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Effects of the plane of nutrition and age on the proliferation and activation of lymphocyte subsets from milk replacer-fed calves were investigated in vitro. Holstein calves were fed a standard (0.45 kg/d of a 20% crude protein, 20% fat milk replacer, n = 4) or intensified (1.14 kg/d of a 28% crude protein, 20% fat milk replacer, n = 4) diet from 1 to 8 wk of age. Average daily weight gain of intensified-diet (0.66 kg/d) calves was greater than that of standard-diet (0.27 kg/d) calves. Relative to the pokeweed mitogen-induced responses of CD4(+) cells from steers (5 to 6 mo of age), CD4(+) cells from 1-wk-old calves showed decreased proliferative activity, delayed increase in CD25 expression, and no demonstrable increase in CD44 expression or decrease in CD62L expression. Calf CD8(+) and gammadeltaT-cell receptor(+) cells, unlike T-cells from the older animals, did not demonstrate decreased expression of CD62L after stimulation with mitogen. The increased expression of CD44 by mitogen-stimulated gammadeltaT-cell receptor(+) cells from older animals was not seen in gammadeltaT-cell receptor(+) cells from 1-wk-old calves. At wk 8 of age, mitogen-induced proliferation and expression of activation antigens by T-cells from standard-fed calves were similar to responses of T-cells from steers indicating rapid maturation of T-cell function during the neonatal period. Feeding calves an intensified milk replacer was associated with decreased proliferation of mitogen-stimulated CD4(+), CD8(+), and gammadeltaT-cell receptor(+) cells; decreased CD25 expression by mitogen-stimulated CD4(+) and CD8(+) cells; and decreased CD44 expression by mitogen-stimulated CD8(+) cells. These results indicate that the functional capacity of the calf's T-cell population becomes more adult-like during the first weeks of life and suggest that nutrition modulates T-cell function during this period of immune maturation.

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Effects of neonatal vaccination on antigen-specific cellular and humoral immune responses of dairy calves have not been well described. The purpose of this study was to characterize the ontogeny of the adaptive immune response in calves sensitized to the attenuated strain of Mycobacterium bovis, bacillus Calmette-Guerín. Holstein bull calves were nonvaccinated (n = 6, vaccination controls) or vaccinated subcutaneously (n = 6) with bacillus Calmette-Guerín at 1 and 7 wk of age. Composition and functional capacities of blood mononuclear cell populations from calves were evaluated at 1 (prevaccination), 3, 6, 7, 8, 9, and 12 wk of age. Young adults (nulliparous heifers, n = 4) vaccinated in an identical manner were sampled concurrently to evaluate effects of animal maturity on the development of the adaptive immune response. Responses of nonvaccinated calves to recall antigen (Mycobacterium bovis purified protein derivative) ex vivo and in vivo (i.e., cutaneous delayed-type hypersensitivity) were minimal or nonexistent. Responses of cells from vaccinated calves and young adults to recall antigen, however, were evident as early as wk 2 after primary vaccination. Antigen-induced T cell subset proliferation, and secretion of interferon-gamma, nitric oxide, and tumor necrosis factor-alpha by cells from vaccinated calves were comparable to or greater than responses of vaccinated adults during the 11-wk study. Eleven weeks after primary vaccination, cutaneous responses of vaccinated calves and young adults to intradermal administration of antigen were pronounced and comparable, demonstrating the capacity of the bovine neonate to develop a vigorous cell-mediated immune response in vivo. Antibody responses (i.e., antibody concentrations in sera and in supernatants from antigen-stimulated cultures of blood mononuclear cells) of vaccinated calves, in contrast, were markedly lower than parallel responses of vaccinated adults. In conclusion, these results suggest that the bovine neonate can mount a vigorous, adult-like cell-mediated immune response when vaccinated at an early age.

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Temporal contrast sensitivity was measured for mirror-image sawtooth (rapid-on and rapid-off) and sine waveforms for a 1.8 deg foveal target. In one experiment, contrast sensitivity was measured for 2-26 Hz stimuli at target mean illuminance levels of 5-1260 td. At 5 td, contrast sensitivity functions for sawtooth and sine waveforms, expressed in terms of the Fourier fundamental amplitude, are equivalent. At higher light levels, sawtooth sensitivity increasingly exceeds sine sensitivity and rapid-off (decremental) sawtooths show progressively greater sensitivity than rapid-on (incremental) sawtooths. This pattern of results was obtained for two color-normal observers and for a deuteranopic observer. In a second experiment, sawtooth and sine sensitivity was tested at 500 td with an extended low-frequency range, to 0.5 Hz. Rapid-off and rapid-on sensitivities declined only slightly at low temporal frequencies in contrast with sine sensitivity. To interpret our data, we evaluate two single-pathway models (last-stage asymmetric detector and compressive response-intensity non-linearity) and a dual-pathway model in which incremental and decremental waveforms are detected by separate ON and OFF visual mechanisms.

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Symptoms and signs were recorded for 1007 infants younger than 6 months of age seen at home (298) or hospital (709) and correlated with four grades of illness severity. Most symptoms, present in the preceding 3 days, were associated with all grades of illness. Only four symptoms were not reported in well infants: a fluid intake less than a third of normal, convulsions, frank blood in the stools, and bile-stained vomiting. By comparison, many signs were seen only in ill infants. Those associated only with moderate or serous illness were marked retraction of the lower ribs, high-pitched or moaning cry, expiratory grunt, loss of alertness, central cyanosis, and severe hypotonia. Although these will not identify all seriously ill infants, parents and professionals should be taught to recognize these important symptoms and signs of serious illness.

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A scoring system has been developed to grade the severity of acute systemic illness in babies under 6 months of age. Data were collected on 28 symptoms and 47 signs from 1007 babies with a spectrum of illness ranging from well to seriously ill. Ordinal regression analysis identified 19 symptoms and signs which in combination graded the severity of the illness most accurately. The coefficients were converted to scores. The higher the score the more serious the illness. When applied to a theoretical cohort of 10,000 babies at home, a score less than 8 has a specificity of 98%, and a score of 13 or more a sensitivity of 92%. The positive predictive value for serious illness increases from zero at a score of zero to approaching 100% at scores over 30. The scoring system has been developed into score cards for parents and professionals.

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This paper defines the normal range of respiratory rate in babies under 6 months of age. It was counted by two observers in 1007 babies of whom 709 were seen when presenting to hospital for assessment of an acute illness, and 298 on a random basis at home. Whether they were asleep, content, or crying was recorded and the severity of their illness graded. The diagnosis was also recorded. The mean (SD) for the respiratory rate in babies seen awake was 61 (18) breaths/minute at hospital and 61 (14) breaths/minute at home. The respiratory rate when awake did not correlate with the severity of a baby's illness or the presence of serious lower respiratory tract infections. Sleeping babies had a significantly lower mean rate than awake babies at 42 (12) breaths/minute. Crying babies had a significantly lower mean rate than awake and content babies: 51 (14) breaths/minute compared with 61 (18) breaths/minute.

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Symptoms were assessed in 298 infants under 6 months old seen at home. Their mothers were asked if they were concerned about their babies and then questioned about the presence, duration, and severity of 28 predefined symptoms. Forty seven mothers expressed concern about their babies (16%), whereas on direct questioning 241 (81%) reported symptoms present within the last 24 hours. One hundred and twenty three (41%) reported three or more. Many of the symptoms occurred in more than 15 babies (5%). The commonest were cold peripheries (117, 39%), noisy breathing (88, 30%), and rash (68, 23%). These had often been present for many days. Only 257/819 reported symptoms (31%) were of recent onset (less than 4 days) with 168 (21%) graded by the mother as moderate or severe. A few highly specific symptoms that were associated with serious conditions were rare. Symptoms cannot be interpreted without detailed questioning taking their severity and duration into account, and most occur too often to be used as indicators for referral.

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