Toxicologic causes of giggling.
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Adolescent↗
Biomedical subjects
A Carlson
Publications and source records attributed to A Carlson.
Emergency medicine standardized letter of recommendation: predictors of guaranteed match.
OBJECTIVE: The Council of Emergency Medicine Residency Directors (CORD) standardized letter of recommendation (SLOR) has become a common, reliable, and useful tool in the evaluation of emergency medicine (EM) applicants. A "guaranteed match" (GM) is the SLOR's bottom-line superlative response. It is also the SLOR's least common superlative response. Because candidates receiving a GM are a select group, the authors thought it would be useful to identify SLOR information that predicts a GM recommendation. METHODS: This was a secondary analysis of a database of all EM SLORs submitted to a single EM residency during the 1998--1999 application cycle to one EM residency program. Response to GM and 16 data points in the background/qualification sections were analyzed by chi-square, univariate analysis, and logistic regression. RESULTS: Four hundred eleven SLORs were analyzed. Qualification information was more predictive than background information for applicants receiving a GM. The highest univariate odds ratios for background information were "staff author" (OR = 1.7, 1.0--2.8), "extended contact" (OR = 2.2, 1.0--4.5), "clinical contact outside the ED" (OR = 3.0, 1.5--5.9), and "honors on EM rotation" (OR = 5.4, 3.0--9.8). The highest univariate odds ratios for qualification information were "outstanding differential diagnosis ability" (OR = 10.1, 5.8--17.4), "outstanding work ethic" (OR = 13.1, 5.2--33.3), and "outstanding global assessment" (OR = 58, 24.2--139). Logistic regression analysis demonstrated "outstanding global assessment" (p < 0.000; r = 0.92) and "outstanding work ethic" (p = 0.028; r = 0.71) to be statistically predictive of GM. CONCLUSIONS: There were both background and qualification data points predictive of a "guaranteed match." Qualification information had a greater predictive value than background information. Medical student applicants, letter writers, and letter evaluators may find this information useful when dealing with SLORS.
Chi-Square Distribution↗
Prenatal diagnosis for congenital adrenal hyperplasia in 532 pregnancies.
Congenital adrenal hyperplasia (CAH) refers to a family of monogenic inherited disorders of adrenal steroidogenesis most often caused by enzyme 21-hydroxylase deficiency (21-OHD). In the classic forms of CAH (simple virilizing and salt wasting), androgen excess causes external genital ambiguity in newborn females and progressive postnatal virilization in males and females. Prenatal treatment of CAH with dexamethasone has been successfully used for over a decade. This article serves as an update on 532 pregnancies prenatally diagnosed using amniocentesis or chorionic villus sampling between 1978 and 2001 at New York Presbyterian Hospital-Weill Medical College of Cornell University. Of the 532 pregnancies, 281 were prenatally treated for CAH due to the risk of 21-hydroxylase deficiency. Follow-up telephone interviews with mothers, genetic counselors, endocrinologists, pediatricians, and obstetricians were performed in all cases. Of the pregnancies evaluated, 116 babies were affected with classic 21-OHD. Of these, 61 were female, 49 of whom were treated prenatally with dexamethasone. Dexamethasone administered at or before 9 wk gestation (in proper doses) was effective in reducing virilization. There were no statistical differences in the symptoms during pregnancy between mothers treated with dexamethasone and those not treated with dexamethasone, except for weight gain, edema, and striae, which were greater in the treated group. No significant or enduring side-effects were noted in the fetuses, indicating that dexamethasone treatment is safe. Prenatally treated newborns did not differ in weight from untreated, unaffected newborns. Based on our experience, prenatal diagnosis and proper prenatal treatment of 21-OHD are effective in significantly reducing or eliminating virilization in the newborn female. This spares the affected female the consequences of genital ambiguity, genital surgery, and possible sex misassignment.
Adrenal Hyperplasia, Congenital↗
The notch receptor and its ligands are selectively expressed during hematopoietic development in the mouse.
Members of the Notch family of transmembrane receptors are found on primitive hematopoietic precursors, and Notch ligand expression has been demonstrated on the surface of stromal cells, suggesting a role for Notch signaling in mammalian blood cell development. The current report examines the expression of Notch receptors and their ligands in murine hematopoietic tissues to determine: A) which blood cell lineages in the adult are influenced by Notch activity, and B) whether fetal hematopoiesis in the embryo involves the Notch pathway. In the adult mouse, a combination of flow cytometry, immunohistochemistry and Northern analysis was used to examine Notch receptor or ligand expression in bone marrow and spleen. In the embryo, Northern analysis and in situ hybridization were used to characterize Notch receptor and ligand expression in fetal liver on embryonic day 12 (E12) through E17, an active period encompassing both erythropoiesis and granulopoeisis. Flow cytometry demonstrated the presence of Notch1 and Notch2 receptors on bone marrow-derived myeloid cells but not on erythroid cells positive for the marker, Ter-119. In situ hybridization of E12 through E17 fetal liver demonstrated widespread expression of Jagged1 and Delta1 in a pattern similar to but less abundant than that of the erythropoietin receptor. Taken together with earlier functional results, the current expression data suggest a role for Notch activity in establishing definitive hematopoiesis in fetal liver, as well as a selective use of Notch signaling in adult erythropoiesis and granulopoiesis. Notch receptors in the adult are most likely utilized by early erythroid precursors and intermediate-stage granulocytes, but not by terminally differentiating cells of either subset.
Animals↗
Family characteristics and life events before the onset of autoimmune type 1 diabetes in young adults: a nationwide study.
OBJECTIVE: To elucidate whether family characteristics and stressful life events were associated with onset of autoimmune type 1 diabetes in young adults. RESEARCH DESIGN AND METHODS: This investigation was based on a nationwide study (Diabetes Incidence Study in Sweden) of newly diagnosed patients aged 15-34 years. Patients clinically classified as type 1 diabetic with antibodies to islet cells and/or to GAD65 were compared with age- and sex-matched control subjects via questionnaire. The questionnaire covered diabetes heredity, social environment, educational level, and life events experienced during the 12 months before diagnosis. RESULTS: The rate of response was 82% for the diabetic patients and 65% for the control subjects. Questionnaires from 349 diabetic patients and 979 control subjects were considered. Diabetes in relatives was more frequent in the patients (odds ratio [OR]2.6) who were born in Sweden and whose mothers were of Swedish origin. No major stress factors were detected in the diabetic patients; however, in comparison with the control subjects, the diabetic patients had experienced fewer conflicts with their parents and had less often broken contacts with friends. CONCLUSIONS: Young adults with recent-onset type 1 diabetes were more exposed to heredity for diabetes, but no major prediabetic stress factors were detected. Our study does not directly support the concept that psychosocial stressful life events are involved in the development of autoimmune type 1 diabetes in young adults.
Adult↗
Relative safety of mirtazapine overdose.
A 43-y-o male with a history of AIDS, atrial fibrillation, and alcohol abuse presented to the emergency department 2 h after ingestion of 25 tablets of 15 mg mirtazapine (total 375 mg) with ethanol in a suicide attempt (no other coingestion). Vital signs were normal except for a mild tachycardia (rate 112). Physical examination was unremarkable except for lethargy. Fifty grams of activated charcoal with sorbitol was given. Electrocardiogram showed sinus tachycardia, left ventricular hypertrophy, and non-specific ST-segment changes. Serum mirtazapine on admission was 530 ng/mL (therapeutic level 20-50 ng/mL). Overnight monitoring revealed no tachyarrythmias, and discharge occurred after psychiatric evaluation. It appears that ingestions of mirtazapine approximately 10-fold of therapeutic exhibit minimal acute toxicity. From this and other cases in the literature exhibiting a 10-fold overdose, we conclude that isolated mirtazapine ingestions of this magnitude require no acute intervention other than short term (about 6 h) observation.
Adult↗
Gender verification in the Olympics.
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Female↗
Extinction dynamics and the regional persistence of a tree frog metapopulation.
The concept of a metapopulation acknowledges local extinctions as a natural part of the dynamics of a patchily distributed population. However, if extinctions are not balanced by recolonizations or if there is a high degree of spatial synchrony of local extinctions, this poses a threat to and will reduce the metapopulation persistence time. Here we show that, in a metapopulation network of 378 pond patches used by the tree frog (Hyla arborea), even though extinctions are frequent (mean extinction probability p(e) = 0.24) they pose no threat to the metapopulation as they are balanced by recolonizations (p(c) = 0.33). In any one year there was a pattern of large populations tending to persist while small populations became extinct. The total number of individuals belonging to populations that went extinct was small (< 5%) compared with those populations that persisted. A spatial autocorrelation analysis indicated no clustering of local extinctions. The tree frog metapopulation studied consisted of a set of larger, persistent populations mixed with smaller populations characterized by high turnover dynamics.
Animals↗
Human skin expresses growth hormone but not the prolactin gene.
Using sensitive reverse transcriptase-polymerase chain reaction (RT-PCR) methods, we showed the expression of mRNA for growth hormone (GH) but not prolactin (PRL) in whole human skin (normal and basal cell carcinoma (BCC)). These RNAs for PRL and GH were below detectability in human epidermal keratinocytes and in human and hamster malignant melanocytes. This is in agreement with previous studies showing GH gene expression in dermal fibroblasts. GH peptide was not detected (by immunocytochemistry) in human skin specimens (normal and pathologic) in either dermal or epidermal compartments. The mRNA coding for the GH mediator insulin-like growth factor-1 (IGF-1) was detectable in whole skin and in malignant melanocytes. Therefore, in the present investigation of hormonal mediators of the cutaneous (epidermal) response to environmental stress, we have excluded the direct participation of PRL and GH in that reaction. Thus the analogy previously noted between the systemic (central) and skin responses to stress, as represented by cutaneous expression of hypothalamic-pituitary-adrenal axis components, does not extend to other pituitary hormones also involved in that response such as PRL and GH.
Adult↗
Clinicopathologic reassessment of primary cutaneous B-cell lymphomas with immunophenotypic and molecular genetic characterization.
Primary cutaneous B-cell lymphomas (PCBLs) may have particular clinicopathologic characteristics distinct from their lymph node-based counterparts. It has been suggested that PCBLs should have a separate classification system. The aim of this study was to determine whether the Revised European-American Lymphoid Neoplasms (REAL) classification is applicable to PCBL. Thirty-nine cases of PCBL from 36 patients, consisting of 20 men and 16 women (median age 66 yrs), were included in this study. Paraffin-section immunohistochemistry for CD3, CD5, CD10, CD20, CD43, Bcl-2, Bcl-6, and cyclin D1 was performed in all cases. Immunostaining for immunoglobulin light chains was also performed on cases histologically diagnosed as extranodal marginal zone lymphoma (MZL) and primary cutaneous B-cell lymphoma unclassifiable (PCBLu). Polymerase chain reaction (PCR) analysis of t(14;18) was performed in all cases. Immunoglobulin heavy chain gene rearrangement (VDJ) was tested by PCR on all follicle center lymphoma (FCL), MZL, and PCBLu cases. The 39 cases consisted of 15 (39%) FCLs, 13 (33%) diffuse large B-cell lymphomas (DLCL), 9 (23%) extranodal MZL, and 2 cases of PCBLu. Anatomically, 59% of PCBLs occurred in the head and neck, of which approximately 57% were FCL. Five of six cases presenting on the lower extremity were DLCL. Follow-up data was available from all 39 patients with a mean of 50.8 months. All but two patients are alive with or without disease at last contact. One patient with DLCL died of lung metastases and the other DLCL patient died of sepsis as a complication of therapy. In all 15 cases of FCL, CD10 and/or Bcl-6 expression supported the follicle center origin of the neoplastic cells. In contrast to previous reports, we found that 53% (8 of 15) of primary cutaneous FCL had either Bcl-2 protein expression or t(14;18). Our data indicate that many cases of primary cutaneous FCL have Bcl-2 alterations similar to their nodal counterpart. We found that 95% (37 of 39) of PCBLs could be classified according to the REAL classification, supporting its applicability in cutaneous lymphomas.
Adult↗
Characteristics of the emergency medicine standardized letter of recommendation.
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Emergency Medicine↗
Genetic diversity and fitness in peripheral and central populations of the European tree frog Hyla arborea.
Genetic diversity is expected to decrease in small and isolated populations as a consequence of founder effects, bottlenecks, inbreeding and genetic drift. In this study we analyse temporal and spatial effects on genetic variation and progeny viability of the European tree frog (Hyla arborea) at two scales. First, the Swedish distribution has been isolated from the continental distribution for more than 8000 thousand years, and secondly, within Sweden, recent habitat alterations that have taken place during this century have increased isolation between local populations. Genetic variation and progeny survival in relation to isolation was studied within the entire Swedish distribution of the tree frog. Allozyme electrophoresis analysis of froglets, sampled across the Swedish distribution, revealed a low overall genetic variation (1.06 alleles/locus) at the protein level in comparison with continental populations (1.54-1.68 alleles/locus). However, egg hatchability (97%) and early larval survival (95%) were not lower than in other parts of the tree frog distribution or in other anuran species. Within the Swedish distribution, early larval survival was lower in isolated breeding ponds than in more central ones. However, no differences in genetic variation were found in relation to isolation. Polymorphism was detected only at a single locus, and was restricted geographically to the eastern part of the Swedish distribution. Bottlenecks due to climatic changes and fragmentation of suitable habitat (primarily natural pastures with ponds) are suggested as possible causes of the low genetic diversity of the Swedish tree frog population.
Animals↗
Calculating the costs of gun injuries. A new methodology.
A new method for assessing the costs of gun injuries to a health system examines data on paid amounts, comprehensive medical expenses, and expenses over time. The authors extracted claims using injury diagnosis codes from billing forms and medical charts. The study demonstrates that a claims database can be used to accurately measure health care costs associated with gun injuries. The study is the first to include gun-related injuries treated in ambulatory care settings and to track actual payments over time.
Adolescent↗
Molecular pathology of soft tissue and bone tumors. A review.
OBJECTIVE: To present recent concepts on the molecular pathogenesis of tumors of soft tissue and bone, and on the use of molecular genetic methods, including their significance as diagnostic markers and prognostic indicators. DATA SOURCES AND STUDY SELECTION: Reports on tumors of bone and/or soft tissue published in the English language literature and observations made using specimens available at the Departments of Pathology at Albany Medical College and Loyola University Medical Center. DATA EXTRACTION AND SYNTHESIS: Studies on bone and soft tissue tumors containing chromosomal or genetic evaluation were selected for further analysis. Specific chromosomal abnormalities, such as numerical aberrations or translocations with production of fusion genes, were classified according to the tumor of origin. Data were also collected on mutations in tumor suppressor genes, genes coding for growth factors or their receptors, and genes coding for tyrosine kinases. Also noted were mutations of uncertain significance, for which the pathogenic connection between tumor production and mutated gene function is still unclear. CONCLUSIONS: In general, the mutations reported interfere with the action of peptide growth factors coordinating mesenchyme proliferation and differentiation, although membrane-bound receptors expressing the intracellular signaling modifier, tyrosine kinase activity, have also been involved. Functional types of genes most commonly affected include tumor suppressors, oncogenes, and nuclear transcription factors. Thus, the mutations involved in the pathogenesis of soft tissue and bone tumors have affected multiple genes. Moreover, aberrant fusion gene products may be formed in tumoral tissue and may then act as transcription regulators stimulating cellular proliferation. Cytogenetic studies help at the clinical level by demonstrating aneuploidy and increased ploidy, which may correlate with malignant behavior. Diagnostic tumor-specific chromosomal translocations may be detected with Southern hybridization analysis, polymerase chain reaction, reverse-transcription polymerase chain reaction, or with the fluorescence in situ hybridization technique. Notably, early metastatic disease may be detectable in blood specimens using polymerase chain reaction or reverse-transcription polymerase chain reaction techniques.
Bone Neoplasms↗
Polarity of 11-cis retinal release from cultured retinal pigment epithelium.
PURPOSE: Fetal bovine retinal pigment epithelium (RPE) was grown on porous supports to investigate the polarity of 11-cis retinal (RAL) release from these cells and the influence that the interphotoreceptor retinoid-binding protein (IRBP) has on this process. METHODS: [3H]all-trans retinol (ROL) was delivered to the basal surface of the cultured RPE by serum retinol-binding protein (RBP). Apo IRBP was added to either the apical or basal medium, or was absent from the incubation entirely. RESULTS: The greatest level of [3H]11-cis RAL was detected in the apical medium but only when apo IRBP was present there. When apo IRBP was present only in the basal medium, or was absent from the incubation entirely, low levels of [3H]11-cis RAL were released apically and basally. CONCLUSIONS: If 11-cis RAL release were constitutive, one would expect to find elevated levels of this retinoid in the apical and basal media in the absence of apo IRBP. Instead, the enhancement of [3H]11-cis RAL release into the apical, but not the basal, medium in the presence of apo IRBP suggests that [3H]11-cis RAL release is polarized and dependent on the presence of apo IRBP. It is postulated, therefore, that a mechanism such as an IRBP membrane receptor in the apical plasma membrane may be responsible for this polarity.
Animals↗
Structural and functional characterization of recombinant human cellular retinaldehyde-binding protein.
Cellular retinaldehyde-binding protein (CRALBP) is abundant in the retinal pigment epithelium (RPE) and Müller cells of the retina where it is thought to function in retinoid metabolism and visual pigment regeneration. The protein carries 11-cis-retinal and/or 11-cis-retinol as endogenous ligands in the RPE and retina and mutations in human CRALBP that destroy retinoid binding functionality have been linked to autosomal recessive retinitis pigmentosa. CRALBP is also present in brain without endogenous retinoids, suggesting other ligands and physiological roles exist for the protein. Human recombinant cellular retinaldehyde-binding protein (rCRALBP) has been over expressed as non-fusion and fusion proteins in Escherichia coli from pET3a and pET19b vectors, respectively. The recombinant proteins typically constitute 15-20% of the soluble bacterial lysate protein and after purification, yield about 3-8 mg per liter of bacterial culture. Liquid chromatography electrospray mass spectrometry, amino acid analysis, and Edman degradation were used to demonstrate that rCRALBP exhibits the correct primary structure and mass. Circular dichroism, retinoid HPLC, UV-visible absorption spectroscopy, and solution state 19F-NMR were used to characterize the secondary structure and retinoid binding properties of rCRALBP. Human rCRALBP appears virtually identical to bovine retinal CRALBP in terms of secondary structure, thermal stability, and stereoselective retinoid-binding properties. Ligand-dependent conformational changes appear to influence a newly detected difference in the bathochromic shift exhibited by bovine and human CRALBP when complexed with 9-cis-retinal. These recombinant preparations provide valid models for human CRALBP structure-function studies.
Amino Acid Sequence↗
A HPLC method for the determination of 9-cis retinoic acid (ALRT1057) and its 4-oxo metabolite in human plasma.
A HPLC method was developed and validated for the quantitation of 9-cis-retinoic acid (ALRT1057) and its major metabolite, 4-oxo-9-cis-retinoic acid (LG100182) in human plasma. Samples were buffered and extracted with methyl-tert-butyl-ether. The analytes and an I.S. were separated on a C18 HPLC column using a shallow gradient of 70-89% organic solvent. The analytes were quantitated by UV detection at 348 nm. Selectivity against endogenous compounds and potential metabolites (retinol, all trans-, 13-cis-, and 4-hydroxy-9-cis-retinoic acid) was demonstrated. The run time was 29 min. The standard curve was linear from 2.5 to 450 ng ml-1. Interassay precision for both analytes in quality control samples was less than 5.0% RSD. Accuracy was within 11.0% RE for both compounds. Analyte stability during sample storage, extraction processing, and chromatography was established. Method ruggedness was tested by two analysts and on two HPLC systems. This method has been applied to the quantitation of clinical samples.
Alitretinoin↗