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Biomedical subjects

R Burke

Publications and source records attributed to R Burke.

At least 37 records · Page 2Linked to original sources

Direct and long-range action of a DPP morphogen gradient.

During development of the Drosophila wing, the decapentaplegic (dpp) gene is expressed in a stripe of cells along the anteroposterior compartment boundary and gives rise to a secreted protein that exerts a long-range organizing influence on both compartments. Using clones of cells that express DPP, or in which DPP receptor activity has been constitutively activated or abolished, we show that DPP acts directly and at long range on responding cells, rather than by proxy through the short-range induction of other signaling molecules. Further, we show that two genes, optomotor-blind and spalt are transcriptionally activated at different distances from DPP-secreting cells and provide evidence that these genes respond to different threshold concentrations of DPP protein. We propose that DPP acts as a gradient morphogen during wing development.

Animals↗

Dpp receptors are autonomously required for cell proliferation in the entire developing Drosophila wing.

The mammalian growth factor TGFbeta negatively regulates cell proliferation in various systems. Here we provide evidence that another TGFbeta superfamily member, Drosophila Decapentaplegic (Dpp), stimulates cell proliferation. In the developing wing blade, somatic clones lacking the Dpp receptors Punt or Thick veins (Tkv), or lacking Schnurri, a transcription factor involved in Dpp signal interpretation, fail to grow when induced early in larval development. Furthermore the spatial requirement for these signaling components indicates that Dpp has to travel several cell diameters from its source in order to reach all cells that require its signal. The requirement for Tkv also depends on the distance of cells from the source of the Dpp signal. We propose that Dpp can act at a distance to positively control cell proliferation.

Animals↗

Schnurri is required for Drosophila Dpp signaling and encodes a zinc finger protein similar to the mammalian transcription factor PRDII-BF1.

Cytokines of the TGF beta superfamily regulate many aspects of cellular function by activating receptor complexes consisting of two distantly related serine/threonine kinases. Previous studies have indicated that Drosophila dpp uses similar signaling complexes and strictly requires the punt and thick veins receptors to transduce the signal across the membrane. Here, we show that the schnurri (shn) gene is required for many aspects of dpp signaling. Genetic epistasis experiments indicate that shn functions downstream of the dpp signal and its receptors. The shn gene encodes a large protein similar to a family of mammalian zinc finger transcription factors. The shn protein might therefore act as a nuclear target in the dpp signaling pathway directly regulating the expression of dpp-responsive genes.

Activin Receptors↗

Comparison of simulated and in-vivo plasma levels of cilastatin following intravenous in-line drug administration.

The primary objective of this work was to establish a method to simulate the plasma levels of cilastatin, a model drug, following an intravenous in-line delivery scheme. In-vivo data in dogs obtained from this work were used to demonstrate the validity of the proposed approach. The in-line drug delivery system consists of a drug containing device which is placed between a large volume parenteral and a patient. Numerous advantages have been identified for this automatic in-line reconstitution delivery system. The numerical convolution integral algorithm was used in this work to perform plasma profile simulation. The results indicated that the simulated cilastatin plasma profile following in-line delivery closely agreed with the in-vivo data.

Animals↗

Refining a case-mix measure for nursing homes: Resource Utilization Groups (RUG-III).

A case-mix classification system for nursing home residents is developed, based on a sample of 7,658 residents in seven states. Data included a broad assessment of resident characteristics, corresponding to items of the Minimum Data Set, and detailed measurement of nursing staff care time over a 24-hour period and therapy staff time over a 1-week period. The Resource Utilization Groups, Version III (RUG-III) system, with 44 distinct groups, achieves 55.5% variance explanation of total (nursing and therapy) per diem cost and meets goals of clinical validity and payment incentives. The mean resource use (case-mix index) of groups spans a nine-fold range. The RUG-III system improves on an earlier version not only by increasing the variance explanation (from 43%), but, more importantly, by identifying residents with "high tech" procedures (e.g., ventilators, respirators, and parenteral feeding) and those with cognitive impairments; by using better multiple activities of daily living; and by providing explicit qualifications for the Medicare nursing home benefit. RUG-III is being implemented for nursing home payment in 11 states (six as part of a federal multistate demonstration) and can be used in management, staffing level determination, and quality assurance.

Costs and Cost Analysis↗

Mental dysfunction and resource use in nursing homes.

The role of dementia and other mental disorders in nursing home case-mix classification systems has been an area of controversy. The role of mental dysfunctions was considered in developing a new case-mix measurement system for facility payment in a national demonstration to understand staff time use in nursing homes. Nursing staff (nurses and aides) time and resident assessment data were collected for 6,663 nursing home residents in 6 states. Measures of signs and symptoms of cognitive impairment (dementia), depression, and delirium were created based on items from the new National Minimum Data Set. These measures then were used to determine whether mental dysfunctions were predictive of resource use (nursing staff times and costs) when controlling for other case-mix variables. Cognitive impairment was associated with slightly higher staff time only in less physically-impaired residents without serious medical conditions and not receiving heavy rehabilitation. Similarly, depression and delirium were associated with higher resource use only in selected types of residents. Based on these findings, the new Resource Utilization Groups Version III (RUG-III) contain a major category of residents who are cognitively impaired but not severely dependent in Activities of Daily Living. Depression is used to differentiate subgroups of residents with major medical conditions such as hemiplegia and aphasia. Delirium, when used together with other resident characteristics, was not found useful in explaining resource use. Case-mix groups defined by mental dysfunctions can foster improved care, but careful consideration must be given to appropriate incentives and documentation requirements for providers.

Aged↗

Bedside diagnostic blood testing. Its accuracy, rapidity, and utility in blood conservation.

OBJECTIVE: --Bedside diagnostic testing utilizing microchemistry instruments potentially offers physicians the opportunity to evaluate urgent blood test results rapidly and reliably using only drops (250 microL) of whole blood. The use of microchemistry technology may also represent an essential component of a blood conservation program in acutely ill patients. We tested the hypothesis that a microchemistry instrument would have important advantages in the intensive care unit, including rapid turnaround time, decreased iatrogenic blood loss, and the provision of accurate analyte results. DESIGN: --One-year prospective, random-sample comparative study. SETTING: --A tertiary, acute care, 1000-bed university teaching hospital and a 450-bed university-affiliated community hospital. PATIENTS: --Blood samples from 850 patients were analyzed. RESULTS: --There were strong correlations (for pH, R2 = .97; PCO2, R2 = .97; PO2, R2 = .99; sodium, R2 = .83; potassium, R2 = .94; chloride, R2 = .90; glucose, R2 = .98; and hematocrit, R2 = .92) when paired samples were analyzed simultaneously in the laboratory comparing the microchemistry instrument and currently accepted clinical laboratory instruments. There were significant correlations (for pH, R2 = .91; PCO2, R2 = .94; PO2, R2 = .97; sodium, R2 = .91; potassium, R2 = .86; chloride, R2 = .91; ionized calcium, R2 = .82; glucose, R2 = .96; and hematocrit, R2 = .75) but increased variability occurred in some analyte results when samples were first analyzed in the intensive care unit (using the microchemistry instrument) and then transported to the laboratory in the routine fashion for "stat" determinations. CONCLUSIONS: --The multichannel microchemistry instrument provided accurate analyte determinations when compared with accepted clinical laboratory instruments. Significant savings of time and blood were also realized by the use of a microchemistry instrument in the intensive care unit. Bedside microchemistry may provide clinically important advantages in emergency departments, operating rooms, and neonatal, pediatric, coronary, adult medical and surgical, trauma, and burn intensive care units.

Blood Chemical Analysis↗

Stereotaxic implantation of autologous adrenal medulla into caudate nucleus in four patients with parkinsonism. One-year follow-up.

Four patients with levodopa-responsive parkinsonism (aged 26, 35, 45, and 49 years) received autologous adrenal medullary implants into or near the left caudate nucleus by stereotaxic implantation after flank adrenalectomy. All patients had an immediate response to implantation lasting several days, during which parkinsonian signs and symptoms decreased. This period was followed by a gradual reappearance of symptoms in all but one patient. This patient had had a dramatic increase in "on" time without dyskinesias and a decrease in the severity and duration of "off" time. He died of multifocal glioblastoma 1 year after transplantation. Autopsy revealed no surviving adrenal cells. In one case, the stereotaxic implantation missed the basal ganglia, resulting in the placement of the adrenal medullary tissue into the medial thalamus and near the third ventricle; the patient did not improve. In the other two cases, a modest but definite increase in "on" time without dyskinesia and a reduction in the severity and duration of "off" time has been observed. The role of autologous adrenal medullary transplantation in patients with parkinsonism remains to be determined. Patients with a family history of cerebral malignancy may be at increased risk for the development of transplant-induced malignancy.

Adrenal Medulla↗

Leptospires in the whistling frog (Eleutherodactylus johnstonei) on Barbados.

Two groups of whistling frogs (Eleutherodactylus johnstonei) comprising 99 and 117 animals were examined for leptospiral infection. Group I animals were caught in 14 areas of Barbados, and Group II animals in seven areas of suburban Bridgetown. Leptospires were isolated from the kidneys or body fluid of six frogs in Group I and the kidneys of 3 frogs in Group II. Two of the Group I isolates died out; the others were identified as bajan (a new serovar in the Australis serogroup) (6) and bim (Autumnalis) (1). The macerated body tissues and fluid of Group I frogs were put into phosphate buffered saline and examined by the microscopic agglutination test using 22 antigens. The results were all negative. For the Group II frogs the methodology was altered; blood was collected onto filter paper discs and allowed to dry out before being agitated in PBS and examined by the MAT. 15/117 (12.8%) animals were positive at greater than or equal to 1:100 and 19 (16.2%) at greater than or equal to 1:50. The geometric mean titre was 179. Seventeen of the sera reacted predominantly to antigens in the Australis serogroup, and two to Pyrogenes on its own. The serological results reflected the identity of the isolates. Serovars of Australis are not known to cause illness on Barbados, but bim is the commonest cause of severe leptospirosis on the island.

Animals↗

Herpes simplex virus glycoprotein treatment of recurrent genital herpes.

We investigated the possibility that herpes simplex virus (HSV) glycoproteins might provide potential immunotherapy for recurrent HSV disease by using the guinea pig model of genital HSV infection. In two experiments, after recovery from initial genital herpes, 58 animals were randomized either to receive a glycoprotein vaccine or to serve as controls. Both a mixture of HSV-2 glycoproteins derived from infected tissue cultures and a mixture of HSV-1 glycoproteins B and D, prepared by genetic engineering in mammalian cells, reduced the frequency (P less than .05) and severity (P less than .05) of subsequent herpetic recurrences. We conclude that recurrences of established herpesvirus disease may be altered by administering immunogenic viral proteins; thus, HSV glycoproteins may be useful as immunotherapeutic agents for controlling recurrent HSV infection in humans.

Animals↗

Impact of the New York Long-Term Home Health Care Program.

The Long-Term Home Health Care Program (LTHHCP), also known as the Nursing Homes Without Walls, is an innovative, comprehensive Medicaid program in New York State that provides nursing home level of care to patients at home. This paper evaluates the performance of the first nine LTHHCP sites over the first 2 years of operation. Across all sites there is clear evidence that the program has been extremely successful in reducing levels of nursing home utilization. In the five upstate sites, considerable cost savings have also been achieved while improving patient survival. In the four New York City sites, patient outcomes have also been favorable, but health care costs for clients have been higher than would have been the case had clients not enrolled in the LTHHCP. Across the entire state, results could have been better if enrollment had been targeted to subsets of the eligible patient groups for whom the LTHHCP is most cost effective.

Aged↗

Effect of acute compartmental pressure change on response to vibratory stimuli in primates.

This study investigated the possibility that a vibratory stimulus could discriminate the effect of relatively low pressures on nerve function in an acute compartmental syndrome in a primate model. The first phase of the study utilized somatosensory-evoked potentials to determine the outcome of varying pressures in an acute carpal tunnel syndrome in the anesthetized monkey. For increasing carpal tunnel pressures above 30 mmHg, the amplitude of the compound action potential of the A beta wave (touch fiber) generated in the median nerve by an electric stimulus to the index finger progressively decreased to a complete conduction block. It took progressively less time to achieve the conduction block at higher compartmental pressures. When compartmental pressure was released, the time required for the conduction block to return to normal was in direct relationship to the time required to complete the block. For carpal tunnel pressure between 15 and 30 mmHg, an increase in the height of this compound action potential was observed. The second phase of the study utilized the perceptual judgments of an awake monkey trained to discriminate differences in amplitude of a 10-Hz vibratory stimulus to the hairs of the dorsum of the foot. An anterior compartment pressure of 37 mmHg for 1 1/2 hours significantly decreased the monkey's ability to discriminate between the two amplitudes. At 50 mmHg in the anterior compartment, ability to discriminate between vibratory stimuli was further impaired. This study supports the use of noninvasive vibratory stimuli, such as a tuning fork, to evaluate acute compartmental syndromes.

Animals↗

Managing programs for the elderly: design of a social information systems.

This paper describes a comprehensive approach to assembling a health care information system to monitor programs for the elderly and disabled in a cost effective manner. The Social Information System (SIS) described in the paper was implemented for the evaluation of the New York State Long-Term Home Health Care Program (LTHHCP). This evaluation required the collection and organization of large amounts of client specific data, including claims, clinical and programatic data. Sources for these data included client medical records, Medicare, Medicaid, and the New York State Food Stamps, Public Assistance, Title XX, and Energy Assistance Programs. Recommendations are made regarding client identification, data elements, access, and structure of the data base.

Home Care Services↗