Genetic correlation between resting metabolic rate and exploratory behaviour in deer mice (Peromyscus maniculatus).

According to the 'pace-of-life' syndrome hypothesis, differences in resting metabolic rate (RMR) should be genetically associated with exploratory behaviour. A large number of studies reported significant heritability for both RMR and exploratory behaviour, but the genetic correlation between the two has yet to be documented. We used a quantitative genetic approach to decompose the phenotypic (co)variance of several metabolic and behavioural measures into components of additive genetic, common environment and permanent environment variance in captive deer mice. We found significant additive genetic variance for two mass-independent metabolic measures (RMR and the average metabolic rate throughout the respirometry run) and two behavioural measures (time spent in centre and distance moved in a novel environment). We also detected positive additive genetic correlation between mass-independent RMR and distance moved (r(A) = 0.78 ± 0.23). Our results suggest that RMR and exploratory behaviour are functionally integrated traits in deer mice, providing empirical support for one of the connections within the pace-of-life syndrome hypothesis.

Reduction of ferric green rust by Shewanella putrefaciens.

AIMS: To reduce carbonated ferric green rust (GR*) using an iron respiring bacterium and obtain its reduced homologue, the mixed Fe(II)-Fe(III) carbonated green rust (GR). METHODS AND RESULTS: The GR* was chemically synthesized by oxidation of the GR and was incubated with Shewanella putrefaciens cells at a defined [Fe(III)]/[cell] ratio. Sodium methanoate served as the sole electron donor. The GR* was quickly transformed in GR (iron reducing rate = 8.7 mmol l(-1) h(-1)). CONCLUSIONS: Ferric green rust is available for S. putrefaciens respiration as an electron acceptor. The reversibility of the GR redox state can be driven by bacterial activity. SIGNIFICANCE AND IMPACT OF THE STUDY: This work suggests that GRs would act as an electronic balance in presence of bacteria. It provides also new perspectives for using iron reducing bacterial activity to regenerate the reactive form of GR during soil or water decontamination processes.

Recognizing, reporting, and reducing adverse drug reactions.

Adverse drug reactions (ADRs) are underreported and consequently are an underestimated cause of morbidity and mortality. Recent epidemiologic evidence estimates that ADRs represent the fourth to the sixth leading cause of death. Public awareness is increasing as reports of ADRs and medication errors become more prevalent in the lay press. Reducing the number of ADRs can be accomplished by systems changes made at an individual and national level. At the individual level, increased diligence should be used with regard to reporting and documenting ADRs. At the national level, ADRs can be reduced by expanding the role of the arm of the Food and Drug Administration (FDA) responsible for postmarketing surveillance.

Insights into a plasma membrane signature.

The plasma membrane (PM) is an organized biological system that serves as a structural barrier and communication interface with the extracellular environment. Many basic questions regarding the PM as a system remain unanswered. In particular, we do not understand the scope of similarity and differences in protein expression at the PM. This study takes an initial step toward addressing these questions by comparing the PM proteomes of fibroblasts and mammary carcinoma cells. Three sets of proteins were revealed by the study. The first set comprises between 9 and 23% of all proteins at the PM and appears to be common to both fibroblasts and mammary carcinoma. A second group of proteins, comprising approximately 40% of the proteins at the PM, is tightly linked to cell lineage. The third set of proteins is unique to each cell line and is independent of cell lineage. It is reasonable to hypothesize then, that this third group of proteins is responsible for unique aspects of cell behavior. In an effort to find proteins linked to the metastatic phenotype, we identified several proteins that are uniquely expressed at the PM of the metastatic MDA-MB-435 cells. These proteins have functions ranging from cell adhesion to the regulation of translation and the control of oxidant stress.

Patient perceptions of the capabilities of internists: a multi-center survey.

PURPOSE: Surveys conducted by the American College of Physicians-American Society of Internal Medicine have shown that the public has varying opinions about the capabilities of internists. However, the perceptions of patients seeking care from internists remain uncertain. We wished to determine how patients visiting general internists perceived them and discover whether patients understood the differences between internists and other primary care physicians. SUBJECTS AND METHODS: We surveyed established adult patients visiting three general internal medicine clinics in Georgia, Iowa, and Vermont. Patients answered 11 questions about their perceptions of an internist's scope of care and selected which of 24 diseases, symptoms, or examination skills they thought an internist could manage. RESULTS: Patients completed 601 (66%) of the 911 surveys distributed. Nearly half of patients (45%) confused internists with family physicians and 39% thought internists could treat children. Patients with college education were more than twice as likely to know that internists were not interns (Odds ratio = 2.6, 95% confidence interval 1.8 to 3.8, P < 0.001) compared with patients having less education. Only 50% of patients thought an internist was trained in women's health. Significantly more (P < 0.001) patients demonstrated confidence in an internist's ability to treat symptoms (76%) than treat specific diseases (59%) or perform clinical examinations (54%). CONCLUSIONS: Established patients seeking care in internal medicine clinics lack consensus on the capabilities of internists, especially on how they differ from other specialties. Continued public education efforts should be considered to promote better understanding of the role of the internist as a specialist in adult medicine.

A direct effect of competition on food choice by pigeons.

Previous research on food choice of pigeons foraging alone and in competition showed an indirect response to the competitor, mediated by the resource depletion associated with the competitor. This experiment showed, in addition, that pigeons can adjust their food choice in direct response to the competitor itself. Pigeons foraged for large, preferred grains of maize and smaller, unpreferred grains of wheat presented in bowls covered with sawdust. In a within-subject design, pigeons were tested alone or in competition with another pigeon. In competition, a higher choice proportion of the wheat grains was observed on the first two choices out of 48 items, and this effect increased with time in the experiment. This result underscores the role of learning in group foraging behaviour. It also suggests a possible ecological implication: that individuals that learn faster may enjoy a competitive advantage in terms of reduced delay in responding to the presence of a conspecific.

A method for application of samples to matrix-assisted laser desorption ionization time-of-flight targets that enhances peptide detection.

Matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry has become a fundamental tool for the identification and analysis of peptides and proteins. MALDI-TOF is well suited for the analysis of complex biological mixtures because samples are crystallized onto a solid support that can be washed to remove contaminants and salts prior to laser desorption. A number of approaches for immobilizing samples onto MALDI targets have been put forth. These include the use of different chemical matrices and the immobilization of samples onto different solid supports. In large part though, the preparation of MALDI targets has been an empirical exercise that often requires a unique series of conditions for every sample. Here, a simple method for the application of peptide mixtures onto MALDI targets is put forth. This method differs because peptides are added directly to a sample of nitrocellulose dissolved in acetone, allowing them to interact in solution-phase organic solvent. This solution-phase mixture is then spotted to the MALDI target and evaporated, forming a homogenous solid surface for laser desorption. This procedure is robust, highly sensitive, tolerant to detergents, and easily learned. In our hands, the method provides as much as a 10-fold enhancement to the detection of tryptic peptide fragments derived from in-gel digests.

A comparison of physicians' and patients' attitudes toward pharmaceutical industry gifts.

OBJECTIVE: To compare physicians' and their patients' attitudes toward pharmaceutical gifts. DESIGN: Survey of physicians and their patients. SETTING: Two tertiary-care medical centers, one military and one civilian. PARTICIPANTS: Two hundred sixty-eight of 392 consecutively surveyed physicians, 100 of 103 randomly selected patients at the military center, and 96 patients in a convenience sample at the civilian center completed the survey. MEASUREMENTS: Participants rated 10 pharmaceutical gifts on whether they were appropriate for physicians to accept and whether they were likely to influence prescribing. Patients found gifts less appropriate and more influential than did their physicians. About half of the patients were aware of such gifts; of those unaware, 24% responded that this knowledge altered their perception of the medical profession. Asked whether they thought their own physician accepted gifts, 27% said yes, 20% no, and 53% were unsure. For patients, feeling that gifts were inappropriate was best predicted by a belief that gifts might influence prescribing, while for physicians, the best predictor was knowledge of guidelines. CONCLUSIONS: Patients feel pharmaceutical gifts are more influential and less appropriate than do their physicians. Physicians may want to consider this in deciding whether to accept particular gifts. Broader dissemination of guidelines may be one means of changing physician behavior. At the same time, future guidelines should further consider the potentially different viewpoints of patients and physicians.

Peroral administration of 14C-poly(D,L-lactic acid) nanoparticles coated with human serum albumin or polyvinyl alcohol to guinea pigs.

Biodegradable 14C-poly(D,L-lactic acid) (PLA50) nanoparticles coated either with a readily digestible protein albumin or with a non-digestible coating agent, polyvinyl alcohol (PVA), were prepared by the solvent evaporation technique. The nanoparticles were administered perorally to guinea pigs to evaluate the gastro-intestinal degradation of their PLA50 matrix. In the case of PLA50 nanoparticles coated with digestible albumin, substantial gastro-intestinal degradation of the PLA50 matrix occurred, leading to the passage of considerable amount (> or =45%) of water-soluble products across the gastrointestinal barrier. When a non-digestible coating agent like PVA was used, the degradation of the PLA50 matrix in the gastro-intestinal tract was at least two times lower (> or =19%). The results show that it is possible to control the in vivo degradation of PLA50 nanoparticles using appropriate coating agents. The present investigations showed a good correlation between previously observed in vitro results and the in vivo findings.

A prospective study to assess the effect of ambulatory teaching on patient satisfaction.

PURPOSE: To assess the effect of ambulatory teaching on patients' satisfaction. METHOD: In 1996, 103 adult patients presenting to the Walter Reed General Medicine Walk-in Clinic completed a patient-satisfaction questionnaire immediately following their visits, during which they were initially seen by a trainee (third-year medical student or intern) and then seen by a faculty preceptor. The questionnaire included five items from the validated Medical Outcomes Study (MOS)-9 questionnaire as well as two open-ended questions. Fourteen staff physicians, 13 students (49% of the visits), and 11 interns (51% of the visits) participated in the study. Satisfaction was analyzed by level of training, and the responses from the study patients were compared with the responses from 372 usual-care (i.e., non-teaching) patients from the same clinic, using the chi-squared test. RESULTS: The study patients were typically pleased with their encounters, rating their overall satisfaction as excellent (61%), very good (29%), or good (9%). Nearly two thirds of the patients rated their satisfaction with waiting time to be very good or excellent. Compared with the usual-care patients, the study patients reported equal or greater satisfaction for all five MOS-9 items. Ninety-five percent of the study patients said they would be willing to be seen by a trainee-staff team on future visits. There was no difference in patient satisfaction by trainee level. The study patients cited enhanced interaction (45%), enhanced education (34%), and improved care (26%) as benefits of trainee-involved care, and increased waiting time (18%) and worse care (5%) as drawbacks. CONCLUSION: The results of this study suggest that ambulatory teaching does not adversely affect patient satisfaction, regardless of trainee level, and that patients who have been seen by trainee-staff teams are willing to experience such encounters again.

Bedside teaching.

BACKGROUND: Clinical teachers have been exhorted to "return to the bedside" so that the three critical parties-teacher, trainee, and patient-can participate together in the educational encounter. The presence of the patient is deemed essential for the optimal demonstration and observation of physical examination, medical interviewing, and interpersonal skills, as well as role-modeling professional and humanistic behavior. METHODS: This essay reviews the challenges inherent in bedside teaching and proposes strategies to enhance both the effectiveness and efficiency of such teaching. RESULTS: Practical suggestions are provided regarding teaching issues (time constraints, group accommodation, selectivity, demonstration, observation, case presentations), learning climate for both teacher and learners, hospital and patient barriers, and selected other issues. CONCLUSIONS: Despite changes in the clinical setting and financing of medical education, patient-centered teaching will remain essential to the training of future clinicians. Techniques described in this paper can be useful in facilitating such bedside teaching.

Increasing the use of advance directives in medical outpatients.

OBJECTIVE: We studied whether a simple educational intervention would increase patient completion of advance directives and discussions on end-of-life issues. DESIGN: Randomized, controlled trial. SETTING: Outpatient clinic of a teaching hospital. SUBJECTS: One hundred eighty-seven outpatients of a primary care internal medicine clinic. INTERVENTION: Study subjects attended a 1-hour interactive seminar and received an informational pamphlet and advance directive forms. Control subjects received by mail the pamphlet and forms only. MEASUREMENTS AND MAIN RESULTS: Completion of the advance directive was the main measurement. There were no significant differences in baseline characteristics of either group. Follow-up at 1 month revealed advance directive completion in 38% of study versus 24% of control subjects (p = .04), and discussions on advance planning in 73% of study versus 57% of control subjects (p = .02). Patients most likely to complete the documents were white, married, or attendees at the educational seminar. CONCLUSIONS: Interactive group seminars for medical outpatients increased discussions and use of written advance directives.

Estradiol activates p60src, p53/56lyn and renatured p50/55 protein tyrosine kinases in the dog prostate.

Protein tyrosine kinases (PTKs) are key enzymes implicated in signal transduction pathways regulated by growth factors (GFs). We have previously shown by immunohistochemistry that the level of phosphotyrosine (pY) proteins is increased in prostatic basal epithelial cells following estrogen treatment in castrated dogs. In this study, we investigated if this treatment increases the level and distribution of prostatic PTK activity, and more specifically, if it alters the expression and/or activity of the Src family members p60src and p53/56lyn. Prostates from normal and hyperplastic dog prostates, as well as those from castrated dogs treated with androgens, were also examined. Only the glands obtained from estrogen-treated dogs had a significantly increased total and specific PTK activity, observed uniquely in the particulate extract, as compared to the other types of prostates studied. In addition, this increased activity was correlated upon gel filtration chromatography with the presence of an additional peak of activity with an apparent molecular weight of 130 kDa, which was absent in other prostate fractions presenting only 50 kDa peaks. Using antibodies, we demonstrate that active p60src and pp53/56lyn kinases accounted for 81% of the activity in this 130 kDa peak. On the other hand, in situ renaturation also revealed the presence of still uncharacterized 50/55 kDa PTKs in the 130 kDa peak. Altogether, these findings raise the possibility that these PTKs contribute to the transmission of mitogenic signals originating directly or indirectly from estrogen stimulation of the basal cell layer of the prostate.

Fatal duodenocaval fistula caused by peptic ulcer.

Gastrointestinal bleeding caused by a duodenocaval fistula is rare, diagnostically challenging, and associated with a high mortality rate. We describe the case of a patient with polymicrobial fungemia and fatal gastrointestinal bleeding related to a duodenocaval fistula caused by peptic ulcer. Polymicrobial fungemia, which has not previously been associated with this condition, raises the possibility of candidal endocarditis.

Regulation and activation of focal adhesion kinase and paxillin during the adhesion, proliferation, and differentiation of prostatic epithelial cells in vitro and in vivo.

Focal adhesion kinase (pp125FAK) is a nonreceptor protein tyrosine kinase transducing signals initiated through integrin activation triggered by cell/extracellular matrix (ECM) interactions. To examine its role in epithelial cell adhesion, proliferation, and differentiation, we have studied pp125FAK expression, activity, and association with paxillin in two canine prostate models in which these functions can be selectively regulated: in vitro by vitronectin (VN) and serum factors, and in vivo by sex steroids. Kinetic studies revealed that the adhesion and spreading of prostatic epithelial cells in primary culture was regulated by serum VN and a natural ECM containing VN produced by prostate cells. While barely detectable in freshly isolated prostate cells, proliferating cells, after 72 h in culture, expressed higher levels of FAK mRNA (8-fold), pp125FAK (50-fold), and paxillin (50-fold). In prostate cells with a reduced growth rate after 2 weeks in culture, we observed a decrease in pp125FAK (4-fold) and its transcript (3-fold), but no change in paxillin. In vivo, both proteins were undetectable in normal and hyperplastic glands composed of a well differentiated epithelium, and in prostates restored by androgen supplementation. In contrast, pp125FAK and paxillin were up-regulated by androgen deprivation (castration) and further increased by estrogen treatment, which yielded metaplastic prostates mostly composed of proliferating basal epithelial cells. Moreover, both proteins were constitutively phosphorylated on tyrosine in the metaplastic prostate, as well as in proliferating cultured cells. Together, these results demonstrate that pp125FAK expression is regulated at the protein and mRNA levels and forms active signaling complexes with paxillin when epithelial cells in contact with ECM proteins are induced to proliferate in vivo and in vitro.

Felodipine as an alternative to more expensive calcium antagonists in mild to moderate hypertension.

We studied the therapeutic substitution of a less expensive but equally effective antihypertensive agent and assessed patient outcome. The medication of 39 patients with hypertension was changed from once-daily diltiazem hydrochloride (Cardizem CD) or nifedipine (Procardia XL) to felodipine (Plendil). Titration to a final dose was based on home and office blood pressure measurements assessed over subsequent follow-up clinic visits. Self-administered questionnaires measured different aspects of well-being and symptoms before and after the change in medication. Eighty percent of the cohort switched successfully to felodipine. Office systolic and diastolic pressures improved after the medication change (systolic: 150 mm Hg versus 144 mm Hg; diastolic: 92 mm Hg versus 87 mm Hg). No statistically significant differences were found among the 39 symptoms measured. A yearly savings potential for our institution was estimated to be $72,000.

Degradation of poly(D,L-lactic acid) nanoparticles coated with albumin in model digestive fluids (USP XXII).

Entirely biodegradable poly(D, L-lactic acid) (PLA50) nanoparticles coated with albumin were prepared by the solvent evaporation technique. Their degradative properties were investigated in simulated gastric and intestinal fluids (USP XXII). The degradation of the albumin coating was monitored by HPLC, whereas PLA50 degradation was determined by size exclusion chromatography (SEC) as well as by the detection of lactate in bulk solution by enzymatic assay. As expected, the coating effect of albumin, a readily digestible protein, rapidly disappeared in both gastric and intestinal media, thus exposing albumin-free PLA50 cores to hydrolytic processes. In pepsin-rich simulated gastric fluid, no degradation of the PLA50 core was observed over 8 h incubation time. In contrast, in pancreatin-rich simulated intestinal fluid, the PLA50 nanoparticles were rapidly converted into lactate. The results showed that the PLA50 degradation was mainly due to an enzymatic cleavage process. Further experiments showed the involvement of lipases in the degradation of the PLA50 core in simulated intestinal fluid.

Cost savings using a stepped-care prescribing protocol for nonsteroidal anti-inflammatory drugs.

OBJECTIVE: To lower nonsteroidal anti-inflammatory drug (NSAID) costs while maintaining quality patient care and clinician satisfaction. DESIGN: Before and after 21-month trial with one study site and two control sites and a questionnaire that was sent to 203 clinicians. SETTING AND SUBJECTS: Two military medical centers and two affiliated primary care clinics. All beneficiaries filling outpatient NSAID prescriptions. INTERVENTIONS: An NSAID prescribing protocol was implemented requiring a trial of either ibuprofen or indomethacin before new prescription of more expensive NSAIDs. One control center used an NSAID computer cost-prompt and the other had no intervention. MAIN OUTCOME MEASURES: The proportion of expensive NSAIDs prescribed at each institution and total NSAID costs adjusted for prescription volume. Clinician acceptance and patient impact were assessed by the questionnaire. RESULTS: Study site clinicians (n=158) reported very few protocol-related patient care problems. A minority (9%) of study site clinicians considered the protocol very bothersome, and only 2% felt it should be discontinued. Quarterly use of expensive NSAIDs at the study site fell from 34% to 21%, decreasing costs by 30% (P<.001). In contrast, the site with a computer cost-prompt had only a 5% decrease in NSAID costs, while costs at the site with no intervention increased 2%. CONCLUSIONS: For drugs with similar benefits and adverse effects, a "stepped formulary" approach requiring an initial trial of one of the less expensive agents can maintain physician prescribing choices and satisfaction while lowering costs.

Benign nocturnal leg cramps. Current controversies over use of quinine.

Benign nocturnal leg cramps are a relatively common and bothersome complaint, particularly among the elderly. Careful history taking and physical examination can exclude the majority of disorders in the differential diagnosis. Mechanical treatment of an acute muscle cramp involves stretching of the affected muscle. Prophylaxis includes both mechanical and pharmacologic measures. The efficacy of quinine sulfate has been supported in the majority of well-designed studies, but its use is controversial, and the FDA has banned over-the-counter quinine-based products used for leg cramps. Potentially fatal hypersensitivity reactions and thrombocytopenia can occur with use of quinine.