Modulation of early immune responses and suppression of Trypanosoma brucei brucei infections by surgical denervation of the spleen

OBJECTIVE: To examine critical interactions between the nervous system and the immune system during experimental African trypanosomiasis. METHODS AND RESULTS: Inoculation of Trypanosoma brucei brucei resulted in early interferon (IFN)-gamma production, elevated corticosterone and prostaglandin E(2) (PGE(2)) levels and increased splenocyte proliferation, as measured by enzyme-linked immunospot assay, radioimmunoassay and thymidine incorporation assay, respectively. Splenic denervation suppressed IFN-gamma, corticosterone and PGE(2) production, enhanced splenocyte proliferation, and significantly reduced parasitemia and prolonged rat survival. CONCLUSIONS: Our data show substantial effects of the nervous system on early immune responses that may influence the outcome of this disease. These effects were not dependent on cytokine inhibitory mediators such as prostaglandins or stress hormones. More investigations are required to understand the evident neural control over the immune system during infectious challenges, which may assist in novel therapeutic approaches.     

Intraoperative changes in coronary resistance during aortic valve replacement

Coronary vascular resistance was investigated in 10 patients undergoing aortic valve replacement using continuous constant-pressure coronary perfusion at 32 degrees C. After coronary flow was initiated, resistance was low but increased steadily until it reached a certain resting level. The plateau was attained faster after a short period of anoxia than after a longer period. The initial postischemic resistance was dependent on the duration preceding anoxia, being of the same magnitude after short and moderate periods of anoxia but significantly higher after a long period. This resistance difference between the groups lasted for the whole perfusion. The total coronary resistance and flow reached a plateau in 30 minutes, while resistance increased threefold but flow decreased to half of the initial postanoxia flow. Our results indicate the importance of initiating coronary perfusion soon after aortic cross-clamping to avoid increase in the initial vascular resistance and subsequent inadequate myocardial flow.     

Fetal but not adult Leydig cells are susceptible to adenoma formation in response to persistently high hCG level: a study on hCG overexpressing transgenic mice

We have previously demonstrated that male transgenic (TG) mice overexpressing human chorionic gonadotropin (hCG+) develop reproductive organ defects, but no tumors, in adult age. In this study, the effects of persistently elevated hCG were followed in TG males between day 5 postpartum and adulthood. Leydig cell (LC) adenomas were found in prepubertal mice, most prominently at the age of 10 days, but not in adult age. Serum testosterone concentrations were significantly increased in TG males at all ages studied. The phenotype of the prepubertal hCG+ males resembled that found in boys upon expression of constitutively activating luteinizing hormone (LH) receptor mutations. The temporal expression patterns of the fetal LC marker gene, thrombospondin 2, and those of adult LCs, hydroxysteroid dehydrogenase-6, delta5-3-beta and prostaglandin D synthase, were similar in wild-type and hCG+ males. Hence, the postnatal adenomas resemble functionally fetal LCs, and only these cells are susceptible to hCG-induced tumorigenesis. Our findings demonstrate a novel intriguing difference between the fetal and adult LC populations and provide further insight into the potential tumorigenic effects of gonadotropins.     

Numbers of mutations to different types of colorectal cancer

Background  

The numbers of oncogenic mutations required for transformation are uncertain but may be inferred from how cancer frequencies increase with aging. Cancers requiring more mutations will tend to appear later in life. This type of approach may be confounded by biologic heterogeneity because different cancer subtypes may require different numbers of mutations. For example, a sporadic cancer should require at least one more somatic mutation relative to its hereditary counterpart.     

Recombinant human growth hormone treatment after liver transplantation in childhood: the 5-year outcome

BACKGROUND: Because the results of short-term recombinant human growth hormone (rhGH) treatment in children with growth impairment after liver transplantation (LTx) have been promising, we have studied the long-term effects of rhGH on growth and graft function after LTx. METHODS: Indications for rhGH treatment were height standard deviation score (hSDS) below -2.0 or growth velocity SDS below 0 and LTx at least 18 months before inclusion. Eight growth-retarded children were treated with rhGH for more than 5 years. RESULTS: During the first year, median growth rate improved from 3.3 to 7.0 cm/year. In the second and third year, growth velocity remained high at 6.6 cm/year and 6.2 cm/year, respectively (P=0.008). In the fourth year, median growth velocity started to decline but still remained above baseline during the fifth year of treatment (4.2 cm/year). The median hSDS improved from -3.6 to -2.7. During the rhGH treatment, no acute rejection episodes were detected, and graft function remained stable in all except one patient. She was diagnosed with chronic rejection in the third year of rhGH treatment. The patient had elevated liver enzymes and abnormal liver function tests already before rhGH treatment. CONCLUSIONS: The efficacy of rhGH treatment is sustained after the first year in liver-transplant children with non-GH-deficient growth retardation. Because of a potential risk of side effects, close monitoring of these patients is required.     

Serum sCD30 in monitoring of alloresponse in well HLA-matched cadaveric kidney transplantations

In kidney transplantation, pretransplant serum sCD30 testing has been proposed in immunological risk estimation together with anti-HLA antibodies. We evaluated the risks associated with high pretransplant serum sCD30 in well HLA-matched cadaveric kidney recipients recruited in a clinical study comparing different immunosuppressive regimens. Rejection rate was similar in 37 recipients with high pretransplant serum sCD30 compared to 117 recipients with low serum sCD30 (16% vs. 15%, P=NS). Compared to pretransplant levels, the posttransplant sCD30 levels generally decreased, also in patients with rejection, although on day 21 posttransplant, rejecting patients had significantly higher relative sCD30 than nonrejecting patients (P<0.01). However, steroid-resistant rejection was associated with increasing posttransplant sCD30 levels. High pretransplant sCD30 values were associated with tubulointerstitial rejection. There was no correlation of sCD30 with delayed graft function. Good HLA matching seems to be effective in neutralizing the negative effect of a high pretransplant serum sCD30.     

Sentinel node metastasectomy in thin ≤1-mm melanoma

Background and aims Sentinel lymph node biopsy (SLNB) has been widely accepted as a precise tool to stage melanoma. In thin T1 melanomas (1 mm), the indication of SLNB is controversial since the risk of nodal metastasis is low. The aim of this study was to assess if SLNB detects occult nodal metastases among patients with thin melanomas.Patients and methods SLNB was performed prospectively in 135 patients with invasive melanoma in any depth category, including 56 T1 melanomas.Results Nodal metastases were detected in 18% by SLNB, and there were three sentinel-positive thin melanomas, constituting 5% of the T1 cases. Histopathologically, there were no factors of the primary tumors that would have predicted these metastases.Conclusion SLNB is a precise method to detect clinically silent nodal metastases in thin invasive melanoma. Certain histopathologic features of a thin primary lesion may correlate with the predictive probability of the sentinel node status. We were unable to identify these predictors, but the conclusions from this study are limited by the small sample size. Advanced melanoma is a lethal disease, and accurate staging is essential also in the T1 group. For stage III patients with occult nodal metastases, metastasectomy is a better option for cure than observation.     

Is there an evidence-based approach to anesthesia education?

Education in anesthesiology offers a variety of unique forums. Examples include focused teaching in the operating room, bedside teaching in critical care settings, and simulations. Many approaches are used by educators with a wide range of effectiveness. Each training program creates its own combination of educational techniques designed to meet national standards. In addition, new and innovative curriculum, teaching skills and evaluative tools develop among individual teachers and within each program. Everyone benefits from cultivating and sharing educational techniques and assessment methods. Educators grow in their ability and effectiveness to teach through awareness and subsequent application of new skills. Developing effective teachers maintains quality in training, promotes interest and enthusiasm for academia, and provides role models for learners. Evidence-based approaches to education are increasing in anesthesiology. This chapter will discuss skills, techniques, and evaluative tools from the literature that illustrate evidence-based effectiveness and applications to anesthesiology.