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Transabdominal amnioinfusion to avoid fetal demise and intestinal damage in fetuses with gastroschisis and severe oligohydramnios.

BACKGROUND/PURPOSE: Despite dramatic improvement in survival rate for neonates with gastroschisis, significant postoperative morbidity and a low mortality rate still occur. Furthermore, even in recent publications, some fetal death has been reported. Does this mean that antenatal diagnosis of gastroschisis is a missed opportunity? In fact, decreased amniotic fluid (AF) volume is observed in some fetuses with gastroschisis. However, oligohydramnios is associated with an increased risk of fetal suffering. When severe oligohydramnios is observed, intrapartum amnioinfusion, to restore AF volume, may help avoid fetal complications. METHODS: Two fetuses with gastroschisis and severe oligohydramnios were treated antenatally with amnioinfusion of saline solution. In one case, fetal heart beat decelerations were observed at 27 weeks' gestation among with the oligohydroamnios and serial transabdominal amnioinfusions were performed. In the second case, severe oligohydramnios was observed at 31, weeks and an amnioinfusion was performed. The 2 babies were delivered at 31 and 34 weeks, respectively. RESULTS: In both cases, exteriorized bowel was nearly normal at birth, and primary closure could be performed. Outcome was favorable, and they were discharged home on day 43 and day 54, respectively. CONCLUSIONS: Because fetuses with gastroschisis and oligohydramnios are part of a particular high-risk group, serial ultrasound examination and computerized fetal heart beat monitoring are necessary during the third trimester. In selected cases of gastroschisis associated with severe oligohydramnios, serial amnioinfusion may be required.

Adult↗

Utility of skin testing in nutritional assessment: a critical review.

To evaluate the claim that delayed cutaneous hypersensitivity skin testing is useful in nutritional assessment of hospitalized patients, we reviewed the English language literature of the last 12 years. Although several hundred publications discussed delayed cutaneous hypersensitivity testing and nutritional status, only 15 provided new, objective data correlating these variables in hospitalized adults. Of these, only three provided age-matched control groups to control for antigen variability, lack of prior exposure, and other technical problems. The majority of reports took no account of diseases (cancer, immune disease, infection) or therapies (radiation, drugs, surgery) known to affect skin test response. In the reports specifying different degrees of malnutrition, the most important group, those with less than obvious malnutrition, were not abnormal by skin testing. Ten reports described serial skin testing during nutritional intervention. Non reported serially tested controls without nutritional intervention, important since serial testing alone can augment skin test response. Nonnutritional intercurrent therapy which might affect skin tests was seldom mentioned. In the few reports specifying that nutritional repletion was even achieved, repleted patients were not separated from unrepleted in subsequent analyses. No report examined skin testing for its predictive accuracy, cost/benefit ratio, or influence on outcome. Because of these problems in experimental design, the frequent lack of appropriate controls, and the low specificity of abnormal delayed cutaneous hypersensitivity responses, we conclude that the utility of skin testing in nutritional assessment remains unproved.

Humans↗

Gene expression in donor corneal endothelium.

OBJECTIVE: To report gene expression profiles of normal human corneal endothelium with microarray analysis and serial analysis of gene expression (SAGE). METHODS: Corneal endothelium was removed from normal human corneas obtained from eye banks. Total RNA was isolated and SAGE analysis was performed. The same RNA source was used to construct a complementary DNA library that was hybridized to microarrays containing 12 558 transcripts. RESULTS: A total of 9530 SAGE tags were sequenced, representing 4724 unique tags. Microarray analysis identified 542 distinct transcripts. A database of human corneal endothelial gene expression was compiled. Of the SAGE tags, 1720 matched known genes, 478 corresponded to expressed sequence tags, and 2526 had no known match to public databases. The 5 most abundantly expressed SAGE tags were cytochrome c oxidase subunit II, adenosine triphosphate synthase F(0) subunit 6, carbonic anhydrase XII, 12S ribosomal RNA, and ferritin, heavy polypeptide 1. Thirty-four percent of the transcripts (n = 1616) were specific to the corneal endothelium, when compared with other publicly available SAGE libraries. The 5 most abundant unique tags were keratin 12, angiopoietinlike factor, annexin A8, and 2 tags with no match to the database. Many endothelial pump function enzymes were confirmed, including several plasma membrane Na( +)/K(+) adenosine triphosphatases and a recently reported bicarbonate transporter. CONCLUSIONS: Corneal endothelial gene expression profiles by the current analysis provide an understanding of endothelial metabolism, structure, and function; enable comparisons to diseased endothelium; and provide baseline data that may lead to the discovery of novel endothelial genes.

Aged↗

Alcohol advertising bans and alcohol abuse: reply.

Young reexamines the work first presented in Saffer (1991) on the relationship between alcohol advertising bans and alcohol use. While there are several interesting possibilities for extending Saffer (1991), Young fails to provide any new insights. Most of his paper is devoted to recreating my data and results. He tries to extend my work with three new specifications. Each of these new specifications is flawed. His errors include a inappropriate application of fixed effects models, inappropriate dependent variables, and incorrect serial correlation computations. The results of these errors are a series of inconsistent advertising ban coefficients. He concludes that these inconsistent results are evidence that advertising bans have no effect of alcohol abuse. It might be better to at least provide a series of consistent regression models before coming to any conclusions.

Advertising↗

Use of TaqMan real-time reverse transcription-PCR for rapid detection, quantification, and typing of norovirus.

Noroviruses (NoVs) are the most commonly identified cause of outbreaks and sporadic cases of acute gastroenteritis. We evaluated and optimized NoV-specific TaqMan real-time reverse transcription (RT)-PCR assays for the rapid detection and typing of NoV strains belonging to genogroups GI and GII and adapted them to the LightCycler platform. We expanded the detection ability of the assays by developing an assay that detects the GIV NoV strain. The assays were validated with 92 clinical samples and 33 water samples from confirmed NoV outbreaks and suspected NoV contamination cases. The assays detected NoV RNA in all of the clinical specimens previously confirmed positive by conventional RT-PCR and sequencing. Additionally, the TaqMan assays successfully detected NoV RNA in water samples containing low viral concentrations and inhibitors of RT and/or PCR, whereas the conventional method with region B primers required dilution of the inhibitors. By means of serially diluted NoV T7 RNA transcripts, a potential detection limit of <10 transcript copies per reaction mixture was observed with the GII assay and a potential detection limit of <100 transcript copies per reaction mixture was observed with the GI assay. These results and the ability to detect virus in water that was negative by RT-PCR demonstrate the higher sensitivity of the TaqMan assay compared with that of a conventional RT-PCR assay. The TaqMan methods dramatically decrease the turnaround time by eliminating post-PCR processing. These assays have proven useful in assisting scientists in public health and diagnostic laboratories report findings quickly to outbreak management teams.

Caliciviridae Infections↗

Imaging osteoarthritis: magnetic resonance imaging versus x-ray.

Until recently, imaging evaluation of osteoarthritis has relied primarily on conventional radiography. Using radiography in clinical practice or clinical research, however, has been fraught with difficulty. Techniques for reproducibly acquiring serial radiographs of joints have improved considerably over the past several years. However, the greatest promise for advancing knowledge about osteoarthritis and its treatment lies in MRI and its unique ability to examine the joint as a whole organ. In contrast to conventional radiography, MRI can directly visualize the articular cartilage, synovium, menisci, and other intra-articular structures important to the functional integrity of joints. There have been considerable advances in MRI of articular cartilage in particular over the past several years. However, much of this has come from small cross-sectional studies. Larger, longitudinal studies are ongoing, and publications are just emerging. This paper reviews the current status of x-ray and MRI in osteoarthritis and points to where changes might be anticipated in the future.

Arthrography↗

Expression of I-region-associated antigen (Ia) and interleukin 1 by subcultured human endothelial cells.

Activation of T cells requires three signals from an antigen-presenting cell: antigen, Ia determinants (HLA-D region determinants in man), and interleukin 1 (IL-1). Recent evidence has suggested that macrophages, dendritic cells, epidermal Langerhan's cells, and endothelial cells can each function as antigen-presenting cells (APC). If these cell types can independently function as APC, they should synthesize Ia determinants and secrete IL-1. To determine if endothelial cells fulfill these requirements, we have propagated human umbilical vein endothelial cells by serial subculture for extended periods of time and assessed Ia expression and IL-1 secretion. The endothelial cells were subcultured for 8 months (approximately 20 subcultures) and were found to display classic morphology and immunofluorescent staining for the endothelial cell-specific marker Factor VIII-related antigen. In a separate paper we have shown that these subcultured endothelial cells can present antigen to T cells in a HLA-D region-restricted fashion (C. R. Wagner, R. M. Vetto, and D. R. Burger, Subcultured human endothelial cells can independently function as fully competent antigen-presenting cells, accepted for publication, Hum. Immunol.). In this paper we present evidence demonstrating that extensively subcultured endothelial cells biosynthesize both HLA-DR and HLA-DS molecules after exposure to T cells and antigen or to a supernatant from antigen-activated T cells. Evidence is also presented that when endothelial cells are cultured in the presence of lipopolysaccharide they secrete a molecule(s) with IL-1 activity as assayed by LBRM-33-IA5 cell line production of interleukin 2.

Antigen-Presenting Cells↗

Novel low-grade glioneuronal neoplasm presenting in an octogenarian: case report and review of the literature.

Glioneuronal neoplasms are rare tumors that typically affect patients in the first three decades of life. Since the publication of the World Health Organization (WHO) 2000 classification of tumors, further variants of these tumors have been reported. We present an 83-year-old gentleman who presented with a history of ataxia and weight loss. MRI and CT scan revealed a ring-enhancing bihemispheric lesion in the premotor cortex consistent with a malignant primary brain tumor crossing the corpus collosum. The patient underwent a sterotactic biopsy with drainage of the cystic component. Histopathologic studies revealed a mixed glioneuronal tumor with benign characteristics. A craniotomy was performed and the tumor was resected. Postoperatively, the patient has been followed with serial MRI scans with no evidence of disease recurrence at 27 months. Glioneuronal tumors are extremely uncommon in the octogenarian population, however, it is important to include them in the differential diagnosis of intracerebral masses. They are histopathologically quite heterogeneous, and in this report we present a novel subtype. Radiographically, these lesions can mimic more aggressive primary brain tumors.

Aged↗

Development of a physiologically based pharmacokinetic model for deltamethrin in the adult male Sprague-Dawley rat.

Deltamethrin (DLT) is a type II pyrethroid insecticide widely used in agriculture and public health. DLT is a potent neurotoxin that is primarily cleared from the body by metabolism. To better understand the dosimetry of DLT in the central nervous system, a physiologically based pharmacokinetic (PBPK) model for DLT was constructed for the adult, male Sprague-Dawley rat that employed both flow-limited (brain, gastrointestinal [GI] tract, liver, and rapidly perfused tissues) and diffusion-limited (fat, blood/plasma, and slowly perfused tissues) rate equations. The blood was divided into plasma and erythrocytes. Cytochrome P450-mediated metabolism was accounted for in the liver and carboxylesterase (CaE)-mediated metabolism in plasma and liver. Serial blood, brain, and fat samples were taken for DLT analysis for up to 48 h after adult rats received 2 or 10 mg DLT/kg po. Hepatic biotransformation accounted for approximately 78% of these administered doses. Plasma CaEs accounted for biotransformation of approximately 8% of each dosage. Refined PBPK model forecasts compared favorably to the 2- and 10-mg/kg po blood, plasma, brain, and fat DLT profiles, as well as profiles subsequently obtained from adult rats given 1 mg/kg iv. DLT kinetic profiles extracted from published reports of oral and iv experiments were also used for verification of the model's simulations. There was generally good agreement in most instances between predicted and the limited amount of empirical data. It became clear from our modeling efforts that there is considerably more to be learned about processes that govern GI absorption and exsorption, transport, binding, brain uptake and egress, fat deposition, and systemic elimination of DLT and other pyrethroids. The current model can serve as a foundation for construction of models for other pyrethroids and can be improved as more definitive information on DLT kinetic processes becomes available.

Adipose Tissue↗

Development of a computer-based battery designed to screen adults for neuropsychological impairment.

The initial step in the development of a new computer-based neuropsychological testing system is described. A new hardware-software system and a screening battery consisting of an orientation task and five cognitive tests has been implemented. This novel screening battery is designed for use in identifying individuals among exposed groups who may require more extensive follow-up neuropsychological evaluation. Sophisticated, but currently available, and relatively inexpensive hardware and software technology are employed, introducing an improvement over existing computer-based batteries. Use of a digitized speech production device for producing instructions facilitates testing of illiterate subjects, use of auditory stimulus materials, and relatively easy translation of the testing instructions to other languages. Use of a pen-based notebook computer enables responding by the subject in a manner that is both natural and analogous to that used in existing paper-and-pencil testing instruments. Five neuropsychological tests were developed to cover a range of cognitive domains: 1) verbal list learning and recognition memory, 2) visual memory span, 3) conceptual and motor tracking, 4) psychomotor speed and accuracy, and 5) delayed verbal recognition. The screening instrument has been pilot-tested for feasibility of use among outpatients at an occupational medicine clinic and among community-dwelling older adults. This instrument is intended to provide a standardized efficient, cost-effective method for widespread use in occupational medicine and public health to detect and track subclinical neurotoxic effects and to prevent additional harmful exposure. Additional aspects of development of the computer-based testing system are discussed.

Adult↗

Barriers in the quest for quality drug information: salutary lessons from TGA-approved sources for thyroid-related medications.

Product information (PI) for thyroid-related medications endorsed by the Therapeutic Goods Administration, as reproduced in the commonly used compilation publications June 2006 MIMS (Monthly index of medical specialties) annual, MIMS Online and the Australian prescription products guide 2006, was evaluated to see whether it reflects contemporary therapeutic practice. Compared with current medical literature, these PI-based sources provide inadequate, inaccurate or outdated therapeutic directives. Examples include: Incorrect advice that thyroxine therapy should always begin at very low dosage. Failure to recommend increased thyroxine dosage early in pregnancy (thus placing the offspring of women being treated for hypothyroidism at risk of impaired fetal brain development). Incorrect and potentially unsafe advice to treat thyrotoxicosis with stable iodide in late pregnancy. Failure to advise serial adjustment of antithyroid drug dosage until after a patient becomes euthyroid (this can result in iatrogenic thyroid dysfunction). Outdated advice that antithyroid drugs are not compatible with breastfeeding. Recent initiatives to upgrade consumer medicine information (CMI) appear to accept PI-based sources as a reliable benchmark for CMI. That inference is not warranted for thyroid-related medications. Accountability for the updating of clinical information in PI needs to be defined, and the process for updating PI may need to be modified. Quality drug information, both PI and CMI, depends on fluent, evidence-based collaboration between suppliers, regulators, prescribers, specialist clinicians and consumers.

Antithyroid Agents↗

Lumbar puncture in pediatric bacterial meningitis: defining the time interval for recovery of cerebrospinal fluid pathogens after parenteral antibiotic pretreatment.

OBJECTIVE: Despite the lack of evidence defining a time interval during which cerebrospinal fluid (CSF) culture yield will not be affected by previous antibiotic therapy, recent publications cite a "minimum window" of 2 to 3 hours for recovery of bacterial pathogens after parenteral antibiotic administration. We conducted a retrospective review of children with bacterial meningitis to describe the rate at which parenteral antibiotic pretreatment sterilizes CSF cultures. METHODS: The medical records of pediatric patients who were discharged from a tertiary children's hospital during a 5-year period with the final diagnosis of bacterial meningitis or suspected bacterial meningitis were reviewed. The decay in yield of CSF cultures over time was evaluated in patients with lumbar punctures (LP) delayed until after initiation of parenteral antibiotics and in patients with serial LPs before and after initiation of parenteral antibiotics. RESULTS: The pathogens that infected the 128 study patients were Streptococcus pneumoniae (49), Neisseria meningitidis (37), group B Streptococcus (21), Haemophilus influenzae (8), other organisms (11), and undetermined (3). Thirty-nine patients (30%) had first LPs after initiation of parenteral antibiotics, and 55 (43%) had serial LPs before and after initiation of parenteral antibiotics. After >/=50 mg/kg of a third-generation cephalosporin, 3 of 9 LPs in meningococcal meningitis were sterile within 1 hour, occurring as early as 15 minutes, and all were sterile by 2 hours. With pneumococcal disease, the first negative CSF culture occurred at 4.3 hours, with 5 of 7 cultures negative from 4 to 10 hours after initiation of parenteral antibiotics. Reduced susceptibility to beta-lactam antibiotics occurred in 11 of 46 pneumococcal isolates. Group B streptococcal cultures were positive through the first 8 hours after parenteral antibiotics. Blood cultures were positive in 74% of cases without pretreatment and in 57% to 68% of cases with negative CSF cultures. CONCLUSIONS: The temptation to initiate antimicrobial therapy may override the principle of obtaining adequate pretreatment culture material. The present study demonstrates that CSF sterilization may occur more rapidly after initiation of parenteral antibiotics than previously suggested, with complete sterilization of meningococcus within 2 hours and the beginning of sterilization of pneumococcus by 4 hours into therapy. Lack of adequate culture material may result in inability to tailor therapy to antimicrobial susceptibility or in unnecessarily prolonged treatment if the clinical presentation and laboratory data cannot exclude the possibility of bacterial meningitis.

Adolescent↗

Utility of the focus technologies west nile virus immunoglobulin M capture enzyme-linked immunosorbent assay for testing cerebrospinal fluid.

Focus Technologies has developed an immunoglobulin M (IgM) capture enzyme-linked immunosorbent assay (ELISA) kit that utilizes recombinant West Nile virus (WNV) antigens to detect WNV IgM in serum. We evaluate here the utility of the kit for detecting WNV IgM in cerebrospinal fluid (CSF). The sensitivity was evaluated by using 52 CSF specimens from the 2002 WNV season that were positive in both the Public Health Service Laboratories WNV IgM ELISA and an in-house WNV IgM ELISA with native WNV antigen. The specificity was evaluated with two groups of specimens: (i). 73 CSF specimens submitted for in-house WNV IgM ELISA testing from February through April 2003 and yielding a negative WNV IgM result and (ii). 60 CSF specimens determined to be positive for another virus by PCR testing. Using these 185 CSF specimens at a screening dilution of 1:2, the kit was determined to be 100% sensitive and 100% specific. Endpoint titers were determined for 20 IgM-positive CSF specimens by testing serial twofold dilutions and ranged from 1:8 to 1:512. Index values (specimen absorbance value/calibrator absorbance value) for the screening dilution (1:2) showed no correlation with IgM titers, whereas index values for higher dilutions showed significant correlation with IgM titers. CSF screening dilutions of greater than 1:2 are not recommended, however, due to the risk of obtaining false-negative results. These findings show that the Focus Technologies WNV IgM capture ELISA, when utilized as recommended, offers accurate qualitative detection of WNV IgM in CSF specimens.

Antibodies, Viral↗

Respiratory diseases in children and outdoor air pollution in São Paulo, Brazil: a time series analysis.

OBJECTIVES: To investigate the short term effects of air pollution on the respiratory morbidity of children living in São Paulo, Brazil, one of the largest cities in the developing world. METHODS: Daily counts of hospital admissions due to respiratory diseases along with daily levels of meteorological variables and air pollutants (PM(10), SO(2), NO(2), O(3), and CO) were analysed with Poisson regression. Final models were adjusted for the effects of time trends, seasonal patterns, weekdays, holidays, meteorological factors, and serial correlation. RESULTS: Daily admissions of children to hospital for total respiratory disease and pneumonia showed significant increases associated with O(3) (5-8%), NO(2) (9%), and with PM(10) (9%) (results are for an increase from the 10th to the 90th percentile of pollution measurements). Consistently, effects for pneumonia were greater than for all respiratory diseases combined. Also, effects on infants (children <1 year old) presented higher estimates. Similar associations were found for asthma admissions. Point estimates for most pollutants were higher for asthma than for other diagnosed admissions. However, these associations were not significant. CONCLUSIONS: These results agree with the limited publications on this subject but indicate a rather smaller magnitude of effects. Nevertheless, given the present concentrations of air pollution in São Paulo and the large population potentially exposed attention should be directed to minimise such effects.

Air Pollutants↗

Idiopathic talipes equinovarus (ITEV) (clubfeet) in Texas.

Idiopathic talipes equinovarus (ITEV) is the most common form of clubfoot with a birth prevalence of 1 per 1,000 births. Serial casting and surgical correction impose a substantial financial burden on families and the health care system. While the etiology of ITEV is considered to be complex, the causes remain elusive. Genetic, maternal, and environmental factors have been suggested to play an etiologic role. This study was undertaken to determine the prevalence of ITEV and define maternal and environmental factors associated with ITEV in Texas from 1996 to 1999. Data on 682 cases of nonsyndromic ITEV were compared with all births (n = 923,543) in Texas during the same period. The overall prevalence and prevalence odds ratios (PORs) were calculated for gender, year of birth, public health region (PHR), race, maternal age, education, folic acid fortification, and parity. The overall prevalence of ITEV was 0.74/1,000 or 1/1,354 live births. Adjusted PORs were similar among blacks and US and foreign-born Hispanics (POR = 0.92, 95% CI = 0.69-1.21; POR = 0.99, 95% CI = 0.79-1.25; and POR = 0.94, 95% CI = 0.74-1.19), respectively, compared to whites. College education and higher parity were significantly associated with a lower risk of giving birth to offspring with ITEV. Babies born after folic acid fortification of grains had a very small decrease in ITEV that may be due to chance.

Adolescent↗

Newly developed primers for the detection of Mycobacterium avium subspecies paratuberculosis.

Recent publications reported the existence of IS900 like sequences in mycobacteria different from Mycobacterium avium subspecies paratuberculosis (Map). The primers used for IS900 detection of Map have amplified these sequences causing false positive results. In this study, we have developed two new PCR assays for the detection of Map. The first assay is based on the IS900 sequence using primers different from the ones previously reported, the second assay on the f57 sequence. The specificity of the tests was checked by analysis of 190 mycobacterial isolates (74 Map and 116 non-Map isolates). All Map strains were positive and all non-Map strains were negative. Serial dilutions of Map bacteria were used to assess the sensitivity of the assays. We achieved a sensitivity of 1CFU per PCR for both assays. In addition, a PCR-simulating computer programme was used to evaluate the specificity of the new IS900 primers. The combination of the two PCR assays has proven to be useful for the identification of Map but validation on a large range of clinical samples still needs to be done.

Animals↗

Topo-optical visualization reactions of carbohydrate-containing amyloid deposits in the respiratory tract.

Staining with Congo red according to is the most commonly used method for the demonstration of amyloid, but structures other than amyloid can give false-positive results. To overcome this problem, introduced an aqueous Congo red staining with gum arabic as the mounting medium, which we have used in this and previous publications. Most histochemical studies on amyloid deposits to date have concentrated on conventional methods including staining with thioflavine, sirius red, alcian blue, methyl and crystal violet. In this study, we used topo-optical reactions with thiazine dyes on both the light and polarization microscopic level to establish the structure, distribution and location of carbohydrate components that occur within amyloid deposits, especially in the respiratory tract. Topo-optical staining reactions for the qualitative analysis of carbohydrate components in amyloid deposits included (1) reactions that identify the carbohydrate residues, (2) reactions that detect sialic acids and, (3) methods that visualize glycosaminoglycans. In conclusion, a comparison of consecutive serial sections stained with Congo red, aldehyde bisulfite toluidine blue reaction, sialic acid-specific topo-optical reaction, toluidine blue topo-optical reaction and chemically intensified basophilic reaction showed correlative staining patterns and anisotropic effects, corresponding to a close pathomorphological relationship between amyloid fibrils, periodate reactive carbohydrates, including sialic acids, and glycosaminoglycans.

Adult↗

Identification and prevention of a GC content bias in SAGE libraries.

Serial Analysis of Gene Expression (SAGE) is becoming a widely used gene expression profiling method for the study of development, cancer and other human diseases. Investigators using SAGE rely heavily on the quantitative aspect of this method for cataloging gene expression and comparing multiple SAGE libraries. We have developed additional computational and statistical tools to assess the quality and reproducibility of a SAGE library. Using these methods, a critical variable in the SAGE protocol was identified that has the potential to bias the Tag distribution relative to the GC content of the 10 bp SAGE Tag DNA sequence. We also detected this bias in a number of publicly available SAGE libraries. It is important to note that the GC content bias went undetected by quality control procedures in the current SAGE protocol and was only identified with the use of these statistical analyses on as few as 750 SAGE Tags. In addition to keeping any solution of free DiTags on ice, an analysis of the GC content should be performed before sequencing large numbers of SAGE Tags to be confident that SAGE libraries are free from experimental bias.

Animals↗