Feasibility of atmospheric pressure desorption/ionization on silicon mass spectrometry in analysis of drugs.

The feasibility of atmospheric pressure desorption/ionization on silicon mass spectrometry (AP-DIOS-MS) for drug analysis was investigated. It was observed that only compounds with relative high proton affinity are efficiently ionized under AP-DIOS conditions. The limits of detection (LODs) achieved in MS mode with midazolam, propranolol, and angiotensin II were 80 fmol, 20 pmol, and 1 pmol, respectively. In MS/MS mode the LODs for midazolam and propranolol were 10 fmol and 5 pmol, respectively. The good linearity (r(2) > 0.991), linear dynamic range of 3 orders of magnitude, and reasonable repeatability showed that the method is suitable for quantitative analysis.

Poly(dimethylsiloxane) electrospray devices fabricated with diamond-like carbon-poly(dimethylsiloxane) coated SU-8 masters.

This study presents coupling of a poly(dimethylsiloxane) (PDMS) micro-chip with electrospray ionization-mass spectrometry (ESI-MS). Stable electrospray is generated directly from a PDMS micro-channel without pressure assistance. Hydrophobic PDMS aids the formation of a small Taylor cone in the ESI process and facilitates straightforward and low-cost batch production of the ESI-MS chips. PDMS chips were replicated with masters fabricated from SU-8 negative photoresist. A novel coating, an amorphous diamond-like carbon-poly(dimethylsiloxane) hybrid, deposited on the masters by the filtered pulsed plasma arc discharge technique, improved significantly the lifetime of the masters in PDMS replications. PDMS chip fabrication conditions were observed to affect the amount of background peaks in the MS spectra. With an optimized fabrication process (PDMS curing agent/silicone elastomer base ratio of 1/8 (w/w), curing at 70 degree C for 48 h) low background spectra were recorded for the analytes. The performance of PDMS devices was examined in the ESI-MS analysis of some pharmaceutical compounds and amino acids.

Preparation of porous n-type silicon sample plates for desorption/ionization on silicon mass spectrometry (DIOS-MS).

This study focuses on porous silicon (pSi) fabrication methods and properties for desorption ionization on silicon mass spectrometry (DIOS-MS). PSi was prepared using electrochemical etching of n-type silicon in HF-ethanol solution. Porous areas were defined by a double-sided illumination arrangement: front-side porous areas were masked by a stencil mask, eliminating the need for standard photolithography, and backside illumination was used for the backside ohmic contact. Backside illumination improved the uniformity of the porosified areas. Porosification conditions, surface derivatizations and storage conditions were explored to optimize pSi area, pore size and pore depth. Chemical derivatization of the pSi surfaces improved the DIOS-MS performance providing better ionization efficiency and signal stability with lower laser energy. Droplet spreading and drying patterns on pSi were also examined. Pore sizes of 50-200 nm were found to be optimal for droplet evaporation and pore filling with the sample liquid, as measured by DIOS efficiency. With DIOS, significantly better detection sensitivity was obtained (e.g. 150 fmol for midazolam) than with desorption ionization from a standard MALDI steel plate without matrix addition (30 pmol for midazolam). Also the noise that disturbs the detection of low-molecular weight compounds at m/z < 500 with MALDI could be clearly reduced with DIOS. Low background MS spectra and good detection sensitivity at the 100-150 fmol level for pharmaceutical compounds were achieved with DIOS-MS.

Association between expression of stratum corneum chymotryptic enzyme and pathological keratinization in human oral mucosa.

Stratum corneum chymotryptic enzyme (SCCE) may function in the degradation of intercellular cohesive structures in the stratum corneum preceding desquamation. Previous results have suggested that SCCE may be specifically expressed in squamous epithelia undergoing terminal differentiation and keratinization. The aim of the present work was to further elucidate the association between SCCE expression and terminal differentiation in squamous epithelia. Using immunohistochemical methods, we have examined the expression of SCCE in two diseases of human oral mucosa, which produce a pathological keratinization of the epithelium at sites which are normally non-keratinized. Affinity-purified polyclonal rabbit antibodies raised against recombinant SCCE and monoclonal antibodies against the differentiation-specific keratins nos. 10 and 13 were used on formaldehyde-fixed and paraffin-embedded biopsies. Whereas there was essentially no expression of SCCE in normal, non-keratinized buccal mucosa, there was a strong expression in suprabasal cells in orthokeratotic and parakeratotic areas of the lesions of oral lichen planus (an inflammatory disease) and benign oral keratosis (a non-inflammatory disease). There was a close association between the expression of SCCE and keratin no. 10, i.e. a keratin which is specifically expressed in cornifying squamous epithelia. The results suggest that SCCE expression may be a true marker of terminal differentiation in squamous epithelia and give further evidence for a role of SCCE in the formation and/or turnover of the stratum corneum.

Life-style survey of patients with oral lichenoid reactions.

The occurrence of different life-style patterns, including marital status, educational level, nutrition, tobacco and alcohol use, and frequency of physical activity, in patients with oral lichenoid reactions (OLR) in total or partial contact with amalgam fillings was examined. When compared with an age- and sex-matched control group, the daily intake of carbohydrates, fibers, and iron was statistically significantly higher in the OLR patients. Regarding marital status, there was a statistically significant difference between the OLR patients and the control subjects, the former group containing more people who were divorced or whose spouse had died. The frequency of physical activity was also statistically significantly higher in the OLR patients than in the control group. Hypothetical mechanisms that may lie behind the results obtained are discussed.

Amalgam-associated oral lichenoid reactions. Clinical and histologic changes after removal of amalgam fillings.

OBJECTIVE AND STUDY DESIGN: Forty-nine consecutive patients with clinically diagnosed oral lichenoid reactions in contact with amalgam fillings were studied clinically and histologically. The long-term effect of replacement of these fillings was also examined. RESULTS: Seventeen (35%) patients showed positive reactions to mercury at the epicutaneous patch test that was carried out before treatment. After treatment, total regression of the lesions was found clinically in 33 (69%) and histologically in 26 (55%) patients. Most of the remaining lesions changed clinically and histologically to a less pronounced tissue reaction. Lesions in direct contact with amalgam fillings (group I) showed significantly better healing results than lesions that exceeded the contact area (group II). No difference in healing capacity was noted in the two groups between patients with positive patch reactions to mercury compared with those with negative reactions. Lesions that histologically were classified as benign oral keratosis showed a similar healing pattern as those classified as oral lichen planus. CONCLUSION: In group I all lesions changed histologically and clinically to a normal mucosa or to a less affected tissue reaction. In group II this change was less pronounced, which suggests that the fillings themselves were not the only factor involved in the cause of these lesions. The results suggest that various etiologic factors are involved in lichenoid reactions and that the effect of removal of amalgam fillings cannot be predicted by epicutaneous patch testing and biopsies.

Psychologic aspects of patients with oral lichenoid reactions.

Psychologic aspects of 49 patients with oral lichenoid reactions (OLR) in contact with amalgam fillings were studied and compared with an age- and sex-matched control group. Psychologic factors such as personality, psychologic functioning, and quality of life were determined by using the Karolinska Scales of Personality (KSP), an additional Personality Scale (PS), a Psychological Functioning Scale (PFS), and a Quality of Life Scale (QLS). With regard to personality the OLR patients had significantly higher scores on the muscular tension and suspicion scales and significantly lower scores on the indirect aggression scale. In addition, the OLR patients were significantly more worried about their health and more helpful. With regard to psychologic functioning the OLR patients had significantly more sad thoughts, became dizzy more easily, found it harder to imagine themselves free from anxiety, and had more difficulty in concentrating. The results indicated that OLR patients had a tendency to be depressive. The need for a systemic investigation including odontologic, medical, and psychologic aspects was expressed.

Prolonged analgesia after epidural injection of a poorly soluble salt of fentanyl.

Epidurally administered fentanyl is commonly used in postoperative pain management. The onset of action is rapid, but the duration of analgesia is short. In this study we examined the hypothesis that a poorly soluble salt of fentanyl (fentanyl pamoate) would create a depot of the drug in the epidural space and thus provide prolonged analgesia. The dose-response relationship and duration of analgesic action of epidural fentanyl citrate (FC) and fentanyl pamoate (FP) were studied in white male Sprague-Dawley rats. Somatic and visceral nociceptive stimulation (tail flick and colorectal distension, respectively) were used to test the analgesic effects of the drugs. The calculated dose producing 100% of the maximum possible effect (100% MPE) for FP was 31 micrograms toward somatic and 33 micrograms toward visceral noxious stimulation, and for FC it was 3 micrograms toward both stimulations. The antinociceptive effects were similar, with 31 micrograms of FP and 3 micrograms of FC. The areas under the time-response curves (AUC) were significantly higher with FP than with FC when high doses (5 micrograms of FC or 50 micrograms of FP) were used, but with doses expected to produce 100% MPE, differences between the study drugs were not observed in the duration of analgesia. We conclude that the duration of antinociceptive effect of fentanyl can be prolonged when administered as a poorly soluble salt.

Oral lichen planus lesions in contact with amalgam fillings: a clinical, histologic, and immunohistochemical study.

Fifty-one consecutive patients had clinically diagnosed oral lichen planus (OLP) lesions in total or partial contact with amalgam fillings. The clinical features of the OLP lesions were characterized and registered, and biopsies were obtained from each OLP lesion. Histologic and immunohistochemical studies were performed, as well as tests for allergy to dental materials. The clinical diagnosis of OLP corresponded to the World Health Organization (WHO) morphologic OLP criteria in 31 (61%) cases. The remaining lesions were histologically diagnosed as mild OLP in 11 (22%) or as benign oral keratosis in nine (17%) cases. The immunohistochemical examination showed a positive reaction to fibrinogen in the basement membrane zone (BMZ) in 10 (20%) patients and to complement C3 in one (2%) patient. No positive reactions in the BMZ were found for IgA, IgG, and IgM. In 17 (33%) patients, an allergic reaction to mercury was found, and candidiasis was diagnosed in 13 (25%) patients. The true nature of OLP-like lesions in contact with amalgam fillings still remains to be explained. For that matter, we do not know whether OLP is one disease or a number of similar immunologic or other responses to various interacting stimuli. One such stimulus might be mercury from corroding amalgam fillings.

Clinical recovery and psychomotor function after brief anesthesia with propofol or thiopental.

Propofol, the new intravenous anesthetic agent, is generally used in outpatient anesthesia with expectations of fast recovery. We assessed recovery from anesthesia in a double-blind, crossover, controlled manner in 12 healthy volunteers using clinical tests during the first hour and several psychomotor tests 0.5, 1, 3, 5, and 7 h after brief anesthesia with propofol (2.5 mg/kg and 1.0 mg/kg 3 min later) or thiopental (5.0 mg/kg and 2.0 mg/kg 3 min later). Subjects were able to respond to command, sit, and stand steadily significantly faster (P less than 0.05) after propofol (time until standing steadily 33 +/- 7 min; mean +/- SD) when compared to thiopental anesthesia (time until standing steadily 62 +/- 29 min; mean +/- SD). Psychomotor performance remained significantly worse (P less than 0.05 to P less than 0.001) compared to control for 1 h after propofol and for 5 h after thiopental anesthesia. We conclude that the rapid and complete recovery makes propofol a suitable anesthetic for patients undergoing brief ambulatory surgery.

Does epidural fentanyl decrease the efficacy of epidural morphine after cesarean delivery?

Earlier studies have suggested that epidural fentanyl improves intraoperative analgesia during cesarean section, but others have suggested that it worsens postoperative analgesia from epidural morphine. The purpose of this study was to determine whether epidural fentanyl given before epidural morphine improves the quality of intraoperative epidural anesthesia without worsening postoperative analgesia provided by epidural morphine. Sixty patients having epidural anesthesia for cesarean delivery were studied. Epidural anesthesia was established using 2% lidocaine with epinephrine 5 micrograms/mL. After delivery, either fentanyl 100 micrograms/10 mL or normal saline-control 10 mL was injected through the epidural catheter in a randomized, double-blind manner. All patients received 3.5 mg of morphine epidurally after uterine repair. After administration of the epidural study drug, there were no significant differences in the pain responses during surgery between the two groups. Patients in the fentanyl group experienced significantly less nausea and vomiting between delivery and the end of surgery than did patients in the normal saline-control group (P = 0.013). Postoperatively, visual analogue scale scores for pain, pruritus, nausea, and sedation were similar at 1, 2, 4, and 8 h in the two groups. We conclude that fentanyl 100 micrograms administered epidurally during cesarean delivery did not improve intraoperative analgesia, but significantly reduced intraoperative nausea and vomiting without diminishing the efficacy of postoperative analgesia provided by epidural morphine.

Sedation and recovery of psychomotor function after intravenous administration of various doses of midazolam and diazepam.

A placebo-controlled, double-blind, crossover trial in 11 healthy male volunteers compared clinical sedation and psychomotor function after intravenous injection of midazolam (0.05, 0.1, or 0.15 mg/kg), diazepam (0.15 or 0.3 mg/kg), or placebo (saline). The depth of sedation was estimated at 5-10-min intervals during the first hour after injection. A comprehensive battery of psychomotor tests was used to collect objective data of psychomotor performance before drug injection and 1, 3, 5, and 7 h after injection. Midazolam (0.15 mg/kg) produced the highest scores of sedation and most impairment of psychomotor performance. In most tests, the maximal psychomotor effects seen after 0.3 mg/kg of diazepam did not reach those of 0.1 mg/kg of midazolam. Although the strongest psychomotor effects were induced by midazolam, these effects disappeared sooner than those of diazepam. By 5 h after injection, 0.3 mg/kg of diazepam showed the highest scores of psychomotor impairment. The authors conclude that at least four times as much diazepam as midazolam is needed to produce equally severe psychomotor impairment. That the residual effects of midazolam terminate sooner than those of diazepam probably accounts for the occasional underestimation of the potency of midazolam in clinical practice.

Is the antiemetic effect of the emulsion formulation of propofol due to the lipid emulsion?

The hypothesis that the lipid emulsion of the emulsion formulation of propofol is responsible for the low frequency of nausea, retching, and vomiting after propofol anesthesia was tested. A randomized, prospective, and comparative study was performed to evaluate the antiemetic effect of 10% lipid solution in 60 women, ASA physical status I and II, scheduled for ambulatory laparoscopic procedures. Two groups of patients were studied. Induction of anesthesia (thiopental) and maintenance of anesthesia (enflurane, nitrous oxide) were similar in both groups. At induction the study group received 10% Intralipid (3 mL/min for 20 min). The control group received 5% dextrose in lactated Ringer's solution at the same rate. Other drugs administered during or after anesthesia were similar among the groups. The groups were similar with respect to duration of anesthesia, characteristics of early and intermediate recovery, as well as pain scores in the postanesthesia care unit. There were no differences in the amount of antiemetic medications administered or postoperative nausea, retching, or vomiting when the patients were evaluated objectively by a blinded observer or subjectively by patient self-evaluation. It is concluded that 10% Intralipid, the lipid in the emulsion formulation of propofol, does not possess significant antiemetic effects.

Randomized comparison of recovery after propofol-nitrous oxide versus thiopentone-isoflurane-nitrous oxide anaesthesia in patients undergoing ambulatory surgery.

A randomized, prospective study was performed to compare recovery characteristics in 41 ASA physical status I-II patients scheduled for ambulatory surgery with either propofol or thiopentone-isoflurane anaesthesia. Particular attention was focused on the recovery time needed to meet discharge criteria. The propofol group received propofol 2 mg.kg-1 for induction followed by propofol infusion (6-9 mg.kg-1.h-1) 1 min after intubation. The thiopentone-isoflurane group received thiopentone 4 mg.kg-1 for induction followed by isoflurane (0.5-2%) 1 min after endotracheal intubation. Other drugs administered during or after anaesthesia were similar between the groups. The propofol group had significantly (P less than 0.05) faster clinical recovery than the isoflurane group with respect to times to response to commands, eye opening, orientation, ability to stand and void, tolerance to oral fluids, "home-readiness", and recovery of perceptual speed. Patients in the propofol group had significantly less (P less than or equal to 0.05) emesis than the patients given isoflurane. We conclude that in patients undergoing ambulatory surgery propofol infusion is preferable to thiopentone-isoflurane anaesthesia, because it may allow faster discharge home.

Circulatory collapse during laparoscopy.

This case report details the intraoperative course of a patient, in her early pregnancy, who had a cardiac arrest during transvaginal insufflation of carbon dioxide (CO2) for laparoscopic tubal ligation. Modern monitoring methods and their ability to detect gas embolism and aid in the diagnosis and treatment of this rare but life-threatening complication are discussed.

Randomized comparison of outcome after propofol-nitrous oxide or enflurane-nitrous oxide anaesthesia in operations of long duration.

A randomized, prospective, comparative study was performed to evaluate induction characteristics, haemodynamic changes and recovery in 60 ASA I-II patients undergoing mainly gynaecological laparotomies with either propofol or thiopentone-enflurane anaesthesia. The propofol group (n = 30) received 2 mg.kg-1 propofol for induction of anaesthesia followed by propofol infusion. The thiopentone-enflurane group (n = 30) received thiopentone 4 mg.kg-1 for induction followed by enflurane (0.5-2 per cent). All patients received nitrous oxide (66 per cent] in oxygen begun one minute after tracheal intubation, and fentanyl (1.5 micrograms.kg-1) four minutes prior to induction. Other drugs administered during or after anaesthesia were similar among the groups. Haemodynamic measurements were similar between propofol and enflurane groups except after tracheal intubation when the mean arterial pressure was lower in the propofol group (P less than 0.05). The propofol group had significantly less (P less than 0.01) emesis in the recovery room than the enflurane group. The propofol group experienced significantly less (P less than 0.05) dizziness, depression/sadness and hunger than the enflurane group in the postoperative period as assessed with a visual analogue questionnaire. We conclude that propofol provided better outcome than enflurane in terms of these nonvital but annoying outcome measures after relatively long intra-abdominal operations.

Metoclopramide versus droperidol for prevention of nausea and vomiting during epidural anesthesia for cesarean section.

In a randomized, double-blind study, we compared the efficacy of metoclopramide hydrochloride with that of low-dose droperidol for prevention of nausea and vomiting during and after elective cesarean section with epidural anesthesia. Immediately after the umbilical cord was clamped, each patient received fentanyl (50 micrograms) and the study drug intravenously over 30 to 60 seconds. In one study group, 40 women received metoclopramide (15 mg); in the other group, 41 women received droperidol (0.5 mg). Twelve women (30%) in the metoclopramide group, versus eight (20%) in the droperidol group, had intraoperative, postdelivery nausea (P = NS). One woman (3%) in the metoclopramide group, versus two women (5%) in the droperidol group, had intraoperative, postdelivery vomiting (P = NS). During the first four postoperative hours, five women (12%) in each group complained of nausea. Three women (7%) in each group had postoperative vomiting. We conclude that metoclopramide (15 mg) and droperidol (0.5 mg) were similarly effective.

Transplacental passage and hemodynamic effects of esmolol in the gravid ewe.

Using a chronic maternal-fetal sheep preparation, the authors determined the transplacental passage and the hemodynamic changes consequent to maternal administration of esmolol. Fifteen experiments were performed in six chronically instrumented pregnant ewes near term. Each animal received esmolol iv, 500 micrograms.kg-1.min-1, for 4 min and then 300 micrograms.kg-1.min-1 for 6 min. Maternal and fetal blood esmolol concentrations (mean +/- SEM) were 1.2 +/- 0.28 and 0.1 +/- 0.03 micrograms/ml, respectively, at the completion of the infusion, and 0.03 +/- 0.01 microgram/ml in the mother and not detectable in the fetus 10 min after stopping the infusion. Despite the relatively low blood esmolol concentration in the fetus compared to the mother, the hemodynamic effects in the fetus were similar to those in the mother. The maximal decrease of maternal mean arterial pressure (MAP) and heart rate (HR) were 7 +/- 2 and 14 +/- 3% (mean +/- SEM), respectively (P less than .05). The maximal decrease of fetal MAP and HR were 7 +/- 2 and 12 +/- 3%, respectively (P less than .05). No changes were seen in maternal or fetal acid-base variables, and intra-amniotic pressure was not affected. The authors conclude that esmolol has a rapid but relatively small transplacental passage, and it is eliminated rapidly from both maternal and fetal plasma.