The effect of systemic administration of G-CSF on a full-thickness cartilage defect in a rabbit model MSC proliferation as presumed mechanism: G-CSF for cartilage repair.

OBJECTIVES: The aim of this study was to investigate the effect of granulocyte-colony stimulating factor (G-CSF) on mesenchymal stem cell (MSC) proliferation in vitro and to determine whether pre-microfracture systemic administration of G-CSF (a bone marrow stimulant) could improve the quality of repaired tissue of a full-thickness cartilage defect in a rabbit model. METHODS: MSCs from rabbits were cultured in a control medium and medium with G-CSF (low-dose: 4 µg, high-dose: 40 µg). At one, three, and five days after culturing, cells were counted. Differential potential of cultured cells were examined by stimulating them with a osteogenic, adipogenic and chondrogenic medium.A total of 30 rabbits were divided into three groups. The low-dose group (n = 10) received 10 µg/kg of G-CSF daily, the high-dose group (n = 10) received 50 µg/kg daily by subcutaneous injection for three days prior to creating cartilage defects. The control group (n = 10) was administered saline for three days. At 48 hours after the first injection, a 5.2 mm diameter cylindrical osteochondral defect was created in the femoral trochlea. At four and 12 weeks post-operatively, repaired tissue was evaluated macroscopically and microscopically. RESULTS: The cell count in the low-dose G-CSF medium was significantly higher than that in the control medium. The differentiation potential of MSCs was preserved after culturing them with G-CSF.Macroscopically, defects were filled and surfaces were smoother in the G-CSF groups than in the control group at four weeks. At 12 weeks, the quality of repaired cartilage improved further, and defects were almost completely filled in all groups. Microscopically, at four weeks, defects were partially filled with hyaline-like cartilage in the G-CSF groups. At 12 weeks, defects were repaired with hyaline-like cartilage in all groups. CONCLUSIONS: G-CSF promoted proliferation of MSCs in vitro. The systemic administration of G-CSF promoted the repair of damaged cartilage possibly through increasing the number of MSCs in a rabbit model.Cite this article: T. Sasaki, R. Akagi, Y. Akatsu, T. Fukawa, H. Hoshi, Y. Yamamoto, T. Enomoto, Y. Sato, R. Nakagawa, K. Takahashi, S. Yamaguchi, T. Sasho. The effect of systemic administration of G-CSF on a full-thickness cartilage defect in a rabbit model MSC proliferation as presumed mechanism: G-CSF for cartilage repair. Bone Joint Res 2017;6:123-131. DOI: 10.1302/2046-3758.63.BJR-2016-0083.

Utility of T2 mapping and dGEMRIC for evaluation of cartilage repair after allograft chondrocyte implantation in a rabbit model.

OBJECTIVE: To investigate the effectiveness of quantitative Magnetic resonance imaging (MRI) for evaluating the quality of cartilage repair over time following allograft chondrocyte implantation using a three-dimensional scaffold for osteochondral lesions. DESIGN: Thirty knees from 15 rabbits were analyzed. An osteochondral defect (diameter, 4 mm; depth, 1 mm) was created on the patellar groove of the femur in both legs. The defects were filled with a chondrocyte-seeded scaffold in the right knee and an empty scaffold in the left knee. Five rabbits each were euthanized at 4, 8, and 12 weeks and their knees were examined via macroscopic inspection, histological and biochemical analysis, and quantitative MRI (T2 mapping and dGEMRIC) to assess the state of tissue repair following allograft chondrocyte implantation with a three-dimensional scaffold for osteochondral lesions. RESULTS: Comparatively good regenerative cartilage was observed both macroscopically and histologically. In both chondrocyte-seeded and control knees, the T2 values of repair tissues were highest at 4 weeks and showed a tendency to decrease with time. ΔR1 values of dGEMRIC also tended to decrease with time in both groups, and the mean ΔR1 was significantly lower in the CS-scaffold group than in the control group at all time points. ΔR1 = 1/r (R1post - R1pre), where r is the relaxivity of Gd-DTPA(2-), R1 = 1/T1 (longitudinal relaxation time). CONCLUSION: T2 mapping and dGEMRIC were both effective for evaluating tissue repair after allograft chondrocyte implantation. ΔR1 values of dGEMRIC represented good correlation with histologically and biochemically even at early stages after the implantation.

Hidden osteophyte formation on plain X-ray is the predictive factor for development of knee osteoarthritis after 48 months--data from the Osteoarthritis Initiative.

OBJECTIVE: To examine whether the detection of osteophytes anywhere in the knee could serve as a pre-radiographic biomarker for osteoarthritis (OA) development. METHODS: Baseline magnetic resonance imaging (MRIs) of 132 participants in the Osteoarthritis Initiative (OAI) were studied. Based on radiographs, 66 knees were assessed as osteoarthritis-free (no-osteoarthritis [NOA], or Kellgren/Lawrence [K/L] severity grade 0/1 both at baseline and 48 months), and another 66 knees were assessed as having radiographic OA changes (pre-radiographic osteoarthritis [PROA], or with K/L grade 0/1 at baseline and grade ≥ 2 at 48 months). Using baseline MRI data, we examined eight sites of osteophyte formation: the medial and lateral femoral condyle (MFC and LFC, respectively); medial and lateral tibial plateau (MTP and LTP, respectively); medial and lateral facets of the patellofemoral joint (PM and PL, respectively); tibial spine (TS); and femoral intercondylar notch (IC). Knee joint osteophyte size was assessed via the 8-point marginal osteophytes item of the whole-organ magnetic resonance imaging score (WORMS). The frequencies and distributions of osteophytes were compared between groups. RESULTS: Mild-size osteophytes (defined as score ≥ 2) were observed more frequently at the MFC (P = 0.00278), MTP (P = 0.0046), TS (P = 0.0146), PM (P < 0.0001), PL (P = 0.0012), and IC (P < 0.0001) in PROA knees than in NOA knees. Moderate-size osteophytes (defined as score ≥ 4) were more frequently observed in PROA knees than in NOA knees only at the IC (P < 0.0001). CONCLUSION: Knees with osteophyte formation at the IC, even those of K/L severity grade 0/1, are at risk for the development of radiographic OA by 48 months.

Preventive effects of hyaluronan from deterioration of gait parameters in surgically induced mice osteoarthritic knee model.

OBJECTIVE: Osteoarthritis (OA) leads to pain and loss of function in affected joints. Gait disturbance results from these symptoms of OA, and gait analysis can be important to evaluate the progression of OA. The purpose of this study was to analyze gait pattern in a rodent model of OA and to assess the effects of intra-articular injection of hyaluronan (IAI-HA) by gait analysis, along with histological evaluation. DESIGN: OA was induced by destabilization of the medial meniscus (DMM) of C57BL/6 mice. IAI-HA started 3 weeks after DMM surgery. Mice were allocated to three groups and were given either 800-kDa HA (800-HA), 6000-kDa HA (6000-HA) or saline. We compared these three groups with a sham group by gait analysis using CatWalk. Histological evaluation was performed to assess articular cartilage changes in the knee joints. RESULTS: Mice injected with 800-HA or 6000-HA showed gait patterns similar to that of the sham mice, while the saline-injected group showed gait disturbances 12 and 16 weeks after DMM surgery. Histological changes in articular cartilage were similar among the 800-HA, 6000-HA and saline-treated groups, demonstrating OA progression throughout the experimental time points. Positive gait-related effects of IAI-HA might occur by its pain relieving effect and/or by preventing contracture. CONCLUSION: IAI-HA prevented gait disturbances in the DMM model, but did not prevent histological changes associated with OA progression.

Volatile organic compound sensing by quartz crystal microbalances coated with nanostructured macromolecular metal complexes.

We report the construction of a molecular recognition layer composed of polyelectrolyte brushes and metal complexes on the surface of a quartz crystal microbalance (QCM) and the sensing abilities for various volatile organic compounds (VOCs). Atom-transfer radical polymerization of 2-(dimethylamino)ethyl acrylate from an initiator-terminated self-assembled monolayer yielded polyelectrolyte brushes on the surface of a weight-detectable quartz crystal microbalance. One end of a poly[(2-dimethylamino)ethyl methacrylate] brush was covalently attached onto the surface of a sensor. We found that metallophthalocyanines with four bulky pentaphenylbenzene substituents could adsorb volatile organic compounds selectively into their cavities. Macromolecular metal complexes were prepared by immersing polymer-brush-modified QCMs into an aqueous solution of sterically protected cobalt phthalocyanine. Anionic cobalt phthalocyanine was trapped in the polymer brushes and acted as a molecular receptor for the sensing of VOC molecules.

Symptomatic cavernous internal carotid artery aneurysms treated with detachable coils.

SUMMARY: We reviewed the cranial nerve dysfunctions of eight patients with symptomatic cavernous internal carotid (CSIC) aneurysms treated by endovascular intraaneurysmal occlusion. Aneurysms were classified into three types according to their location and direction of growth. Anterior type aneurysms, which involved anterior bend of CSIC represented third nerve dysfunction. Posterior type aneurysms, which located posterior bend of CSIC preferred to affect sixth nerve function. CSIC aneurysms that extended over the both bends had total ophthalmoplegia. All patients responded to endovascular treatment, though partial resolution was recorded in the case of upward gaze or lateral gaze impairment. Endovascular treatment with detachable coils offers an excellent alternative with acceptable risks of morbidity.

Significance of fractionated irradiation for the biological therapeutic gain of carbon ions.

It is well established that the RBE (relative biological effectiveness) for cell killing depends on LET (linear energy transfer), and that a maximum RBE is observed at approximately 150 keV.micron-1. However, the therapeutic gain depends on the ratio of the RBEs for the effects on the cancer cell population and the effects on normal tissues. The RBE of a given radiation quality depends not only on LET but also on dose, biological system and effect, and irradiation conditions. There is no data available to answer the question: which LET is suitable to improve the biological therapeutic gain of carbon ions? Here, three different LET values of 290 MeV/u carbon ions were selected, and the relative biological effectiveness was compared between tumour-growth retardation and skin damage using a murine transplantable tumour. Larger RBE values for tumours after than the skin type were obtained when carbon ions of intermediate LET were delivered daily for 2 to 5 fractions. The biological therapeutic gain would be high for the carbon ion SOBP if the number of fractions were correctly selected in clinical trials.

[Health service use and age among the elderly].

The purpose of this study was to analyze differences in health service use among Japanese elderly by age group or by region through patient category, and to evaluate the impact of long-term elderly inpatient on the national health expenditure. We used a large scale data of 1993, based on medical fee claim records. Patient category was made by classifying elderly patients into 12 categories according to their annual inpatient, and outpatient days. Per capita health expenditure of the elderly changed according to age or region, and the main cause of this was the difference in percentage distribution of patient category, A typical example of those who use most of health services was the long-term inpatient, and both age difference and regional differences in per capita health expenditure of the elderly reduced remarkably by excluding such expenditure. Therefore, the impact of long-term elderly inpatient on the national health expenditure was already significant. In considering the effective use of health expenditure for the elderly, it is necessary to focus on those who use health service heavily, but at the same time it is also necessary to keep the entire patient population in mine.

[Costs of health services for the elderly and related factors in cities of Japan].

OBJECTIVES: To estimate the costs of health services for the elderly in 1994 and to examine factors affecting them. METHODS: Questionnaires were sent to 631 cities and responses from 339 cities were received. Data obtained from questionnaires were total cost, proportion of labor sent to total cost, cost per user, cost per person eligible to receive Health services for the elderly. These variables were measured for health counseling service, health education, health examinations, functional training, and home-visit guidance. RESULTS: The proportion of labor cost was smaller for health examinations than for other services. Health examinations and home-visit guidance showed higher correlation coefficients between the number of users and the total cost than other services. In most services, cost per eligible person were negatively correlated with the number of residents in the city and positively correlated with the number of public health nurses per resident. However, costs per user did not show a correlation. The cities which established municipal health centers had lower costs per user of health education and functional training than the cities which did not. Standardized mortality ratios of cerebrovascular disease and stomach cancer were not correlated with total cost, proportion of labor cost, cost per user, cost per eligible person in most services. CONCLUSIONS: For the economic evaluation of health services for the elderly, it is necessary to examine the relationship between cost, both quantity and quality, and effectiveness of health services.

[Distribution of medical expenditures for the elderly].

The distribution in medical service use by the elderly was examined by using data from medical fee claim records of the Medical System for the Elderly for one year. The following are among the main findings: More than 50 percent of the patients consumed less than 300,000 yen per year, and those patients whose annual medical expenditures were between 600,000 yen to 4,000,000 yen consumed 54 percent of the total expenditures of the elderly. The top 10 percent of patients consumed 50 percent of medical expenditures, and top 1 percent consumed 10 percent. Lorenz curves of medical expenditures for different regions were relatively similar despite the large differences in medical expenditures per patient. Medical expenditures per patient did not appear to be related to the concentration in distribution of expenditures, although the former was strongly related to the proportion of long-term hospitalized patients. After various measures to control the increase rate of medical expenditures in 1980's, public attention has shifted slowly to the quality of services provided and cost-effectiveness of medical services. The concentration in distribution of medical expenditures was considered to be a meaningful approach to investigate the effectiveness of medical services.

[The structural analysis of inpatient medical cost of the aged in 81 secondary medical areas of 12 Prefectures in Japan].

In order to understand the structure of the per capita medical care expenditure of inpatients aged 70 years and over, correlational and principal component analyses were performed using several medical cost indices for fiscal 1991 in 81 secondary medical areas of 12 prefectures. Requests were sent to all of 777 municipalities in the 12 prefectures, and there were 763 responses for the response rate of 98.2%. A total of 1,647,187 residents who had been inpatients based on receipts for inpatient medical care expenditure were surveyed. There were 389,456 who responded that they had been inpatients at least once in the preceding 12 months, in 1991. The main results were as follows: 1) Of the residents aged 70 and over, 32.0% of men and 29.7% of women surveyed had at least one episode of hospital admission in the preceding 12 months in 1991. 2) Large differences in the medical care expenditure per inpatient per year for those aged 70 years and over exist in the secondary medical areas in 12 prefectures. 3) In both sexes, per capita expenditures for inpatient care per year are positively correlated with the bed-days in hospitals per inpatient per year, the bed days per receipt, the medical care expenditure per receipt, and the number of receipts per inpatient per year. On the other hand, for women it is negatively correlated with per capita medical care expenditure per day, but it is not statistically significant. 4) The medical care expenditure per inpatient per day is significantly negatively correlated with bed-days in hospital per receipt, the number of receipts per inpatient per year, bed-days in hospital per inpatient per year for both sexes. On the other hand, it is significantly positively correlated with medical care expenditure per receipt for both sexes.(ABSTRACT TRUNCATED AT 250 WORDS)

Future trends of Japanese households through micro-simulation model--an application of INAHSIM.

"INAHSIM (Integrated Analytical Model for Household Simulation) is a micro simulation model, which was first developed in 1984-85 by using actual initial population and a set of transition probabilities derived from vital statistics and other national sample surveys.... This paper is based on a new application of INAHSIM, where initial population of the model has been prepared by using the simulation model itself. In this way, it is confirmed that INAHSIM is applicable to countries where initial population is not available from census or national household surveys.... New simulations were executed for [Japan for] the period of 1991-2040." (SUMMARY IN JPN)

[Differences in inpatient medical costs for the aged within one prefecture].

The rapid increase in the proportion of the elderly population has made the problem of medical costs increasingly important. This problem, however, is not uniform over all regions in Japan. In order to determine what factors are associated with per capita medical care expenditure of inpatients aged 70 years and over, in fiscal 1991, correlation analyses were performed using several indices of medical services, socioeconomic factors and medical supplies among 208 municipalities in one prefecture. Data from a survey in 1992 conducted by the Ministry of Health and Welfare was used in the analysis. Requests were sent to all 218 municipalities in one prefecture, and 208 responses were received a response rate of 95.4%. The main findings were as follows: 1) There were large differences in per capita medical care expenditure for those aged 70 years and over among the secondary medical areas in the prefecture. 2) Both the inpatient expenditures per person per year and bed-days in hospitals per person per year were positively correlated with number of hospital beds per 1,000, the aging population rate and death rate of those aged 70 years and over; but correlated negatively with the primary industry population rate for both sexes. 3) Inpatient expenditure per person per day was negatively correlated with the aging population rate, especially for men. 4) Three major factors that correlated significantly and positively with per capita medical care expenditure for those aged 70 years and over were bed days of inpatients per receipt, the total receipts per inpatient per year, and the number of the admission days of inpatients per year. These three major factors were negatively correlated but not significantly, with the per capita medical care expenditure per day. 5) Multiple regression analyses indicate that the aging population rate, the number of hospital beds per 1,000 of those aged 70 years and over, and death rate of those aged 70 years and over were independently correlated with the inpatient expenditure per person per year for both sexes. 6) Results of this analysis indicate that data from secondary medical regions within the prefecture rather than the municipalities yield a stronger possibility of clarifying those factors contributing to differences in per capita medical care expenditure.

[Characteristics of the medical treatment received by elderly during the month of death].

Data from the Medical Care Activities Survey for 1990 and 1991 were used to analyze characteristics of hospital inpatient medical expenditures of those elderly who died in the month of May, the subject month of the survey. Control data was from elderly inpatients who survived in May and matched in terms of age, sex, disease and length of stay. Three indices were used for analysis: medical expenditures per day, share of each medical care activity in the total medical expenditures, and prevalence rate of each medical care activity. The following are among the main results: The distribution of medical expenditure per day for the dead was higher than the control data, averaging more than twice as much. Medical expenditures of the dead were higher because of higher ratio of injections, examinations, and treatment. Concerning prevalence rate of each medical care activity, injection, emergency treatment, blood transfusion, etc. showed higher rates for the dead compared to the control data. Medical expenditures per day for the dead were also found higher for two main causes of death: malignant neoplasms, 1.4 to 1.9 times; cerebrovascular diseases, 2.3-2.9 times.

The social support system of the Japanese elderly.

The social support system of the Japanese elderly was observed in a national representative sample of elderly community residents. Perceived availability of emotional and instrumental support from family members, children living apart, siblings and relatives, neighbors, and friends was respectively estimated. For both emotional and instrumental support, the perceived most dependable source of support was family members living together, followed by children living apart, while neighbors and friends were less dependable sources of support. The results clearly indicated family-centrality in the social support system of the Japanese elderly. However, the results also indicated differential roles of family members, children living apart, and non-kin others in the social support system of the elderly, and suggested the need to observe dyadic social relationships of Japanese elderly individuals.

[Functional capacity of the elderly: measurement by the TMIG Index of Competence].

The functional capacity of the elderly was assessed in a national representative sample of elderly community residents. A stratified multistage random sampling yielded, 2,240 eligible persons, and 80.8% of them (n = 1,810) were successfully interviewed. The respondents ranged in age from 65 to 96 years, and the average age was 72.5 years; 43.2% of them were men, and the remaining 56.8% were women. The TMIG Index of Competence, a standardized multidimensional 13-item index of competence, was used for measuring the functional capacity. The total score of the index (maximum 13 points) showed a negatively skewed leptokurtic distribution: 69.6% of the respondents scored 11 points or greater while the mean was 10.8 points. A multiple classification analysis of the total score utilizing age, gender, educational attainment, and size of community as independent variables showed significant effects of age and educational attainment; the score significantly decreased with age, and the highly educated elderly showed higher score than those with lower educational attainment. The results of this study show that the majority of the elderly living in the community are well in functional capacity though the capacity tends to decline with age. The distribution of total scores observed in this study can be considered as a national standard of distribution of functional capacity measured by the TMIG Index Competence.

Independence of the elderly and its consideration from demographic and economic points of view.

"Based on the data of Survey on Independence of the Elderly, 1991, several analyses were made on independence of the elderly [in Japan]." Information is provided on age and sex distribution, living arrangements, population size, household structure, income and expenses, and physical and functional ability. (SUMMARY IN JPN)

[Dental anthropological study of Mongoloid in China].

The purpose of this study was to evaluate the craniofacial and occlusal characteristics of the inhabitants in China. The material consisted of cephalograms, pantomograms, dental casts and anthropological measurements taken from 517 inhabitants: 416 Han Chinese in Beijing, Shanghai, Guangzhou and Changchun and 101 Mongolians in Hohhot. The data were compared among the above five regions and also with the Japanese data. The findings were summarized as follows: I. Craniofacial characteristics; a) The Han Chinese and the Mongolians showed brachycephaly. b) The inhabitants in Guangzhou showed a tendency of bimaxillary protrusion with a smaller facial height, and the inhabitants in Changchun showed a larger gonial angle with a larger facial height than those of the other regions. c) The Mongolians had a larger value of the saddle angle and of the bi-gonial breadth. d) Compared with the Japanese, their craniofacial complex was characterized by a larger facial angle, smaller mandibular plane angle and a smaller gonial angle. II. Occlusal characteristics; a) The inhabitants in China had a similar tendency in the dental arch form and in the dental trait frequency. b) The inhabitants in Beijing had a larger mesiodistal crown-diameter of the anterior teeth than those in the other regions. c) Compared with the Japanese, their teeth were characterized by a smaller mesiodistal crown-diameter (especially on the upper first molar), higher frequency of shovel-shape and lower frequency of Carabelli's tuberculum.