A randomized, double-blind placebo-controlled trial of moclobemide in patients with chronic fatigue syndrome

BACKGROUND: Chronic fatigue syndrome is characterized by prolonged and disabling fatigue and a range of neuropsychiatric symptoms including depressed and/or irritable mood. To date, no medical or psychotropic therapies have provided clear symptomatic benefit. METHOD: Ninety patients with chronic fatigue syndrome, diagnosed with our system that approximates CDC criteria, participated in a randomized, placebo-controlled, double-blind trial of 450 to 600 mg/day of moclobemide, a novel reversible inhibitor of monoamine oxidase-A. RESULTS: Fifty-one percent (24/47) of patients receiving moclobemide improved compared with 33% (14/43) of patients receiving placebo (odds ratio = 2.16, 95% confidence interval [CI] = 0.9 to 5.1). Drug response was best characterized symptomatically by an increase in the subjective sense of vigor and energy rather than a reduction in depressed mood. The effect of moclobemide on subjective energy was detectable within the first 2 weeks of treatment and increased across the course of the study. The greatest reduction in clinician-rated disability was in patients with concurrent immunologic dysfunction (mean difference in standardized units of improvement = 0.8, 95% CI = 0.03 to 1.6). CONCLUSION: Moclobemide produces some improvement in key symptoms experienced by patients with chronic fatigue syndrome. This effect is not dependent on the presence of concurrent psychological distress and is likely to be shared with other monoamine oxidase inhibitors.     

The natural history of glaucoma and ocular hypertension after pediatric cataract surgery.

INTRODUCTION: We sought to define the prevalence and natural history of ocular hypertension and glaucoma for at least a 10-year period after pediatric cataract surgery. METHODS: We conducted a prospective observational study of patients who received pediatric cataract surgery. Inclusion criteria included 2 directed ophthalmologic examinations performed at a minimum of 5 and 10 years after surgery. RESULTS: A total of 63 patients (22 with bilateral cataracts and 41 with unilateral cataracts) were examined at a median of 15.1 year (range, 10.3-21.3 years) after surgery. A majority of the subjects had glaucoma or ocular hypertension (ie, 59%; 37/63). Nineteen percent (12/63) had glaucoma (5/22 with bilateral cataracts and 7/41 with unilateral cataracts). Approximately half (7/12) had developed glaucoma during the first 5-year observational period and the remainder (5/12) developed it during the following observational period. Forty percent (25/63) of the patients had ocular hypertension in at least one aphakic eye (9/23 with bilateral cataracts and 16/40 with unilateral cataracts). The rate of progression from ocular hypertension to glaucoma over a mean observational period of 7.2 years (range, 6.2-8.1 years) was 23% (5/22). DISCUSSION: Patients who receive surgery for pediatric cataracts are at very high risk of developing ocular hypertension and glaucoma. Patients can develop late-onset glaucoma and ocular hypertension more than 10 years after surgery. Years of ocular hypertension may precede the diagnosis of late-onset glaucoma.     

Eosinophilic/T-Cell Chorionic Vasculitis

Chorionic vasculitis is the hallmark of a fetal response in chorioamnionitis. There are five highly characteristic findings: (1) leukocyte migration is not concentric but rather radiates toward the infected amniotic fluid; (2) the infiltrate is primarily neutrophils; (3) multiple chorionic vessels, first veins and then arteries, are usually involved; (4) the infiltrate never extends into the vasculature of stem villi; and (5) it is rare in the absence of chorioamnionitis (or its precursors). Here we describe a new form of chorionic vasculitis characterized by an infiltrate composed primarily of eosinophils and CD3+ T lymphocytes that very focally involves a single chorionic vessel (artery or vein), that radiates away from the amniotic fluid (i.e., toward the intervillous spaces), and that may extend into the stem villous vasculature; this lesion occurs in the absence of any evidence of chorioamnionitis. During the past 7+ years, using accepted placental review criteria, we have examined 7104 placentas and identified 14 cases of eosinophilic/T-cell chorionic vasculitis (or related lesions). Although the frequency of diagnosis in the placentas examined was 0.197%, its true incidence cannot be estimated because of its very focal nature and the limited nature of placental disk sampling. Its etiology and significance are unknown, but it may represent a focal immune-mediated vasculitis.     

Acromioplasty: comparison of outcome in patients with and without workers' compensation

Acromioplasty was performed on 24 shoulders in 23 patients who had a diagnosis of impingement syndrome/rotator cuff tendinopathy. Ten patients were female and 13 were male; mean age was 52.3 years. Patients were divided into two groups, depending on whether they were receiving workers' compensation benefits. Clinical outcomes were evaluated preoperatively and at follow-up postoperatively using the University of California Los Angeles (UCLA) Shoulder Rating Scale. All patients had bursectomy, anterior inferior acromioplasty, and coracoacromial ligament release. The two groups showed significantly different postoperative results in terms of pain, function, strength of forward flexion, and total score, with the workers' compensation group consistently having a lower functional score. Pain did improve significantly for workers' compensation patients over the course of treatment, but relief was not nearly as complete as in the noncompensated group. A positive response to a shoulder bursa steroid injection, even if temporary, was a good predictor of final outcome after an acromioplasty.     

Altered electrophysiological responses to mechanical stimulation and abnormal signalling through alpha5beta1 integrin in chondrocytes from osteoarthritic cartilage

OBJECTIVE: To establish whether chondrocytes from normal and osteoarthritic human articular cartilage recognize and respond to pressure induced mechanical strain in a similar manner.DESIGN: Chondrocytes, extracted from macroscopically normal and osteoarthritic human articular cartilage obtained from knee joints at autopsy, were grown in monolayer culture and subjected to cyclical pressure-induced strain (PIS) in the absence or presence of anti-integrin antibodies, agents known to block ion channels and inhibitors of key molecules involved in the integrin-associated signalling pathways. The response of the cells to mechanical stimulation was assessed by measuring changes in membrane potential. RESULTS: Unlike chondrocytes from normal articular cartilage, which showed a membrane hyperpolarization response to PIS, chondrocytes from osteoarthritic cartilage responded by membrane depolarization. The mechanotransduction pathway involves alpha5beta1 integrins, stretch-activated ion channels, tyrosine kinases and phospholipase C but the actin cytoskeleton and protein kinase C, which are important in the membrane hyperpolarization response in normal chondrocytes, are not necessary for membrane depolarization in osteoarthritic chondrocytes in response to PIS. CONCLUSION: Chondrocytes derived from osteoarthritic cartilage show a different signalling pathway via alpha5beta1 integrin in response to mechanical stimulation which may be of importance in the production of phenotypic changes recognized to be present in diseased cartilage.     

Rapacuronium 2.0 or 2.5 mg kg-1 for rapid-sequence induction: comparison with succinylcholine 1.0 mg kg-1

The purpose of this nine-centre study in 602 patients was toshow that the frequency of acceptable intubating conditionsafter rapacuronium 2.0 or 2.5 mg kg^–1 is notmore than 10% lower than the frequency after succinylcholine1.0 mg kg^–1 during rapid-sequence inductionof anaesthesia with fentanyl 1–2 µg kg^–1and thiopental 2–7 mg kg^–1. Laryngoscopyand intubation were carried out 60 s after administrationof muscle relaxant by an anaesthetist blinded to its identity.Intubating conditions were clinically acceptable (excellentor good) in 91.8% of patients given succinylcholine and in 84.1and 87.6% of patients given rapacuronium 2.0 and 2.5 mg kg^–1respectively. With respect to the percentage of clinically acceptableintubating conditions, the estimated difference (and the upperlimit of the one-sided 97.5% confidence interval) between succinylcholineand rapacuronium 2.0 mg kg^–1 was 7.8 (14.4)%and between succinylcholine and rapacuronium 2.5 mg kg^–1it was 4.0 (10.2)%. For both comparisons, the upper limit ofthe one-sided confidence interval exceeded the predefined 10%difference. Hence, it could not be demonstrated that the intubatingconditions with either of the two doses of rapacuronium werenot inferior to those with succinylcholine 1.0 mg kg^–1.The increase in heart rate was significantly greater duringthe first 5 min in the rapacuronium groups, but the arterialpressure increased significantly only in the succinylcholinegroup (P<0.001). Respiratory side-effects were observed in4.0, 13.5 and 18.5% of patients after succinylcholine and rapacuronium2.0 and 2.5 mg kg^–1 respectively (P<0.05).As the non-inferiority of intubating conditions after rapacuronium2.0 and 2.5 mg kg^–1 could not be proven, succinylcholineshould be considered the neuromuscular blocking agent that providesbetter intubating conditions for rapid-sequence induction. Br J Anaesth 2000; 85: 724–31 ^* Corresponding author: Klinik für Anaesthesiologie der TechnischenUniversität München, Klinikum rechts der Isar, IsmaningerStr. 22, D-81675 München, Germany