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1. Serial founder entrepreneurs : careers and corridors, venture choices and outcomes

Author

O'Regan, S. J.

Subjects
658.4
Abstract

Entrepreneurship is important to the development of market economies, in particular founding or ‘starting-up’ new enterprises from scratch. Researchers constantly seek to break down the heterogeneous nature of entrepreneurial behaviour and one suggestion is to focus on experienced habitual entrepreneurs who have owned and managed multiple businesses. Studies have shown that the habitual typology can be divided into more homogenous sub-types. Researchers make a distinction between serial entrepreneurs who focus sequentially on one business at a time and portfolio entrepreneurs who own and manage multiple businesses simultaneously. More is known about portfolio entrepreneurship and drawing on this work a comprehensive set of postulates is beginning to emerge to explain the differences between novice, serial and portfolio entrepreneurs. Therefore, there is an urgent need to focus on the serial entrepreneur. The principal research question is: How is one venture related to the next in the series? Crucially, serial founders possess repeated experience of entry, exit and re-entry into entrepreneurship. Exit from a venture they founded can be positive or negative, i.e. the sale of a business or a managed closure or outright failure. Serial entrepreneurs have to manage the consequences of exit and also make decisions regarding re-entry. An improved understanding of their cyclical, flow-like processes, punctuated with the ‘critical incidents’ of entry and exit is key to understanding the economic selection of entrepreneurs and the accumulation and use of entrepreneurial human capital. Researchers expect ventures to be related and follow industry corridors. This study explores the nature of corridors and goes further by asking if ventures are imitative (i.e. serial entrepreneurs are more cautious) or innovative (i.e. bring new means-ends combinations into existence). Using the commentaries of persistent and active entrepreneurs and details of their ventures, it is clear that experienced founders use particular modes when creating new businesses. Also an unsuccessful exit through closure or outright failure is normal, a common occurrence in a serial career. The study of 112 start-ups reveals that the outcome of the previous venture has a strong bearing on what happens next. Successful exits often lead to start-ups in different industries thereby spreading innovation. Failure of a novice venture leads to a return to essentially the same opportunity to try again. Persistent serial entrepreneurs can recover from unaffordable losses by returning to employment. Exit conditions are also important in understanding portfolio entrepreneurship. Novice or serial ‘singleton’ entrepreneurs transition to portfolio entrepreneurship when their current business is not exited. Unrelated ventures are almost invariably unsuccessful, and consequently attempts to transition are not always successful. Serial entrepreneurs obtain economic benefit from previous ventures through the phenomenon of serial diversification, recycling and reusing knowledge and other resources. There is evidence of learning from experience over the course of a career, as the frequency of negative outcomes falls and each venture in the series survives longer, substantially increasing its chances of a successful exit. On the basis of these findings a new theory of serial entrepreneurship is proposed for further research, and recommendations are made for policy-makers, practitioners and entrepreneurship educators.

Published
2016

2. Breaking the Long Hours Culture.

Author

Sussex Univ., Brighton (England). Inst. for Employment Studies., Kodz, J., Kersley, B., Strebler, M. T., O'Regan, S., Kodz, J., Kersley, B., Strebler, M. T., O'Regan, S., and Sussex Univ., Brighton (England). Inst. for Employment Studies.

Abstract

Case studies of 12 leading British employers were driven by employers' interest in issues related to working long hours in light of introduction of the Working Time Directive, a European Community initiative enacted into British law that sets limits on working hours per week. Data showed over one-fourth of full-time employees worked over 48 hours per week; men were more likely to work longer hours; and women's hours were increasing. Reasons for working long hours fell into four broad categories: workload, a long hours culture, individual commitment to the job, and need to improve pay. Consequences were increased sickness absence, low morale, and high turnover; lower productivity and quality of work outputs; greater health and safety risks; adverse impacts on family and social life; and reduced employment opportunities for those unable or unwilling to work long hours. The few successful interventions to ameliorate consequences were aimed at changing work patterns and changing individual behavior and company culture. Key elements were early consultation with staff and managers; solutions tackling underlying issues; and implementation that includes commitment and sponsorship for change from the very top, a change agent, the bringing of key people on board, communication and publicity, support and counseling, leading by example, a range of initiatives, effective time management, and message reinforcement and maintenance of momentum. Ongoing monitoring and feedback and evaluation were also seen as vital. (Five case studies provide examples of different types of intervention implemented in a range of contexts. The report contains 19 references.) (YLB)

Published
1998

3. Helping Parents to Work: A Study for Kent TEC.

Author

Sussex Univ., Brighton (England). Inst. for Employment Studies., Dench, S., and O'Regan, S.

Abstract

A study evaluated three clubs that provide out-of-school childcare in Kent, England: Out-of-School Childcare, Returners Roadshow and Workshops, and a parenting skills course. Questionnaires collected information from 29 club managers and 282 parents of children in the clubs and 78 participants of Returners events. Thirty participants in the parenting skills course completed evaluation forms; 22 responded to a mail survey. Findings indicated one-fifth of respondents' children attended a club 5 days per week; before the clubs opened, the respondent, usually the mother, had been the main source of childcare; and nearly two-thirds of parents reported work and study related reasons for using the club. Overall, parents reported a high level of satisfaction with most aspects of clubs' provision; three-fourths thought their children benefited positively; and the club had a strong labor market impact on respondents, mostly mothers. The clubs provided active play or sporting activities, quiet activities, and arts and crafts. Difficulties in staff recruitment included hours and pay and availability of qualified staff. Parental fees made up the majority of club income. The series of Roadshows and Workshops were attended by people planning to return to work after a gap and those wanting to change their job or career. Participants in the parenting skills courses were very positive about the course and its content. The course increased confidence and reassured people. (Contains 12 references.) (YLB)

Published
1998

4. Study Protocol for the St James's Hospital, Tallaght University Hospital, Trinity College Dublin Allied Researchers' (STTAR) Bioresource for COVID-19

Author

O'Doherty, Laura, Hendricken Phelan, Stuart, Wood, Nicole, O'Brien, Sorcha, O'Regan, S, Sui, Jacklyn, Mohammed, Noor Adeebah, Mangan, Cian, Salleh, Fara, Dyer, Adam, Howley, Fergal, Kerr, Colm, Conlan, Ciara, Holohan, Samuel, Hughes, Gerry, Reidy, Derval, Sanz, Alberto, Argue, Ruth, Townsend, Liam, Connolly, Emma, Kelly, Andrea, Leacy, Emma, Reddy, Conor, Gargan, Siobhan, Breen, Eamon, Hawerkamp, Heike, Dunne, Jean, Martin Loeches, Ignatio, McLaughlin, Anne Marie, Long, Aideen, Shiels, Orla, Fallon, Padriac, Hennessy, Martina, Bannan, Ciaran, Prior, Anna Rose, Rakovac, Ana, McManus, Ross, Romero-Ortuno, Roman, McCormack, Willam, Donnelly, Seamus, Bergin, Colm, Little, Mark, Ní Cheallaigh, Clíona, and Conlon, Niall

Subjects
COVID-19, Biobank, Vaccine
Abstract

Appendices for STTAR Bioresource COVID-19 Biobanking study. The primary objective of this study is to build a biobank, to understand the clinical characteristics and natural history of COVID-19 infection with the long-term goal of research into improved disease understanding, diagnostic tests and treatments. These appendices include the case report form, informed consent form and online convalescent visit report form related to this study&nbsp

Published
2022
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5. EWork in Europe: The EMERGENCE 18-Country Employer Survey. IES Report 380.

Author

Sussex Univ., Brighton (England). Inst. for Employment Studies., Huws, U., and O'Regan, S.

Abstract

The EMERGENCE project was conducted to map and measure eWork (the processing of information and transmission of it by means of telecommunications located anywhere in the world) in 18 European countries (15 European Union states plus Hungary, Poland, and the Czech Republic). Data for the project were gathered through a survey of 7,268 employers of at least 50 employees through computer-aided telephone interviews. The study found that eWork is taking place on a significant scale in Europe. The dominant forms of eWork are the use of remote offices, many of them call centers, and employment of multilocational workers. Fully home-based eWork by employees remains a minority practice. Such internal forms of eWorking by employees, however, are outweighed by external forms using outsourcers. The strongest driver of eWork is the search for technical expertise, along with cost and quality considerations. Tax breaks, government grants, or subsidies to locate in certain regions appear to play a minimal role in choice of location. The results suggest a need for further research on the impact of eWork and raise a number of questions for policymakers, including issues of employment regulations, employment mobility, continuing education, and the relationship of the "new" economy to the "old" economy. Three appendixes include a chart of the structure of the EMERGENCE questionnaire; a glossary of 10 terms used in the survey; and a list of the most popular destinations for eWork for European customers. (KC)

Published
2001

8. Finding common ground: meta-synthesis of communication frameworks found in patient communication, supervision and simulation literature

Author

Links, MJ, Watterson, L, Martin, P, O'Regan, S, Molloy, E, Links, MJ, Watterson, L, Martin, P, O'Regan, S, and Molloy, E

Abstract

BACKGROUND: Effective communication between patients-clinicians, supervisors-learners and facilitators-participants within a simulation is a key priority in health profession education. There is a plethora of frameworks and recommendations to guide communication in each of these contexts, and they represent separate discourses with separate communities of practice and literature. Finding common ground within these frameworks has the potential to minimise cognitive load and maximise efficiency, which presents an opportunity to consolidate messages, strategies and skills throughout a communication curriculum and the possibility of expanding the research agenda regarding communication, feedback and debriefing in productive ways. METHODS: A meta-synthesis of the feedback, debriefing and clinical communication literature was conducted to achieve these objectives. RESULTS: Our analysis revealed that the concepts underlying the framework can be usefully categorised as stages, goals, strategies, micro-skills and meta-skills. Guidelines for conversations typically shared a common structure, and strategies aligned with a stage. Core transferrable communication skills (i.e., micro-skills) were identified across various types of conversation, and the major differences between frameworks were related to the way that power was distributed in the conversation and the evolution of conversations along the along the path of redistributing power. As part of the synthesis, an overarching framework "prepare-EMPOWER enact" was developed to capture these shared principles across discourses. CONCLUSIONS: Adopting frameworks for work-based communication that promote dialogue and empower individuals to contribute may represent an important step towards learner-centred education and person-centred care for patients.

Published
2020

13. Observer roles that optimise learning in healthcare simulation education: a systematic review.

Author

O'Regan, S, Molloy, E, Watterson, L, Nestel, D, O'Regan, S, Molloy, E, Watterson, L, and Nestel, D

Abstract

BACKGROUND: Simulation is widely used in health professional education. The convention that learners are actively involved may limit access to this educational method. The aim of this paper is to review the evidence for learning methods that employ directed observation as an alternative to hands-on participation in scenario-based simulation training. We sought studies that included either direct comparison of the learning outcomes of observers with those of active participants or identified factors important for the engagement of observers in simulation. We systematically searched health and education databases and reviewed journals and bibliographies for studies investigating or referring to observer roles in simulation using mannequins, simulated patients or role play simulations. A quality framework was used to rate the studies. METHODS: We sought studies that included either direct comparison of the learning outcomes of observers with those of active participants or identified factors important for the engagement of observers in simulation. We systematically searched health and education databases and reviewed journals and bibliographies for studies investigating or referring to observer roles in simulation using mannequins, simulated patients or role play simulations. A quality framework was used to rate the studies. RESULTS: Nine studies met the inclusion criteria. Five studies suggest learning outcomes in observer roles are as good or better than hands-on roles in simulation. Four studies document learner satisfaction in observer roles. Five studies used a tool to guide observers. Eight studies involved observers in the debrief. Learning and satisfaction in observer roles is closely associated with observer tools, learner engagement, role clarity and contribution to the debrief. Learners that valued observer roles described them as affording an overarching view, examination of details from a distance, and meaningful feedback during the debrief. Learners who d

Published
2016

14. Royal academy of medicine Section of medicine/irish thoracic society: Spring meeting at regional hospital, Cork — 25th and 26th March, 1983

Author

O’Dwyer, R., Abrahamson, G., Ingram, P., Pierce, T. H., Murnaghan, D. J., Chadwick, G., Bradley, B., Clancy, L., Ohman, E. M., Butler, J., Fitzgerald, D., Horgan, J., Kelly, J., O’Malley, K., Collins, W. C. J., O’Sullivan, D. J., Fenton, V., Walsh, Eilish, Walsh, Noreen, Ferriss, J. B., Brady, M. P., Feely, M. P., O’Regan, P., Laher, M., Jackson, F., McCarthy, E., Wright, E., Keelan, P., Lanigan, C., Taylor, M. R. H., Kelly, P., Mellor, J., McCormick, P., Barry, M., Cosgrove, P. J., Teo, K. K., Craig, A. J., Horgan, J. H., Nolan, M. T., Hogan, F. P., Prichard, J. S., Jackson, F., Laher, M., O’Regan, P., O’Regan, S., Keelan, P., Counihan, T. B., Salmon, P., Connolly, A., Bloomfield, F. J., Counihan, H. E., Manning, P., Hitchcock, H. T., Broe, P. J., Higgins, D. A., Galvin, R. G., O’Sullivan, D., Bredin, C. P., Slattery, J., Slade, P. R., Hinds, D., Bredin, C., O’Sullivan, Gerald C., DeMeester, T. R., and Bermudez, G.

Published
1984
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18. CHOLINE TRANSPORTER-LIKE1 is required for sieve plate development to mediate long-distance cell-to-cell communication

Author

Dettmer, J, Ursache, R, Campilho, A, Miyashima, S, Belevich, I, O'Regan, S, Mullendore, D, Yadav, S, Lanz, C, Beverina, L, Papagni, A, Schneeberger, K, Weigel, D, Stierhof, Y, Moritz, T, Knoblauch, M, Jokitalo, E, Helariutta, Y, Helariutta, Y., BEVERINA, LUCA, PAPAGNI, ANTONIO, Dettmer, J, Ursache, R, Campilho, A, Miyashima, S, Belevich, I, O'Regan, S, Mullendore, D, Yadav, S, Lanz, C, Beverina, L, Papagni, A, Schneeberger, K, Weigel, D, Stierhof, Y, Moritz, T, Knoblauch, M, Jokitalo, E, Helariutta, Y, Helariutta, Y., BEVERINA, LUCA, and PAPAGNI, ANTONIO

Abstract

Phloem, a plant tissue responsible for long-distance molecular transport, harbours specific junctions, sieve areas, between the conducting cells. To date, little is known about the molecular framework related to the biogenesis of these sieve areas. Here we identify mutations at the CHER1/AtCTL1 locus of Arabidopsis thaliana. The mutations cause several phenotypic abnormalities, including reduced pore density and altered pore structure in the sieve areas associated with impaired phloem function. CHER1 encodes a member of a poorly characterized choline transporter-like protein family in plants and animals. We show that CHER1 facilitates choline transport, localizes to the trans-Golgi network, and during cytokinesis is associated with the phragmoplast. Consistent with its function in the elaboration of the sieve areas, CHER1 has a sustained, polar localization in the forming sieve plates. Our results indicate that the regulation of choline levels is crucial for phloem development and conductivity in plants. © 2014 Macmillan Publishers Limited. All rights reserved.

Published
2014

21. Effects of Hemodialysis on Myocardial Function in Pediatric Patients

Author

L. Revillon, D. Villemand, Davignon A, Ducharme G, O'Regan S, Pierre Robitaille, Centre de recherche de l'hôpital Sainte Justine, CHU Sainte Justine [Montréal], Institut Montpelliérain Alexander Grothendieck (IMAG), and Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Cardiac function curve, Male, medicine.medical_specialty, Cardiac output, Adolescent, medicine.medical_treatment, 030204 cardiovascular system & hematology, Acetates, 03 medical and health sciences, 0302 clinical medicine, Renal Dialysis, [MATH.MATH-ST]Mathematics [math]/Statistics [math.ST], 030225 pediatrics, Internal medicine, medicine, Humans, Chronic hemodialysis, Child, Dialysis, ComputingMilieux_MISCELLANEOUS, Uremia, Adult patients, business.industry, Heart, Water-Electrolyte Balance, Myocardial function, Child, Preschool, Cardiology, Female, Hemodialysis, business
Abstract

The effect of hemodialysis on myocardial function in 10 pediatric chronic hemodialysis patients was assessed utilizing echocardiography. Parameters of cardiac function were measured prior to and immediately after dialysis. A significant decrease in cardiac output was observed post-dialysis. Unlike that observed in adult patients a real improvement in myocardial function as indicated by an increase in the mean velocity of circumferential fibre shortening was evident post-dialysis.

Published
2004

22. Acute Liver Failure from Wilson’s Disease in a Five-Year-Old Child

Author

Andrée Rasquin-Weber, O'Regan S, H. Blanchard, Pierre Russo, Ernest G. Seidman, C. Morin, Khazal Paradis, N Kalach, and Jean-Martin Laberge

Subjects
Wilson's disease, Pediatrics, medicine.medical_specialty, business.industry, Gastroenterology, medicine, Liver failure, lcsh:Diseases of the digestive system. Gastroenterology, General Medicine, lcsh:RC799-869, medicine.disease, business
Published
1993

25. Morphological Classification of Fluvial Environments: An Investigation of the Continuum of Channel Types

Author

Heritage, George, Charlton, Martin, O'Regan, S., Heritage, George, Charlton, Martin, and O'Regan, S.

Abstract

Bedrock-controlled channel systems exhibit considerable morphological variation. Both bedrock-influenced and al- luvial morphological units coexist to form a system of changing channel patterns in response to changes in the relative influence of the controlling process variables. This article investigates the morphological composition of the bedrock- influenced Sabie River, Mpumalanga Province, South Africa, mapping 25 km of river channel at the scale of individual morphological units. Cluster and discriminant analyses define objective reach–scale “channel type” assemblages based on morphological unit composition. A number of robust clusters emerged that could be broadly classified into five channel types, namely, bedrock anastomosed, mixed anastomosed, pool-rapid, braided, and alluvial single-thread. The cluster analysis revealed that these channel types fit on a continuum from bedrock-dominated channels to fully alluvial systems. Each channel type could also be characterized by a certain set of “dominant” morphological units, which changed from bedrock-influenced at one end of the continuum (bedrock anastomosed, pool-rapid) to alluvial deposits at the other (braided, alluvial single-thread). An investigation of the role of controlling process variables in defining these channel types revealed a broad link between the degree of bedrock influence and the amount of available energy within the system as defined by indices such as the flow regime and water-surface slope variation. It is clear that the bedrock-dominated channel types are characterized by energy levels in excess of those accepted for alluvial systems, and an extended river classification is presented for the Sabie River that includes these bedrock channels. The mixed anastomosing channel type on the Sabie River is characterized by higher available energy levels than braided or alluvial single-thread reaches. As such, it appears to be a higher-energy example of an anabranched system, probably formed as a

Published
2001

36. The neuronal choline transporter CHT1 is regulated by immunosuppressor-sensitive pathways.

Author

Guermonprez, L., O'Regan, S., Meunier, F-M., and Morot-Gaudry-Talarmain, Y.

Subjects
*ACETYLCHOLINE, *NEUROCHEMISTRY, *CHOLINE, *IMMUNOSUPPRESSION, *CYCLOSPORINE
Abstract

The immunosuppressor cyclosporin A inhibits the peptidylprolyl-cis/trans-isomerase activity of cyclophilins and the resulting complex inhibits the phosphatase activity of calcineurin. Both enzymes were detected in peripheral nerve endings isolated from the electric organ of Torpedo and shown to be affected by 10 µM cyclosporin A. Among the cholinergic properties studied, choline uptake was specifically inhibited by cyclosporin A to a maximum of 40%. Cyclosporin A decreased the rate of choline transport but not the binding of the nontransportable choline analogue hemicholinium-3, indicating that the number of membrane transporters was not affected. Through the use of two other immunosuppressors, FK506, which also inhibits calcineurin, and rapamycin, which does not, two different mechanisms of choline uptake inhibition were uncovered. FK506 inhibited the rate of choline transport, whereas rapamycin diminished the affinity for choline. The Torpedo homologue of the high affinity choline transporter CHT1 was cloned and its activity was reconstituted in Xenopus oocytes. Choline uptake by oocytes expressing tCHT1 was inhibited by all three immunosuppressors and also by microinjection of the specific calcineurin autoinhibitory domain A[sub 457-481], indicating that the phosphatase calcineurin regulates CHT1 activity and could be the common target of cyclosporin and FK506. Rapamycin, which changed the affinity of the transporter, may have acted through an immunophilin on the isomerization of critical prolines that are found in the tCHT1 sequence. [ABSTRACT FROM AUTHOR]

Published
2002
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37. The clearance of pre-formed immune complexes in rats with Heymann's nephritis.

Author

O'Regan, S.

Subjects
*IMMUNE complexes, *KIDNEY diseases, *BIOLOGICAL membranes, *RETICULO-endothelial system, *RATS, *IMMUNOGLOBULINS
Abstract

Previous studies have indicated the presence of reticuloendothelial system (RES) depression in chronic immune complex nephritis in rabbits. To determine whether RES immune complex clearance was abnormal in Heymann's nephritis in rats, radiolabelled pre-formed immune complexes were infused into rats with membranous nephropathy. There was augmented clearance of complexes from the peripheral circulation in animals with membranous nephropathy relative to controls, indicating the absence of RES saturation. [ABSTRACT FROM AUTHOR]

Published
1979

38. Possible Clq bypass loop activation in the haemolytic uraemic syndrome.

Author

Nolin, L., O'Regan, S., Pelletter, M., Rivard, G. E., Mongeau, J.-G., and Robitaille, P.

Subjects
*HEMOLYTIC-uremic syndrome, *TISSUE analysis, *PATIENTS, *IMMUNE complexes, *IMMUNOGLOBULIN M, *ACUTE kidney failure
Abstract

Ultrastructural and immunofluorescent microscopic studies were performed on renal tissue obtained from nine patients during the acute and convalescent phase of the haemolytic uraemic syndrome (HUS). All had glomerular deposits of IgM in the absence of circulating immune complexes. This was associated with deposition of Clq during the acute phase, and properdin and C3 during the convalescent phase. C4 was consistently absent. Since such a pattern of complement deposition does not fulfil criteria either for alternate or classical pathway activation, the possibility of Clq bypass loop activation by IgM is suggested. [ABSTRACT FROM AUTHOR]

Published
1979

39. Immune complex infusion in the rat.

Author

O'Regan, S., Smith, Marlyn, and Drummond, K. N.

Subjects
*IMMUNOGLOBULINS, *IMMUNE serums, *KIDNEY diseases, *BLOOD pressure, *IMMUNOFLUORESCENCE, *RATS
Abstract

Immune complexes were precipitated from pooled goat antisera to human Cohn Fraction II. After washing the complexes were solubilized in antigen excess. When complexes containing 10 mg of antibody were infused into saline-loaded rats an episode of oligoanuria lasting 4 6 hr resulted followed by transient proteinuria. By 24 hr after complex infusion protein excretion had returned to pie-infusion levels. With infusion of 5 mg of antibody similar functional alterations, though of lesser severity, occurred. Control animals infused with Cohn fraction II alone in an amount and protein concentration equal to the experimental groups exhibited none of these features. Changes in blood pressure did not occur. Immune complex deposition was not detectable in the glomeruli by immunofluorescence microscopy. A mild micro- angiopathy affecting mainly interstitial vessels, with some glomerular endothelial cell swelling, was evident on light microscopy. It is suggested that circulating factors resulting from complex infusion rather than glomerular complex localization account for the changes observed. [ABSTRACT FROM AUTHOR]

Published
1976

40. Delayed rejection of cardiac xenografts in C6-deficient rabbits.

Author

Chartrand, C., O'Regan, S., Robitaille, P., and Pinto-Blonde, M.

Subjects
*GRAFT rejection, *XENOGRAFTS, *HEART transplantation, *TRANSPLANTATION of organs, tissues, etc., *TRANSPLANTATION immunology, *IMMUNOLOGY
Abstract

Puppy hearts were engrafted to C6-deficient rabbits, and also to complement-sufficient animals in order to determine the influence of the sixth component of complement on xenograft rejection. Delayed rejection was observed in the puppy hearts engrafted to the C6-deficient animals indicating that complement sufficiency of C6 is required for hyperacute xenograft rejection. [ABSTRACT FROM AUTHOR]

Published
1979

47. NIH conference. Cystinosis: progress in a prototypic disease.

Author

Gahl, W A, Thoene, J G, Schneider, J A, O'Regan, S, Kaiser-Kupfer, M I, and Kuwabara, T

Subjects
CYSTEINE metabolism, AMINES, BIOLOGICAL transport, COMPARATIVE studies, CRYSTALLIZATION, EYE diseases, HUMAN growth, KIDNEY transplantation, RESEARCH methodology, MEDICAL cooperation, INBORN errors of metabolism, OPHTHALMIC drugs, PRODRUGS, RESEARCH, EVALUATION research, ORGANOTHIOPHOSPHORUS compounds, DISEASE complications
Abstract

Objective: To review the history, basic defect, pathogenesis, clinical manifestations, diagnosis, and treatment of nephropathic cystinosis.Design: Lysosomal membrane transport studies, clinical reports, and a historically controlled 7-year trial of oral cysteamine therapy.Setting: University centers in the United States and Canada.Patients: One hundred forty-eight children, aged 0 to 12, with nephropathic cystinosis before renal transplant, who had renal tubular Fanconi syndrome, failure to grow, corneal cystine crystals, and elevated leukocyte cystine; 34 patients, aged 9 to 29, after transplant, some with visual impairment, corneal erosions, pancreatic dysfunction, or neurologic deterioration.Intervention: Before transplant, replacement of renal losses, and treatment with oral cysteamine (55 mg/kg body weight.d for 1 to 6 years) and topical cysteamine eyedrops (0.1%, 1 drop/h while awake, for 6 months). After transplant, oral cysteamine and symptomatic treatment of late complications.Measurements and Main Results: Untreated patients reached renal failure at age 10. Oral cysteamine lowered leukocyte cystine over 80%, and in patients before transplant, improved growth and preserved renal function (mean creatinine clearance [+/- SE], 0.64 +/- 0.04 mL/s.1.73 m2 [38.5 +/- 2.5 mL/min.1.73 m2] in the cysteamine group compared with 0.50 +/- 0.03 mL/s.1.73 m2 [29.7 +/- 2.0 mL/min.1.73 m2] in controls; 95% CI for the difference, 1.8 to 15.8). Cysteamine eyedrops cleared the corneal crystals of two children less than 2 years old.Conclusions: Cystinosis is a lysosomal storage disease due to impaired transport of cystine out of lysosomes. In young children, growth can be improved and renal deterioration delayed or prevented by oral cysteamine. Nonrenal complications after transplant might be prevented with long-term oral cysteamine. [ABSTRACT FROM AUTHOR]

Published
1988
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48. Reconstitution of carrier-mediated choline transport in proteoliposomes prepared from presynaptic membranes of Torpedo electric organ, and its internal and external ionic requirements.

Author

Vyas, S. and O'Regan, S.

Subjects
FISH metabolism, ANIMAL experimentation, BIOLOGICAL transport, CHOLINE, COMPARATIVE studies, DYNAMICS, ELECTRON microscopy, FISHES, IONS, RESEARCH methodology, MEDICAL cooperation, ARTIFICIAL membranes, RESEARCH, EVALUATION research, CRYOULTRAMICROTOMY
Abstract

Proteoliposomes made by a butanol-sonication technique from electric organ presynaptic membranes showed choline transport activity. In contrast to intact nerve terminals, the uptake of choline was dissociated from its conversion to acetylcholine in this preparation. The kinetics of choline uptake by proteoliposomes was best described by two Michaelis-Menten components. At a low concentration of choline, uptake was inhibited by hemicholinium-3 and required external Na+ and, thus, closely resembled high-affinity choline uptake by intact cholinergic nerve terminals. Choline transport could be driven by the Na+ gradient and by the transmembrane potential (inside negative) but did not directly require ATP. External Cl-, but not a Cl- gradient, was needed for choline transport activity. It is suggested that internal K+ plays a role in the retention of choline inside the proteoliposome. Proteoliposomes should prove a useful tool for both biochemical and functional studies of the high-affinity choline carrier. [ABSTRACT FROM AUTHOR]

Published
1985
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49. Complications in expanded polytetrafluoroethylene arteriovenous grafts: an angiographic study

Author

Lemaitre P, Herba Mj, Kaye M, and O'Regan S

Subjects
medicine.medical_specialty, medicine.diagnostic_test, business.industry, Arterial stenosis, Arterial Occlusive Diseases, General Medicine, Expanded polytetrafluoroethylene, Thrombophlebitis, Aneurysm, Blood Vessel Prosthesis, Surgery, Radiography, surgical procedures, operative, Surgical Wound Dehiscence, Angiography, medicine, Humans, Radiology, Nuclear Medicine and imaging, Chronic hemodialysis, Arteriovenous grafts, Radiology, business, Aneurysm formation, Polytetrafluoroethylene
Abstract

Expanded polytetrafluoroethylene grafts were used for creation of arteriovenous shunts in 35 patients on chronic hemodialysis. When flow studies or mechanical factors indicated abnormal flow in the graft, angiography was performed. Detection of venous backflow or obstruction, arterial stenosis, aneurysm formation, or graft kinking facilitated correction and thus salvage of the grafts.

Published
1978

50. Electrolyte and acid-base disturbances in the management of leukemia

Author

O'Regan, S, Carson, S, Chesney, RW, and Drummond, KN

Abstract

Electrolyte disturbances in leukemia can be the result of the disease process or drug therapy. One group of electrolyte abnormalities is related to the stage of the leukemic process. Included in this group are newly diagnosed patients who may show elevated serum potassium, phosphorus, and magnesium--a result of their release from malignant cells after cytotoxic therapy or their accumulation due to urate nephropathy. Patients in remission usually have normal serum electrolyte concentrations, but acute leukemia patients during relapse may have hypokalemia, hypophosphatemia, and hypomagnesemia. This imbalance may be related to cellular uptake of these electrolytes in the presence of inadequate dietary intake. Other factors contributing to electrolyte derangements, and related to the leukemic process, include hyponatremia and hypochloremia secondary to the SIADH, hypokalemia in acute monocytic or acute myelomonocytic leukemia due to lysozyme-induced tubular damage, hypercalcemia possibly secondary to leukemic infiltration of bone or parathyroid glands (with PTH release), or production of a PTH-like substance by leukemic cells. Nonspecific factors related to the disease process which may aggravate the electrolyte imbalance include gastrointestinal loss through nausea, vomiting, and malnutrition. The drug-related electrolyte abnormalities include cyclophosphamide- and vincristine-induced SIADH; decreased serum sodium, chloride, potassium, and calcium concentrations as a result of polymyxin B nephrotoxicity; hypokalemia and hypomagnesemia secondary to amphotericin B; hypocalcemia, hypophosphatemia, and hyperphosphaturia due to L-asparaginase-induced hypoparathyroidism; hypokalemia due to a nonreabsorbable anion effect of antibiotics in the distal tubule or changes in membrane ionic transport of all cells by large doses of antibiotics. Electrolyte disturbance in leukemia thus have a multifactorial pathogenesis which can best be delineated according to the stage of the leukemic process and the drugs being used. Recognition of the cause or causes in a particular patient is essential for an effective approach to management. This review emphasizes the need for routine measurement of serum electrolytes during all phases of the leukemic process.

Published
1977
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