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S Ali

Publications and source records attributed to S Ali.

At least 19 recordsLinked to original sources

Purified malignant mammary epithelial cells maintain hormone responsiveness in culture.

Currently, the therapy for breast cancer is determined by immunohistochemical staining of the primary tumour for oestrogen receptor alpha (ERalpha). However, a proportion of ERalpha-positive patients fail to respond to tamoxifen and a proportion of ERalpha-negative patients show response. Here, we describe a novel procedure for the purification of malignant breast epithelial cells in an attempt to identify these patients at an early stage. Using this procedure, we are able to purify malignant cells to >90% purity as determined by immunohistochemical staining, cytology and fluorescent in situ hybridisation (FISH). While the malignant cells can be maintained in culture they do not proliferate in contrast to purified breast epithelial cells from reduction mammoplasties. Moreover, ERalpha and progesterone receptor (PR) expression is maintained in malignant cells, whereas normal epithelial cells rapidly lose ERalpha and PR. Functional studies were performed on the separated malignant cells in terms of their response to oestradiol and tamoxifen. Four out of the seven ERalpha-positive tumours showed a significant reduction in cell numbers after tamoxifen treatment compared to oestradiol, ERalpha negative tumours failed to show a response. We conclude that (a) it is possible to purify and maintain breast cancer cells for a sufficient period to permit functional studies and (b) ERalpha is retained in culture facilitating the use of these cells in studies of the mechanism of endocrine response and resistance in vitro.

Breast↗

Development of a DNA marker by minisatellite associated sequence amplification (MASA) from the endangered Indian rhino (Rhinoceros unicornis).

Rhinoceroses are highly endangered species and their protection warrants immediate remedial measures. Development of DNA markers is envisaged to complement global efforts of the conservation of these extant animals. Minisatellite associated sequence amplification (MASA) of DNA from Indian rhinoceros (Rhinoceros unicornis) and three sub-species of South African black rhinoceros (Diceros bicornis) was carried out using a primer based on consensus sequence of the minisatellite repeat locus 33.15. Several bands in the range of 3.0 kilobases (kb) to 650 base pairs (bp) were identified that were useful for successful differentiation of R. unicornis from D. bicornis. Of these fragments, a 688 bp one, unique to R. unicornis was cloned and sequenced (Accession No. AF-296689). The band patterns uncovered by MASA and the species-specific hybridisation of pSG5 may be utilised as a tool for differentiating the R. unicornis genome from that of D. bicornis. This approach may also be adopted for the development of DNA-based genetic marker(s) useful for identification of other endangered species.

Animals↗

Fire and frost!

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Analgesia, Epidural↗

Effect of volume of culture medium on enhanced citric acid productivity by a mutant culture of Aspergillus niger in stirred fermentor.

AIMS: The present study deals with the effect of volume of culture medium on enhanced citric acid productivity by a mutant culture of Aspergillus niger. METHODS AND RESULTS: A laboratory scale stirred fermentor of 15-l capacity was employed for all microbial cultivations. Blackstrap molasses, a by-product of sugar industries is easily and abundantly available for its exploitation as a carbon source in fermentation processes. The parental culture of A. niger was improved by mutation using ultraviolet radiations and N-methyl N-nitro N-nitroso guanidine, i.e. mutagen MNNG. Six MUV and eight MNNG-treated mutant strains were isolated after extensive screening and optimization. Mutant strain of A. niger MNNG-2 showed enhanced citric productivity (87.60 g l-1) over the parental strain BTL-45 (19.53 g l-1) and other mutant derivatives (49.85 g l-1 citric acid in case of mutant MUV-5 and 76.82 g l-1 in case of mutant MNNG-7). The optimal sugar level was found to be 150 g l-1 (optimum volume of the medium, 60%) after 6 days of inoculation, which is economically significant. Specific productivity of the mutant culture MNNG-2 (qp = 0.057 g/g cells h-1) was several folds higher than other strains. SIGNIFICANCE AND IMPACT OF THE STUDY: The results of the present study are of commercial level. All kinetic parameters including yield coefficients and volumetric rates revealed the hyper-producibility of citric acid by mutant MNNG-2 using blackstrap molasses as the basal medium in stirred fermentor.

Aspergillus niger↗

Graphical display of variability and inter-relationships of pressure signals in children with traumatic brain injury.

A prospective observational study was undertaken to examine time series ICU data of pressure variables (mean arterial pressure (MAP), intracranial pressure (ICP) and cerebral perfusion pressure (CPP)) and relate their variability (SD) to outcome, together with simple graphical displays which could be useful at the ICU bedspace. Forty-three children (aged < 1-15 years) were admitted to the intensive care unit for Regional Neurosurgical Service, Edinburgh, following traumatic brain injury (TBI). The standard deviations from 221,291 validated pressure data measurements (representing three variables) were calculated for the duration of ICP monitoring (and in 48 h epochs from the time of injury). Data were displayed on polygraphs, and several well-defined 'patterns' were described. The standard deviations of MAP, ICP and CPP for the total duration of monitoring were found to be significantly related to survival (p = 0.003, <0.001 and 0.005, respectively), while the SD of ICP alone was strongly related to global recovery (p = 0.008) in the first 48 h post-injury. Patterns in 104 epochs (each of 48 h) were identified. Ninety-two were of the type I (MAP > CPP > ICP) pattern and 12 were of the non-type I pattern. Glasgow Outcome Scale scores at 12 months were significantly related to the dichotomized pattern type (Fisher's exact test p < 0.001 for both alive versus dead and independent versus dependent outcomes). Only one patient with type I pattern died in this series. While variability of ICP during the first 48 h post-injury is predictive of the outcome, the pattern behaviour of three pressure signals gives useful outcome prediction information throughout monitoring. These displays may help interpret some of the plethora of data produced at the bedside.

Accidental Falls↗

Chemokines and breast cancer: a gateway to revolutionary targeted cancer treatments?

Breast cancer is an example of a solid tumour which is well treated in the early stages of disease by surgical excision, but once metastatic spread has occurred, medical therapies (chemotherapy and radiotherapy) are highly toxic, expensive and palliative. It is known that certain tumours exhibit specific patterns of metastasis, chemokines may provide a molecular answer to this mystery. Chemokines and their receptors play important roles in the various stages of tumour development and metastasis. Chemokines interact with their specific receptors as well as interacting with the glycosaminoglycan (GAG) component of proteoglycan. We discuss the basic metastatic process and the involvement of chemokines in breast cancer biology. Finally, we summarize potential therapeutic applications of chemokines and chemokine/glycosaminoglycan interactions including chemokine agonists, antagonists, anti-sense therapy, immunotherapy and soluble GAGs, as well as future perspectives in this field.

Antineoplastic Agents↗

Serum lipid profile in hypertensive and normotensive type II diabetes mellitus patients--a comparative study.

A comparative prospective study was done in 10 patients suffering from hypertension with type II diabetes mellitus and 10 patients suffering from type II diabetes without hypertension. The serum Lipid profile was studied on 10 healthy normotensive nondiabetic subject, on 10 patients suffering from hypertension with type II diabetes mellitus and on 10 patients suffering from type II diabetes mellitus without hypertension. In present study a significantly higher level of serum total cholesterol, triglyceride and LDL-Cholesterol concentration were observed in hypertensive type II diabetes mellitus and normotensive type II diabetes mellitus subjects in comparison to control group and serum HDL-cholesterol concentration was significantly lower in both the groups in comparison to healthy control. There was significantly increased level of serum total cholesterol (P < 0.001) and LDL-cholesterol (P < 0.001) in hypertensive type II diabetes mellitus in comparison to normotensive type II diabetes mellitus. Though serum triglyceride level was increased in hypertensive type II diabetes mellitus in comparison to normotensive type II diabetes mellitus, but it was not statistically significant. Serum HDL-cholesterol level was more in normotensive type II diabetes mellitus in comparison to hypertensive type II diabetes mellitus group but it was not statistically significant.

Adult↗

Inducive effect of cresoquinone on microbiological transformation of L-tyrosine to 3,4 dihydroxy phenyl L-alanine by Aspergillus oryzae NG-11(P1).

The present work describes the inducive effect of cresoquinone on microbiological transformation of L-tyrosine to 3,4 dihydroxy phenyl L-alanine ( L-DOPA) by Aspergillus oryzae NG-11(P1). Mould mycelium was used for biochemical conversion of L-tyrosine to L-DOPA because tyrosinases, beta-carboxylases and tyrosine hydroxylases are intracellular enzymes. The maximum conversion of L-tyrosine to L-DOPA (0.428 mg/ml) was achieved after 60 min of biochemical reaction. To enhance the production of L-DOPA, cresoquinone was added to the reaction mixture. Best L-DOPA biosynthesis results were observed when the concentration of cresoquinone was 3.5 x 10(-6) M (1.686 mg/ml L-DOPA produced with 1.525 mg/ml consumption of L-tyrosine). Cresoquinone not only increased enzyme activity but also enhanced cell membrane permeability to facilitate secretion of enzymes into the reaction broth. Comparison of kinetic parameters revealed the ability of the mutant to yield L-DOPA [Y(p/x) [i.e., mg L-DOPA formed (mg cells formed)(-1)] =7.360+/-0.04]. When the culture grown on various cresoquinone levels was monitored for Q(p), Q(s) and q(p) [ Q(p): mg L-DOPA produced ml(-1) x h(-1); Q(s): mg substrate consumed ml(-1) x h(-1); q(p): mg L-DOPA formed (mg cells)(-1) h(-1)], there was significant enhancement ( P<0.025) of these variables.

Aspergillus oryzae↗

Influence of cultivation conditions on citrate production by Aspergillus niger in a semi-pilot-scale plant.

The influence of some fermentation parameters on the semi-pilot scale (alteration of growth conditions, e.g., sugar concentration, incubation temperature and initial pH) on citrate production was demonstrated in parent and mutant strains of Aspergillus niger. Raw material from sugar industry (cane molasses) was examined as basal fermentation medium in a stirred stainless-steel 15-L fermentor. After growth on medium with 150 g/L sugar, the parent strain produced 51.2 g/L citric acid; the mutant strain achieved production maximum of 96.2 g/L. Comparing the growth, kinetic (volumetric substrate uptake rate, rate of substrate consumption and volumetric productivity rate) and production parameters it was found that the mutant strain grows more rapidly, with slightly changed morphology (intermediate, shiny round pellets with diameter 0.6-0.7 mm), and exhibits a higher citrate production and higher efficiency of sugar utilization.

Aspergillus niger↗

Practice audits: reliability of sphygmomanometers and blood pressure recording bias.

It is well established that numerous errors, biases and omissions in recording blood pressure exist. This study had two objectives. Firstly, to measure the accuracy of sphygmomanometers used in general practice and secondly to assess digit bias in blood pressure recording. This study was carried out in the then Northfield PCG, which comprised 18 practices and 67 GPs. A total of 131 mercury and aneroid sphygmomanometers were tested for accuracy by a trained technician in accordance with the methods specified in BS 2743 (1990). Accuracy was defined as an error of greater than 10 mm Hg. The second part of the methodology involved undertaking an audit of the proportion of registered patients aged 35-80 years who had their blood pressure measured within the last 5 years by members of the Primary Health Care Team. The results were that of the mercury and aneroid sphygmomanometers tested, 17% were inaccurate. Of these, 4% recorded an error greater than 10 mm Hg. One percent of mercury and 10% of aneroid sphygmomanometers recorded an error greater than 10 mm Hg respectively. Sixteen (12%) sphygmomanometers were so deteriorated (air leaks, dirt in mercury) that the researcher suggested their immediate withdrawal from service. The results of the blood pressure recording audit suggested digit bias of both systolic and diastolic recordings to the nearest 10 mm Hg. This study suggests that sphygmomanometers used in general practice are very likely to be inaccurate and some may well be so deteriorated that they should be withdrawn from service. The results of the blood pressure audit showed digit bias in systolic and diastolic readings to the nearest 10 mm Hg. The implications for clinical care-both over diagnosis and under diagnosis-although not assessed are likely to be appreciable. PCG Clinical Governance teams in conjunction with Practice Clinical Leads must address these basic issues.

Adult↗

Leucocyte chemotaxis: Examination of mitogen-activated protein kinase and phosphoinositide 3-kinase activation by Monocyte Chemoattractant Proteins-1, -2, -3 and -4.

Monocyte Chemoattractant Proteins (MCPs) form a distinct, structurally-related subclass of CC chemokines. They are major chemoattractants for monocytes and T lymphocytes. The MCPs bind to specific G-protein-coupled receptors, initiating a signal cascade within the cell. Though the signal transduction pathways involved in MCP-1-mediated chemotaxis have been studied, the signalling pathways through which MCP-2, -3 and -4 trigger cell migration are not established. In this study, we examined the mitogen-activated protein kinase (MAPK) activation elicited by the MCPs (1-4) and its specific role in chemotaxis. Within 2 min, the MCPs (1-4) elicited a rapid and transient activation of MAPK in peripheral blood mononuclear cells and in HEK-293 cells expressing CCR2b. U0126, an inhibitor of MAPK-kinase (MEK) activation, not only prevented extracellular signal-regulated kinase 1/2 (ERK1/2) activation but also significantly inhibited the MCP-mediated chemotaxis. PI3K inhibitors Wortmannin and LY294002 also partially inhibited the MCP-induced chemotaxis. However, these compounds did not significantly inhibit ERK1/2 activation. As PI3K inhibitors partially inhibit the MCP-mediated chemotaxis but do not significantly effect ERK1/2 activation, these data suggest that co-ordinated action of distinct signal pathways is required to produce chemokine-mediated chemotaxis.

Cell Line↗

Diabetes UK funded surveys of the structural provision of primary care diabetes services in the UK.

AIM: To describe diabetes service provision in primary care in the UK. METHODS: Postal questionnaires were sent to all UK primary care organizations (PCOs), and to a sample of general practices in England and all practices in Wales and Scotland. The data collection period ended on 30 April 2001. RESULTS: Seventy-nine per cent of the PCOs and 40% of the practices provided usable information. There is evidence that respondents were not significantly biased in relation to their interest in diabetes care. Diabetes was included as a Health Improvement Programme (or equivalent) priority by 62% of PCOs and had been identified as a clinical governance priority by 27%. Sixty-five per cent had information about the ethnic composition of their general population, 57% had an estimate of the number of people with diabetes. Sixty-nine per cent had a local diabetes register but this was said to cover the entire local population in only 64% of these. At least one audit of diabetes care had been carried out (in the previous 5 years) in 75% and, in 76%, clinical guidelines on diabetes care were made available to practices. In the practices, 80% had a designated lead person for diabetes. Seventy-three per cent had at least one general practitioner with a special interest and 87% at least one nurse. Seventy-two per cent of practices ran specific diabetes clinics and 51% had a screening policy. Eighty-six per cent considered that they had adequate systems in place for the delivery of diabetes care. However, only 6% were able to offer a dedicated diabetes telephone help or advice line and only 9% an evening out of hours clinic. Regular practice meetings were held to discuss diabetes in 35%, whereas 39% had a formal shared care protocol. Fourteen per cent held regular joint meetings with the hospital-based team and in 38% there was membership of Diabetes UK for at least one partner or the practice itself. A third (34%) of responding practices were unsure whether a Local Diabetes Services Advisory Group or equivalent existed in their area. Geographical differences in service provision were identified with, for example, practices in London having fewer components in place that were specifically related to the provision of diabetes care. Single-handed practices, wherever they were situated, had in place fewer staff and facilities specifically for diabetes care.

Diabetes Mellitus↗

An integrated approach utilizing artificial neural networks and SELDI mass spectrometry for the classification of human tumours and rapid identification of potential biomarkers.

MOTIVATION: MALDI mass spectrometry is able to elicit macromolecular expression data from cellular material and when used in conjunction with Ciphergen protein chip technology (also referred to as SELDI-Surface Enhanced Laser Desorption/Ionization), it permits a semi-high throughput approach to be taken with respect to sample processing and data acquisition. Due to the large array of data that is generated from a single analysis (8-10000 variables using a mass range of 2-15 kDa-this paper) it is essential to implement the use of algorithms that can detect expression patterns from such large volumes of data correlating to a given biological/pathological phenotype from multiple samples. If successful, the methodology could be extrapolated to larger data sets to enable the identification of validated biomarkers correlating strongly to disease progression. This would not only serve to enable tumours to be classified according to their molecular expression profile but could also focus attention upon a relatively small number of molecules that might warrant further biochemical/molecular characterization to assess their suitability as potential therapeutic targets. RESULTS: Using a multi-layer perceptron Artificial Neural Network (ANN) (Neuroshell 2) with a back propagation algorithm we have developed a prototype approach that uses a model system (comprising five low and seven high-grade human astrocytomas) to identify mass spectral peaks whose relative intensity values correlate strongly to tumour grade. Analyzing data derived from MALDI mass spectrometry in conjunction with Ciphergen protein chip technology we have used relative importance values, determined from the weights of trained ANNs (Balls et al., Water, Air Soil Pollut., 85, 1467-1472, 1996), to identify masses that accurately predict tumour grade. Implementing a three-stage procedure, we have screened a population of approximately 100000-120000 variables and identified two ions (m/z values of 13454 and 13457) whose relative intensity pattern was significantly reduced in high-grade astrocytoma. The data from this initial study suggests that application of ANN-based approaches can identify molecular ion patterns which strongly associate with disease grade and that its application to larger cohorts of patient material could potentially facilitate the rapid identification of validated biomarkers having significant clinical (i.e. diagnostic/prognostic) potential for the field of cancer biology. AVAILIBILITY: Neuroshell 2 is commercially available from ward systems.

Astrocytoma↗

Community knowledge, attitude and practices regarding sexually transmitted infections in a rural district of Pakistan.

OBJECTIVE: To determine knowledge, attitude and practices regarding sexually transmitted infections in district Khairpur, Sindh, Pakistan. DESIGN AND METHODOLOGY: A needs assessment study employing a community based survey, key informant interviews and focus group discussions was conducted in all seven sub-districts of the district. This paper is based on the results of the key informant interviews and the focus group discussions. Thirty interviews and six group discussions were held with members of the community and with the health care providers. RESULTS: There was little awareness regarding causes and prevention of sexually transmitted infections in the community. The situation was slightly better among health care providers. While health care providers believed that the prevalence of sexually transmitted infections is high, the community did not consider themselves at risk. The community believed that these diseases are a problem among a sub-population of male adolescents, especially those who have homosexual relations. However, due to social norms, they rarely discussed such health problems with other family members or elders. Adolescents with any sexual health problems visit hakims and quacks. The community was aware about aetiology and some of the risk factors associated with AIDS and hepatitis, most probably due to the recent public health campaigns against both diseases. CONCLUSION: Considering the suspected high prevalence of sexually transmitted infections and the relative lack of knowledge, it is imperative that a public health intervention be initiated. This must include educating not only the community but also the health workers. The governments' initiative to train community workers in reproductive health is a step in the right direction.

Adolescent↗

Utility of participatory rural appraisal for health needs assessment and planning.

BACKGROUND: While poverty and lack of life opportunities are root causes of a high burden of disease and infant and maternal mortality, inadequate health care contributes heavily. Often those who are left without care are those who need it most. Existing health services are managed without taking into account acceptance and need perspectives. This further reduces the effectiveness of and equity in health care. In order to guide the planning of reproductive health services by a national NGO, health needs were assessed in a district in Sindh using a combination of participatory rural appraisal (PRA) and qualitative and quantitative research methods. PRA is considered as a better framework to assess, analyse and develop programs with communities. OBJECTIVE: The objective of PRA was to initiate community involvement and to understand the needs of health care from a community perspective. METHODOLOGY: PRA was conducted with groups of men and women from three rural areas in a district of Sindh, Pakistan using a life cycle framework. The community members identified various stages of their life with the associated health issues. RESULTS: This research was empowering to community members as it facilitated community involvement. The respondents took charge of the process of identification of health needs at PRA sessions. PRA helped identify health problems considered prevalent and important by the community. More importantly, it helped potential service providers and the community to initiate community involvement in planning. CONCLUSION: PRA is not only an effective tool for assessment and analysis of health issues but also a vehicle to promote community involvement. Additionally, participatory methods contribute to understand the context of quantitative data generated for planning purposes.

Adolescent↗

Molecular diversity of the plasmid genotypes among Rhizobium gene pools of sesbanias from different habitats of a semi-arid region (Delhi).

Plasmid genotypes of root nodulating rhizobial isolates of Sesbania, sampled from six ecologically distinct habitats, were characterized. Plasmid profile analysis revealed nine different plasmid types having molecular masses ranging from 30 to 300 MDa, distributed among six profile types that grouped the isolates into six plasmid classes. The six plasmid profiles were diverged from each other and lack many common plasmid types among them. Variation in number and types of symbiotic (Sym) plasmid was assessed by hybridization of plasmid profiles with sym gene probes. Relatedness among different plasmid types was assessed by hybridization of total DNAs as well as plasmid profiles of different isolates with labelled intact plasmid. Plasticity of plasmid genotype and possible recombination between different plasmid types is suggested from the results obtained. Structural diversity among sym plasmids was assessed by PCR amplified product profiles using primer corresponding to the reiterated nif promoter consensus element (NPC-PCR). A total of 26 NPC-PCR profile types were recognized. Genetic diversity among sym plasmids of isolates belonging to the same plasmid class and having similar sym plasmid suggested recombinations and rearrangements of sequences within the sym plasmids. Cluster analysis based upon similarity among profile types sorted the isolates across the ecological gradient. We suggest that habitat heterogeneity and plasticity of plasmid genotype together contribute for the generation of genetic diversity leading to strainal differentiation in rhizobia.

Fabaceae↗

Death due to bioterrorism-related inhalational anthrax: report of 2 patients.

On October 9, 2001, a letter containing anthrax spores was mailed from New Jersey to Washington, DC. The letter was processed at a major postal facility in Washington, DC, and opened in the Senate's Hart Office Building on October 15. Between October 19 and October 26, there were 5 cases of inhalational anthrax among postal workers who were employed at that major facility or who handled bulk mail originating from that facility. The cases of 2 postal workers who died of inhalational anthrax are reported here. Both patients had nonspecific prodromal illnesses. One patient developed predominantly gastrointestinal symptoms, including nausea, vomiting, and abdominal pain. The other patient had a "flulike" illness associated with myalgias and malaise. Both patients ultimately developed dyspnea, retrosternal chest pressure, and respiratory failure requiring mechanical ventilation. Leukocytosis and hemoconcentration were noted in both cases prior to death. Both patients had evidence of mediastinitis and extensive pulmonary infiltrates late in their course of illness. The durations of illness were 7 days and 5 days from onset of symptoms to death; both patients died within 24 hours of hospitalization. Without a clinician's high index of suspicion, the diagnosis of inhalational anthrax is difficult during nonspecific prodromal illness. Clinicians have an urgent need for prompt communication of vital epidemiologic information that could focus their diagnostic evaluation. Rapid diagnostic assays to distinguish more common infectious processes from agents of bioterrorism also could improve management strategies.

Abdominal Pain↗

Independent effects of intestinal parasite infection and domestic allergen exposure on risk of wheeze in Ethiopia: a nested case-control study.

BACKGROUND: Why asthma is rare in rural subsistence societies is not clear. We tested the hypotheses that the risk of asthma is reduced by intestinal parasites or hepatitis A infection, and increased by exposure to dust-mite allergen or organophosphorus insecticides in urban and rural areas of Jimma, Ethiopia. METHODS: From 12876 individuals who took part in a study of asthma and atopy in urban and rural Jimma in 1996, we identified all who reported wheeze in the previous 12 months, and a random subsample of controls. In 1999, we assessed parasites in faecal samples, Der p 1 levels in bedding, hepatitis A antibodies, serum cholinesterase (a marker of organophosphorus exposure), total and specific serum IgE, and skin sensitisation to Dermatophagoides pteronyssinus in 205 cases and 399 controls aged over 16 years. The effects of parasitosis, Der p 1 level, hepatitis A seropositivity, and cholinesterase concentration on risk of wheeze, and the role of IgE and skin sensitisation in these associations, were analysed by multiple logistic regression. FINDINGS: The risk of wheeze was independently reduced by hookworm infection by an odds ratio of 0.48 (95% CI 0.24-0.93, p=0.03), increased in relation to Der p 1 level (odds ratio per quartile 1.26 [1.00-1.59], p=0.05), and was unrelated to hepatitis A seropositivity or cholinesterase concentration. In the urban population, D pteronyssinus skin sensitisation was more strongly related to wheeze (9.45 [5.03-17.75]) than in the rural areas (1.95 [0.58-6.61], p for interaction=0.017), where D pteronyssinus sensitisation was common, but unrelated to wheeze in the presence of high-intensity parasite infection. INTERPRETATION: High degrees of parasite infection might prevent asthma symptoms in atopic individuals.

Adolescent↗