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Biomedical subjects

R Crowley

Publications and source records attributed to R Crowley.

At least 19 recordsLinked to original sources
PubMed2006

Adipsic diabetes insipidus following pituitary surgery for a macroprolactinoma.

Adipsic diabetes insipidus (ADI) is a rare condition in which thirst, an essential clinical feature for the prevention of hypernatraemic dehydration, is absent. We report the first case of adipsic diabetes insipidus to occur following surgery for a pituitary macroprolactinoma, with loss of both osmoregulated and baroregulated vasopressin release. Following extensive surgery for a vision threatening macroprolactinoma a 14-year-old boy developed profound hypernatraemia with absent thirst sensation. Detailed investigation, with hypertonic saline infusion and trimetaphan infusion, revealed absence of both osmoregulatory and baroregulatory release of vasopressin. We discuss the investigation and management of such patients and the physiology of hypothalamic-neurohypophyseal dysfunction in such patients.

Adolescent↗
PubMed1998

Inhibition of HIV-1 replication by combined expression of gag dominant negative mutant and a human ribonuclease in a tightly controlled HIV-1 inducible vector.

An HIV-1-based expression vector has been constructed that produces protective genes tightly regulated by HIV-1 Tat and Rev proteins. The vector contains either a single protective gene (HIV-1 gag dominant negative mutant (delta-gag)) or a combination of two different protective genes (delta-gag and eosinophil-derived neurotoxin (EDN), a human ribonuclease) which are expressed from a dicistronic mRNA. After stable transfection of CEM T cells and following challenge with HIV-1, viral production was completely inhibited in cells transduced with the vector producing both delta-gag and EDN and delayed in cells producing delta-gag alone. In addition, cotransfection of HeLa-Tat cells with an infectious HIV-1 molecular clone and either protective vector demonstrated that the HIV-1 packaging signals present in the constructs were functional and allowed the efficient assembly of the protective RNAs into HIV-1 virions, thus potentially transmitting protection to the HIV-1 target cells.

Blotting, Northern↗
PubMed1998

Pathological changes in surgically resected angiographically occult vascular malformations after radiation.

OBJECTIVE: The goal of this study was to evaluate the pathological changes associated with radiation treatment (stereotactic radiosurgery or conventional irradiation) of angiographically occult vascular malformations (AOVMs). METHODS: Eleven patients underwent surgical resection of an AOVM in the mesial temporal lobe, brain stem, thalamus, or basal ganglia after previous radiation treatment. The indications for surgery were recurrent symptomatic bleeding from the lesion in 10 patients and recurrent intractable seizures in 1 patient. Radiation was used as the initial therapy because the risk of surgical resection was deemed too high. Three patients received conventional radiation therapy of 3000 to 5400 rads at an outside institution. One patient received radiosurgery with the gamma knife at another institution using a dose of 15 Gy to the margin. The remaining 7 patients received stereotactic radiosurgery with a helium-ion particle beam. The dose range was from 18 to 26 Gy equivalents. The interval from radiation to surgical resection ranged from 1 to 10 years, with a mean of 3.5 years. These lesions were compared with 10 nonirradiated cavernous malformations. RESULTS: One irradiated lesion was identified pathologically as a true arteriovenous malformation despite being angiographically occult. This lesion did not demonstrate significant changes in the vasculature but did have radiation necrosis of the surrounding brain 5 years after 25 Gy equivalents of helium-ion radiosurgery. Two other specimens were too small to identify the type of vascular malformation adequately. Of the remaining eight malformations identified as cavernous malformations, six showed a combination of marked fibrosis of the vascular channels, fibrinoid necrosis, and ferrugination. However, the fibrinoid necrosis was the only finding unique to the irradiated lesions compared with nonirradiated controls. All the irradiated lesions still had patent vascular channels; none were completely thrombosed. CONCLUSION: Radiosurgery or conventional radiation therapy did not cause histologic vascular obliteration in intracranial AOVMs evaluated 1 to 10 years (mean 3.5 yr) after radiation delivery. It should be recognized that these patients are irradiation failures who may not be representative of all irradiated patients. However, recurrent bleeding from AOVMs may relate to poor radiation response in some patients.

Cerebral Angiography↗
PubMed1997

Syncytium formation induced by human immunodeficiency virus type 1 isolates correlates with affinity for CD4.

Different strains of human immunodeficiency virus type 1 (HIV-1) show considerable divergence in genetic content and biological properties. One property that has been closely correlated with clinical prognosis is the ability to induce syncytia formation in susceptible cells. This ability had been correlated with the V3 loop sequence of major envelope glycoprotein, gp120, but recent reports have questioned this connection. We investigated the contributions of different regions of the env gene to syncytia induction using chimeric viruses that contain part of the genome of a strain that lacks this ability (HIV-1(Ba-L)) within the genome of a virus that can form syncytia (HIV-1(HXB-2)). When tested in two cell lines susceptible to both parental viruses, as well as in primary cells, these chimeric viruses demonstrated that the ability to induce syncytia formation was determined by regions of env outside the V3 loop, which encompass residues that contribute to the binding of CD4 by gp120. Further investigation failed to show any difference in the expression of gp120 on the cell surface or cell adhesion molecules by cells infected with SI or NSI variants that would explain the observed differences in the ability to form syncytia. Assays of relative affinity for CD4 indicated that gp120 from SI variants showed a significantly higher affinity for CD4 than gp120 from NSI variants. These observations suggest that areas of the HIV-1 env gene contributing to the CD4 binding site may also contribute to the determination of syncytium-inducing (SI) and non-syncytium-inducing (NSI) phenotypes.

Animals↗
PubMed1996

Teeth for life.

Explore the source record for details and available documents.

Aged↗
PubMed1995

Monoclonal antibodies raised against covalently crosslinked complexes of human immunodeficiency virus type 1 gp120 and CD4 receptor identify a novel complex-dependent epitope on gp 120.

The binding of the human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein, gp120, to its cell surface receptor, CD4, represents a molecular interaction involving distinct alterations in protein structure. Consequently, the pattern of epitopes presented on the gp120-CD4 complex should differ from those on free gp120. To investigate this concept, mice were immunized with covalently crosslinked complexes of viral HIV-1IIIBgp120 and soluble CD4. Two monoclonal antibodies (MoAbs) obtained from the immunized mice exhibited a novel epitope specificity. The MoAbs were marginally reactive with HIV-1IIIBgp120, highly reactive with gp120-CD4 complexes, and unreactive with soluble CD4. The same pattern of reactivity was seen in solid-phase assays using HIV-1(451)gp120. A similar specificity for complexes was evident in flow cytometry experiments, in which MoAb reactivity was dependent upon the attachment of gp120 to CD4-positive cells. In addition, MoAb reactivity was detected upon the interaction of CD4 receptors with purified HIV-1IIIB virions. Notably, seroantibodies from HIV-positive individuals competed for MoAb binding, indicating that the epitope is immunogenic in humans. The results demonstrated that crosslinked gp120-CD4 complexes elicit antibodies to cryptic gp120 epitopes that are exposed during infection in response to receptor binding. These findings may have important implications for the consideration of HIV envelope-receptor complexes as targets for virus neutralization.

Animals↗
PubMed1995

Intracardiac echocardiography without fluoroscopy: potential of a balloon-tipped, flow-directed ultrasound catheter.

Intracardiac echocardiography is a technique that uses catheter-based ultrasound transducers placed within the heart to image cardiac structures. One disadvantage to this technique is that it requires fluoroscopy for catheter placement. This study was performed to evaluate a prototype balloon-tipped, flow-directed catheter for use during intracardiac echocardiography in seven dogs. With the balloon deflated, the catheter could not be successfully advanced without fluoroscopy. Even with fluoroscopic imaging, catheter advancement was often difficult. With the balloon inflated, it could easily be passed into the pulmonary artery without fluoroscopy in 12 of 14 attempts. Images of the cardiac chambers, valves, and pulmonary artery could be obtained. In conclusion, use of a balloon-tipped, flow-directed catheter for intracardiac echocardiography and pulmonary artery imaging can be performed without the use of fluoroscopy. With continued refinements, such as enhancement of the visual field, intracardiac echocardiography could possibly be performed at the bedside to assess cardiac function or assist with interventional procedures.

Animal Population Groups↗
PubMed1995

Prognostic significance of CD44 expression in adenocarcinoma of the lung.

Aims-To determine whether expression of CD44 in neoplasia is associated with tumour grade, stage and prognosis.Methods-The immunohistochemical expression of CD44 was evaluated using the mouse antihuman monoclonal antibody 3G12 which recognises regions shared by all CD44 isoforms to determine whether expression in formalin fixed, paraffin wax embedded tissue correlates with tumour grade, stage or survival in adenocarcinoma of the lung. Thirty one adenocarcinomas of the lung, 16 T2N0 and 15 T2N1, and their nodal metastases were studied.Results-Of the 31 tumours, 25 were positive for the CD44 antigen. CD44 expression correlated with tumour grade, in that intense staining was seen only in moderately and/or poorly differentiated tumours. CD44 did not correlate with nodal status, tumour size, pleural invasion, angiolymphatic invasion, or host inflammatory response, but did correlate with survival. A median survival of 46 months was observed in patients with moderate to strong CD44 expression compared with 24 months for those with no or weak expression. Nine patients were alive without evidence of disease at a median follow up of 61 months. Six (66%) of these nine patients had strong CD44 expression. This contrasts with strong expression in only three (17%) of the 17 patients dying with a median survival of 28 months.Conclusion-In primary adenocarcinoma of the lung loss of CD44 expression is associated with less favorable outcome and may indicate a more aggressive neoplasm. CD44 may be a useful prognostic marker in lung carcinoma.

Journal Article↗
PubMed1993

Antisense phosphorothioate oligodeoxynucleotides targeted to the vpr gene inhibit human immunodeficiency virus type 1 replication in primary human macrophages.

The replication of human immunodeficiency viruses (HIV) in human macrophages is influenced by genetic determinants which have been mapped predominantly to the viral envelope. However, in HIV-2, the vpr gene has also been suggested as an important modulator of viral expression in human macrophages. We synthesized five antisense phosphorothioate oligodeoxynucleotides complementary to the vpr mRNA of HIV-1Ba-L, a highly macrophage-tropic viral strain, and measured their effect on HIV-1Ba-L replication in primary human macrophages. All of the oligodeoxynucleotides displayed some level of non-sequence-specific inhibition of viral replication; however, only the antisense one had an additional effect on viral production in primary macrophages. Of the five antisense oligodeoxynucleotides tested, only one did not show any additional effect on viral production, whereas all the others inhibited viral replication to a similar degree (70 to 100%). Variation in the degree of inhibition was observed by using five different donors of human primary macrophages. The phosphorothioate oligonucleotides, targeted to the initiating methionine of the Vpr protein, had an inhibitory effect at both 20 and 10 microM only when the size was increased from 24 to 27 bases. Thus, HIV-1 replication in human macrophages is modulated by the expression of the vpr gene, and it is conceivable that vpr antisense oligodeoxynucleotides could be used in combination with antisense oligodeoxynucleotides against other HIV-1 regulatory genes to better control viral expression in human macrophages.

Amino Acid Sequence↗
PubMed1993

Ultrasound guide wire-directed stent deployment.

A new mechanically rotated 20 MHz intravascular ultrasound guide wire (0.032 inch) with a transducer core was placed through the central lumen of a peripheral arterial balloon-expandable stent. Using an anesthetized canine model, 11 stents were then deployed into the iliac or femoral arteries. Eight stents were successfully deployed with proper position and full stent expansion documented by ultrasound imaging. Four of the stents were overlapping and the double row of stent struts at the region of overlap was easily seen. Three stents were unsuccessfully deployed because of undersizing, as clearly documented by ultrasound imaging showing stent strut recoil. As a result, the procedure was modified by performing ultrasound measurements of arterial dimensions before stent selection. There were no complications attributed to the ultrasound guide wire. This study demonstrates an effective combination of diagnostic and therapeutic devices that may allow more precise placement of intravascular stents.

Animals↗
PubMed1992

Intraluminal ultrasound imaging through a balloon dilation catheter in an animal model of coarctation of the aorta.

BACKGROUND: Controversy still exists over the optimal balloon size, extent of vascular disruption, and long-term results of balloon dilation therapy for coarctation of the aorta. Intravascular ultrasound imaging has been used in patients with coronary artery disease to provide further insight into the anatomy of atherosclerotic lesions and the results of angioplasty and atherectomy. Initial observations of the results of balloon dilation of coarctations with intravascular ultrasound imaging have shown prominent dissections of the inner vascular layers that are often not detected by angiography. The purpose of this study was to test a new transballoon catheter ultrasonic imaging system capable of on-line direct visualization of lumen diameter and vessel wall structure for imaging before, during, and after dilation in an acute animal model of aortic coarctation. METHODS AND RESULTS: Abdominal aortic coarctations were created surgically in three 14-19-kg mongrel dogs by using Teflon gauze ties. The 6.8F ultrasound balloon catheter was placed percutaneously in the right femoral artery through a 9F sheath. Ultrasound imaging allowed measurement of the coarctation diameter, characterization of the vessel wall structure, localization of the stenosis, and placement of the midportion of the balloon at the narrowest area. Imaging through the balloon was performed through several dilations (five to eight per animal), and after balloon deflation, it provided information on postdilation diameter, intimal tears, long-segment dissections, and intramural thrombi, findings that were confirmed at postmortem examination. CONCLUSIONS: The results of this study demonstrate that imaging with a new intraballoon ultrasound device is feasible during inflation to therapeutic dilation pressures; it allows visualization of the changes in diameter and vascular wall structure after serial dilations without having to recross the obstructed area. Adaptation to larger balloon sizes and lower frequencies should make this system applicable to interventional catheterizations in patients with congenital cardiac and vascular lesions.

Animals↗
PubMed1992

Promoting stimulus control with textual prompts and performance feedback for persons with mild disabilities.

We assessed whether written task analyses would serve as textual prompts for performing functional tasks by persons with mild disabilities. Several variables that could influence the effectiveness of textual prompts to promote stimulus control were examined across four groups. A consistent finding was that written specific task analyses combined with end-of-trial performance feedback were effective for promoting the acquisition and generalization of several tasks. Performance transferred immediately to natural discriminative stimuli when the written task analyses and feedback were withdrawn for most tasks and participants. For 2 participants, transfer of stimulus control was accomplished by prompt fading, using individualized written task analyses either with or without performance feedback (Group 1). When feedback was not provided, the effectiveness of written specific task analyses was inconsistent across groups. In contrast to the controlling effects of written specific task analyses, written generic task analyses, which specified only major task outcomes, when combined with performance feedback (Group 1) did not control responding. Overall, this research demonstrated the effectiveness of written specific task analyses and performance feedback to promote stimulus control for persons with mild disabilities.

Activities of Daily Living↗
PubMed1975

Food satiation as a procedure to decelerate vomiting.

A food satiation procedure was used in two experiments to decelerate the frequency of vomiting responses in two profoundly retarded adults who exhibited well-defined vomiting-ruminatory response chains. For several years prior to this study, the subjects had exhibited a history of vomiting behavior. Satiation was accomplished during regular meals and consisted of allowing the subjects to eat until a satiation criterion of food refusal was achieved. The results revealed a 94 percent reduction of vomiting in Experiment 1 and a 50 percent response reduction in Experiment 2. Ten-day follow-up sessions indicated that the response reduction was maintained in both experiments. In Experiment 1 the subject exhibited a 4.99 kg weight gain at the 10-day follow-up with a total of 13.61 kg weight gain at a 4-week posttreatment weight check.

Feeding Behavior↗
PubMedDate not supplied

Management of patients undergoing splenectomy in an Irish teaching hospital: impact of guidelines.

INTRODUCTION: Overwhelming post-splenectomy infection (OPSI) has a 50-70% mortality rate and carries a lifetime risk for the asplenic patient. Specific British guidelines have been developed to reduce its incidence. AIMS: To determine whether British guidelines were being followed in our own institution and what impact they had on overwhelming post-splenectomy infection. METHODS: Retrospective chart review of 100 splenectomies performed by Department of Surgery, Beaumont Hospital from January 1990 to January 2000. RESULTS: Twenty per cent of patients were discharged without any recommended vaccinations. Prophylactic antibiotics were not prescribed in 53% of patients. Just 12% of charts document a verbal explanation of the complications and management of asplenia to the patient. Overall septic mortality was 12%, of whom 8% died in hospital and 4% after discharge. CONCLUSION: Management of the asplenic patient has improved but is far from complete. A central register of asplenic patients and national asplenic guidelines should be established in Ireland to ensure optimum patient care.

Adolescent↗