The use of quinacrine (Atabrine) in rheumatic diseases: A reexamination

Atabrine has been available for nearly 60 years. It has a variety of actions and has been administered to millions of individuals. Its antirheumatic properties have been well documented but have not been exploited optimally for a variety of reasons. The drug is generally quite safe and could be used in low doses in lupus and rheumatoid arthritis patients as a steroid-sparing agent or synergistically with hydroxychloroquine. Its bothersome side effects should not deter the clinician from using it, because they are easy to deal with or prevent (Table 5). Future studies should attempt to better characterize the immunosuppressive actions of this powerful drug, particularly in the treatment of lupus erythematosus and rheumatoid arthritis. Studies of the role of combination or single-agent antimalarial therapy in combination with other "remittive" drugs could be of great potential benefit.     

The radiologic manifestations of alveolar soft-part sarcoma

Alveolar soft-part sarcoma is a rare soft-tissue tumor of unknown cellular origin that is characterized histologically by its organized "pseudoalveolar" pattern. The radiologic findings in 11 patients with this neoplasm were reviewed. The six men and five women were 16-48 years old (mean, 27 years). Nine patients had untreated primary tumors (thigh, four; forearm, two; and buttock, rectus abdominis muscle, and infratemporal fossa, one each) and two had locally recurrent masses (one each in the retroperitoneum and retrocrural space). All patients were evaluated by conventional radiography, two by sonography, eight by CT, five by angiography, and three by MR. Conventional radiographs showed the soft-tissue mass in only four patients; four lesions caused destruction of adjacent bone and two had soft-tissue calcification. Unenhanced CT showed low-attenuation lesions in four of five patients. The lesions were hypervascular on contrast-enhanced CT or angiography in each of nine patients studied. Prominent draining veins were shown by CT or angiography in five patients. Three lesions had a prolonged capillary stain on angiography. Alveolar soft-part sarcoma should be considered in the differential diagnosis of a hypervascular soft-tissue mass, particularly in the thigh of a young adult.     

Coronary heart disease, chronic inflammation, and pathogenic social hierarchy: a biological limit to possible reductions in morbidity and mortality

We suggest that a particular form of social hierarchy, which we characterize as "pathogenic", can, from the earliest stages of life, exert a formal analog to evolutionary selection pressure, literally writing a permanent developmental image of itself upon immune function as chronic vascular inflammation and its consequences. The staged nature of resulting disease emerges "naturally" as a rough analog to punctuated equilibrium in evolutionary theory, although selection pressure is a passive filter rather than an active agent, like structured psychosocial stress. Exposure differs according to the social constructs of race, class, and ethnicity, accounting in large measure for observed population-level differences in rates of coronary heart disease across industrialized societies. American Apartheid, which enmeshes both majority and minority communities in a social construct of pathogenic hierarchy, appears to present a severe biological limit to continuing declines in coronary heart disease for powerful as well as subordinate subgroups: "Culture"--to use the words of the evolutionary anthropologist Robert Boyd--"is as much a part of human biology as the enamel on our teeth".     

Inflammatory Bowel Disorders

Infiltration of leucocytes into the mucosa is a hallmark feature of a number of inflammatory bowel disorders, most notably Crohn's disease and ulcerative colitis. The interactions between circulating leucocytes and the vascular endothelium that permit leucocyte migration to a site of injury or infection are mediated via a variety of adhesion molecules. There is now ample evidence for alterations in adhesion molecule expression and function in inflammatory bowel disorders. This raises the possibility that adhesion molecules could be targets for novel therapies. Indeed, many existing anti-inflammatory drugs are capable of modulating adhesion molecule expression or function. Moreover, intensive research is under way to develop more selective and effective modulators of adhesion molecules, in the hope that they will be useful for treating various inflammatory disorders.     

Effects of intracerebral implants of steroid hormones on scent marking in the ovariectomized female gerbil (Meriones unguiculatus)

The effects of intracerebral implants of steroid hormones on scent marking in the female gerbil (Meriones unguiculatus) were studied in two experiments. In Experiment 1 various steroids were implanted alone or in combination into the preoptic and anterior hypothalamic area of ovariectomized females. Unilateral implants of testosterone + estrogen, estrogen, estrogen + progesterone, testosterone and testosterone + progesterone stimulated a significant level of marking when compared to controls. Experiment 2 utilized bilateral implants of estrogen dissolved in paraffin in order to explore the distribution hormone sensitive areas in the brain which might be important in the regulation of scent marking in the female gerbil. Pellets of estrogen-paraffin were implanted stereotaxically into either the anterior hypothalamus, preoptic area, septum, hippocampus, thalamus, amygdala or anterior olfactory nucleus of ovariectomized females. Total dosage of hormone implanted was 8.2–8.4 μg. A significant level of marking resulted in animals receiving implants into the anterior hypothalamus, preoptic area and septum when compared to controls. Marking appeared at about the same rate in each of these groups; however, the level of marking attained differed. By the last trial, anterior hypothalamic implanted animals were marking significantly more often than animals in either the preoptic or septum groups. Although there was no evidence of ieakage from the brain, the data suggested that some rapid diffusion of hormone, largely restricted to the brain, was taking place or that the three areas were differentially responsive to the hormone. The data do indicate that some localization of function does exist with respect to regulation of scent marking in the female.