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Biomedical subjects

M Robbins

Publications and source records attributed to M Robbins.

At least 37 records · Page 2Linked to original sources

REACT theory-based intervention to reduce treatment-seeking delay for acute myocardial infarction. Rapid Early Action for Coronary Treatment.

Coronary heart disease (CHD) remains the leading cause of mortality in the U.S. Innovations in reperfusion therapies can potentially reduce CHD morbidity and mortality associated with acute myocardial infarction (AMI) when treatment is initiated within the first few hours of symptom onset. However, delay in seeking treatment for AMI is unacceptably lengthy, resulting in most patients being ineligible for reperfusion therapies. The Rapid Early Action for Coronary Treatment (REACT) Trial is a four-year, 20-community, randomized trial to design and test the effectiveness of a multi-component intervention to reduce patient delay for hospital care-seeking for AMI symptoms. This manuscript describes the development and content of the theoretically-based REACT intervention and summarizes: (1) the research literature used to inform the intervention; (2) the behavioral theories used to guide the development, implementation, and evaluation of the intervention; (3) the formative research undertaken to understand better decision-making processes as well as barriers and facilitators to seeking medical care as perceived by AMI patients, their families, and medical professionals; (4) the intervention design issues that were addressed; (5) the synthesis of data sources in developing the core message content; (6) the conceptualization for determining the intervention target audiences and associated intervention components and strategies, their integration with guiding theoretical approaches and implementation theories for the study, and a description of major intervention materials developed to implement the intervention; and (7) the focus of the outcome, impact, and process measurement based on the intervention components and theories on which they were developed.

Female↗

Health care providers' perspectives on patient delay for seeking care for symptoms of acute myocardial infarction.

To inform intervention development in a multisite randomized community trial, the Rapid Early Action for Coronary Treatment (REACT) project formative research was undertaken for the purpose of investigating the knowledge, beliefs, perceptions, and usual practice of health care professionals. A total of 24 key informant interviews of cardiologists and emergency physicians and 15 focus groups (91 participants) were conducted in five major geographic regions: Northeast, Northwest, Southeast, Southwest, and Midwest. Transcript analyses revealed that clinicians are somewhat unaware of the empirical evidence related to the problem of patient delay, are concerned about the practice constraints they face, and would benefit from concrete suggestions about how to improve patient education and encourage fast action. Findings provide guidance for selection of educational strategies and messages for health providers as well as patients and the public.

Aged↗

Assessment of chest pain onset and out-of-hospital delay using standardized interview questions: the REACT Pilot Study. Rapid Early Action for Coronary Treatment (REACT) Study Group.

OBJECTIVE: To determine the consistency of responses to a standardized 2-part "key" question (Key-Q) about acute symptom onset in patients presenting with chest pain when measured using alternative questions (Qs) about symptom perception and decisions to seek treatment. METHODS: A structured patient interview was performed at 3 university teaching hospitals and 1 community hospital. Convenience samples of adult patients presenting to these EDs with chest pain were asked specific questions related to their symptoms and recognition of illness. Information obtained included the 2-part Key-Q: "What are the symptoms that brought you here today?" and "When did those symptoms start?" The alternative Qs (in order of use) were as follows: Q1 = "When did your very first symptom or sensation begin?"; Q2 = "When did your symptoms lead you to think something was wrong or that you were ill?"; Q3 = "When did your symptoms become serious enough for you to seek medical care?"; and Q4 = "When did you actually call 9-1-1/emergency medical services (EMS) or go to the hospital?" The documented ED arrival time, demographic variables, and whether the patient arrived by ambulance were obtained from the medical record. Patients also were queried regarding potential barriers to seeking medical care and their cardiac risk factors. RESULTS: Of the 135 patients surveyed, 9 were unsure of the date and time of symptom onset. For the 126 patients with analyzable data, the mean (+/- SD) patient age was 62 +/- 16 years, and 59% were male. The general sequence of events reported from acute symptom onset until hospital care was Q1/Key-Q-->Q2-->Q3-->Q4-->ED arrival. The median differences and interquartile ranges (IQRs) in minutes between Q times and the Key-Q response were: Q1 = 0 (0-0); Q2 = 30 (0-210); Q3 = 140 (30-720); Q4 = 265 (90-1,215); and ED arrival = 340 (120-1,230). The interval from the Key-Q response until calling 9-1-1/EMS or going to the hospital was shorter for those who used an ambulance and for those who did not consult a physician first. The interval from the Key-Q response until considering symptoms to be serious was shorter for those with a family history of heart disease, but longer for non-white patients. CONCLUSION: The Key-Q elicited a response recalled near the time of first symptoms and generally before the patient had concluded something was "wrong or that he or she was ill." Measurement of the out-of-hospital delay in chest pain patients using the Key-Q appears promising.

Acute Disease↗

Assembly and regulation of the CD40 receptor complex in human B cells.

CD40 is a member of the tumor necrosis factor (TNF) receptor superfamily. Studies with human B cells show that the binding of CD154 (gp39, CD40L) to CD40 recruits TNF receptor- associated factor 2 (TRAF2) and TRAF3 to the receptor complex, induces the downregulation of the nonreceptor-associated TRAFs in the cell and induces an increased expression of Fas on the cell surface. Combined signaling through the interluekin 4 receptor and CD40 induces an increased expression of Fas with a commensurate increase in the level of TRAF2, but not TRAF3, that is recruited to the receptor complex. In contrast, engagement of the membrane immunoglobulin and CD40 limits Fas upregulation and reduces the recruitment of TRAF2, relative to TRAF3, to the CD40 receptor complex. These studies show that the TRAF composition of the CD40 receptor complex can be altered by signals that influence B cell differentiation.

B-Lymphocytes↗

Use of capillary electrophoresis with laser-induced fluorescence detection to assess messenger ribonucleic acid molecules amplified by the polymerase chain reaction: applications in the cloning of cells.

Progressive and selective degeneration of specific classes of neurons occurs in the Alzheimer's disease (AD) brain. Differential vulnerability in this disease is evident even within supopulations that synthesize and release acetylcholine as a transmitter; i.e., basal forebrain cholinergic neurons degenerate but other classes of cholinergic neurons are relatively preserved. The basis for this selective vulnerability is unknown. Studies of differential neuronal vulnerability in AD would be facilitated if cell lines expressing neurotransmitter-specific phenotypes could be cloned from the brain. Capillary electrophoresis (CE) with laser-induced fluorescence (LIF) has been shown to be a sensitive method of detection and quantitation of the DNA products of the polymerase chain reaction (PCR). CE/LIF was combined with the PCR to detect phenotypic messenger RNA (mRNA) molecules, converted to cDNA using reverse transcriptase (RT), in cultures of virally immortalized brainstem progenitor cells produced during establishment of a cloning strategy. RT/PCR methods were developed for detection of the mRNAs for choline acetyltransferase (ChAT), the neuronal, constitutive isoform of nitric oxide synthase (c-NOS), and the growth-associated protein GAP-43, three genes known to be expressed in central cholinergic neurons. A "nondestructive" method of screening cultured cells for their expression of c-NOS was established using depolarization with medium containing 50 mM potassium ion. These approaches were first validated using cultured SN56 (cholinergic) and N1E-115 (c-NOS-positive) neuroblastoma cells, and with primary brainstem cultures. For the cloning of novel cell lines, progenitor cells were isolated from the embryonic day 13 fetal brainstem and were immortalized by transfection with a retroviral vector that confers a temperature-sensitive SV-40 transforming activity and neomycin resistance. Cell colonies surviving in G418-containing media were isolated and cloned by dilution. Clonal cultures were expanded by growth at 33 degrees C, differentiated by switching to a low-serum medium and growth at 39 degrees C, and screened for depolarization-induced accumulation of nitrite in the medium. The subset of putative c-NOS-positive clones (about 4%) were then screened for their expression of mRNAs using RT/PCR in combination with CE/LIF. This screening protocol proved to be powerful in the rapid isolation and phenotypic characterization of immortalized progenitor cells cloned from embryonic rat brainstem.

Animals↗

Molecular indices of neuronal and glial plasticity in the hippocampal formation in a rodent model of age-induced spatial learning impairment.

Spatial learning ability was quantitated in young and aged Long-Evans rats, and molecular markers were assessed in the striatum and hippocampal formation using immunocytochemical, immunoblotting, and in situ hybridization histochemical procedures. The mRNA for beta-amyloid precursor protein (beta APP), most likely the transcript encoding the 695-amino acid form of this protein, was elevated in pyramidal and granule cells in the hippocampus of aged rats exhibiting poorer spatial learning. In immunoblots of hippocampal protein extracts, however, the level of beta APP-like immunoreactivity was depressed in the more impaired subjects. Similarly, the level in hippocampus of the mRNA for manganese-dependent superoxide dismutase (Mn-SOD), a marker of oxidative stress, was positively correlated with the degree of behavioral impairment, but immunoblotting revealed that Mn-SOD protein was depressed in the aged hippocampus compared with young. The mRNAs for the neuronal form of nitric oxide synthase and for the astrocyte marker glial fibrillary acidic protein (GFAP) were elevated in the hippocampus in correlation with the extent of learning impairment. In the striatum, the levels of mRNA and protein for several candidate genes, including GFAP, were elevated in parallel with the learning index, but these were age effects. Several hippocampal proteins were unchanged (GFAP) or depressed (beta APP and Mn-SOD) in level, despite elevations in corresponding mRNAs. In the aged cohort, hippocampal GFAP mRNA, Mn-SOD mRNA, and beta APP emerged as predictors of behavioral impairment, suggesting the involvement of these hippocampal systems in age-related cognitive impairment.

Aging↗

The mental organization of primitive personalities and its treatment implications.

A description is presented of the mental organization of primitive personalities (American borderlines, British paranoid-schizoid), as well as a generic course of analytic therapy I have sometimes experienced with them. Their mental organization may be qualitatively rather than quantitatively different from that of less disturbed persons. The differences are mostly attributable to a rudimentary psychic differentiation and integration, and compensatory pathological relationships. This configuration is hypothesized to have a unique developmental course, originating from a combination of constitutional factors and adaptation to a pathogenic interpersonal environment. Failure to appreciate the qualitative differences between the minds of the analyst and his less disturbed patients, on the one hand, and the mind of the primitive personality, on the other, may lead the analyst to employ unsuitable modes of analytic intervention with unfortunate consequences.

Borderline Personality Disorder↗

Nature, nurture, and core gender identity.

Literature about gender differences and their possible origins, and contemporary psychoanalytic formulations of gender, is reviewed. There is a broad consensus among investigators from different fields, and among psychoanalysts of different theoretical persuasions, that the modal female personality tends to be more sociocentric, and the modal male personality more self-centric. These modal personality differences may be qualitative rather than quantitative. The concept of core gender identity, which articulates the psychological root of these differences, is reexamined in the light of contemporary research into constitutional differences in the organization and activation of the brain, and an interactional model of core gender identity as a dynamic evolving phenomenon over the course of the life cycle is proposed.

Aging↗

The appropriateness of initial vancomycin dosing.

BACKGROUND: Vancomycin use has markedly increased over the past several years because of an increased incidence of resistant organisms, particularly methicillin-resistant Staphylococcus aureus. Despite the availability of dosing nomograms and the use of peak and trough levels, vancomycin dosing has remained problematic. METHODS: All intravenous vancomycin orders over a 3-month period in a community and teaching hospital were screened for appropriateness of initial dosing based on available dosing nomograms. RESULTS: Of the 48 patients who received intravenous vancomycin, only 19 (39.6%) were given initial doses that achieved the desired serum concentration. There were no significant differences in the appropriateness of initial dosing between family medicine residents, attending physicians, and private staff physicians. Older patients in our study were at higher risk for overdosing, whereas younger patients were more likely to be underdosed. In this study, nomogram use could have yielded correct initial dosages in 40 of the 48 patients (83.3%). CONCLUSIONS: Our study indicates a high percentage of inappropriate initial vancomycin dosing in a community and teaching hospital. The investigators believe inappropriate initial vancomycin dosing is common and may result in unnecessary expense, increased risk of therapeutic failures, and greater potential for adverse drug reactions. Increased use of vancomycin dosing nomograms could improve the rate of correct initial dosages.

Adult↗

The progestin-only oral contraceptive--its place in postpartum contraception.

The progestin-only oral contraceptive (POC) is not a widely-used method of contraception, possibly due to competition from other contemporary contraceptive methods or misunderstanding and prejudices among clients and/or service providers. Because of its underuse, the POC, as a contraceptive method, is under-studied. This article evaluates the general merits of the POC and its disadvantages relative to combined oral contraceptives (COCs) and other contraceptive methods, specifically during the postpartum period and particularly for breastfeeding women. We find that the POC appears to be a safe and acceptable contraceptive method for postpartum women who are fully or nearly fully breastfeeding at six months postpartum or when menstruation returns. The POC could be considered for use at any time by non-breastfeeding postpartum women. The need for empirical studies of the POC is also discussed.

Contraception↗

Purification and characterization of monodehydroascorbate reductase from soybean root nodules.

Soybean (Glycine max (L.) Merr.) root nodules contain the enzymes of the ascorbate-glutathione cycle as an important defense against activated forms of oxygen. A key enzyme in this cycle--monodehydroascorbate reductase (MR)--was purified 646-fold and appeared as a single band on SDS-PAGE with silver or Coomassie blue staining. Purified MR contained 0.7 mol FAD/mol enzyme and had a specific activity of 288 mumol NADH oxidized.min-1.mg protein-1. The enzyme was a single subunit occurring as two isozymes (MR I and MR II) with Mr values of 39,000 and 40,000. Isoelectric focusing revealed that each isozyme consisted of two forms with pl values of 4.6 to 4.7. Ferricyanide and 2,6-dichlorophenol-indophenol were effective as electron acceptors. The purified enzyme did not possess leghemoglobin reductase activity. Inhibition by p-chloromercuribenzoate indicated the involvement of a thiol group in MR activity. The Km values were 5.6, 150, and 7 microM for NADH, NADPH, and monodehydroascorbate, respectively. The pH optimum was 8 to 9. The N-terminal sequence of 10 amino acids of MR II had little homology to known protein sequences.

Amino Acid Sequence↗

Transcriptional regulation of neuromodulin (GAP-43) in mouse neuroblastoma clone N1E-115 as evaluated by the RT/PCR method.

The steady-state level of the neuromodulin transcript in the neuron-like N1E-115 cell line was measured with a method combining reverse transcription and the polymerase chain reaction (RT/PCR). Total RNA was isolated from N1E-115 cells and treated with DNAse to remove residual DNA; cDNA was synthesized from this RNA by priming with random hexamers. For PCR amplification, primers for neuromodulin were designed for regions of the coding sequence that were identical in mouse, rat, and human. In one approach (the 'ratio method'), variations in RNA yield and cDNA synthesis efficiency were controlled for by amplifying a reference (housekeeping) gene (glyceraldehyde phosphate dehydrogenase; GAPDH). To control for inter-experimental variations in PCR amplification efficiencies the data were analyzed on semi-logarithmic plots, with which the relative levels of the starting templates could be determined by extrapolating the plots to cycle number zero (0). In another approach with RT/PCR (the 'spiking method'), the absolute level of N1E-115 neuromodulin cDNA was assessed by adding known amounts of cloned human neuromodulin template to the RT/PCR assay of N1E-115 nucleic acid and comparing the increased yield of product across cycles. When the spike was added at either the cDNA level (in the form of double-stranded DNA) or at the total RNA level (as sense RNA), the levels of N1E-115 calculated were virtually the same: 509 fg and 495 fg of coding region per ug total RNA in confluent N1E-115 cells, respectively. Treatment of N1E-115 cells with 2% dimethylsulfoxide for three days elevated neuromodulin mRNA levels 5.6-fold. Conversely, treatment of N1E-115 cells with 100 nM phorbol myristate acetate for 24 h decreased the level of neuromodulin mRNA by 70%. Under carefully controlled conditions and within certain limits of precision, the RT/PCR method appears to be suitable for assessing the level of low abundance mRNA under various pharmacologically-induced conditions.

Animals↗

Chronic atropine administration up-regulates rat cortical muscarinic m1 receptor mRNA molecules: assessment with the RT/PCR.

The modulation of the rat cortical m1 muscarinic receptor mRNA was studied with a method of quantitation using the polymerase chain reaction after conversion to complementary DNA (cDNA) with AMV reverse transcriptase (RT/PCR). Primers specific to the C3 region of the m1 mRNA were employed. The y-intercepts from the linear regions of semilogarithmic plots of PCR product versus cycle number were used as measures of the levels of m1 muscarinic mRNA-measured relative to that of glyceraldehyde phosphate dehydrogenase (GAPDH) mRNA (the 'ratio' method). Alternatively, m1 mRNA in total cortical RNA samples was quantitated from the increase in product elicited by adding a known amount of exogenous m1 muscarinic cDNA sequence (the 'spiking' method). This allowed calculation of absolute level of m1 mRNA, which was 4.1 pg/micrograms total RNA. We measured the level of the rat cortical m1 mRNA after 1 week of chronic receptor blockade with atropine, showing upregulation of 154% by the GAPDH/m1 ratio method and 145% by the spiking method. That this transcriptional alteration was specific was indicated by the finding that the level of GAP-43 mRNA was not affected by atropine treatment.

Animals↗