Heart allograft tolerance without development of posttransplant cardiac allograft vasculopathy in chimerism-based, drug-induced tolerance

BACKGROUND: Recently, we have described a drug (cyclophosphamide [CP] plus busulfan [BU])-induced skin allograft tolerance in mice that can regularly overcome fully H-2-mismatched barriers. Using this method, we have investigated whether or not this regimen can prolong the survival of heart allografts and inhibit the development of posttransplant cardiac allograft vasculopathy (CAV). METHODS: The components of the method are intravenous administration of 1 x 108 allogeneic spleen cells on day 0, intraperitoneal injection of 200 mg/kg of CP and 30 mg/kg of BU on day 2, and intravenous injection of T cell-depleted 1 x 107 allogeneic bone marrow cells from the same strain of mice on day 3. Heart grafting was performed on day 28. Chimerism in peripheral blood was followed by flow cytometric analysis, and histological analysis was performed at various times after grafting. RESULTS: In a fully major histocompatability complex (MHC)-mismatched combination of B10.D2 (H-2d, IE+)-->B10 (H-2b, IE-), stable, multilineage-mixed chimerism was observed permanently. B10.D2 heart grafts were accepted permanently in a donor-specific manner, and posttransplant CAV did not develop. CONCLUSIONS: These results demonstrated that the drug-induced tolerance recently established by us can regularly induce a long-lasting heart allograft tolerance without development of CAV.     

Risk factors of the progression of abdominal aortic calcification in patients on chronic haemodialysis

Background. Vascular calcification is an independent determinantof cardiovascular events in maintenance haemodialysis (HD) patients.It is not known whether acute changes of the serum calcium concentrationbefore and after HD (Ca) are associated with the developmentof aortic calcification. Methods. We enrolled 71 patients dialysed with a dialysate with3.0 mEq/l calcium and determined their aortic calcificationindex (ACI) by abdominal computed tomography twice at an intervalof 3 years. To identify the factors contributing to the rateof progression of aortic calcification, we analysed the averagevalues for clinical and laboratory data obtained between thefirst and second evaluations of ACI. Results. The second ACI (mean ± SD: 80.2 ± 63.9)was significantly greater than the first ACI (61.0 ±61.0) after an interval of 35.8 ± 4.2 months. The annualizedchange of ACI (ACI/year) was significantly and directly associatedwith the Ca and C-reactive protein (CRP) (both P < 0.001,P for trend). Stepwise multivariate regression analysis revealedthat ACI/year was positively and independently associated withCRP, presence of diabetes mellitus and Ca, but negatively associatedwith a premenopausal status in women. Similarly, Ca was positivelyand independently associated with ACI/year and the ultrafiltrationrate, but was negatively associated with pre-HD Ca. Conclusion. The increase of serum calcium after HD was relatedto the rate of progression of aortic calcification. Excess calciumis transferred into patients on HD when using a dialysate of3.0 mEq/l calcium. This may be a risk factor for the developmentof vascular calcification.     

Prognosis of hepatocellular carcinoma associated with Child class B and C cirrhosis in relation to treatment: a multivariate analysis of 411 patients at a single center

Background/Purpose: Given that the prognosis of patients with hepatocellular carcinoma (HCC) complicating severe cirrhosis remains uncertain, particularly with regard to various therapeutic strategies, we have evaluated the prognosis in a series of patients with homogeneous diagnostic and therapeutic histories. Methods: From 1990 to 1998, 411 consecutive HCC patients associated with Child class B and class C cirrhosis who did not have lymph node or distant metastasis were treated by partial hepatectomy (PH; n = 48), percutaneous ethanol injection (PEI; n = 105), transcatheter arterial chemoembolization (TACE; n = 189), chemotherapy, or supportive care (chemo/supportive; n = 69). Univariate survival curves were estimated. The Cox model, stratified by the treatment groups, was used for multivariate analysis. Results: As of January 1999, 305 patients (74.2%) had died. Overall median survival was 23.4 months. There were statistically significant differences between the survival times of patients receiving PH or PEI and TACE, as compared with those receiving chemo/supportive care. According to multivariate analysis, the independent predictive survival factors were: albumin level (≥3.0 g/dl), esophageal varices (i.e., absence), tumor size (≤3.0 cm), tumor number (solitary), and α-fetoprotein (AFP) level (<400 ng/ml). According to the total number of risk factors and the median survival, all patients were divided into four subgroups. For the score 0 group (no risk factor group), 3- and 5-year survival rates were 83.1% and 68.0% for PH, and 87.5% and 62.3% for PEI, respectively. In the score 1–2 group (one or two risk factors), survival rates at 3 and 5 years were 53.1% and 40.3% for PH, 54.8% and 33.2% for PEI, and 35.4% and 22.8% for TACE, respectively. For patients with a score of 3 or more, there were no differences among the treatment groups, excluding those with chemo/supportive care. Conclusions: These findings indicate that, in HCC patients with complicating Child B and C cirrhosis, PEI and PH should be considered first for subgroups of patients with scores (risk factors) of 0–2, as an acceptable survival rate was obtained in such patients. Therefore, the advantages and disadvantages of these therapies regarding tumor size and location should be counterbalanced. In patients with a score of 3 or more, TACE, when possible, could be a first choice because of its applicability and its adjuvant nature with respect to other therapies such as liver transplantation. Received: February 6, 2002 / Accepted: May 22, 2002 Offprint requests to: S. Ueno     

Detection of the proliferated donor cells in bone grafts in rats, using a PCR for a Y-chromosome-specific gene

Conventional corticocancellous bone grafts are known to revascularize gradually and to become repopulated with osteocytes and other types of cells. This study was conducted to study the origin of the cells found within conventional bone grafts as a function of time, using a new method which accurately identifies donor cells transplanted with the graft. The technique requires the transplantation of a 25-mm tibial diaphyseal bone graft from a male rat to a female isogenous recipient, placed anatomically in the tibia. The presence and relative proportion of cells containing the Y-chromosome (i.e., originating from the bone graft) was determined 4, 8, and 12 weeks after transplantation. At these times, genomic DNA was extracted from the grafted bones and a polymerase chain reaction (PCR) specific for the sex-determining region of the Y-chromosome (Sry) was performed, with appropriate controls. Sry-specific bands were evident in none out of three grafts at 4 weeks, two out of three at 8 weeks, and all grafts at 12 weeks. These data demonstrate that not all cells within a conventional graft result from "creeping substitution" of necrotic bone. Instead, a small number of intrinsic cells from a nonvascularized corticocancellous structural graft survive and proliferate over time. Received: June 19, 2001 / Accepted: October 30, 2001     

Sentinel Node Navigation Surgery for Early Gastric Cancer: Analysis of Factors Which Affect Direction of Lymphatic Drainage

World Journal of Surgery - We started performing sentinel node navigation surgery (SNNS) for patients with early gastric cancer (EGC) using infrared ray electronic endoscopy (IREE) with indocyanine...     

Repeated General Anesthesia in a Patient With Noonan Syndrome

Noonan syndrome (NS) is an autosomal dominant disorder characterized by facial anomalies, short stature, chest deformity, congenital heart diseases, and other comorbidities. The challenges faced during anesthetic management of patients with NS could be due to congenital heart diseases, hemostatic disorders, and airway anomalies. Here we describe dental treatment under general anesthesia performed for a 28-year-old man with NS. He had characteristic features of NS along with mild pulmonary valve stenosis. Dental treatment under general anesthesia was performed successfully on 13 occasions with nasotracheal intubation under curve-tipped suction catheter guidance or insertion of a reinforced laryngeal mask airway. This case suggests that for patients with NS, who might present several challenges, dental anesthesiologists should consider the extent of the patient''s disorders to enable them to perform dental treatment safely under general anesthesia.Key Words: Repeated general anesthesia, Noonan syndromeNoonan syndrome (NS) is an autosomal dominant disorder and was first reported by Noonan and Ehmke.¹ The primary features of this multisystem disorder include hypertelorism, low-set ears, down-slanting eyes, a webbed neck, congenital heart diseases, short stature, chest deformity, and intellectual impairment.^2,3 NS affects males and females equally and has an estimated incidence of 1 in 1000 to 1 in 2500 live births.^2,4The challenges faced during anesthetic management of patients with NS could be due to congenital heart diseases, hemostatic disorders, and airway anomalies.^5–8 The present report describes repeated administration of general anesthesia performed by adopting nasotracheal intubation or reinforced laryngeal mask airway insertion for a patient with NS at the time of dental treatment in our hospital.     

Comparison of the Sliding and Femoral Head Rotation among Three Different Femoral Head Fixation Devices for Trochanteric Fractures

Background

Recently, various femoral head fixation devices (HFDs) for trochanteric fractures have become available. However, there are some cases in which femoral head rotation with excessive sliding of the HFD is observed and it is often followed by cutout. The purpose of this study is to compare the ability of the three types of HFDs to prevent femoral head rotation.

Methods

Between July 2005 and December 2009, 206 patients aged over 60 years with trochanteric fractures who had undergone surgical treatment using a short femoral nail in our institution were enrolled into the study. We used the gamma 3 nail (GMN) as the screw-type HFD in 66 cases, the gliding nail (GLN) as a non-cylindrical blade in 76 cases, and the proximal femoral nail antirotation (PFNA) as a cylindrical blade in 64 cases. The sliding length of HFDs and the occurrence of femoral head rotation were evaluated by assessing radiographs as the main outcome, and the results were compared among these devices.

Results

A comparison of the degree of sliding in the GMN group showed that femoral head rotation was observed significantly more frequently in cases with rotation. Further, it appeared that femoral head rotation occurred more frequently in comminuted fractures. However, no significant differences between the sliding lengths of the different HFDs were observed among three groups. Femoral head rotation was observed in 15 cases of GMN (22.7%), 0 case of GLN, and 5 case of PFNA (7.8%). Significant differences with regard to the occurrence of femoral head rotation were observed among the three groups. Furthermore, significant differences were also observed between GLN and PFNA with respect to the occurrence of femoral head rotation.

Conclusions

The ability to stabilize femoral head appears to be greater with blade-type materials than with screw-type materials. Furthermore, we believe that a non-cylindrical blade is preferable to a cylindrical blade for the surgical treatment of comminuted, unstable trochanteric fractures in order to prevent femoral head rotation and cut-out.     

Pre-anesthetic evaluation can play a crucial role in the determination of airway management in a child with oropharyngeal tumor

We experienced a case of a huge hemangioma occupying the oropharyngeal space in an 11-year-old child. Although urgent surgical tracheostomy under local anesthesia was suggested initially, medical interview and findings of computerized tomography and fiberoptic laryngoscopy revealed that the airway of the patient was relatively stable when she was in the semi-left decubitus position. General anesthetic induction would have had potential risks of airway obstruction. Thus, after placing the patient in the semi-left decubutus position, we chose semi-awake induction to secure the airway. With a small dose of fentanyl, we accomplished orotracheal intubation. In this report, we discuss the importance of referring to an airway management algorithm when encountering a difficult airway.     

The effects of arginine and selective inducible nitric oxide synthase inhibitor on pathophysiology of sepsis in a CLP model

BACKGROUND: Sepsis is an arginine-deficient state and is associated with overproduction of nitric oxide (NO) by inducible nitric oxide synthase (iNOS). It has been indicated that low plasma levels of arginine are related to high mortality rates in sepsis. Arginine, however, is also known to be a precursor of NO. Therefore, administration of arginine in septic patients remains controversial. We examined the effects of co-administration of arginine and aminoguanidine, a selective iNOS inhibitor, on sepsis, using rat models. METHOD: Sepsis was induced in rats by cecal ligation and puncture (CLP). Effects of separate and combined administration of arginine and aminoguanidine were investigated by comparing plasma levels of arginine, expressions of heme oxygenase (HO)-1 and HO-2 in liver and lung, and nitrite + nitrate (NOx) excretion in urine, as well as neuroendocrine responses in urine in the early phase of sepsis. Seven-day survival rates were also examined. RESULTS: A combination of arginine and aminoguanidine recovered the plasma level of arginine at 6 h post-CLP, decreased expression of HO-1 in liver and lung at 24 h post-CLP, decreased urinary excretion of epinephrine, norepinephrine, dopamine, and 17-hydroxycorticosteroid in the first 24 h post-CLP, and increased 7-d survival. CONCLUSION: It is demonstrated that administration of arginine together with the selective iNOS inhibitor in the early phase of sepsis restores plasma arginine, reduces oxidative stress by probably maintaining NO derived from constitutive NOS, and attenuates neuroendocrine stress responses. This co-administration may be a beneficial treatment approach against sepsis.