Pulmonary arterial hypertension (PAH) is a disease with poor prognosis characterized by progressive elevation of pulmonary arterial pressure and vascular resistance due to pulmonary artery hyperconstriction and remodeling. However, the precise mechanism of PAH still remains to be elucidated. Although anticoagulant agents, vasodilators (e.g., prostaglandins, sildenafil, and bosentan), and lung transplantation are currently used for the treatment of PAH, more effective treatment needs to be developed. Rho-kinase causes vascular smooth muscle hyperconstriction and vascular remodeling through inhibition of myosin phosphatase and activation of its downstream effectors. In a series of experimental and clinical studies, we have demonstrated that Rho-kinase-mediated pathway plays an important role in various cellular functions, not only in vascular smooth muscle hyperconstriction but also in actin cytoskeleton organization, cell adhesion and motility, cytokinesis, and gene expression, all of which may be involved in the pathogenesis of arteriosclerosis. We also have recently demonstrated that Rho-kinase is activated in animal models of PAH with different etiologies (monocrotaline and chronic hypoxia) associated with enhanced pulmonary vasoconstricting and proliferating responses, impaired endothelial vasodilator functions, and pulmonary remodeling. Indeed, we were able to demonstrate that intravenous fasudil, a selective Rho-kinase inhibitor, exerts acute pulmonary vasodilator effects in patients with severe PAH who were refractory to conventional therapies. Taken together, our findings indicate that Rho-kinase is a novel and important therapeutic target of PAH in humans and that Rho-kinase inhibitors are a promising new class of drugs for the fatal disorder.
Although the Kidney Disease Quality of Life instrument (KDQOL-SFTM), which was designed to measure the comprehensive quality of life in patients with end stage renal disease, has been tested and widely administered in many other counties, it has not yet been translated, validated and reported for Korea. The primary purpose of this study was to validate a Korean version of KDQOL-SFTM and to evaluate its psychometric properties. The study subjects were 164 patients with hemodialysis or continuous ambulatory peritoneal dialysis in university dialysis centers in Korea. In order to investigate the reliability, test-retest reliability and internal consistency reliability were assessed. Both test-retest reliability and internal consistency reliability were found to be high. In order to investigate the construct validation, all the items of the SF-36 scales, an established generic QOL measures, were compared with an overall health rating scale in kidney disease-targeted scale. They found to be highly correlated with each other. Moreover, overall health rating scale was significantly correlated with symptoms/problems, effects of kidney disease, burden of kidney disease, cognitive function (p < 0.001), and quality of social interaction (p < 0.05). These results suggest that the Korean version of KDQOL-SFTM satisfies its reliability and validity in Korean patients with hemodialysis or continuous ambulatory peritoneal dialysis. This questionnaire provides important and clinically valuable information for understanding the health related quality of life in the Korean patients with dialysis.
Problems of wound healing are commonly observed after coronary bypass grafting (CABG) operations. Our aim is to determine the prevalence and the predictors of saphenous vein harvesting complications after coronary artery bypass surgery. One hundred twenty six patients operated in the specified period were included in this prospective study. In an early period 3 patients were excluded because of their mortality. Twenty patients were female and 103 were male. Forty three patients underwent an open procedure with one incision (35%), 61 patients also underwent an open procedure but with multiple incisions (49%), and 19 patients underwent a closed procedure with stripper (16%). Complications related with leg incisions after surgery were investigated. Multiple incision technique has the longest (49.28 ± 14.7 cm; p < 0.001) total incision length (compare to single incision and stripper technique). As incision length increases, the incidence of drainage (p < 0.01), pain score (p < 0.05), hematoma (p < 0.05) and diffuse ecchymosis (p < 0.05) were increased. Drainage was seen more frequently in female (p < 0.001) and diabetic patients (p < 0.05). Sex (p < 0.001) and incision length (p < 0.05) have been found independent risk factors for drainage complication. Superficial infection (p < 0.05), pain (p < 0.05) and dehiscence (p < 0.05) were significantly higher in female patients. As the incision length of the multiple incision technique became longer, the risk of drainage, pain, hematoma and diffuse ecchymosis were increased. The significantly increased risk for wound complications were also seen in female gender, diabetic and obese patients.
In men, exercise training attenuates age-related reduction in baroreflex sensitivity, which is related to cardiovascular health. It is unknown, however, if this holds true for post-menopausal women. We examined the effects of exercise training on baroreceptor-heart rate (HR) reflex sensitivity in ovariectomized (OVX) and sham-operated (SO) Wistar-Kyoto rats. At the age of 8 weeks, OVX and SO rats were assigned to either sedentary or exercise-trained group. Exercise training was performed on a treadmill 5 days per week. At the age of 20 weeks, baroreflex sensitivity in response to increases in blood pressure (BRSinc) and decreases in blood pressure (BRSdec) were evaluated by injections of phenylephrine and sodium nitroprusside, respectively. Both BRSinc and BRSdec were significantly reduced in sedentary OVX rats compared with sedentary SO rats. Exercise training decreased resting HR and BRSdec, but had no effect on BRSinc in SO rats. In OVX rats, exercise training decreased resting HR but modified neither BRSdec nor BRSinc. We conclude that withdrawal of female sex hormones in normotensive female rats is associated with reduced baroreflex sensitivity in response to both increase and decrease in blood pressure and that exercise training fails to modulate the decline of BRSinc associated with withdrawal of female sex hormones. To maintain high level of BRSinc in post-menopausal women, hormone replacement therapy may be needed.
Adiponectin is a novel polypeptide that modulates endothelial function. Association between high serum adiponectin level and stimulation of new blood vessel formation have been reported in two experimental studies, however, data in humans are lacking. We sought to determine relationship between serum adiponectin and collateral vessel development in patients with coronary artery disease. We included 89 patients with stable angina pectoris and angiographically documented total occlusion in one of the major coronary arteries. Coronary collateral circulation was graded according to Rentrop scoring method in which collateralisation was graded between 0 and 3 from the poorest to the best. Adiponectin was determined by the ELISA method. High serum adiponectin level were significantly associated with increased new collateralisation (p = 0.001). With the increase of body mass index and waist circumference, the collateral development decreased (p = 0.001, p = 0.002; respectively). Presence of the diabetes mellitus (DM) was more frequent in those with poor collateral group than in those with good collateral group. DM was associated with poor collateral development (p = 0.002). In multiple stepwise logistic regression analysis, low level of serum adiponectin (p = 0.0001), waist circumference (p = 0.001), and presence of DM (p = 0.003) were found to be significant independent predictors of poor collateral formation. In conclusion, we have shown for the first time that elevated levels of serum adiponectin are associated with coronary collateral development in patients with coronary artery disease and additionally, the present study confirms many of the metabolic associations reported previously with adiponectin.
Older children, adolescents and adults with prolonged cough should be screened for pertussis, because they can be a major source of transmission for infants who are not yet fully immunized. This study aimed to estimate the incidence of pertussis among schoolchildren of 6-14 years old with prolonged cough attending two government primary schools in central Ankara. A questionnaire and an informed consent form were sent to the parents of 1,859 schoolchildren. The former comprised questions regarding sociodemographics, and the presence and duration of cough. Parents of 1,698 (91.3%) schoolchildren returned the questionnaire. Three hundred and eighty three (22.6%) of the schoolchildren had cough for more than two weeks, and 307 (80.2%) of them, whose parents gave consent, were included in the study. Their blood samples were collected twice, with a two-week interval. Anti-pertussis toxin IgG levels were measured by enzyme-linked immunosorbent assay (ELISA). Fifty-one children (16.6%) had evidence of recent pertussis infection documented by either a titer ≥ 100 ELISA Unit (EU)/ml in one of two serum samples or seroconversion in paired sera. None of the schoolchildren who had attended health care facilities for cough had been diagnosed as pertussis by a physician. In conclusion, pertussis is evident among older children and adolescents in Turkey, and in order to control the disease, priority should be given to strengthen primary immunization services along with the implementation of booster vaccinations beyond childhood.
The survival rate in ABO-incompatible (ABO-I) liver transplantation was much lower than that in ABO-compatible recipients for the early experiences. It is therefore essential to develop the precise and fast measurement of anti-A and anti-B antibodies (Abs) to prevent humoral rejection in ABO-I liver transplantation. Agglutination titer has been the standard method to measure these Abs, but the interpretation of the results is subject to bias. Here, we have developed an objective and quantitative enzyme-linked immunosorbent assay (ELISA) to measure anti-A and anti-B Abs. This test requires only a small amount (10 μl) of recipient's serum. We applied the newly developed ELISA to monitor living donor liver transplant recipients and investigated the correlation between ELISA and agglutination titer. The Spearman's correlation coefficient for Abs ranged from 0.461 to 0.812. Moreover, in one case of humoral rejection, the increase of Abs was detected by ELISA one day earlier than by the agglutination titer. In conclusion, our ELISA method proved useful to detect an increase of anti-A and anti-B Abs titers at an early stage, thereby contributing to a prompt treatment of humoral rejection due to ABO-I.
Epidemiological studies have shown that a high serum uric acid concentration is a risk factor for coronary artery disease (CAD). However, the issue of whether it is an independent cardiovascular risk factor or simply a marker of co-existing conditions is a matter of controversy. In the present case-controlled study, we explored the association between serum uric acid and angiographically defined CAD in middle-aged subjects (356 CAD patients and 350 healthy individuals). Serum uric acid in CAD patients was significantly higher than that in healthy individuals (359 ± 88.7 and 289 ± 79.3 μmol/l, respectively, p < 0.01) and remained significantly higher after adjusting for confounding factors (F = 79.77, p < 0.01). The association between uric acid and CAD was not limited to the hyperuricemic range of values, but was also found in the high-normal range (p < 0.01). An unadjusted odds ratio (OR) of 5.0 was obtained in both genders (p < 0.01). Female patients with > 50% stenosis (clinically significant CAD), regardless of the number of diseased vessels, had higher uric acid concentrations than those with < 50% stenosis even after adjusting for confounders (F = 3.79, p = 0.01). In conclusion, we have demonstrated that high serum uric acid is independently associated with CAD and that uric acid determination could be useful as one of the markers of clinically significant CAD.
Technetium-99m labeled human serum albumin (Tc-99m HSA) is an important radiopharmaceutical for clinical applications, such as cardiac function tests or protein-losing gastroenteropathy assessment. However, because of transfusion-induced infectious diseases, the safety of serum products is a serious concern. In this context, serum products acquired from patients themselves are the most ideal tracer. However, the development of rapid separation and easy clinical labeling methods is not yet well established. Under such situation, products from the same ethnic group or country are now recommended by the World Health Organization as an alternative preparation. This article describes the on-site preparation of Tc-99m HSA from locally supplied serum products. Different formulations were prepared and the labeling efficiency and stability were examined. Radio-labeling efficiencies were more than 90% in all preparation protocols, except for one that omitted the stannous solution. The most cost-effective protocol contained HSA 0.1 mg, treated with stannous fluoride 0.2 mg, and mixed with Tc-99m pertechnetate 30 mCi. A biodistribution study was performed in rats using a gamma camera immediately after intravenous administration of radiolabeled HSA. Tissue/organ uptake was obtained by measuring the radioactivity in organs after sacrificing the rats at timed intervals. The biologic half-life was about 32 min, determined from sequential venous blood collections. These data indicate that our preparation of Tc-99m HSA is useful and potentially applicable clinically. In addition, this on-site preparation provides the possibility of labeling a patient's own serum for subsequent clinical application.
Because of complex pathophysiology and severe consequences, traumatic brain injuries (TBI) are an important medical problem. Pathophysiology of TBI includes local and systemic stress response, in which interleukin-8 (IL-8) is considered as a key mediator of neuroinflammation. However, prognostic relevance of IL-8 measurement in adult patients with severe TBI is not certain. Therefore, IL-8 was determined in blood samples from central venous and jugular bulb catheter and in cerebrospinal fluid of twenty patients with isolated TBI at admission to Intensive Care Unit. None of the patients had history of stroke, dementia, autoimmune diseases, acute infection or medication with anti-inflammatory drugs. Ten patients died due to traumatic brain injury, while the other ten recovered well. While there was no significant difference of IL-8 levels in cerebrospinal fluid between survivors and nonsurvivors, central venous plasma level of IL-8 was significantly lower in survivors (71.00 ± 14.17 pg/ml), than in nonsurvivors (111.26 ± 16.9 pg/ml). Receiver Operating Characteristic (ROC) analysis revealed significant prognostic value for IL-8 in the blood as well as for the age of patients, Glasgow Coma Scale (GCS) and Acute Physiologic and Chronic Health Evaluation (APACHE II). These findings suggest that the central venous plasma values of IL-8 at admission might be an early predictive marker in patients with severe TBI, comparative to standard clinical prognostic markers such as APACHE II and GCS.
Nasal natural killer (NK)/T cell lymphoma is a rare entity of non-Hodgkin's lymphoma which mostly occurs in East Asian countries. The advanced disease above clinical stage III is often refractory to the radiation and chemotherapies, remission is transient even if achieved, and median survival is about 12 months. Thus the prognosis of advanced NK/T cell lymphoma is generally poor, however, the promising results of allogeneic hematopoietic stem cell transplantation for advanced NK/T cell lymphoma have been recently reported. In most of these cases, stem cell sources were human leukocyte antigen (HLA) matched donors and alternative sources were seldom used. We report here a case of a 36-year-old woman who was diagnosed as having an extranodal NK/T cell lymphoma, nasal type. The patient achieved a complete remission after 2 cycles of chemotherapy including Carboplatin, Etoposide, Ifosfamide, and Dexamethasone, but 3-months later relapsed during the search for HLA-matched unrelated donors. She received unrelated cord blood transplantation (CBT) in the second remission achieved by a regimen containing L-asparaginase. The conditioning regimen was 12 Gy of total body irradiation, high-dose cytarabin and cyclophosphamide. FK506 and methotrexate were used for graft-versus-host disease (GVHD) prophylaxis. GVHD involving the intestine and the oral mucosa was observed, but improved without additional immunosuppressive therapies. The patient remains in remission 33 months after CBT. Cord blood thus could be an appropriate stem cell source for patients with advanced NK/T lymphoma who have no HLA matched donors.
Surgical excision is thought to be the standard treatment of choice for lymphatic malformations. However, when the lesions are limited to the face only, surgical scar and facial nerve injury may impair cosmetics and facial expression. Sclerotherapy, an injection of a sclerosing agent directly through the skin into a lesion, is an alternative method. By evaluating facial nerve conduction, we observed the long-term effect of facial lymphatic malformations after intralesional injection of OK-432 and correlated the findings with anatomic outcomes. One 12-year-old boy with a lesion over the right-side preauricular area adjacent to the main trunk of facial nerve and the other 5-year-old boy with a lesion in the left-sided cheek involving the buccinator muscle were enrolled. The follow-up data of more than one year, including clinical appearance, computed tomography (CT) scan and facial nerve evaluation were collected. The facial nerve conduction study was normal in both cases. Blink reflex in both children revealed normal results as well. Complete resolution was noted on outward appearance and CT scan. The neurophysiologic data were compatible with good anatomic and functional outcomes. Our report suggests that the inflammatory reaction of OK-432 did not interfere with adjacent facial nerve conduction.