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Biomedical subjects

M Maguire

Publications and source records attributed to M Maguire.

At least 19 recordsLinked to original sources

The mouse GalR2 galanin receptor: genomic organization, cDNA cloning, and functional characterization.

The diverse physiological actions of galanin are thought to be mediated through activation of galanin receptors (GalRs). We report the genomic and cDNA cloning of a mouse GalR that possesses a genomic structure distinct from that of GalR1 and encodes a functional galanin receptor. The mouse GalR gene consists of two exons separated by a single intron within the protein-coding region. The splicing site for the intron is located at the junction between the third transmembrane domain and the second intracellular loop. The cDNA encodes a 370-amino acid putative G protein-coupled receptor that is markedly different from human GalR1 and rat GalR3 (38 and 57%) but shares high homology with rat GalR2 (94%). In binding studies utilizing membranes from COS-7 cells transfected with mouse GalR2 cDNA, the receptor displayed high affinity (K(D) = 0.47 nM) and saturable binding with 125I-galanin (Bmax = 670 fmol/mg). The radioligand binding can be displaced by galanin and its analogues in a rank order: galanin approximately = M40 approximately = M15 approximately = M35 approximately = C7 approximately = galanin(2-29) approximately = galanin(1-16) >> galanin(10-29) approximately = galanin(3-29), which resembles the pharmacological profile of the rat GalR2. Receptor activation by galanin in COS-7 cells stimulated phosphoinositide metabolism, which was not reversed by pertussis toxin. Thus, the galanin receptor encoded in the cloned mouse GalR gene is the type 2 galanin receptor and is active in both ligand binding and signaling assays.

Amino Acid Sequence

Vision screening of preschool children: evaluating the past, looking toward the future.

Vision problems of preschool children are detectable with a comprehensive eye examination; however, it is estimated that only 14% of children below the age of 6 years receive an eye examination. Screening is advocated as a cost-effective alternative to identify children in need of further vision care. Thirty-four states recommend or require vision screening of preschool children. Although laws and guidelines exist, only 21% of preschool children are actually screened for vision problems. There is little agreement concerning the best screening methods, and no validated, highly effective model for screening vision of preschool children. Newer screening tests have been designed specifically for preschool populations, and can be administered by lay screeners. Many have not been validated. Several are recommended by states or organizations without convincing scientific evidence of their effectiveness. This paper summarizes current laws and guidelines for preschool vision screening in the United States, reviews advantages and disadvantages of several test procedures, and provides recommendations for developing future preschool vision screening programs.

Child, Preschool

Prognostic factors for survival after enucleation for choroidal melanoma.

To evaluate the prognostic value of DNA content-ploidy, agoraphilic nucleolar organizing regions (AgNORs) and proliferating cell nuclear antigen (PCNA) for survival among patients with choroidal melanoma choroidal melanomas managed by enucleation in 55 patients with a follow-up of 5 years were studied. AgNor counts were evaluated by two examiners after sections were specifically processed. Immunohistochemistry was performed to evaluate PCNA expression. Kaplan-Meier estimation of survival curves, the log-rank test, and Cox regression analysis were used to compare survival according to the above mentioned factors. Five years after enucleation 62% of patients had died. Patients with spindle cell type melanomas had the best and those with epithelioid cell type had the worst survival (p=0.004). Patients with small tumors had better survival than those with medium or large tumors (p=0.02). Patients having tumors with aneuploid nuclear DNA content had worse survival than those having tumors with diploid DNA content (p=0.004). A high PCNA level correlated with lower survival rates (p=0.02). Patients having a high AgNor count had a worse survival than those with lower counts (p=0.02). DNA content, PCNA level, and AgNOR count each showed a clinically significant influence on patient survival. However, each of these new evaluated prognostic factors was strongly related to one or both of the classic prognostic factors. It is therefore difficult to separate the effects of the two categories of prognostic factors. Results of the Cox regression analysis suggested that these newer evaluated prognostic factors provided little additional information about patient prognosis.

Adult

Domestic Aedes aegypti breeding site surveillance: limitations of remote sensing as a predictive surveillance tool.

This project tested aerial photography as a surveillance tool in identifying residential premises at high risk of Aedes aegypti breeding by extending the use of a recently developed, ground-based, rapid assessment technique, the modified Premise Condition Index (PCI2). During 1995, we inspected 360 premises in Townsville, Australia for Ae. aegypti breeding, and PCI2 scores were recorded. The PCI2 values were also estimated from 1:3,000 color and infrared aerial photograph interpretation for the same premises. We found that shade levels can be accurately identified from both color and infrared images, and the PCI2 can be accurately identified from infrared photographs. Yard conditions, however, cannot be accurately identified from either aerial photograph type. The airborne PCI2 did not significantly correlate with breeding measures, and logistic regression further demonstrated that neither aerial photograph type allows the accurate prediction of Ae. aegypti breeding risk. Therefore, the ability of low-level aerial photography to enhance Ae. aegypti breeding site surveillance is at present limited, with ground surveillance remaining our most reliable tool for identifying the probability of Ae. aegypti breeding in the residential environment.

Aedes

Electrophysiological effects of long, linear atrial lesions placed under intracardiac ultrasound guidance.

BACKGROUND: A curative atrial fibrillation procedure will most likely rely on creating transmural linear ablative lesions. However, it is currently unknown whether endocardial radiofrequency lesions can create lines of conduction block. METHODS AND RESULTS: In six pigs, intracardiac echocardiography was used to guide the positioning of multiple coil array catheters to bridge endocardial structures in three right atrial locations: (1) from the crista terminalis to the tricuspid annulus; (2) from the fossa ovalis to the crista terminalis; and (3) from the inferior vena cava to the tricuspid annulus. Once the catheter was positioned, linear lesions were made by radiofrequency energy applied sequentially to each of the four coils. After 15 days, the chest was opened and a 112-electrode epicardial plaque was positioned over the atrial free wall lesion to determine activation patterns. Three lesions were placed in each animal, with a mean procedure time of 47+/-11 minutes. Once adequate contact was determined by intracardiac echocardiography, a single series of radiofrequency application was required to achieve tissue heating (65+/-4 degrees C) with a power of 21+/-10 W. Epicardial mapping demonstrated complete conduction block across the lesions in all animals, with split potentials and disparate activation times (64+/-16 ms) across the lesion. At autopsy, all lesions were discrete, continuous, and without evidence of charring. The lesions were within 0.3+/-0.5 mm of their targeted anatomic locations and measured 21+/-4 mm long and 2.8+/-0.6 mm wide. Histology revealed transmural fibrosis throughout the length of each lesion. CONCLUSIONS: Linear lesions that are electrophysiologically transmural and continuous can be placed in the right atrium of normal pigs. With intracardiac echocardiography, adequate tissue contact over several coil electrodes can be ensured, resulting in short procedure times, efficient energy application, and accurate anatomically linked lesion placement.

Animals

Serial changes in cardiac output during normal pregnancy: a Doppler ultrasound study.

OBJECTIVES: To determine the direction and magnitude of change in cardiac output (CO) during pregnancy. STUDY DESIGN: We performed serial measurements of CO on five occasions from 24 weeks gestation to term and once during the puerperium in 26 normal pregnancies (156 measurements) using Doppler ultrasound measurement of flow velocity profiles and aortic root cross sectional area. RESULTS: CO increased to 7.0 l/min by 32 weeks gestation, 49% above baseline values. It fell to 5.7 l/min by term, 21% above baseline. The peak in CO corresponded with an increase in heart rate to 91 beats/min, 32% above baseline. Stroke volume peaked at 36 weeks gestation, by which time CO had already begun to decline. CONCLUSIONS: CO increased in a linear fashion until 32 weeks gestation and then declined to term, but to a value still greater than the postpartum baseline. These findings have obvious management implications for patients with serious heart disease complicating pregnancy.

Blood Pressure

Cigarette smoking and risk for progression of nuclear opacities.

OBJECTIVE: To examine the relationships between smoking and the 5-year incidence of new nuclear opacities and between smoking and the progression of nuclear opacities in a prospective study of a cohort of Chesapeake Bay watermen. METHODS: A total of 442 men (age, > or = 30 years in 1985) with paired, gradable lens photographs in at least one eye in both 1985 and 1990 were studied. Photographs were graded by two readers who used the grading scheme of the Wilmer Institute, Baltimore, Md, with severity ranging in decimal units between 0.0 and 4.0. Data on the smoking history of the subjects were collected by personal interviews that were conducted in 1985 and updated in 1990. RESULTS: The incidence and progression of opacities increased with age. A nonsignificant association was observed between smoking (for both current and ex-smokers) and the incidence of a nuclear opacity. The risk of progression of nuclear opacities of less than grade 3 at baseline to grade 3 or worse was 2.4-fold higher among current smokers in 1985, compared with that among ex-smokers and nonsmokers (95% confidence limits: 1.0, 6.0) after adjustment for age, baseline opacity status, and alcohol use. An 18% increased risk of progression was significantly associated with each pack-year that a subject smoked between 1985 and 1990. CONCLUSION: These data confirm previous findings that smoking is associated with a nuclear opacity, particularly with progression to severe opacities.

Adult

Cortical lenticular opacification: distribution and location in a longitudinal study.

PURPOSE: To examine the distribution of cortical opacification of the lens by lens quadrant in a longitudinal study. METHODS: In 1990, a follow-up assessment of a cohort of Chesapeake Bay watermen, initially studied in 1985, was performed. Four hundred thirty-seven subjects (834 eyes) had gradable cortical photographs for at least one eye in both 1985 and 1990. Cortical photographs were graded by both estimating total area and determining the quadrant with the greatest degree of cortical opacification. RESULTS: The prevalence and severity of cortical opacification increased with age with a high degree of concordance (84%) between eyes. For the 47 eyes with cortical opacification > or = 1/8 at baseline, the principal locations of opacification were: inferonasal 63.8%, inferotemporal 17.0%, superonasal 6.4%, and superotemporal 12.8% (P < 0.001, compared with equal distribution by quadrant). Five-year development of new cortical opacification and five-year progression of existing cortical opacification showed even greater preferential occurrence in the inferonasal quadrant of the lens. CONCLUSIONS: In this population, the inferonasal quadrant of the lens is the principal site of cortical opacification in both cross-sectional and longitudinal assessment. This finding is consistent with the hypothesis that sunlight exposure is a significant risk factor for cortical opacification.

Adult

Impact of diagnosed depression and self-reported mood on mothers' control strategies: a longitudinal study.

Control strategies of 70 well and depressed mothers were assessed twice: when their children were of toddler age (Time 1) and, for 39 of the mothers, when their children were 5 (Time 2). At Time 1 well mothers were more direct with their children, using more direct commands and reprimands, and fewer explanations than depressed mothers. At Time 2 well mothers used fewer direct commands than depressed mothers. Self-reported negative mood preceding the interaction in well mothers was associated with decreased directness at Time 1 but increased directness at Time 2. At Time 1 depressed mothers' negative mood was associated with a decrease in the use of explanations. All mothers used more unclear commands and fewer reprimands and positive incentives with their 5-year-olds than when the children were toddlers. Depressed mothers, but not well mothers, increased their use of direct commands when the children were older. The findings are interpreted in the context of complex interplay between mother's diagnosis of depression, self-reported mood preceding the interaction, and the developmental level of the child.

Anger

Give me a break--benefits of a caregiver support service.

Caregivers of elderly adults experience problems with self-image, stress levels, and the patient-relative relationship. Caregivers often receive relief only when the elderly adult is hospitalized. This study found a reduction in anxiety and suspicious behavior in caregivers, but helplessness was not reduced. Regular psychological evaluation may provide warning signs of the need for a period of relief for the caregiver. Further research is needed to determine which specific behaviors result in high stress for caregivers.

Aged

Complete remission in acute promyelocytic leukemia despite persistence of abnormal bone marrow promyelocytes during induction therapy: experience in 34 patients.

Thirty-four patients with acute promyelocytic leukemia (APL) (median age 37 years, range 20 to 69 years) received induction treatment between 1974 and 1985 with cytosine arabinoside (ara-C) and an anthracycline. Bone marrow hypercellularity was present at the time of diagnosis in all patients, although the median peripheral leukocyte count was 2,600/microL. A second course of induction therapy consisting of further ara-C and anthracycline was initiated 15 days after the start of treatment if bone marrow hypocellularity could not be documented. Karyotypic analysis of bone marrow blasts was performed on 15 of 34 patients; 11 of 15 had abnormalities in chromosomes 15 and/or 17. Twenty-nine of 34 (85%) patients had laboratory evidence of disseminated intravascular coagulopathy. Of the 29 patients surviving 14 days, 24 (83%) received a second course of induction therapy. Complete remission was achieved in 25 of 34 (74%) patients, with four of 25 (16%) requiring one course of induction chemotherapy and 21 of 25 (84%) receiving two courses. Bone marrow specimens obtained 15 days after the start of therapy from the 25 patients who eventually attained complete remission showed the continued presence of dysplastic promyelocytes in 21 cases; three specimens were technically inadequate and only one was truly devoid of promyelocytes. Seventeen of 25 (68%) patients still had persistence of abnormal bone marrow promyelocytes seven or more days after the second course of therapy. Patients in complete remission received various forms of postremission therapy. Ten of the 25 (40%) completely responding patients remain alive in continuous complete remission. Neither the absence of bone marrow hypocellularity nor the persistence of dysplastic promyelocytes during induction exerted any influence on the probability for survival. These findings confirm and extend prior reports that complete remission in APL, in contrast to other subtypes of acute nonlymphocytic leukemia (ANLL), can frequently be achieved without bone marrow aplasia. Whether this observation signifies that complete remission in APL is due to leukemic cell differentiation or selective cytotoxicity is unknown. The absence of therapy-induced bone marrow hypoplasia in APL is not an absolute indication of induction failure or a poor ultimate prognosis.

Acute Disease

Aldosterone responsiveness to metoclopramide in hyperprolactinaemia.

Basal serum aldosterone levels in 13 hyperprolactinaemic females did not differ significantly from those of nine control individuals. There was increased responsiveness of circulating aldosterone levels to the long acting dopamine antagonist metoclopramide (10 mg intravenously) in the hyperprolactinaemic patients as compared with the controls. Prolactin responsiveness to metoclopramide was reduced in the patients as compared with the controls, such being considered characteristic of a prolactinoma. Basal serum thyrotrophin (TSH) levels, although within the euthyroid range, were increased in the patients as compared with the controls. There was no significant difference in the TSH responsiveness to metoclopramide between the study groups. However, in the five patients with exaggerated responses of TSH to metoclopramide, basal TSH levels were significantly higher than in the other patients. One explanation for these results is that prolactin can directly or indirectly modulate the aldosterone response to metoclopramide.

Aldosterone

Is heparin administration necessary during induction chemotherapy for patients with acute promyelocytic leukemia?

The role of heparin in the treatment of the disseminated intravascular coagulation (DIC) associated with acute promyelocytic leukemia (APL) remains unclear. Between 1974 and 1985, we treated 27 patients with APL using four different chemotherapeutic regimens; 23/27 (85%) had evidence of DIC either at presentation or following the initiation of induction chemotherapy. The coagulopathy was treated primarily with fresh frozen plasma and platelet transfusions; only 2/27 (7%) patients received heparin. Twenty of 27 patients (74%) entered complete remission. Major bleeding or thrombotic complications occurred in 5/27 patients (19%), but 2 of these 5 patients presented after hemorrhage had already occurred. None of the 5 patients with bleeding or thrombosis entered complete remission. All of the hemorrhagic complications due to DIC in our study occurred before 1979, which may reflect changes in the management of leukemic patients. This observation emphasizes the risks inherent in the use of historical controls in this population. In conclusion the DIC associated with APL can be successfully treated with intensive blood product support without the use of heparin.

Adult

A case-control study of dietary intake of renal stone patients. II. Urine biochemistry and stone analysis.

The dietary intakes of 88 renal stone cases and 88 age and sex matched controls were assessed by dietary history using a standardised questionnaire. The stone cases were divided into six subgroups established on the basis of urine biochemistry (calcium, oxalate and uric acid) and stone composition. The average intake of each group was then compared with that of their controls using standard statistical procedures. Cases with idiopathic calcium oxalate stones had significantly lower intakes of dietary fibre, non-cellulose polysaccharide, phytate, magnesium, phosphate and thiamine than controls. No significant difference in dietary intake was found between cases with high urinary calcium and uric acid and their respective controls. All cases with a high urinary oxalate had a significantly higher intake of vitamin C than controls. Our results support the belief that dietary intake is an important pre-urinary risk factor of idiopathic renal stone disease.

Calcium

The Markov process as a general method for nonparametric analysis of right-censored medical data.

The product limit method of Kaplan and Meier for estimating survival functions and the logrank test of Mantel are widely employed for analysis of longitudinal medical data. Developed for analysis of one-time events such as death, survival analysis is also commonly adapted to more complex states such as loss of vision or cancer remission by restricting analysis to first occurrences. The nonparametric discrete time nonhomogeneous Markov process is proposed as a better model for any applications of the latter type. This simple stochastic model allows for an arbitrary number of possible states and for transitions in any direction. Maximum likelihood estimators are easily computed for the stochastic model and are identical to the product-limit estimates in the special case represented by the Kaplan-Meier model. The logrank test extends to evaluation of differences between populations with respect to any specified transition.

Actuarial Analysis

Alpha 2-adrenoceptor coupling to adenylate cyclase in adrenaline insensitive human platelets.

Coupling of the alpha 2-adrenoceptor to adenylate cyclase was assessed in platelets from 3 groups of subjects: normal controls and patients with myeloproliferative disorders whose platelets were either sensitive or specifically insensitive to the aggregatory effects of adrenaline. The ability of adrenaline to induce the formation of a complex between the alpha 2-adrenoceptor and the inhibitory guanine nucleotide binding protein was examined in all three groups by assessment of the effect of mono and divalent cations and Gpp(NH)p on the displacement of [3H]yohimbine binding to platelet membranes by adrenaline. Coupling to adenylate cyclase was also assessed in separate studies of the inhibition by adrenaline of PGE1 stimulated cyclic AMP accumulation in whole platelets. Both the formation of the ternary complex and the inhibition by adrenaline of cyclic AMP accumulation was not significantly different in platelets sensitive or insensitive to adrenaline. These results suggest that inhibition of cyclic AMP alone does not explain the mechanisms of adrenaline induced platelet aggregation.

Adenylyl Cyclases