We conducted a study of the epidemiology of myasthenia gravis (MG) in four locations in central and western Virginia from 1970 through 1984. The population surveyed was 555,851 in 1984. A total of 73 new cases of MG occurred during the survey period, producing an overall average annual incidence rate of 9.1 per million. The point prevalence rate in 1980 was 13.4 per 100,000, and in 1984 it was 14.2. Approximately 15% of the population was black, and we found that incidence and prevalence rates for the black population were higher than the corresponding white population. When the population was subdivided into <50 and 50+ age groups, the incidence and prevalence were significantly higher in the older group. The rates we report here are higher than rates reported from any other locality. The reasons for the higher rates include optimal case identification, survey of a population with a higher incidence, and increasing aging of the population.

We previously suggested that cadmium (Cd), an environmental toxicant and constituent of tobacco smoke, inhibits progesterone secretion in cultured human placental trophoblasts by inhibiting low-density lipoprotein receptor mRNA expression. In the current study, we investigated whether Cd also disrupts progesterone synthesis via P450 cholesterol side-chain cleavage (P450(scc)) and 3beta-hydroxysteroid dehydrogenase (3beta-HSD), enzymes that play important roles in placental steroidogenesis. Human cytotrophoblasts were purified by density gradient centrifugation and incubated in Dulbecco modified Eagle medium + 10% fetal bovine serum with 0, 5, 10, or 20 microM CdCl(2) for 96 h. Cells progressed to syncytiotrophoblastic maturity regardless of treatment. No differences (P > 0.05) in cell protein and lactate dehydrogenase activity were observed between untreated trophoblasts and those treated with CdCl(2). However, P450(scc) and 3beta-HSD mRNA transcript levels declined in a dose-dependent manner (P <0.05) in trophoblasts cocultured with 5, 10, or 20 microM CdCl(2). P450(scc) activity was similarly inhibited (P < 0.05) by CdCl(2) treatment, although 3beta-HSD activity was not significantly affected. Coculture with 8-bromo-cAMP enhanced progesterone secretion in untreated cultures but did not reverse the decline in progesterone secretion induced by CdCl(2) treatment. CdCl(2) failed to influence cAMP content in cultured cells. Collectively, results suggest that P450(scc) enzyme is another site at which Cd interferes with placental progesterone production. However, it is unlikely that an inhibition of cAMP is involved with the inhibition of progesterone biosynthesis by Cd in human trophoblasts.

Radioimmunoassayable prolactin rises in postpartum women during nursing and after intravenous thyrotropin-releasing hormone (TRH). Prolactin release induced by TRH can be dissociated from the postsuckling response. In addition to this, increases in endogenous prolactin secretion are followed by marked breast engorgement and milk letdown, especially after intravenous TRH. In this group of breast-feeding women, vaginal smears remained atrophic even up to 410 postpartum days. Prolactin appears to influence the production of breast milk, and the maintenance of a regular nursing pattern seems to promote the maintenance of ovarian unresponsiveness to circulating gonadotropins.

The objective of this study was to characterize the rhesus macaque (RM) as a model for inhalational brucellosis in support of the U.S. Food and Drug Administration's (FDA) Animal Rule. The pathophysiology of chronic Brucella melitensis aerosol infection was monitored in two phases that each occurred over an 8-week time period; dose escalation (8 RMs; targeted doses of 5.0E؉03, 5.0E؉04, or 5.0E؉05 CFU/animal or the unchallenged control) and natural history (12 RMs; targeted dose of 2.50E؉05 CFU/ animal or the unchallenged control). RMs given an aerosol challenge with B. melitensis developed undulating fevers (6/6 phase I; 8/9 phase II), positive enriched blood cultures (5/10; phase II), and bacterial burdens in tissues starting 14 to 21 days postchallenge (6/6 phase I; 10/10 phase II). In addition, 80% (8/10; phase II) of infected RMs seroconverted 14 to 21 days postchallenge. RMs developed elevations in certain liver enzymes and had an increased inflammatory response by 3 weeks postchallenge as shown by increases in C-reactive protein (6/8) and neopterin (4/8), which correlated with the onset of a fever. As early as 14 days postchallenge, positive liver biopsy specimens were detected (2/8), and ultrasound imaging showed the development of splenomegaly. Finally, histopathologic examination found lesions attributed to Brucella infection in the liver, kidney, lung, and/or spleen of all animals. The disease progression observed with the RMs in this study is analogous to human brucellosis pathophysiology. Thus, the results from this study support the use of the RM as an animal model for inhalational brucellosis to evaluate the efficacy of novel vaccines and therapeutics against B. melitensis. Brucella is a Gram-negative coccobacillus that includes certain species that can cause disease in animals and humans. Brucella melitensis, one of the major species of Brucella, is an etiologic agent for brucellosis. This highly infectious pathogen can infect animals and humans, and it is considered to be one of the most severe human pathogens in the Brucella genus (25). Humans are usually infected following contact with infected animals or ingestion of contaminated milk, milk products, and meat. In addition, brucellosis is one of the most common laboratory-acquired infections, as well as the most common zoonosis (11). While B. melitensis is not typically considered a lethal pathogen in humans (less than 5% fatality rate), it can cause significant disease. Human brucellosis presents as a prolonged febrile illness with flu-like symptoms, such as night sweats, headache, depression, and arthritis. Chronic illness can lead to meningitis and endocarditis. In addition, relapses can occur, even with antibiotic treatment (13). Notably, humans can remain asymptomatic for weeks, months, or even years while infected with this pathogen (3).Brucella species are considered potential biological warfare agents due to their high infectivity, ability to debilitate infected people, and the persistent nature of human disease. In addition, Brucella i...

Red swamp crayfish (Procambarus clarkii) were placed for a period of 7 days in Bayou Trepagnier, a Louisiana waterway which received petroleum-laden effluents from a manufacturing complex several decades ago. However, coolant water from the plant continued to be released into the bayou until 1995. Analyses of sediments at the exposure site revealed heavy contamination by lead, chromium, and copper, while concentrations of arsenic and cadmium were very low. Significant bioaccumulation of lead was observed in the hepatopancreas and gills of 7-day-exposed crayfish, whereas chromium accumulated the most in the gills and blood. Concentrations of copper in the crayfish did not change during the course of the study, suggesting that this essential metal constituent of the respiratory pigment is successfully regulated even when crayfish are exposed to relatively high levels of copper in the sediments. There was no metal accumulation in the abdominal muscle of the crayfish. That damage to the hepatopancreas occurred during the exposure is suggested by histopathological studies which revealed swollen and vacuolated R cells and an increase in the pH of the digestive juices. Blood glucose levels, as well as ovarian and hepatopancreatic indices, were unchanged. This study demonstrates that accumulation of nonessential metals in crayfish tissues in a wetland environment contaminated by mixed pollution (metals and hydrocarbons) reflects the concentrations of metals in the sediment.