Patients' perceived walking abilities, daily-life gait behavior and gait quality before and 3 months after total knee arthroplasty.

INTRODUCTION: Functional outcome and patients' daily-life activities after total knee arthroplasty are becoming more important with a younger and more active patient population. In addition to patient-reported outcome measures (PROMs), trunk-based accelerometry has shown to be a promising method for evaluating gait function after total knee arthroplasty. The aim of this study was to evaluate daily-life perceived walking abilities, gait behavior and gait quality before and 3 months after total knee arthroplasty, using PROMs and trunk-based accelerometry. MATERIALS AND METHODS: A cohort of 38 patients completed questionnaires including the Oxford Knee Score and modified Gait Efficacy Scale before and 3 months after primary unilateral total knee arthroplasty. At both time points, they wore a tri-axial accelerometer at the lower back for seven consecutive days and nights. Gait behavior was calculated using gait quantity and walking speed, and multiple gait quality parameters were calculated. RESULTS: Significant improvements were seen after 3 months in the Oxford Knee Score [median (interquartile range) 29 (10) vs 39 (8), p < 0.001] and modified Gait Efficacy Scale [median (interquartile range) 67 (24) vs 79 (25), p = 0.001]. No significant changes were observed in gait behavior (quantity and speed) or gait quality variables. CONCLUSIONS: In contrast to the significant improvements in patients' perception of their walking abilities and PROMs, patients did not show improvements in gait behavior and gait quality. This implies that after 3 months patients' perceived functional abilities after total knee arthroplasty do not necessarily represent their actual daily-life quantity and quality of gait, and that more focus is needed on postoperative rehabilitation to improve gait and functional behavior.

Functional Outcomes of Arthroscopic Partial Meniscectomy Versus Physical Therapy for Degenerative Meniscal Tears Using a Patient-Specific Score: A Randomized Controlled Trial.

BACKGROUND: It is unknown whether the treatment effects of partial meniscectomy and physical therapy differ when focusing on activities most valued by patients with degenerative meniscal tears. PURPOSE: To compare partial meniscectomy with physical therapy in patients with a degenerative meniscal tear, focusing on patients' most important functional limitations as the outcome. STUDY DESIGN: Randomized controlled trial; Level of evidence, 1. METHODS: This study is part of the Cost-effectiveness of Early Surgery versus Conservative Treatment with Optional Delayed Meniscectomy for Patients over 45 years with non-obstructive meniscal tears (ESCAPE) trial, a multicenter noninferiority randomized controlled trial conducted in 9 orthopaedic hospital departments in the Netherlands. The ESCAPE trial included 321 patients aged between 45 and 70 years with a symptomatic, magnetic resonance imaging-confirmed meniscal tear. Exclusion criteria were severe osteoarthritis, body mass index >35 kg/m2, locking of the knee, and prior knee surgery or knee instability due to an anterior or posterior cruciate ligament rupture. This study compared partial meniscectomy with physical therapy consisting of a supervised incremental exercise protocol of 16 sessions over 8 weeks. The main outcome measure was the Dutch-language equivalent of the Patient-Specific Functional Scale (PSFS), a secondary outcome measure of the ESCAPE trial. We used crude and adjusted linear mixed-model analyses to reveal the between-group differences over 24 months. We calculated the minimal important change for the PSFS using an anchor-based method. RESULTS: After 24 months, 286 patients completed the follow-up. The partial meniscectomy group (n = 139) improved on the PSFS by a mean of 4.8 ± 2.6 points (from 6.8 ± 1.9 to 2.0 ± 2.2), and the physical therapy group (n = 147) improved by a mean of 4.0 ± 3.1 points (from 6.7 ± 2.0 to 2.7 ± 2.5). The crude overall between-group difference showed a -0.6-point difference (95% CI, -1.0 to -0.2; P = .004) in favor of the partial meniscectomy group. This improvement was statistically significant but not clinically meaningful, as the calculated minimal important change was 2.5 points on an 11-point scale. CONCLUSION: Both interventions were associated with a clinically meaningful improvement regarding patients' most important functional limitations. Although partial meniscectomy was associated with a statistically larger improvement at some follow-up time points, the difference compared with physical therapy was small and clinically not meaningful at any follow-up time point. REGISTRATION: NCT01850719 (ClinicalTrials.gov identifier) and NTR3908 (the Netherlands Trial Register).

How do the costs of physical therapy and arthroscopic partial meniscectomy compare? A trial-based economic evaluation of two treatments in patients with meniscal tears alongside the ESCAPE study.

OBJECTIVES: To examine whether physical therapy (PT) is cost-effective compared with arthroscopic partial meniscectomy (APM) in patients with a non-obstructive meniscal tear, we performed a full trial-based economic evaluation from a societal perspective. In a secondary analysis-this paper-we examined whether PT is non-inferior to APM. METHODS: We recruited patients aged 45-70 years with a non-obstructive meniscal tear in nine Dutch hospitals. Resource use was measured using web-based questionnaires. Measures of effectiveness included knee function using the International Knee Documentation Committee (IKDC) and quality-adjusted life-years (QALYs). Follow-up was 24 months. Uncertainty was assessed using bootstrapping techniques. The non-inferiority margins for societal costs, the IKDC and QALYs, were €670, 8 points and 0.057 points, respectively. RESULTS: We randomly assigned 321 patients to PT (n=162) or APM (n=159). PT was associated with significantly lower costs after 24 months compared with APM (-€1803; 95% CI -€3008 to -€838). The probability of PT being cost-effective compared with APM was 1.00 at a willingness to pay of €0/unit of effect for the IKDC (knee function) and QALYs (quality of life) and decreased with increasing values of willingness to pay. The probability that PT is non-inferior to APM was 0.97 for all non-inferiority margins for the IKDC and 0.89 for QALYs. CONCLUSIONS: The probability of PT being cost-effective compared with APM was relatively high at reasonable values of willingness to pay for the IKDC and QALYs. Also, PT had a relatively high probability of being non-inferior to APM for both outcomes. This warrants further deimplementation of APM in patients with non-obstructive meniscal tears. TRIAL REGISTRATION NUMBERS: NCT01850719 and NTR3908.

Effect of Early Surgery vs Physical Therapy on Knee Function Among Patients With Nonobstructive Meniscal Tears: The ESCAPE Randomized Clinical Trial.

Importance: Despite recent studies suggesting arthroscopic partial meniscectomy (APM) is not more effective than physical therapy (PT), the procedure is still frequently performed in patients with meniscal tears. Objective: To assess whether PT is noninferior to APM for improving patient-reported knee function in patients with meniscal tears. Design, Setting, and Participants: Noninferiority, multicenter, randomized clinical trial conducted in 9 hospitals in the Netherlands. Participants were aged 45 to 70 years with nonobstructive meniscal tears (ie, no locking of the knee joint). Patients with knee instability, severe osteoarthritis, and body mass index greater than 35 were excluded. Recruitment took place between July 17, 2013, and November 4, 2015. Participants were followed up for 24 months (final participant follow-up, October 11, 2017). Interventions: Three hundred twenty-one participants were randomly assigned to APM (n = 159) or a predefined PT protocol (n = 162). The PT protocol consisted of 16 sessions of exercise therapy over 8 weeks focused on coordination and closed kinetic chain strength exercises. Main Outcomes and Measures: The primary outcome was change in patient-reported knee function on the International Knee Documentation Committee Subjective Knee Form (range, 0 to 100; from worse to best) from baseline over a 24-month follow-up period. The noninferiority margin was defined as a difference between treatment groups of 8 points and was assessed with a 1-sided α of .025. The primary analysis followed the intention-to-treat principle. Results: Among 321 patients who were randomized (mean [SD] age, 58 [6.6] years; 161 women [50%]), 289 (90%) completed the trial (161 women and 158 men). In the PT group, 47 participants (29%) had APM during the 24-month follow-up period, and 8 participants randomized to APM (5%) did not have APM. Over a 24-month follow-up period, knee function improved in the APM group by 26.2 points (from 44.8 to 71.5) and in the PT group by 20.4 points (from 46.5 to 67.7). The overall between-group difference was 3.6 points (97.5% CI, -∞ to 6.5; P value for noninferiority = .001). Adverse events occurred in 18 participants in the APM group and 12 in the PT group. Repeat surgery (3 in the APM group and 1 in the PT group) and additional outpatient visits for knee pain (6 in the APM group and 2 in the PT group) were the most frequent adverse events. Conclusions and Relevance: Among patients with nonobstructive meniscal tears, PT was noninferior to APM for improving patient-reported knee function over a 24-month follow-up period. Based on these results, PT may be considered an alternative to surgery for patients with nonobstructive meniscal tears. Trial Registration: ClinicalTrials.gov Identifier: NCT01850719.

Long-term outcomes of clinical transplantation of pancreatic islets with uncontrolled donors after cardiac death: a multicenter experience in Japan.

BACKGROUND: Pancreatic islet transplantation has emerged as an effective treatment for type 1 diabetes mellitus, but its use is limited due to an insufficient supply of cadaveric pancreata. In Japan, uncontrolled donors after cardiac death (DCD) are not deemed to be suitable for whole-organ pancreatic transplantation, and can provide a source of pancreas for islet transplantation. However, the long-term outcomes and utility of uncontrolled DCD in the clinical setting remain controversial. Here, we summarize the long-term outcomes of islet transplantation employing uncontrolled DCD as reported to the Japan Islet Transplantation Registry. METHODS: Sixty-four isolations and 34 transplantations of pancreatic islets were conducted in 18 subjects with type 1 diabetes mellitus under the cover of immunosuppression with basiliximab, sirolimus, and tacrolimus. All donors were uncontrolled DCD at the time of harvesting. The mean follow-up time was 76 months. RESULTS: Of the 18 recipients, 8, 4, and 6 recipients received 1, 2, and 3 islet infusions, respectively. Overall graft survivals (defined as a C-peptide level ≥0.3 ng/mL) were 72.2%, 44.4%, and 22.2% at 1, 2, and 5 years, respectively, whereas the corresponding graft survivals after multiple infusions were 90.0%, 70.0%, and 30.0%, respectively. Three of these recipients achieved insulin independence in 14, 79, and 215 days. HbA1c levels and the requirement of exogenous insulin were improved before loss of graft function. All recipients became free of severe hypoglycemia unawareness, however, at least 5 of 14 patients who had graft failure experienced recurrence of severe hypoglycemia after the loss of graft function. CONCLUSIONS: Islet transplantation from DCD can relieve glucose instability and problems with hypoglycemia when the graft is functioning. However, islets from uncontrolled DCD may be associated with reduced long-term graft survival. Further improvements in the clinical outcome by modification of islet isolation/transplantation protocols are necessary to establish islet transplantation using DCD.

Topographical arrangement of α- and ß-cells within neo-islet tissues engineered by islet cell sheet transplantation in mice.

BACKGROUND: We established a procedure to engineer therapeutic neo-islets in subcutaneous spaces in mice by transplanting contiguous layers of islet cell sheets. In this study, we investigated the cellular arrangements of α and ß within these engineered neo-islets in vivo as a function of time after sheet transplantation. METHODS AND RESULTS: Temperature-responsive culture dishes optimized for dispersed islet cell culture were prepared by covalently immobilizing a temperature-responsive polymer poly(N-isopropylacrylamide) (PIPAAm) on plastic dishes followed by laminin-5 coating. Dispersed islet cells obtained from Lewis rats were plated onto the PIPAAm dishes. After reaching confluence at day 2, islet cells were harvested as uniformly spread islet cell sheets by lowering the culture temperature from 37°C to 20°C for 20 minutes. Islet sheet transplantation was performed to creat neo-islet tissues in the subcutaneous spaces of SCID mice with streptozotocin-induced diabetes. This neo-islet engineering approach successfully lowered mouse blood glucose levels, achieving euglycemia at day 5 and thereafter. Histologic analyses of samples obtained at day 4 revealed that neo-islet tissues in the subcutaneous spaces showed heterogeneous cellular alignment of α and ß cells. In contrast, analyses of samples at days 14 and 60 revealed α and ß cells predominantly located at the peripheral and central parts of the engineered tissues, respectively. CONCLUSIONS: Reassembly of α and ß cells occurred in neo-islet tissues engineered by sheet transplantation. The unique cellular arrangements in neo-islet tissues, which were similar to those in naïve pancreatic islets, may contribute to their longevity and long-term function.

The start of an islet transplantation program in Japan.

In Japan, pancreas donation had become possible from cadaveric donor sources, both heart-beating or non-heart-beating (NHB). Pancreas allografts have been distributed in the organ allocation system of the Japan Organ Transplant Network. Meanwhile, islet transplantation has been categorized as a tissue transplantation; it is free from legal restraints. Thus, pancreata for islet isolation must be obtained from NHB donors. Herein we report the starting program and preliminary results of islet transplantation in Japan. Selection and listing criteria for transplantation include regional priority, ABO blood type, previous islet transplant status with insulin independence, and a longer waiting time. Five institutes in Japan (Fukushima, Chiba, Kyoto, Kobe, and Fukuoka) are prepared to start programs. A two-layer cold storage method using perfluorocarbons and UW solution is recommended for pancreas preservation. Islet isolation and purification procedures are performed according to institute-specific protocol. Immunosuppression is based on sirolimus/tacrolimus combined with basiliximab induction. Two or three consecutive infusions of >5000 IE/kg are planned for each recipient until achieving insulin independence. Twenty-seven isolations and 14 transplants were performed in eight non-insulin-dependent diabetes mellitus (IDDM) recipients. Almost all (26 of 27) were NHB donors. All recipients are free from hypoglycemic episode after transplantation. One of these recipients is insulin independent; the others are currently on minimal doses of exogenous insulin. The feasibility of islet transplantation using NHB donors was confirmed using a two-layer cold storage method and a steroid-free immunosuppressive protocol, with a high rate of graft function.

Evaluation of energy state of islet independent of size using a newly developed ATP bioluminescence assay.

ATP content or energy charge (EC) of islets may be a good parameter to assess viability. In this study, we examined adenine nucleotides and EC of freshly isolated or 24-hour cultured rat islets of various diameters using a novel bioluminescent enzymatic cycling assay system. For freshly isolated islets, ATP content and islet diameter showed a high correlation (r = 0.842, P < .001), but a significant correlation was not observed for cultured islets (r = 0.284) when all islets were included for the analysis. When only the cultured islets with a diameter <350 microm were included for analysis, a significant correlation was observed (r = 0.719). EC of freshly isolated islets fluctuated widely irrespective of diameter, in contrast with results of 24-hour cultured islets, which showed a stable, high EC, regardless of diameter. These data suggest that the ATP content of islets correlates with the islet size and that EC of islets widely fluctuates following isolation, indicating a significant role of monitoring ATP and EC of islets before transplantation.

Transforming growth factor-beta signaling is enhanced following mitomycin-C treatment of islet xenograft.

Mitomycin-C (MMC) is categorized as an agent that causes genotoxic stress by triggering various intracellular signaling pathways. We have previously shown that MMC pretreatment of highly immunogenic crude islets leads to significant prolongation of graft survival in a rat-to-mouse model. In the present study, we examined whether TH1/TH2 cytokine, including the inflammatory cytokines interferon-gamma and interleukin (IL)-2, or the Th2 group, IL-4, IL-10, TNF-alpha, IL-1 beta, IL-6, GM-CSF, and transforming growth factor (TGF)-beta were up-regulated or down-regulated following MMC treatment of islets. We found changes in TGF-beta messenger RNA (mRNA) transcription as the only events among the measured cytokines. TGF-beta concentration was elevated in blebs formed under the kidney capsule, but not in the serum or ascites among animals given MMC-treated islets than in animals given untreated islets, suggesting local processes induced by MMC might inhibit xenograft rejection.

Sevoflurane anaesthesia in chickens during spontaneous and controlled ventilation.

A crossover study design was used to investigate the dose-related effects of sevoflurane at end-tidal concentrations of 2.2 to 4.4 per cent on the respiratory rate, blood gases, heart rate, arterial blood pressure and ocular signs of chickens during spontaneous and controlled ventilation. The mean (sd) carbon dioxide partial pressure (PaCO2) increased as the concentration of sevoflurane increased, and was 86 (29) mmHg at an end-tidal concentration of 4.4 per cent during spontaneous ventilation, but was maintained between 29 and 42 mmHg during controlled ventilation. The heart rate increased as the concentration of sevoflurane increased during spontaneous ventilation, but did not change during controlled ventilation. Sevoflurane decreased arterial blood pressure during both spontaneous and controlled ventilation, but a dose-dependent decrease in arterial blood pressure was observed only during controlled ventilation. The mean arterial blood pressure at an end-tidal concentration of 4.4 per cent was significantly higher during spontaneous ventilation than during controlled ventilation. Controlled ventilation prevented the increases in PaCO2 and heart rate that were observed during spontaneous ventilation. The decrease in arterial blood pressure during spontaneous ventilation was less than that during controlled ventilation, possibly owing to the effects of hypercapnia.

Targeted deletion of the H-ras gene decreases tumor formation in mouse skin carcinogenesis.

To clarify the role of the H-Ras in vivo, we generated H-ras null mutant mice by gene targeting. In spite of the importance of the Ras in cell proliferation and differentiation, H-ras null mutant mice grew normally and were fertile. The oldest H-ras mutant mice grew to be more than 30 months old. We used the H-ras deficient mice to study the importance of the H-ras and other ras genes in the development of skin tumors induced by initiation with 7, 12-dimethylbenz(a)anthracene (DMBA) followed by promotion with 12-O-tetradecanoylphorbol-13-acetate (TPA). We showed that H-ras null mutant mice develop approximately six times less papillomas compared with wild-type littermates after 20 weeks of TPA treatment. While all papillomas examined (17 out of 17) in wild-type mice have mutations of H-ras at codon 61, 13 (62%) out of 21 papillomas in H-ras null mutant mice have mutations of K-ras gene at codon 12, 13, or 61 and another eight (38%) papillomas have no mutations in these codons of K-ras or N-ras genes. This suggests that the activation of H-ras gene is critical in the wild-type mice, but the activation of K-ras gene can replace the H-ras activation in the initiation step of skin tumor development in the H-ras deficient mice. Oncogene (2000).

Grafting of mitomycin C-treated islet xenograft under the kidney capsule produces a clear bleb.

We have previously shown that mitomycin C (MMC) treatment of donor tissue resulted in significant prolongation of graft survival in allo- and xenotransplantation models. However, the mechanisms involved in this prolongation are not clearly understood. This study aims to shed light on the immune responses to MMC-treated islet xenografting under the kidney capsule. Collagenase-digested WS (RT1k) rat islets incubated for 30 min with MMC and subsequently cultured for 20 h were transplanted into the renal subcapsular space of streptozotocin-induced diabetic C57BL/6 (B6;H-2b) mice. The grafts were harvested on postgrafting day 7 and sections were prepared and stained by hematoxylin and eosin (H&E). Histological study of the grafts in a group not treated with MMC showed marked cellular infiltration and destruction of islet clusters, whereas that of MMC-treated grafts demonstrated a bleb formation under the kidney capsule, in which islet cell clusters were reorganized, creating a layer of cells fixed to the interior of the bleb. Minimal invasion by inflammatory cells was observed only at the edge of the bleb, and most islet cells were protected from these infiltrating cells. In conclusion, MMC treatment induces remodeling of islet structure and forms a bleb under the kidney capsule, where no inflammatory cell infiltration occurs, suggesting that this site is a kind of immunologically privileged environment for xenografted islets.

Volatile components in stored rice [Oryza sativa (L.)] of varieties with and without lipoxygenase-3 in seeds.

Lipoxygenase (LOX) is thought to play an important role in the formation of desirable or undesirable flavor and aroma in many plant products. In rice seeds, LOX activity is localized in the bran fraction and LOX-3 is the major isozyme component. We used gas chromatography-mass spectrometry to determine whether the degree of staleness in the flavor of stored brown rice was related to the presence of LOX-3. We found that the amount of hexanal, pentanal, and pentanol in normal raw LOX-3 rice markedly increased during storage at 35 degrees C. That in LOX-3-less rice increased slightly but was a third to a fifth that of normal LOX-3 rice. In cooked rice, the amount of these components from glutinous rice exceeded that in nonglutinous rice, and that in normal LOX-3 rice exceeded that in LOX-3-less rice. These results indicate that the stale flavor production in LOX-3-less rice during storage is less than that in normal LOX-3 rice.

A keyword search system for medical doctors to introduce their patients to specialists.

We developed an online keyword search system on a WWW server to help medical doctors to introduce their patients to specialists. The system stores special knowledge and advanced techniques of 287 medical specialists in Kyushu University Hospital. The data set was presented by the medical specialists themselves. Specialists can rewrite their data set using the browser anytime to keep their data set up to date. In addition, the specialists are reminded to keep their data set up to date by direct mail once a year. The system does not use any database management systems. We used only two text files and the "grep" command, one of the basic commands of the UNIX system. Then, it takes less than 1 sec to search one medical specialist's data set from 200 specialists' data sets. The system is useful not only inside the hospital but also for practitioners in the local area.

[A case of report--interferon therapy is useful for chronic hepatitis C with human immunodeficiency virus infection].

A 42-year-old male type A hemophiliae who been using coagulates since 1971 was diagnosed Human Immunodeficiency Virus (HIV) positive in 1993. Medical history included liver disfunction in 1987, with chronic hepatitis C (CHC) diagnosed in 1989. He was admitted to the hospital in October, 1994 because of general fatigue. Serum transaminase was elevated, CD4 was 221/micro L, and CD8 was 990. CD4/CD8 ratio was 0.2. HCV was of genotype 2b and 10(6) copies/50 microL, 8 week-Interferon (IFN)-beta treatment was started. HCV RNA was eliminated by week 8 and was sustained for one year with no severe side effects. With careful patient screening, IFN therapy for CHC with HIV may be an effective treatment.

[An autopsy of an HIV infected patient with dilated cardiomyopathy (DCM)].

A case of a HIV infected 61-year-old bisexual male with dilated cardiomyopathy (DCM) is reported. The death was originally recorded as from undetermined causes, but on autopsy, his heart showed left ventricular dilatation macroscopically, variety in size and vacuolation of cardiomyocyte, partial deciduation of cardiac muscle and diffuse perivascular fibrosis microscopically. These findings were compatible with DCM which was compounded by excessive weight loss. The further data indicated that the etiology of DCM in this case was directly related to the HIV infection.

Severe aplastic anemia in a patient with primary immunodeficiency.

This paper reports the case of a 6 year old boy with primary immunodeficiency disease, whose marrow cells showed dyshematopoietic features, that was subsequently transformed to severe aplastic anemia. He was first diagnosed as having congenital immunodeficiency comprising deficiency of immunoglobulin A (IgA), IgG2 and IgG4, depressed mitogen responses, lymphopenia with inverted CD4/CD8 ratio and an increased proportion of T-cell receptor gamma/delta-bearing cells. Cytogenetic study of the peripheral blood showed a normal karyotype of 46,XY, but that of the marked hypoplastic marrow demonstrated one cell with monosomy 7 and another with trisomy 8 in the 20 cells examined.

A case of neonatal spinal cord injury: magnetic resonance imaging and somatosensory evoked potentials.

This is the first case report on the diagnosis of spinal cord injury due to hemorrhage during the neonatal period using magnetic resonance imaging (MRI). Somatosensory evoked potentials are also helpful in the functional demonstration of this lesion. When discrepant signs, alert consciousness and intact cranial nerves are observed in newborn babies with flaccid extremities and respiratory disturbance, the immediate carrying out of MRI is mandatory in order to differentiate spinal cord injury from hypoxic-ischemic encephalopathy, cerebral hemorrhage, and neuromuscular disease.

[Immunogenicity of Chinese hamster ovary cell derived HB vaccine--a comparative study with yeast derived HB vaccine].

To evaluate the immunogenicity of the Chinese hamster ovary cell derived HB vaccine (CHB), CHB and yeast derived HB vaccine (YHB) were given to 110 medical students divided into four groups. CHB was given to group A subcutaneously (0.5 ml, 3 times) and to group B intradermally (0.125 ml, 3 times). YHB was given to group C (Y company) and to group D (Z company) subcutaneously (0.5 ml, 3 times). The anti-HBs positive rate at 7 months was 85.7% in group A, 95.8% in group B, and 100% in groups C and D. The percentage responding with high anti-HBs concentration (> or = 100 mIU/ml by RIA) at 7 months was 67.9% in group A, 79.2% in group B, 58.3% in group C and 63.3% in group D. Thus, although the anti-HBs positive rate was rather low when CHB was given subcutaneously, it was almost the same as YHB when given intradermally. The percentage of high responders to CHB given both subcutaneously and intradermally was high compared to YHB. These data suggest that CHB has almost the same immunogenicity to the conventional YHB.