Yoshiyuki Naito

Responses of Plasma Adrenocorticotropic Hormone, Cortisol, and Cytokines during and after Upper Abdominal Surgery

There is currently accumulating evidence for bidirectional communication between the neuroendocrine and immune systems. Various cytokines have been suggested to be involved in the stimulation of stress hormone secretion during the times of infection and inflammation. To assess the possible involvement and pathophysiologic significance of cytokines in the mechanisms responsible for the perioperative stress response of the hypothalamo-pituitary-adrenal axis, we observed the changes of plasma adrenocorticotropic hormone and cortisol levels together with those of plasma endotoxin and cytokine levels. In patients undergoing pancreatoduodenectomy, perioperative stimulation of adrenocorticotropic hormone and cortisol secretion was accompanied by a significant elevation of plasma cytokine levels. Application of epidural block up to the upper thoracic levels failed to suppress this stress response effectively. In patients undergoing unilateral total hip replacement, the response of plasma hormone levels was smaller and briefer with no significant increase of plasma cytokine levels. Application of epidural block up to the lower thoracic levels suppressed this hormonal response almost completely. In patients undergoing pancreatoduodenectomy, a significant elevation of plasma endotoxin level was followed by a gradual but significant elevation of plasma tumor necrosis factor alpha and interleukin-6 levels. It seems likely that the stimulatory effects of these cytokines on the secretion of adrenocorticotropic hormone and cortisol might be involved in the development of the greater and more prolonged stress response of hypothalamo-pituitary-adrenal axis. Our present study suggests that not only neural input from the surgical wound but also stimulation of cytokine production were responsible for the development of the stress response of the hypothalamo-pituitary-adrenal axis during and after upper abdominal surgery.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of interleukins on plasma arginine vasopressin and oxytocin levels in conscious, freely moving rats

To elucidate whether interleukins are involved in vasopressin or oxytocin release during cytokine-related stressful conditions, we examined the effects of human interleukin-1 beta and interleukin-6 on plasma vasopressin and oxytocin levels in rats. Interleukin-1 beta administrated intravenously stimulated both the vasopressin and oxytocin secretion in dose-dependent manners. Neither hormone release was observed following interleukin-6 administration. Pretreatment with aspirin significantly attenuated the effects of interleukin-1 beta on both the vasopressin and oxytocin levels. SC-19220, a prostaglandin E2 receptor antagonist, did not affect the interleukin-1 beta-induced increase of plasma oxytocin levels, but almost completely abolished its effect on plasma vasopressin levels. These results suggest that under certain stressful conditions which accompany the stimulation of cytokine production, interleukin-1 is involved in the increase of plasma vasopressin and oxytocin levels and, moreover, different kinds of prostaglandins are suggested to participate in these interleukin-1-induced hormone release.

Adrenocorticotropic hormone-releasing activities of interleukins in a homologous invivo system

We compared adrenocorticotropin-releasing activities of several interleukins in a homologous or heterologous in vivo system. Intravenous injection of rat interleukin-1 alpha significantly increased plasma adrenocorticotropin in conscious, freely-moving rats 30 min after the injection, and the effect was 10 times greater than that of human interleukin-1 alpha. Rat interleukin-2 affected plasma adrenocorticotropin in a much slower manner and increased its levels significantly 120 min after the injection. Human interleukin-2 had no effect on plasma adrenocorticotropin. Thus, species difference in the experimental system should be considered to assess the physiological significance of cytokines in the neuroendocrine system.

Chronic effects of interleukin-1 on hypothalamus, pituitary and adrenal glands in rat.

To assess the chronic effects of interleukin-1 (IL-1) and IL-2 on the hypothalamo-pituitary-adrenal axis in vivo, we administered recombinant human (rh) IL-1 alpha, rhIL-1 beta or rhIL-2 (2.0 micrograms/day) repetitively to adult male rats for 10 days. In rhIL-1 beta-treated rats, adrenocorticotropic hormone-like immunoreactivity (ACTH-LI) of the anterior pituitary appeared to increase first on day 3 followed by an increase of corticotropin-releasing hormone (CRH)-LI both in the hypothalamus and in the adrenal gland after day 7. At the end of the 10-day treatment, wet weights of the adrenal glands of rhIL-1 beta-treated rats increased significantly compared with those of control rats. Plasma ACTH levels in rhIL-1 beta-treated rats at the sampling time continued to be elevated throughout the experimental period. Under the same experimental design, rhIL-1 alpha increased plasma ACTH levels at the sampling time without changes in adrenal weight or in the peptide contents investigated. The same amount of rhIL-2 had no effect on these measured variables during the 10-day treatment. These data indicate that the repetitive administration of IL-1 beta resulted in chronic effects in the hypothalamo pituitary-adrenal axis to increase the activities in these organs during the treatment and, moreover, IL-1 possibly has a positive direct effect on the CRH-containing cells in the adrenal glands.

Interleukin-1β analogues with markedly reduced pyrogenic activity can stimulate secretion of adrenocorticotropic hormone in rats

We examined the adrenocorticotropic hormone-releasing activities of several human interleukin-1 beta analogues that have markedly reduced pyrogenic activities in rats. Among the analogues tested, [Gly4]-, [Leu93]- and [1-148]-interleukin-1 beta increased the plasma adrenocorticotropic hormone level to almost that induced by authentic human interleukin-1 beta. Modifications of the N-terminus of the authentic molecule, i.e., [7-153]- and [Des-Ala1, Asp4]-interleukin-1 beta, significantly reduced the hormone-releasing activity. These data suggest that the adrenocorticotropic hormone-releasing activity of human interleukin-1 beta resides in the N-terminal structure of the authentic peptide and can be separated from its pyrogenic activity.

Thyroid Storm Due to Functioning Metastatic Thyroid Carcinoma in a Burn Patient

Thyroid storm as a result of functioning metastatic thyroid carcinoma is exceedingly rare. 1 We describe a patient with functioning distant metastases from adenocarcinoma of the thyroid in whom thyroid storm developed in the course of care for extensive burns.

Marked sensitivity to pancuronium in a patient without clinical manifestations of myasthenia gravis.

It is well known that anesthesia and surgery may precipitate muscle weakness in patients with myasthenia gravis (l), with some patients not recognized as myasthenics until such episodes (2,3). In such instances, the diagnosis of myasthenia gravis is usually based not only on the increased sensitivity to neuromuscular relaxants but also on the development of generalized muscle weakness after surgery, suggestive of exacerbation of mild or restricted type of myasthenia gravis by surgical stress. In this case report, we describe a patient with an increased sensitivity to pancuronium who, in spite of a high titer of antiacetylcholine receptor antibodies, showed no clinical manifestations of myasthenia gravis during the perioperative period.

Comparison of endocrinological stress response associated with transvaginal ultrasound-guided oocyte pick-up under halothane anaesthesia and neuroleptanaesthesia

Twelve patients with mechanical infertility in the in vitrofertilization program were studied. Seven of them received halothane anaesthesia and the other five received neuroleptanaesthesia. Higher plasma prolactin levels and lower plasma progesterone levels were observed in the neuroleptanaesthesia group than in the halothane group during and after transvaginal ultrasound-guided oocyte pick-up. Plasma adrenocorticotropic hormone and cortisol levels of the patients suggested that surgical stress was minimal in both groups. It is likely that droperidol and fentanyl, both used in neuroleptanaesthesia, were responsible for the hyperprolactinaemia which was followed by inhibition of progesterone production. These agents, therefore, are not recommended as anaesthetic agents for transvaginal ultrasound-guided oocyte pick-up.RésuméDans le cadre d’un programme de fertilisation in vitro, on a fait la cueillette d’ovules par voie transvaginale avec échographie chez 12 femmes infertiles. Pour ce faire, nous en avons anesthé siées sept avec de l’halothane et cinq par neuroleptanesthésie. En mesurant les niveaux plasmatiques pendant et après la procédure, nous avons trouvé plus de prolactine et moins de progestérone avec l’halothane qu’avec la neuroleptanesthésie. Les quantités d’ACTH et de cortisol plasmatiques, faibles dans les deux groupes, suggèrent un niveau minimal de stress chirurgical. II est probable que le dropéridol et le fentanyl, utilisés dans le groupe neuroleptanesthésie, soient responsables d’une hyperprolactinémie suivie d’une inhibition de la sécrétion de progestérone et de ce fait, ils devraient être évités lors de la cueillette d’ovules.

Immunoreactive corticotropin-releasing hormone levels in discrete hypothalamic nuclei of genetically obese Zucker rats

The levels of immunoreactive corticotropin-releasing hormone (ir-CRH) were measured in discrete hypothalamic nuclei and the median eminence of obese Zucker rats and their lean littermates. More than 90% of total hypothalamic ir-CRH was detected in the median eminence in both obese and lean rats. Though ir-CRH levels in the paraventricular nucleus of obese rats tended to be lower than those of their lean littermates, no significant difference of ir-CRH levels was observed in any hypothalamic nuclei studied between obese and lean rats. However, ir-CRH levels in the median eminence of obese rats were significantly lower than those of their lean littermates (5263 +/- 438 pg/tissue vs. 7050 +/- 473 pg/tissue, P < 0.05). These results suggest that the hypoactive hypothalamic CRH tonus would play some role in the phenotypic expression of obesity in the genetically obese Zucker rats.

Continuous oxygen insufflation using a speaking tracheostomy tube is effective in preventing aspiration during feeding

ASPIRATION during feeding in patients with tracheostomies and whose lungs are mechanically ventilated is a frequent and serious problem that can result in airway obstruction and pulmonary infection. 1-3 We describe a patient with a cervical cord transection suffering from frequent aspiration during feeding. Fiberoptic examination revealed a disruption of the glottic closure reflex. Continuous insufflation of oxygen into the subglottic airway using a speaking tracheostomy tube restored competent glottic closure reflex and was effective in preventing aspiration.