CD34+ blood cells accelerate vascularization and healing of diabetic mouse skin wounds

Diabetes is characterized by poor circulation and impaired angiogenesis, which appear to contribute to the frequent skin lesions and poor wound healing common in diabetic patients. Therapies to improve circulation commonly improve wound healing in diabetic patients. Administration of circulating CD34+ cells, cells that can function as endothelial cell progenitors, accelerates blood flow restoration to ischemic limbs of diabetic mice. We have investigated the potential of these cells to accelerate revascularization and healing in full-thickness skin wounds of hypoinsulinemic (streptozotocin-treated) diabetic mice. Wounds were injected with human CD34+ or CD34- peripheral blood mononuclear cells or no cells, and analyzed for vascularity and healing at various times thereafter. Treatment with CD34+ enriched cells decreased wound size by 4 days after treatment, accelerated epidermal healing, and rapidly and dramatically accelerated revascularization of the wounds compared to controls. Initially increased vascularization was mediated principally by an increase in vessel diameter, but later, both an increase in vascular size and number were observed. These findings indicate that blood-derived progenitors may have therapeutic potential in the treatment of skin lesions in the setting of diabetes, and give insights into how bone marrow cells exert their effects on neovascularization.     

Pharmacokinetics of artesunate following oral and rectal administration in healthy Sudanese volunteers

The aims of this study were to determine the pharmacokinetic parameters of a single dose of 200 mg oral and rectal artesunate in healthy volunteers, and to suggest a rational dosage regimen for rectal administration. The study design was a randomized open cross-over study of 12 healthy volunteers; the analytical method used was a reversed phase high performance liquid chromatography with post column derivatization and subsequent ultraviolet detection. Pharmacokinetic parameters were derived from the main metabolite alpha-dihydroartemisinin data due to the rapid disappearance of artesunate from the plasma. Dihydroartemisinin following oral administration of artesunate had a significantly higher AUC(0-infinity) (P<0.05 95% confidence interval (CI) -1168.73, -667.61 ng x h/mL(-1)) and Cmax (P<0.05; 95% CI -419.73, -171.44 ng/mL(-1)), and had shorter tmax (P<0.05; 95% CI -0.97, -0.10 h) than that following rectal artesunate. There was no statistically significant difference in the elimination half-life between both routes of administration (P>0.05; 95% CI -0.14, 0.53 h). The relative bioavailability of rectal artesunate was [mean (coefficient of variation %) 54.9 (24.8%) %]. On the basis of these data an 8 hourly dosing regimen per day with rectal artesunate is proposed.     

Impact of Intracranial Pressure Monitor–Guided Therapy on Neurologic Outcome After Spontaneous Nontraumatic Intracranial Hemorrhage

Objectives: Intracranial pressure (ICP) monitors have been used in some patients with spontaneous intracranial hemorrhage (ICH) to provide information to guide treatment without clear evidence for its use in this population. We assessed the impact of ICP monitor placement, including external ventricular drains and intraparenchymal monitors, on neurologic outcome in this population.Materials and MethodsIn this secondary analysis of the Minimally Invasive Surgery Plus Alteplase for Intracerebral Hemorrhage Evacuation III trial, the primary outcome was poor outcome (modified Rankin Scale score 4-6) and the secondary outcome was death, at 1 year from onset. We compared outcomes in patients with or without an ICP monitor using unadjusted and adjusted logistic regression models. The analyses were repeated in a balanced cohort created with propensity score matching.ResultsSeventy patients underwent ICP monitor placement and 424 did not. Poor outcome was seen in 77.1% of patients in the ICP-monitor subgroup compared with 53.8% in the no-monitor subgroup (p<0.001). Of patients in the ICP-monitor subgroup, 31.4% died, compared with 21.0% in the no-monitor subgroup (p=0.053). In multivariate models, ICP monitor placement was associated with a >2-fold greater risk of poor outcome (odds ratio 2.76, 95% CI 1.30–5.85, p=0.008), but not with death (p=0.652). Our findings remained consistent in the propensity score-matched cohort.ConclusionThese results question whether ICP monitor–guided therapy in patients with spontaneous nontraumatic ICH improves outcome. Further work is required to define the causal pathway and improve identification of patients that might benefit from invasive ICP monitoring.     

Parathyroid hormone 1–34 enhances extracellular matrix deposition and organization during flexor tendon repair

Parathyroid hormone (PTH) 1–34 is known to enhance fracture healing. Tendon repair is analogous to bone healing in its dependence on the proliferation and differentiation of mesenchymal stem cells, matrix formation, and tissue remodeling.^1,2,3 We hypothesized that PTH 1–34 enhances tendon healing in a flexor digitorum longus (FDL) tendon repair model. C57Bl/6J mice were treated with either intraperitoneal PTH 1–34 or vehicle‐control (PBS). Tendons were harvested at 3–28 days for histology, gene expression, and biomechanical testing. The metatarsophalangeal joint range of motion was reduced 1.5–2‐fold in PTH 1–34 mice compared to control mice. The gliding coefficient, a measure of adhesion formation, was 2–3.5‐fold higher in PTH 1–34 mice. At 14 days post‐repair, the tensile strength was twofold higher in PTH 1–34 specimens, but at 28 days there were no differences. PTH 1–34 mice had increased fibrous tissue deposition that correlated with elevated expression of collagens and fibronectin as seen on quantitative PCR. PTH 1–34 accelerated the deposition of reparative tissue but increased adhesion formation. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:17–24, 2015.     

Effect of shoulder girdle strengthening on trunk alignment in patients with stroke

[Purpose] This study investigated the effect of shoulder girdle strengthening, particularly the scapular muscles, on poststroke trunk alignment. [Subjects and Methods] The study involved 30 patients with residual hemiparesis following cerebrovascular stroke. Patient assessment included measuring shoulder muscle peak torque, scapular muscles peak force, spinal lateral deviation angle, and motor functional performance. Patients were randomly allocated either to the control group or the study group and received an 18-session strengthening program including active resisted exercises for shoulder abductors and external rotators in addition to trunk control exercises. The study group received additional strengthening exercises for the scapular muscles. [Results] The two groups showed significant improvement in strength of all shoulder and scapular muscles, with higher improvement in the study group. Similarly, the lateral spinal deviation angles significantly improved in both groups, with significantly higher improvement in the study group. Transfer activity, sitting balance, upper limb functions, and hand movements significantly improved in the two groups, with higher improvement in the latter two functions in the study group. [Conclusion] Strengthening of shoulder girdle muscles, particularly scapular muscles, can significantly contribute to improving the postural alignment of the trunk in patients with poststroke hemiparesis.Key words: Stroke, Scapular muscles strengthening, Lateral trunk alignment     

Long-term compliance with continuous positive airway pressure in Saudi patients with obstructive sleep apnea: A prospective cohort study

Objectives:

To evaluate continuous positive airway pressure (CPAP) compliance and define predictors of CPAP compliance among Saudi patients with obstructive sleep apnea (OSA) after applying an educational program.

Methods:

This prospective cohort study included consecutive patients diagnosed to have OSA based on polysomnography between January 2012 and January 2014 in King Saud University, Riyadh, Kingdom of Saudi Arabia. All patients had educational sessions on OSA and CPAP therapy before sleep study, and formal hands-on training on CPAP machines on day one, day 7, and day 14 after diagnosis. The follow-up in the clinic was carried out at one, 4, and 10 months after initiating CPAP therapy. Continuous positive airway pressure compliance was assessed objectively. Logistic regression model was used to assess the predictors of CPAP adherence.

Results:

The study comprised 156 patients with a mean age of 51.9±12.1 years, body mass index of 38.4±10.6 kg/m², and apnea hypopnea index of 63.7±39.3 events/hour. All patients were using CPAP at month one, 89.7% at month 4, and 83% at month 10. The persistence of CPAP-related side effects and comorbid bronchial asthma remained as independent predictors of CPAP compliance at the end of the study.

Conclusion:

With intensive education, support, and close monitoring, more than 80% of Saudi patients with OSA continued to use CPAP after 10 months of initiating CPAP therapy.Continuous positive airway pressure (CPAP) is a standard, safe, and efficacious treatment for obstructive sleep apnea (OSA), a common disorder with established harm to quality of life and adverse consequences for cardiovascular health.1 Obstructive sleep apnea is characterized by recurrent partial (hypopnea) or complete (apnea) upper airway obstruction during sleep. These recurrent respiratory events usually cause intermittent hypoxemia and sleep fragmentation.2 Recent data demonstrated that the estimated prevalence of moderate to severe OSA ranges from 10-17% in middle-aged and elderly men.3 In Saudi Arabia, 3 out of 10 middle-aged Saudi men and 4 out of 10 middle-aged Saudi women are at high risk of having OSA.4,5 The mainstay medical treatment for OSA is CPAP therapy.6 Among various available therapeutic modalities for OSA, CPAP remains the most effective treatment.6 Continuous positive airway pressure is a machine that applies positive airway pressure to the upper air passages via a mask fitted on the mouth or nose to keep the throat open.6 Previous studies in Western countries showed that OSA patients on CPAP therapy use their machines on average from 4.5 to 5.5 hours per night with compliance rates ranging from 30-85%.7,8 Several studies have been conducted to define factors that influence, or predict CPAP use and adherence, and reported conflicting results.6 Moreover, several studies reported that race might influence CPAP adherence. For example, available data suggest lower CPAP adherence among African Americans than Caucasians.9 An earlier study that assessed CPAP compliance subjectively (self-reports) among Saudi patients with OSA after 3 months of initiation of CPAP therapy revealed an overall compliance rate of 39%.10 However, self-reports have been shown to overestimate CPAP use by approximately one hour/night when compared with objectively measured CPAP use.11 In general, there are very few data on objectively assessed long-term CPAP compliance in the literature. Moreover, there is a lack of previous study objectively addressing the rate of CPAP compliance, the predictors of good compliance, and the side effects of CPAP treatment in Saudi OSA patients. Therefore, we established in our center an educational program for patients with OSA and easily accessible medical support, and close follow-up of CPAP compliance. This study was conducted to evaluate CPAP compliance and to define predictors of CPAP compliance among Saudi patients with OSA after applying the new educational program.