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Biomedical subjects

A Roberts

Publications and source records attributed to A Roberts.

At least 217 records · Page 12Linked to original sources
PubMed1992

Does desmopressin acetate prophylaxis reduce blood loss after valvular heart operations? A randomized, double-blind study.

The effectiveness of prophylactic desmopressin acetate in reducing hemorrhage after cardiopulmonary bypass operations is controversial. We conducted a prospective, randomized, placebo-controlled, double-blind trial to determine its effectiveness and safety in such patients. Eighty-three evaluable patients undergoing valvular heart operations were randomized to receive desmopressin (0.3 microgram/kg) (41) or placebo (42) after cardiac bypass. Demographic characteristics were similar in both groups. There was no significant difference in total 24-hour blood loss between groups (desmopressin 1064.8 +/- 647.1 ml versus placebo 844.4 +/- 507.6 ml; p greater than 0.05), or in the requirement for red blood cell, platelet, or fresh frozen plasma transfusion, or for reexploration for control of hemorrhage. Neither was there a difference in the occurrence of thrombotic complications between groups. Analysis of factor VIII activity, von Willebrand factor, or von Willebrand factor multimers failed to show significant correlations with blood loss or differences between groups except for factor VIII activity, which was significantly higher in the desmopressin group 1 hour after operation than in the placebo group. A detailed comparative analysis of similar trials to determine the reasons for different outcomes suggests that desmopressin should not be used routinely as a prophylactic agent to reduce postsurgical hemorrhage, but that it may be beneficial when used in patients who already manifest excessive bleeding postoperatively.

Blood Loss, Surgical↗
PubMed1992

Effect of paracentesis upon the blood-aqueous barrier of cynomolgus monkeys.

Anterior chamber paracentesis disrupts the blood aqueous barrier (BAB) of rabbits and nonhuman primates, but the magnitude and duration of breakdown in monkeys has not been clarified. We have studied anterior chamber paracentesis in cynomolgus monkeys as a potential model of postoperative BAB breakdown. The effect of a single paracentesis upon fluorescein sodium concentration in the anterior chamber after an intravenous injection was measured in 16 eyes of 8 animals. In an additional 10 eyes of 5 animals, aqueous humor was withdrawn for analysis 24 hours and one week following paracentesis. Anterior chamber fluorescein concentration was 57 +/- 22 ng/ml (mean +/- standard deviation) before paracentesis, rose to 81 +/- 47 ng/ml 24 hrs after paracentesis, and was 60 +/- 36 ng/ml at 72-96 hours. Twenty-four hours after paracentesis, total protein concentration was elevated, but ascorbic acid and transforming growth factor-beta levels were not. Paracentesis in monkeys has only a small and short lasting effect upon BAB integrity and is therefore unlikely to be a good model for assessing the effect of agents designed to stabilize the BAB. However, the short-lived effect of paracentesis may permit the repetitive collection of "primary aqueous" for physiologic and biochemical studies.

Animals↗
PubMed1991

Sequence specific protein binding to and activation of the TGF-beta 3 promoter through a repeated TCCC motif.

We have previously characterized the TGF-beta 3 promoter and shown that the activity of this promoter is highly variable in different cell types. Although the promoter contains a proximal cAMP responsive element, which is critical to basal and forskolin-induced promoter activity, this element is not responsible for the variable, cell-specific regulation of the promoter. In this paper, we identify a 25 base pair sequence in the proximal region of the TGF-beta 3 promoter that binds a novel DNA-binding protein. This region includes the sequence T-CCCTCCCTCCC, (3 x TCCC), and mutation of these T-CCC repeats inhibits protein binding. Further, we show that in the cell line A375, which we have previously shown expresses high levels of TGF-beta 3 mRNA, this region is responsible for mediating high level TGF-beta 3 promoter activity. Immediately 3' to the 3 x TCCC sequence is a consensus AP-2 binding site, however, we show that this region does not bind AP-2, and AP-2 does not transactivate the TGF-beta 3 promoter. Therefore, we provide strong evidence that high level expression of TGF-beta 3 in A375 cells results from transactivation of the TGF-beta 3 promoter by a protein that binds to a repeated TCCC motif in the promoter and suggest that this DNA-binding protein likely also regulates aspects of developmental and tissue-specific expression of this cytokine.

Animals↗
PubMed1991

Longitudinal coordination of motor output during swimming in Xenopus embryos.

Little is known about the neural mechanisms that control the phenomenon of rostro-caudal delay. In Xenopus embryos there is a constant rostro-caudal delay of 2-5 ms mm-1 during fictive swimming. Rostro-caudal delay is not significantly correlated with cycle period. When NMDA is applied to the caudal spinal cord there is a decrease and in some cases a reversal in rostro-caudal delay. Conversely applying excitatory antagonists to the caudal spinal cord leads to an increase in delay. When caudal mid-cycle inhibition is reduced either pharmacologically using strychnine or surgically through hemisection of the spinal cord, there is an increase in rostro-caudal delay. Rostro-caudal delays are too small to be explainable on the basis of axonal conduction velocities and synaptic delays. This suggests that the central pattern generator of Xenopus behaves as a series of coupled oscillators and that the nature of the coupling, together with a longitudinal gradient in excitability associated with the oscillators, contributes to the observed rostro-caudal delay.

Animals↗
PubMed1991

Segregation of NMDA and non-NMDA receptors at separate synaptic contacts: evidence from spontaneous EPSPs in Xenopus embryo spinal neurons.

Many excitatory amino acid (EAA)-mediated synaptic potentials are dual-component as a result of the simultaneous activation of N-methyl-D-aspartate (NMDA) and non-NMDA receptor subtypes, the two major classes of EAA receptor in vertebrates. This raises the question of whether the two receptor types are located separately or together at individual synaptic contacts. Support for the segregation of NMDA and non-NMDA receptors in discrete anatomical patches arises from the observation that the fast and slow components of dual-component potentials mediated via NMDA and non-NMDA receptor types can fail independently. We have obtained further support for this by investigating the spontaneous release of EAA neurotransmitter at sensory synapses in the spinal cord of Xenopus laevis embryos. We report the occurrence of spontaneous TTX-resistant EPSPs in sensory interneurons that are mediated by EAA receptors. These spontaneous potentials share the same pharmacological sensitivities as EPSPs evoked by skin sensory afferents, being blocked by kynurenic acid and reduced by (+-)-2-amino-5-phosphonovaleric acid (APV). The spontaneous EPSPs differ from evoked EPSPs in their time courses: while evoked EPSPs are almost exclusively of the dual-component variety, the spontaneous EPSPs are predominantly either fast or slow. These data suggest that spontaneous EPSPs reflect release of EAA neurotransmitter at synaptic contacts overlying homogeneous populations of either NMDA or non-NMDA receptors. Their relatively large size, up to 50% or more of the amplitude of unitary EPSPs evoked by stimulation, also suggests that synapses between skin afferents and sensory interneurons may comprise relatively few points of synaptic contact.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Potential role of PFOB enhanced sonography of the kidney. II. Detection of partial infarction.

Aside from its ability to assess flow velocity within vessels, color Doppler and gray-scale sonography cannot distinguish perfused from non-perfused tissues. In this study we evaluated whether Perfluorooctylbromide (PFOB), a sonographic contrast agent given i.v., could aid sonography with this recognition. Partial renal infarction was produced by a 1 mm bead embolized in the right, the left, or both renal arteries of 20 normal rabbits. The sonographer, unaware of rabbit assignment, attempted to diagnose the infarct 24 hours later. All 20 rabbits were studied with gray-scale and color Doppler sonography, 10 before and after PFOB and 10 only after PFOB. Angiography and post-mortem examination were done for confirmation. Of the 20 kidneys evaluated before PFOB, the sonographer was unable to diagnose the 10 partial infarctions. Color Doppler identified five of the ten infarcted kidneys, but accurately localized the infarction in only two. Of the 40 kidneys evaluated after PFOB infusion, 20 scanned before and 20 scanned only after PFOB, all 20 partial infarctions were accurately diagnosed with both gray-scale and color Doppler. PFOB enhanced the echogenicity of perfused renal tissue allowing the easy detection of the unenhanced infarct. Because of the increased signal from vessels after PFOB, color Doppler displayed the entire vascular tree, allowing the detection of the truncated embolized branch. The ability of PFOB to enhance Doppler signals and the echogenicity of perfused tissues improved the diagnostic accuracy of sonography when used to detect partial renal infarctions.

Animals↗
PubMed1991

Where physicians practicing in Appalachia in 1978 to 1990 were trained and how they were distributed in urban and rural Appalachia.

Medical school graduates who graduated from 1978 to 1986 were analyzed to determine the health professions' ability worldwide to educate and place primary care physicians in rural areas of Appalachia. These data indicate that the University System of West Virginia--consisting of the West Virginia School of Osteopathic Medicine, West Virginia University Medical School, and Marshall University Medical School--produced the most primary care physicians who began practicing in rural Appalachia during the 1980s. The West Virginia School of Osteopathic Medicine successfully retained 106 (26%) of its graduates in primary care practices throughout rural Appalachia, with 77 of them in rural West Virginia, making the institution the nation's leading provider of primary care physicians practicing in rural Appalachia and West Virginia during this eight-year study period. With the exception of West Virginia, these and additional data support concerns of medical educators and public health officials that physicians in Appalachia are distributed disproportionately, more to urban than to rural counties.

Appalachian Region↗
PubMed1991

Vascular cell responses to TGF-beta 3 mimic those of TGF-beta 1 in vitro.

The vascular cell responses to the type 3 isoform of transforming growth factor-beta (TGF-beta 3) were studied using bovine aortic endothelial (BAECs) and smooth muscle cells (BASMCs) as well as rat epididymal fat pad microvascular endothelia (RFCs). Four distinct bioassays indicated that TGF-beta 3 elicits results that do not differ significantly from those of the TGF-beta 1 isoform in all three cell populations. Inhibition of proliferation by TGF-beta 3 at a 5-day time point ranged from 85% on BAECs, to 55% and 53% on RFCs and BASMCs, respectively. The effects of TGF-beta 3 and TGF-beta 1 on cell migration were also found to be similar; migration of large vessel endothelial cells was inhibited 35%, while migration of smooth muscle cells was enhanced 30%. TGF-beta 1 and TGF-beta 3 also had equivalent effects on neovascularization while a 10-fold higher concentration of TGF-beta 2 was required to elicit a similar response. Experimentation to decipher cell surface binding by the different isoforms revealed that iodinated TGF-beta 1 bound to the surface of all three vascular cell types can be competed off in similar fashion by either TGF-beta 1 or TGF-beta 3; however, competition with TGF-beta 2 produced unique binding profiles dependent upon the cell type examined. In summary, both the TGF-beta 1 and TGF-beta 3 isoforms of the transforming growth factor-beta family evoke comparable responses in proliferation, migration, angiogenic and cell surface binding assays using three distinct vascular cell types, while the biofunctions of TGF-beta 2 on these cells are distinct.

Animals↗
PubMed1991

Effect of interval between doses on response of the pony to sodium bicarbonate.

Three pony geldings were given sodium bicarbonate orally in order to study the effect on blood pH and bicarbonate and to determine if frequency of dosing influences the response. In a preliminary study, it appeared that a carry-over effect might occur if the interval between dosing was only 2 days. The ponies received 2 doses of sodium bicarbonate (400 mg/kg) 7 days apart in trial one and then in trial two they received 2 doses of sodium bicarbonate 4 days apart. The sodium bicarbonate was mixed with 2 liters of warm water and given through a nasogastric tube on each trial day. Blood samples were taken before dosing, and every half hour after for five and a half hours. The blood was analyzed for pH and bicarbonate. There did not seem to be a carry-over effect due to sodium bicarbonate administration since there was little difference in the responses between the first and second doses of each trial.

Animals↗
PubMed1990

Chorionic villus sampling for prenatal diagnosis in Wales using DNA probes--5 years' experience.

Chorionic villi were sampled from 125 women who requested prenatal diagnosis, either for genetic disorder or because of advanced maternal age. Of these, 105 samples were obtained by the transcervical route and 20 were obtained by the transabdominal approach. The sampling success rate was 97 per cent (122/125). The mean maternal age of the patients was 31 years (range 17-44) and the mean gestational age at which the chorionic villus sampling was performed was 10 weeks (range 7-13 weeks). Seventy-four of these diagnoses involved the use of DNA markers. The minimal size of the sample used for DNA diagnosis was 5 mg. Maternal contamination was detected in two samples. A diagnosis was provided on all but two samples. The fetal loss rate was high initially but fell to 1.9 per cent in 1988.

Adolescent↗
PubMed1990

Preterm delivery: a risk factor for retained placenta.

The purpose of this study was to determine whether preterm delivery, with and without intraamniotic infection, is a risk factor for retained placenta. This complication occurred more frequently in women with preterm vaginal delivery than in women with term vaginal delivery (9.1% [21/231] vs 1.1% [6/561]; p less than 0.00001; odds ratio = 9.25). There was no significant difference in the prevalence of retained placenta between women with preterm labor and intact membranes and those with preterm premature rupture of membranes (8% [10/125] vs 10.4% [11/106]; p greater than or equal to 0.05). A positive amniotic fluid culture or clinical chorioamnionitis was not associated with a higher incidence of retained placenta. This study indicates that preterm delivery is associated with an increased risk of complications of the third stage of labor.

Adult↗
PubMed1990

Oestrogen binding and risk factors for breast cancer.

Although women with breast cancer tend to have a greater proportion of their circulating oestradiol non-protein bound and albumin bound, and less SHBG-bound, than controls, it remains uncertain whether this has an aetiological role or is an effect of the tumour. Oestradiol and its binding to serum proteins was investigated: (a) in relation to risk factors for breast cancer in a normal population; (b) in women with proliferative benign breast disease as a risk group for breast cancer, and women with non-proliferative benign breast disease as a low risk group, as well as breast cancer patients. The strongest associations were with body mass index; the greater the body mass the greater the bioavailability of oestradiol. Changes in relation to age at menarche and menopause could have been a function of body mass. An interesting change with age was noted with a fall in bioavailability over the menopausal years. There was no relationship apparent for parity, age at first full term pregnancy, family history or country of birth. Similar differences in oestradiol binding between cases and controls were seen for patients with breast cancer, benign epithelial hyperplasia and fibrocystic disease without proliferative changes, but these were not significant. This study provides limited support for the concept that oestradiol binding has an aetiological role in the development of breast cancer.

Adult↗
PubMed1990

Uroporphyrinogen decarboxylase deficiency in hepatoerythropoietic porphyria: further evidence for genetic heterogeneity.

Catalytic and immunoreactive erythrocyte uroporphyrinogen decarboxylase was measured in a woman with hepatoerythropoietic porphyria (HEP). The uroporphyrinogen decarboxylase activity was 24% of the mean value for normal controls and the concentration of the immunoreactive enzyme (106 ng/mgHb), measured with the rocket immunoelectrophoresis technique, did not differ from that of healthy controls. Consequently, catalytically inactive, cross-reactive immunological material (CRIM) was present, and the patient was CRIM-positive. This enzyme activity and immunoreactive enzyme concentration differs from those for previously known HEP patients, and represents a new mutation, evidence for heterogeneity in inherited uroporphyrinogen decarboxylase deficiency.

Carboxy-Lyases↗
PubMed1990

Mutual Re-excitation with Post-Inhibitory Rebound: A Simulation Study on the Mechanisms for Locomotor Rhythm Generation in the Spinal Cord of Xenopus Embryos.

We have used computer simulations as one way to test the hypothesis that locomotor rhythm production for swimming in frog embryo spinal cord depends on rebound from inhibition and is sustained by mutual re-excitation among spinal excitatory interneurons. All simulations were based on physiological and anatomical data on the neurons and circuitry of Xenopus embryo spinal cord. Model 'neurons' had resistively coupled axon, soma, and dendrite compartments. Membrane properties were based on Hodgkin - Huxley equations with resting potential at - 75 mV and where soma and dendrite had reduced K+ and Na+ conductance and slowed K+ conductance. These 'neurons' fired a single non-overshooting spike both to depolarizing current and after hyperpolarizing current given during imposed depolarization. Synapses were made on to the dendrite. Inhibitory and excitatory synaptic channels had Nernst potentials of - 80 and 0 mV, time constants for opening of 1 ms, and closing of 6 and 75 ms. When the short inhibitory postsynaptic potential occurred on the long (N-methyl-D-aspartate-type) excitatory postsynaptic potential, it led to rebound firing. A four 'neuron' symmetrical network was built with reciprocal inhibition and where excitatory 'neurons' re-excited themselves and the inhibitory 'neuron' on their own side. The rhythmic alternating activity with one spike per cycle produced reliably by this network was self-sustaining, initiated by a brief synaptic input, and closely resembled the spinal cord motor pattern during swimming. The robustness of this activity pattern was investigated by varying cellular and synaptic parameters, initiating inputs, and network connectivity. We conclude that cellular, synaptic, and network properties are all important and that mutual re-excitation, a form of positive feedback, could sustain motor rhythm production in the Xenopus embryo spinal cord.

Journal Article↗