Energy and lipid metabolism gene expression of D18 embryos in dairy cows is related to dam physiological status.

We analyzed the change in gene expression related to dam physiological status in day (D)18 embryos from growing heifers (GH), early lactating cows (ELC), and late lactating cows (LLC). Dam energy metabolism was characterized by measurement of circulating concentrations of insulin, glucose, IGF-1, nonesterified fatty acids, ß-hydroxybutyrate, and urea before embryo flush. The metabolic parameters were related to differential gene expression in the extraembryonic tissues by correlation analysis. Embryo development estimated by measuring the length of the conceptuses and the proportion of expected D18 gastrulating stages was not different between the three groups of females. However, embryo metabolism was greatly affected by dam physiological status when we compared GH with ELC and GH with LLC but to a lesser extent when ELC was compared with LLC. Genes involved in glucose, pyruvate, and acetate utilization were upregulated in GH vs. ELC conceptuses (e.g., SLC2A1, PC, ACSS2, ACSS3). This was also true for the pentose pathway ( PGD, TKT), which is involved in synthesis of ribose precursors of RNA and DNA. The pathways involved in lipid synthesis were also upregulated in GH vs. ELC. Despite similar morphological development, the molecular characteristics of the heifers' embryos were consistently different from those of the cows. Most of these differences were strongly related to metabolic/hormone patterns before insemination and during conceptus free-life. Many biosynthetic pathways appeared to be more active in heifer embryos than in cow embryos, and consequently they seemed to be healthier, and this may be more conducive to continue development.

The 'Do not resuscitate' order. A profile of its changing use.

The "do not resuscitate" (DNR) order has wide-ranging ethical, legal, and economic implications. We reviewed the course of 244 patients who died during two three-month periods, in 1982 and 1986. We found that 68% of patients who died had a DNR order written, including 94% with malignancy and half of patients with cardiovascular disease. Most orders (61%) were written within three days of death, with 64% written on medical-surgical floors and 34% in critical care units. Even among patients under the age of 60 years, 57% had a DNR order written by the time of death. Ninety-one percent of DNR orders were written by attending physicians, with accompanying explanatory note in 84%. Documentation showed only 14% of patients but 77% of families being consulted. In 1983 a new two-level DNR order system defined two levels of intensity: "all but cardiopulmonary resuscitation" and "comfort measures only." Equal numbers of patients received each order in the 1986 sample. No patient was transferred to the critical care units after a DNR order had been written. The prevalence of DNR orders written for patients dying of cardiovascular disease increased from 27% to 64% over the four years. We conclude, from study of deaths in this representative community hospital, that an explicit DNR order is now the rule rather than the exception, but decisions are made late and involve family far more than the patient.

Overmedication of the low-weight elderly.

This study analyzes age, weight, and drug doses using cimetidine hydrochloride, flurazepam hydrochloride, and digoxin as tracers. Data were obtained for 1797 patients (mean age, 72 years) filling consecutive prescriptions from a national pharmacy service. With all three drugs, patients with lower weight received substantially higher doses with correlations of weight vs dose, based on milligrams per kilogram of body weight, ranging from -0.34 to -0.40. Because body weight declines with increasing age, lower-weight patients are also older and at greatest risk for drug toxicity. Patients weighing 50 kg or less (n = 155) received milligram-per-kilogram doses that were 31% to 46% higher than the group mean and 70% to 88% higher than patients weighing more than 90 kg. For all three study drugs, as patient weight declines, the mean milligram-per-kilogram dose rose sharply. There was no trend seen toward reducing doses for older patients. Low body weight, in addition to advanced age, is a major risk factor for overmedication. Physicians must recognize the need to reduce drug doses for their low-weight elderly patients.

The clinical course of acute hepatitis in the elderly patient.

We have reviewed the clinical course of acute hepatitis in 23 patients 60 years or older. There were four patients with acute hepatitis B, two patients with sporadic hepatitis, and 17 patients with posttransfusion non-B hepatitis. Hepatitis, in the latter group, is presumed to have been caused by the transmission of non-A, non-B hepatitis agents by blood transfusion. Regardless of the cause, the acute episode of clinical hepatitis resolved in 20 patients. Eight patients had completely normal liver function test results on follow-up. Eleven patients had chronic elevations of bilirubin, alkaline phosphatase, or SGOT values without clinical or biochemical evidence of deterioration of their condition during 20.5 +/- 3.5 months (mean +/- SEM) of observation. The majority of patients with posttransfusion non-B hepatitis either recovered spontaneously or entered into a chronic phase characterized by mildly or intermittently abnormal liver function test results without clinical deterioration of their condition.

Transcervical collection of bovine embryos up to Day 21: an 8-year overview.

Transcervical embryo collection is used routinely in the bovine species throughout the world to collect Day 6 to Day 9 embryos (early embryos) for genetic selection. For research purposes, however, the collection of embryos at later stages of pregnancy, i.e., Days 12 to 21 (late embryos), is needed. So far, for the recovery of late embryos, females are euthanized and embryo collection is performed after recovery of the genital tract. To reduce the number of animals used and still provide valuable material for embryo research, we have therefore developed a transcervical technique to collect late embryos. The objective of this study was to compare embryo recovery results at early and late stages within our laboratory. Altogether, 232 cows were used for this study. One hundred forty-five flushes were performed to collect embryos from Days 6 to 9, and 251 flushes were performed to collect embryos from Days 12 to 21. For the early embryos, a classical three-way collection equipment was used. To collect the late embryos, the same equipment was used, but the extensible flexible catheter that goes inside the external rigid catheter was removed, so that larger embryos could be collected through the remaining larger hole (two-way collection). All females were submitted to ovum pick up to remove the dominant follicle and were subsequently superovulated with FSH. Luteolysis was induced 48 hours before artificial insemination. Two artificial inseminations were performed with frozen semen, 48 and 56 hours after PGF2α injection. Before embryo collection, cows were treated with an epidural injection of a local anesthetic drug. The presence of CL was checked, and they were counted by rectal palpation. For all collections, the cervix was prepared with the initial introduction of a dilator. Then, the catheter was introduced in one horn, and the cuff was inflated as low as possible. For the collection of late embryos, the flushing solution (30 mL) was injected slowly twice to suspend the embryos before flushing the horn with 500 mL, and the same operation was performed on the second horn. There was no significant difference in the number of embryos collected per flush in the early- and late-stage (758 embryos collected, 5.22 ± 6.02 per flush vs. 1238 embryos collected, 4.93 ± 5.07 per flush, respectively). The number of embryos collected per CL, however, was significantly lower in the early versus late group (0.39 ± 0.32% vs. 0.44 ± 0.34%, respectively). The late collection allowed the retrieval of full conceptuses (embryonic and extraembryonic tissues), even at very late stages such as Days 18 to 21. Careful collection is needed, however, so that conceptuses are not damaged or torn: the horn must be massaged gently and the flush should be ideally recovered in one single flow. This technique is a powerful tool to collect the late-stage embryos for research purposes. Because it is not traumatic, animals can be used again for the same procedure.

Sensorimotor functions and cognitive disturbance in psychiatric patients.

The authors studied 109 consecutive admissions to an acute psychiatric unit in a general hospital to determine the relationship of specific sensorimotor impairments to cognitive disturbance. The results indicated a strong but not exclusive correlation between neurological impairment and thought disorder as well as between neurological impairment and schizophrenia. The theoretical and etiological implications are discussed, as well as the relationship of these findings to other variables.

Thermal behavior of collagen and agarose solutions and its possible implications in the cryobehavior of living systems.

Commonly used cryopreservation procedures are empirical and involve incompletely understood phenomena. Our purpose is to study in vitro the cryobehavior of a number of biopolymers participating in cell structure or its environment. Their abilities to interact with water to obtain gelified structures might be a good means to reduce the water mobility, and thereby decrease the often lethal consequences of the latter's crystallization. Our preliminary results concerning collagen and agarose, representative constituents of the extracellular matrix, indicate that cooling/warming rates and the presence of organic solvents may alter the thermal behavior and structure of these biopolymers, and suggest that such types of responses may influence the cryobehavior of cells and extracellular matrices.

Asymptomatic hyperuricemia. Risks and consequences in the Normative Aging Study.

To quantify the consequences of asymptomatic hyperuricemia, this study examined rates for a first episode of gouty arthritis based on 30,147 human-years of prospective observation. A cohort of 2,046 initially healthy men in the Normative Aging Study was followed for 14.9 years with serial examinations and measurement of urate levels. With prior serum urate levels of 9 mg/dl or more, the annual incidence rate of gouty arthritis was 4.9 percent, compared with 0.5 percent for urate levels of 7.0 to 8.9 mg/dl and 0.1 percent for urate levels below 7.0 mg/dl. With urate levels of 9 mg/dl or higher, cumulative incidence of gouty arthritis reached 22 percent after five years. Incidence rates were three times higher for hypertensive patients than for normotensive patients (p less than 0.01). The strongest predictors of gout in a proportional hazards model were age, body mass index, hypertension, and cholesterol level, and alcohol intake. When the serum urate level became a factor in the model, none of these variables retained independent predictive power. At the final examination, only 0.7 percent of participants had a serum creatinine level of 2.0 mg/dl or more, with no evidence of renal deterioration attributable to hyperuricemia. These data support conservative management of asymptomatic hyperuricemia.

Late onset systemic lupus erythematosus.

This study describes the clinical and laboratory features and the natural history of 31 patients with late onset (in the sixth decade or later) systemic lupus erythematosus (SLE). Patients with late onset SLE constitute a distinct subset of the general lupus population that accounts for approximately 12 per cent of the cases. Advanced age modifies the expression of SLE in terms of clinical presentation (pleuritis and/or pericarditis are the most common presenting manifestations) and pattern of organ involvement (pulmonary abnormalities are more common, whereas lymphadenopathy, Raynaud's phenomenon, neuropsychiatric disease, alopecia and skin rash are less common). Because SLE is not usually considered to be a disease that affects the elderly, and because the pattern of SLE in the older age group may differ substantially from the seen in younger patients, there is often a delay in diagnosis (median of 10 months, with a delay of over one year in 32 per cent of patients). In light of the high incidence of steroid complications in older patients (40 per cent in our series), and because these patients with SLE have a relatively good prognosis (five year survival of 92.3 per cent; nine year survival of 83.1 per cent), therapy should be more conservative in late onset SLE.

White blood cell count as a predictor of mortality: results over 18 years from the Normative Aging Study.

The ubiquitous white blood cell count (WBC) has rarely been analyzed as a predictor of future mortality. We examined WBC measured in prospective examinations of 2011 initially healthy men in the Normative Aging Study (mean age 47.5), followed for an average of 13.6 years with 27,402 man-years of observation. Between 1970 and 1987, 183 participants died. Mortality rates for men with baseline WBC over 9000 were 12.2/1000 man-years, 1.8-2.5 times those of men with lower WBC in each of three age groups. Proportional hazards models controlling for established risk factors including age, systolic blood pressure, cholesterol and smoking status, found WBC at the baseline exam to be an independent predictor of mortality over the following years. Even within the normal range, a difference of 1000 in the initial WBC increased the risk ratio by 1.2 (95% CI 1.1, 1.3). The relation of initial WBC to mortality was not affected by baseline age, body mass index (BMI), smoking or blood pressure. These findings are not explained by medication effects. We conclude that the WBC is an independent predictor of all-cause mortality.

Motivating the geriatric patient for rehabilitation.

Geriatric patients often appear unmotivated for rehabilitation, and "poor motivation" is frequently the reason given for excluding them from rehabilitation programs. However, these patients may actually be impeded by specific obstacles to the development of motivation. Appropriate intervention may enable them to make better use of rehabilitation opportunities. In this paper the authors review the concept of human motivation and what is known about aging and motivation. Specific age-related changes are examined and treatment interventions identified to maximize the patients' participation in rehabilitation toward improved functional ability.

Cimetidine use in nursing homes: prolonged therapy and excessive doses.

Patterns of cimetidine use were identified in a survey of 3032 patients in 31 nursing homes. Of these, 60 (2%) were receiving cimetidine. For these patients, ages ranged from 63 to 102 years (mean, 81 years). The patients received a range of 1 to 11 regularly scheduled medications (mean, 5.6 medications). Duration of cimetidine treatment averaged 19.6 months for 48 patients (81%) receiving the drug for longer than an eight-week course of therapy. Prescribing indications appeared unjustified in 54 of 60 patients (90%). Doses were rarely appropriately reduced for patient age, despite established reasons to do so and the well-known potential for adverse effects of cimetidine in the elderly. The risks associated with prolonged drug-induced suppression of gastric acid are not known. This study suggests that use of cimetidine without justifiable indication and for extended periods of time is common in nursing home patients. Studies are needed concerning the safety of long-term cimetidine use in elderly patients.

Acute care hospitals providing elderly and long-term care services: a survey of the Massachusetts experience.

To assess the involvement of hospitals in geriatric, community and long-term care services, a survey was undertaken of the 104 acute care hospitals in Massachusetts. Results show that hospitals (N = 81) are adding geriatric expertise but as yet have taken on community services and long-term care only to a small extent. Hospitals perceive major deficiencies in physician service to nursing homes (89 per cent) and in availability of inpatient geriatric units (94 per cent). Responding hospitals have targeted for development by 1985 geriatric inpatient units (17 per cent), respite care (16 per cent), and hospice care (16 per cent). The financial implications of the survey results are discussed with respect to prospective reimbursement and public health implications.

Attitudinal stumbling blocks to geriatric rehabilitation.

Attitudes held by geriatric patients, their families, and hospital staff are frequent obstacles to successful rehabilitation following acute illness. These attitudes interfere with patients' motivation for increasing physical independence and result in patients' becoming stranded at a more dependent level of function. Three distinct attitudes frequently encountered in geriatric rehabilitation are identified: the prejudice of ageism, the right of dependency, and the apathy of fatigue. Recognition of these attitudinal syndromes permits effective treatment interventions to enable poorly motivated geriatric rehabilitation patients to progress towards functional independence.

Rehabilitation home visits.

This chart review study describes 40 geriatric hip fracture patients focusing on the in-home functional and environmental assessment done before discharge from a rehabilitation hospital. Patients were aged 65 to 96 years. Before hospitalization all ambulated independently and three-quarters required limited or no social support. On discharge, none ambulated independently and all required support. Discharge plans for three patients were changed by the home visit, resulting in two nursing home placements. The role and structure of the rehabilitation home visit are outlined together with the common safety recommendations and equipment needs. The home visit assessment form is presented. The rehabilitation home visit is a practical tool to help achieve successful home discharge for elderly hip fracture patients. It is particularly useful in discharge planning for elderly patients with hip fracture, amputation, or stroke.

An interdisciplinary geriatric consultation service: a controlled trial.

The structure and function of a newly created interdisciplinary Geriatric Consultation Team (GCT) are described. The GCT was introduced on a single medical unit, where consultations were given to 46 consecutive patients aged 75 years and over. The GCT patients had, on the average, 5.5 illnesses and were receiving 3.7 medications. Anemia (50 per cent), were hypoalbuminemia (65 per cent), and elevated blood urea nitrogen (BUN) (58 per cent) were frequent. Functional assessment showed frequent dependence on others for assistance with ambulation (59 per cent), transfers (54 per cent), and dressing (52 per cent); cognitive impairment was found in 52 per cent and clinical depression in 11 per cent of the patients. In comparison with control units, the GCT increased use of physical therapy by 357 per cent, occupational therapy by 390 per cent, and speech therapy by 300 per cent without increasing length of stay. In comparison with control subjects, GCT patients had no decrease in hospital readmission rates (43 per cent) over 10.5 months of follow up. It was concluded that a GCT in an acute-care hospital promotes geriatrics, teaches interdisciplinary teamwork, improves awareness of functional problems of patients, and increases use of rehabilitative services, but does not decrease the high rate of readmission of hospitalized geriatric patients.

Age and the declining rate of autopsy.

To better understand declining autopsy rates, data have been gathered prospectively on 1080 consecutive deaths over six years among patients admitted to a medical intensive care/coronary care unit. Overall autopsy rate was 36%. Autopsy rates declined sharply with age from 60% for those aged 16 to 34 years to 23% for those 85 and over (P less than .001). The highest rates by diagnosis were aortic aneurysm (70%), hepatic failure (52%), heart rhythm disturbance (48%), pulmonary embolism (45%), and sepsis (41%). Patients receiving major procedures had a significantly higher autopsy rate (38 versus 29%, P less than .05) but rates bore little relation to prognoses given at admission by house officers, suddenness of death, sex, marital status or year of admission. Even among intensively treated patients, autopsy rates decline strikingly with age, demanding honest re-appraisal to restore the place of autopsy in medical education, clinical research, and quality of care assessment for an increasingly elderly population.

Correlates of cognitive function scores in elderly outpatients.

OBJECTIVE: To determine medical, ophthalmologic, and demographic predictors of cognitive function scores as measured by the Telephone Interview for Cognitive Status (TICS), an adaptation of the Folstein Mini-Mental Status Exam. A secondary objective was to perform an item-by-item analysis of the TICS scores to determine which items correlated most highly with the overall scores. DESIGN: Cross-sectional cohort study. SETTING: The Glaucoma Consultation Service of the Massachusetts Eye and Ear Infirmary. SUBJECTS: 472 of 565 consecutive patients age 65 and older who were seen at the Glaucoma Consultation Service between November 1, 1987 and October 31, 1988. MEASUREMENTS: Each subject had a standard visual examination and review of medical history at entry, followed by a telephone interview that collected information on demographic characteristics, cognitive status, health status, accidents, falls, symptoms of depression, and alcohol intake. RESULTS: A multivariate linear regression model of correlates of TICS score found the strongest correlates to be education, age, occupation, and the presence of depressive symptoms. The only significant ocular condition that correlated with lower TICS score was the presence of surgical aphakia (model R2 = .46). Forty-six percent (216/472) of patients fell below the established definition of normal on the mental status scale. In a logistic regression analysis, the strongest correlates of an abnormal cognitive function score were age, diabetes, educational status, and occupational status. An item analysis using step-wise linear regression showed that 85 percent of the variance in the TICS score was explained by the ability to perform serial sevens and to repeat 10 items immediately after hearing them. Educational status correlated most highly with both of these items (Kendall Tau R = .43 and Kendall Tau R = .30, respectively). CONCLUSION: Education, occupation, depression, and age were the strongest correlates of the score on this new screening test for assessing cognitive status. These factors were stronger correlates of the TICS score than chronic medical conditions, visual loss, or medications. The Telephone Interview for Cognitive Status is a useful instrument, but it may overestimate the prevalence of dementia in studies with a high prevalence of persons with less than a high school education.

Falls in elderly patients with glaucoma.

We analyzed the determinants of serious falls among 489 ambulatory elders aged 65 years and older who received a comprehensive examination at a glaucoma consultation service. For the previous year, at least one fall requiring medical attention or restricted activity was reported by 9.6% (95% confidence interval [CI], 7.0% to 12.2%) of participants. Using logistic regression to adjust for potential confounding variables, the greatest single risk factor for falls was the use of nonmiotic topical eye medications (odds ratio [OR], 5.4; 95% Cl, 1.8 to 16.4). Additional risk factors for falls were female sex (OR, 2.3; 95% Cl, 1.1 to 4.7) and use of cardiac medications (OR, 2.5; 95% Cl, 1.1 to 5.6). Three other characteristics were also associated with the risk of falls: use of miotic eye medications (OR, 3.2; 95% Cl, 1.0 to 10.1); visual field impairment of 40% or greater (OR, 3.0; 95% Cl, 0.94 to 9.8); and use of sedatives (OR, 2.4; 95% Cl, 0.89 to 6.7). These findings suggest that ocular and systemic medications are the major predictors of falls even in this elderly population seeking ophthalmologic care for glaucoma. Medications appear to pose a greater risk for falls than even major visual impairment.