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Biomedical subjects

John Murphy

Publications and source records attributed to John Murphy.

18 recordsLinked to original sources
PubMed2006

Fatty acid ethyl esters cause pancreatic calcium toxicity via inositol trisphosphate receptors and loss of ATP synthesis.

BACKGROUND & AIMS: Fatty acid ethyl esters are ethanol metabolites inducing sustained, toxic elevations of the acinar cytosolic free calcium ion concentration ([Ca(2+)](C)) implicated in pancreatitis. We sought to define the mechanisms of this elevation. METHODS: Isolated mouse pancreatic acinar cells were loaded with fluorescent dyes for confocal microscopy to measure [Ca(2+)](C) (Fluo 4, Fura Red), endoplasmic reticulum calcium ion concentration ([Ca(2+)](ER), Mg Fluo 4), mitochondrial membrane potential (TMRM), ADP:ATP ratio (Mg Green), and NADH autofluorescence in response to palmitoleic acid ethyl ester and palmitoleic acid (10-100 micromol/L). Whole-cell patch clamp was used to measure the calcium-activated chloride current and apply ethanol metabolites and/or ATP intracellularly. RESULTS: Intracellular delivery of ester induced oscillatory increases of [Ca(2+)](C) and calcium-activated currents, inhibited acutely by caffeine (20 mmol/L), but not atropine, indicating involvement of inositol trisphosphate receptor channels. The stronger effect of extracellular ester or acid caused depletion of [Ca(2+)](ER), not prevented by caffeine, but associated with depleted ATP, depleted NADH autofluorescence, and depolarized mitochondria, suggesting calcium-ATPase pump failure because of lack of ATP. Intracellular ATP abolished the sustained rise in [Ca(2+)](C), although oscillatory signals persisted that were prevented by caffeine. Inhibition of ester hydrolysis markedly reduced its calcium-releasing effect and consequent toxicity. CONCLUSIONS: Fatty acid ethyl ester increases [Ca(2+)](C) through inositol trisphosphate receptors and, following hydrolysis, through calcium-ATPase pump failure from impaired mitochondrial ATP production. Lowering cellular fatty acid substrate concentrations may reduce cell injury in pancreatitis.

Adenosine Triphosphate↗
PubMed2006

Screening, assessment, and management of depression in VA primary care clinics. The Behavioral Health Laboratory.

OBJECTIVES: The purpose of this project was to assess the utility and feasibility of a telephone-based systematic clinical assessment service, the Behavioral Health Laboratory (BHL), in the context of primary care. The BHL is a clinical service that provides primary care providers with an assessment and a summary of mental health and substance abuse (MH/SA) symptoms and provides treatment decision support, including triage to specialty MH/SA services. The BHL was implemented to assist in the evaluation of patients who screened positively for depression at an annual clinical appointment or who were identified through routine care. METHODS: Results from systematic screening of primary care patients were extracted during a period of 6 months prior to implementation of the BHL and after implementation of the BHL. Descriptive results of the 580 evaluations conducted during this time were available. RESULTS: Results suggest an association between the implementation of the BHL and an increase in the proportion of patients screened for depression in primary care. In addition, there was an increase in the proportion of patients who screened positively (2.8% vs 7.0%). The BHL was successful in providing a comprehensive assessment for 78% of those referred. Significant co-occurring mental illness and substance misuse were found among those assessed. CONCLUSIONS: Introducing the BHL into primary care was associated with an apparent change in clinical practice in primary care at the Philadelphia VA Medical Center. Not only were more patients identified, the broad-based approach of the BHL identified significant comorbidity with alcohol misuse, illicit drugs, and suicidal ideation, symptoms likely to have been missed in routine clinical practice. The BHL offers a practical, low-cost method of assessment, monitoring, and treatment planning for patients identified in primary care with MH/SA needs.

Ambulatory Care Facilities↗
PubMed2005

Pseudomonas aeruginosa endophthalmitis in a preterm infant.

Bacterial endophthalmitis is rare in the neonatal period. It occurs in susceptible individuals such as preterm infants. Pseudomonas aeruginosa, a Gram-negative bacillus, has been identified as the causative organism in more than 75% of invasive neonatal eye infections. The source may be endogenous; secondary to septicemia or exogenous, including reports of nosocomial infections and those infections arising from the birth canal. We report the case of a preterm infant who developed pseudomonas endophthalmitis, septicemia, and meningitis after a corneal abrasion.

Cataract↗
PubMed2004

The effect of ethylene exposure on ethylene oxide in blood and on hepatic cytochrome p450 in Fischer rats.

Ethylene (74-85-1) is an important petrochemical and is produced endogenously. It is metabolized to ethylene oxide (EO) by cytochrome P450. We studied the inhibition of cytochrome P450 activity during exposure to ethylene, and verified that this inhibition was reflected in the concentration of EO in the blood. Male F344 rats were exposed to 1000, 600, and 300 ppm ethylene by nose-only inhalation for up to 6 h. Blood samples were obtained during exposure. On exposure to 600 ppm ethylene, blood EO concentration increased during the first hour of exposure and then decreased to approximately half of the peak blood concentration. A less pronounced decrease was observed at 300 ppm, and at 1000 ppm little change was observed between 10 min and 6 h of exposure. For the analysis of cytochrome P450 and isozyme-specific substrate activities, groups of four male F344 rats were removed for the collection of liver at various times after exposure to 300, 600, or 1000 ppm ethylene. At all concentrations, liver microsomal cytochrome P450 decreased during exposure. Of the various monooxygenase activities measured, 4-nitrophenol hydroxylase was the one most consistently altered, with maximal inhibition (approximately 50%) at 2 h of exposure to 1000 ppm ethylene, 4 h at 600 ppm, and 6 h at 300 ppm. Activity recovered to control levels by 6 h after exposure. Cytochrome P450 2E1 appears to be the major isoform of cytochrome P450 inhibited by exposure to ethylene, and this may explain in part the observed alteration in EO blood kinetics.

Animals↗
PubMed2004

(123I) beta-CIT and single-photon emission computed tomographic imaging vs clinical evaluation in Parkinsonian syndrome: unmasking an early diagnosis.

BACKGROUND: The diagnosis of Parkinson disease is currently based on clinical evaluation. Functional neuroimaging using (123I) beta-carboxymethyoxy-3-beta-(4-iodophenyl) tropane (CIT) and single-photon emission computed tomography (SPECT) provides information on the integrity of the dopaminergic system in vivo and is a promising diagnostic tool in early Parkinson disease. OBJECTIVE: To evaluate the diagnostic accuracy of dopamine transporter imaging using (123I)beta-CIT in patients with suspected parkinsonian syndrome (PS). DESIGN: Community neurologists referred patients with suspected PS for imaging evaluation. Clinical diagnoses (positive PS or negative PS) were provided by the community neurologists and 2 movement disorder experts. We performed (123I)beta-CIT and SPECT imaging, and imaging diagnoses of positive PS or negative PS were assigned. A 6-month follow-up clinical diagnosis was assigned by a movement disorder expert blind to the imaging data, which represented the "gold standard" diagnosis for the study. RESULTS: Thirty-five patients with suspected PS were referred. Diagnoses in question included essential tremor, psychogenic parkinsonism, drug-induced parkinsonism, primary dystonia, and unspecified gait disorder. Comparing the community neurologist's diagnoses at referral with the gold standard diagnosis, there was dis agreement in 25.7% (sensitivity, 0.92; specificity, 0.30). Comparing the quantitative imaging diagnoses with the gold standard, there was disagreement in 8.6% (sensitivity, 0.92; specificity, 1.00). CONCLUSION: Performing (123I)beta-CIT and SPECT imaging at baseline appears to be a useful diagnostic tool to detect patients thought to have PS at baseline but who, after follow-up, do not have PS.

Aged↗
PubMed2004

Designing an illustrated patient satisfaction instrument for low-literacy populations.

Up to 25% of adults in the United States have difficulty with everyday reading tasks. As patients, adults with low literacy may not be able to complete many self-administered written questionnaires, which often are used to obtain information from patients and to gauge their satisfaction with care. We developed an illustrated version of a patient satisfaction instrument used by the Veterans Health Administration. This paper describes the extensive design process used to develop, pilot-test, and revise this 63-item illustrated instrument. A total of 438 patients were interviewed over a 1-year period to obtain feedback on illustrations, with at least 15 people viewing and commenting on each picture and revision. All pictures were revised, with the majority revised at least 4 times. We report on this iterative design process as well as on lessons we learned in illustrating questions for low-literacy populations.

Adult↗
PubMed2003

Combination of scoring functions improves discrimination in protein-protein docking.

Two structure-based potentials are used for both filtering (i.e., selecting a subset of conformations generated by rigid-body docking), and rescoring and ranking the selected conformations. ACP (atomic contact potential) is an atom-level extension of the Miyazawa-Jernigan potential parameterized on protein structures, whereas RPScore (residue pair potential score) is a residue-level potential, based on interactions in protein-protein complexes. These potentials are combined with other energy terms and applied to 13 sets of protein decoys, as well as to the results of docking 10 pairs of unbound proteins. For both potentials, the ability to discriminate between near-native and non-native docked structures is substantially improved by refining the structures and by adding a van der Waals energy term. It is observed that ACP and RPScore complement each other in a number of ways (e.g., although RPScore yields more hits than ACP, mainly as a result of its better performance for charged complexes, ACP usually ranks the near-native complexes better). As a general solution to the protein-docking problem, we have found that the best discrimination strategies combine either an RPScore filter with an ACP-based scoring function, or an ACP-based filter with an RPScore-based scoring function. Thus, ACP and RPScore capture complementary structural information, and combining them in a multistage postprocessing protocol provides substantially better discrimination than the use of the same potential for both filtering and ranking the docked conformations.

Algorithms↗
PubMed2003

Admission cardiotocography: a randomised controlled trial.

BACKGROUND: Admission cardiotocography is widely used to identify pregnancies that might benefit from continuous electronic fetal monitoring in labour. We aimed to compare the effect on neonatal outcome of admission cardiotocography versus intermittent auscultation of the fetal heart rate. METHODS: 8580 women admitted to the delivery ward of a Dublin teaching hospital who were at low risk of fetal distress in labour were randomly assigned admission cardiotocography (20 min) or the unit's usual care (intermittent auscultation only, with continuous cardiotocography only if clinically indicated). The primary outcome was moderate to severe neonatal morbidity, or perinatal mortality in the absence of a major congenital malformation. Analyses were by intention to treat. FINDINGS: 44 (1.0%) women assigned admission cardiotocography did not undergo the procedure; 15 (0.4%) assigned usual care had admission cardiotocography. The primary endpoint occurred in 56 (1.3%) of 4298 women assigned admission cardiotocography and 55 (1.3%) of 4282 in the usual-care group (relative risk 1.01; 95% CI 0.70-1.47). Other indices of neonatal morbidity also showed no differences. Despite an increase in use of continuous cardiotocography (1.39; 1.33-1.45) and fetal blood sampling (1.30; 1.14-1.47) with admission cardiotocography, there were no significant differences in the rates of caesarean delivery (1.13; 0.92-1.40), instrumental delivery (1.03; 0.92-1.16), or episiotomy (1.06; 0.99-1.13). INTERPRETATION: Routine use of cardiotocography for 20 min on admission to the delivery ward does not improve neonatal outcome. No significant increase in operative delivery was apparent, probably because of liberal use of fetal blood sampling.

Apgar Score↗
PubMed2003

Meconium passed in labor: how reassuring is clear amniotic fluid?

OBJECTIVE: Clear amniotic fluid is frequently considered a reassuring sign during labor. Our aim was to examine the incidence of meconium that can only have been passed intrapartum and to determine its neonatal associations and whether its absence is a useful sign. METHODS: This was a prospective cohort study of 8394 "low risk" laboring women at term with clear amniotic fluid at early amniotomy. RESULTS: Meconium was passed in 5.2% of labors but was not detected until delivery of the fetal head in 51.5% of these. It was associated with moderate-severe acidosis (odds ratio [OR] 4.40; 95% confidence interval [CI] 3.21, 6.03), low Apgar score at 5 minutes (OR 6.49; 95% CI 2.73, 15.44), and neonatal seizures (OR 4.33; 95% CI 3.17, 5.93). However, the sensitivity for these outcomes of the intrapartum passage of meconium and, particularly, its detection before delivery was very poor. CONCLUSION: Although correlated with adverse neonatal outcomes, most affected infants had clear amniotic fluid throughout labor. The presence of clear amniotic fluid is an unreliable sign of fetal well-being.

Adult↗
PubMed2003

Identification of phase separation in solid dispersions of itraconazole and Eudragit E100 using microthermal analysis.

PURPOSE: To evaluate the phase separation in itraconazole/Eudragit E100 solid dispersions prepared by hot-stage extrusion. METHODS: Extrudates were prepared using a corotating twin-screw extruder at 180 degrees C. Micro-TA was used to evaluate the phase separation, where the AFM mode is used to visualize the different phases and local thermal analysis (LTA) to characterize the different phases RESULTS: Itraconazole formed a homogeneous mixture with Eudragit E100 with drug concentrations up to approximately 20%. Above this concentration, phase separation was observed. MTDSC revealed two Tgs and the mesophase of free glassy itraconazole. Performing micro-TA on the surface of these dispersions indicated an increase in sample roughness in the z-axis piezo signal, which could be an indication of free glassy itraconazole. However, thermal conductivity did not reveal differences between separate phases. Performing LTA, where only a small area (20 x 20 microm) is heated, showed two separate and mixed phases of itraconazole and Eudragit E100. Tip penetration in itraconazole and Eudragit E100 occurred at 332K and 383K respectively. The difference in tip penetration was explained in terms of the difference in fragility. CONCLUSION: Micro-TA makes it possible to characterize separate phases of itraconazole and Eudragit E100, thereby confirming the MTDSC results on phase separation.

Differential Thermal Analysis↗
PubMed2003

Conjugated linoleic acid (CLA)-enriched milk fat inhibits growth and modulates CLA-responsive biomarkers in MCF-7 and SW480 human cancer cell lines.

Milk enriched in conjugated linoleic acid (CLA) was obtained from cows on pasture supplemented with full-fat rapeseeds (FFR; 2.26 g cis 9, trans 11 (c9,t11)-CLA/100 g fatty acid methyl esters) and full-fat soyabeans (1.83 g c9,t11-CLA100 g fatty acid methyl esters). A control milk fat (1.69 g c9,t11-CLA/100 g fatty acid methyl esters) was obtained from cows fed on pasture only. The present study assessed the potency of the CLA-enriched milk fats to modulate biomarkers that had previously been observed to respond to c9,t11-CLA in the MCF-7 and SW480 cell lines. Cell numbers decreased (P<0.05) by up to 61 and 58% following the incubation of MCF-7 and SW480 cells, respectively, for 4 d with milk fats (yielding CLA concentrations between 60.2 and 80.6 microM). The FFR milk fat, containing the highest CLA content, increased (P<0.05) [14C]arachidonic acid (AA) uptake into the monoacylglycerol fraction of MCF-7 and SW480 cells while it decreased (P<0.05) uptake into the phospholipid fraction of the latter. This milk fat also decreased (P<0.05) [14C]AA conversion to prostaglandin (PG) E2 while increasing conversion to PGF2alpha in both cell lines. All milk-fat samples increased (P<0.05) lipid peroxidation as measured by 8-epi-PGF2alpha in both cell lines. In SW480 cells the milk-fat samples decreased (P<0.05) bcl-2 and cytosolic glutathione levels while increasing (P<0.05) membrane-associated annexin V levels. All milk-fat samples decreased (P<0.05) the expression of ras in SW480 cells. These data suggest that milk-fat CLA was effective at modulating synthetic CLA-responsive biomarkers.

Animals↗
PubMed2003

Measles outbreak in Dublin, 2000.

BACKGROUND: An outbreak of measles occurred in Ireland between December 1999 and July 2000. The majority of cases were in north Dublin, the catchment area of The Children's University Hospital (TCUH). METHODS: Details of all of the 111 children attending the hospital with a diagnosis of measles between December 1999 and July 2000 were prospectively entered into a database. Charts were subsequently reviewed to extract epidemiologic and clinical details. National figures were obtained from the National Disease Surveillance Centre. RESULTS: In the study period 355 attended TCUH with a serologic or clinical diagnosis of measles, and 111 were admitted (47% female, 53% male). The main indications for admission were dehydration in 79%, pneumonia or pneumonitis in 47% and tracheitis in 32%. Thirteen children (11.7% of those admitted) required treatment in the intensive care unit, and in 7 of these mechanical ventilation was necessary. There were 3 deaths as a result of measles. Public health measures to curb spread of the disease included promotion of immunization for susceptible children nationally and recommending administration of measles-mumps-rubella vaccine (MMR) from the age of 6 months, in North Dublin. CONCLUSION: This outbreak of measles posed a major challenge to the hospital and the community for the first half of 2000. The national MMR immunization rate before the outbreak was gravely suboptimal at 79%, whereas the rate in North Dublin, the catchment area of TCUH, was <70%. Three children died as a result of a vaccine-preventable illness.

Age Distribution↗
PubMed2003

Geriatric medicine training for family practice residents in the 21st century: a report from the Residency Assistance Program/Harfford Geriatrics Initiative.

Increasing the quality and quantity of geriatric medicine training for family practice residents is a particular challenge for community-based programs. With support from the John A. Hartford Foundation of New York City, the American Academy of Family Physicians (AAFP) implemented in 1995 a multi-part project to improve the amount and quality of geriatric medicine education received by family practice residents. This report summarizes the initial results of the regional geriatric medicine curriculum retreats for residency directors. The goals of the retreats were to build recognition among the residency directors of the skills that future family physicians will require to be successful providers of primary care to older adults and to allow the residency directors to identify and develop solutions to barriers to improving geriatric medicine training for residents. Forty-six program directors participated in the three retreats between February 2000 and February 2001. The participants represented 52 programs and rural tracks in all geographic regions, small and large programs, and urban and rural settings. The program directors developed a consensus on the geriatric medicine knowledge, skills, and attitudes that should be expected of all family practice residency graduates; developed a list of basic, required educational resources for each family practice residency program; and proposed solutions to common obstacles to successful curriculum development.

Attitude of Health Personnel↗
PubMed2002

Neonatal brachial plexus palsy: an unpredictable injury.

OBJECTIVE: Brachial plexus paralysis is a serious form of neonatal morbidity. We determined its incidence and persistence of disability and evaluated whether its occurrence could be predicted by maternal characteristics or partographic analysis in a large cohort of recent cases. STUDY DESIGN: During the years 1994 through 1998, all infants with neonatal evidence of obstetric brachial plexus injury were identified and followed 14;>or=1 year. Obstetric details in these maternal-infant pairs were compared with 108 control pairs, matched for maternal and gestational age, parity, and birth weight. Partographs of cases and control subjects were reviewed, in a blinded manner, by 3 obstetricians who were asked to identify likely cases of nerve injury. A risk score comprising eight recognized associated clinical features was assigned. RESULTS: Fifty-four of 35,796 infants (1.5/1000) had evidence of brachial plexus injury; in 10 cases (19%), neurologic deficit persisted to 1 year. Although the risk factor profile was relatively higher in cases compared with control subjects, the highest score was 5 of 8 in six cases (2 cases, 4 control subjects). Obstetricians' partographic assessment identified "likely brachial plexus injury" in 13 of 54 cases (24%) and 16 of 108 control subjects (15%), and in only 3 cases (6%) did the assessors concur (positive predictive value, 7%-17%; negative predictive value, 5%-12%; sensitivity, 24%-50%; specificity, 66%-68%). Risk scores were similar among persistently and transiently injured cases. CONCLUSION: Our results indicate that brachial plexus injury is not predictable before delivery, either by risk factor scoring or by partographic analysis.

Birth Injuries↗
PubMedDate not supplied

Dropped gallstones post laparoscopic cholecystectomy mimicking peritoneal seeding: CT and ultrasound features.

PURPOSE: The purpose of this work was to investigate the ultrasound (US) and CT features of dropped gallstones mimicking peritoneal seeding in patients after laparoscopic cholecystectomy (LCC). METHOD: We describe the US and CT features of dropped gallstones mimicking peritoneal seeding in eight patients who underwent LCC. We also conducted a retrospective study of consecutive LCC patients who subsequently had CT to determine the prevalence of this condition. RESULTS AND CONCLUSION: The density of dropped gallstones on CT ranged from hypodense to partially or completely calcified nodules. Some stones did not have visible surrounding reaction, whereas others showed an enhancing halo. All stones were echogenic and demonstrated shadowing on US. The stones were located mostly on the right side of the abdomen, and the majority were around the liver. The prevalence of dropped gallstones post laparoscopic cholecystectomy was 4.2%.

Adult↗