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Biomedical subjects

P Robinson

Publications and source records attributed to P Robinson.

At least 235 records · Page 13Linked to original sources

Identification of the molecular species of lysophosphatidic acid produced when platelets are stimulated by thrombin.

Platelets, when stirred with 3 U thrombin/10(9) platelets, produced significant quantities of palmitoyllysophosphatidic acid (2.17 ng/10(9) platelets), stearoyllysophosphatidic acid (2.11 ng/10(9) platelets), and arachidonoyllysophosphatidic acid (1.06 ng/10(9) platelets). When platelets were pretreated with 100 microM of the phospholipase A2 inhibitor U10029A, there was a significant decrease in thrombin-stimulated production of stearoyllysophosphatidic acid (to 0.16 ng/10(9) platelets), while arachidonoyllysophosphatidic acid production was unchanged. U10029A concomitantly increased thrombin-stimulated production of stearoyl-containing phosphatidic acid species (primarily stearoylarachidonoylphosphatidic acid) from 5.99 to 9.71 ng/10(9) platelets. The results are consistent with the concept that stearoyllysophosphatidic acid production in platelets occurs via phospholipase A2 degradation of phosphatidic acid.

Blood Platelets↗

Intravenous injection of [1-14C]arachidonate to examine regional brain lipid metabolism in unanesthetized rats.

We examined the metabolic disposition and brain distribution of an unsaturated fatty acid, [1-14C]arachidonate, between 5 and 240 min following its intravenous bolus injection in unanesthetized adult rats. Injected [1-14C]arachidonate was cleared rapidly from plasma, with less than 10% remaining by 2 min. Total brain radioactivity, 0.2% of the injected dose, was near maximal by 5 min, reached a peak by 15 min, then slowly declined. Radioactivity in brain lipids constituted greater than 82% of the total brain radioactivity at all times. Radioactivity in aqueous-soluble metabolites was greatest at 5 min (13% of total) and declined to 5% by 240 min. Protein pellet-associated radioactivity gradually rose to a peak of 7% by 120 min. Within the lipid fraction, more than 92% of radioactivity was in glycerolipids, with greater than 81% in phospholipids. Radioactivity in inositol phosphoglyceride was maximal at 5 min (47% of phospholipid radioactivity); and declined to 34% by 20 min, whereas radioactivity in choline phosphoglyceride peaked at 15 min (41% of phospholipid radioactivity) and was constant thereafter. In contrast, radioactivity in ethanolamine phosphoglycerides increased from 7 to 17% during the course of the experiment. Quantitative autoradiography of brain sections indicated incorporation of [1-14C]arachidonate into gray-matter regions was 1.5- to threefold that into white-matter regions. The data were analyzed in terms of a model for brain fatty acid uptake from plasma. Estimates of unidirectional transfer constants, k, for [1-14]arachidonate from plasma to brain regions with an intact blood-brain barrier ranged from 0.0005 to 0.0015 ml.sec-1.g-1 and were correlated with those for [9,10-3H]palmitate. The results indicate that brain phospholipid metabolism in awake animals can be examined regionally and quantitatively using intravenous injection of [1-14C]-arachidonate combined with quantitative autoradiography and biochemical analysis.

Animals↗

Cell-free human amniotic fluid as culture medium for mouse and human embryos.

Differences between murine and human preimplantation embryonic growth in cell-free human amniotic fluid and medium F-10 supplemented with human fetal cord serum were assessed. Two-cell mouse embryos cultured in human amniotic fluid developed more consistently to the expanded blastocyst stage than those cultured in F-10. No significant difference in human preimplantation embryo cleavage was observed between the two culture conditions. However, amniotic fluid was significantly worse than F-10 + human serum in its ability to maintain embryos that could establish pregnancy after transfer.

Amniotic Fluid↗

Prospective clinicopathologic study of carotid intraplague hemorrhage.

A prospective study was conducted of 82 carotid endarterectomy plaques from 73 patients to determine the incidence of intraplaque hemorrhage, its relation to the production of cerebral ischemic symptoms, and the role of the antiplatelets. These included 42 with hemispheric transient ischemic attacks (TIA), nine with hemispheric stroke (Group A), and 31 with nonhemispheric TIA's or asymptomatic carotid stenosis (Group B). The plaques were evaluated for the presence of hemorrhage. Intraplaque hemorrhage was present in 63 (76.8%) of 82; 46 (90.2%) of 51 in Group A had hemorrhage, in contrast to 17 (54.8%) of 31 in Group B (P less than .001). Twenty-nine (56.86%) plaques from patients in Group A had multiple hemorrhages and 22 (43.14%) had single or no hemorrhages; in contrast to two (6.45%) that had multiple hemorrhages and 29 (93.55%) that had single or no hemorrhages in patients in Group B (P less than .0005). Forty-seven plaques were removed from patients receiving antiplatelets; 43 (91.48%) of these showed hemorrhages. Of the 35 plaques that were removed from patients not receiving antiplatelets, 26 (74.2%) showed hemorrhages (P = .071). However, when the plaques were studied for multiple hemorrhages, 28 (59.5%) of 47 had multiple hemorrhages in patients receiving antiplatelet agents in contrast to 3 (8.57%) of 35 in patients receiving antiplatelet agents (P less than .00001). The authors conclude that 1) the intraplaque hemorrhage is an important and common feature in symptomatic carotid disease, 2) antiplatelets increase the incidence of plaque hemorrhages, particularly multiple hemorrhages that carry higher incidence of symptoms. Therefore the use of antiplatelet agents in certain patients with carotid artery disease is questioned.

Carotid Arteries↗

Dynamic liver scanning in cirrhosis.

Dynamic hepatic scintigraphy was performed in 49 patients with established cirrhosis, using intravenous 99Tcm-pertechnetate and 99Tcm-sulphur colloid in a prospective study of its predictive value. There was a close correlation between the hepatic perfusion index (reflecting the ratio of arterial to total hepatic blood flow) obtained with pertechnetate (HPI-P) and with sulphur colloid (HPI-C) (r = 0.775; p less than 0.0001), and both indices correlated with disease severity (HPI-P p less than 0.0001; HPI-C p less than 0.01). HPI-P was significantly increased in patients who died, in patients with varices and in those with hepatic encephalopathy. HPI-C was significantly increased in patients with varices, in patients with hepatic encephalopathy and in those who had bled from varices. Neither HPI-P nor HPI-C was able accurately to predict the development of complications during the follow-up period. The trapping index (TI), reflecting a combination of hepatic extraction efficiency, degree of intrahepatic shunting and extrahepatic extraction of colloid, was significantly impaired in patients who died and in those with ascites, varices and/or variceal bleeding, but not in patients with hepatic encephalopathy. The trapping index correlated with disease severity, as did the computer-derived spleen-liver ratio (S-L ratio). Neither TI nor S-L ratio was able to predict the development of complications. The clearance rate constant of colloid from peripheral blood, the uptake rate constants for liver and spleen, and splenic volume were all found to be unhelpful as indicators of disease severity or as predictors of complications. While perfusion indices derived by dynamic hepatic scintigraphy reflect the severity of the underlying liver disease, their determination on a single occasion appears to offer no benefit in predicting the likelihood of major complications.

Adult↗

Complications of carotid endarterectomy: the influence of case load.

We reviewed the records of 508 consecutive carotid endarterectomies done by 19 surgeons during a five-year period in one medical center to evaluate postoperative complications (stroke and death). Each of 16 surgeons did 32 operations or fewer, with case loads ranging from one to 32. Three surgeons did 70, 98, and 172 respectively. The incidence of stroke among patients of the 16 surgeons combined who did 32 cases or fewer in five years (fewer than ten cases per year) was 7%, with a combined stroke and death rate of 8%; in contrast, patients of the combined surgeons who did more than 32 operations in five years (more than ten cases per year) had a stroke rate of 3%, with a combined stroke and death rate of 3%. When the carotid disease was examined separately, it was apparent that the adverse event rate among patients with asymptomatic or nonhemispheric disease accounted for the difference. Patients of surgeons with fewer cases had 18% adverse events, whereas those of more experienced surgeons had 2% adverse events. The adverse events were similar for both groups in patients with focal transient ischemic attacks or stroke. Seven of the 16 surgeons who did fewer than 32 cases had no patients who had stroke, despite the few carotid endarterectomies they had done. Thus, the stroke rate was somewhat lower in the hands of those surgeons who did endarterectomy more often, but the number of carotid endarterectomies done by a surgeon is not the only factor to decrease the stroke rate. Proper selection of patients and attention to risk factors and technique are essential.

Adult↗

Mycobacterium bovis as an occupational hazard in abattoir workers.

Five cases of bovine tuberculosis occurred in a two year period in South Australia, which represents a higher incidence than in previous years. All five patients had a history of employment in an abattoir (although four different abattoirs were involved) and four of the cases had pulmonary or pleural TB. A voluntary survey of one of the abattoirs was conducted which discovered the fifth case of active pulmonary TB. We suggest that bovine TB should be considered an occupational hazard in abattoir workers, and that suitable pre-employment screening programmes for workers be established. The transmission of disease in these cases is almost certainly by inhalation causing pulmonary TB and is therefore different from the 'classic' form of bovine TB transmitted by ingestion of infected milk and resulting in extrapulmonary disease.

Abattoirs↗

Pharmacological constriction of the lower oesophageal sphincter: a simple method of arresting variceal haemorrhage.

The effect of pharmacological constriction of the lower oesophageal sphincter (LOS) on oesophageal varices was investigated in an experimental study followed by a controlled clinical trial. In the experimental study intravariceal pressure was measured just above the LOS in 11 patients before and after constricting the LOS by intravenous pentagastrin. Intravariceal pressure fell from a mean of 23 (range 12-36) mmHg to 4 (range 0-7) mmHg (p less than 0.001). This marked pressure drop indicated the considerable compression of varices that occurred within the LOS. A prospective controlled clinical trial examined whether LOS constriction (effected by the longer acting metoclopramide) would compress varices sufficiently to arrest active variceal bleeding originating from the lowest 2 cm oesophagus--the area encircled by the LOS. Of 11 patients who received metoclopramide, 10 stopped bleeding compared with four of the 11 who received placebo (p less than 0.01). Pharmacological constriction of the LOS appears to offer a new and effective approach for arresting active bleeding from oesophageal varices.

Adult↗

Inosine.adenine base pairs in a B-DNA duplex.

The structure of the synthetic deoxydodecamer d(C-G-C-I-A-A-T-T-A-G-C-G) has been determined by single crystal X-ray diffraction techniques at 2.5A resolution. The refinement converged with a crystallographic residual, R = 0.19 and the location of 64 solvent molecules. The sequence crystallises as a B-DNA helix with 10 Watson-Crick base-pairs (4 A.T. and 6 G.C) and 2 inosine.adenine (I.A) pairs. The present work shows that in the purine.purine base-pairs the adenine adopts syn orientation with respect to the furanose moiety while the inosine is in the trans (anti) orientation. Two hydrogen bonds link the I.A. base-pair, one between N-1(I) and N-7(A), the other between O-6(I) and N-6(A). This bulky purine.purine base-pair is incorporated in the double helix at two positions with little distortion of either local or global conformation. The pairing observed in this study is presented as a model for I.A base-pairs in RNA codon-anticodon interactions and may help explain the thermodynamic stability of inosine containing base-pairs. Conformational parameters and base stacking interactions are presented and where appropriate compared with those of the native compound, d(C-G-C-G-A-A-T-T-C-G-C-G) and with other studies of oligonucleotides containing purine.purine base-pairs.

Adenine↗

Usefulness of manometric assessment of varices in maintenance sclerotherapy. A controlled trial.

In a prospective controlled study, 68 patients undergoing maintenance sclerotherapy were randomized to have intravariceal sclerotherapy based on either manometric assessment (n = 35) or visual assessment (controls, n = 33) of varix patency. For manometric assessment, a perfused variceal needle punctured each variceal column and, if low pressures fluctuating with respiration were obtained, the varix was injected. Control patients had patent varices injected based on visual assessment alone. During a mean follow-up of 13 mo (range 4-16 mo), 1 manometrically assessed patient bled once (0.002 bleeds/patient month) and 7 visually assessed patients bled 14 times from varices (0.03 bleeds/patient-month) (p less than 0.05). Two and nine episodes of ulceration occurred in manometric and visually assessed patients, respectively, (p less than 0.05). Varices were obliterated (i.e., disappeared) in 11 patients undergoing manometric assessment and in 2 patients undergoing visual assessment (p less than 0.01). Comparing results of visual and manometric assessment within "manometric" patients showed a consistent 25% error rate in diagnosing patency or thrombosis by visual assessment. Manometric assessment of varices during maintenance sclerotherapy reduces rebleeding and ulceration to very low levels.

Clinical Trials as Topic↗

Nontransducing rhodopsin.

Rhodopsin is converted by light to an active photoproduct that triggers the transduction cascade. The active photoproduct must then be inactivated by some kind of chemical modification. The question addressed here is whether photoconversion of the inactive photoproduct to rhodopsin creates a modified form of rhodopsin that is unable to support transduction. This question was investigated in ultraviolet receptors of Limulus median eye by measuring the relative quantum efficiency of excitation after photoregeneration of rhodopsin from the inactive photoproduct. The results show that when this newly created rhodopsin absorbs a photon, no receptor potential is generated; i.e., the pigment is nontransducing. A dark process requiring 30-60 min returns rhodopsin to its transducing form.

Animals↗

Effect of Valsalva's manoeuvre and hyoscinbutylbromide on the pressure gradient across the wall of oesophageal varices.

To assess whether Valsalva's manoeuvre might cause variceal bleeding, 22 patients with oesophageal varices were studied. In 12 patients who received no previous treatment to their varices the median pressure gradient across the varix wall at rest was 19 (6-36) mmHg, and in 10 patients whose varices were thrombosed at their distal end the median pressure gradient in the proximal patent varix was 8 (1-6) mmHg. In untreated patients groups, the pressure gradient rose by 6-12 mmHg during Valsalva's manoeuvre in four patients, fell by 4-11 mmHg in five patients and was virtually unchanged in the remainder. These changes seem unlikely to cause variceal bleeding. Patients who repeated Valsalva's manoeuvre showed similar changes on each occasion. Six patients in the untreated group also received hyoscinbutylbromide 20 mg iv. No change was seen in the pressure gradient in five patients, suggesting that it is of little value in preventing variceal bleeding.

Adult↗

A component of Mycobacterium leprae as immunomodulating agent for immune deficient cells of leprosy patients.

The delipidified component of the insoluble portion which presumably is the cell wall of Mycobacterium leprae (DCW) was able to induce lymphocyte proliferation in the leucocyte culture from the peripheral blood of lepromatous leprosy patients. Normally these cells show no lymphocyte proliferation in response to M. leprae or their sonicated extract. The delipidified component (DCW) appears to be proteinaceous and able to induce antibodies in rabbit. The DCW has affinity to the sera from lepromatous leprosy patients but not sera from normal healthy individuals or tuberculoid leprosy patients. The ability to induce lymphocyte proliferation is blocked by agglutination of DCW with patient sera, heat treatment of DCW or protease treatment of the component. Along with lymphocyte proliferation, DCW also induces ability in the macrophages to render phagocytosed M. leprae non viable. Thus it is proposed that DCW of M. leprae could be a potent immunomodulator for immunedeficient cells of leprosy patients. The efficacy of DCW as a probable immunoprotector for M. leprae infection in mice has already been demonstrated earlier.

Adjuvants, Immunologic↗

Transventricular aortic valvotomy for critical aortic stenosis in infants.

Ten infants with critical aortic stenosis underwent transventricular valvotomy between November 1983 and September 1984. The ages of the patients ranged from 1 to 38 days (mean 21.2 days). Three patients were less than 1 week of age. One had undergone a previous valvotomy performed with inflow occlusion. Most infants were critically ill when admitted to the hospital, six required inotropic and ventilatory support, and two had peritoneal dialysis before the operation. Transventricular valvotomy was performed through a left thoracotomy with Hegar dilators. Postvalvotomy peak-to-peak gradients ranged from 0 to 35 mm Hg. Three patients died at 2, 3, and 6 weeks after operation. A severe degree of endocardial fibroelastosis was present in one patient, and a second patient died of septicemia caused by wound infection, empyema, and a bronchopleural fistula. Severe left ventricular hypertrophy, with moderate fibroelastosis, was found at autopsy in the third patient. Aortic incompetence was not detected postoperatively. One patient required reoperation 7 months after the transventricular valvotomy. Transventricular valvotomy has proved to be a simple and effective technique to relieve aortic stenosis in sick infants. It permits the correction of associated coarctation of the aorta and avoids a median sternotomy. Results are comparable with the results obtained with either cardiopulmonary bypass or inflow occlusion as seen in both our experience and in the experience of others.

Aortic Valve↗