Search

In mild-to-moderate inflammatory bowel disease, particularly ulcerative colitis, 5-aminosalicylic acid (5-ASA) remains a cornerstone of therapy. Sulfasalazine, originally synthesized in 1940 as an arthritis treatment for Sweden's King Gustaf V, is an azo-linked compound between 5-ASA and sulfapyridine. This medication was soon discovered to be effective in treating ulcerative colitis. However, dose-related side effects of the sulfapyridine moiety led to considerable effort in developing medications to deliver 5-ASA to the desired parts of the intestine. The newest generation of 5-ASA medications allows high-dose medication delivery with decreased pill burden, thereby improving patient compliance. This review will describe the pharmacokinetics of various 5-ASA preparations, particularly focusing on high-dose formulations and their role in therapy; will examine current scientific literature; and will review clinical outcomes and safety profiles.

The purpose of the present investigation was to determine whether the sensitivity to systemic toxic effects of cocaine is altered in genetically epilepsy-prone rats (GEPRs). Moderate seizure (GEPR-3) and severe seizure (GEPR-9) rats, and the control strain, Sprague-Dawley rats, 10 weeks of age, were lightly anesthetized with halothane and nitrous oxide. Following surgical preparation and stabilization, the animals were given a constant intravenous infusion of cocaine (4 mg/kg per min) until death. Blood pressure, ECG, and EEG were monitored continuously throughout the experiment. Cocaine doses required to produce seizures (i.e., epileptiform activity on the EEG) were not significantly different between GEPRs and control rats (16.8+/-0.6 mg/kg in GEPR-3, 18.7+/-0.7 mg/kg in GEPR-9, and 14.7+/-1.3 mg/kg in Sprague-Dawley). Seizure duration, amplitude and the number of epileptiform bursts were also similar among the three strains. Additionally, there was no significant difference in cocaine doses that produced arrhythmias and cardiac asystole between GEPRs and control. The results indicate that genetically epilepsy-prone rats do not exhibit altered sensitivity to cocaine-induced seizures despite the marked susceptibility to sound-evoked seizures. Local anesthetic-induced seizures and acoustically-evoked seizures apparently have different underlying mechanisms.

To establish and standardize a nociceptive response in anesthetized rats, the hypertensive responses to defined electrical and mechanical stimuli were studied. Rats (n = 7) were given etomidate, 3.8 mg/kg/hr intravenously (i.v.) 2 hr following carotid artery and jugular vein cannulation. At 15 min after beginning the infusion, four types of noxious stimuli were administered sequentially at 1-min intervals (14 stimuli total): Type 1: Square electrical waves, 125 cps, 1.6 msec, 2-sec train duration, varying current from 0.4 to 12 mA (11 stimuli); Type 2: A single 10-mA electrical stimulus, 5-sec train duration; Type 3: Tail clamping; and, Type 4: Skin incision. After each stimulus, maximum change in systolic blood pressure (delta SBP) was measured. delta SBP after the most intense stimuli was as follows: Type 1 (12 mA, 2 sec), 32.1 +/- 2.14 mmHg; Type 2 (10 mA 5 sec), 42.9 +/- 2.4 mmHg; Type 3 (tail-clamping), 34.3 +/- 3.3 mmHg; Type 4 (skin incision), 14.2 +/- 2.8 mmHg. For the multiple Type-2 stimuli, a relationship between current and delta SBP was present. The authors believe that characterized graded electrical stimulation will allow a more quantitative evaluation of the hypertensive response to noxious stimuli in etomidate anesthetized rats, as compared to observing a single response to a single stimulus. The characterization of the electrical stimulation by amplitude, frequency, and wave form makes research work on nociception under anesthesia easily reproducible.

The successful management of a cesarean section in a parturient with a single ventricle and pulmonary atresia using general anesthesia is discussed. After cyanosis at birth, the patient underwent cardiac catheterization, which showed an apparent severe tetralogy of Fallot, atresia of the main pulmonary artery (PA), and a large patent ductus arteriosus. When she was 7 months of age, a Blalock-Taussig shunt (right subclavian artery to right PA) was done. She remained stable until age 11, when cyanosis increased and exercise tolerance decreased. Recatheterization more clearly defined the lesion: closed shunt, pulmonary valvular atresia, severe ductal stenosis, reduced pulmonary flow, double-outlet right ventricle, and severe hypoplasia of the left atrium, mitral valve, and left ventricle. A Potts shunt (left descending aorta to left PA) was done. Compliance with therapy was poor and follow-up difficult. Exercise tolerance was poor, but the patient remained otherwise stable. At 28 weeks' gestation, this 23-year-old parturient presented with severe congestive heart failure (CHF). After initial therapy with oxygen, bed rest, digoxin, and diuretics, she improved and remained stable for a month. At that time (32 weeks' gestation), CHF worsened. Because the cervix was unfavorable for a vaginal delivery, a cesarean section was planned. The patient was then taken to the operating room electively, and an opioid-based general anesthetic was administered. Both mother and infant did well. This case is presented because the physiology of the patient's lesion and her unusual social history presented challenges for her anesthetic management.

Sarcoplasmic/endoplasmic reticulum Ca2+-ATPase 3 (SERCA3), an isoform of the intracellular Ca2+pump that has been shown to mediate endothelium-dependent relaxation of vascular smooth muscle, is also expressed in tracheal epithelium. To determine its possible role in regulation of airway mechanical function, we compared tracheal contractility in gene-targeted mice deficient in SERCA3 (SERCA3−) with that in wild-type tracheae. Cumulative addition of ACh elicited concentration-dependent increases in isometric force (ED50= 2 μM, maximum force = 8 mN/mm2) that were identical in SERCA3−and wild-type tracheae. After ACh stimulation, substance P (SP) elicited a transient relaxation (42.6 ± 3.2%, n = 28) in both tracheae. However, the rate of relaxation was significantly ( P < 0.04, n = 9) more rapid in the wild-type [half-time ( t½) = 34.3 s] than in the SERCA3−( t½= 61.6 s) trachea. The SP relaxation was reduced by rubbing the trachea, indicative of epithelial cell involvement. This was verified using a perfused trachea preparation. SP in the outside medium had no effect, whereas SP in the perfusate bathing the epithelial side elicited a relaxation. Nitric oxide synthase inhibition (0.2 mM Nω-nitro-l-arginine) reduced the SP relaxation by 36.5 ± 12.5%, whereas the SP effect was abolished by eicosanoid inhibition (10 μM indomethacin). ATP also elicited an epithelium-dependent relaxation similar to SP but with a more rapid relaxation in the SERCA3−trachea than in the wild-type trachea. Our results indicate that SERCA3 gene ablation does not directly affect smooth muscle, which is consistent with the distribution of the isoform, but suggest that SERCA3 plays a role in epithelial cell modulation of airway smooth muscle function.

Mivacurium is metabolized by plasma cholinesterase catalyzed ester hydrolysis. Acetylcholinesterase antagonists used in the reversal of muscle relaxation may also inhibit plasma cholinesterase and, therefore, delay the hydrolysis of mivacurium. The clinical interaction between acetylcholinesterase antagonists and mivacurium induced neuromuscular blockade was studied.Intraoperative muscle relaxation was maintained with a mivacurium infusion to achieve a constant intense block (first twitch, T1, 2-3% of control). Patients were randomly divided into three groups. Patients in Group 1 received no anticholinesterase, in Group 2 neostigmine 0.07 mg.kg-1, and in Group 3 edrophonium 1 mg.kg-1. The times between termination of the mivacurium infusion (Group 1) or the administration of the anticholinesterase (Groups 2 and 3) to 25%, 50%, 75% and 95% T1 recovery, and to 50%, 70% and 90% recovery in the ratio, T4/T1 (TR) were recorded.In the neostigmine Group, T1 recovery to 25%, 50% and 75% (2.32 +/- 1.41, 3.90 +/- 1.85 and 6.88 +/- 2.66 min) was accelerated compared with control (3.36 +/- 1.34, 5.78 +/- 2.22, and 8.58 +/- 3.60, and), but recovery to 95% (18.53 +/- 9.09 vs 13.29 +/- 5.24 min) was delayed. Also, TR recovery to 50%, 70%, and 90% was slower (14.47 +/- 8.73, 21.25 +/- 11.06 and 31.37 +/- 12.11 min vs 11.75 +/- 3.74, 13.78 +/- 4.39 and 17.86 +/- 6.44 min). However, all T1 and TR recovery times were decreased in the edrophonium group (0.88 +/- 0.51, 2.00 +/- 1.50, 4.97 +/- 2.96, and 9.35 +/- 5.24 min for T1 and 6.86 +/- 3.93, 9.05 +/- 4.51 and 12.24 +/- 6.66 min for TR).Neostigmine reversal of intense mivacurium neuromuscular block should be avoided, as this may result in prolongation of the block.

BACKGROUND Previous studies have shown that pulse oximeters whose sensors are positioned improperly may yield erroneously low saturation (SpO2) values on normoxemic subjects. The behavior of oximeters with malpositioned sensors during hypoxemia has not been studied. The current study is aimed at determining the behavior of several different pulse oximeters over a wide range of arterial oxygen saturation (SaO2). METHODS In each of 12 healthy volunteers, a radial artery cannula was inserted, and eight different pulse oximeters, five of which had malpositioned sensors, were applied. Subjects breathed controlled mixtures of nitrogen and oxygen to slowly vary their SaO2 from 100% to 70%. Arterial blood samples were analyzed and pulse oximeter data were recorded at five stable SaO2 values for each subject. RESULTS The oximeters with malpositioned sensors vary greatly in their behavior, depending on both the actual SaO2 and the manufacturer and model. One oximeter underestimated saturation at all SaO2 values, while three others underestimated at high SaO2 and overestimated at low SaO2. Linear regression analysis shows a decrease in the slope of SpO2 versus SaO2 in most cases, indicating a loss of sensitivity to SaO2 changes. Between-subject variation in response curves was significant. CONCLUSIONS The calibration curves of the pulse oximeters studied were changed greatly by sensor malpositioning. At low SaO2 values, these changes could cause the oximeter to indicate that a patient was only mildly hypoxemic when, in fact, hypoxemia was profound. It is recommended that sensor position be checked frequently and that inaccessible sensor locations be avoided whenever possible.

Laboratory and clinical evidence of the inhibition of plasma cholinesterase by metoclopramide was demonstrated. When succinylcholine is used as the substrate and the product choline assayed by choline oxidase-peroxidase-quinone dye colorimetry, the rate of the choline production as optical density change was reduced to 50% by 19.5 X 10(-6) M metoclopramide at 20 degrees C. Prolongation of neuromuscular blockade produced by concurrent administration of succinylcholine and metoclopramide was studied in 22 patients aged between 18 and 40 years undergoing elective gynecological surgery. EMG activity in the adductor pollicis muscle was recorded in response to a train-of-four (TOF) stimulus delivered every 10 s. Patients were randomly divided into two groups: A and B. In both groups, anesthesia was induced with thiopental and maintained with sufentanil and nitrous oxide. Tracheal intubation followed intravenous succinylcholine. Intraoperatively, after returning of neuromuscular function, patients in both groups received 20 mg succinylcholine for the determination of duration of neuromuscular blockade. Time from 95% suppression of baseline twitch following a 20 mg increment of succinylcholine until recovery to 25% of control activity was determined. Thereafter, in group A, patients receive metoclopramide (10 mg iv) followed by succinylcholine 20 mg iv, and patients in group B received succinylcholine 20 mg iv alone. Recovery times were again measured and found to be prolonged in patients receiving metoclopramide compared with those not receiving metoclopramide (P less than 0.05). Metoclopramide has no intrinsic neuromuscular blocking activity, but its ability to inhibit plasma cholinesterase probably is the mechanism by which it prolongs succinylcholine block. Reducing the dose of succinylcholine may be appropriate when metoclopramide is given concurrently.