Electrocardiogram abnormalities in older individuals by race and ethnicity.

BACKGROUND: Aging is associated with many ECG changes. ECG abnormalities are known to be more prevalent with age and differ across race and ethnicity, yet there are limited studies categorizing the ECG changes in the older population and the differences seen among racial groups. We sought to determine ECG differences associated with race and ethnicity in this ethnically diverse, elderly population. METHODS: The ECG parameters of subjects between the ages of 75 and 99 years from a large and diverse inner-city patient population were analyzed. Subjects were grouped into one of four categories: Hispanic, Black, Non-Hispanic White, or Other for analysis. Rhythm, axis, voltage, and conduction parameters were determined according to the 12 SL algorithm and interpretation statements (GE Healthcare, Wauwatosa, Wisconsin) that were confirmed by an overreading cardiologist. RESULTS: 38,238 subjects were included. Of all groups, Non-Hispanic Whites exhibited more conduction abnormalities such as bundle branch block compared to the other groups, as well as the highest incidence of atrial fibrillation (AF) (12.6%, p < 0.05). Hispanics had the highest proportion of normal sinus rhythm. Blacks exhibited the least amount of AF (6.3%), as well as the highest incidence of LVH (25.5%), RAD (13.5%), and the largest percentage of abnormal ECGs (72.8%). CONCLUSION: Significant differences among the elderly of different race and ethnicity were noted with most parameters.

Dental clinical attire and infection-control procedures. Patients' attitudes.

BACKGROUND: The authors surveyed adults in military and civilian dental practices about infection-control procedures and clinical attire to see if patients' attitudes had changed with the alteration of infection-control procedures over the last two decades. METHODS: The authors surveyed 1,500 adults, using a written questionnaire at two military hospital dental practices and at four civilian dental offices, which included two general practices, one periodontal practice and one orthodontic practice. RESULTS: The authors found that the use of name tags and patient safety glasses during treatment were preferred by 52.0 percent and 53.4 percent, respectively, of respondents in military facilities. Respondents had no preference about dentists' clothing, use of protective glasses for examinations or head cover use. A majority of respondents preferred that dentists wear glasses when performing treatment (54.1 percent), and 77.4 percent of respondents preferred that dentists wear masks when providing their care. Respondents preferred the use of plastic barriers, and 63.0 percent said it made them feel confident that proper infection-control procedures were followed. A majority of respondents (52.3 percent) said they would be concerned if barriers were not used. CONCLUSIONS: Military and civilian respondents had similar perceptions of infection-control procedures. Respondents said they preferred that dentists wear name tags in group practices and use masks and protective glasses when performing treatment. The use of plastic barriers made respondents feel confident that proper infection-control procedures were being followed. PRACTICE IMPLICATIONS: This study can be used by dental practices to review their infection-control procedures and how patients perceive them. Dentists may decide to implement some of these procedures, especially those that are not required, and that improve customer satisfaction.

Recombinant virus vaccination against "self" antigens using anchor-fixed immunogens.

To study the induction of anti-"self" CD8+ T-cell reactivity against the tumor antigen gp100, we used a mouse transgenic for a chimeric HLA-A*0201/H-2 Kb molecule (A2/Kb). We immunized the mice with a recombinant vaccinia virus encoding a form of gp100 that had been modified at position 210 (from a threonine to a methionine) to increase epitope binding to the restricting class I molecule. Immunogens containing the "anchor-fixed" modification elicited anti-self CD8+ T cells specific for the wild-type gp100(209-217) peptide pulsed onto target cells. More important, these cells specifically recognized the naturally presented epitope on the surface of an A2/Kb-expressing murine melanoma, B16. These data indicate that anchor-fixing epitopes could enhance the function of recombinant virus-based immunogens.

Which end is up? Two representations of orientation in visual search.

What is the orientation of an object? A simple line has an axis of orientation. That line, turned upside-down, is indistinguishable from the original line. Thus, the possible orientations of a line range from 0 to 180 degrees. Most objects, however, have an axis and a polarity. A polar object, turned upside-down, looks upside-down. Accordingly, the orientations of a polar object range from 0 to 360 degrees. A series of visual search experiments were run to determine if preattentive processes represent orientation in a 180 or a 360 degrees framework. Results suggest that preattentive orientation is represented in 180 degrees. Experiments 1 and 4 show that search for a target rotated 90 degrees from the distractors is more efficient than search for a target rotated 180 degrees from the distractors. Experiments 2, 3, and 5 use a variety of different stimuli to demonstrate that search for targets rotated 180 degrees from distractors is inefficient.

Generation of polyclonal rabbit antisera to mouse melanoma associated antigens using gene gun immunization.

Lymphocytes from patients with melanoma have been used to clone melanoma associated antigens which are, for the most part, nonmutated melanocyte tissue differentiation antigens. To establish a mouse model for the use of these 'self' antigens as targets for anti-tumor immune responses, we have employed the mouse homologues of the human melanoma antigens Tyrosinase, Tyrosinase Related Protein-1 (TRP-1), gp100, and MART-1. We sought to generate antisera against these proteins for use in the construction of experimental recombinant and synthetic anti-cancer vaccines, and for use in biologic studies. Using genes cloned from the B16 mouse melanoma or from murine melanocytes, we immunized rabbits with plasmid DNAs coated onto microscopic gold beads that were then delivered using a hand-held, helium-driven 'gene gun'. This strategy enabled us to generate polyclonal rabbit sera containing antibodies that specifically recognized each antigen, as measured by immunostaining of vaccinia virus infected cells. The sera that we generated specifically for TRP-1, gp100, and MART-1 recognized extracts of the spontaneous murine melanoma, B16. The identities of the recognized proteins was confirmed by Western blot analysis. The titers and specificities of these antisera were determined using ELISA. Interestingly, serum samples generated against murine MART-1 and gp100 developed antibodies that were cross-reactive with the corresponding human homologues. Recognition of human gp100 and murine Tyrosinase appeared to be dependent upon conformational epitopes since specificity was lost upon denaturation of the antigens. These antisera may be useful in the detection, purification and characterization of the mouse homologues of recently cloned human tumor associated antigens and may enable the establishment of an animal model of the immune consequences of vaccination against 'self antigens.

Vulnerability factors in Sylvia Plath's suicide.

Using the conceptual framework of a developmental pathway, this study links together events in the life of Sylvia Plath, beginning with her father's death when she was 8 years old and ending with her suicide at age 30. Unresolved grief for her father led to a symbiotic attachment to her mother characterized by a compulsive drive for achievement and praise. After a near-fatal suicide attempt at age 20 following failure to meet perfectionistic ideals, she recompensated, transferring her dependency needs into a symbiotic marriage to an English poet she narcissistically idealized. Her suicide followed soon after the collapse of the marriage. Emphasis is placed throughout on her unwillingness to accept personal imperfections, as well as on the search for a father substitute.

Enhancing efficacy of recombinant anticancer vaccines with prime/boost regimens that use two different vectors.

BACKGROUND: The identification of tumor-associated antigens and the cloning of DNA sequences encoding them have enabled the development of anticancer vaccines. Such vaccines target tumors by stimulating an immune response against the antigens. One method of vaccination involves the delivery of antigen-encoding DNA sequences, and a number of recombinant vectors have been used for this purpose. To optimize the efficacy of recombinant vaccines, we compared primary and booster treatment regimens that used a single vector (i.e., homologous boosting) with regimens that used two different vectors (i.e., heterologous boosting). METHODS: Pulmonary tumors (experimental metastases) were induced in BALB/c mice inoculated with CT26.CL25 murine colon carcinoma cells, which express recombinant bacterial beta-galactosidase (the model antigen). Protocols for subsequent vaccination used three vectors that encoded beta-galactosidase--vaccinia (cowpox) virus, fowlpox virus, naked bacterial plasmid DNA. Mouse survival was evaluated in conjunction with antibody and cytotoxic T-lymphocyte responses to beta-galactosidase. RESULTS: Heterologous boosting resulted in significantly longer mouse survival than homologous boosting (all P<.0001, two-sided). Potent antigen-specific cytotoxic T lymphocytes were generated following heterologous boosting with poxvirus vectors. This response was not observed with any of the homologous boosting regimens. Mice primed with recombinant poxvirus vectors generated highly specific antibodies against viral proteins. CONCLUSIONS: The poor efficacy of homologous boosting regimens with viral vectors was probably a consequence of the induction of a strong antiviral antibody response. Heterologous boosting augmented antitumor immunity by generating a strong antigen-specific cytotoxic T-lymphocyte response. These data suggest that heterologous boosting strategies may be useful in increasing the efficacy of recombinant DNA anticancer vaccines that have now entered clinical trials.

A family intervention to delay nursing home placement of patients with Alzheimer disease. A randomized controlled trial.

OBJECTIVE: To determine the long-term effectiveness of comprehensive support and counseling for spouse-caregivers and families in postponing or preventing nursing home placement of patients with Alzheimer disease (AD). DESIGN: Randomized controlled intervention study. SETTING: Outpatient research clinic in the New York City metropolitan area. PARTICIPANTS: Referred, volunteer sample of 206 spouse-caregivers of AD patients who enrolled in the study during a 3 1/2-year period. All patients were living at home at baseline and had at least 1 relative living in the area. INTERVENTION: Caregivers in the treatment group were provided with 6 sessions of individual and family counseling within 4 months of enrollment in the study and were required to join support groups. In addition, counselors were available for further counseling at any time. MAIN OUTCOME MEASURE: Time from enrollment of caregivers in the study to placement of the AD patients in a nursing home. RESULTS: Using Kaplan-Meier survival analysis, we estimated that the median time (weighted average of estimates for male and female caregivers) from baseline to nursing home placement of AD patients was 329 days longer in the treatment group than in the control group (z=2.29; P=.02). The relative risk (RR) from a Cox proportional hazard model of nursing home placement (intent-to-treat estimate) after adjusting for caregiver sex, patient age, and patient income was 0.65 (95% confidence interval [CI], 0.45 to 0.94; P=.02), indicating that caregivers were approximately two thirds as likely to place their spouses in nursing homes at any point in time if they were in the treatment group than if they were in the control group. Treatment had the greatest effect on risk of placement for patients who were mildly demented (RR, 0.18; 95% CI, 0.04 to 0.77) or moderately demented (RR, 0.38; 95% CI, 0.17 to 0.82). CONCLUSIONS: A program of counseling and support can substantially increase the time spouse-caregivers are able to care for AD patients at home, particularly during the early to middle stages of dementia when nursing home placement is generally least appropriate.

Overview of methodologic issues for pharmacologic trials in mild, moderate, and severe Alzheimer's disease.

To address the issue of mild, moderate, and severe Alzheimer's disease (AD), it is necessary to initially establish some agreement on terminology. In recent decades, these terms have frequently been defined using screening instrument scores with measures such as the Mini-Mental State Examination (MMSE). There are many problems with this approach, perhaps the most salient of which is that it has contributed to the total and tragic neglect of patients with severe AD. An alternative approach to the classification of AD severity is staging. This approach has advanced to the point where moderately severe and severe AD can be described in detail. Procedures for describing this previously neglected latter portion of AD have recently been extensively validated. Staging is also uniquely useful at the other end of the severity spectrum, in differentiating early aging brain/behavior changes, incipient AD, and mild AD. Temporally, with staging procedures, it is possible to track the course of AD approximately three times more accurately than with the MMSE. The net result of the advances in AD delineation is that issues such as prophylaxis, modification of course, treatment of behavioral disturbances, loss of ambulation, progressive rigidity, and the development of contractures in AD patients can now be addressed in a scientifically meaningful way that will hopefully bestow much benefit in AD patients and those who care for them.

Mortality and temporal course of probable Alzheimer's disease: a 5-year prospective study.

Alzheimer's disease (AD) is associated with an increased mortality in comparison with aged control populations. The relationship between the clinical and the temporal course of AD has not been well studied over significant intervals. Community-residing patients with probable AD (N = 103, 42 men, mean age = 70.2 +/- 8.0 years) were studied at baseline on demographic and clinical variables, including measures of global deterioration (Global Deterioration Scale; GDS), mental status and cognition (e.g., Mini-Mental State Examination; MMSE), and functional impairment (Functional Assessment Staging; FAST). Baseline characteristics included a GDS range of Stage 4, 5, or 6 (38.8%, 39.8%, and 21.4%, respectively) and a mean MMSE score of 15.4 +/- 5.6. The mean follow-up interval was 4.6 +/- 1.4 years. Follow-ups were done blind to baseline measures and when necessary were conducted in residential and nursing home settings. Of locatable subjects (n = 95, 92%), 30 (31.6%) were decreased. Survivors (n = 65) had a mean GDS stage of 6.2 +/- 0.9 and a mean MMSE score of 5.1 +/- 6.9; 51% had MMSE scores of 0. Increased age and male gender, but not baseline clinical dementia variables, increased the risk of death (ps < .01). Change in clinical variables correlated significantly with time elapsed (r = .32, p < .05, for MMSE change, to r = .48, p < .001, for GDS change). Significant variance in temporal change (i.e., time elapsed) was accounted for by change in two of the five clinical measures studied (i.e., GDS and FAST; multiple r = .53). The results support previous estimates of mean duration of the GDS and FAST stages. For subjects with probable AD followed over approximately 5 years, clinical variables changed significantly over time in survivors. However, the majority of temporal variance in the course of AD remains unexplained.

A comprehensive support program: effect on depression in spouse-caregivers of AD patients.

Caregivers of Alzheimer's disease patients often suffer from depression. Using a longitudinal treatment/control study, we examined the effects of a comprehensive support program on depression in spouse-caregivers. This psychosocial intervention program treats the primary caregiver and family members over the entire course of the disease through individual and family counseling, the continuous availability of ad hoc counseling, and support group participation. In the first year after intake, the control group became increasingly more depressed, whereas the treatment group remained stable. By the eighth month, treated caregivers were significantly less depressed than those in the control group. These results suggest that enhancing long-term social support can have a significant impact on depression in caregivers.

The use of addition reaction silicone materials in the fabrication of ear plugs.

Ear plugs are currently recommended for patients with tympanostomy tubes or for those requiring noise attenuation. Most techniques used today require a two-step process involving an impression of the ear followed by laboratory fabrication from a cast. This paper presents an alternative technique which is accomplished in one appointment and eliminates the laboratory phase by using addition reaction silicones. The indications for ear plugs and clinical results achieved with this new technique were also reviewed.

Minimal determinant expressed by a recombinant vaccinia virus elicits therapeutic antitumor cytolytic T lymphocyte responses.

Anticancer vaccine strategies can now target intracellular antigens that are involved in the process of malignant transformation, such as oncogene products or mutated tumor suppressor genes. Fragments of these antigens, generally 8-10 amino acids in length and complexed with MHC class I molecules, can be recognized by CD8+ T lymphocytes (TCD8+). To explore the possibility of using a genetically encoded, minimally sized fragment of an intracellular antigen as an immunogen, we constructed a recombinant vaccinia virus encoding an 8-residue peptide derived from chicken ovalbumin that is known to associate with the mouse H-2Kb molecule. Compared to standard methods of immunization, recombinant molecule. Compared to standard methods of immunization, recombinant vaccinia virus expressing the minimal determinant as well as full length ovalbumin were the only approaches that elicited specific primary lytic responses in C57BL/6 mice against E.G7OVA, a transfectant of the murine thymoma EL4 containing the ovalbumin gene. Stimulating these effectors in vitro with OVA257-264 peptide induced H-2Kb-restricted TCD8+ that not only lysed but also specifically secreted IFN-gamma in response to an antigen. Furthermore, when transferred adoptively, these anti-OVA257-264 TCD8+ cells significantly reduced the growth of established ovalbumin-transfected tumors in a pulmonary metastasis model system. Synthetic transfected tumors in a pulmonary metastasis model system. Synthetic oligonucleotides encoding minimal antigenic determinants within expression constructs may be a useful approach for treatment of neoplastic disease, thus avoiding the potential hazards of immunizing with full-length cDNAs that are potentially oncogenic.

An intervention that delays institutionalization of Alzheimer's disease patients: treatment of spouse-caregivers.

Spouse-caregivers of Alzheimer's disease patients were randomly assigned to either a treatment group (individual and family counseling, support group participation, and ad hoc consultation) or a control group (only routine support). In the first year after intake, the treatment group had less than half as many nursing home placements as the control group. This suggests that a comprehensive counseling program can reduce the socioeconomic impact of Alzheimer's disease. Nursing home placement also was affected by the patient's need for assistance with activities of daily living, patient income, and the age of the patients and caregivers.