Pleth variability index can predict spinal anaesthesia-induced hypotension in patients undergoing caesarean delivery.

BACKGROUND: Spinal anaesthesia carries a risk of hypotension. We hypothesized that pleth variability index and perfusion index would assess maternal volume status, and thus, allow identification of patients at higher risk of developing hypotension after spinal anaesthesia for caesarean delivery. METHODS: Fifty patients undergoing elective caesarean delivery were enrolled. All patients received spinal anaesthesia with 0.5% hyperbaric bupivacaine (10 mg) and fentanyl (10 mcg). Blood pressure was measured every minute. Pleth variability index and perfusion index were automatically measured throughout the procedure using pulse oximetry on the index finger. In case of hypotension (systolic blood pressure below 90 mmHg or 80% of the baseline value), ephedrine 5 mg was administered. Receiver-operating characteristic and multivariate logistic regression analyses for spinal anaesthesia-induced hypotension were performed. RESULTS: Hypotension occurred in 32 patients (64%). The areas under the receiver-operating characteristic curve were 0.751 (95% confidence interval: 0.597-0.904) for pleth variability index before anaesthesia, 0.793 (95% confidence interval: 0.655-0.930) for pleth variability index after anaesthesia and 0.731 (95% confidence interval: 0.570-0.892) for perfusion index change (percent change in perfusion index induced by spinal anaesthesia). The optimal threshold value of pleth variability index (after anaesthesia) for predicting hypotension was 18% (sensitivity: 78.1%, specificity: 83.3%). Pleth variability index after spinal anaesthesia was an independent factor for hypotension (odds ratio: 1.21, P = 0.041). CONCLUSIONS: Pleth variability index after spinal anaesthesia was a good predictor of spinal anaesthesia-induced hypotension in patients undergoing caesarean delivery. In addition, perfusion index change after spinal anaesthesia has the potential to predict hypotension.

From duration and distance comparisons to goal encoding in prefrontal cortex.

Timing is a very abstract representation that shares with other magnitudes, such as numerosity, the peculiarity of being independent from any particular sensory modality. Not only we can time stimuli in different modalities but we can also compare the durations of different visual, auditory and somatosensory stimuli. Furthermore, even though time is not directly associated with space, and we are inclined to consider space and time as two different perceptual dimensions of our existence, an increasing number of studies challenge this idea by showing that timing and spatial processing have some relationship that involves sharing computation resources and that time may have a spatial representation. A more general theory, called theory of magnitude (ATOM), considers both timing and spatial computations, together with other magnitudes, as originating from a general magnitude system [Walsh VA, Trends Cogn Sci 7(11):483-8, 2003]. The neural underpinnings of time and its relationship to the processing of spatial information have started to be investigated only recently, but the field is rapidly growing. It is addressing the representation of time in several cortical and subcortical brain areas. Information processing of time and space are not strictly specialized in neural and cognitive mechanisms and we believe that studying them only separately may restrict our understanding of these processes. In this chapter, we will firstly introduce the role of the prefrontal cortex (PF) in coding relative durations. We will point out that the comparison of durations makes use of intermediate computations based on the order of the events. Secondly, we will describe the comparison mechanisms that are implemented by PF to make perceptual decisions about durations in relation to those involved in making decisions about spatial locations and distances. We will distinguish the decision processes from the goal choices, and we will examine which computational resources are shared between different magnitudes and which are domain-specific. We will summarize our results within the context of a more general PF function in promoting the generation of goals from the current context, consisting of domain- and modality-specific coding of stimuli of different modalities or magnitudes.

Endocrine response to a single injection of goserelin 3.6 mg or leuprolide 3.75 mg in men with prostate cancer.

Hormonal responses were assessed in men with prostate cancer (T2-4, Nx, Mx) who were randomized to receive either a single injection of goserelin 3.6 mg or leuprolide 3.75 mg. Testosterone increased over the first week, with a significantly higher mean rate of change of total testosterone (day 3) and free testosterone (days 3 and 7) with leuprolide. Following the initial rise in luteinizing hormone (LH), the rate of decrease in LH levels was significantly greater with goserelin by day 28. There are significant differences in endocrine response to goserelin and leuprolide in the 4 weeks following administration.

[Introduction and clinical evaluation of a new non-invasive cardiac output monitor (NICO) based on Fick partial CO2 rebreathing method].

A newly developed non-invasive monitor, NICO (Novametrix Medical Systems Inc.), measures cardiac output based on changes in respiratory CO2 concentration caused by a brief period of rebreathing. By applying modified form of the CO2 Fick principle, cardiac output is calculated. We determined the accuracy and precision of this technique (RBCO) by comparing it with continuous thermodilution technique (TDCCO) and pulse dye densitometry technique (PDD). The overall difference between RBCO and TDCCO(n = 46) was -0.21 +/- 1.43 (bias +/- 2 SD)l.min-1. On the other hand, the overall difference between RBCO and PDD (n = 53) was -0.1 +/- 2.04 (bias +/- 2 SD)l.min-1. The degree of accuracy of RBCO was thought to be the same as those of TDCCO and PDD. We expect that NICO will be a useful cardiac output monitor in any method of general anesthesia in which PA catheterization is difficult or not indicated.

Apnea during spinal anesthesia in an unsedated patient with central sleep apnea syndrome.

We describe a case of apnea during spinal anesthesia in an unsedated patient with central sleep apnea syndrome. When spinal anesthesia is planned for a patient who is suspected of having this syndrome, apnea may be induced, even if no sedative was administered and the level of anesthesia is only moderate.

Intrarenal mature cystic teratoma associated with renal dysplasia: case report and literature review.

We report a case of intrarenal teratoma in a 6-year-old boy. Two years before his operation, multicystic masses had been found in the left side of his abdomen. In the operation, three main cystic masses were located in the upper and lower poles of the left kidney, which were removed in pieces. Histologically, the cyst wall was lined mainly with keratinizing squamous epithelium with hair follicles, shafts and sebaceous glands. The adjacent renal parenchyma showed atrophy, with partially dysplastic and angiomyolipoma-like lesions. Based on these findings, the lesion was diagnosed as mature cystic teratoma of dermoid cyst type. Extragonadal teratoma occurs predominantly along the median line of the body. Intrarenal teratoma is extremely rare; however, it should be distinguished from teratoid Wilms' tumor and other renal cystic lesions.

The effects of uterine and umbilical blood flows on the transfer of propofol across the human placenta during in vitro perfusion.

UNLABELLED: The safety of using propofol in parturients is controversial, and little information is available on the factors that influence the placental transfer of propofol. In this study, we investigated the effects of uterine and umbilical blood flows on the placental transfer of propofol by using the dually perfused human placental cotyledon. Placental transfer was evaluated on the basis of the placental clearances at various uterine and umbilical flow rates. The placental transfer of propofol was significantly facilitated by the increased uterine flow rates over the range from 7.5 to 25 mL/min. The placental clearances of propofol were also dependent on the umbilical flow rates over the range from 0.5 to 4.0 mL/min. In contrast, the placental transfer of antipyrine was flow dependent when the umbilical flow rate was <2.0 mL/min and became permeability limited when it was >2.0 mL/min. No differences in either maternal or fetal venous concentrations of propofol were observed as umbilical flow rates varied from 0.5 to 4.0 mL/min, suggesting that an equilibration across the placenta occurs at low flow rates. These results indicate that fetal uptake of propofol can be profoundly altered by the changes in both uterine and umbilical blood flows observed in various pathophysiologic conditions and that lipid solubility greatly influences placental transfer of drugs. IMPLICATIONS: Uterine and umbilical blood flows are determinant features in controlling the placental transfer of propofol, and, therefore, changes in these variables would significantly affect the extent of fetal exposure to propofol.

Intravenous injection of oligodeoxynucleotides to the NF-kappaB binding site inhibits hepatic metastasis of M5076 reticulosarcoma in mice.

We have developed synthetic double-stranded oligodeoxynucleotides (ODN) as 'decoy' cis elements that block the binding of nuclear factors to promoter regions of targeted genes, resulting in the inhibition of gene transactivation in vivo. In the present study, we employed decoy ODN targeting the transcription factor nuclear factor-kappaB (NF-kappaB) binding cis-elements to hepatic metastasis of murine reticulosarcoma M5076 in mice. Intravenous inoculation of M5076 into mice caused a marked increase in gene expression of interleukin-1beta, tumor necrosis factor-alpha and intercellular adhesion molecule-1 in the liver, whereas intravenous treatment with NF-kappaB decoy ODN reduced M5076-induced transactivation of these genes. Treatment with NF-kappaB decoy ODN, but not scrambled decoy ODN, significantly inhibited hepatic metastasis of M5076 in mice, and furthermore the combined treatment of NF-kappaB decoy ODN with an anti-cancer drug resulted in complete inhibition of hepatic metastasis in half of the mice, without affecting myelosuppression induced by the anti-cancer drug. Here, NF-kappaB decoy ODN inhibited hepatic metastasis of M5076 in mice possibly through a decrease in transactivation of important NF-kappaB-driven genes and also potentiated the anti-metastatic effect of an anti-cancer drug, demonstrating the first successful in vivo therapy for cancer metastasis using NF-kappaB decoy ODN as a novel molecular decoy approach.

Histomorphometric characteristics and cellular kinetics of colorectal polyps with epithelial serrated proliferation adjacent to carcinoma.

Four cases of colorectal polyps with epithelial serrated proliferation (CP-ESP) with malignant transformation were studied. In CP-ESP adjacent to carcinoma, if the nuclear size in the surface layer was significantly smaller than those in the bottom and the middle layers of the crypts, the specimen was defined as zone formation positive. If there was no significant difference among the layers, the specimen was defined as zone formation negative. Cell kinetics were evaluated using Ki-67 immunostaining. The CP-ESP regions of cases 1 and 2 showed zone formation with inferior and lateral glandular branching, and were qualitatively hyperplastic on cell kinetics. Cases 3 and 4 showed inferior and lateral glandular branching with no zone formation, and were kinetically neoplastic (adenoma). The histogenesis of hyperplastic polyps with atypia (cases 1 and 2) involves the hyperplastic polyp-carcinoma sequence. In contrast, the development of tubulovillous adenoma or serrated adenoma (cases 3 and 4) may involve the tubulovillous adenoma-carcinoma or serrated adenoma-carcinoma sequence.

The radical-chain addition of aldehydes to alkenes by the use of N-hydroxyphthalimide (NHPI) as a polarity-reversal catalyst.

Hydroacylation of simple alkenes with aldehydes via a radical process was successfully achieved by the use of N-hydroxyphthalimide (NHPI) as a polarity-reversal catalyst. Thus, 5-tridecanone was obtained by the reaction of oct-1-ene with pentanal in the presence of small amounts of NHPI and dibenzoyl peroxide (BPO).

[Recurrent abnormal motion of the lower legs during the recovery from spinal anesthesia].

A 33-yr-old pregnant woman developed recurrent motor-ataxia-like abnormal motion of the lower legs during the recovery from spinal anesthesia with hyperbaric tetracaine for repeated cesarean section. This symptom was thought to be due to the disturbance of coordination associated with the loss of positional sensation because deep sensory blockade seemed to be stronger and longer than motor blockade. The etiology of this abnormal motion could not be explained clearly, but her anatomical structure of the spine and her sensitivity to local anesthetic may have been related to this phenomenon.

Cachexia induction by EL-4 lymphoma in mice and possible involvement of impaired lipoprotein lipase activity.

Several lines of evidence have postulated that reduction in the activity of lipoprotein lipase (LPL) is involved in cachexia induction in cancer patients. Recently we have demonstrated that murine melanoma B16 has the ability to reduce the LPL activity and thereby induce cachexia symptoms in mice following intraperitoneal inoculation. In order to further investigate the relationship between LPL activity and cachectic syndrome, cachexia models other than melanoma B16 are required. However, there are few animal cachexia models in which LPL activity is involved in the induction of cachectic symptoms. In this study, cachectic symptoms and plasma LPL activity were investigated in mice bearing EL-4 mouse lymphoma. In EL-4 bearing mice the body weight including tumor weight in the abdominal cavity was rather higher than that of normal mice without tumor, whereas weights of carcass wet and gastrocnemius muscle were significantly decreased in EL-4 bearing mice. Elevated blood levels of triglyceride and non-esterified fatty acid were observed in mice bearing EL-4, associated with the impaired plasma LPL activity. Overall, this study indicated that EL-4 lymphoma in mice results in a severe cachexia which is possibly related to impaired LPL activity and also provided a useful cachexia model for understanding the role of LPL in the development of cancer cachexia.

Effects of protein binding on the placental transfer of propofol in the human dually perfused cotyledon in vitro.

The placental transfer of propofol was investigated using the in vitro dually perfused cotyledon model of the human placenta, and the effects of protein binding in the foetal perfusate were examined. Both maternal and foetal circulations were perfused in a single-pass mode and > 30 min of stabilization was allowed before adding propofol and antipyrine to the maternal perfusate. The placental clearances of propofol were significantly increased by the augmented albumin concentrations in the foetal perfusate (1.68 (SD 0.68), 3.08 (1.55), 4.79 (1.76), 5.75 (1.89) and 7.03 (1.46) ml h-1 g-1 at the albumin concentrations of 4.4, 11, 22, 33 and 44 g litre-1, respectively). Although the total propofol concentration in the foetal vein increased significantly with increasing albumin concentration, the concentration of free propofol remained unchanged. These results indicate that binding to foetal albumin is a determining feature in the control of the placental transfer of propofol, and that the pharmacological effects of propofol on the foetus can be expected to be fairly constant and predictable from the maternal propofol concentration.

Hrs-2 regulates receptor-mediated endocytosis via interactions with Eps15.

Hrs-2, via interactions with SNAP-25, plays a regulatory role on the exocytic machinery. We now show that Hrs-2 physically interacts with Eps15, a protein required for receptor-mediated endocytosis. The Hrs-2/Eps15 interaction is calcium dependent, inhibited by SNAP-25 and alpha-adaptin, and results in the inhibition of receptor-mediated endocytosis. Immunoelectron microscopy reveals Hrs-2 localization on the limiting membrane of multivesicular bodies, organelles in the endosomal pathway. These data show that Hrs-2 regulates endocytosis, delineate a biochemical pathway (Hrs-2-Eps15-AP2) in which Hrs-2 functions, and suggest that Hrs-2 acts to provide communication between endo- and exocytic processes.

Distinct protein domains are responsible for the interaction of Hrs-2 with SNAP-25. The role of Hrs-2 in 7 S complex formation.

Regulated secretion of neurotransmitter at the synapse is likely to be mediated by dynamic protein interactions involving components of the vesicle (vesicle-associated membrane protein; VAMP) and plasma membrane (syntaxin and synaptosomal associated protein of 25 kDa (SNAP-25)) along with additional molecules that allow for the regulation of this process. Recombinant Hrs-2 interacts with SNAP-25 in a calcium-dependent manner (they dissociate at elevated calcium levels) and inhibits neurotransmitter release. Thus, Hrs-2 has been hypothesized to serve a negative regulatory role in secretion through its interaction with SNAP-25. In this report, we show that Hrs-2 and SNAP-25 interact directly through specific coiled-coil domains in each protein. The presence of syntaxin enhances the binding of Hrs-2 to SNAP-25. Moreover, while both Hrs-2 and VAMP can separately bind to SNAP-25, they cannot bind simultaneously. Additionally, the presence of Hrs-2 reduces the incorporation of VAMP into the syntaxin.SNAP-25.VAMP (7 S) complex. These findings suggest that Hrs-2 may modulate exocytosis by regulating the assembly of a protein complex implicated in membrane fusion.

A case of pulmonary arteritis with stenosis of the main pulmonary arteries with positive myeloperoxidase-antineutrophil cytoplasmic autoantibodies.

A 53-year-old woman was referred to our hospital with the main symptoms of productive cough, fever and exertional dyspnoea. Chest X-ray revealed enlargement of the left hilar shadow and cavitary infiltration in the right upper lobe. 99mTechnetium-macroaggregated albumin (99mTc-MAA) perfusion scintigram showed complete hypoperfusion through the entire right lung. A pulmonary angiogram revealed stenotic lesions in the right and left main pulmonary arteries. Right cardiac catheterization showed an elevated right ventricular systolic pressure. There was no evidence of systemic arterial lesions nor vasculitis. The patient was positive for myeloperoxidase (MPO)-antineutrophil cytoplasmic autoantibodies (ANCA) (168 EU). The Mycobacterium avium complex sputum culture was positive. The pulmonary stenotic lesions were surgically resected. The resected pulmonary arterial lesions were pathologically diagnosed as non-specific vasculitis. The cavitary lesion disappeared 6 months after the surgery. Two years after the surgery, although the MPO-ANCA level had decreased to 12 EU, stenosis of the pulmonary arteries reappeared. It is suggested that the patient became positive for MPO-ANCA in association with the Mycobacterium avium complex infection, and that the presence of MPO-ANCA may not be related to the development of pulmonary stenosis of the main pulmonary arteries.

The cellular and developmental expression of hrs-2 in rat.

The molecular events underlying vesicular trafficking probably involve the formation and dissolution of protein complexes between integral components of the vesicle and its target membrane. SNAP-25 is associated with the plasma membrane and is a component of a core protein complex thought to be essential for neurotransmitter release. We have previously characterized a protein, hrs-2, that interacts with SNAP-25 and inhibits secretion from permeabilized PC12 cells. The cellular localization and developmental expression patterns of a number of proteins involved in the secretion machinery have been documented. To understand more about the possible cellular role of hrs-2, we have examined hrs-2 distribution, developmental expression and subcellular localization in rat tissues and cell lines. We show herein that the distribution of hrs-2 in brain and periphery parallels that of SNAP-23/25, and that recombinant hrs-2 binds to both SNAP-23 and SNAP-25. Hrs-2 mRNA and protein are found almost ubiquitously in neurons in the brain. Hrs-2 mRNA is expressed in the neural tube at E10 and thereafter mRNA and protein levels remain relatively constant in the whole brain through adulthood. In cultured PC12 cells, endogenous hrs-2 is expressed in the cytoplasm and on the limiting membranes of multivesicular bodies. Overexpression of hrs-2 in mammalian cells results in the appearance of large intracellular compartments that are labelled with hrs-2 antibodies. The wide distribution, the interaction with SNAP-23 and the localization on multivesicular body membranes suggest a general role for hrs-2 in cellular machinery.

Effects of a novel pyridylsulphonyl thiazole derivative, FR115092, on autoimmune and mitomycin C-induced thrombocytopenia in mice.

Dapsone (4,4'-diaminodiphenyl sulphone), an antileprotic and antimalarial drug, has been reported to be of therapeutic benefit in idiopathic thrombocytopenic purpura in the clinic. However, adverse reactions such as haemolytic anaemia have often been observed. In this study, we found that dapsone increased the number of platelets and decreased the number of red blood cells in male (NZWxBXSB)F1 (W/BF1) mice, an animal model of idiopathic thrombocytopenic purpura. In studies to prepare derivatives of dapsone with weaker side effects than the parent compound, FR115092 (2-[5-(2-pyridylsulphonyl)thiazolyl]amine) was discovered. The effect of FR115092 on the number of blood cells was studied and compared with dapsone in mice. FR 115092 increased the number of platelets without reducing the number of red blood cells in W/BF1 mice. This drug significantly suppressed the increase in circulating autoantibodies against platelets and increased the number of megakaryocytes. Furthermore, FR115092 inhibited the reduction of the number of platelets in mitomycin C-induced thrombocytopenic mice, as a consequence of its enhancement of growth and maturation of megakaryocytes. These findings suggest that FR115092 may be effective against various thrombocytopenias, without inducing haemolytic anaemia.