The effects of hydrostatic pressure on matrix synthesis in articular cartilage

The direct effects of hydrostatic pressure on matrix synthesis in articular cartilage can be studied independently of the other factors that change during loading. We have found that the influence of hydrostatic pressure on incorporation rates of 35SO4 and [3H]proline into adult bovine articular cartilage slices in vitro depends on the pressure level and on the time at pressure. Pressures in the "physiological" range (5-15 MPa) applied for 20 s or for 5 min could stimulate tracer incorporation (30-130%) during the following 2 h, but higher pressures (20-50 MPa) had no effect on incorporation rates. The degree of stimulation in cartilage obtained from different animals was found to vary; in some animals none was seen. Stimulation also varied with position along the joint. Physiological pressures (5-10 MPa) applied continuously for the 2-h incubation period also stimulated incorporation rates, but pressures greater than 20 MPa always produced a decrease that was related to the applied pressure and that was reversible. These results suggests that the hydrostatic pressure that occurs during loading is a signal that can stimulate matrix synthesis rates in articular cartilage.     

GABAB receptor protein and mRNA distribution in rat spinal cord and dorsal root ganglia

The presence of metabotropic receptors for GABA, GABAB, on primary afferent terminals in mammalian spinal cord has been previously reported. In this study we provide further evidence to support this in the rat and show that the GABAB receptor subunits GABAB1 and GABAB2 mRNA and the corresponding subunit proteins are present in the spinal cord and dorsal root ganglion. We also show that the predominant GABAB1 receptor subunit mRNA present in the afferent fibre cell body appears to be the 1a form. In frozen sections of lumbar spinal cord and dorsal root ganglia (DRG) GABAB receptors were labelled with [3H]CGP 62349 or the sections postfixed with paraformaldehyde and subjected to in situ hybridization using oligonucleotides designed to selectively hybridize with the mRNA for GABAB(1a), GABAB(1b) or GABAB2. For immunocytochemistry (ICC), sections were obtained from rats anaesthetized and perfused-fixed with paraformaldehyde. The distribution of binding sites for [3H]CGP 62349 mirrored that previously observed with [3H]GABA at GABAB sites. The density of binding sites was high in the dorsal horn but much lower in the ventral regions. By contrast, the density of mRNA (pan) was more evenly distributed across the laminae of the spinal cord. The density of mRNA detected with the pan probe was high in the DRG and distributed over the neuron cell bodies. This would accord with GABAB receptor protein being formed in the sensory neurons and transported to the primary afferent terminals. Of the GABAB1 mRNA in the DRG, approximately 90% was of the GABAB(1a) form and approximately 10% in the GABAB(1b) form. This would suggest that GABAB(1a) mRNA may be responsible for encoding presynaptic GABAB receptors on primary afferent terminals in a manner similar to that we have previously observed in the cerebellar cortex. GABAB2 mRNA was also evenly distributed across the spinal cord laminae at densities equivalent to those of GABAB1 in the dorsal horn. GABAB2 mRNA was also detected to the same degree within the DRG. Immunocytochemical analysis revealed that GABAB(1a), GABAB(1b) and GABAB2 were all present in the spinal cord. GABAB(1a) labelling appeared to be more dense than GABAB(1b) and within the superficial dorsal horn GABAB(1a) was present in the neuropil whereas GABAB(1b) was associated with cell bodies in this region. Both 1a and 1b immunoreactivity was expressed in motor neurons in lamina IX. GABAB2 immunoreactivity was expressed throughout the spinal cord and was evident within the neuropil of the superficial laminae.     

The CINOD, AZD3582, exhibits an improved gastrointestinal safety profile compared with naproxen in healthy volunteers

COX-inhibiting nitric oxide donators (CINODs) are a new class of drugs in development for the treatment of acute and chronic pain. They comprise a COX-inhibiting moiety linked to a nitric-oxide-donating component and are designed to provide an innovative mechanism of action of balanced COX inhibition and controlled nitric oxide donation. Through these pathways, CINODs should provide analgesic and anti-inflammatory efficacy, while offering gastrointestinal safety through the tissue-protective effects of nitric oxide donation. AZD3582 [4-(nitrooxy)butyl-(2S)-2-(6-methoxy-2-naphthyl)propanoate] is the first agent in the CINOD class to enter extensive clinical development. Pre-clinical studies demonstrate that AZD3582 has a superior gastrointestinal safety profile to naproxen, while demonstrating analgesic and anti-inflammatory efficacy. In healthy human volunteers, AZD3582 caused little gastrointestinal damage compared with equimolar doses of naproxen. Studies to evaluate the longer-term gastrointestinal safety of AZD3582, alongside its efficacy in alleviating chronic and acute pain, are ongoing.     

The Swedish Council on Technology Assessment in Health Care (SBU) Systematic Overview of Radiotherapy for Cancer including a Prospective Survey of Radiotherapy Practice in Sweden 2001--Summary and Conclusions

A systematic assessment of radiotherapy for cancer was conducted by The Swedish Council on Technology Assessment in Health Care (SBU) and published in 1996. The assessment reviewed the scientific literature up to 1993 on the use of radiotherapy in the treatment of solid tumours, and estimated the costs associated with radiotherapy. It also described the current practise of radiotherapy in Sweden 1992 and compared practise with scientific knowledge. The SBU has now conducted a follow-up study on radiotherapy for cancer, including a review of the scientific literature from 1994 and a prospective survey of radiotherapy practise in Sweden 2001. The following conclusions were drawn: The role of radiotherapy as an important form of treatment for cancer with both curative and palliative intent has been further confirmed.The use of radiotherapy in Sweden has increased and is now at the internationally recommended level.Radiotherapy in Sweden is mostly given in accordance with the scientific evidence but may still be underutilized in certain situations.The resources for radiotherapy are being utilized more efficiently.The costs of radiotherapy are still 5% of the total cost of cancer care, while the cost of an individual treatment (fraction) has decreased.The need for radiotherapy capacity will increase. In addition, half of the treatment equipment will have to be replaced in the next few years.     

Diagnostic imaging in femur head necrosis

Diagnosis of avascular necrosis (AVN) of the hip has been improved by the technical progress of imaging modalities during the last decade. For a long period, only plain radiographs had been available. Scintigraphy and computed tomography contributed to differential diagnosis and early detection of bone necrosis. In the meantime, MR imaging has gained special value in the evaluation of AVN. It is now the method of choice for early detection as well as for assessment in later stage disorders. Using the ARCO system, all imaging modalities and their diagnostic viability are described. Findings regarding the different stages of AVN are correlated to tissue-specific changes.     

Postoperative prophylactic administration of beta-adrenergic blockers in patients at risk for myocardial ischemia

Perioperative myocardial ischemia (MI) is associated with postoperative cardiac morbidity. Postoperative sympatholysis may reduce the incidence of MI. This study evaluated such a reduction postoperatively with the administration of prophylactic beta-blockers in patients undergoing elective total knee arthroplasty with epidural anesthesia and postoperative epidural analgesia. One hundred seven patients were preoperatively randomized into two groups, control and beta-blockers, who received postoperative esmolol infusions on the day of surgery and metoprolol for the next 48 h to maintain a heart rate less than 80 bpm. Patients were followed for ST segment depression by using a Holter monitor and adverse cardiac outcomes. Postoperative electrocardiographic ischemia was significantly more prevalent in the control group compared with the beta-blocker group during esmolol blockade (0 of 52 vs 4 of 55; P = 0.04) and tended to be more common in the control group the next two days (8 of 55 vs 3 of 52; P = 0.135). In addition, the number of ischemic events (control, 50; beta-blockers, 16) and total ischemic time (control, 709 min; beta-blocker, 236 min) were also significantly different from the control group. Myocardial infarctions and cardiac events were more common in the control group, but these differences were not significant. Our results suggest that the use of prophylactic beta-blocker therapy may reduce the incidence of postoperative MI. Implications: Prophylactic beta adrenergic blockade administered after elective total knee arthroplasty was associated with a reduced prevalence and duration of postoperative myocardial ischemia detected with Holter monitoring.