Regulation of matrix synthesis rates by the ionic and osmotic environment of articular chondrocytes

Chondrocytes in cartilage are embedded in a matrix containing a high concentration of proteoglycans and hence of fixed negative charges. Their extracellular ionic environment is thus different from that of most cells, with extracellular Na+ being 250-350 mM and extracellular osmolality 350-450 mOsm. When chondrocytes are isolated from the matrix and incubated in standard culture medium (DMEM; osmolality 250-280 mOsm), their extracellular environment changes sharply. We incubated isolated bovine articular chondrocytes and cartilage slices in DMEM whose osmolality was altered over the range 250-450 mOsm by Na+ or sucrose addition. 35S-sulphate and 3H-proline incorporation rates were at a maximum when the extracellular osmolality was 350-400 mOsm for both freshly isolated chondrocytes and for chondrocytes in cartilage. The incorporation rate per cell of isolated chondrocytes was only 10% that of chondrocytes in situ both 4 and 24 hours after isolation. For freshly isolated chondrocytes, the rate increased 30-50% in DMEM to which NaCl or sucrose had been added to increase osmolality. In chondrocytes incubated overnight in DMEM, the rate was greatest in DMEM of normal osmolality and fell from the maximum in proportion to the change in osmolality. The effects of sucrose addition on incorporation rates were similar but not identical to those of Na+ addition. Changes in cell volume might be linked to changes in synthesis rates since the cell volume of chondrocytes (measured by Coulter-counter) increased 30-40% when the cells were removed from their in situ environment into DMEM. Synthesis rates can thus be partly regulated by changes in extracellular osmolality, which in cartilage is controlled by proteoglycan concentration. This provides a mechanism by which the chondrocytes can rapidly respond to changes in extracellular matrix composition.     

The design and performance of an experimental external fixation device with load transducers

It is becoming increasingly common that fracture healing is modelled in the laboratory with an osteotomy in the diaphysis of the ovine tibia. External fixation is often used to hold the bones in these models, presenting the problem that the loads on such devices are poorly understood. To help investigate this, a unilateral device has been developed which is capable of measuring the two components of load considered to be the most important, that of axial compression and bending in the plane of the fixator. The device was found to be a rigid system and easy to apply, with the in-vivo measurements being straightforward. The estimated limits of error of the compression transducer are +37.9 N and -21.4 N and those of the bending transducer are +3.6 Nm and -4.2 Nm. Preliminary measurements showed the maximum load during normal walking to 345 N compression and 28 Nm in-plane bending.     

Intraocular lens performance in air, in water, and in situ: a computer study

Computer analysis is used to predict performance of four intraocular lenses with assigned values of aberration. Cylinder error and asphericity error are used as examples of possible manufacturing errors. Three measures of performance are calculated: maximum optical path difference, root mean square optical path difference, and modulation transfer function. For evaluation in air these standard test conditions are assumed: collimated green light incident on the convex surface of a plano-convex lens, with a 3 mm aperture. All four lenses show substantially improved performance in water compared to air, and a further improvement in the simulated eye (i.e., in situ). However, an aberrated 30 diopter (D) lens with performance in air comparable to an aberrated 20 D lens, performs worse in situ than does the 20 D lens. This suggests that a performance test in air that is suitable for a 20 D lens (e.g., 100 line pairs per millimeter resolution) may not be adequate for a 30 D lens. A test in air at 30% resolution efficiency may be more suitable.     

The natural history of asymptomatic carotid artery disease

PURPOSE: The purpose of this article is to determine the natural history of carotid artery disease among asymptomatic patients with cervical bruits or other risk factors for stroke and to study the value of duplex ultrasonography in predicting future neurologic events. METHODS: Two hundred forty-two asymptomatic, unoperated patients, referred for evaluation of asymptomatic carotid artery disease, were followed prospectively with duplex ultrasonography. RESULTS: Fifteen ischemic strokes (6.2%) and 20 transient ischemic attacks (TIA) (8.3%) occurred in 34 patients during a mean follow-up of 27.4 months. Annual stroke, TIA, and combined event rates were 2.7%, 3.6%, and 6.2%, respectively. Although patients with 80% to 99% lesions had a 20.6% annual event rate, most events occurred contralateral to these lesions; the vessel-specific annual event rate for 80% to 99% disease was 5.1%. Only one of 15 strokes occurred ipsilateral to an 80% to 99% stenosis. Echolucent plaques were associated with TIA and stroke (5.7% annual vessel event rate vs 2.4% for echogenic plaques, p = 0.03). Disease progression was highly correlated with TIA and stroke (p < 0.0001), but it usually occurred in association with rather than before ischemic events, thus proving more useful in explaining pathogenesis than in predicting future events. There was no association between aspirin use and TIA, but patients taking aspirin had a threefold higher annual stroke rate (1.6% vs 4.8%, p = 0.027). CONCLUSIONS: This study, while confirming significant risk for asymptomatic patients with critical stenosis or echolucent plaque, demonstrates the importance of contralateral disease and the absence of orderly progression from minimal disease through high-grade stenosis to symptomatic cerebral ischemia. TIA and stroke commonly occur in association with abrupt, unpredictable, quantum changes in carotid artery disease.     

Apoptosis: molecular regulation of cell death

This article focuses on the few disorders that produce chronic cholestasis in infants and children. Cholestasis is defined, and a framework for thinking about pathophysiology is provided. Medical management is discussed in the context of the consequences and complications of chronic cholestasis. The limited differential for chronic cholestasis is discussed, and approaches to diagnosis and management of specific disorders are provided.