Prevalence and cumulative incidence of food hypersensitivity in the first 3 years of life.

BACKGROUND: Prevalence and incidence of food hypersensitivity (FHS) and its trends in early childhood are unclear. METHODS: A birth cohort born on the Isle of Wight (UK) between 2001 and 2002 was followed-up prospectively. Children were clinically examined and skin prick tested at set times and invited for food challenges when indicated. RESULTS: Nine hundred and sixty-nine children were recruited and 92.9%, 88.5% and 91.9% of them respectively were assessed at 1, 2 and 3 years of age. Prevalence of sensitization to foods was 2.2%, 3.8% and 4.5% respectively at these ages. Cumulatively, 5.3% [95% confidence interval (CI): 3.9-7.1] children were sensitized to a food. Using open food challenge and a good clinical history, the cumulative incidence of FHS was 6.0% (58/969, 95% CI: 4.6-7.7). Based on double-blinded, placebo-controlled, food challenge (DBPCFC) and a good clinical history, the cumulative incidence was 5.0% (48/969, 95% CI: 3.7-6.5). There is no evidence to suggest that the incidence of FHS has increased, comparing these results with previous studies. Overall, 33.7% of parents reported a food-related problem and of these, 16.1% were diagnosed with FHS by open challenge and history and 12.9% by DBPCFC and history. Main foods implicated were milk, egg and peanut. CONCLUSIONS: By the age of 3 years, 5-6% of children suffer from FHS based on food challenges and a good clinical history. There were large discrepancies between reported and diagnosed FHS. Comparing our data with a study performed in the USA more than 20 years ago, there were no significant differences in the cumulative incidence of FHS.

Comparison of open and double-blind placebo-controlled food challenges in diagnosis of food hypersensitivity amongst children.

BACKGROUND: Correct diagnosis of food hypersensitivity (FHS) is important to ensure appropriate patient care and to accurately establish the population prevalence and incidence. Food challenges play a very important role in the diagnosis of FHS, but it is unclear when open food challenges (OFCs) opposed to double-blind placebo-controlled food challenges (DBPCFCs) should be used. This study investigated the use of OFCs and DBPCFCs when diagnosing FHS. METHODS: Children with a reported history of FHS or with sensitization to a food without known previous consumption were invited to undergo food challenges. Children of consenting parents underwent an OFC and those with a positive OFC were approached to undergo a DBPCFC. Food challenges were either performed as 1-day or 1-week challenges depending on sensitization status and clinical history. RESULTS: Forty-one children underwent both OFCs and DBPCFCs. The positive predictive values for 1-day and 1-week OFCs were 73% (8/11; 95% CI: 39-94%) and 57% (20/35; 95% CI: 39-74%) respectively. There was no evidence to indicate that the younger children were more likely to have a positive OFC confirmed by a DBPCFC compared to older children (Fisher's exact P = 0.53). In the 1-day challenges parents indicated a preference for OFC rather than DBPCFC. By contrast, in the 1-week challenge parents indicated a preference for DBPCFC (P = 0.0192). CONCLUSION: Open food challenge may be suitable for diagnosing immediate objective symptoms, whereas DBPCFC may be needed for the diagnosis of delayed and mainly subjective symptoms, irrespective of the child's age.

Government advice on peanut avoidance during pregnancy--is it followed correctly and what is the impact on sensitization?

BACKGROUND: In 1998, the UK government issued precautionary advice that pregnant or breast-feeding women with a family history of atopy, may wish to avoid eating peanuts during pregnancy and lactation. This study aimed to assess the compliance with this recommendation and investigate its impact upon peanut sensitization. METHODS: A total of 858 children born immediately after the advice were followed for 2 years and assessed for peanut sensitization. A standardized questionnaire was used to ascertain history of atopy and maternal exposure to peanuts during pregnancy. Following parental consent children were skin prick tested to assess sensitization to peanuts. RESULTS: Sixty-five per cent of mothers had avoided peanuts during pregnancy. Forty-two per cent of the mothers had heard about the government advice, and half modified their diet as a consequence. Neither maternal nor family history of atopy had any significant effect on peanut consumption. Parity did play a role, and mothers having their first child were twice as likely to change their diet (P<0.001). Mothers of 77% of the children sensitized to peanuts had avoided peanuts during pregnancy. In this cohort study maternal consumption of peanut during pregnancy was not associated with peanut sensitization in the infant. CONCLUSIONS: The majority of mothers in this cohort avoided peanut consumption during pregnancy. It is likely that either the government advice is misunderstood by mothers, or that those who communicate the advice have not fully explained who it is targeted at.

Prevalence of sensitization reported and objectively assessed food hypersensitivity amongst six-year-old children: a population-based study.

There is a paucity of information on food hypersensitivity (FHS) in young children and there are even fewer population-based studies in this area. The aim of the study was to determine the prevalence of parentally reported FHS, and objectively diagnosed FHS amongst six-year-old children and to establish the rates of sensitization to key allergens. This population-based cohort study recruited 798 6-year-olds resident on the Isle of Wight (UK). Sensitization rates, reported rates of FHS and objectively assessed FHS was established using food challenges. A total of 94 (11.8%) 6 yr olds reported a problem with a food or food ingredient. The rate of sensitization to the pre-defined panel of food allergens was 25/700 (3.6%). Based on open food challenge and/or suggestive history and skin tests, the prevalence of FHS was 2.5% (95% CI 1.5-3.8). Based on double-blind challenges, a clinical diagnosis or suggestive history and positive skin tests, the prevalence was 1.6% (95% CI 0.9-2.7). The rates of perception of FHS are higher than the prevalence of sensitization to main food allergens and the prevalence of FHS based on food challenges. Milk, peanut and wheat were the key food allergens amongst those with positive challenges.

Reliability and validity of a maternal food frequency questionnaire designed to estimate consumption of common food allergens.

BACKGROUND: Maternal food intake during pregnancy may influence the development of food hypersensitivity (FHS) in the child. A food frequency questionnaire estimating the frequency with which some of the mains food allergens are consumed was designed and validated. MATERIALS AND METHODS: Pregnant women were recruited at the ante-natal clinic of St. Mary's Hospital, Isle of Wight, UK. A food frequency questionnaire was developed and validated by comparing responses to information recorded in 7 days food diaries. The reliability of the food frequency questionnaire was evaluated by asking women to complete the questionnaire on two separate occasions at 30 and 36 weeks gestation. RESULTS: Fifty-seven women completed the validity study and 91 women completed the reliability study. For both validity and reliability, questions with dichotomous response categories showed the highest level of agreement. Frequency of intake of foods commonly "hidden" in foods produced the lowest validity and reliability scores. In the validity study responses to the food frequency questionnaire identically matched information recorded in the food diaries 80% of the time, on average. In the reliability study, responses were identical on both questionnaires 85% of the time on average. CONCLUSION: In this study a food frequency questionnaire estimating the frequency with which some of the main food allergens are consumed during pregnancy was designed and validated. This food frequency questionnaire could be used in future studies to assess the role of maternal food intake in the development of FHS in the infant.

Radiographic and histological methodologies in estimating the chronology of crown development in modern humans and great apes: a review, with some applications for studies on juvenile hominids.

There has been a burgeoning of interest in the last decade on growth studies in hominids. These studies have relied heavily on dental development, and have compared juvenile hominids to modern human and ape standards, which are usually established using radiographic data. There has been considerable discussion on the most appropriate methods of deriving population standards from radiographs, but very little on the accuracy of the radiographic image itself. Previous histological and dissection studies have shown that age at onset of mineralization is overestimated, and age at crown completion is underestimated using radiographs. This study considers the process of X-ray absorbence by mineralized tissues and the formation of radiographic images of developing teeth. Following tooth initiation a critical mass of mineral is required for the tooth to register superimposed on the absorbence of alveolar crypt bone, which accounts for the late identification of tooth initiation. Determination of completion of crown growth depends upon the identification of the last formed enamel at the cervix. Recognition of this key stage is difficult as crown growth slows towards the cervix, and the last secreted enamel may take months to attain full mineralization levels due to the prolonged maturation process. Morphological and geometric factors have a significant influence on the imaging of the completed crown. The last formed enamel is located on the buccal face, where enamel thins progressively to nothing. X-ray absorption by enamel at the cervix becomes insignificant, and may be counterbalanced by increased dentine absorption. Approximal enamel in contrast is clearly visualized once maturation is complete. However, developmentally this enamel face initiates later, and is completed much earlier than buccal enamel. All of the radiographic estimates of crown completion times are based upon interpretations of approximal enamel completion. These considerations suggest that the human population standards in current usage may not represent true anatomical and chronological stages of crown development, and care should be taken in referring juvenile hominids to these radiological standards.

Chest physiotherapy in cystic fibrosis: a comparative study of autogenic drainage and the active cycle of breathing techniques with postural drainage.

BACKGROUND--Autogenic drainage has been suggested as an alternative method of chest physiotherapy in patients with cystic fibrosis. In this study autogenic drainage was compared with the active cycle of breathing techniques (ACBT) together with postural drainage. METHODS--Eighteen patients with cystic fibrosis took part in a randomised two-day crossover trial. There were two sessions of one method of physiotherapy on each day, either autogenic drainage or ACBT. The study days were one week apart. On each day the patients were monitored for six hours. Mucus movement was quantified by a radioaerosol technique. Airway clearance was studied qualitatively using xenon-133 scintigraphic studies at the start and end of each day. Expectorated sputum was collected during and for one hour after each session of physiotherapy. Pulmonary functions tests were performed before and after each session. Oxygen saturation (SaO2) and heart rate were measured before, during, and after each session. RESULTS--Autogenic drainage cleared mucus from the lungs faster than ACBT over the whole day. Both methods improved ventilation, as assessed by the xenon-133 ventilation studies. No overall differences were found in the pulmonary function test results, but more patients had an improved forced expiratory flow from 25% to 75% with autogenic drainage, while more showed an improved forced vital capacity with ACBT. No differences were found in sputum weight and heart rate, nor in mean SaO2 over the series, but four patients desaturated during ACBT. CONCLUSIONS--Autogenic drainage was found to be as good as ACBT at clearing mucus in patients with cystic fibrosis and is therefore an effective method of home physiotherapy. Patients with cystic fibrosis should be assessed as to which method suits them best.

A new method for measuring the blood volume of the rat using 113mIndium as a tracer.

A new method is described for the estimation of blood volume in the rat using 113mIndium chloride. No in vitro labelling step is necessary as the isotope binds specifically to transferrin in vivo. Under anaesthesia, an external jugular vein was cannulated for blood sampling and indium chloride injected directly into a lateral tail vein. Three blood samples of 0.2 ml were taken at short intervals and radioactivity measured under standard conditions. Blood volume was found to be 7.46 +/- 0.14 (mean +/- SEM) ml/100 g body weight. Repeating the study of 5 animals gave similar values for blood volume on the 2 occasions (7.23 +/- 0.26 and 6.95 +/- 0.23 ml/100 g, P > 0.05). The new technique was compared with established methods using 51Cr labelled red blood cells and 125Iodinated albumin. In each animal, the 113mIndium technique produced values approximately 10% higher than those obtained using the sum of plasma and red cell mass, in keeping with the known difference between whole body and large vein haematocrit (Indium, 7.20 +/- 0.19 and Iodine with Chromium, 6.40 +/- 0.34 ml/100 g). Data on blood volume determined using 125Iodine as the tracer on these same animals were identical (Indium, 7.20 +/- 0.19 and iodine, 7.16 +/- 0.34 ml/100 g). The method is simple to perform and appears to be at least as accurate and reproducible as established methods for measuring blood volume.

The effect of immunosuppression on the development of cerebral oedema in an experimental model of intracerebral haemorrhage: whole body and regional irradiation.

The oedema which forms around an intracerebral haemorrhage has a complex aetiology. The immune response may have a role in its formation. There is clinical and experimental evidence that circulating leucocytes and platelets may mediate oedema formation. Global depletion of circulating leucocytes and platelets by whole body irradiation in a rodent model of intracerebral haemorrhage was found to confer protection against both ischaemia and oedema formation. This was not a direct effect of irradiation of the brain. The possible mechanisms for this protection are discussed.

Immunosuppression by whole-body irradiation and its effect on oedema in experimental cerebral ischaemia.

The effect of global immunosuppression by sublethal whole body X-irradiation on the development of cerebral oedema was assessed 24 h after right middle cerebral artery occlusion in the rat. Irradiation produced a significant leukopenia and thrombocytopaenia, and significantly reduced cortical oedema when compared to non-irradiated control animals.

Thallous chloride uptake and DNA profile in parathyroid adenomas.

Thallium isotope scintigraphy is used to localize parathyroid adenomas but the mechanism underlying the technique is poorly understood. While larger adenomas are reliably localized the results are less certain for small tumours. This study explores the relationship between cellular DNA profile and thallium uptake (localization accuracy) in 24 parathyroid adenomas. The DNA profile was assessed using flow cytometry and standard subtraction thallium scintigraphy was performed before surgery. Fifteen of the 24 adenomas demonstrated excessive mitotic activity and 13 of these glands were accurately localized. Of the remaining nine glands, only five were localized accurately (P less than 0.01, chi 2 test including Yates' correction). This difference in thallium uptake could not be accounted for on the basis of gland weight. Thallium localization of parathyroid adenomas is related to mitotic activity. This may explain some of the limitations of this technique.

Ventilation perfusion lung scans in the management of suspected pulmonary embolism.

The purpose of the study was twofold: (a) to relate the degree of clinical suspicion of pulmonary embolism (PE) to the findings of isotope ventilation-perfusion (V/Q) scans, and (b) to determine the extent to which the scan results influence patient management. A questionnaire was completed by the requesting clinician before V/Q scanning in 60 consecutive in-patients in whom PE had, with varying degrees of probability, been considered possible. Retrospectively, the case notes were reviewed to determine whether or not the patients were anticoagulated when discharged. Prior to scanning, PE was considered probable or almost certain in 35 (58 per cent) patients and unlikely or very unlikely in 25 (42 per cent) patients. Thirty-seven (62 per cent) scans were confidently reported positive or negative for PE; in the remaining 23 (38 per cent) cases, the scan report was necessarily inconclusive. The clinical assessment was supported by the scan result in 23/25 (92 per cent) patients in whom PE was felt unlikely or very unlikely, but in only 14/35 (40 per cent) in whom this diagnosis was felt probable or almost certain. Twenty (33 per cent) patients were already anticoagulated when scanned; this treatment was initiated in nine (15 per cent) and discontinued in eight (13 per cent) in the light of the scan result. Isotope V/Q scans are not always useful in confidently confirming or excluding the presence of PE. Nevertheless, the scan reports, even when necessarily guarded and somewhat at variance with the clinical assessment of the probability of PE, strongly influence clinicians in their decisions as to whether to anticoagulate their patients.

A double-radionuclide autoradiographic method using N-isopropyl-iodoamphetamine for sequential measurements of local cerebral blood flow.

A double-radionuclide autoradiographic method has been assessed for sequential determinations of local CBF (LCBF). It is based on two successive intravascular injections of N-isopropyl-p-iodoamphetamine (IMP) labelled with different radionuclides, whose concentrations can later be differentiated in the same tissue section using double-radionuclide autoradiography. Previous studies suggested that the distribution of IMP, up to 30 min after its administration, still represents LCBFs. Our data indicate that, provided the tracer is injected directly into the left ventricle, there is little back diffusion from normal brain to blood under physiological conditions for at least 35 min following the tracer injection and an injection of unlabelled IMP, in a dose larger than that used for blood flow determination, does not displace any labelled IMP previously taken up by the brain, nor does it displace any labelled IMP previously accumulated in the lung that would lead to secondary brain uptake. On the basis of these results, we conclude that sequential autoradiographic determinations of LCBF using IMP labelled with different radionuclides is possible. This is a promising experimental method for the simultaneous investigation of changes in LCBF in several CNS structures.

Static and sequential dynamic scintigraphy of the tibia following fracture.

Eighty patients who had sustained a fracture of the tibial shaft were studied by scintigraphy using technetium-99m labelled methylene diphosphonate (99Tcm MDP) and a gamma camera. Static scintigrams were obtained in the early stages following injury and examined for the presence of 'cold spots' which may indicate loss of blood supply to fracture fragments; these were found in 10 per cent of cases but did not bear any definite relationship to the normal progression of union. Sequential dynamic scintigrams were obtained at intervals up to 20 weeks after fracture to determine whether a pattern of uptake of tracer could be identified which correlated with the subsequent progression of union, but no significant difference was observed between fractures healing promptly (less than 20 weeks) and those in which healing was delayed (greater than 20 weeks).

Scintigraphy and contrast radiography for epiphora.

During a one-year period 53 patients were referred for the investigation of epiphora. All underwent bilateral dacryoscintigraphy. Following the isotope study the patients had either bilateral or unilateral macrodacryocystography; a total of 66 tear ducts were shown by this procedure. The scintigraphs were more sensitive for obstruction (51/66 systems or 77%) than radiography (33/66 systems or 51%). Normal dacryoscintigraphy was always associated with duct patency on dacryocystography. We have concluded that scintigraphy should always be the first investigation and that, if this is normal, radiography is not necessary. The use of digital subtraction imaging for the lacrimal passages is discussed. It is suggested that this may provide information obtained at present only by combining dacryoscintigraphy with conventional contrast radiography.

Application of Bayes' theorem to the diagnosis of ankylosing spondylitis from radioisotope bone scans.

The ratio of the uptake of radioactivity in each sacroiliac joint to the uptake in the sacrum has been measured in 57 patients with early ankylosing spondylitis and in 51 control subjects. The distribution of ratios of uptake obtained in each of these two groups shows appreciable overlap, and it is shown that the specification of a 'normal range' in this sort of situation can be misleading in the interpretation of the uptake ratio obtained in a given subject. An alternative approach described here is to use Bayes' theorem, which combines a probability based on the numerical value of the measured ratio with the pretest clinical impression about the likelihood of ankylosing spondylitis to yield a post-test probability of the presence of the disease.

Scintigraphic appearance of the tibia in the early stages following fracture.

A scintigraphic study of the human tibia in the early stages following fracture of the shaft was carried out to investigate the condition of the blood supply of the main fracture fragments. Using a gamma camera and 99mTc-MDP, scintigraphs were obtained from less than 24 hours to 21 days after injury. A generalized increase in tracer uptake was found in the tibia in all cases. In some cases very early after injury there was an additional local increase at the fracture site. In 10% of cases "cold spots" were observed, which may indicate an impaired blood supply to bone tissue adjacent to the fracture. Neither the presence of a "cold spot" nor any other scintigraphic feature could be correlated with the progress or time to fracture union.