CAMPATH-1H IN RHEUMATOID ARTHRITIS--AN INTRAVENOUS DOSE-RANGING STUDY

Forty-one patients with active and refractory rheumatoid arthritis(RA) received a total of 100, 250 or 400 mg of CAMPATH-1H (CAMPATHis a trademark of Glaxo-Wellcome group companies, registeredin the US Patent and Trademark Office) over 5 or 10 days inan open, uncontrolled study. Following therapy, patients weremonitored for adverse effects and disease activity for 6 months.Therapy was associated with prolonged peripheral blood lymphopeniain all dosing cohorts. During the month immediately followingtherapy, lymphopenia was most profound in the 400 mg cohorts.The first dose of monoclonal antibody (Mab) was associated witha ‘flu’-like syndrome, more pronounced at higherinitial doses. One patient developed haemolytic-uraemic syndrome.There were a number of dose-related infections during the earlypost-treatment period and one fatal opportunistic infectionwhich followed additional immunosuppressive therapy. Antiglobulinresponses developed in 9 of 31 patients tested. The majorityof patients showed symptomatic improvement following therapyand 20% of patients maintained a 50% Paulus response at 6 months,all of whom were in the 250 or 400 mg cohorts. CAMPATH- 1H appearsto be an effective treatment for RA. Allowing for the smallnumber of patients treated, infections were more common withhigher doses, although this was not true for adverse eventsoverall, and therapeutic responses were more sustained at higherdosing levels. The broad specificity of CAMPATH- 1H may be appropriatefor the immunotherapy of RA and future studies should aim todefine a dose with an optimal therapeutic ratio. KEY WORDS: CAMPATH-1H, Rheumatoid arthritis, Immunotherapy, Monoclonal antibody, Antiglobulin response     

Transgenic models for prostate cancer research

The ability to introduce novel or specifically altered genes into the germ line of mice and directly perturb gene expression in a specific tissue can facilitate characterization of the molecular mechanisms governing transformation of differentiating tissue within the context of an intact developing animal. Transgenics provide a powerful and remarkably flexible system that can be used to study the cooperation between proto-oncogenes, tumor suppressor genes, and other epigenetic factors in the development of cancer.     

Neophobia in the foraging-site selection of a neotropical migrant bird: An experimental study

I hand-raised chestnut-sided warblers (Dendroica pensylvanica) in a room with eight experimental microhabitats; the microhabitats were removed after 6 weeks. I then measured the response of the warblers to the eight “natal” and eight “novel” microhabitats in two experiments conducted 2 and 4 months after removal. Chestnut-sided warblers responded with decreased feeding latency (neophobia) and a greater preference for foraging at the natal microhabitats. I suggest that an ontogenetic increase in neophobia restricts chestnut-sided warblers to foraging at microhabitats most similar to those experienced as juveniles.     

Drug Regulation Reform Act of 1978

Provisions of the Drug Regulation Reform Act of 1978 are discussed. Included in the discussion are drug monographs and product licenses, investigations and approvals of drugs, drug information, labeling, promotion and education, penalties, and the National Center for Clinical Pharmacology. The Act eliminates the individual NDA approach to regulation and replaces it with a system of monographs on "drug entities" and "drug product" licenses. It amplifies and redefines the investigational process to facilitate and promote research while protecting patients' rights. It also divides the commercial investigation process into two phases: drug innovation investigations and drug development investigations.     

Experimental analysis of the ‘happy hour’: Effects of purchase price on alcohol consumption

An experimental analogue of a discount drink policy known as the happy hour was used to study the effects of purchase price on drinking behavior. Male volunteers with a prior history of either casual (N=20) or heavy (N=14) drinking were given free access to beverage alcohol during a 20-day period. Approximately half the subjects could purchase alcohol under a single-price condition (50 ¢/drink), while a matched group was given a price reduction daily (25 ¢/drink) during a three-hour period in the afternoon. The results demonstrated that the afternoon price reduction significantly increased alcohol consumption in both casual and heavy drinkers. Reinstatement of the standard purchase price effectively suppressed drinking in both groups. The findings are discussed in terms of the theoretical and research implications of environmental influences on drinking.     

Do alexithymic traits predict illness?

The common theoretical speculation that alexithymic personality characteristics (impoverished fantasy life and difficulty expressing feelings verbally) lead to psychosomatic disease was tested in a sample of 181 men. Unlike previous investigations, this study used a measure of alexithymic characteristics taken at least 1 year before any of the men became ill. Comparisons were made of the premorbid MMPI alexithymia scale scores of groups of men who remained well for 10 years or within 10 years developed either physical illness (cancer or benign tumors), "classical" psychosomatic disease (hypertension or gastrointestinal ulcers), or psychiatric disorder (schizophrenia). Results did not support the notion that alexithymia leads to illness onset. There were no significant differences among the groups in their premorbid alexithymia scores. Furthermore, the groups did not differ in the percentage of individuals labeled alexithymic with the use of previously established cut-off points. Although the findings cast doubt on alexithymia as a cause of illness, they do not conflict with the idea that alexithymia can result from the stress of disease or that this type of personality configuration may lead to a decreased response to treatment and a prolonged course of illness.     

External gamma-ray counting of selected tissues from a Thorotrast patient.

Results of gamma-ray measurements of selected tissues from a patient who was injected with Thorotrast almost 36 y ago are reported. The purposes of this study were: 1) to determine the relative tissue distribution and activities of specific radionuclides in the 232Th decay chain, specifically 228Ra (as measured by 228Ac), 212Pb, and 224Ra (measured directly and as measured by 212Pb), and 2) to evaluate the level of radioactive disequilibrium among the daughter products. The spleen and liver had the highest concentrations of radioactivity. Bone also appears to be a long-term sink for 232Th daughter products based on estimates from a small portion of one rib. Larynx and esophagus contained measurable activity, which may have been due to their proximity to the "Thorotrastoma." Radioactivity in the remaining measured tissues were low, as expected. Secular equilibrium could be demonstrated in bone, pancreas, larynx, esophagus, and breast. Significant disequilibrium was observed for spleen, liver, kidney, and red blood cells. Radioactivity measurements reported here will be useful in estimating radiation doses to selected tissues. Such dose estimates are valuable in refining current risk estimates (e.g., liver) and in identifying tissues at risk for further epidemiologic studies. These results, while consistent with other published studies, should be interpreted with caution since measurements were made on only one patient.