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Biomedical subjects

D Gifford

Publications and source records attributed to D Gifford.

At least 19 recordsLinked to original sources

Benchmarking and quality in residential and nursing homes: lessons from the US.

BACKGROUND: Performance measurement and benchmarking are common concerns in the delivery of long term care. It is common to measure the performance of providers and to publicly report these data. This paper examines selected technical challenges facing those who design, implement and disseminate health care quality performance measures. METHOD: Review of the application of measures of performance in the US nursing home sector. RESULTS: Using examples drawn from the skilled nursing home arena, problems ranging from data reliability and validity, the multi-dimensional nature of quality measures and selection bias as well as differential measurement abilities are discussed. CONCLUSIONS: Benchmarking of performance is an inherently complex issue. However, to ensure that such comparisons are both fair and valid requires measures to be more technically sophisticated and sensitive to real changes attributable to changes in care.

Benchmarking↗

External threats and nursing home administrator turnover.

External threats and volatility in the long-term-care sector in recent decades have posed serious challenges for nursing home administrators. Greater job complexity and administrative responsibilities resulting from public policies and more specialization and competitiveness in nursing home markets have made turnover a significant issue. This article examines administrator turnover from 1970 through 1997 in New York State and describes how turnover increased markedly in the late 1980s and early 1990s.

Attitude of Health Personnel↗

Functional decline in independent elders after minor traumatic injury.

OBJECTIVES: To describe injury types, patterns, and health status in independently functioning elder patients presenting to the emergency department (ED) after a minor traumatic injury; and 2) to assess short-term functional decline in this population at three-month follow-up. METHODS: This was a prospective observational study of elder patients (age > 65 years) discharged home from the ED after evaluation and treatment for an acute traumatic injury. Patients were excluded if they were not independently functioning or had an acute delirium. Type and mechanism of injury sustained during the ED visit were recorded. Functional status was assessed during the visit and three months later using activities of daily living (ADL) and instrumental activities of daily living (IADL) scores. RESULTS: One hundred six subjects were enrolled in the study. Mean age was 74.8 years. The most common injuries observed were contusion (n = 35, 33%, 95% CI = 24% to 42%), fractures (n = 28, 26%, 95% CI = 18% to 36%), lacerations (n = 20, 19%, 95% CI = 12% to 28%), and sprains (n = 12, 11%, 95% CI = 6% to 19%), which represented more than 90% of the injuries. Eighty-eight (83%) patients completed three-month follow up. Of these, 6 of 88 (6.82%, 95% CI = 3% to 14%) declined in their ADL scores and 20 of 88 (22.73%, 95% CI = 14% to 33%) declined in their IADL scores at three months. Primary injury type, specifically contusion, was more prevalent in patients who had a decline in ADL score, as compared with those who did not have a decline in ADL score (chi-square p<0.001). In addition, anatomic locations of injury were different between those patients with and without a decline in IADL scores (chi-square p = 0.008). Gender differences were also found; females were more likely to be injured by a slip, trip, or fall indoors (36 of 58, 62%) than outdoors (22 of 58, 38%); males injured by this mechanism were more likely to be injured outdoors (14 of 20, 70%) as opposed to indoors (6 of 20, 30%), chi-square p = 0.013. CONCLUSIONS: A significant proportion of functional elder patients with minor traumatic injury are at risk for short-term functional decline. Decline in ADL is related to injury type, while IADL decline is related to anatomic location of injury. Emergency physicians should consider initiating follow-up evaluation and possible intervention in highly functioning elders after minor traumatic injury.

Activities of Daily Living↗

Stroke update.

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Aged↗

Strength of indication for cesarean delivery: comparison of private physician versus resident service labor management.

OBJECTIVE: Our purpose was to compare the strength of indication for cesarean delivery for 2 groups of patients who had undergone cesarean delivery-those treated by physicians in private or group practice and those treated by a clinic or resident service. STUDY DESIGN: From records of 119 cesarean deliveries performed in 1992, data concerning patient history, labor course and management, fetal monitor tracings, and indications for cesarean delivery were extracted, summarized, and presented to 3 reviewers. Each reviewer rated the strength of indication for cesarean delivery on a 10-point visual analog scale and specified how often they would have chosen an alternative management plan. Reviewers were blinded to the research hypothesis and to patient age, type of provider, and insurance status. RESULTS: Using a multivariate linear regression model to adjust for differences in age and indication for cesarean delivery, we found that strength of indication scores were higher among patients treated by a resident service than among those treated by private physicians (P <.0001) and that an alternative action plan was more often suggested for deliveries managed by private physicians (P <.0001). CONCLUSIONS: Among women who underwent cesarean delivery, the strength of indication judged by a panel of reviewers not involved with the patient's care was stronger among resident-treated patients than among cases treated by private physicians. Although there are several possible explanations, the findings may suggest that physicians in private practice use different criteria than do resident physicians for deciding to perform a cesarean.

Adult↗

An analysis of personnel dose records which justifies the application of cost-benefit analysis techniques in the design of an afterloading facility and the use of controlled areas and systems of work within suite to control occupational exposure.

The sealed source operational policies employed at the Bristol Radiotherapy and Oncology Centre were originally designed to meet the requirements of the 1972 Code of Practice by ensuring that individual personnel doses were kept below the relevant quarterly and annual dose limits. In 1982-1983, measures were taken to improve personnel radiation safety within the brachytherapy treatment facility by (a) making preparations for the introduction of Selectron medium-dose-rate (MDR) afterloading systems at the centre for intracavitary brachytherapy and (b) reviewing the operational policies to ensure that they meet the more stringent requirements of the ALARA (as low as reasonably achievable) principle, a principle subsequently embodied in the 1985 UK ionising Radiations Regulations (IRR 85). When considering the implications of making existing single-bedded side wards, originally designed for low-dose-rate brachytherapy and suitable for the new systems, the cost of the extra protection required to reduce the instantaneous dose rate in the ward corridors adjacent to the treatment room to less than 7.5 microSv h-1 had to be determined. On the basis of the cost-benefit analysis, it was decided not to provide additional shielding but rather to introduce administrative controls based on local rules which contained systems of work and the operational policies for the afterloading systems. After using the MDR afterloading systems for 2 years, a period in which there has also been a marked increase in interstitial brachytherapy, an analysis was made of the doses received by nursing staff over the past 8 years. This has shown that, in spite of higher dose rates in the corridor areas because of the use of an MDR system and the increase in interstitial techniques, the doses to ward nurses have been significantly reduced by encouraging staff to comply with the ALARA principle and the introduction of afterloading systems.

Brachytherapy↗

ATP- and polyphosphate-mediated stimulation of pp60c-src kinase activity in extracts from vascular smooth muscle.

Recently, we reported that pp60c-src kinase activity was present in adult bovine coronary arterial smooth muscle and showed that the activity of the enzyme in in vitro immunoprecipitation assays was stimulated 20-60-fold by ATP (Di Salvo, J., Gifford, D., and Kokkinakis, A. (1988) Biochem. Biophys. Res. Commun. 153, 388-394). In the present study, ATP-mediated stimulation of activity was also demonstrated in extracts from aortic vascular smooth muscle. In contrast, no stimulation was apparent in extracts from brain. Stimulation of activity in vascular preparations was also induced with beta,gamma-imidoadenosine 5'-triphosphate (AMP.PNP), a nonmetabolizable analog of ATP, and with several other polyphosphates including ADP and sodium pyrophosphate. No stimulation occurred in response to monophosphates such as AMP or KH2PO4. As expected, the specific activity of pp60c-src in brain extracts did not change when the amount of extracted protein included in immunoprecipitation mixtures was increased. Unexpectedly, however, the specific activity of the vascular enzyme decreased markedly as the amount of extracted protein subjected to immunoprecipitation was increased. Following stimulation of pp60c-src in vascular extracts with ATP, the enzyme behaved in a fashion similar to pp60c-src extracted from brain. That is, the enhanced specific activity of the stimulated vascular enzyme did not decrease with increasing amounts of extracted protein. Moreover, mixing experiments in which vascular smooth muscle extracts were added to brain extracts showed that the muscle extracts contained a factor which inhibited pp60c-src kinase activity. This inhibition was blocked when the mixed extracts were immunoprecipitated in the presence of ATP, or when inhibitory extract was treated with trypsin. Taken together, these data suggest that pp60c-src kinase activity in vascular tissue may be subject to a novel regulatory mechanism involving an inhibitory protein factor which can be nullified by polyphosphates.

Adenosine Diphosphate↗

pp60c-src kinase activity in bovine coronary extracts is stimulated by ATP.

pp60c-src kinase is believed to participate in regulating key cellular mechanisms including signal transduction and differentiation of smooth muscle during early embryogenesis. In this study, pp60c-src kinase activity was demonstrated in extracts from adult bovine coronary arterial smooth muscle. Activity, reflected by autophosphorylation of pp60c-src, phosphorylation of exogenous substrates, and phosphorylation of several endogenous substrates, was enhanced about 2 fold when added Mg2+ was replaced by Mn2+. Unexpectedly, activity was dramatically stimulated 20-50 fold by prior incubation with ATP. Such stimulation appears to be mediated through a novel mechanism which is independent of ATP-induced phosphorylation of reaction components. These new observations strongly suggest that a unique mechanism exists for regulation of coronary arterial pp60c-src kinase activity. Conceivably, this mechanism may serve important roles in modulating signal transduction and contractility of vascular smooth muscle.

Adenosine Triphosphate↗

Glycosaminoglycans and a newly purified aortic chondroitin proteoglycan block polycationic modulation of protein phosphatase activity.

Recently, we described a bovine aortic phosphatase which we called PCM-phosphatase (polycation modulable) because its activity in vitro can be modulated by polycations such as polylysine and histone-H1 (Di Salvo J, Gifford D, Kokkinakis A. Modulation of aortic protein phosphatase activity by polylysine. Proc Soc Exp Biol Med 177:24-32, 1984). We We suspected that polycationic modulation might be inhibited by polyanionic glycosaminoglycans. Accordingly, an aortic anionic substance was purified by sequential steps including (a) heating aortic extracts at 90 degrees C, (b) precipitation of protein with (NH4)2 SO4, and (c) anionic-exchange chromatography on a Mono Q HR 5/5 column using the Pharmacia fast protein liquid chromatography system. Electrophoresis (polyacrylamide-agarose) of the purified substance revealed one band which stained metachromatically with toluidine blue; however, no staining occurred with Coomassie blue. Electrophoretic mobility increased following proteolytic digestion of the substance with papain. The substance produced concentration-dependent reversal of polylysine-mediated inhibition of myosin light chain dephosphorylation, and it also reversed polylysine-mediated stimulation of phosphorylase phosphatase activity expressed by PCM-phosphatase. Its ability to inhibit or reverse polycationic modulation was abolished after incubation with either chondroitinase AC or chondroitinase ABC. Based on these properties the substance was identified as a chondroitin proteoglycan. Commercially available glycosaminoglycans (heparin and chondroitin sulfates) also reversed polycationic modulation. The results show that modulation of phosphatase activity may be significantly modified by naturally occurring glycosaminoglycans. These studies may also have an important bearing on the purported roles of phosphatase(s) and glycosaminoglycans in calcification of soft tissues.

Animals↗

A multisubstrate Ca2+ and cyclic nucleotide independent kinase from vascular smooth muscle: modulation of activity by polycations.

A multisubstrate Ca2+ and cyclic nucleotide independent kinase (Mr = 47,000) was purified from bovine aortic smooth muscle. Phosphorylation of glycogen synthase by this enzyme was polycation modulable. Low concentrations of polylysine (0.04-0.16 microM) stimulated phosphorylation 2-7 fold, whereas higher concentrations suppressed phosphorylation. Glycogen synthase converted to its glucose 6-PO4 dependent form following phosphorylation in either the presence (7 mol 32P/mol synthase) or absence (4 mol 32P/mol synthase) of polylysine: extent of conversion correlated to extent of phosphorylation. Seven of 14 potential substrates tested were phosphorylated: kinase activity was greatest for phosvitin followed by casein, the receptor protein from type 2 cAMP-kinase, histone H2b, phosphorylase kinase, glycogen synthase, and myocardial myosin light chains. Phosphorylation of phosvitin or synthase was inhibited by heparin (1/2 maximally by 0.5 microgram/ml without salt and 37 micrograms/ml with 150 mM NaCl). The results suggest that the enzyme may participate in regulating arterial glycogen metabolism and that such regulation may be modulated by polycationic and polyanionic effectors.

Animals↗

Heat-stable regulatory factors are associated with polycation-modulable phosphatases.

Several protein phosphatases which we designated PCM-I, PCM-II and PCM-IId were identified in preparations from aortic smooth muscle. A unique feature of these enzymes is that phosphatase activities expressed against different substrates are subject to modulation by polycationic effectors such as polylysine and lysine-rich histone-H1. They can be distinguished from each other by virtue of significant quantitative differences regarding (a) relative substrate specificities exhibited against phosphorylated myosin light chains, phosphorylase, and inhibitor-1, (b) apparent molecular weights as determined by sucrose density centrifugation, and (c) differential susceptibility to polylysine-mediated modulation of phosphatase activities. Surprisingly, gel filtration of the very same PCM-phosphatase preparation yields either of two apparently different enzymes: namely PCM-II, or PCM-IId. The enzymes appear similar in that low concentrations of polylysine (0.03-0.13 microM) inhibit dephosphorylation of light chains by either enzyme and high concentrations inhibit dephosphorylation of phosphorylase a. However, PCM-II exhibits higher basal phosphatase activity against myosin light chains (480 U/mg) than against phosphorylase a (175 U/mg). In contrast, PCM-IId is more effective in dephosphorylating phosphorylase a (180 U/mg) than in dephosphorylating the light chains (88 U/mg). Moreover, phosphorylase phosphatase activity of PCM-II is biphasically stimulable by low concentrations of polylysine (0.01-0.5 microM), but no stimulation is seen with PCM-IId. In addition, earlier studies with PCM-I showed that, unlike either PCM-II or PCM-IId polylysine biphasically stimulated the dephosphorylation of both phosphorylase a and the myosin light chains. Nevertheless, in spite of these obvious differences between the enzymes other data suggests that the PCM-phosphatases may be related to each other. Incubation of PCM-II at 90 degrees C for 10 min apparently releases heat-stable regulatory proteins which reverse the modulatory effects of polylysine on light chain and phosphorylase phosphatase activities expressed by either PCM-II or PCM-I. Similarly, heat-stable proteins released from PCM-I also reverse polylysine-mediated modulation of both PCM-I and PCM-II. These findings are consistent with a working hypothesis suggesting that PCM-phosphatase may consist of a modulatory domain containing several regulatory proteins and a catalytic domain.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Prolonged relaxation of detergent-skinned smooth muscle involves decreased endogenous phosphatase activity.

Since contraction of smooth muscle involves Ca2+-dependent phosphorylation of the 20 Kd myosin light chains, changes in endogenous phosphatase activity may participate in regulating smooth muscle contractility. We found that detergent-skinned fibers from 7 of 10 chicken gizzards studied were characterized by relatively high endogenous light chain phosphatase activity (23 mU/mg protein) and rapid relaxation (t1/2 = 1-3 min) in the absence of Ca2+ (less than 10(-8) M). In contrast, skinned fibers from 3 of the gizzards exhibited very low phosphatase activity (3 mU/mg protein) and markedly prolonged relaxation (t1/2 = 50-200 min). However, such slow relaxing fibers were converted to a form resembling rapidly relaxing fibers (t1/2 = 4-10 min) when an aortic polycation-modulable phosphatase was included in the incubation medium. Moreover this phosphatase-enhanced relaxation was associated with dephosphorylation of the light chains. Maximal isometric force (1 mN) and light chain phosphorylation (0.8 mol PO4/mol light chain) were similar in slowly and rapidly relaxing fibers. Thus, the two populations of skinned fibers, though dramatically different with respect to phosphatase activity and relaxation time, appeared to be very similar in terms of Ca2+-dependent contraction. These findings strongly suggest that prolonged relaxation of smooth muscle of the kind noted in this study, and perhaps in hypertensive or aging vascular smooth muscle, may reflect decreased endogenous phosphatase activity.

Animals↗

A new heat-stable regulatory factor is associated with aortic polycation-modulated (PCM)-phosphatase.

An aortic phosphatase which dephosphorylates several proteins including phosphorylase a and the 20-kDa myosin light chains is subject to modulation in vitro by polycationic effectors such as lysine-rich histone-H1 and polylysine. This study was based on the hypothesis that polycationic modulation of expressed enzymic activity involves interactions between the effectors and a regulatory site associated with the polycation-modulated (PCM)-phosphatase. Basal PCM-phosphatase activity expressed against myocardial myosin light chains (MLC, 1258 nmole/min/mg) was about eightfold greater than activity expressed against phosphorylase a (149 nmole/min/mg). However, dephosphorylation of phosphorylase a was stimulated four- to sevenfold by low concentrations of polylysine (Mr = 13,000; 0.01-0.1 microM), whereas MLC phosphatase activity was virtually abolished. Higher concentrations of polylysine inhibited dephosphorylation of either substrate. Interestingly, a heat-stable fraction prepared from the PCM-phosphatase reversed the stimulatory effect of polylysine on phosphorylase phosphatase activity and the inhibitory effect on dephosphorylation of MLC. No reversal of the modulatory effects of polylysine occurred when protein phosphatase inhibitor 1 or inhibitor 2 was substituted for the heat-stable factor derived from the PCM-phosphatase. Sucrose density centrifugation of the enzyme yielded a single peak (Mr = 63,000) exhibiting polycation-modulated activity against phosphorylase a and MLC. Moreover, heating each of the gradient fractions showed the presence of a heat-stable factor which reversed the modulatory effects of polylysine on dephosphorylation of either phosphorylase a or MLC. These results show that a specific heat-stable factor, which differs from both inhibitor 1 and 2, is associated with the PCM-phosphatase. The results suggest that polycationic modulation of expressed PCM-phosphatase activity may involve interactions between the polycationic effector and the enzyme-associated regulatory factor.

Animals↗