Identification of neutrophil chemotactie factors in bronchoalveolar lavage fluid of asthmatic patients

Background Although neutrophils have been implicated in bronchial asthma, the mechanism(s) which bring these cells into the airways is poorly understood. Objective To investigate the presence and identity of neutrophil chemotactic factors in bronchoalveolar lavage (BAL) fluid from atopic asthmatic subjects. Method BAL fluid was obtained from 13 subjects (seven asthmatics and six normals). aged 19 to 60 yr, at bronchoscopy. Separation of neutrophil chemotactic activity (NCA) was achieved by FPLC cation exchange chromatography. Fractions were collected and assayed for chemotaxis multiwell micro-chemotaxes chambers using polycarbonate filters, for the complement peptide C5a/C5a des Arg by radioimmunoassay (RIA) and for interleukin-8 (IL-8) by ELISA. Results NCA was found in FPLC fractions of BAL samples in four out of seven asthmatics and each of these subjects had at least three similar peaks of NCA. The major peak of NCA was found to contain immunoreactive C5a/C5a des Arg and chemotaxis. In response to this NCA could be blocked by desensitization of the neutrophils with recombinant C5a. Purified serum derived C5a/C5a des Arg was found to have altered chromatographic properties when added to BAL fluid; this suggested that BAL fluid contained proteins which interacted with the C5a/C5a des Arg. Immunoreactive IL-8 (iIL-8) was also detected but its concentration or chemical form was insufficient to induce neutropbil chemotaxis. Conclusion This study demonstrates that bronchial asthmatic lavage fluid contains C5a/C5a des/Arg and iL-8, together with other as yet unidentified factors which may contribute to neutropbil recruitment in this disease.     

Are hypodense eosinophils in children activated or immature?

In patients with allergic asthma and rhinitis high numbers of hypodense eosinophils (HE) have been demonstrated. In a previous study we reported that asthmatic and healthy children had more HE than their adult counterparts. We assumed that this might, in part, he due to the presence of immature eosinophils in children. To distinguish between immature and activated eosinophils, determination of eosinophil cationic protein (ECP) might be interesting as it is known that high serum levels of ECP are associated with increased activation of eosinophiis. In this study we determined (he levels of ECP in scrum in asthmatic and healthy children and adults trying to distinguish activated from immature eosinophils. We found that ECP levels were not increased in children (healthy and asthmatic) compared to adults (healthy and asthmatic). This supports the hypothesis that increased numbers of HE in childhood are, at least in part, immature eosinophils. Nevertheless, we could confirm that inflammation was present in children because soluble interleukin-2-receptor (slL-2R), a marker of lymphocyte activation, was higher in asthmatic children as compared to healthy children. IL-6, a marker of macrophage/monocyte activation, was not different in the different patient groups. We conclude that although signs of inflammation are present in childhood asthma, the increased numbers of HE in children are in part due to the presence of immature eosinophils.     

Persistent bone marrow failure with dysplastic features following pentostatin therapy for hairy cell leukaemia

Myelodysplastic syndromes (MDS) have rarely been reported after treatment with nucleoside analogues, and mainly in patients who have also received alkylating agents. We report a patient who developed MDS (refractory anaemia with ring sideroblasts) after treatment with pentostatin (deoxycoformycin) alone.     

Augmentation strategies in geriatric depression

Approximately 30–40% of elderly patients with major depression have inadequate response to an initial therapeutic trial of antidepressant medication. In these cases augmentation of the antidepressant has been recommended as one way of improving the rate of response. This article reviews the literature on augmentation strategies in treatment-resistant geriatric depression. Successful augmentation with lithium, triiodothyronine, stimulants, carbamazepine, valproate and a tricyclic–serotonin reuptake inhibitor combination have been described. However, there have been no controlled trials and, with the exception of two open prospective studies of lithium potentiation, the literature consists entirely of case reports and retrospective case series. As a result, it is difficult to draw conclusions about the efficacy of these strategies in late life, especially since treatment failures seldom get reported. Side-effects may limit the usefulness of some augmentation regimens in old age—up to 25% of patients treated with lithium or carbamazepine discontinued these medications because of adverse events. There is a need for controlled studies to better determine the clinical utility of augmentation strategies in physically well depressed elderly, as well as those with depression complicating medical illness, dementia and other neurological disorders.     

The long-tube single plate Molteno implant for the treatment of recalcitrant glaucoma

One hundred cases of recalcitrant glaucoma were operated with a long tube single-plate Molteno implant (LSMI). At the median follow-up of 15 months an intraocular pressure of 19 mm Hg was obtained in 64 of the 87 eyes (73%) which have a minimum follow-up of 6 months (secondary non-neovascular glaucomas=19; congenital glaucomas=26; secondary neovascular glaucomas=12). The interval probability (percentage±standard error) of obtaining a successful result (IOP19 mmHg) was 79% (±13) at twelve months from surgery, and 53% (±24) at the eighteen month interval. The least favorable results were obtained in the secondary non-neovascular glaucomas. Complications observed included choroidal detachment (24%), tube exposure (4%), tube-endothelium contact (6%), plus band keratopathy, fibrous ingrowth, traction retinal detachment and corneal ulcers.Seventeen cases needed repeate surgery for the management of complications. In order to decrease the post-operative hypotony, we have been using a tourniquet suture around the tube at the time of implantation to occlude it temporarily and limit the outflow.     

Potentiation of allergic bronchoconstriction by repeated exposure to formaldehyde in guinea-pigs in vivo

BACKGROUND: Indoor formaldehyde (FA) might worsen allergies and be an underlying factor for the increasing incidence and severity of asthma; the exact mechanism, however, remains unclear. OBJECTIVE: The present study examined the effects of repeated exposure to FA on methacholine- and antigen-induced bronchoconstriction in guinea-pigs in vivo. METHODS: First, non-sensitized guinea-pigs were transnasally treated with 0.1 or 1.0% FA or saline three times a week for 6 weeks, and increasing concentrations of methacholine (50, 100, and 200 microg/mL) were inhaled at 5-min intervals. Second, guinea-pigs pre-treated with transnasal administration of FA or saline using the same protocol were passively sensitized with anti-ovalbumin (OA) serum 7 days before antigen challenge. Third, guinea-pigs were actively sensitized with OA and pre-treated with transnasal administration of FA or saline using the same protocol. The lateral pressure of the tracheal tube (Pao) was measured under anesthesia and artificial ventilation. RESULTS: The antigen-induced increase in Pao in actively sensitized guinea-pigs was significantly potentiated by FA exposure in a dose-dependent manner. The dose-response curve of the methacholine-induced increase in Pao in non-sensitized guinea-pigs or of the antigen-induced increase in Pao in passively sensitized guinea-pigs was not altered by FA exposure. Transnasal administration of FA significantly increased the serum anti-OA homocytotropic antibody titre (IgG) as measured by the passive cutaneous anaphylaxis reaction in actively sensitized guinea-pigs. CONCLUSION: The results suggest that repeated exposure to FA worsens allergic bronchoconstriction through enhancing antigen sensitization.     

Occupational IgE-mediated allergy to Tribolium confusum (confused flour beetle)

BACKGROUND: We report on IgE-mediated allergy in a worker caused by Tribolium confusum (confused flour beetle). These beetles lived in the "old" flour to which he was exposed in his work. CASE REPORT: A 35-year-old, nonatopic mechanic in a rye crispbread factory developed rhinitis, conjunctivitis, and asthmatic symptoms, as well as urticaria on his wrists, lower arms, hands, neck, and face, during the maintenance and repair of machines contaminated by flour. This flour had been in and on the machines for a long time, and it contained small beetles. The patient did not suffer any symptoms when handling fresh, clean flour. RESULTS: Skin prick tests with standard environmental allergens, storage mites, enzymes, flours, and molds were negative. A prick test with flour from the machines gave a 10-mm reaction. An open application of the same flour caused urticarial whealing on the exposed skin. Prick tests with fresh flour from the factory were negative. A prick test with minced T. confusum from the flour in the machines gave a 7-mm reaction. Histamine hydrochloride 10 mg/ml gave a 7-mm reaction. Specific serum IgE antibodies to T. confusum were elevated at 17.2 kU/l. Prick tests with the flour from the machines were negative in five control patients. CONCLUSIONS: The patient had occupational contact urticaria, rhinitis, conjunctivitis, and asthmatic symptoms from exposure to flour. His symptoms were caused by immediate allergy to the beetle T. confusum. Immediate allergy to this beetle has rarely been reported in connection with respiratory symptoms, but it may be more common. Contact urticaria from this source has not been reported before.     

Prevention of Postinfectious Asthma in Children by Reducing Self-Inoculatory Behavior

Recent studies have shown that the spread of infectious nasalsecretions from hand-to-hand or hand-to-object, followed byself-inoculation is an efficient means of viral transmission.The present study was designed to investigate whether self-inoculationbehavior in asthmatic children could be reduced and, if so,whether this reduction would reduce the frequency of infectionand asthma. Sixteen subjects aged 4 to 8, all diagnosed withpostinfectious asthma, were assigned to a treatment (differentialreinforcement of other behavior and contingent education) orplacebo control condition. Results indicate that self-inoculatorybehavior, infection, and asthma were signjficantly reduced.These findings may indicate an important role for behavioralmedicine inpostinfectious asthma.