Clinical Significance of an Early Protocol Biopsy in Living-Donor Renal Transplantation: Ten-Year Experience at a Single Center

We report here our 10-year experience of a biopsy performed at day 14 after transplantation in 304 patients with stable graft function. The factors that may have influenced subclinical rejection were analyzed according to histology. The incidence of subclinical rejection was 13.2%. Addition of mycophenolate mofetile (MMF) as a primary immunosuppressant significantly decreased the incidence of subclinical rejection compared with patients without such treatment (odds ratio, 0.23; p < 0.05). On the other hand, HLA-DR antigen mismatch (odds ratio, 2.39) and unrelated donor (odds ratio, 2.10) were also significantly associated with decreased subclinical rejection (p < 0.05). The incidence of acute rejection in patients with normal findings was lower than in those with borderline changes or subclinical rejection (0.23 +/- 0.05 vs. 0.48 +/- 0.07 and 0.60 +/- 0.11, respectively; p < 0.05). The graft survival rates in patients with subclinical rejection were lower than in patients with normal or borderline changes at 1 (88.4% vs. 97.9% and 99.1%; p < 0.05), 5 (77.8% vs. 96.2% and 95.9%; p < 0.05) and 10 (62.3% vs. 96.2% and 93.7%; p < 0.05) years. Thus, a protocol biopsy performed on day 14 after transplantation is useful for predicting graft survival. Triple therapy including MMF, related donor and HLA-DR antigen match are important factors for reducing subclinical rejection in living-donor renal transplantation.     

Post-injury regeneration in rat sciatic nerve facilitated by neurotrophic factors secreted by amniotic fluid mesenchymal stem cells.

Amniotic fluid mesenchymal stem cells have the ability to secrete neurotrophic factors that are able to promote neuron survival in vitro. The purpose of this study was to evaluate the effects of neurotrophic factors secreted by rat amniotic fluid mesenchymal stem cells on regeneration of sciatic nerve after crush injury. Fifty Sprague-Dawley rats weighing 250-300 g were used. The left sciatic nerve was crushed with a vessel clamp. Rat amniotic fluid mesenchymal stem cells embedded in fibrin glue were delivered to the injured nerve. Enzyme-linked immunosorbent assay (ELISA) and immunocytochemistry were used to detect neurotrophic factors secreted by the amniotic fluid mesenchymal stem cells. Nerve regeneration was assessed by motor function, electrophysiology, histology, and immunocytochemistry studies. Positive CD29/44, and negative CD11b/45, as well as high levels of expression of brain-derived neurotrophic factor, glia cell line-derived neurotrophic factor, ciliary neurotrophic factor (CNTF), nerve growth factor, and neurotrophin-3 (NT-3) were demonstrated in amniotic fluid mesenchymal stem cells. Motor function recovery, the compound muscle action potential, and nerve conduction latency showed significant improvement in rats treated with amniotic fluid mesenchymal stem cells. ELISA measurement in retrieved nerves displayed statistically significant elevation of CNTF and NT-3. The immunocytochemical studies demonstrated positive staining for NT-3 and CNTF in transplanted cells. The histology and immunocytochemistry studies revealed less fibrosis and a high level of expression of S-100 and glial fibrillary acid protein at the crush site. Rat amniotic fluid mesenchymal stem cells may facilitate regeneration in the sciatic nerve after crush injury. The increased nerve regeneration found in this study may be due to the neurotrophic factors secreted by amniotic fluid mesenchymal stem cells.     

The Role of Donor Bone Marrow Infusions in Withdrawal of Immunosuppression in Adult Liver Allotransplantation

We investigated the role of donor bone marrow cell (DBMC) infusions in immunosuppression withdrawal in adult liver transplantation. Patients enrolled were at least 3 years post-transplantation, with stable graft function. Forty-five (study group: G1) received DBMC, and 59 (control group: G2) did not. Immunosuppression was reduced by one third upon enrollment, by another third the second year of the study and was completely withdrawn the third year. Patient and graft survival were similar between the two groups. Although rejection episodes were significantly less in G1 the first 2 years of the study (35% vs. 57%, p = 0.016), there was no significant difference overall (74% vs. 81%, p = 0.14). Until February 2004, 20 patients, 10 in each group, were immunosuppression free for 1-3 years. Approximately 20% of long-term survivors of liver transplantation can successfully discontinue their immunosuppression. DBMC infusions, do not increase this likelihood.     

Teaching ethics to paediatrics residents: the centrality of the therapeutic alliance

Context Previous research on ethical issues encountered by medical professionals in training and practice have presented the thematic content of the cases they encounter rather than the activities in which clinicians engage and in which they most often encounter ethical issues. We conducted a direct observation study of paediatrics residents and their preceptors seeing patients in an out‐patient general paediatrics clinic. Our objectives were to describe the everyday ethics‐related issues paediatrics residents encounter as they interact with patients. Our ultimate goal is to use this knowledge to enhance current efforts to teach ethics to paediatrics residents. Methods The study team directly observed paediatrics residents discussing patients with their faculty preceptors (19 half‐day sessions, 76 hours) in an out‐patient general paediatrics clinic located in an urban academic medical centre. Each interaction between resident and preceptor about a single patient was considered a case for further analysis. Results A total of 247 cases were recorded. Forty‐one of the cases were coded as having ethics‐related content. A constant comparative method of qualitative data analysis revealed that residents were most likely to encounter ethical issues when engaged in the following activities: (i) maintaining a therapeutic alliance with the caregiver (e.g. the parent); (ii) prioritising patient or family needs; (iii) adjusting to the power embodied by the role of doctors, and (iv) distinguishing suboptimal care from abuse or neglect. In addition, our findings indicate that it is through their efforts to maintain the therapeutic alliance with the caregivers of their patients that residents engage in and integrate three processes: developing their medical knowledge; adhering to professional norms, and balancing the power inherent in the doctor’s role with their responsibility to serve the patient’s interests. Conclusions Medical faculty tasked with teaching ethics to paediatrics residents can utilise the results of this project to better target and enhance their ethics education efforts directed at residents in the out‐patient setting. Future research could further examine and test these findings in other clinical settings (e.g. adult general medicine).     

Reversible Verbal and Visual Memory Deficits after Left Retrosplenial Infarction

The retrosplenial cortex is a cytoarchitecturally distinct brain structure located in the posterior cingulate gyrus and bordering the splenium, precuneus, and calcarine fissure. Functional imaging suggests that the retrosplenium is involved in memory, visuospatial processing, proprioception, and emotion.We report on a patient who developed reversible verbal and visual memory deficits following a stroke. Neuropsychological testing revealed both anterograde and retrograde memory deficits in verbal and visual modalities. Brain diffusion-weighted and T2-weighted magnetic resonance imaging (MRI) demonstrated an acute infarction of the left retrosplenium.     

The study of diethylstilbestrol toxic effect in the mouse sertoli cell line by comparison of miRNA and mRNA expression

It is important to acknowledge the harmful effects of environmental chemicals in human’s lives. The toxic effects of Diethylstilbestrol (DES), one of the endocrine-disrupting chemicals (EDCs), have been documented in many studies. As expected, DES affect male gendal hormone as well as female’s; therefore, epigenetic study should be considered. In this study, microarray technology was used to study harmful effects on the level of genomics, and here, two types of microarray chips- the Agilent mouse genome 4 × 44 K array for gene expression profiling and the Agilent mouse miRNA v13 for miRNA expression profiling-was used to study the relation between gene and miRNA expression profiles. As a result, we identified 4 miRNAs (miR 203, 350, 421, and 466i) that were similarly expressed at 3 hrs and 24 hrs of DES treat times. Twenty one genes matched between predicted target for 4 miRNAs and 118 genes expressed similarly. These genes have functions related to cell differentiation and cell cycle. Therefore, DES affects cellular function and induces toxicity in TM4 cells. In future studies, it is necessary to find more related functions and mechanisms of DES in the system.     

Factors affecting penetration of zona-free hamster ova

The sperm penetration assay is an expensive, time-consuming test to assess male fertility in vitro. Although some investigators are enthusiastic in its application, others feel that it is not sensitive or specific enough to be used as part of the routine infertility evaluation. Indeed, this bioassay is not a faithful reproduction of in vivo conditions. However, if the SPA is abnormal, it is unlikely that sperm will fertilize a human ovum in vivo. Conversely, a normal SPA does not guarantee successful in vivo fertilization. No bioassay can be absolute in its predictive value, but false-negative results must be kept to a minimum for this bioassay to be of any clinical significance. Each laboratory performing the SPA should optimize the assay for sensitivity, reproducibility, and minimization of false-negative results and then establish normal and abnormal ranges of its own. If the limitations of the SPA are kept in mind, and if we employ it very selectively, it may still be useful.     

Effects of acute barbiturate administration, tolerance and dependence on brain GABA system: comparison to alcohol and benzodiazepines

Central nervous system depressants, e.g., barbiturates, alcohol and benzodiazepines, have a wide spectrum of activity in humans and animals. Evidence accumulated suggests that some of the pharmacological actions exerted by these agents may be mediated through GABA system by mimicking GABAergic transmission. This review attempts to summarize the evidence available as to how the GABA system plays a part in the barbiturate actions and the development of tolerance to and physical dependence on barbiturates. The comparisons of the effects of alcohol, barbiturates and benzodiazepines at different steps of GABA synapse are also presented. Furthermore, the results which have been reported in the literature are inconsistent. This may be due to differences in: (a) animal models used; (b) brain regions used; (c) protocols (dose, duration, form and route of administration, etc.) used in treating animals and/or (d) techniques (pharmacological, biochemical, physiological, etc.) used.     

Inhibition of hepatic glucose production by SDZ 51641

The new oral hypoglycemic agent SDZ 51641 was evaluated in nondiabetic rats and a rat model of human non-insulin-dependent diabetes mellitus. Diabetes was induced with a single injection of 37.5 mg/kg streptozocin, and the rats exhibited hyperglycemia in the fed state with normal insulin levels. Treatment of nondiabetic animals with 100 mg/kg SDZ 51641 given orally significantly decreased serum glucose and ketone levels within 4 h without affecting insulin levels. Nonesterified fatty acids increased more than twofold during the same period. Its effect on ketone and fatty acid levels suggests that SDZ 51641 acts as an inhibitor of fatty acid oxidation. Diabetic rats treated with SDZ 51641 exhibited a significant acute hypoglycemic response, which was more pronounced after 3 days of treatment. The compound also significantly decreased serum cholesterol and triglyceride levels 27 and 53%, respectively. When endogenous hepatic glucose production was assessed in nondiabetic and diabetic animals via continuous infusion of [3-3H]glucose, we found that hepatic glucose production was elevated 43% in diabetic compared with control animals. When diabetic rats were treated with 100 mg/kg SDZ 51641, hepatic glucose production decreased to normal levels within 6 h. Hyperinsulinemic-euglycemic clamp studies indicated that SDZ 51641 had no effect on insulin-stimulated glucose utilization. Measurement of [1-14C]oleate oxidation in isolated hepatocytes demonstrated that SDZ 51641 inhibited long-chain fatty acid oxidation in a concentration-dependent manner. The compound was ineffective at inhibiting long-chain fatty acid oxidation in epitrochlearis or soleus muscles.(ABSTRACT TRUNCATED AT 250 WORDS)