Osteoprotegerin is secreted into the coronary circulation: a possible association with the renin-angiotensin system and cardiac hypertrophy.

The circulating osteoprotegerin (OPG) level reflects a series of cardiovascular diseases; however, the source(s) of circulating OPG remain(s) to be determined. This study explored whether OPG is released in the coronary circulation and whether it is associated with cardiac structure and function. Fifty-six patients (67±10 years old, male 57%, hypertension 73%, coronary artery disease 50%) were enrolled, and blood samples were collected simultaneously from the orifice of the left coronary artery (CA) and the coronary sinus (CS) after angiography. The concentration of OPG was higher in the CS than in the CA (7.7±4.1 vs. 6.7±3.6 pmol/l, p<0.001). The trans-cardiac OPG concentration was significantly (p=0.019) decreased in patients who have been prescribed either an angiotensin converting enzyme inhibitor or an angiotensin II type 1 receptor blocker (ACEI/ARB). In patients subgroup who did not take an ACEI/ARB (n=27), the trans-cardiac OPG level was positively correlated with age (r=0.396, p=0.041) and relative wall thickness of left ventricle (r=0.534, p=0.004). In multivariate linear regression analysis, relative wall thickness remained to be the independent variable for the trans-cardiac OPG level (p=0.004). Moreover, trans-cardiac OPG was significantly (p=0.021) increased in patients with relative wall thickness greater than 0.45 but it did not differ if the left ventricular mass index was increased (≥116 for males, or ≥ 104 for females, g/m(2)) or not (p=0.627). This study suggests that OPG is secreted into the coronary circulation and is associated with concentric remodeling/hypertrophy of LV, possibly in interactions with the renin-angiotensin system.

Zyxin, a regulator of actin filament assembly, targets the mitotic apparatus by interacting with h-warts/LATS1 tumor suppressor.

The mitotic apparatus plays a pivotal role in dividing cells to ensure each daughter cell receives a full set of chromosomes and complement of cytoplasm during mitosis. A human homologue of the Drosophila warts tumor suppressor, h-warts/LATS1, is an evolutionarily conserved serine/threonine kinase and a dynamic component of the mitotic apparatus. We have identified an interaction of h-warts/LATS1 with zyxin, a regulator of actin filament assembly. Zyxin is a component of focal adhesion, however, during mitosis a fraction of cytoplasmic-dispersed zyxin becomes associated with h-warts/LATS1 on the mitotic apparatus. We found that zyxin is phosphorylated specifically during mitosis, most likely by Cdc2 kinase, and that the phosphorylation regulates association with h-warts/LATS1. Furthermore, microinjection of truncated h-warts/LATS1 protein, including the zyxin-binding portion, interfered with localization of zyxin to mitotic apparatus, and the duration of mitosis of these injected cells was significantly longer than that of control cells. These findings suggest that h-warts/LATS1 and zyxin play a crucial role in controlling mitosis progression by forming a regulatory complex on mitotic apparatus.

Feedback regulation mechanisms for the control of GTP cyclohydrolase I activity.

Guanosine triphosphate (GTP) cyclohydrolase I, the rate-limiting enzyme in the biosynthesis of tetrahydrobiopterin (BH4), is subject to feedback inhibition by BH4, a cofactor for phenylalanine hydroxylase. Inhibition was found to depend specifically on BH4 and the presence of another protein (p35). The inhibition occurred through BH4-dependent complex formation between p35 protein and GTP cyclohydrolase I. Furthermore, the inhibition was specifically reversed by phenylalanine, and, in conjunction with p35, phenylalanine reduced the cooperativity of GTP cyclohydrolase I. These findings also provide a molecular basis for high plasma BH4 concentrations observed in patients with hyperphenylalaninemia caused by phenylalanine hydroxylase deficiency.

Schwannoma of the esophagus: a case exhibiting high 18F-fluorodeoxyglucose uptake in positron emission tomography imaging.

Esophageal schwannoma is rare and it is difficult preoperatively to confirm a definitive diagnosis, even using current imaging techniques. We present a case of a benign esophageal schwannoma that was surgically excised and confirmed by immunohistochemical staining. Conventional radiological studies, including barium meal, computed tomography and endoscopic examination had shown a solid submucosal tumor of the upper thoracic esophagus but had been unable to confirm the diagnosis. Positron emission tomography was carried out to evaluate the malignant potential and showed a high uptake of 18F-fluorodeoxyglucose (FDG) into the tumor in both the early and delayed phase, suggesting that the tumor was a potentially malignant tumor such as a gastrointestinal stromal tumor. This is the first reported case of esophageal schwannoma that indicated a high FDG uptake. Although consensus has not been reached regarding the precise mechanism of FDG accumulation in schwannomas, we discuss our clinicopathological findings and review other studies of the subject.

De novo autoimmune hepatitis after living donor liver transplantation in a 25-day-old newborn baby: a case report.

De novo autoimmune hepatitis (AIH) has been described recently as a new type of graft dysfunction in pediatric patients receiving liver transplantation. Herein we have reported the case of a boy, diagnosed as neonatal hemochromatosis, who received a reduced left lateral graft 25 days after birth. Pretransplantation autoantibodies and serological tests were negative. The postoperative course was smooth. No episode of vascular or biliary complication or acute cellular rejection was observed. The maintenance immunosuppressant was tacrolimus only. Liver dysfunction occurred 13 months after living donor liver transplantation. Liver biopsies showed no acute cellular rejection, but severe apoptosis and regeneration of liver cells at the centrolobular area. At that time, various autoantibodies including anti-nuclear, anti-double-stranded DNA, and anti-smooth muscle antibodies were positive. In addition, serum immunoglobulin G (IgG) was elevated. Based on these findings, he was diagnosed as de novo AIH. The treatment consisted of reducing the tacrolimus dose and reintroduction of steroids. After 12 months of treatment, liver dysfunction improved, serum autoantibodies became negative, and serum IgG level normalized. Currently his immunosuppressive therapy consists of low-dose tacrolimus and prednisolone. In conclusion, the present case demonstrated that de novo AIH can appear in living donor liver transplant patients despite appropriate immunosuppression. Reducing the tacrolimus dose and reintroduction of prednisolone sustained the graft and prevented retransplantation.

Impact of intraportal donor-specific leukocyte transfusion for adult ABO-incompatible liver transplantation.

INTRODUCTION: We have reported that repeated donor-specific leukocyte transfusions (DSLT) via the portal vein allow rapid reduction of immunosuppressants and decrease the occurrence of acute cellular rejection. Herein, we examined the immunological benefits of DSLT in adult ABO-incompatible living donor liver transplantation (LDLT). MATERIALS AND METHODS: Ten adult patients (MELD score, 19.4 +/- 7.3; range, 12-29) underwent LDLT from ABO-incompatible donors from August 2003 to November 2007. The antirejection therapy included multiple perioperative plasmaphereses, splenectomy, and quadruple immunosuppression. In addition to these conventional approaches, we performed 4 intraportal administrations of DSLT after transplantation. RESULTS: There was no humoral rejection in any patient. Two patients experienced mild cellular rejection requiring steroid pulse therapy. Both donor-specific immunoglobulin (Ig)M and IgG A/B antibodies in all patients decreased following transplantation by 16 fold. By flow cytometry, donor type of CD56+NK T cells existed in the liver graft showing macrochimerism at 1 month after liver transplantation. Furthermore, interleukin (IL)-10 production of Th2 type cytokines was up-regulated after transplantation. Three patients died of sepsis and infection. The 5-year survival rate was 70% by the Kaplan-Meier method. CONCLUSION: Adult ABO-incompatible liver transplantation can be performed with acceptable patient and graft survival rates with a low risk of antibody-mediated rejection using intraportal administration of DSLT. Donor type CD56+NK T cells may induce tolerance by a veto or an anti-idiotype network mechanism.

Feasibility of auxiliary partial living donor liver transplantation for fulminant hepatic failure as an aid for small-for-size graft: single center experience.

Auxiliary partial orthotopic liver transplantation (APOLT) or heterotopic auxiliary partial liver transplantation (HAPLT) was initially indicated for potentially reversible fulminant hepatic failure (FHF). We started auxiliary partial living donor liver transplantation (LDLT) for FHF in February 2002. Since then, 5 FHF patients (3 females and 2 males) underwent auxiliary partial LDLT: 3 cases of APOLT and 2 cases of HAPLT. All of them received a small-for-size graft: graft-to-recipient weight ratio (GRWR) < or = 1.0%. The etiologies of FHF were hepatitis B virus (HBV) in 1, Wilson's disease in 1, and unknown origin in 3 cases. Three were the acute type and 2 the subacute type of FHF. Median age was 45 years (range, 14-54 years). Blood type was identical in all cases. A left lobe graft was used in 4 instances and a right lobe graft in 1 case. Median GRWR was 0.74 (range, 0.42-0.85). Median follow-up was 42 months (range, 3 days to 70 months). Three of 5 patients (60%) were alive (at 42, 67, and 70 months) and 1 was free of immunosuppression after sufficient recovery of the native liver. Two cases succumbed: 1 at postoperative day 3 because of cytomegalovirus pneumonia and 1 at 10 months after APOLT because of sepsis. Complications were seen in all 5 patients: Relaparotomy for hemostasis in 3, decompression surgery of the abdominal cavity in 1, rehepaticojejunostomy in 1, and biliary strictures in 2 cases. Auxiliary partial LDLT may be a choice as an aid for a small-for-size graft in FHF.

Long-term follow-up study of biliary reconstructions and complications after adult living donor liver transplantation: feasibility of duct-to-duct reconstruction with a T-tube stent.

The aim of this study was to analyze the feasibility of duct-to-duct biliary reconstruction (hepaticohepaticostomy) with a T-tube stent (HH-T) after adult living donor liver transplantation (LDLT) based on long-term follow-up. We retrospectively evaluated 63 primary adult LDLTs who had survived >1 month from March 1999 to January 2008. We compared the incidence of bile leaks and biliary strictures (BS) in 3 groups of patients: Roux-en-Y hepaticojejunostomy (HJ; n = 18); duct-to-duct hepaticohepaticostomy with external stents except a T-tube (HH; n = 26); and HH-T (n = 19). Median follow-up was longer among the HJ (63 months) than the other groups (32 months in HH and 25 months in HH-T; P = .04). Bile leaks developed in 8 of the HJ cases (44%); 9 of the HH cases (33%); and 1 of the HH-T cases (5%; P = .02). All cases with bile leaks (n = 18) were treated using continuous drainage, 15 of them (83%) successfully. BS developed in 4 HJ cases (22%); 12 HH cases (46%), and 4 HH-T cases (21%; P = .12). Intervention for BS (n = 20) was successful in 10 cases (50%) via an endoscopic approach and 6 cases (30%) via a percutaneous transhepatic approach. Operative management for BS was required in 4 cases (20%). Biliary reconstruction using HH-T may be effective to prevent bile leaks after LDLT. However, HH-T may not decrease the incidence of BS after adult LDLT.

Early regular examination of biliary strictures by endoscopic retrograde cholangiography for duct-to-duct biliary reconstruction after adult living donor liver transplantation.

In September 2006, we initiated regular screening of biliary strictures (BS) by endoscopic retrograde cholangiography (ERC) within 6 months after removal of external stents among duct-to-duct biliary reconstructed adult living donor liver transplantations (LDLT). From March 2000 to January 2008, we retrospectively evaluated 45 primary adult LDLTs who had survived >1 month. We separated the cases into 2 groups-the early cases (March 2000 to August 2006: n = 34) and the late cases (September 2006 to January 2008: n = 11)-to compare the incidences of BS and the success rates of endoscopic treatments. Median follow-up of the late cases (8.0 months) was shorter than that of the early cases (38.5 months; P = .0003). The overall incidence of BS was 36% (16/45), with 32% (11/34) among the early and 45% (5/11) among the late cases (P = .18). BS was successfully treated by endoscopic management in 4/5 (80%) late cases and 3/11 (27%) early cases (P = .049). Two early patients required operative biliary reconstructions. Endoscopic procedure-related complications developed in 2 patients among the early cases. Early postoperative regular screening of BS by ERC for duct-to-duct biliary reconstructions may be effective to avoid surgical interventions after adult LDLT. However, repeat ERCs have a risk for pancreatitis and other complications. Further investigations and longer follow-up are needed to confirm the efficacy and safety of a regular examination by ERC for duct-to-duct biliary reconstructions in LDLT.

Optimization of acoustic coupling for bottom actuated scattering based subsurface scanning probe microscopy.

The characterization of buried nanoscale structures nondestructively is an important challenge in a number of applications, such as defect detection and metrology in the semiconductor industry. A promising technique is Subsurface Scanning Probe Microscopy (SSPM), which combines ultrasound with Atomic Force Microscopy (AFM). Initially, SSPM was used to measure the viscoelastic contrast between a subsurface feature and its surrounding medium. However, by increasing the ultrasonic frequency to >1 GHz, it has been shown that SSPM can also measure acoustic impedance based contrasts. At these frequencies, it becomes difficult to reliably couple the sound into the sample such that the AFM is able to pick up the scattered sound field. The cause is the existence of strong acoustic resonances in the sample, the transducer, and the coupling layer-the liquid layer used to couple the sound energy from the transducer into the sample-in combination with the nonlinearity of the tip-sample interaction. Thus, it is essential to control and measure the thickness of the coupling layer with nanometer accuracy. Here, we present the design of a mechanical clamp to ensure a stable acoustic coupling. Moreover, an acoustic method is presented to measure the coupling layer thickness in real-time. Stable coupling layers with thicknesses of 700 ± 2 nm were achieved over periods of 2-4 h. Measurements of the downmixed AFM signals showed stable signal intensities for >1 h. The clamp and monitoring method introduced here makes scattering based SSPM practical, robust, and reliable and enables measurement periods of hours.

Thrombotic microangiopathy after ABO-incompatible living donor liver transplantation: a case report.

Thrombotic microangiopathy (TMA) has rarely been reported in the setting of liver transplantation. Herein we have reported a successful case of TMA after ABO-incompatible living donor liver transplantation (LDLT) treated with plasma exchange and high-dose intravenous gamma-globulin infusion. A 50-year-old woman was diagnosed with hepatitis C virus-related cirrhosis. We performed an ABO-incompatible LDLT (group B to O) with preoperative plasma exchange to reduce the anti-B hemagglutinin titers to 1:8. The immunosuppressants consisted of tacrolimus, mycophenolate mofetil, and steroid. On postoperative day (POD) 8, her anti-B hemagglutinin titer suddenly increased to 1:64. The serum lactate dehydrogenase (LDH) level was grossly elevated (1518 IU/L). On POD 13, we suspected infection of an intra-abdominal hematoma (Serratia marcescens) which was drained surgically. On day 5 after the reoperation, thrombocytopenia developed with a platelet count of 3 x 10(4)/mm3. A peripheral blood film showed severe red blood cell (RBC) fragmentation. Thus, we made a clinical diagnosis of TMA and reduced the tacrolimus dose. We started intensive daily plasma exchange (4 L/d) with fresh frozen plasma and high-dose intravenous gamma-globulin infusions. One week thereafter, thrombocytopenia improved with reduced transfusion requirements. The peripheral blood film showed normal RBC morphology. The serum LDH returned to baseline levels. Four factors were considered to have caused TMA in this case: the prescription of tacrolimus, ABO-incompatible liver transplantation, bacterial infection, and surgical stress. These factors may have all contributed by causing significant endothelial injury and TMA.

Living related pancreas transplantation alone with enteric drainage in Japan: case report.

In this study, we report a living donor partial pancreas transplantation using intraportal donor-specific leukocyte transfusion (DSLT). The recipient was a 38-year-old woman who had type I diabetes mellitus for 17 years. Hypoglycemia occurred 2 or 3 times per week. Her hemoglobin A1c level was 9.0%, and she required 70 U of insulin almost every day. The donor was her 64-year-old father. The steroid-minimized immunosuppressive protocol included 1.5mg of thymoglobulin administered with a steroid bolus on days 0, 4, and 7 postoperatively. Steroids were never prescribed thereafter. Postoperative maintenance therapy included tacrolimus (FK506) and mycophenolate mofetil. In addition to these conventional approarches, we administered intraportal DSLT on days 0, 1, 4, and 7 after transplantation. The donor-specific leukocytes (40mL) had been separated from donor whole blood using an apheresis filter (Cellsorba EX; Asahi Kasei medical Co, Ltd, Tokyo, Japan). In the recipient operation, a segmental pancreas graft was transplanted into the right iliac cavity with enteric drainage with a pancreatic duct stent. Operation time was 6 hours. The postoperative course was uneventful. The patient was discharged on day 15 after transplantation. There was no acute rejection for six months after transplantation. The hemoglobin A1c level recovered to 5.1% with 6 U of insulin per day. At immunologic analysis, only interleukine-10 cytokine production was elevated at 7 days after transplantation. At flow cytometry cross-match analysis, the immunoglobulin M antibody decreased from day 7 after transplantation. We conclude that intraportal DSLT may be an effective adjunct to a steroid-free regimen.

Adult ABO-incompatible liver transplantation by intraportal transfusion of donor-specific antigen: a case report.

A 55-year-old-woman suffering from fluminant hepatitis owing to autoimmune hepatitis underwent ABO-incompatible liver transplantation (LRLD) of blood type A to B. In this study, we investigated whether a new immunosuppressive strategy by intraportal transfusion of donor-specific leukocytes (DSLT) separated from whole blood would yield immunological benefit in adult ABO-LRLD. The operative course was uneventful; she was discharged at 46 days postoperatively without humoral or cellular rejection. On immunologic analysis, 54.6% intrahepatic macrochimerism of donor type CD56+ T cells was recognized at 1 month after transplantation. The interleukin-10 Th2 cytokine level was increased on postoperative day 1. Adult ABO-incompatible liver transplantation can be performed with acceptable patient and graft survival rates with a low risk of antibody-mediated rejection with our strategy of immunosuppression by intraportal administration of DSLT. Donor type CD56+ NKT cells may induce tolerance by a veto mechanism and/or an anti-idiotype network. ABO-incompatible liver transplantation may be improved by this strategy.

Temporary cardiac pacing for fatal arrhythmia in living-donor liver transplantation: three case reports.

Cardiac pacing often turns out to be the only effective treatment of severe, life-threatening arrhythmias. We performed 77 living-donor liver transplantations (LDLT) from 1999 to 2007. In these cases, three recipients experienced fatal arrhythmia and required temporary cardiac pacing during the perioperative period. The first case was a 68-year-old woman diagnosed with liver cirrhosis and hepatocellular carcinoma (HCC). Her Model for End-Stage Liver Disease (MELD) score was 34. We performed LDLT using a right lobe graft. She showed complete atrioventricular block with cardiac arrest at postoperative day (POD) 42 after a bacterial infection. We performed a resuscitation and instituted temporary cardiac pacing. However, she was dead at POD 43. Pathologic findings at autopsy showed a diffuse myocardial abscess, which caused the fatal arrhythmia. The second case was a 58-year-old man diagnosed with HCC and liver cirrhosis; his MELD score was 9. We performed LDLT using a right lobe graft. He showed atrial fibrillation after septic shock. He also showed sinus bradycardia with a cardiac arrest at POD 10. We performed resuscitation and emergent temporary pacing. He recovered and was alive without recurrence of arrhythmia or infection. The third case was a 58-year-old woman diagnosed with multiple HCC. During preoperative regular check-up, she was diagnosed to have cardiac hypertrophy and was started on beta-blockers as treatment for cardiac hypertrophy. However, severe bradycardia necessitated temporary cardiac pacing. LDLT was performed safely after implantation of a pacemaker. Early use of temporary cardiac pacing for severe arrhythmias may be effective to maintain the hemodynamic state in LDLT.

Successful super-small-for-size graft liver transplantation by decompression of portal hypertension via splenectomy and construction of a mesocaval shunt: a case report.

We performed a successful super-small-for-size graft liver transplantation by decompressing portal hypertension via splenectomy and a mesocaval shunt. A 46-year-old woman with Child-Pugh class C liver cirrhosis associated with Wilson's disease underwent a living donor liver transplantation (LDLT). The donor had an anomalous portal vein, hepatic vein, and bile duct, so we had to use the right lateral segment for the graft. Preoperative computed tomographic (CT) volumetry showed the volume of this area to be 433 mL; graft-to-recipient weight ratio (GRWR) was 0.72; and graft-to-standard liver volume (GV/SLV) was 39.0%. However, the real volume of the resected right lateral segment was 281 g; GRWR was 0.47; and GV/SLV was 25.3%--a super-small-for-size graft. After implantation, congestion of the small graft was severe due to excessive portal hypertension. Therefore, we tried decompressing the portal vein. First, we performed splenectomy which reduced the portal pressure which remained excessive. Second, a mesocaval shunt was constructed decreasing the portal pressure from 38 to 30 cm H2O. Additionally, we initiated continuous portal injection of prostaglandin E1. The postoperative course was not smooth, but the general status slowly recovered. Over 25 cm H2O of portal hypertension was observed until postoperative day 21 when it improved. At last, the recipient was discharged on postoperative day 156. Accurate preoperative CT volumetry is important to obtain sufficient graft volume. Our case may be one of the smallest-for-size grafts that was successfully transplanted. Management of excessive portal hypertension is important for LDLT, especially using a small-for-size graft. Splenectomy and construction of a mesocaval shunt may be useful strategies to decompress the portal vein.

Successful management of a type 2 diabetic donor in living-donor liver transplantation: a case report.

A 50-year-old woman with a 4-year history of type 2 diabetes history was treated with nateglinide (270 mg/day) and metformin hydrochloride (500 mg/day). The recipient was her 55-year-old husband whose diagnoses were liver cirrhosis with type C chronic hepatitis (Child-Pugh C, score, 10; Model for End-Stage Liver Disease: 15), hepatocellular carcinoma (solitary, 2 cm), and hepatic encephalopathy. Her body weight was 50 kg and body mass index 21.6 kg/m2. Laboratory examinations showed fasting blood glucose of 110 mg/dL and hemoglobin A1c (HbA1c) of 6.6% upon admission. Right liver lobectomy was performed of a 563-g graft. Operative time was 253 minutes and blood loss 50 mL. She was discharged at postoperative day 9 without any complications. We changed nateglinide and metformin hydrochloride to insulin aspart or human insulin after admission. Blood glucose level was strictly controlled using a sliding scale of insulin. She received regular glucose check-ups at our outpatient clinic after discharge. She stopped using insulin and returned to nateglinide and metformin hydrochloride on postoperative day 25. Her blood glucose level was 80 to 150 mg/dL and HbA1c was 5.8% at 5 months after surgery. This type 2 diabetic living liver donor showed good control of the postoperative glucose level without exacerbation or diabetic complications.

Coagulation and fibrinolytic systems during liver regeneration in the early period after adult living related partial liver transplantation.

In this study, we investigated the differences in the perioperative blood coagulation and fibrinolytic systems (BCF) between donor and recipient after adult living related partial liver transplantation (ALRPLT), with particular reference to serum plasminogen-activator inhibitor-1 (PAI-1) and soluble fibinogen level. The BCF were unstable in the recipient compared with the donor. The recipient fibrinolytic system was the same as the donor system except for PAI-1, which was remarkably increased on day 1 after transplantation in the recipient. The recipient is thought to have disseminated intravascular coagulation in the early period after ALRPLT. Soluble fibrinogen may be a useful marker for improvement in the BCF system. The elevation of PAI-1 in recipients on day 1 after transplantation may be a marker of injury from the shear stress from excessive portal hypertension after ALRPLT.

Number of positive lymph nodes independently affects long-term survival after resection in patients with ampullary carcinoma.

AIM: The nodal status is an established prognostic factor in ampullary carcinoma. The aim of this study was to compare the prognostic power of the anatomic location of positive nodes with that of the number of positive nodes. METHODS: Of 73 consecutive patients treated for ampullary carcinoma, 62 underwent pancreaticoduodenectomy with regional lymphadenectomy. A survival analysis of these 62 patients by nodal status was conducted retrospectively. A total of 1942 lymph nodes taken from the patients were examined histologically for metastasis. The location of positive regional nodes was classified into 4 categories, according to the Japanese staging system. The number of positive regional nodes was recorded for each patient. The median follow-up period was 124 months. RESULTS: Nodal disease was found in 31 patients, of whom 23 had 1-3 positive regional nodes and 8 had >or=4 positive regional nodes. Univariate analysis revealed that both the location (p<0.0001) and the number (p<0.0001) of positive nodes were significant prognostic factors. Multivariate analysis revealed that the number of positive nodes was an independent prognostic factor (p=0.007), while the location failed to remain as an independent variable. The median survival time was 59 months with a 5-year survival rate of 48% in patients with 1-3 positive nodes, whereas all patients with >or=4 positive nodes died of the disease within 29 months of resection (p=0.0001). CONCLUSION: The number, not the location, of positive regional lymph nodes independently affects long-term survival after resection in patients with ampullary carcinoma.

Melkersson-Rosenthal syndrome with isolated immunoglobulin E hypogammaglobulinaemia.

Melkersson-Rosenthal syndrome (MRS) is a rare disorder classically presenting with a triad of recurrent orofacial swelling, facial palsy and a fissured tongue. This case report describes a case of MRS in a patient with isolated immunoglobulin E (IgE) hypogammaglobulinaemia. The 52-year-old woman presented with puffy eyelids, lower lip swelling and right facial nerve palsy. Fissures of the tongue were also noted. On investigation she was found to have a markedly low serum IgE level. This case report clearly indicates that IgE-mediated reactions do not play a significant role in the development of MRS.

Co-localization of von Willebrand factor with platelet thrombi, tissue factor and platelets with fibrin, and consistent presence of inflammatory cells in coronary thrombi obtained by an aspiration device from patients with acute myocardial infarction.

BACKGROUND: Detailed histochemical analysis of coronary thrombi obtained freshly from acute phase of myocardial infarction patients may provide information necessary to understand the mechanism of coronary occlusive thrombus formation. METHODS AND RESULTS: Coronary thrombi causing myocardial infarction were obtained from 10 consecutive patients of myocardial infarction in the acute phase, using a newly developed aspiration catheter. All the fixed specimens of coronary thrombi, by hematoxylin and eosin staining, were found to contain three major constituents, namely, platelets, densely packed fibrin and inflammatory cells, including polymorphonuclear and mononuclear cells, although their distribution in each specimen is totally heterogeneous. Immunohistochemical staining revealed the prominent presence of von Willebrand factor (VWF) at the sites of platelet accumulation, presence of tissue factor and platelets at the sites of deposition of fibrin fibrils. It also revealed the presence of CD16-, CD45- and CD34-positive cells, yet the functional roles of these cells have still to be elucidated. There are weak positive correlation between the number of inflammatory cells involved in the unit area of coronary thrombi specimen and the time of collection of the specimens after the onset of chest pain. CONCLUSIONS: In spite of various limitations, our results contain information suggesting the possible role of VWF in platelet-thrombus formation, possible important role played by tissue factor and activated platelets in the formation of fibrin fibrils, and the positive relationship between inflammatory cells migration and the formation of occlusive thrombi in human coronary arteries.