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To evaluate optimal catheter position for PreSep central venous oximetry catheter, we inserted the catheter through a sheath introducer with contamination shield and conducted its in vivo calibration in twenty-eight patients. In the event of calibration failure due to unstable signals, the catheter was advanced until calibration became possible. If SQI rose to 3 or 4 during surgery, we readjusted the catheter position to resume reliable monitoring. At the conclusion of surgery, the catheter position was checked radiologically and the distance between the catheter tip and the upper border of the clavicle was measured.In 70% of the patients, calibration was performed successfully when the catheter was inserted for 12-14 cm from the top of the groove between the sternal and clavicular heads of the sternocleidomastoid muscle, which led to positioning of the catheter tip 5-7 cm from the upper border of the clavicle. However, there was a considerable variation within the total patient sample and no definite correlation was found between catheter positions and patient's height. In 30% of the patient, readjustment of the catheter was required during surgery.Use of a sheath introducer with contamination shield seems to be useful for positioning the PreSep catheter.

The nuclear factor of activated T cells (NFAT) regulates cytokine gene expression in T cells through cis-acting elements located in the promoters of cytokine genes. Here, we report the cDNA cloning, chromosomal localization, and initial characterization of a transcription factor related to NFATp and NFATc. The novel molecule, designated NFATx, exhibits in its middle a region very similar to the Rel homology domain in NFATc and NFATp. The amino-terminal region of NFATx also shows significant similarities to corresponding sequences in NFATc and NFATp and contains three copies of a conspicuous 17-residue motif of unknown function. We provide evidence showing that NFATx can reconstitute binding to the NFAT-binding site from the interleukin 2 promoter when combined with AP1 (c-Fos/c-Jun) polypeptides and that NFATx is capable of activating transcription of the interleukin 2 promoter in COS-7 cells when stimulated with phorbol ester and calcium ionophore. NFATx mRNA is preferentially and remarkably found in the thymus and at lower levels in peripheral blood leukocytes. The expression pattern of NFATx, together with its functional activity, strongly suggests that NFATx plays a role in the regulation of gene expression in T cells and immature thymocytes.

Transesophageal echocardiography is an invaluable hemodynamic monitoring modality. Extended and anatomically based evaluation of cardiac function with transesophageal echocardiography is essential to prompt and accurate decision-making in anesthetic management during cardiac surgery. Fractional shortening and fractional area changes are indices widely used to assess the global systolic performance of the left ventricle. Monitoring regional function using semi-quantitative scoring has been demonstrated to be a more sensitive indicator of myocardial ischemia. Assessment of left ventricular diastolic function should be performed in a systematic way, measuring transmitral flow, pulmonary venous flow, transmitral color M-mode flow propagation velocity, and mitral annulus tissue Doppler imaging. The unique anatomical features of the right ventricle make echocardiographic evaluation complicated and therefore less frequently employed. Right ventricular fractional area change, tricuspid annular plane systolic excursion, maximal systolic tricuspid annular velocity with tissue Doppler imaging, and myocardial performance index are indices successfully incorporated into intraoperative right ventricular assessment. Left ventricular outflow tract obstruction with systolic anterior motion of the mitral valve may develop after cardiac procedures. Transesophageal echocardiography plays a central role in prevention as well as diagnosis of systolic anterior motion. Transesophageal echocardiography is extremely useful not only for detecting and locating intracardiac air, but also for guiding and evaluating the procedures to remove air. Air is likely to persist in the right and left superior pulmonary vein, left ventricular apex, left atrium, right coronary sinus of Valsalva, and ascending aorta. Accurate evaluation of cardiac function depends on performing TEE examination properly and obtaining optimal images.

To assess the usefulness of ultrasound-guided sciatic nerve block in the popliteal fossa in the postoperative pain management after Achilles' tendon repair, we compared 15 patients managed by general anesthesia and sciatic nerve block (Group B) with 17 patients managed by general anesthesia alone (Group G). The time required for the nerve block was about 20 minutes on the average, and the success rate was 100%. No significant complication associated with the nerve block was observed. Fentanyl dosing for the postoperative analgesia was significantly smaller in the Group B. Although the postoperative analgesic requirement was comparable, the time to the first postoperative analgesic administration was significantly longer in the Group B. This retrospective study suggests that ultrasound-guided sciatic nerve block in the popliteal fossa provides safe and effective postoperative pain relief after Achilles' tendon repair.

Substantially decreased oxygen saturation levels were incidentally detected by pulseoxymetry in a patient with spherocytic hemolysis who was undergoing laparoscopic splenectomy. Molecular analysis revealed that he was carrying hemoglobin (Hb) Nishinomiya, a novel Hb variant [Leu-Gly-inserted between codons 69(E13) and 70(E14) of beta]. Amino acid substitutions around positions 70-73(E13-17) of the beta chain are likely to change stability and oxygen affinity, as has been demonstrated in several Hb variants including Hb Seattle. The apparent substitution of the amino acid residues in the heme pocket of the beta chain explains the decreased stability and oxygen affinity of Hb Nishinomiya.

A 91-year-old man underwent aortic valve replacement using a pulmonary artery catheter (PAC). Intraoperative hemodynamic monitoring with the PAC showed no abnormality except for bleeding from optical module connection port. In the intensive care unit, difficulty in withdrawing the PAC was noted. Surgical removal of the PAC was performed, revealing the PAC sutured to the right atrium. When bleeding from the PAC connection ports is noted, it is advisable to suspect that the PAC might have been sutured.

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)

Activation of T cells is initiated by the recognition of antigen on antigen presenting cells to exert the effector functions in immune and inflammatory responses. Two types of helper T cell (Th) clones (Th1 and Th2) are defined on the basis of different patterns of cytokine (lymphokine) secretion. They determine the outcome of an antigenic response toward humoral or cell-mediated immunity. Although lymphokine genes are coordinately regulated upon antigen stimulation, they are regulated by the mechanisms common to all as well as those which are unique to each gene. For most lymphokine genes, a combination of phorbol esters (phorbol 12-myristate 13 acetate, PMA) and calcium ionophores (A23187) is required for their maximal induction. Yet phorbol ester alone or calcium ionophore alone produce several lymphokines. The production of the granulocyte-macrophage colony stimulating factor (GM-CSF) is completely dependent on the two signals. We have previously found a cis-acting region spanning the GM-CSF promoter region (positions -95 to +27) that confers inducibility to reporter genes in transient transfection assays. Further analysis identified three elements required for efficient induction, referred to as GM2, GC-box and conserved lymphokine element (CLE0). GM2 defines a binding site for protein(s) whose binding is inducible by PMA. One protein, NF-GM2 is similar to the transcription factor NF-kB. GC-box is a binding site for constitutively bound proteins. CLEO defines a binding site for protein(s) whose optimum binding is stimulated by PMA and A23187. Viral trans-activators such as Tax (human T cell leukemia virus-1, HTLV-1) and E2 (bovine papilloma virus, BPV) proteins are other agents which activate lymphokine gene expression by bypassing T cell receptor (TCR) mediated signaling. The trans-activation domain of E2 and Tax is interchangeable although they have no obvious sequence homology between them. The viral trans-activators appear to target specific DNA binding protein such as NF-kB and Sp1 to cis-acting DNA site and promote lymphokine gene expression without TCR-mediated stimulation.

Regulatory mechanisms of the hypothalamo-pituitary-adrenal (H-P-A) axis during and after major abdominal surgery were studied in a group of patients who underwent upper abdominal surgery. We first examined the general profile of the changes of the H-P-A axis from the day before surgery to the seventh day after surgery. On the day of surgery, plasma levels of CRH, ACTH, and cortisol were all significantly elevated after skin incision (phase I). During the next 2 days, plasma cortisol levels remained significantly elevated, and the both plasma CRH and ACTH levels were suppressed below the control levels obtained on the day before surgery (phase II). Several additional studies, carried out to analyze the mechanism that maintains the high plasma cortisol levels, revealed the following features of the H-P-A axis during phase II. Plasma free cortisol levels in this phase were higher than those during the preoperative period. The exogenously administered hydrocortisone clearance rate in phase II did not differ from that observed on the day before surgery. Dexamethasone administration resulted in a decrease in plasma cortisol levels similar to that observed preoperatively. Conversely, the ACTH-stimulated cortisol increase was significantly greater in phase II than that observed preoperatively. These results suggest that during and after major surgical stress, the H-P-A axis undergoes a biphasic change in the pattern of the stress response and during the second phase, not the continuous hypothalamo-pituitary drive but the increased adrenal responsiveness to ACTH is responsible at least in part for maintaining the elevated plasma cortisol level.

The effects of interleukins on adrenal steroidogenesis and their mode of action were studied using cultured rat adrenal cells. The addition of rat interleukin-1 alpha (IL-1 alpha) or rat IL-2 increased corticosterone levels in the medium in a concentration-dependent manner during 24 h of incubation. The minimum, half-maximum, and maximum effective concentrations of both rat IL-1 alpha and rat IL-2 were almost same (approximately 3, 10, and 100 U/ml, respectively). After a latent period, the effect became apparent after 12 h of incubation. Human IL-1 beta and human IL-6 also showed a stimulatory effect on corticosterone production, whereas human IL-2 was inactive in this system. To clarify the cellular mechanism of these stimulatory effects, we measured the levels of prostaglandin E2 (PGE2) and cAMP in the cells and media as well as the corticosterone levels. Corticosterone production stimulated by IL-1 alpha or IL-2 was accompanied by intracellular and extracellular cAMP and PGE2 accumulation. Although the stimulation of both cAMP and corticosterone was observed only after 12 h of incubation, PGE2 levels increased during the first 4 h of incubation. Corticosterone, cAMP, and PGE2 production stimulated by ILs was almost completely blocked by the addition of 0.1 mM aspirin, a cyclooxygenase inhibitor. Lipoxygenase inhibitors, i.e. AA-861, nordihydroguaiaretic acid, and 5,8,11,14-eicosatetrynoic acid, did not abolish corticosterone production stimulated by ILs. Submaximal doses of IL-1 alpha and IL-2 synergistically stimulated PGE2 production, but did not have even additional effects on cAMP and corticosterone levels. On the other hand, submaximal doses of ACTH, which did not significantly affect PGE2 levels, acted synergistically with IL to increase cAMP and corticosterone levels in these cells. These results indicate that 1) IL-1 alpha and IL-2 directly stimulate glucocorticoid synthesis in a dose- and time-dependent manner; 2) a half-maximum effective concentration of ACTH acts synergistically with IL in stimulating glucocorticoidogenesis; 3) the stimulatory process initially requires PGs, followed by the activation of the adenylate cyclase system; 4) although the profiles of steroidogenic action of IL-1 alpha and IL-2 are quite similar, they may exert their effects through different mechanisms in their early steps of PGE2 production; and 5) the low effective concentrations of both cytokines suggest possible physiological or pathophysiological roles of circulating cytokines in the glucocorticoidogenesis under certain conditions.

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 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.

We have compared the rapidity and quality of recovery after sevoflurane anaesthesia with those after halothane anaesthesia. Thirty unpremedicated paediatric outpatients undergoing pulsed-dye laser therapy for port-wine stains were allocated randomly to receive either halothane or sevoflurane anaesthesia. Each group received 60% nitrous oxide and 1.0-1.5 MAC of volatile agent in oxygen for approximately 40 min. Patients receiving sevoflurane exhibited more rapid emergence and a significantly shorter postoperative recovery time compared with those receiving halothane. No major adverse effects were encountered in each group. These results suggest that sevoflurane anaesthesia is preferable to halothane anaesthesia for paediatric ambulatory patients.

The ST2 gene, which is specifically induced by growth stimulation, encodes interleukin-1 receptor-related proteins. Using the RT-PCR method, we found that the ST2 gene was broadly expressed in hematopoietic cell lines. It was also expressed specifically in helper T cell lines among lymphocytic cell lines. We analyzed the expression of ST2 in mouse helper T cell subsets with Northern blotting analysis. Mouse Th1 cell lines so far studied did not express ST2 mRNAs. On the other hand, one of the Th2 cell lines, D10, expressed ST2L (transmembrane form) without stimulation, while co-stimulation by PMA and A23187 induced ST2 (soluble form) mRNA. These results suggest that the ST2 gene is involved in the regulation of the immune system. IL-1 alpha, IL-1 beta, and receptor antagonist did not bind to ST2L protein, which prompted us to search for the specific ligand of ST2. The recombinant human ST2 protein was purified and labeled with FITC. The labeled human ST2 protein bound with myeloma-derived RPMI8226 cells among the various B-cell lines, indicating possible involvement of ST2 in T-cell/B-cell interaction.

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.

Mouse thymoma line EL-4 cells produce cytokines such as interleukin (IL)-2, IL-3, IL-4, IL-10, and granulocyte-macrophage colony-stimulating factor in response to phorbol 12-myristate 13-acetate (PMA). EL-4 cells also produce low levels of IL-5 when stimulated by PMA alone; however, cAMP greatly augments PMA-dependent IL-5 production. A transient transfection assay revealed that two signals, PMA and cAMP, are required for optimal activation of the IL-5 promoter. In contrast, cAMP almost completely inhibited the PMA-dependent activation of the endogenous IL-2 gene, as well as the transfected IL-2 promoter. These results indicate that the IL-5 gene is positively regulated by cAMP in a manner opposite to that for the IL-2 gene. One of the nuclear factors (NFs) that regulates the response of the IL-5 promoter to cAMP and PMA has properties similar to NF for activated t cell. The P sequence of the IL-4 gene, defined as a responsive element for PMA and calcium ionophore (A23187), shares sequence similarity with the NF kappa B and the NF-activated T cell binding sites. We attempted to determine whether NF(P), a nuclear factor specific for the P sequence, is related to NF-kappa B and nuclear factor for activated T cell (NF-AT). In electromobility shift assays both NF-kappa B (P65 or P65/P50 heterodimer) and NF-AT bound to the P sequence. However, sequence specificity of NF-AT was more similar to that of NF(P), and only a small amount of P65 was detected in NF(P). These results indicate that a component or components of NF-AT have the potential to reconstitute NF(P), whereas NF-kappa B alone does not account for NF(P) in Jurkat crude extract. Taken together, these results suggest that NF-AT-like factors are involved in the regulation of IL-4 and IL-5 genes.

Granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-2 (IL-2) are produced by stimulation with phorbol-12-myristate acetate (PMA) and calcium ionophore (A23187) in human T cell leukemia Jurkat cells. The expression of GM-CSF and IL-2 is inhibited by immunosuppressive drugs such as cyclosporin A (CsA) and FK506. Earlier studies on the IL-2 gene expression showed that overexpression of calcineurin (CN), a Ca2+/calmodulin-dependent protein phosphatase, can stimulate transcription from the IL-2 promoter through the NF-AT-binding site. In this study, we obtained evidence that transfection of the cDNAs for CN A (catalytic) and CN B (regulatory) subunits also augments transcription from the GM-CSF promoter and recovers the transcription inhibited by CsA. The constitutively active type of the CN A subunit, which lacks the auto-inhibitory and calmodulin-binding domains, acts in synergy with PMA to activate transcription from the GM-CSF promoter. We also found that the active CN partially replaces calcium ionophore in synergy with PMA to induce expression of endogenous GM-CSF and IL-2. By multimerizing the regulatory elements of the GM-CSF promoter, we found that one of the target sites for the CN action is the conserved lymphokine element 0 (CLE0), located at positions between -54 and -40. Mobility shift assays showed that the CLE0 sequence has an AP1-binding site and is associated with an NF-AT-like factor, termed NF-CLE0 gamma. NF-CLE0 gamma binding is induced by PMA/A23187 and is inhibited by treatment with CsA. These results suggest that CN is involved in the coordinated induction of the GM-CSF and IL-2 genes and that the CLE0 sequence of the GM-CSF gene is a functional analogue of the NF-AT-binding site in the IL-2 promoter, which mediates signals downstream of T cell activation.

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.

Twelve patients with mechanical infertility in the in vitro fertilization 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.

We compared adrenocorticotropin-releasing activities of several interleukins in a homologous or heterologous in vivo system. Intravenous injection of rat interleukin-1 α 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 α. 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.

A case of juvenile angina pectoris probably due to congenital syphilis was reported. Both coronary ostial narrowing could be only presumed in usual physical and laboratory examination. And then aortitis and both coronary ostial stenosis demonstrated in vivo by aortography and selective coronary arteriography. The progress of this case has been observed at present with internal treatments, but surgical repair will be necessary in the near future.