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.

Successful and long-lasting treatment of solar urticaria with ultraviolet A rush hardening therapy.

BACKGROUND: Solar urticaria (SU) is a photodermatosis that is thought to be caused through the effects of mast cell mediators released because of an altered chromophore, possibly a photoallergen recognized by IgE. Phototherapy for SU to induce a tolerant state appears to be most effective, but is often time consuming and provides only short-lived remission. Ultraviolet (UV) A rush hardening has been successful and less time consuming in serum factor-negative patients with SU. However, the mechanism of action and long-lasting effects of UVA rush hardening therapy remain unclear. OBJECTIVES: We aimed to evaluate whether UVA rush hardening exhibits long-lasting therapeutic effects in serum factor-positive patients with SU and to examine the action mechanism of tolerance. METHODS: Two serum factor-positive patients with SU were exposed to multiple UVA irradiations at 1-h intervals per day for 2 or 3 days. Intradermal injection of their in vitro-irradiated autologous serum or compound 48/80 and a prick test for histamine were performed before and after UVA rush hardening. RESULTS: The two serum factor-positive patients with SU benefited greatly from UVA rush hardening, as documented by a marked increase in minimal wealing dose, and remained symptom free without using sunscreen in their daily life. Intradermal injection of in vitro-irradiated autologous serum induced wealing before hardening, but not in tolerized skin after hardening. The responses to compound 48/80 and histamine were unaltered. CONCLUSIONS: UVA rush hardening is an effective and long-lasting treatment even in serum factor-positive patients with SU. The mechanism of tolerance may involve continued blockade of photoallergen binding to IgE on mast cells, rather than depletion of mast cell mediators or histamine tachyphylaxis.

Enhanced clinical mastitis resistance in Holsteins with a FEZL p.Gly105(12_13) polymorphism.

Mastitis is a common infectious disease of the mammary gland and a major problem in the dairy industry. We previously reported that forebrain embryonic zinc finger-like (FEZL) encoding a stretch of 12 glycines (p.Gly105[12]) instead of 13 glycines (p.Gly105[13]) is associated with a lower somatic cell score (SCS) in a family derived from Walkway Chief Mark. Here we report that the p.Gly105[12] allele is associated with a significantly decreased incidence of clinical mastitis in a large Holstein population. We genotyped the FEZL polymorphism in 918 randomly collected Holstein sires, and investigated the effect of the polymorphism on the estimated breeding value (EBV) for SCS and milk, fat, solids-not-fat, and protein yield, and on the number of cattle with clinical mastitis among daughters derived from these sires. The average EBV for SCS among sires carrying the heterozygous p.Gly105[12] was significantly lower than that among sires carrying the homozygous p.Gly105[13], whereas we found no unfavorable effects of this polymorphism on EBV for milk, fat, solids-not-fat, and protein yield. The proportion of cows with clinical mastitis derived from sires carrying heterozygous p.Gly105[12] was significantly lower than that of daughters derived from sires carrying the homozygous p.Gly105[13]. Thus, selection of sires carrying p.Gly105[12] could be beneficial in the dairy industry by reducing the incidence of mastitis.

Neuroprotective natural antibodies to assemblies of amyloidogenic peptides decrease with normal aging and advancing Alzheimer's disease.

A number of distinct beta-amyloid (Abeta) variants or multimers have been implicated in Alzheimer's disease (AD), and antibodies recognizing such peptides are in clinical trials. Humans have natural Abeta-specific antibodies, but their diversity, abundance, and function in the general population remain largely unknown. Here, we demonstrate with peptide microarrays the presence of natural antibodies against known toxic Abeta and amyloidogenic non-Abeta species in plasma samples and cerebrospinal fluid of AD patients and healthy controls aged 21-89 years. Antibody reactivity was most prominent against oligomeric assemblies of Abeta and pyroglutamate or oxidized residues, and IgGs specific for oligomeric preparations of Abeta1-42 in particular declined with age and advancing AD. Most individuals showed unexpected antibody reactivities against peptides unique to autosomal dominant forms of dementia (mutant Abeta, ABri, ADan) and IgGs isolated from plasma of AD patients or healthy controls protected primary neurons from Abeta toxicity. Aged vervets showed similar patterns of plasma IgG antibodies against amyloid peptides, and after immunization with Abeta the monkeys developed high titers not only against Abeta peptides but also against ABri and ADan peptides. Our findings support the concept of conformation-specific, cross-reactive antibodies that may protect against amyloidogenic toxic peptides. If a therapeutic benefit of Abeta antibodies can be confirmed in AD patients, stimulating the production of such neuroprotective antibodies or passively administering them to the elderly population may provide a preventive measure toward AD.

Long-term follow-up of interferon-treated chronic hepatitis C and serum hepatic fibrosis markers.

BACKGROUND/AIMS: We investigated the clinical application of serum fibrosis markers in a long-term follow-up of patients with chronic hepatitis C treated with interferon-alpha. METHODOLOGY: This study included 52 patients treated with interferon-alpha (total: 480 MU) for 6 months. They each underwent liver biopsy before and after treatment. Twenty-eight patients who underwent liver biopsy less than 2 years after treatment were classified as group 1, and 24 patients as group 2. The two groups were subdivided into HCV RNA-negative responders and HCV RNA-positive nonresponders. Liver specimens were estimated using grading and staging scores. Serum hyaluronan, PIIIP, and type IV collagen levels were measured before and after treatment. RESULTS: In the responders of groups 1 and 2, grading score after treatment was significantly decreased compared with that before treatment. Staging score after treatment was significantly improved only in the responders of group 2. In the responders of group 2, serum hyaluronan level was significantly decreased compared with that before treatment. In group 2, the grading score was significantly correlated with serum PIIIP and type IV collagen levels, and the staging score was significantly correlated with only serum hyaluronan level. CONCLUSIONS: These findings indicate that the serum PIIIP and type IV collagen levels reflect the activity, and serum hyaluronan reflects the degree of fibrosis in liver specimens of HCV RNA-negative patients in a long-term follow-up of patients after interferon-alpha treatment.

Full-sized RanBPM cDNA encodes a protein possessing a long stretch of proline and glutamine within the N-terminal region, comprising a large protein complex.

Previously isolated RanBPM, a Ran-binding protein in the microtubule-organizing center, which had been thought to play a role in Ran-stimulated microtubule assembly, turned out to be a truncated protein. To clarify the function of RanBPM, we cloned the full-sized RanBPM cDNA that encodes a 90 kDa protein, compared to the previously isolated cDNA that encoded a 55 kDa protein. The newly cloned 5' coding region contains a great number of cytidine and guanidine nucleotides, like the CpG island. Thus, full-sized RanBPM cDNA encodes a long stretch of proline and glutamine residues in the N-terminal region. It comprises a protein complex of more than 670 kDa. Ran was detected in this complex when RanBPM and Ran were both ectopically expressed. New antibodies to RanBPM were prepared against three different regions of RanBPM. All of them detected a 90 kDa protein that is predominantly localized both in the nucleus and in the cytoplasmic region surrounding the centrosome, but none of them stained the centrosome. In this context, our previous notion that RanBPM is a centrosomal protein should be discarded. RanBPM is well conserved in the animal kingdom. It may play an important role in uncovering Ran-dependent nuclear events.

Surfactant-lactoperoxidase complex catalytically active in organic media.

A surfactant-lactoperoxidase (LPO) complex catalytically active in organic solvents was developed by the emulsion coating method. The oxidation of 2,6-dimethoxyphenol (2,6-DMP) was conducted by the surfactant-LPO complex in organic media. The LPO complex efficiently catalyzed the oxidation of 2,6-DMP in various organic solvents, although lyophilized LPO did not display the catalytic activity at all. To optimize the preparation and reaction conditions for the surfactant-LPO complex, we examined the effects of pH value in the water pools of W/O emulsions, kinds of oxidants, and the nature of organic solvents on the oxidation reaction. Its optimum activity was obtained when the pH value of the aqueous enzyme solution was adjusted to ca. 8 at the preparation stage. The LPO complex exhibited the highest catalytic activity in chloroform when H(2)O(2) was employed as the oxidant. Furthermore, the storage stability of the surfactant-LPO complex was far better than that of the surfactant-horseradish peroxidase complex. This high storage stability of the LPO complex will be a benefit for industrial usage of peroxidases.

Ursodeoxycholic acid reduces expression of heat shock proteins in primary biliary cirrhosis.

BACKGROUND: To identify injured cells in the liver of patients with primary biliary cirrhosis (PBC) and to determine the effects of ursodeoxycholic acid (UDCA) on these cells, we examined the cellular expression of heat shock proteins (HSPs) in PBC both before and after treatment with UDCA. METHODS: Expression of HSP70 and ubiquitin in PBC livers (n=34) was evaluated immunohistochemically as well as by immunoblot analysis, and compared with chronic viral hepatitis type C (n= 9), primary sclerosing cholangitis (n=8), and controls (n=7). RESULTS: Immunoblot analysis demonstrated a marked expression of HSP70 and ubiquitin in PBC. Immunohistochemical staining for both HSP70 and ubiquitin was observed to be strong in biliary epithelial cells (BECs) and moderate in both hepatocytes and arteries in PBC. Cellular labelling rates for HSP70 and ubiquitin of bile ducts in PBC were significantly higher (p<0.01) than those in chronic viral hepatitis type C, primary sclerosing cholangitis, or controls. The labelling rates for HSP70 and ubiquitin in bile ducts and in hepatocytes were significantly decreased (p<0.01) after treatment with UDCA in PBC. CONCLUSIONS: The present data suggest that BECs and hepatocytes significantly express HSPs even in the early stages of PBC, and that UDCA treatment significantly improves their condition. The immunohistochemical evaluation of HSPs is a valid and sensitive means to identify injured cells in PBC.

Erythropoietic protoporphyria with fatal liver failure.

A 33-year-old woman with a history of photosensitivity, persistent abdominal pain, and liver dysfunction was admitted to our department because of abdominal pain and progression of liver dysfunction. On admission, levels of protoporphyrin and coproporphyrin within erythrocytes were markedly increased. Autofluorescent erythrocytes were also detected, leading to a diagnosis of erythropoietic protoporphyria. A liver biopsy specimen revealed cirrhosis with dark brown granules filling hepatocytes, bile canaliculi, and bile ductules. Transfusion of washed erythrocytes, hemodialysis, and administration of cholestyramine and beta-carotene transiently improved levels of porphyrins and liver function. The patient died of rupture of esophageal varices followed by multiple organ failure. However, the treatments were believed to have extended survival.

Intraspousal transmission of GB virus C/hepatitis G virus in an hepatitis C virus hyperendemic area in Japan.

OBJECTIVE: An immunoassay for antibodies against an hepatitis G virus (HGV) protein (anti-E2) was recently developed that might serve as a useful marker for diagnosing recovery from HGV infection. METHODS: We investigated the intraspousal transmission of GB virus C/hepatitis G virus (GBV-C/HGV) using both reverse transcription hemipolymerase chain reaction (RT-hemi-PCR for the 5' untranslated region) and a recently developed anti-E2. RESULTS: Thirty-two GBV-C/HGV-infected index subjects were selected from an hepatitis C virus hyperendemic area in Japan. Of the 32 subjects, seven (6.4%) were GBV-C/HGV RNA-positive, 24 (21.8%) were anti-E2-positive, and one (0.9%) was both GBV-C/HGV RNA- and anti-E2-positive. Among the 32 spouses of these subjects, GBV-C/HGV RNA, anti-E2, and both GBV-C/HGV RNA and anti-E2 positivity were detected in 0, 6, (18.8%), and one (3.1%) spouses, respectively (the total prevalence of GBV-C/HGV was 7 spouses [21.9%]). Thus, the intraspousal transmission of GBV-C/HGV was undeniable in these seven couples. The respective positive rates of 175 sex- and age-matched controls were 7 (4.0%), 26 (14.9%), and 0 (the total prevalence of GBV-C/HGV was 34 [19.4%]). No significant difference in positive rates was observed between the subjects/spouses and the controls. Five spouses among the seven couples who were positive for any of GBV-C/HGV markers had parenteral risk factors such as blood transfusion, acupuncture, and major surgery. CONCLUSION: Based on these observations, we cannot draw a definitive conclusion that intraspousal transmission of GBV-C/HGV had occurred among these seven couples.

Unusual accumulation of glycogen in liver parenchymal cells in a patient with anorexia nervosa.

Anorexia nervosa is an eating disorder characterized by a fear of weight gain and a preoccupation with body image. Although hepatic involvement has been reported in patients with anorexia nervosa, the mechanism is not fully understood. We describe a patient with anorexia nervosa with liver function abnormalities. Light and electron microscopic observations revealed a remarkable accumulation of glycogen in hepatocytes. These results suggest that adaptive responses to starvation may alter carbohydrate metabolism in patients with anorexia nervosa.

Two cases of adult varicella accompanied by hepatic dysfunction.

Varicella is a typical acute exanthematous viral infection caused by varicella-zoster virus (VZV). In recently years, as far as hepatic dysfunction caused by viruses other than the hepatitis virus is concerned, there have been a few reports on hepatic dysfunction accompanying varicella following organ transplantation of Europe and America and another report on an immunocompromized adult following treatment for Systemic lupus erythematosis (SLE) in Japan. Nonetheless, we searched the MEDLINE and J MEDICINE listing the publications between 1986 and 1996 and found one report on healthy adults with varicella accompanied by hepatic dysfunction in Europe and America and two reports in Japan. Only Noguchi et al. dealt with the findings of liver biopsy. We examined two healthy adults with varicella and mild-to-moderate hepatic dysfunction, and referred to the results of their liver biopsies. The present paper discusses this issue, citing some references.

The incidence of hepatocellular carcinoma in patients with chronic hepatitis C after interferon treatment.

To determine whether serum hepatitis C virus (HCV) RNA disappearance after interferon (IFN) treatment prevents development of hepatocellular carcinoma (HCC), we evaluated retrospectively the incidence of HCC in patients with chronic hepatitis C. A total of 213 patients were monitored for more than 6 months after completion of IFN treatment. Sixty-three of the 213 patients (29.6%) achieved a complete response (CR) to treatment and 150 (70.4%) had no response (NR). HCC developed in 12 (5.6%), all of whom were NR. Logistic analysis showed age, alpha -fetoprotein, and staging of histological finding before IFN treatment were independent factors to development of HCC. The fact that there was no HCC development from CR provides a basis for IFN treatment in chronic HCV infection.

Long-term evaluation of interferon therapy in hepatitis C virus-associated cirrhosis: does IFN prevent development of hepatocellular carcinoma?

During the course of long-term follow-up, we examined the efficacy of interferon (IFN) in the improvement of liver function and prevention of hepatocellular carcinoma (HCC) in hepatitis C virus (HCV) associated cirrhosis patients. Fifty-five cirrhotic patients, in whom HCC nodules in the liver were not detected by ultrasonography (US) or computed tomography (CT), received 3 or 6 million units of human lymphoblastoid IFN daily for two weeks and 3 times a week for 22 weeks. Complete response (CR) was defined as normalization of serum alanine aminotransferase (ALT) together with negative HCV RNA at 6 months after IFN therapy completion. Any other pattern of response was defined as non-response (NR). After IFN therapy the patients were followed up every 1-3 months for at least 1 year (average follow-up period, about 40 months) with serological tests and US or CT. In the 8 CR patients, the serum ALT levels remained normal and HCV RNA remained negative. Platelet count, white blood cell count, serum albumin and zinc turbidity test have recovered to the normal range at final follow-up. Ten of the 47 patients with NR have developed HCC, whereas no patients with CR has developed HCC during follow-up. We conclude that IFN improves the liver function and may prevent the development of HCC even in cirrhotic patients who show CR to IFN therapy.

Serum vascular endothelial growth factor levels in various liver diseases.

The clinical significance of circulating vascular endothelial growth factor (VEGF) in patients with various liver diseases was investigated. Twenty-one patients with acute hepatitis (AH), 40 with chronic hepatitis (CH), 34 with cirrhosis (LC), 16 with fulminant hepatitis (FH), 10 with primary biliary cirrhosis (PBC), 12 with autoimmune hepatitis (AIH), and 120 healthy individuals were included. Serum VEGF levels were measured by a chemiluminescence enzyme-linked immunosorbent assay. The mean values of serum VEGF levels in the patients with AH, CH, LC, FH, AIH, PBC, and control were 172.7, 58.0, 44.1, 37.3, 49.7, 74.9, and 65.0 pg/ml, respectively. The patients with AH had a level of serum VEGF significantly higher than that of the control group (P < 0.001). The serum VEGF levels in survivors of FH were significantly increased, but not in the nonsurvivors in the recovery phase compared with the levels on admission (P < 0.05). In the LC patients, serum VEGF levels were significantly lower than those of the control group (P < 0.05). These findings suggest that serum VEGF level may be associated with hepatocyte regeneration grade.

Hepatic iron stainings in chronic hepatitis C patients with low HCV RNA levels: a predictive marker for IFN therapy.

OBJECTIVES: Interferon (IFN) therapy is ineffective in about 20-30% of chronic hepatitis C (CH-C) patients who have low HCV RNA levels. Besides the serum HCV RNA level or HCV genotype, hepatic iron concentrations are thought to be correlated with the subsequent response to IFN therapy. Our objective in the present study was to evaluate serum iron, ferritin, and hepatic iron staining in patients with low HCV RNA levels, as predictive markers for IFN therapy. METHODS: We evaluated 75 CH-C patients whose serum HCV RNA levels were below 1 million genome equivalent (mEq)/ml as shown by a bDNA assay. RESULTS: There were no significant differences in age, sex, serum aminotransferase levels, or serum iron concentrations between responders and nonresponders. The total iron scores (TIS) were significantly higher in responders (p < 0.01). The TIS was an independent factor relating to the response to IFN therapy by multivariate analysis (p = 0.0062). The TIS significantly correlated with serum ferritin levels (r = 0.637, p < 0.001), but not with any other parameter. bi] CONCLUSIONS: Among CH-C patients within the limits of low HCV RNA levels, TIS of the liver may be used as a predictive marker for IFN therapy.

Pathology of chronic hepatitis C in children. Child Liver Study Group of Japan.

Limited information is available regarding the histology of hepatitis C virus infection in children. The aim of this study was to determine the histological pattern of chronic hepatitis C (CHC) in children, and liver biopsy specimens from 109 pediatric patients with CHC were examined. Each biopsy specimen was evaluated based on a numerical scoring system for the stage of fibrosis (1-4), the grade of portal/periportal necroinflammation (0-4), the grade of lobular necroinflammation (0-4), and their sum (final grade). The histological lesions considered to be characteristic of chronic hepatitis were also evaluated. None of the children had liver cirrhosis, and 105 cases (97%) were stage 1 or 2. Only 4 children were stage 3. Two of these 4 cases showed hemosiderosis. A significant correlation was observed between the staging score and the final grade in the pediatric patients (r = .59; P < .0001). The histological characteristics of adult CHC, such as lymphoid aggregate, bile duct injury, and fatty changes, were also observed in the children. In conclusion, the majority of children with CHC presented with mild fibrosis, but a few showed CHC with lobular distortion and hemosiderosis. Frequent blood transfusion may aggravate hepatic lesions in pediatric CHC.

Laparoscopic pylorus-preserving gastrectomy with intracorporeal hand-sewn anastomosis.

To prevent stapled stenosis after laparoscopic local gastric resection by using autosuturing devices, we developed a technique for laparoscopic pylorus-preserving gastrectomy with intracorporeal hand-sewn anastomosis. We describe this procedure and present two case reports. The intracorporeal hand-sewn anastomotic technique is an important advance in the field of minimally invasive laparoscopic surgery.