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Biomedical subjects

L Lynch

Publications and source records attributed to L Lynch.

At least 19 recordsLinked to original sources
PubMed2007

Cells with haematopoietic stem cell phenotype in adult human endometrium: relevance to infertility?

BACKGROUND: Uterine lymphoid cell repertoires are specialized in order to meet the twin demands of successful pregnancy and local immunosurveillance. The possibility that some of these populations might differentiate locally from progenitor cells has been proposed. METHODS: Endometrial tissue from women with a history of infertility as well as fertile controls was examined for haematopoietic stem cells (HSCs) and lymphoid progenitors using three-colour flow cytometry. RESULTS: Significant populations of phenotypic HSCs (CD34+ CD45+ ) were detected in all samples, a high proportion of which co-expressed the differentiation marker CD45RA (45.7%), indicating ongoing differentiation. Almost 30% of uterine HSCs co-expressed CD56 and 44% co-expressed CD7, suggesting the presence of lymphoid progenitors. Small proportions expressed CD127 and CD122, receptors for interleukin (IL)-7 and IL-15, respectively. HSC numbers were similar in the endometrial samples from fertile and infertile women. However, the proportion co-expressing the natural killer (NK) antigen CD56 was significantly increased compared with HSCs found in the endometrium of fertile controls (P = 0.002). CONCLUSIONS: This is the first demonstration of cells with an HSC phenotype in the human endometrium, and increased proportions of NK progenitors in endometrium of women with infertility suggests a dysregulation of this pathway that may contribute to infertility.

Adult↗
PubMed2004

Long-term donepezil treatment in 565 patients with Alzheimer's disease (AD2000): randomised double-blind trial.

BACKGROUND: Cholinesterase inhibitors produce small improvements in cognitive and global assessments in Alzheimer's disease. We aimed to determine whether donepezil produces worthwhile improvements in disability, dependency, behavioural and psychological symptoms, carers' psychological wellbeing, or delay in institutionalisation. If so, which patients benefit, from what dose, and for how long? METHODS: 565 community-resident patients with mild to moderate Alzheimer's disease entered a 12-week run-in period in which they were randomly allocated donepezil (5 mg/day) or placebo. 486 who completed this period were rerandomised to either donepezil (5 or 10 mg/day) or placebo, with double-blind treatment continuing as long as judged appropriate. Primary endpoints were entry to institutional care and progression of disability, defined by loss of either two of four basic, or six of 11 instrumental, activities on the Bristol activities of daily living scale (BADLS). Outcome assessments were sought for all patients and analysed by logrank and multilevel models. FINDINGS: Cognition averaged 0.8 MMSE (mini-mental state examination) points better (95% CI 0.5-1.2; p<0.0001) and functionality 1.0 BADLS points better (0.5-1.6; p<0.0001) with donepezil over the first 2 years. No significant benefits were seen with donepezil compared with placebo in institutionalisation (42% vs 44% at 3 years; p=0.4) or progression of disability (58% vs 59% at 3 years; p=0.4). The relative risk of entering institutional care in the donepezil group compared with placebo was 0.97 (95% CI 0.72-1.30; p=0.8); the relative risk of progression of disability or entering institutional care was 0.96 (95% CI 0.74-1.24; p=0.7). Similarly, no significant differences were seen between donepezil and placebo in behavioural and psychological symptoms, carer psychopathology, formal care costs, unpaid caregiver time, adverse events or deaths, or between 5 mg and 10 mg donepezil. INTERPRETATION: Donepezil is not cost effective, with benefits below minimally relevant thresholds. More effective treatments than cholinesterase inhibitors are needed for Alzheimer's disease.

Activities of Daily Living↗
PubMed2001

Distinct ligand-binding modes for integrin alpha(v)beta(3)-mediated adhesion to fibronectin versus vitronectin.

Cell surface integrins can adopt distinct conformations in response to ligand binding and intracellular signals. Several integrins including alpha(v)beta(3) can bind to multiple ligands. The binding of alpha(v)beta(3) to fibronectin and vitronectin was used as a model to determine whether the same or distinct forms of the receptor were utilized in strong binding to the two different ligands. A spinning-disc device was used to measure the relative strength of the alpha(v)beta(3)-ligand bonds. The initial binding reaction for both ligands occurred in the absence of metabolic energy and resulted in a strong adhesion to fibronectin but a weak adhesion to vitronectin. Increases in the strength of the alpha(v)beta(3)-vitronectin bond required phosphorylation of the beta(3) cytoplasmic domain, intracellular signals, and the binding of cytoskeletal proteins to cytoplasmic domains of beta(3) controlled by Tyr-747 and Tyr-759. In contrast, alpha(v)beta(3)-mediated adhesion to fibronectin was unaffected by phorbol 12-myristate 13-acetate, mutations of Tyr-747 and Tyr-759 to phenylalanine, or availability of metabolic energy. This suggests that strong adhesion to fibronectin used the initial binding conformation, whereas strong binding to vitronectin required signaling-induced changes in the conformation of alpha(v)beta(3).

Actins↗
PubMed2001

Dopexamine hydrochloride does not modify hemodynamic response or tissue oxygenation or gut permeability during abdominal aortic surgery.

PURPOSE: To assess the effects of intraoperative infusion of dopexamine (a DA-1 and B2 adrenoreceptor agonist) on hemodynamic function, tissue oxygen delivery and consumption, splanchnic perfusion and gut permeability following aortic cross- clamp and release. METHODS: In a randomised double blind controlled trial 24 patients scheduled for elective infrarenal abdominal aortic aneurysm repair were studied in two centres and were assigned to one of two treatment groups. Group I received a dopexamine infusion starting at 0.5 microg x kg(-1) x min(-1) increased to 2 microg x kg(-1) x min(-1) maintaining a stable heart rate; Group II received a placebo infusion titrated in the same volumes following induction of anesthesia. Measured and derived hemodynamic data, tissue oxygen delivery and extraction and gut permeability were recorded at set time points throughout the procedure. RESULTS: Dopexamine infusion (0.5 -2 microg x kg x min(-1)) was associated with enhanced hemodynamic function (MAP 65 +/- 5.5 vs 92 +/- 5.7 mm Hg, P = <0.05) only during the period of aortic cross clamping. However, during the most part of infrarenal abdominal aortic surgery, dopexamine did not reduce systemic vascular resistance index, mean arterial pressure nor oxygen extraction compared with the control group. The lactulose/ rhamnose permeation ratio was elevated above normal in both groups (0.22 and 0.29 in groups I and II respectively). CONCLUSIONS: Dopexamine infusion (0.5 -2 microg x kg(-1) x min(-1)) did not enhance hemodynamic function and tissue oxygenation values during elective infrarenal abdominal aortic aneurysm repair.

Aged↗
PubMed2001

Difficult airway management of a child impaled through the neck.

We report the difficult airway management of a child impaled through the neck by a wooden plant support. The various options are discussed and the involvement of experienced personnel together with a clear preformulated plan of action is stressed.

Airway Obstruction↗
PubMed2001

Activation of alpha(v)beta3-vitronectin binding is a multistage process in which increases in bond strength are dependent on Y747 and Y759 in the cytoplasmic domain of beta3.

Integrin receptors serve as mechanical links between the cell and its structural environment. Using alpha(v)beta3 integrin expressed in K562 cells as a model system, the process by which the mechanical connection between alpha(v)beta3 and vitronectin develops was analyzed by measuring the resistance of these bonds to mechanical separation. Three distinct stages of activation, as defined by increases in the alpha(v)beta3-vitronectin binding strength, were defined by mutational, biochemical, and biomechanical analyses. Activation to the low binding strength stage 1 occurs through interaction with the vitronectin ligand and leads to the phosphorylation of Y747 in the beta3 subunit. Stage 2 is characterized by a 4-fold increase in binding strength and is dependent on stage1 and the phosphorylation of Y747. Stage 3 is characterized by a further 2.5-fold increase in binding strength and is dependent on stage 2 events and the availability of Y759 for interaction with cellular proteins. The Y747F mutant blocked the transition from stage 1 to stage 2, and the Y759F blocked the transition from stage 2 to stage 3. The data suggest a model for tension-induced activation of alpha(v)beta3 integrin.

Antigens, CD↗
PubMed2000

Chorionic villus sampling before multifetal pregnancy reduction.

OBJECTIVE: This study was undertaken to determine the technical feasibility and accuracy of chorionic villus sampling before multifetal pregnancy reduction and to determine whether sampling increases the pregnancy loss rate after the reduction procedure. STUDY DESIGN: Between January 22, 1986, and January 20, 2000, a total of 1183 patients underwent first-trimester multifetal pregnancy reduction at Mount Sinai Medical Center. Chorionic villus sampling was attempted in 86 patients before the reduction procedure. Information on the technical success and accuracy of chorionic villus sampling, as well as pregnancy outcome, was collected on all patients. Pregnancy loss rates before 24 weeks' gestation in patients undergoing chorionic villus sampling before multifetal pregnancy reduction were compared with rates in patients not undergoing sampling. RESULTS: Chorionic villus sampling was successfully completed in 85 (98.8%) of 86 patients in whom sampling was attempted. Of 166 fetuses, 165 (99.4%) were successfully sampled. Of 165 fetuses, 3 (1.8%) had karyotypic abnormalities. Sampling errors were probably made in 2 (1.2%) of 165 fetuses. Of the 73 patients who have been delivered or are beyond 24 weeks' gestation, only 1 patient (1.4%) had a pregnancy loss after the multifetal pregnancy reduction. CONCLUSIONS: Chorionic villus sampling before multifetal pregnancy reduction is technically feasible and accurate, with an acceptably low sampling error rate. Chorionic villus sampling before multifetal pregnancy reduction appears to be safe and does not increase the risk of loss after the reduction procedure.

Adult↗
PubMed1999

Magma flow instability and cyclic activity at soufriere hills volcano, montserrat, british west indies

Dome growth at the Soufriere Hills volcano (1996 to 1998) was frequently accompanied by repetitive cycles of earthquakes, ground deformation, degassing, and explosive eruptions. The cycles reflected unsteady conduit flow of volatile-charged magma resulting from gas exsolution, rheological stiffening, and pressurization. The cycles, over hours to days, initiated when degassed stiff magma retarded flow in the upper conduit. Conduit pressure built with gas exsolution, causing shallow seismicity and edifice inflation. Magma and gas were then expelled and the edifice deflated. The repeat time-scale is controlled by magma ascent rates, degassing, and microlite crystallization kinetics. Cyclic behavior allows short-term forecasting of timing, and of eruption style related to explosivity potential.

Journal Article↗
PubMed1998

Reduction of distress in children undergoing sexual abuse medical examination.

A participant modeling film to reduce distress in children (5 to 13 years old) undergoing sexual abuse medical examination was tested. Twenty-one children viewing the participant modeling film reported less fear after film viewing and were behaviorally less distressed and more compliant, as rated by nurses and mothers, during gynecological examination than 21 children viewing a nonrelevant film.

Adolescent↗
PubMed1997

First-trimester growth restriction and fetal aneuploidy: the effect of type of aneuploidy and gestational age.

OBJECTIVE: Our purpose was to determine the effect of type of aneuploidy and gestational age on first-trimester fetal growth. STUDY DESIGN: Crown-rump length measurement was obtained in pregnancies undergoing chorionic villus sampling in three large prenatal diagnosis centers. One hundred forty-four aneuploid fetuses, from 9 to 13 weeks' gestation, were compared with 440 matched control fetuses for evidence of crown-rump length shortening. Shortening was defined by the observed/expected crown-rump length. Expected values of crown-rump length based on last menstrual period were obtained from regression equations generated from a separate normal group. Threshold values for aneuploidy screening were determined on the basis of receiver-operator characteristic curves. RESULTS: There was significant crown-rump length shortening in trisomy 18 compared with normal fetuses, with observed/expected values < or = 0.80 (odds ratio 13.78, 95% confidence interval 5.64 to 33.88, p < 0.000001); for trisomy 13 the observed/expected crown-rump length was < or = 0.90 (odds ratio 3.64, 95% confidence interval 1.08 to 12.96, p < 0.03). There was no significant shortening of crown-rump length in Down syndrome, with observed/expected values < or = 0.92 (odds ratio 0.86, 95% confidence interval 0.50 to 1.47, p = 0.6). With shortened crown-rump length (observed/expected value < 0.86) the risk of any aneuploidy is increased (odds ratio 2.52, 95% confidence interval 1.6 to 3.96, p < 0.0001). When the first-trimester crown-rump length was shortened by > or = 14 mm, the aneuploidy risk was high (odds ratio 9.04, 95% confidence interval 3.26 to 28.67, p < 0.00001). CONCLUSION: In the first trimester fetuses with trisomy 18 and 13 appear to be growth restricted, in contrast to fetuses with trisomy 21. In at-risk pregnancies crown-length that is shorter than expected significantly increase the odds that aneuploidy is present.

Aneuploidy↗
PubMed1997

Twin pregnancies conceived by assisted reproductive techniques: maternal and neonatal outcomes.

OBJECTIVE: To determine whether twin pregnancies conceived by assisted reproductive techniques are at increased risk for obstetric complications or perinatal morbidity. METHODS: A computerized perinatal data base was reviewed for all twin pregnancies managed by private obstetricians and delivered between 1990 and 1995. The obstetric and neonatal outcomes of those conceived following in vitro fertilization (IVF) or gamete intrafallopian transfer (GIFT) were compared to the outcomes of those conceived spontaneously. RESULTS: There were 105 twin deliveries following IVF or GIFT and 279 following natural fertilization. Discordant birth weight and low birth weight occurred more frequently in pregnancies conceived by IVF or GIFT (adjusted odds ratio [OR] 2.11, 95% confidence interval [CI] 1.14, 3.91; OR 1.65, 95% CI 0.98, 2.79, respectively). Elective cesarean delivery was more frequent in twin pregnancies conceived after IVF GIFT (relative risk [RR] 4.02, 95% CI 1.28, 12.6). There were no statistically significant differences in the frequency of antepartum or intrapartum complications, preterm delivery, or mean gestational age at delivery. There was no statistically significant increase in the frequency of neonatal complications among infants born after IVF GIFT. CONCLUSION: Although twin pregnancies following IVF or GIFT are more likely to result in discordant birth weight infants, the perinatal outcome is comparable to that of spontaneously conceived twin pregnancies.

Adult↗
PubMed1996

Preterm delivery after selective termination in twin pregnancies.

OBJECTIVE: To determine the effect of selective termination of an abnormal twin on the rate of preterm delivery. METHODS: The study group consisted of 69 patients with twin pregnancies who underwent selective termination between 1987-1994. The comparison groups consisted of singleton (n = 42,362) and twin pregnancies (n = 825) delivered at our institution during the same period. The data were analyzed by Chi2 and Fisher exact test, as appropriate. P < .05 was considered significant. Adjusted odds ratios(OR) and 95% confidence intervals (CI) were calculated by multiple logistic regression. RESULTS: Terminating the presenting twin was associated with a significantly higher risk of delivery before 37 weeks (adjusted OR 4.1, 95% CI 1.4-12.3) and low birth weight (adjusted OR 3.8, 95% CI 1.3-11.4) compared with terminating the nonpresenting twin. When the termination was performed at or after 20 weeks' gestation, only the risk of preterm premature rupture of the membranes or preterm labor was significantly increased (adjusted OR 3.7, 95% CI 1.2-11.5). Selective termination patients had a lower rate of preterm delivery than twin pregnancies (40 versus 58%, P < .005) but higher than singleton pregnancies (40 versus 10%,P < .001). CONCLUSION: Selective termination of the presenting twin at 20 weeks or later was associated with a worse perinatal outcome than terminating the nonpresenting twin or performing the procedure before 20 weeks.

Adult↗
PubMed1996

Pregnancy outcome at age 40 and older.

OBJECTIVE: To examine pregnancy outcome among women age 40 years and older. METHODS: A retrospective cohort study, including 1404 pregnant women at least 40 years of age and 6978 controls age 20-29 years, was conducted. The two groups were stratified, according to parity, to facilitate separate analysis. Associations between maternal age and pregnancy outcomes were assessed with the contingency chi 2 or two-tailed Fisher exact test. Multiple logistic regression was used to evaluate these associations and allowed for calculation of adjusted odds ratios (OR). RESULTS: Older gravidas were more likely to develop gestational diabetes (nulliparas: OR 2.7, 95% confidence interval [CI] 1.9-3.7; multiparas: OR 3.8, 95% CI 2.7-5.4), preeclampsia (nulliparas: OR 1.8, 95% CI 1.3-2.6; multiparas: OR 1.9, 95% CI 1.2-2.9), and placenta previa (nulliparas: OR 13.0, 95% CI 4.8-35.0; multiparas: OR 6.4, 95% CI 2.6-15.6). Older women were also at increased risk for cesarean delivery (nulliparas: OR 3.1, 95% CI 2.6-3.7; multiparas: OR 3.3, 95% CI 2.6-4.1), operative vaginal delivery (nulliparas: OR 2.4, 95% CI 1.9-2.9; multiparas: OR 1.5, 95% CI 1.2-1.9), and induction of labor (nulliparas: OR 1.5, 95% CI 1.2-1.8; multiparas: OR 1.4, 95% CI 1.1-1.7). Older nulliparas had an increased incidence of abnormal labor patterns (OR 1.4, 95% CI 1.2-1.7), neonatal intensive care unit admissions (OR 1.6, 95% CI 1.2-2.2), and low 1-minute Apgar scores (OR 2.3, 95% CI 1.1-4.9). Older multiparas were more likely to experience fetal distress (OR 2.0, 95% CI 1.4-2.8), antepartum vaginal bleeding (OR 1.8, 95% CI 1.1-3.1), and preterm premature rupture of membranes (OR 1.7, 95% CI 1.1-2.9). CONCLUSION: Although maternal morbidity was increased in the older gravidas, the overall neonatal outcome did not appear to be affected.

Adult↗
PubMed1996

Antenatal management of alloimmune thrombocytopenia with intravenous gamma-globulin: a randomized trial of the addition of low-dose steroid to intravenous gamma-globulin.

OBJECTIVES: Our purposes were to investigate maternal infusions of intravenous gamma-globulin, to prevent intracranial hemorrhage, and to determine whether 1.5 mg dexamethasone and 60 mg prednisone per day add to the effect of intravenous gamma-globulin. STUDY DESIGN: Fifty-four women with alloimmune thrombocytopenia and thrombocytopenic fetuses were randomized to intravenous gamma-globulin 1 gm/kg per week with or without dexamethasone. Nonresponders after 4 to 6 weeks received continued intravenous gamma-globulin plus 60 mg of prednisone per day ("salvage"). RESULTS: Dexamethasone did not add to the effect of intravenous gamma-globulin. Overall, there was a mean platelet increase from the first to the second fetal blood sampling of 36,000/microliters (n = 47) and from the first fetal blood sampling to birth of 69,000/microliters (n = 54). A total of 62% to 85% of fetuses responded. There were no intracranial hemorrhages. "Salvage" increased the platelet count in 5 of 10 nonresponders to intravenous gamma-globulin. CONCLUSION: Intravenous gamma-globulin treatment is appropriate for thrombocytopenic fetuses with alloimmune thrombocytopenia before use of weekly in utero platelet transfusions, even in severe thrombocytopenia.

Cerebral Hemorrhage↗