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Mild cognitive impairment in the oldest old.

BACKGROUND: No data exist on whether the syndrome of amnestic mild cognitive impairment occurs in the oldest old, or if the relationships for functional status and neuropsychometric performance based on clinical diagnosis hold true in this age group. DESIGN/METHODS: The authors performed comprehensive neurologic evaluations, neuropsychometric testing, and functional assessments on a sample of 90- to 100-year-old residents of Rochester, MN. Subjects were diagnosed as normal or with amnestic mild cognitive impairment (MCI) or dementia according to well-accepted criteria. Data on the following measures were collected and analyzed: Record of Independent Living (ROIL), Mini-Mental State Examination (MMSE), Dementia Rating Scale (DRS), Trailmaking Test (TMT), and modified version of the Free and Cued Selective Reminding Test (FCSRT). RESULTS: Data on 111 subjects (56 normal, 13 MCI, and 42 dementia) were analyzed. On the ROIL, functional capacity to carry out activities of daily living was worse for patients with dementia compared to patients with MCI and normal subjects, but did not differ between MCI and normal subjects. Scores on the MMSE, DRS, and TMT-A were worse in the dementia group compared to the normal group, and in the dementia group compared to MCI, but scores on these measures for normal subjects compared to patients with MCI were not different. Scores on the FCSRT and memory subtest of the DRS showed differences among all three groups. CONCLUSION: In spite of the advanced age of the cohort, the relationship between cognitive and functional performance and clinical diagnosis follows patterns previously described in younger samples of normal subjects, subjects with amnestic mild cognitive impairment, and subjects with dementia.

Age Distribution↗

The American medical economy: problems and perspectives.

Federal initiatives during the last decade have resulted in considerable changes in the American medical economy. Large sums of money have been infused into the system under Medicare and Medicaid, substantially improving access to care for the aged and the poor. At the same time, the improvements in knowledge and medical technology that have occurred have been largely underwritten by the tremendous increases in third-party payment mechanisms. These costly new technologies have contributed significantly to the high cost of hospital care and to the increased specialization of physician's services. The chronic inflation in medical expenditures and the explosive increases in Federal subsidization of medical care have led to questions concerning the efficacy of medical care for improving health status. There is a considerable lack of evidence for a causal relationship between what is done to the patient and the outcome of the medical care process as measured by mortality, disability, and capacity to carry on activities. Various attempts have been made to control the chronic inflation of medical expenditures, but success is uneven and elusive. Alternatives in financing medical care services currently under debate include various provisions to control costs and utilization, but attention should be directed to organizing American medical care services in general, toward the more rational use of our resources.

Costs and Cost Analysis↗

Transformation of yeast using bioactive beads with surface-immobilized yeast artificial chromosomes.

Yeast artificial chromosomes (YACs) are useful cloning vectors with the capacity to carry large DNA inserts. The largest barrier using such large DNA molecules in transformation experiments has been their physical instability in a solution. We developed a new method for transforming yeast with chromosome-sized DNA. The method uses bioactive beads composed of calcium alginate to immobilize yeast chromosomal DNAs. Chromosomal DNA immobilized on bioactive beads is physically stable when compared with naked chromosomal DNAs. The bead-mediated transformation performed well, not only with respect to the transformation frequency, but also in successful transformation using split chromosomal DNA that exceeded 450 kb in size. In this chapter we introduce a new method for transforming yeast using bioactive beads. In conjunction with genomic YAC libraries and the yeast chromosome-splitting method, this technique will pave the way to stable and effective transfer of YACs into yeast cells.

Alginates↗

Efficient transformation of the beetle Tribolium castaneum using the Minos transposable element: quantitative and qualitative analysis of genomic integration events.

Genetic transformation in insects holds great promise as a tool for genetic manipulation in species of particular scientific, economic, or medical interest. A number of transposable elements have been tested recently as potential vectors for transformation in a range of insects. Minos is one of the most promising elements because it appears to be active in diverse species and has the capacity to carry large inserts. We report here the use of the Minos element as a transformation vector in the red flour beetle Tribolium castaneum (Coleoptera), an important species for comparative developmental and pest management studies. Transgenic G(1) beetles were recovered from 32.4% of fertile G(0)'s injected with a plasmid carrying a 3xP3-EGFP-marked transposon and in vitro synthesized mRNA encoding the Minos transposase. This transformation efficiency is 2.8-fold higher than that observed when using a plasmid helper. Molecular and genetic analyses show that several independent insertions can be recovered from a single injected parent, but that the majority of transformed individuals carry single Minos insertions. These results establish Minos as one of the most efficient vectors for genetic transformation in insects. In combination with piggyBac-based transgenesis, our work allows the introduction of sophisticated multicomponent genetic tools in Tribolium.

Animals↗

Evidence for the presence of a kininogen-like species in a case of total deficiency of low and high molecular weight kininogens.

Low and high molecular weight kininogens (LK and HK), containing 409 and 626 amino acids with masses of approximately 65 and 120 kDa after glycosylation, respectively, are coded by a single gene mapped to the human chromosome 3 by alternative splicing of the transcribed mRNA. The NH2-termini Glu1-Thr383 region, identical in LK and HK, contains bradykinin (BK) moieties Arg363-Arg371. LK, HK and their kinin products Lys-BK and BK are involved in several biologic processes. They are evolutionarily conserved and only 7 patients, all apparently normal, have been reported to lack them. In one of these patients (Williams' trait), a codon mutation (Arg178-->stop) has been blamed for the absence of LK and HK. However, using Western blots with 2 monoclonal anti-HK antibodies, one that recognizes the region common to LK and HK and the other that recognizes only HK, 1 detected approximately 110-kDa bands in the plasma of this LK/HK-deficient patient vs approximately 120-kDa bands in normal human and ape plasmas. With polyclonal anti-Lys-BK antibody, which strongly detects BK cleaved at its COOH-terminus in purified HK, 1 detected approximately 110-kDa bands in the normal and the deficient plasmas. Western blots with a monoclonal anti-prekallikrein (PK) antibody showed that surface activation of PK and distribution of PK activation products, both dependent on HK, were similar in these plasmas. These findings suggest that a mutant gene yielded a kininogen-like species possibly involving aberrant mRNA splicing-structurally different from normal HK, but apparently with the capacity to carry out seemingly vital HK functions.

Antibodies, Monoclonal↗

Transformation of yeast using calcium alginate microbeads with surface-immobilized chromosomal DNA.

Yeast artificial chromosomes (YACs) are useful cloning vectors that have the capacity to carry large DNA inserts. The largest barrier to using such large DNA molecules in transformation experiments has been their physical instability in solution. We developed a new method of transforming yeast using chromosome-sized DNA. The method uses calcium alginate microbeads to immobilize high-density yeast chromosomal DNA. Chromosomal DNA immobilized on microbeads is physically stabilized compared with naked chromosomal DNA. The microbead-mediated transformation performed well, not only with respect to the transformation frequency with large DNA molecules (> 100 kb) but also in successful transformation using split chromosome DNA that exceeded 450 kb.

Adsorption↗

Viral vectors for gene transfer: a review of their use in the treatment of human diseases.

The efficient delivery of therapeutic genes and appropriate gene expression are the crucial issues for clinically relevant gene therapy. Viruses are naturally evolved vehicles which efficiently transfer their genes into host cells. This ability made them desirable for engineering virus vector systems for the delivery of therapeutic genes. The viral vectors recently in laboratory and clinical use are based on RNA and DNA viruses processing very different genomic structures and host ranges. Particular viruses have been selected as gene delivery vehicles because of their capacities to carry foreign genes and their ability to efficiently deliver these genes associated with efficient gene expression. These are the major reasons why viral vectors derived from retroviruses, adenovirus, adeno-associated virus, herpesvirus and poxvirus are employed in more than 70% of clinical gene therapy trials worldwide. Among these vector systems, retrovirus vectors represent the most prominent delivery system, since these vectors have high gene transfer efficiency and mediate high expression of therapeutic genes. Members of the DNA virus family such as adenovirus-, adeno-associated virus or herpesvirus have also become attractive for efficient gene delivery as reflected by the fast growing number of clinical trials using these vectors. The first clinical trials were designed to test the feasibility and safety of viral vectors. Numerous viral vector systems have been developed for ex vivo and in vivo applications. More recently, increasing efforts have been made to improve infectivity, viral targeting, cell type specific expression and the duration of expression. These features are essential for higher efficacy and safety of RNA- and DNA-virus vectors. From the beginning of development and utilisation of viral vectors it was apparent that they harbour risks such as toxicities, immunoresponses towards viral antigens or potential viral recombination, which limit their clinical use. However, many achievements have been made in vector safety, the retargeting of virus vectors and improving the expression properties by refining vector design and virus production. This review addresses important issues of the current status of viral vector design and discusses their key features as delivery systems in gene therapy of human inherited and acquired diseases at the level of laboratory developments and of clinical applications.

Adenoviridae↗

Perfluorocarbon as blood substitute in clinical applications and in war casualties.

The results of infusion of fluorocarbon blood substitute (FCBS) in surgical patients (including war casualties) are presented. One hundred and forty patients (male 82, female 58, age 17-71 years) were infused with 200-1,000 ml of FCBS during operation. Fourteen cases were emergency operations because of trauma and/or hemorrhagic shock and 113 cases were selective operations. Thirteen cases were war casualties. Seventy-three patients also received 300-2,700 ml of banked blood. The vital signs and ECG received normal and blood pressure increased significantly (compared to pre-infusion P 0.01) during and after infusion. Hemoglobin and RBC values did not change significantly, however, WBC counts increased for a week. PaO2 increased significantly (P less than 0.05) compared with preinfusion or the control group (infused with same dose of HES). pH and PaCO2 did not change remarkably. Platelet count decreased transiently, but platelet function did not change, nor did coagulation function. Fibrinolysis was more active, but recovered in 24 hours. The decrease of CH50 was observed immediately after infusion and recovered in 72 hours. There was no change in hepatic and renal function; however, transient increase of SGPT was found in 3 cases. The results suggested that the FCBS had the capacity of carrying oxygen and expanding plasma volume. It is efficient to apply as an alternative to blood transfusion during operation in treatment of traumatic and/or hemorrhagic shock even in war casualties. Transient chest tightness and/or flushing were found in 5 cases at the beginning of the infusion, and disappeared when the infusion slowed down. Urticaria after infusion were observed in 2 cases.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Repetition priming in an auditory lexical decision task: effects of lexical status.

The effect of lexical status on the time course of repetition priming was examined in an auditory lexical decision task. Words and nonwords were repeated at lags of 0, 1, 4, and 8 items (Experiment 1A) and 0, 2, 4, and 8 items (Experiment 1B). The pattern of repetition effects differed for words and nonwords in that repetition priming for nonwords at lag 0 was significantly greater than for words. The magnitude of this effect decreased when one or more items intervened. A second experiment, replicating Experiment 1A with visual presentation, clarified that the greater magnitude of repetition priming for nonwords at lag 0 is unique to the auditory modality. This finding suggests that in the course of forming a stable perceptual representation, the details of the acoustic/phonological information of an auditory stimulus are more readily available for nonwords than for words. The capacity to carry this phonological information is limited, however, and can only be maintained until another stimulus is encountered.

Adult↗

[Critical ischemia in elderly patients. Evaluation of the effect of two different methods of Iloprost therapy on the efficacy, tolerance, modification of quality of life and self-sufficiency].

BACKGROUND: The use of Iloprost in the treatment of critical leg ischemia in very old patients can lead to tolerability problems, related to the drug used and to the kind of patient treated. The aim of this study was to evaluate the impact of this therapy on the activities of daily living and on the quality of life of the patient together with its efficacy and tolerability. METHODS: We studied 20 subjects (mean age 74 +/- 6.8) divided in 2 groups homogeneous for age, seriousness of the disease and presence of diabetes mellitus. In the first group Iloprost was administered for 6 hours, for 28 consecutive days, in the second group for 6 hours, two times a day for 14 consecutive days. In each group we observed the following parameters before and after treatment: clinical evaluation of pain and use of analgesics, ADL and SK39 questionnaire, ankle/arm index c.w. Doppler, strain gauge plethismography of lower limbs, TcPO2 at the back-feet level. RESULTS: Treatment was well tolerated in both groups where we observed a similar reduction of pain, a reduction in the instrumental indexes which express the microcirculatory activity, an improvement in the quality of life and in the capacity to carry out everyday activities. The double daily administration of Iloprost did not cause any significant side effect in the subjects studied, and a better responsiveness to the pain symptomatology was observed. CONCLUSIONS: Iloprost can be used in the treatment of critical leg ischemia even for very old patients with good tolerability and effectiveness. In the double daily administration no relevant side effect was observed. This approach is to be preferred also in terms of cost-effectiveness.

Activities of Daily Living↗

States and health care reform: the importance of program implementation.

The recent debate on national health care reform marked another case of policy being considered without reference to how--or even if--it could be implemented. The debate revolved around broad issues, such as universal versus partial coverage, mandatory versus voluntary alliances, and the respective roles of government and the market in health care. The ease or even the possibility of successful implementation was not an ingredient in evaluating proposals. The burden of making health care reform work falls to the states. Whether in response to national reform or in implementing their own programs, they must move from a general reform blueprint to an actual program that delivers services. The hands-on role of the states in designing and operating programs makes their implementation duties both unavoidable and critical. This chapter explores implementation issues that should be considered an integral part of planning for health care reform, at both the federal and the state level. The chapter has two goals. First, it makes a case for altering the usual approach to designing reform and recommends paying attention to implementation early in the policy process, rather than treating it as an afterthough. Second, it is intended to help policymakers design implementable programs and anticipate pitfalls. To achieve these goals, it examines the state role in health care reform; state capacity to carry out this role; examples of state health care reform initiatives and lessons for implementation drawn from these efforts; and barriers to successful implementation. The chapter concludes with recommendations for policymakers.

Eligibility Determination↗

[The evaluation of mental capability to use firearms: practical and ethical questions].

UNLABELLED: This paper presents the results of a survey of 116 men who underwent psychiatric evaluation of their capacity to carry firearms. The data was collected using a standardized form. The results show the following profile: male, married with children, high school education and requesting the license to carry firearms due to reasons related to their type of work or their place of residence. The results point to several conclusions regarding the way in which these evaluations are performed. RECOMMENDATION: To centralize the process of evaluating the types of dangers within the auspices of one single medical institution.

Child↗

Resistance of MCF-7 cells to dimethylbenz(a)anthracene-induced apoptosis is due to reduced CYP1A1 expression.

We have developed a series of aryl hydrocarbon (AH)-resistant cell lines derived from MCF-7 human breast epithelial cancer cells by continuous exposure to the AH benzo[a]pyrene. These cell lines display cross-resistance to the mammary carcinogen dimethylbenz[a]anthracene (DMBA). Apoptosis induced by exposure to DMBA is greatly decreased in the resistant cell lines compared to the wild-type, in proportion to the level of resistance. Apoptosis induced by DMBA could be blocked by inhibitors of DMBA metabolism such as alpha-naphthoflavone and diosmetin. We therefore examined the resistant cell lines for their ability to metabolize DMBA and for the formation of DMBA-DNA adducts, and found that both parameters were decreased compared to wild-type cells in proportion to the level of resistance. When exposed to DMBA or 2,3,7,8-tetrachlorodibenzo-p-dioxin, the resistant cell lines have a diminished capacity to carry out ethoxyresorufin-O-deethylation, indicating that the induction of cytochrome P450 1A1 (CYP1A1) enzyme is impaired. We therefore examined the expression of the CYP1A1 gene, and found reduced levels of both CYP1A1 mRNA and CYP1A1-promoter controlled transcription in resistant cells compared to the wild-type. The deleterious effects of AHs are believed to be mediated by the aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor which regulates CYP1A1 expression. Resistant cell lines had a reduced expression of the AhR, as measured at the mRNA and protein levels. These data demonstrate that AH resistance in these cells is mediated by changes in the signal transduction pathway which regulates CYP1A1 expression.

9,10-Dimethyl-1,2-benzanthracene↗