Human immunodeficiency virus type 1 replication, immune activation, and circulating cytotoxic T cells against uninfected CD4+ T cells.

Cytotoxic T lymphocytes (CTL) that kill uninfected activated CD4+ T cells can be induced in vitro by stimulating CD8+ T cells with activated autologous CD4+ T cells. Similar CTL have been detected in circulating T cells from human immunodeficiency virus type I (HIV)-infected individuals. To define the in vivo correlates of this CTL activity, we studied plasma beta-2 microglobulin and HIV RNA levels, T-lymphocyte subset counts, and expression of CD28 on CD8+ T cells concurrently with circulating CTL activity against uninfected CD4+ T cells in 75 HIV-infected individuals at different stages of disease progression. Mean values of each parameter were compared in subsets of this group of 75 segregated on the basis of this CTL activity. The group with CTL against uninfected activated CD4+ T lymphocytes had more CD8+ T cells, a higher percentage of CD28 CD8+ T cells, and higher plasma levels of HIV RNA and beta-2 microglobulin. CTL against uninfected activated CD4+ T cells were predominantly CD28 and in HIV-infected individuals were associated with immunological or virological evidence of progressive disease. In HIV infection, circulating CTL activity against uninfected activated CD4+ T lymphocytes is associated with immune activation, CD8+ T cell expansion, accumulation of CD28 CD8+ T cells, and inadequate suppression of HIV replication.

Advances in the diagnosis and management of chancroid.

Improved technologies for the cultural diagnosis of chancroid have resulted in increased interest in the management and control of genital ulcer disease. New treatment regimens have been identified, and new control strategies have evolved. These strategies now permit localized introductions of chancroid into developed countries to be contained rapidly. However, additional work is still necessary in developing countries.

PIP: Physicians paid little attention to chancroid and its causative agent Hemophilus ducreyi until the late 1970s and early 1980s. Therefore diagnoses are insufficient. In addition, physicians do not manage chancroid well and public health officials cannot control its spread. Chancroid is endemic in developing countries, but periodically chancroid epidemics do occur in developed countries. Gram positive cocci which also flourish in chancroid ulcers often overgrow H. ducreyi (a gram negative rod) making it hard to diagnose infection. Besides, for optimal chance of H. ducreyi isolation, a health worker must directly inoculate pus from the ulcer onto either gonococcal or Mueller-Hinton agar in the Petri dish. To further complicate diagnosis, clinical and epidemiological characteristics of patients who are H. ducreyi culture negative are like those of patients who are H. ducreyi culture positive. Moreover genital ulceration varies like it does with Treponema pallidum or herpes simplex virus. In fact, only about 40% of men and 29% of women have an ulcer. Nevertheless a chancroid lesion starts out as papule that soon turns into an ulcer. Around 33% of all patients experience lymphadenopathy. If chancroid is not treated, the lymph nodes swell and exude pus. They eventually burst and drain chronically. Prostitutes and other sexually active females with ulcers tend to be reservoirs of H. ducreyi. As of late 1990, researchers could not culture H. ducreyi from asymptomatic males. Another exacerbation of the problems with chancroid is that H. ducreyi is resistant to most antibiotics. Yet erythromycin, ceftriaxone, and cefotaxime treatment yield positive results. A study in Kenya shows that treatments with 1000 mg, 500 mg, and 250 mg ceftriaxone cured 97% of men with genital ulcer disease. Since diagnosis is difficult; anyone with chancroid and his/her contacts should be treated immediately.

Prostitutes are a major reservoir of sexually transmitted diseases in Nairobi, Kenya.

Prostitutes are a major reservoir of sexually transmitted diseases in many developing nations. In Nairobi we found that 16%, 28%, and 46%, respectively, of upper-, middle-, and lower-social strata prostitutes were infected with Neisseria gonorrhoeae. Genital ulcers and infections with Haemophilus ducreyi were more prevalent among prostitutes of the middle and lower social strata. A group of 97 prostitutes of the lower social strata were followed longitudinally to determine the rate of reinfection with N. gonorrhoeae. The mean time to acquisition of a new infection was 12.0 +/- 9.2 days. These results show that in Nairobi prostitutes are a readily identifiable group of high-frequency transmitters of gonococcal infection. Strategies based on intervention in the prostitute reservoir could prove to be an effective means of control of gonococcal infections in developing nations.

Effect of added elastances on the first loaded breath in man.

Tidal volume together with end-inspiratory pressure was measured in four seated healthy men, during normal breathing and during single inspirations taken from a series of rigid containers which provided added elastances (range: 5-70 cmH2O/l). Experiments were performed both during quiet breathing and during ventilation increased by added dead space. Added elastic loads always resulted in a decreased tidal volume. This decrease was partly compensated by increased pressure developed by the inspiratory muscles; being more so with greater added elastance, control ventilation, or both. Analysis of our results indicates that the load-compensatory response may be attributed to changes in mechanical impedance of the ventilatory pump, due to the mechanical arrangement and the intrinsic properties of the inspiratory muscles (force-length and force-velocity relationships), changes in respiratory frequency with increasing ventilation, and to vagally mediated load compensation.