End-of-life care: challenges and obligations in setting limits to life-sustaining therapy.

It is now generally accepted that the withholding or withdrawal of interventions that serve only to prolong the dying process is appropriate. Setting limits to life-sustaining therapy are now common practice. However, making such decisions can be challenging. They are also not uncommonly a source of disagreement between the physician and the patient or surrogate. The potential for strained patient-physician relationship can be mitigated by patient-centred, goal-specific care with its emphasis on effective communication, a sense of timing and attention to the various dimensions of the illness experience.

Quantitative three-dimensional analysis of chondrocytic kinetic responses to short-term stapling of the rat proximal tibial growth plate.

Although it has been demonstrated clinically that controlled compression across a growth plate will slow the rate of endochondral ossification and thus can be used to correct angular limb deformities, the cellular-based mechanism by which altered growth is achieved is poorly understood. This study used short-term uniaxial stapling of the rat proximal tibial growth plate as an experimental system to study chondrocytic responses in the growth plate that account quantitatively for the decreased rate of growth. Growth plates were labeled with oxytetracycline to measure bone growth, and with bromodeoxyuridine to analyze proliferative cell kinetics. Multiple indicators of chondrocytic activity, measured by stereological parameters, were analyzed using growth rate as the primary dependent variable. The unique feature of this analysis was the creation of three-dimensional reconstructions that allowed analysis of data in all directions with distance from the staple. A significant observation was that for the entire operated limb after both 3 and 6 days, all chondrocytic kinetic parameters were affected, indicating that proliferative and hypertrophic responses both act to decrease growth rate in response to stapling. This contradicted our hypothesis that proliferative and hypertrophic responses could occur independently, and that small changes in rate would be attributed primarily to the former and large changes to the latter. The data from this study also demonstrate that volume regulation during hypertrophy can be affected by a primarily mechanical perturbation. Because changes in hypertrophic cell number and volume throughout the growth plate that occur by day 3 remain similar at day 6, the initial modulation of chondrocytic volume and shape may represent the limit of the response while maintaining a growth plate capable of continued growth.

BMP-5 deficiency alters chondrocytic activity in the mouse proximal tibial growth plate.

The role of bone morphogenetic protein-5 (BMP-5) in regulating chondrocytic activity during endochondral ossification was examined in the mouse proximal tibial growth plate. Short ear mice homozygous for the SEA/Gn point mutation in the coding region for BMP-5 (King, J. A. et al. Dev Biol 166:112122; 1994) and heterozygous long ear littermates were examined at 5 and 9 weeks of age (n = 9/group, four groups). Animals were injected with oxytetracycline to estimate the rate of growth and with bromodeoxyuridine to identify proliferative chondrocytes. Age-related changes in chondrocytic stereological and kinetic parameters were compared by image analysis of 1-microm-thick growth plate sections. The number of proliferative chondrocytes did not vary with age in either genotype, but proliferative phase duration increased significantly (approximately 67%) with age in the long ear mice, whereas no change was detected in the short ear mice. The number of hypertrophic chondrocytes increased significantly (approximately 27%) in the short ears, whereas this number decreased significantly (approximately 40%) in the long ears. There was a small, but significant, increase in hypertrophic phase duration (approximately 45%) in short ear mice, but no change was detected in the long ears. These results indicate that BMP-5 deficiency prevents age-related decelerations in chondrocytic proliferation and initiation of hypertrophic differentiation, suggesting a role of BMP-5 in inhibiting these processes.

Amnesia following right thalamic haemorrhage.

A 52 year old patient with a right thalamic haemorrhage is described. She suffered from anterograde amnesia and memory impairment for both visual and verbal material. At follow-up after 3 months, despite being fully oriented and having good concentration, her memory impairment was still evident. Reassessment 3 years afterwards showed persistent deficits and no further improvement.