Long-term clinical investigation of the hepatobiliary agents: 99mTc-HIDA and 99mTc-p-butyl-IDA.

The organ distribution data for the two hepatobiliary agents HIDA and p-butyl-IDA in mice showed substantial differences in the extent and rate of hepatobiliary clearance of radioactivity. 99mTc-HIDA and 99mTc-p-butyl-IDA were used in computer assisted serial hepatobiliary scintigraphy. In normal subjects, the data of dynamic studies showed that the kidneys were no longer seen after 2.5 min with p-butyl-IDA. Liver radioactivity decreased significantly after 10 min with HIDA compared to 35 min with p-butyl-IDA. The gall bladder was always visualized at the 10-12th min and the 25-30th min with HIDA and p-butyl-IDA respectively. 99mTc-HIDA provided superior hepatic duct images.

Colostrum production by ewes and the amounts ingested by lambs.

Studies involving 49 ewes which were well nourished during the last eight weeks of pregnancy indicated that ewe weight loss during pregnancy and lamb birth weights followed the recognised pattern and were within acceptable "normal" limits. Colostrum production ranged from 1238 to 4593 g per ewe during the 48 h following the first suckling and there was evidence that production levels were related to demand by the lambs. Colostrum consumption by individual lambs was related to litter size. The smaller the litter size the greater was the amount ingested during the first 48 h of life. No clear relationship was established between the amount of colostrum consumed and the level of immunoglobulin in a lamb's circulation. Possible reasons for this are discussed.

Immunoglobulin levels in ewe colostrum and in lamb serum.

The immunoglobulin content of ewe colostrum falls rapidly after the first suckling and reaches a low level 36 h after the first feed. The whey content of colostrum will rise by more than 50 per cent during the same period. The production of colostral immunoglobulin during the 24 h following the first feed was related, in this work, to the amount of colostrum produced; the greater the colostrum production, the greater the immunoglobulin production. Colostrum production ranged from 1216 to 4493 g and immunoglobulin production from 22-21 to 86-34 g during the eight feeds studied. Colostrum production was related to demand by the lambs. There was a clear positive correlation between the total amount of immunoglobulin the lambs' circulation 30 h after the first feed and the immunoglobulin consumed. Approximately 20 to 25 per cent of the immunoglobulin ingested was present in the lambs' circulation at this time.

Immunological unresponsiveness of lambs to infection with Haemonchus contortus. Effect of infection in the ewe on the subsequent responsiveness of lambs.

Specific antigen-induced lymphocyte transformation in vitro and haemagglutinating antibody responses were absent from lambs infected with Haemonchus contortus. However, when lambs were injected with soluble third stage larval antigen of H. contortus, given on five occasions during the first 6 weeks of life, specific antigen-induced lymphocyte transformation and haemagglutinating antibodies were induced to the antigen. In particular, a periparturient increased susceptibility to infection and the resultant presence of heavy infections with H. contortus in ewes appeared to prime their lambs to respond and marked lymphocyte transformation was observed in antigen injected lambs born of heavily infected ewes. The enhancement of this response was associated with the colostral transfer of as yet unidentified factors. The superimposition of an infection with H. contortus in lambs which had been stimulated to respond to antigen, suppressed the in vitro responsiveness of their lymphocytes. Although individual variation was apparent, a direct correlation between the presence of in vitro antigen-induced lymphocyte transformation to third stage larval antigen and susceptibility to infection occurred.

Infection with gastrointestinal helminths. Effect of lactation and maternal transfer of immunity.

Lactation in sheep and mice was associated with a marked increase in susceptibility to newly acquired infection with Haemonchus contortus and Nematospiroides dubius, respectively. In sheep this increased susceptibility to infection with H. contortus occurred in late pregnancy and during lactation and was seen when the ewes were infected with both a single large dose of infective larvae and a "trickle" infection of 200 and 400 infective larvae of H. contortus given weekly for 14 weeks. Nonlactating ewes whose lactation had been terminated were able to reject the parasites which had been acquired in late pregnancy. A relaxation in the protective immune response was evident in immunized mice infected during lactation with N. dubius. However, despite this periparturient relaxation of immunity mice were capable of inducing a marked passive transfer of immunity to their offspring. Thus, neonatal mice born of mothers one or two months after the end of the immunizing schedule were protected against infection with N. dubius at 12 or 20 days of age.

Immunological unresponsiveness of lambs to infection with Haemonchus contortus. Modulation of responsiveness by exposure to soluble larval antigen.

The in vitro transformation of lymphocytes in the presence of antigen was used to assay the response of lambs to antigens of Haemonchus contortus. Neither uninfected lambs nor lambs infected with H. contortus up to 9 weeks of age developed in vitro lymphocyte responsiveness to antigen. A slight and transient increase in reactivity was demonstrable in some of the infected lambs when these were reinfected with H. contortus at 26 weeks of age. This lack of responsiveness could be modulated through the exposure of lambs, early in neonatal life, to multiple parenteral injections of soluble third stage larval antigen of H. contortus. Thus, antigen specific responses were apparent in the lymphocytes from 21-week-old lambs if these were injected with antigen when 2 to 17 weeks of age. In particular, marked antigen specific reactivity developed in 19- or 24-week-old lambs if such lambs were injected with antigen on five occasions over the first 6 weeks of life and subsequently infected with H. contortus when 7 weeks old. This responsiveness was enhanced when the lambs were reinfected with H. contortus at 26 weeks of age.