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J Brostoff

Publications and source records attributed to J Brostoff.

At least 19 recordsLinked to original sources

Molecular characterization of the bacteria adherent to human colorectal mucosa.

AIMS: To study large intestinal mucosal bacterial communities by Denaturing Gradient Gel Electrophoresis (DGGE) profiling and sequencing of 16S rRNA gene polymerase chain reaction (PCR) products amplified from DNA extracted from colorectal biopsies taken from healthy individuals. The specific aims were to determine how similar the mucosa-associated bacterial communities are within and between individuals and also to characterize the phylogenetic origin of isolated DGGE bands. METHODS AND RESULTS: Human colorectal biopsies were taken at routine colonoscopy from 33 patients with normal looking mucosa. The DNA was extracted directly from single biopsies and the bacterial 16S rDNA PCR amplified. The PCR products were profiled using DGGE to generate a fingerprint of the dominant members of the bacterial community associated with the biopsy. The reproducibility of this method was high (>98%). Washed and unwashed biopsies gave similar DGGE banding patterns (Median Similarity Coefficient - MSC 96%, InterQuartile Range - IQR 3.0%, n = 5). Adjacent biopsies sampled from the same patient using different forceps gave similar DGGE profiles (MSC 94%, n = 2). Two colorectal biopsies sampled at locations 2-5 cm apart, from each of 18 patients, resulted in very similar profiles (MSC 100%, IQR 2.8%). Biopsies sampled from different locations within the large intestine of the same patient also gave similar DGGE profiles (MSC 98% IQR 3.3%n = 6). Although all patients (n = 33) gave different DGGE profiles, some similarity (c. 34%) was observed between profiles obtained from 15 patients arbitrarily selected. 35 DGGE bands were excised and sequenced. Many were found to be most closely related to uncultured bacterial sequence entries in the Genbank database. Others belonged to typical gut bacterial genera including Bacteroides, Ruminococcus, Faecalibacterium and Clostridium. CONCLUSIONS: Bacterial communities adherent to colorectal mucosa within a normal patient show little variation; in contrast, mucosal bacterial communities sampled from different patients with normal colorectal mucosa show a high degree of variation. SIGNIFICANCE AND IMPACT OF THE STUDY: This research demonstrates that DGGE profiling of 16S rRNA gene PCR products amplified from DNA extracted directly from mucosal samples offers fresh insight into the bacterial communities that are adherent to colorectal mucosa. These findings are important with respect to further studies on the gastrointestinal tract in health and disease.

Adenomatous Polyposis Coli↗

Mizolastine therapy also has an effect on nasal blockade in perennial allergic rhinoconjunctivitis. RIPERAN Study Group.

BACKGROUND: Mizolastine is a new, nonsedating antihistamine with additional anti-inflammatory properties, providing relief in allergic rhinitis and urticaria. The aim of this study was to determine the efficacy and safety of 10 mg o.d. mizolastine given to patients with perennial allergic rhinoconjunctivitis. METHODS: This double-blind, placebo-controlled study involved 257 patients suffering from the disease for more than 10 years. They were allocated, after a 1-week placebo run-in, to receive mizolastine (n = 133) or placebo (n = 124) for 4 weeks. RESULTS: Mizolastine-treated patients showed significantly greater alleviation of nasal symptoms, with a mean decrease of 36% compared with pretreatment score, compared to a mean decrease of 10% in placebo patients (P < 0.001). Nasal blockade responded favorably to mizolastine compared to placebo and was associated with a significant reduction in rhinoscopy findings (P = 0.030). Likewise, the mean ocular symptom score decreased 40% in mizolastine-treated patients compared to 7% in the placebo group (P < 0.003). The safety profile of mizolastine was satisfactory and similar to that of placebo. CONCLUSIONS: In patients suffering from perennial allergic rhinoconjunctivitis, mizolastine is a safe and potent treatment. Mizolastine's pronounced effect on nasal blockade could possibly be linked to its anti-inflammatory properties.

Adult↗

Brain MR in chronic fatigue syndrome.

PURPOSE: To determine the prevalence of MR white matter abnormalities in patients with chronic fatigue syndrome (CFS). METHODS: Brain MR studies of 43 patients (29 women and 14 men, 22 to 78 years old) with a clinical diagnosis of CFS (n = 15), CFS with associated depression (n = 14), and CFS with associated other psychiatric disorders, namely, anxiety and somatization disorder (n = 14), were compared with brain MR studies in 43 age- and sex-matched control subjects. RESULTS: MR findings were abnormal in 13 (32%) of the patients in the study group (ages 34 to 78 years) and in 12 (28%) of the control subjects (ages 26 to 73 years). One patient with CFS had multiple areas of demyelination in the supratentorial periventricular white matter. Another patient with CFS and associated depression had a single focus of probable demyelination in the supratentorial periventricular white matter. In four patients with CFS (ages 34 to 48 years) MR abnormalities consisted of one or several punctate hyperintense foci in the corona radiata, centrum ovale, and frontal white matter. The remaining seven patients (ages 50 to 78 years) had frontoparietal subcortical white matter foci of high T2 signal. The prevalence of white matter hyperintensities was not different between the patients and the control subjects. CONCLUSIONS: Our findings suggest that no MR pattern of white matter abnormalities is specific to CFS.

Adult↗

Changes in glycosylation of IgG during fasting in patients with rheumatoid arthritis.

Patients with rheumatoid arthritis (RA) have a higher proportion of agalactosyl IgG than healthy individuals. Glycosylation status was examined in 26 RA patients who fasted for 7-10 days and afterwards followed a vegetarian diet for 3.5 months. The decrease in the proportion of agalactosyl IgG correlated significantly with the clinical improvement after the fasting period, but not after the vegetarian diet period. Although the glycosylation status of IgG may have played a role in the improvement of disease during the fasting period, it did not seem to be associated with, and therefore responsible for, the clinical improvement observed after the vegetarian diet.

Adult↗

Association of immunological changes with clinical efficacy in atopic eczema patients treated with traditional Chinese herbal therapy (Zemaphyte).

The efficacy of the Chinese herbal therapy (Zemaphyte) has been well established as a treatment for atopic eczema (AE) in clinical trials. The purpose of this study was to probe the immunological changes that occurred when patients were treated with the herbs for a period of 8 weeks. This treatment decreased serum IgE complexes (p less than 0.05) but did not affect total serum IgE or CD23 expression on peripheral blood monocytes. Peripheral blood mononuclear cells from patients before and after treatment were cultured overnight with interleukin 4 and the ability of this cytokine to induce CD23 on monocytes from treated patients was found to be significantly diminished (p less than 0.01). Soluble interleukin 2 receptor and soluble vascular cell adhesion molecule were both raised in the serum of AE patients compared to control individuals. Both these parameters were decreased following treatment (p less than 0.05). All these changes coincided with improvement in erythema and surface damage scores. There was no alteration in soluble intracellular adhesion molecule or soluble CD23. The results of these investigations would suggest that this herbal treatment has the ability to target various immunological parameters which may be involved in the pathogenesis of AE.

Administration, Oral↗

Razi's report about seasonal allergic rhinitis (hay fever) from the 10th century AD.

Seasonal allergic rhinitis (hay fever) is considered a disease of the postindustrial revolution era. Clinical reports of patients are readily available from the 19th century starting with John Bostock's description of his own summer symptoms. Also patients with "rose catarrh' are described in the 16th and 17th century. Although asthma is well described by Maimonides, clear descriptions of diagnosis, prevention and treatment of hay fever are rare in the first millennium. This report by Razi (prior to 925 AD) is perhaps the earliest such report yet. It is contained in a compendium written by Ibn Sharabeyun ben Ibrahim in the 13th or 14th century AD. The volume also contains work by Avicenna (Abo Ali-Sina; a friend of Razi) and other contemporary writers. Some of the treatments suggested in this early report may not be so acceptable to modern sufferers.

Asthma↗

Efficacy of mizolastine, a new antihistamine, compared with placebo in the treatment of chronic idiopathic urticaria.

A two-centre, double-blind, randomized, placebo (P)-controlled, parallel-group study was conducted in the UK to examine the efficacy and safety of mizolastine (M), a new H1-receptor antagonist, as a once-daily 10-mg dose in chronic idiopathic urticaria. Fifty-six outpatients (M: n = 28; P: n = 28) with a mean age of 38 +/- 15 years, a duration of disease of more than 3 years, and symptoms of urticaria at least twice a week in the absence of treatment were recruited. After a single-blind placebo run-in period, patients were allocated to one of two treatment groups and were evaluated after 7 and 28 days. The main characteristics (age, duration of disease, number of urticarial episodes, and total score) of the two groups were comparable at inclusion. Mizolastine was shown to improve the urticaria symptoms: at the end of the study, mizolastine produced a significantly greater decrease in the global symptom score comprising itch, wheals, and erythema (M: 2.1 +/- 2.1 vs P: 0.4 +/- 2.0; P = 0.002). The patient-rated global discomfort from symptoms measured by visual analog scale was significantly improved with mizolastine (M: 31.4 +/- 36.7) compared to placebo (P: 5.4 +/- 27.6; P = 0.003), with respectively more M responders (74.1%) than P responders (28.6%, P = 0.001), a responder being a patient with a > or = 50% decrease in VAS. Premature dropouts due to lack of efficacy and loss to follow-up mainly occurred at the first evaluation (day 7) and were more often observed in patients in the placebo group (n = 17) than in the mizolastine group (n = 8) (P = 0.031). No serious adverse events were recorded. Somnolence was reported in two mizolastine patients, one of whom discontinued the study. Thus, mizolastine may be considered a new treatment option for the symptoms of chronic urticaria.

Adult↗

Efficacy of traditional Chinese herbal therapy in vitro. A model system for atopic eczema: inhibition of CD23 expression on blood monocytes.

Recently, there has been growing interest in the use of traditional Chinese herbal therapy (TCHT) decoctions for the treatment of atopic eczema (AE). The mode of action of this treatment is still unknown, and in order to investigate this we have analysed the effect of an extract of these herbs (TCHTE) on interleukin 4 (IL-4)-induced CD23 expression on peripheral blood monocytes from non-atopic subjects. We found that TCHTE inhibited CD23 expression up to 60% (P < 0.001), whereas the placebo extract had no significant effect on CD23 expression. This inhibition was dose-dependent, and TCHTE was effective at a concentration of 250 micrograms/ml (P = 0.001). If TCHTE or placebo was added after IL-4, the action of TCHTE could still be seen at 12 h. This inhibition was not due to cell death, as peripheral blood mononuclear cells (PBMCs) cultured with TCHTE or placebo at a concentration used in these experiments had a similar viability to control cultures. Down-regulation of the low affinity receptors for IgE on antigen-presenting cells in patients with AE may contribute to the benefit observed following treatment with TCHT.

Adult↗

Peanut allergy.

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Allergens↗

Follow-up of adult patients with atopic eczema treated with Chinese herbal therapy for 1 year.

Adult patients with severe atopic eczema who had completed a double-blind placebo-controlled crossover trial of a specific formulation of Chinese herbal therapy were offered continued therapy for 1 year. Of 31 patients who completed the original placebo-controlled study and after a washout period and 2 months of further treatment, 17 continued treatment (group 1), 11 chose not to continue treatment (group 2), one was lost to follow-up and two patients originally in group 1 decided to stop treatment and became pregnant. At the end of the year, 12 of the patients in group 1 had greater than 90% reduction and the remaining five had greater than 60% reduction in clinical scores compared with baseline values. Clinical scores of patients in group 2 gradually deteriorated so that by the end of the year the difference between groups 1 and 2 was highly significant (P = 0.005 and P = 0.002 for erythema and surface damage, respectively). At the end of the year no patient in group 1 felt able to discontinue treatment permanently, but eight patients were on an alternate-day regimen by 6 months and remained on this regimen until the end of the year, and seven were able to control their eczema with a 1 in every 3 day treatment by the end of the year. The remaining two patients continued on daily treatments. Toxicology screening revealed no abnormalities in either full blood counts or biochemical parameters in any patient on continued treatment. Improvement in disease was not associated with any significant change in serum IgE level or peripheral blood lymphocyte subsets.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Brainstem perfusion is impaired in chronic fatigue syndrome.

We looked for brain perfusion abnormalities in patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). An initial pilot study revealed widespread reduction of regional brain perfusion in 24 ME/CFS patients, compared with 24 normal volunteers. Hypoperfusion of the brainstem (0.72 +/- 0.05 vs. 0.80 +/- 0.04, p < 0.0001) was marked and constant. We then tested whether perfusion to the brainstem in ME/CFS patients differs from that in normals, patients with major depression, and others with epilepsy. Data from a total of 146 subjects were included in the present study: 40 normal volunteers, 67 patients with ME/CFS (24 in the pilot study, 16 with no psychiatric disorders, 13 with ME/CFS and depression, 14 with ME/CFS and other psychiatric disorders), 10 epileptics, 20 young depressed patients and 9 elderly depressed individuals. Brain perfusion ratios were calculated using 99Tcm-hexamethylpropylene amine oxime (99Tcm-HMPAO) and single-photon emission tomography (SPET) with a dedicated three-detector gamma camera computer/system (GE Neurocam). Brain-stem hypoperfusion was confirmed in all ME/CFS patients. Furthermore, the 16 ME/CFS patients with no psychiatric disorders and the initial 24 patients in the pilot study showed significantly lower brainstem perfusion (0.71 +/- 0.03) than did depressed patients (0.77 +/- 0.03; ANOVA, p < 0.0001). Patients with ME/CFS have a generalized reduction of brain perfusion, with a particular pattern of hypoperfusion of the brainstem.

Adolescent↗

Unexplained illness: the mind versus the environment.

Every doctor in clinical practice is familiar with the patient who presents with multiple 'soft' symptoms. Where organic pathology cannot be demonstrated, there is a tendency to apply psychiatric labels. Indeed, it has been suggested that the risk of psychiatric disorder increases linearly with the number of presented symptoms. In psychiatric practice, the mere absence of an organic cause of disease is often regarded as adequate reason to invoke a psychological mechanism. However, this action precludes the possibility of any other diagnosis, and thus constricts therapeutic management to the psychiatric realm. Such psychologization of illness is commonplace, overworked and infrequently challenged. This highlights the longstanding controversy over multiple allergy and the role of psychiatric disorder.

Environmental Illness↗

Food intolerance.

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Food Hypersensitivity↗

Mapping of T cell epitopes of the major fraction of rye grass using peripheral blood mononuclear cells from atopics and non-atopics. II. Isoallergen clone 5A of Lolium perenne group I (Lol p I).

Rye grass is the major cause of hay fever which currently affects 20% of the population. Lolium perenne group I (Lol p I) is a glycoprotein of 240 amino acid residues, representing the main allergen of rye grass. We have used peripheral blood mononuclear cells (PBMC) from controls and subjects allergic to rye grass and cultured them with L. perenne extract (LPE) and Lol p I and measured lymphocyte activation using thymidine incorporation. Patients were further studied against the 115 overlapping peptides of the iso-allergen clone 5A of Lol p I to see whether the 4 amino acid residue differences between clone 1A and clone 5A affect the T cell epitope and thus, lymphocyte activation. There are 24 peptide differences between isoallergen clone 1A and clone 5A occurring in pools 4, 13, 16 and 19 each one of which could be an immunodominant epitope. The PBMC from all allergic patients studied showed a strong proliferative response to LPE and Lol p I. Five immunogenic peptide pools, pool 6, 15, 16, 17 and 19 of the isoallergen clone 5A were also identified. Most of these pools are in the C-terminal region of Lol p I. Out of 20 pools tested in vitro 1 pool (pool-17) induced PBMC proliferation in five out of six patients who were not restricted to an HLA class II DR gene product. However, three out of the six subjects responded to various other peptide pools in addition to the immunodominant pool. In spite of the amino acid differences between the two clones, pool 17 still remains the immunodominant T cell epitope. Control subjects showed only weak responses to LPE and no detectable response to either Lol p I or peptide pools. From within the most active pool we have defined two peptides of the isoallergen clone 5A (identical in sequence with clone 1A) which stimulate lymphocytes from rye grass-sensitive patients in vitro. Previous studies with the two continuous sequences (193WGAVWRIDTPDK204 and 195AVWRIDTPDKLT206) tested in vivo by intradermal skin testing have shown typical delayed-type hypersensitivity reactions after 24-48 h in one patient. Comparison of amino acid sequences of Lol p I, Lol p II and Lol p III proteins revealed a significant level of structural similarity among them. Interestingly, 50% of the residues of the second peptide sequence are also present in Lol p II and Lol p III.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

The efficacy of traditional Chinese herbal therapy in atopic eczema.

A traditional Chinese herbal therapy (Zemaphyte) for the treatment of atopic eczema (AE) is currently being assessed. This review attempts to highlight its success in patients who are recalcitrant to Western forms of treatment and the rationale behind its use. The herbal preparation is a mixture of 10 herbs with some known pharmacological agents and actions. The concept of such a complex mixture in clinical treatment is anathema to Western medicine but acceptable in traditional Chinese medicine. As this formation has been shown to be effective in two double-blind crossover trials, investigative work on components from the mixture must be established in order to find the active constituent(s) and describe their mode of action. This research will also lead to a greater understanding of the complex immunopathology of AE.

Clinical Trials as Topic↗