Comparative investigation of the influence of nizatidine, ranitidine, and cimetidine on the steady-state pharmacokinetics of theophylline in COPD patients.

The influence of usual regimens of the H2 blocking drugs, cimetidine, ranitidine, and nizatidine on the steady-state plasma concentrations and pharmacokinetic characteristics of theophylline was studied in seventeen patients with chronic obstructive pulmonary disease (COPD). Patients were dosed to steady-state with an oral, sustained-release formulation of theophylline given in therapeutic doses twice daily for 2 weeks. Over the next 4 weeks, each patient received a week-long regimen of each H2 blocker concomitantly with theophylline, and a week-long regimen of theophylline alone (control). At the end of each of the latter 4 weeks the steady-state pharmacokinetics of theophylline were assessed. Neither ranitidine nor nizatidine treatment altered the steady-state pharmacokinetics of theophylline relative to the control phase (i.e. no H2 blocker treatment). Values for theophylline C(ave), Cssmax, AUC0-12, and CLoral were significantly different during cimetidine treatment compared with all other treatments (ranitidine, nizatidine, and control). Cimetidine increased theophylline Cssmax, AUC0-12 and Cave by approximately 32%, and decreased theophylline oral clearance by approximately 23%. The authors conclude that cimetidine alters the steady-state pharmacokinetics of theophylline in COPD patients, whereas ranitidine and nizatidine are without effect.     

Distal interphalangeal joint abnormalities in children with polyarticular juvenile rheumatoid arthritis

Involvement of the distal interphalangeal (DIP) joints was noted radiographically in 24 (43.6%) of 55 patients with polyarticular juvenile rheumatoid arthritis. DIP changes were apparent later in the course of the disease and were less severe than in other affected joints. Soft tissue swelling and joint space narrowing were the most frequent abnormalities in the DIP joints. Erosive changes and angular deformities were uncommon. There was no significant correlation between DIP joint involvement and sex, age at presentation, involvement of the hands and wrists at presentation, or positivity of either rheumatoid factor or antinuclear antibody. There was a strong correlation between the presence of extraarticular signs and symptoms and involvement of the DIP joints; however, this may reflect the greater severity of the disease in these patients generally.     

Surface-coil MR imaging of orbital neoplasms

Fifteen patients with orbital neoplasms demonstrated by CT were studied with magnetic resonance (MR) using a 13 cm surface coil and a 0.6 T superconducting magnet. The use of a surface coil allowed for a reduction in slice thickness and a significant improvement in spatial resolution resulting in better demonstration and improved characterization of orbital lesions. All neoplasms (15/15) were demonstrated by MR. The lesions were grouped into four main categories on the basis of signal intensities on T1- and T2-weighted images. CT was superior to MR in displaying densely calcified or bony lesions (two of 15 cases). MR was at least equal or superior to CT in demonstrating the other lesions (13 of 15 cases) and had the added advantage of improved tissue characterization in some cases. With the use of surface coils, MR could become the primary imaging technique for evaluation of orbital neoplasms.     

Corticosterone controls the developmental emergence of fear and amygdala function to predator odors in infant rat pups

In many altricial species, fear responses such as freezing do not emerge until sometime later in development. In infant rats, fear to natural predator odors emerges around postnatal day (PN) 10 when infant rats begin walking. The behavioral emergence of fear is correlated with two physiological events: functional emergence of the amygdala and increasing corticosterone (CORT) levels. Here, we hypothesize that increasing corticosterone levels influence amygdala activity to permit the emergence of fear expression. We assessed the relationship between fear expression (immobility similar to freezing), amygdala function (c-fos) and the level of corticosterone in pups in response to presentation of novel male odor (predator), littermate odor and no odor. CORT levels were increased in PN8 pups (no fear, normally low CORT) by exogenous CORT (3 mg/kg) and decreased in PN12 pups (express fear, CORT levels higher) through adrenalectomy and CORT replacement. Results showed that PN8 expression of fear to a predator odor and basolateral/lateral amygdala activity could be prematurely evoked with exogenous CORT, while adrenalectomy in PN12 pups prevented both fear expression and amygdala activation. These results suggest that low neonatal CORT level serves to protect pups from responding to fear inducing stimuli and attenuate amygdala activation. This suggests that alteration of the neonatal CORT system by environmental insults such as alcohol, stress and illegal drugs, may also alter the neonatal fear system and its underlying neural control.     

Maculopapular eruption with enlarged macrophages in eight patients receiving G-CSF or GM-CSF

In the last years, granulocyte and granulocyte-macrophage colony-stimulating factors (G-CSF and GM-CSF) are being increasingly used and several cutaneous eruptions have been reported in relation to these treatments. In 1991 Horn et al. described three patients with maculopapular eruption that paralleled the time of infusion of GM-CSF. Two of the cases showed an increase in the number and size of macrophages in the biopsy specimen. Since then, several cases have been reported showing this histopathological alteration that has been considered characteristic of reaction to G-CSF or GM-CSF. Although maculopapular eruption with enlarged macrophages can appear after chemotherapy treatment, we have found that the presentation of this eruption after the beginning of cytokine treatment is suggestive of the involvement of G-CSF and GM-CSF in the eruption. We described eight cases of patients treated with G-CSF or GM-CSF that developed maculopapular eruptions with enlarged macrophages.     

A second look at second-order belief attribution in autism

Compared the performance of autistic and mentally retarded subjects, all of whom had passed a standard first-order test of false belief, on a new second-order belief task 12 autistic and 12 mentally retarded subjects, matched on verbal mental age (assessed by PPVT and a sentence comprehension subtest of the CELF) and full-scale IQ were given two trials of a second-order reasoning task which was significantly shorter and less complex than the standard task used in all previous research. The majority of subjects in both groups passed the new task, and were able to give appropriate justifications to their responses. No group differences were found in performance on the control or test questions. Findings are interpreted as evidence for the role of information processing factors rather than conceptual factors in performance on higher order theory of mind tasks.This study was supported by a grant from the National Institute of Deafness and Other Communication Disorders (1RO1 DC 01234). We thank Jason Barker for his extensive help with this study. We are also very grateful to the schools where the study was conducted including the League School, and the public school systems in the following towns in Massachusetts: Hanover, Hanson, Hingham, Milton, Plymouth, and Rockland. We offer special thanks to Alan Dewey, Mary Dollar, Sandy D'Giacomo, Herman Fishbein, William Griffin, Nancy Kearns, Judy Monahan, Debbie Newhall, Cay Riley, Robert Sherman, and Kathy Staska for their continued support of our research.     

Action on RRSPs remains at top of CMA's priority list in 1995, board decides

Potential changes to registered retirement savings plan (RRSP) regulations “continue to generate a huge amount of concern” among physicians, the Board of Directors was told at its December meeting. That anxiety explains why the RRSP issue and related lobbying will remain at the top of the CMA's priority list in 1995. The other major topic of concern during the 3-day meeting was the federal government's proposed gun-control legislation. If doctors are going to have a responsibility to report patients whose ownership of firearms may make them a danger to themselves or others, the CMA wants to ensure that physicians who make such reports are protected under the law.