Insulin-dependent diabetes mellitus (IDDM) is associated with CTLA4 polymorphisms in multiple ethnic groups.

Linkage disequilibrium (association) analysis was used to evaluate a candidate region near the CTLA4/CD28 genes using a multi-ethnic collection of families with one or more children affected by IDDM. In the data set unique to this study (Spanish, French, Mexican-American, Chinese and Korean), the transmission/disequilibrium test (TDT) revealed a highly significant deviation for transmission of alleles at the (AT)n microsatellite marker in the 3' untranslated region (P = 0.002) and the A/G polymorphism in the first exon (P = 0.00002) of the CTLA4 gene. The overall evidence for transmission deviation of the CTLA4 A/G alleles is also highly significant (P = 0.00005) in the combined data set (669 multiplex and 357 simplex families) from this study and a previous report on families from USA, Italy, UK, Spain and Sardinia. Significant heterogeneity was observed in these data sets. The British, Sardinian and Chinese data sets did not show any deviation for the A/G polymorphism, while the Caucasian-American data set showed a weak transmission deviation. Strong deviation for transmission was seen in the three Mediterranean-European populations (Italian, Spanish and French) (P = 10(-5)), the Mexican-American population (P = 0.002) and the Korean population (P = 0.03). These results suggest that a true IDDM susceptibility locus (designated IDDM12) is located near CTLA4.

Undiagnosed tuberculosis in patients with human immunodeficiency virus infection.

We describe the clinical features of 11 patients with human immunodeficiency virus infection in whom tuberculosis was undiagnosed and untreated prior to death. Most patients (9 of 11) had pulmonary complaints and 8 of 11 had roentgenographic findings suggestive of tuberculosis (hilar or mediastinal adenopathy, pleural effusion, apical infiltrate or miliary pattern). Despite these findings, tuberculin skin tests were not performed in any of the patients. Acid-fast smears of sputum were obtained in three cases and bronchoscopy performed in only four, reflecting the low index of suspicion for tuberculosis. Pneumocystis carinii pneumonia was the presumptive diagnosis in nine cases but was confirmed in only one case. Autopsy revealed tuberculosis as the cause of death in four patients. Of the seven patients who did not undergo autopsy, disseminated tuberculosis, manifest by mycobacteremia, was the only life-threatening illness identified and probably contributed to death. Increased awareness of the clinical and roentgenographic features of tuberculosis in HIV-infected patients, combined with more intensive use of acid-fast smears and tuberculin skin testing, are necessary in order to decrease mortality from this treatable complication of HIV-infection.

Delayed diagnosis of tuberculosis in patients with human immunodeficiency virus infection.

PURPOSE: To determine the frequency with which the diagnosis of tuberculosis is delayed in patients with concomitant human immunodeficiency virus (HIV) infection, and to identify reasons for such delays. PATIENTS AND METHODS: We reviewed medical records of 52 consecutive HIV-infected patients with culture-proven tuberculosis seen at a 1,900-bed general hospital serving a predominantly indigent population in Los Angeles, where the prevalences of HIV infection and tuberculosis are high. The late-treatment (LT) group consisted of 25 patients in whom tuberculosis was untreated prior to death (n = 6) or treated more than 22 days after presentation (n = 19). The early-treatment (ET) group comprised 27 patients in whom antituberculous therapy was begun less than 16 days after presentation. RESULTS: Symptoms, physical and laboratory findings, chest roentgenographic abnormalities suggestive of tuberculosis (hilar adenopathy, pleural effusion, miliary pattern, cavitation, predominant upper lobe infiltrate), and frequencies of concomitant nontuberculous disease were similar in LT and ET groups. Delayed diagnosis of tuberculosis was attributable to errors in management in 21 (84%) of 25 LT group patients. The most common error was failure to obtain at least three sputum samples for acid-fast smear and mycobacterial culture in patients with clinical and chest roentgenographic findings compatible with tuberculosis (15 cases). Acid-fast sputum smears were positive in 25 (61%) of 41 cases of pulmonary tuberculosis. Acid-fast smears of stool were positive in eight (42%) of 19 cases. Blood cultures yielded Mycobacterium tuberculosis in 18 (38%) of 48 cases. CONCLUSIONS: Delayed therapy of tuberculosis in HIV-infected patients at our medical center was common and was not due to atypical manifestations of tuberculosis. In most cases, delays could have been avoided if adequate numbers of sputum samples for acid-fast smear and mycobacterial culture had been obtained, and if empiric antituberculous therapy had been given to symptomatic patients in whom chest roentgenographic findings were suggestive of mycobacterial disease.

Mycobacterial disease in patients with human immunodeficiency virus infection.

We compared the clinical features of disease due to tuberculosis and to Mycobacterium avium complex (MAC) in 94 patients with human immunodeficiency virus infection. Tuberculosis preceded the diagnosis of acquired immunodeficiency syndrome in 26 (67%) of 39 cases, compared with none of 55 with MAC infection. Chest roentgenographic findings suggested mycobacterial infection in 24 (83%) of 29 patients with pulmonary tuberculosis, compared with 7 (25%) of 28 with MAC infection. Sputum smears revealed acid-fast bacilli in 19 (83%) of 23 patients with pulmonary tuberculosis, but only 4 (16%) of 25 cases of pulmonary MAC infection. In 39 patients with tuberculosis, lymphadenitis and pleuritis were present in 13 (33%) and 8 (20%), respectively, but occurrence was rare in patients with MAC infection. In contrast, mycobacteremia was more frequent in MAC infection, occurring in 47 (85%) of 55 cases. In 5 patients, tuberculosis was unsuspected and probably contributed to death. These findings suggest that clinical features often distinguish tuberculosis from MAC infection in patients with human immunodeficiency virus infection. In addition, more intensive diagnostic use of sputum acid-fast smears may improve the outcome in patients with tuberculosis.