Biomedical subjects
Publications and source records attributed to P Cronin.
Carbon dioxide (CO2) is an established alternate angiographic contrast agent, which can be delivered by pump or hand injection. We describe a simple, safe and inexpensive hand injection system that delivers a known volume of CO2 at atmospheric pressure and prevents contamination with room air.
We demonstrate a novel method of parallel, multiwavelength state-of-polarization (SOP) correction. Using a new liquid-crystal modulator array design, we are able to rotate the distorted input SOP spectrum to a fixed linear state on a wavelength-by-wavelength basis. We report experimental correction of up to 25.5-dB polarization-dependent loss over a 13-nm bandwidth around 1550 nm.
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We report the placement of a covered stent within the internal iliac vein (IIV) to occlude a symptomatic iatrogenic internal iliac arteriovenous fistula following an abdominal aortic graft. Angiography revealed a direct communication between an internal iliac graft to artery anastomosis and the right IIV with rapid shunting into the inferior vena cava and a small associated pseudoaneurysm. Femoral, brachial or axillary arterial access was precluded. The fistula was successfully occluded by a stent-graft placed in the IIV. Arteriovenous fistula can be treated in a number of ways including covered stent placement on the arterial side. To the best of our knowledge this is the first time placement in a vein has been described. Where access is difficult or the procedure carries a high risk of complication, a venous covered stent may offer an alternative.
OBJECTIVE: To describe the methodological challenges and decisions made in developing a multisite, controlled study of risperidone in children and adolescents with autism. METHODS: Review the design considerations for clinical trials in children with autistic disorder accompanied by severe tantrums, aggressive and/or self-injurious behaviors. These design considerations include the definition of inclusion criteria that are relevant to clinical practice and matching study design to the goal of evaluating short- and long-term effects. Additional ethical and scientific issues concern the length of trial and sample size. RESULTS: We undertook a short-term, placebo-controlled study to evaluate the efficacy and safety of risperidone in children and adolescents with autistic disorder. This trial design was followed by an extended open-label maintenance on risperidone to confirm durability of treatment effects and to monitor safety. Finally, a placebo-controlled discontinuation study tested the need for continuous treatment. CONCLUSIONS: In the absence of standard pharmacological treatment for children with autistic disorder, a placebo-controlled study remains the most appropriate method of testing efficacy and safety. The clinical relevance of this study is enhanced by the addition of an extended maintenance phase followed by a placebo discontinuation.
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This article has reviewed the background and rationale for the choice of risperidone as the first drug to be studied by the RUPP Autism Network. Risperidone has potent effects on 5-HT and DA neuronal systems, both of which have been implicated in the pathophysiology of autism. Unlike the typical antipsychotics, haloperidol and pimozide, which have been shown to be effective for reducing many of the maladaptive behaviors associated with autism, risperidone's 5-HT2A/DA D2 ratio of receptor blockade appears to produce a lower risk of acute and chronic extrapyramidal side effects, as well as enhanced efficacy for the "negative" symptoms of autism. Indirect clinical and preclinical evidence supports the use of risperidone to treat impaired social behavior, interfering repetitive phenomena, and aggression, targets of pharmacotherapy for many patients with autism. Numerous published open-label trials in children and adolescents with autism and related PDDs and one double-blind, placebo-controlled study in adults suggest that risperidone has promise for the treatment of children and adolescents with autism. Because most of these studies have been short-term, open-label trials in small samples, however, a large-scale controlled study of risperidone in children and adolescents with autism is needed to confirm these results. Finally, because it is likely that children who demonstrate short-term benefit from risperidone will remain on the medication indefinitely, the longer-term effectiveness and safety of risperidone in this population also needs to be determined. The design of this study and the assessments used are described separately.
Human neutrophil PLD activity stimulated with GTP-gamma-S was reconstituted with recombinant ARF1 in cytosol-depleted cells. PMA-pretreatment of intact cells greatly enhanced the subsequent reconstitution of the ARF1-regulated PLD activity. This enhancement was only observed provided that the intact cells were pretreated with PMA, suggesting the stable recruitment of a cytosolic component, presumably protein kinase C, to the membranes. rARF1-reconstituted PLD activity was not dependent on MgATP, but could be considerably enhanced by MgATP. Maximal effects of MgATP were seen at 1 mM. This enhancement by MgATP could not be attributed to protein kinase C. Neomycin was found to inhibit ARF1-regulated PLD activity suggesting the requirement for polyphosphoinositides. We conclude: (i) that many of the observed effects of PMA may be dependent on the presence of the small GTP-binding protein, ARF, and (ii) polyphosphoinositides are required for ARF1-stimulated PLD activity.
Starburst dendrimers are novel, water-soluble polymeric materials, with a well-defined composition and structure. In our application, we used dendrimers composed of poly(amidoamine) groups to which we coupled several specific antibodies, to investigate potential formats based on radial partition immunoassay. The coupled antibodies have retained their stability and immunological binding after coupling, both in solution and when immobilized onto a solid support. On the basis of our feasibility studies with model systems, we conclude that immunoassays can be developed with performance equivalent to or better than that in many established systems. By application of a mixture of the dendrimer-coupled antibody and the analyte of interest to the solid phase, we have investigated the performance characteristics of solution-phase immunoassays. Our experiments demonstrate enhanced sensitivity for creatine kinase MB isoenzyme (CKMB), thyrotropin, and myoglobin assays and reduced instrumental analysis time for the CKMB assay.
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Auditory evoked potentials were recorded in a choice reaction-time task. This test paradigm elicited the attention-related P300 component and was used to study cognitive processing. Compared with age-matched controls, 17 patients with dementia of the Alzheimer type were shown to have significantly longer reaction times as well as delayed latencies of several components of the auditory evoked potentials. The fractional increase in the reaction times was much greater than that of the P300 peak latency. The latter is commonly accepted as an index of stimulus-evaluation time. These findings suggest a delay in both response selection and stimulus evaluation.
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Injecting the local lidocaine into the mystacial pads of primiparous rats rendered the snout insensitive to touch and abolished the dams' ability to retrieve. Injecting the drug into the masseter muscles or intraperitoneally did not render the snout anaptic or abolish retrieval, results indicating that the effect of intramystacial lidocaine treatment could not be attributed to systemic toxicity or to the drug's spreading from the mystacial pads to affect the nearby masseter muscles. Cutting the intraorbital nerves produced a temporary retrieval impairment that was indistinguishable from that produced by intramystacial lidocaine injection. Surgical deafferentation did not affect the latency of dams to approach pups that had been displaced from the nest site, which indicates that the retrieval deficit was not due to postoperative debilitation. In addition, infraorbital section did not interfere with the ability to locate and consume a piece of cheese that had been buried in the home cage, which indicates that the operation did not produce anosmia or interfere with the muscles used to grasp pups. Cutting the facial nerves abolished vibrissal movement but did not disrupt retrieval, results indicating that the effect of infraorbital lesions could not be attributed to the loss of vibrissal cues or to nonspecific effects of nerve section. The possibility was tested that infraorbital deafferentation has a profound effect on retrieval because anaptic dams, in their initial attempts at picking up pups, elicit distress vocalizations from their offspring. Dams injected with lidocaine in the mystacial pads failed to retrieve pups that had been anesthetized with a barbiturate to abolish their distress vocalizations. Thus pup-produced vocalizations are not responsible for the retrieval impairment exhibited by anaptic mothers. It is concluded that perioral tactile sensation plays an important role in the ability of lactating rats to retrieve.
Injecting .05 ml of 1% lidocaine into each vibrissal pad, or cutting the infraorbital nerves, abolished nipple attachment in weanling Wistar rat pups. Nipple attachment recovered following infraorbital section. Injecting the local anesthetic intraperitoneally, or into the region of the masseter muscles, did not disrupt attachment, indicating that the effect of the drug on suckling was specific to the site of injection and could not be attributed to systemic toxicity or paralysis of the masseter muscles. Performance on an olfactory-guided orientation task was not disrupted by lidocaine, indicating that the drug did not render pups anosmic. Tactile sensation in the vibrissal pads, rhinarium, and upper lip was abolished after injecting the drug into the vibrissal pads. Vibrissal movement was absent following injection of lidocaine into either the vibrissal pads or the region of the masseter muscles. Shaving the vibrissae did not disrupt nipple attachment. The results are interpreted as suggesting that the nipples' textural qualities elicit attachment in weanling pups.
In radial partition immunoassay, radial chromatography is used for performing an immunoassay. We describe the application of this technology to the measurement of digoxin in serum by enzyme immunoassay, with the entire testing procedure carried out on glass-fiber filter paper. A sample is applied to a small central area of the filter paper, where it reacts with the antibody to digoxin immobilized there. Subsequently, enzyme-labeled digoxin is applied to react with remaining antibody sites. After incubation, substrate for the enzyme is applied to the center of the reaction area and washes out any unbound label to the periphery of the paper. This step also initiates the enzyme reaction, which is quantified by front-surface fluorescence. A microprocessor-controlled automated instrument has been developed to process the filter paper matrix through the above sequence, and calculate the final result. Total testing time for digoxin is less than 7 min.
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