Biomedical subjects
Publications and source records attributed to A S Kemp.
Food allergy is a common condition among infants. The reactions are usually to milk, egg and peanut products. They frequently improve with time. It is important for the practitioner to recognise the occurrence of these reactions and to advise parents of their significance.
BACKGROUND: N-Formyl-methionyl-leucyl-phenylalanine (FMLP) is a bacterial oligopeptide which stimulates neutrophil chemotaxis, degranulation and superoxide generation. Inhalation of FMLP produces bronchoconstriction in man; in the rabbit this is in part neutrophil dependent. The effects of inhalation of FMLP on peripheral blood leucocytes in normal subjects has been studied. METHODS: This was an open study in non-asthmatic subjects. Change in total peripheral white cell count were studied for 15 minutes after inhalation of 0.4 mumol FMLP in six subjects. Change in total and differential white cell count and spontaneous neutrophil chemiluminescence were then studied five and 30 minutes after inhalation of 0.4 mumol FMLP (n = 7) or diluent (n = 4). Finally, leucocytes from three subjects were labelled ex vivo with technetium-99m labelled sulphur colloid and reinfused. The effect of inhalation of FMLP or diluent on pulmonary neutrophil flux was studied by continuous gamma scanning of a pulmonary window. RESULTS: Leucopenia occurs rapidly after inhalation of FMLP, the nadir of the white cell count (53% of baseline) occurring at four minutes. This was followed by a rebound increase in white cell count evident at 15 minutes (154% of baseline). Five minutes after inhalation of 0.4 mumol FMLP, neutropenia (17% of baseline) and monocytopenia (40% of baseline) were seen followed again by a neutrophilia (213% of baseline at 30 minutes). The eosinophil count was significantly reduced at 30 minutes (24% of baseline). Neutrophil chemiluminescence was elevated (186% of baseline) at the time of the neutropenia. There was no influx of labelled cells to the lung during the period of neutropenia. CONCLUSION: FMLP inhalation activates circulating leucocytes. In vivo production of FMLP in the airway could contribute to bronchial inflammation during bacterial infection.
Recurrent respiratory infections in young children are very common. It may be normal for a toddler or a pre-school child to get up to 10 respiratory infections a year without indicating immunodeficiency. As the natural tendency is for this to improve with time, the major aim of management is to get parents to appreciate that recurrent respiratory infections are a normal part of childhood.
We have prospectively followed 52 children of atopic parents from birth to age 7 years, documenting clinical atopic disease and allergen skin test reactions. We found bronchial hyperresponsiveness (BHR) to histamine in 13 (25%) of the children at 7 years of age with 25 (48%) being atopic on skin testing and 15 (29%) having current wheeze, whereas 30 children (58%) had wheezed at some time during this period. BHR was significantly associated with wheeze and atopy at 5 and 7 years of age, but not during infancy. The six children with moderate to severe BHR (provocative dose causing a 20% fall in FEV1 less than 0.8 mumol) formed a distinct subgroup with significantly more wheeze and atopy both during infancy and at 5 years of age when these children were compared to children with milder degrees of BHR. The group with moderate to severe BHR also differed significantly from the nonhistamine-reactive group, whereas children with milder degrees of BHR were not significantly different. We conclude that subjects most likely to develop the more severe degrees of BHR during later childhood are children who manifest atopy in infancy.
Fifteen children (11 males and four females), on oral Zidovudine (AZT) for symptomatic HIV infection were studied retrospectively. Twelve acquired HIV via blood products, two from vertical transmission (maternal intravenous needle sharing) and one through breast feeding. Their mean age at the start of therapy was 8.6 years (s.d. 4.4 years, range 1.8-15.3 years). The main indications for therapy were failure to thrive (FTT) in 10, recurrent respiratory tract infections (RRTI) in eight, and developmental delay (DD) in one, with overlapping indications being Pneumocystis carinii pneumonia (PCP) in one and pulmonary lymphoid hyperplasia (PLH) in two. The mean commencement dose was 24 mg/kg per day orally in 3-6 divided doses (range 16-35 mg/kg per day). The duration of therapy was 2 weeks-2 1/2 years. Significant improvement in growth was observed by 2 months; at 6 months, growth was sustained in these otherwise ill children, with only two falling below pretreatment weight. Decrease in the frequency of RRTI based on subjective reports of the attending clinicians was observed in seven of the eight evaluable children still on therapy. Improvement in PCP and PLH occurred in two children and modest improvement was subjectively reported in PLH in one while still early in the course of therapy. Overall, AZT was well tolerated. Dose modifications were for neutropenia in three (of which only two were drug related), rapidly falling neutrophil count in one, anaemia in two (with concurrent history of chronic gastrointestinal tract blood loss in one), severe GIT irritation in one and transient sedation in one. Seven opportunistic infections were reported (three in the same patient) of which two occurred following cessation of therapy, one after only 2 weeks of therapy, and one had not been on primary prophylactic therapy. Three deaths occurred, one associated with opportunistic infections and two while off therapy (one respiratory failure, one PCP).
We have prospectively followed 57 children of atopic parents up to 5 years of age, documenting clinical atopic disease and allergen skin test reactions. The cumulative prevalences of the clinical features of atopic disease over the 5 years were: atopic dermatitis (58%), wheeze (49%), recurrent wheeze (33%), rhinitis (68%) and immediate food reactions (18%). Atopic dermatitis and immediate food reactions predominated in infancy (birth to 20 months) while wheezing was more prominent in later childhood (20 months to 5 years). Rhinitis was common in both infancy and childhood. IgE sensitisation to ingested allergens was prominent in early infancy and was usually transient. Inhaled allergen sensitisation occurred later in infancy and was generally permanent with wheal sizes tending to increase with age. There was a significant association between IgE sensitisation to ingested but not inhaled allergens and all atopic manifestations in infancy, with the exception of rhinitis. In contrast IgE sensitisation to inhaled allergens was associated with rhinitis and wheeze in later childhood. We found two clinical groups. One group, with only ingested allergen sensitisation had a high incidence of atopic dermatitis but low incidence of respiratory symptoms at 5 years of age. The other group, who developed evidence of IgE sensitisation to inhaled allergens, had a high incidence of rhinitis and wheeze but low incidence of atopic dermatitis at 5 years of age.
After opsonization with whole human serum, with IgG antibody alone or with C3 fragments alone, the ingestion of zymosan particles by human neutrophils was found to correlate most closely with the efficiency of C3 fragment deposition on the zymosan surface. Selective opsonization of zymosan particles with IgG did not promote phagocytosis at all in suspension, but could promote ingestion after particle-cell contact was induced by centrifugation. In contrast, zymosan particles in suspension selectively opsonized by C3 fragments were ingested as efficiently as those opsonized with whole serum, and we suggest that C3 fragments provide the principal stimulus for phagocytosis of zymosan. The process of vacuolar sealing was not dependent on the state of opsonization of the particles and was significantly more efficient with unopsonized particles, indicating that formation of unsealed vacuoles is not due to a failure of the 'zipper' mechanism of sequential interaction of cell surface receptors and opsonic ligands.
Twenty-three children with chronic urticaria were treated with an elimination diet for two weeks. Eighteen completed the period of dietary elimination; in seven of the 18 children there was a marked remission of the urticaria during the second week of the diet. The administration of challenge capsules provoked an exacerbation of urticaria in five of the 14 (36%) children given aspirin. The incidence of reactions to tartrazine, sodium benzoate and yeast (7%) was not significantly different from those to the lactose placebo (9%). In selected cases, elimination diets with controlled reintroduction of foods have a role in the management of chronic urticaria in childhood.
One-hundred-and-four children were skin-tested with four peanut-allergen preparations, a commercial extract, extracts of raw and roast peanuts prepared by NH4HCO3 extraction, and a wheatgerm lectin-reactive glycoprotein obtained by affinity chromatography. The presence of symptoms after ingestion of peanut or peanut products was also recorded. The roast allergen extract provided the greatest specificity with eight symptomatic children having a positive skin test and only one positive skin-test reaction in an asymptomatic child in the group of 104 children tested. Despite differences in the incidence of skin-test reactions there was a strong correlation between raw, roast and commercial RAST suggesting common allergens were being identified by circulating IgE. Clinical sensitivity was observed particularly in younger children with 75% of the children being under 4 years of age. A positive roast skin test or a RAST test adds confirmation to the clinical history of allergic reactions to peanuts.
A 10 year old girl presented with recurrent febrile episodes over 2 months. A non-typable strain of Neisseria meningitidis was grown from blood cultures on three occasions. She was found to lack functional C8 activity in serum but material with C8 antigenic activity was present. The opsonic activity of the C8 deficient serum for N. meningitidis was equivalent to that of normal controls.
In a prospective study, infants born to atopic parents had a significantly higher prevalence of salivary IgA deficiency at all ages studied than control infants, and the mean non zero IgA level of the potentially atopic infants was significantly lower at 8 and 12 months than of control infants. Of the infants with atopic parents, the prevalence of IgA deficiency was not significantly greater in those who manifested atopic disease during the study period than in those who did not, but the levels were significantly lower at 4 months.
Food reactions in children may be divided into two types: immediate and delayed. Cow's milk, egg and peanuts are the most commonly implicated foods. Immediate food reactions are associated with the presence of specific IgE antibodies to the food concerned, although detection of specific IgE is of no help in the diagnosis of delayed reactions. The only way to definitely confirm a food reaction is by elimination and rechallenge. Food reactions can be expected to improve naturally with time.
We examined the development of skin test reactivity and clinical allergen sensitivity in infancy. Seventy-eight infants of atopic parents were skin prick tested every 4 mo from 4 to 16 mo and an additional 57 of these infants were tested at 20 mo. Wheal diameters were recorded for histamine (1 mg/ml) and specific allergen reactions by use of cow's milk, egg albumen, wheat, and Dermatophagoides pteronyssinus. The histamine mean wheal diameter was significantly lower at 4 and 8 mo compared to the older infants. Infants at 20 mo also had significantly smaller wheals than adult controls. Histamine reactivity was greater in atopic infants at 4 mo compared to nonatopic infants. Reactions to ingested allergens occurred early in infancy but were usually transient. There was a good correlation between skin sensitivity and clinical immediate-food hypersensitivity to the food concerned. In contrast, reactions to the inhaled allergen, D. pteronyssinus, occurred later in infancy, were persistent, and increased in size with age. Although we found no relationship between the acquisition of skin reactivity to D. pteronyssinus and development of the respiratory symptoms of atopic disease during the period of the study, it is possible that inhaled allergen reactivity may be related to respiratory symptoms at later ages. Despite the decreased histamine reactivity in early infancy, skin tests proved reliable markers of clinical disease in ingested but not inhalant allergen sensitivity.
The immunological interaction between related maternal and neonatal human lymphocytes was investigated by assaying monocyte chemotactic factor production in mixed cell culture. Lymphokine was detected in a significantly lower proportion of maternal-neonatal cell cultures compared to mixed cultures of cells from unrelated adults and/or neonates. It is possible that a reduced inflammatory mediator production at the feto-maternal interface may contribute to the survival of the fetal allograft.
We examined the relationship of diet to the development of atopic manifestations in a group of infants with an immediate family history of atopy, followed prospectively from birth for up to 20 months of age. There was no relationship between the development of atopic dermatitis, rhinitis and wheeze and either 2 or 4 months exclusive breast feeding, or the introduction of cow's milk or solids in the first 4 months of life. In addition there was no relationship between the introduction of milk, egg or wheat into the diet and the development of skin-test positivity to these foods. In fact, five infants developed positive skin tests to the food prior to its introduction into the diet, suggesting exposure via maternal breast milk. Thus we have been unable to show a protective effect of either breast feeding or cow's milk or solid avoidance on the development of atopic disease in infancy.
A case of chronic granulomatous disease associated with decreased neutrophil chemotaxis is described. It is suggested that defective neutrophil motility may be more common than previously recognized in chronic granulomatous disease. However, the presence of a chemotactic defect does not necessarily imply a more severe clinical course.
We prospectively followed a group of infants with a family history of atopy, from birth for up to 20 months of age. All infants were seen every 4 months and a history, physical examination and skin tests obtained. Atopic dermatitis and rhinitis occurred in about half the infants at some time during the study, while wheezing occurred in about a quarter. Both atopic dermatitis and rhinitis were more common in the first 12 months whereas wheezing occurred later and increased in prevalence with age. Defining atopy by the presence of atopic dermatitis or positive skin tests, only immediate food reactions were significantly associated with atopic infants. In contrast, rhinitis, a single episode of wheezing, colic, vomiting and delayed food reactions were not associated with atopy and thus are unlikely to be due to IgE-related mechanisms during infancy.
A 9-year-old boy with systemic juvenile chronic arthritis and Brown's syndrome (limitation of elevation of the adducted eye due to limitation of movement of the superior oblique tendon) is described. The resolution in association with steroid treatment suggested a transient tenonsynovitis involving the superior oblique tendon as the cause.