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Biomedical subjects

P Walker

Publications and source records attributed to P Walker.

At least 271 records · Page 15Linked to original sources

Red blood cell catechol O-methyltransferase activity in thyroid dysfunction.

Using a modification of the method of Mannl et al. (Mannl, H.F.K., Hempel, K., and Kubler, W. 1972. Catechol O-methyltransferase in human erythrocytes. Arch. Pharmacol. 272, 265-276), we have measured the activity of catechol O-methyltransferase (COMT) (EC 2.1.1.6) in red blood cells (RBC) of patients with hyperthyroidism and hypothyroidism to establish whether thyroid dysfunction is associated with alterations in catecholamine catabolism. The activity of COMT averaged 4.4+/-0.54 nmol/ml RBC per hour of incubation (mean+/-SEM) in euthyroid subjects compared to 4.76+/-0.64 nmol/ml RBC per hour of incubation in hyperthyroidism and 4.42+/-0.81 nmol/ml RBC per hour of incubation in hypothyroidism; these values are not significantly different. There were no significant differences observed in urinary excretion of vanillylmandelic acid, epinephrine, and norepinephrine among the three groups. These data are compatible with the possibility that thyroid status has little influence on the degradation of circulating catecholamines and suggest that hypothyroidism, with its attendant elevations in serum norepinephrine concentration, may be related to a compensatory noradrenergic response.

Catechol O-Methyltransferase↗

Absence of placental transfer of l-triiodothyronine (T3) in the rat.

To detect placental transfer of L-triiodothyronine (T3) in pregnant rats, we injected 1 muCi [125I]T3 on the 16th, 18th, and 20th day of gestation. Three hours after the injection, which corresponds to the equilibrium time determined by a method of constant infusion, the pregnant rats and their fetuses were killed. The [125I]T3 was extracted from the serum or the homogenate by butanol extractions and alkaline washes. The transfer rate was calculated from the quantity of [125I]T3 in the serum of the fetuses after 3 hr and from the maternal metabolic clearance rate (8.19 +/- 0.45 ml/hr/100 g body weight; mean +/- SEM). At the 16th day of gestation, the placental transfer of T3 was 0.82 +/- 0.11% of the total maternal clearance rate/litter weight; it was 1.05 +/- 0.25% at the 18th day of gestation and 0.58 +/- 0.10% at the 20th day of gestation. There were no significant differences between these results. The maternal T3 concentration was 68.27 +/- 20.6 ng/100 ml and its production rate was 5.57 +/- 0.31 ng/hr/100 g; with these data we calculated a maternal-fetal T3 transfer of 46 +/- 6 pg/hr. Furthermore, there was no T3 transfer observed when the mother received 1.9 mug unlabeled T3, which led to a significant rise in maternal T3 concentration (68.27 +/- 20.6 ng to 102.23 +/- 7.41 ng/100 ml; P less than 0.01); there was no detectable T3 in the fetal serum. From these results we conclude that there is minimal or no placental transfer of T3 in the rat and that the hypothalamic-pituitary-thyroid axis of the fetus develops autonomously.

Animals↗

The development of the hypothalamo-pituitary axis in the neonatal rat: hypothalamic somatostatin and pituitary and serum growth hormone concentrations.

Using a specific radioimmunoassay technique for somatostatin (GHRIH), we have studied the ontogenesis of hypothalamic GHRIH in relation to pituitary and serum GH concentrations in immature rats. Hypothalamic GHRIH concentrations rose from minimal levels of 4.5 +/- 0.2 pg/microgram protein (mean +/- SEM) at 2 days to peak concentrations of 40.6 +/- 4.1 pg/microgram protein at 28 days followed by a progressive decline toward 50 days (7.0 +/- 0.8 pg/microgram protein). Pituitary GH concentration attained peak prepuberal values of 203.5 +/- 22.8 ng/microgram protein at 16 days with a further marked rise after puberty. Serum GH concentration was elevated to 2 days (53.3 +/- 5.7 ng/ml) and declined progressively to 5.9 +/- 1.5 ng/ml at 13 days. There was a highly significant inverse correlation between hypothalamic GHRIH and serum GH concentrations (r = 0.743, P less than 0.005). These data indicate that the hypothalamic regulatory mechanism for pituitary GH release develops during the neonatal period of the rat and suggest that GHRIH may play an important physiological role in this process.

Aging↗

Catecholamine metabolism in thyroid disease. II. Norepinephrine secretion rate in hyperthyroidism and hypothyroidism.

We have measured the secretion rate of norepinephrine (NE) in 6 euthyroid subjects, 6 hyperthyroid and 6 hypothyroid patients, infused at a constant rate (0.1 microC/kg/min) for 1 h with tritiated norepinephrine (New England Nuclear Inc.). Plasma NE concentrations were measured by a modification of the fluorometric method of Anton and Sayre. A significant linear relationship was observed between plasma NE and age in normal subjects. Accordingly, values for plasma NE have been corrected for age. Plasma NE concentration was 18.3 +/- 4.2 ng/100 ml (mean+/-SEM) in normal subjects compared with 17.5 +/- 3.3 ng/100 ml in hyperthyroid patients. There was a significant elevation of plasma NE (30.3 +/- 2.9 ng/100 ml) in hypothyroid patients (P less than 0.05). A significant elevation was observed in plasma NE secretion rates in hypothyroidism 4.62 +/- 0.98 microgram/kg/day (P less than 0.02) when compared to the control group (1.46 +/- 0.35 microgram/kg/day). No significant difference was observed between the hyperthyroid group (1.74 +/- 0.49 microgram/kg/day) and the controls. These data indicate that the plasma NE secretion rate is normal in hyperthyroidism, and is significantly elevated in hypothyroidism thereby explaining the higher plasma NE concentrations seen in hypothyroidism.

Epinephrine↗

Canine tendon studies. II. Biomechanical evaluation of normal and regrown canine tendons.

Some of the mechanical properties of regrown canine tendons are compared to those of normal tendons of young and mature animals. Patellar and Achilles tendons from 12 beagle dogs were removed and studied with their bone origin and insertions. Mechanical tests were performed within 24 hr and test conditions simulated the physiological function of the tendon in vivo at room temperature. Specimens were soaked in Ringers solution and mounted in an Instron testing machine with load deflection curves plotted automatically. The parameters used for analysis were load extension, stress relaxation, elastic limit, and strain rate dependence. The regrown tendons in young animals appeared to quickly adjust in dimension and structure so that their properties were not significantly different from those of normal tendons on a load extension basis. The normal tendons were stiffer than regrown ones but the modulus of elasticity increased with age. The Achilles were stiffer than patellar tendons. Cyclic loading with 25 kg did not affect reconstructed tendon models, although some increase in stiffness was noted. The elastic modulus decreased with an increase in ambient temperature and increasing strain rate.

Achilles Tendon↗

Plasma catecholamine concentrations in hyperthyroidism and hypothyroidism.

Using a modification of the fluorometric method of Anton and Sayre, we have measured the plasma epinephrine (E) and norepinephrine (NE) concentrations in patients with thyroid dysfunction. There was no significant difference in plasma E in hyperthyroid or hypothyroid subjects, the values being similar to those observed in normal subjects. There was a striking relationship between age and plasma NE in the euthyroid individuals (r = 0.685, p less than 0.001, n = 41). Observed plasma NE concentrations were similar in control subjects (21.05 +/- 1.6 ng/100 ml; mean +/- SEM) and hyperthyroid patients (22.33+/- 2.0 ng/100 ml). However, plasma NE was significantly increased in hypothyroidism (35.46 +/- 3.9 ng/100 ml; p less than 0.01) and remained statistically different when the age factor was excluded (31.31 +/- 2.67 ng/100 ml; p less than 0.025). There was no correlation between plasma NE and serum thyroxine (T4), free thyroxine (FT4), or triiodothyronine (T3), in any of the three groups studied. These data indicate that hyperthyroidism is accompanied by normal plasma NE concentrations and that hypothyroidism is associated with significantly increased plasma NE concentrations, possible in an attempt to compensate for the lack of thyroid hormones.

Age Factors↗

Plasma tryptophan concentration in depressive illness and mania.

Total and free plasma trytophan levels were measured in depressive and manic patients before and after recovery. No change was found in total or free plasma trytophan concentration on recovery from depressive illness. Free plasma tryptophan levels were higher in recovered manics than in active manics, and a group of four manic patients tested before and after recovery showed a significant increase in free plasma tryptophan concentration on recovery.

Adult↗

Intra-aortic balloon pump assist: adjunct to surgery for left ventricular dysfunction.

Intra-aortic balloon pump assist (IABPA) was used intraoperatively and postoperatively in 34 patients with severe left ventricular dysfunction: the mean ejection fraction was 0.29 and all patients had angiographic grade IV left ventricular contractility. There were three groups of patients: 11 patients with acute coronary artery insufficiency--10 of whom survived vein bypass surgery (group 1); 16 patients with crescendo-type unstable angina--of whom 15 survived surgery (group 2); 7 patients with single (6) or multivalvular (1) replacement (combined with vein bypass in 3)--of whom 5 survived (group 3). Overall survival was 88%. The mean duration of 1:1 IABPA was 40 hours. Inotropic support was not required, hemolysis was insignificant and hemostasis remained secure. Two patients required tracheostomy and one required dialysis. One patient had a peripheral embolus in the leg used for IABPA. IABPA improves subendocardial perfusion during induction of anesthesia, during cardiopulmonary bypass and into the postoperative period; left ventricular work is decreased with a concomitant increase in coronary artery and vein graft blood flow. Use of IABPA may also improve survival and lessen morbidity in patients with left ventricular dysfunction due to the beneficial effects on myocardial performance and is thus a valuable adjunct to cardiac surgery in high-risk patients.

Adult↗

Total condylar knee replacment: preliminary report.

The Total Condylar Prosthesis is a non-hinged unit designed to: replace the patellofemoral articulation; improve fixation of the tibial component by means of a stout central peg; permit accurate and reproducible insertion. The cruciate ligaments are excised to obtain better tibial fixation. Instability has not been a problem except in a few cases of a technical error (removal of excessive bone from the tibia creates instability in flexion). The prosthesis cannot be positioned by "eye" and the instrumentation must be applied exactly.

Humans↗

Unicondylar knee replacement.

Unicompartmental knee arthroplasty was conceived for the treatment of osteoarthritic knees with deterioration of either the medial or lateral compartment of the knee. The Unicondylar prosthesis was used in 19 medial and 5 lateral compartment arthroplasties. A two to 4 year follow-up evaluation of these patients was somewhat disappointing as only 5 knees could be rated excellent and 6 rated a good result. The best results were seen in the lateral compartment arthroplasties. Such deformities may be the only future indication for the use of this operation as these knees do not do well when treated by tibial osteotomy. However, when only the medial compartment is involved, osteotomy may still remain the treatment of choice.

Female↗

The treatment of connective tissue diseases with antilymphocyte globulin.

Immunosupprissive therapy was carried out using steroids, azathiprine and antilymphocyte globulin in one patient with systemic lupus erythematosus (SLE) and four with dermatomyositis. Response to treatment was based upon clinical evaluation. The patients with SLE and two of the four with dermatomyositis responded favourably to the regime. It is suggested that this preliminary study is sufficiently promising to warrant the creation of a rigidly controlled investigation.

Aged↗

Evidence of platelet complement-fixing and lymphocytotoxic anti-A-1 antibodies.

3 human antisera exhibiting non HL-A specific antibody were studied in micro-complement fixation with platelets and micro-lymphocytotoxicity. Screening studies as well as absorption and elution studies with platelets, lymphocytes and erythrocytes revealed an antibody activity associated with blood group A-1. Within blood group A-1, a subpopulation of A-1 donor cells- provisionally called "weak A-1" - was defined, which had a minor ability for complement-fixing and lymphocytotoxic A-1-antibody absorption. Contrary to HL-A specific antibodies, acid eluates from platelets of these 3 sera were always negative whereas heat and ether eluates gave positive results. From neutralization studies and studies on the hemolytic activity against A-1 erythrocytes it was concluded, that the A-1-specific antibodies probably are immune antibodies belonging to the IgG class of immunoglobulins.

Absorption↗