Health care transition for cerebral palsy with intellectual disabilities: A systematic review.

OBJECTIVE: Today, most individuals with cerebral palsy are adults who need a paediatric-to-adult health care transition. However, many remain in paediatric care for treatment of adult-onset health issues. Therefore, a systematic review based on the 'Triple Aim' framework was performed to determine the status of paediatric-to-adult health care transition for people with cerebral palsy. A comprehensive evaluation of transitional care was proposed for using this framework. It consists of 'experience of care', meaning satisfaction with the care, 'population health', meaning the well-being of patients, and 'cost', meaning cost-effectiveness. METHOD: Electronic database (PubMed) searches were performed. The inclusion criteria were original articles published between 1990 and 2020. The search terms used in this study were ('cerebral palsy' AND 'transition to adult health care') OR ('cerebral palsy' AND 'transition'). The study type had to be epidemiological, case report, case-control, and cross-sectional, but not qualitative. The outcomes of the studies were categorised into 'care experience', 'population health', and 'cost', according to the Triple Aim framework. RESULTS: Thirteen articles met the abovementioned inclusion criteria. Few studies have examined the effect of the intervention of transition for young adults with cerebral palsy. Participants in some studies had no intellectual disability. Young adults were dissatisfied with the 'care experience', 'population health', and 'cost' and had unmet health needs and inadequate social participation. INTERPRETATION: Further transition intervention studies with a comprehensive assessment and proactive involvement of individuals are warranted. The presence of an intellectual disability should be considered.

Gradient subthalamic neurodegeneration and tau pathology in the hypoglossal nucleus as essential pathological markers of progressive supranuclear palsy - Richardson syndrome.

Progressive supranuclear palsy - Richardson syndrome (PSP-RS) was first described in 1964 by Steele et al. Tau pathology has not been reported in the hypoglossal nuclei of PSP-RS patients, whereas Steele et al. described gliosis with no remarkable neuronal losses in the hypoglossal nucleus. This study aimed to investigate the distribution and degree of tau pathology-associated neurodegeneration, with an emphasis on the hypoglossal nucleus, in patients with PSP-RS. Six clinicopathologically proven PSP-RS cases were included in this study. All patients were clinicopathologically and immunohistochemically re-evaluated. This study confirmed the following neuropathological characteristics of PSP-RS: (1) neurodegeneration usually affects the striatonigral system and cerebellar dentate nucleus; (2) the cerebellar afferent system in PSP-RS is affected by absent-to-mild neurodegeneration; and (3) the extent of tau distribution throughout the central nervous system is greater than the extent of neurodegeneration. Furthermore, we found that subthalamic neurodegeneration was more prominent in the ventromedial region than in the dorsolateral region. Nevertheless, the tau pathology showed no remarkable differences between these two sites. Interestingly, the tau pathology was frequently observed in the hypoglossal nuclei of PSP-RS patients. Gradient neurodegeneration of the subthalamus and tau pathology in the hypoglossal nucleus could be regarded as essential pathological features of PSP-RS.

Randomized clinical trial of extensive intraoperative peritoneal lavage versus standard treatment for resectable advanced gastric cancer (CCOG 1102 trial).

BACKGROUND: A survival benefit of extensive intraoperative peritoneal lavage (EIPL) has been reported in patients with gastric cancer with positive peritoneal cytology. The hypothesis of this study was that EIPL may reduce peritoneal recurrence in patients with advanced gastric cancer who undergo surgery with curative intent. METHODS: This was an open-label, multi-institutional, randomized, phase 3 trial to assess the effects of EIPL versus standard treatment after curative gastrectomy for resectable gastric cancer of T3 status or above. The primary endpoint was disease-free survival (DFS); secondary endpoints were overall survival, peritoneal recurrence-free survival and incidence of adverse events. RESULTS: Between July 2011 and January 2014, 314 patients were enrolled from 15 institutions and 295 patients were analysed (145 and 150 in the EIPL and no-EIPL groups respectively). The 3-year DFS rate was 63·9 (95 per cent c.i. 55·5 to 71·2) per cent in the EIPL group and 59·7 (51·3 to 67·1) per cent in the control group (hazard ratio (HR) 0·81, 95 per cent c.i. 0·57 to 1·16; P = 0·249). The 3-year overall survival rate was 75·0 (67·1 to 81·3) per cent in the EIPL group and 73·7 (65·9 to 80·1) per cent in the control group (HR 0·91, 0·60 to 1·37; P = 0·634). Peritoneal recurrence-free survival was not significantly different between the two groups (HR 0·92, 0·62 to 1·36; P = 0·676). No intraoperative complications related to EIPL were observed. CONCLUSION: EIPL did not improve survival or peritoneal recurrence in patients who underwent gastrectomy for advanced gastric cancer. Registration number: 000005907 (http://www.umin.ac.jp/ctr/index.htm).

ANTECEDENTES: Se ha descrito que un lavado peritoneal extenso intraoperatorio (extensive intraoperative peritoneal lavage, EIPL) proporciona un beneficio en la supervivencia en pacientes con cáncer gástrico con citología peritoneal positiva. La hipótesis de este estudio era que el EIPL podría disminuir la recidiva peritoneal en pacientes con cáncer gástrico avanzado sometidos a cirugía con intención curativa. MÉTODOS: Ensayo clínico fase 3, abierto, multicéntrico y aleatorizado para evaluar los efectos de un lavado peritoneal extenso intraoperatorio (EIPL) frente a tratamiento estándar tras gastrectomía curativa por cáncer gástrico ≥T3 resecable. La variable de resultado primaria fue la supervivencia libre de enfermedad (disease-free survival, DFS), y las variables de resultado secundarias fueron la supervivencia global (overall survival, OS), la supervivencia libre de recidiva peritoneal y la incidencia de efectos adversos. RESULTADOS: Entre julio de 2011 y enero de 2014, se reclutaron 314 pacientes de 15 instituciones y se analizaron los datos de 295 pacientes (145 en el grupo con EIPL y 150 en el grupo sin EIPL). La DFS a los 3 años fue 63,9% (i.c. del 95% 55,5-71,2) en el grupo con EIPL y 59,7% (i.c. del 95% 51,3-67,1) en el grupo control (cociente de riesgos instantáneos, hazard ratio, HR 0,81 (i.c. del 95% 0,57-1,16), P = 0,249). La OS a los 3 años fue 75,0% (i.c. del 95% 67,1-81,3) en el grupo con EIPL y 73,7% (i.c. del 95% 65,9-80,1) en el grupo control (HR 0,91 i.c. del 95% 0,60-1,37), P = 0,634). No se observaron diferencias estadísticamente significativas entre los dos grupos en la supervivencia libre de recidiva peritoneal (P = 0,676, HR 0,92 (i.c. del 95% 0,62-1,36). No se observaron complicaciones intraoperatorias relacionadas con EIPL. CONCLUSIÓN: El EIPL no mejoró la supervivencia o la recidiva peritoneal en pacientes sometidos a gastrectomía por cáncer gástrico avanzado.

Sternal Metastasis of Brain Meningioma - A Case Report.

BACKGROUND: Metastases of meningiomas are infrequent and the site of extracranial metastasis such as the bone is extremely rare. CASE REPORT: A 75-year-old male had a history of five sessions of surgery and gamma-knife treatment for brain meningioma over a period of 29 years. He visited our hospital because he noticed a swelling in his anterior chest 2 years and 6 months after the final treatment. After an open biopsy, histopathological analysis revealed the mass to be a metastatic grade II meningioma. We resected the tumor along with the sternum, ribs, pleura, and pericardium. The patient had recurrences in the thoracic cavity and pericardium postoperatively and received radiation therapy. He also had metastasis in the abdominal cavity, which spread rapidly. CONCLUSION: We report on a rare instance of metastasis to the sternum in a case of atypical meningioma, showing rapid growth and invasion after long-term treatment.

Morphogenesis and development of microbodies of hepatocytes of rats during pre- and postnatal growth.

In hepatocytes of fetal rats, cytoplasmic organelles identifiable as microbodies appeared, although only a few of them showed nucleoids and most of them generally had an electronlucent appearance due to the low density of their matrices. Some of these microbodies, especially those lacking the nucleoid, showed a substantial connection with granular endoplasmic reticulum (ER), suggesting that microbodies might be formed from granular ER. Agranular tubular profiles projecting from the surface of microbodies were found with a high frequency in fetal and neonatal rats; however, this phenomenon may not provide crucial evidence suggestive of the derivation of microbodies from agranular ER. Growth and maturation of microbodies are considered to be brought about by an enlargement of these organelles, an increase in their matrices, an appearance and enlargement of the nucleoids, and an increase in the enzyme involved. The specific activity of urate oxidase in the isolated nucleoid fraction was significantly lower in the earlier stages of postnatal growth than later. Increases in the enzyme activity per nucleoid (maturation of the nucleoid), in the number of microbodies containing nucleoids (formation of the nucleoid), and in the size of nucleoids (growth of the nucleoid), may contribute to increases in the enzyme activity of the tissues.

The nucleoids of rat liver cell microbodies. Fine structure and enzymes.

The nucleoids of microbodies of rat liver cells were isolated in a highly homogeneous and pure state, by treating the microbody-rich fraction, prepared from 10% polyvinylpyrrolidone-0.25 M sucrose homogenate, with Triton X-100. Three treatments with 0.1% detergent were enough to render the nucleoids free from contamination with mitochondria, microsomes, lysosomes, and intact microbodies. Electron microscopically, the nucleoids were found to consist of parallel bundles of highly dense hollow tubules, the outer and inner diameters of which are approximately 150 and 50 A, respectively. Ten tubules are arranged around a longitudinal space 190 x 200 A in width. The nucleoids thus show a honeycomb appearance in the cross-plane and a parallel-packed structure in the longitudinal plane. Biochemically, the nucleoids were found to bear only urate oxidase among probably microbody-enzymes, and they might be the only cytoplasmic particles of rat liver cells in which the enzyme locates. Urate oxidase activity, on a unit protein basis, of the nucleoid preparation is approximately 380 times as high as that of the whole homogenate, and is almost comparable with that of a commercial type I enzyme preparation. No enzymes of mitochondrial, microsomal, and lysosomal origins were detected in the nucleoids. The fine structure of the nucleoids is described in detail, and a probable schematic diagram is presented.

The influence of compressive forces across the patellofemoral joint on patient-reported outcome after bi-cruciate stabilized total knee arthroplasty.

AIMS: Patellofemoral problems are a common complication of total knee arthroplasty. A high compressive force across the patellofemoral joint may affect patient-reported outcome. However, the relationship between patient-reported outcome and the intraoperative patellofemoral contact force has not been investigated. The purpose of this study was to determine whether or not a high intraoperative patellofemoral compressive force affects patient-reported outcome. PATIENTS AND METHODS: This prospective study included 42 patients (42 knees) with varus-type osteoarthritis who underwent a bi-cruciate stabilized total knee arthroplasty and in whom the planned alignment was confirmed on 3D CT. Of the 42 patients, 36 were women and six were men. Their mean age was 72.3 years (61 to 87) and their mean body mass index (BMI) was 24.4 kg/m 2 (18.2 to 34.3). After implantation of the femoral and tibial components, the compressive force across the patellofemoral joint was measured at 10°, 30°, 60°, 90°, 120°, and 140° of flexion using a load cell (Kyowa Electronic Instruments Co., Ltd., Tokyo, Japan) manufactured in the same shape as the patellar implant. Multiple regression analyses were conducted to investigate the relationship between intraoperative patellofemoral compressive force and patient-reported outcome two years after implantation. RESULTS: No patient had anterior knee pain after total knee arthroplasty. The compressive force across the patellofemoral joint at 140°of flexion was negatively correlated with patient satisfaction (R 2 = 0.458; ß = -0.706; p = 0. 041) and Forgotten Joint Score-12 (FJS-12; R 2 = .378; ß = -0.636; p = 0. 036). The compressive force across the patellofemoral joint at 60° of flexion was negatively correlated with the patella score (R 2 = 0.417; ß = -0.688; p = 0. 046). CONCLUSION: Patient satisfaction, FJS-12, and patella score were affected by the patellofemoral compressive force at 60° and 140° of flexion. Reduction of the patellofemoral compressive forces at 60° and 140° of flexion angle during total knee arthroplasty may improve patient-reported outcome, but has no effect on anterior knee pain.

The anaphase inhibitor Pds1 binds to the APC/C-associated protein Cdc20 in a destruction box-dependent manner.

An essential aspect of progression through mitosis is the sequential degradation of key mitotic regulators in a process that is mediated by the anaphase promoting complex/cyclosome (APC/C) ubiquitin ligase [1]. In mitotic cells, two forms of the APC/C exist, APC/C(Cdc20) and APC/C(Cdh1), which differ in their associated WD-repeat proteins (Cdc20 and Cdh1, respectively), time of activation, and substrate specificity [2, 3]. How the WD-repeat proteins contribute to APC/C's activation and substrate specificity is not clear. Many APC/C substrates contain a destruction box element that is necessary for their ubiquitination [4-6]. One such APC/C substrate, the budding yeast anaphase inhibitor Pds1 (securin), is degraded prior to anaphase initiation in a destruction box and APC/C(Cdc20)-dependent manner [3, 7]. Here we find that Pds1 interacts directly with Cdc20 and that this interaction requires Pds1's destruction box. Our results suggest that Cdc20 provides a link between the substrate and the core APC/C and that the destruction box is essential for efficient Cdc20-substrate interaction. We also find that Pds1 does not interact with Cdh1. Finally, the effect of spindle assembly checkpoint activation, known to inhibit APC/C function [8], on the Pds1-Cdc20 interaction is examined.

Long-term clinical outcomes and therapeutic benefits of triamcinolone-assisted pars plana vitrectomy for proliferative vitreoretinopathy: a case study.

PURPOSE: To investigate intraoperative visibility and long-term clinical outcome following triamcinolone acetonide (TA)-assisted pars plana vitrectomy (PPV) for proliferative vitreoretinopathy (PVR). METHODS: A retrospective interventional noncomparative clinical study was carried out on 21 eyes from 21 patients with more than grade C2 PVR, all of whom underwent TA-assisted PPV. Two of the specimens were observed with an electron microscope. After treatment, outcome measures, including changes in best-corrected visual acuity (BCVA), intraocular pressure (IOP) elevation, corneal pathology, and occurrence of endophthalmitis, were recorded. Patient follow-up time was >36 months (mean +/-standard deviation = 47.3 +/- 6.7 months). RESULTS: TA improved the intraoperative visualization of the epiretinal membrane (ERM), allowing it to be easily removed together with the partially internal limiting membrane (ILM) using micro forceps. The excised tissue consisted of proliferative cells and an extracellular matrix underlying the ILM. After the operation, 71.4% of the eyes had improved BCVA. Three of the eyes showed sustained IOP elevation (14.3%); two of these cases were controlled by the administration of eyedrops, while the third required filtering surgery. In two cases, an absorption delay of the TA granule on the retinal surface was observed. One eye developed corneal stromal opacity. No other severe complications occurred during the observation period. CONCLUSIONS: TA-assisted PPV offers improved visualization during the surgical management of PVR, and allows surgeons to excise the ERM safely and effectively without the risk of serious complications.

[Surgical technique of displacement and retraction of the heart with a pigtail shaped hook and Tentacles Heart Positioner].

We describe a novel heart retracting system with Tentacles Heart Positioner (Sumitomo Bakelite, Tokyo) during off-pump coronary artery bypass grafting (OPCAB). The heart retracting system is composed of a pigtail shaped hook attached to a flexible Universal Stabilizer Arm (Estech, Minneapolis). After Tentacles suction device is applied on the surface of the heart, the retracting system is fixed on the sternal retracter so that the hook can hang and support the retracting tubes of the sucker. By regulating the shape of the Universal Stabilizer Arm and the position of the hook, the retracting system can lift the heart sufficiently and maintain the optimal position of the heart during OPCAB procedure. Together with Tentacles Heart Positioner, the heart retracting system provides excellent exposure of target coronary arteries with minimal effect on hemodynamics.

Matrical inclusions induced by clofibrate in hepatic microbodies of rats fed 2-acetylaminofluorene.

Abnormal inclusions in microbodies were induced by clofibrate in hepatocytes of hyperplastic liver nodules in rats fed 2-acetylaminofluorene. These were matrical tubules and plates, each with the same ultrastructural features as those reported previously by other investigators. A hyperplastic state of hepatocytes induced by hepatocarcinogens might be related to the formation of these inclusions in response to clofibrate.

Response of microbodies in Morris hepatoma 9618A to clofibrate.

Regulation of the formation of microbodies in Morris hepatoma 9618A was studied by examination of the response of the organelles to clofibrate. The fine structures of microbodies in the hepatoma cells closely resembled those in hepatocytes of normal adult rats. In clofibrate-treated rats, the tumor cells showed a slight increase in the size of microbodies and in catalase activity; however, the tumor microbodies did not increase in number. In contrast, in adult clofibrate-treated rats and rats on the day of birth whose mothers received clofibrate during the gestation period, the hepatocytes showed microbodies that were greater in both number and size, and the catalase activity in the liver was definitely elevated.

Surgical results of combined pars plana vitrectomy, phacoemulsification, and intraocular lens implantation.

PURPOSE: To evaluate the results and complications of combined pars plana vitrectomy (PPV), phacoemulsification and aspiration (PEA), and intraocular lens (IOL) implantation. METHODS: A total of 117 eyes from 114 patients who had undergone PPV combined with PEA and IOL implantation were retrospectively analyzed. Combined surgery was performed for a wide variety of vitreoretinal diseases. Intraoperative and postoperative complications were also reviewed. RESULTS: The postoperative BCVA improved by 2 lines or more in 85 eyes (72.6%). Intraoperative complications consisted of retinal tears in 14 eyes (12.0%) and posterior capsular rupture in 2 eyes (1.7%). Iatrogenic retinal tears occurred more frequently in eyes with a macular hole than in eyes with any other disease (p=0.005, chi-square test). Postoperative complications consisted of posterior capsule opacification (PCO) (21 eyes), transient IOP elevation (29 eyes), vitreous hemorrhage (6 eyes), anterior chamber fibrin exudation (11 eyes), posterior iris synechia (8 eyes), neovascular glaucoma (1 eye), and recurrent retinal detachment (RD) (2 eyes). Fibrin exudation occurred more frequently in eyes with proliferative diabetic retinopathy (PDR) and RD than in eyes with any other disease (p=0.03, chi-square test). PCO occurred more frequently in eyes with PDR than in eyes with any other disease (p=0.03, chi-square test). CONCLUSIONS: The present study suggests that a high success rate can be achieved when recently improved PPV techniques are combined wi th PEA and IOL implantation. The complications that were observed following this combined treatment varied with respect to the vitreoretinal disease present prior to surgery.

Changes in peroxisomes in preneoplastic liver of rats induced by 3'-methyl-4-dimethylaminoazobenzene.

Histochemical investigations used the 3,3'-diaminobenzidine reaction to demonstrate the catalase activity and thus variations in numbers of peroxisomes, and electron microscopic examinations were made of hyperplastic liver lesions in rats fed 0.06%3'-methyl-4-dimethylaminoazobenzene. At the 10th week of carcinogen feeding, hyperplastic lesions (hyperplastic foci, areas, and nodules) appeared and advanced to further stages. Most of the foci and some of the areas and nodules showed very low catalase activity and, correspondingly, a small number of peroxisomes. When rats were administered ethyl-alpha-p-chlorophenoxyisobutyrate, most of the foci, areas, and nodules showed a moderate increase in catalase activity and in peroxisome number. Hyperplastic foci seemed to grow larger with time to form hyperplastic areas and/or nodules, mostly accompanying maturation as well as proliferation of the hepatocytes involved. Maturation is well characterized by an increase in the endogenous level of catalase and in the number of peroxisomes, as well as by an enhancement of the responsiveness to ethyl-alpha-p-chlorophenoxyisobutyrate. However, there was a small proportion of lesions in which all cells or some cells did not mature and thus were considered persistently altered. It is suggested that these altered cells serve mainly as intimate precursors of hepatomas.

Changes in peroxisomes in preneoplastic liver and hepatoma of mice induced by alpha-benzene hexachloride.

Peroxisomes in hepatomas and hyperplastic preneoplastic liver lesions induced in mice by 500 ppm alpha-benzene hexachloride were examined histochemically and electron microscopically. Although most of the hepatomas were well-differentiated tumors and contained a considerable number of peroxisomes, the tumor cells did not respond to ethyl-alpha-p-chlorophenoxyisobutyrate with proliferation of peroxisomes. At the 16th week of carcinogen feeding, hyperplastic nodules appeared and advanced to further stages. A majority of the nodules showed a considerable number of peroxisomes and the inductive proliferation of peroxisomes. Within the nodules, foci of proliferation of the cells that showed no inducibility of proliferation of peroxisomes appeared. These cells proliferated further, replacing the most part of the nodules, and with this process hepatomas appeared to have been formed. No abnormal matrical inclusions of peroxisomes were formed in the cells of hyperplastic nodules by ethyl-alpha-p-chlorophenoxyisobutyrate unlike in the case of rats.

Effect of age on the formation of small-cell colonies in cultures of primary rat hepatocytes.

The proliferation of primary cultured rat hepatocytes was observed in serum-free modified Dulbecco's modified Eagle's medium supplemented with 10 mM nicotinamide and 10 ng/ml of epidermal growth factor. These proliferating cells were mainly mononucleate and formed small-cell colonies after Day 4. The small cells in focal colonies were surrounded by typical hepatocytes and were stained immunocytochemically with anti-rat albumin and anti-cytokeratin 8 antibodies. This suggests that the cells in the small-cell colonies were derived from hepatocytes. The frequency of appearance of small-cell colonies with age was examined by the use of primary cultured hepatocytes isolated from the livers of rats between the ages of 3 wk and 90 wk. In the cells from 4- to 5-wk-old rats, about 58 colonies per 1000 attached cells appeared 144 h after plating; the number of colonies rapidly decreased to about 25 in 6- to 8-wk-old rats. In adult rats, about 17 colonies were seen, and only about five colonies were observed in rats more than 80 wk old.

Immortal epithelial cells of normal C3H mouse liver in culture: possible precursor populations for spontaneous hepatocellular carcinoma.

Long-term culture of primary hepatocytes derived from normal young male C3H/HeNJclMTV+ (C3H) and C57BL/6NJcl (C57) mice, respectively known for very high and low incidences of spontaneous hepatoma, resulted in development of multiple slowly growing epithelial colonies in the C3H case, the number of colonies being increased five-fold when 1.5 mM phenobarbital was added to the culture medium. On the other hand, the primary culture cells from C57 mouse liver gave rise to such epithelial colonies only very rarely, even with phenobarbital. Immunohistochemical investigation revealed alpha-fetoprotein and/or albumin production by the colony cells and ultrastructural analysis also revealed some hepatocytic features in them. Subculturing of individual colonies gave rise to cell lines which could be repeatedly passaged. Two of five lines implanted into athymic nude mice manifested tumorigenicity, the resultant neoplasms being diagnosed as a trabecular hepatocellular carcinoma and an adenocarcinoma. The experimental data suggest that the colony-forming immortal epithelial cells possibly represent early phase precursors of spontaneous mouse hepatocellular carcinomas. This culture system is expected to be useful for future elucidation of the mechanisms underlying spontaneous mouse hepatocarcinogenesis.