Publications by authors named "Pamela Kelly"

16 Publications

  • Page 1 of 1

Circulating Melanoma-Derived Extracellular Vesicles: Impact on Melanoma Diagnosis, Progression Monitoring, and Treatment Response.

Pharmaceuticals (Basel) 2020 Dec 18;13(12). Epub 2020 Dec 18.

UCD School of Medicine, College of Health and Agricultural Sciences, University College Dublin, Belfield, Dublin 4, Ireland.

Malignant melanoma, one of the most aggressive human malignancies, is responsible for 80% of skin cancer deaths. Whilst early detection of disease progression or metastasis can improve patient survival, this remains a challenge due to the lack of reliable biomarkers. Importantly, these clinical challenges are not unique to humans, as melanoma affects many other species, including companion animals, such as the dog and horse. Extracellular vesicles (EVs) are tiny nanoparticles involved in cell-to-cell communication. Several protein and genomic EV markers have been described in the literature, as well as a wide variety of methods for isolating EVs from body fluids. As such, they may be valuable biomarkers in cancer and may address some clinical challenges in the management melanoma. This review aimed to explore the translational applications of EVs as biomarkers in melanoma, as well as their role in the clinical setting in humans and animals. A summary of melanoma-specific protein and genomic EV markers is presented, followed by a discussion of the role EVs in monitoring disease progression and treatment response. Finally, herein, we reviewed the advantages and disadvantages of methods utilised to isolate EVs from bodily fluids in melanoma patients (human and animals) and describe some of the challenges that will need to be addressed before EVs can be introduced in the clinical setting.
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http://dx.doi.org/10.3390/ph13120475DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7766072PMC
December 2020

Exosomes as Biomarkers of Human and Feline Mammary Tumours; A Comparative Medicine Approach to Unravelling the Aggressiveness of TNBC.

Biochim Biophys Acta Rev Cancer 2020 12 17;1874(2):188431. Epub 2020 Sep 17.

UCD Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin 4, Ireland; UCD School of Medicine, College of Health and Agricultural Sciences, University College Dublin, Belfield, Dublin 4, Ireland.

Comparative oncology is defined as the discipline that integrates naturally occurring cancers seen in veterinary medicine, into more general studies of cancer biology and therapy in humans, including the study of cancer-pathogenesis and new cancer treatments. While experimental studies in mice and rodents offer several advantages, including a wealth of genetic information, reduced variation and short generation intervals, their relevance in cancer biology is somewhat limited. Toward this end, as the biomedical research community works to make the promise of precision medicine a reality, more efficient animal cohort studies are critical. Like humans, companion animals such as cats and dogs living in family homes, are exposed to environmental factors that may influence the development of disease. Furthermore, it has been shown that the basic biochemical and physiological processes of companion animals more closely resemble humans compared to rodents. Research has demonstrated that female domestic cats (Felis catus) may represent a comparative model for investigation of mammary carcinogenesis, and in particular, Triple Negative Breast Cancer (TNBC). TNBC is a subtype of breast cancer that typically lacks the expression of the oestrogen receptor (ER), progesterone receptor (PR), and does not overexpress the human epidermal growth factor receptor 2 (HER2). An exciting and rapidly expanding area in cancer biology is the study of exosomes. Exosomes are nanoparticles released from cells and have been found in biological fluids of humans, domestic cats and dogs. In addition to their role as biomarkers, exosomes are implicated in the pathogenesis of certain diseases, including cancer. This review explores the current understanding of exosome biology in human TNBC, and of the potential benefits of comparative research in naturally-occurring mammary tumours in companion animals.
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http://dx.doi.org/10.1016/j.bbcan.2020.188431DOI Listing
December 2020

An unusual presentation of developmental anomalies of the cardiovascular system including tetralogy of fallot, double outlet right ventricle, patent foramen ovale and persistent right aortic arch in a Friesian calf.

BMC Vet Res 2020 Jun 30;16(1):224. Epub 2020 Jun 30.

Section of Herd Health and Animal Husbandry, School of Veterinary Medicine, Veterinary Sciences Centre, University College Dublin, Belfield, Dublin 4, Ireland.

Background: Congenital heart diseases are occasionally encountered in the bovine species. Ventricular septal defects (VSD) and atrial septal defects (ASD) are reported to be the most common; however, a vast collection have been reported [1, 2]. Congenital heart diseases is thought to represent less than 3% of all congenital abnormalities in calves [3]. Various cardiac anomalies arise due to defective embryologic development such as defects of the septae or the cardiac chambers [2]. The exact aetiology of these congenial heart anomalies remains to be fully elucidated [4]. VSDs appear to be the most common congenital cardiac anomaly in calves. Other diseases can be subdivided into cyanotic (e.g. ASD or patent ductus arteriosus) and non-cyanotic (e.g. tetralogy of fallot or eisenmengers complex) [5, 6]. An exceptional presentation of an array of congenital anomalies was identified in a Friesian heifer calf. To the authors' knowledge this concurrent collection of congenital abnormalities has never been reported in this species.

Case Presentation: A 3-day old Friesian heifer presented with a history since birth of regurgitation post feeding. The main finding on clinical examination was tachypnoea with a holosystolic murmur. Echocardiography identified a VSD, patent foramen ovale (PFO) (both with left to right blood flow) and tricuspid insufficiency. The calf was subsequently euthanised and underwent gross post-mortem examination. A persistent right aortic arch (PRAA) was identified. The cardiac anomalies identified on the echocardiogram were confirmed along with additional abnormalities; double outlet right ventricle (DORV), partial transposition of the great vessels, pulmonic stenosis, hypoplasia of the right branch of the pulmonary artery and right ventricular hypertrophy. The final diagnosis was Tetralogy of Fallot with DORV, PFO and PRAA. The lungs appeared oedematous and congested due to cardiac malfunction and cranioventral aspiration pneumonia. Free serous fluid was identified in the thoracic cavity. Unilateral renal agenesis of the left kidney was an incidental finding but is of note due to its coexistence with the cardiac abnormalities.

Conclusions: This is an unusual case as it features numerous congenital abnormalities that appeared to negate each other allowing capability with life. To the authors' knowledge, this collection of concurrent cardiac anomalies has not been previously reported in bovines.
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http://dx.doi.org/10.1186/s12917-020-02439-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7325375PMC
June 2020

Exosomes in triple negative breast cancer: Garbage disposals or Trojan horses?

Cancer Lett 2020 03 2;473:90-97. Epub 2020 Jan 2.

UCD Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield Dublin, Dublin 4, Ireland; UCD School of Medicine, College of Health and Agricultural Sciences (CHAS), University College Dublin, Belfield Dublin, Dublin 4, Ireland.

Triple negative breast cancer (TNBC) is a breast cancer subtype which is particularly aggressive and invasive. The treatment of TNBC has been limited due to the lack of well-defined molecular targets. Exosomes are nano-sized extracellular vesicles that are released from virtually all cell types into the extracellular space. Due to their endocytic origin, exosomes carry valuable information from their cells of origin. Exosomes were first thought to serve as "garbage disposals" that eliminate unwanted cellular components. Later, they were found to be involved in the pathology of many diseases including cancer. Despite their established roles in multiple diseases, only a small number of studies have focused on the role of exosomes in TNBC. In this review, we outline the roles of exosomes in cancer progression, metastasis and drug resistance in this breast cancer subtype. We then further illustrate the potential roles of exosomes as diagnostic tools, therapeutic targets and delivery systems.
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http://dx.doi.org/10.1016/j.canlet.2019.12.046DOI Listing
March 2020

House dust mite-treated PAR2 over-expressor mouse: A novel model of atopic dermatitis.

Exp Dermatol 2019 11 17;28(11):1298-1308. Epub 2019 Sep 17.

Charles Institute of Dermatology, School of Medicine, University College Dublin, Dublin 4, Ireland.

Background: Atopic dermatitis (AD) is a complex skin disease involving causative effects from both intrinsic and extrinsic sources. Murine models of the disease often fall short in one of these components and, as a result, do not fully encapsulate these disease mechanisms.

Objective: We aimed to determine whether the protease-activated receptor 2 over-expressor mouse (PAR2OE) with topical house dust mite (HDM) application is a more comprehensive and clinically representative AD model.

Methods: Following HDM extract application to PAR2OE mice and controls, AD clinical scoring, itching behaviour, skin morphology and structure, barrier function, immune cell infiltration and inflammatory markers were assessed. Skin morphology was analysed using haematoxylin and eosin staining, and barrier function was assessed by transepidermal water loss measurements. Immune infiltrate was characterised by histological and immunofluorescence staining. Finally, an assessment of AD-related gene expression was performed using quantitative RT-PCR.

Results: PAR2OE mice treated with HDM displays all the characteristic clinical symptoms including erythema, dryness and oedema, skin morphology, itch and inflammation typically seen in patients with AD. There is a significant influx of mast cells (P < .01) and eosinophils (P < .0001) into the dermis of these mice. Furthermore, the PAR2OE + HDM mice exhibit similar expression patterns of key differentially expressed genes as seen in human AD.

Conclusion: The PAR2OE + HDM mouse presents with a classic AD pathophysiology and is a valuable model in terms of reproducibility and overall disease representation to study the condition and potential therapeutic approaches.
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http://dx.doi.org/10.1111/exd.14030DOI Listing
November 2019

Self-Management in Epilepsy Care: Untapped Opportunities.

Fed Pract 2018 Apr;35(Suppl 3):S10-S16

is a Nurse Practitioner at the Epilepsy Center of Excellence VA Puget Sound Health Care System in Seattle, Washington. is Regional Administrative Director, Southeast Epilepsy Centers of Excellence, Durham VAMC in North Carolina and an Assistant Professor at Liberty University in Lynchburg, Virginia. is the Director at the Epilepsy Centers of Excellence at Hunter Holmes McGuire Veterans Administration Medical Center and Professor at Virginia Commonwealth University, both in Richmond. is an Associate Professor at University of California, San Francisco and a Staff Physician at the Epilepsy Center of Excellence at the San Francisco VA Medical Center in California.

Constant accessibility, rapid scalability, and modest costs make digital and mobile epilepsy self-management platforms an attractive alternative to resource-intensive in-person programs.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6375434PMC
April 2018

Competency-based Professional Advancement Model for Advanced Practice RNs.

J Nurs Adm 2019 Feb;49(2):66-72

Author Affiliations: Nurse Practitioner (Dr Paul), Center for Motility and Functional Gastrointestinal Disorders; Clinical Nurse Specialist (Ms Abecassis), Medical Intensive Care; Clinical Nurse Specialist (Ms Freiberger), Pulmonary/Pediatric Transplant Center; Clinical Nurse Specialist (Ms Hamilton), Medical Surgical Intensive Care; Nurse Practitioner (Ms Kelly), Urology and Urodynamics; Clinical Nurse Specialist (Ms Klements), Asthma and Medicine Patient Services; Nurse Practitioner (Dr LaGrasta), Cardiovascular Surgical Services; Nurse Practitioner (Mss Lemire, O'Donnell, and Phinney), General Surgery; Nurse Practitioner (Ms Patisteas), Orthopedic Surgery; Professional Development Specialist (Ms Conwell), Clinical Education and Informatics; Nurse Practitioner (Dr Saia), Cardiology; Nurse Practitioner (Ms Whelan), Cardiac Intensive Care; Senior VP, Patient Care Operations and Chief Nursing Officer (Dr Wood); and Nurse Practitioner (Ms O'Brien), Cardiology: Boston Children's Hospital, Massachusetts.

The process of developing a 3-tiered advanced practice RN (APRN) competency-based professional advancement model at Boston Children's Hospital is described. The model recognizes the contributions of entry-level and expert APRNs to advanced clinical practice and outcomes, impact, and leadership, while incorporating the tenets of Patricia Benner's Novice to Expert Model and the American Association of Critical- Care Nurses Synergy Model of Care.
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http://dx.doi.org/10.1097/NNA.0000000000000719DOI Listing
February 2019

Periaortic lymphoma in a cat.

JFMS Open Rep 2017 Jul-Dec;3(2):2055116917729627. Epub 2017 Sep 18.

University College Dublin, Section of Veterinary Clinical Sciences, Dublin, Ireland.

Case Summary: A 14-year-old neutered male Siamese cat was presented with a 3 month history of lethargy, inappetence, dehydration, hindlimb ataxia and intermittent proprioceptive deficits in the hindlimbs. Physical examination revealed low body condition score (1.75/5), pallor and bilateral basilar grade II/VI systolic heart murmur. Neurological examination revealed hindlimb ataxia, severe atrophy of the hindlimb musculature, intermittent hindlimb proprioceptive deficits and normoreflexia. Clinicopathological investigations revealed non-regenerative anaemia (haematocrit 0.17 l/l; reference interval [RI] 0.24-0.45 l/l) and increased feline pancreatic lipase concentration (Spec fPL test [IDEXX] 8.3 μg/l; RI 0.1-3.5 μg/l). Feline leukaemia virus antigen and feline immunodeficiency virus antibody tests were negative. Thoracic and abdominal imaging revealed a soft tissue structure in the area of the thoracoabdominal aorta. CT confirmed a periaortic contrast-enhancing mass extending from the level of T9-L2, with associated intervertebral infiltration at the level of T11-T12. Post-mortem examination confirmed the presence of a solid, white, multinodular, well-demarcated mass encircling the aorta extending from T9-L2. Based on histopathology and immunohistochemistry, a diagnosis of B-cell lymphoma was made. Lymphoma was also identified histopathologically within the kidneys and spleen. Evidence of mild Wallerian degeneration was present within the spinal cord, indicating compression at the level of the periaortic mass.

Relevance And Novel Information: To our knowledge, this is the first report of periaortic lymphoma in the cat. Although periaortic tumours are exceptionally rare in veterinary medicine, lymphoma should be considered as a differential in cats.
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http://dx.doi.org/10.1177/2055116917729627DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5607923PMC
September 2017

Implementation of an established algorithm and modifications for the identification of epilepsy patients in the veterans health administration.

Epilepsy Res 2016 11 23;127:284-290. Epub 2016 Sep 23.

Southeast Epilepsy Centers of Excellence, Durham VA Hospital, Durham, NC, United States; Duke University Medical Center, Durham, NC, United States.

Identification of epilepsy patients from administrative data in large managed healthcare organizations is a challenging task. The objectives of this report are to describe the implementation of an established algorithm and different modifications for the estimation of epilepsy prevalence in the Veterans Health Administration (VHA). For the prevalence estimation during a given time period patients prescribed anti-epileptic drugs and having seizure diagnoses on clinical encounters were identified. In contrast to the established algorithm, which required inclusion of diagnoses data from the time period of interest only, variants were tested by considering diagnoses data beyond prevalence period for improving sensitivity. One variant excluded data from diagnostic EEG and LTM clinics to improve specificity. Another modification also required documentation of seizures on the problem list (electronic list of patients' established diagnoses). Of the variants tested, the one excluding information from diagnostic clinics and extending time beyond base period of interest for clinical encounters was determined to be superior. It can be inferred that the number of patients receiving care for epilepsy in the VHA ranges between 74,000 and 87,000. In the wake of the recent implementation of ICD-10 codes in the VHA, minor tweaks are needed for future prevalence estimation due to significant efforts presented. This review is not only beneficial for researchers interested in VHA related data but can also be helpful for managed healthcare organizations involved in epilepsy care aiming at accurate identification of patients from large administrative databases.
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http://dx.doi.org/10.1016/j.eplepsyres.2016.09.012DOI Listing
November 2016

Pathology in Practice.

J Am Vet Med Assoc 2016 Aug;249(4):387-90

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http://dx.doi.org/10.2460/javma.249.4.387DOI Listing
August 2016

Myeloid Engraftment in Humanized Mice: Impact of Granulocyte-Colony Stimulating Factor Treatment and Transgenic Mouse Strain.

Stem Cells Dev 2016 Apr;25(7):530-41

1 Trinity Health Kidney Centre, Trinity Translational Medicine Institute, Trinity College Dublin , Dublin, Ireland .

Poor myeloid engraftment remains a barrier to experimental use of humanized mice. Focusing primarily on peripheral blood cells, we compared the engraftment profile of NOD-scid-IL2Rγc(-/-) (NSG) mice with that of NSG mice transgenic for human membrane stem cell factor (hu-mSCF mice), NSG mice transgenic for human interleukin (IL)-3, granulocyte-macrophage-colony stimulating factor (GM-CSF), and stem cell factor (SGM3 mice). hu-mSCF and SGM3 mice showed enhanced engraftment of human leukocytes compared to NSG mice, and this was reflected in the number of human neutrophils and monocytes present in these strains. Importantly, discrete classical, intermediate, and nonclassical monocyte populations were identifiable in the blood of NSG and hu-mSCF mice, while the nonclassical population was absent in the blood of SGM3 mice. Granulocyte-colony stimulating factor (GCSF) treatment increased the number of blood monocytes in NSG and hu-mSCF mice, and neutrophils in NSG and SGM3 mice; however, this effect appeared to be at least partially dependent on the stem cell donor used to engraft the mice. Furthermore, GCSF treatment resulted in a preferential expansion of nonclassical monocytes in both NSG and hu-mSCF mice. Human tubulointerstitial CD11c(+) cells were present in the kidneys of hu-mSCF mice, while monocytes and neutrophils were identified in the liver of all strains. Bone marrow-derived macrophages prepared from NSG mice were most effective at phagocytosing polystyrene beads. In conclusion, hu-mSCF mice provide the best environment for the generation of human myeloid cells, with GCSF treatment further enhancing peripheral blood human monocyte cell numbers in this strain.
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http://dx.doi.org/10.1089/scd.2015.0289DOI Listing
April 2016

Characteristics of Veterans diagnosed with seizures within Veterans Health Administration.

J Rehabil Res Dev 2015 ;52(7):751-62

Southeast Epilepsy Centers of Excellence, Durham Department of Veterans Affairs Medical Center, Durham, NC;

The purpose of this report is to describe the demographics of Veterans diagnosed with seizures and taking antiepileptic drugs (AEDs) within the Veterans Health Administration (VHA) during fiscal year (FY) 2011 (October 1, 2010, to September 30, 2011), particularly with regard to comorbid traumatic brain injury (TBI) and posttraumatic stress disorder (PTSD). Information collected included age; sex; Operation Iraqi Freedom/Operation Enduring Freedom/Operation New Dawn (OIF/OEF/OND) status; and relevant encounter diagnosis codes for seizures, TBI, and PTSD. During FY11, 87,377 Veterans with seizures on AEDs were managed within the VHA. Prevalence was 15.5 per 1,000, and annual incidence was 148.2 per 100,000. The percentages of comorbid TBI and PTSD were 15.8% and 24.1%, respectively. For OIF/OEF/OND Veterans, these percentages increased to 52.6% and 70.4%, respectively. PTSD and TBI are risk factors for both epilepsy and psychogenic nonepileptic seizures. Within the VHA, many Veterans experiencing seizures cannot be successfully treated with AEDs. The VHA Epilepsy Centers of Excellence promotes a multidisciplinary approach to increase and improve access to both epilepsy and mental health specialists for the care of epileptic and nonepileptic seizures.
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http://dx.doi.org/10.1682/JRRD.2014.10.0241DOI Listing
October 2016

Nosocomial spread of Mycobacterium bovis in domestic cats.

J Feline Med Surg 2015 Feb 7;17(2):173-80. Epub 2014 Apr 7.

Royal (Dick) School of Veterinary Studies and The Roslin Institute, University of Edinburgh, Hospital for Small Animals, Easter Bush Veterinary Centre, Roslin, UK.

Five domestic cats were euthanased owing to confirmed or suspected Mycobacterium bovis infection. The initial source of infection remains unclear. Cat A was presented to a veterinary clinic in County Kildare, Ireland, with a discharging submandibular lesion. The infection appears to have been transmitted to four other cats through direct (cats B and C living in the same household as cat A) and non-direct (nosocomial spread during routine operations; cats D and E) contact over a 13.5-week period. Of the five cases, two (B and D) had post-mortem examinations in which gross changes consistent with tuberculosis were seen, moderate numbers of acid-fast bacteria (AFB) were seen on microscopy and M bovis (spoligotype SB0978) was confirmed on culture. Of the remaining three cats, one had a swab taken from its draining ovariohysterectomy wound, which revealed large numbers of AFB with morphology consistent with M bovis (cat E). Two cases were euthanased without diagnostic tests; however, their history and clinical presentations were highly suggestive of tuberculosis (cats A and C). To our knowledge, this is the first documented case of nosocomial spread of M bovis in cats.
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http://dx.doi.org/10.1177/1098612X14529768DOI Listing
February 2015

Mycobacteriosis in ostriches (Struthio camelus) due to infection with Mycobacterium bovis and Mycobacterium avium complex.

Avian Dis 2013 Dec;57(4):808-11

Veterinary Pathobiology, UCD School of Veterinary Medicine, Dublin, Ireland.

Avian tuberculosis rarely affects ratites compared to other bird species and is typically caused by Mycobacterium avium species. This study describes the pathological and microbiological findings in three adult ostriches with mycobacteriosis, in one of which Mycobacterium bovis was isolated from the lesions. Post mortem examinations on ostriches from two different zoological collections in Ireland revealed multifocal caseous granulomas affecting the spleen and liver in all cases, with additional involvement of intestines in two cases. In one case, granulomas were present within the pharynx, at the thoracic inlet and multifocally on the pleural surface. Acid-fast bacilli were observed in all lesions. Mycobacterium sp. of the M. avium complex was isolated from the intestinal lesions in the two cases with intestinal involvement, and M. bovis sp. oligotype SB0140 was cultured from the liver of the third ostrich. This represents the first reported case of M. bovis infection in an ostrich. Avian tuberculosis due to M. bovis is rare and to date has been reported in only parrots and experimentally inoculated birds. Mycobacterium bovis needs to be considered as a possible cause of tuberculosis in ostriches because the lesions are similar to those observed with M. avium complex infection.
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http://dx.doi.org/10.1637/10581-052313-Case.1DOI Listing
December 2013

Biofeedback training for lower urinary tract symptoms: factors affecting efficacy.

J Urol 2009 Oct 20;182(4 Suppl):2050-5. Epub 2009 Aug 20.

Children's Hospital Boston, Harvard University, Boston, Massachusetts 02115, USA.

Purpose: Biofeedback therapy is a valuable modality in children with dysfunctional voiding. However, it is unclear what factors contribute to the outcome. To define who may or may not benefit from biofeedback therapy we reviewed our experience with this treatment.

Materials And Methods: We retrospectively reviewed the charts of 77 children referred between July 2005 and September 2008 for biofeedback therapy. An MR 20 Synergy trainer (Prometheus Group, Dover, New Hampshire) provided nonanimated and animated biofeedback. Uroflowmetry was performed at the start and end of each session. A total of 67 females and 10 males with a mean age of 9.0 years (range 4.8 to 18.2) comprised the cohort group. The primary referral diagnosis was nonfebrile urinary tract infection in 52 patients (67.5%), daytime and nighttime wetting in 47 (61%), voiding postponement in 14 (18.2%) and daytime incontinence in 10 (13%). Children were categorized by an outcome of success, improvement or failure. Results were analyzed using the chi-square, Fisher exact probability and Student t tests.

Results: Success, improvement and failure were achieved in 22 (26.8%), 29 (37.7%) and 26 cases (33.7%), respectively. Age and gender were not statistically significant predictors of outcome. A median of 3.0 sessions (range 1 to 8) was administered. Children with 3 or greater sessions were more likely to succeed (p <0.005). The improvement in urinary tract infections was statistically significant (p <0.001). Of 37 children 20 (54%) transformed a staccato voiding pattern to a normal one on uroflowmetry.

Conclusions: Biofeedback therapy can be effective in children with dysfunctional voiding and urinary tract infection. Children with a staccato voiding pattern may require a minimum of 3 visits to improve the voiding pattern. Children who complete 3 sessions are more likely to succeed.
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http://dx.doi.org/10.1016/j.juro.2009.06.003DOI Listing
October 2009

Immunoglobulin deficiency in Stickler syndrome.

Am J Med Genet A 2006 Dec;140(24):2824-7

Healthy Link Asthma Education Program, Children's Hospital, Boston, Massachusetts, USA.

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http://dx.doi.org/10.1002/ajmg.a.31513DOI Listing
December 2006