Gastroenteropancreatic hormones in normal and gestational-diabetic pregnancy: response to oral lipid

The effect of normal and gestational-diabetic pregnancy on the gastroenteropancreatic (GEP) hormone response to lipid ingestion was studied in 17 women, 8 normal and 9 with gestational diabetes, by determination of the plasma concentrations of gastric inhibitory polypeptide (GIP), gut glucagon-like immunoreactivity (gut GLI), insulin, glucagon, and pancreatic polypeptide (PP) following the ingestion of 67 g of triglyceride in late pregnancy and postpartum. Also, the plasma concentrations of free fatty acids (FFA), triglyceride, and glucose were determined. In both groups fasting plasma triglyceride and insulin were increased and PP was decreased. Fasting plasma glucose and gut GLI were decreased in normal pregnancy, but were unaltered in gestational-diabetic pregnancy. Fasting plasma glucagon were unaltered in normal but increased in gestational diabetic pregnancy. In both groups of women the GIP response to triglycerides was impaired in pregnancy. Postpartum, the GIP response was greater in the gestational diabetics than in normal women whereas no difference was found in pregnancy. The other hormones and metabolites responded similarly in pregnancy and postpartum and no difference between normal women and women with gestational diabetes was found. It is concluded that the GIP response to triglycerides is impaired in pregnancy.     

Intrapericardial left atrial aneurysm. Report of a case and a review of the literature

A case of intrapericardial left atrial aneurysm successfully removed and presenting clinically with intermittent atrial fibrillation is described. Fourteen other cases are reported in the literature. The first symptom is either palpitation, an arterial embolus, or precordial pain. The diagnosis is confirmed by angiocardiography. The aneurysm should be removed.     

Characterization of the inhibitory effect of somatostatin upon insulin and glucagon release in the isolated perfused canine pancreas: evidence for interaction with calcium

Somatostatin is a potent inhibitor of insulin and glucagon release from the isolated perfused canine pancreas. The present investigation was undertaken to characterize the pancreatic effects of somatostatin by studying its ability to influence insulin and glucagon release from the same perfusion preparation in response to various well-known stimuli and modulators. Somatostatin inhibited insulin and glucagon release in all test situations chosen but one. Thus, somatostatin inhibits pancreatic hormone secretion irrespective of whether it is modulated by (1) a primary initiator of insulin release--glucose (1.3 or 8.3 mM), leucine (4.1 mM), tolbutamide (2.6 mM); (2) a potentiator of insulin release, i.e., a substance that requires the presence of glucose--arginine (1 mM); (3) substances known to increase the level of cyclic AMP (cAMP) in the islets--glucagon (2 ng/ml), cAMP (1 mM), theophylline (1 mM); (4) an autonomic agent--epinephrine (2 ng/ml), acetylcholine (10 microM); or (5) alpha and beta adrenergic antagonists--phentolamine (1 microM), propranolol (1 microM). In contrast, high Ca++ concentrations (4.8 and 8.2 mM) abolished the inhibitory action of somatostatin on both insulin and glucagon release. These findings lend support to the hypothesis that somatostatin acts at a stage of secretory processes, possibly related to Ca++ inactivation, late in the chain of events leading to hormone release.     

Shortening of paced QRS duration after electrocardiographic optimization of left ventricular pacing vector in patients treated with Cardiac Resynchronization Therapy

Background

Choice of left ventricular pacing vector (LVPV) affects the QRS-duration (QRSd) in patients with Cardiac Resynchronization Therapy (CRT). It is not known whether testing all LVPVs reduces QRSd compared to device-based “standard-programming”.

Exit block in sustained atrial tachycardia in two children.

The electrocardiographic findings in two children with sustained atrial tachycardia and exit block are reported. The exit block was dependent on the atrial pacemaker rate, being present only at rapid rates of discharge. In one case propranolol enhanced the exit block, and on an appropriate dose the heart rate was maintained within a well tolerated range.     

The glucoregulatory response to intravenous glucose infusion in normal man: Roles of insulin and glucose

In order to differentiate the roles of hyperinsulinemia and hyperglycemia per se in the homeostatic response to i.v. glucose administration, two groups of normal subjects were given either glucose alone (3.5 mg kg^?1 min^?1) or glucose (3 mg kg^?1 min^?1) in conjunction with somatostatin (500 μg hr^?1), insulin (0.15 mU kg^?1 min^?1) and glucagon (1 ng kg^?1 min^?1). Glucose kinetics were measured by the primed-constant infusion of 3-³H-glucose. During the infusion of glucose alone, plasma glucose stabilized at levels 45–50 mg/dl above the fasting values. Endogenous glucose output was markedly suppressed by 85%–90% while glucose uptake rose to values very close to the infusion rate of exogenous glucose. Glucose clearance remained unchanged. Plasma insulin rose three-fourfold while plasma glucagon fell by 25%–30%. When glucose was infused with somatostatin, insulin, and glucagon, plasma insulin was maintained at levels 50% above baseline while glucagon remained at preinfusion levels. Under these conditions, the infusion of exogenous glucose resulted in a progressive increase of plasma glucose which did not stabilize until the end of the study period (190 mg/dl at 120 min). Endogenous glucose production was consistently suppressed (52%) but significantly less than observed with the infusion of glucose alone (p < 0.01). Glucose uptake increased to the same extent as with glucose alone, despite the more pronounced hyperglycemia. Thus, glucose clearance fell significantly below baseline (25%–30%; p < 0.01). These data demonstrate that hyperglycemia per se (fixed, near basal levels of insulin and glucagon) certainly contributes to the glucoregulatory response to i.v. glucose administration by both inhibiting endogenous glucose output and increasing tissue glucose uptake. However, the extra-insulin evoked by hyperglycemia is necessary for the glucoregulatory system to respond to the glucose load with maximal effectiveness.     

Effects of dietary changes on cellular insulin binding and in vivo insulin sensitivity

The effect of a low-sucrose, low-fat diet on insulin sensitivity, insulin binding to monocytes, and insulin secretion in nonketotic diabetic patients was studied. Ten obese diabetics were studied for 1 yr before and during treatment with a 1200–1500-kcal diet, whereas six diabetics of normal weight were studied for 3 mo before and after treatment with a 2200–2400-kcal diet. In the obese group, no change was found in the insulin response to i.v. injection of glucose during treatment (p > 0.1), but the insulin sensitivity was normalized after 1 yr (p < 0.01). The clinical normalization and the improvement of insulin sensitivity were accompanied by a parallel normalization of the binding of insulin to monocytes (p < 0.01). In the group of normal-weight diabetics, both the insulin sensitivity (p < 0.05) and the insulin binding to monocytes (p < 0.05) were normalized after a 3-mo treatment period, but the insulin secretion increased (p < 0.05) without reaching normal values. We conclude that most nonketotic diabetic patients can be controlled by diet treatment alone. The mechanism of action of the low-fat, low-sucrose diet seems for the greatest part to be a normalization of the insulin sensitivity, which is partly caused by a normalization of the cellular insulin binding.     

Accuracy of left ventricular ejection fraction determined by the nuclear stethoscope

We assessed left ventricular ejection fraction 47 times in 21 patients with sinus rhythm by a portable non-imaging nuclear probe. After ^99mTc blood pool labelling, left ventricular ejection fraction was determined by probe in two different ways: on a beat-to-beat basis, and by the so-called ventricular function mode, based on the gated equilibrium principle, and subsequently compared with left ventricular ejection fraction measured by gated equilibrium radionuclide angiocardiography using a gamma camera.Left ventricular ejection fraction by probe correlated well with left ventricular ejection fraction by gamma camera: beat-to-beat versus gamma camera: r = 0.90, y = 0.75x + 0.12; ventricular function versus gamma camera: r = 0.88, y = 0.87x + 0.08. Also, left ventricular ejection fraction values determined by the two probe methods correlated closely: r = 0.97, y = 0.83x + 0.07. Compared with the gamma camera, the probe overestimated slightly the small values of left ventricular ejection fraction and underestimated high values. Correct determination of left ventricular ejection fraction by a non-imaging probe depends on correct positioning over the left ventricle and selection of a proper background activity level.The main application of this instrument is probably non-invasive bedside determination and monitoring of changes of left ventricular function occurring spontaneously or caused by cardiac arrhythmias or treatment with cardiac drugs.     

Increased serum low-density lipoprotein cholesterol in men treated short-term with the diuretic chlorthalidone

The effect of the diuretic chlorthalidone (100 mg/day for 6 weeks) on serum lipoproteins was evaluated in 37 subjects. In 19 men with essential hypertension (aged 41 ± 3 yr), 8 normal men (26 ± 3 yr), or all of these men considered together, chlorthalidone significantly increased serum low density lipoprotein-cholesterol (LDL-C) by 20% (p < 0.05 to <0.01). There was also a tendency for increased LDL-C in seven postmenopausal women (+ 15%) but not in three premenopausal women with essential hypertension. High density lipoprotein-cholesterol was not significantly changed in hypertensive women or normal men and decreased slightly (p < 0.05) in hypertensive men. Apolipoproteins A-I, A-II, and B were not changed significantly in women or men. Diuretic-induced lipoprotein alterations were not associated with altered plasma volume and unrelated to variations in serum potassium, glucose, insulin levels, blood pressure, and body weight. Short-term diuretic therapy with chlorthalidone may increase serum LDL-C in young or middle-aged men with normal or high blood pressure.     

Gastric inhibitory polypeptide (GIP) and insulin release in response to oral and intravenous glucose in uremic patients

Eight patients with advanced renal failure of long duration were studied 1 day after hemodialysis. A 50 g oral glucose load (OGTT) and an intravenous glucose infusion (IVGI), giving the same plasma glucose profile as the OGTT, were carried our in order to study the relation between Gastric Inhibitory Polypeptide (GIP) plasma levels after oral glucose and the insulin release during OGTT and IVGI. The plasma GIP increase during OGTT was significantly elevated compared to a group of eight healthy volunteers. The insulin potentiation during OGTT in relation to GIP was significantly depressed in the uremic patients. It is proposed that a factor of intestinal origin is released during intake of carbohydrates, which blocks the B-cell response to the combined glucose-GIP stimulus. Alternatively, the concentrations of plasma GIp measured have included GIp fragments without insulin releasing capability.     

Reversal of diuretic-induced increases in serum low-density-lipoprotein cholesterol by the betablocker pindolol

Seventeen patients with mild to moderate essential hypertension received during three consecutive 4 wk periods a matched placebo, the thiazide-like diuretic, clopamide in a low dosage of 5 mg/day, or this diuretic combined with the betablocker, pindolol in a low dosage of 10 mg/day. Compared to placebo conditions, clopamide monotherapy significantly increased serum low-density lipoprotein cholesterol (LDL-C) by 13% (p < 0.025). Following addition of pindolol, serum LDL-C was restored to control values. These variations in serum LDL-C were unrelated to concomitant changes in blood pressure, plasma potassium, renin activity or aldosterone levels. Blood pressure in the supine position was reduced from $\text{152}\text{99}\text{±}\text{13}\text{9}\text{mm Hg (+SD)}$ to $\text{141}\text{93}\text{±}\text{15}\text{7}\text{mm Hg}$ following diuretic-monotherapy and to $\text{139}\text{90}\text{±}\text{12}\text{9}\text{mm Hg}$ following diuretic-betablocker combination treatment. These findings suggest that antihypertensive combination treatment with low doses of clopamide and pindolol is not only effective and well tolerated, but may also avoid the increase in serum LDL-C levels occurring when the thiazide-like diuretic is given alone.     

An adverse effect of insulin on the oxygen-release capacity of red blood cells in nonacidotic diabetics.

Oxyhemoglobin dissociation curves (ODC) were performed on blood from newly diagnosed, nonketotic diabetics prior to and following initial insulin treatment and from ambulatory juvenile diabetics before and after their usual morning insulin. In 10 newly discovered diabetics the average P50 at in vivo pH was normal prior to insulin (26.2 mm Hg), decreased to 24.5 mm Hg (p less than 0.005) on the day following the initial insulin administration, and was within normal limits (26.9 mm Hg) when the diabetes was finally well controlled and red cell 2,3-diphosphoglycerate (2,3-DPG) had risen to elevated levels. Oxygen affinity of hemoglobin was closely correlated with the content of red cell 2,3-DPG (r = 0.61, p less than 0.001) but was unrelated to the level of hemoglobin Alc. In 40 juvenile patients the average P50 was also normal prior to insulin administration but was significantly lower 3-4 hr after they had received their usual insulin dose (p less than 0.001). The study indicates that insulin administration to diabetics with high blood glucose levels may lead to transient decreases in red cell 2,3-DPG and in oxygen-releasing capacity of the red blood cells.     

Actions of thiazide on vitamin D metabolism: a controlled therapeutic trial in normal women early in the postmenopause

The effect of thiazide on vitamin D metabolism in normal postmenopausal women was studied during a twelve-month placebo-controlled clinical study. Nineteen healthy women in their early menopause were randomized for treatment with bendroflumethiazide (5 mg/d) (n = 11) or placebo (n = 8) for twelve months. All participants were given a calcium supplement of 0.5 g/d throughout the study. A significant increase (p less than 0.01) in the serum concentration of 24,25-dihydroxycholecalciferol was observed in the thiazide group. Moreover, this group showed a tendency toward decreased serum 1,25-dihydroxycholecalciferol, whereas the mean serum 25-hydroxycholecalciferol was unchanged. Except for a highly significant decrease in urinary calcium in the thiazide group (P less than 0.01) all other biochemical indices of calcium metabolism were unchanged. The present data indicate that thiazide given to early postmenopausal women has a primary effect on the renal tubules followed by a secondary change in vitamin D metabolism leading to an increase in serum 24,25-dihydroxycholecalciferol.     

Hemodynamic factors in the genesis of diabetic microangiopathy

There are many candidate mechanisms to explain the phenomenon of delayed microvascular disease in the diabetic. All may play some part in determining the genesis, the evolution or the ultimate degree and form of the angiopathy. General metabolic and humoral factors may provide the pathogenetic background against which special local conditions, e.g., in the retina or renal cortex, will determine the morphology of the angiopathy and its functional and structural consequences. Some of the processes occurring in the diabetic person may, however, be of major importance in initiating and maintaining conditions for the evolution of microvascular disease. The hemodynamic changes and the vascular responses to them that we have described are, we suggest, very likely to be an important component of this sort. Unlike the later structural changes, these hemodynamic phenomena are to be found very early in the diabetic state. Of most clinical importance, perhaps, is that they appear, with the achievement of adequate metabolic correction, to be reversible.     

Acute effects of fat and carbohydrate on metabolic rate in normal, cold-acclimated and lean and obese (fa/fa) Zucker rats

The rise in metabolic rate after intragastric feeding with fat and carbohydrate was enhanced in cold-acclimated (5 degrees C) rats and diminished in warm-acclimated (30 degrees C) rats compared to controls (24 degrees C), but the response was largest in cold-acclimated animals intubated with fat. These acute effects of nutrients were almost completely abolished by beta-adrenergic blockade with propranolol in all groups, while the parasympathetic antagonist atropine sulphate enhanced the responses in control rats, but had little effect in cold-acclimated animals. Feeding carbohydrate produced similar increases in interscapular brown adipose tissue (BAT) temperature in control and cold-acclimated rats, but fat caused a much greater rise in the latter group. The thermic effects of both nutrients were lower in genetically obese Zucker rats than in their lean littermates. Atropine slightly increased the thermic responses to fat and carbohydrate in the lean Zucker rats and caused marked potentiation in obese rats intubated with fat, but did not alter the effect of carbohydrate in the obese animals These data suggest that the size of the acute rise in metabolic rate after fat and carbohydrate is dependent on the thermogenic capacity of the animal. The response to fat was particularly large in cold-acclimated rats, where BAT activity is high, possibly due to a direct action of fat on the tissue.(ABSTRACT TRUNCATED AT 250 WORDS)     

Thiazide for the postponement of postmenopausal bone loss

The effect of thiazide on bone mineral loss in normal postmenopausal women was examined during a 3 yr placebocontrolled clinical trial. Sixty-three healthy women in their early menopause were randomized to treatment with bendroflumethiazide 5 mg/day or placebo for 2 yr, while both groups received placebo for the third year of the trial. Calcium supplement 0.5 g/day was given throughout the 36 mo to all participants. Bone mineral content (BMC) determined by ¹²⁵I-photon absorptiometry of the forearms decreased 2% per year in the placebo group (p < 0.001). In the thiazide group no fall in BMC was seen during the first 6 mo, whereafter BMC declined with the same rate as in the placebo group. At the end of the 3 yr trial BMC averaged 94.1% in the placebo group and 95.2% in the thiazide group (p > 0.05). Despite a daily supplement of 0.5 g calcium, thiazide induced a persistent fall in the urinary calcium excretion of 25% (p < 0.001), whereas the calcium supplement in the placebo group caused a significant increase in mean urine calcium of 10%–20% (p < .001). At stop of thiazide medication a rebound effect caused a marked rise in urine calcium. One month after withdrawal of the calcium supplement the urinary calcium excretion had returned to the initial level in both groups. It is concluded that despite a sustained urine calcium lowering action the effect of thiazide upon postmenopausal bone loss is shortlived.     

Effects of insulin at two dose levels on gluconeogenesis from alanine in fasting man

We have determined the effect of insulin infused at 1 and 5 mU/kg/min on gluconeogenesis from alanine in 48-hr fasted men. The conversion of alanine to glucose was measured by the arterial-hepatic venous catheterization technique combined with the infusion of ¹⁴C-alanine. During insulin infusion, euglycemia was maintained by variable glucose infusion. When insulin was infused at 1 mU/kg/min the net splanchnic production of ¹⁴C-glucose was suppressed by 80% but glucagon infused at the end of the study resulted in substantial release of ¹⁴C-glucose from the liver suggesting marked accumulation of labeled glucose in glycogen. When insulin was infused at 5 mU/kg/min the splanchnic release of ¹⁴C-glucose was also markedly suppressed but in contrast to the lower insulin dose very little labeled glucose accumulated in glycogen. Neither the high nor the low dose insulin infusion had any effect on net splanchnic alanine uptake and plasma glucagon levels fell by 35% in both protocols. These data demonstrate that in 48-hr fasted man, (1) a small increment in insulin concentration will suppress glucose production but mostly by diverting the newly formed glucose into glycogen; (2) at higher concentrations, insulin will inhibit glucose production mainly by suppressing gluconeogenesis; and (3) this insulin-induced suppression of gluconeogenesis is due to an intrahepatic effect rather than an effect on the splanchnic extraction of alanine.     

Complete heart block in acute myocardial infarction: drug therapy

A prospective investigation of medication in the treatment of complete heart block in acute myocardial infarction (AMI) was undertaken in the Coronary Care Unit of the Municipal Hospital, Copenhagen, during the period Nov. 24, 1967, to August 31, 1970.The material comprises 32 consecutive cases, corresponding to 8 per cent of all patients with verified acute myocardial infarction treated in the Unit during the same period. Treatment consisted in atropine, isoprenaline, and occasionally corticosteroids.Twelve patients died. In five the medication was without sufficient effect, and transvenous intracardial demand pacemakers were therefore employed. Three of these patients died. In the remaining nine fatal cases, sinus rhythm had been achieved in seven before death. The causes of death in these cases were: cardiac collapse, pulmonary embolism, or myocardial rupture. Two patients died after ventricular fibrillation.The mortality rate among the patients admitted in a state of cardiogenic shock was high, but with these exceptions it was not possible to predict the prognosis from the condition on admission.Eight out of 15 patients with infarctions of the anterior wall and 3 out of 16 patients with infarctions of the posterior wall died. The highest mortality rate was encountered in the combination of anterior wall infarction and a widened QRS complex.It cannot be ruled out that the chronotropic treatment may have resulted in an increased tendency to ectopic ventricular dysrhythmias, but this did not influence the mortality rate.The results obtained correspond to those observed in comparable materials using prophylactic pacemaker technique.It is concluded that by medication it is as a rule possible to achieve results similar to those of pacemaker therapy in complete heart block in acute myocardial infarction. However, pacemaker implantation may be life-saving in some cases and is indicated under all circumstances in Stokes-Adams attacks, persistent bradycardia with reduced cardiac output, and in repeated ventricular tachycardia during medication. In addition, prophylactic pacemaker implantation should be considered in anterior wall infarction with widened QRS complex, as this type of patient may frequently and suddenly develop complete heart block directly from sinus rhythm.