Survival differences in European patients with AIDS, 1979-89. The AIDS in Europe Study Group.

OBJECTIVES--To examine the pattern of survival and factors associated with the outcome of disease in patients with AIDS. DESIGN--Inception cohort. Data collected retrospectively from patients'' charts. SETTING--52 clinical centres in 17 European countries. SUBJECTS--6578 adults diagnosed with AIDS from 1 January 1979 to 31 December 1989. MAIN OUTCOME MEASURES--Survival after the time of diagnosis. RESULTS--The median survival after diagnosis was 17 months, with an estimated survival at three years of 16% (95% confidence interval 15% to 17%). Patients diagnosed in southern Europe had a shorter survival, particularly immediately after the time of diagnosis, compared with patients diagnosed in central and northern Europe (survival at one year (95% confidence interval) 54% (52% to 56%) 66% (64% to 68%), 65% (63% to 66%), respectively. The three year survival, however, was similar for all regions. The regional differences in survival were less pronounced for patients diagnosed in 1989 compared with earlier years. Improved survival in recent years was observed for patients with a variety of manifestations used to define AIDS but was significant only for patients diagnosed with Pneumocystis carinii pneumonia. The three year survival, however, remains unchanged over time. CONCLUSIONS--Survival of AIDS patients seems to vary within Europe, being shorter in southern than central and northern Europe. The magnitude of these differences, however, has declined gradually over time. Short term survival has improved in recent years, but the long term prognosis has remained equally poor, reflecting the fact that the underlying infection with HIV and many of the complicating diseases remains essentially uncontrolled.     

Relapse rate and long-term management of plaque psoriasis after treatment with photochemotherapy and dithranol.

The relapse rate of plaque psoriasis after initial clearing with the "Ingram" dithranol regimen or photochemotherapy was comparable when no maintenance treatment was given. It was estimated that psoriasis recurs to half of its pretreatment extent after about six months in half the patients. Maintenance treatment with photochemotherapy once a week or once every three weeks was useful in reducing the relapse rate. This study failed to show any statistical difference in relapse rates between these two maintenance schedules. If this finding turns out to be true over longer periods of study the maintenance schedule entailing treatment once every three weeks with its lower cumulative dose of long-wave ultraviolet light will clearly be preferable. The psoriasis in most patients was under better overall control with maintenance treatment than with intermittant clearing courses given when the extent of the psoriasis had become unacceptable to them. There was, however, a group of roughly one-fifth of patients who remained in satisfactory remission for over 16 months after initial clearing. Regular maintenance treatment was unnecessary in them. Much more information is needed on response to treatment in subgroups of patients to permit recognition from the start of which patients are likely to have long remission and which are not.     

The application of databases and PCR in the cloning of glycosidase genes from the protozoan Tritrichomonas foetus

Conserved sequence amplification (CSA) has been used to obtain sequence data for two glycosidase genes from the primitive eukaryote Tritrichomonas foetus. Few genes have been cloned from this organism, and there is little information concerning protein sequence. CSA is reliant on the use of database searches to identify short sequences of 3–9 amino acids conserved within a protein across a wide range of species. PCR primers are then constructed based on this sequence data and the DNA is amplified and sequenced. In the case of the β-galactosidase gene, N-terminal amino acid sequence data were used to construct a primer that replaced the upstream primer to ensure the amplified product was related to β-d galactosidase CSA was also applied to the gene encoding the enzyme β-N-acetyl-d-glucosaminidase from T. foetus, but in this case a segment of DNA was amplified, which, if correct, should contain a third conserved motif. The products of the CSA were sequenced, and the data obtained were compared to data in the SwissProt database. The results obtained suggest that this approach is useful for the cloning of genes to obtain novel sequence data from organisms where little genetic information is available.     

The accuracy of the American College of Sports Medicine metabolic equation for walking at altitude and higher-grade conditions

The purpose of this study was to examine the accuracy of the American College of Sports Medicine (ACSM) walking equation at low walking speeds, altitude (1,550 m), and higher grades. Twenty men and women (mean +/- SD, age, 28 +/- 6 years; height, 171 +/- 13 cm; weight, 67.8 +/- 18.1 kg) completed 2 randomized testing sessions under altitude (AL) (P(I)o(2) = 123.1 mm Hg [20.93%]) and sea level control (SLC) (P(I)o(2) = 147.3 mm Hg [25.00%]) conditions. Steady-state oxygen uptake (Vo(2)) was measured while subjects walked at 50 m.min(-1) at 8 separate grades (0, 5, 10, 15, 18, 21, 24, and 27%). Steady-state Vo(2) measurements from the last 2 minutes of each grade in AL and SLC were compared to the predicted Vo(2) of each grade according to the ACSM walking equation. Mean Vo(2) differences between predicted and AL values ranged from -0.5 to 1.4 ml.kg(-1).min(-1), averaged -0.1 ml.kg(-1).min(-1) across all grades, and were significant (p < 0.05) at 0 percent grade. Mean Vo(2) differences between predicted and SLC values ranged from 0.6 to 3.0 ml.kg(-1).min(-1), averaged 1.4 ml.kg(-1).min(-1) across all grades, and were statistically significant (p < 0.05) at 0 and 5 percent. The standard error of the estimate (SEE) for the prediction of Vo(2) under AL and SLC were 2.2 and 2.0 ml.kg(-1).min(-1), respectively. Total errors for the prediction of Vo(2)max under AL and SLC were 2.3 and 2.6 ml.kg(-1).min(-1), respectively. Overall, the findings indicate that the current ACSM prediction equation for walking is appropriate for application at low speeds, moderate altitude, and higher grades.     

Peptide-specific CD8 T regulatory cells use IFN-gamma to elaborate TGF-beta-based suppression

We identified a murine peptide-specific CD8 T regulatory cell population able to suppress responding CD4 T cells. Immunization with OVA, poly(I:C), and anti-4-1BB generated a population of SIINFEKL-specific CD8 T regulatory cells that profoundly inhibited peptide-responding CD4 T cells from cellular division. The mechanism of suppression required IFN-gamma, but IFN-gamma alone was not sufficient to suppress the responding CD4 T cells. The data show that CD8 T regulatory cells were unable to suppress unless they engaged IFN-gamma. Furthermore, even in the absence of recall with peptide, the CD8 T regulatory cells suppressed CD4 responses as long as IFN-gamma was present. To examine the effector mechanism of suppression, we showed that neutralizing TGF-beta inhibited suppression because inclusion of anti-TGF-beta rescued the proliferative capacity of the responding cells. TGF-beta-based suppression was dependent completely upon the CD8 T regulatory cells being capable of binding IFN-gamma. This was the case, although peptide recall of primed IFN-gamma (-/-) or IFN-gammaR(-/-) CD8 T cells up-regulated pro-TGF-beta protein as measured by surface latency-associated peptide expression but yet were unable to suppress. Finally, we asked whether the CD8 T regulatory cells were exposed to active TGF-beta in vivo and showed that only wild-type CD8 T regulatory cells expressed the TGF-beta-dependent biomarker CD103, suggesting that latency-associated peptide expression is not always congruent with elaboration of active TGF-beta. These data define a novel mechanism whereby IFN-gamma directly stimulates CD8 T regulatory cells to elaborate TGF-beta-based suppression. Ultimately, this mechanism may permit regulation of pathogenic Th1 responses by CD8 T regulatory cells.