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Biomedical subjects

H White

Publications and source records attributed to H White.

At least 73 records · Page 4Linked to original sources

Can physically restrained nursing-home residents be untied safely? Intervention and evaluation design.

OBJECTIVE: To develop an intervention that will enable nursing home personnel to remove physical restraints from nursing-home residents safely and cost effectively. DESIGN: A multicenter prospective pre-post study. SETTING: Sixteen high-restraint-use nursing homes, four each from California, Michigan, New York, and North Carolina. The 16 facilities have 2075 beds. INTERVENTION: A 2-year educational demonstration study, including a 2-day workshop, specially prepared written and video materials, and telephone and on-site clinical consultations. Each nursing home designated a nurse to be the clinical coordinator and to lead a multidisciplinary team in conducting a restraint assessment and devising interventions for removal. OUTCOME MEASURES: We compared pre- and post-study aggregate and individual facility rates of restraint use, incidents and accidents, family attitudes, financial impact, serious injuries, and staff attitudes and work patterns. CONCLUSION: Preliminary data suggest that this intervention was well received and appears to be effective in achieving restraint-free care.

Aged↗

Regularized neural networks: some convergence rate results.

In a recent paper, Poggio and Girosi (1990) proposed a class of neural networks obtained from the theory of regularization. Regularized networks are capable of approximating arbitrarily well any continuous function on a compactum. In this paper we consider in detail the learning problem for the one-dimensional case. We show that in the case of output data observed with noise, regularized networks are capable of learning and approximating (on compacta) elements of certain classes of Sobolev spaces, known as reproducing kernel Hilbert spaces (RKHS), at a nonparametric rate that optimally exploits the smoothness properties of the unknown mapping. In particular we show that the total squared error, given by the sum of the squared bias and the variance, will approach zero at a rate of n(-2m)/(2m+1), where m denotes the order of differentiability of the true unknown function. On the other hand, if the unknown mapping is a continuous function but does not belong to an RKHS, then there still exists a unique regularized solution, but this is no longer guaranteed to converge in mean square to a well-defined limit. Further, even if such a solution converges, the total squared error is bounded away from zero for all n sufficiently large.

Mathematics↗

High-output congestive heart failure following transjugular intrahepatic portal-systemic shunting.

A hyperdynamic circulatory state with elevated cardiac output, decreased peripheral vascular resistance, and sodium retention occurs in patients with portal cirrhosis. Surgical portal-systemic shunts and transjugular intrahepatic portal-systemic shunts (TIPS) have been shown to worsen the high-output state in these patients. However, clinical evidence of high-output congestive heart failure has been reported only rarely to complicate cirrhosis. We describe a patient who developed high-output congestive heart failure with markedly elevated filling pressures after TIPS and had complete resolution of heart failure after liver transplantation.

Cardiac Output, High↗

Millisecond time resolution electron cryo-microscopy of the M-ATP transient kinetic state of the acto-myosin ATPase.

The structure of the AM-ATP transient kinetic state of the acto-myosin ATPase cycle has been examined by electron microscopy using frozen-hydrated specimens prepared in low ionic strength. By spraying grids layered with the acto-S1 complex with ATP immediately before freezing, it was possible to examine the structure of the ternary complex with a time resolution of 10 ms. Disordered binding of the S1 was observed, suggesting more than one attachment geometry. This could be due to the presence of more than one biochemical intermediate, or to a single intermediate binding in more than one conformation.

Adenosine Triphosphate↗

Visceral leishmaniasis: an unusual cervical presentation.

Visceral leishmaniasis is an infectious disease with a classical clinical presentation of fever, anaemia and splenomegaly forming the three cardinal signs. A rare presentation of the disease is described where cervical lymph node enlargement was the only sign and there were no symptoms. It is emphasised that with extensive travel to and from areas of endemic leishmaniasis now established, it is important that clinicians and pathologists become acquainted with the characteristics of the disease.

Animals↗

A model of the release of myosin heads from actin in rapidly contracting muscle fibers.

We describe a model that relates the maximum shortening velocity of a muscle fiber, Vm, to the kinetics of the dissociation of a myosin head from actin. At Vm, the positive work exerted by cross-bridges attached in the powerstroke must be balanced by cross-bridges that have been carried by movement of the filaments into a region where they exert a negative force. This balance allows one to relate Vm and the rate of cross-bridge detachment. Studies of actomyosin kinetics suggest that at high substrate, detachment should be limited by a slow protein isomerization (approximately 50 s-1) that precedes ADP release. This rate is too slow to be easily accommodated in existing models. However, a slow rate for cross-bridge dissociation, similar to that of the isomerization, is predicted if previous models are modified to include rapid detachment of cross-bridges that have been carried so far into the negative force region that their free energy exceeds that of the detached state. The model also explains another aspect of muscle contraction: at high shortening velocities, the observed rate of ATP hydrolysis is low, because a cross-bridge can interact with multiple actin binding sites before releasing the hydrolysis products and binding another ATP.

Actins↗

Electron cryomicroscopy of acto-myosin-S1 during steady-state ATP hydrolysis.

The structure of the complex of actin and myosin subfragment-1 (S1) during steady-state ATP hydrolysis has been examined by electron microscopy. This complex is normally dissociated by ATP in vitro but was stabilized here by low ionic strength. Optimal conditions for attachment were established by light-scattering experiments that showed that approximately 70% of S1 could be bound in the presence of ATP. Micrographs of the unstained complex in vitreous water suggest that S1 attaches to actin in a variety of configurations in ATP; this contrasts with the single attached configuration seen in the presence of ADP. The data are therefore compatible with the idea that a change in attached configuration of the myosin cross-bridge is the origin of muscle force. In control experiments where ATP was allowed to hydrolyze completely the binding of the S1 seemed cooperative.

Adenosine Diphosphate↗

Colour vision screening in glaucoma: the Tritan Album and other simple tests.

Results from simple colour vision tests used for the detection of the Type III colour vision deficiency in glaucoma and ocular hypertension are presented. We assessed 49 patients with primary open angle glaucoma, 16 ocular hypertensives, 54 age matched normals and 50 young normal observers using six established tests and the recently introduced Tritan Album. This test was introduced specifically for acquired colour vision deficiencies. Results show in general that individual tests have low sensitivity and poor screening efficiency. The best screening efficiency was achieved by the City University Colour Vision Test and the AO HRR plate test, no acquired tritan defects were identified by the Farnsworth F2 plate, and the Tritan Album had very low sensitivity (the lowest excluding the F2 plate). Best results were obtained from a combination of City University and HRR test scores and this combination could provide useful additional data on colour vision in a glaucoma screening programme.

Aged↗

Interpretation of automated perimetry for glaucoma by neural network.

PURPOSE: Neural networks were trained to interpret the visual fields from an automated perimeter. The authors evaluated the reliability of the trained neural networks to discriminate between normal eyes and eyes with glaucoma. METHODS: Inclusion criteria for glaucomatous and normal eyes were the intraocular pressure and the appearance of the optic nerve; previous visual fields were not used. The authors compared the backpropagation learning method used by automated neural networks to those used by two specialists in glaucoma to classify the central 24 degrees automated perimetric visual fields from 60 normal and 60 glaucomatous eyes. RESULTS: The glaucoma experts and a trained two-layered network were each correct at approximately 67%. The average sensitivity of this test was 59% for the two glaucoma specialists and 65% for the two-layered network. The corresponding specificities were 74% and 71% for the specialists and the two-layered network, respectively. The experts and the network were in agreement about 74% of the time, which indicated no significant disagreement between the methods of testing. Feature analysis with a one-layered network determined the most important visual field positions. CONCLUSIONS: The authors conclude that a neural network can be taught to be as proficient as a trained reader in interpreting visual fields for glaucoma.

Adult↗

Attitudes and practice of New Zealand doctors in the management of patients with dyslipidaemia.

AIMS: To assess current attitudes and clinical practice of New Zealand doctors in the management of dyslipidaemia. METHODS: Questionnaires were sent to all New Zealand general practitioners, fellows of the Royal Australasian College of Physicians and members of the Cardiac Society. Questions were asked about the present status of plasma lipids as risk factors for coronary heart disease, screening practices, thresholds for dietary and drug intervention and the cost-effectiveness of interventions. RESULTS: A total of 1798 replies were analysed, an effective response rate of 64%. Eighty-six percent were from general practitioners. Cholesterol is regarded as an independent risk factor for coronary heart disease by 88% (95% CI 86-89) of general practitioners, 94% (86-98) of general physicians and 98% (88-100) of cardiologists. High-density lipoprotein cholesterol is regarded as an independent risk factor less by general practitioners (68% (66-70)) than general physicians (87% (76-94)) or cardiologists (89% (76-96)), p < 0.001. Over 80% of doctors believe that reducing cholesterol levels will reduce cardiac death, myocardial infarction and the progression of coronary heart disease. However, in practice only 25% measure lipids in all their adult patients, 92% measure lipids in patients with symptomatic coronary heart disease, 86% in patients with hypertension and 60% in smokers, while 73% percent of doctors have measured their own cholesterol. Whereas 86% thought the population diet should be modified, 71% of doctors would not give dietary advice to asymptomatic patients unless the fasting cholesterol was > 6.5 mmol/L. The reduction in cholesterol achieved by a low fat diet was thought to be < 10% by 68% of responders. Fifty percent of doctors refer less than a quarter of their patients to dietitians although 83% stated that they had ready access to a publicly-funded dietitian. There is wide variation in thresholds for intervention in patients with symptomatic coronary heart disease. The median threshold for dietary intervention was 5.2-6.5 mmol/L, and for drug therapy, 6.6-7 mmol/L among physicians. Eight percent of doctors believe patients > 75 years of age should be treated for dyslipidaemia with drugs. Over half could not answer questions about the relative cost-effectiveness of lipid-modifying drug therapy. CONCLUSIONS: Most New Zealand doctors believe there is an independent relationship between plasma lipid levels and coronary heart disease. In practice, screening is selective and there is wide variation in thresholds for dietary and drug intervention.

Attitude of Health Personnel↗

The use of differing nucleotides to investigate cross-bridge kinetics.

We have investigated the ability of the nucleotides GTP, CTP, and 1-N6-etheno-2-aza-ATP (aza-ATP) to support contraction of chemically skinned rabbit psoas fibers. Working at 10 degrees C, millimolar concentrations of all nucleotides relaxed fibers in the absence of calcium. In active fibers, GTP served as a very poor substrate with isometric tension, isometric GTPase rate, and maximum shortening velocity (Vmax) all less than 10% of those obtained with ATP. Aza-ATP was only a slightly better substrate. CTP, on the other hand, was an effective substrate with mechanical parameters which were 65-100% those obtained with ATP, and with a hydrolysis rate that exceeded that of ATP. For all three ligands, Vmax followed Michaelis-Menten saturation behavior with values for Km which were from 2.5 to 12 times greater than that for ATP, showing that the analogs bound slowly to myosin in the fibers. Increasing concentrations of orthophosphate inhibited tension with CTP, to a lesser extent with aza-ATP, but not all with GTP. A combination of the mechanical data obtained in fibers with the kinetic data obtained in solution (White, H.D., Belknap, B., and Jiang, W. (1993) J. Biol. Chem. 268, 10039-10045) is used to better define the actomyosin interaction in fibers.

Adenosine Triphosphate↗

Haemonectin, a granulocytic-cell-binding protein, is related to the plasma glycoprotein fetuin.

Haemonectin, a protein present in rabbit bone marrow extracellular matrix extracts, has been reported to bind granulocytes in a developmentally regulated manner. We have purified haemonectin from such extracts and determined the partial amino-acid sequence. The sequence obtained shows 60-70% similarity with the sequence of the plasma glycoprotein fetuin from other mammal species. This difference is consistent with the difference between fetuins from different species. We conclude that the rabbit haemonectin molecule is related to fetuin. The similarity between haemonectin and fetuin is reinforced by analysis with Western blots of one- and two-dimensional gels. These show that haemonectin, like fetuin, is present in serum and that migration of haemonectin from serum and extracellular matrix extracts, on two-dimensional gels, co-incides with that of human fetuin (alpha 2HS-glycoprotein) from serum, extracellular matrix extracts and in purified form. Also, antihaemonectin antibodies cross react with human fetuin. These data imply that the rabbit haemonectin molecule is closely related to fetuin, but do not rule out the possibility that these molecules are functionally distinct.

Amino Acid Sequence↗

Determination of the myosin step size from mechanical and kinetic data.

During muscle contraction, work is generated when a myosin cross-bridge attaches to an actin filament and exerts a force on it through some power-stroke distance, h. At the end of this power stroke, attached myosin heads are carried into regions where they exert a negative force on the actin filament (the drag stroke) and where they are released rapidly from actin by ATP binding. Although the length of the power stroke remains controversial, average distance traversed in the drag-stroke region can be determined when one knows both rate of cross-bridge dissociation and filament-sliding velocity. At maximum contraction velocity, the average force exerted in the drag stroke must balance that exerted in the power stroke. We discuss here a simple model of cross-bridge interaction that allows one to calculate the force exerted in the drag stroke and to relate this to the power-stroke distance h traversed by cross-bridges in the positive-force region. Both the rate at which myosin can be dissociated from actin and the velocity at which an actin filament can be translated have been measured for a series of myosin isozymes and for different substrates, producing a wide range of values for each. Nonetheless, we show here that the rate of myosin dissociation from actin correlates well with the velocity of filament sliding, providing support for the simple model presented and suggesting that the power stroke is approximately 10 nm in length.

Actins↗