Predictive performance of the modified Marsh and Schnider models for propofol in underweight patients undergoing general anaesthesia using target-controlled infusion.

BACKGROUND: : In our preliminary study, the modified Marsh (M-Marsh) model caused an inadvertent underdosing of propofol in underweight patients. However, the predictive performance of the M-Marsh and Schnider models incorporated in commercially available target-controlled infusion (TCI) pumps was not evaluated in underweight patients. METHODS: : Thirty underweight patients undergoing elective surgery were randomly allocated to receive propofol via TCI using the M-Marsh or Schnider models. The target effect-site concentrations (Ces) of propofol were, in order, 2.5, 3, 4, 5, 6 and 2 µg ml -1 . Arterial blood samples were obtained at least 7 min after achieving each pseudo-steady-state. RESULTS: A total of 172 plasma samples were used to determine the predictive performance of both models. The pooled median (95% confidence interval) biases and inaccuracies at a target Ce ≤ 3 µg ml -1 were -22.6 (-28.8 to -12.6) and 31.9 (24.8-36.8) for the M-Marsh model and 9.0 (1.7-16.4) and 28.5 (21.7-32.8) for the Schnider model, respectively. These values at Ce ≥ 4 µg ml -1 were -9.6 (-16.0 to -6.0) and 24.7 (21.1-27.9) for the M-Marsh model and 19.8 (12.9-25.7) and 36.2 (31.4-39.7) for the Schnider model, respectively. CONCLUSIONS: The pooled biases and inaccuracies of both models were clinically acceptable. However, the M-Marsh and Schnider models consistently produced negatively and positively biased predictions, respectively, in underweight patients. In particular, the M-Marsh model showed greater inaccuracy at target Ce ≤ 3 µg ml -1 and the Schnider model showed greater inaccuracy at target Ce ≥ 4 µg ml -1 . Therefore, it is necessary to develop a new pharmacokinetic model for propofol in underweight patients. CLINICAL TRIAL REGISTRATION: KCT0001502.

Optimal assessment of lymph node status in gallbladder cancer.

BACKGROUND: Lymph node (LN) metastasis is an important prognostic factor in gallbladder cancer (GBCA). LN status has been adopted as a critical element of staging systems. However, the influence of total lymph node count (TLNC) remains unclear. We determined the optimal minimum TLNC and compared the prognostic significance of LN status indices in GBCA. METHODS: We retrospectively reviewed medical records of 128 patients with T2 or greater GBCA who underwent LN dissection. We analyzed overall survival (OS) and relevance of the number of metastatic LNs, ratio of metastatic LNs to retrieved LNs (LNR), and TLNC in predicting OS. RESULTS: The median OS durations were 120, 35, and 18 months in T2, T3, and T4 GBCA. Five-year OS rates were 73%, 43%, and 0% in T2, T3, and T4 GBCA. LN status did not significantly impact OS in T2 or T4 GBCA. However, all LN indices were significantly correlated with OS in T3 GBCA. Furthermore, multivariate analysis revealed that a metastatic LN count of more than four and a TLNC of more than eight were independent prognostic factors of OS in T3 GBCA. CONCLUSIONS: TLNC and the number of positive LNs may be more important prognostic factors than LNR in T3 GBCA. Additionally, accurate staging may not be achieved in cases of T3 GBCA if the total number of retrieved LNs is less than eight. Thus, to ensure proper staging, we recommend that surgeons harvest more than eight LNs in patients with T3 GBCA.

Results of ABO-incompatible liver transplantation using a simplified protocol at a single institution.

BACKGROUND: Because of the development of various desensitization strategies, ABO-incompatible (ABOi) living donor liver transplantation (LDLT) has become a feasible option for patients with end-stage liver disease. However, there has been no united desensitization protocol for ABOi LDLT. We analyzed the outcomes after establishment of simplified protocol without splenectomy, intravenous immunoglobulin, and local infusion therapy. METHODS: We analyzed 19 ABOi LDLT cases that had been performed between January 2012 and December 2013, without splenectomy and local infusion. We used a single dose of rituximab (375 mg/m(2)) 10 days before transplantation and several series of plasma exchange according to the recipients' iso-agglutinin titer-to-target titer ratio of 1:32. RESULTS: Nineteen recipients received ABOi LTs from living donors. The mean initial immunoglobulin (Ig) M and IgG anti-ABO titers were 76.63 ± 78.81 (range, 8∼256) and 162.53 ± 464.1 (0∼2048). We performed preoperative plasma exchange to 16 recipients (mean number of sessions, 3.58; range, 1-10). After surgery, 9 patients received plasma exchange (mean, 1.84; range 1∼14). One death occurred as the result of pneumonia (5.3%). There were 4 cases of acute rejections (21.1%), and all of them were treated successfully with steroid pulse or thymoglobulin. Antibody-mediated rejection and graft failure did not occur. Six cases of postoperative complications (31.6%) occurred, including 3 cases of infections. There were 2 cases of biliary anastomotic stricture (10.5%) and 1 case of portal vein stenosis (5.3%). CONCLUSIONS: ABOi LDLT with the use of simplified protocol can be safely performed without increased risk of antibody-mediated rejection and other complications.

Characteristics of combined hepatocelluar-cholangiocarcinoma and comparison with intrahepatic cholangiocarcinoma.

BACKGROUND: The 7th American Joint Committee on Cancer (AJCC) currently classifies combined hepatocellular-cholangiocarcinoma (cHCC-CC) and intrahepatic cholangiocarcinoma (ICC) into one category. Study outcomes comparing the two carcinomas have shown contrary results. This study was designed to compare the survival and prognostic factors of both carcinomas. METHODS: We retrospectively reviewed the medical records of 107 patients with cHCC-CC or ICC who underwent liver resection between January 2000 and December 2009. RESULTS: Thirty patients (28%) were diagnosed with cHCC-CC, and 77 patients (72%) had ICC. Disease-free survival (DFS) was poorer in the cHCC-CC patients (six months), and the overall survival (OS) durations were similar (p = 0.477) between cHCC-CC (58 months) and ICC (45 months) patients. A tumor size larger than 5 cm, vascular invasion and lymph node (LN) metastasis were prognostic factors in all patients. However, tumor size and LN metastasis in cHCC-CC patients and carbohydrate antigen 19-9, differentiation and LN metastasis in ICC patients were found to be independent prognostic factors. CONCLUSIONS: Patients with cHCC-CC showed poorer DFS and similar OS rates compared to those with ICC. Our study revealed different prognostic factors in cHCC-CC. To understand more accurately cHCC-CC's prognosis, difference of genetic characteristics and tumor biology should be further evaluated.

Prognostic value of model for end-stage liver disease scores in patients with fulminant hepatic failure.

BACKGROUND: This study was undertaken to investigate risk factors of mortality in patients with fulminant hepatic failure (FHF). METHODS: Fifty-three patients with FHF treated from January 2006 to April 2011 were allocated to a spontaneous survival group (group 1), a death without liver transplantation (LT) group (group 2), and an LT group (group 3). To analyze risk factors associated with mortality in FHF, we excluded group 3 patients. Clinical features, Model for End-Stage Liver Disease (MELD) scores, and King's College Hospital criteria at the time of hepatic encephalopathy in group 2 were compared with those of group 1. RESULTS: The causes of FHF were acute viral infection (n = 29, hepatitis A:B, 28:1), drugs (n = 18; including 4 acetaminophen and 14 herbal medication), autoimmune (n = 4), and miscellaneous (n = 2). Of the 53 patients, 19 were allocated to group 1, 18 to group 2, and 16 to group 3. According to univariate analysis, risk factors for mortality in group 2 were acute renal failure requiring renal replacement therapy and a MELD score ≥30 at the time of hepatic encephalopathy. However, by multivariate analysis, a MELD score ≥30 was the only independent risk factor for mortality in group 2 (P = .042; hazard ratio, 4.500). CONCLUSIONS: A MELD score ≥30 was found to be the only independent risk factor of mortality in FHF patients without LT. Therefore, the findings of this study suggest that these patients may need emergent LT for survival.

Graft function measured by transient elastography in living donor liver transplantation: preliminary.

INTRODUCTION: Liver stiffness measurements (LSMs) using transient elastography (TE) provide a noninvasive means to assess liver fibrosis that correlate with hepatic cholestasis. However, few studies have examined the correlation of TE to obtain LSMs with perioperative clinical and laboratory parameters in living donor liver transplantation (LDLT). PATIENTS AND METHODS: We retrospectively reviewed forty-eight subjects who underwent LDLT between November 2010 and October 2012. All donors and recipients underwent TE, abdominal computed tomography (CT), and biochemical tests within 1 month before and at 1 week after transplantation. Using a cut-off LSM of 7.5 kPa, which we arbitrarily assigned to be indicative of significant fibrosis, we divided our study population into ≤7.5 kPa (group L; n = 15, 31.3%) versus >7.5 kPa; (group H; n = 33, 68.8%). RESULTS: Pretransplantation serum total bilirubin, international normalized ratio, and Model for End-stage Liver Disease scores of recipients were significantly higher in group H than group L. Regarding the pretransplantation donor characteristics, the graft-recipient weight ratio was significantly smaller among those in group H (P = .039). In addition, the post-transplantation 1-week serum total bilirubin level was significantly higher in group H (2.3 mg/dL versus 1.2 mg/dL, P = .015), although neither biliary complications norhepatic congestion was identified by abdominal CT. Among the 1-week post-transplantation laboratory findings, only total bilirubin positively correlated with LSM (P = .044). CONCLUSIONS: This pilot study suggested that a high LSM after LDLT suggests intrahepatic cholestasis and portal hypercirculation in the graft, irrespective of liver fibrosis, outflow obstruction, or biliary obstruction.

Difference of regeneration potential between healthy and diseased liver.

BACKGROUND: We sought to evaluate total and segmental liver regeneration by comparing preoperative computed tomographic (CT) volumetry and CT volumetry on postoperative day (POD) 7 after a right hepatectomy, in patients with various status and surgical indications. METHOD: We included 36 patients who underwent right lobectomy for living donor liver transplantation (healthy group), and 29 for hepatocellular carcinoma treatment (disease group). All of the disease group patients were Child-Turcotte-Pugh (CTP) class A. The regeneration of lateral, medial segment and total remnant liver volumes were assessed on POD 7 using a CT-based program. Total volumes and segmental volumes were measured for total liver, future liver remnant (FLR), and liver remnant. We calculated total and segmental early regeneration indexes, defined as [(VLR-VFLR)/VFLR]×100, where VLR is volume of the liver remnant and VFLR is volume of the FLR. RESULT: The VLR at POD 7 showed a 72.9% increase in volume among the healthy versus 55% in the disease group, (P=.012) In the disease group, segmental volume and regeneration indexes were also significantly lower than among the healthy group: 59.0% versus 46.9% in the medial and 86.8% versus 57.7% in the lateral segment (P=.023 and P<.001) respectively. CONCLUSION: The volume regeneration potential in diseased livers is significantly lower than that of a normal, healthy liver. So, we must consider a patient's liver status and volume profile before an extensive liver.

Does lymphocyte cross-matching predict acute rejection and graft survival in liver transplantation?

INTRODUCTION: The role of lymphocyte cross-matches (LCM) remains controversial in the liver transplant field. The aim of this study was to correlate the risk for acute rejection episodes and graft survival in liver transplantation with pretransplant LCM results. PATIENTS AND METHODS: We enrolled 184 adult liver transplantation patients, excluding pediatric and second grafts. The 129 living donor and 55 deceased donor liver transplantations were divided into 2 groups: LCM (+); (n=20) and LCM (-); (n=164). RESULTS: There were no differences in the demographic features, such as gender and recipient age, original disease, Model for End-Stage Liver Disease score, donor type, number of human leukocyte antigen mismatches, and cold ischemia times. There were no hyperacute rejection episodes in the LCM (+) group. Also, posttransplant complications such as acute rejection episode, biliary complication, or hepatic artery thrombosis were not different. Acute rejection episodes occurred in 5.0% of the LCM (+) group and 15.2% of the LCM (-) group (P=.317). Bile duct complications after transplantation arose in 20.0% of the LCM (+) group and in 32.9% of the LCM (-) group (P=.312). The 2 groups showed no difference in graft survival rate analyzed by the Kaplan-Meier method according to LCM results. CONCLUSION: Pretransplant LCM results were not associated with overall graft survival or acute rejection episodes in this study.

Comparison of the affinity column-mediated immunoassay and microparticle enzyme immunoassay methods as a tacrolimus concentration assay in the early period after liver transplantation.

OBJECTIVE: We compared the results of 2 immunoassay systems (affinity column-mediated immunoassay [ACMIA] and microparticle enzyme immunoassay [MEIA]), regarding hematologic and biochemical values at 2 weeks after liver transplantation. METHODS: We obtained 256 blood samples from 35 patients, at 2 weeks after liver transplantation, excluding those from patients who were treated with interacting medications or renal replacement therapy. We also excluded the early mortality cases within 2 weeks of liver transplantation. A Dimension RxL HM with the tacrolimus Flex reagent cartilage was used for the ACMIA and the IMx tacrolimus II for the MEIA method. RESULTS: The tacrolimus concentrations measured by the ACMIA method correlated closely with those measured by the MEIA method (r = 0.953). However, the weighted concordance correlation coefficient for the repeated-measurement design was 0.74 (95% confidence interval, 0.66-0.85). The discrepancies in the tacrolimus level between the 2 methods was large among samples with low tacrolimus concentrations especially <5 ng/mL. When the difference ratio of the 2 methods ([ACMIA - MEIA]/ACMIA) was analyzed with a linear mixed-effects model to identify significant laboratory findings, there were no significant differences based on hematocrit, renal function, or hepatic function. However, the serum potassium level correlated with the difference ratio of the 2 methods (estimated slope, 10.173; P = .02). CONCLUSIONS: Both the ACMIA and the MEIA methods are precise; however, the ACMIA method has the advantage of fewer pretreatment procedures. In the early liver transplant period, however, there was a difference between the serum tacrolimus concentrations measured by the 2 methods, especially at a low drug concentrations.

Use of the hilar plate looping technique for bile duct dissection in living donor liver transplantation significantly reduces recipient biliary complications.

Biliary complications remain a major cause of morbidity after liver transplantation, especially in living donor liver transplantation (LDLT). Maintaining adequate blood supply to the bile duct is important for the prevention of biliary complications. The objective of this study was to analyze the effects of different techniques for bile duct anastomosis on posttransplantation biliary complications. From August 2005 to August 2008, 121 liver transplantations were performed at our center. Among the total 121 liver transplant recipients, 68 patients underwent a LDLT using a right lobe graft and were enrolled in this study. We used classic dissection for the first 38 recipients and the hilar plate looping technique for the next 30 patients. The hilar plate looping technique involves the looping of the complete hilar plate and Glissonian sheath around the hepatic duct after full dissection of the right hepatic artery and portal vein. Biliary complications were defined as bilomas or strictures that developed within 6 months after transplantation and required surgical or radiological intervention. There were no significant demographic differences between the 2 groups. The incidence of complications was 15 (39.5%) for classic dissection and 3 (18.8%) for hilar plate looping. Furthermore, there were no biliary strictures in the hilar plate looping group, and there was a significant difference in the complication rate between the 2 groups (P = .011). In conclusion, the hilar plate looping technique during LDLT significantly reduces recipient biliary complications.

Impact of graft type on remnant liver regeneration: right hepatectomy versus extended right hepatectomy.

Right hepatectomy with the middle hepatic vein (MHV) affects venous return and function of the remaining liver. We compared the remnant liver volume in the donors of resection with or without the MHV on the remnant liver volume regeneration. Living donors who had undergone right hepatectomy without MHV (RH group; n = 36) and those with MHV (ERH group; n = 19) were reviewed. Volume regeneration of segments I-III, segment IV, and total remnant liver volume was assessed at postoperative day (POD) 7 and 30 using a computed tomography-based volumetry program. According to the measured volume data, we calculated the liver remnant volume and the rate of liver remnant volume increase. The regeneration rate of segment IV was significantly low in the ERH group compared with that in the RH group at POD 7 and POD 30 (160% vs 141%; P = .018 and 189% vs 154%; P = .007). In contrast, the regeneration rate of the total remnant liver volume was not significantly different between the 2 groups (173% vs 175%; P = .758 and 199% vs 198%; P = .880). In conclusion, extended right hepatectomy can be safely performed with careful preoperative evaluation without significant impairment of remnant liver regeneration.

Laparoscopic cholecystectomy only could be an appropriate treatment for selected clinical R0 gallbladder carcinoma.

BACKGROUND: Laparoscopic cholecystectomy (LC) for gallbladder carcinoma still is controversial except for the early stages of gallbladder carcinoma (Tis). This study was designed to evaluate and revisit the role of LC in treating gallbladder carcinoma. METHODS: Available medical records of patients with surgeries for gallbladder carcinoma were retrospectively investigated from August 1992 to February 2005. RESULTS: Among 219 patients treated for gallbladder carcinoma, 57 (26%) underwent LC. A total of 16 patients (28.1%) underwent subsequent radical cholecystectomy (LC-RC), and 41 (71.9%) were only followed up without radical surgery (LC). Tis was found in 11 patients (19.3%), T1a in 3 patients (5.3%), T1b in 8 patients (14%), T2 in 19 patients (33.3%), and T3 in 16 patients (28.1%). The findings showed R0 in 14 cases of the radical cholecystectomy group, and clinical R0 was noted in 30 cases of the LC-only group. No survival differences were noted between LC and LC-RC (p = 0.2575), especially in the case of T2 lesions (p = 0.6274), nor between the R0 and clinical R0 (p = 0.5839). However, significant survival differences were noted between the R2 and R0 groups, and between R2 and clinical R0, respectively (p < 0.001). CONCLUSIONS: The findings show that LC could be appropriate treatment for gallbladder carcinoma only in selected cases of clinical R0 lesions.

The differential flow of epidural local anaesthetic via needle or catheter: a prospective randomized double-blind study.

The extent of epidural anaesthesia and pattern of spread of contrast medium, using different injection techniques, has not been well documented. Therefore, in this prospective, randomized double-blind study, the extent of anaesthesia and pattern of spread of contrast medium following an epidural bolus injection, via either a Tuohy needle or an epidural catheter, were compared. The study had two parts. In the first, 59 of 79 patients scheduled for a lower extremity operation under epidural anaesthesia were randomly allocated to one of the two groups. Anaesthesia was achieved with an epidural injection of 10 to 15 ml (including a 3 ml test dose) of 0.75% ropivacaine and fentanyl 25 microg via either a Tuohy needle (Group N, n=31) or a catheter (Group C, n=28). The level of sensory anaesthesia was recorded. In the second part, the remaining 20 patients were randomized to initially receive 5 ml of contrast medium via either a Tuohy needle (Group NE, n= 10) or a catheter (Group CE, n = 10). The extent of spread was recorded radiologically. Unilateral or missed blocks and additional dose requirement were absent in Groups N and C. No differences were found in the extent of sensory anaesthesia or the spread of contrast medium. Twenty per cent of catheter tips lay outside the lateral margins of the vertebral bodies. We found that an epidural bolus injection, via either a Tuohy needle or a catheter, made no difference in regard to spread of local anaesthetic or contrast medium in the epidural space.

[Refractory idiopathic cold agglutinin disease successfully treated with intermittent high-dose cyclophosphamide].

A 56-year-old woman, who had been suffering from idiopathic cold agglutinin disease and treated unsuccessfully with prednisolone and cyclosporine A for 6 months, was referred to our hospital in November 1998. She was given methylprednisolone pulse therapy followed by low-dose cyclophosphamide, but her anemia did not improve. We then began administration of intermittent high-dose cyclophosphamide (1,200 mg/day, every 4 weeks), and this resulted in a dramatic increase of her hemoglobin level and improvement of her symptoms. She is currently receiving 500 mg of cyclophosphamide every 2 months and showing a good response. Intermittent high-dose cyclophosphamide therapy can be an effective treatment for refractory cold agglutinin disease.

Cloning and sequencing of the gene, fmtC, which affects oxacillin resistance in methicillin-resistant Staphylococcus aureus.

Two Tn551 insertional mutants with reduced methicillin resistance were isolated from methicillin-resistant Staphylococcus aureus KSA8. These two mutants showed increased susceptibility to beta-lactam antibiotics and bacitracin, but not to fosfomycin and vancomycin. Tn551 in these mutants was inserted into the same gene, termed fmtC. The fmtC gene has an open reading frame of 840 amino acid residues with an estimated molecular mass of 96.9 kDa. The N-terminal half of the deduced FmtC protein is very hydrophobic, implying that this protein is a membrane-associated protein.

Primary lymphoma of spermatic cord.

Primary lymphomas of spermatic cord are extremely rare. In a review of the world medical literature, until now, only fourteen cases of spermatic cord lymphoma have been reported, and, furthermore, they have a poor prognosis even in patients with stage I disease. Herein, we report a new case of primary non-Hodgkin's lymphoma of the spermatic cord. In August, 1993, 76-year-old man visited an urological hospital with a compaint of a right intrascoral mass, and underwent orchiectomy. Macroscopically no invasive lesion in the testis was observed, and the tumorous lesion was restricted to the epididymis. The histopathological study indicated that he suffered from primary malignant lymphoma of the spermatic cord (B-cell, diffuse medium-sized cell type). As radiographic investigations showed no other invasive lesion, the patient was diagnosed to be in stage IE. He was followed only with clinical observation, and, in August, 1996, relapsed with extensive disease in the abdoninal cavity, and was transferred to our hospital. Fourty months after the orchiectomy, he died of progression of disease irrespective of the salvage radio-chemotherapies given to him.

Crystallization and preliminary X-ray analysis of UDP-N-acetylenolpyruvylglucosamine reductase (MurB) from Staphylococcus aureus.

UDP-N-acetylenolpyruvylglucosamine reductase (MurB) is an essential enzyme in the bacterial cell-wall biosynthetic pathway, making it a potential therapeutic target for novel antibiotics. Diffraction-quality crystals of both the native and Se-methionine-expressed MurB from Staphylococcus aureus have been prepared by sitting-drop vapour diffusion from solutions containing polyethylene glycol (PEG) 8000, ammonium sulfate, sodium cacodylate pH 6.5 and dimethyl sulfoxide (DMSO). Crystals belong to the cubic space group I2(1)3, with unit-cell parameters a = b = c = 178.99 A. X-ray data from these crystals were collected at the Advanced Photon Source 17-ID beamline and were used to solve the MurB structure to 2.3 A resolution.

A structural variation for MurB: X-ray crystal structure of Staphylococcus aureus UDP-N-acetylenolpyruvylglucosamine reductase (MurB).

The X-ray crystal structure of the substrate free form of Staphylococcus aureus UDP-N-acetylenolpyruvylglucosamine reductase (MurB) has been solved to 2.3 A resolution with an R-factor of 20.3% and a free R-factor of 22.3%. While the overall fold of the S. aureus enzyme is similar to that of the homologous Escherichia coli MurB X-ray crystal structure, notable distinctions between the S. aureus and E. coli MurB protein structures occur in residues involved in substrate binding. Analysis of available MurB sequences from other bacteria suggest that the S. aureus MurB structure is representative of a distinct structural class of UDP-N-acetylenolpyruvylglucosamine reductases including Bacillus subtilis and Helicobacter pylori that are characterized by a modified mechanism for substrate binding.

Correlation of color Doppler sonographic findings with pH measurements in gastroesophageal reflux in children.

PURPOSE: We conducted a prospective study of color Doppler sonography in children with suspected gastroesophageal reflux (GER). The purpose of this study was to compare the accuracy of color Doppler sonography with that of continuous 24-hour pH monitoring of the esophagus in diagnosing GER and to determine how to interpret the reflux episodes detected on color Doppler sonography in children at high risk for reflux. METHODS: Color Doppler sonography and 24-hour esophageal pH monitoring were performed in 54 children ranging in age from 2 months to 10 years (mean, 3 years). The stomach of each patient was filled for adequate gastric distention just before the color Doppler sonographic examination. We counted the number of reflux episodes over a period of 15 minutes. One day after the sonographic examination, the reflux was evaluated with esophageal pH monitoring, and the resultant reflux index (ReI) was obtained. The ReI was considered to be pathologic when it was equal to or greater than 11.99%. The number of refluxes on color Doppler sonography and the ReI were correlated for each patient. RESULTS: The 2 tests showed an 81.5% agreement in the detection of GER. When pH monitoring was taken as the reference test, color Doppler sonography had a high sensitivity (95.5%) for diagnosing GER but a very low specificity (11.0%), with a positive predictive value of 84.3% and a negative predictive value of 33.3%. There was no statistically significant correlation between the frequencies of GER detected on color Doppler sonography and the ReIs on pH monitoring (p = 0.1103). There was no correlation between the reflux grades on sonography and the ReI grades on pH monitoring (p = 0.422). CONCLUSIONS: Color Doppler sonography is highly sensitive and easier to use than pH monitoring. Although there are no definite criteria for evaluating the severity of GER on color Doppler imaging, this modality may be useful in screening children for GER.

Use of a whole genome approach to identify vaccine molecules affording protection against Streptococcus pneumoniae infection.

Microbial targets for protective humoral immunity are typically surface-localized proteins and contain common sequence motifs related to their secretion or surface binding. Exploiting the whole genome sequence of the human bacterial pathogen Streptococcus pneumoniae, we identified 130 open reading frames encoding proteins with secretion motifs or similarity to predicted virulence factors. Mice were immunized with 108 of these proteins, and 6 conferred protection against disseminated S. pneumoniae infection. Flow cytometry confirmed the surface localization of several of these targets. Each of the six protective antigens showed broad strain distribution and immunogenicity during human infection. Our results validate the use of a genomic approach for the identification of novel microbial targets that elicit a protective immune response. These new antigens may play a role in the development of improved vaccines against S. pneumoniae.