Management of Group B streptococcal sepsis risk in well, term newborns.

AIM: To investigate how clinically well, term newborns at risk of early-onset Group B streptococcal (EOGBS) disease are currently managed in the United Kingdom (UK). METHODS: Review of guidelines of UK neonatal units. RESULTS: One hundred and twenty-five guidelines covering 157 neonatal units were received (71% of UK units), three of which were excluded from the review. We found great variation in every aspect for the management of EOGBS disease risk including the following: definition of risk factors; management of at-risk newborns; choice of antibiotics. CONCLUSION: Our findings highlight the need for national consensus guidelines and clinical trials into the management of risk babies at risk of EOGBS disease.

EWS/ETS proteins promote expression and regulate function of the homeodomain transcription factor BRN3A.

Ewing's sarcoma family tumors (ESFTs or EFTs) express neuronal markers, which indicates they may originate from cells at least partly committed to neuronal lineage. However, recent publications suggest EFT originates in mesenchymal stem cells, and EWS/ETS fusion proteins characteristic of EFT activate neuronal marker expression to confer a neural phenotype on EFT. Here we show that the neuronal marker BRN3A/POU4F1 is expressed abundantly at the protein level in primary EFT but not in rhabdomyosarcoma and neuroblastoma, and EFT cells exhibit high activity of the BRN3A proximal autoregulatory region. EWS/FLI-1 siRNA reduces BRN3A expression and promoter activity and EWS/ETS proteins are bound to the BRN3A locus, suggesting a direct function for EWS/ETS proteins in control of BRN3A expression. Differentiation-associated and autoregulatory activities of BRN3A are respectively impaired and altered in EFT cells, and EWS/FLI-1 siRNA can restore some BRN3A function. A potentially novel function for BRN3A in EFT cells is identified. These results extend the hypothesis that EWS/ETS proteins induce expression of neuronal markers such as BRN3A in EFT by showing that the function of those same markers may be restricted or controlled in an EWS/ETS-dependent manner.

The effects of tamoxifen on immunity.

Tamoxifen is a widely known anti-estrogen which has been employed in adjuvant treatment of early-stage, estrogen-sensitive breast cancer for over 20 years. Less well known are the effects of tamoxifen on immune function, which we discuss here. We review the growing body of evidence which demonstrates immunomodulatory effects of tamoxifen, including in vitro and in vivo studies as well as observations made in breast cancer patients treated with tamoxifen. Taken together these studies suggest that tamoxifen is capable of inducing a shift from cellular (T-helper 1) to humoral (T-helper 2) immunity. Interestingly, the immunomodulatory effects of tamoxifen appear to be independent of the estrogen-receptor and may be mediated through the multidrug resistance gene product, Permeability-glycoprotein, for which a role in immunity has recently emerged. We furthermore discuss the clinical implications of the immunomodulatory effects of tamoxifen which are twofold. First, tamoxifen may be useful in the treatment of immune-mediated disorders, particularly of those arising from aberrant T-helper 1 cell activity, including allograft rejection, Crohn's disease, and Th1-mediated autoimmune conditions such as diabetes mellitus, scleroderma, and multiple sclerosis. Second, given that cellular T-helper 1 immunity is targeted against cancer cells, the tamoxifen-induced shift away from cellular immunity represents a significant step in fostering a cancerogenic environment. This may limit the anti-cancer effects of tamoxifen and thus explain why tamoxifen is inferior compared to other anti-estrogens in preventing disease recurrence in early-stage breast tumors.

"When Aneurysm Ain't Aneurysm": sinus of Valsalva aneurysm mimicked by healed abscess cavity under the aortic valve.

In a 70-year-old patient with severe aortic valve stenosis, preoperative standard imaging (transthoracic echocardiography and angiography) detected an unclear subannular cavity structure. Initially interpreted as an aneurysm of Valsalva, the structure was identified intraoperatively as a huge chronic abscess cavity and exclusion was carried out by pericardial patch plasty. This case draws attention to the importance of a differential diagnosis of an abscess due to infective endocarditis in cases of unclear subannular structures rashly diagnosed as aneurysm of Valsalva.

Hypoxic reoxygenation during initial reperfusion attenuates cardiac dysfunction and limits ischemia-reperfusion injury after cardioplegic arrest in a porcine model.

OBJECTIVE: In clinical practice, reperfusion of ischemic myocardium usually occurs under high arterial oxygen levels. However, this might aggravate cardiac ischemia-reperfusion injury caused by excessive oxidative stress. In an experimental in vivo study, the cardioprotective role of hypoxic reoxygenation during initial reperfusion was assessed. METHODS: Twenty-one adult pigs were started on cardiopulmonary bypass with aortic crossclamping (90 minutes) and cardioplegic arrest. During initial reperfusion, 10 pigs underwent standard hypoxic reoxygenation (Pa(O(2)), 250-350 mm Hg), whereas gradual reoxygenation (Pa(O(2)), 40-90 mm Hg) was performed in 11 pigs. Cardiac function was analyzed by means of the thermodilution method and conductance catheter technique. RESULTS: In both groups cardiac index was decreased 10 minutes after cardiopulmonary bypass compared with preoperative values. Sixty minutes after cardiopulmonary bypass, cardiac index improved significantly after gradual reoxygenation compared with that after hypoxic reoxygenation (3.2 +/- 0.6 vs 2.5 +/- 0.5 L min(-1) m(-2), P = .04). Correspondingly, end-systolic pressure-volume relationship and peak left ventricular pressure increase were significantly less decreased in the gradual reoxygenation group. During and after reperfusion, malondialdehyde and troponin T values within the coronary sinus were significantly lower after gradual reoxygenation (60 minutes after declamping: malondialdehyde, 7.6 +/- 0.8 vs 4.6 +/- 0.5 micromol/L [P = .007]; troponin, 0.12 +/- 0.02 vs 0.41 +/- 0.12 ng/mL [P = .02]). CONCLUSION: Hypoxic reoxygenation at the onset of reperfusion attenuates myocardial ischemia-reperfusion injury and helps to preserve cardiac performance after myocardial ischemia in a pig model.

Laparoscopic pyeloplasty in secondary ureteropelvic junction obstruction after failed open surgery.

BACKGROUND AND PURPOSE: Laparoscopic pyeloplasty has been accepted as a helpful option for the treatment of primary ureteropelvic junction (UPJ) obstruction. We report the results of laparoscopic pyeloplasty in cases with secondary UPJ obstruction after failed open pyeloplasty. PATIENTS AND METHODS: Between September 2003 and March 2006, 18 patients with secondary UPJ obstruction secondary to failed open surgery who had undergone laparoscopic pyeloplasty using different techniques were enrolled in this study. The mean age and male-to-female ratio were 29.8 years (range 5-65 years) and 14: 4, respectively. Pain, fever, duration of the operation, changes in renal function, and rate of complications were reviewed. RESULTS: The mean operation time and average hospital stay were 254 +/- 82 minutes and 7.2 days (range 3-12 days), respectively. The mean follow-up was 14.1 months (range 4-25.5 months). No intraoperative complication occurred. Flank pain, urinary-tract infection, and severe hydronephrosis decreased from 88.9% to 22.2%, 33.3% to 0, and 83.3% to 16.6%, respectively. After laparoscopic pyeloplasty, 100% of patients had improvement in renal function. The number of patients with >50% washout on the DTPA scan 10 and 20 minutes after furosemide injection were 0 and 2 before the operation and 5 and 12 after the operation (27.8% and 62.5% increment, respectively). CONCLUSION: Laparoscopic pyeloplasty can be used with acceptable success rate in secondary UPJ obstruction in patients with previous open pyeloplasty.

P-glycoprotein functions as a differentiation switch in antigen presenting cell maturation.

P-glycoprotein (P-gp) expressed on human antigen presenting cells (APC) regulates alloantigen-dependent T-cell activation, but the associated mechanisms are not well understood. Here we demonstrate that P-gp functions in IL-12-dependent monocyte differentiation into dendritic cell (DC) lineages during APC maturation, thereby regulating the capacity of myeloid-derived APCs to elicit alloimmune Th1 responses. Human CD14+ monocytes cultured in vitro in the presence of IL-4/GM-CSF differentiated into CD14(-) CD1A+ APCs of the immature DC phenotype. In contrast, P-gp blockade during differentiation inhibited CD1a induction, down-regulated CD80 expression, enhanced CD86 expression and induced CD68 expression. APCs differentiated in the presence of P-gp blockade stimulated alloimmune T-cell proliferation significantly less than controls and this effect was associated with 97% inhibition of Th1 IFN-gamma production, but preserved Th2 IL-5 secretion. MAb-mediated blockade of the P-gp transport substrate IL-12 in the course of APC differentiation also inhibited IFN-gamma production, while addition of rIL-12 to P-gp-blocked APC differentiation cultures significantly reversed this effect, demonstrating that P-gp functions in APC differentiation in part via IL-12 regulation. Our findings define a novel role for P-gp as a differentiation switch in APC maturation and resultant alloimmune Th1 responses, thereby identifying P-gp as a potential novel therapeutic target in allotransplantation.

Pedicular vascular control in laparoscopic living donor nephrectomy: The use of clips instead of stapler in 341 donors.

PURPOSE: To demonstrate a less expensive approach for laparoscopic donor nephrectomy. MATERIALS AND METHODS: Left donor nephrectomy was done transperitoneally in flank position. Renal vein and artery were exposed and prepared for nephrectomy. Nondisposable trocars and instruments were used. The adrenal vein was clipped and its arteries were bipolar coagulated. Both renal artery and vein were clip-ligated using three medium large nonautomatic metallic clips and divided, instead of using rather expensive vascular endostapler. Kidney was hand-extracted from suprapubic incision (no Endobag was used). RESULTS: Donor nephrectomy was performed in 341 donors. Mean warm ischemia time was 8.17 minutes. Mean operative time was 260.3 minutes. Conversion and reoperation was required in 2.1% and 3.8% of donors, respectively. Ureteral complications were observed in 2.1% of recipients. No vascular accident occurred from pedicular vessels. One-year graft survival in recipients was 92.6%. By this approach, at least $600 was saved in each nephrectomy. CONCLUSION: Laparoscopic donor nephrectomy can be performed with a less expensive setup without adverse effects on graft outcome. Vascular control using nonautomatic clips instead of more costly vascular endostapler and also hand extraction of the kidney is safe, practical, and economical.