Simultaneous assessment of right ventricular function and hypertrophy by Tc-99m MIBI

PURPOSE: Tc-99m MIBI allows the simultaneous performance of cardiac blood pool scintigraphy and myocardial SPECT. The authors performed studies to determine whether right ventricular function and hypertrophy can be evaluated simultaneously using Tc-99m MIBI in patients with right heart disease. METHODS: Using right heart catheterization, several parameters of pulmonary circulation were measured, including right ventricular ejection fraction, in 23 patients with chronic pulmonary disease and pulmonary vascular disease. Within 1 week, right heart blood pool scintigraphy was performed using the first-pass method using Tc-99m MIBI. The right ventricular ejection fraction calculated from right heart blood pool scintigraphy was compared with that measured using right heart catheterization. Myocardial SPECT was performed 1 hour after right heart blood pool scintigraphy. On the short axis images, which allowed optimal visualization of the right ventricle, the right and left ventricular free walls were established as regions of interest. Myocardial wall counts were determined. The right ventricular uptake: left ventricular uptake ratio was calculated to study the relation of that ratio to mean pulmonary artery pressure and total pulmonary resistance. RESULTS: A significant correlation was observed between the right ventricular ejection fraction calculated on right heart catheterization and that calculated on right heart blood pool scintigraphy. The right ventricular uptake:left ventricular uptake ratio correlated positively with pulmonary artery pressure and total pulmonary resistance. CONCLUSION: These results suggest that Tc-99m MIBI allows simultaneous noninvasive evaluation of cardiac function and structure, which previously was considered impossible in patients with right heart disease.     

Pulmonary Resection for Metastases from Hepatocellular Carcinoma

BACKGROUND: Pulmonary metastasectomy has become the standard therapy for various metastatic malignancies to the lungs; however, few data have been available about lung metastasectomy for hepatocellular carcinoma. To confirm the role for resection of pulmonary metastases for such tumors, we reviewed our institutional experience. METHODS: Between 1993 and 2005, 12 patients with pulmonary metastases from hepatocellular carcinomas underwent complete pulmonary resection. All patients had undergone curative resection of their primary hepatocellular carcinomas and also had obtained or had obtainable locoregional control of their primaries. Various perioperative variables were investigated retrospectively to analyze the possible prognostic factors for overall survival and pulmonary metastases-free survival after pulmonary metastasectomy. RESULTS: Nine patients were male and three were female (median age, 53 (range, 43-80) years). Overall survival rate after metastasectomy was 80.8%, 57.7%, and 28.9% at 1, 2, and 5 years, respectively. Pulmonary metastases-free survival rate was 64.2%, 32.1%, and 21.4% at 1, 2, and 5 years, respectively. Five patients presented recurrences in the remaining liver before pulmonary metastases, but hepatic recurrences at this interval did not affect an overall survival after pulmonary metastasectomies. Two patients had undergone living-related liver transplantation. The maximum tumor size of the pulmonary metastasis < 3 cm was the only favorable prognostic factor for overall survival (P = 0.0006), whereas there was no significant prognostic factor for pulmonary metastases-free survival. CONCLUSIONS: Pulmonary metastasectomy for hepatocellular carcinoma in selected patients was well justified when the maximum tumor size was <3 cm.     

Delayed accumulation of activated macrophages and inhibition of remyelination after spinal cord injury in an adult rodent model

OBJECT: Inhibition of remyelination is part of the complex problem of persistent dysfunction after spinal cord injury (SCI), and residual myelin debris may be a factor that inhibits remyelination. Phagocytosis by microglial cells and by macrophages that migrate from blood vessels plays a major role in the clearance of myelin debris. The object of this study was to investigate the mechanisms underlying the failure of significant remyelination after SCI. METHODS: The authors investigated macrophage recruitment and related factors in rats by comparing a contusion model (representing contusive SCI with residual myelin debris and failure of remyelination) with a model consisting of chemical demyelination by lysophosphatidylcholine (representing multiple sclerosis with early clearance of myelin debris and remyelination). The origin of infiltrating macrophages was investigated using mice transplanted with bone marrow cells from green fluorescent protein-transfected mice. The changes in levels of residual myelin debris and the infiltration of activated macrophages in demyelinated lesions were investigated by immunostaining at 2, 4, and 7 days postinjury. To investigate various factors that might be involved, the authors also investigated gene expression of macrophage chemotactic factors and adhesion factors. RESULTS: Activated macrophages coexpressing green fluorescent protein constituted the major cell population in the lesions, indicating that the macrophages in both models were mainly derived from the bone marrow, and that very few were derived from the intrinsic microglia. Immunostaining showed that in the contusion model, myelin debris persisted for a long period, and the infiltration of macrophages was significantly delayed. Among the chemotactic factors, the levels of monocyte chemoattractant protein-1 and granulocyte-macrophage colony-stimulating factor were lower in the contusion model at 2 and 4 days postinjury. CONCLUSIONS: The results suggest that the delayed infiltration of activated macrophages is related to persistence of myelin debris after contusive SCI, resulting in the inhibition of remyelination.     

REG Iα is a Reliable Marker of Chemoradiosensitivity in Squamous Cell Esophageal Cancer Patients

Background A reliable marker of chemoradiosensitivity that would enable appropriate and individualized treatment of thoracic squamous cell esophageal cancer has long been sought. We investigated whether regenerating gene (REG) Iα is such a marker. Methods We assessed expression of REG Iα in untreated endoscopic biopsy specimens and examined the correlation between REG Iα expression and the clinical responses to definitive chemoradiotherapy and prognosis. We also examined the relationship between REG Iα expression in the resected tumor and the prognosis of patients who received esophagectomy for thoracic squamous cell esophageal cancer. Results Among the 42 patients treated with definitive chemoradiotherapy, 8 of the 23 REG I-positive patients (35%) showed complete responses to chemoradiotherapy, while only one of the 19 REG I-negative patients did so. The survival rate among the REG I-positive patients was significantly better than among the REG I-negative patients. For the 76 patients treated surgically, there was no significant difference in the survival rates among the REG I-positive and REG I-negative patients. Conclusions REG Iα expression in squamous cell esophageal carcinoma may be a reliable marker of chemoradiosensitivity. We anticipate that it will enable us to provide more appropriate and individualized treatment to patients of advanced esophageal squamous cell carcinoma.     

Immunomodulatory properties of FK734, a humanized anti-CD28 monoclonal antibody with agonistic and antagonistic activities

BACKGROUND: We describe immunomodulatory effects of FK734, a humanized version of a mouse anti-human CD28 mAb (clone TN228), in vitro and in a chimeric human-mouse model of allograft rejection. METHODS: Cytokine production and proliferation were assessed in a mixed lymphocyte reaction containing FK734, human T cells, and endothelial cells or monocytes. FK734 was also administered to SCID mice engrafted with human skin and adoptively transferred with human peripheral blood mononuclear cells allogeneic to the skin graft. RESULTS: In vitro, FK734 enhanced secretion of interleukin-2 and interferon-gamma as well as proliferation of CD4+ and CD8+ T cells stimulated by allogeneic human leukocyte antigen (HLA)-DR+ human umbilical vein endothelial cells (which lack B7 molecules and FcgammaRs) or by blood monocytes (which express low levels of B7 molecules and FcgammaRs) compared with control mAb, but these effects were significantly smaller than those provided by mAb 28.2, a stimulatory mouse anti-human CD28 mAb, at comparable concentrations. However, FK734 generally inhibited cytokine secretion and T cell proliferation in cocultures with human umbilical vein endothelial cells transduced to express CD86. In vivo using SCID/beige mice bearing human skin with adoptively transferred peripheral blood mononuclear cells, administration of FK734 protected human endothelial cell-lined microvessels, significantly but incompletely reducing endothelial cell injury and T cell infiltration into the graft one or two weeks later. CONCLUSIONS: FK734 is a partial agonist of CD28 signaling that can reduce human T cell alloresponses in the presence of strong costimulation by B7 molecules in vitro and can reduce T cell-mediated skin allograft rejection in vivo.     

Idiopathic calcinosis cutis in fingertip treated with occlusive dressing using aluminum foil: a case report.

Calcium deposition in the skin, known as calcinosis cutis, is an uncommon disorder caused by an abnormal deposit of calcium phosphate in the skin. We report a case of idiopathic calcinosis cutis in fingertip treated with surgical excision followed by the occlusive dressing using aluminum foil, and obtained significant pain relief and round-shaped fingertip which looked normal.     

Long-Term Outcomes and Prognostic Factors with Reductive Hepatectomy and Sequential Percutaneous Isolated Hepatic Perfusion for Multiple Bilobar Hepatocellular Carcinoma

Background

Sorafenib is currently recommended as first-line therapy for patients with intermediate or advanced hepatocellular carcinoma (HCC) per Barcelona Clinic Liver Cancer staging. However, the median overall survival (OS) with sorafenib in these patients is 10.7 months with an overall response rate of 2 %. We retrospectively investigated the long-term outcomes and prognostic factors with reductive hepatectomy and sequential percutaneous isolated hepatic perfusion (PIHP) for refractory intermediate or advanced HCC.

Methods

A total of 68 patients who had intermediate or advanced stage HCC without extrahepatic metastases were scheduled for reductive hepatectomy plus PIHP. All patients underwent reductive hepatectomy and PIHP with mitomycin C 20–40 mg/m² and/or doxorubicin 60–120 mg/m² 1–3 months after surgery (mean, 1.51 times/patient).

Results

The objective response rate of PIHP was 70.6 % (complete plus partial response). The median OS of all 68 patients was 25 months, and the 5-year OS rate was 27.6 %. Univariate and multivariate analyses indicated that tumor response to PIHP and normalization of serum des-γ-carboxy prothrombin concentrations after PIHP were independent prognostic factors for OS.

Conclusions

The median OS of the study population treated by reductive hepatectomy and sequential PIHP was 25 months. This treatment strategy can offer a possible curative treatment to patients with refractory intermediate and advanced HCC.     

The effects of pantethine on lipid and lipoprotein abnormalities in survivors of cerebral infarction

A daily 1000 mg of pantethine was orally administered to 12 male survivors of cerebral infarction for 3 months. Before and after the medication, plasma lipoproteins were ultracentrifugally separated. Plasma concentrations of total cholesterol, triglyceride, phospholipid, and VLDL- and LDL-cholesterol tended to decrease. On the contrary, HDL-cholesterol concentration and HDL:LDL-cholesterol ratio significantly increased. HDL2-cholesterol concentration significantly increased, whereas HDL3-cholesterol concentration remained unchanged, resulting in a significant elevation of HDL2:HDL3-cholesterol ratio. In HDL2 the percentage content of cholesterol and triglyceride decreased, while that of phospholipid increased. However, no significant changes were found in the chemical composition of HDL3. The plasma concentrations of apo A-I and, to a lesser extent, A-II increased, with a slight increase in A-I:A-II ratio but A-I:A-II ratio in either HDL2 or HDL3 remained unchanged.     

Anti‐TCRβ mAb Induces Long‐Term Allograft Survival by Reducing Antigen‐Reactive T Cells and Sparing Regulatory T Cells

TCR specific antibodies may modulate the TCR engagement with antigen–MHC complexes, and in turn regulate in vivo T cell responses to alloantigens. Herein, we found that in vivo administration of mAbs specific for mouse TCRβ (H57–597), TCRα or CD3 promptly reduced the number of CD4⁺ and CD8⁺ T cells in normal mice, but H57–597 mAb most potently increased the frequency of CD4⁺Foxp3⁺ Treg cells. When mice were injected with staphylococcal enterotoxin B (SEB) superantigen and H57–597 mAb, the expansion of SEB‐reactive Vβ8⁺ T cells was completely abrogated while SEB‐nonreactive Vβ2⁺ T cells remained unaffected. More importantly, transient H57–597 mAb treatment exerted long‐lasting effect in preventing T cell responses to alloantigens, and produced long‐term cardiac allograft survival (>100 days) in 10 out of 11 recipients. While Treg cells were involved in maintaining donor‐specific long‐term graft survival, T cell homeostasis recovered over time and immunity was retained against third party allografts. Moreover, transient H57–597 mAb treatment significantly prolonged survival of skin allografts in naïve recipients as well as heart allografts in skin‐sensitized recipients. Thus, transient modulation of the TCRβ chain by H57–597 mAb exhibits potent, long‐lasting therapeutic effects to control alloimmune responses.     

Rosai-Dorfman disease presenting with multiple intracranial and intraspinal masses: a case report

Rosai-Dorfman disease (RDD), a systemic histioproliferative disorder, was first described by Rosai and Dorfman in 1969. However, only 41 cases involving the central nervous system have been reported. The authors present a rare case of RDD with multiple intracranial and spinal lesions mimicking multiple meningioma. A 59-year-old woman was admitted to our hospital with a history of bilateral visual impairment. MRI demonstrated multiple central nervous system lesions in the suprasellar region, right temporal convexity, left frontal convexity, left cerebello-pontine angle and C5 level of the spinal cord. Preoperative neuro-imaging studies suggested multiple meningioma. Subtotal removal of the suprasellar lesion was performed, followed by gamma knife radiosurgery to the residual lesion and the other intracranial lesions. All intracranial lesions disappeared following gamma knife radiotherapy. The spinal lesion, however, was completely excised one year after the initial operation following the appearance of sensory disturbance. Both intracranial and spinal lesions were diagnosed as RDD on histological examination. No recurrences have been detected on MRI two years after the initial operation. Seeing the good results already achieved by surgical removal of RDD, this case suggests that the combination of surgery and gamma knife radiotherapy might improve further.