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Biomedical subjects

L Gray

Publications and source records attributed to L Gray.

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

Selected contribution: Effects of gender on reduced-size liver ischemia and reperfusion injury.

Hepatic resection with concomitant periods of ischemia and reperfusion (I/R) is a common occurrence in resectional surgery as well as reduced-size liver transplantation (e.g., split liver or living donor transplantation). However, the I/R induced by these types of surgical manipulations may impair liver regeneration, ultimately leading to liver failure. The objectives of the study were to develop a murine model of reduced-size liver I/R and assess the role of gender in this model of hepatocellular injury. We found that 100% of female mice survived the surgery indefinitely, whereas all male mice had greater initial liver injury and died within 5 days after surgery. The protective effect observed in females appeared to be due to ovarian 17beta-estradiol, as ovariectomy of females or administration of a selective estrogen antagonist to female mice resulted in enhanced liver injury and greater mortality following reduced-size liver I/R. Conversely, 17beta-estradiol-treated male mice exhibited less hepatocellular damage and survived indefinitely. Taken together, these data demonstrate an estrogen-mediated protective pathway(s) that limits or attenuates hepatocellular injury induced by reduced-size liver I/R.

Animals↗
PubMed2001

Fluctuations in symptoms in human immunodeficiency virus-infected children: the first 10 years of life.

OBJECTIVE: To describe patterns of clinical and immunologic progression in children who are vertically infected with the human immunodeficiency virus. METHODS: Children who were born to mothers who were infected with the human immunodeficiency virus in 11 European centers were enrolled at birth in a prospective study and followed according to a standard protocol. At each visit, a clinical and immunologic class was allocated according to guidelines of the Centers for Disease Control and Prevention (CDC). Progression to serious disease and death was assessed, allowing for available and actual antiretroviral therapy (ART). CDC class at each visit was assessed cross-sectionally. RESULTS: More than 15% of infected children will have progressed to category C or death by age 1 year and nearly 50% by 10 years. Just under 20% of children will have evidence of severe immunodeficiency by age 1 and 75% by 10 years. In general, immune status poorly reflected clinical condition. Children who were born after 1994, when the recommendation of earlier initiation of more active therapy was introduced, were significantly less likely to progress than those who were born when treatment was not widely available or was largely confined to zidovudine monotherapy. Estimated progression to CDC class C or death initially was faster in untreated than in treated children, but by 10 years estimated cumulative progression was similar in both groups. Treatment started before class C disease was associated with significantly slower progression. Cross-sectional analysis showed that children largely are symptom-free throughout their lives. After 4 years of age, fewer than 25% of infected children had symptoms at any one time, irrespective of ART received. CONCLUSION: Vertically infected children are without serious symptoms or signs for most of the time. The prognosis has improved with more widespread availability and use of combination ART. These findings have implications for health, education, and other support-service provision.

Age Distribution↗
PubMed2000

Nitric oxide synthase and postischemic liver injury.

The objective of this study was to determine what roles the endothelial cell and inducible isoforms of nitric oxide synthase (eNOS, iNOS) play in ischemia and reperfusion (I/R)-induced liver injury in vivo in mice genetically deficient in each isoform of NOS. We found that 45 min of partial (70%) liver ischemia and 5 h of reperfusion induced substantial liver injury as assessed by the release of large and significant amounts of the liver-specific enzyme alanine aminotransferase (ALT) into the serum of wild-type (wt) mice. The enhanced ALT levels were not due to increased recruitment of potentially damaging PMNs, which could mediate hepatocyte injury, as neither histopathological inspection nor quantitative MPO determinations revealed the presence of PMNs in the liver at this time point. In addition, we observed a significant enhancement in liver injury in eNOS-deficient but not iNOS-deficient mice subjected to liver I/R compared to postischemic wt mice. Taken together, these data suggest that eNOS- but not iNOS-derived NO plays an important role in limiting or downregulating I/R-induced liver injury in vivo following 5 h of reperfusion.

Alanine Transaminase↗
PubMed2000

Co-receptor usage of HIV-1 primary isolates, viral burden, and CCR5 genotype in mother-to-child HIV-1 transmission.

OBJECTIVE: To investigate the relationship between CC chemokine receptor 5 (CCR5) genotype, viral load and co-receptor usage of maternal HIV-1 isolates in perinatal HIV-1 transmission. PATIENTS AND METHODS: A total of 181 mothers and infants were studied at the time of delivery. Wild-type (wt) and delta32 CCR5 alleles were determined by means of polymerase chain reaction (PCR). The viral load in maternal plasma samples was determined by a quantitative reverse transcriptase-PCR assay; co-receptor usage of maternal isolates was determined by viral infection in cells stably expressing CCR5 or CXC chemokine receptor 4 (CXCR4) co-receptors. RESULTS: HIV-1 transmission rates in wt/wt and wt/delta32 mothers (14.7 versus 15.8%), and in wt/wt and wt/delta32 infants (14.6 versus 14.3%) were similar. Mothers transmitting infection to wt/delta32 infants had significantly higher HIV-1-RNA levels than those who transmitted infection to wt/wt infants (5.4 versus 4.1 log10 copies/ml, P = 0.03). In wt/wt children there was a positive relationship between transmission rate and maternal viral load over the entire range of HIV-1 values, whereas in wt/delta32 children transmission occurred only at viral loads greater than 4.0 log10 copies/ml. Logistic regression analysis confirmed that the relationship between viral load and transmission varied according to the child's CCR5 genotype (P = 0.035; adjusted for zidovudine prophylaxis and mode of delivery, P = 0.090). Moreover, the majority of wt/wt transmitting mothers had R5-type isolates, whereas none of the wt/delta32 mothers with an R5-type virus transmitted HIV-1 to their wt/delta32 infants. CONCLUSION: Taken together, these findings suggest that CCR5 delta32 heterozygosity exerts a protective effect against perinatal transmission in children exposed to a low maternal viral burden of an R5-type isolate.

Cetirizine↗
PubMed2000

S-nitrosothiol formation in blood of lipopolysaccharide-treated rats.

The administration of the gram-negative bacterial cell wall component lipopolysaccharide (LPS) to experimental animals results in the dramatic up-regulation of the inducible form of nitric oxide synthase (iNOS). The resulting sustained overproduction of nitric oxide (NO) is thought to contribute to the septic shock-like state in these animals. Numerous studies have characterized the kinetics and magnitude of expression of iNOS as well as the production of NO-derived nitrite and nitrate. However, little is known regarding the ability of iNOS-derived NO to interact with physiological substrates such as thiols to yield biologically active S-nitrosothiols during endotoxemia. It has been hypothesized that these relatively stable, vaso-active compounds may serve as a storage system for NO and they may thus play an important role in the pathophysiology associated with endotoxemia. In the present study, we demonstrate that 5 h after i.p. administration of LPS in rats, circulating S-nitrosoalbumin was increased by approximately 3. 4-fold over control. S-nitrosohemoglobin was increased by approximately 25-fold over controls and by threefold over S-nitrosoalbumin. No increase in low molecular weight S-nitrosothiols (i.e., S-nitrosoglutathione and S-nitrosocysteine) could be detected under our experimental conditions. Taken together these data demonstrate that endotoxemia dramatically enhances circulating S-nitrosothiol formation.

Animals↗
PubMed2000

E-Selectin expression in a murine model of chronic colitis.

The objective of this study was to quantify E-selectin surface expression in the colon as well as other tissues in a CD4(+) T-cell model of chronic colitis in mice using the newly developed dual radiolabel monoclonal antibody technique. Male SCID mice were reconstituted with either 5 x 10(5) CD4(+) CD45RB(low) or CD45RB(high) T-cells isolated from normal CB-17 donor mouse spleens and subsequently monitored for clinical signs of colitis. We found that animals injected with CD45RB(high) but not CD45RB(low) T-cells nor PBS developed colitis at 6-8 weeks following reconstitution as assessed by loss of body weight, development of loose stools and/or diarrhea, and histopathology. Concurrent with the onset of distal bowel inflammation was enhanced expression of E-selectin compared to SCID mice injected with PBS or reconstituted with CD45RB(low) T-cells, both of which did not develop colitis. We also observed significant increases in E-selectin expression in cecum, small intestine, mesentery, and liver of colitic mice. Our data confirm that reconstitution of SCID mice with CD45RB(high) but not CD45RB(low) T-cells induces chronic colitis and demonstrate that this chronic colitis is associated with enhanced expression of an endothelial cell-specific adhesion molecule. Furthermore, our studies demonstrate that reconstitution of SCID mice with CD45RB(high) T-cells enhances E-selectin expression in a variety of tissues distant from the site of active inflammation.

Animals↗
PubMed2000

Chemoreflexes: an experimental study.

HYPOTHESIS: Transmyocardial laser revascularization (TMLR) will not denervate the heart, because it does not destroy all of the afferents. This study was designed to determine if stimulation of cardiac sympathetic and vagal afferents from an area of the left ventricle treated with TMLR could evoke reflex effects, and thus whether TMLR would denervate the heart. METHODS: The effect of TMLR on reflexes evoked by chemically stimulating cardiac afferents was examined in 9 dogs. Bradykinin and capsaicin were applied topically or injected into the left anterior descending coronary artery before and after TMLR and after bilateral vagotomy and sympathectomy. Aortic (AoP) and left ventricular pressures (LVP) and electrocardiography were monitored. The first derivatives of LVP (dP/dt) were calculated. RESULTS: Topical bradykinin elicited variable hemodynamic responses. Topical capsaicin evoked pressor responses, increasing mean (+/- SEM) AoP (105+/-9 to 115+/-9 mm Hg; P<.001) and positive dP/dt (+dP/dt) (1032+/-81 to 1159+/-10 mm Hg/s; P<.01) before TMLR. Intracoronary capsaicin evoked a depressor response before TMLR. Pressor responses remained intact after TMLR with increases in mean AoP and +dP/dt (115+/-6 to 128+/-5 mm Hg and 1039+/-98 to 1136+/-100 mm Hg/s, respectively; P<.01). Depressor responses also remained intact after TMLR (91+/-10 vs 101+/-11 mm Hg [P<.02], and 865+/-104 vs 931+/-104 mm Hg/s [P<.05], respectively). Hemodynamic responses were diminished after bilateral vagotomy and abolished after bilateral sympathectomy. CONCLUSION: Since activation of cardiac afferent nerves and reflex responses remained intact after TMLR, but changed after vagotomy or sympathectomy, TMLR does not denervate the heart sufficiently to be the cause of improved angina after TMLR.

Afferent Pathways↗
PubMed2000

Functional and ultrastructural cell pathology induced by fuel oil in cultured dolphin renal cells.

Investigations were undertaken to elucidate in a marine mammal renal cell culture system the toxicity and some of the mechanisms of cytopathology in a standardized preparation following exposure to No. 1 fuel oil. Cell survivability of a cultured SP1K renal cell line from the Atlantic spotted dolphin Stenella plagiodon was reduced in a dose-dependent manner after a 12-h exposure to fuel oil. Early morphologic changes reflecting cytotoxicity, as revealed by transmission electron microscopy, included enlarged rough endoplasmic reticula, cytoplasmic vacuolization, and degenerative cytoplasmic inclusions, but mitochondria remained resistant. Assessment of extracellular proton loss by microphysiometry of cultured cells revealed fuel oil-induced enhancement of proton loss that was dependent upon both protein kinase C and renal epithelial Na(+)/H(+) counter-transport functioning, as the specific inhibitors H-7 and amiloride reduced this stimulatory petroleum effect. Cell cycle progression and apoptosis (programmed cell death) were studied in dolphin renal cells exposed to fuel oil for 12, 24, and 48 hours. The toxicant increased the percentage of cells in GO/GI phase and decreased the percentage of cells in S phase starting after 24 hours. The number of cells undergoing early apoptosis was also increased after 24 hours.

Animals↗
PubMed2000

Duration of the hemodynamic effects of N(G)-nitro-L-arginine methyl ester in vivo.

The objective of this study was to quantify the duration of the hemodynamic activity of N(G)-nitro-l-arginine methyl ester (l-NAME) in a variety of different tissues following a single bolus injection of this nitric oxide synthase inhibitor to healthy rats. l-NAME (15 micromol x kg(-1)) was injected (ip) into rats to produce maximal inhibition of endothelial cell NOS. Animals were subsequently anesthetized and blood flow was quantified using the radioactive microsphere/reference organ technique. At 1 h following a single bolus injection of l-NAME blood flow was reduced to the entire gastrointestinal tract, pancreas, and liver. Three hours following l-NAME administration, blood flow to the stomach and upper small intestine had returned to pretreatment levels; however, blood flow to the jejunum, ileal-jejunal junction, and colon remained significantly reduced. Splenic blood flow was significantly reduced and hepatic arterial blood flow was further reduced at this time as well. After 6 h following l-NAME administration, blood flow in all organs had completely recovered to control levels. Although cardiac index and total peripheral resistance had also returned to preinjection values at this time, mean arterial pressure remained elevated at 6 h posttreatment. Blood flow to the brain, lungs, and psoas muscle were unaffected by l-NAME administration at any time point. Taken together, these data demonstrate a differential regulation of vascular tone by NO in different vascular beds and, depending upon the organ system in question, the vasoactive activity of l-NAME may last from 3 to 6 h following a single bolus injection of this NOS inhibitor.

Animals↗
PubMed2000

Parasitic lesion of the insula suggesting cerebral sparganosis: case report.

Cerebral sparganosis, a parasitic disease, rarely produces a chronic active inflammatory response in the brain. Clinically and radiographically the process may mimic a neoplasm. We report a 30-year-old man who underwent surgical exploration for a mass in the insular cortex. Histology revealed a densely fibrotic mass heavily infiltrated with plasma cells and lymphocytes, in which were embedded parasitic forms consistent with sparganosis. We describe the MRI appearances and pathologic features. Intracranial mass lesions secondary to sparganosis must be considered in patients with a history of travel to endemic areas, especially Asia.

Adult↗
PubMed2000

Comparison of university of wisconsin, euro-collins, low-potassium dextran, and krebs-henseleit solutions for hypothermic lung preservation.

OBJECTIVE: We sought to test the effectiveness of 4 different solutions for hypothermic rat lung preservation. METHODS: One hundred ninety-two rats were used. The rats were divided into 4 groups, and University of Wisconsin, Euro-Collins, low-potassium dextran, or Krebs-Henseleit solution was used in each group. They were further divided into 6 subgroups of 8 rats each. The lungs were preserved at 4 degrees C for 0, 4, 6, 8, 12, or 24 hours, respectively, and lung function was studied by using a living rat perfusion model. RESULTS: Pulmonary arterial flow decreased in each group after 4 to 6 hours of preservation; the low-potassium dextran group decreased the least and the Krebs-Henseleit group decreased the most. Pulmonary vascular resistance increased in each group after 6 hours of preservation; the Krebs-Henseleit group increased the most. Although airway pressure increased, static lung compliance and gas exchange capacity decreased after 8 hours of preservation; the Krebs-Henseleit group exhibited the worst values. Lung tissue wet/dry weight ratio increased gradually during preservation; the University of Wisconsin group exhibited the least increase. An ultrastructural study indicated the least morphologic changes in the low-potassium dextran group at 24 hours. CONCLUSIONS: At 4 degrees C, all solutions preserved rat lungs for 4 hours with acceptable function. However, 6 hours of preservation resulted in damaged pulmonary function in some lungs, and this damage increased when preservation time was extended. The lungs preserved in low-potassium dextran solution had the best overall function, but the lungs preserved in University of Wisconsin solution had less edema.

Adenosine↗
PubMed2000

Management of patients with suspected deep vein thrombosis in the emergency department: combining use of a clinical diagnosis model with D-dimer testing.

The management of patients presenting to hospital Emergency Departments with suspected deep vein thrombosis is problematic since urgent diagnostic imaging is at times unavailable. We evaluated the accuracy of a rapidly available D-dimer test and the potential of combining D-dimer testing with an explicit clinical model to improve the management of patients with suspected deep vein thrombosis. Two hundred and fourteen patients with suspected deep vein thrombosis presenting to the Emergency Departments of two tertiary care institutions were enrolled in this prospective cohort study. Patients were evaluated by an Emergency Physician who determined the pre-test probability for deep vein thrombosis to be either low, moderate, or high using an explicit clinical model. Patients were managed according to their pre-test probability category by specific algorithms that in all cases included venous ultrasound imaging within 24 h and a 90-day follow-up for the development of thromboembolic complications. Patients also underwent fingerstick SimpliRED(R) whole blood agglutination D-dimer testing; however, D-dimer results did not influence subsequent patient management. D-dimer had a sensitivity of 82.5% and a specificity of 84.9% for the diagnosis of deep vein thrombosis. The observed negative predictive value of D-dimer was 96.9% (95% CI, 93.0% to 99.1%) overall, and 100% (95% CI, 96.3% to 100%) in low probability patients, 94.1% (95% CI, 83.8% to 98.8%) in moderate probability patients, and 86.7% (95% CI, 59.4% to 98.3%) in high probability patients. SimpliRED(R) D-dimer has a high negative predictive value and may be useful in excluding the diagnosis in patients at low pre-test probability for deep vein thrombosis.

Agglutination Tests↗
PubMed2000

Measuring sound in hospital nurseries.

This article provides practical advice on how to document sound levels in a nursery: How do you use sound-level meters, noise dosimeters, and spectrum analyzers? Where is the best position for microphones in a sound survey? How do you present results to nursery staff? The goal is to provide informal instruction on how to use these devices and interpret their measurements. The intended audience is medical personnel, not engineers. A companion article in this issue provides background on the technical aspects of sound measurement. There is an appendix with hints about finding help and purchasing equipment.

Acoustics↗
PubMed2000

Properties of sound.

Basic concepts about sound exposure are reviewed without extensive reliance on the technical details of physical acoustics or psychoacoustics. The frequencies and intensities of sounds that might be encountered in a hospital nursery are described. Examples of the nonlinear properties of sound levels are provided. The complexities of adding and subtracting decibels are discussed. Some important noise standards are reviewed, along with an explanation of why some sounds might be more annoying than others. A companion article in this issue gives practical information on how to make sound-level measurements.

Acoustics↗
PubMed2000

Family patterns of asthma, atopy and airway hyperresponsiveness: an epidemiological study.

BACKGROUND: The patterns of inheritance of asthma have largely been explored using data of symptom history collected by questionnaires which are subject to bias and which may therefore distort the measured relationship. OBJECTIVE: The purpose of this study was to examine family patterns of allergic disease using objective measurements of atopy and of airway hyperresponsiveness (AHR). METHODS: A large random sample of children aged 8-11 years was studied and 3 months later, their parents were also invited for study. Of the sample of 1655 children, both parents of 661 children were studied. In all subjects, respiratory illness history was measured by questionnaire, atopy by skin tests and AHR by responsiveness to histamine. RESULTS: The odds ratio for a child to have AHR if either parent had the same condition was approximately 2. 0, which was the same as the odds ratio for wheeze or diagnosed asthma in the presence of the same condition in either parent. The odds ratio for atopy was smaller (approximately 1.4, NS) but the risk of a nonatopic child having AHR if the parent had AHR was 3.0 (P = 0.01). The correlation between weal size in the child and parent was poor and the severity of AHR in the child was only modestly correlated with the severity of AHR in the parent (R = 0.51, P = 0.04). CONCLUSION: The use of objective measurements did not strengthen the association between atopic or asthmatic conditions in the parent and child, but did suggest that atopy and AHR are inherited independently.

Adult↗
PubMed2000

A functional map of cervical metastases from oral squamous cell carcinoma.

A visual summary of underlying patterns in metastases from oral squamous cell carcinoma (SCC) was created by the mathematical technique of multidimensional scaling (MDS). MDS creates a "functional" map of the neck, such that adjacent sites share similar probabilities of disease. We mapped the metastases from 130 sequential cases of oral SCC in the UK. Binary Euclidean distances were calculated from tallies of metastases at all possible pairs of neck levels (I-V on each side) for each of seven different primary sites: buccal mucosa, lower alveolus, floor of mouth, ventral tongue/floor of mouth, lateral tongue, retromolar trigone, and oropharynx. A two-dimensional functional map of the neck was made from these distances. The map explains 82% of the input data (p < 0.01). This is the first functional mapping of neck levels. The technique can now be used to summarize and compare patterns of metastases in different populations.

Carcinoma, Squamous Cell↗
PubMed2000

Role of nitric oxide in the regulation of acute and chronic inflammation.

Recent studies by a number of different laboratories have implicated nitric oxide (NO) as an important modulator of a variety of acute and chronic inflammatory disorders. A hallmark of inflammation is the adhesion of leukocytes to post-capillary venular endothelium and the infiltration of leukocytes into the tissue interstitium. Leukocyte adhesion and infiltration is known to be dependent on interaction of the leukocytes with the endothelial cell surface via a class of glycoproteins collectively known as endothelial cell adhesion molecules (ECAMs). Several recent studies suggest that NO may modulate cytokine-induced ECAM expression in cultured endothelial cells in vitro by regulating the activation of nuclear transcription factor kappa B (NF-kappaB). This discussion reviews some of the more recent studies that assess the role of the different NOS isoforms on the inflammatory response in vivo.

Animals↗