Forgotten denture in a hemiplegic patient.

A 74-yr-old man developed left hemiplegia because of a right middle cerebral artery territory infarction and also had clinical features of dysphagia and speech difficulty. At that time, he complained of neck pain, but the symptom was ignored because he had a nasogastric tube and had been diagnosed with a huge epiglottic cyst that had already shown several symptoms such as severe hoarseness and throat discomfort. A videofluoroscopic swallowing study was planned to find out the cause and the type of dysphagia. On the videofluoroscopic swallowing study, a foreign body was found at the hypopharynx. Surprisingly, it was confirmed as a denture. After removing the denture, the patient's swallowing and speech difficulty were significantly improved. This case emphasizes the need for elderly stoke patients presenting with dysphagia or communication problems to receive more careful history taking and a more complete physical examination, with the cooperation of several clinical departments.

Korean Brain Rehabilitation Registry for rehabilitation of persons with brain disorders: annual report in 2009.

This first annual report provides a description of patients discharged from rehabilitation facilities in Korea based on secondary data analysis of Korean Brain Rehabilitation Registry V1.0 subscribed in 2009. The analysis included 1,697 records of patients with brain disorders including stroke, traumatic brain injury, brain tumor and other disorders from 24 rehabilitation facilities across Korea. The data comprised 1,380 cases of stroke, 104 cases of brain injury, 55 cases of brain tumor, and 58 cases of other brain diseases. The functional status of each patient was measured using the Korean version of the Modified Barthel Index (KMBI). The average change in the KMBI score was 15.9 for all patients in the inpatient rehabilitation facility. The average length of stay for inpatient rehabilitation was 36.9 days. The transfer rates to other hospitals were high, being 62.4% when all patients were considered. Patients with brain disorders of Korea in 2009 and measurable functional improvement was observed in patients. However, relatively high percentages of patients were not discharged to the community after inpatient rehabilitation. Based on the results of this study, consecutive reports of the status of rehabilitation need to be conducted in order to provide useful information to many practitioners.

Mortality after surgery in patients with liver cirrhosis: comparison of Child-Turcotte-Pugh, MELD and MELDNa score.

BACKGROUND/AIMS: This study was aimed at determining the postoperative mortality in patients with cirrhosis by Child-Turcotte-Pugh (CTP), Model for End-stage Liver Disease score (MELD), and Model for End-stage Liver Disease and Serum Sodium Concentration score (MELDNa) systems and to compare the predictability of the scoring systems. METHODS: Analysis was performed on clinical records of 490 patients with cirrhosis who underwent surgery under general anesthesia from January 2003 to December 2008. RESULTS: (i) Ninety-day mortality in patients with CTP A, B, and C class were 2.1, 22.1 and 54.5%, respectively. (ii) Ninety-day mortality according to MELD score was as follows: 6-9, 3.5%; 10-14, 8.9%; 15-19, 14.3%; 20-24, 12.5%; and ≥25, 63.6%. (iii) Ninety-day mortality according to MELDNa score was as follows: 6-9, 1.9%; 10-14, 6.2%; 15-19, 13.2%; 20-24, 20.6%; and ≥25, 50%. (iv) Multivariable analysis showed that emergency surgery, American Society of Anesthesiologist class ≥IV, CTP score ≥7, MELD score ≥10, and MELDNa score ≥10 were independent risk factors for 90-day mortality. (v) The area under the receiver operating curve of CTP, MELD, and MELDNa in predicting 90-day mortality were 0.859, 0.761, 0.818, and nonparametric approach using the generalized U-statistic showed that the CTP score was equal to the MELDNa score (P=0.855) and the CTP and MELDNa scores were superior to the MELD score (P=0.027 and 0.047) in predicting postoperative 90-day mortality. CONCLUSION: Mortality according to the CTP, MELD, and MELDNa scoring systems were determined and all scoring systems predicted postoperative mortality in patients with cirrhosis. The CTP score and MELDNa score were superior to the MELD score in predicting postoperative 90-day mortality.

Stabilizing peptide fusion for solving the stability and solubility problems of therapeutic proteins.

PURPOSE: Protein aggregation is a major stability problem of therapeutic proteins. We investigated whether a novel stabilizing peptide [acidic tail of synuclein (ATS) peptide] could be generally used to make a more stable and soluble form of therapeutic proteins, particularly those having solubility or aggregation problems. METHODS: We produced ATS fusion proteins by fusing the stabilizing peptide to three representative therapeutic proteins, and then compared the stress-induced aggregation profiles, thermostability, and solubility of them. We also compared the in vivo stability of these ATS fusion proteins by studying their pharmacokinetics in rats. RESULTS: The human growth hormone-ATS (hGH-ATS) and granulocyte colony-stimulating factor-ATS (G-CSF-ATS) fusion proteins were fully functional as determined by cell proliferation assay, and the ATS fusion proteins seemed to be very resistant to agitation, freeze/thaw, and heat stresses. The introduction of the ATS peptide significantly increased the storage and thermal stabilities of hGH and G-CSF. The human leptin-ATS fusion protein also seemed to be very resistant to aggregation induced by agitation, freeze/thaw, and heat stresses. Furthermore, the ATS peptide greatly increased the solubility of the fusion proteins. Finally, pharmacokinetic studies in rats revealed that the ATS fusion proteins are also more stable in vivo. CONCLUSION: Our data demonstrate that a more stable and soluble form of therapeutic proteins can be produced by fusing the ATS peptide.

Effects of novel peptides derived from the acidic tail of synuclein (ATS) on the aggregation and stability of fusion proteins.

The acidic tail of alpha-synuclein (ATSalpha) has been shown to protect the glutathione S-transferase (GST)-ATSalpha fusion protein from environmental stresses, such as heat, pH and metal ions. In this study, we further demonstrated that the introduction of ATSalpha into other proteins, such as dehydrofolate reductase and adiponectin, renders the fusion proteins resistant to heat-induced aggregation and that the acidic tail of beta- or gamma-synuclein can also protect the fusion proteins from heat-induced aggregation. Interestingly, the heat resistance of GST-ATSalpha deletion mutants, which contain shorter peptides derived from the highly charged regions of ATSalpha, was approximately proportional to the number of added Glu/Asp residues. However, the negative charges in the ATSalpha-derived peptides appear insufficient to explain the extreme heat resistance of the fusion proteins, since polyglutamates appeared to be much less effective than the ATSalpha-derived peptides in conferring heat resistance on the fusion proteins. These results suggest that not only the negatively charged residues but also the specific amino acid sequence of ATSalpha play an important role in conferring extreme heat resistance on the fusion proteins. Furthermore, the heat-induced secondary structural changes and thermal inactivation curves of GST-ATSalpha deletion mutants indicated that the introduction of ATSalpha-derived peptides does not significantly affect the intrinsic stability of the fusion proteins.

Distinct roles of the N-terminal-binding domain and the C-terminal-solubilizing domain of alpha-synuclein, a molecular chaperone.

alpha-Synuclein, an acidic neuronal protein of 140 amino acids, is extremely heat-resistant and is natively unfolded. Recent studies have demonstrated that alpha-synuclein has chaperone activity both in vitro and in vivo, and that this activity is lost upon removing its C-terminal acidic tail. However, the detailed mechanism of the chaperone action of alpha-synuclein remains unknown. In this study, we investigated the molecular mechanism of the chaperone action of alpha-synuclein by analyzing the roles of its N-terminal and C-terminal domains. The N-terminal domain (residues 1-95) was found to bind to substrate proteins to form high molecular weight complexes, whereas the C-terminal acidic tail (residues 96-140) appears to be primarily involved in solubilizing the high molecular weight complexes. Because the substrate-binding domain and the solubilizing domain for chaperone function are well separated in alpha-synuclein, the N-terminal-binding domain can be substituted by other proteins or peptides. Interestingly, the resultant engineered chaperone proteins appeared to display differential efficiency and specificity in terms of the chaperone function, which depended upon the nature of the binding domain. This finding implies that the C-terminal acidic tail of alpha-synuclein can be fused with other proteins or peptides to engineer synthetic chaperones for specific purposes.