Percutaneous closure of the small (less than 2.5 mm) patent ductus arteriosus using coil embolization.
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Biomedical subjects
Publications and source records attributed to J W Moore.
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OBJECTIVES: The purpose of our study was to establish an in vitro tissue culture system to study eicosanoid metabolism in first-trimester trophoblastic tissue. Thromboxane A2, a potent vasoconstrictor, and prostacyclin, a potent vasodilator, were analyzed to evaluate their production in early pregnancy. STUDY DESIGN: Trophoblastic tissue was obtained via transabdominal chorionic villous sampling from 33 pregnancies at 9 to 12 weeks' gestation for cytogenetic diagnosis. Initially, tissue obtained from the cytogenetics lab was morphologically consistent with villous core cells. Through altering cell density and passage, the cells became morphologically consistent with cytotrophoblasts. The cell lines were exposed to arachidonic acid (50 mumol/L) and aspirin (1 to 100 mumol/L) for 24 hours. Thromboxane B2 and 6-keto prostaglandin F2 alpha were measured by radioimmunoassay. RESULTS: Villous core cells and cytotrophoblasts increased production of thromboxane A2 and prostacyclin in the presence of arachidonic acid (p < 0.002). The villous core cells produced more thromboxane A2 and prostacyclin than cytotrophoblasts (p < 0.02). A significant inhibition of both thromboxane A2 and prostacyclin production was seen in the presence of 100 mumol/L aspirin in both cell types (p < 0.05). CONCLUSIONS: This model may be useful for studying placental function in the first trimester because individual placental compartments can be evaluated in tissue culture. At the cellular level we were not able to detect a preferential decrease in thromboxane A2 production in the presence of aspirin (1 to 100 mumol/L).
Plasma sex hormone-binding globulin (SHBG), testosterone, total oestradiol (E2) and proportion of E2 not bound to blood proteins (percentage free E2) have been measured in a case-control study to test whether any of these factors are related to the risk of breast cancer. The cases studied were 27 premenopausal and 34 postmenopausal women with newly diagnosed localized breast cancer who were admitted to the All-Union Cancer Research Centre, Moscow. The controls were an equivalent number of women from the same neighbourhood. These were matched for age (within 2 years) and menopausal status. The average levels of E2 in cases were significantly higher than controls (p = 0.004 and p < 0.001 for pre- and postmenopausal groups, respectively). Percentage free E2 was significantly raised only in premenopausal cases (p = 0.019). The plasma concentrations of testosterone and SHBG were similar for both pre- and postmenopausal groups. Raised E2 or percentage free E2 was associated with an increased relative risk of breast cancer. However, only E2 levels (crude or adjusted for body build) were significantly related to risk in the two menopausal sets (p = 0.022 and p = 0.002, respectively). High percentage free E2 was associated with almost a threefold increase in the risk of breast cancer in premenopausal women; however, this increase was not statistically significant (p = 0.083). The levels of SHBG or testosterone, crude or adjusted for body build and E2 concentration, were not related to risk of breast cancer.
A sample of 142 subjects free of neurological or psychiatric disorder were administered the National Adult Reading Test (NART) and a verbal fluency (VF) test. A highly significant correlation between the NART and VF was obtained indicating that premorbid ability should be taken into account when interpreting VF performance. A regression equation was built to estimate premorbid performance on VF from the NART. A highly significant difference between predicted and obtained VF was obtained in a sample of neurological patients (N = 38). For ease of use, a table converting NART errors to predicted VF scores is presented.
Rabbits were trained on a Pavlovian conditioned inhibition (CI) task using light as the reinforced conditioned stimulus (CS+) and the same light compounded with a tone as the nonreinforced CS-. The conditioned response was the nictitating membrane response. After attaining a criterion of CI performance, animals received radio-frequency lesions of the hypothalamus (n = 11) or midbrain (n = 14). For the hypothalamic lesion cases, primary damage extended from the optic chiasm to the pretectal region. For the mesencephalic lesion cases, primary damage ranged from the most rostral portions of the periaqueductal grey (PAG) caudally to the tegmental reticular formation at the level of the third nerve. Prior research suggested that the hypothalamic lesions would disrupt retention of CI by increasing responding to the CS-. Except where a lesion impinged upon the zona incerta, no CI disruption was observed. In accordance with previous studies (Berthier, N.E. and Moore, J.W., Physiol. Behav., 25 (1980) 667-673; Mis, F.W., J. Comp. Physiol. Psychol., 91 (1977) 975-988), post-lesioning CI disruption was observed in some of the mesencephalic lesion cases involving the posterior commissure, PAG and/or accessory oculomotor nuclei. However, CI performance recovered over the course of retraining.
Spinal trigeminal nucleus pars oralis (SpoV) is anatomically linked to brain circuitry thought to subserve unconditioned and conditioned nictitating membrane responses in rabbit. Single-unit recording from SpoV and adjacent reticular formation obtained during conditioning from awake, behaving animals revealed modulation of unit firing related to CS, US, and CR occurrence. SpoV participates directly in the unconditioned response and probably relays US information to other brain areas subserving conditioning. The presence of CR-related activity suggests that SpoV may participate in the CR motor output pathway, and may also provide CR-related information to cerebellum. Sensory convergence and CR-related activity in reticular formation mark this structure as a candidate locus of primary neuronal plasticity in this example of conditioning.
In classical trace conditioning, the interstimulus interval (ISI) is equal to the conditioned stimulus (CS) duration plus the trace interval (TI), the interval between CS offset and unconditioned stimulus (US) onset. The Sutton-Barto-Desmond neural-network model of classical conditioning predicts that, with a sufficiently long TI, conditioning will be faster with a CS of relatively long duration than with one of shorter duration. This prediction is illustrated with simulations and tested with the rabbit nictitating membrane response. Animals were trained with a tone CS of 350- or 700-ms duration. The TI was fixed at 300 ms, so that the ISI for the two durations was 650 or 1000 ms, respectively. Another factor in the experimental design was tone intensity (63 or 83 dB). Consistent with the model's prediction, conditioning was faster with the longer ISI, but only with the louder tone. The results have implications for computational models of classical conditioning.
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Intraosseous infusion has been advocated as an emergency route in sick infants and children when intravenous access is not readily obtainable. Dobutamine hydrochloride and isoproterenol hydrochloride are useful emergency drugs that have not been studied when administered into the bone marrow. In a swine model, we compared the physiologic responses (heart rate, arterial pressure, and cardiac output) of dobutamine and isoproterenol infusions delivered intravenously and intraosseously during 20-minute intervals. We observed statistically significant effects of both dobutamine and isoproterenol delivered by the intraosseous route. In addition, the effects resulting from intraosseous infusion were statistically similar to those resulting from intravenous administration of these drugs. We conclude that the intraosseous infusion of dobutamine and isoproterenol is an effective and useful method for emergency administration of these medications.
A previously described neural-network model (Desmond 1991; Desmond and Moore 1988; Moore et al. 1989) predicts that both CS-onset-evoked and CS-offset-evoked stimulus trace processes acquire associative strength during classical conditioning, and that CR waveforms can be altered by manipulating the time at which the processes are activated. In a trace conditioning paradigm, where CS offset precedes US onset, the model predicts that onset and offset traces act in synchrony to generate unimodal CR waveforms. However, if the CS duration is subsequently lengthened on CS-alone probe trials, the model predicts that onset and offset traces will asynchronously contribute to CR output and bimodal CRs will be generated. In a delay conditioning paradigm, in which US onset occurs prior to CS offset, the model predicts that only the onset process will gain associative strength, and hence, only unimodal CRs will occur. Using the rabbit conditioned nictitating membrane response preparation, we found experimental support for these predictions.
The correlation of the activity of neurons in the interposed and dentate nuclei of the cerebellum with conditioned movements of the nictitating membrane was investigated using linear systems analysis. The activity of single deep cerebellar nuclear cells was assumed to be the input to a linear system that produced nictitating membrane movement. Data were initially analyzed with a causal model to assess the degree to which past neural activity predicted the conditioned response. 55 of 165 cells had correlation coefficients of 0.50 or greater between the model's moment-to-moment output and the actual output, with two interpositus cells having correlation coefficients of greater than 0.90. Double-sided impulse responses indicated that afference from the face and efference copy probably affect deep cerebellar neural activity. Nonlinearities were also found in the relationship between neuronal activity and conditioned movement. It was concluded that cerebellar deep nuclear firing is highly correlated with future nictitating membrane movements but that the firing-movement relationship contains noncausal and nonlinear components.
In a cross-sectional study, serum estradiol (E2) and sex hormone-binding globulin (SHBG) concentrations were not significantly related to age at menarche in premenopausal British women in the luteal or follicular phases of the cycle. In Japanese subjects in the luteal phase, a marginally higher concentration of E2 was observed in those who had undergone an early rather than a late menarche. In British women, previous oral contraceptive users had significantly lower luteal phase E2 concentrations than never users.
Previous investigations have suggested that the cerebellum and associated brainstem structures, including the red nucleus, are essential for the expression of the classically conditioned nictitating membrane (NM) response. The present study examined the firing patterns of extracellularly-recorded single units in the red nucleus of the awake rabbit during differential conditioning. Tones were used as conditioned stimulus (CS+ and CS-) and periocular electrostimulation was used as the unconditioned stimulus (US). Most units exhibited one or more changes in firing rate during the presentation of the CS, and increases in firing were much more common than decreases. The onset of some of these changes appeared to be time-locked to the onset of the CS ('CS-locked' responses), while other changes were time-locked to the onset of the CR ('CR-locked' responses). About one-third of all CS-locked changes were CR-dependent, meaning that the neuronal response was reduced when the CR did not occur. About two-thirds of all CR-locked responses preceded the onset of the CR, and lead times varied considerably across units. Many CR-locked units were located in what has been described as a dorsal face region of the red nucleus. Most units responded to the US, and some of the US responses were CR-dependent: i.e., a smaller US response was evoked when a CR preceded the US than when the CR was absent. Our results support the notion that cerebellum-brainstem circuits are involved in generating NM CRs.
Epidemiological evidence has suggested that cigarette smoking has an anti-oestrogenic effect in women, but the effects of smoking on steroid hormone metabolism are not fully understood. We compared serum concentrations of oestradiol, progesterone (luteal phase) and dehydroepiandrosterone sulphate (DHEA-S), and urinary excretion rates of six steroids of predominantly adrenal origin, in healthy premenopausal and postmenopausal female smokers and non-smokers. Serum concentrations of oestradiol, progesterone and DHEA-S did not differ between smokers and non-smokers by greater than 5%, and none of these differences was statistically significant. Mean urinary excretion rates of androsterone, aetiocholanolone, DHEA, 11-keto-aetiocholanolone, 11-hydroxyandrosterone and 11-hydroxyaetiocholanolone were very similar in smokers and non-smokers in premenopausal women, but were from 2-44% higher in smokers than non-smokers in postmenopausal women. The difference was statistically significant only for 11-hydroxyandrosterone. These results confirm previous reports that cigarette smoking does not affect serum oestradiol in premenopausal or postmenopausal women, but provide only weak evidence to support previous findings of increased levels of some adrenal steroids in postmenopausal women smokers. The mechanism for the apparent anti-oestrogenic effect of cigarette smoking remains unclear.
Congenital heart defects (CHD) are a group of structural abnormalities that in humans have a combined incidence of approximately 1%. It is estimated that 4-5% of CHD are associated with chromosome abnormalities, 1-2% are associated with single gene syndromes, 1-2% are due to known teratogens, with the rest presumably determined multifactorially. We report on a brother and sister with tetralogy of Fallot with pulmonary atresia, and review the inheritance of familial conotruncal anomalies. We feel the small number of family clusters and the rare instances of consanguinity in non-syndromal conotruncal defects are consistent with multifactorial determination. While it is prudent in counseling families with 2 or more individuals with conotruncal CHD to raise the possibility of single gene inheritance, we believe that current empiric recurrence risk estimates most accurately reflect their risks.
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The recent availability of Y DNA probes has made it possible to identify two forms of 46,XX male syndrome: Y DNA positive and Y DNA negative. The Y DNA positive male results from a X;Y translocation with a low recurrence risk; the Y DNA negative males are due to a mutation with a high recurrence risk. 46,XX males and mosaic forms are phenotypically indistinguishable. A review of the case histories for 11 individuals indicates that affected males have highly variable genital and nongenital phenotypes. Physical findings may be clearly apparent or nonexistent. With the exception of external genitalia, the basis for this variability is unknown. It may be related to differences in Y chromatin expression as the result of variable inactivation of the X chromosomes, or to the existence of minor deletions or point mutations secondary to an exchange of genetic material. Common and uncommon clinical problems in these individuals require evaluation and follow-up care that is provided through a cooperative, interdisciplinary approach.
Acidic and basic fibroblast growth factors (FGFs) are members of a family of proteins that exert pleiotropic effects in a range of cell types including skeletal myocytes. Previous studies demonstrate that exogenously supplied FGFs stimulate proliferation of myoblasts and inhibit their differentiation in culture, but little information is available concerning endogenous expression of FGFs by skeletal myocytes. In this study acidic and basic FGF mRNAs were found to be expressed in murine and rat skeletal muscle, and expression was demonstrated to vary with the tissue and species examined. Myogenic cell lines were then analyzed to determine if FGFs are expressed in myoblasts, and if so, whether expression is regulated during myogenic differentiation. Murine Sol 8 and rat L6 myoblasts were found to express acidic and basic FGF mRNAs, and the expression of both growth factors was downregulated at the transcriptional level during myogenic differentiation. A decrease in expression of the mouse homologue of the human FGF receptor paralleled the decrease in acidic and basic FGF mRNAs in Sol 8 cells, indicating that the decrease in FGF receptor abundance previously observed during myogenic differentiation is regulated at the mRNA level. The results of this study suggest that a coordinate decrease in endogenously produced acidic and basic FGFs and their cognate receptor may participate in the regulation of myogenic differentiation. Furthermore, the observation that expression of a myogenic determination gene, myogenin, increases as FGF transcripts decline, together with previous data demonstrating suppression of myogenin expression by FGF, suggest a mechanism whereby endogenously produced FGFs may exert their effect on differentiation.