Automated Radiographic Measurements of Knee Osteoarthritis.

OBJECTIVE: Herewith, we report the development of Orthopedic Digital Image Analysis (ODIA) software that is developed to obtain quantitative measurements of knee osteoarthritis (OA) radiographs automatically. Manual segmentation and measurement of OA parameters currently hamper large-cohort analyses, and therefore, automated and reproducible methods are a valuable addition in OA research. This study aims to test the automated ODIA measurements and compare them with available manual Knee Imaging Digital Analysis (KIDA) measurements as comparison. DESIGN: This study included data from the CHECK (Cohort Hip and Cohort Knee) initiative, a prospective multicentre cohort study in the Netherlands with 1,002 participants. Knee radiographs obtained at baseline of the CHECK cohort were included and mean medial/lateral joint space width (JSW), minimal JSW, joint line convergence angle (JLCA), eminence heights, and subchondral bone intensities were compared between ODIA and KIDA. RESULTS: Of the potential 2,004 radiographs, 1,743 were included for analyses. Poor intraclass correlation coefficients (ICCs) were reported for the JLCA (0.422) and minimal JSW (0.299). The mean medial and lateral JSW, eminence height, and subchondral bone intensities reported a moderate to good ICC (0.7 or higher). Discrepancies in JLCA and minimal JSW between the 2 methods were mostly a problem in the lateral tibia plateau. CONCLUSIONS: The current ODIA tool provides important measurements of OA parameters in an automated manner from standard radiographs of the knee. Given the automated and computerized methodology that has very high reproducibility, ODIA is suitable for large epidemiological cohorts with various follow-up time points to investigate structural progression, such as CHECK or the Osteoarthritis Initiative (OAI).

Type 2 diabetes is associated with higher trabecular bone density but lower cortical bone density: the Vietnam Osteoporosis Study.

It is not clear why type 2 diabetes (T2D) has an increased risk of fracture despite higher areal bone mineral density. This study showed that compared with controls, T2D patients had higher trabecular bone density but lower cortical bone density, resulting in a lower bone strength. INTRODUCTION: To define the association between type 2 diabetes and bone architecture and measures of bone strength. METHODS: The study was part of the Vietnam Osteoporosis Study, in which 1115 women and 614 men aged ≥ 30 were randomly recruited from Ho Chi Minh City. HbA1c levels were measured with analyzers ADAMS™ A1c HA-8160 (Arkray, Kyoto, Japan). The diagnosis of T2D was made if HbA1c was ≥ 6.5%. Trabecular and cortical volumetric bone density (vBMD) was measured in the forearm and leg by a pQCT XCT2000 (Stratec, Germany). Polar stress strain index (pSSI) was derived from the pQCT measurements. Difference in bone parameters between T2D and non-diabetic individuals was assessed by the number of standard deviations (effect size [ES]) by the propensity score analysis. RESULTS: The prevalence of T2D was ~ 8%. The results of propensity score matching for age, sex, and body mass index in 137 pairs of diabetic and non-diabetic individuals showed that T2D patients had significantly higher distal radius trabecular vBMD (ES 0.26; 95% CI, 0.02 to 0.50), but lower cortical vBMD (ES - 0.22; - 0.46 to 0.00) and reduced pSSI (ES - 0.23; - 0.47 to - 0.02) compared with non-diabetic individuals. Multiple linear regression analysis based on the entire sample confirmed the results of the propensity score analysis. CONCLUSION: Compared with non-diabetic individuals, patients with T2D have greater trabecular but lower cortical vBMD which leads to lower bone strength.

64×64 pixel smart sensor array for laser Doppler blood flow imaging.

What is believed to be the first fully integrated two-dimensional complementary metal oxide semiconductor (CMOS) imaging array for laser Doppler blood flow imaging is demonstrated. The sensor has 64×64 pixels and includes both analog and digital on-chip processing electronics. This offers several potential advantages over commercial sensors as the processing is tailored to the signals of interest and the data bottleneck that exists between the sensor and processing electronics is overcome. To obtain a space efficient design over 64×64 pixels means that standard processing electronics used off-chip cannot be implemented. Images of both simulated blood flow responses and a blood flow occlusion test demonstrate the capability.

Heat stress induces epithelial plasticity and cell migration independent of heat shock factor 1.

Current cancer therapies including cytotoxic chemotherapy, radiation and hyperthermic therapy induce acute proteotoxic stress in tumour cells. A major challenge to cancer therapeutic efficacy is the recurrence of therapy-resistant tumours and how to overcome their emergence. The current study examines the concept that tumour cell exposure to acute proteotoxic stress results in the acquisition of a more advanced and aggressive cancer cell phenotype. Specifically, we determined whether heat stress resulted in an epithelial-to-mesenchymal transition (EMT) and/or the enhancement of cell migration, components of an advanced and therapeutically resistant cancer phenotype. We identified that heat stress enhanced cell migration in both the lung A549, and breast MDA-MB-468 human adenocarcinoma cell lines, with A549 cells also undergoing a partial EMT. Moreover, in an in vivo model of thermally ablated liver metastases of the mouse colorectal MoCR cell line, immunohistological analysis of classical EMT markers demonstrated a shift to a more mesenchymal phenotype in the surviving tumour fraction, further demonstrating that thermal stress can induce epithelial plasticity. To identify a mechanism by which thermal stress modulates epithelial plasticity, we examined whether the major transcriptional regulator of the heat shock response, heat shock factor 1 (HSF1), was a required component. Knockdown of HSF1 in the A549 model did not prevent the associated morphological changes or enhanced migratory profile of heat stressed cells. Therefore, this study provides evidence that heat stress significantly impacts upon cancer cell epithelial plasticity and the migratory phenotype independent of HSF1. These findings further our understanding of novel biological downstream effects of heat stress and their potential independence from the classical heat shock pathway.

A field-programmable gate array based system for high frame rate laser Doppler blood flow imaging.

This paper presents a general embedded processing system implemented in a field-programmable gate array providing high frame rate and high accuracy for a laser Doppler blood flow imaging system. The proposed system can achieve a basic frame rate of flow images at 1 frame/second for 256 x 256 images with 1024 fast Fourier transform (FFT) points used in the processing algorithm. Mixed fixed-floating point calculations are utilized to achieve high accuracy but with a reasonable resource usage. The implementation has a root mean square deviation of the relative difference in flow values below 0.1% when compared with a double-precision floating point implementation. The system can contain from one or more processing units to obtain the required frame rate and accuracy. The performance of the system is significantly higher than other methods reported to date. Furthermore, a dedicated field-programmable gate array (FPGA) board has been designed to test the proposed processing system. The board is linked with a laser line scanning system, which uses a 64 x 1 photodetector array. Test results with various operating parameters show that the performance of the new system is better, in terms of noise and imaging speed, than has been previously achieved.

Enhanced Kerr nonlinearity in sub-wavelength diameter As(2)Se(3) chalcogenide fiber tapers.

We experimentally demonstrate enhanced Kerr nonlinear effects in highly nonlinear As(2)Se(3) chalcogenide fiber tapered down to sub-wavelength waist diameter of 1.2 mum. Based on self phase modulation measurements, we infer an enhanced nonlinearity of 68 W(-1)m(-1). This is 62,000 times larger than in standard silica singlemode fiber, owing to the 500 times larger n(2) and almost 125 times smaller effective mode area. We also consider the potential to exploit the modified dispersion in these tapers for ultra-low threshold supercontinuum generation.

Using cartilage to repair bone: an alternative approach in tissue engineering.

Materials and techniques currently used for bone replacement/repair conform to the current paradigm, relying on bone or bone products to produce bone or induce bone formation. Yet, nature forms and heals most of the skeleton by ossification of a cartilaginous model. In this study, we cultured aggregates of E10.5 or E12 mouse embryonic limb cells in the bioreactor for 3 weeks, determined the stages of cartilage differentiation attained, and assessed the ossification and bone healing potential of the spheroids by implantation adjacent to, or directly in, a skull defect. Cultured spheroids had large cartilaginous areas, sometimes with cellular arrangements characteristic of growth plate zones. Aggregates implanted for 2 weeks adjacent to a defect mineralized and ossified (histology, micro-CT). Defects with implants had a central mass of differentiated and differentiating bone, with osteoclast activity, filling the defect. Controls had considerable remodeling on the bone edges demarcating the still present defect. This study shows that cartilage, grown in the bioreactor for 3 weeks, ossified when implanted adjacent to a bone defect, and when implanted directly in a defect, contributed to its healing. Our ability to grow differentiated bone-forming cartilage for implantation is an alternative approach in the field of bone repair.

Percutaneous nephrolithotomy in the management of complex upper urinary tract calculi: the Singapore General Hospital experience.

INTRODUCTION AND OBJECTIVES: Presently, percutaneous nephrolithotomy (PCNL) is a well-established and effective method of treating upper urinary tract stones at our institution. The aim of this paper was to evaluate a single surgeon's four-year experience of PCNL in the Singapore General Hospital. MATERIALS AND METHODS: Between January 1996 and December 2000, 300 PCNLs were performed on 280 renal units. The mean age was 53.7 years. PCNL was performed on 57 complete staghorn calculi (20.4%), 83 partial staghorn calculi (29.6%), 66 large pelvic calculi (23.6%), 60 impacted uretero-pelvic junction (UPJ) and upper ureteric stones (21.4%) that failed extracorporeal shock wave lithotripsy (ESWL) and 14 symptomatic lower pole calculi (5%). RESULTS: The stone-free rate on discharge was 88.2% (n = 247). At 3 months and 1-year post PCNL, the stone-free rate was 91.1% (n = 255) and 95.7% (n = 268), respectively. The average postoperative stay was 4.5 days. Complications included 1 urosepsis post-PCNL (0.4%) and 2 arterio-venous fistulae (0.7%). Only 1 patient (0.4%) required blood transfusion. Thirty-four patients (12.1%) required ESWL and 4 needed ureteroscopy (1.3%). CONCLUSION: In experienced hands, the use of PCNL for upper urinary tract calculi is safe and effective.

Off-loading the diabetic foot wound: a randomized clinical trial.

OBJECTIVE: To compare the effectiveness of total-contact casts (TCCs), removable cast walkers (RCWs), and half-shoes to heal neuropathic foot ulcerations in individuals with diabetes. RESEARCH DESIGN AND METHODS: In this prospective clinical trial, 63 patients with superficial noninfected, nonischemic diabetic plantar foot ulcers were randomized to one of three off-loading modalities: TCC, half-shoe, or RCW. Outcomes were assessed at wound healing or at 12 weeks, whichever came first. Primary outcome measures included proportion of complete wound healing at 12 weeks and activity (defined as steps per day). RESULTS: The proportions of healing for patients treated with TCC, RCW, and half-shoe were 89.5, 65.0, and 58.3%, respectively. A significantly higher proportion of patients were healed by 12 weeks in the TCC group when compared with the two other modalities (89.5 vs. 61.4%, P = 0.026, odds ratio 5.4, 95% CI 1.1-26.1). There was also a significant difference in survival distribution (time to healing) between patients treated with a TCC and both an RCW (P = 0.033) and half-shoe (P = 0.012). Patients were significantly less active in the TCC (600.1 +/- 320.0 daily steps) compared with the half-shoe (1,461.8 +/- 1,452.3 daily steps, P = 0.04). There was no significant difference in the average number of steps between the TCC and the RCW (767.6 +/- 563.3 daily steps, P = 0.67) or the RCW and the half-shoe (P = 0.15). CONCLUSIONS: The TCC seems to heal a higher proportion of wounds in a shorter amount of time than two other widely used off-loading modalities, the RCW and the half-shoe.

The effects of ulcer size and site, patient's age, sex and type and duration of diabetes on the outcome of diabetic foot ulcers.

AIMS: The outcome of foot ulcers is affected by wound depth, infection, ischaemia and glycaemic control. The aim of this study was to determine the effects of ulcer size, site, patient's age, sex and type and duration of diabetes on the outcome of diabetic foot ulcers. METHODS: Diabetic patients with new foot ulcers presenting during a 12-month period had demographics and ulcer characteristics recorded at presentation. Ulcers were followed-up until an outcome was noted. RESULTS: One hundred and ninety-four patients (77% males) with a mean (+/- SD) age and duration of diabetes of 56.6 +/- 12.6 and 15.4 +/- 9.9 years, respectively, were included in the study. The majority of ulcers were neuropathic (67.0%) and present on the forefoot (77.8%) with a median (interquartile range) area of 1.5 (0.6-4.0) cm2. Amputations were performed for 15% of ulcers; 65% healed; 16% remained unhealed and 4% of patients died. The median (95% confidence interval) time to healing was 10 (8.8-11.6) weeks. Ulcer area at presentation was greater in the amputation group compared to healed ulcers (3.9 vs. 1.2 cm2, P < 0.0001). Ulcer area correlated with healing time (rs = 0.27, P < 0.0001) and predicted healing (P = 0.04). Patient's age, sex, duration/type of diabetes, and ulcer site had no effect on outcome. CONCLUSIONS: Ulcer area, a measure of ulcer size, predicts the outcome of foot ulcers. Its inclusion into a diabetic wound classification system will make that system a better predictor of outcome.

A comparison of two diabetic foot ulcer classification systems: the Wagner and the University of Texas wound classification systems.

OBJECTIVE: In this study the following two ulcer classification systems were applied to new foot ulcers to compare them as predictors of outcome: the Wagner (grade) and the University of Texas (LT) (grade and stage) wound classification systems. RESEARCH DESIGN AND METHODS: Ulcer size, appearance, clinical evidence of infection, ischemia, and neuropathy at presentation were recorded, and patients were followed up until healing or for 6 months. RESULTS: Of 194 patients with new foot ulcers, 67.0% were neuropathic, 26.3% were neuroischemic, 1.0% were ischemic, and 5.7% had no identified underlying factors. Median (interquartile range [IQR]) ulcer size at presentation was 1.5 cm2 (0.6-4.0). Lower-limb amputations were performed for 15% of ulcers, whereas 65% healed [median (IQR) healing time 5 (3-10) weeks] and 16% were not healed at study termination; 4% of patients died. Wagner grade (P < 0.0001), and UT grade (P < 0.0001) and stage (P < 0.001) showed positive trends with increased number of amputations. For UT stage, the risk of amputation increased with infection both alone (odds ratio [OR] = 11.1, P < 0.0001) and in combination with ischemia (OR = 14.7, P < 0.0001), but not significantly with ischemia alone (OR = 4.6, P = 0.09). Healing times were not significantly different for each grade of the Wagner (P = 0.1) or the UT system (P = 0.07), but there was a significant stepwise increase in healing time with each stage of the UT system (P < 0.05), and stage predicted healing (P < 0.05). CONCLUSIONS: Increasing stage, regardless of grade, is associated with increased risk of amputation and prolonged ulcer healing time. The UT system's inclusion of stage makes it a better predictor of outcome.

Improvement in healing with aggressive edema reduction after debridement of foot infection in persons with diabetes.

BACKGROUND: Infected foot wounds in patients with diabetes are the most common reason for diabetes-related hospital admission in the United States. Nonhealing foot wounds are the major precipitant of lower-extremity amputation in the diabetic population. HYPOTHESIS: The null hypothesis was that there would be no difference in proportion of healing with or without use of a foot-level mechanical compression device. DESIGN: Twelve-week, double-blind, randomized, controlled trial. SETTING: A university teaching hospital and related clinics. PATIENTS: One hundred fifteen patients with diabetes, 74% male, with foot infections requiring incision and debridement. INTERVENTION: All patients received either a functioning or placebo (nonfunctioning) foot compression device (Kinetic Concepts Inc, San Antonio, Tex). Patients and investigators were blinded to the functionality of the device. PRIMARY OUTCOME MEASURE: Proportion of wound healing in each group. RESULTS: There was a significantly higher proportion of healing in the active group than in the placebo group (39 [75%] of 52 patients vs 23 [51%] of 45; chi(2) = 6.0; P<.02; odds ratio, 2.9; 95% confidence interval, 1. 2-6.8). In the placebo group, there was no difference in proportion of healing between those identified as compliant (>/=50 hours of use per week) vs noncompliant (P =.10). In patients receiving active units, more patients in the compliant subgroup experienced wound healing (P<.03). When compared as a whole, there was a significant trend toward an increasing proportion of healing from the placebo-noncompliant to the placebo-compliant to the active-noncompliant to the active-compliant groups (chi(2)(trend) = 8.3; P<.005). CONCLUSIONS: Edema reduction achieved in this study by way of a pump and wrap system may increase the proportion of wound healing in patients after debridement of foot infections in patients with diabetes. Furthermore, the data suggest a potential association between increased compliance with use of the device and an increased trend toward wound healing. Arch Surg. 2000;135:1405-1409

Incidence of childhood cancer in Ho Chi Minh City, Vietnam, 1995-97.

Incidence rates of childhood cancer for the city of Ho Chi Minh are presented for the first time. For the 3-year period 1995-97, a total of 302 cancer cases were registered in children under 15 years of age, with a male to female ratio of 1.1. The overall crude rate was 78.8 and the age-standardised incidence rate was 88.4 per million person-years, which was low in comparison with other countries in eastern Asia and with the predominantly white population of Australia. Leukaemia (principally acute lymphocytic), brain tumours and lymphomas were the most common childhood neoplasms, which is consistent with the pattern observed in other registries of the region. The rate of retinoblastoma was higher than in the other regional registries. On the other hand, no cases of hepatocellular carcinoma were registered.

Factors associated with bone regrowth following diabetes-related partial amputation of the foot.

BACKGROUND: The formation of hypertrophic bone after partial resection of metatarsal bone has the potential to cause abnormal foci of high pressure in people who have diabetes mellitus; this may increase the risk of reulceration and reamputation. However, we are not aware of previous studies evaluating the risk factors for this entity. METHODS: The records of ninety-two adults (mean age, 54+/-10.1 years; range, thirty to seventy-four years) with diabetes who had had an isolated partial amputation of a ray were abstracted. Repeat radiographs were made for all of these subjects at a mean of 22+/-6.1 months (range, thirteen to thirty-five months) after the initial procedure. The formation of hypertrophic bone was defined as more than three millimeters of regrowth. RESULTS: A total of forty-one (45 percent) of the subjects had formation of hypertrophic bone at the time of radiographic analysis after isolated partial amputation of a ray. On multivariate analysis, the factors that were significantly associated with this regrowth of bone were male gender (88 percent [thirty-six] of the forty-one patients who had bone regrowth were male compared with 51 percent [twenty-six] of the fifty-one patients who did not have bone regrowth; p<0.01, odds ratio = 5.7, 95 percent confidence interval = 1.8 to 18.9), the use of manual bone-cutting instruments (used in 56 percent [twenty-three] of the forty-one patients who had bone regrowth compared with 16 percent [eight] of the fifty-one who did not; p<0.01, odds ratio = 4.7, 95 percent confidence interval = 1.6 to 13.8), and a resection made distal to the surgical neck of the metatarsal (used in 34 percent [fourteen] of the forty-one patients who had bone regrowth compared with 12 percent [six] of the fifty-one who did not; p<0.03, odds ratio = 4.5, 95 percent confidence interval = 1.2 to 16.9). The patients who had regrowth of bone were approximately eight times more likely to have reulceration at the site of the amputation than were those who did not have regrowth (24 percent [ten] of the patients with regrowth had reulceration compared with 4 percent [two] of the patients without regrowth; p<0.01, chi square = 8.4, odds ratio = 7.9, 95 percent confidence interval = 1.6 to 38.5). CONCLUSIONS: Overgrowth of the bone of a transected metatarsal predisposes patients to ulceration. Male gender, the use of manual bone-cutting instruments, and metaphyseal amputation may be associated with long-term regrowth of bone following isolated partial amputation of a ray. The use of power instruments during these procedures may lead to a lower prevalence of this reaction, thereby potentially reducing the risk of ulceration, infection, and reamputation.

Role of photoperiod and the pineal gland in T cell-dependent humoral immune reactivity in the Siberian hamster.

The present study tested the hypothesis that antibody production in response to xenoantigen is modulated by daylength and dependent upon the pineal gland. Alter injection of sheep erythrocytes (SRBC), serum immunoglobulin (Ig) concentrations were 5-fold lower in hamsters in short versus long days. Pinealectomy (Pinx) abolished the nocturnal melatonin rhythm, blocked short-day-mediated testis regression, and eliminated the short-day reduction in Ig production after SRBC treatment. Antibody titers in response to SRBC were equivalently augmented in short-day Pinx and long-day sham hamsters. The results indicate that photoperiodic effects on T cell-dependent humoral immunity are dependent upon the pineal gland. These findings raise the possibility that day length-associated changes in some immune system functions are mediated by the pineal melatonin rhythm.

Cancer incidence in Ho Chi Minh City, Viet Nam, 1995-1996.

The results from the population-based cancer registry for the city of Ho Chi Minh in 1995-1996 represent the first information on the incidence of cancer in southern Viet Nam. A total of 4,080 cancer cases in males and 4,338 in females were registered, corresponding to age-standardized incidence rates (ASRs) of 130.9 per 100,000 in men and 100.7 per 100,000 in women. As elsewhere in South East Asia, the principal cancer of men was liver cancer (ASR 25.3), with moderately high rates of lung cancer (ASR 24.6) and stomach cancer (ASR 16.5); cancer of the penis, reportedly very common in early case series from Viet Nam, is now rarely seen. In women, cervical cancer was the dominant malignancy (ASR 26.0) followed by breast cancer (ASR 12.2) and stomach cancer (ASR 7.5). Although there may be some under-registration in these early years of operation, the recorded rates of cervical cancer and liver cancer are already high and suggest that southern Viet Nam would benefit from an effective cervical cancer screening programme, as well as efforts to interrupt the transmission of hepatitis B virus to reduce liver cancer incidence and effective anti-smoking programs.

Zenker's diverticulum.

Symptomatic Zenker's diverticula are usually treated with diverticulectomy and myotomy. Other, more conservative open procedures consist of diverticulopexy, imbrication, and myotomy alone. These more conservative procedures do not result in a breach of esophageal mucosa and should have more rapid postoperative recovery. We performed a retrospective chart review of all open surgical procedures performed at the Marshfield Clinic and St. Joseph's Hospital between 1975 and 1996. Using Wilcoxon's rank sum test, the conservative procedures were compared with the standard diverticulectomy for duration of hospitalization and length of time to resumption of oral intake. Fifty-nine patients are reported. Statistically significant differences between the surgery groups were found for hospitalization (P < 0.001) and days to resumption of oral intake (P < 0.001). Conservative open surgical procedures for repair of Zenker's diverticula result in decreased hospitalization and earlier resumption of oral diet compared with diverticulectomy.