Profound approach to check legitimacy of an old technique used to gauge palatal rugae.

AIMS: The present study aimed at assessing two fixed points of reference from where the mesial and distal point of all rugae can be measured so that the exact movement of particular rugae in any direction can be evaluated and assessing the changes in the palatal rugae after orthodontic treatment. METHODS: A longitudinal study conducted among a sample of 20 (8 male and 12 female) adult patients. Pre- and post-orthodontic treatment casts of patients were obtained from the Department of Orthodontics College of Dentistry Jazan University. Antero-posterior linear distances (Technique I) between medial and lateral points of primary, secondary and tertiary rugae were measured. Also, the transverse linear distance (Technique II) between medial and lateral points of right and left rugae were measured. Technique III involved marking two fixed points and using these two points a third point is located on the medial or lateral end of rugae of right and left side in pre and post-treatment orthodontic casts. The independent sample t-test was employed to compare gender. Difference between the pre- and post-treatment mean values were checked by the paired t-test. RESULTS: Technique III successfully showed the statistically significant difference (P ≤ 0.05, 95% CI) in the overall pre and post-treatment values on the patients' cast (N = 20) which was not observed with a technique I and technique II. CONCLUSION: The triangle created by the three reference points in the technique III was able to identify the changes in the palatine rugae more precisely than the technique I and Technique II.

Exercise tolerance in obstructive sleep apnea-hypopnea (OSAH), before and after CPAP treatment: Effects of autonomic dysfunction improvement.

BACKGROUND: Obstructive sleep apnea hypopnea (OSAH) is associated with decreased exercise tolerance and autonomic abnormalities and represents a risk for cardiovascular diseases. The aim of the study was to evaluate the effects of CPAP on cardiovascular autonomic abnormalities and exercise performance in patients with OSAH without changes in lifestyle and body weight during treatment. METHODS: Twelve overweight subjects with OSAH underwent anthropometric measures, autonomic cardiovascular and incremental symptom-limited cardio-respiratory exercise tests before and after two months of treatment with CPAP. RESULTS: Lower frequency component of power spectrum of heart rate variability (59.5±24.2 msec2 vs 43.2±25.9 msec2; p<0.05) and improvements of maximal workload (99.3±13.5 vs 108.3±16.8%pred.; p<0.05) and peak oxygen consumption (95.3±7.6 vs 105.5±7.9%pred.; p<0.05) were observed in these patients after CPAP, being their BMI unchanged. CONCLUSIONS: CPAP-induced decrease of sympathetic hyperactivity is associated with better tolerance to the effort in OSAH patients that did not change their BMI and lifestyle, suggesting that OSAH limits per se the exercise capacity.

Knowledge, attitudes and practices of sweet food and beverage consumption and its association with dental caries among schoolchildren in Jazan, Saudi Arabia.

The prevalence of dental decay is expected to rise in many developing countries due to the growing consumption of sugars. This study aimed to assess knowledge, attitudes and practices of sweet food and beverage consumption among schoolchildren in Jazan, Saudi Arabia and to determine the relationship with dental caries. In a cross-sectional, descriptive study 853 children aged 6-15 years (520 boys and 333 girls) were assessed by questionnaire and clinical examinations. Caries prevalence (≥ 1 dft/DMFT) was high (91.3%). While knowledge was generally good, 83.5% boys and 85.8% girls had poor attitudes to sweet foods and > 90% frequently consumed sweet foods/beverages. Multiple regression analysis showed that children whose mothers were less educated (OR 2.46; 95% CI: 1.15-5.28) and children with poor dietary attitudes and practices (OR 4.05; 95% CI: 2.33-7.03 and OR 7.80; 95% CI: 4.50-13.52 respectively) were more likely to have dental caries. Well-directed health promotion programmes are needed in Jazan.

Knowledge, attitudes and practices of sweet food and beverage consumption and its association with dental caries among schoolchildren in Jazan, Saudi Arabia

من المتوقع أن يرتفع انتشار نخر الأسنان في العديد من البلدان النامية بسبب تزايد استهلاك السكريات. ولقد هدفت هذه الدراسة إلى تقييم المعارف والاتجاهات والممارسات المتعلقة باستهلاك الأطعمة والأشربة الحلوة لدى أطفال المدارس في جازان بالمملكة العربية السعودية، وإلى تحديد علاقة ذلك بتسوس الأسنان. ففي دراسة وصفية مقطعية تم تقييم 853 طفلاً تتراوح أعمارهم بين 6-15 سنة [520 فتى و 333 فتاة]، وذلك باستخدام استبيان وفحوص سريرية. فكان انتشار التسوس [ 1 DMFT/dft >/= الأسنان المنخورة والمقلوعة والمحشوة ..] مرتفعاً [91.3%]. وعلى الرغم من أن المعرفة كانت جيدة عموماً فإن 83.5% من الفتيان و 85.8% من الفتيات كانت اتجاهاتهم نحو الأطعمة الحلوة سيئة، وكان %90 <منهم يستهلكون الأطعمة/الأشربة الحلوة بكثرة. وأظهر تحليل التحوف المتعدد أن الأطفال الذين كانت أمهاتهم أقل تعليماً [OR 2.46;%95 CI:1.15-5.28]والأطفال الذين لديهم اتجاهات وممارسات تغذوية سيئة [OR 4.05;%95 CI:2.33-7.03 OR 7.80;%95 CI:4.50-13.52 على التوالي]كانوا أكثر عرضة لتسوس الأسنان. تحتاج جازان إلى برامج لتعزيز الصحة موجهة توجيهاً جيداً

The prevalence of dental decay is expected to rise in many developing countries due to the growing consumption of sugars. This study aimed to assess knowledge, attitudes and practices of sweet food and beverage consumption among schoolchildren in Jazan, Saudi Arabia and to determine the relationship with dental caries. In a cross-sectional, descriptive study 853 children aged 6–15 years (520 boys and 333 girls) were assessed by questionnaire and clinical examinations. Caries prevalence (≥ 1 dft/DMFT) was high (91.3%). While knowledge was generally good, 83.5% boys and 85.8% girls had poor attitudes to sweet foods and > 90% frequently consumed sweet foods/beverages. Multiple regression analysis showed that children whose mothers were less educated (OR 2.46; 95% CI: 1.15–5.28)and children with poor dietary attitudes and practices (OR 4.05; 95% CI: 2.33–7.03 and OR 7.80; 95% CI: 4.50–13.52 respectively) were more likely to have dental caries. Well-directed health promotion programmes are needed in Jazan.

Dans de nombreux pays en développement, la prévalence des caries dentaires devrait augmenter en raison de la consommation croissante de sucres. La présente étude visait à évaluer les connaissances, attitudes et pratiques en matière de consommation d'aliments et de boissons sucrés chez des écoliers de Jazan (Arabie saoudite), et à déterminer leur lien avec les caries dentaires. Dans une étude descriptive et transversale, 853 enfants âgés de 6 à 15 ans (520 garçons et 333 filles) ont été évalués à l'aide d'un questionnaire et d'examens cliniques. La prévalence de caries (1 ≥ indice des dents cariées, absentes ou obturées) était forte (91,3 %). Si le niveau de connaissances était élevé en général, 83,5 % des garçons et 85,8 % des filles avaient de mauvaises attitudes face aux aliments sucrés et plus de 90 % en consommaient fréquemment. Une analyse de régression multiple a démontré que les enfants dont les mères avaient un niveau d'études plus faible (OR 2,46 ; IC à 95 % : 1,15–5,28) mais aussi ceux ayant de mauvaises attitudes et pratiques (OR 4,05 ; IC à 95 % : 2,33–7,03 et OR 7,80 ; IC à 95 % : 4,50–13,52 respectivement) étaient plus à risque de présenter des caries dentaires. Des programmes de promotion de la santé convenablement ciblés sont nécessaires à Jazan.

Diagnosis and management of chronic obstructive pulmonary disease: the Swiss guidelines. Official guidelines of the Swiss Respiratory Society.

The new Swiss Chronic Obstructive Pulmonary Disease (COPD) Guidelines are based on a previous version, which was published 10 years ago. The Swiss Respiratory Society felt the need to update the previous document due to new knowledge and novel therapeutic developments about this prevalent and important disease. The recommendations and statements are based on the available literature, on other national guidelines and, in particular, on the GOLD (Global Initiative for Chronic Obstructive Lung Disease) report. Our aim is to advise pulmonary physicians, general practitioners and other health care workers on the early detection and diagnosis, prevention, best symptomatic control, and avoidance of COPD as well as its complications and deterioration.

Excretion profile of boldenone and its metabolites after oral administration to veal calves.

The residue profiles of boldenone (17beta-Bol), its epimer (17alpha-Bol) and the related compound androsta-1,4-diene-3,17-dione (ADD), were investigated by liquid chromatography-tandem mass spectrometry (LC-MS/MS) in urine of male calves orally treated with boldenone, boldenone esters, and/or ADD. In all the experiments with the administered steroids residues of 17alpha-Bol decreased rapidly after end of treatment; detectable amounts of 17alpha-Bol were however noticed along the withdrawal observation period after end of treatment. Differently, residues of 17beta-Bol were detectable only shortly after administration. This in vivo research concerning oral treatments of cattle with boldenone related substances proves ADD to be a very active boldenone precursor in bovine animals.

A disposable immunosensor for detection of 17beta-estradiol in non-extracted bovine serum.

This paper reports the assembly of a disposable immunosensor based on the direct competitive enzyme-linked immunosorbent assay (ELISA), for simple and fast measurement of 17beta-estradiol (17beta-E2) in bovine serum, using screen-printed electrodes (SPEs) and a Palm-Sens portable electrochemical detector. The immunosensor strip was assembled immobilising, by passive adsorption, anti-rabbit IgG onto the surface of the working SPE electrode. After the interaction between anti-rabbit IgG and rabbit anti-17beta-E2 polyclonal antibodies (PAb), the competition was performed using 17beta-estradiol-alkaline phosphatase conjugate (17beta-E2-AP) synthesised in our laboratory. The enzymatic substrate used for signal generation was 1-naphthylphosphate and its conversion to an electroactive product (1-naphthol) was measured using differential pulse voltammetry (DPV). To develop a prototype for field measurements, the entire competitive protocol has been optimised directly in a blank non-extracted bovine serum. According to the new EU criteria established by the Commission Decision 2002/657/EC for qualitative and quantitative screening methods, the detection capability (CCbeta), was determined. The CCbeta value resulted below the action limit (40 pg mL(-1)) fixed for 17beta-E2) Spiked and real samples were analysed using the electrochemical immunostrips obtaining precision values (relative standard deviation, R.S.D.%) ranging from 8.6 to 17.0% and a recovery (R%) from 88.2 to 120.0%. Results obtained on real samples were confirmed by liquid chromatography coupled on-line with tandem mass spectrometry (LC-MS/MS) using an atmospheric pressure chemical ionisation (APCI) source and a heated nebulizer (HN) interface; this is the method currently used to confirm illegal hormone administration for regulatory purposes. The disposable immunosensor appears suitable as a screening tool for field analysis of bovine serum estradiol.

Analysis of erythromycin and tylosin in bovine muscle using disposable screen printed electrodes.

A disposable electrochemical enzyme-linked immunosorbent assay (ELISA) for the detection of two macrolides (erythromycin and tylosin) in bovine muscle was developed using a screen printed electrode (SPE) system as a differential pulse voltammetry (DPV) transducer with mouse anti-erythromycin (and anti-tylosin) monoclonal antibodies (MAb) serving as molecular recognition elements. The immunochemical system makes use of the competition assay principle, and employs an erythromycin (or tylosin)-BSA conjugate as coating molecule. After competition between free and coated analyte for the antibodies, the activity of the alkaline phosphatase labelled antiglobulins was measured electrochemically using 1-naphthylphosphate as substrate. Using standard solutions of erythromycin and tylosin, the detection limit of the assay was 0.2 ng mL(-1) determined to be for erythromycin and 2.0 ng mL(-1) for tylosin, while the sensitivity (25% inhibition concentration) was 1.0 ng mL(-1) for erythromycin and 3.0 ng mL(-1) for tylosin. The suitability of the assay for quantification of erythromycin and tylosin in bovine muscle was also studied. Spiked and real samples were analysed using the immunosensor system developed here. The ELISA showed precision values (relative standard deviation, RSD%) ranging from 4 to 9% for erythromycin and from 8 to 15% for tylosin; the accuracy (relative error, RE%) ranged from -11 to 6% and from -4 to 12% for erythromycin and tylosin, respectively. Results obtained on real samples were confirmed by micro-liquid chromatography coupled on line with tandem mass spectrometry (micro-LC-MS-MS), using an atmospheric pressure ionisation (API) source and an ionspray (IS) interface. The latter provides unequivocal identification and quantification of the analytes at the level of interest.

Familial adenomatous polyposis. Surgical treatment: when and how.

Familial adenomatous polyposis is an autosomal dominated inherited disease, caused by the mutation of the tumour suppressor gene adenomatous polyposis coli on chromosome 5. Despite being a rare disorder, accounting for some 1% of colorectal cancers, it represents an interesting model of hereditary disease, because of its intrinsic characteristics, conventionally defined by the presence of more than 100 colorectal polyps, as well as extra-colon manifestations, the attenuated form of the disease, genetic aspects, the inevitable progression to colorectal cancer and hence the correct therapy to treat or prevent the fatal evolution of the disease. Surgical treatment is based above all on two techniques: ileorectal anastomosis, which requires careful surveillance of rectal remnant, and ileal pouch-anal anastomosis, which totally eradicates the disease. The suitability of using these two techniques is discussed in view of new genetic and clinical findings, acquired from personal experience and from the literature.

[The minimal bowel resection in Crohn's disease: analysis of prognostic factors on the surgical recurrence]. / Le resezioni di minima per Morbo di Crohn: valutazione di alcuni fattori di rischio di recidiva.

OBJECTIVE: To assess the effect of disease pattern and involvement of the margins on early and late results of enteric resections with hand-sewn anastomosis for Crohns disease. BACKGROUND: Bowel sparing is one of the aims of the surgery for CD. When strictureplasties are not possible, "minimal surgery" (the resection just of the grossly involved tract of bowel) is the current choice. METHODS: One hundred and forty-six cases of resections in 128 patients were performed in the years 1991-2001. We investigated if there is a relationship between disease pattern (perforating and non-perforating) or hystologic involvement of the margins and recurrence (reoperation for recurrent preanastomotic disease). Hand-sewn anastomosis were performed almost in all the cases; we compared the results with the main series of stapled and hand-sewn sutures. RESULTS: Nine surgical complications occurred (7%), requiring six relaparotomies and three conservative treatments. Overall rate of recurrence (median follow-up 44 months) is 17%: 9% in patients with non perforating disease and 19% in patients with perforating disease. The rate of recurrence is 6% in the group of patients with involved margins and 23% in the group with non involved margins. CONCLUSIONS: Limited surgery for CD doesn't increase rate of recurrence; the involvement of margins is not a risk factor for early reoperation. Hand-sewn anastomosis seem to be as safe as stapled ones.

Production of antibodies and development of highly sensitive formats of enzyme immunoassay for saxitoxin analysis.

In this paper the production of antibodies against saxitoxin (STX) is described, as is the optimization and comparison of two competitive ELISA formats (direct and indirect) for the detection of this toxin. Tests were performed in a 96-well microplate using the toxin-specific polyclonal antibodies produced in our laboratory, obtained from rabbits immunized with saxitoxin-keyhole limpet hemocyanin (STX-KLH). In indirect ELISA format saxitoxin, conjugated to bovine serum albumin (STX-BSA) was coated onto the microtitre plate and incubated with standard toxin and anti-STX antibody. A goat anti-rabbit IgG Peroxidase conjugate was used to enable detection. In the direct ELISA format, STX standard, STX conjugate to horseradish peroxidase (STX-HRP), and enzyme substrate/chromogen solution were sequentially added to the microplate after antibody coating.Results showed the saxitoxin detection limit to be 3 and 10 pg mL(-1) for direct and indirect ELISA formats, respectively. The suitability of the assay for quantification of saxitoxin in mussels was also studied. Samples were spiked with saxitoxin before and after sample treatment to study the extraction efficiency and matrix effect, respectively. After treatment, samples were analysed at 1:1000 v/v dilution in PBS to minimize the matrix effect and to detect the regulatory limit of 40-80 micro g saxitoxin per 100 g mussels as stipulated by the Food and Drug Administration. The efficiency of extraction of saxitoxin was from 72 to 102%. These data were confirmed by liquid chromatography coupled with fluorimetric detection, the technique currently used for quantitative determination of toxins in seafood.

[Intestinal carcinoma in Crohn's disease. Report of four cases and review of the literature]. / Carcinoma intestinale e moro di Crohn. Presentazione di 4 casi e revisione della Letteratura.

BACKGROUND: Increasing numbers of intestinal carcinomas in patients affected by Crohn's disease have been reported by several authors, even if the strength of this associations (age, longstanding of the disease, its characteristics and distribution) still has to be elucidated. METHODS: From January 1992 to July 2000, 130 patients with Crohn's disease were submitted to surgery. RESULTS: Four patients showed an associated intestinal carcinoma at operation, in 3 cases located in the ileum, and in 1 case in the colon. Patients' mean age was 54 years. Mean duration time of the Crohn's disease was 7 years. One patient died 3 months after surgery for disseminated peritoneal carcinomatosis, whereas 3 patients are still alive with malignancy free at 5, 8, and 11 years after the tumor resection. CONCLUSIONS: These results suggest the difficulty in recognizing patients with Crohn's disease who are at risk for intestinal carcinoma. Longstanding disease, previous intestinal exclusion surgery, enterocutaneous or other types of fistulas should be considered for the development of cancer. Therefore, the prognosis may be good if early diagnosis and treatment are made.

Confirmatory analysis of residues of stanozolol and its major metabolite in bovine urine by liquid chromatography-tandem mass spectrometry.

A reliable method for the confirmation of the synthetic hormone stanozolol and its major metabolite, 16beta-hydroxystanozolol, in bovine urine by liquid chromatography coupled with tandem mass spectrometry has been developed. [2H3]Stanozolol was used as internal standard. Sample preparation involved enzymatic hydrolysis, liquid-liquid extraction and purification on an amino solid-phase extraction column. The analytes were ionized using atmospheric pressure chemical ionization with a heated nebulizer interface operating in the positive ion mode, where only the protonated molecules, [M+H]+, at m/z 329 and m/z 345, for stanozolol and 16beta-hydroxystanozolol, respectively, were generated. These served as precursor ions for collision-induced dissociation and three diagnostic product ions for each analyte were identified for the unambiguous hormone confirmation by selected reaction monitoring liquid chromatography-tandem mass spectrometry. The accuracy ranged from 19.7 to 14.9% and from 18.9 to 13.2% for stanozolol and 16beta-hydroxystanozolol, respectively. The precision ranged from 12.4 to 2.4% and from 13.1 to 1.8% for stanozolol and 16beta-hydroxystanozolol, respectively. The limit of quantification of the method was 1 ng/ml in the bovine urine for both stanozolol and 16beta-hydroxystanozolol. The developed method fulfils the European Union requirements for confirmatory methods.

A new electrochemical enzyme-linked immunosorbent assay for the screening of macrolide antibiotic residues in bovine meat.

A new sensitive electrochemical enzyme-linked immunosorbent assay (ELISA) for the detection of two macrolides (erythromycin and tylosin) in bovine muscle was developed, using the mouse monoclonal antibodies anti-erythromycin and anti-tylosin. The competitive indirect assay was performed using an erythromycin (or tylosin)-BSA conjugate as a coating molecule; after competition between free and coated analytes for the antibodies, the activity of the horseradish peroxidase-labelled antiglobulins was measured electrochemically using 3,3',5,5'-tetramethylbenzidine (TMB) as substrate. The detection limit of the assay was 0.4 ng ml(-1) for erythromycin and 4.0 ng ml(-1) for tylosin, while the sensitivity (25% inhibition concentration) was 1.4 ng ml(-1) for erythromycin and 13.0 ng ml(-1) for tylosin. The specificity of the assay was assessed by studying the cross-reactivity of various macrolides other than erythromycin and tylosin. The results indicate that the monoclonal antibodies anti-erythromycin and anti-tylosin can readily distinguish the target compound from other macrolides, with the exception of roxithromycin, a semisynthetic macrolide antibiotic derived from erythromycin. Fortified and real samples were analysed by the developed ELISA method and results confirmed by micro-LC-MS-MS using an atmospheric pressure ionisation (API) source and an ionspray (IS) interface. The latter provides unequivocal identification and quantification of the analytes at the level of interest. The ELISA assay showed precision (RSD) values ranging from 6.3 to 11.4% for erythromycin and from 7.5 to 12.6% for tylosin; the accuracy (relative error, RE) ranged from -16.0 to -9.8% and from -9.5 to 8.0% for erythromycin and tylosin, respectively. All results obtained demonstrate that the electrochemical ELISA is a suitable method for a sensitive, simple, rapid and reliable screening of the two macrolides in animal tissues.

Development of an electrochemical ELISA for the screening of 17 beta-estradiol and application to bovine serum.

A sensitive electrochemical enzyme-linked immunosorbent assay (ELISA) for the detection of 17 beta-estradiol (17 beta-E2) was developed. Optimisation of two ELISA competition assays, using monoclonal or polyclonal antibodies anti-17 beta-estradiol, coupled with the electrochemical detection was firstly performed. The activity of the label enzyme (horseradish peroxidase) was measured electrochemically using 3,3',5,5'-tetramethylbenzidine as substrate. The use of the polyclonal antibody resulted in a more sensitive assay and the detection limit of the assay was estimated to be 20 pg ml-1. The analytical performances of the method were compared to those obtained using a dissociation enhanced lanthanide fluorescence immunoassay (DELFIA). Although sample extraction is not usually required by DELFIA, both extracted and non extracted samples were assayed. The comparison between the two screening techniques revealed similar results for the extracted samples and showed a comparable precision (RSD%), ranging from 6.2 to 13.4 and from 6.7 to 14.3 for DELFIA and ELISA, respectively. The results obtained by these screening assays were confirmed by liquid chromatography atmospheric pressure chemical ionisation tandem mass spectrometry which is currently used to confirm illegal hormone administration for regulatory purposes. The electrochemical enzyme immunoassay appears suitable as a screening tool for routine analysis of bovine serum estradiol and can be extended to other anabolic hormones using appropriate antibodies.

Insufficient control of asthma: increase the dose of inhaled steroids or add long-acting beta 2-agonists?

Internationally accepted treatment guidelines for bronchial asthma have established the early introduction of inhaled corticosteroids as a disease-modifying treatment, in addition to bronchodilator treatment as needed. In a small group of patients this approach does not lead to sufficient control of asthma. It is a matter of debate whether in this situation the dose of inhaled steroids should be increased or the bronchodilator treatment intensified by the introduction of long-acting beta 2-agonists. Advantages and limitations of both treatment strategies are discussed in the light of recent data. Guidelines for the use of long-acting beta 2-agonists are proposed.

Conservative management of a broncho-oesophageal fistula in a patient with non-Hodgkin's lymphoma.

We describe the case of a 56-year-old male patient with a 2-year history of productive cough and weight loss. The diagnosis of a broncho-oesophageal fistula due to a low-grade Non-Hodgkin's lymphoma was made. The patient was referred for surgical closure of the fistula and resection of the left lower lobe because of intractable severe pneumonia. As an alternative treatment option, oesophageal or bronchial stent placement was considered. Because of the relatively favourable prognosis of this type of lymphoma, treatment with chemotherapy alone and a feeding gastrostomy were started. After eight cycles of cyclophosphamide and prednisone, the fistula healed spontaneously. Two years later, the patient continues to do well and is in remission. In patients with Non-Hodgkin's lymphoma and an oesophagorespiratory fistula, treatment should first be conservative; surgery or stent placement should be postponed.

[Poisoning with cholinesterase inhibitors]. / Intoxikation mit Cholinesterasehemmern.

A 32-year-old woman who had ingested 300 ml of a potent cholinesterase inhibitor insecticide (Fonofos) with suicidal intent became progressively comatose and finally suffered respiratory arrest. Tracheal intubation, mechanical ventilation, vigorous gastric lavage and intravenous administration of atropine and obidoxime brought about complete clinical recovery within 24 hours of ingestion of this potentially fatal dose of Fonofos.

[Severe acute pneumopathy following low-dose methotrexate therapy in chronic polyarthritis]. / Schwere akute Pneumopathie nach "low-dose"-Methotrexat-Therapie bei chronischer Polyarthritis.

A 70-year-old patient with a history of rheumatoid arthritis was hospitalized for severe acute pneumonitis after 36 weeks of treatment with low-dose methotrexate (7.5 mg/week). High dose corticotherapy and assisted ventilation were necessary to obtain a clinical response. Medical history, clinical signs, laboratory findings. X-ray films of the chest and special investigations suggest the diagnosis of acute low-dose methotrexate pneumonitis.