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The formal evaluation of scientific literature by invited referees (peer reviewers) is a relatively recent phenomenon and now is considered a cornerstone of modern science. However, its roots can be traced back to antiquity. As the speed and complexity of scientific information and publishing increases in the digital age, peer review must continue to evolve. To understand the future direction of peer review, we must understand its past. Here, we briefly explore the history of scientific peer review. This may help us predict and design appropriate peer review for the new era. This work was originally presented at the Pediatric Academic Societies Annual Meeting in Baltimore, Maryland in the Spring of 2016.

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It is now accepted that local changes to the balance of Th1/Th2-type cytokines occur during pregnancy within the maternal uterus and fetoplacental unit. These changes in cytokine profiles contribute to implantation of the embryo, development of the placenta, and survival of the fetus to term. Overall within the placenta there is a bias in the ratio of Th1:Th2 cytokines towards the Th2-type cytokines. However, there are specific fluctuations in this balance at implantation and during the initiation of parturition. The predominant cytokines at each stage of gestation function both to limit maternal immune rejection of the semi-allogeneic embryo/fetus, especially at the maternofetal interface; and to facilitate the on-going physiological processes within the maternal reproductive tract. These two, at times conflicting, roles are discussed in this review, with key evidence concerning cytokine expression and function from mouse and humans.

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OBJECTIVE: To describe the changes occurring over a 3-year period after implementation of an evidence-based clinical practice guideline for the care of infants with bronchiolitis. DESIGN: Before and after study. SETTING: Children's Hospital Medical Center, Cincinnati, Ohio. PATIENTS: Infants 1 year or younger admitted to the hospital with a first-time episode of typical bronchiolitis. INTERVENTION: The guideline was implemented January 15, 1997. Data on all patients discharged from the hospital with bronchiolitis, from January 15 through March 27, in 1997, 1998, and 1999, were stratified by year and compared with data on similar patients discharged from the hospital in the same periods in the years 1993 through 1996. MAIN OUTCOME MEASURES: Patient volumes, length of stay for admissions, and use of specific laboratory and therapeutic resources ancillary to bed occupancy. RESULTS: After implementation of the guideline, admissions decreased 30% and mean length of stay decreased 17% (P<.001). Nasopharyngeal washings for respiratory syncytial virus were obtained in 52% fewer patients (P<.001); 14% fewer chest x-ray films were ordered (P<.001). There were significant reductions in the use of all respiratory therapies, with a 17% decrease in the use of at least 1 beta(2)-agonist inhalation therapy (P<.001). In addition, 28% fewer repeated inhalations were administered (P<.001); mean costs for all resources ancillary to bed occupancy fell 41% (P<.001); and mean costs for respiratory care services fell 72% (P<.001). CONCLUSIONS: An evidence-based clinical practice guideline for the care of patients encountered in major pediatric care facility has been successfully sustained beyond the initial year of its introduction to practitioners in southwest Ohio.

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OBJECTIVE: To describe the effect of implementing an evidence-based clinical practice guideline for the inpatient care of infants with bronchiolitis at the Children's Hospital Medical Center in Cincinnati, Ohio. METHODOLOGY: A multidisciplinary team generated the guideline for infants < or = 1 year old who were admitted to the hospital with a first-time episode of typical bronchiolitis. The guideline was implemented January 15, 1997, and data on all patients admitted with bronchiolitis from that date through March 27, 1997, were compared with data on similar patients admitted in the same periods in the years 1993 through 1996. Data were extracted from hospital charts and clinical and financial databases. They included LOS and use and costs of resources ancillary to bed occupancy. RESULTS: After implementation of the guideline, admissions decreased 29% and mean LOS decreased 17%. Nasopharyngeal washings for respiratory syncytial virus were obtained in 52% fewer patients. Twenty percent fewer chest radiographs were ordered. There were significant reductions in the use of all respiratory therapies, with a 30% decrease in the use of at least 1 beta-agonist inhalation therapy. In addition, 51% fewer repeated inhalations were administered. Mean costs for all resources ancillary to bed occupancy decreased 37%. Mean costs for respiratory care services decreased 77%. CONCLUSIONS: An evidence-based clinical practice guideline for managing bronchiolitis was highly successful in modifying care during its first year of implementation.guideline, bronchiolitis, evidence-based medicine, pediatrics, outcome research.

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One of the immediate reactions of the mammalian cell to many environmental stresses is a massive synthesis of poly(ADP-ribose), catalyzed by poly(ADP-ribose) polymerase (PARP). Most of the biological functions attributed to PARP are inferred from experimentation with mammalian cells. In plants, the biology of PARP may be more complicated and diverse than was previously thought. Two poly(ADP-ribose) polymerase homologues were found in plants, the classical Zn-finger-containing polymerase (ZAP) and the structurally non-classical PARP proteins (APP and NAP), which lack the characteristic N-terminal Zn-finger domain. By enzymatic and cytological experiments the recombinant APP protein was shown to be located in the nucleus and to possess DNA-dependent poly(ADP-ribose) polymerase activity in yeast. The nuclear localization was further confirmed by the analysis of transgenic tobacco plants that expressed a translational gene fusion between APP and the bacterial beta-glucuronidase. The app promoter was transcriptionally up-regulated in cells pre-determined to die because of deficiency in a DNA ligase I.

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To determine whether children with short bowel syndrome had evidence of metabolic bone disease, total body bone mineral content was measured by dual-energy x-ray absorptiometry in 18 patients and 36 age-, sex-, and race-matched control subjects. Children with short bowel syndrome had decreased bone mineral content compared with control subjects; however, it was not significant when adjusted for differences in weight and height. Whether these children will have normal bone accretion throughout puberty is not known.

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BACKGROUND: We evaluated the clinical utility of the 13C-xylose breath test for the diagnosis of small bowel bacterial overgrowth in children. METHODS: To determine the optimal dose of 13C-xylose, 29 healthy children, 3 to 12 years old, were randomly assigned to receive one of three doses of 13C-xylose (10, 25, or 50 mg). After an overnight fast, the oral dose of 13C-xylose was administered, and breath samples were collected every 30 minutes for 4 hours. Samples were analyzed for 13CO2 by gas chromatography with mass spectrometry. Using the 50 mg dose, we then performed nine breath tests with concurrent duodenal bacterial cultures in 6 children, 3 to 12 years old, with short-bowel syndrome (n = 2), immunodeficiency states (n = 1), and motility disorders (n = 3). RESULTS: Excretion of 13CO2 in breath peaked at 2.5 hours in all three control groups. The 50-mg dose produced the highest median peak and the smallest range of 13CO2 excretion in breath within each time period. The time of peak 13CO2 excretion in breath varied among the diseased children; however, the six patients with small-bowel bacterial overgrowth (2 x 10(5)-3.5 x 10(5) gram negative rods) all had peak 13CO2 that exceeded the maximum breath 13CO2 level in breath of the control subjects at the corresponding time period (100% sensitivity). Of the three patients with negative cultures, two had negative breath test results and one had positive results (67% specificity). One subject had normalization of both duodenal culture and breath test results after antibiotic treatment of small-bowel bacterial overgrowth. CONCLUSIONS: Our preliminary results suggest that with a dose of 50 mg 13C-xylose, breath test results reliably predict small-bowel bacterial overgrowth in susceptible children.

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Management of extreme short bowel syndrome (SBS) has changed dramatically over the last 20 years with notable improvements in survival and quality of life in patients with this syndrome. A review of our institution's medical records over a 12-year period (1980-1992) revealed 32 patients with < 100 cm (range, 14-94; median, 40) of functional small bowel after intestinal resection. The causes of intestinal loss included necrotizing enterocolitis (11 cases), atresias (8 cases), long-segment Hirschsprung's disease (5 cases), midgut volvulus (5 cases) and gastroschisis (3 cases). The mean follow-up period was 4.2 years, and four deaths were recorded (12.5%). Survival of eight of nine (88.9%) patients without an ileocecal valve (ICV) and with < 40 cm of small bowel was noted. The absence of an ICV, however, was associated with significantly prolonged total parenteral nutrition. Follow-up surgical procedures, including intestinal lengthening, tapering enteroplasty. Martin's procedure, longitudinal myectomy-myotomy, and ostomy take-down, were performed in 20 of the patients (64%). Prolonged survival and normal development can be expected for the patient with severe SBS who is given meticulous nutritional support and treated with carefully planned secondary surgical intervention. These results are also seen in patients with extreme SBS (< 40 cm residual small bowel length) and no ICV.

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The value of sonography in assessing chronic abdominal pain (CAP) in children, the characteristics of CAP, and the local pediatrician's practice in evaluating CAP are reported. Fifty-seven patients with CAP had abdominal and/or pelvic sonography; 56 were normal. One sonogram showed an ovarian cyst on the side opposite the CAP; the cyst later resolved. Pain was usually localized in the periumbilical area (56%). Follow-up data were obtained from referring physicians and patients' medical records. No serious diagnosis related to CAP was missed. After six months, CAP had resolved in 43% of patients. Of the responding physicians, 61% indicated they would have used more and costlier contrast studies if ultrasonography had been unavailable.

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An evaluation of a large pediatric residency program by its alumni was undertaken to determine whether the program is providing quality education and relevant training for pediatricians. A questionnaire was mailed to physicians who began their training at Children's Hospital Medical Center in July 1974 or later and finished prior to July 1990. Of the 372 questionnaires sent, 274 were returned (74% response rate). Current positions included primary care physicians (41%), academic pediatricians (33%), and other (26%). Fifty-seven percent pursued fellowship training. Overall, 94% of the responders believed that their pediatric training was adequate in preparing them for their current position. The variety of patients seen, the inpatient experience, resident camaraderie, and neonatology training were rated the highest quality, means 4.38 to 4.75 (1 = poor, 3 = average, 5 = excellent quality). Behavioral/developmental pediatrics, adolescent medicine, well-child care/continuity clinic, the outpatient experience, and pediatric surgery were rated the poorest quality, means 2.66 to 3.08, and judged to have too little quantity of training relative to the other aspects of training, means 1.93 to 2.42 (1 = too little, 3 = just enough, 5 = too much quantity). The quantity of neonatology training, the volume of patients, on-call experience, subspecialty inpatient services, such as bone marrow transplantation, and overall inpatient experience were considered too high relative to other components, means 3.51 to 4.08. There were no significant differences in responses by whether the alumni were in academic or primary care positions nor by year of training, and few differences by whether or not the training was considered adequate preparation for their current position.(ABSTRACT TRUNCATED AT 250 WORDS)

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Treatment of spontaneously differentiated PSMB embryonal carcinoma cells with murine interferon beta results in a transient decrease in the expression of the nuclear lamins A and C. Reduced levels of mRNAs were observed 4 h after the addition of interferon beta, with reductions in the polypeptides and assembled proteins within the nuclear lamina seen after 8 h of treatment. Expression of the 72-kDa (lamin A) and the 62-kDa (lamin C) polypeptides remained down regulated for 8 h, returning to control levels after 16 h of interferon treatment. The specificity of this response is indicated by the inhibitory action of a neutralizing antibody to interferon.

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Murine interferon beta increases expression of the 58-kDa intermediate filament protein vimentin by differentiated PSMB cells. Enhanced amounts of vimentin mRNA and protein have been detected using Northern hybridization and Western blotting techniques. Immunocytochemical analysis demonstrates the increased assembly of the protein into the intermediate filament network and its relocalization around the cell nucleus. Induction follows a defined time course, with peak protein levels 16 h post interferon addition, followed by a gradual decline over the next 36 h.

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We studied the incidence of hypophosphatemia in patients during the nutritional recovery syndrome. The charts of 150 patients receiving a complete nutritional assessment for 18 months were reviewed; 45 met established nutritional risk criteria. Only 9 of these 45 had serial phosphorus values measured during nutritional repletion, and 5 of these 9 patients had hypophosphatemia (phosphorus levels less than 0.97 mmol/L). Anthropometric measurements of arm circumference and arm muscle circumference were less than the fifth percentile in all patients developing hypophosphatemia. We concluded that hypophosphatemia is an underrecognized complication of nutritional repletion and that anthropometric measurements may be predictive of patients at risk. All patients with significant malnutrition should be evaluated for this complication of refeeding.

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The adequacy of low dose vitamin D (25 IU/dl) parenteral nutrition (PN) solution was studied in 18 infants. All infants had surgical indications for PN. The birth weights were 2810 +/- 135 g and gestational ages 37.4 +/- 0.5 wk (mean +/- SEM). Duration of study ranged from 5 to 175 days. Thirteen infants were studied for up to 6 weeks and five infants for 71 to 175 days. Results showed that studied infants maintained growth along normal percentiles for weight, length, and head circumference. Vitamin D status as indicated by serum 25 hydroxyvitamin D (25 OHD) rose from 15 +/- 1.9 ng/ml to 26 +/- 2.8 ng/ml, mean +/- SEM (p less than 0.001) after 9 days, and remained normal up to 6 months. Five infants with biochemical liver dysfunction also had normal serum 25 OHD concentrations, indicating the hepatic 25 hydroxylation process was not severely impaired. Serum total and ionized calcium, phosphorus, and vitamin D-binding protein concentrations were normal. Serum magnesium was mildly elevated in five infants (2.6 to 3 mg/dl) on one occasion and resolved spontaneously. Serum alkaline phosphatase (AP) concentrations rose above baseline values in 12 of 17 infants, but remained within normal range (less than 400 IU/liter at 30 degrees C). Another infant with markedly elevated AP values died from liver dysfunction. Radiographs of the forearms were normal except for marked demineralization in one infant in spite of normal 25 OHD concentrations. We conclude that 25 IU vitamin D/dl of nutrient infusate is adequate to maintain normal vitamin D status, as indicated by normal serum 25 OHD concentrations in infants receiving PN for as long as 6 months.

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