Allergic susceptibility associated with diesel exhaust particle exposure: clear as mud

Exposure to elevated levels of particulate air pollution from motor vehicles is frequently associated with increased morbidity and mortality from cardiovascular conditions, lung cancer, and nonmalignant respiratory illnesses (e.g., asthma, bronchitis, respiratory tract infections). It appears, however, that less attention has been paid to the potential role of road traffic fumes in the induction of allergic conditions. Laboratory studies in humans and animals have shown that particulate toxic pollutants-particularly diesel exhaust particulates-can enhance allergic inflammation and can induce allergic immune responses. Most of these immune responses are mediated by the carbon core of diesel exhaust particulates. Polyaromatic hydrocarbons (e.g., anthracene, fluoranthene, pyrene, phenanthrene) are major chemical components of diesel exhaust particulates, and they have enhanced the production of immunoglobulin E. Although several large epidemiological studies have demonstrated a strong association between exposure to motor vehicle traffic emissions and allergic symptoms and reduced lung function, the evidence for the development of allergic sensitization from diesel exhaust particulates is less abundant than for the aforementioned associations. Recent comparisons of the prevalence of hay fever, as well as positive skin-prick tests, between citizens of former West and East Germany and between Hong Kong and China civilians, have demonstrated marked differences. Crucial variations in the level of particulate air pollution from motor vehicles in these countries may account for the observed increased prevalence of atopy. Although road-traffic pollution from automobile exhausts may be a risk factor for atopic sensitization, the evidence in support of this view remains conflictive. Some investigators have reported a clear association between the prevalence of allergy and road-traffic-related air pollution, whereas such a difference was not observed in other studies. Most discrepancies have been related to important variations in study design and methodology. In addition, inasmuch as exposure to ambient particles differs substantially in worldwide urban environments, perhaps qualitative-rather than quantitative-variations in particulate air pollution at different locations account for differences in the prevalence and/or severity of respiratory allergies.     

Human isolated small intestine: motor responses of the longitudinal muscle to field stimulation and exogenous neuropeptides

Summary (1) Longitudinal muscle strips from the human small intestine (jejunum/ileum) responded to electrical field stimulation (1–50 Hz) with frequency-related primary contractions which were largely atropine- (3 M) sensitive. When the tone was raised by addition of galanin (0.3 – 1 M), prostaglandin (PG) E₂ (1–10 M) or neurokinin A (NKA, 0.1 M), a frequency-related relaxation was evident which was potentiated by atropine. All the responses to field stimulation were abolished by tetrodotoxin (1 M), thus indicating their neural origin. (2) The atropine-sensitive primary contraction to field stimulation was virtually abolished by omega conotoxin fraction GVIA (CTX, 0.1–0.3 M) while the relaxations were CTX-resistant. The field stimulation-induced relaxations, which were observed in the presence of atropine and guanethidine (3 M), were also unaffected by apamin (0.1 M). (3) NKA and substance P (SP) produced a concentration- (1 nM–1 M for both peptides) related contraction, NKA being about 53 times more potent than SP. [Pro⁹]SP sulphone and [MePhe⁷]-NKB, selective agonists of the NK-1 and NK-3 receptor, respectively, were barely effective. On the other hand, [\Ala⁸]NKA(4–10), a selective NK-2 receptor agonist, had a potent contractile activity, similar to that of NKA. (4) Galanin (1 nM–1M) produced an atropine- and tetrodotoxin-resistant concentration-related contraction of longitudinal muscle of human isolated small intestine. The response to galanin did not show any sign of fading and was particularly suitable to study the evoked relaxations. (5) Calcitonin gene-related peptide (CGRP) (10–100 nM) consistently inhibited the nerve-mediated contractions of strips from the ileum while the effect on the jejunum was less pronounced. Vasoactive intestinal polypeptide (VIP, 0.1–1 M) inhibited nerve-mediated contractions both in the ileum and the jejunum. (6) These experiments indicate that both cholinergic excitatory and non-adrenergic non-cholinergic nerves affect motility of the longitudinal muscle of the human small intestine. Furthermore, several neuropeptides produce potent motor effects, the contractile response to tachykinins being apparently mediated by activation of NK-2 receptors.     

Assessment of the scatter fraction evaluation methodology using Monte Carlo simulation techniques

To evaluate scatter fraction and scatter pair spatial distribution, experimental methods are generally used. These methods make use of a line source, placed along the FOV axis, inserted in a cylindrical phantom filled with air or water. The accuracy of these experimental methodologies can be tested by the use of a Monte Carlo method. In fact, the simulation allows the shape of the scatter event projection and the scatter fraction to be defined. An example of this application is the simulation package PETSI (PET SImulation). In this paper the comparison between the predicted scatter fraction and the experimentally evaluated one, obtained using an ECAT III PT 911/02 double ring whole body scanner are presented. PETSI permits additional data to be obtained: a) the true and scatter component of the energy spectrum; b) the spatial distribution, in the FOV plane, of the detected scatter events at different energy thresholds; c) the scatter to total detected events ratio; d) the predicted scatter fraction at both energy thresholds and FOV diameters. This information is very useful for optimizing both energy threshold and FOV size and to improve the accuracy of the currently used methods for the scatter fraction evaluation. Preliminary results of the predicted scatter fraction in a uniform phantom are presented.This article was presented at the 1st EEC workshop on accuracy determination in PET, January 19–20th. 1989 Pisa, Italy (COMAC-BME Concerted Project Characterization and Standardization of PET Instrumentation)     

The interaction between particulate air pollution and allergens in enhancing allergic and airway responses

Although the detrimental effects of air pollution on human health have been brought widely to public notice, it appears that less attention has been given to the potential role of toxic air pollutants in the induction of allergic conditions such as asthma, rhinoconjunctivitis, and atopic eczema. A number of large epidemiologic studies have shown that people exposed to intense motor vehicle traffic and its associated emissions are at major risk for allergic symptoms, reduced lung function, and increased sensitization to common airborne allergens. Several laboratory-based studies have demonstrated that particulate air pollutants emitted from motor vehicles can induce allergic inflammation, enhance IgE responses, and increase airway hyperresponsiveness, which could provide an underlying mechanism for the increasing prevalence of allergic diseases. This article reviews the evidence that supports the causative link between particulate air pollution and the sharp increase in the prevalence of type I allergies in developed countries.     

Is salvage chemotherapy for metastatic breast cancer always effective and well tolerated? A phase II randomized trial of vinorelbine versus 5-fluorouracil plus leucovorin versus combination of mitoxantrone, 5-fluorouracil plus leucovorin

Metastatic breast cancer remains an incurable disease and the median overall survival has not significantly improved over the past two decades. Aims of the present randomized phase II trial were to analyse activity and toxicity of chemotherapies with single agent or with combination regimens in previously treated patients with advanced breast cancer. Ninety-nine eligible patients were randomized to receive the following chemotherapies: Arm A – 30mg/m² i.v. weekly; Arm B – leucovorin 100mg/m² i.v. followed by 5-fluorouracil 370mg/m² i.v. days 15, q 28days; Arm C – mitoxantrone 12mg/m² i.v. only day 1+leucovorin 100mg/m² i.v. followed by 5-fluorouracil 370mg/m² i.v. days 13, q 28days. Patients characteristics are comparable in the three groups. The median number of chemotherapy courses administered was 7, 6 and 5 in arm A, B and C, respectively. Objective responses were 24%, 30% and 21% and the median duration of responses were 2, 2.5 and 5.5 months in the arm A, B and C, respectively. Median overall survivals were 9.5, 9 and 9 months in the three arms. No difference was noted comparing the survivals of responding or non responding patients. General toxicity was not mild, with 27.5% of patients experiencing WHO grade 3–4 toxicities.Our results are similar in the three groups of patients and comparable to those reported by other authors. Chemotherapy applied to patients with second or subsequent recurrence allow objective responses in a small percentage of patients. Moreover responders have a negligible prolongation of survival.     

Effects of capsaicin,tachykinins, calcitonin gene-related peptide and bradykinin in the pig iris sphincter muscle

Summary Capsaicin-sensitive sensory neurons of the rabbit iris, by releasing tachykinins, exert a major role in the control of pupil motility in response to various noxious stimuli. However, the contribution of sensory innervation to the regulation of iris smooth muscle tone in other mammals species is not known. We have studied the effects produced by electrical field stimulation, capsaicin, substance P, neurokinin A, calcitonin gene-related peptide (CGRP), and bradykinin in the isolated iris sphincter muscle of the pig.Capsaicin (10 M): a) contracted the isolated sphincter muscle and; b) released immunoreactivity for substance P (SP-LI) and CGRP (CGRP-LI) from this preparation. These two effects were no longer observed at the second exposure to the drug. Electrical field stimulation (10 Hz, 60 V, 0.5 ms for 5 s) produced a biphasic contractile response. The rapid component was inhibited by atropine (1 M), while the delayed response was blocked by previous exposure to capsaicin (10 M).Substance P and neurokinin A consistently produced contraction of the pig iris sphincter muscle, substance P being more potent than neurokinin A. CGRP induced a contractile response in more than 50% of the preparations. The tachykinin antagonist [D-Argl, D-Trp^7,9, Leu¹¹-substance P (3 M) blocked: a) the effect of substance P (1 nM); b) the delayed response to electrical field stimulation and; c) reduced by more than 50% response to capsaicin. Bradykinin (10 M) failed to release either SP-LI or CGRP-LI. The contractile response evoked by bradykinin was unaffected by in vitro pretreatment with capsaicin (10 M).The existence in the pig iris of capsaicin-sensitive sensory fibres releasing neuropeptides and thus regulating sphincter muscle tone is proposed. Send offprint requests to Dr. P. Geppetti at the above address     

Capsaicin-like activity of some natural pungent substances on peripheral endings of visceral primary afferents

Summary 1. The effects of some naturally occurring pungent substances, piperine, mustard oil, eugenol and curcumin, were compared to those of capsaicin in the rat isolated urinary bladder. 2. All test compounds dose-dependently contracted the rat bladder and produced desensitization toward capsaicin (1 mol/l). Development of cross-tachyphylaxis among the natural pungent substances on one hand and capsaicin on the other, suggested a common site of action on visceral primary afferents. 3. Contractile responses to piperine, mustard oil and eugenol were partially tetrodotoxin and ruthenium red-sensitive, suggesting that activation of sensory terminals by these agents takes place indirectly, as well as by a direct action on sensory receptors. 4. The presence of the secondary acylamide linkage (present in the backbone of capsaicin, but not in that of test compounds) does not appear to be essential to produce desensitization of sensory nerve terminals. Send offprint requests to R. Patacchini at the above address     

Does the level of stapled ileoanal anastomosis influence physiologic and functional outcome?

PURPOSE: The aim of this investigation was to ascertain how the length of anal canal preserved above the dentate line in stapled end-to-end ileoanal anastomosis influenced late outcome. METHODS: Two groups, high cuff group and low cuff group of nine subjects with stapled anastomosis, matched for sex, age, pouch configuration, and mean follow-up, representing the highest (median, 2.5 cm) and lowest (median, 0.7 cm) anal cuff lengths in our series, were selected. Physiologic and functional parameters were appraised preoperatively, at the time of ileostomy closure, and at 1, 3, 6, and 12 months after reestablishment of intestinal continuity. RESULTS: At one year, the drop in mean anal canal resting pressure was 13 percent in the high cuff group (not signficant) and 31 percent in the low cuff group (P <0.05); mean maximum squeezing pressure did not differ significantly from preoperative values in both groups. The mean volume of the ileal pouch was higher in the low cuff group at all insufflation pressures. The rectoanal inhibition reflex reappeared in four high cuff group patients and in none of the low cuff group patients. Mean distention pressure (cm H ₂ O) and volume (ml) eliciting urge sensation were 80 and 360 in the low cuff group compared with 40 and 240 in the high cuff group (P ?0.05). Daytime bowel movements and night incontinence were significantly better in the low cuff group. No statistical differences were observed for night stool frequency, daytime incontinence, pad use (day and night), discrimination between gas and feces, ability to defer evacuation, and difficulty in emptying the pouch. CONCLUSION: Patients with stapled anastomoses and a low rectal cuff length, despite presenting lower anal resting pressure and absence of rectoanal inhibition reflex, had a better functional outcome in terms of continence than those with a high cuff length.