In vivo induction of Ia expression in murine cornea after intravitreal injection of interferon-gamma

Intravitreal injection of interferon gamma (IFN-gamma) induces increased expression of Class II major histocompatibility complex (Ia) antigen expression on corneal endothelial cells and stromal fibroblasts. In contrast, IFN-gamma has no detectable effect on Ia antigen expression in epithelium. Induction of Ia antigen expression was rapid with increases detectable as early as 6-12 hours after a single injection of 1 x 10(5) units. Expression peaked at 24-48 hours and decreased to background levels by 120 hours. The Ia antigen expression increased in a dose-dependent manner, and IFN-gamma treatment also induced the synthesis of increased amounts of a 65-kilodalton (kD) protein in the cornea. Increased levels of this 65-kd protein are seen as early as 12 hours after treatment and can be induced with as little as 1 x 10(2) units of IFN-gamma. The function of the 65-kd protein is unknown. This model should be useful in studies on in vivo modulation of Ia antigen expression.     

The natural history of uveitis

Summary Inflammatory diseases of the eye were known to the ancients, but only recently have the underlying mechanisms to this problem become better defined. During the middle portion of this century, most cases of uveitis thought to be caused by infectious agents, such as those responsible for syphilis and tuberculosis. Since then, it has become clear that endogenous mechanisms of immunomodulation play an important role in these disorders, which along with environmental and genetic factors make up an important triad. Animals studies have indicated the pivotal role of the T-cell in many of these disorders. The development of T-cell lines has helped to further delineate cell to cell interactions that occur during an ocular inflammatory event. The presence in the eye of uveitogenic antigens raises the strong possibility of autoimmune driven processes as well, similar to what is seen in the animal models. The better understanding of ocular inflammatory mechanisms has led to improved therapeutic strategies, including Sandimmune, and more recently Cyclosporine G, a related compound that may be less nephrotoxic. Newer therapeutic strategies will focus on even more novel modes of immunomodulation, probably without the use of medications.     

Dual-search coil for measuring 3-dimensional eye movements in experimental animals

The design and fabrication of a dual-search coil for measuring three-dimensional eye movements in experimental animals is described. The coil configuration is rigid and allows reliable precalibration in the magnetic field. It is implanted beneath the conjunctiva on the eye ball using the conventional implantation technique.     

Lifetime toxicity/carcinogenicity studies of FD & C Blue No. 1 (brilliant blue FCF) in rats and mice

FD & C Blue No. 1 was fed to Charles River CD rats and CD-1 mice as a dietary admixture in lifetime toxicity/carcinogenicity studies. The rat study was conducted with an in utero phase in which the compound was administered to the F0 generation rats (60/sex/group) at dietary concentrations of 0.0%, 0.0%, 0.1%, 1.0% or 2.0%. After randomly selecting the F1 animals, the lifetime phase was initiated at the same levels with 70 rats/sex/group, including two control groups. The maximum exposure times were 116 and 111 wk for males and females, respectively. The no-observed-adverse-effect levels are dietary concentrations of 2.0% for males (1072 mg/kg body weight/day), and 1.0% for females (631 mg/kg/day) based on a 15.0% decrease in terminal body weight and decreased survival in the high-dose females compared with the combined control groups. Charles River CD-1 mice (60/sex/group) were fed FD & C Blue No. 1 as a dietary admixture at levels of 0.0%, 0.0%, 0.5%, 1.5% or 5.0% in a lifetime toxicity/carcinogenicity study. The maximum exposure time was 104 wk for both males and females. No consistent, significant compound-related adverse effects were noted. The no-observed-adverse-effect level established in this study is a dietary concentration of 5.0% (7354 mg/kg/day and 8966 mg/kg/day for male and female mice, respectively.     

Tyramine-Induced cardiac arrhythmias

Five out of 12 physically healthy patients with depression undergoing a tyramine pressor test developed cardiac arrhythmias. These arrhythmias occurred in drug-free patients in three out of 12 infusions following as little as 0.03 mg/kg of tyramine and after moclobemide, a reversible inhibitor of monoamine oxidase-A, in four out of 14 tyramine infusions with as little as 0.04 mg/kg of tyramine. The arrhythmias seen were independent of patient's age and occurred both before and after 30 mmHg elevations in systolic blood pressure. Electrocardiographic abnormalities and arrhythmias seen were a loss of p waves, sinus tachycardia, frequent atrial ectopic beats, atrial premature beats, Wenckebach phenomenon, junctional rhythm, ventricular ectopics, varying QRS configurations, and ventricular bigeminy. Tyramine, both oral and intravenous, caused similar reproducible changes in dogs, though not in rats, mice or guinea pigs. Practical implications are that tyramine pressor testing in humans should be performed cautiously and only with adequate cardiac monitoring and resuscitation facilities at hand. These findings suggest that a normal dietary component can induce serious cardiac arrhythmias, and that a low-tyramine diet may be of value for patients who are susceptible to cardiac arrhythmias.     

Limited lists and the purchase of pharmaceutical products by government agencies in the RSA

The use of a limited list to restrict the range and type of medication used by medical institutions that operate under the auspices of the provincial authorities has been mooted as one possible method of cost containment. This study discusses the implementation of such measures in other countries and then quantifies the cost savings that might be obtained in the South African case. The possible savings are somewhat offset by other costs such a measure would introduce.     

AIDS and tuberculosis

The diagnostic and therapeutic implications of human immunodeficiency virus (HIV) infection and tuberculosis in South Africa, where tuberculosis remains a major health problem, are reviewed. Mycobacterium tuberculosis is a high-grade pathogen and is able to establish infection early in immunodeficiency. With HIV infection showing significant entry into the heterosexual population in the RSA, an increasing number of cases with both infections can be expected to occur. The radiological appearance in combined infection is variable, ranging from a formal cavitatory picture to the more common finding of diffuse pulmonary infiltration. Intrathoracic adenopathy is a more specific sign of tuberculosis in HIV infection, since it is not associated with persistent generalised lymphadenopathy and pulmonary opportunistic infections, such as Pneumocystis carinii pneumonia. Intercurrent pneumonic infections and other pulmonary manifestations of HIV disease render the interpretation of new infiltrates on chest radiography problematical. Tuberculin skin testing remains useful in HIV infection and should be performed in all HIV-infected patients. The value of tuberculosis serology still remains questionable. Standard antituberculosis drug regimens are effective, but maintenance treatment must be continued for life and should include isoniazid and rifampicin. BCG vaccination is recommended routinely at birth in infants with HIV infection and for asymptomatic HIV-infected individuals who have not previously been immunised.