Etanercept combined with conventional treatment in Wegener's granulomatosis: a six-month open-label trial to evaluate safety.

OBJECTIVE: To evaluate the safety of etanercept (Enbrel) in patients receiving conventional treatment for Wegener's granulomatosis (WG). METHODS: We performed a 6-month open-label trial of etanercept (25 mg subcutaneously twice weekly) which was added to standard therapies for WG (glucocorticoids, methotrexate, cyclophosphamide, azathioprine, cyclosporine) and prescribed according to disease severity. Evaluations of clinical response were determined by the Birmingham Vasculitis Activity Score for WG (BVAS/WG) in 20 patients with persistently active disease or with new flares of previously established WG. Fourteen of the 20 patients (70%) had etanercept added as the only new therapeutic variable. RESULTS: Injection site reactions (ISRs) were the most common adverse event related to etanercept (8 episodes in 5 patients [25%]; < 1% of all injections). All ISRs were mild. Two patients had a combined total of 5 hospitalizations (1 patient had 4), but no hospitalizations were attributable solely to etanercept-related adverse events. One patient with severe subglottic stenosis developed pneumococcal tracheobronchitis and subsequently had a localized Herpes zoster infection. Nineteen patients (95%) were still taking etanercept at 6 months, the single exception being a patient who developed progression of orbital (retro-bulbar) disease at 4 months. There were no deaths. The mean BVAS/WG at entry was 3.6 (range 1-8), which decreased at 6 months to 0.6 (P < 0.001, 95% confidence interval [95% CI] -4.0 to -2.1). Among the 14 patients in whom etanercept was the only new treatment variable, the mean daily prednisone dose decreased from 12.9 mg at entry to 6.4 mg at 6 months. This comparison did not achieve statistical significance (difference -6.5; P = 0.19, 95% CI -16.6 to +3.6). Sixteen of the patients (80%) achieved BVAS/WG scores of 0 at some point. However, intermittently active disease was observed in 15 patients (75%). CONCLUSION: In this open-label trial, etanercept used in combination with standard treatments was well-tolerated in patients with WG. Adverse events were few. BVAS/WG scores improved at 6 months, but intermittently active WG (occasionally severe) was common. A randomized, double-masked trial to assess the efficacy of etanercept in WG has begun.

The effect of posture on the induction of epidural anesthesia for peripheral vascular surgery.

BACKGROUND AND OBJECTIVES: A study was done to determine whether a difference existed in the quality and time to maximum anesthesia between the induction of lumbar epidural anesthesia in the sitting and supine position in patients undergoing infrainguinal arterial reconstruction. METHODS: An epidural catheter was inserted at L3-L4 in 40 patients who were randomly assigned to two groups. In group 1, with the patient sitting, 3 mL lidocaine 1.5% with 5 micrograms/mL epinephrine was given as a test dose, followed 3 minutes later by 12 mL bupivacaine 0.75% injected over 2 minutes through the catheter. After remaining in the sitting position for 5 minutes, the patient was placed supine and the quality of anesthesia assessed at 3-minute intervals for 30 minutes. Anesthesia was assessed by loss of sensation to pinprick and the Bromage scale for loss of motor function. In group 2, after placement of the catheter, the patient was immediately placed supine, the same doses of local anesthesia were given at the same time intervals as in group 1, and the onset of anesthesia was similarly assessed. In addition to a comparison between groups in the quality and time to maximum anesthesia, a correlation was sought between these variables and the age, weight, height, and body surface area (BSA) of the patients in each group. RESULTS: The demographically similar groups showed no difference in maximum cephalad spread of anesthesia (median, interquartile range; group 1: T4, T2.5-T6; group 2: T4, T2.5-T7), motor block (group 1: 3, 2-4; group 2: 4, 4-6), or time to maximum motor block (mean +/- SD; group 1, 17.4 +/- 8.7 minutes; group 2, 17.9 +/- 6.8 minutes). The time to maximum cephalad spread of anesthesia was shorter in group 1 (13.8 +/- 6.9 minutes; group 2, 18.6 +/- 6.6 minutes; P = .03). Neither the age nor weight of the patients in either group had any influence on the quality and time to maximum anesthesia. There was, however, a significant correlation between the height (r = 0.48, P = .0303) and BSA (r = 0.48, P = .0318) of the patients in group 1 and the time to maximum cephalad spread of anesthesia. CONCLUSIONS: When lumbar epidural anesthesia was induced in the sitting rather than supine position, the time to maximum cephalad spread was shorter and correlated directly with the height and BSA of the patient. The position of the patient during induction had no effect on the final level of cephalad spread and degree of motor block.

The hemodynamic responses to an intravenous test dose in vascular surgical patients.

The study was designed to investigate the hemodynamic responses to intravenous (IV) injections of various epidural test doses in vascular surgical patients to determine whether previously established criteria in healthier populations were valid in this inherently sicker population. A double-blind, prospective randomized study was performed on 50 patients, not receiving beta-adrenergic antagonists, presenting for vascular surgery and requiring an arterial line. Patients were randomly assigned to receive a 3-mL injection of one of five solutions, either saline (Group 1), lidocaine 45 mg (Group 2), lidocaine 45 mg and epinephrine 5 micrograms (Group 3), lidocaine 45 mg and epinephrine 10 micrograms (Group 4), or lidocaine 45 mg and epinephrine 15 micrograms (Group 5). After injection, a blinded observer recorded arterial blood pressure and heart rate (HR) every 15 s for 3 min. The changes in HR, systolic (SBP), mean (MBP), and diastolic (DBP) blood pressure as well as time to maximum change were analyzed both within and between groups. Only Group 5 had significant within-group changes for all hemodynamic variables measured. Only in the comparison between Groups 1 and 5 and between Groups 2 and 5 were there significant changes in both HR and SBP. The mean increase in HR and SBP within Group 5 was 17.0 +/- 5.9 bpm and 31.0 +/- 10.5 mm Hg, respectively. No differences were found between groups for time to maximum change for HR and SBP which for Group 5 were 64.5 +/- 37.4 s and 90.0 +/- 56.7 s, respectively. To achieve 100% sensitivity and specificity for HR increase, the criterion established was > or = 9 bpm.(ABSTRACT TRUNCATED AT 250 WORDS)

Recovery of neuromuscular function after atracurium and pancuronium maintenance of pancuronium block.

The study was undertaken to determine whether a neuromuscular blockade induced with pancuronium but maintained with atracurium was associated with a shorter time to complete recovery after administration of neostigmine than if the blockade was maintained with pancuronium alone. Anaesthesia consisted of thiopentone, N2O/O2/enflurane and fentanyl, and the neuromuscular blockade, induced by pancuronium 0.1 mg.kg-1 was monitored by the force of contraction of adductor pollicis during major abdominal surgery lasting 2-5 hr. In 24 patients--Group 1--atracurium 0.07 mg.kg-1 was repeated when the first twitch of the train-of-four (TOF) returned to 25% of control (T1/TC 25). In 28 patients--Group 2--pancuronium 0.015 mg.kg-1 was given at similar recovery of T1/TC. At the end of surgery, neostigmine 0.07 mg.kg-1 and glycopyrolate 0.015 mg.kg-1 were given to reverse the residual neuromuscular blockade which was indicated by a T1/TC of less than 25% in all patients. The time from injection of the reversal drugs to a TOF ratio of 70% was similar in both groups (Group 1, 11.6 +/- 7.6 min; Group 2, 10.1 +/- 6 min; P = NS), but the recovery index was smaller in Group 2 (Group 1, 4 +/- 2.6 min; Group 2, 2.61 +/- 1.2 min; P < 0.05). Furthermore, there was no difference between groups in the duration of action of each redose. The study showed that when compared with pancuronium, equipotent doses of atracurium were not associated with (a) a shorter time to complete recovery from a neuromuscular blockade induced with pancuronium or (b) a shorter duration of action.

Menstrual dysfunction in hirsute women.

Hirsutism in women is frequently associated with increased levels of androgens. Studies of biochemical changes, however, have yielded conflicting results. This study compares the findings in 30 hirsute women with normal menses and those of 30 hirsute women with abnormal cycles. Of the women with abnormal menstruation, 73% had oligoamenorrhea only and the others had dysfunctional uterine bleeding. The abnormally menstruating group had a similar mean age but tended to have heavier body weights than those with normal cycles. Free and total testosterone levels were significantly higher in the abnormal group (total testosterone, 54 +/- 35 ng/dl vs 35 +/- 12 ng/dl, p = 0.004; free testosterone, 7.8 +/- 4.9 pg/ml vs 4.2 +/- 1.4 pg/ml, p = 0.002). The abnormal group tended to have higher levels of androstenedione than the normal group (227 +/- 116 ng/dl vs 139 +/- 59 ng/dl) but dehydroepiandrosterone sulfate (DHEAS) levels were similar (320 +/- 142 mg/dl vs 298 +/- 169 pg/dl). Levels of thyroxin, thyrotropin, and prolactin were comparable in the two groups. Among hirsute women those with abnormal menses tended to be heavier and to have higher levels of total testosterone, free testosterone, and androstenedione. This is consistent with the clinical impression, not previously documented, that of hirsute women, those with abnormal menses have more severe endocrine abnormalities than those with normal cycles.

Treatment of androgenic disorders with dexamethasone: dose-response relationship for suppression of dehydroepiandrosterone sulfate.

Glucocorticoids are effective in suppressing androgens in many women whose levels of these steroids are elevated. Their use has been controversial because of inconsistent reports about efficacy and concern about safety. We investigated the dose-response relationship for suppression of dehydroepiandrosterone sulfate (DHEAS) with the use of dexamethasone. Thirty women with an initial DHEAS value of greater than or equal to 300 micrograms/dl were studied. All had cystic or inflammatory acne, hirsutism, or androgenic alopecia. Dexamethasone was given as a single bedtime dosage of 0.125, 0.250, or 0.375 mg. Mean dosage required for suppression was 0.256 mg daily. Suppression of the DHEAS level to less than or equal to 200 micrograms/dl was achieved with 0.125 mg in 25% of women, 0.250 mg in an additional 50%, and 0.375 mg in a further 20%. Most patients were taking spironolactone when the study was performed. Effective suppression is attained with dexamethasone doses significantly lower than previously thought. Use of these doses was not associated with a significant incidence of adverse effects.