A modified enzymatic technique for production of cell suspensions of a murine fibrosarcoma.

Collagenase, elastase, and mild mechanical procedures were used to obtain numerous viable single cells in suspension from a murine fibrosarcoma of C57BL/6 origin. This technique produced suspensions with minimal debris. The suspensions were more than 90% viable and yielded over 1.25 x 10(8) cells/g of solid tumor.

The clinical relevance of certain observations on the histology of the thyroglossal tract.

A study of all patients operated on with a clinical diagnosis of midline neck cyst at the Children's Hospital of Eastern Ontario confirms our impression that certain important facts regarding the microanatomy of thyroglossal duct cyst and its associated tract are the subject of a number of misconceptions entrenched both in surgeon's minds and in some standard reference texts. Our own observations and a review of the literature dating back to Sistrunk's own original contribution in 1920 lead us to emphasize the following: (1) thyroglossal duct cysts seldom have an intact lining; (2) the thyroglossal duct is frequently multiple and arborizes; (3) its course is always anterior to the hyoid bone; (4) it is seldom discernible to the naked eye and it is futile to attempt to dissect it out at operation. By the same token, a full Sistrunk procedure must be done even if the tract is not seen; and (5) deep cervical dermoid cysts may mimic thyroglossal duct cyst when firmly fixed to the hyoid bone, but the presence of sebaceous material in the cyst will identify it as a dermoid because thyroglossal duct cysts do not undergo keratinizing squamous metaplasia.

Interaction of intrathecal morphine with bupivacaine and lidocaine in the rat.

The interaction in the rat between intrathecal morphine and local anesthetics (bupivacaine and lidocaine) on nociception (52.5 degrees C hot plate and paw pressure), motor function, and autonomic function (blood pressure [BP] and heart rate [HR]) was examined over a range of doses for both morphine and the local anesthetics. High doses of intrathecal bupivacaine (75 micrograms) or lidocaine (500 micrograms) produced motor block and hypotension (150 micrograms bupivacaine) lasting approximately 15 and 7 min, respectively, whereas low doses of intrathecal bupivacaine (25 micrograms) and lidocaine (100 micrograms) produced only a transient motor weakness lasting 2 min or less. Alone, neither agent altered the hot plate or paw pressure response at doses, or at times, where the agents had no effect upon motor function. In contrast, at the low dose of either local anesthetic, after the resolution of the transient motor weakness, these doses resulted in a significant leftward shift in the dose-response curves for intrathecal morphine on both the hot plate and paw pressure, as measured by the maximum observed peak effect and by the area under the time-effect curve. Thus, for example, the morphine ED50 (95% confidence intervals) for morphine/saline was 1.7 micrograms (0.7-1.9) on the hot plate and 1.1 micrograms (0.8-1.4) on the paw pressure versus for morphine/bupivacaine (25 micrograms): hot plate 0.25 micrograms (0.21-0.42) and paw pressure 0.28 micrograms (0.2-0.4). Intrathecal morphine was not observed to have any effect on the dose-dependent effects of intrathecal bupivacaine on motor or autonomic blockade. Comparable results were also observed with lidocaine (bupivacaine was found to have no significant effect on spinal cord morphine clearance). We conclude that low doses of intrathecal lidocaine and bupivacaine, which alone have no antinociceptive effect, at times when motor function was clearly unimpaired, are able to significantly augment the antinociceptive activity of intrathecal morphine on the hot plate and paw pressure tests. This prominent and selective potentiation appears to occur via a non-pharmacokinetic mechanism and probably reflects upon the interaction of low concentrations of local anesthetics with systems in the spinal dorsal horn that process acute high threshold afferent input.

[Simultaneous recording of visually evoked potentials (VEP) and registration of simple visual reaction times (RT) in the maximum range of ethanol influence (author's transl)]. / Gleichzeitige Ableitung visuell evozierter Potentiale (VEP) und Registrierung einfacher visueller Reaktionszeiten (RZ) im "Maximalbereich" de Athanolwirkung

The method of simultaneous recording of visual-evoked response (1 occipit-vertex) and simple reaction time to periodic foveal visual stimuli of 1/" per sec was applied to 16 normal individuals. On two successive days the conditions were kept constant except for an independent variable, i.e., ethanol with an average peak of 1.32%; the range of 0.1% below the peak being examined. The amplitude of the component N2-P3 (120-170 msec after the stimuli) was depressed in all individuals. The latencies of N2 and P3 were increased concurrently. The latency of P3, for example, was increased by 10.7% (P less than or equal 0.01) and that of the means of simultaneously recorded reaction time by 14.8% (P less than or equal 0.01). The amount of the increase, however, showed no significant correlation between the two when using Spearman's correlation coefficient and t-test.

Reversal of epidural morphine-induced respiratory depression and pruritus with nalbuphine.

The effect of nalbuphine on the respiratory depression, pruritus and analgesia induced by epidural morphine was determined in a randomized, prospective, double-blind, placebo-controlled fashion. Twenty ASA physical status I women received 0.1 mg.kg-1 epidural morphine at induction of general anaesthesia for elective total abdominal hysterectomy. Group 1 (n = 14) received 0.3 mg.kg-1 nalbuphine intravenously six hours after the epidural morphine administration. Group 2 (n = 6) received saline. Prior to agent administration, six patients from the nalbuphine group and four patients from the saline group had respiratory depression indicated by a PaCO2 greater than 45 mmHg. After nalbuphine administration the PaCO2 (mean +/- SE) decreased from 49.5 +/- 1.2 mmHg to 42.5 +/- 0.7 mmHg (p less than 0.005) while there was no significant change after saline administration. Nine of the 14 patients receiving nalbuphine appeared to become more sedated, despite an improvement in ventilation. Pruritus was antagonized by 0.1 mg.kg-1 nalbuphine (p less than 0.006). There was no reversal of analgesia after administration of 0.3 mg.kg-1 nalbuphine.

A study of the analgesic interaction between intrathecal morphine and subcutaneous nalbuphine in the rat.

Nalbuphine reverses opioid-induced respiratory depression, but the effect on analgesia is unclear. The analgesic interaction between subcutaneous (sc) nalbuphine and intrathecal morphine in conscious, male, Sprague-Dawley rats implanted with chronic intrathecal catheters was investigated. Nalbuphine (10 mg/kg) injected 30 min after intrathecal morphine (4 micrograms) significantly antagonized the effect of morphine in the tail flick test. The antagonism was rapid in onset and persisted beyond the experimental period of 240 min. The magnitude and the duration of the effect were comparable to that observed with sc naloxone (1 mg/kg). In contrast to the results in the tail flick test, nalbuphine enhanced the effect of intrathecal morphine in the noninflamed paw pressure test. Nalbuphine (10 mg/kg) alone had no effect on the time course of tail flick latency but significantly increased paw pressure threshold during the 15-90 min interval after sc injection. Nalbuphine (0.5 mg/kg, sc) alone had no antinociceptive effect in either pain test and did not antagonize the antinociceptive effect of intrathecal morphine (4 micrograms) in the tail flick test. However, sc nalbuphine (0.5 mg/kg), injected 30 min after intrathecal morphine (1.5 micrograms), significantly enhanced the effect of morphine in the paw pressure test compared with intrathecal morphine + sc saline-treated rats. The results indicate a complex analgesic interaction between intrathecal morphine and sc nalbuphine. The net analgesic effect during the interaction was determined by the following: 1) the doses of morphine and nalbuphine; 2) the time after nalbuphine administration; and 3) the nature of the nociceptive stimulus. At lower doses, sc nalbuphine appeared to potentiate the effect of intrathecal morphine in the noninflamed paw pressure test.

[Spectral-analytical studies of the action of etifoxin on the human EEG]. / Spektralanalytische Untersuchungen zur Wirkung von Etifoxin auf das menschliche EEG

Spectral analysis of EEG in healthy volunteers shows that Etifoxin, the hydrochloride of 6-chloro-4-methyl-4-phenyl-2-ethylamino-4H-3,1-benzoxazine (Hoe 36,801), in an oral dosage of 100 mg has a differential effect in function of the individual alpha organization. This differential effect appearing in the course of the quantitative evaluation can be interpreted, from a morphological point of view, as an expression of various partial phases and patterns of a process leading to reduced vigilance.

Renal prostaglandin E2 synthesis and degradation in the developing rat.

Postnatal development of glomerular filtration rate (GFR) and renal blood flow is associated with a fall in renal vascular resistance that may be mediated by vasoactive substances. We examined differences in the regulation of one such substance, prostaglandin E2 (PGE2). The present studies examined renal cortical and medullary PGE2 synthesis and degradation in rats aged 20 days (30.7 g), 31 days (101 g), and 120 days (413 g). PGE2 synthesis in cortical microsomes was highest in 20-day-old rats compared to 31- and 120-day-old rats. In contrast, medullary PGE2 synthesis was lowest in 20-day-old rats compared to 31- and 120-day-old rats. Both cortical and medullary PGE2 degradation were highest in 20-day-old rats and decreased with age. Despite demonstrating significant age-dependent differences in cortical and medullary PGE2 synthesis, 11 days of aspirin given between age 20-31 days blocked PGE2 synthesis in cortex and medulla by 60 and 76%, respectively, but GFR was similar to control 31-day-old rats (0.78 +/- 0.04 ml/min/g kidney weight, aspirin-treated, versus 0.85 +/- 0.03 ml/min/g kidney weight, control), suggesting that observed age-dependent differences in renal PGE2 synthesis is not a major determinant of development of GFR. A more important determinant of GFR may be age- related differences in renal cortical prostaglandin turnover.

Patient-controlled analgesia with epidural meperidine after elective cesarean section.

BACKGROUND AND OBJECTIVES: We report the first controlled analysis of the use of patient-controlled epidural meperidine. This randomized, prospective study compares the efficacy and safety of patient-controlled epidural meperidine to conventional intramuscular meperidine for the management of postoperative pain after elective cesarean delivery. METHODS: After delivery, 60 patients were randomly assigned to receive either conventional intramuscular meperidine therapy or epidural meperidine by a patient-controlled analgesia pump, which was programmed to deliver bolus doses in addition to a continuous background infusion. RESULTS: Patients in the patient-controlled epidural analgesia group used significantly less meperidine in the first 24 hours after surgery (p < 0.05) and had significantly lower visual analog pain scores (p < 0.05) from three hours postoperatively until study completion at 24 hours. Patients in the patient-controlled epidural analgesia group ambulated sooner (19 +/- 7.8 versus 29.2 +/- 2.2 hours, p < 0.005) and cared for their infants earlier (4.6 +/- 0.9 versus 8.1 +/- 6.8 hours, p < 0.05) than patients receiving intramuscular meperidine. One patient developed a respiratory rate of four breaths per minute, 25 minutes after receiving 75 mg epidural meperidine in the operating room. This was treated with intravenous naloxone. No other serious side effects occurred in either group. Both groups were similar with regard to minor intraoperative and postoperative side effects. CONCLUSIONS: Patient-controlled epidural meperidine after cesarean delivery more effectively manages postoperative pain than conventional intramuscular use. The technique is preferred by both patients and nursing staff and can be used in the ward setting with appropriate organization and education. Respiratory depression, if it occurs, should present early after epidural bolus administration.

Spinal and systemic action of the alpha 2 receptor agonist dexmedetomidine in dogs. Antinociception and carbon dioxide response.

BACKGROUND: alpha 2 Agonists are powerful analgesics after spinal delivery. The current work characterizes the dose-dependent antinociception and effects upon respiratory function of dexmedetomidine after intrathecal, epidural, intravenous, and intracisternal delivery in chronically prepared dogs. METHODS: Dogs were prepared with chronic tracheostomies and trained to perform rebreathing studies. These animals were then prepared with chronic lumbar intrathecal, epidural, or intracisternal catheters. RESULTS: A rapid dose-dependent increase in the thermal skin twitch response latency and paw withdrawal to mechanical pinch was observed after intrathecal, epidural, and intravenous dexmedetomidine (dose required to reach 50% of maximal effect for skin twitch = 1.8, 10, and 15 micrograms, respectively) but not after intracisternal dexmedetomidine (> 15 microgram), with the maximally effective dose lasting approximately 90 min. The spinal effect was unaccompanied by effects upon behavioral alertness, motor function, or changes in CO2 response. In contrast, intravenous dexmedetomidine (1-10 micrograms/kg) resulted in a dose-dependent sedation and a significant reduction in heart rate and respiratory rate and a diminished response to increased CO2, these effects lasting approximately 2 h. Intracisternal administration of up to 15 micrograms had no effect upon the nociceptive threshold, and CO2 response, and failed to result in a significant reduction in alertness. All of the effects of dexmedetomidine were antagonized by the alpha 2-antagonist atipamezole (30-300 micrograms/kg, intravenous), but not by the opioid antagonist naloxone (30 micrograms/kg, intravenous), while atipamezole did not reverse the antinociceptive or respiratory depressant actions of intravenous sufentanil (50 micrograms), effects which were reversible by naloxone. CONCLUSIONS: Dexmedetomidine, acting through an alpha 2-receptor, produces a powerful antinociceptive effect, mediated at the spinal level, while systemic redistribution of the drug leads to a hypnotic state with significant cardiorespiratory effects.

The role of prostaglandins in early polyuria induced by cisplatin in the rat.

To assess a possible role of prostaglandins in the early phase of cisplatin-induced abnormalities in renal concentrating ability, three groups of rats were studied. In a first group we measured prostaglandin production from renal medullary microsomes isolated from rats sacrificed at different time periods after cisplatin, 5 mg/kg alone (PB/CP) or cisplatin plus aspirin, 300 mg/kg p.o., 1 h before cisplatin and daily (ASA/CP). In a second group of rats, balance studies were performed in PB/CP and ASA/CP animals for 4 days after cisplatin to determine the effect of such treatment on the renal excretion of solute and water. In another group of rats inulin clearance was measured in PB/CP and ASA/CP animals 4 days after such treatment. The rats received aspirin or phosphate buffer alone (50 mg/ml sodium phosphate, pH 8) to determine the effect of such treatment on prostaglandin production and renal function. In PB/CP Uosm fell and prostaglandin synthesis increased on days 1-3. Prostaglandin synthesis returned to baseline values by day 4, but Uosm remained low. Inulin clearance was low 4 days after cisplatin. In ASA/CP rats prostaglandin synthesis did not increase and the early polyuria was ameliorated. Aspirin did not prevent the later polyuria. Inulin clearance in the ASA/CP group was markedly reduced to levels below those observed with cisplatin alone. These data demonstrate that elevated rates of prostaglandin synthesis occur early in the course of cisplatin-induced renal failure and suggest that prostaglandins may play a role in the early cisplatin-induced concentrating defect.

Prevention of epidural morphine-induced respiratory depression with intravenous nalbuphine infusion in post-thoracotomy patients.

The efficacy of nalbuphine, an agonist/antagonist opioid, in preventing respiratory depression from epidural morphine analgesia after thoracotomy, was assessed in a randomized double-blind placebo controlled trial. After a standardized general anaesthetic and 0.15 mg.kg-1 of epidural morphine, patients received a bolus and then a 24 h infusion of nalbuphine (200 micrograms.kg-1 + 50 micrograms.kg-1.hr-1, 100 micrograms.kg-1 + 25 micrograms.kg-1.hr-1, or 50 micrograms.kg-1 + 12.5 micrograms.kg-1.hr-1) or placebo. Blood gases, analgesia, sedation, side effects, and blood nalbuphine concentrations were assessed every two hours for the next 24 h. Fifty-three per cent of placebo-treated patients had a PaCO2 greater than 50 mmHg and 89 per cent of these received naloxone. A 200 micrograms.kg-1 bolus of nalbuphine followed by a 50 micrograms.kg-1.hr-1 infusion achieved a mean steady state blood level of 38.2 ng.ml-1 and prevented CO2 retention greater than 50 mmHg in all but two patients, neither of whom required naloxone. There was no difference in the incidence of side effects among groups, and analgesia appeared to be unaffected by nalbuphine.

Visualization of a looped and knotted epidural catheter with a guidewire.

PURPOSE: To describe the management of a looped and knotted epidural catheter after analgesia for labour and delivery. CLINICAL FEATURES: Obstetrical epidural pain relief was provided for a 37-yr old woman in early labour. A 20-gauge Portex catheter was inserted at the L2-L3 interspace. Six centimetres of catheter was left in the epidural space. After vaginal delivery the catheter could not be removed. The catheter was left in situ for 24 hr. Repeated attempts at removal were again unsuccessful. The epidural catheter was not visible with fluoroscopy and it was impossible to inject radiopaque dye into the catheter. However, we successfully advanced a 0.016 inch guidewire through the epidural catheter and radiologically demonstrated a knot and part of a loop. The catheter was removed by an orthopedic surgeon using blunt dissection under local anesthetic from the soft tissue just lateral to the interspinous ligament. CONCLUSIONS: A knot can be a rare cause of a trapped epidural catheter. A suggested approach to the trapped lumbar epidural catheter: 1) Gentle traction on the catheter with the patient in various positions and in various degrees of lumbar flexion. 2) Test for catheter patency by injecting sterile, preservative-free, normal saline through the catheter. 3) Radiological imaging to determine if a knot is present and to determine its location, using radiopaque contrast for patent catheters or a guidewire for occluded catheters. 4) The approach to definitive management is based on the position of the knot. This can range from excision under local anesthetic to consultation with a surgical specialty for more invasive retrieval.

Complex morphology of melt-spun nylon-6 fibres investigated by 1H double-quantum-filtered NMR spin-diffusion experiments.

The complex morphology of high-speed melt-spun nylon-6 fibres hydrated with D2O was investigated using 1H double-quantum-filtered spin-diffusion NMR experiments. The magnetisation exchange from selected crystalline domains along the fibrils and interfibrils was simulated with the help of a three-dimensional solution of a spin-diffusion equation approximated by a product of one-dimensional analytical NMR signals, which correspond to a lamellar morphology. This allows to measure the sizes of crystalline and less-mobile amorphous domains along the fibrils, as well as the diameter of the fibrils and interfibril distances. A series of nylon-6 fibres with extreme values of winding speed and draw ratio was investigated. The changes detected in the domain size along the fibrils and interfibrils show the same trend in the data obtained from wide-angle X-ray diffraction and small-angle X-ray scattering.

[Signal analysis of EEG-changes induced by nomifensin - a new antidepressant (author's transl)]. / Signalanalytische Untersuchungen zur Wirkung des Antidepressivums Nomifensin auf das EEG gesunder Probanden

Ten healthy volunteers received a single oral dose of 100 mg nomifensive, a new antidepressant (tetragtdriusiqyubikube deruvatuve; Hoe 36-984). The drug-induced effects on the EEG were compared with those of placebo. The statistically proved results show that nomifensine causes a distinct shift in vigilance with two different partial processes. After an initially occurring stabilization of the dominant alpha-frequency there appears a polyrhythmic disintegration of the alpha-rhythm with increase of slower and faster frequencies. At the same time a shifting takes place within the beta-range with increasing of 23.5-32.0 Hz-components. Accordingly it is evident that nomifensine results in a typical pharmaco-electroencephalographic profile.