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Biomedical subjects

L Mullen

Publications and source records attributed to L Mullen.

At least 19 recordsLinked to original sources
PubMed2003

Changes in lipophorins are related to the activation of phenoloxidase in the haemolymph of Locusta migratoria in response to injection of immunogens.

In Locusta migratoria, activation of phenoloxidase in the haemolymph in response to injection of laminarin is age-dependent: being absent in fifth instar nymphs and newly emerged adults, and only becoming evident four days after the final moult. This pattern of change in phenoloxidase activation correlates with the pattern of change in the concentration of apolipophorin-III (apoLp-III) in the haemolymph. Injection of a conspecific adipokinetic hormone (Lom-AKH-I) has no effect on the phenoloxidase response in nymphs or newly emerged adults but, in adults older than four days, co-injection of the hormone with laminarin prolongs the activation of phenoloxidase in the haemolymph: a similar enhancement of the response to laminarin is observed in locusts that have been starved for 48 h but not injected with AKH-I. During most of the fifth stadium, injection of laminarin results in a decrease in the level of prophenoloxidase in the haemolymph; an effect that is not observed in adults of any age. Marked changes in the concentration of apoLp-III, and the formation of LDLp in the haemolymph, are observed after injection of laminarin (or LPS) and these are remarkably similar, at least qualitatively, to those that occur after injection of AKH-I. The involvement of lipophorins in the activation of locust prophenoloxidase in response to immunogens is discussed.

Animals↗
PubMed2002

Choroid plexus cysts in the mid-trimester fetus--practical application suggests superiority of an individualized risk method of counseling for trisomy 18.

OBJECTIVES: Analysis of a referral population of patients with choroid plexus cysts (CPCs) was performed to compare an average risk method of counseling to an individualized risk method. METHODS: A total of 395 patients referred to a Prenatal Diagnosis Center were included, of whom 341 had isolated CPCs and 54 had associated ultrasound abnormalities. For isolated CPCs, an average risk of 1/150 for aneuploidy was compared to an individualized risk assessment [prior risk as determined by maternal age or serum screening multiplied by the likelihood ratio established by Gupta et al. (1997)]. Accuracy, cost, and procedure-related losses were assessed. RESULTS: Both methods resulted in 100% sensitivity. The individualized method resulted in greater specificity, decreased costs, and (theoretically) fewer procedure-related pregnancy losses. CONCLUSIONS: An individualized risk method of counseling utilizing the likelihood ratios established by Gupta et al. (1997) was superior to an average risk method for assessing trisomy 18 risk in the setting of CPC detected in mid-trimester.

Adult↗
PubMed2001

Ras/MEK but not p38 signaling mediates NT-3-induced neurite extension from spiral ganglion neurons.

Neurotrophin (NT)-3 is expressed in the neuronal target tissue of the developing rat cochlea and has been shown to promote the survival and neurite outgrowth of spiral ganglion (SG) neurons, suggesting a role for this protein during the innervation of the organ of Corti. In other neurons, NT-3 can mediate neuritogenesis and survival via a number of intracellular signal pathways. To date, the intracellular transduction pathways involved in the mediation of NT-3 effects have not been investigated in SG neurons. To determine whether the activities of NT-3 on SG neurons are dependent on the activation of mitogen-activated protein kinase kinases (MEK)/extracellular-signal-regulated kinases (ERK), Ras, and/or p38, SG explants from postnatal-day 4 rats were cultured with NT-3 and increasing concentrations of the MEK inhibitor U0126, the Ras farnesyl-transferase inhibitor (FTI)-277, and the p38 inhibitor SB203580. After fixation and immunocytochemical labeling, neurite growth was evaluated. A dose-dependent decrease of the effects of NT-3 on length and number of processes was observed in the U0126- and FTI-277-treated SG neurons. In contrast, SB203580 had no significant effect on NT-3-mediated stimulation of neurite growth, in terms of either number or length. The results suggest that NT-3 effects on SG neurons are mediated primarily by the Ras/MEK/ERK signaling pathway.

Animals↗
PubMed2001

An analysis of 15-19-year-old first attenders at the Dublin Needle Exchange, 1990-97.

AIMS: Identification of characteristics and trends over time in young injecting drug users at first attendance at needle exchange. DESIGN: Retrospective cross-sectional survey of routinely collected data. SETTING: Dublin needle exchange programme which consists of 11 sites in the greater Dublin area. PARTICIPANTS: First-time attenders (n = 1224) at the needle exchange from 1990 to 1997, between the ages of 15 and 19. MEASUREMENT: Factors associated with a likelihood of needle sharing and condom use were tested using logistic regression. FINDINGS: Increases in both the number and proportion of young injectors, particularly young female injectors, have occurred over the 8 years. Forty-eight per cent of the young injectors were injecting for less than 1 year. Needle sharing prevalence in the year previous to first attendance was 39% and condom use was 61%. The proportion of females not using a condom during sexual relationships was significantly higher than males. Very few of the young attenders had received any treatment for drug dependence. CONCLUSIONS: After the first year of injecting drug use the likelihood of needle sharing increased and we recommend that interventions occur early on and are targeted to the needs of young injecting drug users, in particular young females. It is essential that services are accessible to the young injecting drug user and that barriers to contact with services are minimized or eliminated. Some high-risk behaviours are occurring in the context of the sexual relationship and this should be taken into account when designing prevention programmes, especially for young females.

Adolescent↗
PubMed2000

Modification of general practitioner prescribing of antibiotics by use of a therapeutics adviser (academic detailer).

AIMS: This was a pilot study of the use of a clinical pharmacist as a therapeutics adviser (academic detailer) to modify antibiotic prescribing by general practitioners. METHODS: Following a visit by the adviser (March-May), 112 general practitioners were recruited and randomised to control or active groups. A panel of experts prepared a best practice chart of recommended drugs for upper and lower respiratory tract infections, otitis media and urinary tract infections. The adviser made a 10-15 min visit to each prescriber in the active group (June-July), gave them the chart and discussed its recommendations briefly. Doctors in the control group were not visited nor given the chart. Prescription numbers for all prescribers were obtained from the Commonwealth Health Insurance Commission for the pre(March-May) and postdetailing (August-September) periods using a three month lag time for data collection. Data for total numbers of prescriptions and for selected individual antibiotics used in these two periods were analysed using nonparametric statistics. RESULTS: Prescribing patterns were similar for the control and active groups in the predetailing period. For both groups, there were significant (P<0.03) increases (45% for control and 40% for active) in total number of antibiotic prescriptions in the post compared with the predetailing period. This trend was anticipated on the basis of the winter seasonal increase in respiratory infections. In line with the chart recommendations for first-line treatment, doctors in the active group prescribed significantly more amoxycillin (P<0.02) and doxycycline (P<0.001) in the post vs predetailing periods. By contrast, doctors in the control group prescribed significantly more cefaclor (P<0.03) and roxithromycin (P<0.03), drugs that were not recommended. The total cost of antibiotics prescribed by doctors in the control group increased by 48% ($37 150) from the preto postdetailing periods. In the same time period, the costs for the active group increased by only 35% ($21 020). CONCLUSIONS: We conclude that the academic detailing process was successful in modifying prescribing patterns and that it also decreased prescription numbers and costs. Application of the scheme on a nationwide basis could not only improve prescriber choice of the most appropriate antibiotic but also result in a significant saving of health care dollars.

Anti-Bacterial Agents↗
PubMed1998

Characterization of a tight molecular complex between integrin alpha 6 beta 4 and laminin-5 extracellular matrix.

In many adult epithelia, e.g., epidermis or intestine, adhesion of epithelial cells to basement membrane requires the integrin alpha6 beta4 and laminin-5 (Ln-5). In the absence of one or the other, extensive blistering and exfoliation occur. While alpha6 beta4 was reported to be a receptor for Ln-5, this interaction is poorly understood. We characterize complexes between alpha6 beta4 and Ln-5 in cell-free preparations of extracellular matrix (ECM) from the epithelial cell line, 804G. By microsequencing, Ln-5 and alpha6 beta4 were the major proteins in this ECM and were likely engaged in receptor/ligand complexes because, by immunofluorescence, alpha6 beta4 was colocalized with Ln-5 both in cell monolayers and in cell-free ECM preparations, but they disappeared after preincubation of the monolayers with alpha6 beta4 or Ln-5 function-blocking antibodies. The alpha6 beta4/Ln-5 complexes were resistant to dissociation by extreme pH, urea, chaotropes, eDTA, non-ionic detergents, and b-mercaptoethanol. They were only dissociated by strong anionic detergents, e.g., 1% SDS, suggesting receptor/ligand interactions based on high affinity or avidity. We propose that these alpha6 beta4/Ln-5 complexes may provide links between plasma membrane and basement membrane that resist mechanical stress and support epithelial integrity.

Amino Acid Sequence↗
PubMed1998

A North Carolina macular dystrophy phenotype in a Belizean family maps to the MCDR1 locus.

PURPOSE: To describe the clinical findings of an autosomal dominant macular dystrophy in a family of Mayan Indian ancestry in Belize, Central America, and to determine its molecular genetic relationship with the original North Carolinian family. METHODS: We performed comprehensive ophthalmic examinations on 56 members of a single family living in Chicago, Illinois, and Belize, Central America. Fundus photography and fluorescein angiography were performed on 17 affected subjects and six affected family members were serially examined over a 12-year period. Blood was collected from 26 individuals, and DNA was extracted for genotyping. Two-point linkage, multipoint linkage, and haplotype analysis was performed. RESULTS: In 17 affected individuals, the clinical features were consistent with the diagnosis of North Carolina macular dystrophy. Multipoint linkage analysis generated a peak lod score of 5.6 in the MCDR1 region. The haplotype associated with the disease was, however, different from that of the original North Carolinian family. CONCLUSIONS: This family has an autosomal dominant macular dystrophy that is clinically indistinguishable from North Carolina macular dystrophy (MCDR1). Our findings indicate that the mutated gene in this Belizean family maps precisely to the same region as that of the North Carolina macular dystrophy (MCDR1) locus. This study provides evidence that MCDR1 occurs in various ethnic groups and that there is no evidence of genetic heterogeneity.

Adolescent↗
PubMed1997

North Carolina macular dystrophy phenotype in France maps to the MCDR1 locus.

PURPOSE: To determine if a family in France, which manifests an autosomal dominant macular dystrophy, has North Carolina macular dystrophy (MCDR1) and to determine its possible molecular genetic relationship with the original North Carolina family. METHODS: A family from Northern France with a macular dystrophy underwent comprehensive ophthalmic examinations and were ascertained for genetic studies. Blood collection and examinations were performed on 38 individuals. Fundus photographs with a hand held KOWA camera were obtained on affected subjects. DNA was extracted and genotyping performed using new microsatellite genetic markers, which have recently been found in the MCDR1 (North Carolina macular dystrophy) region. Standard two - point linkage and haplotype analysis was performed. RESULTS: Eleven individuals were found with the clinical manifestations of North Carolina macular dystrophy. Two - point linkage analysis generated a maximum peak LOD score of 4.5 with a recombination of 0% between D6S1717 and the macular dystrophy locus in the French family. The haplotype associated with the disease is, however, different from that of the original North Carolina family. CONCLUSIONS: These findings indicate that the macular dystrophy gene in this French family maps to the same region as that of North Carolina macular dystrophy (MCDR1) locus but that independent mutations are involved. The disease in the French family is clinically and genetically similar to North Carolina macular dystrophy. Therefore MCDR1 occurs in various ethnic groups, is present world-wide, and there remains no evidence of genetic heterogeneity for this clinically distinct form of macular degeneration.

Adolescent↗
PubMed1997

The retina: genetic studies of several retinopathies located on the short arm of chromosome 17.

The short arm of chromosome 17 has emerged as a hot spot where several phenotypically distinct retinal disorders have been mapped in the past year. An autosomal dominant retinitis pigmentosa, Leber's congenital amaurosis, autosomal dominant cone degeneration, central areolar choroidal dystrophy and Sjogren-Larsson syndrome were all recently mapped to chromosome 17p. These disorders, their genetic linkage, possible candidate genes and the possibility that several of these disorders may share candidate genes are discussed.

Chromosome Aberrations↗
PubMed1996

Mapping of Reis-Bücklers' corneal dystrophy to chromosome 5q.

PURPOSE: Recently several autosomal dominant corneal stromal dystrophies have been mapped to chromosome 5q. Therefore, we tested whether Reis-Bücklers' corneal dystrophy, an autosomal dominant trait, was also linked to the same region. METHODS: Five generations of a single family with Reis-Bücklers' corneal dystrophy were ascertained. Twenty-two family members were examined, and 11 were found to be affected. Blood was obtained for genetic linkage analysis. RESULTS: Several genetic markers on chromosome 5q were strongly suggestive of linkage or confirmed linkage (LOD score > 3.0). Multipoint analysis generated a maximum LOD score of 4.25 between D5S414 and IL-9. CONCLUSIONS: Reis-Bücklers', lattice type 1, Avillino, and granular corneal dystrophies all map to the same genetic locus. This suggests that one of the following might be true: (1) that a corneal gene family exists in this region; (2) that these corneal dystrophies represent allelic heterogeneity (that is, different mutations within the same gene manifest as different phenotypes); or (3) that these are all the same disease.

Basement Membrane↗
PubMed1996

Mapping of autosomal dominant cone degeneration to chromosome 17p.

PURPOSE: We studied a single, large family with autosomal dominant cone degeneration in order to map the disease-causing gene. METHODS: Seventy-three individuals in this family were examined, and 34 were found to be affected. Blood samples from 34 affected and unaffected family members were obtained for DNA analysis and linkage mapping. Fifty-three genetic markers were analyzed in this family by using short tandem repeat markers. These markers were primarily in candidate genomic regions. RESULTS: Marker D17S796 generated a significantly positive LOD score of 4.21 (theta = .04; 10,000:1 odds in favor of linkage). Marker D17S513 gave a significant LOD score of 3.1 (theta = .096; 1,000:1 odds in favor of linkage). Other markers in the region generated suggestive findings, such as D17S786, with a LOD score of 2.7, and D17S945, with a LOD score of 2.41. CONCLUSIONS: Our results indicate that a genetic defect that causes autosomal dominant cone degeneration is located on chromosome 17p in the region of recoverin. Recoverin, a retinal expressed gene, is an appealing candidate for this disease.

Adolescent↗
PubMed1996

Exceptionally high seizure threshold: ECT device limitations.

Three patients had exceptionally high seizure threshold, as determined by an empirical titration procedure. Initial seizure threshold was 896 mC in two of the patients. The third patient had an initial threshold of 336 mC that increased to 840 mC at the end of the course of electroconvulsive therapy (ECT), and remained elevated during a second course of ECT. All three patients were elderly men with complicated medical histories and ongoing low-dose benzodiazepine use. Each patient had an excellent response to ECT delivered with a custom modified device, capable of delivering more than twice the charge of ECT devices presently commercially available in the United States. Implications for the administration of ECT in patients with exceptionally high seizure threshold and the limitations of current device output are discussed.

Aged↗
PubMed1995

Blepharophimosis syndrome is linked to chromosome 3q.

Blepharophimosis syndrome (BPES, blepharophimosis eyelid syndrome) is a distinctive congenital eyelid malformation which can occur sporadically or be inherited in an autosomal dominant fashion. Previous reports have described associated cytogenetic abnormalities on chromosome 3q. We have ascertained and sampled two BPES families with apparent autosomal dominant inheritance and have tested for linkage with 17 polymorphic markers on 3q. Multipoint analysis generated a maximum LOD score of 3.23 using the markers RHO, ACPP and D3S1238. No evidence of genetic heterogeneity was observed. These studies provide the first non-cytogenetic evidence that a defective gene responsible for BPES is located on 3q22.

Blepharophimosis↗
PubMed1995

Compulsive and impulsive symptomatology in trichotillomania.

Although classified as a disorder of impulse control, trichotillomania (hair pulling) may have some phenomenological overlap with obsessive-compulsive disorder (OCD). The question arises as to whether trichotillomania is best conceptualized as a disorder characterized by impulsivity or compulsivity. Impulsive and compulsive symptoms and traits were compared in 43 patients who presented for treatment of trichotillomania, OCD or impulsive personality disorder. Trichotillomania patients had significantly lower scores of obsessive-compulsive symptoms than OCD patients, and significantly higher impulsiveness scores than this group. Measures of aggression did not differ significantly between groups.

Adult↗
PubMed1995

Safety of a freestanding surgical unit for the assisted reproductive technologies.

OBJECTIVE: To determine the safety of a freestanding surgical unit for assisted reproductive technology (ART), using the rate of unplanned admissions to a hospital within 24 hours of surgery. DESIGN: Prospective. SETTING: A freestanding surgical unit within a medical office building. PATIENTS: A mixture of private and university-referred patients undergoing 6,776 ART surgical procedures. MAIN OUTCOME MEASURES: Patients admitted during the first 24 hours of surgery were recorded and hospital progress was monitored for invasive procedures, treatments, time of discharge, and residual complications. Variables tabulated included age, fertility diagnosis, ART procedure, E2 level, number of follicles by ultrasound, previous surgery, and type of anesthesia. RESULTS: There were 11 hospital admissions (0.16%). Four patients required surgery: one laparoscopy and three laparotomies. Admissions after vaginal oocyte retrieval were no different from those after GIFT via laparoscopy, 0.16% versus 0.18%, respectively. The number of admissions after monitored anesthesia care was higher than expected compared with general anesthesia. Profiles of hospitalized patients showed no apparent differences from the nonhospitalized patients. CONCLUSIONS: Surgical procedures for ART performed in a freestanding surgical unit can be performed safely with a low hospitalization rate and minimal morbidity.

Female↗
PubMed1991

Obsessive compulsive disorder, depression, and fluoxetine.

BACKGROUND: Fluoxetine, a selective serotonin reuptake blocker, is an antidepressant medication that has also been shown in open clinical trials and one controlled trial to be effective in the treatment of obsessive compulsive disorder (OCD). OCD is often complicated by depression, and depressive symptoms may interfere with response to both pharmacologic and behavioral treatments. METHOD: We describe pilot data from 10 outpatients who met DSM-III-R criteria for OCD in whom the possibility of a depressive reaction or lack of antidepressant response occurred during an open trial of fluoxetine. RESULTS: Rapid increase in fluoxetine dose to high doses was associated with depressive symptoms in 6 patients. In 8 patients, improvement in depression was associated with addition of a tricyclic antidepressant to fluoxetine treatment. In 5 patients, both OCD and depressive symptoms improved when the patient was switched to the partially selective serotonin reuptake blocker clomipramine. CONCLUSION: This paper serves to alert clinicians to the possibility of a depressive reaction, or lack of antidepressant response, to fluoxetine in OCD patients. This possibility can only be resolved scientifically by adequately controlled experimental trials. If depression occurs, combined fluoxetine and tricyclic treatment, or a switch to a partially selective serotonin reuptake inhibitor, may be helpful. Special considerations and side effects of combined fluoxetine-tricyclic treatment are described.

Adolescent↗