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R M Curley

Publications and source records attributed to R M Curley.

11 recordsLinked to original sources

Modem remote support of pulmonary-function testing and quality control systems.

The data coordinating center (DCC) of the Asthma Clinical Research Network (ACRN) is responsible for the support of 11 pulmonary-function testing systems and two quality control systems. Pulmonary-function data from these systems are used as outcome indicators in studies conducted by the ACRN. Each of these systems is composed of a spirometer, a personal computer for data acquisition from the spirometer, a modem, and a printer. These systems are located at six clinical centers nationwide. An analysis conducted at the beginning of the first ACRN protocol identified the following requirements: (1) standard pulmonary-function testing, (2) standard methacholine-challenge testing, (3) the ability to handle simultaneous multiple protocols as well as have data from non-ACRN subjects, (4) the ability to separate data from different protocols as well as separate ACRN and non-ACRN data, (5) the ability to transmit data from the remote clinical centers to the DCC, (6) the ability to ensure quality data and to report on those results, and (7) the ability to provide remote support.

Asthma↗

Development and deployment of an internet-based data management system for use by the Asthma Clinical Research Network.

Data management system development for the first Asthma Clinical Research Network (ACRN) study began at the data coordinating center (DCC) in May 1995 with the requirement for delivery of a production system by November 1995. Special methods had to be used to establish an internet local area network (LAN), place clinical client systems, and achieve an accelerated software development cycle. The development of a fully integrated data management system prior to the start of the study was not possible. Therefore an early analysis focused on identifying discrete groupings of data management functions that would allow development of distinct database modules to provide specific functionality such as subject randomization, subject registration, and data entry. The modules were categorized as either being associated with clinical centers or the DCC so that the clinical center modules could be developed and delivered to meet the start date of the study. In the second phase of development during the relatively slow patient-enrollment period, the DCC functional modules were delivered discretely over time. While at the time this development model was a necessity due to limited DCC resources, it continues to be used today as it permits the DCC to implement studies more rapidly and efficiently for the ACRN. This paper describes the methodologies used to develop an internet-based LAN, establish clinical center client systems, establish DCC client and server operations, and develop a data management system. It describes the circumstances that contributed to the development of these systems and the special methodologies developed. The technical aspects of the data management system and LAN are presented as well as a description of the requirements and constraints analysis used to develop the hardware and software systems.

Asthma↗

Bladder dysfunction in the spontaneously diabetic male Abyssinian-Hartley guinea pig.

The spontaneously diabetic adult male Abyssinian-Hartley guinea pig develops bladder hypertrophy and voiding dysfunction. In contrast to animals with chemically induced diabetes, this animal demonstrates changes in bladder function in the absence of diuresis. The diabetic guinea pigs void a total daily volume similar to that of control animals, but have a greater mean volume per void and a longer interval between voiding. Cystometry demonstrates that the diabetic guinea pig produces greater intraluminal bladder pressure, but maintains voiding pressure for a shorter interval. A significantly decreased contractile response of the diabetic bladder base may be responsible for the bladder hypertrophy and voiding dysfunction.

Analysis of Variance↗

Comparison of computerized cystometry/micturition and contractile responses of the diabetic rat bladder.

Computerized data acquisition was used to achieve a comprehensive assessment of micturition and cystometry in rats made diabetic with streptozotocin. Diabetic rats had a greater mean voided volume and a significantly shorter interval between voiding during the light cycle. During volume expulsion, the rate of intraluminal pressure development was greater, but the mean duration of volume expulsion was less in the diabetic bladder. The increased rate of intraluminal pressure development in the diabetic bladder at the time of volume expulsion correlated with the greater tension development in bladder body strips in response to acetylcholine stimulation. The inability of the diabetic bladder body to maintain peak intraluminal pressure may contribute to the development of residual urine, increased bladder volume and increased voiding frequency in the diabetic rat.

Acetylcholine↗

Calcium channel agonist/antagonist effects on cholinergic stimulation of the diabetic rat bladder.

The in vitro effects of a calcium channel agonist (BAY K8644) and antagonist (nifedipine) on the cholinergic responses of the streptozotocin-induced diabetic rat bladder were investigated. the bladder body and bladder base were studied separately. There were significant differences in contractile responses to acetylcholine stimulation in the diabetic bladder body compared to the control body. Similarly, the diabetic bladder base demonstrated significantly increased contractile responses compared to the control base. Contractile responses in the diabetic bladder body and base were significantly increased from the control in the absence of extracellular calcium. Differences were found in the effects on maximum responses between diabetic and control tissues treated with nifedipine and BAY K8644. BAY K8644 did not completely reverse the effect of nifedipine on the contractile responses. Rates of contractile response were significantly different between controls and diabetics and between body and base. Alterations in calcium channel activity in diabetic bladder smooth muscle may be responsible at least in part for the nonspecific pharmacologic responses found in smooth muscle strips.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

Cytosol-free calcium concentration in single bladder smooth muscle cells from normal and diabetic rats.

The effect of diabetes mellitus on intracellular calcium concentration was measured in single rat bladder smooth muscle cells using the fluorescent calcium indicator dye fura-2 AM. Techniques were developed for isolation and short-term culture of rat bladder smooth muscle cells. Cytosol-free calcium concentrations were measured at rest and during carbachol stimulation. Peak intracellular calcium concentration, rate of increase in intracellular calcium concentration and the integral of accumulation of intracellular calcium were determined. The techniques used to isolate and culture bladder smooth muscle cells produced live, physiologically responsive cells. Resting intracellular free calcium levels and were similar in control and diabetic cells. Both control and diabetic cells responded to carbachol stimulation. No significant differences between these cells were noted in peak calcium concentrations, rate of response or integral of response, but standard errors were large. Two patterns of intracellular response to carbachol stimulation were identified, and may explain the large variability in intracellular calcium response to carbachol stimulation.

Animals↗

Neurogenic function of the diabetic rat bladder: alteration by calcium channel effectors.

The in vitro effects of a calcium channel antagonist (nifedipine) and agonist (BAY K8644) on the neurogenic responses of the streptozotocin-induced diabetic rat bladder were investigated. The bladder body and bladder base were studied separately. There were no significant differences in neurogenic responses in diabetic bladder body compared to control body, but the diabetic bladder base demonstrated an increased contractile response at each frequency compared to control base. The rate of contractile response was similar in controls and diabetics but was significantly different between body and base. Although declining with time, contractile responses in the diabetic bladder body and base were increased from control in the absence of extracellular calcium. Differences were found in effects upon maximum responses between diabetic and control tissues treated with nifedipine and BAY K8644. BAY K8644 did not completely reverse the effect of nifedipine on the neurogenic responses in the diabetic bladder body. Effects of diabetes on the bladder body and base are associated with changes in calcium channel activity of bladder smooth muscle.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

Cytometrically monitored neoplastic progression in the Nb bladder cancer model: selective proliferation of variant subpopulations.

The identification and understanding of neoplasm heterogeneity is essential to allow for more individually oriented treatment modalities. There is a tendency to limit the analysis of neoplasm heterogeneity to diagnostic classification only; however, recently refined methods of rapid subpopulation analysis should expand this restricted usage to monitoring of chemotherapeutic treatment. The documentation of the neoplastic progression of the Nb rat bladder cancer model as a function of variant subpopulation proliferation and selection is reported herein. This documentation represents the efforts of this laboratory to develop a flow cytometrically monitored animal bladder tumor model to evaluate the in vivo effects of chemotherapies on neoplastic subpopulations; particularly those subpopulations potentially metastatic or resistant to therapy. It is anticipated that this will increase our understanding of this model, and more specifically, tumor biology. This particular tumor initially occurred in an aged Noble male breeder rat.

Animals↗

Nb rat prostate adenocarcinoma model: metastasis.

The Nb rat prostate adenocarcinomas - androgen insensitive II and III - were utilized in three experiments utilizing protamine sulfate, persantine (dipyridamole), and heparin-cortisone combination as agents evaluated for their ability to affect the incidence of systemic metastasis in this animal model. The results indicate that all agents tested were effective in reducing metastasis; protamine and persantine (10 mg/kg/day) being the most effective with 0% metastasis. In addition, animals treated with protamine had a statistically significant decrease in tumor volume. The mechanism responsible for this decrease remains unclear at present.

Adenocarcinoma↗