Initial steroid bolus injection promotes vigorous CD8+ alloreactive responses toward early graft acceptance immediately after liver transplantation in humans.

We have found that steroid bolus withdrawal prior to graft reperfusion increased the incidence of acute cellular rejection (ACR). This study aims to clarify how initial steroid bolus (ISB) injection at reperfusion influences the kinetics of CD8(+) alloreactive immune responses immediately after living donor liver transplantation (LDLT). A total of 49 hepatitis C virus (HCV)-infected recipients were classified into 3 groups according to hierarchical clustering by preoperative CD8(+)CD45 isoforms. The naive T cell proportion was considerably higher in Group I than in Groups II and III, whereas Group II recipients had the highest effector memory (EM) T cells and Group III the highest effector T cells. The frequency of ACR was significantly higher in recipients without ISB than in those with ISB. In particular, the ACR rates were the highest in Group II without ISB. Following ISB, the proportion of effector T cells was promptly upregulated within 6 hours after graft reperfusion, simultaneously with the upregulation of CD27(-)CD28(-) subsets, interferon-gamma (IFN-gamma), tumor necrosis factor-alpha and perforin expression, which significantly correlated with increasing interleukin (IL)-12 receptor beta 1 cells. These were then downregulated to below preoperative levels by tacrolimus (Tac) administered at 24 hours. These changes did not occur in the absence of ISB. In Group II without ISB, the downregulation of IL-12Rbeta1(+) cells was the greatest, consistent with the highest rates of ACR and mortality (60%). In conclusion, ISB must be done in place, especially in Group II with preexisting high EM T cells, to enable the development of early allograft acceptance.     

Dopamine agonists and valvular heart disease in Japanese patients with Parkinson's disease

Journal of Neurology - A high incidence of valvular heart disease in Parkinson's disease (PD) patients treated with ergot-derived dopamine agonists, such as cabergoline and pergolide, has been...     

Double congenital bronchoesophageal fistulae in an adult

We report adult congenital bronchoesophageal fistula with both symptomatic fistula and asymptomatic one. A 56-year-old woman with a history of cough after drinking fluids was diagnosed as bronchoesophageal fistula by upper gastrointestinal series that showed a diverticulum in the middle portion of the esophagus with a fistula between the esophagus and right lower lung. Esophagoscopy revealed an orifice of the fistula located 27 cm from the incisors. Computed tomography showed chronic inflammatory change with bronchiectasis in the S6 segment of the right lung. The patient underwent video assisted thoracic surgery that identified two fistulae without missing a symptomatic one, and both were successfully resected. The fistulae were lined by squamous epithelium and smooth muscle without evidence of malignancy, infection or chronic inflammation that were histologically compatible with congenital fistulae.     

Effects of Hemoglobin Concentration, Skull Thickness, and the Area of the Cerebrospinal Fluid Layer on Near-infrared Spectroscopy Measurements

Background: Previous studies documented that near-infrared spectroscopy values were affected by factors related to optical path length, such as hemoglobin concentration, the differential path length factor, skull thickness (t-skull), and the area of the cerebrospinal fluid layer (a-CSFL). Lately, the NIRO-100 (Hamamatsu Photonics, Hamamatsu, Japan) has provided a tissue oxygen index (TOI) that theoretically is not supposed to be affected by optical path length. Therefore, the authors hypothesized that TOI is not influenced by the above-described individual factors.

Methods: Cardiac surgical or neurosurgical 103 patients (65 men and 39 women; aged 63 +/- 14 yr) were studied. TOI and regional cerebral oxygen saturation (rSO2) (INVOS 4100; Somanetics, Troy, MI) were measured sequentially on patients in a resting state. The t-skull and a-CSFL were calculated using computed tomographic image slices of the head corresponding with the position of near-infrared spectroscopy sensors. The effects of these two factors, hemoglobin concentration and mean arterial pressure, on TOI and rSO2 values were evaluated by linear regression analysis.

Results: Simple linear regression analysis showed that mean arterial pressure (r = 0.27, P = 0.008), t-skull (r = 0.22, P = 0.034), a-CSFL (0.26, P = 0.012), and hemoglobin concentration (r = 0.42, P < 0.0001) were significant determinants of rSO2. Multiple linear regression analysis showed that hemoglobin concentration (r = 0.34, P < 0.001), a-CSFL (r = -0.252, P = 0.012), and t-skull (r = 0.22, P = 0.037) were significant determinants of rSO2. On the other hand, simple and multiple linear regression analysis showed that there was no significant determinant of TOI.     

Influences of angiogenesis and lymphangiogenesis on cancerous invasion in experimentally induced tongue carcinoma

BACKGROUND: Although it is clear that dissemination via the blood system involves angiogenesis, it is uncertain whether tumors also induce lymphangiogenesis or simply invade existing peritumoral vessels. The purpose of this study was to elucidate changes in tumor blood and lymph vessels in cases involving the invasion of squamous cell carcinoma in the oral cavity, and its significance. Blood and lymph vessels densities in tongue carcinomas induced in hamsters were investigated. METHODS: Tongue cancer was induced by abrading the right margin of the tongue of each hamster with an endodontic barbed broach and subsequently applying 1.0% 9,10-dimenthl-1,2-benzanthracene (DMBA) dissolved in acetone, three times a week, at the same site. Fresh frozen sections were prepared and blood vessels stained blue by perfusion with Coomassie Brilliant Blue and lymph vessels stained brown for 5'-nucleotidase. The effects on the blood vessels and lymph vessels were observed. RESULTS: The results showed that blood and lymph vessel densities were greater in the advanced carcinoma tissues than in normal tissue. These were compared in terms of the mode of cancer invasion. As tumor invasion progressed, the blood vessel density decreased but lymph vessel density tended to be higher in high-degree tumor invasion than in low-degree tumor invasion. The expression of vascular endothelial growth factor-C was seen more frequently as tumor invasion progressed. CONCLUSIONS: The present findings indicated that angiogenesis and lymphangiogenesis are affected by cancerous invasion.     

Differentiation of blast cells from a Down's syndrome patient with transient myeloproliferative disorder

A male neonate with Down's syndrome and congenital myeloproliferative disorder was studied. His blood picture showed the unique coexistence of leukocytosis with matured cells and a large number of blast cells. The in vitro proliferation and differentiation of blast cells into various lineages in the presence of phytohemagglutinin-stimulated leukocyte conditioned medium (PHA-LCM) was examined by using a liquid culture and a methylcellulose culture system. The differentiation of blast cells into myeloid cells was confirmed by specific cytochemical stainings, electron microscopy, and an immunologic study. No specific factors in the plasma of the patient promoted the proliferation or differentiation of blast cells. The cellular composition of colonies grown in methylcellulose culture from single blast cells was studied by a micromanipulation technique. High plating efficiency was observed. Of 136 cultures, 78 showed colony growth. Half of the blast cells were colony-forming cells that could proliferate and differentiate into basophils, neutrophils, eosinophils, macrophages, and erythrocytes in the presence of PHA-LCM. Using the blast cells with a high differentiation capacity to the basophil pathway, we studied the effect of recombinant granulocyte-macrophage colony-stimulating factor (GM- CSF). Recombinant GM-CSF support neutrophils, eosinophils, and macrophages but not typical basophils. These findings of the cell differentiation of blast cells into various kinds of cells in vitro were in agreement with the finding of neutrophilia, eosinophilia, basophilia, and thrombocythemia in this patient.     

Muscle strength in patients with gastrointestinal carcinoma--an important role of muscle strength as a nutritional parameter

The relationship between nutritional status and muscle strength was examined in 73 patients with gastrointestinal carcinoma preoperatively. Nutritional status was assessed by measuring various nutritional parameters. Muscle strength was determined by measurements of %grip strength and respiratory muscle strength expressed as %maximal expiratory and inspiratory pressure (%MEP and %MIP). The results were as follows: %GS was significantly low in the patients who showed low values in body weight (%ideal body weight: %IBW), mid-arm muscle circumference (%AMC), serum albumin (Alb), serum prealbumin (PA), total peripheral lymphocyte count (TLC), and/or nutritional surgical risk index (NRI). %MEP was significantly low in the patients who showed low values in %IBW, %AMC, triceps skin fold, Alb, PA, retinol binding protein, NRI, and/or nutritional assessment index (NAI). %MIP was significantly low in the patients who showed low values in %IBW, %AMC, creatinine height index, Alb, PA, NRI, and/or NAI. %MEP and %MIP were significantly correlated with %GS. Preoperative %GS value was significantly low in the esophageal cancer patients with postoperative pulmonary complications. It was suggested that %GS was a simple and useful nutritional parameter for detecting depletion of the muscle mass and visceral proteins, for respiratory muscle strength, and for functional capacity of muscle.     

Augmentation and subsequent attenuation of Ca2+ current due to lipid peroxidation of the membrane caused by t-butyl hydroperoxide in the rabbit sinoatrial node.

Cellular electrophysiological effects of membrane lipid peroxidation by t-butyl hydroperoxide (TBH) were studied in the rabbit sinoatrial (SA) node. Superfusion for 1-5 min with 300 microM TBH caused an initial increase and subsequent decrease in the spontaneous firing frequency of the SA node. Voltage clamp experiments revealed that TBH initially enhanced but later blocked the Ca2+ current. Thus, membrane lipid peroxidation appears to accelerate and then suppress physiological automaticity by causing biphasic changes in the Ca2+ current.