Biological monitoring of a xenomaterial for grafting: an evaluation in critical-size calvarial defects

Our purpose was to evaluate the osteoconduction potential of mixed bovine bone (MBB) xenografts as an alternative for bone grafting of critical-size defects in the calvaria of rats. After surgery, in the time intervals of 1, 3, 6, and 9 months, rats were killed and their skulls collected, radiographed and histologically prepared for analysis. The data obtained from histological analysis reported that the particles of MBB did not promote an intense immunological response, evidencing its biocompatibility in rats. Our results clearly showed the interesting evidence that MBB was not completely reabsorbed at 9 months while a small amount of newly formed bone was deposited by osteoprogenitor cells bordering the defect. However, this discrete bone-forming stimulation was unable to regenerate the bone defect. Overall, our results suggest that the properties of MBB are not suitable for stimulating intense bone regeneration in critical bone defects in rats.

Population pharmacokinetics of perhexiline from very sparse, routine monitoring data

Using NONMEM, the population pharmacokinetics of perhexiline were studied in 88 patients (34 F, 54 M) who were being treated for refractory angina. Their mean +/- SD (range) age was 75 +/- 9.9 years (46-92), and the length of perhexiline treatment was 56 +/- 77 weeks (0.3-416). The sampling time after a dose was 14.1 +/- 21.4 hours (0.5-200), and the perhexiline plasma concentrations were 0.39 +/- 0.32 mg/L (0.03-1.56). A one-compartment model with first-order absorption was fitted to the data using the first-order (FO) approximation. The best model contained 2 subpopulations (obtained via the $MIXTURE subroutine) of 77 subjects (subgroup A) and 11 subjects (subgroup B) that had typical values for clearance (CL/F) of 21.8 L/h and 2.06 L/h, respectively. The volumes of distribution (V/F) were 1470 L and 260 L, respectively, which suggested a reduction in presystemic metabolism in subgroup B. The interindividual variability (CV%) was modeled logarithmically and for CL/F ranged from 69.1% (subgroup A) to 86.3% (subgroup B). The interindividual variability in V/F was 111%. The residual variability unexplained by the population model was 28.2%. These results confirm and extend the existing pharmacokinetic data on perhexiline, especially the bimodal distribution of CL/F manifested via an inherited deficiency in hepatic and extrahepatic CYP2D6 activity.

A proposal for developing a large patient population cohort for longterm safety monitoring in rheumatoid arthritis

This paper proposes the creation of an objectively acquired reference database to more accurately characterize the incidence and longterm risk of relatively infrequent, but serious, adverse events. Such a database would be maintained longitudinally to provide for ongoing comparison with new rheumatologic drug safety databases collecting the occurrences and treatments of rare events, We propose the establishment of product-specific registries to prospectively follow a cohort of patients with rheumatoid arthritis (RA) who receive newly approved therapies. In addition, a database is required of a much larger cohort of RA patients treated with multiple second line agents of sufficient size to enable case-controlled determinations of the relative incidence of rare but serious events in the treated (registry) versus the larger disease population, The number of patients necessary for agent-specific registries and a larger patient population adequate to supply a matched case-control cohort will depend upon estimates of the detectability of an increased incidence over background. We suggest a system to carry out this proposal that will involve an umbrella organization. responsible for establishment of this large patient cohort, envisioned to be drawn from around the world.

The application of statistical process control charts to the detection and monitoring of hospital-acquired infections

The monitoring of infection control indicators including hospital-acquired infections is an established part of quality maintenance programmes in many health-care facilities. However, surveillance data use can be frustrated by the infrequent nature of many infections. Traditional methods of analysis often provide delayed identification of increasing infection occurrence, placing patients at preventable risk. The application of Shewhart, Cumulative Sum (CUSUM) and Exponentially Weighted Moving Average (EWMA) statistical process control charts to the monitoring of indicator infections allows continuous real-time assessment. The Shewhart chart will detect large changes, while CUSUM and EWMA methods are more suited to recognition of small to moderate sustained change. When used together, Shewhart and EWMA methods are ideal for monitoring bacteraemia and multiresistant organism rates. Shewhart and CUSUM charts are suitable for surgical infection surveillance.

Monitoring tissue oxygenation during resuscitation of major burns

BACKGROUND: Because subcutaneous and splanchnic oxygenation indices are sensitive indicators of evolving hemorrhagic shock and adequacy of resuscitation, we postulated that these indices might have an equivalent role in the monitoring of severely burned patients. This observational study was undertaken to examine changes in tissue oxygenation indices during burn resuscitation. METHODS: Seven patients with major burns (54 +/- 21% total body surface area) were studied during the first 36 hours of fluid resuscitation. Silastic tubing was placed in the subcutaneous tissue just beneath both normal skin and deep partial thickness burn. Fiberoptic sensors inserted into the tubing measured subcutaneous oxygen and carbon dioxide tensions in the burnt skin (PO2scb and PCO2scb) and normal skin (PO2scn and PCO2scn) continuously. Gastric intramucosal pH (pHi) and the mucosal CO2 (PCO2m) gap were calculated using gastric tonometers. Mean arterial pressure, arterial pH, lactate, and pHi measurements were obtained for 36 hours. RESULTS: There were no significant differences in mean arterial pressure, arterial pH, or lactate concentrations throughout the study period, whereas indices of tissue oxygenation showed deterioration: pHi decreased from 7.2 +/- 0.1 to 6.7 +/- 0.3 (p = 0.06), the PCO2m gap increased from 12 +/- 17 to 108 +/- 123 mm Hg (p < 0.01), PO2scn decreased from 112 +/- 18 to 50 +/- 11 mm Hg (p < 0.01), PO2scb decreased from 62 +/- 23 to 29 +/- 16 mm Hg (p < 0.01), PCO2scn increased from 42 +/- 4 to 46 +/- 10 mm Hg (p = 0.2), and PCO2scb increased from 42 +/- 10 to 52 +/- 5 mm Hg (p = 0.05). CONCLUSION: Despite adequate global indices of tissue perfusion after 36 hours of resuscitation, tissue monitoring indicated significant deterioration in the splanchnic circulation and in the normal and burnt skin.