Routine follow-up examinations in breast cancer patients have minimal impact on life expectancy: a simulation study.

BACKGROUND: Little is known about the effects of routine follow-up examinations on life expectancy in cancer patients. Lately, the benefits of follow-up examinations have been debated, which has given rise to less extensive, though still frequent, follow-up strategies. In this study, a simulation model was applied to evaluate the impact of different follow-up strategies on life expectancy in breast cancer patients. MATERIALS AND METHODS: A five-state Markov chain model was developed, with which various follow-up strategies with regard to frequency and elaborateness were simulated. Calculations were based on a hypothetical population of breast cancer patients treated with curative intent. Medical aspects were studied, such as life expectancy and the proportion of patients who died from breast cancer. Social and psychological aspects and quality of life were not taken into account. Data from the literature were used to estimate the parameters needed for the model. RESULTS: The gain in life expectancy with standard follow-up compared to no follow-up examination, was about 2 months in breast cancer patients aged 50 years treated with curative intent. The percentage of patients who died from breast cancer was 45.4% with standard follow-up, versus 45.8% without follow-up. In older women, the gain was even less. Sensitivity analyses showed that the effects on life expectancy were robust. CONCLUSIONS: Our model showed that standard follow-up had minimal impact on the prognosis of breast cancer patients. It may be unnecessary to continue standard follow-up by medical specialists after the end of the surveillance period of the primary therapy, provided that the patients continue to have easy access to health care facilities in the case of symptoms or concern. However, future research is needed to study quality of life aspects of follow-up.

Vaccination against the gastrointestinal nematode, Haemonchus contortus, using a purified larval surface antigen.

Sheep were immunized with a purified antigen (Hc-sL3) expressed on the surface of L3 larvae of the gastro-intestinal parasite, Haemonchus contortus, using different adjuvant and immunization routes. In the first experiment, intradermal immunization of sheep with Hc-sL3 and QuilA did not result in reductions in faecal egg counts after subsequent challenge infection while significant reductions were obtained when aluminium hydroxide (AH) was used as the adjuvant. Significant protection with Hc-sL3 absorbed on AH was confirmed in a second experiment and this protection was maintained when dextran sulphate was added to the Hc-sL3/AH mixture while the addition of pertussis toxin abrogated the protective effect. Significant levels of protection, as determined by reductions in both faecal egg counts and worm burdens, were also obtained when the Hc-sL3/AH mixture was injected into the rectal mucosa or the Hc-sL3 antigen was deposited on the surface of the rectal mucosa with cholera toxin. No correlations with antibody levels or isotype and protection were observed.

An in vivo mammary infusion model for tissue migration of leucocytes during inflammation.

Infusion of LPS or nematode larvae into the mammary glands of sheep induces recruitment of neutrophils or eosinophils respectively. While neutrophil recruitment required only a single infusion of LPS, repeated infusions of parasite larvae were required to induce significant eosinophil migration into the lumen of the glands. Eosinophil recruitment was accompanied by a distinct population of lymphocytes consisting mainly of activated (MHC class II and CD25+) T cells. L-selectin was expressed at reduced levels on both neutrophils and eosinophils collected from the mammary gland compared with cells present in the blood of the same sheep. In addition, VLA-4 and beta 1-integrin were down-regulated or negative in mammary eosinophils compared with strong expression in the blood while neutrophils were negative for these markers in both mammary washes and blood. Eosinophils in blood and mammary glands were negative for MHC class II, CD25 and CD4. Mast cells and lymphocyte aggregates were present in the tissue of glands chronically stimulated with parasite larvae while eosinophils were only present if the gland had been recently stimulated. These studies show that detailed in vivo analysis of leucocyte migration can be easily performed in the sheep mammary infusion model which allows non-invasive and repeated sampling of inflammatory cells before and after tissue migration.

Distribution of antigen specific memory T cells in lymph nodes after immunization at peripheral or mucosal sites.

The distribution of antigen-specific memory T cells in different lymph nodes of sheep was determined using an antigen-specific in vitro proliferation assay. Lymph nodes were collected from sheep immunized simultaneously with avidin or ovalbumin in a peripheral tissue site (hind leg muscle) and keyhole limpet haemocyanin (KLH) in an intestinal tissue site (gut wall or colonic mucosa). The results showed a consistently high proliferative response in typical peripheral lymph nodes (popliteal and prescapular) and a low or negative response in gastrointestinal lymph nodes (abomasal and jejunal) while the response in other nodes was variable. The low proliferative response in the gastrointestinal lymph nodes was not due to the presence of suppressor CD8- lymphocytes and the proliferative response could not be raised to peripheral lymph nodes levels with the addition to cultures of IL-2 or mitomycin-C treated peripheral lymph node cells. The high proliferative response in the peripheral lymph nodes was not suppressed by the addition of mitomycin-C-treated gastric lymph node cells but was dramatically reduced by the addition of mAb against the IL-2-receptor or by depletion of CD4- T cells. The results suggest that antigen-specific proliferative memory T cells, which may be Th1-like memory cells, preferentially migrate to peripheral lymph nodes independent of their site of induction.

Humoral and cellular responses following local immunization with a surface antigen of the gastrointestinal parasite Haemonchus contortus.

A purified, larval specific antigen of the abomasal parasite Haemonchus contortus was used to immunize sheep. In an attempt to induce a local immune response in the abomasum, the antigen was injected twice into the abomasal wall after one peripheral immunization. Serum antibody responses were boosted by each intra-abomasal immunization but not by the challenge infection given 3.5 weeks after the last immunization. Examination of the specific antibody secreting cells (ASC) recirculating in the peripheral blood indicated that there was an increase in blood ASC 5 days after local stimulation. This increase was maintained only after immunization and not after infection, probably reflecting the different responses induced when antigen is presented by injection in an adjuvant or by the parasite during infection. High proliferative T cell responses in the abomasal lymph nodes were only observed in one of the five sheep immunized with antigen; this was also the only sheep in this group to maintain an adult parasite burden at postmortem corresponding with the lowest antibody response. Peak faecal egg counts after infection were reduced by 54% in the immunized group compared to control sheep. Egg counts in the control sheep were, however, variable and dropped quickly, probably as a consequence of the inflammatory response induced by the injection of aluminium hydroxide into the abomasal wall.

Resistance against Taenia hydatigena in sheep after passive transfer of serum or colostrum.

The role of antibody in the resistance of sheep to infection with Taenia hydatigena metacestodes was examined using passive transfer of immunoglobulin. The immunoglobulin either was experimentally transferred in serum, or was transferred from immune ewes to their new-born lambs in colostrum. Pooled serum from donor lambs which had received one, light, oral infection did not protect recipients although the donors themselves were immune. However, transfer of pooled serum from donors which had either received three oral infections, or three immunizations with solubilized T. hydatigena oncospheres in a water-in-oil adjuvant, resulted in 70-80% fewer cysts in the recipients. Colostrum from ewes infected with three high or low doses of T. hydatigena eggs was transferred to their lambs. A short acting protection (one to three weeks) was observed in the lambs. Comparisons by ELISA and Western blot, of the anti-T. hydatigena oncosphere antibody content of the donor sera, the sera of the recipients collected 24 h and seven days after transfer, the sera of the lambs and ewes, and the colostrum of the ewes, indicated that resistance to the challenge infection depends upon a critical level of antibody.

De novo deletion (2) (p11.2p13): clinical, cytogenetic, and immunological data.

We report a case of a boy with a de novo interstitial deletion of chromosome (2) (p11.2p13). Clinical features included dysmorphism of the face, genital region, and limbs, psychomotor retardation, and vitiligo. A reduced ratio of immunoglobulin (Ig) light chain expression (kappa/lambda ratio: 0.7) was found, compatible with deletion of one Ig kappa allele on chromosome 2p12. The patient had no clinical or laboratory signs of immunodeficiency.

Recombinant cytokines as immunological adjuvants.

This paper describes the bacterial expression and purification of bioactive recombinant ovine interleukin-2 (rovIL-2), interleukin-1 alpha (rovIL-1 alpha) and tumour necrosis factor alpha. These purified proteins had specific activities in appropriate bioassays of 1 x 10(7) 1 x 10(7) and 1 x 10(5) U/mg, respectively. Recombinant ovIL-1 alpha was assessed as an immunological adjuvant for the sheep response to the model protein avidin. When delivered either intradermally or intramuscularly in conjunction with avidin in aluminium hydroxide the rovIL-1 alpha significantly enhanced the secondary humoral response. Doses of 1, 10 or 100 micrograms per sheep enhanced the humoral response to a similar extent. Recombinant ovIL-1 beta had similar adjuvant activity in that it was demonstrated to significantly enhance the sheep humoral response to an experimental H. contortus antigen. This increase in specific antibody, however, did not correlate with enhanced protection against infection with third stage H. contortus larvae. In addition incorporation of rovIL-1 beta into the formulation was shown not to alter the isotype profile of H. contortus antigen specific antibody.

Blastomycosis: report of the first case from Alberta Canada.

The first known case of laboratory confirmed blastomycosis in Alberta occurred in 1970. The patient, who is believed never to have left Alberta, presented with of headaches, sore neck and impaired intellect. Initially, tuberculous or cryptococcal meningitis was suspected, but laboratory findings did not support the diagnosis. A fungus resembling Blastomyces dermatitidis was isolated from the venticular cerebrospinal fluid and lung at autopsy. A few yeast cells suggestive of B. dermatitidis were seen in lung and brain tissue sections. Initial attempts at in vitro conversion of the mycelial form of the isolate into yeast form on several enriched media were unsuccessful. The fungus gave +/- to ++ reactions B. dermatitidis specific conjugate by the direct fluorescent antibody technique, it was not pathogenic for mice and guinea pigs, and no asexual spores were produced in slide cultures. Further investigation indicated that the mycelial form of the fungus converted into its yeast form when an actively growing inoculum was used, although the yeast cells varied considerably in size. The yeast form produced disseminated infection in mice within 10 days. Exoantigenic analysis demonstrated an 'A' antigen specific for B. dermatitidis, which revealed the identity of this organism as an atypical strain of B. dermatitidis.