Biomedical subjects

H Takahashi

Publications and source records attributed to H Takahashi.

At least 19 recordsLinked to original sources

PubMed2007

Influence of attachment wear on retention of mandibular overdenture.

UNLABELLED: The aims of this study were: (i) to evaluate and compare retention of two-teeth (implant) supported mandibular overdenture with either stud or magnetic attachments during linear (axial) and rotational (paraxial) dislodgements; (ii) to compare retentive properties before and after wear simulation. The test group consisted of five magnetic and four stud overdenture attachments (n = 12 specimens for each attachment type). Retention in axial direction was evaluated on one-tooth (implant) model by measuring maximum retentive force (N) and range of retention (mm) during the linear dislodgement. Retention in the paraxial direction was evaluated on mandibular-overdenture model by measuring the maximum retentive force (N) during three types of rotational dislodgements - anterior, lateral and posterior. The minimum number of cycles required to simulate wear was determined by special wear test. Afterwards, the wear was simulated in the test group, and retention in axial and paraxial directions was measured again. STATISTICAL ANALYSIS: one-way anova, Scheffe post hoc and paired-samples t-tests (P < 0.05). Initially, studs had higher retention (4-11 N) than magnets (4.5-6 N) in axial direction. After the wear simulation, it had decreased from 76% to 48% for some of the studs and had become similar to the retention of magnetic attachments. Magnets had lower retention range (0.2-0.3 mm) than studs (0.5-1.1 mm). Studs provided similar or higher retention in paraxial directions than magnetic attachments both before and after wear simulation. Retentive properties of magnets decreased mostly with posterior rotational dislodgement. Retentive properties of stud overdenture attachments were less constant.

Dental Abutments↗

PubMed2007

Anti-MuSK-positive myasthenia gravis: neuromuscular transmission failure in facial and limb muscles.

The presence of antibodies against muscle-specific receptor tyrosine kinase (MuSK) appears to define a subgroup of patients with myasthenia gravis (MG) characterized by weakness predominant in bulbar, facial and neck muscles compared with anti-acetylcholine receptor (AChR) antibody-positive MG. To investigate the patterns and severity of neuromuscular transmission failure in different muscles in MuSK-positive MG, we performed single fiber electromyography (SFEMG) in the facial (frontalis) and limb (extensor digitorum communis, EDC) muscles in three anti-Musk-positive patients, and compared results with those of 11 anti-AChR-positive patients. Only one of the three MuSK-positive patients had abnormal jitter in EDC, but all the three showed clearly increased jitter in the frontalis. By contrast, the AChR-positive patients showed similarly abnormal jitter for the two muscles. These results suggest that when the diagnosis of anti-MuSK-positive MG is suspected, SFEMG should be performed in most prominently affected muscles.

Antibodies↗

PubMed2007

Apparent diffusion coefficient mapping of salivary gland tumors: prediction of the benignancy and malignancy.

BACKGROUND AND PURPOSE: Preoperative prediction of tumor malignancy is clinically very important, because this information strongly influences the surgical plan. We evaluate the preoperative apparent diffusion coefficient (ADC) maps of benign and malignant salivary gland tumors. MATERIALS AND METHODS: High-resolution MR imaging was performed on 31 patients with benign or malignant salivary gland tumors; ADC maps of the tumors were also obtained. Surface coils of 47 or 110 mm diameter were used to improve the image resolution. The ADCs were compared with histologic features of the excised tumors. RESULTS: The ADC maps effectively depicted the histologic features of the salivary gland tumors, such as presence of cancer cells, myxomatous tissues, fibrosis, necrosis, cyst formation, and lymphoid tissues. The ADC maps showed that more frequent areas with high ADCs (> or = 1.8 x 10(-3) mm(2)/s) were significantly greater in benign tumors than in malignant tumors. The sensitivity and specificity for high ADC occupying fewer than 5% of the area of a tumor was 89% and 100%, respectively, resulting in 97% accuracy, 100% positive predictive value, and 96% negative predictive value. CONCLUSION: The ADC may provide preoperative tissue characterization of the salivary gland tumors.

Aged↗

PubMed2006

Risk factors for chronic kidney disease in a community-based population: a 10-year follow-up study.

The purpose of this study was to explore risk factors affecting the incidence of chronic kidney disease (CKD) in general population. We conducted a 10-year follow-up study with 123 764 (male: 41 012, female: 82 752) adults aged 40 years and over who received community-based annual examinations. The primary outcome for the analysis was the development of CKD during the follow-up period. Predictors for the development of CKD were obtained by the significant hazard ratios (HR) in Cox regression model by sex. During the follow-up period, 4307 subjects (male: 2048, female: 2259) developed CKD stage I or II, and 19 411 subjects (male: 4257, female: 15 154) developed CKD stage III or higher. The baseline-adjusted predictor of developing CKD included age, glomerular filtration rate, hematuria, hypertension, diabetes, serum lipids, obesity, smoking status, and consumption of alcohol. Treated diabetes in male subjects, and treated hypertension, systolic blood pressure >160 mm Hg and/or diastolic blood pressure >100 mm Hg, diabetes, and treated diabetes in female subjects were associated with more than a doubling of the HR. For the development of CKD stage III or higher, proteinuria of >or= + +, and proteinuria and hematuria were associated with more than a doubling of the HR in male subjects. The prevalence of newly developed CKD over 10 years was 23 718 subjects (19.2%) in adults. This study suggested that not only hypertension and diabetes but also several metabolic abnormalities were independent risk factors for developing CKD.

Adult↗

PubMed2006

Neonatal cavernous angioma located in the basal ganglia with profuse intraoperative bleeding.

CASE REPORT: A rare case of congenital cavernous angioma detected during pregnancy is described. The tumor was pointed out by ultrasound in a fetus at 39 weeks gestation. The male baby was delivered by cesarean section. Computed tomography and magnetic resonance imaging revealed a tumor in the left basal ganglia. Because the tumor gradually enlarged and right hemiparesis became evident, a decision was made to remove the tumor. Because of profuse intraoperative bleeding, surgical total removal was not accomplished. Histopathological specimens revealed cavernous angioma. The patient was treated postoperatively with 30.4 Gy of local irradiation. His right hemiparesis improved and the tumor gradually decreased in size. DISCUSSION: The literatures are reviewed and discussed about clinical features and management controversies of this rare tumor.

Basal Ganglia↗

PubMed2006

Effectiveness of an 'half elemental diet' as maintenance therapy for Crohn's disease: A randomized-controlled trial.

BACKGROUND: Although thiopurines have a proven role in maintenance therapy for Crohn's disease, an alternative therapy is needed for patients intolerant or resistant to thiopurines. AIM: To evaluate the effectiveness of home enteral nutrition as a maintenance therapy regimen in which half of the daily calorie requirement is provided by an elemental diet and the remaining half by a free diet. We refer to this home enteral nutrition therapy as 'half elemental diet'. METHODS: Between 2002 and 2005, 51 patients in remission from two hospitals were randomly assigned to a half elemental diet group (n = 26) or a free diet group (n = 25). The primary outcome measure of this study was the occurrence of relapse over the 2-year period. RESULTS: The relapse rate in the half elemental diet group was significantly lower [34.6% vs. 64.0%; multivariate hazard ratio 0.40 (95% CI: 0.16-0.98)] than that in the free diet group after a mean follow-up of 11.9 months. Compliance was similar in the two groups. No adverse event occurred in any of the patients throughout the study. CONCLUSION: This randomized-controlled trial shows the effectiveness of an half elemental diet, which is a promising maintenance therapy for Crohn's disease patients.

Adult↗

PubMed2006

Upregulated EMMPRIN/CD147 might contribute to growth and angiogenesis of gastric carcinoma: a good marker for local invasion and prognosis.

Tumour growth depends on angiogenesis, which is closely associated with vascular endothelial growth factor (VEGF) and matrix metalloproteinases (MMPs). Extracellular MMP inducer (EMMPRIN) was reported to involve in the progression of malignancies by regulating expression of VEGF and MMPs in stromal cells. To clarify the role of EMMPRIN in progression and angiogenesis of gastric carcinoma, expression of EMMPRIN, ki-67, MMP-2, MMP-9 and VEGF was examined on tissue microarray containing gastric carcinomas (n=234) and non-cancerous mucosa adjacent to carcinoma (n=85) by immunohistochemistry. Additionally, microvessel density (MVD) was assessed after labelling with anti-CD34 antibody. Extracellular MMP inducer expression was compared with clinicopathological parameters of tumours, including levels of ki-67, MMP-2, MMP-9 and vascular endothelial growth factor (VEGF), MVD as well as survival time of carcinoma patients. Gastric carcinoma cell lines (HGC-27, MKN28 and MKN45) were studied for EMMPRIN expression by immunohistochemistry and Western blot. Extracellular MMP inducer expression was gradually increased from normal mucosa to carcinomas through hyperplastic or metaplastic mucosa of the stomach (P<0.05). There was strong EMMPRIN expression in all gastric carcinoma cell lines despite different levels of glycosylation. Extracellular MMP inducer expression was positively correlated with tumour size, depth of invasion, lymphatic invasion, expression of ki-67, MMP-2, MMP-9 and VEGF of tumours (P<0.05), but not with lymph node metastasis, UICC staging or differentiation (P>0.05). Interestingly, there was a significantly positive relationship between EMMPRIN expression and MVD in gastric carcinomas (P<0.05). Survival analysis indicated EMMPRIN expression to be negatively linked to favourable prognosis (P<0.05), but not be independent factor for prognosis (P>0.05). Further analysis showed three independent prognostic factors, depth of invasion, lymphatic and venous invasion, to influence the relationship between EMMPRIN expression and prognosis. Upregulated expression of EMMPRIN possibly contributes to genesis, growth and local invasion of gastric carcinomas. Altered EMMPRIN expression might enhance growth, invasion and angiogenesis of gastric carcinoma via upregulating MMP expression of both stromal fibroblasts and gastric cancer cells and could be considered as an objective and effective marker to predict invasion and prognosis.

Adenocarcinoma↗

PubMed2006

Triamcinolone acetonide suppresses early proangiogenic response in retinal pigment epithelial cells after photodynamic therapy in vitro.

OBJECTIVE: To investigate the expression of proangiogenic and antiangiogenic factors, vascular endothelial growth factor (VEGF) and pigment epithelium-derived factor (PEDF) in retinal pigment epithelial (RPE) cells after photodynamic therapy (PDT), especially focusing on their change in the presence of triamcinolone acetonide. METHODS: Firstly, the cellular uptake of verteporfin was quantified after confluent ARPE-19 (human retinal pigment epithelial) cells were exposed to 5 microg/ml verteporfin combined with or without 1 microg/ml triamcinolone acetonide for 1 h. Secondly, ARPE-19 cells exposed to various doses of verteporfin were irradiated with 120 mJ/cm(2) light. After incubation with or without 1 microg/ml triamcinolone acetonide for 2 days, cell viability and expressions of VEGF and PEDF were assessed. RESULTS: Cellular uptake of verteporfin was not significantly changed by the presence of 1 microg/ml triamcinolone acetonide. In addition, 0.01-0.1 microg/ml of verteporfin showed a dose-dependent toxicity on the ARPE-19 cells 2 days after the light exposure. The presence of verteporfin at a concentration of 0.01 microg/ml did not affect the cell viability but significantly increased VEGF (p<0.001) and reduced PEDF (p = 0.03) expression. Administration of triamcinolone acetonide significantly suppressed both this increase in VEGF (p<0.001) and decrease in PEDF (p = 0.001). CONCLUSIONS: VEGF was increased and PEDF reduced in cultured RPE cells shortly after PDT even at a sublethal dose. Triamcinolone acetonide suppressed this proangiogenic response.

Cell Line↗

PubMed2006

Effects of tetrabromobisphenol A, brominated flame retardant, in ICR mice after prenatal and postnatal exposure.

Tetrabromobisphenol A (TBBPA), brominated flame retardant, is produced in the largest amounts globally for use in plastics or building materials. TBBPA has been detected in sediment, air at the dismantling plant or human serum samples. In the present study, we examined the effects of prenatal and postnatal exposure to TBBPA in mice. TBBPA (99.1% pure) in diet was administered to pregnant ICR mice at doses of 0% (control), 0.01%, 0.1% or 1.0% from gestational day 0 to weaning at postnatal day 27. The average daily food intake and body weight of dams showed no significant differences between the control and treated groups. There were no dose-related effects on reproductive data. Serum concentrations of total-cholesterol and liver weights of treated dams and offspring were higher than those of the control mice. Histological findings in treated dams or offspring showed the increase of focal necrosis of hepatocytes and inflammatory cell infiltration in the liver, and increase of dilation or atrophy of renal tubules and cyst in the kidney. TBBPA was developed as a new, safe class of flame retardant and was not highly toxic. However, the present data suggested that TBBPA caused a lipid metabolic disorder and hepatic or kidney lesion, under these conditions.

Alanine Transaminase↗

PubMed2006

Cell proliferation and apoptosis in the anterior intestine of an amphibious, euryhaline mudskipper (Periophthalmus modestus).

In order to replace the diffusive loss of water to the surrounding environment, seawater (SW)-acclimated euryhaline fishes have gastrointestinal tracts with higher ion/water flux in concert with greater permeability, and contrast that to freshwater (FW)-acclimated fish. To understand the cellular basis for these differences, we examined cell proliferation and apoptosis in the anterior intestine of mudskipper transferred from one-third SW to FW or to SW for 1 and 7 days, and those kept out of water for 1 day. The intestinal apoptosis (indicated by DNA laddering) increased during seawater acclimation. TUNEL staining detected numerous apoptotic cells over the epithelium of SW-acclimated fish. Cell proliferation ([3H]thymidine incorporation) in the FW fish was greater than those in SW 7 days after transfer. Labeling with a Proliferating cell nuclear antigen (PCNA) antibody indicated that proliferating cells were greater in number and randomly distributed in the epithelium of FW fish, whereas in SW fish they were almost entirely in the troughs of the intestinal folds. There were no changes in cell turnover in fish kept out of water. During acclimation to different salinities, modification of the cell turnover and abundance may play an important role in regulating the permeability (and transport capacity) of the gastrointestinal tract of fish.

Acclimatization↗

PubMed2006

PTEN activity could be a predictive marker of trastuzumab efficacy in the treatment of ErbB2-overexpressing breast cancer.

Trastuzumab is the only HER2/neu-directed therapy to have received Food and Drug Administration approval for the treatment of patients with metastatic breast cancer. The efficacy of trastuzumab depends on the HER2/neu status of the tumour and the patient's prior treatment, but even when patients are selected on the basis of HER2/neu gene amplification, the single-agent response rate ranges from 12 to 30% and few patients respond to trastuzumab monotherapy. Here, we propose PTEN as a predictive biomarker for trastuzumab efficacy. Human breast cancer SKBR3 and drug-resistant SKBR3/R cells were investigated. We also examined clinical samples from patients who had been treated with trastuzumab and analysed the relationship between trastuzumab efficacy and PTEN level. The PI3K/Akt signalling pathway was observed to be highly active in the drug-resistant cells, and their level of PTEN was low. Delivery of antisense PTEN duplex siRNA significantly decreased the trastuzumab chemosensitivity of parental SKBR3 cells, and marked activation of Akt signalling pathway was also recognised. Moreover, immunohistochemical investigation revealed that trastuzumab treatment was remarkably successful in cells with elevated PTEN expression. Along with the immune-system-associated cytotoxic mechanism, several mechanisms have been proposed for the effect of trastuzumab. PTEN activity might play an important and major role in its HER2/PI3K/Akt-mediated antitumour effect, and could be a useful biomarker for predicting the efficacy of trastuzumab in the treatment of breast cancer.

Antibodies, Monoclonal↗

PubMed2006

Integrin-linked kinase activity is associated with interleukin-1 alpha-induced progressive behavior of pancreatic cancer and poor patient survival.

Cancer cell adhesion and invasion into extracellular matrix are regulated by integrin-linked kinase (ILK) activity in a phosphatidylinositol 3-kinase (PI3-K)-dependent manner. In this study, we demonstrated that ILK and beta(1)-integrin play important roles in interleukin (IL)-1alpha-induced enhancement of adhesion and invasion of pancreatic cancer cells through p38 mitogen-activated protein kinase (MAPK) signaling pathway and activator protein-1 (AP-1) activation. Alteration of ILK kinase activity controlled IL-1alpha-induced p38 MAPK phosphorylation and its downstream AP-1 activation with subsequent regulation of pancreatic cancer cell adhesion and invasion. Overexpressed ILK enhances the IL-1alpha-induced p38 MAPK phosphorylation more strongly through glycogen synthase kinase 3 (GSK-3) activation, and subsequently induces AP-1 activation, which promotes aggressive capabilities of pancreatic cancer cells. In contrast, knockdown of ILK kinase activity inhibits the IL-1alpha-induced activation of MAPK/AP-1 pathway via inhibition of GSK-3 phosphorylation. In immunohistochemical analysis, statistically significant association between strong expression of ILK and poor prognosis of pancreatic cancer patients were observed, and strong expression of ILK in cancerous tissues can be a significant prognostic indicator of pancreatic cancer patients. Our results suggest that ILK is involved with aggressive capability in pancreatic cancer and that these regulations can be helpful to understand biological processes for a better translational treatment for pancreatic cancer patients.

Cell Adhesion↗

PubMed2006

Disrupted galectin-3 causes non-alcoholic fatty liver disease in male mice.

Galectin-3, a beta-galactoside-binding animal lectin, is a multifunctional protein. Previous studies have suggested that galectin-3 may play an important role in inflammatory responses. Non-alcoholic fatty liver disease (NAFLD) is increasingly recognized as a liver condition that may progress to end-stage liver disease and based on the known functions of galectin-3, it was hypothesized that galectin-3 might play a role in the development of NAFLD. Thus, this study investigated the role of galectin-3 in NAFLD by comparing galectin-3 knockout (gal3(-/-)) mice and wild-type (gal3(+/+)) mice. The livers of gal3(-/-) male mice at 6 months of age histologically displayed mild to severe fatty change. The liver weight per body weight ratio, serum alanine aminotransferase levels, liver triglyceride levels, and liver lipid peroxide in gal3(-/-) mice were significantly increased compared with those in gal3(+/+) mice. Furthermore, the hepatic protein levels of advanced glycation end-products (AGE), receptor for AGE (RAGE), and peroxisome proliferator-activated receptor gamma (PPARgamma) were increased in gal3(-/-) mice relative to gal3(+/+) mice. In conclusion, this study suggests that the absence of gal3 can cause clinico-pathological features in male mice similar to those of NAFLD.

Alanine Transaminase↗

PubMed2006

Routine use of auxiliary partial orthotopic liver transplantation for children with fulminant hepatic failure: Preliminary report.

Auxiliary partial orthotopic liver transplantation (APOLT) has been performed for both metabolic disorders and fulminant liver failure (FHF). When the native liver regenerates, the patients with FHF who undergo APOLT have a chance to withdraw immunosuppression. It may be most beneficial for children. This preliminary report describes our start to routinely offer APOLT as an option to standard OLT for children with FHF in 2005. Six children (ages 8 months to 8 years) received APOLT: 1 in 1996 and the others in 2005 and 2006. The donor ages ranged from 4 to 40 years. We used either a left lateral segment or a left lobe graft. The recipient left lobe, which was removed, showed submassive to massive necrosis at the time of transplantation. All children are alive and well. The first patient who received APOLT in 1996 is currently off immunosuppression with a fully recovered native liver; the grafted liver underwent complete atrophy. The 5 remaining subjects are receiving reduced levels of immunosuppression with close monitoring. Their serial liver biopsy specimens show slight to significant recovery. One developed hepatic artery thrombosis, requiring retransplantation. The native liver was retained at the time of retransplantation (redo APOLT). Other postoperative complications included a bile leak (n = 1), invasive mucomycosis of the arm (preexisting condition; n = 1), biliary stricture (n = 1), and acute cellular rejection (n = 3). Posttransplantation length of stay was 6 to 60 days (median, 15 days). In conclusion, APOLT can be safely performed in children with FHF displaying short-term outcomes comparable to standard transplantations.

Adolescent↗

PubMed2006

Insulin resistance and impaired myocardial fatty acid metabolism in dialysis patients with normal coronary arteries.

We investigated whether insulin resistance is associated with impaired cardiac fatty acid metabolism in maintenance hemodialysis patients without coronary artery disease. We studied 55 nondiabetic (63+/-11 years old) and 51 diabetic (61+/-10 years old) hemodialysis patients with normal coronary arteries, using single-photon emission computed tomography (SPECT) with an iodinated fatty acid analogue, iodine-123-beta-methyl iodophenyl-pentadecanoic acid ((123)I-BMIPP), to evaluate cardiac fatty acid metabolism. SPECT imaging was graded regionally from 0 (normal) to 4 (absence of tracer) to calculate a summed score for 17 left ventricular segments. Insulin resistance was determined using the homeostasis model assessment index of insulin resistance (HOMA-IR). HOMA-IR correlated with summed BMIPP score in nondiabetic and diabetic patients. Stepwise multiple regression analysis showed that HOMA-IR was independently associated with BMIPP summed score in nondiabetic (beta=0.774, t=9.218, P=0.0001) and diabetic patients (beta=0.792, t=9.079, P=0.0001). Left ventricular ejection fraction was lower in nondiabetic subjects with BMIPP summed score of at least 6 plus HOMA-IR of at least 4 than in others with lower values for both assessments (53.1+/-13.8%, n=20 vs 67.7+/-9.1%, n=23, P=0.0002); this was also true in diabetic subjects (50.9+/-15.2%, n=24 vs 71.0+/-13.6%, n=11, P=0.0007). Association between insulin resistance and impaired cardiac fatty acid metabolism may contribute to left ventricular dysfunction in patients with maintenance hemodialysis without coronary diseases.

Aged↗

PubMed2006

Management of childhood and adolescent thyroid carcinoma: long-term follow-up and clinical characteristics.

AIM: This analysis was performed to evaluate clinical factors such as local tumor control, control of distant metastasis, survival, and complications in children and adolescents with thyroid carcinoma. MATERIALS AND METHODS: From 1960 to 2003, 21 children and adolescents (16 girls and 5 boys, aged 4 to 15 years) were treated for thyroid carcinoma in our departments. Clinical data, operative findings, pathological findings, operative procedures, intra- and postoperative complications and follow-up were evaluated. Follow-up of patients ranged from 3 to 42 years (median, 20 years). RESULTS: Papillary carcinoma was found in 20 patients (95%) and follicular carcinoma in one patient. Cervical lymph node metastases were found in 12 out of 21 patients (57.1%) when thyroid carcinoma was diagnosed, and 5 patients (23.8%) had pulmonary metastasis. In patients with pulmonary metastasis, total thyroidectomy and bilateral radical lymph node resection was performed in 3 patients, lobectomy of the thyroid and radical lymph node resection in one patient, and partial thyroidectomy in one patient. All three patients who underwent total thyroidectomy are still alive. Internal irradiation by 131I and thyroid hormone replacement therapy was administered to 2 of 3 patients with pulmonary metastasis. CONCLUSION: Despite metastasis in the lymph nodes and even the lungs, the prognosis for patients with papillary carcinoma is good. Total thyroidectomy and positive 131I therapy are recommended for childhood and adolescent thyroid carcinoma with pulmonary metastasis.

Adenocarcinoma, Follicular↗

PubMed2006

A method for discriminating a Japanese chicken, the Nagoya breed, using microsatellite markers.

The Nagoya breed native to Japan is popular as a dual-purpose breed for eggs and meat. The current study describes a method to discriminate between the Nagoya breed and other breeds and commercial stocks of chicken. Four strains of the Nagoya breed established at the Aichi-ken Agricultural Research Center were analyzed using 25 microsatellite markers. In these strains, 5 of the markers (ABR0015, ABR0257, ABR0417, ABR0495, and ADL0262) had a single allele. Other chicken samples (448) of various breeds and hybrids were analyzed using the same 5 markers. None of these chicken samples had the same allele combination as the Nagoya breed strains. These 5 microsatellite markers provide a practical method to accurately discriminate the Nagoya breed from other chicken breeds.

Animals↗

PubMed2006

A case of drug-induced hypersensitivity syndrome showing transient immunosuppression before viral reactivation during treatment for pemphigus foliaceus.

Drug-induced hypersensitivity syndrome (DIHS) is one of the most severe drug adverse reactions, with characteristic biphasic symptoms. Reactivation of human herpesvirus-6 (HHV-6) is frequently observed, although the cause of DIHS is still unknown. A patient developed DIHS during treatment with diaminodiphenylsulphone for pemphigus foliaceus. The number of lymphocytes in his peripheral blood, and titres of serum total IgG and IgM and anti-desmoglein1 antibody transiently decreased just before reactivation of HHV-6, cytomegalovirus and Epstein-Barr virus. This observation suggests that transient suppression of both cellular and humoral immunity may trigger viral reactivation, which leads to the development of the second phase of DIHS.

Administration, Oral↗