observed in urinary catecholamines may be explained by differences in arterial pH.     

Mechanism of DNA flexibility enhancement by HMGB proteins

The mechanism by which sequence non-specific DNA-binding proteins enhance DNA flexibility is studied by examining complexes of double-stranded DNA with the high mobility group type B proteins HMGB2 (Box A) and HMGB1 (Box A+B) using atomic force microscopy. DNA end-to-end distances and local DNA bend angle distributions are analyzed for protein complexes deposited on a mica surface. For HMGB2 (Box A) binding we find a mean induced DNA bend angle of 78°, with a standard error of 1.3° and a SD of 23°, while HMGB1 (Box A+B) binding gives a mean bend angle of 67°, with a standard error of 1.3° and a SD of 21°. These results are consistent with analysis of the observed global persistence length changes derived from end-to-end distance measurements, and with results of DNA-stretching experiments. The moderately broad distributions of bend angles induced by both proteins are inconsistent with either a static kink model, or a purely flexible hinge model for DNA distortion by protein binding. Therefore, the mechanism by which HMGB proteins enhance the flexibility of DNA must differ from that of the Escherichia coli HU protein, which in previous studies showed a flat angle distribution consistent with a flexible hinge model.     

Euvolemic cirrhotic dogs in sodium balance maintain normal systemic hemodynamics

Dogs with chronic biliary cirrhosis and portal hypertension commonly develop plasma volume expansion, urinary sodium retention, ascites, and perturbed systemic hemodynamics, i.e., a rise in cardiac output and a fall in peripheral vascular resistance. Our laboratory has previously demonstrated that creating a side-side portacaval anastomosis in such animals, and so venting hepatoportal pressure, will prevent sodium retention and ascites formation and will maintain the animals euvolemic. In the present study, in four cirrhotic dogs with such an anastomosis, observations made at 12 weeks postbiliary duct ligation, and in the presence of grossly disturbed liver function and morphology, failed to demonstrate any change from control conditions in arterial blood pressure, cardiac output, or peripheral vascular resistance. We conclude that venting hepatoportal pressure in cirrhotic dogs with markedly disturbed liver function prevents the advent of a hyperdynamic circulation, possibly by preventing volume expansion.     

Automatic gas tank switching system for CO2 incubators.

The use and construction of an automatic gas tank switching system are described. This device monitors the gas pressure in a CO2 incubator gas system and automatically switches to a reserve tank when the main supply tank is depleted. The unit contains an alarm system that signals either loss of power or gas pressure in the supply system.     

Discriminating the loosening behaviour of cemented hip prostheses using measurements of migration and inducible displacement.

In vitro pre-clinical tests of hip prostheses have not yet been developed to the extent that inferior prostheses can be 'screened-out' prior to animal or clinical trials. This paper reports the experimental part of a project to develop a pre-clinical testing platform for cemented femoral hip implants. It is based on the clinical observation (K?rrholm et al. JBJS, 76B (1994) 912-916) that higher subsidence (distal migration) correlates with early revision of hip prostheses. A protocol to measure the relative movement between implant and bone was designed to test whether or not such a measurement, if made in a laboratory, could discriminate between hip prostheses. The protocol was applied to the Lubinus SPII prosthesis (W. Link, Germany) and a Müller Curved Stem (JRI Ltd., UK)-these prostheses were chosen because they are known to have different loosening rates in vivo. Five prostheses of each design were tested. The migration, the rate-of-migration, and the inducible displacement of each prosthesis was recorded over two million cycles of loading.For each implant, rapid initial migration was found, followed by a period of steady-state migration. In the majority of cases, the prostheses migrated medially, distally and posteriorly. On average, the Lubinus migrated less than the Müller in all directions. The average Lubinus migration was less than half that of the Müller, and this difference was significant at a level of p=0.05. Inducible displacement was greater for the Müller compared to the Lubinus. Furthermore, the inducible displacement decreased over time for the majority of Lubinus prostheses whereas it increased over time for the majority of the Müller prostheses leading to the conclusion that a rapid pre-clinical test based on measurement of inducible displacement may be possible.