Policies, practices, and attitudes of North American medical journal editors

OBJECTIVE: To describe U.S. and Canadian medical journals, their editors, and policies that affect the dissemination of medical information. DESIGN: Mailed survey. PARTICIPANTS: Senior editors of all 269 leading medical journals published at least quarterly in the United States and Canada, of whom 221 (82%) responded. MAIN MEASURES: The questionnaire asked about characteristics of journal editors and their journals and about journals' policies toward peer review, conflicts of interest, prepublication discussions with the press, and pharmaceutical advertisements. RESULTS: The editors were overwhelmingly men (96%), middle-aged (mean age 61 years), and trained as physicians (82%). Although 98% claimed that their journals were "peer-reviewed," the editors differed in how they defined a "peer" and in the number of peers they deemed optimal for review. Sixty-three percent thought journals should check on reviewers' potential conflicts of interest, but only a minority supported masking authors' names and affiliations (46%), checking reviewers' financial conflicts of interest (40%), or revealing reviewers' names to authors (8%). The respondents advocated discussion of scientific findings with the press (84%), but only in accord with the Ingelfinger rule, i.e., after publication of the article (77%). Fifty-seven percent of the editors agreed that journals have a responsibility to ensure the truthfulness of pharmaceutical advertisements, and 40% favored subjecting advertisements to the same rigorous peer review as scientific articles. CONCLUSIONS: The responding editors were relatively homogeneous demographically and professionally, and they tended to support the editorial status quo. There was little sentiment in favor of tampering with the current peer-review system (however defined) or the Ingelfinger rule, but a surprisingly large percentage of the respondents favored more stringent review of drug advertisements.     

Treatment orientation and associated characteristics of North American academic psychiatrists

We present data showing the degree to which a "biological-psychotherapeutic" division persists in American psychiatry, and how psychiatrists' treatment orientation is associated with personal and professional characteristics. Almost two thirds of academic psychiatrists who responded to our survey (N = 435) could be classified as either biological (27%) or psychotherapeutic (37%) in orientation, according to the proportion of their caseload to which they provided psychotherapy (< or = 25% vs. > 75%). There appears to have been an increase over the last 35 years in the proportion of psychiatrists who can be classified as biologically oriented and a decrease in the proportion who can be classified as psychotherapeutically oriented, as well as the emergence of a large class of intermediate or "eclectic" practitioners (36%). Several personal and professional attributes were distributed differentially according to treatment orientation. Psychotherapeutically oriented respondents more frequently reported personal histories of psychiatric disorders than did biologically oriented respondents (64% vs. 39%) as well as greater satisfaction with clinical work (81% vs. 53% "very satisfied"). Differences were also found in age, gender, history of personal psychotherapy, family history of psychiatric disorder, history of marijuana use, degrees of involvement in research, teaching and clinical care of patients, and overall work satisfaction, as well as other characteristics.     

Reduction in enkephalin and substance P messenger RNA in the striatum of early grade Huntington's disease: a detailed cellular in situ hybridization study

The expression of enkephalin and substance P messenger RNAs was examined in the caudate-putamen of human post mortem tissue from control and Huntington's disease tissue using in situ hybridization techniques and human specific enkephalin and substance P [35S] oligonucleotides. Macroscopic and microscopic quantification of enkephalin and substance P gene expression was carried out using computer-assisted image analysis. Tissue was collected from six control cases with no sign of neurological disease and six Huntington's disease cases ranging from grades 0 to 3 as determined by neuropathological evaluation. The clinical and pathological diagnosis of Huntington's disease was confirmed unequivocally by genetic analysis of the CAG repeat length in both copies of IT15, the Huntington's disease gene. A marked reduction in both enkephalin and substance P messenger RNAs was detected in all regions of the caudate nucleus and putamen in Huntington's disease grades 2/3 when compared to controls; in the dorsal caudate few enkephalin or substance P messenger RNA-positive cells were detected. For the early grade (0/1) Huntington's disease cases, a heterogeneous reduction in both enkephalin and substance P messenger RNAs were noted; for enkephalin messenger RNA the striatal autoradiograms displayed a conspicuous patchy appearance. Detailed cellular analysis of the dorsal caudate revealed a striking reduction in the number of enkephalin and substance P messenger RNA-positive cells detected and in the intensity of hybridization signal/cell. These data suggest that both the "indirect" GABA/enkephalin and "direct" GABA/substance P pathways are perturbed very early in the course of the disease and that these early changes in chemical signalling may possibly underlie the onset of clinical symptoms.     

Intracellular fatty acid-binding proteins: putting lower vertebrates in perspective

Intracellular fatty acid-binding proteins (FABPs) are small (15 kDa), highly conserved cytoplasmic proteins that bind long-chain fatty acids and other hydrophobic ligands. Fifteen isoforms have been identified and characterized to date. Members of the FABP protein family share many common characteristics: they have a common "clamshell" tertiary structure despite significant variation in primary structure; they bind their ligands with 1:1 molar stoichiometry and micromolar affinity (with the exception of liver type FABP, which binds two fatty acids per FABP); they are ubiquitously expressed, yet are found at greatest concentration in tissues with high capacities to oxidize or store lipids; and their level of expression changes with conditions that affect overall lipid metabolism. Because of the ligands bound by FABP and FABP's tissue distribution, it is thought that FABPs play a role in the intracellular metabolism of lipids; however, a precise function(s) for FABP has not been defined. This review highlights contributions from researchers studying FABP in nonmammalian systems. FABPs isolated from birds, fish, amphibians, insects, and flatworms have similar structures to mammals in FABPs, yet they are expressed in systems with unique lipid metabolisms. Because mammals are closely related and have relatively invariant fatty acid metabolisms, non-mammals provide alternative systems that may reveal the elusive function(s) of this protein family.     

Polymerase chain reaction and other amplification techniques in mycobacteriology

Amplification methods for detection of Mycobacterium tuberculosis, such as polymerase chain reaction (PCR), have undergone much research and development in the last several years. The most common methods for extraction, amplification, and detection of mycobacterial nucleic acid sequences used in "in-house" PCR assays are discussed. A list of commercially prepared PCR and non-PCR amplification assays that should be available soon is included. The pros and cons of "in-house" versus commercial technology and issues of implementation of molecular technology in the clinical laboratory are reviewed.     

Nitric oxide production by mouse bone marrow-derived dendritic cells: implications for the regulation of allogeneic T cell responses

Dendritic cells (DC) are the most potent known antigen presenting cells, and play important roles both in immunity and tolerance induction. Nitric oxide (NO) is an important effector molecule that is involved in numerous aspects of the immune response. There have been no accounts to date of efforts to determine NO generation by well-characterized DC. In this report we describe the production of NO by highly purified DEC 205+ DC propagated from mouse bone marrow in response to granulocyte/macrophage-colony stimulating factor (GM-CSF) + interleukin-4 (IL-4). NO synthesis was induced in DC by interferon-gamma (IFN-gamma) and lipopolysaccharide (LPS), and was blocked by the inhibitor of nitric oxide synthase (NOS), NG-monomethyl-L-arginine (NMMA). Both "mature" B7-2+ (CD86+) DC and B7-2- (CD86-) DC progenitors could be induced to release NO. NO was also recovered from the supernatants of primary mixed leukocyte cultures containing comparatively high concentrations of B7-2+ DC in relation to purified allogeneic T cells. Furthermore, inhibition of NO release in these cultures by NMMA resulted in an increase in T cell proliferation. These observations suggest that NO may be an important soluble mediator of the interaction between DC and activated T cells. In addition to its ability to inhibit T cell proliferation, NO was also shown to induce programmed cell death in DC. This was visualized by the detection of DNA strand breaks with in situ nick translation. The percentage of DC apoptosis correlated with the level of NO in the cultures. Apoptosis was inhibited by the addition of NMMA. These results indicate that DC have the capacity both to stimulate and potentially limit the same allogeneic T cell response, in accordance with their production of NO.     

Multiple T cell expansions are found in the blood and synovial fluid of patients with reactive arthritis

OBJECTIVE: To look for evidence of T lymphocyte expansions in the blood and synovial fluid (SF) of patients with reactive arthritis (ReA). METHODS: Paired peripheral blood and synovial samples from 10 patients with ReA were studied by dual color flow cytometry using T cell receptor (TCR) V beta specific and CD4 or CD8 specific antibodies. Two synovial CD8 expansions were studied by 3 color flow cytometry. Peripheral blood samples from 13 healthy, age matched individuals were studied as controls. RESULTS: Statistically significant expansions were observed in all patients, occurring in blood and SF CD4 and CD8 compartments, but were most common in the synovial CD8 compartment. Expansions studied in further detail displayed an activated "memory" phenotype. A synovial BV22S1/CD8 expansion was seen in 5/6 patients with sexually acquired ReA. CONCLUSION: Multiple T lymphocyte expansions are found in both the blood and SF of patients with ReA. Expansions were most commonly found in the synovial CD8 compartment, where they appeared to express both activation and memory markers. This indicates that T lymphocytes (and in particular cytotoxic T cells) may play a pathogenic role in ReA. These findings are consistent with either an antigen or a superantigen driven response.     

Response properties of neurons in the inferior colliculus of the monaurally deafened ferret to acoustic stimulation of the intact ear

Response properties of neurons in the central nucleus of the inferior colliculus (ICC) were investigated after unilateral cochlear removal at various ages during infancy. Nineteen ferrets had the right cochlea surgically ablated, either in adulthood or on postnatal day (P) 5, 25, or 40, 3-18 mo before recording. Adult ablations were made on the same day as ("acute," n = 3), or 2-3 mo before ("chronic," n = 3), recording. Two ferrets were left binaurally intact. Single-unit (n = 702) and multiunit (n = 1,819) recordings were made in the ICC of barbiturate-anesthetized ferrets ipsilateral (all ages) or contralateral (P5 and acute adult only) to the intact ear. In binaurally intact animals, tonal stimulation of the contralateral ear evoked excitatory activity at the majority (94%) of recording loci, whereas stimulation of the ipsilateral ear evoked activity at only 33% of recording loci. In acutely ablated animals, the majority of contralateral (90%) and ipsilateral (70%) loci were excited by tonal stimulation of the intact ear. In chronically ablated animals, 80-90% of loci were excited by ipsilateral stimulation. Single-unit thresholds were generally higher for low-best frequency (BF) than for high-BF units, and higher in the ipsilateral than in the contralateral ICC. Analysis of covariance showed highly significant differences between all of the ipsilateral and contralateral groups, but no effects of age at ablation or survival time following ablation, other than that the group ablated at P25 had higher mean ipsilateral thresholds than the groups ablated at P5 or, acutely, in adulthood. Cochlear ablation at P5, 25, or 40 resulted in a significant increase in dynamic ranges of ipsilateral ICC unit rate-intensity functions relative to acutely ablated animals. Dynamic ranges of units in the contralateral ICC of P5-ablated ferrets were also significantly increased compared with those of acutely ablated animals. Cochlear ablation at P5, 25, or 40 resulted in a significant increase in single-unit spontaneous discharge rates in the ICC ipsilateral but not contralateral (P5 only) to the intact ear. These data show that unilateral cochlear removal in adult ferrets leads to a rapid and dramatic increase in the proportion of neurons in the ICC ipsilateral to the intact ear that is excited by acoustic stimulation of that ear. In addition, the data confirm that, in ferrets, cochlear removal in infancy leads to a further increase in responsiveness of individual neurons in the ipsilateral ICC. Finally, the data show that responses in the ICC contralateral to the intact ear are largely but not completely unchanged by unilateral cochlear removal.     

The CT halo sign: a new finding in intestinal lymphangiectasia

A "halo sign" has been described in patients with Crohn disease, ulcerative colitis, radiation enteritis, ischemic colitis, and pseudomembranous colitis. This sign is characterized by an inner ring of low CT attenuation surrounded by a higher attenuation outer ring. We present a patient with primary intestinal lymphangiectasia in whom CT demonstrated a halo sign correlated with mucosal biopsy.     

Current practices of preoperative bowel preparation among North American colorectal surgeons

In North America, the rate of infections following colorectal surgery decreased after the introduction of oral antibiotic bowel preparation against colonic microflora. Eight hundred eight board-certified colorectal surgeons were surveyed for their current bowel preparation practices before elective procedures. The 471 responders (58%) all use mechanical preparation: oral polyethylene glycol solution (70.9% of the respondents), oral sodium phosphate solution with or without bisacodyl (28.4%), and "traditional" methods of dietary restriction, cathartics, and enemas (28.4%). Most surgeons (86.5%) add oral and parenteral antibiotics to the regimen; 11.5% add only parenteral antibiotics, 1.1% add only oral antibiotics, and 0.9% add no antibiotics. Generally (77.8% of cases), oral neomycin and erythromycin or metronidazole are combined with a perioperative parenteral antibiotic. Most individuals start the preparation as outpatients the day before surgery, and the parenteral drugs are added to the regimen 1-2 hours before the procedure. The use of outpatient bowel preparation is increasing; however, patient selection is critical, and education is needed to reduce the rate of complications.