A tailored approach for the treatment of indirect inguinal hernia in adults--an old problem revisited.

A patent processus vaginalis peritonei (PPV) presents typically as an indirect hernia with an intact inguinal canal floor during childhood. Little is known however about PPV in adults and its best treatment. A cohort study included all consecutive patients admitted for ambulatory open hernia repair. In patients with a PPV, demographics, hernia characteristics, and outcome were prospectively assessed. Annulorrhaphy was the treatment of choice in patients with an internal inguinal ring diameter of < 30 mm. Between 1998 and 2006, 92 PPVs (two bilateral) were diagnosed in 676 open hernia repairs (incidence of 14%). Eighty nine of the 90 patients were males, the median age was 34 years (range: 17-85). A PPV was right-sided in 67% and partially obliterated in 66%. Forty-one patients had an annulorrhaphy and 51 patients had a tension-free mesh repair. The median operation time was significantly shorter in the annulorrhaphy group (38 vs. 48 min, P <.0001). In a median follow-up period of 56 months (27-128), both groups did not differ concerning recurrence (1/41 vs. 2/51), chronic pain (3/41 vs. 4/51), and hypoesthesia (5/41 vs. 9/51). There was however a clear trend to less neuropathic symptoms in favor of annulorrhaphy (0/41 vs. 5/51, P < 0.066). PPV occurs in 14% of adults undergoing hernia repair. In selected patients, annulorrhaphy takes less time and is associated with equally low recurrence but less potential for neuropathic symptoms.

T helper 1 (Th1) and Th2 characteristics start to develop during T cell priming and are associated with an immediate ability to induce immunoglobulin class switching.

The respective production of specific immunoglobulin (Ig)G2a or IgG1 within 5 d of primary immunization with Swiss type mouse mammary tumor virus [MMTV(SW)] or haptenated protein provides a model for the development of T helper 1 (Th1) and Th2 responses. The antibody-producing cells arise from cognate T cell B cell interaction, revealed by the respective induction of Cgamma2a and Cgamma1 switch transcript production, on the third day after immunization. T cell proliferation and upregulation of mRNA for interferon gamma in response to MMTV(SW) and interleukin 4 in response to haptenated protein also starts during this day. It follows that there is minimal delay in these responses between T cell priming and the onset of cognate interaction between T and B cells leading to class switching and exponential growth. The Th1 or Th2 profile is at least partially established at the time of the first cognate T cell interaction with B cells in the T zone. The addition of killed Bordetella pertussis to the hapten-protein induces nonhapten-specific IgG2a and IgG1 plasma cells, whereas the anti-hapten response continues to be IgG1 dominated. This indicates that a Th2 response to hapten-protein can proceed in a node where there is substantial Th1 activity.

Parents' willingness to pay for diminishing children's pain during blood sampling.

BACKGROUND: Blood sampling is a frequent medical procedure, very often considered as a stressful experience by children. Local anesthetics have been developed, but are expensive and not reimbursed by insurance companies in our country. We wanted to assess parents' willingness to pay (WTP) for this kind of drug. PATIENTS AND METHODS: Over 6 months, all parents of children presenting for general (GV) or specialized visit (SV) with blood sampling. WTP was assessed through three scenarios [avoiding blood sampling (ABS), using the drug on prescription (PD), or over the counter (OTC)], with a payment card system randomized to ascending or descending order of prices (AO or DO). RESULTS: Fifty-six responses were collected (34 GV, 22 SV, 27 AO and 29 DO), response rate 40%. Response distribution was wide, with median WTP of 40 for ABS, 25 for PD, 10 for OTC, which is close to the drug's real price. Responses were similar for GV and SV. Median WTP amounted to 0.71, 0.67, 0.20% of respondents' monthly income for the three scenarios, respectively, with a maximum at 10%. CONCLUSIONS: Assessing parents' WTP in an outpatient setting is difficult, with wide result distribution, but median WTP is close to the real drug price. This finding could be used to promote insurance coverage for this drug.

Quorum-sensing-negative (lasR) mutants of Pseudomonas aeruginosa avoid cell lysis and death.

In Pseudomonas aeruginosa, N-acylhomoserine lactone signals regulate the expression of several hundreds of genes, via the transcriptional regulator LasR and, in part, also via the subordinate regulator RhlR. This regulatory network termed quorum sensing contributes to the virulence of P. aeruginosa as a pathogen. The fact that two supposed PAO1 wild-type strains from strain collections were found to be defective for LasR function because of independent point mutations in the lasR gene led to the hypothesis that loss of quorum sensing might confer a selective advantage on P. aeruginosa under certain environmental conditions. A convenient plate assay for LasR function was devised, based on the observation that lasR mutants did not grow on adenosine as the sole carbon source because a key degradative enzyme, nucleoside hydrolase (Nuh), is positively controlled by LasR. The wild-type PAO1 and lasR mutants showed similar growth rates when incubated in nutrient yeast broth at pH 6.8 and 37 degrees C with good aeration. However, after termination of growth during 30 to 54 h of incubation, when the pH rose to > or = 9, the lasR mutants were significantly more resistant to cell lysis and death than was the wild type. As a consequence, the lasR mutant-to-wild-type ratio increased about 10-fold in mixed cultures incubated for 54 h. In a PAO1 culture, five consecutive cycles of 48 h of incubation sufficed to enrich for about 10% of spontaneous mutants with a Nuh(-) phenotype, and five of these mutants, which were functionally complemented by lasR(+), had mutations in lasR. The observation that, in buffered nutrient yeast broth, the wild type and lasR mutants exhibited similar low tendencies to undergo cell lysis and death suggests that alkaline stress may be a critical factor providing a selective survival advantage to lasR mutants.

Ly49D-mediated ITAM signaling in immature thymocytes impairs development by bypassing the pre-TCR checkpoint.

Activating and inhibitory NK receptors regulate the development and effector functions of NK cells via their ITAM and ITIM motifs, which recruit protein tyrosine kinases and phosphatases, respectively. In the T cell lineage, inhibitory Ly49 receptors are expressed by a subset of activated T cells and by CD1d-restricted NKT cells, but virtually no expression of activating Ly49 receptors is observed. Using mice transgenic for the activating receptor Ly49D and its associated ITAM signaling DAP12 chain, we show in this article that Ly49D-mediated ITAM signaling in immature thymocytes impairs development due to a block in maturation from the double negative (DN) to double positive (DP) stages. A large proportion of Ly49D/DAP12 transgenic thymocytes were able to bypass the pre-TCR checkpoint at the DN3 stage, leading to the appearance of unusual populations of DN4 and DP cells that lacked expression of intracellular (ic) TCRβ-chain. High levels of CD5 were expressed on ic TCRβ(-) DN and DP thymocytes from Ly49D/DAP12 transgenic mice, further suggesting that Ly49D-mediated ITAM signaling mimics physiological ITAM signaling via the pre-TCR. We also observed unusual ic TCRβ(-) single positive thymocytes with an immature CD24(high) phenotype that were not found in the periphery. Importantly, thymocyte development was completely rescued by expression of an Ly49A transgene in Ly49D/DAP12 transgenic mice, indicating that Ly49A-mediated ITIM signaling can fully counteract ITAM signaling via Ly49D/DAP12. Collectively, our data indicate that inappropriate ITAM signaling by activating NK receptors on immature thymocytes can subvert T cell development by bypassing the pre-TCR checkpoint.

Changes in protein turnover and resting energy expenditure after treatment of malaria in Gambian children.

To explore the changes in resting energy expenditure (REE) and whole body protein turnover induced by malaria, 23 children aged 6 to 14 y (23.9 +/- 1.0 kg, 1.3 +/- 0.02 m) were studied on three separate days after treatment (d 1, d 2, and 15 d later). REE was assessed by indirect calorimetry (hood), whereas whole body protein turnover was estimated using a single dose of [15N]glycine administered p.o. by measuring the isotopic enrichment of [15N]ammonia in urine over 12 h. Within the first 3.5 h after treatment, the body temperature dropped from 39.8 +/- 0.1 to 37.8 +/- 0.1 degrees C (p < 0.0001), and REE followed the same pattern, decreasing rapidly from 223 +/- 6 to 187 +/- 4 kJ/kg/d (p < 0.0001). Whole body protein synthesis and breakdown were significantly higher during the 1st day (5.65 +/- 0.38 and 6.21 +/- 0.43 g/kg/d, respectively) than at d 15 (2.95 +/- 0.17 and 2.77 +/- 0.2 g/kg/d). It is concluded that Gambian children suffering from an acute episode of malaria have an increased REE averaging 37% of the control value (d 15) and that this was associated with a substantial increase (by a factor of 2) in whole body protein turnover. A rapid normalization of the hypermetabolism and protein hypercatabolism states after treatment was observed.

Developmentally regulated extinction of Ly-49 receptor expression permits maturation and selection of NK1.1+ T cells.

Clonally distributed inhibitory receptors negatively regulate natural killer (NK) cell function via specific interactions with allelic forms of major histocompatibility complex (MHC) class I molecules. In the mouse, the Ly-49 family of inhibitory receptors is found not only on NK cells but also on a minor (NK1.1+) T cell subset. Using Ly-49 transgenic mice, we show here that the development of NK1.1+ T cells, in contrast to NK or conventional T cells, is impaired when their Ly-49 receptors engage self-MHC class I molecules. Impaired NK1.1+ T cell development in transgenic mice is associated with a failure to select the appropriate CD1-reactive T cell receptor repertoire. In normal mice, NK1.1+ T cell maturation is accompanied by extinction of Ly-49 receptor expression. Collectively, our data imply that developmentally regulated extinction of inhibitory MHC-specific receptors is required for normal NK1.1+ T cell maturation and selection.

Sentinel lymph node biopsy in nonmelanoma skin cancer patients.

The management of lymph nodes in nonmelanoma skin cancer patients is currently still debated. Merkel cell carcinoma (MCC), squamous cell carcinoma (SCC), pigmented epithelioid melanocytoma (PEM), and other rare skin neoplasms have a well-known risk to spread to regional lymph nodes. The use of sentinel lymph node biopsy (SLNB) could be a promising procedure to assess this risk in clinically N0 patients. Metastatic SNs have been observed in 4.5-28% SCC (according to risk factors), in 9-42% MCC, and in 14-57% PEM. We observed overall 30.8% positive SNs in 13 consecutive patients operated for high-risk nonmelanoma skin cancer between 2002 and 2011 in our institution. These high rates support recommendation to implement SLNB for nonmelanoma skin cancer especially for SCC patients. Completion lymph node dissection following positive SNs is also a matter of discussion especially in PEM. It must be remembered that a definitive survival benefit of SLNB in melanoma patients has not been proven yet. However, because of its low morbidity when compared to empiric elective lymph node dissection or radiation therapy of lymphatic basins, SLNB has allowed sparing a lot of morbidity and could therefore be used in nonmelanoma skin cancer patients, even though a significant impact on survival has not been demonstrated.

Effect of a governmentally-led physical activity program on motor skills in young children attending child care centers: a cluster randomized controlled trial.

OBJECTIVE: To assess the effect of a governmentally-led center based child care physical activity program (Youp'la Bouge) on child motor skills.Patients and methods: We conducted a single blinded cluster randomized controlled trial in 58 Swiss child care centers. Centers were randomly selected and 1:1 assigned to a control or intervention group. The intervention lasted from September 2009 to June 2010 and included training of the educators, adaptation of the child care built environment, parental involvement and daily physical activity. Motor skill was the primary outcome and body mass index (BMI), physical activity and quality of life secondary outcomes. The intervention implementation was also assessed. RESULTS: At baseline, 648 children present on the motor test day were included (age 3.3 +/- 0.6, BMI 16.3 +/- 1.3 kg/m2, 13.2% overweight, 49% girls) and 313 received the intervention. Relative to children in the control group (n = 201), children in the intervention group (n = 187) showed no significant increase in motor skills (delta of mean change (95% confidence interval: -0.2 (-0.8 to 0.3), p = 0.43) or in any of the secondary outcomes. Not all child care centers implemented all the intervention components. Within the intervention group, several predictors were positively associated with trial outcomes: 1) free-access to a movement space and parental information session for motor skills 2) highly motivated and trained educators for BMI 3) free-access to a movement space and purchase of mobile equipment for physical activity (all p < 0.05). CONCLUSION: This "real-life" physical activity program in child care centers confirms the complexity of implementing an intervention outside a study setting and identified potentially relevant predictors that could improve future programs.Trial registration: Trial registration number: clinical trials.gov NCT00967460 http://clinicaltrials.gov/ct2/show/NCT00967460.

PTLD Burkitt Lymphoma in a Patient with Remote Lymphomatoid Granulomatosis.

Posttransplant lymphoproliferative disorder (PTLD) is a potentially fatal complication of solid organ transplantation. The majority of PTLD is of B-cell origin, and 90% are associated with the Epstein-Barr virus (EBV). Lymphomatoid granulomatosis (LG) is a rare, EBV-associated systemic angiodestructive lymphoproliferative disorder, which has rarely been described in patients with renal transplantation. We report the case of a patient with renal transplantation for SLE, who presented, 9 months after renal transplantation, an EBV-associated LG limited to the intracranial structures that recovered completely after adjustment of her immunosuppressive treatment. Nine years later, she developed a second PTLD disorder with central nervous system initial manifestation. Workup revealed an EBV-positive PTLD Burkitt lymphoma, widely disseminated in most organs. In summary, the reported patient presented two lymphoproliferative disorders (LG and Burkitt's lymphoma), both with initial neurological manifestation, at 9 years interval. With careful reduction of the immunosuppression after the first manifestation and with the use of chemotherapy combined with radiotherapy after the second manifestation, our patient showed complete disappearance of neurologic symptoms and she is clinically well with good kidney function. No recurrence has been observed by radiological imaging until now.

The Cul3-KLHL21 E3 ubiquitin ligase targets aurora B to midzone microtubules in anaphase and is required for cytokinesis.

Cul3 (Cullin3)-based E3 ubiquitin ligases recently emerged as critical regulators of mitosis. In this study, we identify two mammalian BTB (Bric-a-brac-Tramtrack-Broad complex)-Kelch proteins, KLHL21 and KLHL22, that interact with Cul3 and are required for efficient chromosome alignment. Interestingly, KLHL21 but not KLHL22 is necessary for cytokinesis and regulates translocation of the chromosomal passenger complex (CPC) from chromosomes to the spindle midzone in anaphase, similar to the previously described BTB-Kelch proteins KLHL9 and KLHL13. KLHL21 directly binds to aurora B and mediates ubiquitination of aurora B in vitro. In contrast to KLHL9 and KLHL13, KLHL21 localizes to midzone microtubules in anaphase and recruits aurora B and Cul3 to this region. Together, our results suggest that different Cul3 adaptors nonredundantly regulate aurora B during mitosis, possibly by ubiquitinating different pools of aurora B at distinct subcellular localizations.

Splenium of corpus callosum: patterns of interhemispheric interaction in children and adults.

The splenium of the corpus callosum connects the posterior cortices with fibers varying in size from thin late-myelinating axons in the anterior part, predominantly connecting parietal and temporal areas, to thick early-myelinating fibers in the posterior part, linking primary and secondary visual areas. In the adult human brain, the function of the splenium in a given area is defined by the specialization of the area and implemented via excitation and/or suppression of the contralateral homotopic and heterotopic areas at the same or different level of visual hierarchy. These mechanisms are facilitated by interhemispheric synchronization of oscillatory activity, also supported by the splenium. In postnatal ontogenesis, structural MRI reveals a protracted formation of the splenium during the first two decades of human life. In doing so, the slow myelination of the splenium correlates with the formation of interhemispheric excitatory influences in the extrastriate areas and the EEG synchronization, while the gradual increase of inhibitory effects in the striate cortex is linked to the local inhibitory circuitry. Reshaping interactions between interhemispherically distributed networks under various perceptual contexts allows sparsification of responses to superfluous information from the visual environment, leading to a reduction of metabolic and structural redundancy in a child's brain.

Inflammatory myofibroblastic tumor of the trachea with concomitant granulomatous lymph node lesions.

We report herein the case of a 57-year-old lady who had two concomittant lesions, an inflammatory myofibroblastic tumor in the trachea, and severe granulomatous lesions in the adjacent hilar lymph nodes. While these two lesions shared histological and some immunohistochemical features lesions. They differed in terms of ALK-1 expression, which was positive in the tracheal tumor and negative in the lymph nodes. The discussion of the case circles around putative pathophysiological links between the lesions. The authors favor the idea that the lymph nodes present a sarcoid-like granulomatous reaction to the inflammatory myofibroblastic tumor in the trachea over a coexistence of two independent entities. However, no conclusive evidence for this interpretation can be presented based on the existing literature.