Recurrent amiodarone pulmonary toxicity.

Amiodarone, a widely used antiarrhythmic drug, is associated with pulmonary toxicity, with an estimated mortality of 1% to 33%. Standard treatment for amiodarone pulmonary toxicity (APT) has been discontinuance of the drug and steroid therapy. We report a case of APT that recurred after withdrawal of steroids and failed to respond to reinstatement of steroid therapy. Recurrent APT is a rare clinical entity that has been reported only twice in recent literature.

Selective neurohormonal interactions in islet cell secretion in the isolated perfused human pancreas.

To investigate the effects of stimulant interactions on alpha- and beta-cell secretions, the differential effects of gastric inhibitory polypeptide (GIP) and cholinergic stimulation (CS) on insulin (IRI) and glucagon (IRG) release were examined during euglycemic, single-pass perfusion in the isolated human pancreas. Pancreata obtained from 12 cadaver organ donors were perfused for 15-min test periods with (a) 1 nM GIP (b) intrinsic CS via bipolar electrical stimulation (10 V, 5 msec, 10 Hz) of the splanchnic neural fibers during simultaneous perfusion with 4 microM phentolamine and 6 microM propranolol, or (c) GIP and CS. The integrated response of IRI and IRG demonstrated that IRI release was stimulated 308 +/- 52 microU/g-min by GIP, 366 +/- 73 microU/g-min by CS, and 560 +/- 50 microU/g-min by GIP and CS (P less than 0.05). IRG release was stimulated 111 +/- 33 pg/g-min by GIP, 34 +/- 12 pg/g-min by CS, and 90 +/- 36 pg/g-min by GIP and CS. Combined hormonal and cholinergic stimulation was additive for IRI release, but not for IRG release. We conclude that the interaction of neural and hormonal islet cell stimuli is cell-type specific. This may result in selective impairment of hormone release after pancreatic denervation.

Splanchnic neural regulation of pancreatic polypeptide release in the isolated perfused human pancreas.

The isolated perfused human pancreas was employed as a model in which electrical stimulation of the celiac mixed neural bundle was performed in the presence and absence of selective neural antagonists. Stimulation of the celiac neural bundle in the presence of hyperglycemia resulted in augmentation of pancreatic polypeptide release. Cholinergic stimulation appears to predominate, whereas beta-adrenergic fibers stimulate pancreatic polypeptide-cell secretion, and alpha-adrenergic fibers inhibit pancreatic polypeptide release. During euglycemia, both cholinergic stimulation and gastric inhibitory polypeptide infusion resulted in a marked release of pancreatic polypeptide. These stimulatory effects were additive, which suggests a linked hormonal and neural mechanism of pancreatic polypeptide release after a meal. In this in vitro human model, our data confirm that the splanchnic innervation of the pancreas has a potent regulatory role in pancreatic hormone release in man.

Regulation of pancreatic polypeptide secretion in the isolated perfused human pancreas.

The isolated perfused human pancreas was used as a model to assess factors mediating the pancreatic polypeptide cell response to glucose, insulin, gastric inhibitory polypeptide, and splanchnic nerve stimulation. Pancreases obtained from 18 cadaveric organ donors were isolated and perfused by way of the splenic artery utilizing a Krebs bicarbonate buffer in a single-pass perfusion system. Hormonal stimulation and inhibition of pancreatic polypeptide secretion were assessed, as was the influence of direct electrical stimulation of celiac neural fibers innervating the pancreas. In this in vitro human model, pancreatic polypeptide cell secretion was inhibited by hyperglycemia, although the presence of gastric inhibitory polypeptide augmented the pancreatic polypeptide cell response. Perfusion with low levels of insulin and splanchnic nerve stimulation augmented the response of the pancreatic polypeptide cell to hyperglycemia and gastric inhibitory polypeptide. Since the immunoreactive pancreatic polypeptide response was augmented when insulin and somatostatin release was inhibited by perfusion insulin or nerve stimulation, we conclude that the pancreatic polypeptide cell is regulated by the ambient degree of somatostatin release, insulin release, or both. These findings support a centrifugal pattern of intraislet blood flow.

Splanchnic neural regulation of insulin and glucagon secretion in the isolated perfused human pancreas.

The isolated perfused human pancreas was employed as a model in which electrical stimulation of the celiac mixed neural bundle was performed in the presence or absence of selective neural blockers. The insulin and glucagon responses to hyperglycemia alone or in the presence of splanchnic nerve stimulation were similar in magnitude to the results obtained in a preliminary report on isolated human pancreatic function and in studies using animal models. Stimulation of the celiac neural bundle in the presence of hyperglycemia resulted in an inhibition of insulin release and in an augmentation of glucagon release. alpha-adrenergic stimulation resulted in a strong suppression of insulin secretion and a mild suppression of glucagon secretion. beta-adrenergic fiber stimulation caused a mild augmentation of both insulin and glucagon release, whereas the cholinergic fibers strongly stimulated both alpha- and beta-cell secretion. The predominant effects of celiac neural bundle stimulation are insulin inhibition by was of an alpha-adrenergic effect and glucagon stimulation by way of a cholinergic effect. Thus, in this in vitro human model, our data confirm that the splanchnic innervation of the pancreas has a potent regulatory role on pancreatic hormone release in human subjects.

Reversal of abnormal glucose metabolism in chronic pancreatitis by administration of pancreatic polypeptide.

Chronic pancreatitis, induced in dogs by pancreatic duct ligation, is associated with glucose intolerance due to insulin deficiency, reduced hepatic sensitivity to insulin, and a marked deficiency of pancreatic polypeptide. Treatment with a 14 day continuous subcutaneous infusion of pancreatic polypeptide resulted in improved oral glucose tolerance and improved hepatic glucose responses to insulin in dogs with chronic pancreatitis. No effect of continuous subcutaneous infusion of pancreatic polypeptide was seen in the control dogs. The time course of the effect of continuous subcutaneous infusion on the hepatic response to insulin was relatively immediate, whereas the effects on improvement in oral glucose tolerance were prolonged. We conclude that pancreatic polypeptide may function physiologically to enhance the hepatic glucose response to insulin and that alterations in glucose metabolism seen in chronic pancreatitis may be due, in part, to a deficiency in pancreatic polypeptide. Since treatment with continuous subcutaneous infusion of pancreatic polypeptide restored the hepatic response to insulin and oral glucose tolerance to more normal levels in our animal model, administration of pancreatic polypeptide may play a therapeutic role in the treatment of certain forms of pancreatogenic diabetes.

Social facilitation in a 'non-social' animal, the centipede Lithobius forficatus.

In a series of experiments in which centipedes ran alone (control), with a passive audience, and in coaction (two together), on a simple escape runway, significant differences from controls in latency and running speed were observed under audience conditions. The relevance of this apparent demonstration of social facilitation in an animal which is essentially not social is discussed in relation to the Zajonc (1965) 'mere presence' and Cottrell (1972) 'evaluation-apprehension' hypotheses of social facilitation.

The histochemical demonstration of guanase: observations in the human central nervous system.

1. A method is described for the histochemical demonstration of the purine catabolizing enzyme guanase, employing glutaraldehyde fixation and Nitro blue tetrazolium (NBT). Parallel biochemical studies confirm that enzyme activity is not significantly inhibited by exposure to glutaraldehyde. 2. By this procedure guanase activity has been visualized in neurons and glial elements of the human central nervous system (CNS). 3. Controls consisted of direct incubation of cryostat sections with a specific inhibitor of guanase (5-amino-4-imidazole carboxamide) and omission successively of the substrate guanine, of xanthine oxidase and of NBT. Enzyme activity was completely inhibited by the above procedures, and by boiling of tissues for 10 min prior to fixation. 4. Levels of enzyme activity in spinal cord and brain were assessed by a subjective scoring method, and showed close comparability with biochemical assay data in brainstem and cerebral hemispheres; whereas a low correlation for enzyme activity was observed in spinal cord and cerebellum. Differences between biochemical and histochemical assessments of CNS guanase activity are discussed.