Acute effect of inhaled beta(2)-agonists with different type of intrinsic activity on airway resistance in healthy volunteers]

Inhaled beta(2)-agonists (long-acting as well as short acting) are used world-wide for the relief of asthma symptoms. However, there are few reports which have evaluated the additive effect of short-acting beta(2)-agonists to long-acting beta(2)-agonists on airway resistance measured by a plethysmography. This study was designed to evaluate the additive effect of inhaled short-acting beta(2)-agonists (protecarol) to long-acting beta(2)-agonists (salmeterol) on airway resistance in normal healthy volunteers (S+P group). In addition, to compare the effects of beta(2)-agonists which have different types of intrinsic activities, acute effect of inhaled procaterol adding to procaterol was also evaluated (P+P group). Seven healthy volunteers (all male and all non-smokers) were entered in this study. Pulmonary function was measured by a body plethysmography. Forced expiratory volume per 1 second (FEV1), the maximum flow rate at 25% (V(.) 25), the maximum flow rate at 50% of forced vital capacity (V(.) 50), and airway resistance were measured before and after inhalation of salmeterol (1 dry powder, 50 microg) or procaterol (2 puffs, 20 microg). Sixty minutes after inhalation of salmeterol, or 15 minutes after inhalation of procaterol, inhalation of procaterol (2 puffs, 20 microg) was added, and then pulmonary function was monitored. FEV1, V(.) 25, and V(.) 50 were significantly increased after inhalation of salmeterol as well as procaterol. In addition, airway resistance decreased significantly after inhalation of salmeterol as well as procaterol. In the S+P group, additional decrease of airway resistance after inhalation of procaterol was relatively small compared with the P+P group. In conclusion, although additional bronchodilatoric effects were observed in the S+P and P+P group, the effects seemed to be different based on the intrinsic activity of each beta(2)-agonist.     

The plasminogen activation system reduces fibrosis in the lung by a hepatocyte growth factor-dependent mechanism

Mice deficient in the plasminogen activator inhibitor-1 gene (PAI-1-/- mice) are relatively protected from developing pulmonary fibrosis from bleomycin administration. We hypothesized that one of the protective mechanisms may be the ability of the plasminogen system to enhance hepatocyte growth factor (HGF) effects, which have been reported to be anti-fibrotic in the lung. HGF is known to be sequestered in tissues by binding to extracellular matrix components. Following bleomycin administration, we found that HGF protein levels were higher in bronchoalveolar lavage fluid from PAI-1-/- mice compared to wild-type (PAI-1+/+) mice. This increase could be suppressed by administering tranexamic acid, which inhibits plasmin activity. Conversely, intratracheal instillation of urokinase into bleomycin-injured PAI-1+/+ mice to activate plasminogen caused a significant increase in HGF within bronchoalveolar lavage and caused less collagen accumulation in the lungs. Administration of an anti-HGF neutralizing antibody markedly increased collagen accumulation in the lungs of bleomycin-injured PAI-1-/- mice. These results support the hypothesis that increasing the availability of HGF, possibly by enhancing its release from extracellular matrix by a plasmin-dependent mechanism, is an important means by which activation of the plasminogen system can limit pulmonary fibrosis.     

Antitumor immune response by CX3CL1 fractalkine gene transfer depends on both NK and T cells

The CX3C chemokine fractalkine (CX3CL1) exists as both a membrane-bound form promoting firm cell-cell adhesion and a soluble form chemoattracting leukocytes expressing its receptor CX3CR1. When adenoviral vector expressing mouse fractalkine (AdFKN) was transduced to the tumor cells, fractalkine was expressed as both membrane-bound form on the tumor cells and soluble form in the supernatant in vitro. Intratumoral injection of AdFKN (1 x 10(9)PFU/tumor) into C26 and B16F10 tumors resulted in marked reduction of tumor growth compared to control (C26: 86.5%, p<0.001; B16F10: 85.5%, p<0.001). Histological examination of tumor tissues revealed abundant infiltration of NK cells, dendritic cells, and CD8(+) T lymphocytes 3 and/or 6 days after treatment with AdFKN. Splenocytes from mice treated by AdFKN developed tumor-specific cytotoxic T cells, and thereby protected from rechallenging with parental tumor cells. Antitumor effects by AdFKN were completely abrogated in both NK cell-depleted mice and CD8(-/-) mice, and partially blocked in CD4(-/-) mice. These data indicated that fractalkine mediates antitumor effects by both NK cell-dependent and T cell-dependent mechanisms. This study suggests that fractalkine can be a suitable candidate for immunogene therapy of cancer because fractalkine induces both innate and adaptive immunity.     

Diagnostic utility of galectin-3 and CD26/DPPIV as preoperative diagnostic markers for thyroid nodules

The aim of this study was to search for diagnostic markers that could correctly identify thyroid nodular lesions requiring urgent surgical treatment. We investigated whether galectin-3 and dipeptidyl peptidase IV (CD26/DPPIV) could be potential markers for improving the diagnostic accuracy of conventional cytology. Seventy-nine patients with histologically proven thyroid diseases were analyzed. The immunocytochemical staining results showed galectin-3 expression in neoplastic cells of all 37 papillary carcinomas, five of six follicular carcinomas, all three anaplastic carcinomas, one of three medullary carcinomas, and two of 14 follicular adenomas. All 16 adenomatous goiters were negative for galectin-3 immunostaining. On the other hand, all 37 papillary carcinomas, all six follicular carcinomas, and one of three anaplastic carcinomas revealed CD26/DPPIV expression, whereas all three medullary carcinomas were negative. Among benign thyroid lesions, four of 14 follicular adenomas and two of 16 adenomatous goiters exhibited varying degrees of immunoreactivity for CD26/DPPIV. RT-PCR analysis demonstrated overexpression of galectin-3 and CD26/DPPIV mRNAs in all six papillary and all three follicular carcinomas analyzed, whereas the mRNA expressions of these molecules were barely or not detectable in benign thyroid lesions and normal thyroid tissues, except for one case of follicular adenoma. In conclusion, we demonstrate that galectin-3 and CD26/DPPIV were consistently coexpressed at protein and mRNA levels in differentiated thyroid carcinomas. We propose that combined immunostaining for galectin-3 and CD26/DPPIV in the preoperative evaluation of thyroid nodules may play a role in accurate cytodiagnosis.     

Can random bladder biopsies be eliminated after bacillus Calmette–Guérin therapy against carcinoma in situ?

Purpose

Intravesical bacillus Calmette–Guérin (BCG) is the standard of care for bladder carcinoma in situ (CIS). The response to BCG therapy against CIS is generally assessed by random bladder biopsy (RBB). In this study, we examined the necessity of routine RBB after BCG therapy.

Methods

We retrospectively identified 102 patients who were initially diagnosed with CIS with or without papillary tumor and received subsequent 6–8-week BCG therapy. Thereafter, all patients underwent voiding cytology analysis, cystoscopy, and RBB to evaluate the effects of BCG therapy. We evaluated the association between clinical parameters (voiding cytology and cystoscopy findings) and the final pathological results by RBB specimens.

Results

According to the pathological results of RBB, 30 (29%) patients had BCG-unresponsive disease (remaining urothelial carcinoma was confirmed pathologically) and 20 were diagnosed with CIS. Positive/suspicious voiding cytology and positive cystoscopy findings were well observed in patients who had BCG-unresponsive disease compared with their counterparts (p?=?0.116, and p?<?0.001, respectively). The sensitivity (Sen.), specificity (Spe.), positive predictive value (PPV), and negative predictive value (NPV) of voiding cytology were 50%, 68%, 39%, and 77%, respectively. The values for cystoscopy findings were as follows: Sen.: 87%, Spe.: 57%, PPV: 46%, and NPV: 91%. The values for their combination (having either of them) were as follows: Sen.: 100%, Spe.: 44%, PPV: 43%, and NPV: 100%.

Conclusion

RBB after BCG therapy for patients with negative voiding cytology and negative cystoscopy may be omitted because their risk of BCG-unresponsive disease is significantly low (NPV: 100%).

     

Effect of Enteral Nutrition on In-hospital Infection and Hospital Expense in Stroke Patients: A Retrospective Assessment

Infection is a common complication of stroke and is associated with unfavorable outcomes. Although nutritional intervention reduces the risk of postoperative infection, the impact of specific nutritional products remains unclear. From a hospital management perspective, we aimed to determine whether the provision of specific types of enteral nutrition in acute stroke patients affects infection control and hospital costs. In all, 45 acute hemorrhagic stroke patients receiving enteral nutrition in a single center (April 2017–March 2019) were retrospectively assessed. Patients were divided into two groups according to nutritional interventions: the 1.0-group with general nutrition (1.0 kcal/mL) (24 patients) and the 1.5+α-group with an initial high-protein, whey peptide-digested liquid diet (1.5 kcal/mL), followed by a highly fermentable fiber-containing liquid diet (1.5 kcal/mL initiated after 4 days) (21 patients). Changes in body mass index (BMI), duration of antibiotic use, incidence of postoperative infection, and medical cost were evaluated. Baseline patient characteristics were similar between groups. The mean BMI change was lower in the 1.5+α-group than in the 1.0-group, and the mean duration of antibiotic use throughout hospitalization was 12.8 and 18.3 days, respectively. Antibiotic use in the 1.5+α-group was lesser than that in Japanese patients from other hospitals. The incidence of postoperative infections was lower in the 1.5+α-group. Injection costs for the 1.5+α group (615 USD/patient) were lower than those for the 1.0-group. Enteral nutrition provided to acute stroke patients reduced the risk of hospital infection and medical costs.     

Peliosis Hepatis in a Child with X-Linked Myotubular Myopathy Treated with Living-Donor Liver Transplant: A Case Report

BackgroundMyotubular myopathy is a rare disease sometimes accompanied by peliosis hepatis, a leading cause of fatal liver hemorrhage.Case ReportWe present a case of a 2-year-old boy with myotubular myopathy who developed liver hemorrhage because of peliosis hepatis and was successfully treated with living-donor liver transplant. The patient initially presented with fever, anemia, and liver dysfunction. A computed tomographic scan revealed hemorrhages in the liver, and the patient underwent hepatic artery embolization twice. After the second embolization, multiple peliosis hepatis cavities appeared in the left lobe of the liver that had increased in size. Therefore, the patient underwent ABO-incompatible living-donor liver transplant using a lateral segment graft from his father. The patient developed severe septic shock with an unknown focus on postoperative day 18, which resolved with antibiotic therapy. On postoperative day 62, he was discharged. Fourteen months after undergoing living-donor liver transplant, the patient showed no recurrence of peliosis hepatis.ConclusionsAlthough the long-term prognosis of peliosis hepatis due to myotubular myopathy after living-donor liver transplant remains unclear, liver transplant may be a curative treatment for patients with myotubular myopathy who have uncontrollable peliosis hepatis.     

New lidocaine ester derivatives with a prolonged anesthetic effect

In order to find a new long acting local anesthetic, methyl, ethyl, and butyl ester derivatives of lidocaine were synthesized in our laboratory. The topical anesthetic activity was studied with the effects on corneal reflex in rabbits, and the duration of action with those on the action potential of rabbit vagus nerve was studied in vitro. All drugs showed adequate topical anesthetic activities. The onset time to induce a complete blockage of the action potential in the excised vagus nerve was 97.1 +/- 6.3 s for lidocaine, 289.3 +/- 29.0 s for methyl ester, 186.3 +/- 18.4 s for ethyl ester, and 85.3 +/- 9.0 s for butyl ester. The mean duration of action, which was assessed as the time to recover from the complete block to 30% of control amplitude in a drug-free medium, was 32.5 +/- 3.1 min for lidocaine, 39.9 +/- 11.3 min for methyl ester, 68.2 +/- 4.2 min for ethyl ester, and 108.7 +/- 12.3 min for butyl ester. The differences in the duration of action between the ester derivatives and the original lidocaine were all statistically significant. The duration of action of all drugs studied paralleled with their protein binding capacities. These findings indicate the possibility that the ester derivatives studied, especially butyl ester, can be used as a long acting local anesthetic.     

Spontaneous perforation of the rectosigmoid colon: a report of 2 cases

Spontaneous perforation of rectosigmoid colon is rare but usually results in severe peritonitis, with very high mortality. Two cases of spontaneous rectosigmoid perforations are reported here along with a brief literatures review.