Cystathionine beta-synthase (CBS) deficiency is a rare inherited disorder in the methionine catabolic pathway, in which the impaired synthesis of cystathionine leads to accumulation of homocysteine. Patients can present to many different specialists and diagnosis is often delayed. Severely affected patients usually present in childhood with ectopia lentis, learning difficulties and skeletal abnormalities. These patients generally require treatment with a low-methionine diet and/or betaine. In contrast, mildly affected patients are likely to present as adults with thromboembolism and to respond to treatment with pyridoxine. In this article, we present recommendations for the diagnosis and management of CBS deficiency, based on a systematic review of the literature. Unfortunately, the quality of the evidence is poor, as it often is for rare diseases. We strongly recommend measuring the plasma total homocysteine concentrations in any patient whose clinical features suggest the diagnosis. Our recommendations may help to standardise testing for pyridoxine responsiveness. Current evidence suggests that patients are unlikely to develop complications if the plasma total homocysteine concentration is maintained below 120 μmol/L. Nevertheless, we recommend keeping the concentration below 100 μmol/L because levels fluctuate and the complications associated with high levels are so serious.

Nuts are high in fat but have a fatty acid profile that may be beneficial in relation to risk of coronary heart disease. Nuts also contain other potentially cardioprotective constituents including phytosterols, tocopherols and squalene. In the present study, the total oil content, peroxide value, composition of fatty acids, tocopherols, phytosterols and squalene content were determined in the oil extracted from freshly ground walnuts, almonds, peanuts, hazelnuts and the macadamia nut. The total oil content of the nuts ranged from 37.9 to 59.2%, while the peroxide values ranged from 0.19 to 0.43 meq O2/kg oil. The main monounsaturated fatty acid was oleic acid (C18:1) with substantial levels of palmitoleic acid (C16:1) present in the macadamia nut. The main polyunsaturated fatty acids present were linoleic acid (C18:2) and linolenic acid (C18:3). alpha-Tocopherol was the most prevalent tocopherol except in walnuts. The levels of squalene detected ranged from 9.4 to 186.4 microg/g. beta-Sitosterol was the most abundant sterol, ranging in concentration from 991.2 to 2071.7 microg/g oil. Campesterol and stigmasterol were also present in significant concentrations. Our data indicate that all five nuts are a good source of monounsaturated fatty acid, tocopherols, squalene and phytosterols.

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This study investigates the presence of CD8(+) T lymphocytes and their possible association with viral infection in bronchi of victims of fatal asthma. Postmortem samples from the peribronchial region of the lung were obtained from seven patients who died an asthma death (AD), seven asthmatic patients who died of unrelated causes (AUC), and seven postmortem cases with no history of lung disease (control subjects). Using immunohistochemical techniques, the CD8(+) cytotoxic T-cell population in peribronchial tissue was characterized in three patient groups. The percentage of CD8(+) cells expressing the activation marker CD25 was higher in the AD group than in both the AUC and control groups (11.91 +/- 1.92% versus 3.93 +/- 1.63% and 1.09 +/- 0.56%, respectively (p < 0.001). Perforin expression, a marker of cytotoxicity, was highest in the AD group (9.16 +/- 1.5%) compared with 1.39 +/- 0.9; 1.8 +/- 0.6% in the AUC and control groups respectively (p < 0.001). Expression of interleukin-4 (IL-4) and interferon gamma (IFN-gamma) by CD8(+) T cells was higher in the AD group than the control group (p < 0.05). Furthermore, the IFN-gamma/IL-4 ratio in the AD group was less than half that of the control group (1.46 +/- 0.2 versus 3.2 +/- 0.1; p = 0.02). Using polymerase chain reaction (PCR), viral genome for rhinovirus (RV) was detected in lung tissue from three of the seven cases in the AD group. Two of these cases also had detectable respiratory syncytial virus (RSV). Viral genome for RSV was detected in five of the AUC group and in one of these cases, RV was also detected. No viral genome was detected in the lungs of the control group. In conclusion, this study provides novel evidence of an aberrant CD8(+) T-cell population, possibly in response to viral infection in subjects who die of acute asthma.

The Castang Foundation, Bath Unit for Research in Paediatrics, National Institute of Health Research, the Royal United Hospitals Bath NHS Foundation Trust, BRONNER-BENDER Stiftung/Gernsbach, University Children's Hospital Zurich.

Some patients with severe asthma cannot be controlled with high doses of inhaled steroids (ICS), which may be related to ongoing environmental allergen exposure. We investigated whether 10 weeks of high altitude allergen avoidance leads to sustained benefits regarding clinical and inflammatory markers of disease control in adolescents with persistent asthma despite treatment with high dose ICS. Eighteen atopic asthmatic adolescents (12–18 yr, 500–2000 µg ICS daily) with established house dust mite allergy, participated in a parallel‐group study. Quality of life (PAQL), lung function, bronchial hyperresponsiveness (BHR) to adenosine and histamine, induced sputum and urine samples were collected repeatedly from 10 patients during a 10‐week admission period to the Swiss Alps (alt. 1560 m) and at 6 weeks after return to sea level. Results were compared with those in eight patients, studied in their home environment at sea level for a similar time period. Throughout the study, asthma medication remained unchanged in both groups. During admission to high altitude, PAQL, lung function, BHR to adenosine and histamine, and urinary levels of eosinophil protein X (U‐EPX), leukotriene E4 (U‐LTE4) and 9α11β prostaglandin F2 (U‐9α11β PGF2) improved significantly (P < 0.05), with a similar tendency for sputum eosinophils (P < 0.07). Furthermore, the changes in PAQL and BHR to adenosine and histamine were greater in the altitude than in the control group (P < 0.05). At 6 weeks after renewed allergen exposure at sea level, the improvements in PAQL (P < 0.05), BHR to adenosine (P < 0.07) and histamine (P < 0.05), as well as U‐EPX (P < 0.05) and U‐LTE4 (P < 0.05) were maintained. A short period of high altitude allergen avoidance, on top of regular treatment with ICS and long‐acting β2‐agonists, results in improvement of asthma, as assessed by clinical and inflammatory markers of disease severity. These findings indicate that short‐term, rigorous allergen avoidance can improve the long‐term control of severe asthma over and above what can be achieved even by high doses of inhaled steroids.

These results indicate that mast cell activation is a feature not only of the early but also the late asthmatic response. Finally, increased LTE4 supports the contribution of the leukotrienes to airway obstruction during both phases of the asthmatic response to allergen.

Exercise-induced bronchoconstriction (EIB) is thought to occur in 70-80% of asthmatics, most commonly amongst those with moderate-to-severe airway hyperresponsiveness [1]. It is characterized by transient airflow obstruction resulting in a Š15% decrease in forced expiratory volume in one second (FEV1) following 5-8 min of exercise. The fall in FEV1 reaches a maximum approximately 10 min after exercise and gradually normalizes over the next hour [2]. The precise pathophysiology of EIB remains unclear, although it is widely accepted that during exercise the upper airways are unable to adequately warm and humidify the increased volumes of inspired air. This results in airway cooling and increased airway fluid osmolality in the lower airways [3,4]. One hypothesis suggests that hyperosmolar triggering of mast cells and possibly other inflammatory cells results in the release of bronchoconstricting mediators, e.g. cysteinyl-leukotrienes (cys-LTs), histamine and prostaglandin (PG)D 2 [5].Previous indications for the participation of mast cell mediators in the pathogenesis of EIB are based on pharmacological data. For example, disodium cromoglycate (DSCG), a drug which stabilizes mast cell membranes, is effective in blunting exercise-induced asthma [6,7]. Pretreatment with a number of H 1 receptor antagonists has been shown to attenuate EIB [8][9][10]; however, the degree of protection afforded by this class of drugs has been modest. More recently, studies employing leukotriene receptor antagonists [11,12] and biosynthesis inhibitors [13] have implicated leukotrienes in the airway bronchoconstrictor response to exercise.The direct approach of measuring mast cell mediator release in response to exercise challenge has yielded ambiguous results. Some studies have reported an elevation in plasma and whole blood histamine concentrations following EIB [14,15], while other studies have failed to verify those findings [16,17]. Apart from the methodological problems encountered when sampling plasma histamine [18] and its short half-life in the circulation, approximately 1 min [19], it has been suggested that elevations in plasma histamine mainly reflect the basophilia which normally accompanies exercise [20]. Increases in the levels of tryptase and PGD 2 , both specific mast cell markers, have been detected in nasal lavage following nasal provocation with cold dry air [21], but not after exercise [22,23].The purpose of this study was to provide evidence to establish mast cell activation as a feature of EIB. To this end, a combination of mast cell markers, 9α,11β-PGF 2 Sullivan, A. Roquet, B. Dahlén, F. Larsen, A. Eklund, M. Kumlin, P.M. O'Byrne, S-E. Dahlén. ©ERS Journals 1998. ABSTRACT: Controversy remains about the causative mediators in the bronchoconstrictive response to exercise in asthma. This study examined whether mast cell activation is a feature of exercise-induced bronchoconstriction by measuring urinary metabolites of mast cell mediators. Evidence for mast cell activation during exercise-induced bronchoconstriction....