Outcome measures for chronic rhinosinusitis with nasal polyps.

BACKGROUND: With the recent proliferation of novel therapeutics for chronic rhinosinusitis with nasal polyps (CRSwNP), there is an immediate need for comprehensive means to assess CRSwNP disease status as well as to determine treatment efficacy. Outcome measures exist in different forms. Patient-reported outcome measures (PROMs) allow patients to provide direct input about their condition that is not possible to obtain in any other way. Common constructs that are measured using PROMs include quality of life or the burden of disease manifestations (e.g., symptom severity). Outcomes may also include the results of objective diagnostic testing/measurement of clinical signs or measured using psychophysical tests. Biomarkers represent an emerging class of outcome measures for CRSwNP and are chosen to directly reflect the active pathophysiologic processes of CRSwNP in the peripheral blood, sinus/polyp tissues, and sinonasal mucus. METHODS: Narrative review of the literature, identifying and describing outcome measures that may be used in the evaluation of CRSwNP and for assessment of treatment responses. RESULTS: In this review, we identify many different outcome measures for CRSwNP that fall under the categories of PROM, objective test, psychophysical test or biomarker. We describe the history of each - including seminal studies - and demonstrate the formal validation, psychometric performance, and limitations of each. CONCLUSIONS: PROMs, objective tests, psychophysical tests and biomarkers represent different classes of outcome measures that are complementary means of assessing CRSwNP disease status and treatment efficacy. The choice or interpretation of a CRSwNP outcome measure should be undertaken with full knowledge of its formal validation, psychometric performance, and limitations.

Home environment and psychosocial predictors of obesity status among community-residing men and women.

BACKGROUND/OBJECTIVES: Prior research indicates that features of the home environment (for example, televisions, exercise equipment) may be associated with obesity, but no prior study has examined objective features of the home food environment (for example, location of food) in combination with behavioral (for example, food purchasing), psychological (for example, self-efficacy) and social factors among obese adults. This study identified factors associated with obesity status from measures of home environment, food purchasing behavior, eating behavior and psychosocial functioning. SUBJECTS/METHODS: One hundred community-residing obese (mean body mass index (BMI)=36.8, s.e.=0.60) and nonobese (mean BMI=23.7, s.e.=0.57) adults (mean age=42.7, s.e.=1.50; range=20-78 years) completed an observational study with 2-h home interview/assessment and 2-week follow-up evaluation of food purchases and physical activity. Data were analyzed with analysis of variance and logistic regression, controlling for sex. RESULTS: Univariate analyses revealed that homes of obese individuals had less healthy food available than homes of nonobese (F(1,97)=6.49, P=0.012), with food distributed across a greater number of highly visible locations (F(1,96)=6.20, P=0.01). Although there was no group difference in household income or size, obese individuals reported greater food insecurity (F(1,97)=9.70, P<0.001), more reliance on fast food (F(1,97)=7.63, P=0.01) and more long-term food storage capacity in number of refrigerators (F(1,97)=3.79, P=0.05) and freezers (F(1,97)=5.11, P=0.03). Obese individuals also reported greater depressive symptoms (F(1,97)=10.41, P=0.002) and lower ability to control eating in various situations (F(1,97)=20.62, P<0.001). Multiple logistic regression revealed that obesity status was associated with lower self-esteem (odds ratio (OR) 0.58, P=0.011), less healthy food consumption (OR 0.94, P=0.048) and more food available in the home (OR 1.04, P=0.036). CONCLUSIONS: The overall pattern of results reflected that home food environment and psychosocial functioning of obese individuals differed in meaningful ways from that of nonobese individuals. In particular, lower self-esteem may be an important psychosocial aspect of obesity, especially in the context of greater food consumption and food storage/availability.

Lysozyme expression is increased in the sinus mucosa of patients with chronic rhinosinusitis.

BACKGROUND: The presence of fungi and bacteria in the paranasal sinuses may contribute to ongoing inflammation. Lysozyme is an innate immune peptide with bactericidal and fungicidal activity. The expression of lysozyme in chronic rhinosinusitis (CRS) is poorly understood and deficiencies in lysozyme expression may contribute to the ongoing inflammation in CRS patients. OBJECTIVE: Determine lysozyme expression in sinus mucosa of normal and CRS patients with (CRSwNP) and without (CRSsNP) nasal polyps. METHODOLOGY: Sinus mucosa specimens (n = 82) were processed for standard histology, immunohistochemical localisation of lysozyme, immunofluorescent localisation of fungi, and qPCR analysis of lysozyme expression. RESULTS: CRS specimens displayed high-levels of lysozyme immunoreactivity in many of the abundant serous cells. Moderate levels were detected in some epithelial cells and inflammatory cells. Low levels were detected in some subepithelial glands of control specimens. No difference in immunoreactivity was detected between CRSwNP and CRSsNP specimens. Fungal elements were not visualised in any sinus specimen. qPCR analysis demonstrated variable lysozyme expression between individuals. CONCLUSIONS: Lysozyme protein expression is increased in patients with CRS, suggesting a defect in lysozyme expression is not responsible for the microbial colonisation often associated with CRS. The functional activity of lysozyme in CRS patients needs to be further investigated.

Work function modification of PEDOT:PSS by mixing with barium acetylacetonate.

Poly(3,4-ethylenedioxythiophene)polystyrene sulfonate (PEDOT:PSS) is often used as a hole injection and extractor for various organic electronic devices. This study investigated whether it is possible to n-dope PEDOT:PSS with barium acetylacetonate (Ba(acac)2) to change its work function so that to be more suitable for electron injection and extraction. Molecular dynamics simulations suggested that barium cations can interact with the aromatic rings of PEDOT and the negatively charged sulfonate in PSS. At high doping concentration, we found that PEDOT became dedoped and precipitated resulting in a clear solution after filtration. The absence of the absorption peak of PEDOT at 263 nm indicates the removal of PEDOT after filtration. The shift in O 1s to a lower binding energy as seen in X-ray photoelectron spectroscopy suggested that the polystyrene sulfonic acids are being ionized to form barium polystyrene sulfonate (Ba-PSS). By spin-coating the solution on top of indium tin oxide, the work function can be adjusted to as low as 3.6 eV. The ability of such a mixture to inject and extract electrons is demonstrated using 2,7-bis(diphenylphosphoryl)-9,9'-spirobifluorene as an electron transporting layer. We attributed the lowering of the work function as the result of the formation of an interfacial dipole as large as 1.37 eV at the ITO/Ba-PSS interface.

Impact-induced osteochondral fracture in the tibial plateau.

In this study, human tibia plateaus with the meniscus removed were impacted on various regions of the plateau surface via a drop test using a 5mm indenter. Osteochondral blocks containing the failure site were then extracted, chemically fixed, dehydrated, gold-particle coated, and sent for X-ray micro-CT imaging to obtain 3-D image reconstructions of the cartilage and underlying bone. Cartilage failure upon impact appeared to be characteristically brittle in nature. Impacted cartilage from the region not protected by the meniscus showed a relatively large cavernous disruption with microcrack propagation extending radially into the subchondral bone, while impacted cartilage from beneath the meniscus showed less dramatic surface disruption and with no underlying bone failure.

Stable thrombus formation on irradiated microvascular endothelial cells under pulsatile flow: Pre-testing annexin V-thrombin conjugate for treatment of brain arteriovenous malformations.

BACKGROUND: Our goal is to develop a vascular targeting treatment for brain arteriovenous malformations (AVMs). Externalized phosphatidylserine has been established as a potential biomarker on the endothelium of irradiated AVM blood vessels. We hypothesize that phosphatidylserine could be selectively targeted after AVM radiosurgery with a ligand-directed vascular targeting agent to achieve localized thrombosis and rapid occlusion of pathological AVM vessels. OBJECTIVE: The study aim was to establish an in vitro parallel-plate flow chamber to test the efficacy of a pro-thrombotic conjugate targeting phosphatidylserine. METHODS: Conjugate was prepared by Lys-Lys cross-linking of thrombin with the phosphatidylserine-targeting ligand, annexin V. Cerebral microvascular endothelial cells were irradiated (5, 15, and 25 Gy) and after 1 or 3 days assembled in a parallel-plate flow chamber containing whole human blood and conjugate (1.25 or 2.5 µg/mL). Confocal microscopy was used to assess thrombus formation after flow via binding and aggregation of fluorescently-labelled platelets and fibrinogen. RESULTS AND CONCLUSIONS: The annexin V-thrombin conjugate induced rapid thrombosis (fibrin deposition) on irradiated endothelial cells under shear stress in the parallel-plate flow device. Unconjugated, non-targeting thrombin did not induce fibrin deposition. A synergistic interaction between radiation and conjugate dose was observed. Thrombosis was greatest at the highest combined doses of radiation (25 Gy) and conjugate (2.5 µg/mL). The parallel-plate flow system provides a rapid method to pre-test pro-thrombotic vascular targeting agents. These findings validate the translation of the annexin V-thrombin conjugate to pre-clinical studies.

Expression of CD44 in human lung tumors.

CD44 is an integral membrane glycoprotein that functions as a receptor for the extracellular matrix glycan, hyaluronan. Here we report that CD44 is a novel biomarker for non-small cell lung tumors, squamous metaplasia of the lung, and activated type II pneumocytes. We have examined the expression of CD44 in 12 human lung tumor cell lines and 23 fixed, paraffin-embedded lung cancers. CD44 transcription and translation is consistently high among non-small cell tumors (5 of 5 cell lines, 10 of 14 tumors) but rare in small cell tumors (1 of 6 cell lines, 0 of 9 tumors). In normal lung, CD44 was confined to the surface of bronchial basal cells and alveolar macrophages. Squamous metaplasia of the lung showed strong CD44 immunoreactivity. Resting type II pneumocytes were largely CD44 negative but rows of active, surfactant-secreting type II cells had significant amounts of CD44 located on lateral surfaces of adjacent cells. The correlation between CD44 and the non-small cell phenotype was further demonstrated in studies of a cultured small cell lung cancer line induced to exhibit characteristics of a non-small lung cancer by infection with v-Ha-ras. Following ras gen insertion, these cells showed a 40-fold increase in CD44 expression. The CD44 detected in lung cancer cells throughout these studies was predominantly the "standard" rather than the "variant" species. Taken together, these results suggest that CD44 is a protein expressed on non-small cell lung tumors, squamous metaplasia, and activated type II cells. In addition, CD44 in cultured small cell lung cancer cells is transcriptionally activated following differentiation by the ras oncogene. The fact that immunohistochemistry can be used to discriminate among the cell types makes CD44 a valuable new marker for lung neoplasia.

Development of proliferative retinopathy in NIDDM. A follow-up study of American Indians in Oklahoma.

To determine the incidence of and risk factors for the development of proliferative diabetic retinopathy (PDR) in Oklahoma Indians, we performed a cohort follow-up study of 927 Indians who underwent detailed eye examinations between 1972 and 1980. The mean age of participants was 52 yr with a duration of diabetes of 6.9 yr at baseline. At follow-up, 513 (55.3%) were alive, 407 (43.9%) were deceased, and 7 (0.8%) could not be traced. After a mean follow-up time of 12.7 yr, the overall incidence of PDR among those who survived and who underwent follow-up ophthalmic examinations (354 participants) was 18.6%; 45% of those with background retinopathy at baseline developed PDR. Significant independent predictors of PDR, determined by multivariate analysis, were fasting plasma glucose level, duration of diabetes, plasma cholesterol, systolic blood pressure, and therapeutic regimen. A fasting plasma glucose level greater than or equal to 11.1 mM (200 mg/dl) increased the risk of retinopathy to 3.6 times that for a level less than 7.8 mM (140 mg/dl); 74% of those who had background retinopathy and a baseline fasting glucose greater than or equal to 11.1 mM (200 mg/dl) developed PDR. Over half of all participants with plasma cholesterol levels greater than or equal to 7.8 mM (300 mg/dl) developed PDR in the follow-up interval. Elevated systolic blood pressure was a particularly significant risk factor for those with a long duration of diabetes. Proliferative retinopathy poses a serious health threat to Oklahoma Indians and represents a cause of visual impairment that may be preventable by early diagnosis of PDR and intervention with photocoagulation therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Lower-extremity amputation. Incidence, risk factors, and mortality in the Oklahoma Indian Diabetes Study.

Oklahoma Indians with NIDDM (n = 1012) underwent a baseline examination in 1972-1980. The incidence of and risk factors for first lower-extremity amputation were estimated. The mortality rates of amputees using data from 875 patients who had no previous history of amputation and who underwent follow-up examination between 1987 and 1991 are presented. The mean age of the 875 patients was 51.6 +/- 10.8 yr, and the mean duration of diabetes was 6.6 +/- 6.1 yr. After a mean follow-up time of 9.9 +/- 4.3 yr, the incidence rate of first LEA among diabetic Oklahoma Indians was 18.0/1000 person-yr. The incidence rate was two times higher in men than in women. In both sexes, significant risk factors (P < 0.05) were retinopathy and duration of diabetes. Fasting plasma glucose, use of insulin, and systolic blood pressure were significant for men only. For women, plasma cholesterol and diastolic blood pressure were additional risk factors. Compared with the mortality rate of 33.5/1000 person-yr among nonamputees, the rate among amputees was 55.5/1000 person-yr. The 5-yr survival rate after first amputation was 40.4%. For the amputees, the most common causes of death were diabetes (37.3%), cardiovascular disease (29.1%), and renal disease (7.3%). The incidence and mortality rates in diabetic Oklahoma Indians were higher than those reported in Pima Indians and other diabetic populations. To lower the incidence of lower-extremity amputation in this high-risk population, preventive action through education, foot care programs, and early detection of lesions must be intensified.

Incidence of renal failure in NIDDM. The Oklahoma Indian Diabetes Study.

The incidence of and risk factors for renal failure were determined in 912 Oklahoma Indians with non-insulin-dependent diabetes mellitus in a follow-up study conducted between 1987 and 1990. The incidence rate was 15.7/1,000 person-years after an average follow-up time of 10.2 years. Among those who had no qualitatively positive proteinuria at baseline, the incidence of renal failure was 10.3/1,000 person-years compared with 19.3- and 56.2/1,000 person-years, respectively, in those with slight and heavy proteinuria at baseline. Fasting plasma glucose (FPG) > or = 11.1 mM (200 mg/dl) increased the risk of renal failure to 2.9-fold (95% confidence interval [CI] = 1.9-4.6) higher than a level < 7.8 mM (140 mg/dl), and twofold (95% CI = 1.4-3.1) higher than a level between 7.8 (140 mg/dl) and 11.1 mM (200 mg/dl). The hypertensive patient had twice the incidence of renal failure than the normotensive subject (rate ratio = 2.1, 95% CI = 1.4-3.0). Patients with a lower blood pressure under antihypertensive medication had a lower incidence of renal failure than those whose hypertension remained uncontrolled with or without use of medication. Significant independent risk factors for renal failure, identified from Cox's proportional hazards model, were duration of diabetes, FPG, age, hypertension, and insulin use (P < 0.05). In patients without proteinuria at baseline, FPG and hypertension were significant predictors of renal failure as identified by multivariate analyses, whereas in patients who had proteinuria at baseline, insulin use was significant. Thus, hyperglycemic and hypertension control are suggested strongly for diabetic Oklahoma Indians as potential strategies to prevent the development of renal failure.

Diabetic retinopathy in Oklahoma Indians with NIDDM. Incidence and risk factors.

OBJECTIVE: To determine the incidence rates and risk factors for development of diabetic retinopathy in Oklahoma Indians. RESEARCH DESIGN AND METHODS: Cohort follow-up study with baseline examination between 1972 and 1980 and follow-up examination between 1987 and 1991. Mean +/- SD follow-up time was 12.8 +/- 1.7 yr. Eleven Indian Health Service facilities (clinics and hospitals) in Oklahoma participated in the study. Study participants were a quasirandom sample of 1012 American Indians (379 men, 633 women) in Oklahoma with NIDDM, 927 of whom received a detailed eye examination at baseline. The mean age of participants was 52 yr with a duration of diabetes of 6.9 yr at baseline. The average quantum of Indian blood was 92% (77% full blood). At follow-up, 515 (55.6%) were alive, 408 (44.0%) were deceased, and 4 (0.4%) could not be traced. Of the living participants, 380 (73.8%) underwent an ophthalmoscopic examination. RESULTS: The incidence of retinopathy among the participants who were free of disease at baseline and who survived the follow-up interval was 72.3%. By multivariate analysis, significant independent predictors of retinopathy recorded at baseline were FPG level, therapeutic regimen, systolic blood pressure, and duration of diabetes. FPG levels > or = 11.1 mM (200 mg/dl) increased the risk of retinopathy 1.7 times that for levels < 7.8 mM (140 mg/dl). Insulin use was associated with a 20% greater incidence. Hypertension was a particularly significant risk factor for those with lower FPG levels. CONCLUSIONS: Given that NIDDM is reaching epidemic proportions in Oklahoma Indians and that most may be afflicted with retinopathy, frequent ophthalmological examinations are clearly indicated for this high-risk population. The role of intervention, namely glycemic and hypertensive control, deserves further study.

High-output cardiac failure: an unusual manifestation of intravenous leiomyomatosis.

Intravenous leiomyomatosis is a rare uterine neoplasm characterized by nodular or wormlike masses of histologically benign smooth muscle growing within myometrial veins and extending variable distances into the veins of contiguous organs and major pelvic veins. In some cases, there has been extension into the gonadal or iliac veins to the vena cava and right atrium, causing symptoms of congestive heart failure and an eventual fatal outcome. We present a report of the first case in which high-output cardiac failure was caused by the development of arteriovenous shunting within the intravenous component of the tumor that involved the pelvic organs and retroperitoneal and gonadal veins but not the vena cava. Treatment by total abdominal hysterectomy, bilateral oopherectomy, and tumor mass excision from the retroperitoneum was successful.

Atheromas of the thoracic aorta: A comparison of transesophageal echocardiography and breath-hold gadolinium-enhanced 3-dimensional magnetic resonance angiography.

Transesophageal echocardiography (TEE) has been the procedure of choice for identifying thoracic aortic atheromas. All patients over a 2-year period who underwent both TEE and magnetic resonance angiography of the thoracic aorta within 1 month were identified. The largest plaque in 3 aortic segments (ascending, arch, and descending) was measured. Thirty patients (16 men; 66.8 +/- 12.9 years) were studied. The mean size of the atheromas in the arch was larger as measured by TEE compared with magnetic resonance angiography (3.4 vs 1.4 mm, P =.01). However, the mean atheroma size was similar in the ascending aorta (1.9 vs 1.3 mm, P =.5) and descending aorta (3.9 vs 3.5 mm, P =.66). Of 24 aortic segments with plaques measuring >/=5 mm (with high embolic risk), 22 (92%) were seen on TEE and only 13 (54%) on magnetic resonance angiography (P =. 003). In conclusion, although both techniques are complementary, TEE does identify more high-risk plaques.

Comparison of the effects of ascorbyl palmitate and L-ascorbic acid on paracetamol-induced hepatotoxicity in the mouse.

The effects of ascorbyl palmitate (ASCP) and free L-ascorbic acid (LAA) on the hepatotoxicity of paracetamol (acetaminophen) and the in vivo covalent binding of reactive paracetamol metabolites to hepatic proteins has been studied in male MF1 mice. The oral administration of [3H(G)]paracetamol (600 mg/kg) resulted in covalent binding to hepatic proteins, a depletion of hepatic non-protein sulphydryl (NPS) groups after 2 h, and a marked elevation of plasma alanine aminotransferase (ALAT) activity after 24 h. The co-administration of paracetamol and ASCP (1412 mg/kg, equivalent to 600 mg/kg free LAA), but not paracetamol and LAA (600 mg/kg), significantly reduced covalent binding of paracetamol metabolites at 2 and 4 h after treatment. In addition ASCP, but not LAA, significantly reduced the depletion of NPS groups and the elevation of plasma ALAT activity. ASCP also completely prevented the 35% mortality observed at 24 h in paracetamol treated mice. These results demonstrate that ASCP, but not LAA, when co-administered orally with the analgesic is an effective inhibitor of paracetamol-induced hepatotoxicity in the mouse. The mechanism by which ASCP prevents liver injury appears to involve destruction of reactive paracetamol metabolites which is associated with a sparing action on hepatic reduced glutathione levels.

Complications of laparoscopic cholecystectomy.

Laparoscopic cholecystectomy is a safe and effective treatment of cholelithiasis in experienced hands. Mortality is rare. The Southern Surgeons Club data and several other recent large series indicate that major complications occur in less than 3% of patients. The most significant common complication is injury to the bile duct, for which the greatest risk factor is inexperience. Major biliary injury usually requires reoperations. Roux-en-Y hepaticojejunostomies, often multiple, are usually necessary for repair. The popularity of this technique continues, and further efforts should be focused on elimination of the learning curve for major biliary injury. If injuries do occur, they should be recognized early, and patients should be referred to centers experienced in their treatment.

Statistical factorial analysis on the material property sensitivity of the mechanical responses of the C4-C6 under compression, anterior and posterior shear.

A systematic approach using factorial analysis was conducted on the C4-C6 finite element model to analyse the influence of six spinal components (cortical shell, vertebral body, posterior elements, endplate, disc annulus and disc nucleus) on the internal stresses and external biomechanical responses under compression, anterior and posterior shear. Results indicated that the material properties variation of the disc annulus has a significant influence on both the external biomechanical responses and internal stress of the disc annulus and its neighboring hard bones. The study reveals for the first time, the significant influence of the cancellous bone under compression, while variation in the cortical shell modulus has a high influence under anterior and posterior shear. The study also reveals that the effects of interaction between two main components are insignificant.

An optical method for the determination of platelet count in platelet samples contaminated with red blood cells.

We present a simple photometric method to determine the total concentration of platelets present in a sample independently of red blood cell concentration. Standard optical density curves for platelet samples ranging in concentration from 0 to 1.5 x 10(9) cells/ml and contaminated with red blood cells ranging in concentration from 0 to 0.03 x 10(9) cells/ml are determined. A study of the absorbance spectra of red blood cells and platelets suggests that by calculating the absorbance difference between two wavelengths, an estimate of red blood cell concentration can be made. Then, in the second step of this two-step method, the individual absorbance measurements at the two wavelengths are matched to the standard values determined previously to derive an estimate of platelet concentration. In a trial of 62 unknown platelet samples contaminated with red blood cells, the standard deviation for the error in platelet count was 0.16 x 10(9) cells/ml with a mean difference of 0.011 x 10(9) platelets/ml. We conclude that our method may be useful in laboratories not equipped with electronic cell counters as well as in applications such as the development of noninvasive measurements of platelet concentration in platelet transfusion packs.

Residential randon exposure and lung cancer risk in Misasa, Japan: a case-control study.

In order to investigate an association between residential radon exposure and risk of lung cancer, a case-control study was conducted in Misasa Town, Tottori Prefecture, Japan. The case series consisted of 28 people who had died of lung cancer in the years 1976-96 and 36 controls chosen randomly from the residents in 1976, matched by sex and year of birth. Individual residential radon concentrations were measured for 1 year with alpha track detectors. The average radon concentration was 46 Bq/m3 for cases and 51 Bq/m3 for controls. Compared to the level of 24 or less Bq/m3, the adjusted odds ratios of lung cancer associated with radon levels of 25-49, 50-99 and 100 or more Bq/m3, were 1.13 (95% confidence interval; 0.29-4.40), 1.23 (0.16-9.39) and 0.25 (0.03-2.33), respectively. None of the estimates showed statistical significance, due to small sample size. When the subjects were limited to only include residents of more than 30 years, the estimates did not change substantially. This study did not find that the risk pattern of lung cancer, possibly associated with residential radon exposure, in Misasa Town differed from patterns observed in other countries.

Volumetric MR imaging of the liver and applications.

Recent improvements in MR technology have enabled the development of volumetric three-dimensional (3D) imaging methods for fat-suppressed T1-weighted images of the entire upper abdomen with pixel sizes of approximately 2 mm in all dimensions and with acquisition times of less than 25 seconds for breath-hold imaging. When performed with a timing scheme, dynamic contrast-enhanced volumetric imaging of the liver can be performed with selective imaging during the arterial phase and portal venous phase of enhancement. The volumetric data sets can be reconstructed in any oblique plane, enabling improved detection, localization, and characterization of small liver lesions. The combination of high-resolution isotropic pixels and accurate timing also permits angiographic reconstructions of the 3D images, producing MR angiography and venography that can be useful in therapeutic planning, such as for catheter-based interventions or surgical resections or transplantation. Additionally, with use of a hepatobiliary contrast agent such as mangafodipir, T1-weighted volumetric MR cholangiography can be performed in patients with nonobstructed systems for depiction of intrahepatic biliary anatomy.

Automatic segmentation of magnetic resonance images of the trans-femoral residual limb.

An automatic algorithm for the extraction of the skin and bone boundaries from axial magnetic resonance images of the residual limb of trans-femoral amputees is presented. The method makes use of K-means clustering and mathematical morphology. Statistical analysis of the results indicates that the computer-generated boundaries compare favourably to those drawn by human observers. The boundaries may be used in biomechanical modelling of the interaction between the residual limb and the prosthetic socket. The limb/socket interface determines the quality of prosthetic fit, therefore knowledge of this interface is important for the improvement of socket design in order to achieve patient comfort and mobility.