Influence of a dexamethasone-eluting covered stent on tissue reaction: an experimental study in a canine bronchial model

This study was designed to evaluate the feasibility and efficacy of a dexamethasone (DXM)-eluting, covered, self-expanding metallic stent to reduce tissue reaction following stent placement in a canine bronchial model. We placed a DXM-eluting, polyurethane-covered, self-expanding metallic stent (drug stent, DS) and a polyurethane-covered, self-expanding metallic stent (control stent, CS) alternately in each left main bronchus and left lower lobe bronchus in 12 dogs. The stents were 20 mm in diameter and length when fully expanded. The dose of DXM was approximately 36.7 mg in each DS, but was absent in the CS. The dogs were euthanased 1 week (n=4), 2 weeks (n=4) or 4 weeks (n=4) after stent placement. Histologic findings, such as epithelial erosion/ulcer or granulation tissue thickness, were obtained from the mid-portion of the bronchus, where the stent had been placed, and evaluated between DS and CS. There were no procedure-related complications or malpositioning of any of the bronchial stents. Stent migration was detected in one dog just before euthanasia 1 week following stent placement. Stent patency was maintained until euthanasia in all dogs. Epithelial erosion/ulcer (%) was significantly less in the DS (mean±standard deviation, 46.88±23.75) than in the CS (73.75±14.08) (P=0.026) for all time-points. There was a decrease in epithelial erosion/ulcer as the follow-up period increased in both DS and CS. The granulation tissue thickness (mm) was less in DS (2.63±2.05) than in CS (3.49±2.95), although the difference was not significant (P=0.751) for all time-points. There was a tendency toward an increase in granulation tissue thickness and chronic lymphocytic infiltration as the follow-up period increased in both DS and CS. In conclusion, DXM-eluting, covered, self-expanding metallic stent seems to be effective in reducing tissue reaction secondary to stent placement in a canine bronchial model.     

Tacrolimus dosage requirements after initiation of azole antifungal therapy in pediatric thoracic organ transplantation

Azole antifungals inhibit the metabolism of tacrolimus mediated by CYP3A4. Upon initiation of azole therapy, the required dose reduction of tacrolimus is unknown. We reviewed our experience with azole antifungals in our pediatric thoracic transplant population receiving tacrolimus. Tacrolimus levels and dosage requirements were compared before and during azole therapy. Thirty-one patients received both tacrolimus and an azole antifungal (fluconazole = 9, itraconazole = 22). The tacrolimus dose was empirically reduced by approximately one-third when azole therapy was initiated. Mean tacrolimus dose requirements decreased by 68% within the first month of therapy (pre-azole: 0.27 +/- 0.14 mg/kg/day; 30 day post-azole: 0.087 +/- 0.069 mg/kg/day; p < 0.001). Despite a mean decrease in tacrolimus dose from baseline of 33, 42, and 55% on day 1, 2, and 4 of azole therapy, respectively, there was still an unintended 38% increase in tacrolimus levels during the first month of azole therapy. A calculated dose-reduction protocol of 50% on day of azole initiation, 70% on day 3, and 75% on day 14 should result in minimal mean changes in the tacrolimus levels. There was no difference in tacrolimus dose reduction between fluconazole and itraconazole groups. Azole antifungals markedly decrease tacrolimus requirements within the first few days of therapy. An initial reduction in tacrolimus dose by one-third is insufficient, and dose reduction of at least 50% upon azole initiation seems warranted. Once azole antifungal therapy is initiated, frequent therapeutic drug monitoring is required.     

The effectiveness of a cardiac rehabilitation program on self-efficacy and exercise tolerance

This study evaluates the effectiveness of graded physical exercise on self-efficacy and exercise tolerance among a group of cardiac patients (N = 43). These patients were aged from 41 years to 82 years (mean age = 63.5 years, SD = 10.0 years). Results of the study show that efficacy of physical activity was significantly associated with exercise tolerance. After a 3-month rehabilitation with graded physical exercise, both efficacy of activity and exercise tolerance were significantly enhanced. The enhancement was relatively independent of patients' gender, age, education, and diagnostic category. Limitations of the study are discussed and future research suggested.     

The effect of progressive muscle relaxation training on anxiety and quality of life after stoma surgery in colorectal cancer patients

The aim of the study was to evaluate the effects of the use of progressive muscle relaxation training (PMRT) on anxiety and quality of life in colorectal cancer patients after stoma surgery. A randomised controlled trial was used with repeated measures assessment over 10 weeks post-stoma surgery. Fifty-nine patients participated in the study and were randomised to a control group receiving routine care (n=30) and an experimental group receiving routine care and PMRT through two teaching sessions and practice at home for the first 10 weeks. The State-Trait Anxiety Inventory and two Quality of Life Scales were used to collect the data of interest in three occasions, namely during hospitalisation, at week 5 and at week 10 post-surgery. The use of PMRT significantly decreased state anxiety and improved generic quality of life in the experimental group (P<0.05), especially in the domains of physical health, psychological health, social concerns and environment. Social relationships decreased in both groups. In relation to the disease-specific quality of life measure, differences were observed only in the 10-week assessment, with the experimental group reporting better quality of life at 10 weeks, but not over time as compared to the control group. The use of PMRT should be incorporated in the long-term care of colorectal cancer patients, as it can improve their psychological health and quality of life. This may be a cost-effective intervention that needs minimal training and could easily be offered to those patients that they would like to use it as part of the specialist care provided to stoma patients.     

Polymeric microspheres composed of pH/temperature-sensitive polymer complex

A new pH/temperature-sensitive polymer system with transitions resulting both from polymer-water and polymer-polymer interactions has been demonstrated using the mixture of poly(N,N-dimethylamino)ethyl methacrylate (DMAEMA) and polyethyl acrylamide (EAAm). Based on the pH/temperature sensitivity of polymer mixture, the microsphere for pH/temperature-sensitive drug release have been designed and characterized. Hydrocortisone was used as a model drug. This gave the control of hydrocortisone release in an on-off manner without considerable lag time.     

Recurrent primary cutaneous adenoid cystic carcinoma of the scrotum

A 60‐year‐old man had asymptomatic erythematous nodule on the right inguinal area, which had progressively grown for 2 years. Excision was performed at the Department of Urology of our hospital. Two months later, there was local recurrence on the excision site, and it extended locally to make several tender erythematous nodules on the right inguinal area and firm plaque on the scrotum ( Fig. 1 ). Histopathologic examination of the excision specimen revealed large cell masses with tubular or cribriform pattern and many small, solid epithelial islands unattached to the overlying epidermis. The tumor was confined to the dermis and subcutaneous tissue. Round spaces formed by malignant epithelial cells and containing amorphophilic basement membrane‐like material occured inside the tumor masses. The tumor cells were basaloid cells with scanty cytoplasm and deeply stained round‐to‐oval nucleus ( Fig. 2 ). There was clear perineural involvement by the tumor cells. A substance in the pseudoglandular spaces, cystic spaces and the stroma was stained strongly with periodic acid‐Schiff (PAS) and alcian blue (pH 2.5). A PAS‐positive substance was digested by diastase pretreatment. These findings suggested the substance to be a neutral mucopolysaccharide. Immunoperoxidase staining for S‐100 protein and cytokeratin were strongly positive with the tumor cells but not with carcinoembryonic antigen. A histopathologic diagnosis of ACC was made. Salivary glands, bronchi, esophagus, and other organs were examined, but there was no evidence of neoplasm in other organs. A diagnosis of primary cutaneous adenoid cystic carcinoma was made but the patient refused all the treatment, including surgery.

Figure 1 Open in figure viewer PowerPoint Several erythematous nodules on the right inguinal area and indurated plaque on the adjacent scrotum     

1,25-dihydroxycholecalciferol in renal osteodystrophy. Epiphysiolysis--anticonvulsant therapy

Three children with azotaemic renal osteodystrophy were treated with 1,25-dihydroxycholecalciferol (1,25(OH)2D3). All showed clinical, biochemical, and radiological improvement within 6 months of starting treatment. There were no complications. The dose of 1,25(OH)2D3 required was 0-5 microgram per day for 2 children aged 22 and 30 months, and 2 microgram per day for a 15-year-old boy. 2 of the patients were receiving phenobarbitone and phenytoin and in one of them prior treatment with dihydrotachysterol 0-5 mg daily and 6 microgram 1alpha-hydroxycholecalciferol (1alphaOHD3) daily had failed to induce improvement. In one patient, in whom serial iliac bone samples were available, 2 microgram 1,25(OH)2D3 resulted in histological improvement in previously severe osteomalacia. 1,25(OH)2D3 appears to be an effective and safe drug in the treatment of uraemic osteodystrophy.     

Solitary bronchioloalveolar carcinoma: CT criteria

The computed tomographic (CT) scans of 30 patients with solitary bronchioloalveolar carcinoma were reviewed. Common features at CT included the peripheral or subpleural location of a pulmonary mass (25 cases), pseudocavitation (18 cases), heterogeneous attenuation (17 cases), irregular margins forming a star pattern (22 cases), and pleural tags (21 cases). Using these CT criteria, four independent observers attempted to identify cases of bronchioloalveolar carcinoma from a larger sample of lung cancers and benign lesions by categorizing a series of test cases into four probability categories. Although the bronchioloalveolar carcinomas were correctly ranked in the two highest probability categories 75% of the time (in 45 of 60 cases), there was considerable overlap with other lung lesions, particularly with adenocarcinoma and large cell undifferentiated carcinoma. However, even though the typical features of bronchioloalveolar carcinoma are not invariable or highly specific, they are characteristic enough to suggest the diagnosis.     

The FLK2/FLT3 ligand synergizes with interleukin-7 in promoting stromal- cell-independent expansion and differentiation of human fetal pro-B cells in vitro

The effects of a novel cytokine FLK2/FLT3 ligand (FL) on human fetal bone marrow-derived CD34+CD19+ pro-B cells were analyzed in a stromal- cell-independent, serum-deprived culture system. FL, like interleukin-3 (IL-3), synergized with IL-7 in promoting pro-B cell growth, and differentiation of these cells into CD34-CD19+clgM+slgM- pre-B cells, whereas a small proportion of these cells even differentiate into more mature slgM+ B cells. In contrast, KIT ligand (KL) and granulocyte- macrophage colony-stimulating factor (GM-CSF) were ineffective in promoting IL-7-dependent pro-B cell growth and differentiation. Maximal levels of pro-B cell expansion, generally resulting in 15- to 30-fold increases in cellularity, were obtained in cultures supplemented with optimal doses of FL + IL-7 + IL-3. The addition of mouse bone marrow stromal cells further enhanced the proliferation and differentiation of pro-B cells obtained in the presence of these three cytokines. Under these conditions, cultures could be maintained for more than 4 weeks, and in general 40- to 50-fold increases in cell numbers were observed by 3 weeks of culture. The percentages of clgM+ and slgM+ B cells increased 1.5- to 3-fold and 2-fold, respectively, suggesting that stromal cells may provide additional costimulatory signals for human B- cell growth and differentiation that are different from IL-7, IL-3, and FL. Collectively, our results indicate that FL, in contrast to KL, strongly promotes long-term expansion and differentiation of human pro- B cells in the presence of IL-7 or in combination of IL-7 and IL-3, which is a novel property of this hematopoietic growth factor.     

The preterm gut microbiota: changes associated with necrotizing enterocolitis and infection

Aim: To describe gut colonization in preterm infants using standard culture and 16S gene rRNA profiling, exploring differences in healthy infants and those who developed NEC/late onset sepsis (LOS). Methods: Ninety‐nine stools from 38 infants of median 27‐week gestation were cultured; 44 stools from 27 infants had their microbial profiles determined by 16S. Ordination analyses explored effects of patient variables on gut communities. Results: Standard microbiological culture identified a mean of two organisms (range 0–7), DGGE 12 (range 3–18) per patient. Enterococcus faecalis and coagulase negative staphylococci (CONS) were most common by culture (40% and 39% of specimens). Meconium was not sterile. No fungi were cultured. Bacterial community structures in infants with NEC and LOS differed from healthy infants. Infants who developed NEC carried more CONS (45% vs 30%) and less Enterococcus faecalis (31% vs 57%). 16S identified Enterobacter and Staphylococcus presence associated with NEC/LOS, respectively. Conclusions: Important differences were found in the gut microbiota of preterm infants who develop NEC/LOS. The relationship of these changes to current practices in neonatal intensive care requires further exploration.