Metabolism of proteoglycans in tendon.

Tendons are dense, fibrous connective tissues that are responsible for transmitting mechanical forces from skeletal muscle to bone. From a clinical perspective, tendinopathy (defined as a syndrome of tendon pain, tenderness and swelling that affects function) is very common, both within the sporting arena and in the workplace. Importantly, proteoglycans are essential components of the tendon extracellular matrix (ECM) and changes in their expression and metabolism/turnover have been associated with tendinopathy. Within tendons, the small leucine-rich proteoglycans (SLPRs), decorin, fibromodulin, lumican and keratocan predominate within tensional regions, while in tendon fibrocartilage, increased concentrations of proteoglycans common to the articular cartilage phenotype are present, including aggrecan, biglycan and proteoglycan 4. However, the rate of proteoglycan turnover within tendon is markedly higher than that of cartilage, mediated via the "aggrecanases," which are constitutively active in the tendon matrix. Data suggest that this increased proteoglycan turnover is likely to be required to maintain normal tendon homeostasis, with perturbations in proteoglycan metabolism contributing to tissue dysfunction. Thus, future studies aimed at furthering our fundamental knowledge of tendon proteoglycan metabolism in health and disease are important in the development of improved treatments for tendon disorders.

Prospective multidisciplinary audit of obstetric general anaesthesia in a district general hospital.

In the 3 years leading up to March 2001, the general anaesthesia rate for emergency and elective caesarean sections at our hospital was higher than that recommended by the Royal College of Anaesthetists. There were also concerns regarding the quality of communication between surgeon and anaesthetist prior to emergency caesarean section. A multidisciplinary audit was undertaken on both the indications for obstetric general anaesthesia and quality of communication between staff members during the perioperative period between January and August 2002. The results of the audit highlighted potential serious shortfalls in communication and teamworking; however, there was insufficient information to assess the appropriateness of the indication for general anaesthesia. Following this audit recommendations were made to improve communication channels between the personnel on labour ward and this coincided with a reduction in the use of general anaesthesia.

Maternal cardiovascular consequences of positioning after spinal anaesthesia for Caesarean section: left 15 degree table tilt vs. left lateral.

Sixty healthy women undergoing elective Caesarean section were randomly allocated to either a measured 15 degrees left table tilt position (n = 31) or full left lateral position (n = 29) for a 15-min period after spinal blockade. Arm and leg blood pressure, ephedrine requirements, symptoms, fetal heart rate, cord gases and Apgar scores were recorded. Mean ephedrine requirements and incidence of hypotension were similar in the two groups. Arm systolic arterial pressure over time was similar in both groups, but leg systolic arterial pressure over time was significantly lower in the tilt group (p < 0.001); the mean leg systolic arterial pressure was lower for all 15 sequential recordings in the tilt group, reaching statistical significance (p < 0.05) at 4, 5, 6 and 8 min. Differences in maternal nausea, vomiting and bradycardia and fetal outcome were not statistically significant. Following spinal anaesthesia, even a true 15 degrees left table tilt position is associated with aortic compression.

Interaction of bone proteoglycans and proteoglycan components with hydroxyapatite.

The small leucine-rich proteoglycans (SLRPs) of bone interact with hydroxyapatite (HAP) and are proposed to play an important role in the regulation of the mineralisation process. The present study has examined the interaction of bone SLRPs, purified, liberated bone glycosaminoglycan (GAG) chains and core proteins, as well as commercial chondroitin 4-sulphate (C4S) with HAP. Isotherm data (0.02 M sodium acetate) revealed that the intact proteoglycans (PGs) and bone GAGs showed greater binding onto HAP with higher adsorption maxima than the constituent core proteins and commercial C4S. Adsorption was dependent on pH and ionic strength, increasing with decreasing pH and in the presence of calcium whilst decreasing in the presence of phosphate, suggesting that electrostatic effects are important. The data indicates that PG/GAG chemistry and conformation in solution are significant determinants in the adsorption process and provides important information concerning interfacial adsorption phenomena between the organic-inorganic phases of mineralised systems.

The cuffed oropharyngeal airway in resuscitation.

The cuffed oropharyngeal airway (COPA, Mallinckrodt) may prove a useful airway adjunct in resuscitation by non-anaesthetists. Many hospital workers are familiar with the standard oropharyngeal airway but find it difficult to use with a face-mask to provide effective positive pressure ventilation of the lungs. However, most inexperienced hospital basic life support providers can use the COPA effectively with minimal instruction. Recommended COPA size and cuff volumes for manual ventilation in adult males and females are respectively size 11 and 10 with up to 60 ml and 50 ml in each cuff. Simple airway manoeuvres taught in basic life support (lifting the chin, tilting back the head) also apply to use of the COPA. A leak around the cuff is common but does not usually impair the ability to ventilate the lungs. Future developments may include more widespread evaluation of the COPA in resuscitation and direct comparisons with other devices.

Catabolism of aggrecan, decorin and biglycan in tendon.

We have examined the catabolism of the proteoglycans aggrecan, decorin and biglycan in fresh tendon samples and in explant cultures of tissue from the tensional and compressed regions of young and mature bovine tendons. A panel of well-characterized antibodies that recognize glycosaminoglycan or protein (linear or neoepitope) sequences was used to detect proteoglycans and proteoglycan degradation products that were both retained within the tissue and released into the culture medium. In addition, a reverse-transcriptase-mediated PCR analysis was used to examine the mRNA expression patterns of tendon proteoglycans and aggrecanases. The results of this study indicate a major role for aggrecanase(s) in the catabolism of aggrecan in bovine tendon. The study also provides a characterization of glycosaminoglycan epitopes associated with the proteoglycans of tendon, illustrating age-related changes in the isomers of chondroitin sulphate disaccharides that remain attached to the core protein glycosaminoglycan linkage region after digestion with chondroitinase ABC. Evidence for a rapid turnover of the small proteoglycans decorin and biglycan was also observed, indicating additional molecular pathways that might compromise the integrity of the collagen matrix and potentially contribute to tendon dysfunction after injury and during disease.

Use of the cuffed oropharyngeal airway for manual ventilation by nonanaesthetists.

We studied the use of the cuffed oropharyngeal airway in 100 ASA I and II anaesthetised patients. In the first 50 patients (group A), an experienced anaesthetist inserted the airway. The optimum sizes and cuff volumes for manual ventilation in adult males and females were found to be sizes 11 and 10 with up to 60 ml and 50 ml in each cuff, respectively. Manual ventilation was clinically successful in 49/50 (98%) of these patients. Using these recommendations and following a brief tutorial, a group of 50 nonanaesthetic, basic life-support providers attempted to insert a cuffed oropharyngeal airway and manually ventilate the lungs of a subsequent 50 patients (group NA). Clinically adequate tidal volumes were achieved within 45 s in 47/50 (94%) patients in this group. A persistent leak was present in 21/49 (43%) and 24/47 (51%) of the successful insertions in each group, but this did not affect the ability to ventilate the lungs adequately. The cuffed oropharyngeal airway may offer an effective method of providing adequate ventilation during resuscitation by nonanaesthetic hospital staff.

Effect of preoperative paracetamol on gastric volumes and pH in children.

The effect preoperative paracetamol elixir has on gastric contents is unknown. Children presenting for elective adenotonsillectomy were randomized to receive either paracetamol elixir (40 mg x kg(-1)) 90 min before surgery or paracetamol suppositories (40 mg x kg(-1)) intraoperatively. Following induction of anaesthesia a 16 Fr multiple-oriface orogastric tube was passed into the stomach and measure taken of the residual gastric volume and pH. The children had a mean age of 8.5 years (SD 3.2) with a weight of 35 kg (SD 16.5). Children given elixir (n=41) had a mean residual gastric volume of 0.083 ml x kg(-1) (95% CI; 0.006, 1.24) and a pH of 1.83 (95% CI; 0.75, 4.49), while those given suppositories (n=40) had a mean residual gastric volume of 0.083 ml x kg(-1)(95% CI; 0.008, 0.9) and a pH of 2.07 (95% CI; 0.84, 5.12). There was no significant difference between these two groups. Paracetamol elixir is rapidly absorbed in the gastrointestinal system of children and preoperative administration has no effect on gastric contents. Given paracetamol's slow equilibration rate constant from the central to the effect compartment, children may be given this medication preoperatively for routine surgical procedures.

The modification of alveolar bone proteoglycans by reactive oxygen species in vitro.

Reactive oxygen species (ROS) are being increasingly implicated in the connective tissue degradation associated with chronic inflammatory conditions, such as periodontal disease. The present study investigated the effects of ROS on the proteoglycans (PG) of alveolar bone which are important structural components within the periodontium. PG were isolated from ovine alveolar bone and exposed to increasing concentrations of hydrogen peroxide (H2O2) or to a hydroxyl radical (.OH) flux for 1 h or 24 h, and the degradation products examined for depolymerisation and chemical modification of the PG structure. ROS were demonstrated to be capable of degrading alveolar bone PG in vitro, the .OH species resulting in greater modification than H2O2. The degradative effects observed included cleavage of the protein core and depolymerisation of the GAG chains. The core proteins were more susceptible to degradation than the GAG chains in the presence of H2O2 alone, although both the core proteins and the GAG chains were extensively degraded in the presence of a .OH flux for both 1 h and 24 h. Exposure of the PG to .OH for 24 h resulted in significant modification to the amino acid composition with decreases in the proportion of leucine and the complete loss of proline, tyrosine and phenylalanine evident. The results highlight the potential role of ROS as an important mechanism in considering the pathology of periodontal tissue destruction.

The Christmas feast.

Twenty two normal subjects and 13 maturity onset diabetic patients completed an observational study with repeated weighing and fasting blood tests from one month before to one month after Christmas. Over the Christmas period in all subjects an increase in weight was observed (mean 0.8 (SD 0.1) kg, p less than 0.001), which was maintained through January. This may signify an average additional 6000 kcal ingested. By three to six days after Christmas a slight but significant increase in fasting plasma triglyceride (p less than 0.03) and cholesterol (p less than 0.02) concentrations occurred, with a subsequent rise in glycosylated haemoglobin concentration (p less than 0.001). This study is not likely to affect any future Christmas.

Patient-orientated metered capillary blood collection.

A small collector bottle, with a precision-moulded top, allows capillary blood from a finger-prick to be automatically metered into a diluent for subsequent laboratory analysis. This device, which has been successfully used by patients to obtain full blood counts, glycosylated haemoglobin values and blood glucose measurements, may have wide application.