Primary lymphedema in three dogs.
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Biomedical subjects
Publications and source records attributed to R Larsen.
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Arterial hypotension to about 50 mm Hg mean pressure was induced in anaesthetized and artificially ventilated dogs by halothane, nitroprusside, and trimethaphan to study their effects on cerebral blood flow and intracranial pressure during hypotension. During nitroprusside induced hypotension there was a 32% increase in cerebral blood flow above control and a marked decrease in cerebral arteriovenous oxygen content difference indicating luxury perfusion of the brain. Cerebral blood flow remained high even 30 min after termination of hypotension. During halothane and trimethaphan hypotension cerebral blood flow remained unchanged. In all groups epidural pressure did not change substantially during hypotension but increased during recovery from nitroprusside hypotension by a maximum of 72% above control. It is concluded that during and after nitroprusside hypotension loss of cerebral autoregulation occurs which may result in a marked rise in intracranial pressure. Special vulnerability seems to exist shortly after termination of induced hypotension when arterial pressure begins to rise and brain perfusion follows a pressure-flow relationship.
In experiments on 11 closed chest dogs the behaviour of pulmonary gas exchange and haemodynamics during isovolaemic haemodilution with 6% dextran was studied. The dogs were ventilated artificially (IPPB, PEEP = 0) with room air. After haemodilution a slight increase of arterial PO2 from 86 to 92 mm Hg was found. In another series of experiments an inspiratory O2-concentration of 25% was applied resulting in an increase of arterial PO2 from 106 to 113 mm Hg. In both series a decrease of alveolararterial PO2 gradients was observed. Effective pulmonary capillary blood flow varied in accordance with changes of cardiac output. Thus intrapulmonary shunt is supposed to have remained constant. The changes of pulmonary O2 diffusing capacity could be explained by the effect of haemodilution per se. At the end of the experiments ventilation was changed by adding a positive endexpiratory pressure of 8 cm H2O resulting in a decrease of arterial PO2 and a steep fall of cardiac output. In conclusion, isovolaemic haemodilution leads to only negligible variations of pulmonary gas exchange which should not be of any clinical importance.
Various indices of thyroid function were measured in rats at early (2 to 26 days) and at late (up to 55 weeks) intervals after the onset of an iodine deficient diet (LID). Control groups received the same diet with iodine-supplemented drinking water. The measurements included: thyroid total 127I concentration, thyroid weight, [131i] mit/[131i]dit and [131i]t3/[131i]t4 after a labeling period of 18--24 h, serum T4, serum T3, and serum TSH. In the acute experiments serum T4 was significantly decreased at 6--7 days. Thereafter, the decrease was rapid and progressive, and by 26 days serum T4 was reduced to undetectable levels (less than .05 mug per 100 ml). Thyroid T4 decreased more rapidly than serum T4, suggesting that the turnover rate of thyroid T4 increased soon after the onset of LID. Serum T3, in contrast to serum T4 showed no significant change during the 26 day period. Thyroid T3 decreased less rapidly than thyroid T4, but was greatly reduced by 26 days. Presumably the turnover rate of thyroih was slightly but significantly elevated at 4 days, before there was any detectable decrease in serum T4. Thereafter, the results were somewhat variable, but there appeared to be no significant further rise in serum TSH up to about day 15, despite the observation that serum T4 fell rapidly during this period. Only after 15 days did serum TSH display a sharp increase. It is apparent from these results that there is no simple inverse relationship between plasma T4 and plasma TSH. In the chronic experiments serum T4 remained undetectable. Serum T3 was decreased to about 50% of the normal level at 7 weeks but there appeared to be no further decrease even at 55 weeks. Serum TSH rose to very high levels at 12 weeks but showed no further increase thereafter. Thyroid 127I concentration reached its lowest value at 15 weeks and showed no further decrease. Thyroid weight, on the other hand, appeared to increase progressively. To evaluate the effect of severe iodine deficiency on thyroid status, rats that had been on LID for 3-4 months were exposed to a cold environment (4--5 C). Body temperature and survival rates were compared with those of matched controls receiving LID + KI drinking water. The body temperatures of the latter group increased significantly on exposure to cold, and all animals survived. On the other hand, the body temperature of rats on LID alone began to decrease about 5 days after the onset of cold exposure, and when the diet was sufficiently low in iodine the majority of the rats died within 15 days. These results suggest that thyroid function in severely iodine deficient rats is not adequate to meet the challenge of acute cold stress. In this sense, therefore, these animals may be daid to display signs of hypothyroidism.
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The influence of thiopental (Trapanal) on coronary blood flow (MPF), myocardial oxygen consumption (MVO2), and general haemodynamics was investigated in seven patients without heart disease. Besides measurement of MBF, the amount of substrates (glucose, lactate, pyruvate and free fatty acids (FFA) was also determined in arterial and coronary sinus blood samples. Thiopental was given intravenously in a mean dose of 4 mg/kg b,w, MBF was measured by means of the argon method. After injection of thiopental, all seven patients showed a significant increase of MBF and MVO2, a fact which can essentially be explained by the increase of heart rate. The effects of thiopental on arterial concentrations, arterior-coronary substrate differences, myocardial uptake, and O2-extraction ratio of the different substrates are discussed.
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Emotional numbing (EN) symptoms are an important but poorly understood component of the response to trauma. To try to demonstrate EN, this laboratory study examined subjective and psychophysiological emotion responses to standardized visual stimuli in combat veterans with posttraumatic stress disorder (PTSD), combat veterans without PTSD, and nontraumatized controls. PTSD subjects showed no evidence of generalized reduction in subjective or psychophysiological emotion responses. In response to a subset of more evocative stimuli, PTSD subjects reported less experience of Positive Emotions, and more experience of Negative Emotions than controls. For controls, valence and arousal were uncorrelated, while they were negatively correlated for PTSD subjects. Verbal and nonverbal subjective emotion measures were positively correlated for all subject groups, but there was little correlation between subjective emotion measures and psychophysiological indices. Viewing time was positively correlated with Positive Emotions for PTSD subjects, and with Negative Emotions for combat controls.
Using the geographically and socioeconomically varied collaborative Lipid Research Clinics Prevalence Study data, this report focuses upon relationships between dietary intake and plasma lipids and lipoproteins in 1234 white children, 661 boys and 573 girls, aged 6-19 years who were sampled in a random recall (Visit 2) from large populations in six Lipid Research Clinics. Using multiple regression analysis, we found that in 6- to 12-year-old boys the dietary polyunsaturated-to-saturated fat ratio was inversely associated with plasma total and low density lipoprotein cholesterol and dietary cholesterol was positively associated with plasma high density lipoprotein cholesterol. In 13- to 19-year-old boys, high density lipoprotein cholesterol and the ratio of high density lipoprotein cholesterol to total cholesterol were inversely related to sucrose intake. In 6- to 12-year-old girls, plasma triglycerides were positively related to dietary sucrose. Using analysis of covariance in children having the lowest, middle, and top decile nutrient intakes, we found that higher carbohydrate intakes were associated with lower plasma total cholesterol in boys. The highest polyunsaturated fat intake (in 6- to 12-year-old girls) was associated with the lowest plasma cholesterol and very low density lipoprotein cholesterol. The highest cholesterol intake (in 6- to 12-year-old boys) was associated with the highest high density lipoprotein cholesterol levels. In girls, the highest sucrose intakes were associated with the highest plasma triglyceride levels. We conclude that the weak, but statistically significant, associations that we observed were meaningful relative to etiologies of nutrient-lipoprotein interrelationships, and should be useful in forming new hypotheses for focused metabolic ward studies.
BACKGROUND: Etanercept (Enbrel) induces a rapid and sustained decline in disease activity in the majority of patients with refractory juvenile idiopathic arthritis (JIA). For unknown reasons, however, a number of JIA patients fail to respond to this therapy. During this treatment neutralisation of tumour necrosis factor (TNF, previously termed TNF alpha) and lymphotoxin (LT, previously termed TNF beta) may be mediated by etanercept itself as well as by naturally occurring soluble TNF receptors. In light of this, it was of interest to study the total TNF neutralizing capacity in plasma before and during treatment with etanercept. RESULTS: In initial experiments plasma samples from healthy individuals were incubated with etanercept, and spiked with TNF or LT to a final concentration of 1000 pg/mL. Detection of TNF and LT by ELISA was found to be reduced by approximately 50% and 80% respectively, at a concentration of etanercept of 5-500 ng/mL, which is close to the pharmacological plasma concentrations. Plasma samples (n = 80) were then collected from 12 JIA patients (5 with pauciarticular, 5 with polyarticular and 2 with the systemic onset type) during treatment with etanercept (0.4 mg/kg twice weekly) for a period of 20.8 (15.6-23.9) months (median, range). The plasma samples were spiked with LT, and the inhibition of LT detection in ELISA was measured. In samples obtained 3 months after the start of etanercept, the inhibition of LT detection was augmented [72% (60-85)] compared with pre-treatment samples [16% (0.32)] (p = 0.0039). These findings were confirmed in binding assays using radiolabelled TNF. Among patients who responded insufficiently to therapy, reduced LT binding capacity, coinciding with flares of disease activity, was observed. CONCLUSION: We have developed an assay by which LT binding capacity, reflecting the level of free, pharmacologically active etanercept, may be monitored in the blood of patients treated with etanercept. This assay may prove to be useful in guiding dose adjustments in patients with an incomplete response to etanercept.