New areas for therapeutic intervention in the treatment of rheumatic disease.

Anti-rheumatic therapy has been targeted against the symptoms arising from chronic inflammation of the joint. This has resulted in the extensive use of non-steroidal anti-inflammatory drugs. It is now becoming apparent that these agents have no beneficial effect on disease progression. This mini review concentrates on the formation and maintenance of pannus, the granulomatous tissue responsible for cartilage and bone erosion. This reveals a number of possible therapeutic targets. Protease inhibitors could be used to interfere with the degradatory processes. The diverse functions of endothelial cells suggest oedema formation, cell accumulation and supply of nutrients to the granulomatous tissue could all be targeted by appropriate therapy. Alternatively the immune processes that control pannus formation and state of activation could be regulated by interfering with antigen presentation and the cytokine network.     

Scalp electrical recording during paralysis: quantitative evidence that EEG frequencies above 20 Hz are contaminated by EMG.

OBJECTIVE: To identify the possible contribution of electromyogram (EMG) to scalp electroencephalogram (EEG) rhythms at rest and induced or evoked by cognitive tasks. METHODS: Scalp EEG recordings were made on two subjects in presence and absence of complete neuromuscular blockade, sparing the dominant arm. The subjects undertook cognitive tasks in both states to allow direct comparison of electrical recordings. RESULTS: EEG rhythms in the paralysed state differed significantly compared with the unparalysed state, with 10- to 200-fold differences in the power of frequencies above 20 Hz during paralysis. CONCLUSIONS: Most of the scalp EEG recording above 20 Hz is of EMG origin. Previous studies measuring gamma EEG need to be re-evaluated. SIGNIFICANCE: This has a significant impact on measurements of gamma rhythms from the scalp EEG in unparalysed humans. It is to be hoped that signal separation methods will be able to rectify this situation.     

Origin of serotonin innervation of the arcuate and ventromedial hypothalamic region

Combined fluorescence serotonin immunohistochemistry and retrograde transport labelling with Fast blue and Fluoro-gold were used to identify serotonin-immunoreactive neurons in the midbrain and pons which project to the region of the arcuate and ventrome-dial hypothalamic nuclei. Approximately 90% of doubly labelled neurons were located in the 3 major mesencephalic serotonin-containing cell groups: dorsal raphe (38%), median raphe (21%) and medial lemniscus group (29%). Within these groups, there were numerous non-retrogradely labelled serotonin-immunoreactive neurons as well as numerous non-serotonin-immunoreactive retrogradely labelled neurons. No doubly labelled neurons were observed caudal to raphe pontis although non-serotonin-immunoreactive neurons were retrogradely labelled in the more caudal raphe nuclei.     

Release of soluble transferrin receptor from the surface of human leukemic HL60 cells

Information regarding transferrin (Tf) receptor degradation is largely incomplete. HL60 cells were shown to release to their growth medium a Tf-binding protein which could be immunoprecipitated by anti-Tf receptor monoclonal antibodies (MoAbs) B3/25 and OKT9. Soluble Tf receptor was detected in the medium within one hour of replating of cells, and its release was inhibited at 4 degrees C. The affinity of Tf for the soluble receptor released by cells (kd = 2.3 x 10(-10) mol/L) was slightly lower than its affinity for the detergent-solubilized cellular receptor (kd = 1.2 x 10(-10) mol/L). 125I-Tf internalized and released by cells subsequently bound to Tf receptor released by the same cells, and soluble Tf receptor in the conditioned medium (CM) inhibited 125I-Tf binding to intact cells. The soluble Tf receptor isolated from the CM was smaller (78,000 daltons) than the cell surface receptor (94,000 daltons) when analyzed by gel electrophoresis under reducing conditions. Isolated cell membranes readily released soluble receptor; however, this release could be blocked by protease inhibitors. The soluble Tf receptor may represent the extracytoplasmic domain of the cellular Tf receptor released from the surface of HL60 cells through proteolytic cleavage by a membrane-based protease.     

Intrathoracic carcinoma in an 11-year-old girl showing a translocation t(15;19).

We report here a rare case of intrathoracic undifferentiated carcinoma in an 11-year-old girl. The biopsy tissue stained with antibodies against cytokeratin and carcino-embryonic antigen. The same staining was obtained using a cell line, PER-403, which was derived from the tumor. DNA from PER-403 cells was tested for the presence of Epstein-Barr virus genes, yielding a negative result. The cytogenetic analysis found a translocation t(15;19) (p12;q13), which has not previously been described in a carcinoma.     

Infarction of the conus medullaris

We describe 5 patients who presented with an acute cauda equina syndrome, which we believe was due to infarction of the conus medullaris. In 3 patients, the onset was spontaneous, and in 2 patients it was secondary to temporary occlusion of the distal aorta during medical manipulation. Pain in the buttocks and posterior thighs was a prominent initial symptom in the 3 patients with unprovoked attacks. The main clinical features were profound impairment of bowel and bladder function and of perianal and perineal sensation (S3 to S5 segments). There was sensory and motor impairment in the legs of variable extent, most marked in the S1 and S2 segments, but extending as high as L4 in 2 patients. In 1 patient, ischemic changes in the conus medullaris were confirmed post mortem. Ischemia confined to the caudal tip of the spinal cord is rare, and an underlying anomaly of the pattern of arterial supply is a likely predisposing factor. Four patients had partial return of function over a period of weeks.     

Pneumothorax and other lung diseases: effect of altered resolution and edge enhancement on diagnosis with digitized radiographs

Prior studies have shown that pneumothorax is one of the more difficult entities to diagnose with digitized radiography. This study was designed to test whether increasing resolution from 1.25 to 2.5 line pairs per millimeter (lp/mm) and image processing (edge enhancement from unsharp masking) would increase accuracy and confidence in the diagnosis of pneumothorax, as well as normal cases and other forms of lung disease. Conventional radiographs were digitized with use of a laser reader and then reformatted as film hard copy. Eleven observers read 35 cases reformatted in three different ways (1.25 lp/mm, 2.5 lp/mm, 1.25 lp/mm unsharp mask). The images with finer resolution (2.5 lp/mm) and unsharp mask images were superior to those with coarser resolution (1.25 lp/mm) for the diagnosis of pneumothorax. There was no difference in diagnostic accuracy for normal patients. For abnormalities other than pneumothorax, the unsharp mask images were significantly worse. Confidence in the diagnosis of pneumothorax and other abnormalities was highest with the finest resolution (2.5 lp/mm).