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Biomedical subjects

C Flohr

Publications and source records attributed to C Flohr.

6 recordsLinked to original sources

Atopic dermatitis and the 'hygiene hypothesis': too clean to be true?

BACKGROUND: The so-called 'hygiene hypothesis' postulates an inverse relationship between atopic dermatitis (AD) and an environment that leads to increased pathogen exposure. OBJECTIVES: We sought to systematically identify, summarize and critically appraise: (i) the epidemiological evidence to suggest that environmental exposures that lead to an increase in microbial burden reduce the risk of AD; (ii) whether any specific infections have been shown to reduce AD risk; (iii) whether there is a link between immunizations, use of antibiotics and AD risk; and (iv) to comment on the new therapeutic approaches in AD that have evolved out of the 'hygiene hypothesis'. METHODS: We searched Medline from 1966 until August 2004 to identify relevant studies for inclusion. Differences in study design and populations did not allow formal meta-analysis. Studies were therefore described qualitatively. RESULTS: We identified 64 studies that were relevant to our review, 27 (42%) of which were of prospective design. There was prospective evidence to support an inverse relationship between AD and endotoxins, early day care and animal exposure. Two well-designed cohort studies have found a positive association between infections in early life and AD, and measles vaccination and AD. Antibiotic use was consistently associated with an increase in AD risk even into the antenatal period, although a few studies did not reach conventional statistical significance. A few small randomized controlled trials have suggested that probiotics can reduce AD severity and that probiotics may also be able to prevent AD to some degree. CONCLUSIONS: Although population-based studies have suggested a consistent inverse relationship between AD and increasing family size, this does not seem to be explained by a straightforward increased exposure to a single environmental pathogen. The effect seen with early day care, endotoxin and animal exposure may be due to a nonpathogenic microbial stimulus of a chronic or recurrent nature. This would also explain the risk increase associated with antibiotic use. Caution should prevail in the prescribing of antibiotics early in life, especially in children with a family history of AD. Larger well-designed pragmatic trials on probiotics and the prevention and treatment of AD are now needed to inform whether such interventions should be used in routine clinical practice.

Adolescent↗

Prevalence and associated factors of atopic dermatitis symptoms in rural and urban Ethiopia.

BACKGROUND: Allergic diseases, including atopic dermatitis (AD), are increasingly becoming a clinical problem in developing countries. OBJECTIVE: We investigated the prevalence of AD symptoms and the effects of potential environmental aetiologies in rural and urban areas of Jimma in southwestern Ethiopia. METHODS: Information on allergic disease symptoms and lifestyle factors was gathered in an interviewer-led cross-sectional questionnaire-based population survey of 9844 urban and 3032 rural participants of all ages. A one-in-four subsample underwent skin prick testing for hypersensitivity to Dermatophagoides pteronyssinus, mixed threshings, and aspergillus. RESULTS: Around 95% of those eligible took part in the survey. Lifetime cumulative prevalence of AD symptoms was generally low with an overall prevalence of 1.2%, but was higher in the urban (1.5%) than in the rural area (0.3%; odds ratio (OR)=4.45 [95% CI 2.34-8.47]). AD symptoms were strongly associated with wheeze (adjusted OR=22.03 [15.45-31.42]) and rhinitis symptoms (61.94 [42.66-89.95]). Of several environmental exposures assessed, residence in a house made of brick (rather than mud) walls with wooden (rather than clay) floor, exposure to cigarette smoke as a child, having lived outside of Jimma in the past, and being of the Tigrean ethnic group were associated with an increased risk of AD symptoms. CONCLUSION: Although the overall prevalence of AD symptoms was low in this Ethiopian population, a marked urban-rural gradient was evident. Lifestyle factors linked to urbanization were associated with an increased risk of AD symptoms.

Adolescent↗

Dirt, worms and atopic dermatitis.

The past three decades have witnessed a marked rise in the prevalence of atopic diseases in industrialized countries and urban centres in less developed regions. This has led to an intense search for aetiological factors that may explain such a pattern. Epidemiological and immunological data suggest the eradication of nonparasitic and endoparasitic infections as possible aetiological elements. This has been formulated as the 'hygiene hypothesis', linking a reduced frequency of childhood infections with allergy. So far, most work in this area has focused on asthma. The potential relationship between endoparasites and atopic dermatitis has received much less attention. This paper reviews the scientific literature on the links between atopic dermatitis and endoparasites. At present, there is no clear evidence for a direct relationship between the two. This may be due to the overall small number of studies and insufficient methodological rigour in the existing body of research.

Asthma↗

A mutation in subunit B of the DNA polymerase alpha-primase complex from Novikoff hepatoma cells concomitant with a conformational change and abnormal catalytic properties of the DNA polymerase alpha-primase complex.

Mutated constituents of the DNA replication complex might contribute to the mutational load of the genome during tumor development by impairing DNA synthesis as well as cell cycle-related control of DNA replication. To prove or disprove this hypothesis, we looked for mutations in the cDNA sequences of the four subunits of DNA polymerase alpha-primase from both highly malignant Novikoff hepatoma cells and regenerating normal rat liver and compared physicochemical and catalytic properties of the DNA polymerase alpha-primase complexes purified from both sources. Sequence analysis showed two mutations in subunit B from Novikoff cells: one in nucleotide position 855 (CCG-->CCA) that did not result in an amino acid exchange and one in position 862 (GTG-->ATG) that caused a change of valine to methionine in codon 288. No mutation was found in the three other subunits. The wild-type and mutated sequences of subunit B were cloned and expressed in vitro. Sedimentation analysis of the expressed polypeptides revealed different sedimentation constants, indicating that the amino acid exchange affected the conformation of subunit B. The analysis of the purified DNA polymerase alpha-primase complexes showed a sedimentation value that was significantly higher for the enzyme complex from normal liver than for that from Novikoff cells. In addition, DNA polymerase alpha-primase complexes from Novikoff cells showed higher sensitivity to camptothecin, topotecan, and structurally related compounds (such as (R,S)-7-ethyl-10-hydroxy camptothecin, 9-aminocamptothecin, and 10-hydroxycamptothecin) than the enzyme from normal rat liver. Thus, the amino acid change found in subunit B appears to result in a conformational change of the DNA polymerase alpha-primase complex from Novikoff hepatoma cells. Whether this mutation influences genetic instability or tumor development needs to be explored.

Animals↗

The plague fighter: Wu Lien-teh and the beginning of the Chinese public health system.

At the end of 1910, when the Qing dynasty was on the verge of collapse and the whole Chinese empire in a process of transformation, North Manchuria was devastated by a large pneumonic plague epidemic. The Russian and Japanese governments wanted to use the outbreak of the disease as a pretext to invade north-east China, making plague an issue of international politics. At this dramatic moment the empire relied on the skills of the young Chinese doctor Wu Lien-teh, the first Chinese medical graduate from Cambridge. Wu investigated the disease on the spot, chaired an international plague conference in Shenyang (Manchuria) in April 1911, and, later on, became the figurehead of fundamental public health reforms in Republican China. Highly ambitious, striving for personal fame and international renown for China, supported by an excellent network of personal connections, and equipped with a medical training considered the best in the world at the time, he launched on a startling career as one of China's key medical reformers and international representatives. His history is an example of the inseparable links between personal fate and historical events, and between the interests of scientists, medical men, politicians, and businessmen on the national and international stages.

China↗