Early postoperative endoscopic sphincterotomy for retained biliary stones.
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Biomedical subjects
Publications and source records attributed to D Martin.
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The role of d(GATC) sites in determining the efficiency of methyl-directed mismatch repair in Escherichia coli was investigated. Transfection of host bacteria, both proficient and deficient in mismatch repair, with a series of artificially constructed M13 heteroduplexes showed that a decrease in the total number of d(GATC) sequences within these vectors lowered the efficiency of repair in vivo. Single hemimethylated d(GATC) sequences were still able to direct the correction event to the unmethylated strand, providing that the mismatch to d(GATC) site distance was shorter than approximately 1 kb. In excess of this distance, the effect of hemimethylated d(GATC) sites on mismatch correction was almost unnoticeable. The directionality of the repair event could be dictated by d(GATC) sequences situated both upstream and downstream of the mispair, suggesting that this important antimutagenic pathway can proceed bidirectionally.
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We have used microelectrophoretic and intravenous administration of drugs to rat spinal cord neurones in vivo and bath application to rat cortical wedges in vitro to evaluate MK-801 and other phencyclidine (PCP) receptor ligands as N-methylaspartate (NMA) antagonists, paying particular regard to the possible use-dependent nature of their action. MK-801, 0.1-0.5 mg/kg, was a selective and long-lasting NMA antagonist. We were unable to demonstrate significant use-dependent onset of antagonism of NMA by any of the drugs in vivo. Recovery, however, for MK-801 was use-dependent. In vitro there was a gradation with MK-801 being very use-dependent, followed by (PCP), cyclazocine and ketamine, the last showing little or no use-dependence. Results of experiments modulating the in vitro environment suggest that a significant difference between the in vitro and in vivo systems was temperature. Raising the temperature of the wedge chamber from 23 to 33 degrees C reduced the use-dependence of MK-801, and lowering the temperature to 13 degrees C increased the use-dependence of PCP. The mechanism of action of PCP receptor ligands is discussed in the light of these results.
Seven human monoclonal antibodies (HmAb) directed against outer membrane antigens of Haemophilus influenzae type b (Hib) were produced by fusing Sp2/HPT heteromyeloma cells with human tonsillar lymphocytes sensitized in vitro for 6 days. The heterohybridomas were maintained in culture for at least one year and secreted, when cultured in Dulbecco's modified Eagle's medium without fetal calf serum, between 1 and 15 micrograms/10(6) cells/ml/24 h. All of the HmAb were IgGs except HiH-12 which is an IgM. Antibodies directed against the lipopolysaccharide and proteins of apparent molecular masses of 43, 37 and 27 kDa were identified by immunoblotting of sodium dodecyl sulfate-polyacrylamide gel electrophoresis patterns of outer membrane. Binding radioimmunoassay with live bacteria showed that five out of seven HmAb adsorbed to cell surface-exposed antigenic determinants. HmAb HiH-6, HiH-7 and HiH-10 reacted with a surface-accessible determinant on the 43-kDa outer membrane protein. In a dot enzyme immunoassay, these HmAb recognized 103 out of 111 Hib strains isolated worldwide. The strains were selected to represent the most common genotypic variations among Hib. None of these HmAb reacted with other bacterial species tested. These HmAb may serve to study the bacterial surface antigens implicated in the human humoral response and protection to Hib infections.
A series of functional and cell surface markers associated with a significantly increased risk of rheumatic heart disease were analyzed for the contribution of genetic factors in their presence. Peripheral blood lymphocytes from nine large kindreds from the New Zealand Maori, Polynesian, and Caucasian populations were isolated, purified, and evaluated with lymphocyte surface markers (monoclonals 83S.19.23 and D8103), as well as studied for blastogenic response to a purified group A streptococcal extracellular product, blastogen A. Segregation analysis of blastogenic response and percent of cells positive for these cell surface markers was consistent with genetic control by single major genes; however, the contribution by polygenes varied by marker, indicating heterogeneity of genetic control of identification of cell surface glycoproteins and blastogenic response to streptococcal products.
Using cortical wedges and isolated frog spinal cords, the potency of a series of psychoactive phencyclidine (PCP) and sigma receptor ligands as antagonists of N-methyl-D-aspartate (NMDA) has been compared with their potency in neurochemical and behavioural studies. Phencyclidine receptor, but not sigma or kappa, ligands were selective antagonists of NMDA on both preparations. Combination studies suggested that dissociative anaesthetics and sigma benzomorphans act at the same site. The relative potencies of the drugs as NMDA antagonists correlated well with their potency in PCP receptor binding studies in vitro and in PCP discrimination studies in vivo.
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The diagnosis of iliofemoral venous thrombosis prior to its progression to phlegmasia cerulea dolens can be difficult and, at times, confusing. The Doppler ultrasound examination in experienced hands can be extremely reliable and rapid in diagnosing the condition. During an 18 month period, we used the Doppler examination to diagnose iliofemoral venous thrombosis in 21 patients, 15 of whom had corroboration by venogram. The key to successful treatment and avoidance of significant complications was early and accurate diagnosis by the Doppler examination. No patient underwent operation or progressed to venous gangrene. Six were treated with streptokinase and the rest, with intravenous heparin, leg elevation, and stockings. We believe that iliofemoral venous thrombosis is a much more common disease than previously recognized and should be vigorously diagnosed and treated when a patient presents with a symptomatic extremity. The Doppler ultrasound examination represents a rapid, reliable alternative to the venogram in the early diagnosis of iliofemoral venous thrombosis.
Hemodynamically unstable patients will benefit from therapy to control their blood pressure only if this pressure can be determined with accuracy. We compared the accuracy of arterial blood pressure measurements taken aboard helicopters by palpation with a Doppler device and with an oscillometric device. Twenty critically ill patients who required an intra-arterial line had simultaneous blood pressures taken invasively and with one or more of the nonivasive techniques. A total of 222 comparisons was made. Error measurements are reported as mean +/- standard deviation; a high standard deviation implies inaccuracy in individual noninvasive measurements. Mean palpation error was 19 +/- 22 torr, mean Doppler error was 8 +/- 17 torr, mean oscillometric systolic error was 0 +/- 33 torr, and mean oscillometric mean blood pressure measurement error was 10 +/- 15 torr. A blood pressure undetectable by noninvasive means was no guarantee of a low arterial pressure: four patients with arterial systolic pressures from 45 to 138 torr had nonpalpable pulses; three patients had systolic pressures between 98 and 143 torr that were not detectable with the Doppler device; and two patients had systolic pressures of 70 and 110 torr that were undetectable by the oscillometric device. We conclude that aboard helicopters some ill patients cannot have accurate noninvasive measurement of their arterial blood pressure made with present technology. Relying on inaccurate blood pressure measurements may lead to therapeutic mishaps.
The lateral arm flap is located on the lower lateral portion of the arm. The blood supply is via the profunda brachii artery. The flap is based on the lateral intermuscular septum of the arm, the septum being always taken with the flap; the flap can be composite and include the anterior skin of the arm or a segment of humerus, or the nerve of passage, which can be used as a vascularized nerve graft. The lateral arm flap has an important relation with three nerves: the radial nerve, which should always be preserved, the posterior cutaneous nerve of the arm, which can give a sensory innervation for the flap, and the posterior cutaneous nerve of the forearm, which can be used as a vascularized nerve graft. The authors recount the anatomic variations of the artery of the flap and describe the variations of the posterior cutaneous nerve of the arm and the forearm. The knowledge of the relation between these nerves is very important, when one wants to use one of the nerves for sensory innervation of the flap and the other as a vascularized nerve graft. The practical application of this principle is illustrated by the example of one clinical case.
The renal adaptations that maintain potassium homeostasis in diffuse forms of glomerular disease are not well defined. Thus, handling of potassium by superficial nephron segments was examined in a rat model of antiglomerular basement membrane nephritis. Sampling the same nephron successively from the end and beginning of the distal tubule and the end of the proximal tubule allowed a segmental analysis. Despite a 40% reduction in GFR, potassium excretion in the glomerulonephritis animals was normal due to an increase in FEK. The proximal tubule and loop segment did not contribute to the enhanced FEK seen in these animals. In contrast, potassium entry along the distal tubule was significantly greater in the experimental group averaging 13.7 +/- 4.3 pmol/min compared to 1.2 +/- 1.7 pmol/min in controls (P less than 0.01). Multiple linear regression analysis showed that distal tubule potassium entry at any level of flow was enhanced in glomerulonephritis compared to controls (P less than 0.0001). Plasma aldosterone levels were similar in both groups of animals. Thus, the adaptation to potassium excretion seen in glomerulonephritis is partly achieved by the distal tubule through flow-rate independent mechanisms and appears to be independent of plasma aldosterone levels.
A cheap (under 100 pounds at current prices) and simple analogue device is described which permits one to demonstrate, according to an adjustable configuration of the photoreceptive elements, some of the main properties of (i) circularly-symmetrical, (ii) 'simple' elongated opponent-flank, and (iii) multiple-discharge-centre visual receptive fields. The design and construction of the device are described, together with some suggested demonstrations.
The clinical use of exercise rehabilitation programs has increased for patients with coronary artery disease. Exercise testing in these programs typically is conducted on a treadmill or cycle ergometer, although many patients' vocations require upper extremity activities and some patients cannot perform lower extremity exercises. To compare the hemodynamic responses and the incidence of angina and ST-segment depression during upper and lower extremity exercise in patients with coronary artery disease, we administered symptom-limited arm ergometer and submaximal or maximal symptom-limited treadmill tests to 95 cardiac rehabilitation patients who had completed an eight-week exercise training program. Treadmill testing resulted in significantly higher heart rates, systolic blood pressures, and double products than arm ergometer testing. The incidence of ST-segment depression was significantly greater with treadmill testing than with arm ergometer testing, but the incidence of angina was not different between tests. Ten patients had ST-segment depression during both arm ergometer and treadmill testing, and the double products at the onset of ST-segment depression were not different. Our data suggest that arm ergometer testing is less likely to result in ST-segment depression than treadmill testing in patients with coronary artery disease, possibly because of the lower hemodynamic responses during arm ergometer testing.
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1. Two quinozalinediones, FG9041 and FG9065, which had previously been shown to displace binding to the quisqualate receptor, were tested on rat neocortex and frog spinal cord in vitro against depolarizations induced by quisqualate, kainate and N-methyl-D-aspartate (NMDA). In both preparations effects of quisqualate were reduced the most and those of NMDA the least. 2. The near unitary slopes of the Schild plots were consistent with a competitive type of interaction. pA2 values for FG9041 were estimated to be 6.6, 6.1 and 5.1 in frog cord and 5.9, 5.3 and and about 4 in the rat neocortex for quisqualate, kainate and NMDA antagonism, respectively. FG9065 gave equivalent pA2 values of 6.2, 5.6 and 4.5. 3. At concentrations, which were without effect on depolarizations induced by NMDA, FG9041 and FG9065 reduced or blocked synaptically-evoked field potentials in hippocampal and neocortical slices superfused with normal magnesium-containing medium. Since these synaptic components are also insensitive to NMDA antagonists, these results are consistent with their mediation by postsynaptic receptors of the quisqualate (or kainate) type. 4. By contrast, quinoxalinediones had only limited effects on spontaneous epileptiform activity seen in both neocortical and hippocampal preparations when superfused with magnesium-free medium. These burst discharges were, however, abolished by NMDA antagonists. 5. In the frog spinal cord the early component of the dorsal root to ventral root reflexes was selectively reduced by FG9041 whereas NMDA antagonists reduced the longer latency components. 6. Our results suggest that the quinoxalinediones are likely to be useful pharmacological probes for elucidating the role of non-NMDA receptors in the vertebrate central nervous system.