Do antibodies to myelin basic protein isolated from multiple sclerosis cross-react with measles and other common virus antigens?

Immunological activity to various antigens, including brain components, measles and other viruses, has been associated with IgG in multiple sclerosis (MS). One possible explanation for the presence of anti-viral antibodies and antibody to myelin basic protein (MBP) in MS patients is that there are antigenic determinants common to certain viruses and MBP. To assess this possibility, IgG from individual brains and sera from patients with MS, subacute sclerosing panencephalitis (SSPE) and controls was isolated by protein A and MBP-Sepharose affinity chromatography. Antibody to MBP was measured with a solid phase radioimmunoassay and antibody to measles and other viruses by immunofluorescence and/or complement fixation. Anti-MBP activity was detected in brain extracts and sera of all MS patients tested. In contrast to the low levels of antibody to MBP in control brains, high levels of anti-MBP antibodies were found in most of the normal sera. There was no correlation between the presence and levels of serum anti-measles antibodies and the anti-MBP activity. None of the anti-MBP antibodies affinity purified from brain and serum of MS patients reacted with any of the viruses tested, including measles. IgG purified from SSPE patients or from a rabbit hyperimmunized with measles antigen had no reactivity to MBP, despite high levels of anti-measles antibody. It is concluded that there is not direct link between the presence of antibody to MBP and antibody to measles and other viruses in MS patients.     

The use of natural interferon alpha conjugated to a monoclonal antibody anti mammary epithelial mucin (Mc5) for the treatment of human breast cancer xenografts

Summary An immunoconjugate composed of natural interferon (nIFN) bound in a noncleavable fashion to a monoclonal antibody (MoAb) recognizing a breast epithelial membrane mucin (Mc5) was used to treat xenografts of a human mammary carcinoma cell line (MCF-7) growing in nude mice. The immunoconjugate (nIFN/Mc5) was administered as 20 intralesional (i.l.) injections to 1 of 2 xenografts in each animal. It was found that nIFN/Mc5 produced a significant enhancement of the growth inhibitory actions of nIFN on the injected tumors. Further enhancement was obtained when nIFN or nIFN together with Mc5 (at a dose 10 times larger than that present in nIFN/Mc5) were added to the immunoconjugate. Biodistribution experiments showed that the uptake of¹²⁵I-nIFN/Mc5 by the tumors was greater and its elimination slower than for¹²⁵I-nIFN alone or conjugated to irrelevant mouse IgG₁. In addition, the immunoconjugate up-regulated the antigenic expression of a breast epithelial membrane mucin by the carcinoma cells, an up-regulation which was not significantly different from that produced by nIFN alone. The contralateral noninjected tumors exposed to systemic levels of the immunoconjugate showed an enhancement of antitumor effects, but to a lesser extent than the injected tumors. These findings suggest that the enhancement of the growth inhibitory action of the immunoconjugate was related to the specific binding of Mc5 which targeted the IFN to the carcinoma cells and impeded its elimination. It is likely that the targeting was favored by the IFN-mediated up-regulation of antigenic expression by the carcinoma cells, thereby producing a cascade of interrelated effects. The results of this study point out the feasibility and potential usefulness of IFN treatment by means of immunoconjugates as well as the worth of pursuing and improving this form of therapy.     

Massive blood transfusion exceeding 50 units of plasma poor red cells or whole blood: the survival rate and the occurrence of leukopenia and acidosis

The survival rate after bleeding requiring massive blood transfusions exceeding 50 units has been reported to be low or zero. There seems to be no reports of leukopenia in connection with massive blood transfusion. This retrospective study was carried out to investigate the survival rate and the occurrence of leukopenia and acidosis in patients who were transfused with more than 50 units of plasma poor red cells or whole blood. The survival rate was 16 of 23. Three of the five patients with a blood transfusion of over 100 units survived. Pure component therapy was used on 18 occasions. All patients had a leukopenia, which lasted up to five days. All patients had an acidosis. The range of the lowest pH values in patients who did not survive was from 6.77 to 7.27 and in survivors from 6.87 to 7.28. The survival rate was considerably higher than reported in previous studies. Pure component therapy appeared to be particularly suited to massive transfusion. Leukopenia was a regular phenomenon. Severe acidosis did not predict a poor outcome.     

Informed consent, parental awareness, and reasons for participating in a randomised controlled study

BACKGROUND: The informed consent procedure plays a central role in randomised controlled trials but has only been explored in a few studies on children. AIM: To assess the quality of the informed consent process in a paediatric setting. METHODS: A questionnaire was sent to parents who volunteered their child (230 children) for a randomised, double blind, placebo controlled trial of ibuprofen syrup to prevent recurrent febrile seizures. RESULTS: 181 (79%) parents responded. On average, 73% of parents were aware of the major study characteristics. A few had difficulty understanding the information provided. Major factors in parents granting approval were the contribution to clinical science (51%) and benefit to the child (32%). Sociodemographic status did not influence initial participation but west European origin of the father was associated with willingness to participate in future trials. 89% of participants felt positive about the informed consent procedure; however, 25% stated that they felt obliged to participate. Although their reasons for granting approval and their evaluation of the informed consent procedure did not differ, relatively more were hesitant about participating in future. Parents appreciated the investigator being on call 24 hours a day (38%) and the extra medical care and information provided (37%) as advantages of participation. Disadvantages were mainly the time consuming aspects and the work involved (23%). CONCLUSIONS: Parents' understanding of trial characteristics might be improved by designing less difficult informed consent forms and by the investigator giving extra attention and information to non-west European parents. Adequate measures should be taken to avoid parents feeling obliged to participate, rather than giving true informed consent.     

NITRIC OXIDE ALONE IS AN INSUFFICIENT BIOMARKER OF EXPOSURE TO MICROBES IN A MOISTURE-DAMAGED BUILDING

Several epidemiological studies have revealed a large variety of adverse health effects related to exposure to microbes in moisture damaged buildings. Recently some evidence has been reported for a biochemical linkage between microbial exposure and the respiratory symptoms suffered by the occupants. The objective of the current study was to evaluate the value of nitric oxide (NO) measurements in determining the inflammatory status of airways in inhabitants of problem buildings. NO was measured by a chemiluminescence analyzer from the exhaled air. In addition, NO was determined as its metabolite nitrite from nasal lavage (NL) and induced sputum (IS) samples and also via the expression of inducible nitric oxide synthase (iNOS) in the cells. Occupants of moisture-damaged and reference schools were studied. The sampling was performed at the end of the spring term, at the end of the summer vacation, during the winter term, and after a 1-wk winter holiday. No statistically significant differences in NO levels were detected between the studied groups or between exposure and vacation periods. iNOS was not detected from IS or NL samples of the exposed occupants. These results suggest that NO measurements alone are not sufficient to quantify airway inflammation when evaluating subjects exposed to microbes present in moisture-damaged buildings.     

Carbon Monoxide and Driving Skills

Eighty milliliters of carbon monoxide (CO) or 80 ml of air was administered doubleblind to 50 adults (32 men, 18 women). Blood carboxyhemoglobin (COHb) levels increased by 3.4% in those receiving CO. Brake reaction time, night vision, glare vision, glare recovery, hand-steadiness, and depth perception all showed small and individually insignificant deterioration in the group receiving CO; grouping data in a nonparametric analysis, the performance difference became significant (P < .005). During operation of a driving simulator, the CO-exposed group showed a highly significant deficit in “careful driving” skills (P < .005), with a statistically insignificant facilitation of emergency-type movements. Since a 3.4% increase of COHb level is sufficient to prejudice safe driving, there is a need to revise the permitted eight-hour industrial CO exposure level of 50 ppm.