Airway occlusion pressure (P0.1) — A useful predictor for the weaning outcome in patients with acute respiratory failure —

Twenty-five patients who required mechanical ventilatory support (MVS) after major surgery or severe burns were studied to determine whether airway occlusion pressure (P_0.1) is a clinically useful indicator to predict the success or failure of the weaning trial. A total of 33 weaning trials were attempted on these patients. Of the 33 trials, 24 were followed by successful weaning and 9 by failure. Although the success group, when compared with the failure group, had a lower respiratory rate (P 0.001), a lower minute ventilation (P 0.001), a higher maximal voluntary ventilation to minute ventilation ratio (P 0.01) and a higher forced vital capacity (P 0.05), no threshold values separated the success from the failure group. The alveolar-arterial P_{O 2} gradient, with an Fi _{O 2} of 1.0, in weaning success and failure showed no statistical difference. In contrast, all patients in the success group had a P_0.1 of less than 3.5cmH₂O and those in the failure group had a P_0.1 of greater than 3.5cmH₂O (P 0.001). We conclude that P_0.1 is a clinically superior indicator for discontinuing MVS in patients with acute respiratory failure.(Okamoto K, Sato T, Morioka T: Airway occlusion pressure (P_0.1)—A useful predictor for the weaning outcome in patients with acute respiratory failure—. J Anesth 4: 95–101, 1990)     

A Prostacyclin Analogue,OP-41483α-CD,Restores the Ability of a β<Subscript>2</Subscript>-Adrenergic Agonist to Stimulate Alveolar Fluid Clearance in Rats

Purpose. It is not yet known whether a prostacyclin analogue can affect alveolar fluid clearance. According to recent studies, high-dose (10^–3M) terbutaline, a ₂-adrenergic agonist, failed to increase alveolar fluid clearance. Therefore, we examined the effects of OP-41483-CD, a prostacyclin analogue, on alveolar fluid clearance in the presence of high-dose terbutaline in rats.Methods. Albumin solution containing Evans blue dye and various drugs was instilled into the alveolar airspaces of isolated rat lungs, which were then inflated with 100% oxygen at an airway pressure of 8cmH₂O. Alveolar fluid clearance was measured by the progressive increase in dye concentrations over 1h.Results. Although 10^–5 and 10^–4M terbutaline increased alveolar fluid clearance, 10^–3M terbutaline did not. OP-41483-CD restored the ability of 10^–3M terbutaline to stimulate alveolar fluid clearance. The effect of OP-41483-CD was consistent with the effect of atenolol, a ₁-adrenergic antagonist. The effect of OP-41483-CD on alveolar fluid clearance was unchanged in lungs inflated with nitrogen. Prostaglandin E (PGE)₁ and PGE₂ analogues had similar effects to OP-41483-CD on alveolar fluid clearance.Conclusion. These results indicate that a prostacyclin analogue restores the ability of high-dose terbutaline to stimulate alveolar fluid clearance.     

Comparison of anesthetic effects of epidural and intravenous administration of buprenorphine during operation

Thirty six patients were received epidural anesthesia with or without buprenorphine (BPN) during upper abdominal surgery. They were divided into three groups of 12 patients as follows; G-I received 20ml of 1% lidocaine epidurally, G-II received 20ml of 1% lidocaine epidurally and 0.6mg BPN intravenously, G-III received 20ml of 1% lidocaine with 0.6mg BPN epidurally. Additional 5ml of 1% lidocaine was given to any patient if systolic blood pressure or heart rate increased 10% compared to control value. Trachea was intubated following anesthetic induction with thiopental. The lungs were ventilated with a mixture of N₂O/O₂ (33%) and pancuronium was used for muscle relaxation. The total required doses of lidocaine in G-II and G-III were decreased 60% compared to control group (G-I) (P 0.05). The mean period of time until the first administration of pentazocine for postoperative pain was 13 ± 10hr (mean ± SD) in G-II and 19 ± 24hr in G-III compared to 5 ± 4hr in G-I (P 0.001). The dose of the administration of pentazocine that was required for pain relief during the first 48 postoperative hr in G-III was 54 ± 10mg (mean ± SD) compared to 150 ± 21mg in G-I (P 0.02) and 106 ± 28mg in G-II (P 0.05). Recovery from anesthesia in G-III was more rapid than that in G-I (P 0.05). The Pa_{CO 2} values in G-II and G-III increased 15% compared to control group at about 4hr and 8hr after administration of BPN, but any clinical treatment was not needed for them. Nonrespiratory side effects, e.g., nausea, vomiting, fatigue and headache, were comparably common in all groups. Mild hematuria associated with acute hypotension occurred in two patients in G-II (17%) immediately after the intravenous injection of 0.6mg of BPN. The results showed that 0.6mg of BPN given epidurally demonstrated better anesthetic and more potent postoperative analgesic effects and lesser side effects than 0.6mg of BPN given intravenously in patients undergoing upper abdominal surgery.(Yonemura E, Fukushima K.: Comparison of anesthetic effects of epidural and intravenous administration of buprenorphine during operation. J Anesth 4: 242–248, 1990)     

Combined effects of Inversed Ratio Ventilation (IRV) with positive end-expiratory pressure ventilation (PEEP) on cardiorespiratory function in acute respiratory failure

Combined effects of inversed ratio ventilation (IRV) with positive end-expiratory pressure (PEEP) on cardiorespiratory function were examined in 24 patients with acute respiratory failure. Patients were divided into two groups: the IRV group (n = 12) who showed no significant increase in Pa_{O 2} with a 6cmH₂O of PEEP and PEEP group (n = 12) who were ventilated mechanically with PEEP only at maximum level of 10cmH₂O. In IRV group step-wise prolongation of the I:E ratio from 1:1.9 to 2.6:1 or 4:1 was applied as a Pa_{O 2} was improved and in PEEP group also level of PEEP was increased from 0, 5 to 10cmH₂O after one hour period irrespective of Pa_{O 2}. Inversed ratio ventilation and PEEP increased significantly Pa_{O 2}/Fi _{O 2}, the increase being observed 6hrs (I:E = 2:1) and 2hrs (10cmH₂O) after starting IRV or PEEP. Further improvement of oxygenation was not observed in IRV even if I:E ratio was prolonged up to 2.6:1 or 4:1. These results suggested that combinations of IRV with PEEP were effective and an I:E ratio of 2:1 may be optimal, and IRV is advantageous compared to PEEP, but will take more long time to improve oxygenation than PEEP.(Sari A, Toriumi T, Yamashita S, et al.: Combined effects of inversed ratio ventilation (IRV) with positive end-expiratory pressure ventilation (PEEP) on cardiorespiratory function in acute respiratory failure. J Anesth 5: 105–113, 1991)     

242. Korrelation klinischer und biochemischer Befunde mit dem Schweregrad einer bakteriellen Peritonitis

Zusammenfassung Anhand von Verlaufsdaten 66 chirurgischer Patienten mit einer bakteriologisch gesicherten Peritonitis sollten harte und weiche Kriterien zur Beurteilung des Schweregrades differenziert werden. Untersuchungskriterien: 1) regionale Ausbreitung, 2) Entwicklung eines Organod. Systemversagens, 3) Leukocytose/Thrombopenie, Körpertemperatur, 4) die Plasmamediatoren Endotoxin/Prostaglandin F₂ (PGF₂), 5) Anamnesedauer (Erstsymptom bis OP), 6) Anzahl erforderlicher Reoperationen und 7) Lebensalter. Zuzuordnende Schweregrade: Grad 1: überlebt, Grad 2: mit Komplikationen überlebt, Grad 3: nicht überlebt. Danach erweisen sich als harte Kriterien: 1) Lokalisation, 2) Anamnesedauer, 3) Leukocytose, 4) Endotoxin > 100 Eu/ml, PGF₂ > 500 pg/ml, 5) Körpertemperatur 38,5°C.     

Comparison of adrenoceptor subtype expression in porcine and human bladder and prostate

We have quantified and characterized ₁-, ₂-and -adrenoceptor subtypes in porcine bladder detrusor and bladder neck, human bladder detrusor, and porcine and human prostate. ₁-, ₂- and -adrenoceptor were identified in radioligand binding studies using [³H]prazosin, [³H]RX 821002 and [¹²⁵I]iodocyanopindolol, respectively, as the radioligands. In porcine male and female detrusor and bladder neck and male prostate, adrenoceptors were detected in the order of abundance > _{2 1} (not detectable), with no major differences between the sexes or between detrusor and bladder neck. In human detrusor and prostate the order of abundance was > _{2 1} (not detectable) and ₁ > ₂. respectively. The ₂-adrenoceptors in all tissues were homogeneously of the _2A-subtype as evidenced by competition binding studies with yohimbine, prazosin, ARC 239 and oxymetazoline. The -adrenoceptors represented a mixed population with a dominance of the ₂-subtype in all tissues as demonstrated by competition binding with ICI 118,551 and CGP 20,712A. We conclude that pigs may be a suitable model for studies of detrusor function with respect to adrenoceptor expression. They may be less suitable for studies of bladder neck or prostate function.     

Absorptiometry and “osteoporosis”: problems

connecting the dots between diverse clinical and other matters and an updated bone physiology reveals relationships that could modify some ideas about the roles and uses of absorptiometry in osteoporosis work. Herein, absorptiometry means that part of clinical densitometry that depends on X-ray absorption by bone and other tissues, thus excluding ultrasound methods and magnetic resonance imaging. The modifications concern, in part, some limitations of bone mineral density data, the kinds of physiological information that absorptiometry can and cannot provide, the relative importance of bone mass and whole-bone strength, how to define and study bone health and osteoporosis, and two kinds of osteoporotic fractures. As those modifications concern important national health care issues, they deserve answers based on hard evidence. Identifying those modifications might help others to evaluate them.     

Changes of local brain tissue oxygen pressure after vasopressin during spontaneous circulation

Summary. Background. Brain tissue oxygen pressure (PbtO₂) correlates to cerebral blood flow (CBF) during spontaneous circulation, with one important regulator being nitric oxide (NO). Although it is established that arginine vasopressin (AVP) improves CBF and global cerebral oxygenation during cardiopulmonary resuscitation, it is unknown whether similar beneficial effects are present during spontaneous circulation. The purpose of this study was to investigate the effects of AVP with and without pre-treatment with the NO synthase inhibitor N-omega-nitro-L-arginine methyl ester (L-NAME) on local brain tissue oxygenation in a beating heart model.Methods. Following approval of the Animal Investigational Committee, nine healthy piglets underwent general anaesthesia, and were instrumented with a probe in the cerebral cortex to measure PbtO₂. Each animal was assigned to receive AVP (0.4U·kg^–1), and after a wash-out period, L-NAME (25mg·kg^–1 over 20min) followed by AVP (0.4U·kg^–1). After each AVP administration, nitroglycerine (25µg·kg^–1 over 1min) as a NO donor was infused to test the vascular reactivity independently from NOS inhibition.Findings. Three minutes after administration of AVP, PbtO₂ increased significantly (P<.05; mean±SEM, 31±11 versus 43±14mmHg, +39%), compared with baseline. After pre-treatment with L-NAME, the changes of PbtO₂ after AVP were not significant (32±11 versus 28±10, –13%) when compared with the baseline.Conclusion. In this beating heart porcine model, local brain tissue oxygenation was improved after AVP alone, but not after inhibition of NO synthesis with L-NAME.     

Standardization of Ischemic Hepatic Failure in Pigs as a Model for Bioartificial Liver Assessment

Purpose. A standard protocol of ischemic liver failure in pigs was examined to establish a system for assessing the efficacy of a bioartificial liver, based on clinical practice. Methods. The portal blood flow was extracorporeally bypassed into the cervical jugular vein, using a centrifugal blood pump. The portal vein and hepatic artery were then ligated. Results. The maintenance protocol was established as follows: (1) the concentration of the inhaled anesthetic was decreased by 0.2% when the systolic blood pressure was 100mmHg; (2) the volume of an infusion containing 5% glucose was increased to 10ml/kg per hour when central venous pressure was 5mmHg; (3) 20ml of 50% glucose was injected intravenously when the blood glucose was 50mg/dl; (4) 2000 units of heparin was injected intravenously when the activated clotting time was 150s; (5) sodium bicarbonate was given when the blood pH was 7.3; (6) tidal volume was increased by 1ml/kg when the pCO₂ was 80mmHg; (7) oxygen was increased by 25% when the pO₂ was 100mmHg. No vasopressors were used in the experiment. Conclusion. Our protocol reduced the operating time and minimized the risk of data deviation that can arise from variations in operating techniques and individual animal conditions. This experimental model is also easy to use as a bridge to transplantation.     

Altered Integrin Expression and the Malignant Phenotype: The Contribution of Multiple Integrated Integrin Receptors

The integrins are a family of cell surfaceadhesion receptors that mediate adhesion to eithercomponents of the extracellular matrix or to othercells. The ₁ family of integrinsrepresent the major class of cell substrate receptors withspecificities primarily for collagens, laminins, andfibronectins. The role of the integrin family of cellsurface adhesion receptors in normal mammary glandmorphogenesis and the contributions of altered integrinreceptor expression to the invasive and metastaticphenotype have been the primary focus of our lab, aswell as a number of other laboratories. The_{2 1} integrin is expressed at high levels by normaldifferentiated epithelial cells including those of thenormal breast. Using breast cancer as a model, weevaluated changes in integrin expression in malignancy. We and other investigators made the keyobservation that _{2 1}integrin expression is decreased in adenocarcinoma ofthe breast in a manner that correlates with the stage ofdifferentiation. Studies of other adenocarcinomas have yielded similarresults. When the _{2 1}integrin was reexpressed in a poorly differentiatedmammary carcinoma that expressed no detectable₂ integrin subunit, a dramatic reversion of malignant phenotype to adifferentiated epithelial phenotype was observed,indicating a critical role for₂₁ expression inmammary gland differentiation. Other laboratories using monoclonal antibodies to competitivelyinhibit _{2 1} integrinadhesion or oncogenic transformation using c-erb2 haveconfirmed the important role of that ₂₁ integrin in mammary gland morphogenesis. Re-expression of the_{2 1} integrin alsoresults in upregulation of both the ₆and ₄ integrin subunits. To determinethe contribution of enhanced ₆ and₄ integrin expression to the abrogation of the malignantphenotype by _{2 1}integrin expression, we have now separately re-expressedthe human ₆ or ₄integrin subunit in the breast cancer model.     

Dose-finding study of intravenous midazolam for sedation and amnesia during spinal anesthesia in patients premedicated with intramuscular midazolam

Purpose We investigated the effective and safe dose of intravenous midazolam for sedation and amnesia during spinal anesthesia in patients premedicated with intramuscular midazolam.Methods One hundred and eighty patients aged 20–50 years scheduled for spinal anesthesia received midazolam 0.06mg·kg^–1 and atropine 0.01mg·kg^–1 intramuscularly 15min before entering the operating room. Spinal anesthesia was performed with 0.5% hyperbaric tetracaine. Five minutes after starting surgery, midazolam 0 (control group), 0.01, 0.02, 0.03, 0.04, or 0.05mg·kg^–1 was intravenously administered (30 patients each). Blood pressure, heart rate, respiratory rate, percutaneous oxygen saturation (S_{p O 2}), verbal response, eyelash reflex, and involuntary body movement were measured every 5min for 30min. Memory during surgery was also investigated.Results The number of the patients with loss of verbal response, with loss of eyelash reflex, and with no memory during surgery were significantly larger in the groups receiving midazolam 0.03mg·kg^–1, 0.04mg·kg^–1, and 0.02mg·kg^–1, respectively. The decrease in blood pressure or increase in respiratory rate with decrease in S_{p O 2} was significantly larger in the groups receiving midazolam 0.03mg·kg^–1 or 0.05mg·kg^–1, respectively.Conclusion For sedation and amnesia of the patients aged 20–50 years in spinal anesthesia with about 1h duration receiving intramuscular midazolam 0.06mg·kg^–1 as a premedication, intravenous midazolam 0.02mg·kg^–1 might be effective and safe.     

Rodent Osteoblastic Cells Express Voltage-Sensitive Calcium Channels Lacking a γ Subunit

Voltage-sensitive calcium channels (VSCC) open in response to external stimuli, including calcitropic hormones, that alter plasma membrane calcium (Ca²⁺) permeability. Ca²⁺ that enters the cell through these channels serves a second messenger function, eliciting cellular responses that include secretion and changes in gene expression. In osteoblasts, VSCCs serve as key regulators of Ca²⁺ permeability and are a major class of calcitropic hormone-sensitive Ca²⁺ channels present in the plasma membrane. The members of the VSCC family exist as a complex of polypeptide subunits that are comprised of a pore-forming ₁ subunit, an intracellular subunit, a dimer of disulfide-linked ₂ and subunits, and in some tissues, a subunit. Previous studies in our laboratory have shown that the major functional ₁ subunit present in osteoblasts is the _1C (Ca_V1.2). To determine the complement of auxiliary subunits present in rodent osteoblastic cells, we employed RT-PCR using a battery of subunit specific primers and appropriate tissue controls. Immunohistochemistry also was performed, using available subunit specific antibodies, to measure protein expression and localization. Cell types examined included MC3T3-E1 at various stages of differentiation, ROS 17/2.8 osteosarcoma, and primary cultures of rat calvarial osteoblasts. The results indicate that all cells expressed multiple subunit classes and ₂ dimers, but no subunits, regardless of differentiation state. We propose a structure for the functional osteoblast VSCC that consists of ₁, , ₂ subunits and is devoid of a subunit.     

Changes in respiratory pattern during continuous positive airway pressure in infants after cardiac surgery

Purpose Spontaneous breathing trials are commonly used in adults to enable smooth weaning from mechanical ventilation. However, few investigations have examined spontaneous breathing tests in infants. We investigated how respiratory patterns of infants changed during continuous positive airway pressure (CPAP) and whether successful extubation followed CPAP.Methods Fifty-one consecutive post—cardiac surgery infants satisfied the following weaning criteria: stable hemodynamics, pH > 7.30, tidal volume > 5ml·kg^–1, and respiratory rate < 50 breaths·min^–1 with pressure control of 10–16cm H₂O. We applied CPAP of 3cm H₂O for 30min to these 51 infants. During CPAP, tidal volume, respiratory rate, and arterial blood gases were measured. CPAP was terminated if the patient showed a sustained increase or decrease in heart rate or blood pressure (>20%), a decrease in arterial oxygen saturation (>5%), agitation, or diaphoresis. After the completion of CPAP, tracheal extubation was performed. We considered extubation successful if no reintubation was required in the ensuing 48h.Results Although hemodynamic and ventilatory variables were unstable for the first 5min, they stabilized after 10min of CPAP. Fifty infants completed the CPAP trial safely. Of these, 46 (92%) underwent successful extubation after the CPAP trial. The failure group (4 infants) showed lower pH, higher arterial carbon dioxide tension, and more rapid shallow breathing during CPAP than the success group.Conclusion After cardiac surgery, when infants recovered stable hemodynamics and spontaneous breathing, the ventilatory pattern and hemodynamics became stable after 10min of CPAP. Ninety-two percent of the patients were successfully extubated following a 30-min CPAP trial.     

Expression of Transforming Growth Factor Betas and Their Signaling Receptors in Stone-containing Intrahepatic Bile Ducts and Cholangiocarcinoma

Transforming growth factor betas (TGF-s) are multifunctional polypeptides that either inhibit or stimulate cell proliferation. They mediate their functions through their signaling receptors. Clinically, hepatolithiasis has been regarded as a risk factor for cholangiocarcinoma. The aim of this study was to examine the expression of TGF-s and their receptors in stone-containing intrahepatic bile ducts (IHD) and cholangiocarcinoma and try to predict whether hepatolithiasis has a predisposition to development of cholangiocarcinoma. Twenty-eight surgically resected specimens of stone-containing IHD and 15 specimens of cholangiocarcinoma were subjects for this study. Immunohistochemical analysis was done on three TGF-s and their signaling receptors to check their expression in non-neoplastic and neoplastic bile ducts. No immunoreactivity of TGF-₁ was found in any specimens. The overexpression of TGF-₂ and TGF-₃ was found in both hepatolithiasis (93%–100%) and cholangiocarcinoma (80%) at levels significantly higher than those of normal controls (10%–20%) (p < 0.001). The immunoreactivity of type I receptor (TRI) and type II receptor (TRII) also showed increased expression in stone-containing IHD, whereas TRII was absent in cholangiocarcinoma. We conclude that the overexpression of TGF-₂ and TGF-₃ and the absence of TRII in cholangiocarcinoma could lead to enhanced tumor cell proliferation. At the same time, the overexpression of TGF-s and their receptors in stone-containing IHD could suggest a close relationship between hepatolithiasis and cholangiocarcinoma.     

A comparative study of coagulation effects on the cortex of the rat using Nd-YAG (1.32 μm), Nd-YAG (1.06 μm) and CO2 lasers

This paper represents a comparative study on brain tissue of three lasers: Nd-YAG (1.32m); Nd-YAG (1.06 m); and CO₂ laser. The experimental studies were performed on rats. They consisted of a comparison between the thermal effects and the consequent histological lesions produced. The surface temperature of the cortex induced by each laser shot was measured with an infrared camera. The results show that there exists an excellent correlation between surface temperature and the histology of the lesions produced. It appears that for equivalent surface temperatures the cortical lesions 8 days after irradiation were similar for Nd-YAG (1.32m) and for CO₂ lasers but significantly different for the Nd-YAG (1.06m) laser. For example the depth of coagulation necrosis varied between 20 to 250m with the CO₂ laser using the power of 3 to 10 W at an exposure of 0.05 s with a fluence of 5J/cm² and varied from 210 to 260m using the Nd-YAG (1.32m) with the power of 5 to 14 W with an exposure of 0.4 s with a fluence of 50–170 J/cm². With the Nd-YAG (1.06m) the depth of coagulation necrosis varied from 490m to 550m using a power of 12 to 19 W with an exposure of 0.4 s with a fluence of 150–250 J/cm². It would appear that the Nd-YAG laser at a wavelength of 1.32m should be valuable in neurosurgery as this wavelength is highly absorbed by brain parenchyma and is transmissible with a fibre optic delivery system.

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Résumé Les auteurs presentent une étude comparative de la coagulation du parenchyme cérébral au moyen de différents lasers. Les études expérimentales ont été effectuées sur le cortex du rat. Elles ont consisté à comparer les effets thermiques et histologiques de 3 longueurs d'onde: Nd-YAG (1.32m), Nd-YAG (1.06m) et CO₂ (10.6m). La température corticale de surface induite par le tir laser a été mesurée au moyen d'une caméra infrarouge. Les courbes du profil thermique de chaque tir et de son évolution au cours du temps ont ainsi été obtenues. Les résultats montrent qu'il existe une excellente corrélation entre les données thermiques et les données histologiques recueillies pour chaque tir. Il apparaît ainsi que pour des augmentations de température équivalentes, les lésions corticales 8 jours après le tir sont similaires pour les lasers Nd-YAG (1.32m) et CO₂, mais significativement différentes pour le laser Nd-YAG (1.06m).Par exemple, le profondeur de nécrose varie entre 200 et 250m pour le laser CO₂ utilisé avec une puissance de 3 à 10 W, un temps d'exposition de 0.05 s et une fluence de 5 J/cm². La profondeur de nécrose varie entre 210m et 260m lorsqu'on utilise le laser Nd-YAG (1.32m) avec une puissance de 5 à 14 W, un temps d'exposition de 0.4 s et une fluence de 50 à 170 J/cm². Avec le laser Nd-YAG (1.06m), la profondeur de nécrose est beaucoup plus importante. Elle varie entre 490m et 550m pour une puissance comprise entre 12 et 19 W, un temps d'exposition de 0.4 s et une fluence de 150 à 250 J/cm².Ces résultats expérimentaux montrent que la longueur d'onde 1.32m est bien adaptée à la neurochirurgie puisqu'elle est bien asbsorbée par le parenchyme cérébral et qu'elle est transmissible par une fibre optique.

     

Clinical trial of risedronate in Japanese volunteers: single and multiple oral dose studies

The tolerability and pharmacokinetics of risedronate after a single oral administration and during multiple oral administrations were examined in healthy adult male volunteers. In the single dose study, the dose was increased gradually from 1mg to 2.5, 5, 10, or 20mg. Subsequently, risedronate was given by multiple administration, 5mg per dosing, once daily, for 7 days. The observed adverse events, whose causality was possibly related or unknown, included headache, diarrhea, increased body temperature, increased CK-BB, and increased urinary ₂-microglobulin excretion rate. However, none of these adverse events was clinically significant. The results thus showed that risedronate was well tolerated when delivered as a single administration of up to 20mg or as a multiple administration of up to 5mg/day. In the multiple dose study, changes in urinary deoxypyridinoline suggested the bone antiresorptive activity of risedronate. In the single dose study, AUC and C_max, after the administration of risedronate at 1, 2.5, 5, 10, and 20mg, increased dose dependently, and the T_max, t_1/2, and urinary excretion rates were nearly constant. Therefore, the pharmacokinetic profile of risedronate was considered to show linearity in a dosage range of up to 20mg. Furthermore, the results obtained in the multiple administration study indicated that the plasma concentrations of risedronate reached a steady state on day 4 of administration. The plasma concentrations of risedronate after the administration of 2.5mg risedronate to the Japanese population were nearly comparable to the serum concentrations after the administration of 5mg risedronate to the United Kingdom study population.     

Beneficial Effects of Apolipoprotein A-I on Endotoxemia

Purpose. Although many studies have shown the beneficial effects of lipoproteins on animals with endotoxemia, little is known about the impact of apolipoprotein A-I (apoA-I) on tumor necrosis factor (TNF-) release in response to lipopolysaccharide (LPS). The present study was conducted to determine whether the administration of apoA-I inhibits the release of TNF- and influences the survival rate of rats with endotoxemia.Methods. Forty male Wistar rats were divided randomly into four groups. Rats in the first and second groups were given 1mg/kg LPS intraperitoneally (i.p.) and blood was collected 1h later to measure the serum levels of TNF-. Either 10mg/kg apoA-I or Tris-buffered saline was injected i.p. and the serum TNF- levels were measured again 2h later. Rats in the third and fourth groups were given 5mg/kg LPS. Following the administration of 10mg/kg apoA-I or Tris-buffered saline, animals were observed for 5 days and survival rates were determined.Results. ApoA-I inhibited the release of serum TNF- and improved the survival rates of rats with endotoxemia.Conclusion. The administration of apoA-I suppressed the TNF- release in endotoxemia and decreased the mortality rates of rats.     

Effects of lead on osteoclast-like cell formation in mouse bone marrow cell cultures

To examine an effect of lead (Pb) on the process of osteoclast-like cell formation from its progenitors, we used a mouse bone marrow culture system in which osteoclast-like multinucleated cells (MNCs) were formed in response to bone-resorbing agents. In a 9-day culture period, Pb dose-dependently stimulated MNC formation over the concentration range 2–10 M, whereas at 40 M Pb, MNC formation declined. In an 11-day culture period, MNC formation reached a maximum at 5 M Pb and decreased with increasing concentration of Pb at 10–40 M. Pb-stimulated MNC formation was inhibited by both indomethacin and SC19220, an antagonist of prostaglandin E₂ (PGE₂) receptor. Pb stimulated the production of PGE₂ in marrow cell cultures, suggesting that Pb-stimulated MNC formation is dependent on the production of PGE₂. 3-Isobutyl-1-methylxanthine potentiated Pb-stimulated MNC formation and 2,5-dideoxyadenosine, an inhibitor of adenylate cyclase, inhibited it. A calcium ionophore A23187 increased Pb-induced MNC formation and verapamil, a calcium channel blocker, depressed it. It is possible that a PGE₂-induced increase in the levels of cyclic adenosine 3,5-monophosphate (cAMP) and calcium ions in marrow cells is involved in Pb-induced MNC formation. Pb and parathyroid hormone showed a synergistic stimulation on MNC formation. From these results, Pb is thought to induce osteoclast-like cell formation by a mechanism involving PGE₂ which increases the intracellular levels of cAMP and calcium ions.     

Demonstration of the 5-flap technique

Summary Demonstration of the 5-flap technique which is double opposed Z-plasty and Y – V advancement is presented. A 4×4 gauze serves to demonstrate this technique.The authors dedicate this paper to the dear memory of their teacher, the late Prof. Zvi Neuman, who passed away untimely on March 22, 1977     

Quantitative determination of atracurium in human plasma using high-performance liquid chromatography

The authors have established a new method for extraction and determination of atracurium in human plasma that employs a reversed phase high-performance liquid chromatography (HPLC). This method made use of a fluorescent spectrophotometer at an excitation wavelength of 240nm and an emission wavelength of 310nm. The mobile phase was made of a phosphate buffer, distilled water and acetonitrile (20V:30V:50V). The analytical column used was a Little Champ C₁₈.In a Bond Elute C₁₈ extraction column, which had been prewashed with a phosphate buffer and a 50% methanol solution, atracurium was extracted from acidified plasma samples using a mixture of methanol and phosphate buffer. A standard curve was prepared by the internal standard method using metocurine. A high linear correlation between atracurium concentration and the ratio of the atracurium peak height to the metocurine peak height was observed (r = 0.9994). The lowest threshold for detection of atracurium was 15ng/ml. When the plasma concentrations of atracurium were determined in 2 clinical cases, t_1/2 was 2.10 and 1.73min and t_1/2 was 15.57 and 21.57min, respectively. These results indicate that this method of extraction and determination is appropriate for studying the pharmacokinetics of atracurium because it allows a high reproducibility, and provides an extremely accurate, simple and quick analysis.(Okutani R, Kono K, Frederic M. deBros et al.: Quantitative determination of atracurium in human plasma using high-performance liquid chromatography. J Anesth 2: –, 1988)