Is treatment needed for mild impairment of glucose tolerance in pregnancy? A randomized controlled trial.
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Female↗
Biomedical subjects
R Fraser
Publications and source records attributed to R Fraser.
Obstructive pneumonitis: a pathologic and pathogenetic reappraisal.
It is widely accepted that pneumonitis distal to an obstructing airway tumor is the result of infection. The authors performed a prospective study to reevaluate this concept and to clarify the nature of the pathologic findings underlying the observed radiographic changes. Specimens were examined for 50 consecutive patients undergoing resection of pulmonary carcinoma. Histologic changes interpreted as noninfectious were found in 42 cases. Findings suggestive of recent or remote infection were also present in nine of these 42 specimens and were localized predominantly in relation to small- to medium-sized airways (acute bronchitis or bronchiolitis); these changes were always present in a background of noninfectious pneumonitis. The authors conclude that the radiographic changes seen in airway obstruction in surgically excised lungs are usually due to consolidation of lung parenchyma by a noninfectious process. When infection does occur, it involves primarily the airways and is not likely to be radiographically detectable.
Adenocarcinoma↗
Parathyroid hormone-like immunoreactivity in brains of tetrapod vertebrates.
Heat-stable nondialyzable immunoreactive (IR) parathyroid hormone (PTH)-like activity, that coelutes with authentic PTH on Sep-Pak C18 columns and reverse-phase high-performance liquid chromatography, was measured in the brain, hypothalamus, and pituitary of amphibian, reptilian, avian, and mammalian species, using two specific antisera raised against the 48-64 region of the intact PTH molecule. In each case the IR PTH concentration was greater than that present in peripheral plasma and in rats was not affected by dietary calcium status. Extracts of muscle, liver, and kidney tissue were without IR PTH activity. These results demonstrate the extraparathyroidal occurrence of PTH-like peptides in nontumorous neuroendocrine tissues of vertebrate species. These findings may have evolutionary significance, since IR PTH was present in the brain and plasma of species that lack encapsulated parathyroid glands.
Amphibians↗
Effects of sodium intake and aldosterone on the renal pressure-natriuresis.
To study the effects of dietary sodium and plasma aldosterone on pressure-natriuresis (PN) we examined six groups of adult, male Sprague-Dawley rats. Group 1 received normal-sodium diet, group 2 high-sodium diet, and group 3 low-sodium diet for 3 wk; group 4 was given low sodium for 3 wk then high sodium for 3 wk; groups 5 and 6 received high sodium for 3 wk but during the 3rd wk were also given aldosterone by subcutaneous infusion to mimic the plasma aldosterone seen in groups 1 and 3, respectively. After the diets, rats were killed, and urinary sodium excretion, glomerular filtration rate (GFR), and calculated tubular sodium reabsorption (FRNa) were measured during stepwise increases in perfusion pressure in isolated perfused kidneys from each group. No significant differences in blood pressure were seen between any of the groups. The PN curves for groups 2 and 3 were significantly different (P less than 0.001) and shifted to the left and right of group 1, respectively. These shifts appeared to be the result of significant (P less than 0.001) differences in FRNa rather than changes in GFR. PN was not significantly different in groups 4 and 2, indicating that the effects of low-sodium diet were reversible. The infusion of aldosterone in groups 5 and 6 was associated with modest and significant (P less than 0.001) shifts, respectively, of the PN curve to the right of the curve of rats in group 2. In group 6 this shift appeared to be due to significant (P less than 0.001) changes in FRNa, so as to resemble that seen in low-sodium rats of group 3.(ABSTRACT TRUNCATED AT 250 WORDS)
Aldosterone↗
Early stage ovarian cancer: a randomized clinical trial comparing whole abdominal radiotherapy, melphalan, and intraperitoneal chromic phosphate: a National Cancer Institute of Canada Clinical Trials Group report.
Two hundred fifty-seven eligible patients with stage I, IIA "high risk" ovarian carcinoma and IIB, IIIO (disease confined to pelvis), were randomized to either total abdominal radiotherapy (arm A) 2,250 rad in 20 fractions (107 patients), melphalan (arm B) 8 mg/m2/d X 4 every 4 weeks X 18 courses (106 patients), or intraperitoneal chromic phosphate (arm C) 10 to 20 mCi (44 patients). All patients were initially treated with pelvic radiotherapy; arm A, 2,250 rad in ten fractions; and arms B and C, 4,500 rad in 20 fractions. Entry to arm C was discontinued early because of toxicity. In a multifactor analysis using proportional hazards models, no significant difference in survival was observed although there was a marginally significant difference in disease-free survival (P = .015) with arm B being superior to arm A. Stage (P less than .0001), grade (P less than .0001), and histology (P less than .008) were predictors of survival in the multifactor analysis. Performance status, age, and residual disease were significant predictors in the single factor analysis but were not predictive when correction was made for the effects of stage, grade, and histology. Five-year survival rates are 62% for arm A, 61% for arm B, and 66% for arm C. Median duration of follow-up is 8 years. Long-term complications of radiotherapy were seen in 19 patients on arm A, 11 on arm B, and 11 on arm C. Four patients who had received melphalan developed either a myelodysplastic syndrome or acute leukemia. Violations in covering the whole abdominal target volume were correlated with survival.
Chromium↗
Low dose infusions of 26- and 28-amino acid human atrial natriuretic peptides in normal man.
To investigate the effects of a small rise in the plasma atrial natriuretic peptide (ANP) concentration, 6 normal subjects received 2-h low dose (2 pmol/kg.min) infusions of both 28 [human alpha hANP-(99-126)]- and 26 [human ANP-(101-126)]-amino acid peptides in a placebo-controlled study. Both peptides induced more than 2-fold increases in urinary sodium, calcium, and magnesium excretion. Effective renal plasma flow was slightly reduced, glomerular filtration rate did not change, and renal filtration fraction increased during the ANP infusions. Plasma renin, angiotensin II, and aldosterone concentrations fell by about 50%. Arterial blood pressure and plasma catecholamines did not change. Hematocrit and serum albumin concentrations rose significantly. ANP effects on urinary electrolytes and the renin-angiotensin-aldosterone system were sustained for over an hour after completion of the ANP infusions. The two peptides did not differ in their effects. These results are consistent with a physiological role for plasma ANP in the regulation of extracellular fluid volume and demonstrate that minor N-terminal truncation of alpha hANP has little effect on its biological activity.
Adult↗
Stimulation of cortisol production in isolated bovine zona fasciculata cells by phorbol ester: role of ion fluxes.
The role of protein kinase C activation in the control of cortisol synthesis was studied using the phorbol ester 12-O-tetradecanoyl phorbol-13-acetate (TPA). Bovine zona fasciculata cells were incubated with various concentrations of TPA in the presence and absence of EGTA, verapamil or nitrendipine to see whether cortisol stimulation was dependent on extra-cellular calcium ions. When free extracellular concentration of Ca2+ was reduced to approximately 10 mumol/l the cortisol response at all concentrations of TPA was reduced by approximately 25% indicating that protein kinase C activation is only partially dependent on extracellular calcium ions. This is confirmed by the effects of the voltage-dependent calcium channel blocker verapamil, which partially inhibited the cortisol response to a maximally effective concentration of TPA (1 mumol/l). However, a second channel blocker, nitrendipine, proved to be ten times more potent than verapamil and totally inhibited the TPA response. The partial effects of EGTA and verapamil and the contrast between verapamil and nitrendipine do not exclude the possibility that intracellular calcium ions are important in protein kinase C activation and may indicate that nitrendipine has better access to an additional site of inhibitory action than verapamil. It is significant that the ionophore A23187, which facilitates Ca2+ entry independently of voltage-sensitive channels, failed to overcome the inhibitory effects of nitrendipine in TPA-stimulated cells. In some other tissues, the effects of protein kinase C activation are mediated by the opening of Na+/H+ exchange ports. The involvement of this port in the cortisol response has been tested by incubating TPA- and ACTH-treated cells with amiloride, an inhibitor of Na+/H+ exchange.(ABSTRACT TRUNCATED AT 250 WORDS)
Adrenal Cortex↗
Choriogonadotropin and its beta subunit separated by hydrophobic-interaction chromatography and quantified in serum during pregnancy by time-resolved immunofluorometric assays.
Concentrations of human choriogonadotropin (hCG) and its free beta subunit (beta hCG) were measured in serum by highly sensitive and specific time-resolved immunofluorometric assays (IFMAS). The results were confirmed by completely separating beta hCG and hCG by a novel method based on hydrophobic-interaction chromatography. We used three monoclonal antibodies in two different combinations. In both assays an antibody reacting with both free beta hCG and with intact hCG was immobilized onto the wall of a microtiter strip well. For assay of intact hCG we used as the indicator antibody an antibody against the alpha subunit, labeled with a europium chelate. For assay of beta hCG we used an indicator antibody that reacted only with the free beta subunit. hCG cross-reacted in the assay of beta hCG by 0.6%. Quantifying hCG in serum after in vitro fertilization showed that, seven to eight days after embryo transfer, the hCG concentration started to increase, thereafter increasing with a doubling time of 1.9 days during the following three weeks. hCG concentrations in serum peaked six to 10 weeks later, corresponding to eight to 12 weeks after the last menstrual period. Throughout pregnancy, measurable amounts of beta hCG were present in serum. The highest beta hCG/hCG ratio (maximum 7.3%, median 3.0%) was observed during early gestation. During the fourth to 13th weeks after the last menstrual period the ratio of beta hCG/hCG decreased gradually, being 1.0% during the second and third trimesters.
Chorionic Gonadotropin↗
Haemodynamic, hormonal and renal effects of adrenocorticotrophic hormone in sodium-restricted man.
The effect of a dietary sodium restriction (15 mmol/day) on the development of adrenocorticotrophic hormone (ACTH) hypertension was examined in six normal male subjects. When ACTH (1 mg/day) was given for 5 days to subjects on a sodium-restricted diet, systolic blood pressure rose (116 +/- 4 to 125 +/- 4 mmHg, P less than 0.001), while diastolic blood pressure was unchanged. There was a modest antinatriuresis (cumulative Na+ balance, 59 +/- 2 mmol) which was reflected in a small rise in exchangeable body sodium (65 +/- 15 mmol); plasma concentrations of active renin and angiotensin II both fell during ACTH treatment. Plasma volume rose (2.8 +/- 0.2 to 3.6 +/- 0.16 l, P less than 0.01) while extracellular fluid volume was unchanged. Plasma concentration of atrial natriuretic peptide (ANP) rose to more than twice basal. Glomerular filtration rate (inulin clearance) increased (111 +/- 9 to 131 +/- 7 ml/min, P less than 0.001), renal plasma flow, measured as the rate of para-aminohippurate (PAH) clearance, was unaltered and calculated filtration fraction rose. Dietary sodium restriction did not, therefore, prevent an ACTH-induced increase in blood pressure. The increase in plasma volume with ACTH is not dependent on renal sodium retention and is associated with increased concentrations of ANP. When these data are compared with findings previously reported in subjects given the same dose of ACTH when on normal or high sodium intakes, it is clear that, although the action of ACTH in raising blood pressure is not dependent on exogenous sodium or extracellular fluid volume expansion, sodium retention can modify the level of blood pressure attained.
Adrenocorticotropic Hormone↗
Chronic low-dose infusions of dexamethasone in rats: effects on blood pressure, body weight and plasma atrial natriuretic peptide.
Glucocorticoid-induced hypertension in rats has been studied using long-term, low-dose dexamethasone treatment. Dose-related increases in systolic blood pressure were achieved, without loss in body weight, with subcutaneous continuous infusions of 1, 2 and 5 micrograms dexamethasone per day, respectively, for 4 weeks. Rats treated with 10 micrograms dexamethasone per day lost weight at a rate of 10 g per week. Lower doses caused a significant reduction in weight gain compared with controls. Renin, aldosterone, plasma sodium and potassium concentrations were unaffected by dexamethasone treatment. Plasma atrial natriuretic peptide (ANP) concentrations were decreased by 40-50% by dexamethasone. These decreases were negatively correlated with increases in systolic blood pressure and haematocrit. Glucocorticoid-induced decreases in ANP contrast with ANP increases in response to mineralocorticoid treatment in rats with deoxycorticosterone-induced hypertension. Plasma concentrations of the endogenous glucocorticoid, corticosterone, were suppressed to the same very low levels by 5 and 10 micrograms dexamethasone per day; 1 and 2 micrograms doses were less effective. Unlike mineralocorticoid-induced hypertension, the pressor effects of dexamethasone were ameliorated but not abolished by dietary sodium restriction and were unaffected by sodium loading. Two micrograms of dexamethasone reduced plasma ANP in rats on either high- or low-sodium diets by 29 and 34%, respectively. We conclude that low-dose infusions (less than 5 micrograms/day) of dexamethasone are suitable for studying glucocorticoid-induced hypertension without the complications of weight loss that have been reported by others or of the mineralocorticoid-like side effects which endogenous glucocorticoids may exhibit.
Animals↗
The history of the use of vacuum extraction.
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Europe↗
Role of renin as a blood-borne hormone tested by infusion of renin inhibitor (H.77).
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Adrenal Cortex Hormones↗
Nicotine decreases the porosity of the rat liver sieve: a possible mechanism for hypercholesterolaemia.
Nicotine was fed to rats for 6 weeks, as a weight adjusted dose equivalent to that of a human being smoking 50 to 100 cigarettes per day. Those rats fed nicotine developed hypercholesterolaemia. Scanning electron microscopy showed the porosity of the hepatic sinusoidal endothelium of nicotine fed animals was about 40% that of control animals. The decline in porosity was found to be due to a reduction in diameter rather than number of fenestrae. We believe that this decreased hepatic sinusoidal porosity may alter cholesterol homeostasis by increasing the circulation time of chylomicron remnants too large to pass through the fenestrae. This phenomenon may be an aetiological factor in the known correlation between cigarette smoking, atherosclerosis, and coronary heart disease in humans.
Animals↗
Ensure 'Jeanette' case doesn't set a precedent.
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Adolescent↗
Left ventricular full-thickness cardiomyoplasty with pericardial neoendocardium: experimental development of a surgical procedure.
Cardiomyoplasty, a surgical procedure using stimulated skeletal muscle graft to replace or repair damaged myocardium, has been successfully performed in experimental animals and clinical patients. Whenever feasible, endocardium of the damaged myocardial segment is retained and partial-thickness cardiomyoplasty should be carried out. However, if this procedure were to be applied to enlarge a hypoplastic ventricle or to maintain normal dimensions of the ventricular cavity in some repairs in adults, full-thickness replacement of the ventricular wall with contractile skeletal muscle mass would be required. To develop such a technique, several canine experiments were carried out. In 7 dogs, "simple full-thickness cardiomyoplasty" was performed by using a latissimus dorsi muscle graft to repair a full-thickness left ventricular wall defect. We found it was difficult to obtain adequate hemostasis between the nonscarred myocardial tissue and the skeletal muscle graft, and excessive suturing to obtain hemostasis resulted in strangulation of the muscle grafts. The skeletal muscle-blood interface in the left ventricle was found to be highly thrombogenic. The perioperative hemorrhage and the risk of muscle graft strangulation by excessive sutures were avoided by using a pericardial patch as neoendocardium in 5 dogs that underwent similar full-thickness cardiomyoplasty procedures. Although the pericardial neoendocardium was not fully antithrombogenic in this canine model, endothelialization of the endocardium occurred within several weeks after operation. Thus, when combined with an implantable synchronized burst stimulator, this technique may in the future provide an effective "full-thickness dynamic cardiomyoplasty" to enlarge the ventricles and augment myocardial function in select patients.
Animals↗
Effects of a single moderate dose of alcohol on blood pressure, heart rate and associated metabolic and endocrine changes.
1. The effects of a single moderate dose of alcohol on blood pressure, heart rate and associated metabolic and endocrine changes were studied in 10 healthy subjects and compared with those of an isocaloric glucose control drink. 2. Systolic blood pressure rose at 1 h after both alcohol and the control drink. Therefore this early change was not specifically due to alcohol ingestion. Subsequently, there was a tendency (not statistically significant) for supine and erect systolic blood pressure to be reduced up to 8 h after alcohol ingestion. There were no consistent late changes in blood pressure observed over 7 days after alcohol. 3. Alcohol caused a marked tachycardia in both supine and erect postures which persisted beyond the time of detectable blood alcohol levels. 4. Blood sugar rose by a similar amount after alcohol and the isocaloric glucose control drink, but peak plasma insulin levels were higher after the control drink. 5. Plasma sodium rose in keeping with alcohol induced water diuresis. No significant changes in plasma potassium or magnesium were seen after alcohol. 6. Compared with the control drink there was no evidence from measurements of circulating adrenaline, noradrenaline, cortisol, aldosterone or renin of activation of the sympathoadrenal axis, adrenal cortex or renin-angiotensin systems after alcohol.
Adolescent↗
Diurnal change in plasma atrial natriuretic peptide concentrations.
1. Diurnal changes in plasma concentrations of atrial natriuretic peptide (ANP), renin, angiotensin II, aldosterone, cortisol and antidiuretic hormone were investigated in seven normal volunteers studied under standardized conditions of dietary sodium, posture and physical activity. After completion of the diurnal study serial measurements of these variables were continued during, and on recovery from, a 2 day period of severe sodium depletion. 2. Clear diurnal variations in plasma concentrations of renin, angiotensin II, aldosterone, cortisol and antidiuretic hormone were observed. 3. Plasma ANP concentrations also varied significantly over 24 h. Values peaked about mid-day and a distinct trough in peptide concentrations occurred in the early evening. However, variations in plasma ANP values were of relatively small amplitude and not clearly independent of modest parallel shifts in sodium balance. 4. Changes in plasma ANP concentrations both within the diurnal study period and during sodium deprivation were closely and positively correlated with concomitant changes in cumulative sodium balance. 5. No simple parallel or reciprocal relationships between plasma concentrations of ANP, on the one hand, and concurrent plasma concentrations of other hormones or in the rate of urinary sodium excretion, on the other, were observed during the 25 h of the diurnal study.
Adult↗
Round atelectasis. Pathologic and pathogenetic features.
Round atelectasis is an uncommon pulmonary condition usually presenting in an asymptomatic individual as a peripheral parenchymal opacity on a chest roentgenogram. Pathologic examination of eight cases revealed localized fibrosis of the visceral pleura overlying the roentgenographic abnormality in all instances. Beneath the region of fibrosis, the pleura showed extensive wrinkling and folding, occasionally with deep invaginations into the pulmonary parenchyma. No discrete mass corresponding to the roentgenographic opacity was identified; however, lung parenchyma adjacent to the fibrotic and folded pleura appeared compressed, and in some cases, showed interstitial fibrosis. These findings support the hypothesis that round atelectasis is due to contraction of a focus of visceral pleural fibrosis that results in buckling of the pleura and collapse of underlying lung parenchyma.
Female↗