Magnetic sensor for arterial distension and blood pressure monitoring

A novel sensor for measuring arterial distension, pulse and pressure waveform is developed and evaluated. The system consists of a magnetic sensor which is applied and fixed to arterial vessels without any blood vessel constriction, hence avoiding stenosis. The measurement principle could be validated by in vitro experiments on silicone tubes, and by in vivo experiments in an animal model, thereby indicating the non-linear viscoelastic characteristics of real blood vessels. The sensor is capable to provide absolute measurements of the dynamically varying arterial diameter. By calibrating the sensor, a long-term monitoring system for continuously measuring blood pressure and other cardiovascular parameters could be developed based on the method described. This will improve diagnostics for high risk patients and enable a better, specific treatment.     

Role of endotoxin on hypoglycaemia in acute hepatic failure. Relationship between hypoglycaemia and hepatic injury following endotoxaemia in diabetic and nondiabetic rats

To clarify the relation of endotoxaemia to hypoglycaemia and consequent death in acute hepatic failure, the interrelationship between the degree of hepatic injury, blood glucose level and mortality following endotoxaemia were examined in streptozotocin-induced diabetic and nondiabetic rats. Endotoxin hepatotoxicity was not enhanced in diabetic state. Blood glucose level was markedly reduced after endotoxin administration in the nondiabetic rats, and the reduction of blood glucose level closely correlated with the degree of hepatic injury (serum transaminase activities), namely, the more severe the hepatic injury, the lower the blood glucose level. Hypoglycaemia due to endotoxaemia occurred also in the diabetic rats when the hepatic injury was severe, but the reduction of blood glucose level was slight when it was mild. The mortality for endotoxaemia in diabetic rats was significantly lower than that in the nondiabetic rats. These experimental data suggest that endotoxaemia may play a role in the development of hypoglycaemia in acute hepatic failure, and that the diabetic state may lower the mortality for endotoxaemia.     

糖尿病大鼠皮肤的组织化学改变

目的：研究糖尿病(DM)大鼠皮肤的组织化学改变，探讨DM难愈创面形成和发展的病理机制。方法： 用链脲佐菌素（STZ）将SD大鼠诱导成速发型DM大鼠模型，并以正常大鼠作对照，分别于致病后4、8和12周获取大鼠背部中央的皮肤标本。应用HE染色，观察皮肤组织学的改变；应用Beckman’s生化自动分析仪检测皮肤组织匀浆的糖含量；采用F－3010荧光分光光度计测定皮肤胶原提取液的荧光强度；应用免疫组化和图像分析技术检测皮肤组织晚期糖基化终末产物（AGEs）含量。结果： 组织学观察可见，DM大鼠表皮组织变薄，表皮细胞层次欠清晰，部分表皮缺乏复层排列；真皮层部分胶原萎缩、肿胀，退化变性，并伴有程度不等的炎性细胞浸润；皮下脂肪进行性萎缩或消失。皮肤糖含量在各时相点均显著高于正常对照（P<0.01）。皮肤胶原提取液的荧光值亦高于相应年龄正常鼠（P<0.05），并随病程增加。AGEs蛋白主要沉积于真皮基质和细胞中，以及皮肤血管基底膜周围，并随病程的发展，染色逐渐加深，呈片状。结论： DM皮肤在损伤前就已发生明显的组织化学改变，而这些改变可能是由于局部高糖和AGEs累积所引发，并可能是DM难愈创面形成和发展的病理基础之一。     

Using a fuzzy controller optimized by a genetic algorithm to regulate blood glucose level in type 1 diabetes

In this paper a closed-loop control algorithm for blood glucose regulation in type 1 diabetic patients is proposed by using the Mamdani-type fuzzy method. Because of the presence of high-pass proportional derivatives in fuzzy designing, optimal values are applied for two inputs and one output membership functions in order to prevent the fluctuations due to derivatives in fuzzy design. Therefore, 19 values which are related to membership functions of the two inputs and one output are obtained by using a genetic algorithm (GA). The new model, termed the Augmented Minimal Model (AMM), is used in simulations. This controller is capable of stabilizing the blood glucose concentration at a normoglycaemic level of 90?mg dl^?1. The operation of the controller under various situations including multiple meal disturbances, and noise due to inaccurate effects of measuring blood glucose level are considered. Uncertainties in the meal disturbance function and variations of model parameters were also taken into consideration in simulations and the controller was found to be robust to such uncertainties.     

Using a fuzzy controller optimized by a genetic algorithm to regulate blood glucose level in type 1 diabetes

In this paper a closed-loop control algorithm for blood glucose regulation in type 1 diabetic patients is proposed by using the Mamdani-type fuzzy method. Because of the presence of high-pass proportional derivatives in fuzzy designing, optimal values are applied for two inputs and one output membership functions in order to prevent the fluctuations due to derivatives in fuzzy design. Therefore, 19 values which are related to membership functions of the two inputs and one output are obtained by using a genetic algorithm (GA). The new model, termed the Augmented Minimal Model (AMM), is used in simulations. This controller is capable of stabilizing the blood glucose concentration at a normoglycaemic level of 90 mg dl(-1). The operation of the controller under various situations including multiple meal disturbances, and noise due to inaccurate effects of measuring blood glucose level are considered. Uncertainties in the meal disturbance function and variations of model parameters were also taken into consideration in simulations and the controller was found to be robust to such uncertainties.     

Specificity of noninvasive blood glucose sensing using optical coherence tomography technique: a pilot study

Noninvasive monitoring of blood glucose concentration in diabetic patients would significantly reduce complications and mortality associated with this disease. In this paper, we experimentally and theoretically studied specificity of noninvasive blood glucose monitoring with the optical coherence tomography (OCT) technique. OCT images and signals were obtained from skin of Yucatan micropigs and New Zealand rabbits. Obtained results demonstrate that: (1) several body osmolytes may change the refractive index mismatch between the interstitial fluid (ISF) and scattering centres in tissue, however the effect of the glucose is approximately one to two orders of magnitude higher; (2) an increase of the ISF glucose concentration in the physiological range (3-30 mM) may decrease the scattering coefficient by 0.22% mM(-1) due to cell volume change; (3) stability of the OCT signal slope is dependent on tissue heterogeneity and motion artefacts; and (4) moderate skin temperature fluctuations (+/- 1 degree C) do not decrease accuracy and specificity of the OCT-based glucose sensor, however substantial skin heating or cooling (several degrees C) significantly change the OCT signal slope. These results suggest that the OCT technique may provide blood glucose concentration monitoring with sufficient specificity under normal physiological conditions.     

胰岛素不同给药方式治疗2型糖尿病合并社区获得性肺炎研究

目的观察应用双C和MSII治疗2型糖尿病（type 2 diabetes mellitus,T2DM）合并社区获得性肺炎（community acquired pneumonia,CAP）患者强化血糖控制的有效性和安全性。方法将2004年10月至2009年10月在我院住院的未使用过胰岛素治疗的T2DM合并CAP患者99例随机分为双C组（50例）和MSII组（49例）,分别给予双C和MSII。双C是应用持续皮下胰岛素输注（CSII）结合动态血糖监测系统（CGMS）一即“双C”方案。MSII是每日多次皮下注射胰岛素（MSII）结合每日八次指尖血糖监测。两组患者应用胰岛素和抗生素治疗后,观察CAP主要症状缓解时间、血糖达标时间、胰岛素用量、低血糖发生频率及肺炎控制时间的差异。结果双C组和MSII组患者治疗后空腹血糖分别为（6．3±0．2）mmol／L和（6．8±1．2）mmol／L,餐后2h血糖分别为（8．7±0．4）mmol／L和（9．3±1．2）mmol／L,均能达标。治疗后双C组患者果糖胺（7．2±0．13）mmol／L与MSII组（9．0±0．11）mmol／L比较,差异有统计学意义（P〈0．01）。双C组患者肺炎主要症状（发热、胸痛、咳黄痰、剧烈咳嗽、呼吸困难和湿啰音）缓解时间分别为（4．2±1．8）d、（3．7±1．2）d、（d．7±1．8）d、（8．2±1．3）d、（8．3±1．1）d和（9．2±2．6）d,血糖达标时间为（3．7±0．6）d、肺炎控制时间（12．8±4．5）d、胰岛素用量（37．6±6．5）次／d及低血糖发生频率（0．6±0．4）次／例;MSII组分别为（6．2±1．7）d、（4．3±1．4）d、（8．4±2．5）d、（9．6±3．5）d、（9．6±3．4）d、（12．4±4．1）d、（7．2±1．2）d、（18．2±6．8）d、（57．2±10．3）U／d和（4．3±0．7）次／例,两组比较差异均有统计学意义（P〈0．05）。结论在配合抗生素的前提下,“双C”方案治疗能及时、有效地控制T2DM合并CAP患者的血糖水平．肺炎症状缓解时间及治愈肺炎的时间均较MSII组短,而且胰岛素用量少,低血糖发生率低,是理想的治疗方法。     

The effects of insulin on the new-born calf

1. The normal variations in the concentrations of glucose, fructose and lactic acid in the blood of the calf which occur during the first few weeks after birth have been examined.

2. The responses of calves of different ages to intravenous injections of insulin have been examined by recording both the incidence of convulsions and the changes in the concentration of glucose, fructose and lactic acid in the blood.

3. New-born calves rarely convulsed during prolonged and severe hypoglycaemia and, if convulsions occurred, the onset was delayed by 6-8 hr. At 7 days of age convulsions usually followed the injection of insulin within 1½-2 hr.

4. No relationship could be found between the duration of hypoglycaemia and the incidence of convulsions at different ages. Hypoglycaemia was most prolonged in new-born calves which rarely convulsed.

5. Insulin hypoglycaemia during the first 24 hr after birth was associated with a rise in the concentration of lactate in the blood. Similar changes did not occur in calves at 7 days of age, in which the incidence of convulsions was much higher, or in weaned animals.

6. After both splanchnic nerves had been cut, insulin always caused convulsions in 24-hr-old calves. There was no rise in the blood lactate concentration in these animals.

7. Intravenous infusions of adrenaline but not noradrenaline in amounts similar to those known to be released from the adrenal medulla of the calf of this age prevented convulsions in 24-hr-old calves after section of the splanchnic nerves. These infusions had little effect on the blood glucose concentration but caused a similar rise in the lactic acid concentration to that found in normal animals at this age during hypoglycaemia.

8. At 7 days of age convulsions could only be prevented during hypoglycaemia by infusing larger doses of adrenaline which significantly raised the blood glucose concentration. The increase in the blood lactate concentration was less than that in the new-born animals.

9. The resistance to insulin hypoglycaemia which occurs immediately after birth is transient; it depends upon the release of adrenaline from the adrenal medulla and is associated with high concentrations of lactate in the blood during hypoglycaemia.

     

Dynamic thermographic imaging method for quantifying dermal perfusion: potential and limitations

A new method of quantifying dermal perfusion on a regional basis using a dynamic thermographic technique is investigated. The technique is based on the relationship between dermal perfusion and the rate of skin surface reheating following the application of a transient cold challenge predicted by a theoretical model. Measurements were made using images from a Philips thermographic camera under rigorously controlled conditions. Experimentation on undisturbed volar forerm skin of normal subjects showed that measurements could be repeated with good accuracy but that differences in normalised reheat temperatures between subjects were highly dependent on subcutaneous fat thickness. Comparisons between normal and occluded foreams indicated that reheat temperatures were not sensitive to changes in low levels of dermal perfusion. Conversely, stimulation of dermal blood flow with prostaglandin E₂ did produce significant differences from control conditions, but quantifying the axtent of this hyperaemia was limited by the effects of intersubject variations in fat thickness. Quantifying skin blood flow from skin temperature reheat rates is shown to be limited by a lack of sensitivity and a dependence on subcutaneous fat thickness, although dynamic thermography is able to provide useful information on regional variations in skin perfusion which could not be reliably obtained from static temperature measurements alone.     

Emotional changes during experimentally induced hypoglycaemia in type 1 diabetes

Emotional changes during experimentally induced hypoglycaemia in type 1 diabetic patients were investigated using a hyperinsulinaemic glucose clamp. In the experimental group (n=11), blood glucose was stabilised at euglycaemia (5.6 mmol/l, phase 1), then lowered to 2.5 mmol/l (phase 2) and raised to 5.6 mmol/l (phase 3). In the control group (n=11), euglycaemia was maintained during all phases. Hypoglycaemia elicited the expected endocrine, symptomatic and neuroglycopenic effects. During hypoglycaemia negative mood states increased significantly, whereas positive mood states decreased. Hypoglycaemia prolonged rating time of emotional stimuli (drawn from IAPS) significantly. The arousal ratings of the slides were higher during hypoglycaemia. Valence and dominance ratings were not affected. Epinephrine and norepinephrine release correlated with a higher arousal rating and a decrease in positive mood states. Deterioration in neuropsychological tasks correlated with an increase in negative mood states. Experimental induction of hypoglycaemia can offer a new research model to study emotional processes.     

Epidermal nerve fiber quantification in the assessment of diabetic neuropathy

Assessment of cutaneous innervation in skin biopsies is emerging as a valuable means of both diagnosing and staging diabetic neuropathy. Immunolabeling, using antibodies to neuronal proteins such as protein gene product 9.5, allows for the visualization and quantification of intraepidermal nerve fibers. Multiple studies have shown reductions in intraepidermal nerve fiber density in skin biopsies from patients with both type 1 and type 2 diabetes. More recent studies have focused on correlating these changes with other measures of diabetic neuropathy. A loss of epidermal innervation similar to that observed in diabetic patients has been observed in rodent models of both type 1 and type 2 diabetes and several therapeutics have been reported to prevent reductions in intraepidermal nerve fiber density in these models. This review discusses the current literature describing diabetes-induced changes in cutaneous innervation in both human and animal models of diabetic neuropathy.     

红外多波长无创人体血糖检测阵列模型的研究

无创血糖监测不仅可以减少患者的痛苦，还能进行连续测量，从而降低并发症的发生，它是一种不需收集血样进行体内血糖浓度测量的新技术。本文根据朗伯-比尔定律(The Lambert—Beer Law)原理，为克服无创血糖检测研究中的难点和缺陷，详细分析了血糖红外光谱的吸收特性，利用阵列技术设计了红外多波长无创血糖检测传感器阵列模型，对关键技术进行了讨论。用ME算法建立了信号检测和标定数学模型，结合了人体各种影响因素，使红外无创血糖检测的精度和稳定性得到了改善。列举了详细的实验实施步骤，同时叙述了系统调试的详细过程，讨论了无创血糖检测中需要注意的问题。     

A portable system for monitoring physiological responses to hypoglycaemia

Hypoglycaemia is the most common complication affecting people with Type 1 insulin dependent diabetes mellitus. Its onset is characterized by symptoms which include sweating, tremor, palpitations, loss of concentration and tiredness. As part of a research project to investigate the mechanisms of hypoglycaemia we have developed an ambulatory system to monitor and. record pulsatile changes in blood flow, pulse internal, body temperature and skin impedance. The system uses a pocket computer (Atari Portfolio) to collect and store the data on a memory card. The analogue system consists of two thermocouples, an infrared photoplethysmograph and skin impedance monitoring circuit. To conserve power the system is programmed to make measurements for 2 min every 10 min; using this regimen over 16 h of data can be stored. Data collected during a spontaneous overnight hypoglycaemic episode are presented and also a comparison between continuous and intermittent data collection during a period of induced hypoglycaemia. The system is being used to investigate the physiological responses to hypoglycaemia but could easily be adapted for monitoring other physiological signals.     

Novel control system for blood glucose using a model predictive method

We developed a novel blood glucose control system, using a model predictive method, to achieve optimal control of the blood glucose level in severely diabetic or pancreatectomized patients. This system is designed to predict glucose level changes in advance, considering delayed response time and the administered doses of insulin. This method is also designed to calculate the most appropriate insulin infusion rate by considering differences in individual response to insulin. In this study, we compared our system with a conventional proportional and differential controller (PD controller) to determine whether the new system could regulate the glucose level efficiently in pancreatectomized dogs. The model predictive control method resulted in a significant reduction of mean insulin infusion rate compared with the conventional PD controller (0.71 mU/kg per min vs. 1.81 mU/kg per min, p = 0.0005), when the glucose level in both methods reached the planned target level (100 mg/dl). The new system also tended to have a reduced mean glucose infusion rate for compensating for overshooting of the glucose level compared with the PD controller (0.7 mg/kg per min vs. 1.1 mg/kg per min, p = 0.16). These results indicate that the new system should be a useful tool for regulating the glucose level in severely diabetic patients.     

Development of a wearable glucose sensor; studies in healthy volunteers and in diabetic patients

A glucose sensor with a subcutaneous dialysis system was tested in six healthy volunteers during an oral glucose tolerance test and in ten diabetic patients with hyperglycemia during rapid decline of blood glucose levels. There was a good correlation between sensor and blood glucose values. During oral glucose tolerance tests in the volunteers, there was a mean delay of 4.4 minutes in the rise of the value registered subcutaneously and of 8.2 minutes in the fall of the curves. In the diabetic patients the maximum delay was 22 minutes. Nine days after insertion of the dialysis system it was still functioning well.     

无创性动态测定血糖的动物实验

探索一种无创性动态测定血糖的原理和建立实验方法。使用共价键固定法 ,制作葡萄糖氧化酶传感器 ,选择传感器最佳制作方法和稳定的工作条件。设立超声前、后组 ,注射葡萄糖前、后及高频、低频超声对照组。在 10只日本大耳兔的皮肤表面 ,用高频或低频超声波处理皮肤 5 m in后 ,用葡萄糖氧化酶传感器测定其微电流信号的变化。采用葡萄糖氧化酶传感器和微电流检测仪 ,可观察到经超声波处理后 ,兔皮肤表面 ,微电流信号明显增高变化(P<0 .0 1)和在注射葡萄糖后的进一步增高变化 (P<0 .0 1)。兔皮肤表面经超声波处理后 ,对葡萄糖的通透性明显增高 ,经葡萄糖氧化酶传感器转化为微电流信号的变化 ,与兔体内的葡萄糖水平呈正相关。在活体动物皮肤表面 ,用葡萄糖氧化酶传感器测定血糖是可行的     

Characteristics of skin admittance for dry electrodes and the measurement of skin moisturisation

The properties of skin adminttance were investigated with the intention of applying them to skin moisturisation measurement. Skin admittance is determined by measuring relative permittivity and the resistivity of the stratum corneum, and by contact ratio between dry electrode and stratum corneum. It was found, however, that the contact ratio is the predominant factor producing the change of skin admittance induced by changes in the water content of skin. To measure skin admittance, the following conditions were found to be approriate: (a) frequency of about 100 kHz; (b) concentric electrodes, the diameter of the measuring (inner) electrode being about 5 mm, and (c) an electrode pressure of about 100 g cm⁻². Based on these optimal conditions, a system for measuring skin admittance was constructed. All measuring procedures were automated. Experimental observations made with this system have indicated its usefulness for the measurement of skin moisturisation.     

Blood-stage malaria infection in diabetic mice.

Infection of mice with blood-stage Plasmodium yoelii and P. chabaudi malaria induced hypoglycaemia in normal mice and normalized the hyperglycaemia of mice made moderately diabetic with streptozotocin (STZ). Injection of parasite supernatants induced hypoglycaemia accompanied by hyperinsulinaemia in normal mice, and in STZ-diabetic mice induced a profound drop in blood glucose and restored insulin secretion; however, severely diabetic mice (two injections of STZ) remained hyperglycaemic with no change in insulin levels. We conclude that malaria infection and parasite-derived molecules lower blood glucose concentration, but only in the presence of some residual pancreatic function. Diabetic mice were less anaemic, exerted a significant control of parasitaemia, and showed enhanced phagocytic activity compared with normal mice.     

The self-aware diabetic patient software agent model

This work presents a self-aware diabetic patient software agent for representing a human diabetic patient. To develop a 24 h, stochastic and self-aware patient agent, we extend the original seminal work of Ackerman et al. [1] in creating a mathematical model of human blood glucose levels in three aspects. (1) We incorporate the stochastic and unpredictable effects of daily living. (2) The Ackerman model is extended into the period of night-time. (3) Patients' awareness of their own conditions is incorporated. Simulation results are quantitatively assessed to demonstrate the effectiveness of lifestyle management, such as adjusting the amount of food consumed, meal schedule, intensity of exercise and level of medication. In this work we show through the simulation that the average blood glucose can be reduced by as much as 51% due to careful lifestyle management. Self monitoring blood glucose is also quantitatively evaluated. The simulation results show that the average blood glucose is further dropped by 25% with the assistance of blood glucose samples. In addition, the blood glucose is perfectly controlled in the target range during the simulation period as a result of joint efforts of lifestyle management and self monitoring blood glucose. This study focuses on demonstrating how human patients' behavior, specifically lifestyle and self monitoring of blood glucose, affects blood glucose controls on a daily basis. This work does not focus on the insulin–glucose interaction of an individual human patient. Our conclusion is that this self-aware patient agent model is capable of adequately representing diabetic patients and of evaluating their dynamic behaviors. It can also be incorporated into a multi-agent system by introducing other healthcare components so that more interesting insights such as the healthcare quality, cost and performance can be observed.