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Biomedical subjects

E Olson

Publications and source records attributed to E Olson.

At least 37 records · Page 2Linked to original sources

Depressed adolescents with a history of sexual abuse: diagnostic comorbidity and suicidality.

OBJECTIVE: To determine the nature of comorbid psychopathology and suicidality associated with a history of sexual abuse in depressed adolescents. METHOD: Twenty-four depressed adolescent inpatients with a history of sexual abuse were compared with a matched control group of 24 depressed adolescent inpatients on measures of depression, suicidal ideation and behavior, and posttraumatic stress disorder (PTSD) symptoms. RESULTS: Depressed adolescents with a history of sexual abuse had a higher prevalence of comorbid PTSD than did those without such a history. Chronicity and severity of abuse were significant contributors to a PTSD diagnosis. No differences were found in depression severity, specific depressive symptoms, or suicidal behavior. CONCLUSION: Comorbidity of depressive disorders and PTSD are common among adolescent inpatients with a history of chronic sexual abuse. The need for thorough assessment of depression and PTSD with appropriate interventions for sexually abused adolescents is clear.

Adolescent↗

Sequential outbreak of influenza A and B in a nursing home: efficacy of vaccine and amantadine.

OBJECTIVE: To describe the sequential occurrence of influenza A and B in a nursing home, and to determine the efficacy of influenza vaccine and/or amantadine treatment with respect to incidence and sequelae. SETTING: The Jewish Home and Hospital for Aged, a skilled-care nursing facility. PARTICIPANTS: Of 499 frail older nursing home residents, 139 contracted influenza during the study period (mean age 87.5 years; SD = 6.7). The residents were followed from February through April 1988. INTERVENTION: Influenza vaccine and/or amantadine. MEASUREMENTS: Episodes of influenza and their sequelae, i.e., pneumonia, hospitalization, and death. RESULTS: The vaccine had no effect on the incidence of influenza-like illness, length of illness, or the associated death rate. It reduced the rate of pneumonia secondary to influenza A and B (relative risk = .57; 95% CI: .37 to .89; P = .023). Amantadine did not affect the attack rate of influenza nor the rate of pneumonia secondary to influenza. It was associated with decreased mortality (relative risk = 0; P = .001), and shorter length of influenza A illness (PWilcoxon = .082). Although the combination of amantadine and vaccine did not affect length of influenza (A or B) illness, it was associated with a significantly lower rate of sequelae (relative risk = .58; 95% CI: .36 to .95; P = .024). CONCLUSION: In this epidemic, the combination of amantadine and vaccine was most effective in reducing the rate of influenza-associated sequelae. The possibility of a "biphasic" epidemic prompts consideration of vaccinating nonimmunized nursing home residents, even though it may be late in the influenza season.

Aged↗

Baseline (laser) eye examination program.

Eye injury is the primary hazard associated with laser use. A baseline laser eye examination program allows for pre-injury examination and preventive early diagnosis of eye problems (glaucoma). Using portable equipment and a simplified exam format, and staffed by corpsmen and eye care providers, a rapid and accurate large-scale program that is cost efficient can be instituted. A single location for ophthalmic information coupled with recent refraction data will enhance readiness for deployment. For service members and their providers, a new and well-run eye care program will foster a strong and positive bond with the medical department.

Continuity of Patient Care↗

The inaccessibility of advance directives on transfer from ambulatory to acute care settings.

OBJECTIVE: To investigate the accessibility of patients' previously executed advance directives during an acute hospitalization. DESIGN: Retrospective chart review. SETTING: A large metropolitan teaching hospital, a 514-bed skilled nursing facility, a geriatrics ambulatory care clinic, and a geriatrics group practice office. PATIENTS: One hundred fourteen geriatric patients who had previously executed an advance directive. MAIN OUTCOME MEASURES: The medical records of 180 admissions over 3 years, 1991 through 1993, were reviewed for documentation of patients' advance directive status. RESULTS: Twenty-six percent of patients who had previously executed advance directives had their directives recognized during their hospitalization. Of the subgroup of patients who were judged not to have the capacity to make medical decisions during their admissions, 26% (14/53) had their directives recognized. When the advance directive was recognized, it appeared to influence treatment decisions in 12 (86%) of 14 cases. CONCLUSIONS: Previously executed advance directives are not accessible when patients are admitted to hospitals for acute illness. When such directives are recognized, they are used to influence medical treatment decisions. Further research is needed to define and overcome barriers to this inaccessibility.

Advance Directives↗

Spontaneous calcium transients regulate neuronal plasticity in developing neurons.

Calcium ions play critical roles in neuronal differentiation. We have recorded transient, repeated elevations of calcium in embryonic Xenopus spinal neurons over periods of 1 h in vitro and in vivo, confocally imaging fluo 3-loaded cells at 5 s intervals. Calcium spikes and calcium waves are found both in neurons in culture and in the intact spinal cord. Spikes rise rapidly to approximately 400% of baseline fluorescence and have a double exponential decay, whereas waves rise slowly to approximately 200% of baseline fluorescence and decay slowly as well. Imaging of fura 2-loaded neurons indicates that intracellular calcium increases from 50 to 500 nM during spikes. Both spikes and waves are abolished by removal of extracellular calcium. Developmentally, the incidence and frequency of spikes decrease, whereas the incidence and frequency of waves are constant. Spikes are generated by spontaneous calcium-dependent action potentials and also utilize intracellular calcium stores. Waves are produced by a mechanism that does not involve classic voltage-dependent calcium channels. Spikes are required for expression of the transmitter GABA and for potassium channel modulation. Waves in growth cones are likely to regulate neurite extension. The results demonstrate the roles of a novel signaling system in regulating neuronal plasticity, that operates on a time scale 10(4) times slower than that of action potentials.

Animals↗

Ceramide structure predicts tumor ganglioside immunosuppressive activity.

Molecular determinants of biological activity of gangliosides are generally believed to be carbohydrate in nature. However, our studies of immunomodulation by highly purified naturally occurring tumor gangliosides provide another perspective: while the immunosuppressive activity of gangliosides requires the intact molecule (both carbohydrate and ceramide moieties), ceramide structure strikingly influences ganglioside immunosuppressive activity. Molecular species of human neuroblastoma GD2 ganglioside in which the ceramide contains a shorter fatty acyl chain (C16:0, C18:0) were 6- to 10-fold more active than those with a longer fatty acyl chain (C22:0/C24:1, C24:0). These findings were confirmed in studies of ceramide species of human leukemia sialosylparagloboside and murine lymphoma GalNAcGM1b. Gangliosides that contain shorter-chain fatty acids (and are most immunosuppressive) are known to be preferentially shed by tumor cells. Therefore, the results suggest that the tumor cell is optimized to protect itself from host immune destruction by selective shedding of highly active ceramide species of gangliosides.

Animals↗

Action potentials, calcium transients and the control of differentiation of excitable cells.

Calcium influx via action potentials in differentiating nerve and muscle is regulated principally by the expression of potassium currents. Transient elevations of intracellular calcium in spontaneously active cells are necessary for normal neuronal development. The mechanisms that connect calcium elevations to long term developmental change are likely to be utilized in the mature nervous system.

Action Potentials↗

Nuclear assembly with lambda DNA in fractionated Xenopus egg extracts: an unexpected role for glycogen in formation of a higher order chromatin intermediate.

Crude extracts of Xenopus eggs are capable of nuclear assembly around chromatin templates or even around protein-free, naked DNA templates. Here the requirements for nuclear assembly around a naked DNA template were investigated. Extracts were separated by ultracentrifugation into cytosol, membrane, and gelatinous pellet fractions. It was found that, in addition to the cytosolic and membrane fractions, a component of the gelatinous pellet fraction was required for the assembly of functional nuclei around a naked DNA template. In the absence of this component, membrane-bound but functionally inert spheres of lambda DNA were formed. Purification of the active pellet factor unexpectedly demonstrated the component to be glycogen. The assembly of functionally active nuclei, as assayed by DNA replication and nuclear transport, required that glycogen be pre-incubated with the lambda DNA and cytosol during the period of chromatin and higher order intermediate formation, before the addition of membranes. Hydrolysis of glycogen with alpha-amylase in the extract blocked nuclear formation. Upon analysis, chromatin formed in the presence of cytosol and glycogen alone appeared highly condensed, reminiscent of the nuclear assembly intermediate described by Newport in crude extracts (Newport, J. 1987. Cell. 48:205-217). In contrast, chromatin formed from phage lambda DNA in cytosol lacking glycogen formed "fluffy chromatin-like" structures. Using sucrose gradient centrifugation, the highly condensed intermediates formed in the presence of glycogen could be isolated and were now able to serve as nuclear assembly templates in extracts lacking glycogen, arguing that the requirement for glycogen is temporally restricted to the time of intermediate formation and function. Glycogen does not act simply by inducing condensation of the chromatin, since similarly isolated mitotically condensed chromatin intermediates do not form functional nuclei. However, both mitotic and fluffy interphase chromatin intermediates formed in the absence of glycogen can be rescued to form functional nuclei when added to a second extract which contains glycogen. This study presents a novel role for a carbohydrate in nuclear assembly, a role which involves the formation of a particular chromatin intermediate. Potential models for the role of glycogen are discussed.

Animals↗

Maternal regulation of adrenocortical activity in the infant rat: effects of feeding.

Basal and stress-induced corticosterone release in the infant rat has been shown to be inhibited by some aspect of maternal care. The following studies examined specific maternal cues that might be responsible for this regulation. In Experiments 1 and 2, 12-day-old pups remained with their dam but were either prevented or not from feeding; at the end of 24 hr, basal and stress-induced corticosterone levels were measured. Only those animals that were able to feed showed the hyporesponsiveness characteristic of nondeprived animals, suggesting that feeding rather than some other aspect of maternal care was the critical variable. In Experiment 3, all animals were maternally deprived, and some of them were fed via an intracheek cannula. Once again, feeding led to a pronounced diminution in both basal and stress-induced levels of corticosterone. Our results point to feeding as one of the critical features responsible for the inhibitory effect of the dam on the infant's adrenocortical activity.

Animals↗

A center on ethics in long-term care.

Long-term care institutions are beginning to grapple with ethical issues on a regular basis. This has encouraged facilities to develop new mechanisms to deal with these issues. Described is a tripartite program that incorporates direct service, education, and research in ethics.

Biomedical Research↗

Ethical issues in the nursing home.

The nursing home is the site of many ethical dilemmas. The majority of these are linked to the high prevalence of dementia and other disorders that affect decisional capacity, thus dictating the need for surrogate decision-making. Even when nursing home residents have utilized advance directives to guide their future care, many issues remain in the decision-making process. This article explores the challenges of medical decision-making for a frail elderly population.

Advance Directive Adherence↗

Deletion of the regulatory domain of protein kinase C alpha exposes regions in the hinge and catalytic domains that mediate nuclear targeting.

Members of the protein kinase C (PKC) family are characterized by an NH2-terminal regulatory domain containing binding sites for calcium, phosphatidylserine, and diacylglycerol (or tumor-promoting phorbol esters), a small central hinge region and a COOH-terminal catalytic domain. We have constructed fusion proteins in which the regulatory domain of PKC alpha was removed and replaced by a 19-amino acid leader sequence containing a myristoylation consensus or by the same sequence in which the amino-terminal glycine was changed to alanine to prevent myristoylation. The goal was to generate constitutively active mutants of PKC that were either membrane bound, due to their myristoylation, or cytoplasmic. Western blotting of fractions from COS cells transfected with plasmids encoding wild-type and mutant proteins revealed that PKC alpha resided entirely in a Triton X-100 soluble (TS) fraction, whereas both the myristoylated and nonmyristoylated mutants were associated primarily with the nuclear envelope fraction. A similar mutant that lacked the 19 amino acid leader sequence was also found almost entirely in the nuclear envelope, as was a truncation mutant containing only the regulatory domain, hinge region, and a small portion of the catalytic domain. However, an additional truncation mutant consisting of only the regulatory domain plus the first one-third of the hinge region was almost entirely in the TS fraction. A nonmyristoylated fusion protein containing only the catalytic domain was also found in the nuclear envelope. Immunostaining of cells transfected with these constructs revealed that both the myristoylated and nonmyristoylated mutants were localized in nuclei, whereas wild-type PKC alpha was primarily cytoplasmic and perinuclear. Phorbol dibutyrate treatment of PKC alpha-transfected cells resulted in increased perinuclear and nuclear staining. The results are consistent with a model in which activation of PKC, by phorbol esters or by deletion of the regulatory domain, exposes regions in the hinge and catalytic domains that interact with a PKC "receptor" present in the nuclear envelope, and may explain the ability of wild-type PKC to be translocated to the nucleus under certain conditions.

Animals↗

Ethics rounds at the nursing home: an alternative to an ethics committee.

The increased attention in US medicine to medical ethics reflects in large part the "new" demography of a growing elderly population and the conflict of whether decisions regarding medical care should be based on cost-effectiveness or "human-effectiveness." Currently, about 40 percent of the nation's elderly end up in nursing homes where they confront ethical and legal dilemmas that would not arise in their own homes. In the nursing home, difficult medical-ethical decisions generally rely on two approaches: the often used but frequently invalid concept of informed consent and little used ethics committees. At The Jewish Home and Hospital for Aged in New York City we have developed a program of "ethics rounds" as an alternative to ethics committees. We conduct the rounds in the open style of a forum or clinical conference rather than with the aura of a decision-making group. We encourage the participation of patients and family and seek to educate the staff, any one of whom may choose to attend. The rounds consist of a multidisciplinary case presentation, an interview of patient and/or family, a discussion by the staff, and an overview by an ethicist. Staff response to the educational and interdisciplinary aspects of the rounds has been remarkably positive.

Ethical Review↗

Geriatric education. Part I: Efficacy of a mandatory clinical rotation for fourth year medical students.

OBJECTIVES: To describe the curriculum of a mandatory, fourth-year geriatrics clerkship and assess its impact on medical students' knowledge of geriatric medicine and attitudes toward the elderly. DESIGN: One group, before/after trial. SETTING: Mount Sinai School of Medicine of the City University of New York. PARTICIPANTS: Entire fourth year class of medical students (n = 127). INTERVENTION: Four-week-long clinical geriatrics clerkship. MEASUREMENTS: Pre- and post-rotation: test of knowledge; Aging Semantic Differential (ASD) attitude scale; Modified Maxwell-Sullivan attitude scale; questionnaire. MAIN RESULTS: Seventy percent of students found the rotation to be educationally valuable; however, only one-third of students would have taken the clerkship had it not been required. Mean geriatric knowledge score increased by 18.7% (P less than 0.001). Mean ASD attitude score did not change significantly (130.5 +/- 19.2 pre-rotation versus 126.6 +/- 18.8 post-rotation, P = 0.15), but students started the rotation with a neutral attitude. Over 90% of students agreed they would welcome elderly into their future practice. CONCLUSION: If a national curricular goal is to improve medical students' knowledge of geriatric medicine, required rather than elective rotations may be in order.

Adult↗

Activation of muscle-specific transcription by myogenic helix-loop-helix proteins.

Myogenin is a muscle-specific transcription factor that acts as a molecular switch to induce myogenesis. Myogenin shares homology with MyoD and other myogenic regulatory proteins within a basic region and helix-loop-helix (HLH) motif that mediate binding to a conserved DNA sequence (CANNTG) present in the regulatory regions of numerous muscle-specific genes. Binding of myogenin and other members of the MyoD family to DNA can be augmented upon heterodimerization with the widely expressed HLH protein E12. We have used the muscle creatine kinase (MCK) enhancer as a target to study the mechanism whereby myogenin activates muscle-specific transcription. Full activity of the MCK enhancer requires cooperative interactions between myogenin (or other myogenic HLH proteins that bind the same site) and a complex array of ubiquitous and cell type-specific nuclear factors. To define the domains of myogenin responsible for sequence-specific DNA binding, activation of muscle-specific transcription, and cooperativity with other transcription factors, we have generated an extensive series of mutants by site-directed mutagenesis and domain swapping. These mutants have revealed strong transcriptional activation domains in the N- and C-termini of myogenin that rely on a specific amino acid sequence within the DNA binding domain for activity. Myogenin's ability to induce muscle-specific transcription is subject to negative regulation by growth factor and oncogenic signals. Mechanisms through which growth signals may repress myogenin function are discussed.

Animals↗