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Biomedical subjects

R Lam

Publications and source records attributed to R Lam.

At least 37 records · Page 2Linked to original sources

Effects of adrenergic agonists and adenosine on cholinergic neurotransmission in human tracheal smooth muscle.

There is only limited information available on the prejunctional regulation of acetylcholine (ACh) release from cholinergic nerves in human airway smooth muscle. Stimulation of cholinergic nerves in fresh postmortem tracheal muscle strips with electrical field stimulation (EFS) causes reproducible contractions. We have studied the effect on contractile responses of: 1) The alpha 2-adrenoceptor agonist effect of noradrenaline (NA, 0.1-30 microM) and clonidine (10 nM-30 microM), in the presence of 1 microM propranolol and prazosin +/- idazoxan (0.1 microM); 2) The beta-adrenoceptor agonist effect of fenoterol (FEN) and isoprenaline (ISO, 1 nM-30 microM) +/- ICI 118,551 (10 nM), comparing EFS responses to comparable responses to exogenous ACh; 3) The A1 and A2 adenosine receptor agonists effects of L-PIA and NECA (1 nM-10 microM). NA caused a concentration-dependent depression of the cholinergic frequency-response curve. However responses at 5 Hz were not modified by the addition of idazoxan. Similarly clonidine did not reduce contractile responses. The concentrations of isoprenaline (56 nM) and fenoterol (165 nM) required to inhibit EFS (5 Hz) by 50% (IC50) were significantly less than those required to inhibit closely matched ACh responses to a comparable degree (ISO = 117 and FEN = 304 nM), and the maximum inhibition of EFS was greater. Following isoprenaline and the beta 2-antagonist ICI 118,551 the IC50's for EFS and ACh were not different. NECA and PIA had no effect on cholinergic EFS. We conclude that a prejunctional beta 2 receptor may be present on cholinergic nerves in post-mortem tracheal smooth muscle but no evidence for alpha 2-adrenoceptor or adenosine-receptor regulation was obtained.

Adenosine↗

Idiopathic degeneration of the aortic valve: a common cause of isolated aortic regurgitation.

To establish the etiology of isolated aortic valvular regurgitation, histologic examination was carried out on 27 consecutive surgically removed aortic valves from patients with aortic regurgitation. In 12 patients, the regurgitation was due to rheumatic or syphilitic valvular disease or a congenital bicuspid aortic valve. In the remaining 15, no etiology was apparent. In the latter group, seven aortic valves were identified by the surgeon as redundant and eight as thickened and retracted. Despite these gross differences, the histologic features of the 15 valves were similar and consisted of increased and disorganized elastic and collagen fibers, with variable quantities of acid mucopolysaccharide and calcium. Although small foci of myxomatous stroma were present, they did not differ substantially from those observed in age-matched competent aortic valves removed at necropsy, nor were they as extensive as described in reports of floppy aortic valves. Idiopathic degeneration was the most common cause of aortic regurgitation, occurring in more than half of the surgically treated patients. An underlying defect in the synthesis of collagen or elastic fibers, similar to that described in mitral valve prolapse, may be an important feature in aortic valve degeneration.

Adult↗

Ovine fetal-maternal water transfer is independent of fetal prolactin levels.

To examine the effect of prolactin (PRL) on transplacental water flow, we infused mannitol (500 ml; 20% solution) over 10 min into five chronically catheterized ewes (121-134 days' gestation), producing a peak maternal plasma osmolality by 10 min and fetal osmolality by 20 min. One day before or after, an identical amount of mannitol was infused into the same ewe during the 2nd h of a 2-h infusion of PRL (40 +/- 2.2 micrograms/h) into a fetal leg vein. Mean (+/- SE) fetal plasma PRL levels were 6.9 +/- 3.2 ng/ml at baseline. Steady state fetal PRL levels were 17.7 +/- 7.4 ng/ml during PRL infusion. Maternal mannitol infused without administration of PRL to the fetus evoked a rise in fetal plasma osmolality similar to that following maternal mannitol during PRL administration to the fetus. Thus, as shown previously, PRL affects water permeability across the membranous chorioamnion, whereas results of the present study indicate that the hormone does not affect water transfer across the ovine chorionic villi (placenta).

Animals↗

A protein from airways of premature lambs that inhibits surfactant function.

A protein that interfered with surfactant function was isolated from the alveolar washes of prematurely delivered and ventilated lambs. This inhibitor was recovered following sequential precipitation with polyethylene glycol, Affi-Gel Blue, and diethylaminoethyl (DEAE) cellulose chromatography as a protein of approximately 110,000 mol wt. Compared to surfactant alone or surfactant and bovine serum albumin, the purified inhibitor increased the time required for surfactant to spread, increased both maximal and minimal surface tensions, increased the percent surface area that had to be compressed to reach a minimum surface tension of less than 15 dyn/cm, and delayed the surface adsorption of surfactant. The effect of inhibitor on the minimum surface tensions of surfactant solutions was inversely related to surfactant concentration. A radioimmunoassay was used to estimate that approximately 10% of the protein from plasma of premature lambs and alveolar washes after 4 h of ventilation was inhibitory. Following the simultaneous intravascular injection of labeled inhibitor and bovine serum albumin, about 4% of the radioactivity associated with both proteins was recovered in alveolar washes and 6% was associated with lung tissue after alveolar wash. This large proportionate leakage of both proteins did not occur in other tissues. The inhibitor affected multiple measurements of surfactant function in vitro and its presence may contribute to a surfactant deficiency state in the immature lung.

Animals↗

Autosomal dominant idiopathic hypoparathyroidism and nervous system dysfunction: report of three cases and review of the literature.

The neurological manifestations of idiopathic hypoparathyroidism in a father, his son, and his daughter are reported. In all three epilepsy was the first manifestation of the disease. Father and son also showed mental deterioration and striocerebellar symptoms; their CT scans revealed symmetrical calcification in the basal ganglia and dentate nuclei. The extent of this calcification increased during normocalcemia, which was produced by dihydrotachysterol therapy. This indicates that other factors than merely hypocalcemia influence the intracerebral calcifying process. Somatosensory evoked potentials (SSEP) showed an abnormal nonspecific complex, indicating dysfunction of the cortical gray matter. It is suggested that in the evaluation of idiopathic hypoparathyroidism one also must be beware of the possibility of epilepsy, mental deterioration, striocerebellar symptoms, intracerebral calcification and SSEP disturbances.

Adult↗

The tumourigenicity of smoke condensates from cigarettes containing different amounts of cytrel, as assessed by mouse skin painting.

Smoke condensates derived from cigarettes containing different amounts of the tobacco supplement Cytrel were painted onto the banks of mice 3 times a week for 104 weeks. Cigarette samples contained 0, 25, 50 or 100% Cytrel, blended with tobacco, and 3 dose levels were used for each sample. Statistical analyses were made of tumour incidence using a mathematical model based on the Weibull distribution. Good dose relationships were observed for each product; and for samples containing Cytrel there was a reduction in smoke condensate production and in tumourigenicity (per unit weight of smoke condensate) approximately proportional to the level of inclusion. Histopathological examinations of tumours indicated a reduction in malignancy of approximately 50% for all-Cytrel samples when compared with all-tobacco samples.

Animals↗

The rabbit: a suitable model for investigation of vascular responsiveness during pregnancy.

The decreased vascular response to angiotensin II that characterizes normal pregnancy is lost in pregnancy induced hypertension and associated with an increase in response to norepinephrine. These alterations in vascular responsiveness have not been thoroughly investigated and are poorly understood. Suitable models manifesting physiologic conditions known to exist in human pregnancy have not been satisfactorily demonstrated. We investigated the chronically catheterized and unmedicated rabbit for similarities of four conditions known to occur during human pregnancy. We compared mean arterial pressure and vascular response to angiotensin II and to norepinephrine in 19 non-pregnant and 16 pregnant animals. Plasma levels of angiotensin II, norepinephrine, epinephrine, and dopamine levels were measured and compared. We found striking similarities for conditions investigated in our rabbit model when compared with data reported in the literature for human pregnancy. We conclude the rabbit is a suitable model for investigating alterations of vascular response during pregnancy.

Angiotensin II↗

Cigarette smoke induced pathology of the rat respiratory tract: a comparison of the effects of the particulate and vapour phases.

Changes in the rat respiratory tract produced by a 12-week exposure to the particulate or vapour phases of cigarette smoke are described and compared with the changes produced by combined exposure to both phases. The most extensive changge in the upper respiratory tract was a pronounced squamous metaplasia of the laryngeal epithelium, along with extensive deciliation and squame cell production. In the lung, smoke exposure produced marked increase in the numbers of bronchial goblet cells and intra-alveolar brown-gold macrophages. None of the above changes could be directly attributed to exposure to vapour phase alone, and in many cases the lesions produced by whole smoke and by carbon filtered smoke were directly comparable. For lesions to occur in some ciliated areas of the tract both phases of the smoke were required.

Animals↗

Transient epithelial loss in rat larynx after acute exposure to tobacco smoke.

After a single 1 h exposure to cigarette smoke by inhalation, the degree of damage to the epithelial layer lining the ventral wall of the rat larynx has been assessed using a semi-quantitative scoring system. The damage was characterised mainly by partial or complete loss of epithelium. The time at which a maximal response was observed depended upon the smoke concentration. Regeneration was rapid and was followed by development of hyperplasia; the regenerative phase was progressively more delayed with higher concentrations of smoke. Smoke concentrations have been compared during the regenerative phase and an approximately linear dose-response relationship has been found. The causative agents were in the smoke particulate phase. The severity of the damage response may parallel the extent of subsequent hyperplasia and metaplasia. Laryngeal damage may thus provide a short-term bio-assay for the inhalation toxicity of cigarette smoke.

Animals↗

Plasma catecholamine concentrations in infants at birth and during the first 48 hours of life.

A radioenzymatic assay was used to measure plasma concentrations of the catecholamines, norepinephrine, and epinephrine in the perinatal period. Samples were obtained at birth from the umbilical artery and vein of infants born by vaginal and by cesarean section delivery; from peripheral venous samples of normal infants during the first 48 hours of life; and from peripheral venous samples of mothers prior to delivery. Concentrations of NE and E were elevated in umbilical samples, with umbilical artery levels exceeding umbilical venous concentrations. Umbilical plasma CAT concentrations were similar in vaginal and cesarean section delivered infants. Plasma concentrations of NE consistently predominated over E in all samples from neonates. Plasma CAT concentrations rapidly fell from cord levels within 15 minutes of delivery and remained at a lower plateau during the first three hours of life. By 12 hours of age plasma CAT concentrations fell to the levels of supine adult resting concentrations. Maternal plasma CAT concentration prior to delivery demonstrated a predominance of E over NE. These elevations of plasma CAT in the early neonatal period may play a rola in nonshivering heat production as well as in cardiovascular alterations associated with birth.

Catechol O-Methyltransferase↗

The effect of acute maternal hemorrhage on the release of catecholamines in the pregnant ewe and the fetus.

Five chronically instrumented pregnant ewes and their fetuses were studied to assess the effect of acute maternal hemorrhage. The hemorrhage was produced in two stages; during the first stage 15% of the total maternal blood volume was removed, and then in a second stage an additional 15% was removed. Biophysical and biochemical variables were monitored. Plasma dopamine, norepinephrine, and epinephrine were determined by a sensitive radioenzymatic assay. A significant rise in maternal and fetal catecholamines was observed following an estimated maternal blood volume depletion of 30%. During a 15-minute recovery period, the maternal catecholamine concentrations returned to normal, while the fetal concentrations remained elevated. These changes were accompanied by significant changes in maternal and fetal homeostasis. The significance of these findings is discussed.

Animals↗

Free metanephrine in human amniotic fluid as an index of fetal sympathetic nervous system maturation.

Free metanephrine, a major metabolite of catecholamines, was measured in the amniotic fluid of 113 pregnant patients at various gestational ages. The results indicate that prior to 30 weeks the levels of free metanephrine are below the level of assay sensitivity. After 30 weeks' gestation there is a positive correlation of free metanephrine concentrations in amniotic fluid with gestational age. In addition there is a further increase in free metanephrine levels in amniotic fluid with labor.

Amniotic Fluid↗

Small angle x-ray diffraction studies of mucopolysaccharides in collagen.

Small angle X-ray diffraction (SAXD) was used to locate mucopolysaccharides (MPS) at regular intervals along the collagen axis under physiological conditions. Ruthenium red was used to stain the MPS specifically. The difference in electron density between ruthenium red-stained and unstained moist native rat tail tendon should correspond to the position of the MPS. This difference was calculated from the SAXD intensity data by using difference Fourier transform calculations. Phases calculated independently from the amino acid sequence of collagen by two laboratories were used in this calculation, and the results were compared. At least four to seven bands of MPS per 660 A were found at regular intervals along the collagen axis. Some of these bands match in position to the cross-striations observed by freeze-etching. Electron micrographs of ruthenium red-stained native fibrils also showed bands close in position to the ones calculated.

Amino Acid Sequence↗

Myocardial alterations associated with aortocoronary saphenous vein bypass.

Clinical observations and gross and microscopic morphology of the hearts of 50 patients who dies at various intervals following aortocoronary saphenous vein bypass procedures are presented. Time of total cardiopulmonary bypass varied inversely with survival time among these patients. Myocardial necrosis with contraction bands and/or hemorrhagic myocardial necrosis was observed in the hearts of 44 of the 50 patients. Pathogenesis of the acute myocardial necrosis with contraction bands was multifactorial: anoxic arrest, cardiotonic drugs, electrical defibrillation, electrolyte imbalance, microthrombi, and hypoperfusion are incriminated. Subendocardial hemorrhagic necrosis was present in 17 of 40 patients whose postoperative survivals were four days or less. Its frequency increased with duration of survival. Hypoperfusion of the myocardium is suggested as the major etiologic factor of the subendocardial hemorrhagic necrosis. Myocardial lesions observed among these 50 patients did not differ from those in patients who had open-heart surgery for other reasons.

Arterioles↗

Aortic dissection complicating aortocoronary saphenous vein bypass.

A high autopsy incidence, 7 of 50 cases (14%), of aortic dissection as the major cause of death in patients who died following aortocoronary saphenous vein bypass is reported. The patients ranged in age from 45 to 61 years, and all had moderately severe aortic atherosclerosis. None was hypertensive, and no significant predisposing aortic medial disease was recognized. Trauma during surgical cannulation with retrograde perfusion through atherosclerotic femoral or iliac arteries was considered the initiating event leading to ileo-aortic dissection in five of the seven patients. Damage secondary to aortic cross-clamping is suggested as the pathogenetic mechanism leading to dissection in the other two patients. In six patients, the dissection was Type I of DeBakey, and in one patient, Type II. Dissection was recognized intra-operatively in five of the seven patients. In older patients, particularly those likely to have atherosclerosis of the aorta and its main branches, vigilance regarding the possibility of aortic dissection developing during the course of cardiopulmonary bypass must be constant.

Animals↗

Thyroxine in human amniotic fluid.

Total and free T3 and T4 concentrations were measured in human amniotic fluid and in fetal and maternal blood. Before 20 weeks, the mean AF-T4 level was 0.24 mug/dl; there is a progressive increase in concentration with gestational age. At term, the mean AF total T4 level was much less (0.64 mug/dl) than in fetal or maternal serum (9.3 and 11.3 mug/dl, respectively). Most of the T4 (99.4%) in AF is protein bound, presumably to TBG as in serum, but the mean FT4 concentration in AF at term (4.13 ng/dl) was significantly greater than the levels in fetal or maternal serum (2.67 or 2.56 ng/dl, respectively). The mean TBG level in AF at term was 0.26 mg/dl. T3 was not measurable in AF (less than 15 ng/dl). There were no significant correlations between the total or free T4 concentrations in maternal or fetal sera and in amniotic fluid. Thus AF thyroid hormone concentrations in the euthyroid fetus do not reliably reflect fetal serum T4 or T3 concentrations.

Amniocentesis↗