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C A Hicks

Publications and source records attributed to C A Hicks.

26 records · Page 2Linked to original sources

An in vivo investigation of the effect of anthraquinones on the turnover of aggrecans in spontaneous osteoarthritis in the guinea pig.

We present details of a method which allows for the determination of chondroitin sulphate turnover in vivo using the guinea pig. Such methods have been utilised to examine the effects of diacetyl rhein, a compound with purported anti-osteoarthritic activity, and several related anthraquinone analogues on the turnover of chondroitin. Since the guinea pig develops spontaneous osteoarthritis, this may give useful information on the potential for such compounds to inhibit the progression of osteoarthritis. The results show that several of the anthraquinones are capable of reducing the turnover of chondroitin 4- but not 6-sulphate. This may indicate potential mechanisms for the breakdown of guinea pig cartilage aggrecans. We propose that these techniques could be useful for the screening of chemical agents with useful activity against osteoarthritis.

Aggrecans↗

The anatomy of the tibial intramedullary canal.

An autopsy study was done to determine the relationship of the tibial plateau and the intramedullary canal of the tibia. Rods were placed in 10 adult anatomic specimen tibias. Computed axial tomography scans were obtained of the proximal tibia at 1 cm, 1.5 cm, 2 cm, and 2.5 cm from the most proximal plateau. Based on these sections, the position of the tibial canal was measured relative to the plateau. The center of the tibial canal on the plateau varied from 28% to 53% of the depth of the tibia from the anterior cortex and from 37% to 56% of the width of the tibia from the medial cortex. Actual measurements ranged from 15 mm anterior to the center to 1.5 mm posterior to the center and 8 mm medial to the center to 4.5 mm lateral. Because of this variability in location of the tibial canal, a mobile stem attachment site on the tibial tray or an offset stem may be beneficial for some patients having total knee arthroplasty.

Adult↗

Cell migration studies in the adoptive transfer of adjuvant arthritis in the Lewis rat.

Adjuvant arthritis (AA) can be induced in Lewis rats by a single injection of either heat-killed Mycobacterium tuberculosis or the lipoidal amine CP20961. Concanavalin A (Con A)-stimulated T cells isolated from AA rats are able to adoptively transfer the disease to naive syngeneic recipients. It is unclear, however, whether these transferred cells traffic directly to the joint and initiate arthritis, or whether secondary host cells are responsible for activation of the disease. In the current investigation, T cells labelled with the vital fluorescent dyes Hoechst H33342 and Zynaxis PKH26-G were used to adoptively transfer adjuvant disease to naive recipients. At various stages of disease development sections of ankle joints, together with a range of soft tissues, were examined by fluorescence microscopy to determine the distribution of labelled donor cells in the recipients. Intensely fluorescent lymphocytes were observed in the liver, spleen and lymph nodes within 24 hr of adoptive transfer. Foci of such cells were clearly visible in the primary lymphoid tissues as late as 14 days after transfer. However, close examination of both ankle joint sections and patellar fat pad cells throughout the time-course of the study failed to detect any labelled cells at the lesion site. To develop these observations further, we performed adoptive transfers to nude Lewis rats (rnu/rnu) and found that they were only moderately sensitive and developed, at best, a transient arthritis. This observed difference could not be explained by a generalized lack of an inflammatory response, since we were able to elicit a zymosan peritonitis in the nude rats. However, in nude Lewis rats a striking increase in adoptively transferred AA was obtained after reconstitution with 4 x 10(8) naive syngeneic spleen cells. These combined observations suggest that a host-derived immune cell population is crucial for arthritis induction in the adoptive transfer system.

Animals↗

In vitro and in vivo effects of proteoglycan fractions in adjuvant treated rats.

Differential stimulatory effects by proteoglycan fractions: chondroitin (CS)- and keratan-sulphate regions; link protein and binding region were observed in cultures of spleen and lymph node lymphocytes taken from normal and adjuvant treated Lewis rats. In vivo, none of the fractions induced symptoms of arthritis but that pretreatment with the CS rich region produced an inhibition of Mycobacterium tuberculosis induced arthritis.

Adjuvants, Immunologic↗

Bacterial osteomyelitis. Adjunctive hyperbaric oxygen therapy.

Mechanistically, hyperbaric oxygen (HBO) appears useful for the treatment of osteomyelitis. HBO increases the oxygen tension in infected tissue, including bone. An adequate oxygen tension is necessary for oxygen-dependent killing of organisms by polymorphonuclear leukocytes, and for fibroblast activity leading to angiogenesis and wound healing. In addition, HBO augments the killing of Pseudomonas aeruginosa by the aminoglycoside tobramycin. At the University of Texas Medical Branch in Galveston, adjunctive HBO is used for Cierny-Mader stage 3B and 4B osteomyelitis.

Bacterial Infections↗

Decahydroisoquinolines: novel competitive AMPA/kainate antagonists with neuroprotective effects in global cerebral ischaemia.

In the present studies, we have evaluated the activity of a series of glutamate receptor antagonists from the decahydroisoquinoline group of compounds both in vitro and in vivo. Compound activity at alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) and kainate receptors was assessed using ligand binding to cloned iGluR2 and iGluR5 receptors and on responses evoked by AMPA and N-methyl-D-aspartate (NMDA) in the cortical wedge preparation. In vivo, compounds were examined for antagonist activity electrophysiologically in the rat spinal cord preparation and in the gerbil model of global cerebral ischaemia. Compounds tested were LY293558, which has been shown to protect in models of focal cerebral ischaemia, LY202157 (an NMDA antagonist), LY246492 (an NMDA and AMPA receptor antagonist), LY302679, LY292025, LY307190, LY280263, LY289178, LY289525, LY294486 (AMPA/kainate antagonists) and LY382884 (an iGluR5 selective antagonist). Results obtained support a role for AMPA receptors in cerebral ischemia. LY377770 (a mixed AMPA/iGluR5 antagonist and active isomer of LY294486) demonstrated good neuroprotection with a 2-h time window and may therefore be useful in the treatment of ischaemic conditions.

Animals↗

Treatment options for infected knee arthroplasties.

Twenty-four total knee arthroplasty infections in 23 patients treated over a 9-year period at the University of Texas Medical Branch at Galveston were retrospectively reviewed. Staphylococcus epidermidis was isolated from 11 of 24 and Staphylococcus aureus from eight of 24 knees, respectively. Eleven infections were polymicrobic. Control of infection was obtained in 13 of 13 patients treated initially with resection arthroplasty, and 11 of these were ambulatory at follow-up. Infection was controlled in three of 10 knees treated initially with debridement, and six of these nine patients were ambulatory at follow-up. One patient was initially treated with amputation. Four of four patients treated by resection arthroplasty and then by reimplantation were ambulatory without signs of infection at follow-up. Resection arthroplasty reliably controls infection but produces a painful unstable joint that requires brace support or subsequent surgery for pain-free ambulation. Reimplantation in selected patients offers the best chance for pain-free ambulation.

Adult↗