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PubMed2002

Complexities in ETS-domain transcription factor function and regulation: lessons from the TCF (ternary complex factor) subfamily. The Colworth Medal Lecture.

The ETS-domain transcription factor family can be divided into a series of subfamilies. Elk-1 represents the founding member of the ternary complex factor (TCF) subfamily. By focusing on the TCF subfamily, we can demonstrate the complexities that exist in the function and regulation of ETS-domain transcription factors. This article focuses on Elk-1 in detail and summarizes the functions of other TCFs. The key themes covered include the domain structure of the TCFs, the mechanisms of complex formation with serum response factor, regulation of TCFs by mitogen-activated protein kinase cascades, and transcriptional regulatory properties of the TCFs. Finally, the emerging role of the TCFs in vivo is discussed. A picture is developing indicating that, while these proteins exhibit significant sequence and functional conservation, key differences in their structure and regulation are being identified which may relate to unique functions of these proteins in vivo.

Amino Acid Sequence↗
PubMed2002

Incidence of functional limitation in older adults: the impact of gender, race, and chronic conditions.

OBJECTIVES: To evaluate the relation of chronic conditions, gender, and race to the incidence of activities of daily living (ADLs) limitation in older adults. DESIGN: The 2-year cumulative incidence of functional limitation was estimated from survival analysis methods by using elders without baseline functional limitations. SETTING: Longitudinal Study of Aging (LSOA). Initial interviews: 1984; reinterviews: 1986, 1988, and 1990. PARTICIPANTS: A total of 4205 elderly subjects from the LSOA. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES DEPENDENT VARIABLES: self-reported moderate (1-2 ADLs) and severe (> or =3 ADLs) functional limitation. INDEPENDENT VARIABLES: sociodemographics, self-reported chronic conditions, and prior levels of functional limitation. RESULTS: Gender and race predicted moderate functional limitation onset, after controlling for age and education. Arthritis, diabetes, prior cerebrovascular disease (CVD), incontinence, and impaired vision were significant predictors of moderate functional limitation onset after controlling for demographics. Differences in the prevalence of chronic conditions appear to explain why moderate functional limitation incidence rates are higher in older women and blacks. Gender, but not race, predicted onset of severe functional limitation, after controlling for age and education. Prior moderate functional limitation, CVD, and vision impairment predicted onset of severe functional limitation after controlling for demographics. CONCLUSION: Prevention of functional decline should target chronic conditions and moderate functional limitation in older adults.

Activities of Daily Living↗
PubMed2000

A prospective study of limiting longstanding illness in early adulthood.

BACKGROUND: Chronic illness and disability are of increasing public health importance but little is known about the lifetime influences involved in their onset and progression. We aim to (i) establish whether an individual's rating of limiting illness is stable over a 10-year period from age 23 to 33; (ii) assess the relationship between childhood and adult disability; and (iii) identify lifecourse influences on limiting illness in early adulthood. METHODS: Data were from the 1958 British birth cohort, including the original birth survey and follow-ups at ages 7, 11, 16, 23 and 33 years. Limiting longstanding illness was the outcome at both ages 23 and 33. Potential predictors included childhood health and physical development, socioeconomic conditions in early life and adulthood, and behavioural factors. We estimated the effect of potential explanatory factors using logistic regression, in both univariate and multivariate analyses, separately for limiting illness at 23 and 33 years. RESULTS: Prevalence of limiting illness increased from 5.1% (men) and 4.1% (women) at age 23 to 6% for both sexes at age 33. Risk of limiting illness at age 33 was greater for those reporting an illness at age 23 (29.4%, compared with 4.7% of those without illness), though the majority (66%) of 33-year limiting illnesses had no previous record at age 23 or for childhood. Multivariate analysis of limiting illness at age 23 confirmed the high risk for those with childhood disability and also established two further major predictors, namely, injury (adjusted odds ratio [OR] = 1.42, 95% CI: 1.09-1.86) and intermediate socio-emotional status (adjusted OR = 1.73, 95% CI: 1.29-2.31). Additional risks were identified for limiting illness at age 33, including: (i) injury in the preceding 10 years (adjusted OR = 1.55, 95% CI : 1.18-2.04); (ii) body mass index (BMI), for which the relationship was non-linear, with elevated risks for the underweight (adjusted OR = 1.53, 95% CI: 1.03-2.26) and overweight (OR = 1.28, 95% CI: 0.87-1.89); (iii) childhood disadvantage at either or both ages 7 and 11 (adjusted OR = 1.53, 95% CI : 1.07-2.17); and (iv) height at age 7, with a significant non-linear relationship (the adjusted OR for height less than 15th percentile was 1.43 and for height more than the 85th percentile, 1.30). CONCLUSIONS: Both childhood and adult factors predict limiting illness in early adulthood. Childhood is important because some adult illnesses originate in early life, and also because childhood environment influences the risk of adult limiting illness several years later. Our findings suggest that studies seeking to understand the causes of limiting illness, that currently tend to focus exclusively on contemporary factors, need also to consider the contribution of environment in early life.

Adaptation, Psychological↗
PubMed1994

Randomized, prospective trial of pressure-limited versus volume-controlled ventilation in severe respiratory failure.

OBJECTIVE: Volume-controlled ventilation is frequently chosen as the initial mode of ventilatory support in patients with hypoxic respiratory failure. Recent data, however, suggest that pressure-limited ventilation, using a rapidly decelerating flow delivery pattern, may produce a more desirable clinical effect through reduced peak airway pressures and increased static compliance, tissue oxygen delivery, and consumption. This study was performed to assess the feasibility and utility of early and sustained use of pressure-limited ventilation in patients with this clinical syndrome. DESIGN: Randomized, prospective trial. SETTING: Medical intensive care unit (ICU) of a university hospital. PATIENTS: The study encompassed all patients (n = 27) receiving care in a medical ICU for acute, severe hypoxic respiratory failure (PaO2/FIO2 ratio of < 150) during a 6-month period. INTERVENTIONS: Ventilatory support via either pressure-limited or volume-controlled ventilation, initiated within 24 hrs of endotracheal intubation. MEASUREMENTS: On-line monitoring of the following ten ventilatory variables at 1-min intervals for 72 hrs or until extubation or death (maximum of 43,200 data points per patient): peak airway pressure, mean airway pressure, end-tidal CO2 concentration, CO2 minute excretion, inspiratory tidal volume, expiratory tidal volume, pause pressure, end-expiratory pressure, static thoracic compliance, and inspiratory resistance. Additionally, PaO2/FIO2 values and Acute Physiology and Chronic Health Evaluation (APACHE) II scores were recorded on a daily basis, as were significant clinical events and changes in ventilator settings. RESULTS: Although the severity of illness at study entry as determined by APACHE II score and PaO2/FIO2 was similar in patients treated with pressure-limited or volume-controlled ventilation, peak airway pressure was consistently lower in patients randomized to pressure-limited ventilation (p = .05 at 12 hrs postintubation). The use of pressure-limited ventilation also was associated with a more rapid increase in static compliance (p = .05) than that found with volume-controlled ventilation. There was a trend toward more rapid normalization of CO2 minute excretion in patients treated with pressure-limited ventilation. Pressure-limited treated patients who survived their illness and were extubated, required fewer days of mechanical ventilation than did patients randomized to volume-controlled treated ventilation (p = .05). No pneumothoraces occurred in any study patients. One volume-controlled patient developed subcutaneous emphysema. Pressure-limited ventilation was well tolerated, and sedation requirements were equivalent in the two groups. CONCLUSIONS: Pressure-limited ventilation can be used safely and is well tolerated as an initial mode of ventilatory support in patients with acute hypoxic respiratory failure. Because the early initiation of pressure-limited ventilation is associated with lower peak airway pressure and more rapid improvement in static thoracic compliance than volume-controlled ventilation, pressure-limited ventilation may have a beneficial role when used as the primary ventilatory modality in patients with this clinical condition.

Adult↗
PubMed1977

Variations in the adenylate energy charge during phased growth (cell cycle) of Candida utilis under energy excess and energy-limiting growth conditions.

The variations in the levels of adenine nucleotides during the phased growth (cell cycle) of the yeast Candida utilis growing under nitrogen, sulfate, or iron limitation with glycerol as carbon source have been determined. Synchronous cultures were obtained by the continuous phasing technique, and the results were compared with those of chemostat cultures growing at similar growth rates and under the same types of nutrient limitation. Whereas the chemostat experiments indicated only the average energy status of cultures growing at random, results from phased cultures showed that the adenylate energy charge, defined as (ATP + (1/2)ADP)/(ATP + ADP + AMP) (where ATP, ADP, and AMP signify adenosine 5'-triphosphate, -diphosphate, and -monophosphate, respectively), varied during the phased growth of the yeast. These variations were related to the stage of development of the cells and to the type of nutrient limitation. In every case the energy charge dropped to a low value during the first half of the phasing cycle (cell cycle). Whereas the energy charge was maintained at relatively high levels (ranging from 0.78 to 0.94), for sulfate- or nitrogen-limited cultures, it was very low when iron was the growth-limiting nutrient (0.44 to 0.78). In spite of the low energy charge, the yeast continued to grow under iron limitation. The main component of the adenylate pool of the iron-limited culture was ADP and not ATP as observed with other types of nutrient limitation. It is concluded that under iron limitation the growth of the organism is limited by energy and that under energy-limited growth the energy charge of a growing organism is maintained at low levels. The reason for maintaining a low energy charge in an energy-limited culture is discussed.

Adenine Nucleotides↗
PubMed2001

Medicaid program; revision to Medicaid upper payment limit requirements for hospital services, nursing facility services, intermediate care facility services for the mentally retarded, and clinic services. Health Care Financing Administration (HCFA), HHS. Final rule.

This final rule modifies the Medicaid upper payment limits for inpatient hospital services, outpatient hospital services, nursing facility services, intermediate care facility services for the mentally retarded, and clinic services. For each type of Medicaid inpatient service, existing regulations place an upper limit on overall aggregate payments to all facilities and a separate aggregate upper limit on payments made to State-operated facilities. This final rule establishes an aggregate upper limit that applies to payments made to government facilities that are not State government-owned or operated, and a separate aggregate upper limit on payments made to privately-owned and operated facilities. This rule also eliminates the overall aggregate upper limit that had applied to these services. With respect to outpatient hospital and clinic services, this final rule establishes an aggregate upper limit on payments made to State government-owned or operated facilities, an aggregate upper limit on payments made to government facilities that are not State government-owned or operated, and an aggregate upper limit on payments made to privately-owned and operated facilities. These separate upper limits are necessary to ensure State Medicaid payment systems promote economy and efficiency. We are allowing a higher upper limit for payment to non-State public hospitals to recognize the higher costs of inpatient and outpatient services in public hospitals. In addition, to ensure continued beneficiary access to care and the ability of States to adjust to the changes in the upper payment limits, the final rule includes a transition period for States with approved rate enhancement State plan amendments.

Centers for Medicare and Medicaid Services, U.S.↗
PubMed2001

Rhamnolipid production by Pseudomonas aeruginosa under denitrification: effects of limiting nutrients and carbon substrates.

Being biosurfactants, rhamnolipids create severe foaming when produced in aerobic Pseudomonas aeruginosa fermentation. The necessary reduction of aeration causes oxygen limitation and restricts cell and product concentrations. In this study, we evaluate the new strategy of rhamnolipid production under denitrification conditions. Because hydrocarbons used in earlier aerobic fermentations were not metabolizable in the absence of oxygen, other potential C substrates were examined, including palmitic acid, stearic acid, oleic acid, linoleic acid, glycerol, vegetable oil, and glucose. All were found able to support cell growth under anaerobic denitrification. The growth on the two solid substrates (palmitic acid and stearic acid) was slower but could be enhanced substantially by initial addition of rhamnolipids (0.06 g/L). The effects of different limiting nutrients (N, P, S, Mg, Ca, and Fe) were also investigated. The commonly used N limitation could not be adopted in the denitrifying fermentation because the nitrate added for anaerobic respiration would also be assimilated for growth. P limitation was most effective, giving four- to fivefold higher specific productivity than the conventional N limitation. S limitation was comparable to N limitation; Mg limitation was much poorer. Ca and Fe were ineffective in limiting cell growth. The new strategy was further evaluated in a P-limited fermentation with palmitic acid as the substrate. The fermentation was first carried out under denitrification and later switched to aerobic condition. The specific productivity under denitrification was found to be about one-third that of the aerobic condition. The denitrification process was, however, free of foaming or respiratory limitation. Much higher cell concentrations may be employed to attain higher volumetric productivity and product concentrations, for more economical product recovery and/or purification.

Aerobiosis↗
PubMed1999

Laboratory data in healthy volunteers: reference values, reference changes, screening and laboratory adverse event limits in Phase I clinical trials.

OBJECTIVE: Laboratory data are key evaluation procedures for Phase I clinical pharmacology for two reasons. Firstly, laboratory data are used within the screening process to exclude subjects with asymptomatic diseases, which could result in increased danger to themselves or confuse interpretation of the study results. Secondly, during study implementation, safety evaluation and in particular maximum tolerated dose determination have to be done by a case-by-case analysis, sometimes using laboratory adverse events (LAEs). Thus, relevant limits are needed to discriminate between a usual common variation and a significant abnormality, which is considered to be a LAE. This report presents laboratory data distribution, reference values and reference changes and, based on previously published new methods, suggests inclusion limits at screening and laboratory adverse event limits for analysis during study implementation. SUBJECTS AND METHODS: Nine hundred and twenty-seven young healthy male volunteers were recruited in one centre (Association de Recherche Thérapeutique). A standard screening process was carried out. Protocols were approved by the local ethics committee. Blood sampling was performed in the same conditions. Reference values (at screening and at baseline) were determined by a non-parametric procedure selecting 2.5% and 97.5% of the distribution of data. Reference changes were also defined as the 2.5-97.5% interval of distribution of the variations between the end of treatment and baseline. Inclusion limit and LAE limit methods of determination used had been specified in previous articles. RESULTS: Detailed results of laboratory data distribution, reference values at screening and at baseline, reference changes, inclusion limits and LAE limits are presented in tables with number of subjects, mean, median, standard deviation, minimal and maximal values and the 2.5-97.5% interval for each laboratory parameter. CONCLUSION: The key aims of this paper are to provide clinical pharmacologists with data, reference values or changes obtained in the real conditions of Phase I study implementation, and to propose relevant limits, either for screening as inclusion limits, or during studies as LAE limits. Thus, these data, reference values and specific limits improve the capacity to screen healthy volunteers and to analyse LAEs during Phase I studies.

Adult↗
PubMed1990

Effects of the 65 mph speed limit on injury morbidity and mortality.

Effective December 1987 and January 1988, the maximum speed limit on rural limited access highways in Michigan was raised from 55 mph to 65 mph. This study examined the effects of the raised limit on injury morbidity and mortality. A multiple time-series design was used, comparing roads where the speed limit was raised with roads where the limit remained unchanged. Data were collected on numbers and rates of automobile crashes, injuries, and deaths from January 1978 through December 1988. Time-series intervention analyses were conducted to estimate effects associated with the speed limit change while controlling for long-term trends, seasonal cycles, and other patterns. Statistical controls were also included for major factors known to influence crash and injury rates. Results revealed significant increases in casualties on roads where the speed limit was raised, including a 19.2% increase in fatalities, a 39.8% increase in serious injuries, and a 25.4% increase in moderate injuries. Fatalities also increased on 55 mph limited access freeways, suggesting that the 65 mph limit may have spillover effects on segments of freeways where the limit was not changed. No significant changes in fatalities or injuries were found on other types of roads. The increased convenience of reduced travel time with the higher speed limit is obtained at a significant cost in terms of injury morbidity and mortality.

Accidents, Traffic↗
PubMed2005

Racial differences in activities of daily living limitation onset in older adults with arthritis: a national cohort study.

OBJECTIVE: To investigate factors that predict the onset of limitations in activities of daily living (ADLs) in adults 65 years old or older who have arthritis, in order to develop public health programs for minorities (African and Hispanic Americans) and white Americans. DESIGN: Longitudinal cohort study. SETTING: National probability sample. PARTICIPANTS: Older adults with arthritis (N=3541) who participated in the 1998 and 2000 Health and Retirement Study interviews and who had no baseline ADL limitations. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE: Onset of ADL limitations was identified from reports of 1 or more ADL task limitations at 2-year follow-up. RESULTS: Onset is most frequent among African Americans (24.4%), followed by Hispanics (22.2%), and whites (16.9%). Race specific multivariate analysis showed that the strongest risk factor predicting onset of limitations across all racial and ethnic groups is physical limitations. Low household income was significant for older minorities but not for whites. Comorbid cardiovascular disease was a unique multivariate risk factor among African Americans. CONCLUSIONS: Physical limitation is a strong risk factor for ADL limitation onset that is shared by all racial and ethnic groups. Early identification and treatment of physical limitations may prevent the onset of ADL limitations and thus improve quality of life. Race specific public health interventions should be considered to reduce the development of ADL limitations among older adults with arthritis.

Activities of Daily Living↗
PubMed2003

Limits for the scaled average bioequivalence of highly variable drugs and drug products.

PURPOSE: To provide a rational procedure for establishing regulatory bioequivalence (BE) limits that can be applied in determinations of scaled average BE for highly-variable (HV) drugs and drug products. METHODS: Two-period crossover BE investigations with either 24 or 36 subjects were simulated with assumptions of a coefficient of variation of 10, 20, 30, or 40%. The decline in the fraction of accepted studies was recorded as the ratio of geometric means (GMR) for the two formulations was raised from 1.00 to 1.45. Acceptance of BE was evaluated by scaled average BE, assuming various BE limits, and, for comparison, by unscaled average BE. A procedure for calculating exact confidence limits in two-period studies is presented, and an approximate method, based on the linearization of the regulatory model, is applied. RESULTS: A mixed model is proposed for average BE. Accordingly, at low variabilities, the BE limit is constant, +/-BELo, generally log(1.25). Beyond a logarithmic, limiting, "switching" variability (sigma(o)), in the region of HV drugs, the approach of scaled average BE is applied with limits of +/-(BEL(o)/sigma(o)). It is demonstrated that the performance of the mixed model corresponds to these expectations. The effect of sigma(o), and of the resulting BE limits is also demonstrated. Scaled average BE, with all reasonable limits for HV drugs, requires fewer subjects than an unscaled average BE. In two-period studies, the exact and approximate methods calculating confidence limits yield very comparable inferences. CONCLUSIONS: Scaled average BE can be effectively applied, with the recommended limits, for determining the BE of HV drugs and drug products. The limiting, "switching" variability (sigma(o)) will have to be established by regulatory authorities.

Computer Simulation↗
PubMed2002

Functional limitations of school-aged children seen in primary care.

OBJECTIVE: The purpose of the present study was to assess the prevalence of functional limitations in children seen in a large paediatric practice network and to identify sociodemographic, family and psychosocial factors related to functional limitations. STUDY DESIGN: Cross-sectional analysis. POPULATION: Children were recruited from two large, practice-based primary care research networks during their paediatric office visits. For the present study, participants included 14 630 school-aged children (ages 6-15 years) and their caregivers. OUTCOMES MEASURED: Parents completed written questionnaires including the Pediatric Symptom Checklist, the Family Apgar and the Functional Limitations Index. RESULTS: Findings indicated that 15% of children surveyed had some limitation in their daily functioning. More children had schoolwork and physical function limitations than limitations in personal and self-care. Logistic regression equations predicted functional limitations and health status in children from a model of sociodemographic factors, psychosocial symptoms and family functioning. CONCLUSIONS: A low but significant number of school-age children seen in the primary care setting experience functional limitations. Children with any psychosocial symptoms were at increased risk for functional limitations, indicating the critical need to screen for functional impairment in children with suspected behavioural or emotional problems. A screening tool of functional limitations may be useful for assessing the presence or absence of such limitations in children's daily function and warrants further investigation.

Activities of Daily Living↗
PubMed2001

Airflow limitation is underrecognized in well-functioning older people.

OBJECTIVES: Dyspnea is a common symptom in older people. A reduced forced expiratory volume in 1 second (FEV1) is associated with a higher mortality rate from cardiovascular and respiratory disease, and increased admissions to hospitals. Underrecognized or undertreated airflow limitation may exacerbate the problem. The purpose of this study was to assess the prevalence and treatment of airflow limitation in a cohort of well-functioning older people. DESIGN: Cross-sectional study. SETTING: Baseline of a clinical-epidemiological study of incident functional limitation. PARTICIPANTS: Participants attended the baseline examination of the Health, Aging, and Body Composition study, a prospective cohort study of 3,075 well-functioning subjects age 70 to 79. MEASUREMENTS: Demographic and clinical data were collected by interview. Spirometry was performed unless contraindicated and repeated until three acceptable sets of flow-volume loops were obtained. Patients on bronchodilator medications had spirometry performed posttherapy. Blinded readers assessed the flow-volume loops, and inadequate tests were omitted from analysis. Airflow limitation was defined as a reduced forced expiratory volume in 1 second/forced vital capacity (FEV1/FVC) as determined by age-, sex-, and race-normalized values. Severity of airflow limitation was defined by American Thoracic Society criteria. RESULTS: Two thousand four hundred eighty-five subjects (80.8%) had assessable spirometry and data on treatment and diagnosis (1,265 men, 1,220 women). The mean age was 73.6 years. Two hundred sixty-two subjects (10.5%) had airflow limitation; 43 (16.4%) of these never smoked. Only 37.4% of participants with airflow limitation and 55.6% of participants with severe airflow limitation reported a diagnosis of lung disease. Only 20.5% of subjects with at least moderate airflow limitation had used a bronchodilator in the previous 2 weeks. CONCLUSION: Despite their good functional status, airflow limitation was present, and underrecognized, in a considerable proportion of our older population. The low bronchodilator use suggests a significant reservoir of untreated disease. Physicians caring for older people need to be more vigilant for both the presence, and the need for treatment, of airflow limitation.

Aged↗
PubMed1986

Corporate occupational exposure limits: the current state of affairs.

It has been claimed that the implementation of occupational exposure limits has been instrumental for the near elimination of serious occupational disease in the Western world. Although exposure limits or guides for most large volume chemicals have been established, the majority of the 10,000 chemicals which are routinely used in industry do not have them. As a result, many firms have chosen to establish internal limits to protect their employees as well as the persons who purchase those chemicals. This paper reviews the most important issues discussed in a 2-day symposium on corporate exposure limits which was sponsored by the AIHA Workplace Environment Exposure Limits Committee (WEEL). Thirteen representatives of industry and professional organizations presented papers which addressed various aspects of the process for setting internal exposure limits. The various policies and methodologies used by large American companies which have set limits for many years and their benefits were discussed. The history and function of Threshold Limit Values (TLVs) Maximum Allowable Concentrations (MACs), Permissible Exposure Limits (PELs) and Workplace Environment Exposure Limits (WEELs) also were reviewed. Some of the legal aspects of setting corporate limits and their role in the Product Safety arena were discussed.

Air Pollutants, Occupational↗
PubMed1998

Disaggregating pain and its effect on physical functional limitations.

BACKGROUND: Pain is a common impairment that limits the abilities of older persons. The purposes of this article are to: (i) describe the distribution of pain location using the McGill Pain Map (MPM) in a community-based cohort of aged subjects; (ii) investigate whether individual areas of pain could be sensibly grouped into regions of pain; (iii) determine whether intensity, frequency, and location constitute independent dimensions of pain; and (iv) determine whether these three pain dimensions make differential contributions to the presence of self-reported physical functional limitations. METHODS: A total of 833 Mexican American and European American subjects, aged 65-79 years, were enrolled in the San Antonio Longitudinal Study of Aging and were interviewed in their homes between 1992 and 1996. A total of 373 (46%) of the subjects reported having pain in the past week. Physical functional limitations were ascertained using the nine items from the Nagi scale. Three composite scales were created: upper extremity, lower extremity, and total. Pain intensity and frequency were ascertained using the McGill Pain Questionnaire. Pain location was ascertained by using the MPM. RESULTS: Pain was reported in every area of the MPM. Using multiple groups confirmatory factor analysis, the 36 areas were grouped into 7 regions of pain: head, arms, hands and wrists, trunk, back, upper leg, and lower leg. Among persons with pain, pain frequency, intensity, and location were weakly associated with each other. Pain regions were primarily independent of each other, yet weak associations existed between 6 of the 21 pair-wise correlations between regions. Pain regions were differentially associated with individual physical functional limitations. Pain in the upper leg was associated with 8 of the 9 physical tasks. In multivariate analyses, age, gender, and ethnic group accounted for only 2-3% of the variance in physical tasks. In multivariate analyses, age, gender, and ethnic group accounted for only 2-3% of the variance in physical functional limitations. Pain intensity accounted for 5-6% of the variance in the composite scores of functional limitation. Pain frequency accounted for 4-5% of the variance in upper extremity limitations but did not contribute to the modeling of lower extremity limitations. In contrast, pain location accounted for 9-14% of the variance in physical functional limitations. CONCLUSIONS: We tested a method for ascertaining pain location and clearly demonstrated that pain location is an important determinant of self-reported physical functional limitations. The MPM methodology may be used in population-based studies or in clinical samples that focus on specific impairments and seek to control for pain frequency and intensity. Future studies can link specific diseases with the common impairment of pain and tease out the pathways that lead to other impairments (e.g., weakness), functional limitations, and disability.

Aged↗
PubMed2000

Attitudes toward limitation of support in a pediatric intensive care unit.

OBJECTIVE: To prospectively determine opinions of members of a pediatric intensive care unit (PICU) team regarding the appropriateness of aggressive care. The types of support that caregivers sought to limit and their reasons for wanting these limits were collected over time. DESIGN: Prospective survey of caregiver opinions. SETTING: PICU in an academic tertiary care children's hospital. SUBJECTS: A total of 68 intensive care nurses, 11 physicians attending in the PICU, 10 critical care and anesthesia fellows, and 24 anesthesia and pediatric residents. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: During a 6-month period, 503 patients were admitted to the PICU. Within this time period, 52.4% of all deaths were preceded by limitation of support, with 100% of noncardiac surgical deaths preceded by limitation of medical interventions. At least one caregiver wished to limit care for 63 of these patients (12.5%). When caregivers wished to limit support they most frequently wished to limit invasive modes of support such as cardiopulmonary resuscitation (94%) and hemodialysis (83%). The ethical rationales identified most often for wishing to limit support were burden vs. benefit (88%) and qualitative futility (83%). Preadmission quality of life was cited less frequently (50%). Caregivers were less likely to limit care on the basis of quality of life. Nurses and physicians in the PICU were very similar to each other in the types of support they thought should be limited and their ethical rationales. CONCLUSIONS: When making decisions about whether or not to limit care for a patient, caregivers were more likely to rely on the perceived benefit to the patient than preadmission quality of life.

Caregivers↗
PubMed2005

Quantifying the risks associated with exceeding recommended drinking limits.

BACKGROUND: Although daily and weekly drinking limits demonstrate strong sensitivity and specificity in identifying alcohol use disorders (AUDs), there are no descriptive data that present the risks associated with exceeding these limits in a format suitable for presentation to patients, students, and the general public. METHODS: Data collected in the 2001-2002 National Epidemiologic Survey on Alcohol and Related Conditions were used to estimate the risks of past-year DSM-IV alcohol abuse and dependence associated with various frequencies of exceeding daily drinking limits (no more than 4 drinks for men; no more than 3 drinks for women) in a nationally representative sample of 26,946 US drinkers 18 years of age and older. These risks were further categorized by whether weekly drinking limits (no more than 14 drinks for men; no more than 7 drinks for women) were exceeded and by maximum number of drinks consumed in the past year. RESULTS: The prevalence of alcohol dependence with abuse increased in a fairly linear fashion with frequency of exceeding daily drinking limits. The prevalence of dependence alone (no abuse) and abuse alone (no dependence) peaked among persons who exceeded the daily limits twice a week and then leveled off, because individuals became increasingly likely to have both disorders at higher frequencies. Exceeding the weekly limits generally increased the risks of both disorders after accounting for frequency of exceeding the daily limits, but not always to a significant extent. Likewise, maximum quantity of drinks consumed was positively associated with the risks of AUDs even after accounting for frequency of risk drinking. There were few gender differences in the risk of dependence after adjusting for frequency of exceeding daily drinking limits, but the risk of alcohol abuse remained greater among men. CONCLUSIONS: These data provide a useful tool for illustrating the broad range of risk of AUDs associated with exceeding recommended drinking limits, and they support the utility of the daily and weekly drinking limits in predicting AUDs.

Adult↗
PubMed1984

Influence of nutrient limitation and growth rate on the outer membrane proteins of Klebsiella aerogenes NCTC 418.

Four major proteins with molecular weights of 78 000, 37 000, 34 000 and 20 000 were present in the envelope of Klebsiella aerogenes when cultured at a high specific growth rate. However, at lower growth rates, the protein content and composition of the envelope depended on the imposed nutrient limitation. Under potassium-, carbon-, sulphur- and phosphorus-limited conditions, derepression of synthesis of limitation-specific proteins was observed, their apparent molecular weights being 90 000, 48 000, 41 000 and 36 000, respectively. Nitrogen-limited cells had no additional proteins. For a particular limiting nutrient, expression of the limitation-specific proteins was independent of the chemical or physical form in which the nutrient was supplied. Under potassium or sulphur limitation the specific proteins were present maximally at the lowest imposed growth rate, whereas under carbon limitation a maximum expression of these proteins was found at moderate growth rates. It is concluded that limitation-specific proteins which are associated with the outer membrane function in the uptake of limiting nutrients or, possibly, limitation-releasing compounds.

Ammonia↗