Interleukin-2 induced immune effects in human immunodeficiency virus-infected patients receiving intermittent interleukin-2 immunotherapy

To characterize the immunological effects of intermittent IL-2 therapy, which leads to selective increases in CD4+ T lymphocytes in HIV-infected patients, 11 patients underwent extensive immunological evaluation. While IL-2 induced changes in both CD4+ and CD8+ cell number acutely, only CD4+ cells showed sustained increases following discontinuation of IL-2. Transient increases in expression of the activation markers CD38 and HLA-DR were seen on both CD4+ and CD8+ cells, but CD25 (a chain of the IL-2 receptor) increased exclusively on CD4+ cells. This increase in CD25 expression was sustained for months following discontinuation of IL-2, and was seen in naive as well as memory cells. IL-2 induced cell proliferation, but tachyphylaxis to these proliferative effects developed after 1 week despite continued IL-2 administration. It thus appears that sustained CD25 expression selectively on CD4+ cells is a critical component of the immunological response to IL-2, and that intermittent administration of IL-2 is necessary to overcome the tachyphylaxis to IL-2-induced proliferation.     

A new HLA-A allele, HLA-A*6824, identified in three unrelated individuals

A novel allele, human leukocyte antigen (HLA)-A*6824, has been identified in three unrelated individuals of northwestern European origin in a period of less than 4 months, implying that this allele may be quite common in this population. HLA-A*6824 differs from A*680102 by a single nucleotide change at position 275 in exon 2, which results in a conservative amino acid substitution from lysine to arginine in the peptide-binding groove at codon 68.     

Repeat consultations after antibiotic prescribing for respiratory infection: a study in one general practice.

BACKGROUND. Several new antibacterial drugs have been introduced in the last 10 years with the aim of improved treatment of respiratory tract infection. AIM. The study set out to use repeat consultations as a measure of the outcome of antibiotic treatment for respiratory tract infection, and to develop a simple model for discussion of the cost effectiveness of alternative antibiotic treatments. METHOD. All consultations to one practice during a single winter were reviewed by one general practitioner. RESULTS. A total of 1140 patients had acute symptoms suggestive of respiratory infection. Of these, 899 patients (79%) were prescribed antibiotics at the first consultation and 160 of the 899 patients (18%) returned for one or more repeat consultations; only nine repeat consultations were due to adverse effects of the antibiotics prescribed. Only two patients were admitted to hospital for respiratory symptoms following initial antibiotic therapy and both patients had additional reasons for their admission. Using the highest estimates, the cost of a repeat consultation was found to be 28.54 pounds. These data were used to calculate how much more might be spent on more effective antibiotics at the first consultation. It would be difficult to justify increasing the cost of antibiotic treatment by more than 5 pounds per patient, even if the new treatment were 100% effective and all repeat consultations were due to treatment failure (5 pounds is equal to 28.54 pounds x 0.18, which is the maximum cost of a repeat consultation multiplied by the proportion of patients prescribed antibiotics who make repeat consultations). CONCLUSION. From these results and a review of the literature it can be concluded that new antibacterial drugs will have to be carefully targeted if they are to prove cost effective in practice. Other methods for reducing repeat consultation merit investigation.     

Gamma globulin inhibition of fibrin clot formation.

Myeloma gamma globulins have been reported to interfere with fibrinogen-fibrin conversion. A patient with multiple myeloma is described with a gamma globulin IgG1lambda concentration of 11 g per dl, prolonged thrombin time and poor clot retraction. Purified gamma globulin from the patient's serum and from normal serum caused prolongation of the thrombin time and reptilase clotting time assays in both normal plasma and in solutions of bovine fibrinogen. In addition, fibrin clots formed during the thrombin time assays were found to be ultrastructurally abnormal. This data suggests that the interaction of gamma globulin in the polymerization of fibrin may, in at least some cases, be due to nonspecific protein interaction.     

Therapeutic and persistent efficacy of a single application of doramectin applied either as a pour-on or injection to cattle infested with Boophilus microplus (Acari: Ixodidae)

The efficacy of a single treatment with a pour-on application or a subcutaneous injection of the macrocyclic lactone endectocide, doramectin, was evaluated in separate trials on Hereford heifers infested with Boophilus microplus (Canestrini). Significantly fewer ticks per calf were recovered from both groups of treated animals than from the complimentary untreated calves. The mean weights of engorged females and egg masses from both pour-on-treated and injectable-treated calves were also significantly smaller than the complimentary variables for the two groups of untreated calves. Among the treated groups, the mean weight of females from calves treated with the subcutaneous injection was 55% less than females from cattle that received the pour-on treatment and the weights of egg masses were 71% lighter than those from the pour-on-treated group. The estimates of percentage control for the two treatments were 88.6 for the pour-on formulation and a notably higher 99.8 for the injectable formulation. To obtain estimates of the effect of the treatments on the parasitic stages of the tick, cattle were infested with B. microplus larvae at three weekly intervals beginning 18 d pretreatment to ensure that, on the day of treatment, ticks in all three parasitic stages (adult, nymph, larva) would be on the cattle. The effect of the treatments on each parasitic stage was estimated by partitioning detached females into three groups by noting in which of the three 7-d intervals after detachment of engorged females began that detachment occurred. There was no difference for either the pour-on or injectable in the effect of the specific treatment on each parasitic stage. The persistent efficacy of the pour-on treatment against larvae placed on the hosts 1 wk after treatment was zero. The persistent efficacy of the injectable treatment ranged from 100 to 82.1% (mean, 93.7%) against the larvae placed on calves the first 3 wk after treatment and was still 44% against the fourth weekly posttreatment infestation. The injectable doramectin is a potential alternative to the coumaphos product now used as a precautionary treatment at USDA, Veterinary Services, Livestock Import Stations, for cattle exported from Mexico.     

In vitro assessment of virulence in Yersinia enterocolitica and related species.

We have examined 136 isolates of Yersinia species, comprising 112 strains of Yersinia enterocolitica, 12 of Y. frederiksenii, 8 of Y. intermedia, and 5 of Y. kristensenii, for the presence of 40- to 50-megadalton virulence-associated plasmids and expression of the following plasmid-associated characteristics: Congo red pigmentation (CR), calcium dependence, autoagglutination, hydrophobicity, resistance to normal human serum, and pathogenicity in mice. All 136 strains yielded both pigmented (CR+) and nonpigmented (CR-) variants. Only CR+ variants, however, were virulent for iron-overloaded, desferrioxamine B-treated mice (R. M. Robins-Browne and J. K. Prpic, Infect. Immun. 47:744-779, 1985). Although the in vitro virulence-associated characteristics generally occurred together, each one could be expressed independently. Strains of Y. frederiksenii, Y. intermedia, and Y. kristensenii also expressed individual virulence-associated properties. Of 53 Y. enterocolitica strains which were virulent for iron-overloaded, desferrioxamine-treated mice, all but one expressed every virulence-associated characteristic. Several strains which were avirulent for mice, however, demonstrated these characteristics in various combinations. Because many Yersinia strains, particularly environmental isolates, carried plasmids of 40 to 50 megadaltons, detection of plasmids provided little information about bacterial pathogenicity unless virulence-associated properties were also sought. The best in vitro predictor of virulence was autoagglutination, followed by calcium dependence. Because only CR+ variants expressed virulence-associated determinants, Congo red pigmentation is useful for selecting potentially virulent strains.