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D Kearney

Publications and source records attributed to D Kearney.

At least 19 recordsLinked to original sources
PubMed2001

A simple method for measuring of intestinal solute transport in mucosal biopsy specimens.

Accurate in vitro measurements of intestinal mucosal solute uptake in humans are often difficult because only small amounts of tissue material are available. We describe a miniaturized everted sleeve method of measuring intestinal solute uptake in endoscopy biopsy samples that combines simplicity, good tissue viability and reproducibility. Biopsies were mounted on a dressmaker needle head stationed immediately over a stirring bar rotating at 1200 rpm. This approach was used to measure taurocholate uptake in sheep and human endoscopy biopsies. Comparison was made to conventional standardized everted sleeve preparations. Na+-dependent uptake rates correlated well among individual sheep (R2 = 0.88, P < 0.05). There was excellent correlation between conventional and biopsy preparations in humans (R2 = 0.98; P < 0.05). The biopsy method overestimated diffusional uptake rates in sheep and humans by two to three fold when compared to conventional everted sleeve preparations. We conclude that this method is valuable to measure Na+-dependent solute uptake rates in biopsy samples from human intestine.

Animals↗
PubMed2000

Cyclooxygenase-1 and -2-dependent prostacyclin formation in patients with atherosclerosis.

BACKGROUND: The formation of prostacyclin (PGI(2)), thromboxane (TX) A(2), and isoprostanes is markedly enhanced in atherosclerosis. We examined the relative contribution of cyclooxygenase (COX)-1 and -2 to the generation of these eicosanoids in patients with atherosclerosis. METHODS AND RESULTS: The study population consisted of 42 patients with atherosclerosis who were undergoing surgical revascularization. COX-2 mRNA was detected in areas of atherosclerosis but not in normal blood vessel walls, and there was evidence of COX-1 induction. The use of immunohistochemical studies localized the COX-2 to proliferating vascular smooth muscle cells and macrophages. Twenty-four patients who did not previously receive aspirin were randomized to receive either no treatment or nimesulide at 24 hours before surgery and then for 3 days. Eighteen patients who were receiving aspirin were continued on a protocol of either aspirin alone or a combination of aspirin and nimesulide. Urinary levels of 11-dehydro-TXB(2) and 2,3-dinor-6-keto-PGF(1alpha), metabolites of TXA(2) and PGI(2), respectively, were elevated in patients with atherosclerosis compared with normal subjects (3211+/-533 versus 679+/-63 pg/mg creatinine, P<0.001; 594+/-156 versus 130+/-22 pg/mg creatinine, P<0.05, respectively), as was the level of the isoprostane 8-iso-PGF(2alpha). Nimesulide reduced 2, 3-dinor-6-keto-PGF(1alpha) excretion by 46+/-5% (378.3+/-103 to 167+/-37 pg/mg creatinine, P<0.01) preoperatively and blunted the increase after surgery. Nimesulide had no significant effect on 11-dehydro-TXB(2) before (2678+/-694 to 2110+/-282 pg/mg creatinine) or after surgery. The levels of both products were lower in patients who were taking aspirin, and no further reduction was seen with the addition of nimesulide. None of the treatments influenced urinary 8-iso-PGF(2alpha) excretion. CONCLUSIONS: Both COX-1 and -2 are expressed and contribute to the increase in PGI(2) in patients with atherosclerosis, whereas TXA(2) is generated by COX-1.

6-Ketoprostaglandin F1 alpha↗
PubMed2000

Health profile preferences of hepatitis C patients.

The side effects of interferon-alpha for chronic hepatitis C are well-known. Patients may differ with respect to their tolerance of these side effects and also with respect to their individual preferences. We administered a brief questionnaire to 67 outpatients with hepatitis C virus infection. Patients were asked to make hypothetical choices between six-month profiles of health. The results were as follows: (1) patients preferred to expedite rather than postpone intervals of poor health; (2) preferences of patients with low quality-of-life were quite similar to preferences of healthier patients; (3) patients' choices satisfied transitivity; (4) patients' choices satisfied preferential independence; and (5) patients gave a variety of reasons for their choices. These results corroborate other investigations of health preferences, and serve to introduce the field of preference elicitation to gastroenterologists.

Antiviral Agents↗
PubMed2000

Appropriate timing of the 14C-urea breath test to establish eradication of Helicobacter pylori infection.

OBJECTIVE: The aim of this study was to determine the performance characteristics of the 14C-urea breath test (UBT) performed 2 wk after the completion of therapy for Helicobacter pylori using a 4 to 6 wk study as the gold standard. METHODS: Patients with active Helicobacter pylori infection at four medical centers received proton pump inhibitor-based triple or quadruple therapy for 10-14 days. Patients underwent the 14C-UBT 2 and 4-6 wk after the completion of therapy. A positive test was defined as 14CO2 excretion of >200 dpm, a negative test as <50 dpm, and an equivocal test as >50 but <200 dpm. Performance characteristics of the 2-wk UBT were calculated using the 4 to 6-wk result as a gold standard. RESULTS: Eighty-five patients were enrolled and 82 patients (mean +/- SD age, 62 +/- 15 yr; 15 women) completed the protocol. Four patients had equivocal UBT results and were excluded from the analysis. Of the 78 patients, 68 (87%) had a negative 4 to 6-wk UBT. The 2-week UBT yielded a sensitivity of 90% (95% confidence interval 72-100%), specificity of 99% (97-100%), and accuracy of 97% (93-100%). In patients with a persistently positive UBT, 14CO2 excretion at 2 wk was significantly lower than at 4-6 wk after therapy (p = 0.03). CONCLUSIONS: A UBT performed 2 wk after therapy yielded results comparable to 4 to 6 wk testing. Further studies to evaluate the optimal time of confirmatory testing in the age of more effective proton pump inhibitor-based triple therapies are warranted.

Breath Tests↗
PubMed2000

Activation of direct and indirect pathways of glycogen synthesis by hepatic overexpression of protein targeting to glycogen.

Glycogen-targeting subunits of protein phosphatase-1, such as protein targeting to glycogen (PTG), direct the phosphatase to the glycogen particle, where it stimulates glycogenesis. We have investigated the metabolic impact of overexpressing PTG in liver of normal rats. After administration of PTG cDNA in a recombinant adenovirus, animals were fasted or allowed to continue feeding for 24 hours. Liver glycogen was nearly completely depleted in fasted control animals, whereas glycogen levels in fasted or fed PTG-overexpressing animals were 70% higher than in fed controls. Nevertheless, transgenic animals regulated plasma glucose, triglycerides, FFAs, ketones, and insulin normally in the fasted and fed states. Fasted PTG-overexpressing animals receiving an oral bolus of [U-(13)C]glucose exhibited a large increase in hepatic glycogen content and a 70% increase in incorporation of [(13)C]glucose into glycogen. However, incorporation of labeled glucose accounted for only a small portion of the glycogen synthesized in PTG-overexpressing animals, consistent with our earlier finding that PTG promotes glycogen synthesis from gluconeogenic precursors. We conclude that hepatic PTG overexpression activates both direct and indirect pathways of glycogen synthesis. Because of its ability to enhance glucose storage without affecting other metabolic indicators, the glycogen-targeting subunit may prove valuable in controlling blood glucose levels in diabetes.

Adenoviridae↗
PubMed1998

Long-term results of triple-drug-based immunosuppression in nonneonatal pediatric heart transplant recipients.

BACKGROUND: Few reports document long-term results of pediatric cardiac transplantation in which triple therapy (cyclosporine, azathioprine, and corticosteroids) was the mainstay of immunosuppression. This report details a single center's pediatric transplant experience and analyzes the relative contributions of selected pre/posttransplant risk factors on long-term morbidity and mortality. METHODS: Retrospective data were collected for all non-neonatal pediatric transplant recipients including: presenting diagnosis, cardiac hemodynamics (particularly pulmonary vascular resistance index), donor ischemic time, occurrence of postoperative infections, episodes of allograft rejection, incidence of posttransplant lymphoproliferative disease or coronary artery disease (CAD), and overall survival. Analysis of single variables and a Cox-proportional hazards model were utilized to determine the impact of pre/posttransplant risk factors on long-term survival. RESULTS: From 1984 to 1995, 64 patients (mean age, 8.3 years), 46 of whom had cardiomyopathy and 18 who had inoperable complex congenital heart disease, underwent cardiac transplantation and received triple-drug immunosuppression. Orthotopic transplantation was performed unless the pulmonary vascular resistance index remained >6 um2 (despite use of pulmonary vasodilator). One patient required heterotopic transplantation. Average donor ischemic time was 217 min. An average of 1.2 rejection episodes/patient occurred (average follow-up period: 50 months). No patient developed posttransplant lymphoproliferative disease, but 22 patients (34%) developed CAD. Overall survival was 80%, 60%, and 57% at 1, 5, and 10 years, respectively. Of outcome variables analyzed, rejection frequency was significantly increased in patients who subsequently developed CAD, but the presence of CAD was not significantly correlated with mortality. CONCLUSION: Triple-drug-based immunosuppressive maintenance therapy in pediatric heart transplant recipients results in good long-term graft survival.

Adolescent↗
PubMed1998

An analysis of admission, discharge and bed occupancy of stroke patients aged 65 and over in English hospitals.

Stroke illness is a common problem in the UK. Factors such as incidence, age, and ethnicity have already been shown to affect admission patterns and discharge outcomes. Our analysis of an English Hospital Episode Statistics database shows that weekends and public holidays also influence the admission and discharge patterns of elderly stroke patients. We discuss the possible reasons for this.

Aged↗
PubMed1998

Left-sided atrioventricular nodal ablation using the transseptal approach: clinico-histopathologic correlation.

To our knowledge, prograde access to the left ventricle to perform a left-sided AV node (AVN) ablation has not been reported. We present the case of a patient with Noonan's syndrome and supravalve aortic stenosis who required aortic valve replacement with a mechanical valve. Due to chronic atrial fibrillation, a transvenous pacing system was implanted and transcatheter radiofrequency ablation of the AVN was performed. Attempts at right-sided AVN ablation were unsuccessful. Due to the presence of the mechanical aortic valve, a left-sided AVN ablation was performed successfully using the transseptal approach. The patient died suddenly 6 months after the procedure, and the histologic study of the heart is reported.

Adult↗
PubMed1997

Viral infection of the myocardium in endocardial fibroelastosis. Molecular evidence for the role of mumps virus as an etiologic agent.

BACKGROUND: Endocardial fibroelastosis, previously a common disease of children, often resulted in congestive heart failure and death. Virus-induced myocarditis was the suspected first step in the pathogenesis of the disease, with enteroviruses and mumps virus considered potential causes. Direct evidence for their involvement was limited, however, and during the past two decades, a significant decline in the incidence of endocardial fibroelastosis occurred. Recently, we demonstrated polymerase chain reaction to be a rapid and sensitive method for identification of the viral genome in the myocardium of patients with myocarditis and dilated cardiomyopathy. The purpose of this study was to analyze myocardial samples of patients with endocardial fibroelastosis for the viral genome. METHODS AND RESULTS: Myocardial samples from 29 patients with autopsy-proven endocardial fibroelastosis were analyzed for viral genome (enterovirus, adenovirus, mumps, cytomegalovirus, parvovirus, influenza, herpes simplex virus) by use of polymerase chain reaction or reverse transcriptase-polymerase chain reaction. In 90% of samples, the viral genome was amplified; > 70% of the samples were positive for mumps viral RNA, while 28% amplified adenovirus. In contrast, only 1 of 65 control samples amplified a virus (enterovirus). Two regions of mumps virus were amplified: the nucleocapsid gene and the polymerase-associated protein gene. Interestingly, only 3 of the 21 samples that were positive for mumps RNA were positive with both sets of primers, indicating that the persistence of mumps virus in the myocardium may be related to the selection of defective virus mutants. CONCLUSIONS: These data suggest an etiologic role for viral infection in endocardial fibroelastosis, supporting the hypothesis that endocardial fibroelastosis is a sequela of a viral myocarditis, in particular of that due to mumps virus.

Child↗
PubMed1997

The value of immediate cytologic evaluation for needle aspiration lung biopsy.

RATIONALE AND OBJECTIVES: The authors evaluate the role of immediate cytologic evaluation (ICE) with fine-needle aspiration biopsy (FNAB) for lung lesions at highest risk for pneumothorax. METHODS: A prospective randomized study was conducted of 80 patients with lung lesions surrounded by aerated parenchyma undergoing FNAB with and without ICE (47 and 33 patients, respectively). An analysis of needle passes, procedure time, complications, specimen adequacy, diagnostic yield, and accuracy of procedure was made. RESULTS: There was an increased number of needle passes with ICE (> or = three passes: 23% [11 biopsies] versus 3% [1 biopsy]; P = 0.01). Fluoroscopic procedures took longer with ICE (median time: 15 versus 9 minutes; P = 0.002) with no difference in complication rates. Specimen adequacy was similar (74% and 64%) and the procedure was diagnostic in 79% (37 biopsies) with ICE and in 70% (33 biopsies) without ICE. There were no significant differences in the sensitivity, specificity, or accuracy of the biopsy. CONCLUSIONS: Immediate cytologic evaluation improved results marginally with increased procedure time and needle passes. Immediate cytologic evaluation may be most useful for lesions at lowest risk of complications to assure that a second procedure is not required.

Biopsy, Needle↗
PubMed1996

Diagnosis, surveillance, and epidemiologic evaluation of viral infections in pediatric cardiac transplant recipients with the use of the polymerase chain reaction.

BACKGROUND: Viral infections, particularly those caused by cytomegalovirus, are a major cause of postoperative morbidity and mortality in heart transplant recipients. These infections have classically been diagnosed by history, physical examination, peripheral viral cultures, and serologic studies. These methods are often time-consuming and lack sensitivity. Positive viral cultures from the heart are rarely obtained, and viral myocarditis and acute cellular rejection are unable to be differentiated histologically. We have therefore used the polymerse chain reaction to diagnose possible viral infection in pediatric heart transplant recipients with findings consistent with acute unexplained rejection. METHODS: Polymerase chain reaction was used as an aid to diagnose cytomegalovirus infection of cardiac tissue obtained by right ventricular endomyocardial biopsy and follow its long-term course. In addition, polymerase chain reaction was used to diagnose infection of the heart by other viruses in patients with clinical and histologic evidence of rejection, especially those with unexplained late rejection or chronic rejection. Polymerase chain reaction primers were designed to amplify nucleic acid sequences from cytomegalovirus, parvovirus, adenovirus, herpes simplex virus, Epstein-Barr virus, and the RNA viruses of the Enterovirus family. RESULTS: Forty patients underwent serial right ventricular endomyocardial biopsy (129 samples) for rejection surveillance with positive results obtained in 41 samples (32%) from 21 patients. Viral genome amplified included cytomegalovirus in 16 samples, adenovirus in 14, enterovirus in 6, parvovirus in 3, and herpes simplex virus in 2. In 13 of the 21 patients positive for viral genome (62%), endomyocardial biopsy histologic scores were consistent with multifocal moderate to severe rejection (Internal Society for Heart and Lung Transplantation scores of 3A or greater). CONCLUSIONS: Polymerase chain reactions may be used as a rapid and sensitive method to evaluate postoperative viral infections in heart transplant recipients, especially in those with late-onset rejection or chronic rejection. Polymerase chain reaction may also be useful in the serial analysis of cytomegalovirus status in transplant recipients. The use of multiple viral primers improves the diagnostic evaluation of these patients and may lead to a better understanding of the epidemiologic characteristics of posttransplantation viral infections and the cause of late or chronic rejection.

Adenoviruses, Human↗
PubMed1994

Acute myocarditis. Rapid diagnosis by PCR in children.

BACKGROUND: The diagnosis of viral myocarditis remains difficult and generally depends on clinical and histological criteria. Viral cultures and serology are often unrewarding, with low yields. The purpose of this study was to analyze the usefulness of polymerase chain reaction (PCR) in the rapid diagnosis of acute myocarditis in children. METHODS AND RESULTS: PCR was used to analyze 38 myocardial tissue samples from 34 patients with suspected acute viral myocarditis and 17 control patients with congenital heart disease (14) or hypertrophic cardiomyopathy (3). Myocardial samples were obtained at the time of right ventricular biopsy (13 samples), from explanted hearts (18 samples) at transplantation, and from cardiac autopsy specimens (24 samples) and were evaluated for the presence of enterovirus, cytomegalovirus (CMV), adenovirus, and herpes simplex virus (HSV) using PCR primers designed to consensus and unique sequences of these viral genomes. Blood also was obtained at the time of biopsy (11) or transplant (18). In 26 of 38 myocardial samples (68%), viral genome was detected by PCR (15 adenoviral, 8 enteroviral, 2 HSV, 1 CMV), whereas all control myocardial samples and blood samples were negative. Four patients had positive viral cultures, and these matched the PCR findings. Disagreement with histopathology occurred in 13 of 26 PCR-positive specimens, usually associated with adenovirus. CONCLUSIONS: PCR offers a rapid, sensitive diagnostic method for myocardial viral infection. While enterovirus is an important etiological agent, adenovirus was more prevalent in this series and should be evaluated when etiology is sought. PCR used in conjunction with standard endomyocardial biopsy appears to enhance the likelihood of detecting viral genome in the myocardium of patients with clinical evidence of myocarditis.

Acute Disease↗
PubMed1993

Craniopharyngioma and the moustache sign.

Craniopharyngiomas are common suprasellar tumours but these are rarely associated with vasogenic oedema. Because the oedema extends into the optic tracts and optic radiations, a characteristic pattern is produced that resembles a moustache. The oedema is though to be due to leakage of craniopharyngioma contents. Such a case is presented in this communication.

Adult↗
PubMed1991

A case of fibrolamellar hepatocellular carcinoma.

Fibrolamellar hepatocellular carcinoma is an uncommon histologic subtype of hepatocellular carcinoma, comprising 3.5% of all hepatocellular carcinomas in one large study (Brandt et al 1988). It usually occurs in young people, the average age being 18 years (Farhi et al 1983). It is not associated with cirrhosis and the serum alphafetoprotein is usually normal (Craig et al 1980). Fibrolamellar hepatocellular carcinoma has a more favourable prognosis than the usual hepatocellular carcinoma, with an average survival of 32 months from onset of symptoms, compared to 6 months for the usual type. The resectability rate and 5 year survival figures are also much better (Craig et al 1980). Hence distinguishing this histological subtype is important for surgical management and survival prognosis. This report describes a full radiological evaluation of such a case, covering the wide spectrum of relevant imaging modalities.

Adolescent↗