Baseline experience with Modified Mini Mental State Exam: The Women's Health Initiative Memory Study (WHIMS).

The Modified Mini Mental State Exam (3MS) is widely used for screening global cognitive functioning, however little is known about its performance in clinical trials. We report the distribution of 3MS scores among women enrolled in the Women's Health Initiative Memory Study (WHIMS) and describe differences in these scores associated with age, education, and ethnicity. The 3MS exams were administered to 7,480 women aged 65-80 who had volunteered for and were eligible for a clinical trial on postmenopausal hormone therapy. General linear models were used to describe demographic differences among scores. Factor analysis was used to characterize the correlational structure of exam subscales.The distribution of 3MS scores at baseline was compressed in WHIMS compared to population-based data. Mean 3MS scores (overall 95.1) tended to decrease with age and increase with education, however these associations varied among ethnic groups (p< 0.0001) even after adjustment for health, physical disability and occupation attainment. Four factors accounted for 37% of the total variance. Each varied with education and ethnicity; the two most prominent factors also varied with age. Despite relatively narrow distributions in WHIMS, baseline 3MS scores retained associations with age and education. These associations varied among ethnic groups, so that care must be taken in comparing data across populations.

Telemedicine and geriatric psychiatry: directions for future research and policy.

The use of telecommunications to provide mental health services at a distance has grown rapidly in the past 10 years. The overall experience has been positive, but evaluations and reliability studies have been preliminary. A fundamental question of what constitutes adequate technology for telepsychiatry remains unanswered. As technology and equipment capability change rapidly, a more important question may be what clinical decisions and behavioral observations are required to produce high standards of distance mental health care. Geriatric patients may have sensory impairments and unique aspects to their psychiatric problems that can make telemental health assessments more challenging. It is not clear what model of telepsychiatry constitutes the best practice for geriatric psychiatry. Future research and program evaluations should address these questions to guide the use of telepsychiatry in productive directions.

Reliability of telepsychiatry assessments: subjective versus observational ratings.

Geriatric patients in underserved areas could benefit from the use of telecommunications to expand access to mental health services. It is important to determine the clinical limitations of using videoconferencing for psychiatric assessments, particularly in the elderly. The goal of this study was to test the hypothesis that videoconferencing ratings based on visual observations of behavior would be less reliable than ratings based on patients' verbal reports of symptoms. Videoconferencing assessments of 30 geriatric patients using low-bandwidth (ISDN) equipment were compared to gold standard face-to-face assessments. The Brief Psychiatric Rating Scale (BPRS) was dichotomized into subjective items based on patients' verbal reports and observational items based on visual ratings of behavior. Reliability of the BPRS subjective items was consistently higher than for the observational items. Future studies should emphasize the accuracy of telemedicine ratings that require visual observation of behavior, which is crucial to clinical assessment of psychogeriatric conditions.

Telepsychiatry consultations to a rural nursing facility: a 2-year experience.

This report describes the operation of a telepsychiatry consultation service provided from an academic medical center to a skilled nursing facility in a rural setting. Seventy-one consultations via low-cost ISDN videoconferencing equipment were provided over the 2-year period to 40 patients. The average duration of the consultation period was about 3 months. A wide variety of diagnostic conditions were encountered, with the majority being either depression or dementia-related behavior problems. Advantages of the program included the ability to respond promptly to rural patients' clinical needs, the flexibility to consult more frequently if clinically indicated, and more efficient use of the consultant's time, as travel time was eliminated. The program is an example of how telepsychiatry can successfully expand access to mental health services to residents of long-term care facilities.

Telemedicine use and the reduction of psychiatric admissions from a long-term care facility.

Copper Ridge is a long-term care facility that provides care for persons with dementia and their families from early diagnosis to end of life. A low-cost videoconferencing system was employed in the development of a comprehensive, integrated continuum of care for Copper Ridge residents by bridging long-term care with inpatient psychiatric care at Johns Hopkins Hospital. In this article, we discuss the Copper Ridge/Johns Hopkins telemedicine project and how its operation appears to have brought about a reduction in psychiatric admissions. Telemedicine projects using inexpensive technology over standard telephone lines can be successfully used in long-term care settings.

Telepsychiatry and geriatric care.

The use of telecommunications--telephone, computer, videoconferencing equipment--to provide mental health services at a distance has grown rapidly. This review encompasses reports from programs that provide telepsychiatry services, including telephone- and computer- based education and support services, telephone screening for dementia, and the use of videoconferencing to provide psychiatric consultations, health education, and administrative support. The extensive experience to date supports the value of telepsychiatry. Applications in geriatric settings and research involving geriatric subjects are reviewed. Cost analyses and economic evaluations of telepsychiatry are preliminary at this time and need further refinement. There is great potential for using telecommunications to expand access to mental health services to underserved geriatric populations.

Service use and financial performance in a replication program on adult day centers.

The authors describe results from Partners in Caregiving: The Dementia Services Program, and present information on service utilization and financial performance among a group of 48 adult day centers across the United States from 1992 to 1996. Centers, with nonrandom assignment, received either grant support (average value: $93,000) or intensive technical assistance (average value: $39,000). Sites reported baseline data and submitted utilization information (enrollment and census) and financial data (revenue and expenses) quarterly. Overall, there were significant increases in enrollment, census, and financial performance (percent of cash expenses met through operating revenue) over the 4-year period. The grant-supported and technical-assistance sites had similar rates of improvement. Results provide data on service utilization and financial performance and demonstrate gains that can be achieved in these areas through improved marketing and financial management.

Relating competency status to functional status at discharge in patients with chronic mental illness.

This study assessed performance on a screening test of competency to consent to treatment, the Hopkins Competency Assessment Test (HCAT), in a population diagnosed with chronic mental illness, and examined the relationship between HCAT performance and functional status at discharge. We hypothesized that patients with chronic mental illness who failed the HCAT would also have problems in performing activities of daily living at the time of discharge. Forty-three patients on a short-stay psychiatric service were administered the following screening tests: (1) Mini-Mental State Exam (MMSE), on admission; (2) the HCAT, approximately four to five days after admission; (3) At discharge, the Milwaukee Evaluation of Daily Living Skills (MEDLS), and the Occupational Therapy Task Observation Scale (OTTOS). Analyses included correlation between the competency measure HCAT and the functional measures; sensitivity, specificity, and positive and negative predictive values of the HCAT score; and odds ratio and chi-square analysis. The HCAT was highly correlated with the MEDLS and OTTOS. The HCAT was not sensitive in identifying impairment on either functional measure, but when patients failed the HCAT, they were likely to be functionally impaired at discharge. The negative predictive value of the HCAT was greater than the positive predictive value. Patients who failed HCAT were significantly more likely to have an MMSE score lower than 27 and less than 12 years of school. Seven of forty-three (16.3%) patients failed a screening measure of competency, indicating that there is a subgroup of chronically mentally ill patients who may not understand issues of informed consent. Patients who failed the HCAT were more likely to be functionally impaired at discharge. Cognitive impairment and low education are important factors in failure to pass competency screening. Competency screening along with screening for cognitive impairment can be useful in identifying patients at risk for poor functional status at discharge.

The Women's Health Initiative Memory Study (WHIMS): a trial of the effect of estrogen therapy in preventing and slowing the progression of dementia.

Evidence from animal, human cross-sectional, case-control, and prospective studies indicate that hormone replacement therapy (HRT) is a promising treatment to delay the onset of symptoms of dementia. The Women's Health Initiative Memory Study (WHIMS) is the first double-masked, randomized, placebo-controlled, long-term clinical trial designed to test the hypothesis that HRT reduces the incidence of all-cause dementia in women aged 65 and older. WHIMS, an ancillary study to the Women's Health Initiative (WHI) funded by the National Institutes of Health, will recruit a subgroup of women aged 65 and older from among those enrolling in the HRT trial of the WHI. The WHI clinical centers and 10 affiliated satellites plan to enroll approximately 8300 women into WHIMS over a 2-year period. Participants will be followed annually for 6 years, receiving cognitive assessments via the Modified Mini-Mental State (3MS) Examination. Women who screen positively for cognitive impairment on the basis of an educational and age-adjusted 3MS cutpoint proceed to more extensive neuropsychological testing and neurologic evaluation. Each woman suspected to have dementia then undergoes a series of laboratory tests that confirm the clinical diagnosis and classify the type of dementia. WHIMS is designed to provide more than 80% statistical power to detect a 40% reduction in the rate of all-cause dementia, an effect that could have profound public health implications for older women's health and functioning.

Identification of new autolytic sites of recombinant truncated mature human fibroblast stromelysin by mass spectrometry.

Stromelysin has been proposed to play a major role in the pathologic degradation of diseased cartilage of osteoarthritis and rheumatoid arthritis patients. A truncated, recombinant form of this enzyme, with the sequence Phe83 to Thr260 (mSL-t), has been expressed and purified from E. coli to investigate its biochemical and biophysical properties, and to develop inhibitors for arthritis treatment. LC/ESI-MS technique was utilized for the characterization of mSL-t. The mass spectra of mSL-t showed the presence of a number of different protein components in addition to the full-length mSL-t form. We have demonstrated that protein degradation arose from autolysis. Molecular weights determined by LC/ESI-MS of these autolysis products allowed for the identification of new autolytic sites in mSL-t. Furthermore, two strategies were undertaken to prepare mSL-t free of degradation products. These include preparation of a mutant form of the enzyme in which Arg163 was substituted for Leu163 and purification of mSL-t using affinity chromatography. The LC/ESI-MS data of the mutant protein confirmed the Leu to Arg mutation. The affinity-purified material showed only one LC peak in the LC/MS chromatograms, and the mass spectrum of the peak identified only the intact protein, demonstrating that the full-length protein has been successfully separated from the autodegradation products and further autolysis of the enzyme has been prevented.

Production of selenomethionine-labeled recombinant human neutrophil collagenase in Escherichia coli.

Molecular analogs of amino acids can be incorporated into proteins. The amino acid analog selenomethionine (SeMet) has been shown to be efficiently incorporated into the proteins of growing Escherichia coli. SeMet-containing proteins are known to produce sufficiently strong anomalous scatter permitting the solution of the selenomethionyl crystal structure by multiwavelength anomalous diffraction (MAD) techniques. The recombinant protein chosen for these studies is mature, truncated neutrophil collagenase (rmNC-t). The rmNC-t protein is a monomer of 163 amino acid residues featuring one active site and two Met residues. We developed a T7 polymerase expression system allowing incorporation of SeMet into rmNC-t protein produced in E. coli. Substitution of Met with SeMet was accomplished by culturing E. coli DL41(DE3), a SeMet-tolerant strain with metA lesion, in a defined medium containing SeMet as the sole source of Met. The SeMet-labeled rmNC-t was isolated from inclusion bodies by solubilizing in urea, purified by anion column chromatography, and then refolded in the presence of Ca2+ and Zn2+. Analysis of SeMet-labeled rmNC-t demonstrated that Met replacement was 100%. Enzymatic characterization revealed no obvious differences in activity or inhibitor binding between rmNC-t and the SeMet-labeled product. We have produced pure, active SeMet-labeled rmNC-t in sufficient quantities for macromolecular crystallography studies.

Depression coexisting with dementia. Evaluation and treatment.

Depression and dementia are the most common syndromes of geriatric psychiatry. Although emphasis is often placed on distinguishing the two, patients frequently have both disorders. Treating the complications of irreversible dementia, while unaltering the underlying disease process, can result in significant functional improvement in affected patients.

A new bedside test of cognition for patients with HIV infection.

OBJECTIVE: To compare the Mental Alternation Test, a new 60-second bedside test of cognition, with the Mini-Mental State Exam (MMSE) and the Trailmaking Test, parts A and B, in patients with human immunodeficiency virus (HIV) infection. DESIGN: Cohort study. PARTICIPANTS: Sixty-two inpatients with HIV infection. SETTING: The AIDS service of a referral hospital. MEASUREMENTS: Scores on the MMSE; the Trailmaking Test, parts A and B; and the Mental Alternation Test were compared using correlation calculations and analyses of variance. Receiver operating curves were constructed to identify the best cutoff score on the Mental Alternation Test for detecting impaired performance on the MMSE and the Trailmaking Test. MAIN RESULTS: The Mental Alternation Test score correlated significantly with MMSE (r = 0.68, P < 0.01) and Trailmaking Test, part B, scores (r = -0.54, P < 0.01). The receiver operating curves showed that a Mental Alternation Test cutoff score of 15 yielded the best results for the detection of abnormal performance on the MMSE (sensitivity, 95% [95% CI, 90% to 100%]; specificity, 79% [CI, 69% to 89%]) and the Trailmaking Test, part B (sensitivity, 78% [CI, 68% to 88%]; specificity 93% [CI, 90% to 100%]). Patients making fewer than 15 alternations in 30 seconds were significantly more likely to have abnormal MMSE (P < 0.0001) and Trailmaking Test, part B, scores (P < 0.0001). The Mental Alternation Test had good reproducibility; analyses of reliability included test-retest correlation (r = 0.80) and inter-rater reliability (r = 0.85, kappa = 0.84). Time of administration was approximately 60 seconds. CONCLUSIONS: The Mental Alternation Test of cognition has good sensitivity and specificity and is easily administered. It is a valuable test to identify patients who may need further cognitive evaluation.

The areas ratio of normal arterial junctions and its implications in pulse wave reflections.

STUDY OBJECTIVE: The aim of the study was to establish measurements for the area ratios of normal arterial junctions at various anatomical sites in order to estimate the significance of pulse wave reflections in the healthy arterial system. DESIGN: Coronary cineangiograms were used for the coronary junctions measurements and routine arteriograms for the rest of the junctions studied. A pair of digital calipers served to take measurements at a distance of one vessel diameter from the junction centre. MEASUREMENTS AND MAIN RESULTS: A bell shaped distribution of arterial area ratios was found with mean value for coronary bifurcations of 1.179 (95% confidence limits, 1.138-1.220). Slightly higher values were found for the higher order coronary junctions. Other junctions had similar area ratio values with the exception of the aortoiliac junctions where the area ratio was found 0.848 (0.775-0.920). Overall area ratio was 1.14 (1.113-1.167). Asymmetrical coronary bifurcations had higher area ratio than symmetrical ones (p less than 0.05). CONCLUSIONS: In the majority of cases the area ratios are in close agreement with the theoretically predicted values for forward matched junctions. Minimal pulse wave reflections are therefore expected to arise from the junctions of a healthy arterial system. We therefore consider that, contrary to the established view, the presence of reflected waves in the central arterial system is a potential pathological phenomenon and not a characteristic of the healthy system. This may have important theoretical implications for the way hemodynamic findings are interpreted. Finally we suggest that arterial area ratio can be considered as another criterion of normality of arterial junctions in the interpretation of angiograms.

Cloning and characterization of two alternatively spliced rat alpha-amidating enzyme cDNAs from rat medullary thyroid carcinoma.

The alpha-amidating enzyme activity in rat medullary thyroid carcinoma (MTC) consists of multiple, active enzymes that can be resolved by ion-exchange chromatography. Amino acid sequences from one form of purified rat MTC alpha-amidating enzyme have been utilized to design oligonucleotide probes for isolating cDNAs encoding this protein. Sequence analysis of multiple cDNA clones indicates that there are at least two types of cDNA in rat tissues. These cDNAs differ primarily by the absence (type A) or the presence (type B) of a 315-base internal sequence. Additional heterogeneity in the 3' coding regions of the different mRNAs has also been found. Both types of cDNA predict primary translation products that are preproenzymes which must be post-translationally processed at both their amino and carboxyl termini. Sequence analysis of the purified peak III protein from rat MTC demonstrates that the type A mRNA encodes this 75-kDa protein. This analysis also provides support for the assignment of the C-terminal processing site. In addition, data are presented which demonstrate that type B mRNA is also functional. The implications of the internal and carboxyl-end heterogeneity are discussed.

Peptide substrate specificity of the alpha-amidating enzyme isolated from rat medullary thyroid CA-77 cells.

The kinetic parameters were obtained for enzymatic alpha-amidation of peptides of the form N-dansyl-(Gly)4-X-Gly-OH, in which the amino acid at position X was substituted with each of the 20 natural amino acids. The enzyme used in these studies was a highly enriched preparation of alpha-amidating enzyme secreted by a clonal (CA-77) cell line which actively expresses mature alpha-amidated peptides. A 130-fold and 11-fold variation respectively in apparent Km and Vmax values was observed. The effect of the amino acid side chain at position X in stabilization of the enzyme-substrate complex decreased through the series X = planar aromatic or sulfur containing greater than neutral aliphatic greater than polar and basic greater than cyclic aliphatic or acidic.