Functional outcome and general health status in patients after arthroscopic release in adhesive capsulitis

Frozen shoulder is said to be a self-limiting entity but full recovery often takes more than 2 years. For that, most patients are unwilling to tolerate painful restriction while awaiting resolution. We prospectively investigated 30 patients (16 women, 14 men) for the outcome of arthroscopic capsular release in idiopathic frozen shoulder. Results were determined by the assessment of subjective and objective parameters to estimate both shoulder function and general health status. Symptoms persisted without improvement for a minimum of 6 months of conservative treatment. Preoperative average American shoulder and elbow surgeons score (ASES) was 35, visual analog scale (VAS) to measure pain was 7, and simple shoulder test (SST) was 4. Mean scores of the physical component of SF-36 were considerably reduced. Mean forward elevation was 85°, average abduction was 70°, mean internal rotation was 15°, and mean external rotation was 10°. Patients were followed-up at 6 weeks, 3, 6, 12 months and by a mean of 36 months. Range of motion for all planes improved (P < 0.05). Median VAS reduced to 2, average ASES increased to 91, and SST enhanced to a mean of 10 (P < 0.05). We stated improvement of the physical components in the SF-36 questionnaire in particular bodily pain and the role-physical score. There were no significant differences between the measurements in the early postoperative phase compared to the mid-term follow-up (P > 0.05). Our results demonstrate that arthroscopic release of refractory idiopathic frozen shoulder combined with a gentle manipulation provides reliable expectations for improvement in both clinical and general health status for most patients. We recommend the use of a limb-specific and a general-health-status questionnaire to conclude the benefit of the surgical intervention and contribute the optimization of a therapy concept more effectively.     

A Tissue-Engineered Artificial Bile Duct Grown to Resemble The Native Bile Duct

The aim of this study was to fabricate an artificial bile duct for the development of a new treatment for biliary diseases. Eighteen hybrid pigs were implanted with a bile duct organoid unit (BDOU) made of a bioabsorbable polymer. Twelve of the transplanted BDOUs had been seeded with autologous bone marrow cells (BMCs) in advance. Six animals, the controls, were grafted with the scaffold alone with no BMCs seeded. The common bile duct was cut, the hepatic cut end of the native common bile duct was anastomosed to the BDOU and the other end was anastomosed to the duodenum. The controls underwent a similar operation. The neo-bile duct was removed at pre-determined time points and investigated histologically. All 18 recipient pigs survived until their sacrifice at 6 weeks, 10 weeks or 6 months. Histological examination revealed incomplete epithelialization of the neo-bile duct at 6 weeks and 10 weeks after transplantation. At 6 months, the organoid exhibited a morphology almost identical to that of the native common bile duct. No differences were found between the controls and BMC-seeded pigs. These results show that the artificial bile duct thus fabricated can serve as a substitute for the native bile duct.     

Excess caloric intake induced severe hypercapnia in a patient with Duchenne muscular dystrophy on noninvansive positive pressure ventilation]

In many patients with neuromuscular diseases, respiratory failure is mainly caused by alveolar hypoventilation in their terminal stages. Malnutrition is one of the common and serious problems in patients with chronic respiratory failure. Energy consumption for breathing is remarkably high in respiratory compromised patients, causing subsequent increase of total energy expenditure. However, most patients have limited capacity of oral intake. Nutritional depletion is associated with wasting of respiratory muscles, impairment of respiratory drive, alteration of respiratory pattern, and pathological change of pulmonary parenchyma. These indicate that nutritional and ventilatory support is very important in these patients. However, overfeeding also may have detrimental influence on respiratory failure. We experienced a Duchenne muscular dystrophy (DMD) patient on noninvasive positive pressure ventilation (NIPPV) who developed hypercapnia after total parenteral nutrition (TPN). Analysis of clinical course of this patient revealed that there is a significant correlation between PaCO2 and caloric intake. Excess carbohydrate intake can precipitate fat synthesis which induces over-production of carbon dioxide (CO2). Since NIPPV doesn't have a closed circuit, there are some difficulties in respiratory management, such as air leakage to stomach and mouth, and airway obstruction. Failure to optimize NIPPV setting against increased CO2 load might cause hypercapnia in this patient. These suggest that evaluation of energy expenditure and design of nutritional program are essential to avoid hypercapnia due to nutritional support.     

A case of cleidocranial dysostosis associated with arachnoid cyst

Cleidocranial dysostosis (CCD) is a rare congenital disorder characterized by the heredity, the disturbance of the ossification of the skull and clavicles, and dental anomaly. The entity of CCD was established by Marie and Sainton in 1898. In Japan about 150 cases have been reported since Haneda's first report in 1933. Recently we experienced a rare case of CCD associated with the temporal arachnoid cyst. The patient was a 61-year-old male who had suffered from mild spastic paresis of the left upper extremity since his childhood. One morning he suddenly noticed motor weakness of the left upper and lower extremities and was transferred to our hospital. On admission we observed the left hemiparesis (MMT 3/5), the left central type facial palsy, and the left long tract signs. Physical examination disclosed frontal bossing, depression of the forehead, sloped shoulders, cone-shaped thorax, and thoracic scoliosis. Plain skull radiograph showed persistent metopic suture and frontal fontanelle, many wormian bones around coronal and lambdoid sutures. Plain radiographs of the systemic bones also showed typical features of CCD such as dysplasia of the lateral third of the bilateral clavicles, deformities of the cervical vertebral bodies, thoracic scoliosis, and wide symphysis. CT scan disclosed the right putaminal hemorrhage, the right temporal arachnoid cyst, enlargement of the right middle fossa, thinning of the temporal bone adjacent to the arachnoid cyst. It also showed the atrophy of the right cerebral peduncle and midbrain. Surgical treatment was performed to remove the hematoma and release the cyst. Several neurological disorders associated with CCD have been reported such as epilepsy, mental retardation, spastic paresis etc.(ABSTRACT TRUNCATED AT 250 WORDS)     

Microarray analysis on Phase II drug metabolizing enzymes expression in pregnant rats after treatment with pregnenolone-16alpha-carbonitrile or phenobarbital

We previously reported the expression profiles of 9 cytochrome P450 isozymes (CYPs) proteins and those of 40 CYPs genes in pregnant rat's liver, placenta and fetal liver after treatment with pregnenolone-16alpha-carbonitrile (PCN) or phenobarbital (PB). This study was carried out focusing on the gene expression profiles of Phase II drug metabolizing enzymes, Glutathione S-transferase isozymes (GSTs) and UDP-glycosyltransferase isozymes (UDPGTs). Fischer 344 (F344) pregnant rats were daily treated intraperitoneally with 50 mg/kg of PCN or 80 mg/kg of PB from 13 to 16 days of gestation (DG). They were sacrificed on 17 DG, and microarray analysis using Affymetrix Rat Expression Array 230 A was performed. Among 16 GSTs genes examined in this study, 7 genes were significantly induced in dam's liver and 3 genes in fetal liver, respectively, in the PCN-group, while 8 genes were significantly induced in dam's liver and 1 gene in fetal liver, respectively, in the PB-group. On the other hand, among 11 UDPGTs genes examined, 5 genes were significantly induced in dam's liver and 3 genes in fetal liver, respectively, in the PCN-group, while 5 genes were significantly induced in dam's liver and 1 gene in fetal liver, respectively, in the PB-group. There were no significant changes in the placenta of all groups. This is the first report of the gene expression profiles of Phase II drug metabolizing enzymes in pregnant rat and fetal livers and placenta after treatment with typical inducers of drug metabolizing enzymes.     

Human serum albumin incorporating synthetic heme: red blood cell substitute without hypertension by nitric oxide scavenging

The administration of extracellular, hemoglobin-based oxygen carriers often elicits an acute increase in blood pressure by vasoconstriction. This side effect is now recognized to be due to the depletion of nitric oxide (endothelial-derived relaxing factor) by the extravasuated hemoglobins. We have recently found that the administration of a recombinant human serum albumin (rHSA)-based oxygen carrier involving synthetic tetraphenyporphinatoiron(II) derivative (FeP) (rHSA-FeP) does not induce such hypertensive action, because of its low permeability through the vascular endothelium. The heart rate responses after the rHSA-FeP injection were also negligibly small. Visualization of the intestinal microcirculatory changes clearly revealed the widths of the venule and arteriole to be fairly constant. The entirely synthetic rHSA-FeP becomes a promising material as a new type of red blood cell substitute.     

Inhibition of BMP-induced ectopic bone formation by an antiangiogenic agent (epigallocatechin 3-gallate)

Epigallocatechin 3-gallate (EGCG), which is one of the components of green tea, was recently shown to inhibit endothelial cell growth in vitro and angiogenesis in vivo [5]. We have previously shown that bone and cartilage formation by bone morphogenetic protein (BMP) is highly dependent on the geometry of the carrier (vasculature-inducing or -inhibiting geometry [2]. To verify the function of angiogenesis in the BMP induction system, we examine in this article whether inhibition of angiogenesis enhances chondrogenesis and suppresses osteogenesis. Fibrous glass membrane used as a BMP carrier was mixed with 1.2 micrograms rhBMP-2 and 1-10 micrograms of EGCG and was implanted into rats subcutaneously. As the dose of EGCG increased, alkaline phosphatase activity and calcium content were decreased, whereas the type II collagen content was increased. The results clearly indicated that inhibition of vascularization enhanced chondrogenesis and suppressed osteogenesis.     

Synergism between interleukin-11 and bone morphogenetic protein-2 in the healing of segmental bone defects in a rabbit model.

Recombinant human interleukin-11 (rHuIL-11) and recombinant human bone morphogenetic protein-2 (rHuBMP-2) have been shown to act synergistically in the induction of osteoblast differentiation. To determine whether these two proteins can be used clinically in fracture healing and reconstructive surgery, we investigated whether rHuIL-11 and rHuBMP-2 act synergistically to heal segmental bone defects in a rabbit model. A 1.5-cm segmental defect was created in the right ulnar diaphysis of 20 Japanese white rabbits. Polylactic-co-glycolic acid (PLGA)-coated gelatin sponges (PGS) permeated with rHuBMP-2 (n = 8), rHuIL-11 plus rHuBMP-2 (n = 8), or rHuIL-11 (n = 4) were implanted into the bone defects. Radiographs were scored by two independent observers for bone formation and union rates after 2, 3, 4, and 8 weeks. Bone formation was higher in rabbits implanted with rHuBMP-2 plus rHuIL-11 than in those implanted with rHuBMP-2 alone, reaching statistical significance after 4 weeks. At early time points, the union rate in rabbits implanted with rHuBMP-2 plus rHuIL-11 was higher than in rabbits implanted with rHuBMP-2. At 2, 4, and 8 weeks, new bone volume was significantly higher in rabbits administered rHuIL-11 plus rHuBMP-2 than in those given rHuBMP-2 alone. In contrast, mechanical testing after 8 weeks showed that bone strength in the two groups of rabbits was equivalent. These findings show that rHuIL-11 and rHuBMP-2 act synergistically to accelerate bone formation without affecting bone strength. Treatment with a combination of rHuIL-11 and rHuBMP-2 may thus be of great benefit in fracture healing and for patients undergoing reconstructive surgery.     

Whole genome association study of rheumatoid arthritis using 27 039 microsatellites

A major goal of current human genome-wide studies is to identify the genetic basis of complex disorders. However, the availability of an unbiased, reliable, cost efficient and comprehensive methodology to analyze the entire genome for complex disease association is still largely lacking or problematic. Therefore, we have developed a practical and efficient strategy for whole genome association studies of complex diseases by charting the human genome at 100 kb intervals using a collection of 27,039 microsatellites and the DNA pooling method in three successive genomic screens of independent case-control populations. The final step in our methodology consists of fine mapping of the candidate susceptible DNA regions by single nucleotide polymorphisms (SNPs) analysis. This approach was validated upon application to rheumatoid arthritis, a destructive joint disease affecting up to 1% of the population. A total of 47 candidate regions were identified. The top seven loci, withstanding the most stringent statistical tests, were dissected down to individual genes and/or SNPs on four chromosomes, including the previously known 6p21.3-encoded Major Histocompatibility Complex gene, HLA-DRB1. Hence, microsatellite-based genome-wide association analysis complemented by end stage SNP typing provides a new tool for genetic dissection of multifactorial pathologies including common diseases.