Diurnal variation of carbohydrate insulin ratio in adult type 1 diabetic patients treated with continuous subcutaneous insulin infusion

To estimate the carbohydrate‐to‐insulin ratio (CIR), a formula dividing a constant, usually 300–500, by the total daily dose (TDD) of insulin, is widely utilized. An appropriate CIR varies for each meal of the day, however. Here, we investigate diurnal variation of CIR in hospitalized Japanese type 1 diabetic patients treated with continuous subcutaneous insulin infusion. After optimization of the insulin dose, TDD and total basal insulin dose (TBD) were 34.9 ± 10.2 and 9.3 ± 2.8 units, respectively, with a percentage of TBD to TDD of 27.3 ± 6.0%. The products of CIR and TDD at breakfast, lunch and dinner were 311 ± 63, 530 ± 161, and 396 ± 63, respectively, suggesting that in the formula estimating CIR using TDD, the constant should vary for each meal of the day, and that 300, 500, and 400 are appropriate for breakfast, lunch, and dinner, respectively.     

Multicystic biliary hamartoma mimicking intrahepatic cholangiocarcinoma: report of a case

Multicystic biliary hamartoma (MCBH) is a rare cystic disease of the liver. A 69-year-old man was referred to our hospital with radiographic abnormality. Physical examination of the patient was unremarkable, and he denied any previous medical, travel, or surgical history. An abdominal computed tomography (CT) scan demonstrated a 3-cm low-density lesion in segment 3 of the liver, with dilation of the intrahepatic bile duct. The peripheral site of this lesion was slightly enhanced in the arterial phase. In the portal phase, the peripheral site was enhanced more clearly and showed a honeycomb-like dilated bile duct. Ultrasonography also revealed that the lesion was an irregularly shaped mass. On magnetic resonance imaging (MRI), T1-weighted images revealed a low-density mass and T2-weighted images revealed a dappled-density mass with honeycomb-like dilated bile duct and dilation of major intrahepatic bile duct. The patient was diagnosed with intrahepatic cholangiocarcinoma (ICC) and underwent left hepatectomy. However, pathological findings revealed that the lesion was MCBH. Our case highlights the potential difficulties in differentiating between MCBH and ICC under such circumstances.     

Is a composite score of physical performance measures more useful than usual gait speed alone in assessing functional status?

Overall physical performance can be represented by a composite score that is derived from upper and lower extremity performance measures. We aimed to identify whether composite scores of performance measures, particularly the lower extremity performance (LEP) score, upper extremity performance (UEP) score, and an overall score, are more accurate than usual gait speed (UGS) for assessing a wide range of functional status. We conducted a cross-sectional analysis on data from 701 community-dwelling older women (mean age 74.3 years). Trained testers measured UGS and the seven tests included in the composite scores. Using self-reported questionnaires, we assessed multiphasic functional status: physical function, higher-level functional capacity, mobility limitation, activities of daily living (ADLs), and falls. We compared the areas under the receiver operating characteristic curves (AUCs) of UGS with LEP, UEP, and overall scores for each status. We found no significant differences between the AUCs of UGS and LEP score for each status. The UEP score had significantly smaller AUCs for low physical function (0.73) and mobility limitation (0.78) than UGS alone (0.81 and 0.85, respectively), and the differences were substantial. Although the overall score had significantly greater AUCs for low higher-level functional capacity (0.83) and ADLs disability (0.83) than UGS alone (0.78 and 0.80, respectively), the differences were only 3-5%. The UGS should not be regarded solely as a measure of lower extremity function; this single test may represent overall physical performance. The UGS alone, which can be measured quickly and easily, suffice for assessing a wide range of functional status in older women.     

Antialbuminuric advantage of cilnidipine compared with L-type calcium channel blockers in type 2 diabetic patients with normoalbuminuria and microalbuminuria

We evaluated the antialbuminuric advantage of cilnidipine, an N/L-type calcium channel blocker (CCB), compared with L-type CCBs in diabetic patients with normoalbuminuria and microalbuminuria. The study was a multicenter, non-randomized crossover trial. Participants were 90 type 2 diabetic patients exhibiting either normo- or microalbuminuria, and undergoing CCB treatment for ≥6 months prior to study entry. The CCB at the time of entry was continued for the first 6 months (Period 1). Treatment was subsequently switched from cilnidipine to an L-type CCB, or vice versa, for the second 6-month observation period (Period 2). During Period 1, the L-type CCB group showed a significant increase of urinary albumin excretion (UAE) over time, while the cilnidipine group showed no significant elevation. During Period 2, switching of the treatment from the L-type CCB to cilnidipine resulted in significant reduction of the UAE, whereas switching from cilnidipine to the L-type CCB resulted in no significant change in the UAE. This study demonstrated that the antialbuminuric effect of Cilnidipine, but not the L-type CCBs, was sustained even in patients treated for a long time. In addition, the antialbuminuric effect can be anticipated after switching from an L-type CCB to cilnidipine, but not vice versa.     

Association of gene expression involving innate immunity and genetic variation in interleukin 28B with antiviral response

Innate immunity plays an important role in host antiviral response to hepatitis C viral (HCV) infection. Recently, single nucleotide polymorphisms (SNPs) of IL28B and host response to peginterferon α (PEG-IFNα) and ribavirin (RBV) were shown to be strongly associated. We aimed to determine the gene expression involving innate immunity in IL28B genotypes and elucidate its relation to response to antiviral treatment. We genotyped IL28B SNPs (rs8099917 and rs12979860) in 88 chronic hepatitis C patients treated with PEG-IFNα-2b/RBV and quantified expressions of viral sensors (RIG-I, MDA5, and LGP2), adaptor molecule (IPS-1), related ubiquitin E3-ligase (RNF125), modulators (ISG15 and USP18), and IL28 (IFNλ). Both IL28B SNPs were 100% identical; 54 patients possessed rs8099917 TT/rs12979860 CC (IL28B major patients) and 34 possessed rs8099917 TG/rs12979860 CT (IL28B minor patients). Hepatic expressions of viral sensors and modulators in IL28B minor patients were significantly up-regulated compared with that in IL28B major patients (≈ 3.3-fold, P < 0.001). However, expression of IPS-1 was significantly lower in IL28B minor patients (1.2-fold, P = 0.028). Expressions of viral sensors and modulators were significantly higher in nonvirological responders (NVR) than that in others despite stratification by IL28B genotype (≈ 2.6-fold, P < 0.001). Multivariate and ROC analyses indicated that higher RIG-I and ISG15 expressions and RIG-I/IPS-1 expression ratio were independent factors for NVR. IPS-1 down-regulation in IL28B minor patients was confirmed by western blotting, and the extent of IPS-1 protein cleavage was associated with the variable treatment response. CONCLUSION: Gene expression involving innate immunity is strongly associated with IL28B genotype and response to PEG-IFNα/RBV. Both IL28B minor allele and higher RIG-I and ISG15 expressions and RIG-I/IPS-1 ratio are independent factors for NVR.     

LecT-hepa, a glyco-marker derived from multiple lectins, as a predictor of liver fibrosis in chronic hepatitis C patients

Assessment of liver fibrosis in patients with chronic hepatitis C (CHC) is critical for predicting disease progression and determining future antiviral therapy. LecT-Hepa, a new glyco-marker derived from fibrosis-related glyco-alteration of serum alpha 1-acid glycoprotein, was used to differentiate cirrhosis from chronic hepatitis in a single-center study. Herein, we aimed to validate this new glyco-marker for estimating liver fibrosis in a multicenter study. Overall, 183 CHC patients were recruited from 5 liver centers. The parameters Aspergillus oryzae lectin (AOL) / Dature stramonium lectin (DSA) and Maackia amurensis lectin (MAL)/DSA were measured using a bedside clinical chemistry analyzer in order to calculate LecT-Hepa levels. The data were compared with those of seven other noninvasive biochemical markers and tests (hyaluronic acid, tissue inhibitor of metalloproteases-1, platelet count, aspartate aminotransferase-to-platelet ratio index [APRI], Forns index, Fib-4 index, and Zeng's score) for assessing liver fibrosis using the receiver-operating characteristic curve. LecT-Hepa correlated well with the fibrosis stage as determined by liver biopsy. The area under the curve (AUC), sensitivity, and specificity of LecT-Hepa were 0.802, 59.6%, and 89.9%, respectively, for significant fibrosis; 0.882, 83.3%, and 80.0%, respectively, for severe fibrosis; and 0.929, 84.6%, and 88.5%, respectively, for cirrhosis. AUC scores of LecT-Hepa at each fibrosis stage were greater than those of the seven aforementioned noninvasive tests and markers. Conclusion: The efficacy of LecT-Hepa, a glyco-marker developed using glycoproteomics, for estimating liver fibrosis was demonstrated in a multicenter study. LecT-Hepa given by a combination of the two glyco-parameters is a reliable method for determining the fibrosis stage and is a potential substitute for liver biopsy. (HEPATOLOGY 2012).     

Conservative treatment for adolescent idiopathic scoliosis: can it reduce the incidence of surgical treatment?

Since 1986, the authors have been conducting conservative treatment for idiopathic scoliosis with the combination of brace treatment and physical treatment (side shift exercise and hitch exercise). A total of 328 female patients with adolescent idiopathic scoliosis who were at least 10 years of age at the first visit, with Cobb angle of 10° at the minimum and followed until after 15 years of age or skeletal maturity were included. The average Cobb angle was 32.4° and the average age was 13.8 years at the first visit. Surgery was recommended when curvature progressed to >50°. Twenty of 328 patients (6.1%) with more severe curves to begin with (mean Cobb angle at admission of 48.5?±?9.3°) progressed to 62.2?±?8.5° and were treated with spinal fusion by the age of 16.0?±?2.6 years. The remaining 308 patients, of comparable age at inception of treatment but with a smaller original mean Cobb angle (32.4?±?11.1°), showed no significant increase in magnitude of curvature (mean 33.6?±?11.5°) by the time of discharge (18.6?±?3.1 years). The fact that curvature magnitude was maintained at <35° means that these patients will have a good prognosis for avoiding dramatic progression during adulthood.     

Clinical study on anti-fungal drug activity against clinically isolated strains of oral Candida species

ObjectivesThe present study was undertaken to evaluate the anti-fungal activity of amphotericin B (AMPH-B), flucytosine (5-FC), fluconazole (FLCZ), miconazole (MCZ), itraconazole (ITCZ), and micafungin (MCFG) against clinically isolated Candida strains from oral candidiasis (OC) patients and to collect information useful for the treatment of OC.Subjects and methodsThe study includes 116 strains of Candida isolated from patients. The Candida species were identified by polymerase chain reaction. The minimum inhibitory concentration (MIC) of each drug against each Candida species was determined.ResultsOf the 106 participants (30 males and 76 females), 57 had OC, including 42 cases of pseudomembranous OC, 11 cases of erythematous OC, 2 cases of hypertrophic OC, and 2 cases of mixed pseudomembranous/erythematous OC. The Candida species isolated were Candida albicans (93 strains), C. glabrata (19 strains), and C. tropicalis (4 strains). AMPH-B and 5-FC had low MIC values against all species of Candida and a low incidence of resistance development. In some species of Candida, FLCZ and ITCZ showed high MICs, but MCZ had a low MIC value. AMPH-B, MCZ, and ITCZ prescribed to OC patients were effective against OC with respect to alleviation of OC symptoms.ConclusionMIC values of anti-fungal drugs against Candida strains isolated from OC patients were obtained and the 3 anti-fungal drugs given to OC patients were found to be effective against OC in spite of differences in their MIC values and in the number of resistant strains (or strains with a high MIC value).     

Recent trends in cartilage regenerative medicine and its application to oral and maxillofacial surgery

Greater progress has been made in the clinical application of cartilage regenerative medicine, compared with that of other organs. A typical example of cartilage regenerative medicine is autologous chondrocyte implantation, in which chondrocytes isolated from the patient's cartilage are cultured and injected into the cartilage defects in a liquid- or gel-form. However, the classic autologous chondrocyte implantation has been applicable to only limited diseases, including focal cartilage lesion. Therefore, we developed “implant-type” tissue-engineered cartilage that shows mechanical strength and three-dimensional shape. This type of tissue-engineered cartilage uses scaffold composed of atelocollagen hydrogel and poly-l-lactic acid porous material, which is administered with cultured autologous auricular chondrocytes. Its clinical application to nasal deformity of cleft lip and palate patients has been ongoing at present. This review presents an overview of the current situation regarding cartilage regenerative medicine, as well as introducing our research and the development of implant-type tissue-engineered cartilage for the cleft-lip nose. The discussion of the future development of regenerative medicine is also mentioned.