Many studies in the literature have clearly shown the increase in creatine kinase-myocardial subfraction (CK-MB) levels and changes in electrocardiography (ECG) after stroke. However, the studies on cardiac troponin T (cTnT) which is more sensitive and specific to myocardium after stroke are relatively scarce. Moreover, its associations with volume of stroke lesions and type of stroke have not been investigated thoroughly. Thus, the aims of this study were to investigate a predictive value of cTnT in assessing myocardial injury and cardiac dysfunction in different types of stroke (hemorrhagic or ischemic stroke) and its relationship with stroke size and volume. This study included 62 patients (30 males and 32 females) with acute stroke confirmed by computed tomography (CT). Blood samples were obtained within 24 hours of stroke onset to measure the serum levels of creatin kinase (CK), CK-MB, lactate dehydrogenate (LDH), and cTnT. ECG and echocardiography were performed to assess myocardial function and left ventricular ejection fraction (LVEF). Of all patients included in the study, 20 patients (32%) demonstrated elevations in cTnT, while 28 patients (45%) had increased CK-MB levels. Serum levels of cTnT were positively correlated with stroke volume (r = 0.65, p < 0.0001), while inversely correlated with LVEF (r = −0.53, p < 0001). Serum levels of both CK-MB and cTnT were higher in patients with hemorrhagic stroke than those with ischemic stroke but this difference was not significant (p > 0.05). As a conclusion, cTnT has a higher specificity and sensitivity in detecting myocardial injury after stroke of both ischemic and hemorrhagic origins. Measurement of the serum levels of cTnT is of clinical importance in evaluating myocardial injury and provides a useful aid in estimating the volume of stroke lesions.
The role of proteinase inhibitor (PI)-9 in hematopoietic cells remains unclear. To clarify the role of PI-9 in these cells, we compared the expressions of PI-9 mRNA and antigen with those of granzyme B (GrB). While the strongest expression of PI-9 mRNA was observed in a NK cell line YT-N10, it was also expressed in a B-acute lymphoblastic leukemia cell line U-Tree02, an Epstein-Barr Virus (EBV)-transformed B cell clone, a CD8+ T lymphocyte clone and a megakaryocytic cell line CMK, but not in a T cell line Jurkat. Phorbol 12-myristate 13 acetate (PMA) enhanced PI-9 mRNA expression in the CD8+ T lymphocyte clone and YT-N10 cells prior to GrB mRNA expression. IL-2 and IL-12 also had similar effects. PMA increased PI-9 mRNA expression in the EBV-transformed B cell clone and CMK cells, but IL-6 showed no effect. No changes were noted in PI-9 and GrB antigens after the addition of these agonists. Patients with graft-versus-host disease (GVHD) may have activated CTLs and NK cells. We therefore examined the expression of PI-9 and GrB mRNAs in eight patients after allogeneic hematopoietic stem cell transplantation with GVHD (n = 4) or without chronic GVHD (n = 4). Expression of GrB mRNA was significantly increased in three patients with GVHD and one patient without GVHD. Surprisingly, PI-9 mRNA expression was decreased in the eight patients. These results indicate that earlier synthesis of PI-9 may be essential for the prevention of autolysis of immunocompetent cells, and that the expression of PI-9 and GrB mRNAs may be controlled through different pathways.
This study was designed to establish a more effective and safe culture system for adoptive immunotherapy by investigating the use of homologous cord blood plasma (HCBP) instead of fetal bovine serum (FBS), which has various limitations including ethical problems for the ex vivo expansion of human umbilical T lymphocytes. Fresh human umbilical mononuclear cell fractions were isolated by Ficoll-Hypaque density centrifugation. Nonadherent mononuclear cell fractions were cultured with anti-CD3 antibody (5 μg/ml), IL-2 (175 U/ml), and either 10% FBS or 10% HCBP. On day 8, the cellular proliferation rate and cell surface markers were assessed. There was no significant difference in proliferation when human umbilical cord blood T lymphocytes were grown in medium supplemented with FBS or HCBP (p > 0.05). In medium containing FBS, the proportion of CD3+CD4+ (markers for helper T cell), CD3+CD8+ (cytotoxic T cell), CD3+CD25+ (activated T cell), CD3+CD38+ (immature T cell), and CD3+CD45RO+ (memory T cell) cells was significantly increased (p < 0.05), whereas proportion of CD3+CD45RA+ (naive T cell) and CD16+CD56+ (NK cell) cells was significantly decreased (p < 0.05). In HCBP supplemented medium, the proportion of CD3+CD8+, CD3+CD25+, CD3+CD45RA+, and CD3+CD45RO+ cells was significantly increased (p < 0.05). The proportion of CD3+CD4+, CD3+CD45RO+ and CD3+CD38+ cells was significantly higher, but proportion of CD3+CD45RA+ and CD3+CD8+ cells was significantly lower in FBS compared with HCBP supplemented medium (p < 0.05). Our results support the feasibility of ex vivo expansion of human umbilical cord blood T lymphocytes in medium supplemented with HCBP for future adoptive cellular immunotherapy.
Familial glucocorticoid deficiency (FGD) is characterized clinically by severe glucocorticoid deficiency associated with failure of adrenal responsiveness to ACTH but not with mineralcorticoid deficiency. Excessive growth was described previously in some patients with FGD, many of whom were shown to have mutations in the ACTH receptor gene. The mechanisms responsible for their excessive growth are unknown. We analyzed the ACTH receptor gene in three patients with FGD and discussed the causes of excessive growth in FGD. No mutations were detected in the coding and promoter regions of the ACTH receptor gene of one female patient who had tall stature (+ 2.41S.D.) and advanced bone age (10 years 9 months) when she was 4 years 9 months old. Her plasma ACTH level had been elevated until then (124-2,684 pg/ml). Moreover, plasma estradiol was elevated for her age (21.3 pg/ml), and it decreased in response to the dexamethasone suppression test (from 25.4 to 6.9 pg/ml). Elevated plasma estradiol was apparently related to the increase in plasma ACTH and played a major role in excessive growth in this patient. On the other hand, the genetic analysis showed that the other two patients who were siblings were homozygous for the R137W mutation. Clinically, they responded well to hydrocortisone replacement therapy with almost normal plasma ACTH levels. Although all patients with the R137W mutation reported previously were tall, our patients were of normal height. We speculate that the major causes of excessive growth in FGD are not only from ACTH receptor mutation, but also from the action of elevated plasma ACTH.
Reperfusion injury is a consequence of inadequate energy supply and acidosis in ischemic tissues and a chain of events triggered by oxygen-derived free radicals released in response to exposure of oxygen. In this study, we aimed to assess the effects of clopidogrel, an antithrombotic agent, on experimental ischemia-reperfusion model in rats. The ischemia was performed by blockade of the circulation of right lower extremity at trochanter major level for 6 hours. Then, the extremity was reperfused for 4 hours. Another group of rats pretreated with clopidogrel (0.2 mg/kg/day) for 10 days prior to ischemia-reperfusion. After the reperfusion period, all rats were anesthetized with ketamine. Blood and tissue samples from the gastrocnemius muscle, liver and lungs were taken for the measurement of malondialdehyde (MDA), glutathione (GSH) levels and superoxide dismutase (SOD) activity. The results revealed that clopidogrel prevented the increase in MDA level and the decrease in GSH level and SOD activity caused by ischemia-reperfusion both in tissue samples and plasma. These findings suggest that clopidogrel is beneficial in prevention of ischemia-reperfusion injury probably via its effects on inflammatory cells, platelets, and endothelial cells.
No epidemiological surveys have examined risk factors related to the death of very low birth weight infants (VLBWIs) in Japan. The objectives of this study were to examine the death rate and fatalities related to complications among VLBWIs, and to analyze factors possibly determining the death of VLBWIs. The subjects of this study were 811 VLBWIs admitted to the Neonatal Care Center of Niigata City General Hospital between April 1987 and March 2003. We obtained information on gender, birth weight, gestational age, Apgar scores, single/multiple pregnancy, postnatal transfer, mode of delivery, complications and outcome (alive or deceased) at the time of discharge from medical records. Of the 811 infants, 98 died prior to discharge (12.1%). Logistic regression analysis showed that independent risk factors for death of VLBWIs were male gender (relative risk [RR]: 2.0), low birth weight (RR: 0.56), necrotizing enterocolitis (RR: 58.0), pulmonary hypoplasia (RR: 37.8), chromosomal abnormalities (RR: 36.3), congenital heart diseases (RR: 9.8), persistent fetal circulation (RR: 9.6), neonatal asphyxia (RR: 6.3) and sepsis (RR: 4.4). The risk for death rises 1.8-fold if birth weight decreases by 100 g. A very high risk of perinatal death is associated with necrotizing enterocolitis, pulmonary hypoplasia or chromosomal abnormalities. The risk of death due to congenital heart diseases or neonatal asphyxia is relatively lower, but the incidences of these two disorders are high (8% and 6%, respectively). From the viewpoint of prophylactic treatment aimed at reducing the death rate of VLBWIs, measures to increase birth weight are of primary importance. Furthermore, early treatment and improved perinatal management of congenital heart diseases and neonatal asphyxia are anticipated to reduce the overall death rate of VLBWIs.
An intraoral ranula is a retention cyst arises from the sublingual gland on the floor of the mouth as a result of ductal obstruction and fluid retention. Many techniques for management of ranulas have been described in the literature. The purpose of this study was to analyze our surgically treated pediatric patients with intraoral ranulas and to discuss the results in the light of the literature. Nine pediatric patients (six females and three males) with intraoral ranulas surgically treated were analyzed retrospectively regarding their treatment methods and results. The surgical specimens were also re-examined histologically. Seven cases of superficial, protruded and smaller than 2 cm ranulas were treated with marsupialization (unroofing). Two cases who were previously operated and then recurred had bigger than 2 cm ranulas. In these two cases, marsupialization of the ranula plus removal of the sublingual gland was performed. The most common complication was intraoperative cyst rupture of the ranula, which was noted in four cases. A recurrence was observed in only one case in the 16th months of follow up period. Our findings show that marsupialization is a suitable and effective method for pediatric intraoral ranulas, whereas in recurrent cases marsupialization of the ranula combined with total excision of sublingual gland may be preferred.
In Turkey, the first aiders are few in quantity and yet they are required in many settings, such as earthquakes. It was thought that training first year university students in first aid and basic life support (FA-BLS) techniques would serve to increase the number of first aiders. It was also thought that another problem, the lack of first aid trainers, might be addressed by training medical students to perform this function. A project aimed at training first year university students in FA-BLS was conducted at Hacettepe University. In the first phase, medical student first aid trainers (MeSFAT) were trained in FA-BLS training techniques by academic trainers and in the second phase, first year university students were trained in FA-BLS techniques by these peer trainers under the academic trainers' supervision. The purpose of this study was to assess the participants' evaluation of this project and to propose a new program to increase the number of first aiders in the country. In total, 31 medical students were certified as MeSFATs and 12 of these trained 40 first year university students in FA-BLS. Various questionnaires were applied to the participants to determine their evaluation of the training program. Most of the participants and the authors considered the program to be successful and effective. This method may be used to increase the number of first aid trainers and first aiders in the community.
Copper (Cu) is an essential element for life, however, is toxic at excessive doses, whereas exposure to ethanol (EtOH) has been known to cause morphological changes, degeneration and neuronal loss in central nervous system (CNS). In this study, the effect of overdose co-exposure to Cu and EtOH on dentate gyrus was investigated in rats. Analysis of apoptotic cell death on the basis of TdT-mediated dUTP nick end labeling (TUNEL) assay revealed that the rate of apoptosis was increased by 1.84 folds in treated group in comparison to that in controls (p < 0.0001). Analysis of cell proliferation on the basis of 5-bromo-2'-deoxy-uridine labeling assay, on the other hand, revealed a 1.49 fold increase in treated group when compared to controls (p < 0.006). Total number of granule cells in dentate gyrus of each group was estimated using the optical fractionator method. The results showed that mean granule cell number in dentate gyrus was 4.64% lower in treated group than that in control group, but this difference was not statistically significant (p > 0.05). These results suggest that the apoptotic effect of overdose Cu and EtOH on granule cells of dentate gyrus may be counterbalanced by the co-induced cellular proliferation, thereby maintaining the total granule cell number unaltered.
After an unsuccessful midwife-assisted delivery in which a head was born but delivery could not be advanced, episiotomy performed at Sanliurfa Maternity Hospital allowed vaginal delivery of female conjoined twins. Visual and x-ray examination showed two heads, two vertebral columns, two feet, two arms, and fusion at the level of the pelvis. The baby was born dead, but the mother made an uneventful recovery. Parapagus (anterolaterally joined) dicephalus (two-headed) twins account for only 11-13% of all conjoined twins, and they rarely survive. Complex malformations of hearts, lungs and abdominal organs, duplication of the tracheae, upper gastrointestinal tract and spinal column, and either double or single versions of other organs have been reported in parapagus dicephalus cases. The incidence, anatomical, embryological, diagnostic, prognostic, obstetrical, perinatal, and ethical aspects of conjoined twins are reviewed, with a focus on parapagus dicephalus conjoined twins.
Gorham disease is an extremely rare condition of unknown etiology characterized by progressive osteolysis. Only 28 cases of its spinal involvement have been reported, and some of those cases showed kyphosis, kyphoscoliosis, subluxation or dislocation. No definite regimen of treatment has been established yet. A 10-year-old boy presented with a severe and progressive kyphosis over 90 degrees caused by Gorham disease from T3 to T12. In situ posterior fusion with a hook and rod system and iliac bone grafts were performed, but after surgery, he had complete paraplegia and its cause was uncertain. Based on the unfortunate consequence of the present case and the review of the literature, we propose the treatment strategies for spinal Gorham disease.
Fulminant hepatic failure, which is represented by fulminant hepatitis, is fatal in most cases unless prompt liver transplantation is performed. Even if liver transplantation is performed, irreversible neurological damage is often complicated. In this case report, we describe two cases of fulminant hepatitis induced by acute hepatitis B virus infection, both of which were successfully rescued by living related liver transplantation without significant complications. The case 1 was a 45-year-old Japanese male. He complained general malaise and anorexia. His local physician diagnosed him as acute hepatitis B, and referred to our hospital. Due to severe coagulopathy, plasma exchange was performed 3 times. However, his hepatic coma progressed rapidly along with rapid decrease of both his direct/indirect bilirubin (D/T) ratio and serum blood urea nitrogen (BUN) levels. Living related liver transplantation was performed under the diagnosis of acute fulminant hepatitis B. The case 2 was a 34-year-old Japanese male. His complaints were fever and skin rush. He was referred to our hospital under the diagnosis of acute hepatitis B. On the second day after admission, he developed grade II hepatic coma, which deteriorated into grade III in spite of intensive therapy including plasma exchange. He also demonstrated rapid decrease of both D/T ratio and serum BUN level. Living related liver transplantation was performed on the next day. Both cases recovered without any evidence of neurological sequelae. In general, it is extremely difficult to rescue fulminant hepatitis by conservative treatments, particularly in cases with rapid progression. Although emergency liver transplantation may be an only option to rescue in such a case, living related liver transplantation has an advantage in view of urgent organ donation over cadeveric transplantation.