Effect of local injection of mesenchymal stem cells on healing of sutured gastric perforation in an experimental model.

BACKGROUND: Mesenchymal stem cells are proposed to facilitate repair of organ injuries. The aim of this study was to investigate whether local injection of mesenchymal stem cells could accelerate healing of sutured gastric perforations. METHODS: Sutured gastric perforations in rats were treated either with local injection of mesenchymal stem cells (injected MSC group) or by topically spraying with fibrin glue containing mesenchymal stem cells (sprayed MSC group). Controls were treated by local injection of saline or topical spray of fibrin glue without mesenchymal stem cells. Healing of sutured gastric perforations was assessed on days 3, 5 and 7. RESULTS: Local injection of mesenchymal stem cells significantly promoted the healing of gastric perforations, with the highest pneumatic bursting pressure (mean(s.e.m.) 112·3(30·2) mmHg on day 5 versus 71·2(17·4) mmHg in saline controls; P = 0·001), minimal wound adhesions, and lowest incidence of wound dehiscence (3, 6, 5 and 1 animal on day 5 in control, fibrin, sprayed MSC and injected MSC groups respectively; n = 10 per group) and abdominal abscess (2, 2, 1 and no animals respectively on day 5). Histological examination showed that gastric perforations in the injected MSC group displayed reduced inflammation, and increased granulation and re-epithelialization. Sutured gastric perforations in the injected MSC group showed decreased expression of interleukin 6, and increased expression of transforming growth factor ß1 and epithelial proliferating cell nuclear antigen, compared with the other groups. CONCLUSION: Local injection of mesenchymal stem cells was more effective than topical application, and enhanced the healing of sutured gastric perforations by an anti-inflammatory process, enhanced cellular proliferation and earlier onset of granulation. Surgical relevance Abnormal healing of gastric perforation may cause morbidity and increase the risk of death. Adipose tissue-derived mesenchymal stem cells have been found to promote the healing of organ injuries through cellular differentiation and secretion of cytokines that stimulate cellular proliferation and angiogenesis, and suppress inflammation. This study explored the therapeutic potential of such mesenchymal stem cells for promotion of the healing of sutured gastric perforations. Mesenchymal stem cells delivered by local injection significantly enhanced the healing of gastric perforations with reduced severity of wound adhesion, and a decreased incidence of wound dehiscence and abdominal abscess. The increased expression of transforming growth factor ß1, proliferating cell nuclear antigen and reduced level of interleukin 6 provide evidence for enhancement of the healing process. Engrafted mesenchymal stem cells expressed α-smooth muscle actin as a marker of myofibroblasts. This preclinical study indicates that local injection of allogeneic adipose tissue-derived mesenchymal stem cells may have a potential therapeutic role in enhancing the healing of peptic ulcer disease and prevention of ulcer-related complications.

A mucoadhesive endoluminal wearable sensory system.

Bio- or muco-adhesive anchoring is a challenge for the development of advanced gastrointestinal (GI) surgical instruments, endoluminal monitoring devices and drug delivery systems. In this paper, we present a polymeric bio-adhesive film embedded with an optical sensor that can potentially be used to detect gastrointestinal bleeding. Four different formulas of mucoadhesive polymers were synthesized based on various chemical components and concentration combinations, and they were further layered with miniature photoplethymographic (PPG) sensors. The adhesive ability of the proposed mucoadhesive-sensor module was tested by attaching it to the lumen of a porcine stomach and compared amongst the four formulas. pH testing was also implemented to simulate the performance of the film in gastric cavity. To demonstrate the signal quality of this module, we also tested on the skin of five healthy subjects for hours. The observed shear detachment force between mucoadhesive film and porcine stomach tissue of all four formulations ranged from 0.09 to 1.38 N, and the performance of mucoadhesive film in pH 7 and pH 2 were similar. The module can attach firmly onto the skin for 3-10 hours with comparable PPG signal quality to traditional clip-based setup. With the advent of mucosal tissue anchoring by means of bioadhensive film, a wider extent of endoluminal procedures may become feasible. This emerging technology can also help shape the future of in-body wearable devices in the GI tract or other endoluminal cavities.

Evaluation of a novel cardiac output index on healthy elderly, cardiovascular and heart failure patients during dynamic exercise.

We have recently proposed a novel CO index, namely pulse time reflection ratio (PTRR), which is extracted from photoplethysmogram and electrocardiogram and measurable from wearable devices, and proved that this index is potentially useful for dynamic CO monitoring in a preliminary study carried out on young, healthy subjects. In this study, we presented an evaluation of this technique against impedance cardiography on 64 subjects undergoing incremental maximal exercise testing, including 15 healthy elderly, 19 cardiovascular patients and 30 heart failure patients. Results showed significant intra-subject correlations (r) between PTRR and reference CO in all subjects (mean r: 0.93, p<0.05) and no significant differences on mean r among subject populations (one-way ANOVA, p=0.48). With further development and testing on mobile subjects, this technique can be applied for long-term CO monitoring at home or in other dynamic situations.

The non-invasive and continuous estimation of cardiac output using a photoplethysmogram and electrocardiogram during incremental exercise.

Cardiac output (CO) monitoring is not only essential for critically ill patients in the hospital, but also for patients at home and those undergoing cardiopulmonary exercise testing. However, CO is difficult to monitor during daily activities and exercise. In this paper, we aim at developing a novel CO estimation method that can be used under these challenging conditions. The tube model was utilized to derive a CO index, namely the pulse time reflection ratio (PTRR) from an electrocardiogram and photoplethysmogram. After calibration, the PTRR can be used to estimate beat-to-beat CO. The proposed method was verified against CO measured by impedance cardiography on 19 healthy subjects in an incremental intensity exercise test. Results showed that there were strong correlations (r) between the PTRR and reference CO in 18 subjects (mean r: 0.88, n = 245 trials). Two calibration approaches reported in the literature were applied to the proposed method and the corresponding bias +/- precisions of estimation errors were 0 +/- 1.89 L min(-1) and -0.22 +/- 2.12 L min(-1), respectively. The percent errors were 21.94% and 24.90%, smaller than the clinical acceptance limit (30%). To conclude, after calibration, this method can be used to monitor CO on healthy subjects during incremental intensity exercise.

A novel method for the contactless and continuous measurement of arterial blood pressure on a sleeping bed.

Nighttime blood pressure (BP) is found to best predict the 5-year risk of cardiovascular death in comparison to daytime BP, BP measured over a 24-hour period and clinical BP. In view of this, a novel contactless system has been developed on a sleeping bed for the cuffless and continuous estimation of BP at night. Experiments were conducted on 11 subjects to evaluate the contactless system, particularly its performance compared to a contact system. The results of this study showed that the accuracy of the contactless system to estimate BP by a cuffless approach is comparable to that of the contact system when measured at the same posture. More studies have to be conducted in order to understand the difference of the cuffless BP estimation approach when measuring at supine and sitting postures.

Some perspectives on affordable healthcare systems in China.

Consistent with the global population trend, China is becoming an aging society. Over one-fifth of the world's elderly population (aged 65 and over) lives in China. Statistics show that the elderly populace in China constitutes 8% of the total population in 2006 and the percentage will be tripled to become 24% in 2050. As a result, there is inevitably an increase in the prevalence of chronic disease that accounted for almost 80% of all deaths in China in 2005. On the other hand, from 1978 to 2003, the total expenditure on healthcare in China increased from 11.02 billion RMB up to 658.41 billion RMB, and in terms of GDP, it is an increase from 3.04% to 5.62%. The annual average increase (12.1%) in healthcare investment is therefore even higher than the annual rate of GDP increase (9.38%) during the last two decades. Meeting the long-term healthcare needs of this growing elderly population and escalating healthcare expenditure pose a grim challenge to the current Chinese healthcare system and the solvency of state budgets. In fact, the healthcare services in China have become less accessible since the early 1980s when its costs soared up. The rising costs have prevented many Chinese people from seeking early medical care. The phenomenon has created a wide disparity in seeking healthcare between urban and rural areas. These trends are of particular concern to the elderly, who have higher healthcare needs yet lesser means to afford the services. Furthermore, according to the 3rd National Health Service Survey, 79.1% of rural residents and 44.8% of urban citizens did not have any form of medical insurance. Such a low percentage of coverage of medical insurance indicates that many people may not be able to afford medical services when they suffer from severe diseases. Therefore, there is a great need of a more effective and low-cost healthcare system. A new system that can allow multi-level, multi-dimensional and standardized healthcare services for urban and rural citizens is proposed based on the development of miniaturized, integrated, networked, digitalized, and smart (MINDS) medical devices. Different from the traditional healthcare systems, the new one should bridge individuals and hospitals through a four-layer (PHCH) system structure: wearable intelligent sensors and devices for p-Healthcare system (PHS), home healthcare system (HHS), community healthcare system (CHS), and hospital health information system (H2IS). This four-layer structure should ensure people be monitored by the new system as closely as it can, resulting in the novel transformation of the function of healthcare systems from symptoms treatment to early risk detection and prevention. The new system is of particular importance to the cost reduction of healthcare services. It can reduce the chance of individual providers taking advantage of the provider-patient information asymmetry to prescribe unnecessary or inappropriate (but profitable) care. It also allows people to self-monitor their health conditions at their convenience in an attempt to lighten the workload of doctors and nurses. Moreover, more people can benefit from the new system with much lower medical insurance fees due to the reduced risk of developing severe diseases through regular, long-term and effective monitoring of citizens' health conditions nation-wide.

Can the timing-characteristics of phonocardiographic signal be used for cuffless systolic blood pressure estimation?

Continuous and non-invasive measurement of blood pressure (BP) is always important to critically ill patients. To achieve continuous and cuffless BP monitoring, pulse transit time (PTT) has been reported as a potential parameter. Recently a novel parameter RS2 (defined as the time interval measured from the R wave of electrocardiographic (ECG) signal to the peak of second heart sound of phonocardiographic (PCG) signal) is proposed for the same purpose. In this study, the relationship between systolic BP (SBP) and PTT as well as the relationship between SBP and RS2 on 25 healthy subjects, aged 24 +/- 3 years, were compared after exercise. The results in current study showed that SBP is correlated with both PTT and RS2, where the mean individual correlations are r=-0.95 and r=-0.85 respectively. The mean standard deviation of the differences between the measured SBP and the SBP predicted from the regression lines in scatter plots of SBP~PTT and SBP~RS2 are 4.1 mmHg and 7.2 mmHg respectively. In summary, the results showed that RS2 is possible to be used for continuous and non-invasive monitoring of SBP after exercise. In the future, it is important to investigate more robust techniques for locating characteristic points on the PCG signals.

Cuff-less and noninvasive measurements of arterial blood pressure by pulse transit time.

The current blood pressure (BP) measurement devices are mostly built on the principle of auscultation, oscillometry or tonometry, all of which use an inflatable cuff to occlude or unload the artery. The need of a cuff in these devices limits the further reduction in size and power consumption, and restricts the frequency and ease of their usage. Therefore, this study aims to develop a cuff-less and noninvasive technique for measuring BP by pulse transit time. The technique was evaluated on 85 subjects, aged 57+/-29 yrs., including 36 males and 39 hypertensives, over an average period of 6.4 wks. A total of 999 pairs of systolic BP (SBP) and diastolic BP (DBP) estimations were made. The average of BP readings reported by an experienced registered nurse and those obtained from a clinically approved automatic BP meter was used as reference. It is found that the estimated SBP and DBP differed from the reference BP by 0.6+/-9.8mmHg and 0.9+/-5.6mmHg respectively. When compared to the AAMI requirement (5+/-8mmHg for both SBP and DBP estimation), the results suggest that the cuff-less technology has great potential to be developed into wearable devices that are useful in self BP monitoring for home healthcare and eventually in clinical diagnosis.