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Biomedical subjects

J Brennan

Publications and source records attributed to J Brennan.

At least 37 records · Page 2Linked to original sources
PubMed2001

Medullomyoblastoma: case report.

This 7-year-old boy presented with a 2-week history of headache, nausea, vomiting, anorexia, lethargy, and unsteadiness of gait. Brain magnetic resonance imaging (MRI) revealed a cystic mass within the vermis of the cerebellum. A suboccipital craniectomy was performed to remove a tumor that contained primitive neuroectodermal cells with florid skeletal muscle differentiation. Immunohistochemical studies and electron microscopy confirmed the presence of both a primitive neuroectodermal component and rhabdomyoblastic differentiation, consistent with the diagnosis of medullomyoblastoma. This exceedingly rare tumor of the cerebellar vermis of children is characterized by two components: primitive neuroectodermal tumor cells and skeletal muscle. Although the histogenesis remains uncertain, advances in immunohistochemistry and electron microscopy suggest the origin of this tumor from a multipotential stem cell precursor.

Child↗
PubMed2001

Changes and tracking of physical activity across seven years in Mexican-American and European-American mothers.

Longitudinal changes in physical activity among 129 Mexican-American (mean age 30.8; SD = 5.6) and 97 European-American (mean age 31.2; SD = 5.4) women were studied. Two physical activity recall interviews were administered at baseline and 7 years later. At baseline, European-American women reported more vigorous leisure activity (p < .005) than Mexican-Americans, and Mexican-Americans reported more moderate work activity (p < .02) than European-Americans. Virtually all components of physical activity increased significantly over the 7 years. Pearson tracking correlations for total energy expenditure were about r = 0.30. The finding that both groups increased physical activity overtime was unexpected and was unrelated to a reduction in the number of preschool children in the homes over time.

Adult↗
PubMed2000

An LDL-receptor-related protein mediates Wnt signalling in mice.

Wnt genes comprise a large family of secreted polypeptides that are expressed in spatially and tissue-restricted patterns during vertebrate embryonic development. Mutational analysis in mice has shown the importance of Wnts in controlling diverse developmental processes such as patterning of the body axis, central nervous system and limbs, and the regulation of inductive events during organogenesis. Although many components of the Wnt signalling pathway have been identified, little is known about how Wnts and their cognate Frizzled receptors signal to downstream effector molecules. Here we present evidence that a new member of the low-density lipoprotein (LDL)-receptor-related protein family, LRP6 (ref. 3), is critical for Wnt signalling in mice. Embryos homozygous for an insertion mutation in the LRP6 gene exhibit developmental defects that are a striking composite of those caused by mutations in individual Wnt genes. Furthermore, we show a genetic enhancement of a Wnt mutant phenotype in mice lacking one functional copy of LRP6. Together, our results support a broad role for LRP6 in the transduction of several Wnt signals in mammals.

Animals↗
PubMed2000

Reperfusion injury of cardiac myocytes: mechanisms, treatment, and implications for advanced practice nursing.

Reperfusion injury is a major complication associated with the restoration of blood flow to previously ischemic myocardium. The deleterious effects associated with reperfusion injury result from several complex pathologic mechanisms. The complexity of these mechanisms makes development of treatment protocols difficult. The purpose of this article is to review the pathophysiology of reperfusion injury and currently indicated therapies. Implications for advanced practice nursing and areas for further research are presented.

Critical Care↗
PubMed2000

Should pediatric emergency care be decentralized?: an out-of-hospital destination model for critically ill children.

OBJECTIVES: A time-to-initial-stabilization model for out-of-hospital destinations of critically ill children (CICs) was developed. Application of this model to assess the impact of changes in different parameters of an emergency medical services for children (EMSC) system is described. METHODS: A computer model created a 2,500-square-mile community containing ten community hospitals (CHs) and one pediatric critical care center (PCC). Community hospitals capable of providing initial immediate stabilization of CICs were defined as emergency departments accepting pediatrics (EDAPs). Critically ill children were randomly selected in proportion to population densities across the modeled community. Time to initial stabilization (TIS) was defined as the time to arrival at either an EDAP or a PCC or time to arrival at a non-EDAP CH + travel time for a team from the PCC to the non-EDAP CH + preparation/dispatch (P/D) time. The following parameters of the model were varied and their effect on TIS was evaluated: location of CHs, location of PCC, primary destinations for CICs, percent of CHs meeting EDAP standards, out-of-hospital compliance with designated hospitals for CICs, P/D time, and ambulance speed. RESULTS: The computer model selected 1,000 CICs in accordance with the population densities of the community. The scenario with the shortest TIS was one in which every CH achieved EDAP designation (9.8 +/- 0.5 minutes). The scenario with the longest TIS involved a model in which every CIC was transported directly to the PCC (28.6 +/- 0.33 minutes). The number of EDAPs in a community and out-of-hospital compliance with use of EDAPs produced comparable effects on the TIS. Travel speeds had a direct effect on TIS but also exaggerated inefficiencies between scenarios. The P/D time had little effect on the TIS. CONCLUSIONS: An out-of-hospital destination model has been developed with the ability to modify multiple EMSC system variables. Application of this model demonstrates the shortest times to stabilization of critically ill children occur in systems that maximize the number of hospitals that meet EDAP standards and decentralize pediatric emergency care.

Adolescent↗
PubMed2000

Two liquid medium systems, mycobacteria growth indicator tube and MB redox tube, for Mycobacterium tuberculosis isolation from sputum specimens.

Two manual liquid medium systems, the Mycobacteria Growth Indicator Tube (MGIT) and MB Redox tube systems, were evaluated in comparison to the radiometric BACTEC-460 semiautomated system for recovery of Mycobacterium tuberculosis from sputum specimens. The highest level of recovery, from a total of 77 culture-positive specimens, occurred with the BACTEC-460 system (92.2%), followed by the MB Redox tube (80.5%) and the MGIT (63.6%) systems. The shortest time to detection was observed also among the cultures in BACTEC-460: a mean of 12 days to a growth index (GI) of 10 and 15 days to a GI of 500. The mean times for the other systems were 16 days for the MB Redox tube system and 17.4 days for the MGIT system. The proportion of cultures grown after more than 3 weeks of incubation was only 2.8 or 8.4% in BACTEC-460 (for a GI of 10 or 500) but 17.7% in MB Redox and 22.5% in MGIT. Despite these differences in comparison to the BACTEC-460 system and some differences between the MGIT and MB Redox tube systems, either of the two manual liquid medium systems presents a reasonable alternative to the BACTEC-460 system, especially for laboratories with a limited workload, and a valuable element in the laboratory protocol, in conjunction with solid media, for obtaining rapid detection of growth from about 80% of culture-positive specimens and for better overall recovery of M. tuberculosis.

Automation↗
PubMed1999

The cannabinoid receptor agonist WIN 55,212-2 mesylate blocks the development of hyperalgesia produced by capsaicin in rats.

Although it is well known that cannabinoids produce antinociception in acute pain models, there is less information on the ability of cannabinoids to alleviate hyperalgesia. In the present study, we determined whether cannabinoids attenuated the development of hyperalgesia produced by intraplantar injection of capsaicin in rats. In normal, untreated animals, intraplantar injection of 10 microg capsaicin produces nocifensive behavior (elevation of the injected paw) suggestive of pain, an increase in the frequency of withdrawal from punctate mechanical stimuli applied to the paw (mechanical hyperalgesia) and a decrease in the latency of withdrawal from noxious heat (heat hyperalgesia). Separate groups of animals were pretreated intravenously with vehicle, the cannabinoid receptor agonist WIN 55,212-2 at doses of 1, 10, 100 or 200 microg/kg, or the enantiomer WIN 55,212-3 (100 microg/kg) 5 min before intraplantar injection of capsaicin into one paw. The duration of nocifensive behavior was measured during the first 5 min after capsaicin injection. Withdrawal responses to mechanical and heat stimuli applied to the plantar surface of both hindpaws were measured before and at 5 and 30 min after capsaicin. Pretreatment with WIN 55,212-2 produced a dose-dependent decrease in nocifensive behavior and in hyperalgesia to mechanical and heat stimuli produced by capsaicin, as compared with vehicle pretreatment. Doses of 100 and 200 microg/kg WIN 55,212-2 completely blocked the development of hyperalgesia to mechanical and heat stimuli without altering withdrawal responses on the contralateral control paw. Furthermore, these doses of WIN 55,212-2 had no effect on basal withdrawal responses to heat in animals that did not receive capsaicin. The inactive enantiomer WIN 55,212-3 did not alter the development of capsaicin-evoked pain or hyperalgesia. These data suggest that low doses of cannabinoids, which do not produce analgesia or impair motor function, attenuate chemogenic pain and possess antihyperalgesic properties.

Analgesics↗
PubMed1999

Efficient gene-specific expression of cre recombinase in the mouse embryo by targeted insertion of a novel IRES-Cre cassette into endogenous loci.

Site specific recombinases have provided the experimental strategy necessary to modulate the expression of gene products in the mouse embryo. In this study we have exploited Cre recombinase to develop a widely applicable cell marking system which functions efficiently even at early post-implantation embryonic stages. Importantly, the techniques and reagents derived in this study are generally applicable to any recombinase driven approach, including strategies to temporally and spatially modulate endogenous or ectopic gene expression in the embryo. The cell marking scheme has two essential components which were derived as separate mouse lines. The first line carries a universal conditional lacZ reporter (UCR) locus which was prepared by using gene targeting in a novel approach to modify a ubiquitously expressed retroviral lacZ promoter trap insertion. The UCR locus is silent until it undergoes a Cre mediated DNA rearrangement to restore lacZ expression. To generate the Cre expressing allele, we outline a flexible strategy which requires the introduction of a novel IRES-Cre cassette into exon sequence of an endogenous locus by gene targeting. We successfully demonstrate this approach by generating a Cre expressing allele of the EphA2 gene, an Eph receptor protein tyrosine kinase expressed early in development. Analysis of double heterozygote embryos clearly demonstrates that Cre recombinase is expressed in vivo from the EphA2 IRES-Cre allele, and that the conditional reporter locus is efficiently restored in EphA2-expressing cells as early as 7.5 dpc. This cell marking experiment establishes the feasibility of expressing Cre recombinase from a single copy allele in the embryo and demonstrates the utility of the conditional reporter mouse which can be used in the analysis of any Cre expressing allele.

Animals↗
PubMed1999

Use of contrast-enhanced ultrasound in follow-up after endovascular aortic aneurysm repair.

PURPOSE: To investigate the use of contrast-enhanced ultrasound in the detection of endoleak after endovascular repair of abdominal aortic aneurysm. MATERIALS AND METHODS: Eighteen patients underwent follow-up on 20 occasions after endovascular aortic aneurysm repair by arterial-phase contrast-enhanced spiral computed tomography (CT). All patients had unenhanced color Doppler ultrasound and Levovist-enhanced ultrasound on the same day. The ultrasound examinations were reported in a manner that was blind to the CT results. CT was regarded as the gold standard for the purposes of the study. RESULTS: There were three endoleaks shown by CT. Unenhanced ultrasound detected only one endoleak (sensitivity, 33%). Levovist-enhanced ultrasound detected all three endoleaks (sensitivity, 100%). Levovist-enhanced ultrasound indicated an additional six endoleaks that were not confirmed by CT (specificity, 67%; positive predictive value, 33%). In one of these six cases, the aneurysm increased in size, which indicates a likelihood of endoleak. Two of the remaining false-positive results occurred in patients known to have a distal implantation leak at completion angiography. CONCLUSION: In this small group of patients, contrast-enhanced ultrasound appears to be a reliable screening test for endoleak. The false-positive results with enhanced ultrasound may be due to the failure of CT to detect slow flow collateral pathways. Although the number of patients in this study is small, enhanced ultrasound may be more reliable than CT in detecting endoleak.

Aged↗
PubMed1999

Vascular surgical society of great britain and ireland: endovascular aneurysm repair: the need for randomized controlled trials

BACKGROUND: An audit of endovascular aneurysm repair (EVAR) was undertaken in order to assess the efficacy of this new approach in the treatment of abdominal aortic aneurysm. METHODS: An international register of EVAR was started in 1996, with emphasis on close follow-up. RESULTS: Data have now been accumulated for 895 cases. The 30-day mortality rate is low at 3 per cent; patients who died generally had major co-morbidity. At discharge 14 per cent were identified as having an endoleak (persistent blood flow outside the lumen of the endoluminal graft but within the aneurysm sac) and another 18 per cent developed new endoleaks during the first year of follow-up. Continued expansion of the aneurysm was observed in 22 per cent. This occurred in 53 per cent of patients with an identified endoleak compared with 11 per cent of those in whom no endoleak was demonstrated (P < 0.01). Aneurysm rupture after EVAR occurred in six patients, three of whom died. CONCLUSION: That EVAR is technically feasible is beyond doubt. Close follow-up has identified problems specific to the minimally invasive approach. The significance of endoleaks in particular remains unclear, but the strong association with continued aneurysm expansion is of concern. The primary purpose of EVAR, however, is to prolong life and in this study the cumulative 2-year survival rate (including operative deaths) was 85 per cent. In patients without any complications the benefits of the minimally invasive approach are readily apparent. Thus, while there is no place for unrealistic optimism, there certainly appears to be a role for EVAR. To prevent inappropriate widespread application of this new approach, or indeed unwarranted condemnation, randomized controlled trials comparing EVAR with conventional management are essential.

Journal Article↗
PubMed1999

Storage temperatures of out-of-hospital medications.

OBJECTIVES: To determine whether temperatures inside drug boxes used in the out-of-hospital setting are within the U.S. Pharmacopeia recommendations for "controlled room temperature," which is defined as a temperature maintained between 15 degrees C and 30 degrees C with a mean kinetic temperature less than 25 degrees C, and to determine whether time-temperature indicator labels can reliably monitor mean kinetic temperatures. METHODS: Two methods were used to monitor temperatures: miniature electronic temperature recorders and color-changing time-temperature indicator labels. These were placed in drug storage boxes of advanced life support units over three summer months and two winter months. RESULTS: In summer, the electronic recorders logged temperatures exceeding 30 degrees C in all drug storage boxes, ranging from 3% to 29% of the total time. The mean kinetic temperatures by location for the whole period ranged from 21 degrees C to 30 degrees C. In the winter, the electronic recorders logged temperatures exceeding 30 degrees C at one location 2% of the total time. There were significant temperature excursions below 15 degrees C at all locations, ranging from 16% to 90% of the total time. At one location, there were temperature readings below 0 degrees C for 9% of the total time. The mean kinetic temperatures obtained from the electronic recorders and the indicator labels differed by less than 1 degrees C. CONCLUSIONS: This study demonstrates that out-of-hospital medications are subject to temperatures both above and below recommended storage temperatures. Time-temperature indicator labels can reliably monitor exposure to elevated temperatures.

Cold Temperature↗
PubMed1999

Longitudinal aneurysm shrinkage following endovascular aortic aneurysm repair: a source of intermediate and late complications.

PURPOSE: To report the incidence of delayed complications following endovascular abdominal aortic aneurysm (AAA) repair and the relationship of these sequelae to morphological changes in the sac and endograft. METHODS: Twenty-six AAA patients treated with Vanguard endografts had completed > or = 1-year follow-up. Postoperative angiograms and spiral computed tomographic (CT) scans with 3-dimensional reconstruction were compared to the 1-year images to determine morphological changes in the aneurysm sac and the endograft. These changes were then related to complications occurring between 1 and 12 months postoperatively in the study group. RESULTS: Comparison of angiograms uncovered endograft buckling in 18 (69%) patients and acutely angled or kinked endografts in 10 (38%). Measurements from the CT scans found that undistorted endografts had a mean change in sac length of +6.6 mm. Mean sac length change in buckled endografts was -3.1 mm, while kinked endografts displayed a mean change of -6.2 mm (p < 0.002, Student's t-test). Five (19%) patients, all with distorted endografts, demonstrated late (1 to 12 months) complications (4 endoleaks and 1 graft limb thrombosis) owing to component separation, distal stent migration, and acute angulation. No movement in the proximal stent was observed. Elongation of the endograft (flow line measurement) was observed in one tube graft only. CONCLUSIONS: In this study, longitudinal shrinkage of the sac following endovascular aortic aneurysm repair led to buckling or kinking of the endograft within 1 year in 69% of patients. This appears to be an important source of delayed complications.

Aged↗
PubMed1999

Endotension after endovascular aneurysm repair: definition, classification, and strategies for surveillance and intervention.

In the ongoing evolution of a categorization system for endoleak, the authors propose the term endotension to define persistent or recurrent pressurization of the aortic aneurysm sac after endovascular repair. Endotension is evidence that the aneurysm remains at risk of rupture and should, therefore, be considered an indication for secondary intervention. Management strategies and a grading system for endotension are offered.

Aneurysm, Ruptured↗
PubMed1999

Fosinopril and hydrochlorothiazide combination versus individual components: lack of a pharmacokinetic interaction.

OBJECTIVE: To evaluate the pharmacokinetic interaction and bioequivalence of a combination formulation of the angiotensin-converting enzyme inhibitor fosinopril and the diuretic hydrochlorothiazide (HCTZ). METHODS: In an open-label, balanced, randomized incomplete block, three-way crossover fashion, healthy men received single doses of three of four regimens in one of two independent studies. Regimens for study A (36 subjects): (1) fosinopril 10-mg tablet, (2) HCTZ 12.5-mg tablet, (3) a combination tablet of fosinopril 10 mg plus HCTZ 12.5 mg, or (4) coadministered tablets of fosinopril 10 mg and HCTZ 12.5 mg. Study B (40 subjects) received: (1) fosinopril 20-mg tablet, (2) HCTZ 12.5-mg tablet, (3) a combination tablet of fosinopril 20 mg plus HCTZ 12.5 mg, or (4) coadministered tablets of fosinopril 20 mg and HCTZ 12.5 mg. RESULTS: There was no evidence of any significant effect of HCTZ on the pharmacokinetics of fosinoprilat, based on maximum concentration value, AUC, or cumulative urinary recovery over 24 hours. Fosinoprilat had no clinically important effect on the pharmacokinetics of HCTZ only slightly decreasing its AUC by 14% in study A. Coadministration was well tolerated; no new adverse events were reported with the combination tablet. CONCLUSIONS: Fosinopril and HCTZ in a combination tablet display pharmacokinetic profiles similar to those achieved when either drug is administered alone or when coadministered in separate tablets. When used with HCTZ, the favorable pharmacokinetic feature of fosinopril, dual and compensatory pathways of renal and hepatic elimination, is preserved.

Adolescent↗
PubMed1998

Sry and the testis: molecular pathways of organogenesis.

The gene Sry acts as a switch, initiating pathways leading to the differentiation of a testis rather than an ovary from the indifferent gonad (genital ridge) in mammals. The early events following Sry expression include rapid changes in the topographical organization of cells in the XY gonad. Sry must therefore initiate signaling pathways that direct male-specific patterns of proliferation, migration, cell-cell organization, and vascularization. We have identified an increase in male-specific proliferation by 12.0 days post coitum, while proliferation in the female gonad declines. We have also observed male-specific cell migration from the mesonephros into the gonad in a composite organ culture system in which gonads from wild-type mice (CD1) and mesonephroi from a transgenic strain expressing beta-galactosidase in all its cells (ROSA26) were grafted together in vitro at the indifferent stage of gonadogenesis. Migration depends on an active signal that requires the presence of a Y chromosome in the gonadal portion of the graft. The signals that trigger migration operate over considerable distances, suggesting either a long-range diffusible factor or the involvement of a rapid and efficient relay mechanism. Identification of the somatic cells contributed from the mesonephros with cell-specific markers indicated that some of the migrating cells were endothelial, revealing differences in processes of vascularization between male and female gonads. A second distinct population of migrating cells lay in close apposition to endothelial cells, and a third population occupied positions circumscribing areas of condensing Sertoli cells.

Animals↗
PubMed1998

Control of cyclin B1 localization through regulated binding of the nuclear export factor CRM1.

Activation of the Cyclin B/Cdc2 kinase complex triggers entry into mitosis in all eukaryotic cells. Cyclin B1 localization changes dramatically during the cell cycle, precipitously transiting from the cytoplasm to the nucleus at the beginning of mitosis. Presumably, this relocalization promotes the phosphorylation of nuclear targets critical for chromatin condensation and nuclear envelope breakdown. We show here that the previously characterized cytoplasmic retention sequence of Cyclin B1, responsible for its interphase cytoplasmic localization, is actually an autonomous nuclear export sequence, capable of directing nuclear export of a heterologous protein, and able to bind specifically to the recently identified export mediator, CRM1. We propose that the observed cytoplasmic localization of Cyclin B1 during interphase reflects the equilibrium between ongoing nuclear import and rapid CRM1-mediated export. In support of this hypothesis, we found that treatment of cells with leptomycin B, which disrupted Cyclin B1-CRM1 interactions, led to a marked nuclear accumulation of Cyclin B1. In mitosis, Cyclin B1 undergoes phosphorylation at several sites, a subset of which have been proposed to play a role in Cyclin B1 accumulation in the nucleus. Both CRM1 binding and the ability to direct nuclear export were affected by mutation of these phosphorylation sites; thus, we propose that Cyclin B1 phosphorylation at the G2/M transition prevents its interaction with CRM1, thereby reducing nuclear export and facilitating nuclear accumulation.

Animals↗