North Carolina macular dystrophy, revisited

Progression of the maculopathy in North Carolina macular dystrophy (NCMD) was not well documented. Thus, the author recently examined 22 affected members of the original kindred. Evidence of progression of the macular disease was sought through comparison of the recent fundus findings with old fundus photographs and from subjective complaints of worsening visual acuity. Only 1 of the 22 affected subjects had evidence of such change. Additionally, two new findings of NCMD were observed: (1) severe macular lesions which were staphylomatous or excavated in appearance, not flat, and atrophic as previously described; and (2) peripheral retinal drusen variably present in affected subjects, in contrast to the "normal peripheral retina" originally described. These new findings, along with the generally stable course of the disease would seem to alter our understanding of the relationship of NCMD to other dominant macular dystrophies.     

A Mycobacterium ulcerans toxin, mycolactone, causes apoptosis in guinea pig ulcers and tissue culture cells

Mycobacterium ulcerans is the causative agent of Buruli ulcer, a tropical ulcerative skin disease. One of the most intriguing aspects of this disease is the presence of extensive tissue damage in the absence of an acute inflammatory response. We recently purified and characterized a macrolide toxin, mycolactone, from M. ulcerans. Injection of this molecule into guinea pig skin reproduced cell death and lack of acute inflammatory response similar to that seen following the injection of viable bacteria. We also showed that mycolactone causes a cytopathic effect on mouse fibroblast L929 cells that is characterized by cytoskeletal rearrangements and growth arrest within 48 h. However, these results could not account for the extensive cell death which occurs in Buruli ulcer. The results presented here demonstrate that L929 and J774 mouse macrophage cells die via apoptosis after 3 to 5 days of exposure to mycolactone. Treatment of cells with a pan-caspase inhibitor can inhibit mycolactone-induced apoptosis. We demonstrate that injection of mycolactone into guinea pig skin results in cell death via apoptosis and that the extent of apoptosis increases as the lesion progresses. These results may help to explain why tissue damage in Buruli ulcer is not accompanied by an acute inflammatory response.     

Mycobacterium ulcerans cytotoxicity in an adipose cell model

An adipose cell (SW872) model was developed to observe cellular necrosis and apoptosis upon Mycobacterium ulcerans infection and treatment with mycobacterial exudate. Apoptosis was likely due to secreted proteins, while necrosis was likely due to mycolactone. Our data suggest that additional factors in M. ulcerans may be involved in Buruli ulcer pathogenesis.     

Does resistance to pyrazinamide accurately indicate the presence of Mycobacterium bovis?

Mycobacterium bovis is best identified by screening those isolates of the Mycobacterium tuberculosis complex that have any pyrazinamide (PZA) resistance, using a confirmatory test such as spoligotyping, biochemical testing, or genomic deletion analysis. The sensitivity for detection of M. bovis is lowered to 82% when only PZA-monoresistant isolates are screened.     

Oesophagostomum species in pigs in england: 2. Oesophagostomum quadrispinulatum: Resistance to reinfection

Under experimental conditions, repeated infection with 500 larvae of Oesophagostomum quadrispinulatum induced a solid resistance in about 50 days, this being manifested by a failure of third-stage larvae to develop. An apparently stable population of a few hundred adult worms remained in the pigs for at least 200 days.     

Hyperthyroidism and polycythemia vera with chronic urticaria and angioedema

Of 154 patients with chronic urticaria, six manifested concomitant hyperthyroidism and four polycythemia vera. Investigations of serum IgE, immune complex quantitation, complement and skin biopsies failed to elucidate a causal relationship. Polycythemia vera and hyperthyroidism should be considered as possible associations in the evaluation of chronic urticaria.     

Treatment of tuberculosis in patients with advanced human immunodeficiency virus infection

BACKGROUND AND METHODS. Infection with the human immunodeficiency virus (HIV) increases the risk of tuberculosis and may interfere with the effectiveness of antituberculosis chemotherapy. To examine the outcomes in patients with both diagnoses, we conducted a retrospective study of all 132 patients listed in both the acquired immunodeficiency syndrome (AIDS) and tuberculosis case registries in San Francisco from 1981 through 1988. RESULTS. At the time of the diagnosis of tuberculosis, 78 patients (59 percent) did not yet have a diagnosis of AIDS, 18 patients (14 percent) were given a concomitant diagnosis of AIDS (as determined by the presence of an AIDS-defining disease other than tuberculosis), and the remaining 36 patients (27 percent) already had AIDS. The manifestations of tuberculosis were entirely pulmonary in 50 patients (38 percent), entirely extrapulmonary in 40 patients (30 percent), and both pulmonary and extrapulmonary in 42 patients (32 percent). The treatment regimens were as follows: isoniazid and rifampin supplemented by ethambutol for the first two months, 52 patients; isoniazid and rifampin supplemented by pyrazinamide and ethambutol for the first two months, 39 patients; isoniazid and rifampin, 13 patients; isoniazid and rifampin supplemented by pyrazinamide for the first two months, 4 patients; and other drug regimens, 17 patients. The intended duration of treatment for patients whose regimen included pyrazinamide was six months, and for patients who did not receive pyrazinamide, nine months. Seven patients received no treatment because tuberculosis was first diagnosed after death. Sputum samples became clear of acid-fast organisms after a median of 10 weeks of therapy. Abnormalities on all chest radiographs taken after three months of treatment were stable or improved except for those of patients who had new nontuberculous infections. The only treatment failure occurred in a man infected with multiple drug-resistant organisms who did not comply with therapy. Adverse drug reactions occurred in 23 patients (18 percent). For all 125 treated patients, median survival was 16 months from the diagnosis of tuberculosis. Tuberculosis was a major contributor to death in 5 of the 7 untreated patients and 8 of the 125 treated patients. Three of 58 patients who completed therapy had a relapse (5 percent); compliance was poor in all 3. CONCLUSIONS. Tuberculosis causes substantial mortality in patients with advanced HIV infection. In patients who comply with the regimen, conventional therapy results in rapid sterilization of sputum, radiographic improvement, and low rates of relapse.