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PubMed1987

Special considerations in integrating elderly patients into a general hospital psychiatric unit.

Geriatric patients with psychiatric disorders are highly treatable in an acute general hospital setting, but they require special attention in assessment, treatment, and discharge planning. Assessment must include the active involvement of a broad multidisciplinary team led by the psychiatrist. In the treatment process, staff must stay aware of the psychiatric symptoms, which may be obscured by medical problems, and should take therapeutic advantage of the transference issues that an age-mixed population can generate. Discharge planning must attend to resistances and the realistic dilemmas that are unique to the geriatric population. In discussing these issues, the authors describe how a university hospital inpatient unit with a full age range of adult patients adapted its milieu and staffing to treat a larger proportion of geriatric patients.

Aged↗

PubMed2002

The application of electroporation to transfect hematopoietic cells and to deliver drugs and vaccines transcutaneously for cancer treatment.

Electroporation and the associated phenomenon of electrofusion have been widely adapted as tools to a broad range of biomedical research and therapy. In this article, we summarize our adaptation of the electroporation and electrofusion technology in two fronts of cancer research and treatment. The first is genetic manipulation of hematopoietic cells for the purpose of cancer treatment. High efficiency transfection methods have been developed to transfect NK cells, peripheral blood stem cells, and bone marrow derived dendritic cells. Hybrids of tumor cells and bone marrow derived dendritic cells have been formed by electrofusion for the purpose of tumor vaccines. The second front is the use of transcutaneous electroporation to deliver anticancer drugs and vaccines across the skin. Methods to extend the upper molecular weight limit of transcutaneous electroporation have been developed. The pro-photosensitizer drug, delta-amino levulinic acid, the anticancer drug methotrexate, and peptide vaccines designed for cancer prevention and immunotherapy have been delivered transcutaneously by electroporation. These studies hold promise for the treatment of cancers in human.

Administration, Cutaneous↗

PubMed2005

Mechanical cell injury.

The tissues of the body are continually subjected to mechanical stimulation by external forces, such as gravity, and internally generated forces, such as the pumping of blood or muscle contraction. Within a physiological range, the forces elicit adaptive responses acutely (to rapidly alter function) and chronically (to remodel tissue structure to optimize load-bearing capabilities). When the forces exceed certain thresholds, injury results. To understand the mechanisms of mechanical injury at the cellular level, we must analyze the structural response of the cell to various modes of deformation and examine the biological consequences of the structural alterations caused by the trauma. This chapter reviews the mechanics of cell membrane deformation and failure. Evidence for the strain-rate-dependent, transient disruption of cell membranes, or mechanoporation, is presented for a variety of cell types. The complex interactions between the structural damage and the biological sequelae are illustrated using clinically relevant forms of cell injury. Finally, novel therapeutic approaches targeting membrane integrity are described.

Angioplasty↗

PubMed1997

Prey ingestion revealed by oesophagus and stomach temperature recordings in cormorants.

We examined the accuracy of both stomach and oesophagus temperature sensors-deployed on captive Brandt's cormorants-for determination of the mass of food ingested and the number of prey items swallowed. The oesophageal temperature sensor was a better detector of all feeding events, including that of small prey which were missed by the stomach sensor. Adapted to free-ranging animals (and coupled to data loggers for recording seawater temperature), oesophagus temperature recorders, in conjunction with both recordings of energy expenditure (e.g. doubly labelled water, heart rate) and determination of position (e.g. Argos transmitter, time/depth recorder), should provide further important insights into the foraging success of marine endotherms.

Animals↗

PubMedDate not supplied

Salvage therapy with ritonavir-boosted amprenavir/fosamprenavir: virological and immunological response in two years follow-up.

OBJECTIVE: To evaluate the efficacy of salvage regimens containing ritonavir-boosted amprenavir (APV/r) or fosamprenavir (FPV/r) in heavily pretreated protease inhibitor (PI)-experienced HIV-1 patients. METHOD: Evaluation of APV/r- or FPV/r-containing antiretroviral regimens in PI-experienced HIV-1 patients with 2 or more antiretroviral failures. Follow-up continued to 96 weeks with prospective collection of data. RESULTS: 54 episodes (48 on APV/r and 6 on FPV/r) were considered in 45 patients who had received a median of 5 prior antiretroviral regimens (range, 2-13) including a median of 3 PIs (range, 2-4). Median time of treatment at analysis was 72 weeks (range, 12-210). At baseline, plasma viral load (pVL) and CD4 cell count was 67,000 copies/mL and 167 cell/mm(3), respectively. At week 96, the median pVL was < 50 copies/mL and CD4 cell count was 519 cells/mm(3). Proportion of patients with pVL below detection was 62% at week 48 and 61% at week 96. Fifteen patients stopped treatment because of virologic failure; one presented a full resistance profile to APV/r, based on the ANRS 2003 resistance algorithm. Median trough APV plasma concentration 4 weeks after treatment initiation was 1406 ng/mL (range, 452-4321); dose adaptation was required in only 7 patients. CONCLUSION: This study provides long-term follow-up of APV/r and FPV/r in the setting of salvage therapy, showing a high and sustained rate of virologic and immunologic response.

Adult↗

PubMed2006

Model of chromosome motility in Drosophila embryos: adaptation of a general mechanism for rapid mitosis.

During mitosis, ensembles of dynamic MTs and motors exert forces that coordinate chromosome segregation. Typically, chromosomes align at the metaphase spindle equator where they oscillate along the pole-pole axis before disjoining and moving poleward during anaphase A, but spindles in different cell types display differences in MT dynamicity, in the amplitude of chromosome oscillations and in rates of chromatid-to-pole motion. Drosophila embryonic mitotic spindles, for example, display remarkably dynamic MTs, barely detectable metaphase chromosome oscillations, and a rapid rate of "flux-pacman-dependent" anaphase chromatid-to-pole motility. Here we develop a force-balance model that describes Drosophila embryo chromosome motility in terms of a balance of forces acting on kinetochores and kMTs that is generated by multiple polymer ratchets and mitotic motors coupled to tension-dependent kMT dynamics. The model shows that i), multiple MTs displaying high dynamic instability can drive steady and rapid chromosome motion; ii), chromosome motility during metaphase and anaphase A can be described by a single mechanism; iii), high kinetochore dynein activity is deployed to dampen metaphase oscillations, to augment the basic flux-pacman mechanism, and to drive rapid anaphase A; iv), modulation of the MT rescue frequency by the kinetochore-associated kinesin-13 depolymerase promotes metaphase chromosome oscillations; and v), this basic mechanism can be adapted to a broad range of spindles.

Anaphase↗

PubMedDate not supplied

Photochemistry and photobiology of cryptochrome blue-light photopigments: the search for a photocycle.

Cryptochromes are flavoproteins that exhibit high sequence and structural similarity to the light-dependent DNA-repair enzyme, photolyase. Cryptochromes have lost the ability to repair DNA; instead, they use the energy from near-UV/blue light to regulate a variety of growth and adaptive processes in organisms ranging from bacteria to humans. The photocycle of cryptochrome is not yet known, although it is hypothesized that it may share some similarity to that of photolyase, which utilizes light-driven electron transfer from the catalytic flavin chromophore. In this review, we present genetic evidence for the photoreceptive role of cryptochromes and discuss recent biochemical studies that have furthered our understanding of the cryptochrome photocycle. In particular, the role of the unique C-terminal domain in cryptochrome phototransduction is discussed.

Animals↗

PubMed2006

Growth status and academic performance in Brazilian school age children: growth retardation impairs mathematical, but not reading and spelling abilities.

AIM: To assess the effect of child growth status on academic achievement and the association between child growth and academic standing. METHOD: The heights of 722 middle-school children were measured using standard procedures and height-for-age z (HAZ) scores were calculated based on an international reference. Academic performance was assessed by an adaptation of the Wide Range Achievement Test (WRAT3) composed of Reading, Arithmetic and Spelling. RESULTS: Children in the group with higher HAZ scores performed better than children in the group with lower HAZ scores only on the Arithmetic subtest. This finding was confirmed by a multiple regression model analysis of the data. In addition, only performance on the Arithmetic subtest was positively associated with HAZ. CONCLUSION: These results indicate that growth retardation impacts specifically on the development of arithmetic (numeracy) skills and are consistent with a three-fold model of life course influences on health including latency, cumulative and pathway effects.

Achievement↗

PubMed1997

Controlling tuberculosis in an urban emergency department: a rapid decision instrument for patient isolation.

OBJECTIVES: This study examined whether data routinely available in emergency departments could be used to improve isolation decisions for tuberculosis patients. METHODS: In a large emergency department in New York City, we compared the exposure histories of tuberculosis culture-positive and culture-negative patients and used these data to develop a rapid decision instrument to predict culture-positive tuberculosis. The screen used only data that are routinely available to emergency physicians. RESULTS: The method had high sensitivity (.96) and moderate specificity (.54). CONCLUSIONS: The method is easily adaptable for a broad range of settings and illustrates the potential benefits of applying basic epidemiologic methods in a clinical setting.

Adult↗

PubMed2002

A simple method of capturing PACS and other radiographic images for digital teaching files or other image repositories.

OBJECTIVE: We sought to develop an easy-to-use method of capturing and storing radiographic images. CONCLUSION: The method that we developed can capture any digital image-including an image from a picture archiving and communication system (PACS)-using widely available, inexpensive software. Our method is easy to learn, simple to use, and inexpensive to implement. It is adaptable in a wide range of networking environments and can capture and store images rapidly for a variety of uses. It can be used without interfering with clinical workflow at the PACS workstation.

Humans↗

PubMed1985

Suppression, stress, and accommodation of transplanted islets of Langerhans.

Successful intrasplenic islet autotransplantation in dogs requires an islet cell mass considerably greater than what might be expected based on studies of subtotal pancreatectomy. Grafts of marginal function ultimately fail, suggesting severe limitations in the capacity of an islet graft to adapt. Accommodation was tested in established intrasplenic grafts by either chronically stressing the graft with mild carbohydrate intolerance induced by exogenous corticosteroids or chronically suppressing the graft with exogenous insulin. After these manipulations, insulin output into the portal vein in response to intravenous (i.v.) glucose was measured and compared with that of normal dogs and dogs receiving islet autografts with no further treatment with either steroids or insulin. Transplanted islets tolerated the two manipulations well in that neither exogenous steroid nor insulin led to failure of the graft as a consequence of either stress or protracted diminished demand. The major determinant of successful islet grafting is the endocrine competence of the initial graft. If that competence is provided at the outset, the graft can adapt to a considerable range of demand for insulin secretion.

Animals↗

PubMed1979

Response mechanisms underlying kinesthetic short-term memory.

The variables of reproduction cue, activity during retention interval, and orientation of the recall movement were manipulated to assess simultaneously the viability of two hypotheses of motor short-term memory. Data partially supported hypotheses as positive response biasing was evident in recall after a filled retention interval (Pepper & Herman, 1970) and that for a given range of movements some adaption to a central reference level occurred (Laabs, 1973).

Cues↗

PubMed1984

Mechanism for testing operant conditioning and body rocking in developmental disabilities.

A mechanism is described for testing operant conditioning and body rocking in developmentally disabled persons. The system is made up of a reinforcement dispenser, a lever-pulling mechanism, and flexible chair back for testing body rocking. Experience with the system has shown it to be sturdy and reliable, and the reinforcement dispenser to be adaptable to a wide range of food preferences.

Conditioning, Operant↗

PubMedDate not supplied

Immunoassay of human Neisseria meningitidis serogroup A antibody.

An enzyme immunoassay is described which quantitates antibodies to Neisseria meningitidis serogroup A capsular polysaccharide in human sera. Modifications of a previously developed two-day assay by Carlone et al. were made to permit analysis in one day and to be compatible with automation. The allowable variations in assay conditions and the areas in which stringent control must be maintained for consistent assay performance are described. Antigen-coating parameters, the kinetics of primary and secondary antibody incubation steps, the buffer compositions, including detergents, serum requirements, and the need for blocking steps were examined. Our modified one-day assay showed excellent agreement with the standardized method of Carlone, with a correlation coefficient between the two methods of 0.989. This assay is adaptable within a permissible range of parameters thus facilitating the implementation of the standardized assay. This will maximize the consistency of results from serum analysis for conjugate vaccine trials related to serotype A Neisseria meningitidis.

Albumins↗

PubMedDate not supplied

Immunoassay of human Neisseria meningitidis serogroup A antibody.

Adult↗

PubMed1992

The auto-regulation model: a unified concept of how HIV regulates its infectivity, pathogenesis and persistence.

The life cycle of HIV can be divided into two distinct stages: intracellular and extracellular. The prevailing view is that the intracellular stage provides the only locus for regulating the virus in response to physiologic stimuli. Such regulation is accomplished by modulating the rates of transcription, translation and viral assembly. The extracellular stage consists of physical processes such as diffusion, adhesion and penetration of cells by viral particles. These latter processes are commonly thought to be "automatic" and not subject to regulation. For the past several years, we have developed means of more carefully measuring and characterizing the extracellular stage of HIV infection, and we have obtained evidence indicating that novel regulatory processes do, in fact, take place during this extracellular stage. We believe that this extracellular regulation permits HIV to adapt to a wide range of physiologic cell densities, to maintain persistent but slow growing infection, and to defeat the protective activity of humoral blockers. The overall purpose of this review is to consider our evidence for this hypothesis.

CD4 Antigens↗

PubMed2000

Mapping of the region of complement receptor (CR) 1 required for Plasmodium falciparum rosetting and demonstration of the importance of CR1 in rosetting in field isolates.

The malaria parasite Plasmodium falciparum induces a number of novel adhesion properties in the erythrocytes that it infects. One of these properties, the ability of infected erythrocytes to bind uninfected erythrocytes to form rosettes, is associated with severe malaria and may play a direct role in the pathogenesis of disease. Previous work has shown that erythrocytes deficient in complement receptor (CR) 1 (CR1, CD35; C3b/C4b receptor) have greatly reduced rosetting capacity, indicating an essential role for CR1 in rosette formation. Using deletion mutants and mAbs, we have localized the region of CR1 required for the formation of P. falciparum rosettes to the area of long homologous repeat regions B and C that also acts as the binding site for the activated complement component C3b. This result raises the possibility that C3b could be an intermediary in rosetting, bridging between the infected erythrocyte and CR1. We were able to exclude this hypothesis, however, as parasites grown in C3-deficient human serum formed rosettes normally. We have also shown in this report that rosettes can be reversed by mAb J3B11 that recognizes the C3b binding site of CR1. This rosette-reversing activity was demonstrated in a range of laboratory-adapted parasite strains and field isolates from Kenya and Malawi. Thus, we have mapped the region of CR1 required for rosetting and demonstrated that the CR1-dependent rosetting mechanism occurs commonly in P. falciparum isolates, and could therefore be a potential target for future therapeutic interventions to treat severe malaria.

Animals↗

PubMed2004

Conformational restraints and flexibility of 14-meric peptides in complex with HLA-B*3501.

Human HLA-B*3501 binds an antigenic peptide of 14-aa length derived from an alternative reading frame of M-CSF with high affinity. Due to its extraordinary length, the exact HLA binding mode was unpredictable. The crystal structure of HLA-B*3501 at 1.5 A shows that the N and C termini of the peptide are embedded in the A and F pockets, respectively, similar to a peptide of normal length. The central part of the 14-meric peptide bulges flexibly out of the groove. Two variants of the alternative reading frame of M-CSF peptide substituted at P2 or P2 and P9 with Ala display weak or no T cell activation. Their structure differs mainly in flexibility and conformation from the agonistic peptide. Moreover, the variants induce subtle changes of MHC alpha-helical regions implicated as critical for TCR contact. The TCR specifically recognizing this peptide/MHC complex exhibits CDR3 length within the normal range, suggesting major conformational adaptations of this receptor upon peptide/MHC binding. Thus, the potential antigenic repertoire recognizable by CTLs is larger than currently thought.

Alanine↗