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Biomedical subjects

A S Hall

Publications and source records attributed to A S Hall.

At least 19 recordsLinked to original sources

Thiol group identification at or near the agonist binding site of the vascular dopamine receptor.

Cultured mesenteric artery vascular smooth muscle cells derived from male Wistar rats, expressing both beta 2-adrenoceptors and dopamine DA1 receptors, were prelabelled for 2 h with [3H]adenine. [3H]cAMP formation stimulated by the addition of dopamine (plus propranolol 10 microM), isoprenaline or forskolin, in the presence of the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX) (0.5 mM) was then determined. Exposure of cells to the thiol-oxidizing agent DTNB (5,5'-dithiobis-2-nitrobenzoic acid) following prelabelling, and prior to cAMP assay, resulted in a time-dependent inhibition of dopamine (0.1 mM)-induced cAMP formation, which obeyed the rules of first-order kinetics, being complete by 60 min. This inhibitory effect was observed to be dose related with 50% inhibition achieved at a concentration of 0.5 mM. Exposure to DTNB (5 mM) for 45 min abolished the cAMP response to dopamine (0.1 mM) with little effect on the response to forskolin (10 microM) or isoprenaline (10 microM). Prior addition of the dopamine DA1/D1 receptor selective partial agonist (+)-SKF 38393 (1 microM) preserved the dopamine induced cAMP formation despite DTNB exposure, while its stereo-enantiomer (-)-SKF 38393 (1 microM) protected only 25% of the response. Sequential exposure of cells to DTNB (5 mM) and then either vehicle or DTT (DL-dithiothreitol; 1 mM), each for 20 min periods, resulted in a 70% inhibition of dopamine induced cAMP formation which was almost completely reversed by the disulphide bridge cleaving compound DTT.(ABSTRACT TRUNCATED AT 250 WORDS)

1-Methyl-3-isobutylxanthine

Characterization of the dopamine receptor expressed by rat glomerular mesangial cells in culture.

Incubation of cultured rat glomerular mesangial cells with dopamine caused an increase in cyclic AMP formation in a concentration-dependent manner (Ka apparent 2.2 microM). The selective dopamine D1 receptor agonists, fenoldopam, SKF 38393 and (+/-)-2-amino-6,7-dihydroxy-1,2,3,4-tetrahydronaphthalene (6,7-ADTN) also produced concentration-dependent increases in cyclic AMP with mean Ka apparent values of 0.04 microM, 0.02 microM and 1.02 microM, respectively. Although fenoldopam and SKF 38393 were more potent than dopamine, they were partial agonists with efficacies, relative to dopamine, of approximately 60 and 35%, respectively. The dopamine analogue, 6,7-ADTN, in contrast, behaved as a full agonist. Dopamine-stimulated cAMP formation was inhibited in a concentration-dependent manner by the D1-selective antagonist, SCH 23390, with a Ki of 0.06 nM. In contrast, the D2-selective antagonist, domperidone, was four orders of magnitude less potent than SCH 23390, having a Ki of 2072 nM. In addition, SCH 23388, the stereoisomer of SCH 23390, was observed to be two orders of magnitude less potent than SCH 23390, indicating the stereoselective nature of the receptor. The potency series for the selective agonists and antagonists is the same as that described, using identical experimental conditions, for the D1 receptor expressed by a cell line of central origin confirming that the peripheral DA1 and the central D1 dopamine receptor are pharmacologically similar.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben

Magnetic resonance for the anaesthetist. Part I: Physical principles, applications, safety aspects.

Anaesthetists are being increasingly involved in magnetic resonance (MR) procedures, both in patient care and as a research tool. This paper outlines the physical basis of nuclear magnetic resonance and describes its application in magnetic resonance imaging and spectroscopy. Principles of magnet design and safety relevant to anaesthetic practice in a magnetic resonance environment are discussed and guidelines for anaesthetic practice suggested. Some recent clinical magnetic resonance studies of anaesthetic interest are reviewed.

Anesthesiology

Magnetic resonance for the anaesthetist. Part II: Anaesthesia and monitoring in MR units.

Anaesthetists are increasingly involved in patient care during magnetic resonance imaging and spectroscopy. This paper describes a system which has been developed for the management of critically ill patients and the conduct of anaesthesia in a magnetic resonance unit with a 1.6 tesla whole body magnet. Difficulties which arise from working in a confined space in a high magnetic field are highlighted. Different approaches to anaesthesia, sedation and the modification of equipment for use in this environment are reviewed. The problems associated with patient monitoring within a magnetic field are discussed and some solutions are suggested. A transport system for critically ill patients is described and a protocol for management is outlined.

Anesthesia

Use of high temperature superconductor in a receiver coil for magnetic resonance imaging.

A planar YBa2Cu3Ox (YBCO) coil has been used as a pick-up coil in a nuclear magnetic resonance imager. It was found that the quality factor (Q) of the YBCO coil was greater than its copper counterpart by approaching 50% even in a field of 0.15 T. The Q of the copper coil at 77 K and in a field of 0.15 T was 1200 while that of the YBCO coil under identical conditions was 1700.

Equipment Design

The Acute Infarction Ramipril Efficacy (AIRE) Study: rationale, design, organization, and outcome definitions.

The rationale, design, organization, and outcome definitions of the Acute Infarction Ramipril Efficacy (AIRE) Study are described prospectively. A total of 2,000 patients (1,000 per treatment group) will be recruited to this multicenter, multinational, double-blind, randomized, placebo-controlled study investigating the effect of oral treatment with ramipril (2.5 or 5 mg twice daily) on the total mortality of survivors of an acute myocardial infarction (AMI) with early clinical evidence of heart failure. Secondary outcomes of the study include progression to severe/resistant heart failure (at which time the patient will be withdrawn from the study treatment), reinfarction, and stroke. Treatment will be initiated in hospital between day 3 and day 10 following AMI, and follow-up continued for an average of 15 months and a minimum of 6 months. The study data will be analyzed on an intention-to-treat basis: a single formal interim analysis will be conducted after 175 deaths. An Independent Adjudicating Panel will act as the overall ethical supervisory body for the study and will retain the randomization code. An International Steering Committee will be responsible for the clinical definitions of the secondary study outcomes, and will regularly review progress of the study. We believe that early treatment with ramipril may reduce the total mortality of patients surviving an AMI with clinical evidence of heart failure.

Acute Disease

Some observations of the design of rf coils for human internal use.

Some features of the design and implementation of NMR probes for insertion into peripheral orifices of the body are described. In particular, the possibilities of using parasitic coils without direct connections in conjunction with conventional whole body coils are examined. The use of windings around the NMR probe carrying gradient pulses as a means of eliminating the very high signals from tissue immediately adjacent to the coil windings is also evaluated. These approaches are, in practice, difficult to combine, and hence need to be viewed almost as alternative possibilities. Practical results of experimental investigations are presented using both phantoms and volunteers.

Catheterization

The design of a multiple inversion recovery sequence for T1 measurement.

Inversion recovery has the potential to be a powerful method of determining the values of T1 in in vivo studies. However, because of its relative slowness it is not practical to undertake several experiments with different values of the interval between the magnetization inverting 180 degree pulse and the interrogating 90 degree one. The multiple inversion recovery method described here uses a series of sampling pulses, most much less than 90 degrees, to produce a series of images. It is shown that slice shape is relatively reproducible from one sample to another and that, largely as a result, the accuracy of the sequence in measuring T1 is encouraging.

Brain

Do particles translocate from the vagina to the oviducts and beyond?

To investigate whether particles deposited in the vagina translocate to the oviducts, 0.3 ml of a 4% bone black suspension was deposited in the posterior vaginal fornix of each of five cynomolgus monkeys (Macaca fascicularis) during their mid-menstrual cycle. Simultaneously, each animal received 10 units of oxytocin by intramuscular injection. The oviducts of three animals were removed 1 hr after administration of the bone black, while those of the remaining two animals were removed 72 hr after dosing. The removed oviducts were flushed with Hank's solution and then with collagenase solution. The solutions were collected in clean vials and filtered. The filters were examined for bone black particles by light microscopy, as were filters through which solution blanks (negative controls) had been passed. Particles resembling bone black were found on all filters. There were no appreciable differences in the number or shape of these particles between the solution-blank filters and the oviduct-flush filters. The particles on both the solution-blank filters and on the oviduct-flush filters probably originated from environmental contamination by ubiquitous carbon particles. While these results suggested that no translocation took place, translocation could not be ruled out with certainty in the absence of quantitative analyses. A more definitive pilot study was then conducted with two dosed monkeys and one control, using talc labelled by neutron activation to circumvent the problem of environmental contamination. Gamma-Ray analysis of tissue and peritoneal lavage samples for the radionuclides 46Sc, 59Fe and 60Co indicated that no measurable quantities (i.e. greater than 0.5 micrograms) of talc translocated from the deposition site in the vagina to the uterine cavity and beyond.

Animals

Gadolinium-DTPA as a contrast agent in MRI: initial clinical experience in 20 patients.

Magnetic resonance imaging (MRI) was performed in 20 patients before and after intravenous administration of gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA) in a dose of 0.1 mmol/kg. Twelve of the patients had clinical and histologic diagnoses of cerebral tumor, six had hepatic tumors, one had hepatic cysts, and one had transitional cell carcinoma of the bladder. Contrast enhancement was seen with all tumors, but not with the hepatic cysts. The degree of enhancement was greater than that seen with computed tomography (CT) in 13 cases, equal to it in six, and less in one. Contrast enhancement was detectable as long as 18 hr after injection of Gd-DTPA in one case of cerebral tumor. The margin between cerebral tumor and peritumoral edema could be delineated with contrast-enhanced MRI to the degree possible with contrast-enhanced CT. In the liver isointense enhancement was seen with saturation-recovery (SR), inversion-recovery (IR), and spin-echo (SE) sequences although not with all three sequences simultaneously. In general IR sequences were most sensitive for display of the contrast agent, but the enhancement often decreased the difference between abnormal and normal tissue. No short-term side effects were encountered and no significant change was seen in urea, creatinine, electrolytes, liver function tests, blood coagulation, or urine testing after injection of Gd-DTPA. Although much more work will be required to evaluate this contrast agent, these initial experiences are very promising.

Abdomen

Standard nomenclature for primate breeding and husbandry.

Managers of primate colonies seek to record colony data in a systematic way which will be helpful in daily management. Each colony develops individual record systems, tailored to its specific operations and budget. These diversified systems provide the base for a set of uniform record items, which enables information to be shared among institutions, and used for the overall management of a self-sustaining captive primate population, as well as for national planning of primate resources. The present report identifies basic information needed for local colony management and data items that require standard nomenclature. Such data will provide the basic demographic profiles unavailable at most primate colonies today.

Animal Husbandry

Clinical NMR imaging of the brain: 140 cases.

Cranial nuclear magnetic resonance (NMR) scans were performed on 13 healthy volunteers and 140 patients with a broad spectrum of neurologic disease and compared with x-ray computed tomography (CT) scans. The NMR scans included a variety of sequences reflecting proton density, blood flow, T1, and T2 as well as transverse, sagittal, and coronal images. White matter, gray matter, and cerebrospinal fluid were clearly distinguished in the normal brain with inversion-recovery (IR) sequences, and normal progressive myelination was demonstrated in infants and children. Acute hemorrhages displayed short T1 values, but other pathologic processes such as infarction, infection, demyelination, edema, and malignancy were associated with long T1 values. Cysts had very long T1 values (about that of cerebrospinal fluid). Spin-echo (SE) sequences showed increased values of T2 in a variety of conditions and highlighted lesions against the relatively featureless background of the remaining brain. With inversion-recovery scans, different stages of infarction were recognized in the hemispheres. NMR was more useful than CT in demonstrating brainstem infarction. The white matter lesions in demyelinating diseases were well demonstrated with NMR scans. Many more lesions were observed in multiple sclerosis with NMR than with CT. Benign tumors were well seen and usually had shorter T1 values than malignant tumors. Mass effects from tumors were generally better demonstrated with NMR than with CT, including more subtle mass effects such as displacement of the external capsule. Abnormalities were seen in diseases of the basal ganglia, including marked atrophy of the head of the caudate nucleus in Huntington chorea. Advantages of NMR imaging include the high level of gray-white matter contrast, lack of bone artifact, variety of possible sequences, transverse, sagittal, and coronal imaging, sensitivity to pathologic change, and lack of known hazard. Disadvantages include lack of bone detail, limited spatial resolution, lack of contrast agents, and cost. Promising directions for future clinical research include developmental neurology, tissue characterization with T1 and T2, assessment of blood flow, and the development of contrast agents. Much more detailed evaluation will be required, but NMR seems to be a potentially important addition to existing techniques of neurologic diagnosis.

Adolescent

Nuclear magnetic resonance imaging of the brain in multiple sclerosis.

Ten patients with multiple sclerosis (MS) were scanned by means of cranial X-ray computed tomography (CT) with and without intravenous contrast enhancement, and by nuclear magnetic resonance (NMR) using an inversion-recovery sequence. Altogether 19 lesions varying in size between about 7 mm X 5 mm and 13 mm X 8 mm were demonstrated by CT. They were all situated in the periventricular region. Two patients also showed moderate ventricular enlargement. In addition to these abnormalities 112 further lesions were demonstrated on the NMR scans. These lesions varied in size from 4 mm X 3 mm to 12 mm X 7 mm and were particularly well seen in the periventricular region and brainstem. Care is required in the assessment of NMR scans to exclude artefacts, background noise, and mottle as well as normally situated grey matter and partial volume effects from cerebral sulci. NMR nevertheless demonstrates abnormalities in MS on a scale not previously seen except at necropsy.

Adolescent

Magnetic resonance properties of hydrogen: imaging the posterior fossa.

Posterior fossa scans were performed on five healthy volunteers using a nuclear magnetic resonance (NMR) machine constructed by Thorn-EMI Ltd. Three different NMR scanning sequences were used. In the first, a type of saturation-recovery technique was used to produce images strongly dependent on the density of hydrogen nuclei, but with some dependence on the spin-lattice relaxation time (T1). In the second, an inversion-recovery technique was used to produce images with a stronger dependence on the spin-lattice relaxation time. In the third, a spin-echo technique was used to obtain images with a dependence on the spin-spin relaxation time (T2). All three types of NMR image were unaffected by bone artifact. Visualization of brain adjacent to the skull base was obtained without loss of detail due to partial-volume effect from bone. The saturation-recovery images highlighted arteries and veins that were clearly visible without the use of contrast agents. The inversion-recovery images showed remarkable gray-white matter differentiation enabling internal structure to be seen within the brainstem and cerebellum. The trigeminal nerve and ganglion were also seen outside the brain. Experience with the spin-echo technique is limited, but the images at the base of the brain show considerable soft-tissue detail. The NMR images of the posterior fossa in this study were comparable in quality to those obtained from a new rotate-rotate x-ray computed tomography machine and were superior in several respects.

Adult

Tomographic diagnosis of palatal defects.

We present the results of a pilot study conducted to evaluate the effectiveness of palatal tomography in patients suspected of having palatal defects not detectable by other methods. Twelve patients were involved in the projects, ranging in age from 3 to 11 years. There were 8 boys and 4 girls. Each patient was evaluated with voice recordings, lateral cineradiographic x-rays, and palatal tomograms. Nine of the 12 patients were found by tomography to have palatal defects that had not been detected either by cineradiography or by clinical investigation, including physical examination of the palate. The results of this study are presented with clinical findings.

Child