Biomedical subjects

J Wiley

Publications and source records attributed to J Wiley.

At least 19 recordsLinked to original sources

PubMed2005

Filamin A mutations cause periventricular heterotopia with Ehlers-Danlos syndrome.

OBJECTIVE: To define the clinical, radiologic, and genetic features of periventricular heterotopia (PH) with Ehlers-Danlos syndrome (EDS). METHODS: Exonic sequencing and single stranded conformational polymorphism (SSCP) analysis was performed on affected individuals. Linkage analysis using microsatellite markers on the X-chromosome was performed on a single pedigree. Western blotting evaluated for loss of filamin A (FLNA) protein and Southern blotting assessed for any potential chromosome rearrangement in this region. RESULTS: The authors report two familial cases and nine additional sporadic cases of the EDS-variant form of PH, which is characterized by nodular brain heterotopia, joint hypermobility, and development of aortic dilatation in early adulthood. MRI typically demonstrated bilateral nodular PH, indistinguishable from PH due to FLNA mutations. Exonic sequencing or SSCP analyses of FLNA revealed a 2762 delG single base pair deletion in one affected female. Another affected female harbored a C116 single point mutation, resulting in an A39G change. A third affected female had a 4147 delG single base pair deletion. One pedigree with no detectable exonic mutation demonstrated positive linkage to the FLNA locus Xq28, an affected individual in this family also had no detectable FLNA protein, but no chromosomal rearrangement was detected. CONCLUSION: These results suggest that the Ehlers-Danlos variant of periventricular heterotopia (PH), in part, represents an overlapping syndrome with X-linked dominant PH due to filamin A mutations.

Adolescent↗

PubMed2004

Spinal anesthesia for cesarean section following inadequate labor epidural analgesia: a retrospective audit.

BACKGROUND: High blocks have been reported when spinal anesthesia is used for cesarean section following inadequate labor epidural analgesia. We have therefore modified the practice at our institution to minimize this risk and conducted a retrospective observational study of outcome following the change of practice. METHOD: The records of 115 women with inadequate epidural labor analgesia who required cesarean section between July 1998 and January 2002 were studied. No epidural boluses were administered in the 30 min preceding spinal anesthesia and a reduced spinal dose, median (range) 9.38 mg (7.5-11.3 mg) of 0.75% hyperbaric bupivacaine and fentanyl 15 microg (10-25 microg) was used. Patients were left sitting for 2 min and then positioned supine with left uterine displacement and were closely monitored for symptoms or signs that would suggest a high block. RESULTS: No parturient developed a high spinal necessitating intubation, and there was no adverse neonatal outcome. CONCLUSION: These findings do not conclusively establish this method as safe, but should spinal anesthesia for cesarean section following suboptimal labor epidural analgesia be considered, avoiding epidural boluses immediately preceding spinal injection, using a lower spinal dose, and delayed supine positioning following spinal injection may be advisable.

Adult↗

PubMed2003

Parkin-proven disease: common founders but divergent phenotypes.

OBJECTIVE: To compare and contrast clinical and genetic findings in six probands with parkinsonism with a parkin exon 3 438- to 477-bp deletion (Ex3Delta40) to search for evidence of a common founder. METHOD: Clinical review, parkin gene sequencing, dosage studies, and high-resolution genotype/haplotype analysis were performed. RESULTS: All subjects had two or more signs consistent with a diagnosis of possible or probable PD with age at onset younger than 45 years (mean +/- SD 29.3 +/- 10.2 years, range 16 to 42 years). Affected individuals were either homozygotes, compound heterozygotes, or Ex3Delta40 carriers with one normal parkin allele. Haplotype analysis revealed both Ex3Delta40 and Ex7 924 C-->T (R275W) mutations originated from common founders, the former most probably of Irish descent. Although three cases had Ex7 924 C-->T (R275W) and Ex3Delta40 mutations, their clinical presentation and mode of inheritance were variable. CONCLUSION: Parkin mutations on common parkin haplotypes provide testable hypotheses of parkin function in genetically defined parkinsonism.

Adult↗

PubMed2001

Accessibility of potential referents following categorical anaphors.

In 4 experiments, the authors investigated the accessibility of potential antecedents that were either referents or nonreferents of categorical anaphors using several methodologies. In 2 preliminary experiments, using an immediate probe recognition task, the authors replicated previous findings of inhibition for nonreferents following categorical anaphors. In Experiments 1-3, naming times to nonreferent probes were inhibited, but only at a delay and at the end of the sentence. Eye movements were monitored in Experiment 4, and reading times were found to be slower in end-of-sentence regions following the remention of the nonreferent but not on the nonreferent itself. These results suggest that decreases in nonreferent accessibility are due to postanaphoric processes, such as integrating the nonreferent into the discourse structure, and are not due to more immediate changes in activation occurring as part of the resolution process. Further, some inhibition effects may result from the use of probe tasks that require decisions.

Adult↗

PubMed2001

A randomized trial of labor analgesia in women with pregnancy-induced hypertension.

OBJECTIVE: The purpose of this study was to compare the peripartum and perinatal effects of epidural with intravenous labor analgesia in women with pregnancy-induced hypertension. STUDY DESIGN: Women with pregnancy-induced hypertension who had consented to participate were randomized to receive either epidural or intravenous analgesia for labor pain. Both methods were given according to standardized protocols. All women received magnesium sulfate seizure prophylaxis. Obstetric and neonatal outcomes were compared according to intent-to-treat allocation. RESULTS: Seven hundred thirty-eight women were randomized: 372 women were given epidural analgesia, and 366 women were given intravenous analgesia. Maternal characteristics were similar, including the severity of hypertension. Epidural analgesia was associated with a significantly prolonged second-stage labor, an increase in forceps deliveries, and an increase in chorioamnionitis. Cesarean delivery rates and neonatal outcomes were similar. Pain relief was superior with the epidural method. Hypotension required treatment in 11% of women in the epidural group. CONCLUSION: Epidural labor analgesia provides superior pain relief but no additional therapeutic benefit to women with pregnancy-induced hypertension.

Adolescent↗

PubMed2001

Transient neurologic symptoms after spinal anesthesia with lidocaine in obstetric patients.

We investigated the relationship between intrathecal lidocaine and transient neurologic symptoms in the obstetric population because lidocaine spinal anesthetics are commonly used for various obstetric procedures, and little has been reported in this regard from within this population. In this study, 58 ASA physical status I patients presenting for postpartum bilateral tubal ligation under spinal anesthesia were randomized to receive either hyperbaric 5% lidocaine or 0.75% bupivacaine in a double-blinded manner. All patients were in the supine position for their surgery. Postoperatively, all patients were followed by a blinded investigator using a standardized symptom checklist. The incidence of transient neurologic symptoms with lidocaine was 3% (95% confidence interval = 0.1%--17.8%) and that with bupivacaine was 7% (95% confidence interval = 0.9%--23.5%), (P = not significant). Symptoms consistent with this syndrome occurred within 24 h without any associated sensory or motor deficits or functional impairment, and resolved within 48 h without any intervention.

Adult↗

PubMed2001

Intensity of labor pain and cesarean delivery.

Some authors have suggested that the intensity of labor pain may be related to labor dystocia. We performed a secondary analysis of a previously published randomized investigation of the effects of epidural analgesia during labor compared with patient-controlled IV meperidine on cesarean delivery. Two-hundred-fifty-nine women who received patient-controlled IV meperidine were identified for analysis. All women were in spontaneous labor with a singleton, term gestation. Women requiring 50 mg or more of meperidine per hour during labor were compared with those who required <50 mg/h. In addition, their pain scores (visual analog scale) were compared before and after analgesia administration. Pain scores were significantly higher in women requiring 50 mg/h of meperidine (8.7 vs 8.0, P = 0.05), and their labors tended to be longer (9 vs 5 h, P = 0.09). More cesarean deliveries for obstructed labor were performed in women requiring >50 mg/h of meperidine (14% vs 1.4%, P = 0.001). Neonatal outcomes were similar in the two groups.

Adult↗

PubMed2001

Impaired transendothelial migration of B-CLL lymphocytes: a defect linked to low L-selectin expression.

The emigration of lymphocytes from blood into lymph nodes is regulated by the expression of the adhesion molecule, L-selectin on the lymphocyte surface which arrests the rolling of the cell on the vessel wall and allows firmer adhesive interactions to develop. The expression of L-selectin on B-CLL lymphocytes is less than half that on normal lymphocytes and this difference correlates with an impaired capacity of B-CLL lymphocytes to migrate beneath a monolayer of human umbilical vein endothelial cells. Both the B-cell and T-cell lymphocytes from normal subjects and B-CLL patients show down-regulation of L-selectin and CD23 after transendothelial migration. The reduced expression of L-selectin on B-CLL lymphocytes leads to a relative "trapping" of these cells in the vascular space and is one factor contributing to the elevation of peripheral lymphocyte count.

B-Lymphocytes↗

PubMed2000

Impact of bone marrow transplantation for symptomatic sickle cell disease: an interim report. Multicenter investigation of bone marrow transplantation for sickle cell disease.

Fifty children who had symptomatic sickle cell disease received matched sibling marrow allografts between September 1991 and March 1999, with Kaplan-Meier probabilities of survival and event-free survival of 94% and 84%, respectively. Twenty-six patients (16 male, 10 female) had at least 2 years of follow-up after transplantation and were evaluated for late effects of transplantation and for its impact on sickle cell-related central nervous system (CNS) and pulmonary disease. Patients ranged between 3.3 and 14.0 (median, 9. 4) years of age and had a median follow-up of 57.9 (range 38-95) months after transplantation. Among 22 of 26 patients who had stable donor engraftment, complications related to sickle cell disease resolved, and none experienced further episodes of pain, stroke, or acute chest syndrome. All 10 engrafted patients with a prior history of stroke had stable or improved cerebral magnetic resonance imaging results. Pulmonary function tests were stable in 22 of the 26 patients, worse in two, and not studied in two. Seven of eight patients transplanted for recurrent acute chest syndrome had stable pulmonary function. Linear growth measured by median height standard deviation score improved from -0.7 before transplantation to -0.2 after transplantation. An adverse effect of busulfan conditioning on ovarian function was demonstrated in five of seven evaluable females who are currently at least 13 years of age. None of the four males tested had elevated serum gonadotropin levels. These data confirm that allogenic bone marrow transplantation establishes normal erythropoiesis and is associated with improved growth and stable CNS imaging and pulmonary function in most patients. (Blood. 2000;95:1918-1924)

Adolescent↗

PubMed2000

Cytokine-mobilized allogeneic peripheral blood stem cell transplants in children result in rapid engraftment and a high incidence of chronic GVHD.

Between October 1995 and October 1998, 24 children aged 9 months to 17 years (median 11 years) underwent cytokine-mobilized allogeneic peripheral blood stem cell (PBSC) transplantation for treatment of hematological disorders. All of the transplants were the first allogeneic transplant for the recipient. Twenty patients were transplanted for hematological malignancies (ALL = 8, AML = 6, CML = 4, MDS = 2) and four patients were transplanted for non-malignant disease (thalassemia major = 2, Wiskott-Aldrich syndrome = 1, Kostmann's syndrome = 1). Nineteen donors were HLA-identical siblings, four were HLA-matched or single antigen mismatched parents, and one was a syngeneic transplant. Donors aged 8 to 38 years (median 15 years, 14 donors <18 years) received G-CSF 10 microg/kg/day subcutaneously beginning 4 days before PBSC collection and were submitted to one to three leukapheresis collections. The median CD34+ cell yield was 7.8 x 106 cells/kg recipient body weight. All patients achieved an ANC >0.5 x 109/l after a median of 13 days (range 10-21). Twenty-three patients eventually achieved platelet transfusion independence. One patient died on day 63 without ever achieving platelet transfusion independence. Four patients received platelet transfusions to maintain a platelet count well above 20 x 109/l due to bleeding complications. Of the 19 evaluable patients, the median time to a non-transfused platelet count of 20 x 109/l was 12 days (range 0-44). Ten of 23 at-risk patients developed acute GVHD grades II to IV, with grades III to IV in four patients. Twelve of 19 patients followed for at least 100 days have developed chronic GVHD (extensive = 2, limited = 10) with an actuarial risk of chronic GVHD of 75% at 1 year. The Kaplan-Meier estimate of event-free survival is 65% at 2 years. Four patients died (GVHD = 3, VOD = 1), three patients relapsed, and one patient with thalassemia major had a late graft failure with autologous recovery. Based upon our experience, allogeneic PBSCT is safe for both pediatric donors and recipients and engraftment of neutrophils and platelets is rapid. Bone Marrow Transplantation (2000) 25, 13-18.

Adolescent↗

PubMed2000

Comparison of preparative regimens in transplants for children with acute lymphoblastic leukemia.

PURPOSE: Preparative regimens involving total-body irradiation (TBI) produce significant late toxicities in some children who receive bone marrow transplants, including impaired growth and intellectual development. Busulfan is often used as an alternative to TBI, but there are few data regarding its relative efficacy. PATIENTS AND METHODS: We compared outcomes of HLA-identical sibling transplants for acute lymphoblastic leukemia (ALL) in children (< 20 years of age) who received cyclophosphamide plus TBI (CY/TBI) (n = 451) versus those who received busulfan plus cyclophosphamide (Bu/CY) (n = 176) for pretransplant conditioning. Patients received transplants between 1988 and 1995 and their results were reported to the International Bone Marrow Transplant Registry by 144 participating institutions. The CY/TBI and Bu/CY groups did not differ in gender, immune phenotype, leukocyte count at the time of diagnosis, chromosome abnormalities, remission status, or length of initial remission. T-cell depletion was used more frequently in the CY/TBI group; the Bu/CY group included a higher proportion of children who were less than 5 years of age. The median follow-up period was 37 months. RESULTS: The 3-year probabilities of survival were 55% (95% confidence interval [CI], 50% to 60%) with TBI/CY and 40% (95% CI, 32% to 48%) with Bu/CY (univariate P =.003). The 3-year probabilities of leukemia-free survival were 50% (95% CI, 45% to 55%) and 35% (95% CI, 28% to 43%), respectively (univariate P =.005). In a multivariate analysis, the risks of relapse were similar in the two groups (relative risk [RR], 1.30 for Bu/CY v CY/TBI; P =.1). Treatment-related mortality was higher in the Bu/CY group (RR, 1.68; P =.012). Death and treatment failure (relapse or death, inverse of leukemia-free survival) were more frequent in the Bu/CY group (RR, 1. 39; P =.017 for death; RR, 1.42; P =.006 for treatment failure). CONCLUSION: These data indicate superior survival with CY/TBI conditioning, compared with Bu/CY conditioning, for HLA-identical sibling bone marrow transplants in children with ALL.

Adolescent↗

PubMed2000

Statewide adolescent asthma surveillance.

We assessed the prevalence of diagnosed asthma, wheezing, healthcare utilization, and environmental triggers in children ages 13-14 years, and evaluated the feasibility of statewide asthma surveillance in North Carolina. A cross-sectional study (N = 1,596) was conducted using the International Survey for Asthma and Allergies in Childhood (ISAAC) questionnaire. Ten percent reported current diagnosed asthma. Nineteen percent reported wheezing symptoms with no diagnosis of asthma. Children with frequent wheezing were more likely to be poor, African-American, and female. Thirty percent of diagnosed asthmatics made 1 or more emergency room visits in the last year. Undiagnosed asthmatics were unmedicated. These results highlight the magnitude of the asthma epidemic in early adolescence, and illustrate that statewide surveillance using ISAAC is feasible.

Adolescent↗

PubMed2000

Effects of titles on the processing of text and lexically ambiguous words: evidence from eye movements.

Providing titles for passages improves the comprehension and memorability of text. Titles have generally been thought to facilitate comprehension at later stages of processing. Consistent with prior research, we found that passages presented with titles were better recalled than those without titles. Furthermore, in Experiment 1, the presence of titles led to fewer regressive eye movements, shorter end-of-sentence reading times, and shorter fixation times on target nouns. Experiments 2 and 3, using ambiguous target words, indicated that except when a very infrequent sense of a word is required, titles provide a strong enough context to allow for ambiguous words to be processed as quickly as control words. The results of the three experiments suggest that titles affect processing at both integrative and lexical stages of reading.

Adult↗

PubMed1999

Epidural analgesia during labor and maternal fever.

BACKGROUND: In recent observational studies, epidural analgesia during labor at patient request has been associated with maternal fever. The authors report a secondary analysis of fever in women who were randomized to receive either epidural or patient-controlled intravenous analgesia during labor. METHODS: Maternal tympanic temperature was measured during spontaneous labor in 715 women at term who were randomized to either epidural analgesia with bupivacaine and fentanyl or to patient-controlled intravenous analgesia with meperidine. Intent-to-treat analysis of women with fever (temperature > or = 38.0 degrees C) versus those without was performed using Student t test and Fisher exact test to determine statistical significance (P < 0.05). RESULTS: Epidural analgesia was associated with maternal fever (odds ratio = 4.0; 95% confidence interval = 2.0-7.7), as was nulliparity (odds ratio = 4.1; 95% confidence interval = 1.8-9.1) and labor longer than 12 h (odds ratio = 5.4; 95% confidence interval = 2.9-9.9). These factors were all independent variables for maternal fever when analyzed using logistic regression. CONCLUSIONS: Epidural analgesia is associated with maternal fever. However, nulliparity and dysfunctional labor are also significant cofactors in the fever attributed to epidural analgesia.

Analgesia, Epidural↗

PubMed1998

A randomized study of combined spinal-epidural analgesia versus intravenous meperidine during labor: impact on cesarean delivery rate.

BACKGROUND: Combined spinal-epidural (CSE) analgesia produces rapid-onset pain relief and allows ambulation in early labor. Epidural local anesthetics may contribute to an increase in operative deliveries by decreasing perineal sensation and causing motor weakness. Operative delivery rates might be reduced with CSE, by avoiding or delaying administration of local anesthetics. This study compares the operative delivery rates associated with a CSE technique and those associated with intravenous meperidine for labor analgesia. METHODS: Healthy parturients at full term were assigned randomly to receive CSE or intravenous meperidine analgesia. The CSE group received 10 microg intrathecal sufentanil, followed by epidural bupivacaine and fentanyl at their next request for analgesia. Parturients receiving intravenous meperidine had 50 mg on demand (maximum, 200 mg in 4 h). Labor and delivery outcomes in both groups were recorded and compared. RESULTS: An intent-to-treat analysis of 1,223 women indicated that CSE does not increase the rate of cesarean delivery for dystocia in nulliparous and parous women (CSE, 3.5% vs. intravenous meperidine, 4; P=not significant) or in nulliparous women alone (CSE, 7% vs. intravenous meperidine, 8%; P=not significant). Profound fetal bradycardia that necessitated emergency cesarean delivery within 1 h of the time the mother received sufentanil occurred in 8 of 400 parturients (compared with 0 of 352 who received meperidine; P < 0.01). However, the method of fetal monitoring differed between the two groups. Despite this, neonatal outcomes were similar overall. CONCLUSIONS: Combined spinal-epidural analgesia during labor does not increase the cesarean delivery rate for dystocia in healthy parturient patients at full term, regardless of parity. However, an unexpected increase in the number of cesarean deliveries for profound fetal bradycardia after intrathecal sufentanil was observed. Further investigation is warranted.

Adult↗

PubMed1998

Heterozygosity for Lep(ob) or Lep(rdb) affects body composition and leptin homeostasis in adult mice.

In an effort to understand the genetics of human obesity, we have studied the physiology and molecular genetics of rodent models with monogenetic forms of obesity including the leptin gene-defective (Lep(ob)/Lep(ob)) and leptin receptor gene-defective (Lep(rdb)/Lep(rdb)) mouse. In the experiments reported here, we investigated the effects of heterozygosity at Lep(ob) and Lep(rdb) on body composition and circulating leptin concentration in +/+, Lep(rdb)/+, and Lep(ob)/+ adult mice to identify possible gene dosage effects of these mutations that might elucidate their physiology. Adult mice heterozygous for the Lep(ob) or Lep(rdb) allele had equivalent fat mass and percentage body fat, which was increased 27-47% and 23-35%, respectively, relative to +/+ littermates. Plasma leptin concentrations adjusted for fat mass were 6.5 ng/ml in the Lep(ob)/+, 9.6 ng/ml in the +/+, and 11.5 ng/ml in the Lep(rdb)/+ mice. Sex had no effect on plasma leptin after controlling for fat mass. These data, and data from a small number of mice heterozygous at both Lep(ob) and Lep(rdb) (compound heterozygotes), suggest that leptin protein produced per mass of body fat is reduced in Lep(ob)/+ mice and that body fat is increased in Lep(ob)/+ mice until plasma leptin concentrations reach that of a normal +/+ mouse. The elevated plasma leptin concentration in the Lep(rdb)/+ mice suggests that LEPR may mediate autocrine suppression of Lep expression. These results raise the possibility that human mutations that have even subtle effects on the leptin/leptin receptor system in either the homozygous or heterozygous state may have significant effects on adiposity.

Adipose Tissue↗

PubMed1998

Substance abuse and the course of welfare dependency.

OBJECTIVES: New provisions in welfare reform target recipients with addictions, even though there is limited research on how substance abuse affects people's experiences on welfare. This prospective study examined substance abuse as a determinant of subsequent welfare dependency. METHODS: Representative samples of clients on Aid to Families with Dependent Children (AFDC) and general assistance in a California county were interviewed while applying for services in 1989 and were reinterviewed in 1995. RESULTS: Among AFDC recipients, substance abuse was not a significant determinant of long welfare stays, repeat welfare use, or the total time a person remained on welfare during the 6-year period. However, substance abuse was a strong predictor of repeat welfare use among general assistance recipients. CONCLUSIONS: Alcohol and drug problems have played dramatically different roles in welfare dependency within the AFDC and general assistance populations. Under welfare reform, local general assistance programs will be the final safety net for recipients removed from federal entitlement programs. These programs will probably be confronted with clients with more complex disabilities related to addiction, as well as with greater family needs for cash assistance.

Adult↗

PubMed1998

Expertise as mental set: the effects of domain knowledge in creative problem solving.

Experts generally solve problems in their fields more effectively than novices because their well-structured, easily activated knowledge allows for efficient search of a solution space. But what happens when a problem requires a broad search for a solution? One concern is that subjects with a large amount of domain knowledge may actually be at a disadvantage, because their knowledge may confine them to an area of the search space in which the solution does not reside. In other words, domain knowledge may act as a mental set, promoting fixation in creative problem-solving attempts. A series of three experiments in which an adapted version of Mednick's (1962) remote associates task was used demonstrates conditions under which domain knowledge may inhibit creative problem solving.

Achievement↗