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1.
Acta Biomater ; 10(11): 4878-4886, 2014 Nov.
Article in English | MEDLINE | ID: mdl-25072619

ABSTRACT

The devitrification of the 45S5 variety of bioactive glasses (BGs) in relation to phase separation is studied with scanning electron microscopy, X-ray powder diffraction, Fourier transform infrared spectroscopy, differential scanning calorimetry and positron annihilation lifetime spectroscopy techniques. It is shown that the type of phase separation (such as spinodal vs. droplet-like) has a pronounced effect on the activation energy of viscous flow and crystallization, the onset temperature of crystallization and the void size distribution at the nanoscale. Generally, the Johnson-Mehl-Avrami (JMA) relation does not describe crystallization kinetics in bulk 45S5 BG. However, for powder samples (<300 µm) the difference in crystallization kinetics, which is surface-driven for the two kinds of glasses, becomes much smaller, and can be described with the JMA relation under some circumstances.


Subject(s)
Ceramics/chemistry , Glass/chemistry , Phase Transition , Calorimetry, Differential Scanning , Crystallization , Photoelectron Spectroscopy , Spectroscopy, Fourier Transform Infrared , X-Ray Diffraction
2.
J Minim Access Surg ; 1(2): 63-9, 2005 Jun.
Article in English | MEDLINE | ID: mdl-21206648

ABSTRACT

INTRODUCTION: Laparoscopic splenectomy (LS) is an accepted procedure for elective splenectomy. Advancement in technology has extended the possibility of LS in massive splenomegaly [Choy et al., J Laparoendosc Adv Surg Tech A 14(4), 197-200 (2004)], trauma [Ren et al., Surg Endosc 15(3), 324 (2001); Mostafa et al., Surg Laparosc Endosc Percutan Tech 12(4), 283-286 (2002)], and cirrhosis with portal hypertension [Hashizume et al., Hepatogastroenterology 49(45), 847-852 (2002)]. In a developing country, these advanced gadgets may not be always available. We performed LS using conventional and reusable instruments in a public teaching the hospital without the use of the advanced technology. The technique of LS and the outcome in these patients is reported. MATERIALS AND METHODS: Patients undergoing LS for various hematological disorders from 1998 to 2004 were included. Electrocoagulation, clips, and intracorporeal knotting were the techniques used for tackling short-gastric vessels and splenic pedicle. Specimen was delivered through a Pfannensteil incision. RESULTS: A total of 26 patients underwent LS. Twenty-two (85%) of patients had spleen size more than 500 g (average weight being 942.55 g). Mean operative time was 214 min (45-390 min). The conversion rate was 11.5% (n = 3). Average duration of stay was 5.65 days (3-30 days). Accessory spleen was detected and successfully removed in two patients. One patient developed subphrenic abscess. There was no mortality. There was no recurrence of hematological disease. CONCLUSION: Laparoscopic splenectomy using conventional equipment and instruments is safe and effective. Advanced technology has a definite advantage but is not a deterrent to the practice of LS.

5.
Indian J Gastroenterol ; 20(1): 33-5, 2001.
Article in English | MEDLINE | ID: mdl-11206877

ABSTRACT

We report a 49-year-old lady who presented with acute Budd-Chiari syndrome. Spiral CT scan showed inferior vein cava (IVC) tumor and ischemia of the right liver secondary to hepatic vein blockage. These were confirmed by MRI scan and IVC gram, at which time tissue diagnosis was obtained. At surgery, the tumor was seen to originate from the infrahepatic IVC and extended to the level of the diaphragm, blocking the hepatic vein outflow. The tumor was excised completely. Histology confirmed it to be leiomyosarcoma of the IVC. The patient is well, without recurrence of symptoms or tumor, 10 months later.


Subject(s)
Budd-Chiari Syndrome/diagnosis , Leiomyosarcoma/diagnosis , Vascular Neoplasms/diagnosis , Vena Cava, Inferior , Acute Disease , Diagnosis, Differential , Female , Follow-Up Studies , Humans , Leiomyosarcoma/physiopathology , Leiomyosarcoma/surgery , Middle Aged , Vascular Neoplasms/physiopathology , Vascular Neoplasms/surgery
6.
Indian J Gastroenterol ; 19(3): 139-40, 2000.
Article in English | MEDLINE | ID: mdl-10918727

ABSTRACT

We report a 48-year-old woman with foregut ischemia with splenic infarct due to isolated celiac artery obstruction. The patient presented with acute-onset pain in the epigastrium 10-15 min after every meal. Investigations revealed obstruction of the celiac artery by artheromatous plaque. This patient had an acute thrombosis, which responded to anticoagulation.


Subject(s)
Celiac Artery , Ischemia/etiology , Splenic Infarction/etiology , Stomach/blood supply , Thrombosis/complications , Acute Disease , Anticoagulants/therapeutic use , Female , Follow-Up Studies , Humans , Ischemia/diagnosis , Ischemia/drug therapy , Microvascular Angina/etiology , Middle Aged , Splenic Infarction/diagnosis , Splenic Infarction/drug therapy , Thrombosis/diagnosis , Tomography, X-Ray Computed
8.
Anesth Analg ; 84(3): 668-71, 1997 Mar.
Article in English | MEDLINE | ID: mdl-9052321

ABSTRACT

This study was designed to verify a technique in which the pharmacologic profile of mivacurium infusions could be altered by small doses of pancuronium to reduce the infusion requirement without altering the subsequent recovery kinetics. Thirty ASA physical status I or II patients were randomized into two groups in a blinded fashion. One group was administered pancuronium 10 micrograms/kg followed by pancuronium 2.5 micrograms.kg-1.h-1 thereafter. The control group was given identical volumes of saline. Subsequently, all patients were given an initial bolus of mivacurium, and anesthesia was maintained using a nitrous oxide/ alfentanil technique. When the thenar electromyogram response to supramaximal train-of-four stimulation returned to 5% of baseline, a mivacurium infusion was begun in both groups, and the infusion rate required to maintain the electromyographic response at 1%-10% of baseline was determined. At the conclusion of the procedure, the infusion was terminated and the recovery profile ascertained. The mivacurium infusion requirement for the group receiving the pancuronium supplementation was 2.77 +/- 1.38 micrograms.kg-1.min-1 (mean +/- SD), which represented a 49% decrease compared with the group that used mivacurium alone which required an infusion rate of 5.43 +/- 1.85 micrograms.kg-1.min-1. No statistically significant difference was found in the recovery profiles of the two groups when the infusion was terminated. We conclude that the addition of a small amount of pancuronium decreased the required mivacurium infusion rate by nearly 50% without affecting the spontaneous recovery when terminating the infusion.


Subject(s)
Isoquinolines/administration & dosage , Neuromuscular Depolarizing Agents/administration & dosage , Pancuronium/administration & dosage , Adult , Aged , Dose-Response Relationship, Drug , Drug Administration Schedule , Drug Synergism , Female , Humans , Male , Middle Aged , Mivacurium , Neuromuscular Blockade
9.
J Clin Anesth ; 8(6): 469-74, 1996 Sep.
Article in English | MEDLINE | ID: mdl-8872686

ABSTRACT

STUDY OBJECTIVE: To determine whether subanesthetic doses of propofol have analgesic effects in healthy volunteers. DESIGN: Prospective, double-blind, placebo-controlled, randomized, crossover trial. SETTING: Human psychomotor performance laboratory within our anesthesia and critical care department. SUBJECTS: 12, non-drug abusing volunteers, aged 22 to 38 years. INTERVENTIONS: Five drug conditions were used in which a loading injection was followed by a 20-minute infusion period: placebo [saline (Intralipid)] injection, Intralipid infusion; propofol 0.125 mg/kg injection, propofol 12.5 mcg/kg/min infusion; propofol 0.25 mg/kg injection, propofol 25 mcg/kg/min infusion; propofol 0.5 mg/kg injection, propofol 50 mcg/kg/min infusion; fentanyl 1.4 mcg/kg injection (positive control), Intralipid infusion. Five minutes into the infusion period and 115 minutes after the infusion period was terminated, subjects immersed their forearms in ice-cold water for three minutes while pain assessments were recorded. MEASUREMENTS AND MAIN RESULTS: Propofol at the two higher doses during part of the first immersion produced a significant reduction (p < 0.05) in pain intensity and bothersomeness ratings. However, relative to fentanyl, the analgesia was mild. Propofol did not affect any ratings on the 15-item short-form McGill Pain Questionnaire, whereas fentanyl reduced 10 of the ratings. CONCLUSION: Our laboratory results are consistent with the commonly accepted clinical practice of supplementing propofol with an opioid in conscious sedation procedures to provide a satisfactory level of pain relief.


Subject(s)
Anesthetics, Intravenous/pharmacology , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Hypnotics and Sedatives/pharmacology , Pain Measurement/drug effects , Propofol/pharmacology , Adult , Anesthetics, Intravenous/administration & dosage , Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Cold Temperature , Cross-Over Studies , Double-Blind Method , Female , Humans , Immersion , Injections, Intravenous , Male , Propofol/administration & dosage , Prospective Studies
10.
Anesth Analg ; 82(1): 153-7, 1996 Jan.
Article in English | MEDLINE | ID: mdl-8712393

ABSTRACT

A blind, randomized, cross-over trial was conducted to determine the degree of psychomotor/cognitive impairment and the recovery profile produced by combinations of subanesthetic concentrations of isoflurane and nitrous oxide in healthy volunteers. In the experiment, subjects (n = 10) inhaled 100% oxygen-placebo, 30% nitrous oxide in oxygen, and 0.2% and 0.4% isoflurane in oxygen, alone, and in combination with 30% nitrous oxide, in different sessions. Dependent measures included psychomotor and cognitive performance. Impairment was profound with the combination of inhaled anesthetics, and from an analysis of control conditions (the anesthetics alone), it appeared that isoflurane produced more impairment than did nitrous oxide. The time course of recovery was extremely rapid, with subjects returning to control-level functioning 5 min after cessation of the drug inhalation. The drug combination of isoflurane and nitrous oxide appears to be a promising candidate for conscious sedation procedures, although its analgesic and mood-altering effects need to be studied more systematically.


Subject(s)
Anesthetics, Inhalation/pharmacology , Cognition/drug effects , Isoflurane/pharmacology , Nitrous Oxide/pharmacology , Psychomotor Performance/drug effects , Adult , Anesthetics, Inhalation/pharmacokinetics , Cognition Disorders/chemically induced , Cross-Over Studies , Dose-Response Relationship, Drug , Drug Therapy, Combination , Female , Humans , Isoflurane/pharmacokinetics , Male , Nitrous Oxide/pharmacokinetics , Psychomotor Disorders/chemically induced , Single-Blind Method
11.
Pharmacol Biochem Behav ; 51(4): 815-9, 1995 Aug.
Article in English | MEDLINE | ID: mdl-7675863

ABSTRACT

Two double-blind, randomized, crossover trials were conducted to study whether the benzodiazepine antagonist, flumazenil, would interact with the subjective and psychomotor effects of nitrous oxide in healthy volunteers. In both experiments, eight subjects inhaled 30% nitrous oxide in oxygen for 35 min and were challenged, 10 min into the inhalation, with flumazenil. Experiment 1 tested a range of flumazenil doses used clinically (0, 0.25, 0.5, and 1.0 mg/70 kg) whereas Experiment 2 tested a supraclinical flumazenil dose (0 and 5.0 mg/70 kg). Nitrous oxide increased mood ratings of "high," "drunk," and "tingling," and decreased psychomotor performance as assessed by the Digit Substitution Test. Flumazenil, at the supraclinical dose, significantly lowered the mood rating of "high." Decreases, though not significant (p < 0.10), were also obtained on the ratings "drunk," "elated," and "drug liking". Flumazenil, in both experiments, did not interact with the psychomotor effects of nitrous oxide. It appears that flumazenil, at a dose higher than that used clinically, may antagonize some of the subjective effects produced by nitrous oxide in humans.


Subject(s)
Flumazenil/pharmacology , Nitrous Oxide/antagonists & inhibitors , Adult , Cross-Over Studies , Double-Blind Method , Euphoria/drug effects , Female , Humans , Male , Nitrous Oxide/pharmacology , Psychomotor Performance/drug effects
12.
Anesth Analg ; 80(6): 1092-8, 1995 Jun.
Article in English | MEDLINE | ID: mdl-7762835

ABSTRACT

Impairment caused by different sedative/analgesic combinations commonly used in ambulatory settings was compared to that of alcohol at blood alcohol concentrations (BACs) higher than or equal to 0.10%. Impairment was measured via subjective (mood) and objective (psychomotor performance) assays. Twelve healthy human volunteers (10 males and 2 females; age range 21-34 yr) participated in this prospective, double-blind, randomized, cross-over study. Each subject was exposed to five drug conditions across 5 wk. Each of the following drug conditions were adjusted for body weight (per 70 kg):fentanyl 50 micrograms and propofol 35 mg (FP), fentanyl 50 micrograms and midazolam 2 mg (FM), fentanyl 50 micrograms, midazolam 2 mg, and propofol 35 mg (FMP), alcohol 56 g (orally administered), and placebo (PLC). With the exception of alcohol, the other drugs were administered via the intravenous route. Tests for psychomotor performance, subjective effects, and short-term memory were done at baseline, and at different intervals until 240 min postinjection. Psychomotor impairment caused by alcohol at 15 min postingestion (at a BAC of 0.11% +/- 0.03% [mean +/- SE]) was used as a benchmark with which impairment caused by other sedative/analgesic combinations was compared. All the study drug combinations produced impairment (i.e., impairment greater than that seen with PLC), similar to that observed with alcohol at a BAC of 0.11%. We have demonstrated that some sedative/analgesic drug combinations used in anesthesia for ambulatory procedures produce impairment similar to or greater than that observed with a large dose of alcohol.


Subject(s)
Affect/drug effects , Ambulatory Surgical Procedures , Analgesics/pharmacology , Ethanol/pharmacology , Hypnotics and Sedatives/pharmacology , Psychomotor Performance/drug effects , Adult , Analgesics/administration & dosage , Cross-Over Studies , Double-Blind Method , Female , Fentanyl/administration & dosage , Fentanyl/pharmacology , Humans , Hypnotics and Sedatives/administration & dosage , Male , Memory, Short-Term/drug effects , Midazolam/administration & dosage , Midazolam/pharmacology , Propofol/administration & dosage , Propofol/pharmacology , Prospective Studies
13.
Pharmacol Biochem Behav ; 51(2-3): 323-9, 1995.
Article in English | MEDLINE | ID: mdl-7667348

ABSTRACT

Nitrous oxide (N2O) has analgesic properties as determined in both animal and human research. In the present study, we sought to determine whether N2O given in subanesthetic concentrations would reduce cold pressor (CP)-induced pain. A crossover, double-blind study was conducted in 10 healthy volunteers. Each subject participated in four separate sessions, and in each session the effects of one of four concentrations of N2O in oxygen (0, 20, 30, and 40%) were assessed. The duration of inhalation was 40 min, and within each session, subjects immersed their nondominant arm in water (2-3 degrees C) twice for 3 min (at 10 and 30 min intrainhalation). Pain intensity, the degree to which the pain was bothersome (measured on a verbal scale of 0-10, 0 = "not at all" and 10 = "extremely" painful/bothersome), and pain quality [measured by the short-form McGill Pain Questionnaire (SF-MPQ)] were assessed during the forearm immersion. Mood effects were measured with the use of visual analogue scales (VAS) in the presence and absence of pain. Self-reported pain intensity and bothersomeness, SF-MPQ ratings of "sharp pain" and "throbbing pain," and VAS rating of "unpleasant bodily sensations" were significantly reduced by N2O (p < 0.05) in a concentration-dependent manner. Nitrous oxide had a number of effects on mood (e.g., increased VAS ratings of "stimulated," "high," "coasting," "carefree," and "having pleasant bodily sensations"). The cold-water immersion also influenced mood, but had little impact on modulating N2O effects.(ABSTRACT TRUNCATED AT 250 WORDS)


Subject(s)
Nitrous Oxide/pharmacology , Pain Measurement/drug effects , Adult , Affect/drug effects , Cold Temperature/adverse effects , Cross-Over Studies , Female , Hemodynamics/drug effects , Humans , Male , Pressure/adverse effects , Psychomotor Performance/drug effects
14.
Anesth Analg ; 80(3): 521-5, 1995 Mar.
Article in English | MEDLINE | ID: mdl-7864418

ABSTRACT

The effects of intravenous midazolam (0.75, 1.5, and 3 mg/70 kg) were examined and compared to that of fentanyl (0.1 mg/70 kg; positive control) and saline on pain induced by a cold pressor test. Both sensory and affective components of the pain response were assessed, as there is some evidence that benzodiazepines reduce the affective component. Healthy volunteers (three females, nine males) were enrolled in a prospective, double-blind, randomized, cross-over trial in which mood and psychomotor performance were also examined. Five minutes and 135 min postinjection, subjects immersed their forearm in ice-cold water for 3 min while assessments of pain were recorded. During the first immersion, subjects reported significantly lower pain intensity and bothersomeness ratings after having been injected with fentanyl, relative to the saline and midazolam conditions, which did not differ significantly from each other. Fentanyl and midazolam had prototypical mood altering and psychomotor impairing effects. We conclude that midazolam in our laboratory setting at the doses and route of administration studied had no effects on either the sensory or affective components of the pain experience.


Subject(s)
Cold Temperature , Midazolam/administration & dosage , Pain Threshold/drug effects , Adult , Affect/drug effects , Dose-Response Relationship, Drug , Double-Blind Method , Female , Fentanyl/administration & dosage , Fentanyl/pharmacology , Humans , Injections, Intravenous , Male , Midazolam/pharmacology , Pain/etiology , Pain Measurement , Prospective Studies , Psychomotor Performance/drug effects
15.
Anesthesiology ; 82(1): 53-9, 1995 Jan.
Article in English | MEDLINE | ID: mdl-7832334

ABSTRACT

BACKGROUND: There is a need for a standard by which to compare the degree of subjective and behavioral impairment caused by anesthetic drugs, because anesthesiologists may not be able to gauge how extreme or important a statistically significant change in psychomotor functioning is. This study examined the psychomotor and subjective effects of alcohol at blood concentrations equal or greater than 0.10% as a standard with which to compare those effects caused by sedative and analgesic agents commonly used in ambulatory surgery. METHODS: Twelve healthy human volunteers (11 men and 1 nonpregnant woman), with an average age of 28 yr (range 24-34 yr) and an average alcohol consumption of four drinks per week, were selected in this institutional review board-approved study. Each subject was exposed to five drug conditions (70 mg/70 kg propofol intravenously, 2 mg/70 kg midazolam intravenously, 50 micrograms/70 kg fentanyl intravenously, 0.8 g/kg alcohol orally, and placebo orally and intravenously) in a double-blind randomized fashion over five weekly sessions. Testing was done at baseline and at different intervals until 240 min after drug administration. Testing included psychomotor performance (Maddox Wing, eye-hand coordination, auditory reaction time test, and digit symbol substitution test), subjective effects (strength of drug effect scale, drug liking scale, and visual analog scale), and short-term memory. Psychomotor performance was used as an index of objective impairment, and mood was used as an index of subjective impairment. RESULTS: After consumption of the alcoholic beverage, a blood alcohol level of 0.11 +/- 0.003% (mean +/- SE) was obtained at 15 min after injection. The study drugs not only produced statistically significant impairment (i.e., impairment greater than that seen with placebo) but also, at one or more times after injection, produced impairment similar to that observed with alcohol at a blood alcohol concentration of 0.11%. Midazolam produced a similar degree of impairment to that of alcohol for a longer duration than did fentanyl and propofol. CONCLUSIONS: This study provides evidence that degree of impairment caused by sedative and analgesic drugs used in ambulatory surgery is similar to that obtained with a dose of alcohol that produces a blood alcohol concentration of 0.11%. We suggest that anesthesiologists can use alcohol as a standard by which to assess degree of impairment produced by drugs used for sedation/analgesia.


Subject(s)
Ambulatory Surgical Procedures , Ethanol/adverse effects , Fentanyl/adverse effects , Midazolam/adverse effects , Propofol/adverse effects , Psychomotor Performance/drug effects , Administration, Oral , Adult , Double-Blind Method , Ethanol/blood , Female , Hemodynamics/drug effects , Humans , Injections, Intravenous , Male , Memory, Short-Term/drug effects , Prospective Studies , Reference Standards
16.
Drug Alcohol Depend ; 36(3): 227-36, 1994 Dec.
Article in English | MEDLINE | ID: mdl-7889814

ABSTRACT

An experiment using marijuana users and non-users was conducted to assess whether the reinforcing, subjective, or psychomotor effects of nitrous oxide were influenced by a subject's drug history. Subjects in the first four sessions sampled 40% nitrous oxide in oxygen and 100% oxygen (placebo), and then over the next three sessions, chose which agent they wished to inhale. Choice distributions between the two groups did not differ significantly, and nitrous oxide choice rates were less than 50% in both groups. However, a history of marijuana use appeared to intensify some of the subjective effects induced by nitrous oxide inhalation.


Subject(s)
Affect/drug effects , Arousal/drug effects , Marijuana Abuse/psychology , Motivation , Nitrous Oxide/pharmacology , Psychomotor Performance/drug effects , Administration, Inhalation , Adult , Attention/drug effects , Female , Humans , Male , Neuropsychological Tests , Personality Inventory
17.
Pharmacol Biochem Behav ; 49(3): 573-8, 1994 Nov.
Article in English | MEDLINE | ID: mdl-7862710

ABSTRACT

The effects of naloxone on the mood-altering and psychomotor-impairing effects of nitrous oxide were examined in two studies. Each of the double-blind, randomized trials tested effects of three doses of naloxone or saline placebo during inhalation of 30% nitrous oxide in oxygen or 100% oxygen placebo. Experiment 1 tested a range of naloxone doses used clinically to reverse opiate-induced respiratory depression (0, 0.01, 0.1 1.0 mg/70 kg) and Experiment 2 included a dose approximately 25 times higher than that needed to reverse opiate-induced respiratory depression (0, 1.0, 3.0, 10 mg/70 kg). Nitrous oxide increased subject-rated reports of "feel drug effect," "carefree," "drunk," "sedated," and "high", and decreased psychomotor performance in both experiments. Naloxone had no effects by itself in either experiment, and, for the most part, did not significantly interact with nitrous oxide-induced changes in mood or psychomotor performance. Naloxone, in doses of 10 mg or less, does not appear to affect the subjective and psychomotor effects of nitrous oxide.


Subject(s)
Affect/drug effects , Naloxone/pharmacology , Nitrous Oxide/pharmacology , Psychomotor Performance/drug effects , Adult , Double-Blind Method , Drug Interactions , Female , Humans , Male
18.
J Pharmacol Exp Ther ; 270(2): 579-88, 1994 Aug.
Article in English | MEDLINE | ID: mdl-8071850

ABSTRACT

The purposes of this study were to characterize the subjective, psychomotor and physiological effects of butorphanol in healthy nondrug-abusing volunteers and to compare and contrast the effects of butorphanol to those of morphine. Into an antecubital vein, the subjects (seven men and five women), who had no history of opiate dependence, were injected with 0, 0.5, 1.0 or 2.0 mg/70 kg of butorphanol or 10 mg/70 kg of morphine; a randomized, double-blind, crossover design was used. The subjective effects of butorphanol included increased scores on the Pentobarbital-Chlorpromazine-Alcohol Group scale and Lysergic Acid Diethylamide scale of the Addiction Research Center inventory; increased visual analog scale ratings of "sedated," "coasting or spaced out" and "difficulty concentrating;" increased adjective checklist ratings of "sweating," "skin itchy" and "sleepy;" and increased "feel drug effect" and drug-liking ratings. Morphine had some subjective effects of a magnitude similar to those of an equianalgesic dose of butorphanol (2 mg) (e.g., "strength of drug effect," "sedated," "heavy or sluggish feeling" and "high"). However, other effects of morphine were lesser in magnitude (e.g., "coasting or spaced out," "drunken" and "lightheaded") than those of butorphanol. Also, morphine did not affect a number of ratings that were affected by butorphanol (e.g., "confused," "dreamy," "stimulated," "difficulty concentrating," "floating" or "sweating"). The psychomotor impairing effects of butorphanol, as measured by the Maddox Wing test, an eye-hand coordination test, and the Digit Symbol Substitution Test, were dose related; in contrast, morphine had no effect on psychomotor functioning. Both butorphanol and morphine induced miosis.(ABSTRACT TRUNCATED AT 250 WORDS)


Subject(s)
Butorphanol/pharmacology , Hemodynamics/drug effects , Morphine/pharmacology , Psychomotor Performance/drug effects , Adult , Double-Blind Method , Female , Humans , Male , Miosis/chemically induced , Oxygen/blood , Reference Values
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