Effects of pre-surgical nasoalveolar moulding on maxillary arch and nasal form in unilateral cleft lip and palate before lip surgery.

OBJECTIVES: To investigate the effects of pre-surgical nasoalveolar moulding (PNAM) on the maxillary arch and nasal form in patients with unilateral cleft lip and palate (UCLP). SETTING AND SAMPLE POPULATION: This is a retrospective case series study. The subjects were infants with complete UCLP who were treated with PNAM (n = 18) at Kagoshima University Medical and Dental Hospital (Japan) between 2006 and 2013. MATERIAL AND METHODS: Maxillary dental casts and facial photographs were taken at the time of the first visit and immediately prior to lip surgery to evaluate the maxillary arch and nasal form changes. The dental casts were scanned with a laser scanner, and changes in the 3-Dimensional coordinates of anatomical landmarks and alveolar cleft width were analysed. Moreover, we investigated the correlation between the changes in the maxillary alveolar arch and nasal form. RESULTS: Regarding the maxillary alveolar arch form, the anterior points of the major segment had moved significantly to the cleft side just prior to the time of lip repair, and the alveolar cleft width was significantly decreased. For nasal form, the inclination and displacement of the columella were significantly improved. The improvement of columella inclination was moderately correlated with the posterior movement of the anterior points of the major segment. CONCLUSIONS: These findings indicate that PNAM for infants with UCLP enhanced symmetry in the maxillary alveolar arch and nasolabial form. In addition, the posterior movement of the anterior points of the maxillary alveolar arch was correlated with the improvement of columella deformation.

Clinical Experience of Late Conversion From Antimetabolites With Standard Exposure Calcineurin Inhibitors to Everolimus With Calcineurin Inhibitor Minimization in Stable Kidney Transplant Recipients With Good Renal Function.

INTRODUCTION: This study describes our clinical experience of late conversion from antimetabolites with standard exposure calcineurin inhibitors (CNIs) to everolimus with CNI minimization in stable kidney transplant recipients with good graft function. PATIENTS AND METHODS: A 1-year retrospective pilot study of 26 kidney recipients converted from antimetabolites with standard exposure CNIs to everolimus with CNI minimization was performed. The recipients enrolled in this study had normal or slightly impaired renal function defined as a serum creatinine value <2.0 mg/dL, and normal or slightly increased albuminuria defined as a urinary albumin excretion rate <100 mg/g creatinine. RESULTS: The median time from transplant to conversion was 39.5 months posttransplant (range, 3-275). Treatment with everolimus was stopped owing to adverse events in 11 patients (42.3%). In the analysis of the patients in whom everolimus was maintained, the mean estimated glomerular filtration rate (eGFR) significantly increased from 50.7 ± 11.9 mL/min/1.73 m(2) at baseline to 53.6 ± 13.9 mL/min/1.73 m(2) at 1 year after conversion. In the patients in whom everolimus was stopped during the observation period, there was no difference in eGFR between baseline and 1 year after conversion. CONCLUSIONS: This study demonstrated that, among the patients converted to everolimus at a late stage, there was no deterioration in renal function whether everolimus was maintained or stopped within 1 year after conversion.

Carcinosarcoma of the fallopian tube with disappearance of carcinoma cells by neoadjuvant chemotherapy: case study.

The authors report a case of carcinosarcoma (CS) of the fimbria of the fallopian tube in which carcinoma cells disappeared with neoadjuvant chemotherapy (NAC). A 74-year-old woman visited the present hospital with a large pelvic mass and pleural effusion. A magnetic resonance image of the tumor was highly suggestive of ovarian carcinoma. Due to the presence of both serous.adenocarcinoma cells in pleural effusion and pulmonary thrombosis, the patient was given NAC consisting of carboplatin plus paclitaxel (TC) and anticoagulant therapy with warfarin potassium. With six courses of NAC, the pleural effusion and pulmonary thrombosis disappeared, and the tumor decreased 36.2% in greatest diameter. Maximum debulking surgery was then performed. The tumor was found to be located in the fimbria of the right fallopian tube. Hysterectomy and bilateral salpingo-oophorectomy were performed, and histologic examination revealed chondrosarcoma with the presence of necrotic epithelial cells. The necrotic areas were interspersed with papillary structures, and immunohistochemical study showed positivity for CK7 and negativity for CK20, p53, and estrogen receptor (ER), indicating serous adenocarcinoma. Thus, heterologous CS with disappearance of viable carcinoma cells by NAC was diagnosed. The patient was given adjuvant chemotherapy consisting of three courses of TC, and there has been no evidence of disease for 20 months. The authors' experience in this case of gynecologic CS indicates that a serous adenocarcinomatous component of tubal CS can be well cured by TC-based NAC.

Study of cysteinyl leukotriene-1 receptor in rat renal ischemia-reperfusion injury.

Renal ischemia-reperfusion (I/R) injury is a major cause of renal transplant dysfunction. Recent studies of I/R injury have focused on the function of neutrophils, the mechanisms of action of inflammatory cytokines, and oxygen free radicals, as well as other mediators. However, few reports address the cysteinyl leukotriene-1 receptor (CysLT1R), an important mediator of bronchial asthma in human beings. We examined the expression of CysLT1R in rat renal I/R injury. At laparotomy, the right kidney was harvested and the left renal artery and vein were clamped. The kidney was reperfused after 90 minutes of ischemia, and the rats were killed after 0, 3, 5, 12, or 24 hours. Expression of CysLT1R analyzed at immunohistochemistry was observed only in endothelial cells in nonischemic kidney. At 0 to 3 hours after reperfusion, CysLT1R expression on endothelial cells gradually became stronger, being most intense at 3 hours after reperfusion. Twelve hours after reperfusion, necrosis extended throughout the ischemic kidney; nearly all of the tubular epithelial cells were destroyed. At 3 to 12 hours after reperfusion, CysLT1R expression gradually became weaker on endothelial cells. At 24 hours after reperfusion, CysLT1R expression was almost at the level of that in nonischemic kidney. Expression of CysLT1R was noted in a rat model of renal I/R injury. Several hours after the maximal CysLT1R expression, we observed the maximum renal I/R injury. These results may suggest a relationship between the CysLT1R and renal I/R injury.

Differential distribution of orexin-A-like and orexin receptor 1 (OX1R)-like immunoreactivities in the Xenopus pituitary.

Immunohistochemical techniques were employed to investigate orexin-A-like and orexin receptor 1 (OX1R)-like immunoreactivities in the Xenopus pituitary gland. Orexin-A-immunoreactive cells were mainly scattered in the posterior half of the pars distalis. They corresponded to thyroid-stimulating hormone (TSH)-containing cells and so far have not corresponded to other types of pituitary adenocytes. On the other hand, OX1R-immunoreactive cells were mainly distributed in the anterior half of the pars distalis and corresponded to prolactin (PRL)-containing cells; however, we found that OX1R-immunoreactive cells did not correspond to other types of adenocytes in the Xenopus pituitary. These results suggest that an orexin-A-like substance secretes with and/or without TSH from TSH-containing cells and that the peptide modulates the functions of PRL-containing cells via OX1R in a paracrine fashion.

Study of peroxisome proliferator-activated receptor (PPAR)-gamma in renal ischemia-reperfusion injury.

Recent studies of ischemia-reperfusion (I/R) injury have focused on the function of neutrophils, the action mechanism of inflammatory cytokines. However, few reports have addressed peroxisome proliferator-activated receptor (PPAR)-gamma. PPAR-gamma is a ligand-activated transcriptional factor belonging to the steroid receptor superfamily. It plays a role in both adipocyte differentiation and tumorigenesis. We researched the expression of PPAR-gamma in renal I/R injury of the rat. Male Lewis rats were used. The right kidney was harvested and the left renal artery and vein were clamped at 90 minutes of ischemic time. Rats were killed at 0, 1.5, 3, 5, and 12 hours after reperfusion. PPAR-gamma expression was studied by immunohistostaining. PPAR-gamma expression was observed only on mesangial and endothelial cells of normal kidney. From 1.5 to 3 hours after reperfusion, PPAR-gamma expression gradually became stronger on mesangial and endothelial cells. PPAR-gamma expression was most intense on mesangial cells and endothelial cells at 3 hours after reperfusion. Twelve hours after reperfusion, necrosis extended throughout the ischemic kidney and nearly all the tubular epithelial cells were destroyed, but 12 hours after reperfusion PPAR-gamma expression gradually became weaker on mesangial and endothelial cells. PPAR-gamma was expressed in the rat model having renal I/R injury. Several hours after maximal of PPAR-gamma expression, maximal renal I/R injury was observed. These results may indicate a relationship between PPAR-gamma expression and renal I/R injury.

Early detection of cardiac involvement in patients with sarcoidosis by a non-invasive method with ultrasonic tissue characterisation.

OBJECTIVES: To clarify the value of cycle dependent variation of myocardial integrated backscatter (CV-IB) analysis, which non-invasively measures acoustic properties of the myocardium, for early detection of cardiac involvement in patients with sarcoidosis. METHODS: The study population consisted of 22 consecutive patients with biopsy proven sarcoidosis who did not have any abnormal findings on conventional two dimensional echocardiogram. Cardiac sarcoidosis was diagnosed by radionuclide testing including thallium-201 scintigraphy, gallium-67 scintigraphy, and cardiac fluorine-18-deoxyglucose positron emission tomography. The magnitude and delay of the CV-IB were analysed in the basal mid septum and the basal mid posterior wall of the left ventricle of all patients. RESULTS: The patients were divided into two groups: 8 patients with cardiac involvement and 14 patients without cardiac involvement. In the basal septum, a major reduction in the magnitude (mean (SD) 1.8 (4.4) v 6.6 (1.3), p = 0.012) and an increase in the time delay (1.3 (0.5) v 1.0 (0.1), p = 0.038) of CV-IB were observed in patients with cardiac sarcoidosis even in the absence of two dimensional echocardiographic abnormalities. The sensitivity for detecting cardiac involvement was such that the magnitude of CV-IB in the basal septum discriminated 75% of patients with cardiac sarcoidosis from those with non-cardiac sarcoidosis, whereas two dimensional echocardiographic parameters did not discriminate between these two groups. CONCLUSIONS: The CV-IB is decreased in the basal septum in patients with cardiac sarcoidosis even in the absence of two dimensional echocardiographic abnormalities. Analysis of CV-IB may be a useful method to detect early myocardial involvement in patients with sarcoidosis.

Reduced-intensity non-T-cell depleted HLA-haploidentical stem cell transplantation for older patients based on the concept of feto-maternal tolerance.

With the recent progress in reduced-intensity conditioning stem cell transplantation (RIST) and taking into consideration the concept of feto-maternal immunological tolerance, we carried out non-T-cell depleted HLA haploidentical RIST from noninherited maternal antigen (NIMA) complementary siblings or offspring donors for four older patients: a patient with myeloplastic syndrome (MDS) and three patients with adult T-cell leukemia (ATL) in partial remission or with progressive disease. All patients showed early, durable engraftment, and no serious toxicities were observed apart from grade III mucositis in one case. Grade II acute GVHD occurred in two cases, which was well-controlled. In one ATL patient whose donor did not have NIMA microchimerism, tacrolimus could not be continued after engraftment due to renal dysfunction, and grade III acute GVHD (gut: stage 4) occurred on day 35. A patient with MDS was free from disease (requiring no transfusions and with a normal bone marrow) for 15 months. Two cases of ATL relapsed. Feto-maternal tolerance may lead to new RIST strategies in the haploidentical reduced-intensity situation, but further evaluation is required.

Endothelial damage caused by cytomegalovirus and human herpesvirus-6.

Infection with cytomegalovirus (CMV) or human herpesvirus-6 (HHV-6) may have a role in vascular endothelial damage after bone marrow transplantation (BMT). In total, 41 patients who underwent BMT were classified into four groups (12, 10, 7, and 12 patients who were infected with both CMV and HHV-6, CMV alone, HHV-6, and neither virus, respectively). Levels of thrombomodulin, plasminogen activator inhibitor-1, and cyclic GMP were 7.5+/-1.7 FU/ml, 76.4+/-24.1 ng/ml, and 9.51+/-1.1 pmol/ml, respectively, in the patients with both viruses, while the respective values were 2.9+/-0.67 FU/ml, 33.8+/-8.09 ng/ml, and 2.90+/-1.4 pmol/ml in patients infected with CMV alone, 4.8+/-0.96 FU/ml, 47.7+/-9.21 ng/ml, and 5.48+/-0.55 pmol/ml in patients with HHV-6 alone, and 1.6+/-0.39, 17.5+/-7.88 ng/ml, and 0.45+/-0.3 in those with neither virus. All three markers were significantly higher in the three groups with at least one virus than in the uninfected patients (P<0.05), and were also higher in patients with HHV-6 alone than in those with CMV alone (P<0.05). These results suggest that infection by CMV or HHV-6 causes vascular endothelial injury, with HHV-6 having a stronger effect than CMV, and combined infection having a stronger effect than either virus alone. Such viral infection may be a cause of thrombotic microangiopathy after BMT.

Superior vena cava syndrome after bone marrow transplantation caused by aspergillosis: a case report.

Aspergillosis is known for the variety of unusual presentations in immuno-suppressed patients. We report a patient in whom aspergillosis caused the superior vena cava (SVC) syndrome. A 37-year-old woman became febrile soon after bone marrow transplantation (BMT). Chest radiography demonstrated a 5-cm mass extending from the right lung apex to the right supraclavicular fossa beside her Hickman catheter. She then developed SVC syndrome, which progressed despite treatment. Despite recovery of the white blood cell count, the patient continued to deteriorate, became comatose, suffered a cardiac arrest and died 31 days after BMT. Autopsy revealed Aspergillus infection at the apex of the right lung associated with innominate artery thrombosis.

Similarity between eruptions induced by sulfhydryl drugs and acute cutaneous graft-versus-host disease after bone marrow transplantation.

Cutaneous GVHD is histologically similar to eruptions induced by drugs containing a sulfhydryl group. The levels of interleukin-2 and interleukin-2 receptor were determined in a group of patients undergoing bone marrow transplantation (BMT) without graft-versus-host disease or any other complications and in a group with cutaneous graft-versus-host disease (GVHD) alone. In patients who only developed cutaneous GVHD, both interleukin-2 and inter-leukin-2 receptor levels were elevated when the disease was evident. As the elevation of these parameters became more marked, the grade of cutaneous graft versus-host disease also increased. In some patients, only one of the two parameters was elevated and the grade of graft-versus-host disease was low or no skin manifestations were seen. These findings suggest that interleukin-2 and interleukin-2 receptor act together in the development of cutaneous GVHD. This study also showed that the mechanism of cutaneous GVHD resembles that involved in the induction of eruptions by sulfhydryl-containing drugs.

Oral eicosapentaenoic acid for acute colonic graft-versus-host disease after bone marrow transplantation.

We investigated whether pretreatment with eicosapentaenoic acid, an inhibitor of leukotriene (LT) B4, could ameliorate acute colonic graft-versus-host disease (GVHD) after bone marrow transplantation (BMT). Seventeen patients undergoing unrelated BMT were divided into two groups, with eight patients receiving eicosapentaenoic acid and nine not receiving it. The grade of GVHD after transplantation was compared with that estimated from the pretransplantation LTB4 level. The levels of LTB4 and several cytokines were also monitored. The actual grade of GVHD was lower than that estimated from LTB4 levels in three of the eight patients from the treated group, and there was a significant difference between the treated and untreated groups (p < 0.05, chi 2 test). The levels of LTB4, tumor necrosis factor-alpha (TNF-alpha), and interferon-gamma (IFN-gamma) were all significantly lower in the treated group (p < 0.05, Student's t-test). These findings suggest that eicosapentaenoic acid may ameliorate acute colonic GVHD when administered from before BMT.

Treatment of intestinal graft-versus-host disease using betamethasone enemas.

Intestinal graft-versus-host disease (GVHD) can readily easily induce generalized metabolic disturbance that influences morbidity and mortality after allogeneic bone marrow transplantation. Although adding a new drug or increasing the doses of immunosuppressive agents will probably be effective for controlling intestinal GVHD, the systemic side effects of such therapy cannot be ignored. In this study, we used betamethasone retention enemas as a local treatment for eight patients with refractory and/or severe intestinal GVHD. Six of the eight patients showed improvement of diarrhea and/or abdominal pain, with a reduction in the stage of GVHD. When treatment with betamethasone enemas was continued for 10 to 27 days in the 6 responding patients, no severe toxicity was observed. One patient failed to respond to treatment and another could not tolerate the enemas. Despite some uncertainty regarding the indications and duration of treatment, betamethasone enemas seem to be a potential alternative method for the management of intestinal GVHD.

Left atrial volume: important risk marker of incident atrial fibrillation in 1655 older men and women.

OBJECTIVE: To evaluate the contribution of left atrial (LA) volume in predicting atrial fibrillation (AF). PATIENTS AND METHODS: In this retrospective cohort study, a random sample of 2200 adults was identified from all Olmsted County, Minnesota, residents who had undergone transthoracic echocardiographic assessment between 1990 and 1998 and were 65 years of age or older at the time of examination, were in sinus rhythm, and had no history of AF or other atrial arrhythmias, stroke, pacemaker, congenital heart disease, or valve surgery. The LA volume was measured off-line by using a biplane area-length method. Clinical characteristics and the outcome event of incident AF were determined by retrospective review of medical records. Echocardiographic data were retrieved from the laboratory database. From this cohort, 1655 patients in whom LA size data were available were followed from baseline echocardiogram until development of AF or death. The clinical and echocardiographic associations of AF, especially with respect to the role of LA volume in predicting AF, were determined. RESULTS: A total of 666 men and 989 women, mean +/- SD age of 75.2 +/- 7.3 years (range, 65-105 years), were followed for a mean +/- SD of 3.97 +/- 2.75 years (range, < 1.00-10.78 years); 189 (11.4%) developed AF. Cox model 5-year cumulative risks of AF by quartiles of LA volume were 3%, 12%, 15%, and 26%, respectively. With Cox proportional hazards multivariate models, logarithmic LA volume was an independent predictor of AF, incremental to clinical risk factors. After adjusting for age, sex, valvular heart disease, and hypertension, a 30% larger LA volume was associated with a 43% greater risk of AF, incremental to history of congestive heart failure (hazard ratio [HR], 1.887; 95% confidence interval [CI], 1.230-2.895; P = .004), myocardial infarction (HR, 1.751; 95% CI, 1.189-2.577; P = .004), and diabetes (HR, 1.734; 95% CI, 1.066-2.819; P = .03). Left atrial volume remained incremental to combined clinical risk factors and M-mode LA dimension for prediction of AF (P < .001). CONCLUSION: This study showed that a larger LA volume was associated with a higher risk of AF in older patients. The predictive value of LA volume was incremental to that of clinical risk profile and conventional M-mode LA dimension.

Aluminum-controlled reactivity and diastereoselectivity toward radical reactions of optically active aldimines with metallic samarium.

The intermolecular pinacol-type coupling reaction and allylation reaction of optically active imines bearing a beta-hydroxy group were performed stereoselectively with metallic samarium after treatment of the imines with trimethylaluminum.

Urinary trypsin inhibitor concentration can predict the immunological insult of chemotherapy and complications after bone marrow transplantation.

Urinary trypsin inhibitor has attracted attention as an index of the systemic inflammatory response syndrome. In this study, the urine concentration of trypsin inhibitor was measured to compare the immunological insult of conventional chemotherapy and conditioning chemotherapy for bone marrow transplantation. We also investigated whether urinary trypsin inhibitor was a useful index of the complications and outcome of bone marrow transplantation. Urinary trypsin inhibitor concentration was determined before chemotherapy, on the day after finishing chemotherapy (day 0 of transplantation), and during recovery of the white cell count, in 17 patients (seven receiving conventional chemotherapy and 10 receiving conditioning for bone marrow transplantation). Urinary trypsin inhibitor concentrations were significantly higher after conditioning for bone marrow transplantation than after conventional chemotherapy (P < 0.001), indicating that conditioning was more invasive. After bone marrow transplantation, the incidence of severe complications and the mortality rate were higher in patients whose urinary trypsin inhibitor concentrations rose during recovery of the white cell count. Comparison of urinary trypsin inhibitor concentrations suggested that conditioning for bone marrow transplantation was more invasive than conventional chemotherapy. This study also suggested that the urine concentration of trypsin inhibitor could be useful for predicting the risk of complications and outcome of bone marrow transplantation.

Oral eicosapentaenoic acid for complications of bone marrow transplantation.

The 'systemic inflammatory response syndrome' (SIRS) may represent the underlying cause of complications after bone marrow transplantation (BMT). This study was conducted to determine whether blocking the etiologic factors of SIRS could improve the complications of BMT. Sixteen consecutive patients with unrelated donors were allocated alternately to two groups. Seven patients received 1.8 g/day of eicosapentaenoic acid (EPA) orally from 3 weeks before to about 180 days after transplantation, while nine patients did not. These two groups were compared with respect to complications, survival, and various cytokines and factors causing vascular endothelial damage. All seven patients receiving EPA survived and only two had grade III graft-versus-host disease (GVHD). Among the nine patients not receiving EPA, three had grade III or IV GVHD. In addition, thrombotic microangiopathy developed in four patients and cytomegalovirus disease occurred in four. Five patients died in this group. The levels of leukotriene B(4), thromboxane A(2), and prostaglandin I(2) were significantly lower in patients receiving EPA than in those not receiving it (all P < 0.01). Cytokines such as tumor necrosis factor-alpha, interferon-gamma, and interleukin-10 were also significantly decreased by EPA (P < 0.05), as were factors causing vascular endothelial damage such as thrombomodulin and plasminogen activator inhibitor-1 (P < 0.05). The survival rate was significantly higher in the group given EPA (P < 0.01). EPA significantly reduced the complications of BMT, indicating that these complications may be manifestations of the systemic inflammatory response syndrome.

Acute Colonic Graft-versus-host Disease and Ulcerative Colitis with Respect to Cytokines.

Colonic graft-versus-host disease (GVHD) occurring after allogeneic bone marrow transplantation (BMT) resembles ulcerative colitis (UC) with respect to pathological features. In addition, therapy for UC has been reported to be effective for the treatment of refractory GVHD. The relationship of these two conditions with respect to cytokines was investigated in the present study. Among 27 patients who underwent allogeneic BMT during the previous two years, six developed GVHD of grade 3 or higher, and these six patients were compared with the other 21 patients. In six patients, the levels of the following cytokines were significantly elevated at the onset of GVHD: tumor necrosis factor-α (p<0.05), interleukin-6 (p<0.05), interleukin-8 (p<0.01), interferon-γ (p<0.05), and interleukin-7 (p<0.0001). These findings indicate that GVHD and UC are similar in terms of their cytokine profile.