Selection of the dose of angiotensin converting enzyme inhibitor for patients with diabetic nephropathy depends on the presence or absence of left ventricular hypertrophy.

The coexistence of hypertension increases cardiovascular risks and the rate of deterioration of renal function for diabetic patients. For patients with left ventricular hypertrophy (LVH), the use of an angiotensin converting enzyme (ACE) inhibitor is known to be effective and well tolerated and to be protective against chronic renal insufficiency (CRI). However, serious adverse reactions to ACE inhibitors, such as the rapid deterioration of renal function, have been reported, making physicians hesitant to use these agents. To resolve this dilemma, we compared changes in renal function and left ventricular function and the safety and effectiveness of benazepril, an ACE inhibitor, in patients with diabetic nephropathy, with or without LVH. The age, sex, duration of diabetes, levels of blood pressure and blood glucose and rates of creatinine clearance (CrCl) were compared between 36 diabetic patients with LVH and 36 matched diabetic patients without LVH. The rates of CrCl in all patients were between 14 and 35 ml/min, and all patients received an ACE inhibitor before enrollment. The group comprised 43 men and 29 women, with a mean age of 56 +/- 4 years. These patients were divided into three groups, each of which was subdivided into a group with and a group without LVH. Group I (without LVH) or I-L (with LVH) received a half dose of benazepril (2.5 mg daily), Group II (without LVH) or II-L (with LVH) received a normal daily dose of 5 mg benazepril, and Group III (without LVH) or III-L (with LVH) discontinued the administration of the ACE inhibitor. The follow-up period was 1 year and, during the study, blood pressure was maintained at less than 140/90 mmHg. If the blood pressure control was not satisfactory, benidipine, a calcium antagonist, and/or furosemide, a loop diuretic, and/or guanabenz, a central acting antihypertensive agent, were administered. In the diabetic patients with LVH, the administration of a normal dose of benazepril inhibited the decline of renal function and cardiac function (CrCl: 24.2 +/- 1.5 to 22.0 +/- 2.5 ml/min; EF (ejection fraction): 56 +/- 3 to 54 +/- 6%) compared to the other two groups. In patients without LVH, a half dose of benazepril preserved renal function (23.4 +/- 2.6 to 22.0 +/- 3.1 ml/min; EF: 54 +/- 3 to 56 +/- 3%). Discontinuation of the administration of ACE inhibitor led to the further progression of renal dysfunction and decreases in EF in patients with or without LVH. Our results provide some indications for the use of ACE inhibitors in diabetic patients when renal dysfunction and/or cardiac hypertrophy are present.     

Reattachment of an osteotomized greater trochanter in total hip arthroplasty using an ultra-high molecular weight polyethylene fiber cable

Background

The optimum approach in total hip arthroplasty (THA) should reduce the risk of postoperative dislocation or limping, be applicable in every case, and be reusable in the future. The purpose of this study was to introduce our transgluteal approach for THA and to evaluate the type and frequency of complications around the greater trochanter.

Breast masses with mixed cystic-solid sonographic appearance

Retrospective analysis was performed for 56 breast masses with mixed cystic and solid sonographic patterns encountered in the last 5 years at Keio University Hospital, with the objective of elucidating their significance. The lesions were classified into two major groups: tumor with cyst (TWC—solid mass with cystic component) and intracystic tumor (ICT—cystic mass with solid component). According to the pathological diagnosis, 57% were benign and 43% were malignant. Fifty eight percent of malignant lesions were shown to have a TWC pattern and 42% an ICT pattern. Among benign lesions, 66% were shown to be TWC and 34% ICT. In malignant tumors, 96% of the cases showed irregular shape and heterogeneous internal content. Even in benign lesions, a high incidence of irregular shape and rough border was found, although the predominant internal echo texture was homogeneous, and threedimensional (3-D) contour was not clear. In conclusion, we observed that in the TWC group, the lack of a defined 3-D contour is the most important criterion, and tumors with multiples cysts tend to be benign. © 1993 John Wiley & Sons, Inc.     

Blocking intrahepatic inflow and backflow using Chang's needle during hepatic resection: Chang's maneuver

Background. Chang''s needle is a straight, 18-gauge stainless steel needle with a hook near its top to catch the thread and can be used for various hepatic resections. Since its introduction in 1996, accumulated experience has shown that using Chang''s needle is simple and safe. We recently explored a new application for the needle with an intrahepatic vascular block during hepatic resections. Methods. Using Chang''s needle makes whole-thickness interlocking sutures of the liver possible. One or two rows of multiple sutures secure the inflow and backflow while allowing a hepatic parenchymal division with less blood loss. Under ultrasound guidance, single temporary sutures can be made in the respective branches of the Glisson sheath to block inflow, and, on the right or left hepatic vein, to block backflow as well. Results. We did 89 hepatic resections without specifically aimed inflow or backflow blocks, including 12 right lobectomies, three trisegmentectomies, 21 bisegmentectomies, and 15 segmentectomies. Twenty-seven patients had mild to severe liver cirrhosis. Specifically aimed inflow blocks for partial hepatic resections were done on the Glisson sheath (G) of segment 8 (two patients), segment 6 (one patient), and segment 3 (one patient). One patient with a G8 block had a concomitant backflow block of the right hepatic vein. Overall, there was no procedure-related mortality or hepatic failure. Ischemia and reperfusion induced liver function deterioration was minimal in the group with this kind of temporary vascular blocks. Conclusion. In addition to hepatic resections, Chang''s maneuver can be used for intrahepatic individual inflow or backflow blocks, or both, to minimize ischemic and reperfusion injuries.     

Evaluation of acoustic radiation force impulse elastography for fibrosis staging of chronic liver disease: a pilot study

Background: Acoustic radiation force impulse (ARFI) is a new technology integrated into conventional B‐mode ultrasonography. ARFI is used to evaluate tissue stiffness in several organs, but this method has not been applied for liver fibrosis. Aim: The aim of this study was to determine whether ARFI elastography is useful for the evaluation of liver fibrosis. Methods: This study enrolled 55 consecutive patients with chronic liver disease who underwent a liver biopsy for histological assessment of liver fibrosis by the Metavir scoring system. Liver stiffness of the 55 patients and 25 healthy volunteers was evaluated by ARFI elastography and was expressed as the shear wave velocity. Cut‐off values were determined using receiver‐operating characteristic (ROC) curves. Results: Histological liver fibrosis was evaluated by Metavir scoring; F0: six cases, F1: 14 cases, F2: nine cases, F3: nine cases and F4: 17 cases. Liver stiffness determined by ARFI elastography was correlated with histological liver fibrosis (P<0.0001). The areas under the ROC curves were 0.94 (95% confidence intervals, 0.87–0.99) for F2–F4, 0.94 (0.88–0.99) for F3–F4 and 0.96 (0.91–1.01) for F4. The cut‐off values of the shear wave velocity were as follows: >1.34 m/s for F2–F4 (sensitivity 91.4%, specificity 80%); >1.44 m/s for F3–F4 (sensitivity 96.2%, specificity 79.3%); and >1.80 m/s for F4 (sensitivity 94.1%, specificity 86.8%). Conclusions: Ultrasonic ARFI elastography is a novel, non‐invasive and reliable method for the assessment of liver fibrosis in patients with chronic liver disease.     

Relationships between periodontal inflammation, lipid peroxide and oxidative damage of multiple organs in rats

Gingival response to periodontal inflammation generates excessive lipid peroxide and such a condition may augment systemic health through increased circulating lipid peroxide. The purpose of the present study was to investigate whether the generation of lipid peroxide in periodontal inflammation could induce tissue injury in the liver, heart, kidney and brain using a rat model. Twelve Wistar rats (8 week-old male) were divided into 2 groups: the periodontal inflammation group, receiving topical application of lipopolysaccharide and proteases to the gingival sulcus for 4 weeks, and the control group using instead pyrogen-free water. After blood samples were collected, specimens from the brain, heart, liver and kidney were resected to determine the concentration of 8-hydroxydeoxyguanosine (an indicator of oxidative DNA damage). Gingival and serum levels for hexanoyl-lysine were measured to evaluate lipid peroxide. Administration of lipopolysaccharide and proteases induced periodontal inflammation, with increasing gingival and serum levels of hexanoyl- lysine. The level of 8-hydroxydeoxyguanosine increased 2.27, 2.01, 1.49 and 1.40 times in mitochondrial DNA from the liver, heart, kidney and brain of rats with periodontal inflammation, respectively. The results reveal that excessive production of lipid peroxide following periodontal inflammation is involved in oxidative DNA damage of the brain, heart, liver and kidney.     

Optimal therapeutic concentration of tacrolimus in adult patients undergoing reduced-intensity cord blood transplantation

To investigate the effectiveness and safety of GVHD prophylaxis using FK506 alone as a continuous infusion, 104 patients who underwent reduced-intensity cord blood transplantation were retrospectively reviewed. The respective incidence of acute GVHD was 25 grade 1(24. 1%), 19 grade2(18. 3%), 15 grade3(14. 4%), and 4 grade4(3. 8%), which are comparable to that in the literature. The incidences of grade 2 and greater acute GVHD were 32 out of 69(46. 4%)for those whose wholeblood concentration of FK506 werele ss than 13 ng/mL, whereas 6 out of 35(17. 1%)for those FK5 06 were greater than 13 ng/mL. The differenceies between above and below 13 ng/mL were statistically significant(p=0. 008). There were 19 cases(18. 3%)of renal dysfunction, although none required hemodialysis. There were only 4 patients who discontinued FK506, which further confirmed the safety of FK506 alone. Together with our previous report on the upper limit of FK506(17 ng/mL)and these results, we recommend the optimal serum concentration of FK506 to range from 13 to 17 ng/ mL.     

A vesicle carrier that mediates peroxisome protein traffic from the endoplasmic reticulum

Pex19p, a soluble cytoplasmic transport protein, is required for the traffic of the peroxisomal membrane proteins Pex3p and Pex15p from the endoplasmic reticulum (ER) to the peroxisome. We documented Pex15p traffic from the ER using a chimeric protein containing a C-terminal glycosylation acceptor peptide. Pex15Gp expressed in wild-type yeast cells is N-glycosylated and functions properly in the peroxisome. In contrast, pex19Δ-mutant cells accumulate the glycoprotein Pex15Gp in the ER. We developed a cell-free preperoxisomal vesicle-budding reaction in which Pex15Gp and Pex3p are packaged into small vesicles in the presence of cytosol, Pex19p, and ATP. Secretory vesicle budding (COPII) detected by the packaging of a SNARE protein (soluble N-ethylmaleimide-sensitive attachment protein receptor) occurs in the same incubation but does not depend on Pex19p. Conversely a dominant GTPase mutant Sar1p which inhibits COPII has no effect on Pex3p packaging. Pex15Gp and Pex3p budded vesicles sediment as low-buoyant-density membranes on a Nycodenz gradient and copurify by affinity isolation using native but not Triton X-100-treated budded vesicles. ER-peroxisome transport vesicles appear to rely on a novel budding mechanism requiring Pex19p and additional unknown factors.     

Blocking TNF-alpha in mice reduces colorectal carcinogenesis associated with chronic colitis

The inflammatory bowel disease ulcerative colitis (UC) frequently progresses to colon cancer. To understand the mechanisms by which UC patients develop colon carcinomas, we used a mouse model of the disease whereby administration of azoxymethane (AOM) followed by repeated dextran sulfate sodium (DSS) ingestion causes severe colonic inflammation and the subsequent development of multiple tumors. We found that treating WT mice with AOM and DSS increased TNF-alpha expression and the number of infiltrating leukocytes expressing its major receptor, p55 (TNF-Rp55), in the lamina propria and submucosal regions of the colon. This was followed by the development of multiple colonic tumors. Mice lacking TNF-Rp55 and treated with AOM and DSS showed reduced mucosal damage, reduced infiltration of macrophages and neutrophils, and attenuated subsequent tumor formation. WT mice transplanted with TNF-Rp55-deficient bone marrow also developed significantly fewer tumors after AOM and DSS treatment than either WT mice or TNF-Rp55-deficient mice transplanted with WT bone marrow. Furthermore, administration of etanercept, a specific antagonist of TNF-alpha, to WT mice after treatment with AOM and DSS markedly reduced the number and size of tumors and reduced colonic infiltration by neutrophils and macrophages. These observations identify TNF-alpha as a crucial mediator of the initiation and progression of colitis-associated colon carcinogenesis and suggest that targeting TNF-alpha may be useful in treating colon cancer in individuals with UC.