A randomized phase II trial of interferon-α2b versus 5-fluorouracil after trabeculectomy*

Purpose: The aim of the present study was to investigate the safety and potential efficacy of subconjunctival interferon-α2b (IFN-α), either alone or in combination with 5-fluorouracil (5-FU), in reducing the risk of failure of glaucoma surgery. Methods: A prospective, masked randomized phase II study was undertaken in which patients received three subconjunctival injections per week for 3–4 weeks postoperatively. Three treatments were compared: (i) IFN-α (1 × 10 ⁶ IU per dose); (ii) 5-FU (5 mg per dose); and (iii) alternating IFN-α and 5-FU (BOTH). The primary outcome measures were: (i) rate of successful control of intra-ocular pressure without further surgery; and (ii) the incidence of side effects. Results: Fifty-seven patients undergoing glaucoma surgery with an increased risk of failure were evaluated, including 23 patients (40%) undergoing trabeculectomy combined with extracapsular cataract extraction as well as other conventional high-risk groups. With 53 patients (93%) completing 2 years follow up, there was no significant difference in success rates among the three groups. Intra-ocular pressure was controlled without further surgery in 79% of patients (95% confidence interval (CI): 61, 97%) receiving IFN-α, in 89% of patients (76, 100%) receiving 5-FU and in 89% of patients (76, 100%) receiving BOTH. Side effects were similar among the three groups. Conclusions: These results are consistent with a beneficial effect of IFN-α2b given either alone or in combination with 5-FU after glaucoma filtering surgery. However, the lack of a clear and substantial benefit over conventional anti-fibrotic therapy does not support the further clinical evaluation of these treatments.     

Inhibition of dopamine uptake into PC-12 cells by analogues of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)

The inhibition of uptake of radioactive dopamine into PC-12 cells by analogues of MPTP with systematic variations of structure was studied in order to assess the steric constraints of the transmembrane dopamine transporter. Of 15 analogues tested, 11 were found to inhibit dopamine uptake, all being competitive inhibitors. Major changes to the phenyl ring of MPTP, e.g. replacement of the phenyl by a naphthyl group, had a relatively modest effect on the inhibition of uptake of dopamine. Minor modifications to the N-methyl moiety reduced the ability to inhibit uptake, although the unmethylated analogue still had inhibitory properties. Therefore, in considering environmental agents resembling MPTP as potential causes of idiopathic Parkinson's disease, the size of aromatic groups attached to the alicyclic ring appears not to be critical in terms of the dopamine transporter. Uptake of unmethylated secondary amines is also possible, but these are likely to need to be bioactivated by transamination as well as oxidation to generate neurotoxins.     

Testing the reliability of a new measure of life events and experiences in childhood: The Psychosocial Assessment of Childhood Experiences (PACE)

There are few well validated instruments for measuring the impact of life events and experiences in childhood and adolescence. This study examines the reliability of a new instrument, the Psychosocial Assessment of Childhood Experiences of PACE. Fifteen children and parents were interviewed on two cassions ten days apart for the main test-retest reliability study. About half of the events recorded were reported on both occasions (0.45% and 0.55% concordance). When the impact of specific events was examined much higher levels of agreement were found. Inter-rater reliability tests also yielded higher rate (Kappa 0.74 and above). Possible reasons for these important differences are discussed and the inherent methodological difficulties considered.

---

Zusammenfassung Es existieren nur wenige gut validierte Meßinstrumente zur Erfassung von Lebensereignissen und Erfahrungen im Kindes- und Jugendalter. Diese Studie untersucht die Reliabilität eines neuen Verfahrens, des Psychosocial Assessment of Childhood Experiences oder PACE. 15 Kinder und Elternteile wurden zweimal im Abstand von 10 Tagen für die Überprüfung der Haupttest-Retest-Reliabilität interviewt. Ca. die Hälfte aller Ereignisse, die beim Interview berichtet wurden, wurdem beim Zweitinterview ebenfalls angegeben (Konkordanzen 0,45 und 0.55). Deutlich höhere Übereinstimmungen fanden sich bei Untersuchung der Auswirkungen spezifischer Ereignisse. Die Inter-Rater-Reliabilitätstests ergaben ebenfalls höhere Werte (Kappa 0.74). Mögliche Ursachen dieser wichtigen Unterschiede werden unter Berücksichtigung der inhärenten methodischen Schwierigkeiten diskutiert.

---

Résumé II y a peu d'instruments correctement validés de mesures de l'impact des événements de vie des expériences dans l'enfance et l'adolescence. Cette étude examine la fiabilité d'un nouvel instrument, l'évaluation psycho-sociale des expériences infantiles (Psychosocial Assessment of Childhood Experiences ou PACE). 15 enfants et parents furent interrogés à deux reprises à 10 jours d'intervalle pour evaluer la fiabilité test-retest. Environ la moitié des événements rapportés le furent dans les deux occasions (0.45% et 0.55% de concordance). Quand l'impact des événements déviés spécifiques fut étudié un niveau plus élevé de concordance fut trouvé. La fidélité inter-cotateurs des tests obtinet également des taux plus élevés (kappa 0.74 et audessus). Les raisons possibles de ces différences sont discutées et les difficultés méthodologiques inhérentes prises en compte.

     

Alcohol ablation of atrioventricular conduction

Transcoronary ablation of atrioventricular conduction by dehydrated alcohol was attempted in 14 patients with refractory atrial arrhythmias. Alcohol (0.5 or 1.0 ml) was delivered after selective catheterisation of the atrioventricular nodal artery in the 10 patients in whom the artery could be identified by cineangiography. The other four patients underwent electrical ablation when the nodal artery could not be catheterised. Temporary atrioventricular block induced by dilute contrast and cold saline (0.9%) confirmed that the catheter was in the correct position before the alcohol was delivered. In all 10 patients complete atrioventricular block developed after alcohol ablation. The block persisted in all four patients given 1.0 ml alcohol but not in four of the six given 0.5 ml. The mean (SD) creatine kinase (MB fraction) at four to six hours after ablation was 76.5 (49.5) IU after 1.0 ml and 75.5 (43.1) IU after 0.5 ml alcohol (normal less than 20 IU). The overall success rate of alcohol ablation in the whole group on an "intention to treat" basis was 43%. The procedure was a technical success in six of the 10 patients in whom the nodal artery was identified. Transcoronary alcohol ablation of atrioventricular conduction should be considered in patients in whom electrical techniques have been unsuccessful.     

A possible mechanism of insulin resistance in the rat adipose cell with high-fat/low-carbohydrate feeding. Depletion of intracellular glucose transport systems

The effects of high-fat/low-carbohydrate feeding on glucose transport activity and on the concentrations of glucose transport systems in the plasma and low-density microsomal membranes in isolated rat adipose cells have been examined. Glucose transport activity was assessed by measuring 3-O-methylglucose transport and the concentration of glucose transport systems estimated by measuring specific D-glucose-inhibitable cytochalasin B-binding. Basal glucose transport activity is not significantly influenced by high-fat/low-carbohydrate relative to low-fat/high-carbohydrate feeding and is accompanied by a constant 10 pmol of glucose transport systems/mg of membrane protein in the plasma membrane fraction. In contrast, maximally insulin-stimulated glucose transport activity decreases from 4.72 to 2.29 fmol/cell/min and is accompanied by a decrease from 44 to 26 pmol of glucose transport systems/mg of plasma membrane protein. These diminished effects of insulin on glucose transport activity and the concentration of glucose transport systems in the plasma membrane fraction are paralleled by a 48% decrease in the basal number of glucose transport systems/mg of membrane protein in the low-density microsomal membrane fraction, the source of those glucose transport systems appearing in the plasma membrane in response to insulin. Thus, the "insulin-resistant" glucose transport of the adipose cell with high-fat/low-carbohydrate feeding may be the consequence of a depletion of glucose transport systems in the intracellular pool.     

Addict death rates during a four-year posttreatment follow-up.

Mortality rates were examined among 3,324 Black and White daily opioid drug users for a four-year period following treatment in community-based agencies located across the United States. A total of 179 of these addicts died during this follow-up period, yielding a death rate of 15.2 per 1,000 person-years at risk. When adjusted for age, addict death rates were found to be three to 14 times higher than those in the general US population. Life table analysis was also used to examine these rates in relation to client demographic, background, and treatment variables obtained prospectively, both prior to and during treatment. Age, alcohol use, and criminal history were positively associated with higher death rates. With regard to causes of death, age proved to be the only significant predictor; older addicts (over 30) had the highest percentages of deaths due to "natural" causes, while over three-fourths of the deaths among younger addicts were drug related or involved violence.