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Twenty-one children with migraine and/or hyperkinetic behavior disorder which was successfully treated with an oligoantigenic (few-foods) diet also suffered from nocturnal and/or diurnal enuresis. On diet, the enuresis stopped in 12 of these children and improved in an additional four. Identification of provoking foods was by sequential reintroduction of the foods that were avoided on the oligoantigenic diet. In eight of the 12 children who recovered on the oligoantigenic diet and in the four who improved, reintroduction of one or more foods provoked a reproducible relapse of the enuresis. Nine children were subjected to a placebo-controlled, double-blind reintroduction of provoking foods. Six children relapsed during testing with incriminated foods; none reacted to placebo. Enuresis in food-induced migraine and/or behavior disorder seems to respond, in some patients, to avoidance of provoking foods.

Most (18/21) children with perennial asthma gave dual (immediate and late) responses to bronchial provocation with two of Dermatophagoides pteronyssinus, and either timothy grass pollen or cat fur. Most (19/21) also showed dual responses to skin prick tests, only half (11/21) gave dual responses in the nose, mainly with timothy grass pollen, and these were associated with allergic rhinitis. Only two children gave dual responses in lung, skin and nose to both antigens, and only two gave immediate reactions without late reactions in all positive tests; most showed different patterns of response according to the organ tested or the antigen used for provocation. Our results suggest that local factors may be important in determining the pattern of allergic response in a 'target' organ, and that dual responses are strongly associated with the patient's symptoms.

Passively transferred MOPC 315 IgA myeloma protein accelerated the elimination of DNP-ovalbumin, to which the myeloma protein bound with antibody-like affinity, from the circulation and increased the subsequent antibody response to hapten and to carrier, when injected with or without adjuvant.

36 parents of infants who had died suddenly did not differ in frequency of atopic symptoms, immediate skin tests, IgE, IgE antibody, immunoglobulin G, A, and M, or yeast opsonisation, from 36 matched controls, although atopy was common (about half had atopy in both groups.

An 8-week course of 3 mg. per kg. body-weight per day of cyclophosphamide was administered to eighty-two children with steroid-senstitive nephrotic syndrome. One died, and of the remainder, 69% were in remission after 1 year and 44% after 4-years. Older children and those in whom cyclophosphamide was given during a steroid-maintained remission fared better.

T lymphocyte mobility is low in patients with low neutrophil mobility. Thymocytes move comparably with normal mature T lymphocytes. Histamine accelerates T lymphocyte mobility in healthy subjects, patients with defective lymphocyte mobility and thymocytes. Ascorbic acid increases lymphocyte mobility of healthy subjects and thymocytes. Inhibition of mobility of T- or Tmu-depleted T lymphocytes by complexed IgG casts doubt on previous reports that the T gamma cells do not move.

Among 377 patients with primary hypogammaglobulinaemia, mainly common variable immunodeficiency (CVID), 316 patients survived the first 2 years after diagnosis and were the subject of a study of cancer incidence. Among the 220 patients with CVID, there was a 5-fold increase of cancer due mainly to large excesses of stomach cancer (47-fold) and lymphomas (30-fold). The excess of stomach cancer is probably related to the high frequency of achlorhydria in CVID. 3 of the 7 patients with stomach cancer and CVID survived for 5 years or longer.

Selected immunologic functions were assessed in 14 patients with the Shwachman syndrome. Nine patients were neutropenic and four had low levels of IgA or of IgM. Neutrophil mobility was significantly defective in the group of patients as a whole (in 12 it was below the lower limit of normal) and in their parents. No other consistent abnormality in immunity was found. These results suggest that the defective neutrophil mobility is a feature of Shwachman syndrome which may contribute to the vulnerability of these patients to frequent infections. The defect appears to be a primary genetic one, inherited as an autosomal recessive characteristic consistent with the assumed inheritance of Shwachman syndrome.

Members of four generations of a family had a defect of serum opsonization for yeast phagocytosis consistent with dominant inheritance. 2 were healthy, one had chronic osteomyelitis, and the fourth developed a fatal illness in infancy characterized by exfoliative dermatitis, diarrhoea, multiple bacterial infections, and failure to thrive, which resembled the two prevously reported cases with this opsonization defect. At necropsy the infant also had lymphoid depletion, which was possibly secondary, and massive histiocytic infiltration.

Fifteen patients with infantile bone and joint infections were studied immunologically and clinically, 3 at the time of illness and 12 later. Abnormality of immunoglobulins, or complement, or phagocytes was found in 9 patients; 6 were within normal limits for the tests undertaken. Immunodeficiency is probably responsible for the subdued clinical signs of infection and for delayed diagnosis in some patients. It was also related to the extent of femoral head damage in infective arthritis of the hip and to the incidence of wound infection in late elective surgery.

Atopic systems were more common in children with steroid-responsive nephrotic syndrome (S.R.N.S.) than in matched controls, and HLA-B12 was more common in children with S.R.N.S. than in adult controls. Atopic symptoms (particularly hayfever), positive prick tests with grass pollen antigens, and a higher mean serum concentration of IgE antibody to timothy grass pollen were more common in nephrotic children with HLA-B12 than in those without HLA-B12. There was also an increased frequency of the haplotype HLA-A1 and HLA-B8, mainly among the non-atopic patients.

The effect of feeding ovalbumin was studied in CBA, C3H, SWR/J and A inbred strains of mice. In non-immune animals differences were observed in their abilities to absorb intact antigen and eliminate it from their circulation. Following oral immunization, C3H mice were able to absorb significantly less ovalbumin than controls, however no evidence for immune exclusion was found in the other strains. Oral tolerance could be induced in all strains tested but in CBA and SWR/J mice oral immunization had to be continual, via the drinking rather than a single daily gastric intubation. The results suggest that genetic differences exist in the handling of antigen by the gut. If similar differences exist in man they may underly differences in susceptibility to food allergy.

In a controlled trial, symptomatic treatment alone, or 12 weeks of cyclophosphamide or azathioprine were compared in Nigerian children with nephrotic syndrome (mainly quartan malarial nephropathy) and poorly selective proteinuria. Full remission in 2 patients in each of the two groups treated with drugs, and diminution of proteinuria in most patients in the cyclophosphamide group showed possible evidence of benefit. Infections during treatment were significantly more common in the drug-treated groups but were controllable. Mortality from renal failure in the 2nd year after treatment was significantly greater in the azathioprine-treated group than in the other two, suggesting that the drug may have exacerbated the nephritis. The 5-year survival rate was similar in the cyclophosphamide and the control group.

76 selected overactive children were treated with an oligoantigenic diet, 62 improved, and a normal range of behaviour was achieved in 21 of these. Other symptoms, such as headaches, abdominal pain, and fits, also often improved. 28 of the children who improved completed a double-blind, crossover, placebo-controlled trial in which foods thought to provoke symptoms were reintroduced. Symptoms returned or were exacerbated much more often when patients were on active material than on placebo. 48 foods were incriminated. Artificial colorants and preservatives were the commonest provoking substances, but no child was sensitive to these alone.

Remission followed prednisolone therapy in 9 out of 21 Nigerian children with the nephrotic syndrome who had highly selective proteinuria (CG/CA less than 15%). Of these, 5 patients have remained well off all treatment during a follow-up of nearly 5 years, 4 have relapsed more than once but have responded to further courses of prednisolone. 3 of 21 with less selective proteinuria also remitted but all relapsed and only one of these has responded again. The other two have relapsed and further courses of prednisolone have not totally abolished their proteinuria though they are asymptomatic and in good health. Toxicity (hypertension, sometimes with encephalopathy and infection) was commoner in the patients with less selective proteinuria treated with steroids than in those with highly selective proteinuria. 3 steroid-sensitive patients who had had repeated relapses became free from relapse off all treatment after a course of cyclophosphamide, given during steroid-maintained remission. All but 2 of the renal biopsies taken were regarded as abnormal. The lesions were less severe in those who responded than in those who did not. There is some evidence to suggest that Plasmodium malariae may be a cause of some of the steroid-sensitive disease, as well as the steroid-resistant.

Antigenic proteins may be absorbed intact. We report here results from in vivo experiments in mice showing that the prior feeding of protein antigen may reduce the subsequent absorption of that antigen without altering its elimination from the circulation. This may be a function of local immunity. We have also shown that the same feeding regime can paradoxically induce a state of systemic tolerance and suggest that the two phenomena contribute to the safe handling of these antigens.

Four patients with defective yeast opsonisation and protracted diarrhoea are reported. Plasma infusions improved the opsonising function in all 4 and the diarrhoea in 3. This immunological abnormality was assessed in 100 sequential patients with chronic diarrhoea associated with various gastrointestinal disorders; 52 with protracted diarrhoea and failure to thrive of undetermined cause, 26 with 'toddler diarrhoea', 8 with coeliac disease, 5 with chronic inflammatory bowel disease, and 9 with miscellaneous disorders. 23% of the patients with protracted diarrhoea of undetermined cause had defective opsonisation, a greater proportion (P less than 0.05) than that in 'toddler diarrhoea' or the remaining patients, in whom the frequency (4%) was similar to that (5%) in healthy populations. We suggest that yeast opsonisation be tested in children with protracted diarrhoea, as plasma infusions can be an effective form of treatment.

Raised levels of circulating soluble immune complexes were found in sera of 21 of 29 patients with lupus nephritis. They correlated well with clinical disease activity in the group as a whole and with the course of individual patients. In 2 patients, high-dose methylprednisolone reduced levels of immune complexes and led to clinical improvement. The size of the IgG complexes was studied in 7 patients. The complexes were very large (2-5-4X10(6) M.W.) in 6, but only the 4 with diffuse proliferative glomerulonephritis had medium-sized IgG complexes (1-1-5X10(6) M.W.) as well.

We analyzed serums from 39 children with steroid-responsive nephrotic syndrome for the presence of circulating soluble immune complexes. Seventeen of 18 children in relapse had raised levels of IgG complexes: median titers were significantly higher in these patients than in control children (P less than 0.001) or in nephrotic children in sustained remission (P less than 0.001). Seven of nine children followed sequentially had raised complex levels in early remission but became normal after six weeks in remission. In contrast to patients with systemic lupus erythematosus these IgG complexes were not able to bind C1q. Serums from five patients in relapse contained complexes intermediate in size (2 to 2.5 X 10(6) daltons) as compared to those seen in systemic lupus erythematosus, and four of the five had small complexes as well (3 to 5 X 10(5) daltons). These findings suggest that immune complexes may have a pathologic role in steroid-responsive nephrotic syndrome, but the mechanism by which proteinuria is effected remains unclear.

Successful hyposensitization to Dermatophagoides pteronyssinus in perennial childhood asthma was associated with a slight mean rise of serum IgG antibody to the mite antigen in contrast to a placebo group in whom this antibody fell slightly. No relationship was detected between the effect on asthma and the magnitude of this change. Nor was there any consistent effect on IgE or IgA antibody. There was a wide range of total serum IgE and IgE, IgG and IgA antibody to D. pteronyssinus before treatment; this level did not predict the effect of treatment. Some patients lacked IgA antibody. IgE antibody to timothy grass pollen was raised in some but not others. These levels did not change systematically during the study and improvement occurred in those who had this antibody as well as IgE antibody to D. pteronyssinus. IgG and IgE antibodies to D. pteronyssinus were significantly correlated in the pre-treatment samples. Lymphocyte thymidine uptake was lower after 8 weeks of treatment than in the control group, not only after stimulus with D. pteronyssinus antigen, in vitro, but also with antigen from Candida albicans. This was not a serum effect. The late bronchial provocation response was lost only in those with serum IgA less than the log mean for age.

The factor in sera of patients with cystic fibrosis (CF) and their parents which agglutinates Proteus vulgaris has characteristics similar to those of IgG antibody to this organism. Sera of patients without CF who have P. vulgaris infections agglutinate the organism similarly. At present there are too many false-positives in a control population for the test to be widely useful for heterozygote identification.

A second patient is described with the syndrome of hypogammaglobulinaemia and malakoplakia; he too responded dramatically to bethanechol treatment and remains well on it.

Serum opsonization of yeasts for phagocytosis by normal polymorphonuclear leucocytes was defective in 11 of 43 children with unexplained frequent infections. The children had a range of infections, largely bacterial, and only 3 had diarrhoea and rash in infancy. A similar defect in at least 6 of the 9 mothers of these children (of either sex), with normal function in the fathers, suggests that the defect was primary and was transmitted by an unusual form of dominant inheritance. Four of 72 healthy adults and 1 of 11 children with unrelated disease showed similar defective function, but the incidence of the defect in the patients with frequent infection was significantly greater than this. The defective function can be corrected, in vitro and in vivo, by normal plasma at concentrations too low to be effective alone. This suggests that there is a defective factor rather than an inhibitor, and that different factors are limiting in normal and in defective plasma. Sera from affected members of the same family do not correct each other, but defective sera from different families usually do.