Prophylaxis of venous thrombosis following total hip and total knee replacement using antithrombin III and heparin.
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Antithrombin III↗
Biomedical subjects
C M Harris
Publications and source records attributed to C M Harris.
Ankle arthrodesis with vertical Steinmann's pins in rheumatoid arthritis.
Many techniques for ankle arthrodesis have been described but some of them are not applicable in patients with severe rheumatoid arthritis (RA) who have also developed osteopenia and decreased bone density. A technique utilizing two longitudinally placed Steinmann's pins to fixate and align the joint was used in five patients with severe RA and is described here. Results showed a 100% fusion rate and patient satisfaction over an average follow-up time of six years. This ankle arthrodesis technique was found to be applicable in arthritic patients with osteopenia and decreased bone density caused by RA.
Ankle Joint↗
Pipecolic acid biosynthesis in Rhizoctonia leguminicola. I. The lysine saccharopine, delta 1-piperideine-6-carboxylic acid pathway.
The biosynthesis of pipecolic acid from L-lysine in the fungal parasite, Rhizoctonia leguminicola has been reinvestigated. Pipecolate is then utilized to form the toxic octahydroindolizine alkaloids, slaframine and swainsonine. Incorporation studies of L-versus D-[U-14C]lysine into R. leguminicola metabolites confirmed earlier findings that L-lysine is the predominant substrate for pipecolate formation and D-lysine for alpha-N-acetyllysine (concerned in lysine catabolism). However [alpha-15N]lysine, not [epsilon-15N]lysine as previously reported, labeled pipecolate. Such findings implied that delta 1-piperideine-6-carboxylate, not delta 1-piperideine-2-carboxylate, was formed from lysine and was the immediate precursor of pipecolate. Evidence from cell-free enzyme systems established the following biosynthetic events: L-lysine A----saccharopine B----delta 1-piperideine-6-carboxylate C----pipecolate. Products of reactions A and C were identified from biological and chemical considerations. Reaction B was carried out by a previously undescribed flavin enzyme termed saccharopine oxidase. The product of reaction B, which reacted with p-dimethylaminobenzaldehyde, was reduced with Na-CNB2H3. Its NMR spectrum was identical with that of deuteriated pipecolate prepared from authentic delta 1-piperideine-6-carboxylate, but not from authentic delta 1-piperideine-2-carboxylate. Reaction B represents a branching of primary lysine metabolism from saccharopine to a secondary pathway leading to pipecolate and to octahydroindolizine alkaloids in R. leguminicola.
Lysine↗
Fourier analysis of saccades in monkeys and humans.
1. By recording eye movements with the search coil technique and subjecting them to an accurate infinite Fourier transform algorithm, we describe the Fourier spectra of human and monkey saccades. In both species we find heretofore undescribed features consisting of a regular pattern of local minima in the power plot, which cannot be attributed to noise. The frequency of these minima is well correlated with saccade duration. 2. Computer simulation shows that if the pulse component of the saccade is considered to be rectangular, then the first of these minima (called M1) occurs at a frequency that is the reciprocal of the duration of the pulse. 3. Comparing the position of this component during individual monkey saccades with electrophysiological recordings of motoneurons during the same saccades leads to the conclusion that these minima are related to the burst components in ocular motoneuron discharges. Specifically, the reciprocals of the frequencies of these minima are correlated with the duration of the burst component in the motoneuron discharge. 4. In the Fourier spectra of human saccades, the relationship of the frequency of M1 to saccadic duration is a function similar to that in the monkey. This adds to the evidence that the human saccade also is driven by a pulse-step signal. 5. In both monkeys and humans, T1, the reciprocal of the frequency of M1, is shorter than both the saccade duration and the burst duration of individual motoneurons, even though neurophysiological studies in monkeys generally report the saccadic burst duration to be equal to the saccade duration. This probably arises because the saccadic pulse is not rectangular, with the extremes contributing very little energy to the Fourier spectrum. By further computer modeling we show these shape effects explicitly: as the rise- and falltime increase, making the pulse less rectangular, T1 becomes shorter; in addition, as the asymmetry of rise and fall increases, the depth of the minima is reduced. We conclude that T1 measures the "effective pulse" duration of the motoneuron. 6. There is a difference in the relationship of effective pulse duration to the saccade duration between short and long saccades. For saccades shorter than approximately 40 ms in the human and 50 ms in the monkey, the pulse width as measured by this technique varies little with saccade duration. For longer saccades, effective pulse width increases linearly with duration. We agree with others that for short saccades the pulse is both height- and width-modulated; but for longer saccades, height modulation saturates and only width modulation remains.(ABSTRACT TRUNCATED AT 400 WORDS)
Adult↗
The relationship of physician assistants to an orthopedic residency program.
In 1979, coincident with a planned decrease in the size of the general surgery training program, the orthopedic department of the senior author's university-affiliated teaching hospital began to employ physician assistants. The intent of using physician assistants was to relieve the two orthopedic residents assigned to the hospital of many service responsibilities and patient care that previously had been rendered by the general surgical residents and interns. The non-M.D. physician assistants record a comprehensive past and present medical history, carry out physical exams, and assist at surgery. They are directly under the supervision of and responsible to the attending surgeon. It was hoped the addition of these individuals will help maintain a quality educational experience for the orthopedic residents. The general response to the use of physician assistants in this affiliated hospital has been favorable.
Hospital Bed Capacity, 300 to 499↗
Bilateral hip and bilateral knee arthroplasties in a patient with ochronotic arthropathy.
Alkaptonuria is a rare, autosomal-recessive, inborn, metabolic disease that causes ochronotic arthropathy leading to disabling arthritis. Few reports of arthroplasty in patients with this disease have been published, and none documents four total joint replacements in the same patient. This case report describes the history and findings in a 70-year-old man who underwent bilateral hip and knee total joint arthroplasties with significant improvement in pain and exercise tolerance. The metabolic and clinical aspects of alkaptonuria are also discussed.
Aged↗
Antithrombin III prophylaxis of venous thromboembolic disease after total hip or total knee replacement.
The use of antithrombin III (ATIII) replacement in combination with low-dose heparin therapy in prevention of postoperative venous thrombosis in patients following total hip replacement or total knee replacement was evaluated. A randomized prospective venographically controlled trial in hip replacement compared treatment with dextran 40 with a regimen of ATIII (1,500 units preoperatively and 1,000 units daily for five days) and low-dose heparin. Patients receiving ATIII/heparin had significantly higher postoperative ATIII concentrations than dextran-treated patients and also had a low incidence of venous thromboembolic disease (7 percent). The ATIII/heparin regimen was well tolerated with no increase in bleeding or significant prolongation of the activated partial thromboplastin time. Two cohorts of patients undergoing total knee replacement were studied using different doses of ATIII in combination with heparin. An initial 10 patients were treated with the same ATIII dose used for patients undergoing total hip replacement, with a 50 percent incidence of venous thrombosis. A second group of 11 patients was treated with twice the dose of ATIII, and an incidence of venous thrombosis of 27 percent was found. The higher ATIII dose resulted in significantly higher ATIII concentrations and maintained the postoperative ATIII concentration above normal. Among patients receiving prophylaxis with either warfarin. dextran, or ATIII/heparin, no clear association was found between reduced ATIII concentrations and occurrence of venous thrombosis. It is concluded that ATIII replacement following total hip or knee replacement corrects the postoperative ATIII deficiency and that the combination of ATIII and low-dose heparin is an effective prophylactic regimen following total hip replacement.
Antithrombin III↗
The ethology of saccades: a non-cognitive model.
It is proposed that there is a low-level automatic component of visual scanning in which saccades are triggered probabilistically in time by non-foveal stimulus features. By ignoring cognitive factors and memory, a first-order Markov approach is taken, which is tractable for spatially homogeneous stimuli. The predicted distributions of saccade magnitude, fixation duration, fixation position, and how they are related to stimulus size are in good agreement with empirical observations by Bahill et al. (1975), Enoch (1959), and Harris et al. (1988). Ways in which this low-level process could be modulated by cognitive factors are discussed.
Eye Movements↗
Sensitivity of pentylenetetrazol discrimination increased by a stimulus fading technique.
The interoceptive stimulus produced by pentylenetetrazol (PTZ) is pharmacologically similar to anxiety and is used in a behavioral assay for anxiety-related stimuli (the PTZ model of anxiety). The stimulus fading technique was tested as a method to increase the sensitivity of this assay. Rats were trained with food-reward to press one lever after injection of PTZ and an alternate lever after saline. Rats initially learned the discrimination at a PTZ dose of 20 mg/kg. They were then trained with sequentially lower doses until they reliably discriminated a PTZ dose of 10 mg/kg. Substitution tests with other doses and drugs showed that, after the fading procedure, dose-response curves were shifted to lower doses for PTZ, Ro 5-3663, and nicotine Similarly, the dose of diazepam required to block the low dose of PTZ was lower than that required to block the higher dose of PTZ. These results indicated that the sensitivity of the discrimination was enhanced in rats trained to discriminate a lower dose of PTZ. Doses of nikethamide, cocaine, and yohimbine that did not substitute for the higher dose of PTZ also did not substitute for the lower dose. These data suggest that rats can be trained to discriminate a low dose of PTZ by the stimulus fading technique. Moreover, they suggest that this training method does not compromise the specificity of the discrimination.
Animals↗
Prevention of venous thrombosis after total hip arthroplasty. Antithrombin III and low-dose heparin compared with dextran 40.
The anticoagulant action of heparin is mediated through antithrombin III, and the postoperative decrease in the plasma concentration of antithrombin III may contribute to the relative ineffectiveness of prophylaxis with low-dose heparin in preventing venous thrombosis after total hip arthroplasty. We conducted a prospective, randomized trial to compare the effectiveness of a regimen of antithrombin III, given intravenously once daily, and low-dose heparin with a regimen of dextran 40, given intravenously, in preventing venographically documented venous thrombosis after total hip arthroplasty. The results demonstrated an incidence of venous thrombosis of 4.9 per cent in patients who received antithrombin III and heparin; this was significantly lower than the incidence (28.6 per cent) in patients who received dextran 40 (p less than 0.005). Venous thrombosis occurred only in patients who had total hip arthroplasty with a cemented prosthesis (fourteen of fifty-seven patients, or 24.6 per cent); none of the twenty-six patients in whom a non-cemented prosthesis was used had venous thrombosis (p less than 0.01). Of the patients in whom a cemented prosthesis had been inserted, the incidence of venous thrombosis was lower in those who were treated with antithrombin III and heparin (7.4 per cent) than in those who were treated with dextran 40 (40 per cent) (p less than 0.005). Postoperative levels of antithrombin III were maintained at more than 90 per cent of the baseline level in patients who received it; this was significantly higher than in patients who received dextran 40.(ABSTRACT TRUNCATED AT 250 WORDS)
Antithrombin III↗
William Pickles lecture 1989. Seeing sunflowers.
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England↗
Improving our prescribing.
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Drug Prescriptions↗
Quantal detection and homogeneous sensitivity in a pentylenetetrazol discrimination.
Rats were trained to discriminate pentylenetetrazol (PTZ, 20 mg/kg) from saline in a two-lever operant task. Correct lever presses were reinforced with food under the control of a fixed ratio 10 schedule. In tests of the effect of PTZ dose on lever selection, rats selected the PTZ lever in a dose-dependent manner, with peak latency at the approximate ED50 dose (10 mg/kg). Rats usually pressed only the selected lever, regardless of dose, indicating that lever selection was a quantal (or bimodal) function of stimulus intensity. Lever biases observed during training sessions did not predict the performance of individual rats in tests with the ED50 dose. In three independent trials with this intermediate dosage, the rats selecting the PTZ lever varied from trial to trial, suggesting that rats detecting this dose did not form a stable subgroup. The pattern of lever selections across these three trials was not significantly different from that predicted by a model in which all subjects shared the same probability for detecting the drug stimulus. These results demonstrate that lever selection in a two-lever drug-discrimination task can be quantal in nature, and suggest that rats trained with PTZ, 20 mg/kg, are homogeneous in sensitivity to this stimulus.
Animals↗
The effects of in vitro lipid peroxidation on the activity of rat liver microsomal glutathione S-transferase from rats supplemented or deficient in antioxidants.
Glutathione S-transferases are a group of multifunctional isozymes that play a central role in the detoxification of hydrophobic xenobiotics with electrophilic centers (1). In this study we investigated the effects of in vitro lipid peroxidation on the activity of liver microsomal glutathione S-transferases from rats either supplemented or deficient in both vitamin E and selenium. Increased formation of malondialdehyde (MDA), a by-product of lipid peroxidation, was associated with a decreased activity of rat liver microsomal glutathione S-transferase. The inhibition of glutathione S-transferase occurred rapidly in microsomes from rats fed a diet deficient in both vitamin E and selenium (the B diet) but was delayed for 15 minutes in microsomes from rats fed the same diet but supplemented with these micro-nutrients (B+E+Se diet). Lipid peroxidation inhibits microsomal glutathione S-transferase and this inhibition is modulated by dietary antioxidants.
Animals↗
The distribution of fixation durations in infants and naive adults.
The distributions of durations of fixations from infants and free-viewing adults are shown to be basically exponential for different stimulus conditions. It is found that fixation duration can be divided into two periods. One, the alpha-period, is a refractory period during which a saccade does not occur and fluctuates across fixations. The other, the beta-period, is a random variable intrinsic to each fixation and constitutes a waiting-time for a saccade that occurs with constant probability per unit time. It is shown that mean duration decreases when stimulus size increases. These results suggest that fixations are terminated by saccades triggered by non-foveal stimulation.
Adult↗
Withdrawal from diazepam substitutes for the discriminative stimulus properties of pentylenetetrazol.
Rats were trained to discriminate pentylenetetrazol (PTZ, an anxiogenic drug), 20.0 mg/kg, from saline using a food-maintained two-lever-choice task. When treated chronically with diazepam (DZP) and tested with the benzodiazepine-receptor antagonist Ro 15-1788, withdrawal from DZP produced a PTZ-like stimulus in these subjects that was related directly to the dose of DZP given every 8 hr for 6 days. In contrast, only the highest dose of DZP (80 mg/kg/8 hr) given chronically produced even minimal physical signs of precipitated abstinence after Ro 15-1788. In a separate experiment, Ro 15-1788 produced a PTZ-like stimulus when given at 2-day intervals during chronic administration of DZP. In this experiment, rats were maintained on DZP, 40.0 mg/kg/6 hr for 14 days. These subjects were tested with Ro 15-1788, 40.0 mg/kg, every 2 days during days 6 through 14 of chronic DZP, and Ro 15-1788 substituted for PTZ on 4 of these 5 tests. Because these experiments involved periods of nontraining on the discrimination task, a final experiment was performed to test the stability of stimulus control in rats trained to detect PTZ. DZP was administered for up to 20 days, withdrawal was precipitated by Ro 15-1788 and after an additional 16 to 40 days of nontraining, stimulus control was tested. There was no significant decline in stimulus control over this period. These results suggest that PTZ discrimination provides a sensitive, stable assay for the detection of withdrawal from benzodiazepine dependence.
Animals↗
Characterization of a pentylenetetrazol-like interoceptive stimulus produced by ethanol withdrawal.
Rats were trained with food reinforcement to discriminate the anxiogenic drug pentylenetetrazol (PTZ, 20 mg/kg) from saline in a two-lever-choice task. In Experiment 1, ethanol, 8.25% w/v was given by gavage (7/day) for 4 days, with doses titrated to maintain moderate intoxication. After termination of ethanol, the rats exhibited mild overt signs of withdrawal and, in discrimination tests with saline as the test substance, they selected the PTZ lever, an effect reversed by ethanol, 2 g/kg, and by diazepam, 5 mg/kg. In Experiment 2, rats drank a nutritionally complete liquid diet containing ethanol, 4.5% w/v, for 1 week. They became tolerant to the intoxicating effect of ethanol, and blood ethanol concentration mounted with continued dosing. On termination of chronic ethanol, rats selected the PTZ lever before the onset of overt physical signs of withdrawal, and both measures returned to base line within 3 days. In Experiment 3 the percentage of rats selecting the PTZ lever after termination of ethanol depended upon the dose (up to 12.5 g/kg) and duration (up to a ceiling effect by 3 days) of ethanol administered chronically. These results indicate that a PTZ-like stimulus produced interoceptively can be demonstrated in the rat as an objective measure of ethanol withdrawal. This paradigm may provide insight into the symptom of anxiety associated with ethanol withdrawal.
Animals↗
Involvement of the hip in juvenile rheumatoid arthritis. A longitudinal study.
Thirty-five children who had rheumatoid arthritis were followed for three to twenty-two years. Four categories of involvement of the hip were seen. In the first group, thirteen patients had mild disability and slight radiographic changes. In six of those patients the disease was in remission at the time of writing, and the patients were asymptomatic. In the second group, two patients had episodic disability that correlated with the activity of the disease. In the third group, fourteen patients had progressive disability and radiographic changes. Fifty-five of the fifty-nine procedures that were performed on the hip and knee in this series were done on those fourteen patients. In the fourth group, six patients had dramatic clinical and radiographic findings but, at the time of the latest follow-up, had little functional disability. In all six of these patients, the disease was in remission. In the children in this study, protrusio acetabuli was more cephalad than has been found in adults who have rheumatoid arthritis. All of the children had psychosocial problems, but they responded well to counseling. These problems influenced the timing of the surgical treatment.
Adolescent↗