Systematic review of visual rehabilitation interventions for oculomotor deficits in patients with brain injury.

Purpose: Secondary to brain injury, many people develop eye movement disorders (oculomotor deficits). To clarify, optimize, and standardize the development of oculomotor rehabilitation programs, we systematically reviewed the literature on vision rehabilitation interventions for oculomotor deficits in brain injury, focusing on those with broad clinical feasibility.Materials and Methods: We searched MEDLINE (PubMed), CENTRAL, Scopus, and CINAHL databases for key title terms "oculomotor", "rehabilitation", or a related term, and "brain injury" or a related term in the title or abstract. We excluded case reports of a single patient, studies of non-oculomotor visual deficits, and articles in which the intervention and assessment methods were not explicitly identified.Results: Nine articles were included, six of which utilized computer-based training programs to elicit characteristic fixation, saccades, pursuit, vergence, and accommodative movements. Within the entire sample, interventions ranged from 3 to 10 weeks, and involved 2 to 5 training sessions per week.Conclusions: Oculomotor rehabilitation interventions showed some efficacy in treating patients with brain injury; however, there were very few studies overall. Several eye movement types - fixation, saccades, pursuit, vergence, and accommodation - can be elicited manually by therapists. We eagerly await the development and implementation of new intervention programs for broad-based clinical practice.

Beneficial falls in stroke patients: evaluation using a mixed method design.

Purpose To use a mixed method design to evaluate how clinicians judge falls in stroke patients as a beneficial event, and to identify patient-specific characteristics associated with beneficial falls. Methods The definition of beneficial falls was based on interviews with six experienced clinicians in stroke rehabilitation. Interview data were analyzed using the grounded theory approach, with outcomes used to develop a checklist to judge falls as beneficial. We subsequently used the checklist to identify falls sustained by patients in our rehabilitation unit as beneficial events. The characteristics of beneficial fallers were investigated in this retrospective study. Results According to experienced clinicians, beneficial falls result from patient-specific factors and level of independence. Beneficial falls are not associated with after-effects or a diagnosis of cognitive impairment, do not result in physical injury and post-fall syndrome, and do not alter the course of rehabilitation. These falls are considered to enhance patients' self-awareness of their physical status and abilities. Among the 123 stroke patients who experienced a fall in our study group, 23 patients (18.7%) were identified as beneficial fallers according to our checklist. The majority had a left hemiplegia and perceptual impairments, and were at low risk of recurrent falls and made functional gains during rehabilitation. Conclusions Based on our results, we created a 10-item checklist to differentiate beneficial from adverse falls. This differentiation is important to target fall prevention programs to adverse fallers in rehabilitation units.

Formation mechanism of 2-methyl-2-buten-1,4-diol and 2-methyl-3-buten-1,2-diol from 2-methyl-1,3-butadiene on a head-to-head pivalamidato-bridged cis-diammineplatinum(III) binuclear complex.

Reactions of a pivalamidato-bridged head-to-head (HH) platinum(III) binuclear complex with 2-methyl-1,3-butadiene (isoprene) and p-styrenesulfonate and of an α-pyrrolidonato-bridged HH platinum(III) binuclear complex with p-styrenesulfonate were studied kinetically using UV-vis spectrophotometry and (1)H NMR spectroscopy, and detailed reaction mechanisms are proposed. Pt(III) binuclear complexes react with p-styrenesulfonate in four successive steps with mechanisms similar to that for an HH α-pyridonato-bridged Pt(III) binuclear complex with p-styrenesulfonate. In the case of isoprene, four steps were observed on the basis of UV-vis spectrophotometry. However, the reaction kinetics for steps 1 and 2 correspond to those for the previous reaction system, and those for steps 3 and 4 do not correspond to those for the previous system or to those observed by using (1)H NMR spectroscopy for the present isoprene system. By using UV-vis spectrophotometry, it was shown that isoprene preferentially π-coordinates to the Pt(N(2)O(2)) atom via the double bond adjacent to the methyl group in step 1. In step 2, a second isoprene molecule π-coordinates to the Pt(N(4)) atom, which is the rate-determining step, followed by nucleophilic attack of a water molecule on the π-coordinated isoprene on the Pt(N(2)O(2)) atom to form two isomeric σ-complexes. In the same step, π-coordinated isoprene on the Pt(N(4)) atom of the σ-complexes is released. This is different from the reaction of the Pt(III) binuclear complexes with other olefins. In step 3, reductive elimination of the σ-complexes occurs to form two diols and the HH pivalamidato-bridged Pt(II) binuclear complex. Finally, acid decomposition of the Pt(II) binuclear complex occurs to form monomers in step 4. From (1)H NMR spectroscopic observations, fast isomerization between σ-complexes and reductive elimination of the σ-complexes occurs in step 3, and isomerization from a 1,4-diol to a 1,2-diol occurs in step 4.

Transcription and reverse transcription of artificial nucleic acids involving backbone modification by template-directed DNA polymerase reactions.

Oligodeoxyribonucleotides (ODN) where the phosphodiester linkage had been replaced with an amide-type linker [-CH(2)C=ONH-] or an amine-type linker [-CH(2)CH(2)NH-] were synthesized to investigate the effect of these backbone modifications on polymerase reactions. In addition, a triphosphate analogue of thymidine dinucleotide with the amide-type linker was synthesized and enzymatic insertion of the amide linkage into ODN was attempted using this analogue for the polymerase reaction. Primer extension reactions using three types of thermostable DNA polymerases, KOD(exo-), Vent(exo-) and Taq were performed for the assays. Analysis of these data indicate that (i) the polymerase reaction tends to be affected much more by insertion of the cationic flexible amine-type linker than by insertion of the neutral rigid amide-type linker; (ii) the backbone modification has a greater effect on the polymerase reaction when it is adjacent to the 3'-end of a primer as the elongation terminus than when it is on the template, as well as in base or sugar modification; (iii) although the modified linker in the modified DNA template is passed beyond by the polymerase, it still affects the extension reaction several bases downstream from its location; (iv) the modified linker in the template, in some cases, also affects the extension reaction upstream from its location; (v) further improvement of the chemical structure is required for dinucleotide-mimic incorporation.

Smart conferring of nuclease resistance to DNA by 3'-end protection using 2',4'-bridged nucleoside-5'-triphosphates.

Incorporation of 2',4'-bridged nucleotides into the 3'-end of oligodeoxyribonucleotide (ODN) was examined using terminal deoxynucleotidyl transferase (TdT). The three types of 2',4'-bridged nucleoside-5'-triphospates with different bridging structures used were incorporated efficiently into the 3'-end of DNA by TdT, although only single nucleotide incorporation was observed. Nuclease resistance was conferred on DNA, depending on the types of bridging nucleotides added.

Effect of backbone-modification of oligodeoxyribonucleic acid on primer extension reactions.

We synthesized two types of modified DNA templates in which the phosphodiester linkage was replaced with an amide-type linker [-CH(2)C=ONH-] or an amine-type linker [-CH(2)CH(2)NH-]. Primer extension reactions were performed using these modified DNA templates to investigate the effect of backbone modification on polymerase reactions. Our results indicated that the polymerase reaction was affected much more by the insertion of the cationic flexible amine-type linker than by insertion of the neutral rigid amide-type linker.

Systematic analysis of enzymatic DNA polymerization using oligo-DNA templates and triphosphate analogs involving 2',4'-bridged nucleosides.

In order to systematically analyze the effects of nucleoside modification of sugar moieties in DNA polymerase reactions, we synthesized 16 modified templates containing 2',4'-bridged nucleotides and three types of 2',4'-bridged nucleoside-5'-triphospates with different bridging structures. Among the five types of thermostable DNA polymerases used, Taq, Phusion HF, Vent(exo-), KOD Dash and KOD(exo-), the KOD Dash and KOD(exo-) DNA polymerases could smoothly read through the modified templates containing 2'-O,4'-C-methylene-linked nucleotides at intervals of a few nucleotides, even at standard enzyme concentrations for 5 min. Although the Vent(exo-) DNA polymerase also read through these modified templates, kinetic study indicates that the KOD(exo-) DNA polymerase was found to be far superior to the Vent(exo-) DNA polymerase in accurate incorporation of nucleotides. When either of the DNA polymerase was used, the presence of 2',4'-bridged nucleotides on a template strand substantially decreased the reaction rates of nucleotide incorporations. The modified templates containing sequences of seven successive 2',4'-bridged nucleotides could not be completely transcribed by any of the DNA polymerases used; yields of longer elongated products decreased in the order of steric bulkiness of the modified sugars. Successive incorporation of 2',4'-bridged nucleotides into extending strands using 2',4'-bridged nucleoside-5'-triphospates was much more difficult. These data indicate that the sugar modification would have a greater effect on the polymerase reaction when it is adjacent to the elongation terminus than when it is on the template as well, as in base modification.

Arginine-modified DNA aptamers that show enantioselective recognition of the dicarboxylic acid moiety of glutamic acid.

We have screened glutamic acid-binding aptamers from a modified DNA pool containing arginine residues using the method of systematic evolution of ligands by exponential enrichment (SELEX). Thirty-one modified DNA molecules were obtained from the enriched pool after the 17th round of selection, and their binding affinities for the target were evaluated by binding assays using affinity gels. Three modified DNA molecules having higher affinity were sequenced and we determined their affinity and specificity for the target by surface plasmon resonance (SPR) measurements. The SPR studies indicated that two of these three aptamers distinguished the dicarboxylic acid moiety of the D-isomer from that of the L-isomer; however, the third aptamer did not show enantioselectivity.

Polymerisation of a DNA strand using oligo-DNA template with modified bases, sugars and phosphates.

We have attempted to synthesise a complimentary strand using oligo-DNA with modified bases, sugars and phosphates as a template strand by polymerase reaction. Analogues bearing C5-substituted uracil, those with amide linkage [-CH2C=ONH-] in place of phospho-diester linkage and those bearing 2'-O, 4'-C-bridged sugar were used. Primer extension reactions were carried out to synthesise complimentary DNA strands. The reactions depended on the thermostable DNA polymerase used, the type of modification or the number of the modified position on the template strand.

Substrate property and incorporation accuracy of various dATP analogs during enzymatic polymerization using thermostable DNA polymerases.

DNA aptamers and DNAzymes with similar function to antibodies and enzymes can be produced by in vitro selection. They would be useful as research tools for molecular biology and as indicators of specific substances for the analysis of clinical and food samples. Furthermore, development of modified DNA molecules aimed to diversify function and improve activity has recently proceeded by introducing functionalities to these DNA molecules. Such functional modified DNA molecules with an aimed activity screened from a random sequence pool of modified DNA prepared by a polymerase reaction. To enhance potential of selection library and expand diversity of modified DNA that can be synthesized enzymatically, modified analogs of 2'-deoxyadenosine triphosphate were synthesized and their substrate properties for some thermostable DNA polymerases in polymerase chain reactions (PCR) were investigated. Modified DNAs were sequenced in order to analyze incorporation accuracy of modified dATP during PCR.

Systematic characterization of 2'-deoxynucleoside- 5'-triphosphate analogs as substrates for DNA polymerases by polymerase chain reaction and kinetic studies on enzymatic production of modified DNA.

We synthesized C5-modified analogs of 2'-deoxyuridine triphosphate and 2'-deoxycytidine triphosphate and investigated them as substrates for PCRs using Taq, Tth, Vent(exo-), KOD Dash and KOD(exo-) polymerases and pUC 18 plasmid DNA as a template. These assays were performed on two different amplifying regions of pUC18 with different T/C contents that are expected to have relatively high barriers for incorporation of either modified dU or dC. On the basis of 260 different assays (26 modified triphosphates x 5 DNA polymerases x 2 amplifying regions), it appears that generation of the full-length PCR product depends not only on the chemical structures of the substitution and the nature of the polymerase but also on whether the substitution is on dU or dC. Furthermore, the template sequence greatly affected generation of the PCR product, depending on the combination of the DNA polymerase and modified triphosphate. By examining primer extension reactions using primers and templates containing C5-modified dUs, we found that a modified dU at the 3' end of the elongation strand greatly affects the catalytic efficiency of DNA polymerases, whereas a modified dU opposite the elongation site on the template strand has less of an influence on the catalytic efficiency.

A case of benign bile duct stricture causing difficulty in differential diagnosis from bile duct carcinoma.

We report a patient with benign bile duct stricture causing difficulty in differential diagnosis from bile duct carcinoma. A 66-year-old woman consulted a local physician because of general fatigue. Blood biochemical tests showed increased levels of biliary tract enzymes. Abdominal ultrasonography (US) revealed tapering and blockage of the midportion of the bile duct and dilation of the intrahepatic bile ducts. Magnetic resonance cholangiopancreatography (MRCP) demonstrated obstruction of the midportion of the bile duct. Later, because a marked increase in biliary tract enzymes and jaundice appeared, percutaneous transhepatic biliary drainage (PTBD) was performed. Post-PTBD cytological examination of bile was negative for cancer. A third biopsy showed slight hyperplasia with no malignant findings. Recholangiography, performed through PTBD, suggested gradual improvement of bile duct stricture, but could not completely exclude the possibility of malignancy; thus, resection of the bile duct including the stricture site was performed, and the resected specimen was submitted for intraoperative frozen section examination. Histopathological diagnosis did not reveal malignant findings. After cholecystectomy and bile duct resection, hepaticojejunostomy (Roux-en-Y) was performed. Because only erosion and desquamation of the mucosal epithelium and mild submucosal inflammatory cell infiltration and fibrosis were observed, chronic cholangitis was diagnosed histopathologically. Surgical resection of the bile duct should be considered for potentially malignant stricture of the bile duct.

A serous oligocystic adenoma of the head of the pancreas successfully treated by dome resection and chemocautery: a new approach to serous oligocystic adenoma.

Serous oligocystic adenoma (SOA) is an extremely rare benign tumor and ill-demarcated large cyst. We report a case of pancreatic SOA. During abdominal ultrasonography (US) for a routine health examination and computed tomography (CT), a 69-year-old woman was found to have a 9-cm unilocular cyst located in the head of her pancreas. After a 2-year follow up, the cyst was seen to increase in size. The results of US, CT, magnetic resonance imaging, endoscopic retrograde cholangiopancreatography (ERCP), and angiography led to suspicion of a benign or low grade malignancy cystadenoma of the pancreas adjacent to the peripheral organs. Fluid analysis and frozen section pathological studies revealed a serous oligocystic adenoma with no malignancy. Dome resection, chemocautery, and omental filling were performed, and the postoperative course was uneventful. SOAs are difficult to diagnose without surgery. When the cyst exists in the head of the pancreas, adjacent to the biliary tract, portal system, or visceral vessels, it is also difficult to perform complete resection without the threat of morbidity or mortality. We have developed a new approach to SOA diagnosis and treatment that involves minimally invasive procedures.

Surgical treatment for chronic pancreatitis: results of pancreatic duct drainage operation and pancreatic resection.

Between 1978 and 1999, 86 patients with chronic pancreatitis were surgically treated at the Surgical Department of Kurume University Hospital. Of these patients, 30 were treated by pancreatic duct drainage operation (drainage operation), while 40 were treated by pancreatic resection, and the results were compared between the two groups. In patients who underwent drainage operation, pain disappeared in 85.7%, slightly relieved in 10.7%, and not relieved in 3.6%. In patients who underwent pancreatic resection, pain disappeared in 73.4%, slightly relieved in 13.3%, and not relieved in 13.3%. Therefore, there was no significant difference in the pain-relieving effect between the two groups. However, the pain-relieving effect was poorer in patients who underwent pancreatic resection than in those who underwent drainage operation. In addition, all patients who showed poor results for pain relief had alcoholic pancreatitis. Endocrine and exocrine functions of the pancreas were improved in 6, maintained in 2, and exacerbated in 4 patients who underwent drainage operation. In patients who underwent pancreatic resection, endocrine and exocrine function of the pancreas were improved in 3, maintained in 3, and exacerbated in 13. Therefore, endocrine and exocrine function of the pancreas were poorer in patients who underwent pancreatic resection than in those who underwent drainage operation. Distant results in patients who underwent drainage operation were good in 75.0%, fair in 15.0%, and poor in 10.0%. In patients who underwent pancreatic resection, distant results were good in 80.0%, fair in 13.3%, and poor in 6.7%. Therefore, favorable distant results were obtained in both groups. These findings suggest that surgical techniques that preserve functions of the pancreas should be selected during surgical treatment for chronic pancreatitis. We consider that the presence or absence of main pancreatic duct dilation and the site of pancreatic lesions are important indices for selecting surgical techniques. Therefore, drainage operation consisting of pancreaticojejunostomy should be indicated for patients with main pancreatic duct dilation, while pancreatic resection should be indicated for those without main pancreatic duct dilation, those with localized pancreatic lesions, and those with suspected pancreatic cancer.