Aerosolised ribavirin in patients with advanced cryptogenic fibrosing alveolitis: a pilot study

BACKGROUND: A report has recently been published concerning a patient with a cryptogenic fibrosing alveolitis who showed a striking improvement after being treated with the antiviral drug ribavirin (tribavirin, Virazid). The objective of this study was to further evaluate, in an open trial, the efficacy of rivabirin in cryptogenic fibrosing alveolitis. METHODS: Ten patients (eight women) with advanced cryptogenic fibrosing alveolitis received aerosolised ribavirin (6 g/day for 15 days). Chest radiographs, lung function, and severity of dyspnoea were evaluated before and after two weeks of rivabirin treatment and also at three and 12 months. RESULTS: No differences in radiographs, lung function impairment, or severity of dyspnoea were found after treatment. No side effects were detected. CONCLUSIONS: Administration of high doses of aerosolised ribavirin has no beneficial effects in patients with advanced cryptogenic fibrosing alveolitis.     

Resting energy expenditure in cryptogenic fibrosing alveolitis

A proportion of patients with chronic airflow limitation appear to have a raised resting energy expenditure (REE). This has been suggested as the reason for weight loss which may occur in these patients. A previous study found an increased REE in patients with interstitial lung disease of mixed aetiology. We were interested in studying REE in a more homogeneous group, with cryptogenic fibrosing alveolitis (CFA). Twenty patients with CFA were studied. They were compared with 18 controls matched for age, sex, weight and height. REE was measured by indirect calorimetry. Fat-free mass (FFM), was estimated by anthropometry. Patients had respiratory function tests performed, disability related to breathlessness was assessed by the activity section of the St George's Respiratory Questionnaire. Mean REE in the CFA group was not different from the control group: 5.20 (0.56) versus 5.12 (0.51) kj x h(-1) x kgFFM(-1). REE was elevated to greater than 110% of the value predicted by the Harris-Benedict equation in one CFA patient and in no control subjects. There was no correlation of REE with weight, pulmonary function tests, arterial oxygen saturation or activity score. The prevalence of a raised resting energy expenditure in cryptogenic fibrosing alveolitis patients with low transfer factor and relatively preserved vital capacity is low, and is less than that reported previously in a group of patients with interstitial lung disease of mixed aetiology.     

Re-mediastinoscopy in the assessment of resectability of lung cancer

OBJECTIVE: Thirty-one patients underwent re-mediastinoscopy in the diagnostic assessment of lung cancer. The reason for a repeat mediastinoscopy was either a negative result at the first operation in spite of CT indication of enlarged nodes or an incomplete first mediastinoscopy. METHODS: All patients underwent a conventional mediastinoscopy. RESULTS: In 22 patients with enlarged mediastinal lymph nodes at computed tomography, 10 had a positive lymph node histology at re-mediastinoscopy, while 12 were negative. In 9 patients with no enlarged mediastinal nodes at CT scan, but incomplete biopsies at the first mediastinoscopy, 1 patient had lymph node metastases. The median duration from the first to the second mediastinoscopy was 43 days. No major complications occurred. The staging of the patients was greatly affected by the re-mediastinoscopy. Of 31 patients judged as operable according to the initial mediastinoscopy only 60% were found to be operable following the second mediastinoscopy. CONCLUSION: This study has demonstrated the value of re-mediastinoscopy in assessment of resectability of lung cancer.     

US case of the day. Diffuse large B-cell lymphoma (posttransplant lymphoproliferative disorder [PTLD])

OBJECTIVE: We describe two new CT findings of congestive heart failure (CHF): enlarged mediastinal lymph nodes and hazy heterogeneous mediastinal fat. MATERIALS AND METHODS: Forty-six patients were retrospectively identified who had major and minor clinical signs of congestive heart failure and had undergone chest CT during their symptomatic period. Two radiologists reviewed the CT studies and by consensus documented the presence or absence of imaging findings of CHF, including interstitial abnormalities, vascular redistribution, axial thickening, pleural effusions, cardiac enlargement, and mediastinal abnormalities. RESULTS: Smooth septal thickening, bilateral pleural effusions, vascular redistribution, and cardiac enlargement were the most common CT findings in patients with CHF. Enlarged mediastinal lymph nodes and hazy mediastinal fat were seen in 55% and 33% of cases, respectively. In a cohort of 17 patients with elevated pressures in the pulmonary capillary wedge documented within 24 hr of CT, CT scans revealed lymphadenopathy in 14 patients (82%) and inhomogeneous fat in 10 patients (59%). CONCLUSION: Enlarged mediastinal lymph nodes and hazy mediastinal fat occur in patients with CHF and are revealed by CT. Lymphadenopathy in patients with CHF does not necessarily indicate malignancy or an infectious process.     

Alpha1-antitrypsin phenotypes in patients with cryptogenic fibrosing alveolitis: a case-control study

Cryptogenic fibrosing alveolitis (CFA) is an interstitial lung disease, which by definition is of unknown aetiology. Recent evidence has suggested that smoking and occupational exposure to dusts may be environmental risk factors for the disease, but there has been little research into potential host risk factors. One previous study has suggested that the prevalence of abnormal alpha1-antitrypsin phenotypes may be increased in patients with CFA. Since alpha1-antitrypsin is important in regulating inflammation within the lung in response to environmental exposures, such abnormalities may be of aetiological importance in this disease. We have compared the alpha1-antitrypsin phenotypes of 189 patients with CFA with 189 age-, sex-, and community-matched controls. This sample size was sufficient to provide more than 95% power to detect an odds ratio (OR) of 2.5. Alpha1-antitrypsin phenotype was established by isoelectric focusing, and the prevalence of abnormal phenotypes in cases and controls was compared by conditional logistic regression. Personal smoking histories were obtained by postal questionnaire. The prevalence of abnormal alpha1-antitrypsin phenotypes was similar in cases and controls (12.7 versus 15.3%; OR 0.88; 95% confidence interval 0.49-1.57; p=0.66). No interaction was found between the presence of abnormal alpha1-antitrypsin phenotypes and a history of smoking. We conclude that cryptogenic fibrosing alveolitis is not associated with abnormal alpha1-antitrypsin phenotypes.     

Variability in the detection of enlarged mediastinal lymph nodes in staging lung cancer: a comparison of contrast-enhanced and unenhanced CT

OBJECTIVE: Because CT protocols for staging lung cancer vary and little information exists regarding the diagnostic importance of using i.v. contrast material, our intent was to evaluate intra- and interobserver agreement in the detection of enlarged mediastinal lymph nodes, comparing i.v. contrast-enhanced and unenhanced CT. SUBJECTS AND METHODS: Fifty patients with known or suspected bronchogenic carcinoma underwent unenhanced thoracic CT followed by contrast-enhanced CT. Three observers noted enlarged lymph nodes (> 10 mm in the short axis) and assigned the enlarged nodes to American Thoracic Society nodal station designations. Enlarged lymph nodes were grouped two ways: by assigning the exact number of enlarged lymph nodes found (zero, one, two, three, four or more), and by assigning whether at least one, or no, enlarged mediastinal lymph nodes were found at a station ("one or none"). Agreement levels were determined for inter- and intraobserver interpretations using weighted kappa statistics and the McNemar test. RESULTS: The number of enlarged lymph nodes with enhanced CT was 11% higher than on unenhanced studies (418 versus 377; p = .044). Numbers of enlarged lymph nodes were different for five stations; however, the numbers were small except for the right upper paratracheal station (2R) (contrast-enhanced, 68 enlarged lymph nodes; unenhanced, 44 enlarged lymph nodes; p = .014). With regard to all stations together, intraobserver agreement between contrast-enhanced and unenhanced studies was almost perfect (kappa range, .85-.94), and no difference was found for any observer in the proportion of patients with at least one enlarged lymph node. Interobserver agreement was substantial or almost perfect for the total number of enlarged lymph nodes. For specific stations, the lowest kappa value was .48 at 2R. One observer reported more patients with at least one enlarged lymph node with contrast enhancement at station 2R (p = .031). Greater agreement existed between two observers at station 2R with contrast enhancement versus no enhancement (kappa = .85 versus .48; p = .02). Conclusions matched, and calculations of estimated kappa values gave similar results for determination of the specific number of enlarged lymph nodes at a station and the "one or none" category. CONCLUSION: We found high agreement for intra- and interobserver interpretations for contrast-enhanced and unenhanced CT, although contrast-enhanced CT revealed more enlarged lymph nodes, especially at station 2R.     

Mediastinal lymph node metastasis from lung cancer: evaluation with Tl-201 SPECT--comparison with CT

PURPOSE: To assess the usefulness of thallium-201 single photon emission computed tomography (SPECT) in detection of mediastinal lymph node metastasis from lung cancer. MATERIALS AND METHODS: Computed tomography (CT) and Tl-201 SPECT were performed in 113 patients with lung cancer. Surgical staging was performed in all patients, and the results of the two modalities were compared with the pathologic findings in 364 node stations. RESULTS: Cancerous nodes were found in 32.7% of the patients. The sensitivity of CT in detecting mediastinal node metastasis was 62%; specificity was 80%. These rates were higher for Tl-201 SPECT (76% and 92%, respectively). Furthermore, these rates were excellent in patients with enlarged mediastinal nodes at CT (87% and 93%, respectively). However, Tl-201 SPECT had more limited spatial resolution than did CT. CONCLUSION: Tl-201 SPECT is useful in evaluation of mediastinal node metastasis in lung cancer, especially for patients with enlarged nodes at CT.     

Survival in patients with cryptogenic fibrosing alveolitis: a population-based cohort study

STUDY OBJECTIVES: To determine the median survival of patients with cryptogenic fibrosing alveolitis, in comparison to that expected of individuals of the same age and sex from the general population. To estimate the effect of survival bias incurred by studying both incident and prevalent cases. To identify factors associated with survival. DESIGN: Cohort study. SETTING: Nine hospitals from the Trent Region of England. PATIENTS: Two hundred forty-four cases of cryptogenic fibrosing alveolitis: 168 patients were alive on day 1 of the study (prevalent cases), and 76 patients had newly diagnosed conditions over a prospective 18-month period of patient recruitment (incident cases). MEASUREMENTS: Age, sex, date of diagnosis, lung function at presentation, and details of treatment prescribed were extracted from hospital clinical records. Data on lifetime smoking habits were collected by postal questionnaire. Vital status was established from the general practitioner. The expected survival of each case was extracted from the English life tables. RESULTS: Median survival for incident cases was 2.9 years and for prevalent cases 9 years, compared to expected values of 10 and 13 years, respectively. Incident cases had significantly worse survival than prevalent cases, even after adjustment for the effects of age, sex, smoking history, lung function at presentation, and treatment (hazard ratio, 4.53 [95% confidence interval, 2.71 to 7.56]; p<0.001). Lower FVC at presentation and the use of corticosteroid treatment were both associated with worse survival. CONCLUSIONS: The inclusion of prevalent cases leads to significant overestimation of the median survival for patients with cryptogenic fibrosing alveolitis. In newly diagnosed cases of cryptogenic fibrosing alveolitis, median survival is only 2.9 years, and expected life span is reduced by approximately 7 years.     

Comparative study on effects of pentoxifylline, prednisolone and colchicine in experimental alveolitis

Neutrophil alveolitis is a hallmark of cryptogenic fibrosing alveolitis (CFA), known for its poor prognosis. Corticosteroids, as the remedy of choice, are ineffective in a majority of patients. More and more evidence indicates that pentoxifylline (POF) could be an effective therapeutic alternative. Furthermore, colchicine has been proposed for therapy of CFA for many years now. We conducted an experimental study comparing the efficacy of these drugs in preventing neutrophil alveolitis in vivo. Alveolitis was induced in male rats by intratracheal instillation of bleomycin. Treatment consisted of daily injections of POF i.p., colchicine i.p., or prednisolone i.m. After 8 days the animals were sacrificed and body weights, cell differentials in BAL, amount of proliferating interstitial cells as determined by KI-67 staining of lung tissue, and collagen concentrations in lungs were determined. Bleomycin instillation was followed by a significant weight loss in the animals, a neutrophil alveolitis in BAL and an increased amount of proliferating cells in lung interstitium. POF significantly inhibited any of the parameters named, whereas prednisolone and colchicine had little effect. Data cannot be applied directly in human disease. There are however many similarities between CFA and bleomycin-induced lung injury and alveolitis. We conclude that POF is an effective inhibitor of neutrophil alveolitis, whereas neither colchicine nor prednisolone exerted significant influence in our model. We suggest POF effects should be further investigated regarding anti-inflammatory and anti-fibrotic properties.     

Axillary lymph node metastases of bronchogenic carcinoma

BACKGROUND: Metastasis of bronchogenic carcinoma to axillary lymph nodes is rare. The pathways and possible significance of axillary lymph node metastasis from bronchogenic carcinoma were investigated. METHODS: Seventeen patients with probable axillary lymph node metastases from bronchogenic carcinoma were identified by computed tomography. There were 15 nonsmall cell lung cancers and 2 small cell lung cancers. Axillary lymph node metastasis was proven by biopsy in six cases. Metastases were presumed because of an increase in the size of axillary lymph nodes compared with prior studies in six patients and enlarged axillary lymph nodes associated with biopsy-proven ipsilateral supraclavicular lymph node metastasis in five patients. RESULTS: Four of 10 right-sided lung cancers had ipsilateral and six had contralateral axillary lymph node metastases. Six of seven left-sided cancers had ipsilateral and one had contralateral axillary lymph node metastases. Patients with ipsilateral lymph node disease had chest wall involvement and/or supraclavicular and mediastinal lymph node metastases. All seven patients with contralateral axillary lymph node metastases had supraclavicular and/or mediastinal lymph node metastases. CONCLUSION: Bronchogenic carcinoma may involve ipsilateral axillary lymph nodes via either chest wall invasion or retrograde spread from supraclavicular lymph nodes. Contralateral axillary lymph node involvement requires involvement of contralateral mediastinal and supraclavicular lymph nodes with retrograde spread to the axillary lymph nodes.     

The value of extensive lymphadenectomy in cancer of the lower esophagus and cardia

Between 1980 and 1997, 1194 patients with a malignant tumor of the lower esophagus have been observed and treated in our Institution. There were 555 patients (46.5%) presenting with squamous-cell carcinoma, 101 (8.5%), with Barrett's adenocarcinoma and 538 (45%) with cardia adenocarcinoma. Most patient underwent a transthoracic esophagectomy with esophagogastroplasty; transhiatal approach was mainly reserved to high-risk patients. Over the past two years sixty-three patients (42 with adenocarcinoma and 21 with squamous cell carcinoma) underwent enlarged mediastinal lymphadenectomy. Three patients (4.7%) died post-operatively: one sepsis, in pulmonary embolism and one myocardial infarction. Four patients (6.3%) developed pulmonary complications: no patient had recuriential palsy. Pathologic exam revealed 1342 nodes (807 thoracic and 827 abdominal). Twenty patients (31.7%) had mediastinal nodal metastases, of which 8 in the upper mediastinum. Median follow-up was 19 months (2-36 months). Seven of the sixteen patients with recurrent disease (12 systemic, 3 mediastinal and 1 anastomotic) died. The number of metastatic nodes increased with serial section and even more with immunohistochemical staining technique (from 11.7% to 13% to 15.5%, respectively). Two patients were up-staged from M0 to M1 because of peripancreatic nodal micrometastases. We conclude that enlarged mediastinal lymphadenectomy allowed to detect upper mediastinal lymph node metastases in 12.8% of patients without increasing post-operative complication rate. A longer follow-up is required to evaluate the impact on long term survival.     

Cryptogenic fibrosing alveolitis: have we made any progress?

The interstitial lung diseases (ILD) are a heterogeneous group of disorders the most common of which is cryptogenic fibrosing alveolitis (CFA). This article has summarized recent work in particular on the diagnosis, pathogenesis and treatment of CFA, by reviewing published data accessed through Medline searching. Recent reports suggest a higher prevalence of CFA than previously documented (13.2-20.2/100,000 population) and a rising mortality rate. The prognosis is universally poor with 50% of patients dying within 5 years. Although approximately 30% of patients may live for long periods (> 10 years), morbidity is significant and quality of life in the long-term survivors is poor. Diagnosis is traditionally based on an open lung biopsy, however, more recently the high resolution computer tomography (HRCT) is often used; however, its use without a tissue diagnosis remains controversial. In conclusion, we know substantially more about the pathogenesis of the disease and from this work have a number of possibilities for new therapeutic strategies that will hopefully reach the bedside in the near future. Additionally we have some new non-invasive tests that offer hope for stratifying patients but require further evaluation. For assessing both therapy and investigations we will need substantial groups of patients in multicentre studies to provide sufficient power to allow a conclusion to be reached. To ensure any further progress we must collaborate and enter our patients into such trials.     

Blood pressure changes during short-term fluoxetine treatment

PURPOSE: To evaluate the potential diagnostic role of mediastinal sonography in patients with cystic fibrosis (CF), we screened the mediastinum of adult CF patients with and without signs of infection and healthy controls. METHODS: Fifty-four consecutive adult patients with CF and 53 healthy volunteers underwent high-resolution mediastinal sonography. The paratracheal region and aorticopulmonary window of each subject were examined for lymph nodes. Each patient was screened for clinical signs of infection. RESULTS: Lymph nodes were detectable in the mediastinum of 39 of 50 CF patients (78%); the mean total lymph node volume was 1.5 +/- 1.7 cm3. Lymph nodes were detectable in the mediastinum of 31 of 50 controls (62%); the mean total lymph node volume in this group was 0.3 +/- 0.3 cm3 (p < 0.001). In the 30 CF patients with signs of infection, the mean total lymph node volume was larger (2.0 +/- 1.8 cm3) than in the 20 CF patients without signs of infection (0.7 +/- 0.9 cm3; p = 0.002). CONCLUSIONS: These results indicate that lymph node volume determination by high-resolution mediastinal sonography may help assess inflammatory activity in patients with CF.     

Mediastinal tuberculous lymphadenitis: CT findings of active and inactive disease

OBJECTIVE: The purpose of this study was to analyze CT findings of active and inactive disease in patients with mediastinal tuberculous lymphadenitis. MATERIALS AND METHODS: Using biopsy and culture results, we categorized 49 consecutive patients with mediastinal tuberculous lymphadenitis studied with CT scans as patients with active disease (n = 37) or patients with inactive disease (n = 12). Follow-up CT scans were obtained after antituberculous therapy in 25 patients with active disease and three patients with inactive disease. In 10 patients (seven with active disease and three with inactive disease), CT findings were analyzed and correlated with pathologic findings. RESULTS: In all 37 patients with active disease, the nodes (n = 151) varied in size (1.5-6.7 cm; mean, 2.8 +/- 1.0 cm) and had central low attenuation and peripheral rim enhancement. Calcifications within the nodes were seen in seven patients (19%). In the 12 patients with inactive disease, the nodes (n = 34) varied in size (1.0-4.7 cm; mean, 2.1 +/- 1.0 cm) but were usually smaller than nodes in patients with active disease. In the patients with inactive disease, the diseased nodes were homogeneous and without low-attenuation areas. Calcifications within the nodes were seen in 10 (83%) of the 12 patients with inactive disease. Low-attenuation areas within the nodes corresponded pathologically to areas of caseation necrosis in seven patients with active disease and in no patients with inactive disease. After treatment, enlarged mediastinal nodes in patients with active disease shrunk and low-attenuation areas within the nodes disappeared in all 25 patients. However, the findings of calcified nodes in the three patients with inactive disease did not change after 6 months of follow-up. CONCLUSION: In these 49 patients with mediastinal tuberculous lymphadenitis, CT findings of nodes with central low attenuation and peripheral rim enhancement suggested active disease, and findings of homogeneous and calcified nodes suggested inactive disease. Low-attenuation areas within the nodes had pathologic correspondence to areas of caseation necrosis and may be a reliable indicator for disease activity.     

Bronchogenic carcinoma: utility of CT in the evaluation of patients with suspected lesions

PURPOSE: To assess the utility of computed tomography (CT) in the evaluation of suspected bronchogenic carcinoma. MATERIALS AND METHODS: CT scans were reviewed of 362 patients who had undergone CT for suspected bronchogenic carcinoma. RESULTS: CT findings of 275 patients were consistent with bronchogenic carcinoma. Sixty-five tumors were deemed unresectable on the basis of CT findings, 21 were deemed unresectable on the basis of CT findings and poor surgical risk, 26 proved to be benign, six were metastatic disease from an extrathoracic primary tumor, and 157 were potentially resectable bronchogenic carcinoma. Surgical mediastinal nodal sampling enabled documentation of metastases in 60 of 159 patients. According to nodal station, the sensitivity of CT for metastases was 67% for nodes measured in the long axis and 58% for nodes measured in the short axis; specificity was 56% and 86%, respectively. CONCLUSION: CT can be used to confirm or exclude the presence of bronchogenic carcinoma and to obviate thoracotomy. The specificity of CT is limited, and a histologic diagnosis or follow-up evaluation is necessary. CT has limited value in staging mediastinal lymph nodes.     

Metastasis of an adenocarcinoma of unknown origin to mediastinal lymph nodes, and transient regression

A 67-year-old woman was admitted to our hospital because of fever. Chest roentgenogram showed an enlargement of mediastinal lymph nodes. Despite thorough examination, no definite diagnosis could be made. The mediastinal lymph nodes got smaller over the next 3 weeks and a chest roentgenogram taken 4 months later showed no mediastinal lymphadenopathy. The mediastinal lymphadenopathy and fever recurred 5 months later. She underwent thoracotomy and the mediastinal lymph nodes were excised. Microscopic examination of pretracheal lymph node specimens showed invasion of poorly differentiated adenocarcinoma associated with abundant tumor-infiltrating lymphocytes. The other lymph nodes showed sarcoid reaction. Although she has been followed for one year and 11 months, no primary site of the cancer has been found. Metastasis of cancer of unknown origin to mediastinal lymph nodes is extremely rare. It is also interesting that the lymph node swelling diminished spontaneously. The tumor-infiltrating lymphocytes and sarcoid reactions may have been immunological responses to the cancer and may have caused the transient regression.     

Scintigraphic evaluation of 67GA citrate in the comprehensive study of diffuse pulmonary lesions

Scintigraphic evaluation of 67Ga citrate was made in 102 patients with diffuse pulmonary lesions (DPL) of various genesis. There was respiratory sarcoidosis in 40 patients, exogenous allergic alveolitis in 47, idiopathic fibrosing alveolitis in 3, histiocytosis X in 6, and carcinomatosis in 6. Radionuclide findings indicated that the radioagent accumulated in intrathoracic lymph nodes of the mediastinum and partially in the lung tissue in 75.5% of cases at the acute stage of the disease, negative results were in 24.5%, as explained by the fact that the studies were conducted at remission or in the presence of pneumosclerosis. Reexaminations of DPL patients using 67Ga citrate may yield objective information on the treatment performed and, if the latter fails, correct it.     

Intrathoracic lymphadenopathy in patients with empyema

PURPOSE: Our goal was to determine the prevalence of intrathoracic lymphadenopathy on chest CT in patients with empyema. METHOD: We retrospectively identified 27 patients (14 men, 13 women, mean age 43 years) with nontuberculous empyema examined with chest CT. All scans were reviewed by two of three board-certified radiologists for the presence of intrathoracic lymphadenopathy (> or = 1 cm, short axis) in an American Thoracic Society (ATS) nodal station or the internal mammary region. Differences were resolved by consensus. RESULTS: Thirteen (48%) patients with empyema had lymphadenopathy on chest CT. The mean number of enlarged lymph nodes for the patients with lymphadenopathy was 3.2 (SD +/-2.3, range 1-8). The mean size of the largest lymph node was 1.4 cm (range 1.0-2.5 cm). The lymphadenopathy was unilateral and ipsilateral to the empyema in seven (54%), bilateral in five (38%), and unilateral contralateral to the empyema in one. The distribution of lymphadenopathy according to ATS nodal stations was 4R (n = 8), 7 (n = 6), 10R (n = 5); n = 2 each 2R, 10L, 11L; and n = 1 each 11R, 2L, 4L, and 6. Four patients had internal mammary lymphadenopathy. Pleural fluid and smooth pleural thickening were present in each case. Four patients had follow-up CT after treatment. There was a decrease or resolution of the lymphadenopathy in each case. CONCLUSION: Intrathoracic lymphadenopathy is a common CT finding in patients with empyema and occurred in 48% of this series. In patients with smooth pleural thickening and pleural effusion, intrathoracic lymphadenopathy should not be used as a criterion to differentiate empyema from malignant or tuberculous pleural effusion.     

Congenital ptosis: longterm results using stored fascia lata

A 67-year-old woman was admitted for intestinal pseudoobstruction associated with peripheral sensitive neuropathy. Jejunal biopsies performed during laparotomy, showed axonal degeneration and lympho-plasmocytic infiltration in myenteric plexus. High titer of seric anti-Hu antibodies suggested a paraneoplastic syndrome. Thoracic CT scan showed mediastinal lymph nodes. Their histological examination confirmed the diagnosis of metastatic small-cell lung carcinoma. Her condition gradually deteriorated despite supportive parenteral nutrition, chemotherapy, steroids and intravenous immunoglobulins. She died 12 months after the onset of symptoms.     

O-GlcNAcylation of key nuclear and cytoskeletal proteins: reciprocity with O-phosphorylation and putative roles in protein multimerization

BACKGROUND: Registered mortality from cryptogenic fibrosing alveolitis (CFA) in England and Wales has increased substantially since the specific International Classification of Diseases code for CFA was introduced in 1979. However, since a significant proportion of deaths from CFA are misclassified as post inflammatory fibrosis (PIF), it is possible that the observed rise in CFA mortality is due to diagnostic transfer from this code. To investigate this, and to assess mortality trends in other countries, annual CFA and PIF mortality data from England and Wales, USA, Australia, Scotland, Canada, New Zealand, and Germany were analysed. METHODS: Crude annual mortality rates were calculated and rates standardised by Poisson regression to allow assessment of changes over time and comparison between countries, sexes, and age groups. The relative trends in mortality from CFA and PIF were assessed by calculating the annual ratio of CFA to PIF deaths. RESULTS: Men were more likely than women to die from both CFA and PIF in all countries. The highest standardised CFA mortality rate occurred in England and Wales, and the lowest in Germany. Since 1979 mortality from CFA has increased in England and Wales, Australia, Scotland and Canada, but there was no trend in CFA mortality in New Zealand or Germany. In the USA mortality from CFA was low and has fallen. Mortality from PIF increased in all countries except New Zealand and Germany, and the highest PIF mortality, together with the greatest increase over time, was seen in the USA. Changes over time in the annual ratio of CFA to PIF deaths in all countries were small, implying that diagnostic transfer is not a major cause of the increasing CFA mortality. CONCLUSIONS: Mortality from CFA continues to increase in England and Wales and in many other countries. Diagnostic transfer from PIF does not appear to be a major cause of this.