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Biomedical subjects

D K Miller

Publications and source records attributed to D K Miller.

At least 73 records · Page 4Linked to original sources
PubMed1995

The Sepulveda GEU Study revisited: long-term outcomes, use of services, and costs.

The randomized controlled trial of the Geriatric Evaluation Unit (GEU) at the Sepulveda Veterans Hospital was the first to document the clinical and cost-effectiveness of hospital-based comprehensive geriatric assessment (CGA). Frail elderly inpatients were assigned randomly to the GEU for CGA, therapy, rehabilitation, and placement (N = 63), or to standard hospital care (N = 60). At one year, GEU patients had much lower mortality (24% vs 48%) and were less likely to have been discharged to a nursing home (NH) (13% vs 30%), or to have spent any time in NHs (27% vs 47%). GEU patients were more likely to improve in personal self-maintenance and morale. Further, controls had substantially more acute-care hospital days, NH days, and hospital readmissions, resulting in higher direct institutional care costs, especially after survival adjustment. Here, we report the results of long-term follow-up. There was a significant survival effect through two years. Despite prolongation of life, there was no indication that quality of life was worse for survivors in the GEU group. In fact, the proportion of persons independent in > or = 2 ADLs at two years was somewhat higher for GEU patients (0.44) than controls (0.33) (z = 1.27; p = 0.056). By three years, 43% of GEU subjects and 38% of controls were still alive. Over the entire 3-year period, the per capita direct cost difference was not significant, either before or after survival adjustment (unadjusted: $37,091 GEU vs $34,205 control; survival-adjusted: $54,315 GEU vs $63,362 control; p = 0.17).(ABSTRACT TRUNCATED AT 250 WORDS)

Activities of Daily Living↗
PubMed1995

Unrecognized delirium in ED geriatric patients.

To determine the sensitivity of an emergency physician's conventional evaluation compared with the validated Confusion Assessment Method (CAM) regarding the recognition of acute confusional states (delirium) in elderly Emergency Department (ED) patients, a cohort of 385 patients presenting to an urban teaching hospital ED was systematically assembled. Patients had to be conscious, able to speak and older than 64 years of age. After the ED physician had examined the patient and test results had been obtained, a series of geriatric assessment results, including one for the likely presence of delirium, was made available to the ED physician; however, no result was specifically highlighted. All patients were assessed by an attending ED physician in the customary fashion. In addition, a study nurse interviewed patients using the CAM and followed patient outcomes for three months. The ED record for all patients with delirium or "probable" delirium, as determined by the CAM, were reviewed for physician diagnosis and disposition to determine how often delirium had been recognized by the emergency physician. Thirty-eight of the 385 patients screened (10%) met criteria for delirium or "probable" delirium; ED charts were complete for 35 of these, which constituted the study sample. The ED diagnosis included delirium or an acceptable synonym in 6 (17%) of these patients. In the 21 patients (62%) admitted to the hospital, the most common ED diagnosis was infection "rule out sepsis" (n = 7). Six of 13 patients discharged (46%) were diagnosed as "status post fall" without evidence of significant injury.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1995

Ocular Halicephalobus (syn. Micronema) deletrix in a horse.

Ocular contents from a horse with a 4-week history of severe unilateral uveitis were submitted for histopathologic examination. A severe unilateral granulomatous chorioretinitis with intralesional Halicephalobus deletrix was diagnosed. The horse developed progressive neurologic signs several days following the surgery to remove ocular contents and implant a prosthesis and was subsequently euthanatized. A severe multifocal granulomatous encephalitis with intralesional H. deletrix, localized primarily to the optic chiasm, thalamus, and brain stem, was diagnosed from tissues acquired at necropsy. The other eye was not affected. This is the first report of ocular parasitism by H. deletrix and suggests possible systemic dissemination from a primary site in the eye.

Animals↗
PubMed1994

Specific cleavage of the 70-kDa protein component of the U1 small nuclear ribonucleoprotein is a characteristic biochemical feature of apoptotic cell death.

The U1 small nuclear ribonucleoprotein particle is essential for splicing of precursor mRNA, an activity that depends upon both the RNA and protein components of the U1 particle. One of the U1-specific proteins that is functionally important in this splicing reaction is the 70-kDa protein (U1-70kDa). We report here that U1-70kDa is specifically cleaved in apoptotic cells, resulting in the generation of a 40-kDa fragment. The kinetics of this cleavage coincided with the appearance of cells with apoptotic morphology in the population, and the proportion of 40-kDa fragment observed was markedly increased in apoptotic cells that had become detached from the substratum. Although the inhibitor characteristics of the activity cleaving U1-70kDa suggest that interleukin 1 beta-converting enzyme (ICE) might be responsible, the specific ICE inhibitor N-(N-acetyl-tyrosinyl-valinyl-alaninyl)-3-amino-4-oxob utanoic acid (YVAD-CHO) did not prevent cleavage, and U1-70kDa was not cleaved by purified ICE in vitro. Further study of this novel cleavage and the enzyme responsible will yield information about proteolytic events that might be central in the mechanism and control of apoptosis.

Apoptosis↗
PubMed1994

IL-1 beta-converting enzyme is present in monocytic cells as an inactive 45-kDa precursor.

The major form of IL-1 beta-converting enzyme (ICE) identified in THP.1 monocytic cells and human monocytes is the 45-kDa precursor protein (p45), which is found in the cytoplasm. Cytoplasmic extracts of these cells show no pIL-1 beta cleavage activity, indicating that the p45 has no detectable catalytic activity. pIL-1 beta cleavage activity can only be observed after incubation in vitro when p45 breaks down to the active p20 form of the enzyme. LPS stimulation of human monocytes or THP.1 monocytic cells results in no change in the amount of p45 or its activity and no detectable appearance of p20 ICE. Immunoprecipitation of [35S]Met-labeled LPS-stimulated monocyte extracts revealed only p45 with no other co-precipitating protein. The inability to identify active ICE in stimulated monocytic cells was probably a reflection of the very low levels of active ICE present.

Caspase 1↗
PubMed1993

Processing proIL-1 beta decreases detection by a proIL-1 beta specific ELISA but increases detection by a conventional ELISA.

Recent investigations have noted that conventional IL-1 beta enzyme linked immunoassays (ELISA) may underestimate proIL-1 beta concentrations. In an attempt to circumvent this problem, we have devised a proIL-1 beta specific ELISA which sandwiches proIL-1 beta between a carboxy-terminus specific, capture antibody, and an amino-terminus specific, detection antibody. The amino-terminus specific antibody was generated against amino acids 3-21 of the intact proIL-1 beta molecule. This sandwich ELISA does not recognize mature 17 kDa IL-1 beta and is not inhibited by the coexistence of mature, 17 kDa IL-1 beta. We compared this proIL-1 beta specific ELISA (amino-terminus ELISA) to the conventional IL-1 beta ELISA (carboxy-terminus ELISA) on test samples that contained either proIL-1 beta or mature IL-1 beta. When purified proIL-1 beta is cleaved by increasing concentrations of IL-1 beta converting enzyme or porcine pancreatic elastase, there is a dose dependent increase in the signal from the conventional IL-1 beta ELISA and a concurrent decrease in signal from the proIL-1 beta specific ELISA. Furthermore, when the proIL-1 beta specific ELISA is used to quantify cellular sources of IL-1 beta, there is no detectable release of proIL-1 beta into the supernatants from either fresh blood monocytes or alveolar macrophages, despite detectable mature IL-1 beta. The cell associated compartment of IL-1 beta is largely proIL-1 beta and the relative amounts of IL-1 beta that remain intracellularly are quite large. Specifically, when assayed at 18 h, the proIL-1 beta ELISA detected 4.6 +/- 1.4 ng/ml per 10(6) monocytes and 13.8 ng/ml per 10(6) macrophages vs. 0.8 +/- 0.3 ng/ml/10(6) monocytes and 1.6 ng/ml/10(6) macrophages by conventional IL-1 beta ELISA. Thus, the 5-10-fold deficit in the detection of intracellular IL-1 beta by a conventional IL-1 beta ELISA, combined with the enhanced detection after enzymatic processing of proIL-1 beta, confirms that a proIL-1 beta specific ELISA is needed to accurately quantify proIL-1 beta.

Enzyme-Linked Immunosorbent Assay↗
PubMed1993

Purification and characterization of active human interleukin-1 beta-converting enzyme from THP.1 monocytic cells.

Interleukin-1 beta-converting enzyme (ICE) was purified from dialyzed cytoplasmic extracts of THP.1 human monocytic cells by a combination of DEAE-5PW and SP-5PW ion exchange and C4 reverse phase high performance liquid chromatography. Sequence information from tryptic and Asp.N peptides on the isolated 20-kDa (p20) and a 10-kDa (p10) proteins enabled the subsequent cloning of ICE (Thornberry, N. A., Bull, H. G., Calaycay, J. R., Chapman, K. T., Howard, A. D., Kostura, M. J., Miller, D. K., Molineaux, S. M., Weidner, J. R., Aunins, J., Elliston, K. O., Ayala, J. M., Casano, F. J., Chin, J., Ding, G. J.-F., Egger, L. A., Gaffney, E. P., Limjuco, G., Palyha, O. C., Raju, S. M., Rolando, A. M., Salley, J. P., Yamin, T.-T., Lee, T. D., Shively, J. E., MacCross, M., Mumford, R. A., Schmidt, J. A., and Tocci, M. J. (1992) Nature 356, 768-774) and localized the active site Cys. Immunoblots with ICE specific antibodies and NH2-terminal sequencing indicated that ICE active column fractions contained in addition to p20 and p10 an alternatively processed form of the p20 protein (p22) containing an extra 16 amino acids NH2-terminal to the p20. Furthermore, immunoblot analysis of the ion exchange column effluent showed that p20 and p22 were found together in three separate fractions distinguished by differences in p10: an intact p10 with complete ICE activity, a COOH-terminally truncated form of p10 with decreased ICE activity, and an absence of p10 with no ICE activity. These results indicate that the p10 protein is essential for ICE activity and that the ICE holoenzyme contains an intact p10 subunit paired with a p20 or p22 catalytic subunit.

Amino Acid Sequence↗
PubMed1993

Nutritional risk and survival in elderly veterans: a five-year follow-up.

The purpose of this study was to identify predictors of survival over five years in a sample of 377 elderly (age 55+) chronically ill men. Subjects were selected at baseline from consecutive appointments at a geriatric clinic and given extensive medical and psychosocial assessment. Five years later, subjects who could be located were interviewed by telephone. Interviews were completed with 194 (51.4%) subjects, 90 others were confirmed as deceased, 29 subjects could not be interviewed, and 64 more were not located although VA records did not show that any were deceased. The predictor variable of interest was the Nutritional Risk Index (NRI), a 16 item index which measures nutritional dimensions of health status. Other variables included functional health status [Activities of Daily Living (ADL), Instrumental Activities of Daily Living (IADL)], mental health status [Mini-Mental Status Exam (MMSE), morale], health habits (smoking, alcohol use and exercise), use of health services (physician visits, emergency room (ER) visits, hospital stays), and demographic factors (age, income, marital status and living arrangements). Proportional hazard models showed that the variables with statistically significant direct effects on survival time were younger age, higher functional health status on IADL, non-smoking, moderate alcohol use, and perception of adequate income. Nutritional status was indirectly associated with survival.

Activities of Daily Living↗
PubMed1993

A preliminary report of vitamin D and calcium metabolism in older African Americans.

OBJECTIVE: To determine normal serum bone-related biochemical variables in older African-Americans. DESIGN: A convenience sample of older African-Americans who had a health screening and blood testing for calciotropic hormones was compared with white Americans who were recruited at the end of the Systolic Hypertension in the Elderly Program (SHEP) study and were not on a thiazide diuretic. SETTING: Community-dwelling African-Americans who participated in SHEP or who attended one of two mass health screenings. PARTICIPANTS: Thirty-two African-Americans aged 68-93 years and 43 white Americans aged 70-89 years. MEASUREMENTS: Twenty-five hydroxyvitamin D (25OHD), parathyroid hormone, osteocalcin, and calcitonin. RESULTS: Serum 25OHD levels in 38% of the African-American men and 38% of African-American women were less than 8 ng/mL compared with 22% of Caucasian men and 40% of Caucasian women. Serum parathyroid hormone (PTH) was above the normal range in 25% of men and 33% of women of African-American descent and 14% of Caucasian men and 30% of Caucasian women. Serum 25OHD was lower (P < 0.05) in individuals with a previous history of fracture. Serum albumin (P < 0.05), calcitonin (P < 0.05), and osteocalcin (P < 0.05), but not 25OHD, were lower in African-Americans (men and women) when compared with Caucasians (P < 0.05). Serum calcium corrected for albumin was higher in the African-Americans than in the Caucasians (P < 0.05). As previously reported in Caucasians, PTH was inversely related to log 25OHD in African-Americans. Serum osteocalcin was positively correlated to PTH in African-Americans, as previously reported in Caucasians. Log 25OHD correlated inversely with osteocalcin in African-Americans, but this was not seen in Caucasians. CONCLUSIONS: In this limited sample, hypovitaminosis D (as assessed by 25OHD level) with secondary hyperparathyroidism occurred frequently in elderly African-Americans. Osteocalcin, a measure of osteoblast activity, correlated with 25OHD and parathyroid hormone. Osteocalcin serum levels were lower in African-Americans than Caucasians, but serum calcium corrected for albumin was higher in the former compared to the latter.

Aged↗
PubMed1993

Assessment of the older woman.

Our knowledge of the aging woman will continue to grow, and that knowledge will begin with obtaining assessments that are appropriate and complete for this population. It is important to recognize that assessment can lead to improved diagnoses, more appropriate intervention, and improved outcomes, which hopefully will contribute to an improved quality of life for all older women.

Activities of Daily Living↗
PubMed1992

A novel heterodimeric cysteine protease is required for interleukin-1 beta processing in monocytes.

Interleukin-1 beta (IL-1 beta)-converting enzyme cleaves the IL-1 beta precursor to mature IL-1 beta, an important mediator of inflammation. The identification of the enzyme as a unique cysteine protease and the design of potent peptide aldehyde inhibitors are described. Purification and cloning of the complementary DNA indicates that IL-1 beta-converting enzyme is composed of two nonidentical subunits that are derived from a single proenzyme, possibly by autoproteolysis. Selective inhibition of the enzyme in human blood monocytes blocks production of mature IL-1 beta, indicating that it is a potential therapeutic target.

Amino Acid Sequence↗