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There are four themes in this teaching exercise for Professor McCance. The first challenge was to explain how a premature infant with Bartter's syndrome could survive despite having such a severe degree of renal salt wasting. Second, the medical team wanted to know why there was such a dramatic decrease in the natriuresis in response to therapy, despite the presence of a permanent molecular defect that affected the loop of Henle. Third, Professor McCance was asked why this patient seemed to have a second rare disease, AQP2 deficiency type of nephrogenic diabetes insipidus. The fourth challenge was to develop a diagnostic test to help the parents of this baby titrate the dose of indomethacin to ensure an effective dose while minimizing the likelihood of developing nephrotoxicity. The missing links in this interesting story emerge during a discussion between the medical team and its mentor.

This study was carried out to develop a two-layered finite element model of the oesophagus. The outer muscle and inner mucosal layer were constructed individually with different mechanical properties and zero-stress opening angles. With the model, two simulations were performed. First, the distention of oesophageal wall under the pressurized state was investigated, from which the effects of residual strains on the stress distribution were evaluated. Second, the buckling modes were determined using a linear eigenvalue analysis. The self-contact capability in ABAQUS was applied to simulate the folding of mucosa under the muscle contraction. The first simulation indicated that, by taking the residual strains into account, the mucosa undertook a very small portion of stress and the luminal pressure almost transmitted completely to the outer muscle layer. On the other hand, the folding of mucosa was shown to be able to reduce the contractile force of circular muscle to maintain the lumen closure. In conclusion, the preliminary study demonstrated the feasibility of simulating the oesophageal peristaltic transport using finite element analysis.

The mucosal folding is a phenomenon observed for some biological tissues, including the pulmonary airway and gastrointestinal tract. In order to understand the mechanism of the formation of mucosal folding, a thick-walled two-layered cylindrical mathematical model was developed to investigate the buckling behavior under the external pressure and circular outer boundary condition. With the finite element method, the validity and accuracy of the proposed model was verified. The results showed that the fold number was in the range of 4-6, which was agreed with the experimental observation for the mucosal folding of a porcine esophagus. The fold number was found to decrease with the increase in the ratio of the inner to outer material stiffness. The increase in the thickness of inner layer also caused a slight declination of the fold number. Since the effects of both the material and geometrical nonlinearities have been accounted for, this model is more general to be used for the prediction of the buckling behavior of the layered structure with a wide range of thickness ratios and/or stiffness ratios.

The time-dependent mechanical properties of porcine esophagus were investigated experimentally and theoretically. It was hypothesized that the viscoelasticity was quasi-linear. The incremental stress-relaxation test was conducted to identify the material constants included in the quasi-linear viscoelastic (QLV) model. To verify the predictive ability of the model, the incremental cyclic test was performed. Hysteresis was calculated and compared with that predicted by the model. Results showed that stresses relaxed by 20–30% within the first 10 s and stabilized at 50% at 300 s. The QLV model was shown to be able to describe the viscoelasticity of esophagus across various stretch levels. The model could also predict the hysteresis during cyclic test well. It suggested that the QLV could be used as the material characterization of esophageal tissue.

An integrated computer aided design/computer aided manufacture system has been used to model the complex geometry of blood vessel anastomoses. Computer models are first constructed with key dimensions derived from radiological images of bypass grafts, and from casts of actual blood vessel anastomoses. Physical models are then fabricated in one of two ways: the surface geometry data can be used to control the movement of a three-axis milling machine; alternatively, the same data can be exported in a form that can be interpreted by a stereolithography apparatus. Both methods produce geometrically defined solid investments that can be used in a multistep casting process that yields high-quality physical models for vascular fluid dynamic studies. This technique is useful for parametric studies.

Blackfoot disease (BFD) is an endemic peripheral arterial disease confined to the southwestern coast of Taiwan. The cause of the disease has been ascribed to the high-arsenic artesian well water. The purpose of this study was to examine the possible association between the long-term exposure to artesian well water and the change in microvascular circulation in the absence of peripheral arterial insufficiency. A total of 45 men living in the BFD-hyperendemic villages and another 51 age- sex- body-mass index-matched men who lived in nonendemic villages nearby were recruited into this study. All subjects were free from peripheral vascular disease (resting ankle-brachial index1.00), clinical claudication, cigarette smoking, diabetes mellitus, hypertension, ischemic heart disease, cerebral infarction and obesity. Laser Doppler flowmetry was used to measure the peripheral microcirculation on the big toes both at 36 degrees C (basal perfusion, Pb) and after a hyperthermic test at 42 degrees C (Ph). The time required to reach Ph (T), and the average rate (R) of increase from Pb to Ph measured by (Ph-Pb)/T were also calculated. Results showed that those living in the BFD-hyperendemic area had a lower Pb [32.8 +/- 6.0 perfusion units (PU) vs. 67.0 +/- 4.3 PU, p0.001], a lower Ph (193.2 +/- 13.6 vs. 231.1 +/- 6.3 PU, p0.005), a longer T (3.04 +/- 0.19 vs. 1.31 +/- 0.08 min, p0.001) and a slower rate of increase from Pb to Ph (48.0 +/- 4.8 vs. 76.2 +/- 5.4 PU/min, p0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

The effects of inhibition of bradykinin and prostaglandin on the renal and blood pressure responses to atrial natriuretic factor (ANF) were studied in anesthetized rats. Intraarterial infusion of the receptor antagonist D-Arg[Hyp3,Thi5,8,D-Phe7]bradykinin (BKA) at 14 μg/min, a rate sufficient to block the hypotensive response to 250 μg of bradykinin, did not affect the natriuresis due to injection of ANF (UNaV: control, before ANF, 393 ± 101, after ANF, 2322 ± 400 nmol/min; BKA, before ANF, 261 ± 72, after ANF, 2259 ± 390 nmol/min). In contrast, infusion of indomethacin (Indo) reduced the level of sodium excretion both before and especially after ANF administration (UNaV: Indo, before ANF, 75 ± 15, after ANF, 320 nmol/min). The effect of combining BKA with Indo was not different from the effect of Indo alone (UNaV: BKA + Indo, before ANF, 119 ± 26, after ANF, 469 ± 167 nmol/min). The bradykinin antagonist, with or without Indo, was associated with significant hypotension relative to control. Indo, both in the absence and presence of the antagonist, was associated with a progressive decrease in blood pressure compared with control. However, in each case the hypotensive responses to ANF were not different from those in the control group. We conclude that under the present experimental conditions bradykinin does not modify ANF-induced natriuresis. However, inhibition of prostaglandin synthesis by Indo is associated with renal salt retention, reducing natriuresis both before and after ANF administration.Key words: prostaglandin inhibition, D-Arg[Hyp3,Thi5,8,D-Phe7]bradykinin, atrial natriuretic factor.

Background: Metabolic syndrome (MS) and chronic kidney disease (CKD) are both strongly associated with coronary artery disease (CAD). Components of MS also cause CKD. The incremental effect of CKD on CAD prevalence in MS patients referred for stress imaging studies is unknown. Methods: From January to December 2005, consecutive subjects referred for a stress imaging study were prospectively enrolled. CAD was defined as fixed or reversible defects on nuclear imaging and as resting or stress-induced wall motion abnormalities on echocardiography. MS was defined using NCEP-ATP III criteria. CKD definition was based on calculated glomerular filtration rate. The independent effect of CKD on stress results was assessed using multiple variable logistic regression. Stepwise model selection was used for variable reduction, and areas under the receiver operating characteristic curves (ROC) were calculated. Results: Of 1,122 patients enrolled (mean age 61.4 years, 97% male), 535 (47%) had MS. Among MS patients, 156/535 (29%) had CKD while 116/587 (19%) subjects without MS had CKD. Subjects with CKD were older (p < 0.001) in subjects with and without MS. The presence of CKD affected prevalence of CAD in the non-MS group only, almost doubling it (20% vs. 38%, p < 0.001). Further, using the ordered nature of the 5 CKD stages, worsening severity of CKD had greater prevalence of CAD, in non-MS subjects only (p < 0.001). Conclusions: MS attenuates the effect of CKD on CAD prevalence, regardless of CKD severity. CKD almost doubles the prevalence of CAD in non-MS subjects. CKD severity is associated with greater CAD burden in the non-MS group.

Atherosclerotic plaque formation due to lipid accumulation in the arterial wall is the major cause of stenotic coronary disease. To restore distal coronary blood supply and overcome restenotic events presented by bare wire stents, drug-eluting stent (DES) implantation is now commonly used to treat stenotic coronary disease. However, while its long-term outcome is still unavailable, early clinical results appear to be inconsistent. The use of computational models is believed to be important in understanding DES and to elucidate the delivery of drug and improve the efficacy of DES. The presence of plaque in the stented region is expected to affect drug pharmacokinetics related to DES. In this study, a 2-dimensional model which drug transfer was coupled with both luminal and transmural flows was presented to investigate drug deposition and distribution in the arterial wall. Paclitaxel was used as a model drug and its interaction with the binding sites in the tissue was treated as a reversible binding process. As predicted, the presence of plaque dramatically affects the local pharmacokinetics. Thick plaque absorbs more drugs and provides higher resistance to drug transfer in the arterial wall compared to thin plaque. Study on the effect of drug diffusivity in the plaque on drug deposition reveals that higher diffusion coefficient results in lower drug content in the arterial wall. Meanwhile, when drug partition coefficient in the plaque was varied within the range for paclitaxel, it showed negligible effect on drug deposition. In conclusion, the presence and property of plaque have an effect on the delivery of drugs in arterial wall and should be included in the modeling of drug delivery from a DES to improve the design of stent to achieve the best therapeutic outcome.

Background The effect of traditional risk factors on the association between angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism and stroke was rarely studied previously. We investigated such effect in Taiwanese type 2 diabetic patients. Materials and methods A total of 872 (422 men and 450 women) patients aged 63·5 (SD: 11·6) years were recruited. Among them, 92 cases (48 men and 44 women) had stroke. Polymerase chain reaction was used to classify the genotypes as II, ID and DD. Analyses were performed in separate sexes. Results The adjusted odds ratios for stroke for ID vs. II and DD vs. II were 0·837 (0·413–1·697) and 1·778 (0·596–5·300), respectively, for men; but were 1·700 (0·824–3·505) and 3·706 (1·375–9·985), respectively, for women. In models assuming recessive (DD vs. II + ID), dominant (DD + ID vs. II) and additive (II = 0, ID = 1 and DD = 2) transmission, none of the odds ratios was significant for men; but were all significant for women: 2·784 (1·137–6·818), 1·996 (1·006–3·962) and 1·877 (1·155–3·050), respectively. In models using patients without risk factors (hypertension, obesity, smoking or dyslipidaemia ) as a referent group and comparing them to patients with the risk factor and with ID/II, and with DD genotypes, all models (except for smoking) favoured an increasing trend of risk with patients having the risk factor and DD genotype at the highest risk in women. Similar trends for hypertension and dyslipidaemia were also observed in men. Conclusion Traditional risk factors play an important role in the association between the ACE genotypes and stroke. Patients with DD genotype and having traditional risk factors are at the highest risk.

The time-dependent mechanical properties of the porcine esophagus were investigated experimentally and theoretically. It was hypothesized that the viscoelasticity was quasilinear, i.e., the time and strain effects were independent. In order to verify the separability of time and strain effects, the stress-relaxation test was conducted at various strains and the data were fitted with the Fung's quasilinear viscoelastic (QLV) model. By using the material parameters obtained from the stress relaxation test, the cyclic peak stress and hysteresis were predicted. Results showed that the stress relaxed by 20-30% of the peak stress within the first 10 s and stabilized at approximately 50% at the time of 300 s. The relative stress relaxation R(2) (i.e., the difference of stress at a particular time to the final equilibrium stress normalized by the total difference of the peak and final stress) was not different significantly for various strains. It was also found that, by using the stress-time data during both the ramp and relaxation phases, the correlation between parameters was substantially reduced. The model could also predict the cyclic peak stress and hysteresis except for the underestimate of valley stress. We conclude that the QLV model could be used as the material characterization of the esophageal tissue.

The identification of a three dimensional constitutive model is useful for describing the complex mechanical behavior of a nonlinear and anisotropic biological tissue such as the esophagus. The inflation tests at the fixed axial extension of 1, 1.125, and 1.25 were conducted on the muscle and mucosa layer of a porcine esophagus separately and the pressure-radius-axial force was recorded. The experimental data were fitted with the constitutive model to obtain the structure-related parameters, including the collagen amount and fiber orientation. Results showed that a bilinear strain energy function (SEF) with four parameters could fit the inflation data at an individual extension very well while a six-parameter model had to be used to capture the inflation behaviors at all three extensions simultaneously. It was found that the collagen distribution was axial preferred in both layers and the mucosa contained more collagen, which were in agreement with the findings through a pair of uniaxial tensile test in our previous study. The model was expected to be used for the prediction of stress distribution within the esophageal wall under the physiological state and provide some useful information in the clinical studies of the esophageal diseases.

The esophagus, like other soft tissues, exhibits nonlinear and anisotropic mechanical properties. As a composite structure, the properties of the outer muscle and inner mucosal layer are different. It is expected that the complex mechanical properties will induce nonhomogeneous stress distributions in the wall and nonuniform tissue remodeling. Both are important factors which influence the function of mechanosensitive receptor located in various layers of the wall. Hence, the characterization of the mechanical properties is essential to understand the neuromuscular motion of the esophagus. In this study, the uniaxial tensile tests were conducted along two mutually orthogonal directions of porcine esophageal tissue to identify the directional (circumferential and axial), regional (abdominal, thoracic, and cervical), and layer (muscle and mucosa) variations of the mechanical properties. A structure-based constitutive model, which took the architectures of the tissue’s microstructures into account, was applied to describe the mechanical behavior of the esophagus. Results showed that the constitutive model successfully described the mechanical behavior and provided robust estimates of the material parameters. In conclusion, the model was demonstrated to be a good descriptor of the mechanical properties of the esophagus and it was able to facilitate the directional, layer, and regional comparisons of the mechanical properties in terms of the associated material parameters.

Epidemiological evidence shows an increasing prevalence of type 2 diabetes in Taiwan. The aim of this study was to assess the yearly incidence for this country during 1992-1996.Data obtained by telephone interviews of 93,484 diagnosed diabetic patients enrolled in Taiwan's National Health Insurance programme formed the basis of this study. A total of 36,153 incident cases of type 2 diabetes (17,097 men and 19,056 women) were identified and incidence rates calculated. The trends of obesity and parental diabetes were also evaluated.The overall 5-year incidences for men and women were 187.1 and 218.4 per 100,000 population, respectively. The trends from 1992-1996 were increased for all age groups in men and for most age groups in women. A 2.8-fold increase in incidence was observed for the youngest age group (35 years), in which the increase in incidence was higher than in the older age groups. Men showed a higher fold increase in incidence than did women (3.5 vs 2.1). Obesity at interview increased from 39.2% in 1992 to 47.6% in 1996 (p0.001) and was significant for all ages. Parental diabetes showed no yearly change when all patients were analysed together, but there was a trend towards a decrease in the youngest age group (35 years) and a trend towards an increase in the oldest age groups (/=55 years).An increasing incidence of diagnosed type 2 diabetes was observed for each sex in most age groups in Taiwan, but was most marked in the youngest age group. A parallel increase in obesity was observed with the increasing incidence of diabetes.

We report a rare case of gastrointestinal tumor of the anus with an unusual presentation as a perianal lipoma. A 65-year-old man presented with a 2-month history of a painless perianal lump clinically resembling a perianal lipoma. Endoanal ultrasonography revealed a 3 x 3 cm2 mass in the intersphincteric plane. Following initial excision of the lesion, histological analysis revealed a stromal lesion comprising fascicles of spindle cells with a mitotic count of 4 per 50 x high power field. Immunohistochemical analysis displayed positive reactivity for CD34 with focal staining for CD117; S100, smooth muscle actin and desmin were not expressed. No evidence of local or distant metastatic disease was found on computed tomography of the abdomen and pelvis. The patient subsequently underwent abdominoperineal resection. The resected specimen contained a mural nodule measuring 0.7 cm, located 5 cm from the distal margin and 2 mm from the radial margin. Histological analysis confirmed a stromal tumor composed of spindle cells with mitoses up to 2 per 10 x high power field. The patient's recovery was uneventful and he was free of recurrence at the 1-year follow-up. Gastrointestinal stromal tumors of the anal canal are an extremely rare occurrence, and may mimic benign perianal lesions. Tumor size and mitotic count are the most important factors in prognosticating outcome. Oncologic resection and protracted follow-up must factor in their predilection for late recurrence and metastatic spread. The role of adjuvant therapy with STI571 here remains to be clearly defined.

The design and development of a simulator for endovascular repair of abdominal aortic aneurysm (AAA) is described. The simulator consists of an interchangeable model of a human AAA based on computed tomography data and is produced by means of computer-aided design and manufacture (CAD/CAM) techniques. The model has renal, iliac, and femoral arteries, and is perfused with a temperature controlled blood–analog fluid under simulated physiological flow conditions. “Fluoroscopic imaging” is simulated by a computerized imaging system that uses visible light. A movable video camera relays images in the antero–posterior and lateral planes of the AAA to a monitor. The imaging system allows “arteriography” and “road-mapping” to be performed so as to facilitate accurate deployment of endovascular stent-grafts. The system has been used for teaching and demonstrating endovascular techniques to clinicians, as well as the evaluation of new stent-graft devices. Its successful incorporation into endovascular workshops has demonstrated its role in the training of clinicians in endovascular repair of AAA. © 1998 Biomedical Engineering Society.

Weanling Dahl rats of the salt-sensitive and salt-resistant strains were kept either on a low salt diet for 10–15 weeks, or the diet was supplemented with 7% NaCl for the last 30 days. Animals were anesthetized and the renal responses to acute saline infusion and infusion of synthetic atrial natriuretic factor (ANF) were studied on both dietary regimens. Arterial blood pressures of sensitive and resistant groups were not different on the low salt intake. As expected, addition of dietary salt increased pressure markedly in the sensitive animals. Resistant rats also had smaller, but statistically significant, increases in pressure. On the low salt diet, salt-sensitive rats showed a larger renal response to saline infusion, whereas on the high salt diet there were no significant differences between strains. The responses to ANF infusion were not different between groups on either diet, although NaCl feeding potentiated the natriuresis and diuresis. Under the conditions of the present experiments there was, therefore, no indication that Dahl salt-sensitive rats had a relative inability to respond either to an acute saline load or to exogenous ANF administration.

1. The possible involvement of renal nerves in the diuresis and natriuresis of blood volume expansion was studied in anaesthetized rats. Acute unilateral renal denervation caused increased excretion of fluid, sodium and potassium. 2. Renal blood and plasma flows were elevated without change in filtration rate. Intracortical blood flow distribution was not affected by the denervation. 3. Blood infusion caused diuresis, natriuresis and kaliuresis in both denervated and shamdenervated kidneys, associated with comparable initial increases in filtration and decreases in renal blood flow. No change in flow distribution was found, whether or not renal nerves were intact. 4. Although the magnitude of the excretory response to hypervolaemia was greater in denervated kidneys, the temporal pattern was identical with that of sham-operated kidneys. Our data thus do not show an effect of efferent renal nerve activity on volume natriuresis.

A gyro-TWT is often plagued by absolute instabilities in lower order modes and even in the operating mode itself. These problems will be avoided by performing an experiment in the lowest order mode in cylindrical waveguide ( TE/sub 11/ ) and using a low a beam to excite a wave with large k/sub 11/. A gyroresionant wiggler WM partiany transform the axial velocity of a high quality Pierce beam into transverse velocity. A 100 keV, 5 A, /spl alpha/ = 0.5 bewn will generate 9 GHz rf in a 3 kG magnetic field. Magnetic tapering will be used to enchance the efficiency. The theoretical gam is predicted to be 60 dB with a bandwidth in excess of 20%.

We recently discovered a potent natriuretic factor in cardiac atrial tissue. The present experiments were designed to determine whether hypertension was associated with altered tissue content of this atrial natriuretic factor. Extracts were prepared using fresh atria from spontaneously hypertensive rats of the Okamoto strain and from their Wistar-Kyoto controls. Two groups of anesthetized, normovolemic rats (Sprague-Dawley) were used to measure the renal natriuretic and chloriuretic effect of each type of extract. Results indicate that atrial content of natriuretic factor is reduced in hypertensive rats compared to control animals. We speculate that chronic release of the factor could have depleted atrial stores, and that increased blood levels of atrial natriuretic factor may be involved in the generation and maintenance of hypertension in this model.

An extract of rat heart atria causes a saluresis in bioassay rats. When organic acid secretion in the proximal tubule was blocked by probenecid, the saluretic response to the extract was significantly reduced. Similarly, the natriuretic response to acute hypervolemia was reduced by probenecid administration. The data indicate that the atrial natriuretic factor, like the "loop" diuretic drugs, requires proximal tubular secretion for maximal renal activity. Furthermore, the factor may play a role in the renal response to acute blood volume expansion.