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.     

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.     

Prenatal and adult presymptomatic testing for Huntington's disease

The discovery of a fragment of DNA that is linked closely to the Huntington's-disease autosomal locus offers the opportunity for the presymptomatic diagnosis of this dominantly-inherited neurodegenerative disorder. Presymptomatic testing will present individuals and society with difficult choices and responsibilities. A pilot adult presymptomatic test programme is under way for SA families. Presymptomatic testing requires intensive counselling both before and after the test. A form of prenatal test, which is applicable to a significant proportion of couples with one partner at risk of Huntington's disease, is available also. As this form of prenatal test does not change the risk status of the parent, less extensive counselling is required and testing is available nationally through the SA programme. It is anticipated that other states will develop their own diagnostic programmes in the near future. This article explains the basis for the test, its accuracy and the importance of obtaining DNA from key individuals in pedigrees of Huntington's disease.     

Human immunodeficiency virus infection in pregnant women under care at AIDS clinical trials centers in the United States.

The federal government supports a nationwide network of medical centers to evaluate promising therapies against the human immunodeficiency virus (HIV) and the opportunistic infections and cancers that characterize AIDS. Forty-five obstetricians from the 49 medical centers receiving federal research support for the conduct of AIDS-related clinical trials, in preparation for a meeting, provided summary information about the number and clinical status of the known HIV-infected pregnant women under their care and the prenatal screening policies for HIV infection at their institutions. In the 12-month period before December 1989, an estimated 1000-1801 HIV-infected women delivered at these centers. The majority (82%) were asymptomatic, 12% were symptomatic, and 6% had AIDS. Routine T-cell testing of infected women was done as part of prenatal care in only 30 of 45 centers. Pneumocystis carinii pneumonia was reported in 35 women. Zidovudine was administered during pregnancy in 29 women. Formal prenatal screening policies have been implemented at the majority (43 of 45) of the medical centers. Most of the infected women identified at these centers chose to continue the pregnancy. With the increasing incidence of HIV infection in women, information concerning the clinical and immunologic state of pregnant infected women and the present use of antiretroviral and other related therapeutics during pregnancy can guide the approach to women's health care and is crucial to the design and implementation of AIDS clinical trials.     

Implementation of a successful endovascular surgical program in a non-teaching tertiary-care centre in Ontario.

Endovascular surgical techniques have become an accepted standard of care for high-risk patients with abdominal aortic aneurysms and for certain patients with thoracic aortic pathology and peripheral arterial aneurysms. In Canada, endovascular surgery has been concentrated in tertiary-care academic teaching institutions. As the technology evolves and as expertise advances, the applicability of endovascular techniques will expand. With time, and as the demand for endovascular techniques rises, this expertise will increasingly need to be delivered by dedicated vascular surgical services in nonteaching institutions. The dissemination of endovascular surgical capabilities represent a unique challenge. We report the successful implementation of an endovascular surgical program in a tertiary-care nonteaching institution using a carefully planned preceptorship model. We review our initial 49 cases and discuss 6 factors important to the successful establishment of an endovascular surgical service: education, teamwork, strict selection of patients, use of a single stent-graft manufacturer, industry support and endovascular preceptorship. Our experience may be used as a model by other institutions in Canada.     

Effect of cicletanine on reperfusion-induced arrhythmias and ion shifts in isolated rat hearts.

Isolated hearts from normotensive (NT) and spontaneously hypertensive (SH) rats, subjected to normothermic global ischemia, were used to study whether cicletanine (a new antihypertensive drug) treatment exerts an antiarrhythmic effect against reperfusion-induced arrhythmias. The effect of the drug on myocardial ion contents (Na+, K+, Ca2+, and Mg2+) during ischemia and reperfusion was also determined. Using the optimal doses of cicletanine (30 and 100 mg/kg orally for 14 days), the incidence of reperfusion-induced ventricular fibrillation (VF) and ventricular tachycardia (VT) was reduced from their control values of 91 and 100% (after 30 min of ischemia) to 41 (p less than 0.05), 50 (p less than 0.05) and 41 (p less than 0.05), 58% in the NT group, while the corresponding value in the SH group for VF and VT were 17 (p less than 0.001), 33 (p less than 0.01) and 17 (p less than 0.001), 25% (p less than 0.001), respectively. The results obtained indicate that the cardioprotective effect of cicletanine was greater in the SH group than in the NT group. Cicletanine significantly reduced the ischemia- and reperfusion-induced myocardial Na+ and Ca2+ gains and inhibited the loss of myocardial K+ and Mg2+ in both NT and SH groups. The antiarrhythmic effect of cicletanine appears to be correlated with the preservation of myocardial Na+, K+, Ca2+, and Mg2+ contents via an ion transport modulation.