Asthma -- a need for a rethink?

Asthma is a major medical problem but, despite decades of research, the mechanisms that underlie this condition remain elusive. Although the eosinophil has been regarded as a cell that is central to the pathogenesis of asthma, the failure to abrogate asthma symptoms by novel treatments that are designed to suppress the recruitment of eosinophils to the airways challenges this dogma. Our approach to understanding bronchial asthma needs to be broadened to include alterations in the function of afferent nerves that supply airways. Changes in the activity of these nerves offer a possible mechanism by which asthmatic subjects are uniquely responsive to a wide range of physiological and chemical stimuli. Here, we review the current status of asthma research.     

Real-time measurement of indoor particulate matter originating from environmental tobacco smoke: a pilot study

Short-term measurement of suspended particulate matter has been recently made possible since the release of laser-operating portable instruments. Data of a pilot study of field evaluation of environmental tobacco smoke (ETS) with a portable instrument are reported. We analysed the concentrations of total suspended particle (TSP) and of the fine particles PM10, PM7, PM2.5 and PM1 released indoor from a single cigarette, and their levels inside smoking- and non-smoking-areas of a restaurant. The results indicate that ETS creates high level indoor particulate pollution, with concentrations of PM10 exceeding air quality standards. This kind of field evaluation could allow a more careful assessing of short-term exposure to ETS and its relevance to public health.     

Characterization of the anandamide induced depolarization of guinea-pig isolated vagus nerve

1. There is considerable interest in elucidating potential endogenously derived agonists of the vanilloid receptor and the role of anandamide in this regard has received considerable attention. In the present study, we have used an electrophysiological technique to investigate the mechanism of activation of vanilloid receptors in an isolated vagal preparation. 2. Both capsaicin and anandamide depolarized de-sheathed whole vagal nerve preparations that was antagonized by the VR1 antagonist, capsazepine (P<0.05) whilst this response was unaltered by the cannabinoid (CB1) selective antagonist SR141716A or the CB2 selective antagonist, SR144528, thereby ruling out a role for cannabinoid receptors in this response. 3. The PKC activator, phorbol-12-myristate-13-acetate (PMA) augmented depolarization to both anandamide and capsaicin and this response was significantly inhibited with the PKC inhibitor, bisindolylmaleimide (BIM) (P<0.05). 4. The role of lipoxygenase products in the depolarization to anandamide was investigated in the presence of the lipoxygenase inhibitor, 5,8,11-Eicosatriynoic acid (ETI). Depolarization to anandamide and arachidonic acid was significantly inhibited in the presence of ET1 (P<0.05). However, in the absence of calcium depolarization to anandamide was not inhibited by ETI. 5. Using confocal microscopy we have demonstrated the presence of vanilloid receptors on both neuropeptide containing nerves and nerves that did not stain for sensory neuropeptides. 6. These results demonstrate that anandamide evokes depolarization of guinea-pig vagus nerve, following activation of vanilloid receptors, a component of which involves the generation of lipoxygenase products. Furthermore, these receptors are distributed in both neuropeptide and non-neuropeptide containing nerves.     

Humoral and cellular immunity against Cryptosporidium infection

Protozoans of the genus Cryptosporidium are the etiological agents of opportunistic infections mainly of the gastrointestinal tract of animals and humans. Young and elderly persons, those with concomitant infections, with AIDS, under an immunosuppressive therapy, with congenital T-cell, B-cell or other effector cell deficiencies develop persistent progressive infections of different degree of severity related to the level of immunodepression. Both humoral and cellular immunity play a role in the control of this infection, but the latter plays the major role, mainly in the intestinal mucosa. However, a natural resistance to these coccidian parasites is also involved. IgG, IgM and IgA have been detected in serum and mucosa of humans and animals with the resolution of the infection; but also high levels of these immunoglobulins have been detected in persons with AIDS with chronic cryptosporidiosis. In HIV-positive persons, CD4+ T-cells are required to prevent the establishment of the infection and IFN-gamma and CD4+ T-cells can also limit the duration and the clinical manifestations of the infection. In persons exposed to cryptosporidial infections, it has been possible to show the important role of IFN-gamma in both the innate and acquired cell mediated immunity. The severity of cryptosporidiosis has been also associated with the inability to produce IFN-gamma. An antibody therapy using bovine colostrum from cows hyperimmunised with Cryptosporidium oocysts or monoclonal antibodies against sporozoite antigens has been developed at the experimental level mainly for persons with AIDS or with other immunodeficiencies; however, these preparations of antibodies have shown only a limited degree of efficacy both in animals and humans.     

Extracorporeal photochemotherapy for paediatric patients with graft-versus-host disease after haematopoietic stem cell transplantation

This study aimed to ascertain whether extracorporeal photochemotherapy (ECP) is an effective treatment for paediatric patients with refractory graft-versus-host disease (GVHD). From January 1992 to December 2000, 77 children (median age 8.6 years) with either acute (n = 33) or chronic (n = 44) GVHD, resistant to conventional immunosuppressive therapy, were treated with ECP in four Italian paediatric hospitals. After ECP, acute GVHD involving skin, liver and gut responded completely in 76%, 60% and 75% of patients respectively. The 5-year overall survival was 69% for responding patients vs 12% for non-responders (P = 0.001). Among the 44 children with chronic GVHD, 15 (44%) showed a complete response and 10 (29%) a significant improvement after ECP. The 5-year overall survival was 96% for responders vs 58% for non-responders (P = 0.04). Our results suggest that ECP is an effective treatment that may be useful in paediatric patients with either acute or chronic GVHD who have failed to respond to standard immunosuppressive therapy.     

Multicentre evaluation of IL Test Free PS: a fully automated assay to quantify free protein S

Deficiency of the anticoagulant vitamin K-dependent protein S (PS) is associated with increased risk of venous thrombosis. In human plasma, PS circulates in two forms: as free protein (free PS) and PS bound to C4b-binding protein (C4BP), a regulator of the complement system. Assays for free PS have higher sensitivity and specificity for protein S deficiency than assays for total protein S. We have extensively evaluated the analytical performance of a novel assay for free PS, the IL Test Free Protein S, which takes advantage of the affinity of C4BP for free PS, and compared its performance to existing methods. IL Test Free Protein S is a rapid, fully automated turbidimetric assay consisting of two reagents: a C4BP coated latex and an anti-PS monoclonal antibody coated latex. The test range, precision and linearity were adequate and the assay tolerated high concentrations of interfering substances of clinical significance. The reference range agreed with previously published studies. The analysis of 903 patient samples belonging to 20 different clinical categories with the new assay yielded free PS results that agreed well with those obtained using the assays established in the participating laboratories. The study demonstrated the IL Test Free Protein S to be rapid, reliable and easy to perform.     

Feeling touches in someone else's hand

Cerebral damage may induce a delusional belief so that patients claim that their limbs contralateral to the side of the lesion belong to someone else (somatoparaphrenia). This disorder, which is not due to a general delirium, is frequently accompanied by the inability to feel tactile sensations in the 'non-belonging' part of the body. We report the unique case of a patient with somatoparaphrenia in whom dense tactile imperception in the left hand dramatically recovered when she was instructed to report touches delivered to her niece's hand, rather than to her own hand. We suggest that, through this verbal instruction, the mismatch between the patient's belief about the ownership of her left hand and her ability to perceive touch on it was transiently recomposed. This is evidence that apparently elementary deficits, such as hemianesthesia, and selective delusional behavior, such as somatoparaphrenia, may both originate from an impairment of the body image.     

Amitriptyline in neuropathic cancer pain in patients on morphine therapy: a randomized placebo-controlled,double-blind crossover study

AIMS AND BACKGROUND: Amitriptyline is the most common analgesic adjuvant used in cancer patients with neuropathic pain, even though no specific studies have demonstrated a benefit. A randomized placebo-controlled, double-blind crossover study was designed to evidence the effects of amitriptyline in patients with neuropathic cancer pain. METHODS: Sixteen advanced cancer patients with neuropathic pain on systemic morphine therapy, no longer receiving oncologic treatment, presenting moderate pain (about 4 or more, but less than 7, on a numerical scale of 0-10) in the last week, and given a stable morphine dose in the last 2 days were admitted to the study. During the first week of study, patients were administered 25 mg of amitriptyline or equivalent drops of placebo at night for 3 days and 50 mg for the following 4 days. Doses for patients aged more than 65 years were 15 mg (first 3 days) and 30 mg (3 days after). After a week, a crossover took place for the second week, with the other treatment at an inverse sequence. Opioid consumption, pain intensity, symptoms and adverse effects, mood, sleep, patient's preference, quality of life before starting the study, the first week after and the second week after were recorded. RESULTS: No significant benefits in analgesia were found in the global pain intensity of the previous week of treatment, the least pain intensity or the pain evaluated just after a week of treatment, at the moment of the visit, when amitriptyline was compared with placebo. A significant difference was evidenced for the worst pain (P < 0.035). No differences in opioid doses during the period of study were found. Drowsiness, confusion and dry mouth were significantly more intense with amitriptyline than with placebo (P < 0.036, 0.003, and 0.034, respectively). There were no substantial differences between the two treatments in Spitzer's quality of life score and for each item. No differences in patients' preference for the two treatment periods were found. The analgesic effects of amitriptyline were slight and associated with adverse effects. CONCLUSIONS: In light of the results obtained in the study, the extensive use of the drug for cancer pain should be questioned.