Use of a high-density DNA probe array for detecting mutations involved in rifampicin resistance in Mycobacterium tuberculosis.

A Mycobacterium high-density DNA probe array designed to detect rpoB mutations conferring rifampicin resistance in Mycobacterium tuberculosis was evaluated. The rpoB hybridisation patterns produced by 41 susceptible (RifS) and 59 rifampicin-resistant (RifR) clinical isolates of M. tuberculosis were compared with the results of conventional dideoxynucleotide sequencing of the rpoB gene. For all the RifR isolates, the rpoB hybridisation patterns correlated with the rpoB sequencing results. Among the 59 isolates, 11 distinct amino-acid changes were detected by the DNA probe array. Of these, 36 (61%) corresponded to replacement of the serine residue found in position 531 (S531L in 34 isolates and S531W in two isolates), 16 (27%) affected histidine 526 (five H526D, five H526Y, four H526L, one H526N and one H526R), four (6.8%) replaced aspartate 516 with a valine, and one (1.7%) replaced glutamine 513 with a leucine. Deletion of the asparagine residue at position 519 was detected in one isolate susceptible to rifampicin, but yielding c. 0.1% resistant colonies on rifampicin-containing medium. No mutation was detected in the rpoB region from one isolate yielding c. 5% of resistant colonies on rifampicin-containing medium. Finally, a D516Y substitution was detected in association with an unexpected mutation, G523W, not tiled on the DNA probe array, but which could be detected by analysing the hybridisation pattern obtained with the wild-type probes covering codon 523. In conclusion, the Mycobacterium probe array is a promising approach to rapid detection of mutations involved in rifampicin resistance in M. tuberculosis.

Treatment of homosexual alcoholics in government-funded agencies: provider training and attitudes.

Alcoholism treatment providers in 36 government-funded agencies in New York City were surveyed for information about their training for and attitudes toward the treatment of homosexual patients. The 164 respondents had limited knowledge about how to evaluate and treat homosexual alcoholics and frequently did not discuss sexual orientation with their clients even though they considered it important. The training and supervision of most providers in the treatment of alcoholic homosexual clients was substandard or nonexistent. About half of the providers believed that treatment programs would benefit from having openly gay staff and felt that being openly gay carried little professional risk. Respondents also reported that development of programs for homosexual alcoholics had little priority in their facilities. Many believed that homosexual alcoholics are less likely to seek help and may have more difficulty achieving sobriety.

Reasoning with contrary-to-fact propositions.

In the initial study, the ability of subjects at four age levels (10, 13, 15, 18 years) (1) to accept if-then premises as a basis for reasoning and (2) to reason correctly with if-then premises was examined. Half the subjects were assessed with four reasoning problems involving factually accurate premises. The other half received factually inaccurate premises which were derived from the preceding ones by altering a single term. Both tests included an abstract problem which preceded the concrete propositions. Results indicate that the 10 year olds, and to a lesser extent the 13 year olds, did have difficulty in accepting contrary-to-fact premises as a basis for reasoning. The 15 and 18 year olds did not, but did find reasoning correctly more difficult with contrary-to-fact premises. The second study examined the ability of 5 and 7 year olds to accept contrary-to-fact premises. Subjects were given factually false premises either alone or within a fantasy context. Results indicate that the fantasy context decreases the extent to which empirical knowledge interferes with accepting contrary-to-fact premises. This result supports the notion that a representational process may be involved in accepting contrary-to-fact premises.

PAs and HIV-antibody testing. The need for guidelines when the practitioner is at risk. Discussion.

The PA profession should establish guidelines for PAs at risk for infection with the human immunodeficiency virus (HIV) who wish to be tested for HIV antibody. Confidentiality and anonymity are critical factors, along with the employer's established policies. PAs working in emergency and surgical settings may be at greater professional risk of exposure to HIV; those with personal risk factors may consider being tested if their work exposes them to opportunistic infections. A clearinghouse for information should be established through the American Academy of Physician Assistants and state chapters.