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1.
Phys Rev Lett ; 126(9): 091101, 2021 Mar 05.
Article in English | MEDLINE | ID: mdl-33750144

ABSTRACT

We perform a comprehensive study of Milky Way (MW) satellite galaxies to constrain the fundamental properties of dark matter (DM). This analysis fully incorporates inhomogeneities in the spatial distribution and detectability of MW satellites and marginalizes over uncertainties in the mapping between galaxies and DM halos, the properties of the MW system, and the disruption of subhalos by the MW disk. Our results are consistent with the cold, collisionless DM paradigm and yield the strongest cosmological constraints to date on particle models of warm, interacting, and fuzzy dark matter. At 95% confidence, we report limits on (i) the mass of thermal relic warm DM, m_{WDM}>6.5 keV (free-streaming length, λ_{fs}≲10h^{-1} kpc), (ii) the velocity-independent DM-proton scattering cross section, σ_{0}<8.8×10^{-29} cm^{2} for a 100 MeV DM particle mass [DM-proton coupling, c_{p}≲(0.3 GeV)^{-2}], and (iii) the mass of fuzzy DM, m_{ϕ}>2.9×10^{-21} eV (de Broglie wavelength, λ_{dB}≲0.5 kpc). These constraints are complementary to other observational and laboratory constraints on DM properties.

2.
Clin Obes ; 7(2): 86-91, 2017 Apr.
Article in English | MEDLINE | ID: mdl-28211992

ABSTRACT

The obesity epidemic continues to affect millions of children and adolescents. Non-surgical options do not result in significant or sustained weight loss; thus bariatric surgery has become increasingly utilized. Limited data exist regarding safety for paediatric bariatric surgery, especially outside of National Institutes of Health (NIH)-funded centres. We hypothesized that the perioperative outcomes of paediatric patients undergoing laparoscopic sleeve gastrectomy (LSG) at our free-standing children's hospital would provide adequate safety profiles. We retrospectively reviewed demographics, comorbidities and 30-d outcomes for all patients who underwent LSG from 2010 to 2015 at a free-standing children's hospital. A total of 105 patients underwent 107 LSG procedures (two revisions). Mean age was 17.2 ± 2.4 years. Male to female ratio was 1:4. The majority were Black (57.1%), followed by White (21.0%) and Hispanic (18.1%). The mean body mass index was 51.0 ± 9.8 kg/m2 . Comorbidities included obstructive sleep apnea (59.0%), hypertension (15.2%), polycystic ovarian disease (16.7% of females only), depression (12.4%) and diabetes (11.4%). Median length of stay was 2.0 d (1-7 d). There were no deaths. Major complications occurred in four patients (3.8%); three required reoperation. Four patients (3.8%) experienced minor complications. Laparoscopic sleeve gastrectomy can be safely performed for children and adolescents at a free-standing children's hospital without NIH-support.


Subject(s)
Bariatric Surgery/methods , Gastrectomy/methods , Pediatric Obesity/surgery , Adolescent , Body Mass Index , Depression/complications , Diabetes Complications/complications , Female , Hospitals, Pediatric/statistics & numerical data , Hospitals, Private/statistics & numerical data , Humans , Laparoscopy , Length of Stay , Male , Pediatric Obesity/complications , Polycystic Ovary Syndrome/complications , Reoperation , Retrospective Studies , Sleep Apnea, Obstructive/complications , Treatment Outcome , Young Adult
3.
Surg. infect.,(Larchmt.) ; 18(1)Jan. 2017.
Article in English | BIGG - GRADE guidelines | ID: biblio-948602

ABSTRACT

BACKGROUND: Previous evidence-based guidelines on the management of intra-abdominal infection (IAI) were published by the Surgical Infection Society (SIS) in 1992, 2002, and 2010. At the time the most recent guideline was released, the plan was to update the guideline every five years to ensure the timeliness and appropriateness of the recommendations. METHODS: Based on the previous guidelines, the task force outlined a number of topics related to the treatment of patients with IAI and then developed key questions on these various topics. All questions were approached using general and specific literature searches, focusing on articles and other information published since 2008. These publications and additional materials published before 2008 were reviewed by the task force as a whole or by individual subgroups as to relevance to individual questions. Recommendations were developed by a process of iterative consensus, with all task force members voting to accept or reject each recommendation. Grading was based on the GRADE (Grades of Recommendation Assessment, Development, and Evaluation) system; the quality of the evidence was graded as high, moderate, or weak, and the strength of the recommendation was graded as strong or weak. Review of the document was performed by members of the SIS who were not on the task force. After responses were made to all critiques, the document was approved as an official guideline of the SIS by the Executive Council. RESULTS: This guideline summarizes the current recommendations developed by the task force on the treatment of patients who have IAI. Evidence-based recommendations have been made regarding risk assessment in individual patients; source control; the timing, selection, and duration of antimicrobial therapy; and suggested approaches to patients who fail initial therapy. Additional recommendations related to the treatment of pediatric patients with IAI have been included. SUMMARY: The current recommendations of the SIS regarding the treatment of patients with IAI are provided in this guideline.(AU)


Subject(s)
Humans , Surgical Wound Infection/therapy , Intraabdominal Infections/therapy , Laparotomy/methods , Anti-Bacterial Agents/therapeutic use , GRADE Approach
4.
Int J Obes (Lond) ; 40(3): 550-3, 2016 Mar.
Article in English | MEDLINE | ID: mdl-26538186

ABSTRACT

Homozygous or compound heterozygous melanocortin-4 receptor (MC4R) mutations are rare with fewer than 10 patients described in current literature. Here we report the short- and long-term outcomes for four children ages 4.5-14 who are homozygous for loss-of-function mutations in the MC4R and underwent laparoscopic sleeve gastrectomy. All four patients experienced significant weight loss and improvement in, or resolution of, their comorbidities in the short term. One patient, however, has had significant weight regain in the long term. We conclude that MC4R signaling is not required for short-term weight loss after laparoscopic sleeve gastrectomy in children. Behavior modification may be more important for long-term weight maintenance, but patients with homozygous MC4R deficiency should not be excluded from consideration for sleeve gastrectomy. However, as at least one copy of functional MC4R is necessary and sufficient to induce long-term postoperative weight loss benefits, patients with complete loss of MC4R functionality might be less likely to exhibit the same benefits resulting from bariatric surgery.


Subject(s)
Gastric Bypass , Laparoscopy , Obesity, Morbid/surgery , Receptor, Melanocortin, Type 4/metabolism , Weight Gain , Comorbidity , Female , Humans , Male , Obesity, Morbid/genetics , Signal Transduction/genetics , Treatment Outcome , Weight Gain/genetics , Weight Loss/genetics
5.
Lung Cancer ; 82(3): 469-76, 2013 Dec.
Article in English | MEDLINE | ID: mdl-24396885

ABSTRACT

OBJECTIVES: This retrospective study used the US Oncology iKnowMed(TM) database, billing claims, and chart reviews to report treatment patterns and outcomes in late-stage non-small cell lung cancer (NSCLC) in US community oncology practices. MATERIALS AND METHODS: Eligibility criteria included non-squamous NSCLC, stage IIIB/IV at diagnosis, ECOG performance status (PS) <3, and initiation of 2nd-line therapy (defined as index date) between 1/1/2007 and 6/30/2011 with ≥ 1 year follow-up. Key outcomes were overall survival (OS), progression-free survival(PFS), time-to-progression (TTP), and time-to-hospitalization (post-index date). Kaplan­Meier and Cox proportional hazard models were used to characterize the distribution and predictors of outcomes. RESULTS: 1168 patients were eligible for the study. The most frequent 2nd-line therapies were pemetrexed(54.4%), erlotinib-containing regimens (17.6%), and docetaxel (10.0%). Median OS and PFS were 7.5 (95%confidence interval [CI]: 6.6­8.4) and 4.1 (95% CI: 3.7­4.5) months, respectively; 57% of patients were hospitalized post-index date. EGFR testing rates were 2.3% before 2010, 15.2% in 2010, and 32.0% in 2011 (P < .001). Of EGFR-positive patients, 50.0% received erlotinib-containing regimens compared with 16.9% of EGFR-negative patients (P = 0.001). An increased risk of shorter time-to-hospitalization, after controlling for other covariates, was associated with PS = 1 (hazard ratio [HR] = 1.51; P < .001) or PS = 2(HR = 1.68; P = .001) compared with PS = 0, pre-existing comorbid fatigue (HR = 1.64; P = .003) compared with no comorbid fatigue, and progression (HR = 1.92; P < .001), when it occurred, compared with no progression. Compared with other 2nd-line treatment, erlotinib-containing regimens prolonged adjusted TTP (HR = 0.69; P = .015). CONCLUSIONS: This retrospective observational study provides new insights into treatment patterns,biomarker testing, and outcomes in advanced NSCLC within the context of a large community oncology network. Outcomes of these community practice patients, although poor, were similar to those reported in 2nd-line clinical trials for relevant regimens. EGFR testing in community practice rose rapidly after 2010.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Non-Small-Cell Lung/diagnosis , Carcinoma, Non-Small-Cell Lung/drug therapy , Lung Neoplasms/diagnosis , Lung Neoplasms/drug therapy , Aged , Carcinoma, Non-Small-Cell Lung/mortality , Community Networks , Docetaxel , Erlotinib Hydrochloride , Female , Follow-Up Studies , Glutamates/administration & dosage , Glutamates/adverse effects , Guanine/administration & dosage , Guanine/adverse effects , Guanine/analogs & derivatives , Humans , Lung Neoplasms/mortality , Male , Medical Oncology , Neoplasm Staging , Pemetrexed , Practice Patterns, Physicians' , Prognosis , Quinazolines/administration & dosage , Quinazolines/adverse effects , Retrospective Studies , Survival Analysis , Taxoids/administration & dosage , Taxoids/adverse effects , Treatment Outcome , United States
6.
Hernia ; 16(5): 597-9, 2012 Oct.
Article in English | MEDLINE | ID: mdl-21259029

ABSTRACT

Giant inguinoscrotal hernias are a rare entity seen largely in the adult population. Presentation in the child is more unusual, with only one case previously documented. As there is scant literature regarding these hernias in children, their management may be challenging. Here, we present the case of a newborn born with giant bilateral inguinal hernias complicated by in utero perforation and meconium peritonitis managed by laparoscopy and then laparotomy for repair. The case illustrates several points that may be useful for pediatric surgeons who may encounter this condition.


Subject(s)
Colonic Diseases/complications , Hernia, Inguinal/diagnosis , Hernia, Inguinal/surgery , Intestinal Perforation/complications , Colonic Diseases/surgery , Hernia, Inguinal/congenital , Humans , Infant, Newborn , Intestinal Perforation/surgery , Male , Peritonitis/etiology , Scrotum/diagnostic imaging , Scrotum/pathology , Ultrasonography, Prenatal
7.
Hernia ; 14(6): 639-42, 2010 Dec.
Article in English | MEDLINE | ID: mdl-20012455

ABSTRACT

Amyand's hernia is a rare presentation of an appendix within an inguinal hernia sac. It is commonly mistaken for an incarcerated or strangulated hernia. Prompt diagnosis requires awareness of this entity, as well as associated radiologic findings on computed tomography (CT) and ultrasound. Treatment includes antibiotics and surgical intervention involving appendectomy and hernia repair. We present a case of a premature infant who developed systemic symptoms after a circumcision and was eventually diagnosed with an Amyand's hernia with concurrent appendicitis.


Subject(s)
Appendicitis/diagnosis , Circumcision, Male , Hernia, Inguinal/diagnosis , Postoperative Complications , Appendicitis/surgery , Appendix , Hernia, Inguinal/surgery , Humans , Infant, Newborn , Infant, Premature , Male
8.
J Pediatr Surg ; 36(8): 1122-9, 2001 Aug.
Article in English | MEDLINE | ID: mdl-11479840

ABSTRACT

BACKGROUND/PURPOSE: The authors have shown previously that surgical specimens from infants with acute necrotizing enterocolitis (NEC) show upregulation of inducible nitric oxide (NO) synthase (iNOS) and interferon-gamma mRNA. However, the contribution of other inflammatory cytokines such as interleukin-8 (IL-8), IL-11, and IL-12 has not been defined. Likewise, the role of GTP-cyclohydrolase, the rate-limiting enzyme in tetrahydrobiopterin synthesis, and thus NO production by iNOS is unclear. In this study, the authors sought to further define the pattern of cytokine expression seen in infants with acute NEC. METHODS: The authors measured intestinal cytokine mRNA expression by semiquantitative reverse transcriptase polymerase chain reaction in 21 infants with histologically confirmed NEC, 18 with other inflammatory conditions, and in 9 patients without intestinal inflammation. Guanosine triphosphate-cyclohydrolase (GTP-CH) activity was measured by specific enzyme assay. Univariate exact logistic regression analysis was performed to identify predictors of outcome. RESULTS: IL-8 and IL-11 mRNA were upregulated in patients with acute NEC compared with those with other inflammatory conditions or those without disease; these levels returned to baseline at the time of stoma closure. Increased IL-11 mRNA decreased the likelihood of pan-necrosis (odds ratio, 0.93; P =.002). Increased IL-12 levels (but not IL-8) seemed to protect against pan-necrosis (odds ratio, 0.70; P =.06). CONCLUSIONS: Local upregulation of IL-11 may represent an adaptive response designed to limit the extent of intestinal damage in NEC. Decreased IL-12 levels may contribute to the pathogenesis of NEC by allowing bacteria to escape host defenses.


Subject(s)
Cytokines/genetics , Enterocolitis, Necrotizing/genetics , Enterocolitis, Necrotizing/metabolism , Guanosine Triphosphate/analysis , Interleukin-11/genetics , RNA, Messenger/analysis , Acute Disease , Analysis of Variance , Culture Techniques , Cytokines/analysis , Enterocolitis, Necrotizing/pathology , Female , Gene Expression Regulation , Genetic Markers/genetics , Humans , Immunohistochemistry , Infant , Infant, Newborn , Interleukin-12/analysis , Interleukin-8/analysis , Logistic Models , Male , Prognosis , Reference Values , Reverse Transcriptase Polymerase Chain Reaction , Sensitivity and Specificity , Severity of Illness Index
9.
Pediatrics ; 108(2): 326-8, 2001 Aug.
Article in English | MEDLINE | ID: mdl-11483795

ABSTRACT

BACKGROUND/PURPOSE: Injuries that occur around the driveway are not typically regarded as reportable to the police and thus are often underrecognized. The aim of this study was to characterize the pattern and consequences of motor vehicle collisions that occur in the driveway. METHODS: Over the past 13 years, 64 patients admitted to the Children's Hospital of Pittsburgh sustained motor vehicle-related injuries in a driveway. These injuries resulted from a vehicle driven by an adult driver striking a child (group 1) or a child shifting an idle vehicle out of gear (group 2). We compared demographic variables and outcome measures between the 2 groups. RESULTS: There was no difference in gender, injury pattern, Injury Severity Score, length of stay, or operations performed between the groups. Patients in group 1 were younger, smaller, had a lower Glasgow Coma Scale, and had poorer outcomes. The majority of collisions (~65%) in group 1 resulted from a truck or sport-utility vehicle going in reverse. CONCLUSIONS: Younger children are more severely injured in driveway-related crashes, which are most likely to be caused by a truck or sport-utility vehicle going in reverse. These vehicles should be equipped with additional safety features such as extended mirrors to visualize small children.


Subject(s)
Accidents, Traffic/statistics & numerical data , Wounds and Injuries/epidemiology , Wounds and Injuries/mortality , Accidents, Home/mortality , Accidents, Home/statistics & numerical data , Accidents, Traffic/mortality , Age Factors , Automobiles/standards , Body Constitution , Child , Child, Preschool , Female , Glasgow Coma Scale , Hospitals, Pediatric/statistics & numerical data , Humans , Infant , Male , Pennsylvania/epidemiology , Prevalence , Risk Factors , Trauma Severity Indices , Wounds and Injuries/diagnosis
10.
Am J Physiol Gastrointest Liver Physiol ; 281(1): G173-81, 2001 Jul.
Article in English | MEDLINE | ID: mdl-11408270

ABSTRACT

Sustained upregulation of inducible nitric oxide (NO) synthase in the liver after endotoxin [lipopolysaccharide (LPS)] challenge may result in hepatocellular injury. We hypothesized that administration of a NO scavenger, NOX, may attenuate LPS-induced hepatocellular injury. Sprague-Dawley rats received NOX or saline via subcutaneous osmotic pumps, followed 18 h later by LPS challenge. Hepatocellular injury was assessed using biochemical assays, light, and transmission electron microscopy (TEM). Interleukin (IL)-6 mRNA was measured by RT-PCR. Tumor necrosis factor (TNF)-alpha protein expression was determined by immunohistochemistry. NOX significantly reduced serum levels of ornithine carbamoyltransferase and aspartate aminotransferase. TNF-alpha and IL-6 expression were increased in the livers of saline-treated but not NOX-treated rats. Although there was no difference between groups by light microscopy, TEM revealed obliteration of the space of Disse in saline-treated but not in NOX-treated animals. Electron paramagnetic resonance showed the characteristic mononitrosyl complex in NOX-treated rats. We conclude that NOX reduces hepatocellular injury after endotoxemia. NOX may be useful in the management of hepatic dysfunction secondary to sepsis or other diseases associated with excessive NO production.


Subject(s)
Endotoxemia/metabolism , Free Radical Scavengers/pharmacology , Liver/metabolism , Nitric Oxide/metabolism , Nitric Oxide/pharmacology , Animals , Electron Spin Resonance Spectroscopy , Endotoxemia/drug therapy , Endotoxemia/pathology , Gene Expression/physiology , Hepatocytes/metabolism , Hepatocytes/pathology , Hepatocytes/ultrastructure , Interleukin-6/genetics , Kupffer Cells/metabolism , Kupffer Cells/pathology , Lipopolysaccharides/pharmacology , Liver/chemistry , Liver/pathology , Male , Microscopy, Electron , Neutrophils/immunology , Nitric Oxide Synthase/metabolism , Nitric Oxide Synthase Type II , RNA, Messenger/analysis , Rats , Rats, Sprague-Dawley , Sorbitol/analogs & derivatives , Tumor Necrosis Factor-alpha/analysis
11.
Surg Infect (Larchmt) ; 2(2): 113-9; discussion 119-20, 2001.
Article in English | MEDLINE | ID: mdl-12594866

ABSTRACT

BACKGROUND: Necrotizing enterocolitis (NEC) is the most frequent and lethal disease that affects the gastrointestinal tract of the premature infant. Controversy persists as to the most appropriate management once the diagnosis is confirmed. METHODS: Review of the pertinent medical literature. RESULTS: The incidence of NEC is increasing, but the survival rate is not. Initial management of NEC consists of bowel rest, orogastric decompression, intravenous hydration, and broad-spectrum antibiotics; surgical intervention is typically reserved for infants with advanced disease or evidence of intestinal perforation. There is no consensus in the literature regarding the optimal treatment strategy for patients who require surgical intervention. There exists a lack of randomized trials comparing definitive intestinal resection with or without primary anastomosis, intestinal diversion with limited resection, or peritoneal drainage without resection. CONCLUSION: An individualized approach must be taken to achieve optimum survival for patients with NEC. Isolated perforation, in our opinion, is best managed with resection and enterostomy, whereas pan-intestinal involvement is best managed with proximal diversion alone.


Subject(s)
Attitude of Health Personnel , Enterocolitis, Necrotizing/diagnosis , Enterocolitis, Necrotizing/therapy , Infant, Premature , Humans , Infant, Newborn
12.
Shock ; 14(3): 366-73, 2000 Sep.
Article in English | MEDLINE | ID: mdl-11028558

ABSTRACT

Nuclear factor-kappaB (N-kappaB) plays a key role in gut inflammation. NF-kappaB up-regulates proinflammatory genes encoding cytokines, adhesion molecules, and inducible nitric oxide synthase (iNOS). However, NF-kappaB has also been shown to up-regulate protective or anti-apoptotic factors. We utilized an adenoviral vector carrying a super-repressor form of the inhibitor of NF-kappaB, IkappaB, to examine the effects of NF-kappaB inhibition on cytokine-induced nitric oxide production and apoptosis in rat small intestinal epithelial cells (IEC-6). Chemical inhibitors of NF-kappaB, including pyrrolidine dithiocarbamate (PDTC), tosyl-lysine-chloromethylketone (TLCK), genistein, and N-acetyl-leu-leu-norleucinal (n-LLnL) were also utilized. Treatment of AdIkappaB-transfected cells with cytomix [1000 U/mL IFN-gamma, 1 nM IL-1beta, and 10 ng/mL tumor necrosis factor alpha (TNFalpha)] or TNFalpha-containing cytokine combinations resulted in inhibition of cytokine-induced nitrite production and a marked increase in apoptosis compared to control cells. Apoptosis occurred independently of nitric oxide (NO) production since exogenous sources of NO did not inhibit apoptosis. Inducible NOS and clAP were down-regulated in AdIkappaB-transfected cells treated with cytomix. TLCK and LLnL treatment also induced apoptosis in cytomix-treated cells, while PDTC and genistein did not. Thus, although NF-kappaB up-regulates various pro-inflammatory genes, it may also have protective or anti-apoptotic effects in enterocytes. NF-kappaB appears necessary for upregulating cIAP in IEC-6 cells upon cytokine exposure.


Subject(s)
Apoptosis/physiology , Cytokines/physiology , Enterocytes/cytology , I-kappa B Proteins/metabolism , NF-kappa B/metabolism , Nitric Oxide/metabolism , Animals , Apoptosis/drug effects , Cells, Cultured , Cysteine Endopeptidases/drug effects , Cysteine Endopeptidases/metabolism , Enterocytes/drug effects , Enzyme Inhibitors/pharmacology , Genistein/pharmacology , I-kappa B Proteins/genetics , Leupeptins/pharmacology , Multienzyme Complexes/drug effects , Multienzyme Complexes/metabolism , NF-kappa B/antagonists & inhibitors , Neoplasm Proteins/genetics , Neoplasm Proteins/metabolism , Nitric Oxide Donors/pharmacology , Nitric Oxide Synthase/drug effects , Nitric Oxide Synthase/metabolism , Nitric Oxide Synthase Type II , Nitrites/metabolism , Penicillamine/analogs & derivatives , Penicillamine/pharmacology , Proteasome Endopeptidase Complex , Protein Transport , Pyrrolidines/pharmacology , Rats , Recombinant Proteins/genetics , Recombinant Proteins/metabolism , Thiocarbamates/pharmacology , Tosyllysine Chloromethyl Ketone/pharmacology , Up-Regulation
13.
Semin Pediatr Surg ; 9(3): 156-64, 2000 Aug.
Article in English | MEDLINE | ID: mdl-10949426

ABSTRACT

The incidence of neonatal adrenal tumors is increasing due to the expanded use and accuracy of prenatal ultrasonography in routine obstetric care. Although adrenal and juxtarenal masses may represent benign lesions (adrenal hemorrhage, subdiapragmatic extralobar pulmonary sequestration), the majority of masses either are premalignant or malignant. Previous algorithms for the diagnosis and management of these lesions have been guided primarily by the high incidence of neuroblastomas within this group. Improved insight into the relatively benign behavior of many neonatal neuroblastomas has stimulated debate regarding the appropriate management schema for neonatal adrenal masses. Moreover, the increasing recognition of benign juxtarenal lesions further challenges the conventional dogma. This review discusses the major categories of adrenal masses to help generate a rational algorithm for diagnosis and therapy.


Subject(s)
Adrenal Gland Diseases/diagnosis , Adrenal Gland Neoplasms/diagnosis , Adrenal Cortex Neoplasms/diagnosis , Adrenal Cortex Neoplasms/therapy , Adrenal Gland Diseases/diagnostic imaging , Adrenal Gland Diseases/surgery , Adrenal Gland Neoplasms/diagnostic imaging , Adrenal Gland Neoplasms/surgery , Adrenal Hyperplasia, Congenital/diagnosis , Adrenal Hyperplasia, Congenital/therapy , Bronchopulmonary Sequestration/diagnostic imaging , Female , Hemorrhage/diagnosis , Humans , Infant, Newborn , Neuroblastoma/diagnosis , Neuroblastoma/surgery , Pheochromocytoma/diagnosis , Pheochromocytoma/surgery , Pregnancy , Prognosis , Ultrasonography, Prenatal
14.
J Pediatr Surg ; 35(7): 1079-83, 2000 Jul.
Article in English | MEDLINE | ID: mdl-10917300

ABSTRACT

BACKGROUND: Mucosal atrophy and bowel shortening are the hallmark of proximal intestinal diversion for extensive necrotizing enterocolitis (NEC) or Thiry-Vella fistulas (TVF), in which the ends of a defunctionalized loop of intestine are exteriorized as stomas. Recombinant human interleukin-11 (rhIL-11) is a pleiotropic cytokine that promotes epithelial regeneration and enhances adaptation after bowel resection. The authors hypothesized that rhIL-11 may prevent mucosal atrophy and bowel shortening in rats with TVF METHODS: After creation of ileal TVF, Sprague-Dawley rats were selected randomly to receive either rhIL-11 or equal volume of 0.1% bovine serum albumin (BSA) subcutaneously daily. On day 14, the TVF were excised and examined morphologically. Enterocyte apoptosis was measured using the TUNEL assay. Mucosal DNA and protein content were measured. RESULTS: Administration of rhIL-11 resulted in a significantly greater weight gain and less shortening of TVF than BSA treatment. TVF from the rhIL-11-treated group showed evidence of hyperplasia and hypertrophy and increased crypt to villus ratio. The BSA group had substantial mucosal atrophy. There was a qualitative decrease in the incidence of apoptosis in the rhIL-11 group. CONCLUSIONS: Recombinant human IL-11 prevents mucosal atrophy and shortening of defunctionalized intestinal loops. It may help reduce the incidence of short gut syndrome in infants with extensive NEC.


Subject(s)
Interleukin-11/therapeutic use , Intestinal Mucosa/pathology , Recombinant Proteins/therapeutic use , Short Bowel Syndrome/complications , Animals , Atrophy/prevention & control , Humans , Male , Rats , Rats, Sprague-Dawley
15.
J Surg Res ; 92(1): 71-7, 2000 Jul.
Article in English | MEDLINE | ID: mdl-10864485

ABSTRACT

BACKGROUND: Previous investigators have relied on administration of pro-inflammatory cytokines or invasive surgical procedures to reproduce the morphologic changes of necrotizing enterocolitis (NEC) in rats. However, these artificial insults do not mimic the human disease. We developed a reproducible model of NEC in rats that more closely resembles human NEC and determined the pattern of inflammatory cytokine expression in this model. MATERIALS AND METHODS: Newborn rats were randomized into four groups. Groups 1 and 2 were breast-fed, while Groups 3 and 4 were gavaged with formula thrice daily. In addition, Groups 2 and 4 were subjected to 3 min of hypoxia thrice daily, prior to each feeding. The rats were killed on day 4 and the distal 2 cm of terminal ileum was harvested for morphological studies and analysis of inflammatory cytokine mRNA expression. RESULTS: Nearly 70% of formula-fed neonatal rats displayed moderate or severe morphological abnormalities resembling human NEC. Breast-fed pups had normal histology. The terminal ileum from rats with abnormal histology demonstrated increased inducible nitric oxide synthase (iNOS) expression, decreased interleukin-12 (IL-12) mRNA expression, and enterocyte apoptosis. There was a trend toward upregulation of IFN-gamma mRNA, but no difference in expression of TNF-alpha mRNA. Hypoxia did not significantly alter intestinal morphology or mRNA expression. CONCLUSIONS: Formula-fed neonatal rats, with or without hypoxia, exhibit morphological changes in the intestinal epithelium similar to those seen in patients with acute NEC. The mechanism likely involves upregulation of iNOS mRNA, enterocyte apoptosis, and decreased IL-12 production in the intestinal epithelium. This model may offer a simple reproducible method for inducing experimental NEC.


Subject(s)
Enterocolitis, Necrotizing/enzymology , Enterocolitis, Necrotizing/pathology , Interleukin-12/metabolism , Nitric Oxide Synthase/metabolism , Animals , Animals, Suckling , Apoptosis/physiology , Disease Models, Animal , Enterocolitis, Necrotizing/immunology , Female , Gene Expression Regulation, Enzymologic/physiology , Hypoxia/enzymology , Hypoxia/immunology , Infant Food , Interferon-gamma/genetics , Interferon-gamma/immunology , Interferon-gamma/metabolism , Interleukin-12/genetics , Interleukin-12/immunology , Intestinal Mucosa/enzymology , Intestinal Mucosa/immunology , Intestinal Mucosa/pathology , Milk , Nitric Oxide Synthase/genetics , Nitric Oxide Synthase Type II , Pregnancy , RNA, Messenger/analysis , Rats , Rats, Sprague-Dawley , Tumor Necrosis Factor-alpha/genetics , Tumor Necrosis Factor-alpha/immunology , Tumor Necrosis Factor-alpha/metabolism , Weight Gain
16.
Pediatr Surg Int ; 16(3): 165-8, 2000.
Article in English | MEDLINE | ID: mdl-10786973

ABSTRACT

Nitric oxide (NO) appears to play a paradoxical role in intestinal physiology. Although NO has potent bactericidal effects, a growing body of evidence suggests that it mediates intestinal injury and breakdown of gut barrier function. Data from our lab and others show an increased incidence of bacterial translocation following endotoxin challenge, and upregulation of inducible NO synthase (iNOS) mRNA and protein in the intestine. These phenomena co-localize with enterocyte apoptosis at the tips of the intestinal villi and immunoreactivity to nitrotyrosine. Electron microscopy reveals swollen mitochondria, implicating these organelles as putative targets for NO or its reactive nitrogen intermediates. We review some of the literature and discuss our current work in trying to define this mechanism.


Subject(s)
Bacterial Translocation , Nitric Oxide/physiology , Animals , Humans , Intestinal Mucosa/metabolism , Intestines/ultrastructure , Nitric Oxide/metabolism , Nitric Oxide Synthase/biosynthesis , Nitric Oxide Synthase Type II , RNA, Messenger/genetics , Up-Regulation
17.
J Pediatr Surg ; 35(2): 303-7; discussion 308, 2000 Feb.
Article in English | MEDLINE | ID: mdl-10693685

ABSTRACT

BACKGROUND/PURPOSE: Extended left hepatectomy, also referred to as left hepatic trisegmentectomy, in which segments II, III, IV, V, and VIII are excised, is rarely performed in children. Experience with 7 such resections is reported to describe the anatomy, technique, indications, and outcomes of the operation. METHODS: The medical records of all pediatric patients treated at our institution over the last 15 years who underwent extended left hepatectomy were reviewed. Demographic information as well as operative, pathological, and follow-up data were analyzed. RESULTS: Seven patients underwent extended left hepatectomy over this period. There were 5 boys and 2 girls ranging in age between 4 months and 9 years with a median age of 3.1 years. Follow-up ranged from 8 months to 5 years with a median of 3.5 years. Diagnoses included hepatoblastoma (HB, n = 3), focal nodular hyperplasia (FNH, n = 1), leiomyosarcoma (LMS, n = 1), hepatocellularcarcinoma (HCC, n = 1), and metastatic neuroblastoma (NB, n = 1). All surgical margins were grossly negative. Median operative blood loss was 13 mL/kg (range, 5 to 32 mL/kg), and mean hospital stay was 9 days (range, 7 to 12 days). No major intra- or postoperative complications were encountered, and there was no perioperative mortality. The 3 HB patients, 1 FNH patient, 1 LMS patient, and 1 NB patient are without evidence of disease, whereas the 1 child with HCC died of recurrent and distant disease. The 6 surviving children have normal hepatic function. CONCLUSION: Although technically challenging and rarely performed, extended resection of the left hepatic lobe is feasible in children and can yield curative results with minimal morbidity.


Subject(s)
Hepatectomy/methods , Hepatoblastoma/surgery , Liver Neoplasms/surgery , Carcinoma, Hepatocellular/surgery , Child , Child, Preschool , Female , Ganglioneuroblastoma/surgery , Humans , Infant , Leiomyosarcoma/surgery , Male , Retrospective Studies
18.
Surg Infect (Larchmt) ; 1(4): 265-72, 2000.
Article in English | MEDLINE | ID: mdl-12594882

ABSTRACT

The mechanisms underlying the process of bacterial translocation are poorly defined. Possible routes for transmucosal passage of bacteria include transcellular and paracellular channels. Bacterial engulfment is a prerequisite for transcellular transport. To determine whether transcellular transport is required for transmucosal bacterial passage, we examined the effect of various inhibitors of endocytosis, such as colchicine, cytochalasin B, and sodium fluoride on transmucosal passage of bacteria across an ileal mucosal membrane mounted in the Ussing chamber. Colchicine and sodium fluoride increased the rate of decline of the potential difference across the membranes. However, neither colchicine, cytochalasin B, nor sodium fluoride affected the incidence of transmucosal bacterial passage. Sodium fluoride, which depletes intracellular ATP, significantly decreased the number of bacteria that passed per membrane. Our data suggest that transcellular transport may not be required for spontaneous transmucosal passage of bacteria, and furthermore bacterial passage may be, at least in part, an energy-dependent process.


Subject(s)
Bacterial Translocation/physiology , Endocytosis/physiology , Animals , Bacterial Translocation/drug effects , Colchicine/pharmacology , Cytochalasin B/pharmacology , Endocytosis/drug effects , Energy Metabolism/drug effects , Energy Metabolism/physiology , Escherichia coli/drug effects , Escherichia coli/physiology , Ileum/drug effects , Ileum/microbiology , Ileum/pathology , In Vitro Techniques , Intestinal Mucosa/drug effects , Intestinal Mucosa/microbiology , Intestinal Mucosa/pathology , Male , Rats , Rats, Sprague-Dawley , Sodium Fluoride/pharmacology
19.
Med Care ; 38(4): 383-91, 2000 Apr.
Article in English | MEDLINE | ID: mdl-10752970

ABSTRACT

BACKGROUND: The medical record serves as an important source of information regarding the care process, but few studies have examined whether thoroughness of documentation is associated with outcomes. OBJECTIVE: The objectives of this study were to analyze the initial visit note for 513 patients presenting with acute musculoskeletal pain, compare thoroughness of documentation by physician specialty, and determine whether thoroughness of documentation was associated with clinical improvement or patient satisfaction. METHODS: A structured medical record abstraction was performed to examine whether treating physicians documented key historical and physical exam findings. Satisfaction with care, symptom relief, and functional improvement were assessed after 3 months with validated survey instruments. RESULTS: In the initial visit note, 43+/-16% of selected historical findings and 28+/-17% of physical examination findings were documented. Orthopedic surgeons documented 2 to 4 more historical and physical examination items (P <0.01) and assigned more specific diagnoses (P <0.01) than rheumatologists and general internists. Multivariate models showed a very weak association between all aspects of documentation and patient satisfaction with the provider-patient interaction (all partial R2 <0.016) and no association between documentation and 3-month pain relief or functional status. Patients' perception of physician communication was more highly associated with patient satisfaction (P = 0.0001) than was documentation. CONCLUSIONS: No provider types consistently documented many important historical items and physical examination findings. While thoroughness of documentation was not associated with clinical outcomes, there was a very weak relationship between documentation and patient satisfaction with provider-patient interactions.


Subject(s)
Medical History Taking , Physical Examination , Quality Assurance, Health Care , Acute Disease , Documentation , Female , Humans , Knee Injuries/diagnosis , Male , Medical Records, Problem-Oriented , Medicine , Middle Aged , Osteoarthritis, Knee/diagnosis , Pain/etiology , Patient Satisfaction , Shoulder Pain/etiology , Specialization
20.
J Trauma ; 47(6): 1098-103, 1999 Dec.
Article in English | MEDLINE | ID: mdl-10608540

ABSTRACT

BACKGROUND AND METHODS: Controversy persists regarding the management of pancreatic transection. Over the past 10 years, 51 patients admitted to the Children's Hospital of Pittsburgh sustained blunt pancreatic injuries. We reviewed their medical records to clarify the optimal management strategy and to define distinguishing characteristics, if any, of patients with pancreatic transection. RESULTS: Patients who sustained pancreatic transection had a significantly higher Injury Severity Score, length of stay, serum amylase, and serum lipase, than those patients who sustained pancreatic contusion. Patients who underwent laparotomy within 48 hours of injury for pancreatic transection had a significantly shorter length of stay than those who underwent laparotomy more than 48 hours after injury. CONCLUSION: Serum amylase greater than 200 and serum lipase greater than 1,800 may be useful clinical markers for major pancreatic ductal injury when combined with physical examination. Early operative intervention for pancreatic transection results in shorter length of stay and fewer complications.


Subject(s)
Pancreas/injuries , Pancreatectomy/statistics & numerical data , Pancreaticojejunostomy/statistics & numerical data , Patient Selection , Wounds, Nonpenetrating/diagnosis , Wounds, Nonpenetrating/therapy , Age Factors , Algorithms , Amylases/blood , Biomarkers/blood , Child , Decision Trees , Female , Humans , Injury Severity Score , Length of Stay/statistics & numerical data , Lipase/blood , Logistic Models , Male , Pancreatectomy/adverse effects , Pancreaticojejunostomy/adverse effects , Retrospective Studies , Treatment Outcome , Wounds, Nonpenetrating/blood , Wounds, Nonpenetrating/enzymology
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