Widening the differential for brain masses in human immunodeficiency virus-positive patients: syphilitic cerebral gummata.

A 39-year-old man with newly diagnosed human immunodeficiency virus (HIV) infection was admitted with right-sided weakness, right-sided vision loss and slurred speech, which worsened over several weeks. Brain imaging revealed bilateral intraparenchymal ring-enhancing lesions and enhancement of the right optic nerve. Serological findings were positive for venereal disease research laboratory test, whereas the cerebrospinal fluid venereal disease research laboratory test was nonreactive. Brain biopsy suggested a diagnosis of syphilitic cerebral gummata, and the patient's improvement with penicillin and dexamethasone further supported this etiology. Syphilitic cerebral gummata have rarely been reported in patients with HIV infection. This patient demonstrates that cerebral gummata should be considered in the differential diagnosis in immunocompromised patients with characteristic brain masses, that HIV and syphilis often coexist with early neurosyphilis appearing more frequently in this patient population and that normal cerebrospinal fluid studies may not represent a true lack of syphilitic activity in HIV patients.

Intestinal CFTR expression alleviates meconium ileus in cystic fibrosis pigs.

Cystic fibrosis (CF) pigs develop disease with features remarkably similar to those in people with CF, including exocrine pancreatic destruction, focal biliary cirrhosis, micro-gallbladder, vas deferens loss, airway disease, and meconium ileus. Whereas meconium ileus occurs in 15% of babies with CF, the penetrance is 100% in newborn CF pigs. We hypothesized that transgenic expression of porcine CF transmembrane conductance regulator (pCFTR) cDNA under control of the intestinal fatty acid-binding protein (iFABP) promoter would alleviate the meconium ileus. We produced 5 CFTR-/-;TgFABP>pCFTR lines. In 3 lines, intestinal expression of CFTR at least partially restored CFTR-mediated anion transport and improved the intestinal phenotype. In contrast, these pigs still had pancreatic destruction, liver disease, and reduced weight gain, and within weeks of birth, they developed sinus and lung disease, the severity of which varied over time. These data indicate that expressing CFTR in intestine without pancreatic or hepatic correction is sufficient to rescue meconium ileus. Comparing CFTR expression in different lines revealed that approximately 20% of wild-type CFTR mRNA largely prevented meconium ileus. This model may be of value for understanding CF pathophysiology and testing new preventions and therapies.

Cystic fibrosis pigs develop lung disease and exhibit defective bacterial eradication at birth.

Lung disease causes most of the morbidity and mortality in cystic fibrosis (CF). Understanding the pathogenesis of this disease has been hindered, however, by the lack of an animal model with characteristic features of CF. To overcome this problem, we recently generated pigs with mutated CFTR genes. We now report that, within months of birth, CF pigs spontaneously developed hallmark features of CF lung disease, including airway inflammation, remodeling, mucus accumulation, and infection. Their lungs contained multiple bacterial species, suggesting that the lungs of CF pigs have a host defense defect against a wide spectrum of bacteria. In humans, the temporal and causal relations between inflammation and infection have remained uncertain. To investigate these processes, we studied newborn pigs. Their lungs showed no inflammation but were less often sterile than controls. Moreover, after introduction of bacteria into their lungs, pigs with CF failed to eradicate bacteria as effectively as wild-type pigs. These results suggest that impaired bacterial elimination is the pathogenic event that initiates a cascade of inflammation and pathology in CF lungs. Our finding that pigs with CF have a host defense defect against bacteria within hours of birth provides an opportunity to further investigate CF pathogenesis and to test therapeutic and preventive strategies that could be deployed before secondary consequences develop.