Search PubMed⌕ Search

Biomedical subjects

A D Friedman

Publications and source records attributed to A D Friedman.

At least 55 records · Page 3Linked to original sources

Stress in pediatric faculty. Results of a national survey.

OBJECTIVES: To determine current levels of pediatric faculty stress experienced by pediatric faculty and to examine contributors to and consequences of this stress. DESIGN: Random survey, using attitude questionnaire. SETTING: Twenty-six medical school-based pediatric programs nationwide. PARTICIPANTS: Two hundred fifty-two full-time pediatric faculty members. MAIN OUTCOME MEASURES: Stress level; importance of specific sources of stress and fulfillment; satisfaction with time allotted to various activities; social support; satisfaction with career choices. RESULTS: The return rate was 64%. Forty-six percent of respondents reported "high" or "very high" levels of usual stress; 64% were stressed beyond a "comfortable" level at least "frequently." Women (P < .05), assistant or associate professors (P < .001), and faculty on the tenure track (P < .006) reported feeling "overstressed" more often. Major sources of stress were pressure to do research, family needs (48%), and lack of personal time (40%). About half (51%) agreed that the recent emphasis on reducing resident stress has led to increased pressure on faculty members. Frequency of feeling overstressed was reduced if respondents felt valued by their chairperson (P < .001) and by other faculty (P < .01). Within the last year, 47% had considered moving to another medical school. Another 43% had considered leaving academia. The more frequently the respondent felt overstressed, the more likely he or she was to have considered such changes (P < .001). CONCLUSIONS: The stress currently experienced by pediatric faculty is substantial and seems to affect long-term commitment to academic medicine. Creative solutions to this issue should be explored.

Adult↗

Stress and the residency program director.

A survey of pediatric program directors was performed to identify stressors on pediatric residents as perceived by the directors and to ascertain the relationship of stress experienced by house staff and faculty. Major stressors for pediatric residents were acuity/complexity of patient diseases and financial concerns. Major stressors for program directors were administrative duties. Although nearly three fourths of the program directors had completed a fellowship, only one half were on the tenured track. The majority of program directors believed that as resident working hours and stress decreased, faculty workload and stress increased. Stress experienced by faculty appears to require further investigation and remediation.

Humans↗

PEBP2/CBF, the murine homolog of the human myeloid AML1 and PEBP2 beta/CBF beta proto-oncoproteins, regulates the murine myeloperoxidase and neutrophil elastase genes in immature myeloid cells.

The myeloperoxidase (MPO) and neutrophil elastase genes are expressed specifically in immature myeloid cells. The integrity of a polyomavirus enhancer core sequence, 5'-AACCACA-3', is critical to the activity of the murine MPO proximal enhancer. This element binds two species, myeloid nuclear factors 1 alpha and 1 beta (MyNF1 alpha and -beta), present in 32D cl3 myeloid cell nuclear extracts. The levels of the MyNF1s increase during early 32D cl3 cell granulocytic differentiation. Both MyNF1 alpha and -beta supershift with an antiserum raised by using a peptide derived from the N terminus of polyomavirus enhancer-binding protein 2/core-binding factor (PEBP2/CBF) alpha subunit. The specific peptide inhibits these supershifts. In vitro-translated PEBP2/CBF DNA-binding domain binds the murine MPO PEBP2/CBF site. An alternate PEBP2/CBF consensus site, 5'-GACCGCA-3', but not a simian virus 40 enhancer core sequence, 5'-TTCCACA-3', binds the MyNF1s in vitro and activates a minimal murine MPO-thymidine kinase promoter in vivo. The murine neutrophil elastase gene 100-bp 5'-flanking sequences contain several functional elements, including potential binding sites for PU.1, C/EBP, c-Myb, and PEBP2/CBF. The functional element 5'-GGCCACA-3' located at positions -66 to 72 differs from the PEBP2/CBF consensus (5'-PuACCPuCA-3') only by an A-to-G transition at position 2. This DNA element binds MyNF1 alpha and -beta weakly. The N terminis of two PEBP2/CBF alpha subunit family members, PEBP2 alpha A and PEBP2 alpha B (murine AML1), are nearly identical, and 32D c13 cl3 cells contain both corresponding mRNAs. Since t(8;21), t(3;21), and inv(16), associated with myeloid leukemias, disrupt subunits of PEBP2/CBF, we speculate that the resulting oncoproteins, AML1-ETO, AML1-EAP, AML1-Evi1, and CBF beta-MYH11, inhibit early myeloid differentiation.

Animals↗

The murine myeloperoxidase promoter contains several functional elements, one of which binds a cell type-restricted transcription factor, myeloid nuclear factor 1 (MyNF1).

The myeloperoxidase (MPO) gene is expressed specifically in myeloid cells. There is significant homology between the murine and human MPO genes in the 1.6-kb region located upstream of the murine MPO transcription initiation sites. 5',3', and internal deletions of this DNA segment localized several cis-acting DNA elements in the murine MPO promoter which are functional in 32D cl3 cells, a murine myeloblast cell line which expresses MPO. These DNA elements did not function well in mouse L-cell fibroblasts. Additional mutagenesis of the most active promoter region allowed the delimitation of a functional 20-bp segment. Mutation of the enhancer core motif within this segment was functionally deleterious, and an oligonucleotide containing these base pairs increased the activity of a minimal promoter. This same oligonucleotide, but not a mutant variant, could bind a set of nuclear proteins, myeloid nuclear factors 1 alpha and 1 beta (MyNF1 alpha and -1 beta), present in 32D cl3 cells but absent from L cells, murine erythroleukemia cells, and SP2 lymphoid cells.

Animals↗

A novel temporal expression pattern of three C/EBP family members in differentiating myelomonocytic cells.

Members of the CCAAT/enhancer binding protein (C/EBP) family have been shown to regulate the terminal differentiation of adipocytes and hepatocytes. In these cell lineages, high levels of C/EBP alpha are found only in mature, nondividing cells. Using Western blotting and immunohistochemical staining, we have determined the temporal order of expression for C/EBP alpha, C/EBP beta, and C/EBP delta in differentiating myelomonocytic marrow cells. These studies show a unique temporal pattern of C/EBP isoform expression in the myeloid lineage. In particular, C/EBP alpha expression is very high in proliferative myelomonocytic cells, and diminishes during phenotypic maturation. While we have detected C/EBP alpha, C/EBP beta, and C/EBP delta in multiple myeloid leukemia cell lines, and C/EBP alpha in normal myeloid cells and in de novo human myeloid leukemias, we have not detected these C/EBP isoforms in either erythroid or lymphoid cells. Finally, we show that C/EBP alpha, C/EBP beta, and C/EBP delta protein and messenger RNA levels correlate in maturing granulocytic cells. The formation of tissue-specific combinations of C/EBP homodimers and heterodimers may allow this family of transcription factors to regulate different sets of genes in adipocytes, hepatocytes, and myelomonocytes.

Antigens, Surface↗

Superficial fungal infections of the skin. Diagnosis and current treatment recommendations.

Superficial fungal infections are common. Most diagnoses of fungal infections of the skin can be made by physical examination, assisted by the use of a Wood's lamp, skin scrapings for microscopic examination, and fungal cultures. Dermatophyte infections are common at all ages, in both sexes, and they have a worldwide distribution. These infections include tinea capitis, tinea cruris, tinea pedis, tinea corporis, tinea manuum and tinea barbae. Tinea versicolor, caused by Malassezia furfur, and candidal infections are also common. Treatment modalities include oral and topical agents. Good personal hygiene is an important adjunct to antifungal therapy. Decisions regarding the appropriateness of therapy in a given patient must take into account the extent and location of the infection, the benefits and risks of each of the treatments, and cost. Oral therapies include griseofulvin, ketoconazole, and itraconazole. There are a large variety of topical treatments, including nystatin, selenium sulfide, tolnaftate, haloprogin, miconazole, clotrimazole, and sodium thiosulfate. Important to successful treatment is compliance with what is sometimes a long course of treatment, and good personal hygiene.

Administration, Topical↗

Transcriptional regulation of two myeloid-specific genes, myeloperoxidase and lactoferrin, during differentiation of the murine cell line 32D C13.

The transcriptional regulation of myeloperoxidase (MPO) and lactoferrin (LF) was examined during terminal myeloid differentiation of the murine cell line 32D C13. The rates of transcription initiation for MPO and LF, determined by an in vitro nuclear run-on assay, increased approximately ninefold. The accumulation of MPO mRNA in 32D C13 cells, determined by Northern blot analysis, correlated temporally with the observed increase in MPO transcription initiation. On the other hand, accumulation of LF mRNA lagged behind the observed increase in LF transcription initiation. In mouse L cells, the LF gene was transcribed more frequently than the MPO gene, though neither mRNA accumulated. Finally, murine MPO transcription is shown, by Northern blot and primer extension analysis, to initiate at multiple sites. These results indicate that whereas transcription induction may largely account for the accumulation of MPO mRNA during terminal myeloid differentiation, both transcriptional and posttranscriptional mechanisms operate to allow accumulation of LF mRNA. The 32D C13 cell system will be a useful model for elucidating these mechanisms.

Animals↗

CCAAT-enhancer binding protein: a component of a differentiation switch.

The CCAAT-enhancer binding protein (C/EBP) has now been found to promote the terminal differentiation of adipocytes. During the normal course of adipogenesis, C/EBP expression is restricted to a terminal phase wherein proliferative growth is arrested, and specialized cell phenotype is first manifested. A conditional form of C/EBP was developed, making it feasible to test its capacity to regulate the differentiation of cultured adipocytes. Premature expression of C/EBP in adipoblasts caused a direct cessation of mitotic growth. Moreover, when abetted by the effects of three adipogenic hormones, C/EBP promoted terminal cell differentiation. Since C/EBP is expressed in a variety of tissues, it may have a fundamental role in regulating the balance between cell growth and differentiation in higher animals.

Adipose Tissue↗

Pancreatic enlargement in alcoholic pancreatitis: prevalence and natural history.

We determined the prevalence and natural history of pancreatic enlargement by abdominal ultrasonography or computed tomography in 72 patients with alcoholic pancreatitis. Pancreatic enlargement was observed in 54 patients (75%); it was diffuse in 28 (52%) and focal in 26 (48%). The focal enlargement was frequently cystic (50%), while the diffuse enlargement was only occasionally cystic (7%). Sequential imaging of the pancreas in 29 patients demonstrated partial to total resolution of pancreatic enlargement in greater than 50% during 6 months of follow-up. Determination of serum amylase and p-isoamylase activity was neither sensitive nor specific for pancreatic enlargement in alcoholic pancreatitis.

Acute Disease↗

Long term radiologic outcome of Pseudomonas osteomyelitis of the foot.

The medical records of 27 patients with puncture wound-induced Pseudomonas aeruginosa osteomyelitis/septic arthritis of the foot hospitalized from 1980 through 1988 were reviewed. Twenty patients received anti-Pseudomonas therapy for greater than 21 days and 7 patients received anti-Pseudomonas therapy for less than or equal to 21 days. There was no difference in age, sex, race, duration of wound or symptoms before admission or in admission physical findings including temperature, lymphadenopathy, puncture site appearance or admission laboratory data including white blood cell count or erythrocyte sedimentation rate between the two groups. All children but two in the long term therapy group had surgical as well as parenteral anti-Pseudomonas therapy. Fifteen patients returned for follow-up radiographs 1 to 8 1/2 years after hospitalization, 10 of 20 who had received therapy for greater than 21 days and 5 of 7 who had received therapy for less than or equal to 21 days. Poor radiologic outcome, ranging from bony deformity to joint space abnormality, was noted in 4 patients, of whom 3 had had joint involvement. Clinical abnormality was noted in only one adolescent male, and he had the most severe radiologic sequelae. The longer term functional significance of these radiologic anomalies awaits further delineation.

Adolescent↗

Impetigo therapy.

Explore the source record for details and available documents.

Anti-Bacterial Agents↗

Efficacy of sponging vs acetaminophen for reduction of fever. Sponging Study Group.

Seventy-three children with acute febrile illnesses were enrolled in a study to compare the efficacy of sponging, sponging plus acetaminophen, and acetaminophen alone as methods of lowering body temperature. The greatest temperature reduction was seen in the combined acetaminophen plus sponging group. The smallest temperature reduction was noted in children who received sponging alone. We urge reconsideration of routine sponging of febrile young patients.

Acetaminophen↗