Sclerostin in the development of osteoarthritis: A mini review.

Wnt signalling plays an important role in bone and cartilage metabolism. Activation of Wnt signalling promotes bone formation but cartilage degradation. Sclerostin (SOST) can inhibit Wnt signalling. It is expressed by chondrocytes in the articular cartilage and osteocytes in the subchondral bone. Since osteoarthritis (OA) is a joint degenerative disease involving both bone and joint compartments, SOST may have a role in mediating the progression of this disease. This review examined the current literature on the role of SOST in the pathogenesis of OA and its usefulness as a biomarker of OA. Most studies agree that SOST is upregulated as a rescue mechanism in OA to prevent further degenerative changes of the joint. It antagonises inflammation-induced cartilage catabolism while preserving chondrocyte anabolic activities. It also prevents abnormal bone mineralisation and osteophyte formation. However, studies on the performance of SOST as a biomarker to detect and stage OA are limited. Further studies are required to determine whether SOST can be a biomarker or therapeutic target for OA.

Abnormal connexin expression in human chronic wounds.

BACKGROUND: Regulated alteration of connexin expression has been shown to be integral to acute wound repair. Downregulation of the gap-junction protein connexin 43 at the wound edge has been correlated with keratinocyte and fibroblast migration, while abnormal overexpression of connexin 43 significantly perturbs healing, as shown in the streptozotocin diabetic rodent impaired healing model. OBJECTIVES: To examine the protein expression levels of connexin 43, in addition to connexins 26 and 30, in a variety of human chronic wounds. METHODS: Wound-edge punch biopsies and a matched control from the arm were taken from a cohort of patients with venous leg, diabetic foot or pressure ulcers. Wound connexin expression in each patient was compared with that in a matched, nonwounded arm punch. Tissue was sectioned, stained and imaged by confocal microscopy using identical parameters per patient to permit quantification. RESULTS: Epidermal connexin 43, connexin 26 and connexin 30, and dermal connexin 43 were discovered to be strikingly upregulated in every ulcer from all three wound types, pointing to connexin upregulation as a common feature between chronic wounds. CONCLUSIONS: This result supports efforts to target connexin 43 to promote cell migration and wound healing in chronic ulcers.

Relating external compressing pressure to mean arterial pressure in non-invasive blood pressure measurements.

Arterial volume clamping uses external compression of an artery to provide continuous non-invasive measurement of arterial blood pressure. It has been assumed that mean arterial pressure (MAP) corresponds to the point where unloading leads to the maximum oscillation of the arterial wall as reflected by photoplethysmogram (PPG), an assumption that has been challenged. Five subjects were recruited for the study (three males, mean age (SD) = 32 (15) years). The PPG waveform was analysed to identify the relationship between the external compressing pressure, PPG pulse amplitude and MAP. Two separate tests were carried out at compression step intervals of 10 mmHg and 2 mmHg, respectively. No significant differences were found between the two tests. The bias between the compressing pressure and the MAP was -4.7 ± 5.63 mmHg (p < 0.001) showing a normal distribution. Further research is needed to identify optimal algorithms for estimation of MAP using PPG associated with arterial compression.

Total testosterone and sex hormone-binding globulin are significantly associated with metabolic syndrome in middle-aged and elderly men.

Testosterone and sex hormone-binding globulin (SHBG) have been shown to be associated with metabolic syndrome (MS) in men. This study aimed at validating these relationships in a group of middle-aged and elderly men and assessing their strength of association to MS. A cross-sectional study of 332 Malaysian men aged 40 years and above was conducted. The blood of subject was collected under fasting condition for determination of testosterone, SHBG, glucose and lipid levels. Their medical history, smoking and alcohol consumption status, waist circumference (WC), body mass index (BMI) and blood pressure (BP) were recorded. All testosterone and SHBG levels were significantly reduced in MS subjects compared to non-MS subjects (p<0.05). Testosterone and SHBG were correlated significantly with most of the MS indicators without adjustments. In multiple regression analysis, the triglyceride level was the only MS indicator that was significantly, inversely and independently associated with all testosterone measurements and SHBG (p<0.05). Waist circumference was significantly and negatively associated with SHBG level (p<0.05) though not independent of BMI. Total testosterone and SHBG were significantly and inversely associated with the presence of MS. Testosterone and SHBG are potential intervention targets for the prevention of MS in men.

A new noninvasive device for continuous arterial blood pressure monitoring in the superficial temporal artery.

Continuous recording of arterial blood pressure (ABP) has many applications in cardiovascular physiology, but existing alternatives rely on measurements performed in the fingers or radial artery. Peripheral recordings have significant differences from central ABP regarding the pattern of the waveform and corresponding systolic and diastolic values. To address the need for noninvasive measurements closer to the ascending aorta, a new device was constructed to measure ABP in the superficial temporal artery (STA) using photoplethysmography and the arterial volume clamping technique. The optoelectronic circuitry to generate the photoplethysmogram is contained in a specially designed probe placed over the STA and kept in place with a head frame. The prototype (STAbp) also includes original designs for the pneumatic, electronic, signal processing, control and display sub-systems. A self-calibration feature regularly updates the photoplethysmogram operating point to improve accuracy. The performance of the STAbp was compared against the Finapres in 19 healthy subjects. At rest, the bias (SDd) was -23.1 (15.05), -10.8 (13.83) and -12.4 (12.93) mmHg for systolic, mean and diastolic pressures respectively, without significant differences in drift between the two devices. The 99% bandwidth (SD) for the spectral distribution of ABP waveforms was 5.3 (1.46) Hz for STAbp and 6.8 (0.73) Hz for the Finapres (p < 0.01). Handgrip manoeuvre showed a very similar response to the Finapres, including the rapid return to baseline on release. The new STAbp device has considerable potential as a new tool for clinical and research applications where continuous recording of more central ABP is advantageous compared to peripheral alternatives.

Breast reconstruction in the high risk patient with systemic connective tissue disease: a case series.

INTRODUCTION: The presence of severe underlying connective tissue disease may restrict the reconstructive options offered to a woman in the event of mastectomy. Putative concerns about reconstructive surgery include the effects of connective tissue disease and immunosuppression on wound healing and donor site morbidity, and increased risks of deranged clotting and thrombophilia after free tissue transfer. There is also the possibility of an unpredictable tissue reaction after oncological resection surgery and adjuvant radiotherapy. METHODOLOGY: Here we present a review of the current sparse evidence regarding reconstructive breast surgery in this challenging group of patients. In addition we present a series of six consecutive patients with a spectrum of connective tissue disorders including combinations of longstanding Systemic Lupus Erythematosis (SLE), Rheumatoid arthritis and Raynaud's Disease who underwent successful post-mastectomy reconstruction with an extended autologous latissimus dorsi flap, along with subsequent successful correction of asymmetry and/or nipple reconstruction. RESULTS: There is a paucity of literature on this subject perhaps suggesting that surgeons are reluctant to offer reconstruction or that uptake is poor in this group. Complications related to radiotherapy and free tissue transfer in patients with severe CTD is less than may be expected. The most common complications experienced by our patients with CTD after extended ALD breast reconstruction were persistent donor site seroma, wound dehiscence and delayed haematoma formation, reflecting the abnormal inflammatory response and deranged haemostatic cascade common to connective tissue disease. However, all six patients made a full recovery from surgery without residual donor site morbidity and with an acceptable aesthetic breast reconstruction. CONCLUSION: Careful peri-operative management is crucial in this group of patients, but good outcomes are possible using a variety of reconstructive techniques. This is the first reported series of patients with severe connective tissue disease who have been managed with extended ALD breast reconstruction. The majority of complications relate to the donor site but the favourable outcomes demonstrate that the extended ALD flap remains a reliable reconstructive option for this group.

Temporary catheter first perfusion during hand replantation with prolonged warm ischaemia.

INTRODUCTION: Since the first successful arm replantation reported by Malt and McKhann in 1962, developments and refinements to upper extremity replantation techniques have led to higher success rates with better functional outcomes. One of the most important determinants of a successful macroreplantation is the ischaemic time of the amputated part, as irreversible muscle necrosis begins after 6 hours of warm ischaemia. With major trauma and plastic surgery units usually covering a wide geographical area, it is often difficult to ensure patient injury to revascularization time is less than 6 hours. In 1981, Nunley et al described the temporary catheter perfusion technique in upper limb replantation surgery to reduce ischaemia time without any significant complications. When used in appropriate cases this technique can reduce complication rates in upper limb replantation surgeries. MATERIAL AND METHODS: Temporary catheter first perfusion was used in a hand replantation after 6 hours of warm ischaemia, with preservation of the intrinsic muscles, as evidenced by return of function. The technique used is described, along with relevant literature. RESULTS: Temporary catheter perfusion allowed early reperfusion of the amputated hand, improving the chance of intrinsic muscle preservation despite delayed presentation. It allowed better wound evaluation and debridement, and facilitated better bone stabilisation prior to vascular repair. CONCLUSION: Temporary catheter perfusion is well described in proximal upper limb replantation procedures. This case shows that it is also a useful adjunct for hand replantation, particularly when the patient presents with a critical duration of warm ischaemia.

Connexins, a new target in wound treatment.

Wound healing is a complex process requiring interaction between different cell types, each playing their part within the four main phases of wound healing. This process requires careful regulation, with communication between the different cell types via gap junction channels, which allow the passage of small molecules, including ions and second messengers, between cells. Gap junction protein (connexin) expression changes with the different stages of wound healing, playing important roles in regulating the process. The field of research looking into intercellular communication via gap junctions in skin and wound healing has shown encouraging results in experimental studies. As further developments and clinical studies are being carried out, practitioners should be introduced to this field, as a promising new wound treatment is currently in clinical trials. This paper aims to introduce practitioners to this field of study with a review of current available literature.