Sympathetic activation triggers endogenous opioid release and analgesia within peripheral inflamed tissue

Stress induces analgesia by mechanisms within and outside the brain. Here we show that the sympathetic nervous system is an essential trigger of intrinsic opioid analgesia within peripheral injured tissue. Noradrenaline, injected directly into inflamed hind paws of male Wistar rats, produced dose-dependent antinociception, reversible by alpha(1)-, alpha(2)- and beta(2)-antagonists. alpha(1)-, alpha(2)- and beta(2)-adrenergic receptors were demonstrated on beta-endorphin-containing immune cells and noradrenaline induced adrenergic receptor-specific release of beta-endorphin from immune cell suspensions. This antinociceptive effect of noradrenaline was reversed by micro - and delta-opioid antagonists as well as by anti-beta-endorphin. Stress-induced peripheral analgesia was abolished by chemical sympathectomy and by adrenergic antagonists. These findings indicate that sympathetic neuron-derived noradrenaline stimulates adrenergic receptors on inflammatory cells to release beta-endorphin, which induces analgesia via activation of peripheral opioid receptors.     

Purification and partial characterization of a 32-kilodalton sialic acid-specific lectin from Aspergillus fumigatus

Adherence of the opportunistic fungus Aspergillus fumigatus to the extracellular matrix components is considered a crucial step in the establishment of the infection. Given the high carbohydrate content of these glycoproteins and the role of carbohydrate-protein interactions in numerous adherence processes, the presence of a lectin in A. fumigatus was investigated. Different fungal extracts obtained by sonication or grinding in liquid nitrogen from resting or swollen conidia, as well as from germ tubes and mycelium, were tested by hemagglutination assays using rabbit erythrocytes. A lectin activity was recovered in all the extracts tested. However, sonication of resting conidia resulted in the highest specific activity. Purification of the lectin was achieved by gel filtration followed by ion-exchange and hydrophobic-interaction chromatographies. Analysis of the purified lectin by sodium dodecyl sulfate-polyacrylamide gel electrophoresis showed an apparent molecular mass of 32 kDa, which is similar to that of the alkaline protease already identified from different strains of A. fumigatus. However, as evidenced by the use of an alkaline protease-deficient mutant, the two activities were supported by distinct proteins. In addition, hemagglutination inhibition experiments using different saccharides and glycoproteins demonstrated the specificity of the lectin for sialic acid residues. Together these results suggest that this lectin may contribute to the attachment of conidia to the extracellular matrix components through the recognition of the numerous terminal sialic acid residues of their carbohydrate chains.     

Prenatal diagnosis of congenital upper limb differences: a current concept review

Congenital upper limb differences are frequently associated with complex syndromes. Ultrasonography is considered as the first-line diagnostic modality, and fetal MRI can be useful to further evaluate ill-defined areas. Genetic and non-invasive prenatal testing help to identify the underlying genetic disorder. The diagnostic assessment is a multidisciplinary task that should involve early prenatal consultations with specialists involved in case management and treatment planning. Obstetricians, geneticists, radiologists, psychologists and dedicated surgeons are needed to provide good parental education, prenatal and postnatal care, and successful outcomes. The purpose of this review is to provide an overview of the clinicopathologic background, current diagnostic and imaging procedures in affected fetuses.     

Optimal care for the child with cancer: A summary statement from the SIOP working committee on psychosocial issues in pediatric oncology

Since its foundation in 1991, the SIOP Working Committee on Psychosocial Issues in Paediatric Oncology 1 has developed and published 12 sets of Guidelines for health‐care professionals treating children with cancer and their families. Those elements considered essential in the process of cure and care of children with cancer are summarized in this document as a formal statement, developed at the 2007 SIOP annual meeting in Mumbai. Elaboration of the concepts with detailed strategies for practice can be found in the referenced guidelines [1–12] and in a companion publication [13]. This article is a summary of what practitioners considered critical elements in the optimal care of the child with cancer, with the goal of stimulating a broader application of these elements throughout the SIOP membership. Pediatr Blood Cancer 2009;52:904–907. © 2009 Wiley‐Liss, Inc.     

Insulin-related metabolism following hematopoietic stem cell transplantation in childhood

Objectives:  To assess insulin-related metabolism following hematopoietic stem cell transplantation (HSCT) in childhood.
Study design:  Thirty-four patients who underwent HSCT were compared with 21 patients with similar diseases who were not transplanted. Median follow-up was 3.6 yr after HSCT. Anthropometric parameters, fasting plasma glucose and insulin levels, hemoglobin A_1c (HbA_1c) and lipid profile were measured and compared.
Results:  HbA_1c was significantly higher (p = 0.001) in the study group. Two (5.8%) patients in the study group developed type 2 diabetes mellitus. Among thalassemic patients, significantly lower insulin resistance indices (p = 0.05) and fasting plasma insulin levels (p = 0.033) were found in the study group compared with the control group.
Conclusions:  Attentive follow-up of insulin-related metabolism following HSCT in children is needed. The significance of the higher HbA1c values in the study group remains to be evaluated in a larger cohort of patients.     

High-dose methotrexate therapy of childhood acute lymphoblastic leukemia: lack of relation between serum methotrexate concentration and creatinine clearance.

BACKGROUND: The objectives of this study were: (1) to analyze the relation of serum methotrexate (MTX) concentration with creatinine clearance, (2) to compare the leucovorin rescue dose administered to the patients based on creatinine clearance, with the one calculated according to serum MTX levels, and (3) to determine MTX-related toxicity. PROCEDURE: Thirty children with high-risk non-B acute lymphoblastic leukemia (ALL) treated according to the national protocol (PINDA 92) based on ALL BFM 90, were randomized to receive consolidation with four doses of either 1 or 2 g/m(2) MTX as a 24-hr infusion, at 2-week intervals (group M1 and M2, respectively). Serum MTX concentrations were measured at 24, 42, and 48 hr after beginning the infusion and were analyzed retrospectively. The creatinine clearance was calculated after 12-hr intravenous hydration prior to each MTX dose. Leucovorin dosage was adjusted according to creatinine clearance. RESULTS: Serum MTX concentrations at 24, 42, and 48 hr after starting the infusion were not related to creatinine clearance in both treatment groups. Leucovorin rescue administered according to creatinine clearance was excessive in 43% in group M1 and in 51% in group M2, as compared to the dose calculated according to serum MTX levels. No serious clinical complications were observed. CONCLUSIONS: These results suggest that creatinine clearance is not a good parameter to calculate leucovorin rescue. MTX-related toxicity in this group of patients receiving a dose of 1 or 2 g/m(2) and rescued with leucovorin without monitoring serum MTX levels was acceptable.     

Teaching communication skills to medical students,a challenge in the curriculum?

INTRODUCTION: As communication skills become more and more important in medical practice, the new medical curriculum at Ghent University (1999) implemented a communication curriculum. METHOD: Communication training or experiences in 'real life' settings are provided every year of the medical curriculum. The training starts with simple basic skills but gradually slips into medical communication or consultation training and results in communication in different contextual situations or with special groups of patients. Rehearsal is important and seen as inevitable. Poorly performing students get extra training. Several didactical methods are used: the skills are demonstrated by means of videotapes and paper cases of patient stories. Skills are trained in small groups (10-15 students), with focus on role-playing with colleague students or simulated patients (SP). Videotapes of real consultations give an idea of the performance of each student. Every year the students are assessed by means of an OSCE (objective structured clinical examination). CONCLUSION: After 6 years of experience with the new curriculum, several remarks and questions need to be answered. Small group training gives a huge workload and with different trainers discrepancies between groups can appear. Choosing the most suitable trainer for communication skills is not easy; several options are available: specialists in communication like psychologists with interest in medical practice, GPs with interest in medical communication, medical specialists for communication topics concerning medical problems within their domain. As the most important didactical approach lies in practising the skills, the selection and training of simulated patients remains a challenge. PRACTICE IMPLICATION: A communication continuum during the whole curriculum seems to be worthwhile. Students with specific communicative problems are detected early, remediation is provided. Rehearsal every year seems to lead to better acquisition. The most positive point is that communication is embedded in a global patient-, student- and community-oriented curriculum and that communication skills are seen as core elements of good doctoring.     

Spermatocytic seminoma. A clinicopathological and immunohistochemical study of 7 cases

Spermatocytic seminoma is an uncommon tumor, representing less than 1% of the testicular tumors, occurring most often in old patients. We report 7 cases of this entity. The average age at presentation was 66 years. Tumors had a polymorphic appearance with small, intermediate and large cells, and "spireme" figures. They were pure, with no sarcomatous component. In all cases, the tumor was limited to the testis. In the peritumoral tissue, there was no intratubular germ cell proliferation, and no atrophic testis. Immunostaining was negative for all the classical antibodies tested (cytokeratins, PLAP, lymphoid markers), but all the cases expressed c-kit (100%). This membranous positivity was focal in 4 cases, very strong, and diffuse in the 3 others. Spermatocytic seminoma must be recognized, because its favorable evolution in absence of a sarcomatous component. Adequate treatment consists of orchidectomy alone. Positive staining for c-kit may be helpful for the diagnosis of spermatocytic seminoma.     

Influence of the number of motile spermatozoa inseminated and of their morphology on the success of intrauterine insemination

BACKGROUND: Although intrauterine insemination (IUI) is one of the most common assisted reproductive technology methods in the world, the relative influence of various semen characteristics on the likelihood of a successful outcome is controversial. The aim of our study was to assess the results of IUI as a function of both the number of motile spermatozoa inseminated (NMSI) and the percentage of morphologically normal spermatozoa after preparation. METHODS: This was a retrospective study of 889 couples who underwent 2564 IUI cycles of ovarian stimulation with HMG or recombinant FSH in our centre between January 1991 and December 2000. RESULTS: A total of 331 clinical pregnancies were obtained, for a pregnancy rate/cycle of 12.91%. When the NMSI was < 1 x 10(6), the pregnancy rate/cycle was significantly lower (3.13%) than in any of the subgroups with NMSI > or = 2 x 10(6). Sperm morphology, assessed before or after preparation, was not in itself a significant factor that affected the likelihood of IUI success. Nonetheless, when the post-migration rate of normal sperm was < 30%, the pregnancy rate/cycle was 5.43% when NMSI was < 5 x 10(6) and 18.42% when NMSI was > or = 5 x 10(6) (P = 0.008). Pregnancy rates did not differ significantly according to NMSI when the percentage of normal sperm after preparation was > or = 30%, or according to percentage of normal sperm when the NMSI was > or = 5 x 10(6). CONCLUSIONS: Our results show that a minimum of 5 x 10(6) motile spermatozoa should be inseminated when the normal morphology of the sperm after preparation is < 30%; the quantity compensates at least in part for the defective quality. If this threshold of NMSI cannot be obtained, IVF should be recommended.