A smartphone-based medication self-management system with realtime medication monitoring.

BACKGROUND: Most patients cannot remember their entire medication regimen and occasionally forget to take their medication. OBJECTIVES: The objective of the study was to design, develop, and demonstrate the feasibility of a new type of medication self-management system using smartphones with real-time medication monitoring. METHODS: We designed and developed a smartphone-based medication self-management system (SMSS) based on interviews of 116 patients. The system offered patients two main functions by means of smartphones: (1) storage and provision of an accurate, portable medication history and medication-taking records of patients; and (2) provision of a reminder to take medication only when the patient has forgotten to take his/her medication. These functions were realized by two data input methods: (a) reading of prescription data represented in two-dimensional barcodes using the smartphone camera and getting the photographic images of the pills; and (b) real-time medication monitoring by novel user-friendly wireless pillboxes. RESULTS: Interviews suggested that a pocket-sized pillbox was demanded to support patient's medication-taking outside the home and pillboxes for home use should be adaptable to the different means of pillbox storage. In accordance with the result, we designed and developed SMSS. Ten patients participated in the feasibility study. In 17 out of 47 cases (36.2%), patients took their medication upon being presented with reminders by the system. Correct medication-taking occurrence was improved using this system. CONCLUSIONS: The SMSS is acceptable to patients and has the advantage of supporting ubiquitous medication self-management using a smartphone. We believe that the proposed system is feasible and provides an innovative solution to encourage medication self-management.

IL28B polymorphism may guide pegylated interferon plus ribavirin therapy even after curative treatment for hepatitis C virus-related hepatocellular carcinoma.

The present study was designed to determine the predictive factors for the viral response to pegylated interferon-alpha plus ribavirin combination therapy (PEGIFN/RBV) administered after curative treatment for hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC). The study group was 78 patients treated between January 2005 and January 2009. The sustained viral response (SVR) rate was 25.8% (15/58) in patients infected with HCV-genotype 1 and 55.0% (11/20) in those with genotype 2. Among the 78 patients, 32 (41.0%) could not complete the treatment protocol, and this was because of HCC recurrence in 17 (53%) of them. Multivariate analysis identified partial early viral response (pEVR) as the only independent determinant of SVR [odds ratio (OR) 14.73, P = 0.013] for patients with genotype 1. Multivariate analysis identified male gender (OR 8.72, P = 0.001) and interleukin-28B (IL-28B) genotype (rs8099917) TT (OR 7.93, P = 0.007) as independent predictors of pEVR. Multivariate analysis also identified IL-28B genotype GG+TG (OR 14.1, P = 0.021) and α-fetoprotein >30 (OR 5.4, P = 0.031) as independent predictors of null response. Patients with SVR showed a better survival rate than those without SVR (P = 0.034). The second HCC recurrence rate tended to be lower in patients with SVR than in those without SVR (P = 0.054). With regard to the prognosis of patients with SVR, it is desirable to achieve SVR with interferon therapy even when administered after HCC treatment. IL-28B genotype is a potentially useful marker for the response to PEGIFN/RBV therapy administered after curative treatment of HCV-related HCC.

Living-donor liver transplantation at the University of Tokyo, 1996-2011: the impact of HLA matching and a positive crossmatch on long-term survival and tolerance.

OBJECTIVE: We analyzed a single center's experience during 16 years of living-donor liver transplantation (LDLT). The impacts of HLA mismatches and positive crossmatches on long term outcomes and tolerance were evaluated. METHODS: This study was of primary LDLTs of consecutive patients from January 1996 to December 2011; re-transplants were not included. Long-term survival was compared by primary disease, number of HLA mismatches, and crossmatches. Demographics and complications after transplantation between pediatric recipients who achieved clinical operational tolerance and those who did not were compared. RESULTS: One-year liver graft survival rates for adult and pediatric cases were 90.4% and 91.9%, respectively; the 5-year rates were 83.1% and 89.2%, respectively; the 10-year rates were 79.7% and 89.2%, respectively; and 15-year rates were 65.9% and 83.8%, respectively. For the grafts that survived more than one year, the 10-year rates for adult and pediatric cases were 88.2% and 97.0%, respectively. The 10-year rates for adult LDLT in 0 mismatches, 1-2 mismatches, 3-4 mismatches, and 5-6 mismatches were 79.2%, 86.8%, 77.4%, and 69.4%, respectively. Although the survival rates were not significantly different, the survival rates were lowest in LDLT recipients with 5-6 HLA mismatches. Ten-year liver graft survival rates for adult LDLT with negative T-cell crossmatch, and positive T-cell crossmatch were 80.0% and 71.1%, respectively. The 1-year liver graft survival rates for adult LDLT with negative B-cell crossmatch, and positive B-cell crossmatch were 90.6% and 88.2%, respectively. None of the factors--age of recipients and donors, primary disease, donor gender, relationship of donors to recipients, positive crossmatches, or number of HLA mismatches--was significantly different between COT and non-COT recipients, except for recipient gender (p = 0.01); in COT cases, there were more female recipients (88.9%) than male (11.1%). Post-transplant complications--acute rejection rate in one year post-transplant, biliary complications rate, and vascular complication rate--were not significantly different between COT and non-COT recipients. CONCLUSIONS: High long-term survival was achieved by both adult and pediatric recipients. Even higher survival can be achieved by improving early graft loss. Further studies are necessary to determine the impact of HLA mismatches and positive crossmatches on long-term outcomes and tolerance.

Simultaneous pancreas-kidney transplantation in the United States: an analysis of the UNOS registry.

The rate of chronic pancreas graft loss in simultaneous pancreas kidney transplantation has remained almost unchanged despite induction therapy. Since 1987, seven major immunosuppressive induction agents-basiliximab, daclizumab, ALG, eATG, OKT 3, alembuzumab, rATG-have been used as immunosuppressive induction agents. Those agents improved short-term survival by preventing acute rejection, but improvement of short-term survival has not translated into improved long-term graft survival. As with most solid organ transplants, there is a need for means to control chronic rejection to improve long-term graft survival.

No improvement in long-term liver transplant graft survival in the last decade: an analysis of the UNOS data.

We analyzed change in outcomes during two successive 5-year periods (period I = 1992-1996 vs period II = 1997-2002) among 35 186 deceased adult liver transplant recipients reported to the United Network for Organ Sharing (UNOS) Registry. The 5-year graft survival was 67.4% in the first period and 67.5% in the second, though the 1-year survival had improved from 81.0 to 83.5%. Comparison of blended survival rates during the two study periods showed decreased long-term graft survival in period II, explicable by an increased number of hepatitis C virus cirrhosis (HCV) patients and an increase in patients with HCV antibodies (HCVab) during this later period. Analysis wherein these patients with HCV were excluded revealed the same long-term graft survival during both periods. Non-HCV patients who had HCVab also had worse 5-year graft survival. We conclude that hepatitis C prevented improved outcomes during period II and that improved, more effective, treatment for hepatitis C virus would have great positive impact on overall survival of liver transplant recipients.

Antisense transcription in the mammalian transcriptome.

Antisense transcription (transcription from the opposite strand to a protein-coding or sense strand) has been ascribed roles in gene regulation involving degradation of the corresponding sense transcripts (RNA interference), as well as gene silencing at the chromatin level. Global transcriptome analysis provides evidence that a large proportion of the genome can produce transcripts from both strands, and that antisense transcripts commonly link neighboring "genes" in complex loci into chains of linked transcriptional units. Expression profiling reveals frequent concordant regulation of sense/antisense pairs. We present experimental evidence that perturbation of an antisense RNA can alter the expression of sense messenger RNAs, suggesting that antisense transcription contributes to control of transcriptional outputs in mammals.

Alcohol consumption and other risk factors for self-reported diabetes among middle-aged Japanese: a population-based prospective study in the JPHC study cohort I.

AIMS: Few prospective studies have examined the relationship between lifestyle characteristics and the incidence of diabetes mellitus in an Asian general population. This study was undertaken to evaluate the risk factors for Type 2 diabetes in a population-based prospective study of middle-aged Japanese. METHODS: We investigated 12,913 men and 15,980 women, aged 40-59 years at baseline (year 0), who participated in the Japan Public Health Center-based prospective study on cancer and cardiovascular diseases (JPHC Study) Cohort I. The participants were followed for up to 10 years. Incident cases of diabetes were identified by self-reporting of a physician's diagnosis on two questionnaires sent to each participant, one at year 5 and the second at year 10. RESULTS: During the 10-year follow-up, 703 men and 482 women reported newly diagnosed diabetes. Age, body mass index (BMI), family history of diabetes and cigarette smoking were independent risk factors in both genders by multivariate analysis. Among men with a BMI < or = 22 kg/m2, a significant positive association was observed between the diabetes incidence and moderate (23.0 < 46.0 g/day) to high (> 46.0 g/day) alcohol consumption, odds ratio 1.91 (95% CI, 1.05-3.46) and 2.89 (1.63-5.11), respectively. Among men with a BMI > 22 kg/m2, a small non-significant increase in odds ratio was observed with alcohol consumption. CONCLUSIONS: Established risk factors for diabetes in western populations were also identified as predictors of the disease among Japanese. Moderate to high alcohol consumption was positively associated with the incidence of diabetes in Japanese lean (BMI < or = 22 kg/m2) men.

Effects of antioxidants on X-ray- or hyperthermia-induced apoptosis in human lymphoma U937 cells.

Hydroxyl radicals (.OH) and superoxide anion radicals (O2.-) are known to play cardinal roles in cell killing and various types of cell damage. In order to elucidate the mechanism of the involvement of both free radicals on apoptosis, the correlation between anti-apoptotic effects and free radical scavenging abilities of anti-oxidants was studied. As an indicator of anti-apoptotic effects, C1/2 (antioxidant concentration to inhibit DNA fragmentation by 50%) was evaluated in human lymphoma cell line U937 cells 6 hr after X-ray (10 Gy) or hyperthermia (44 degrees C, 30 min) treatment. Rate constants of the reactions between antioxidants and .OH or O2.- were calculated as the scavenging ability of the antioxidants with graded concentration estimated by EPR spectroscopy. No apparent correlation between C1/2 obtained in apoptosis induced by X-rays or hyperthermia and the rate constants of antioxidants for .OH or O2.- was observed. On the other hand, the partition coefficients in 1-octanol/water of the antioxidants, an indicator of hydrophobicity, revealed a correlation with the C1/2 of the agents with hyperthermia, but not with X-ray irradiation. These results indicate that the prevention of apoptosis by an antioxidant is not simply associated with its scavenging ability for .OH or O2.-. The hydrophobicity of the antioxidant, among other possible factors, is involved in the inhibition of hyperthermia- induced apoptosis.

Cloning of a cDNA encoding EIN3-like protein (DC-EIL1) and decrease in its mRNA level during senescence in carnation flower tissues.

A cDNA clone encoding a putative EIN3-like protein (DC-EIL1) was obtained from total RNA isolated from senescing carnation (Dianthus caryophyllus L.) petals using RT-PCR and RACE techniques. The cDNA (2382 bp) contained an open reading frame of 1986 bp corresponding to 662 amino acids. The amino acid sequence of the N-terminal half of the protein, ranging from 80-300 amino acid residues, had 84% identity with that of the corresponding regions of Arabidopsis EIN3 and tobacco TEIL, although the overall identity was 49% and 52%, respectively. Northern blot analysis revealed that the amount of mRNA corresponding to DC-EIL1 decreased in flower tissues, especially in petals, during natural senescence and senescence induced by exogenously applied ethylene or ABA.

Morphology of the human atrioventricular node is age dependent: a feature of potential clinical significance.

INTRODUCTION: Advances in catheter ablation procedures have created the need to understand better the morphology of the AV node (AVN), particularly as it relates to age. METHODS AND RESULTS: This study was based on 40 normally structured hearts obtained at autopsy from patients without a history of tachyarrhythmia in the following age ranges: < 1 year (n = 19); 1-12 years (n = 11); and 12-20 years (n = 10). In 38 hearts, the AV septal junctional area was removed en bloc and serially sectioned at 10-microm thickness at right angles to the AV annulus. The length of the compact node and the rightward and leftward inferior extensions were calculated. Computer-assisted three-dimensional reconstructions were made of six hearts. The ratio of right extension to compact AVN showed a statistically significant increase with age; the increase in ratio of left extension to compact AVN was not statistically significant. In addition, with increasing age the geometry of the AVN changed from a half-oval to a spindle shape, concomitant with development of a distinct so-called muscular AV septum. The three-dimensional reconstructions showed widening of the transitional cell zone with an increase in fibrofatty tissue related to age. CONCLUSION: The AVN, inferior extensions, and transitional cell zone show distinct age-related changes that may be clinically relevant. The increase in length of the inferior extensions may set the scene for AVN reentry and could explain why this condition is more frequent in young adults than in infants.

Photooxidation mechanism of nitrogen-containing compounds at TiO2/H2O interfaces: an experimental and theoretical examination of hydrazine derivatives.

The photocatalytic oxidation of oxalyldihydrazide, N,N'-bis(hydrazocarbonyl)hydrazide, N,N'-bis(ethoxycarbonyl)hydrazide, malonyldihydrazide, N-malonyl-bis[(N'-ethoxycarbonyl)hydrazide] was examined in aqueous TiO2 dispersions under UV illumination. The photomineralization of nitrogen and carbon atoms in the substrates into N2 gas, NH4+ (and/or NO3-) ions, and CO2 gas was determined by HPLC and GC analysis. The formation of carboxylic acid intermediates also occurred in the photooxidation process. The photocatalytic mechanism is discussed on the basis of the experimental results, and with molecular orbital (MO) simulation of frontier electron density and point charge. Substrate carbonyl groups readily adsorb on the TiO2 surface, and the bonds between carbonyl group carbon atoms and adjacent hydrazo group nitrogen atoms are cleaved predominantly in the initial photooxidation process. The hydrazo groups were photoconverted mainly into N2 gas (in mineralization yields above 70%) and partially to NH4 ions (below 10%). The formation of NO3- ions was scarcely recognized.

Left atrial myocardial extension onto pulmonary veins in humans: anatomic observations relevant for atrial arrhythmias.

INTRODUCTION: Electrophysiologic studies have shown that spontaneous initiation of atrial fibrillation (AF) by ectopic beats may originate from within pulmonary veins. The extensions of left atrial myocardium are considered to play a role, but there is little detailed anatomic information available, particularly in humans. METHODS AND RESULTS: Thirty-nine human autopsy hearts were studied; 22 with AF and 17 without atrial arrhythmias. The muscle fiber arrangement of the left atrial wall and pulmonary veins was dissected. In 18 hearts, myocardial sleeves were studied microscopically; in five hearts, three-dimensional reconstruction of the fiber arrangement in the myocardial sleeves was performed. Of 99 pulmonary veins examined, 96 contained a myocardial sleeve. The length of the sleeves was largest in the superior pulmonary veins (P < 0.01). There were no statistically significant differences between uniform and nonuniform muscle fiber arrangements. Microscopic evaluation revealed myocardial sleeves positioned on the adventitial side of the pulmonary vein, separated from the muscular media by a fibrofatty tissue plane. The most distal zone of the myocardial sleeves showed increasing fibrosis with encapsulation of small groups of myocardial cells and eventually with total disappearance of atrophic cells within fibrous tissue. Node-like structures were not encountered. There was no relationship with presence or absence of AF. CONCLUSION: The observation that the peripheral zones of myocardial sleeves are associated with increasing connective tissue deposition between myocardial muscle groups suggests a degenerative change that, from the histologic viewpoint, fits with progressive ischemia. These changes could provide a basis for microreentry and, hence, for atrial arrhythmias.

Right atrial flutter isthmus revisited: normal anatomy favors nonuniform anisotropic conduction.

INTRODUCTION: The "flutter isthmus," the part of the lower right atrium between the eustachian valve and the tricuspid annulus inferior to the coronary sinus os, is considered the crucial zone for conduction delay necessary for the genesis of atrial flutter. However, the underlying mechanism remains unclear. METHODS AND RESULTS: We studied the "flutter isthmus" in 50 hearts obtained at autopsy from patients without atrial tachyarrhythmias. The muscular trabecular arrangement was dissected carefully by peeling off the endocardium. Documentation of the trabecular arrangement focused, in particular, on the question of whether there was a uniform pattern of well-aligned muscle trabeculae or a nonuniform architecture. It appeared that a nonuniform trabecular pattern prevailed (37/50 [74%]). In these hearts, the muscular arrangement showed abundant cross-overs and interlacing trabeculae, particularly in the zone immediately inferior to the coronary sinus os. Connections also occurred along the inferior rim of the os. CONCLUSION: The normal anatomy of the lower right atrium favors nonuniform muscular trabeculation, with interlacing bundles and a multitude of cross-overs. The potential for conduction delay is present in the vast majority of normal hearts. This raises the question as to what has changed in the hearts of patients with atrial flutter such that the potential for conduction delay and reentry has become effective.

A case of lymphocytic infundibuloneurohypophysitis: histophathological studies.

A 57-year-old woman presented with 2-year history of polyuria and polydipsia. Hormonal studies revealed almost normal anterior pituitary function and central diabetes insipidus. Magnetic resonance imaging showed thickening of the pituitary stalk and enlargement of the neurohypophysis without high intensity of the posterior lobe on T1-weighted images, which were compatible with lymphocytic infundibuloneurohypophysitis. Transsphenoidal biopsy was done and histological examination disclosed moderate fibrosis and lymphocytic infiltration not only in the posterior pituitary, but also in the adjacent anterior pituitary part of the gland. The lymphocytes both in the anterior and posterior pituitary were mainly T cells that were positive for UCHL 1, CD 3, and CD 8. Immunofluorescence of frozen tissue detected immunecomplex deposition in small vessels and the interstitium. These findings suggested that allergic reactions may play an important role in the pathogenesis of lymphocytic infundibuloneurohypophysitis.

Coronary risk factors in acute Kawasaki disease: correlation of serum immunoglobulin levels with coronary complications.

BACKGROUND: To determine the usefulness of the IgG z-score (age and sex-standardized serum IgG level) before intravenous gamma globulin therapy (IVGG) in predicting the occurrence or severity of coronary complications in Kawasaki disease (KD). METHODS: A case-control study of clinical and laboratory findings with 88 children in the early stage of acute KD who received IVGG (100 or 200 mg/kg for 2-5 days) therapy. Of these, 20 cases had persistent coronary arterial lesions (small aneurysm, moderate aneurysm or large aneurysm persisting more than 1 month). The controls comprised 68 children with no coronary aneurysms or transient small aneurysm only observed within 1 month after the onset of KD. The association between serum levels of immunoglobulin G (IgG). IgM, IgA as well as other coronary risk factors previously reported and the occurrence of the coronary arterial lesions was evaluated using logistic regression analysis. RESULTS: After adjustment for age, gender, total IVGG dose before the 9th illness day and other traditional coronary risk factors, the odds ratio for the persistent coronary aneurysm associated with lower serum IgG z-score (< -0.7485 vs > or = -0.7485), was 30.3 (95% confidence interval, 3.8-243.2). Furthermore, the serum IgG z-score was inversely correlated with the severity of the coronary arterial lesion. CONCLUSIONS: The IgG z-score before IVGG therapy in the early stage of KD provides useful information on the risk factors for persistent coronary aneurysm and is a novel, additional indicator for therapy to prevent the coronary complications in acute KD.

Downsizing of an HIV-cell fusion inhibitor, T22 ([Tyr5,12, Lys7]-polyphemusin II), with the maintenance of anti-HIV activity and solution structure.

T22 ([Tyr5,12,Lys7]-polyphemusin II) has been shown to have strong anti-human immunodeficiency virus (HIV) activity comparable to that of 3'-azido-2',3'-dideoxythymidine (AZT). T22, an 18-residue peptide amide, takes an antiparallel beta-sheet structure that is maintained by two disulfide bridges. Herein we synthesized several shortened analogs of T22 in order to search for a more suitable lead compound. A 14-residue analog having one disulfide bridge, TW70 (des-[Cys8,13, Tyr9,12]-[D-Lys10, Pro11]-T22), was found to have highly potent activity comparable to that of T22, and to take an antiparallel beta-sheet structure similar to that of T22. This indicates that the molecular size of T22 can be reduced without loss of activity or significant change in the secondary structure, and that TW70 may represent a novel lead compound. Furthermore, modifying the N-terminal alpha-amino group of TW70 with a fluoresceinthiocarbamoyl group, and the epsilon-amino group of D-Lys8 at the turn portion with a 5-aminopentanoyl group remarkably increased the selectivity index (50% cytotoxic concentration/50% effective concentration).

A case of Kawasaki disease with coronary artery aneurysms documenting Yersinia pseudotuberculosis infection.

A case of a 5-year-old boy who fulfilled all the criteria for Kawasaki disease (KD) was described. He had associated bilateral coronary artery aneurysms. Our study revealed the isolation of Yersinia pseudotuberculosis in stool cultures, and the elevation and seroconversion of the agglutination antibody titres, and hence he was diagnosed as Y. pseudotuberculosis infection-positive. We also demonstrated the positive mitogenic activity of the culture supernatant of the isolated bacterium from the patient and detected Y. pseudotuberculosis-derived mitogen by PCR. This case therefore suggests that Y. pseudotuberculosis might be closely related to the cause of KD.

Treatment of children with congenital heart disease and growth retardation with recombinant human growth hormone.

Seven prepubertal short children with congenital heart disease were treated with recombinant human growth hormone (GH). Although complete surgical correction was performed for their heart disease at least 2 years before the start of GH therapy, improvement in growth was less than expected in these children. They received 0.5 IU kg-1 week-1 of GH daily for 2 years or more. The growth rate increased from a mean of 4.3 cm year-1 before treatment to a mean of 7.8 cm year-1 in the first year and to a mean of 6.3 cm year-1 in the second year of treatment. Their mean standardized height improved from -3.41 +/- 0.78 to -2.54 +/- 0.62 after 2 years. The mean height age difference minus the bone age difference became positive in these children. We conclude that recombinant GH increases the growth rate in children with congenital heart disease and prepubertal growth retardation.